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1

Wen, Zuhuang, Yijuan Long, Lili Yang, Jiangang Hu, Ning Huang, Yuan Cheng, Li Zhao, and Huzhi Zheng. "Constructing H+-triggered bubble generating nano-drug delivery systems using bicarbonate and carbonate." RSC Advances 6, no. 107 (2016): 105814–20. http://dx.doi.org/10.1039/c6ra19863e.

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2

Proulx, Gilbert, and Dwight Rodtka. "Killing Traps and Snares in North America: The Need for Stricter Checking Time Periods." Animals 9, no. 8 (August 17, 2019): 570. http://dx.doi.org/10.3390/ani9080570.

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Анотація:
In this review, we make the point that current checking times for killing traps and snares are inadequate or nonexistent in most North American jurisdictions. We use Conibear 120 rotating-jaw traps and killing neck snares as examples of trapping devices that may fail to consistently and humanely kill furbearers. Because these killing devices are not powerful enough for the target species, the trigger systems do not properly position the animals in traps, or trappers are inexperienced and improperly set traps or snares, these killing devices become restraining devices, and animals suffer long and painful deaths. Because trappers use a variety of trigger configurations and trap sets, all killing devices, even those certified by trapper organizations or governments, should be monitored at least once every 24 h on traplines, but preferably every 12 h, because one cannot know a priori whether traps will strike animals in appropriate locations for a quick kill. However, when using trapping devices such as killing neck snares that are legal and allowed by government agencies despite being inhumane, trappers should check them every 12 h. When traplines are situated near urban areas, e.g., within 10 km, checks should be done every 12 h to release pets and non-target animals.
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3

Rahman, Md Mokhlesur, Md Shahjahan Ali Sarker, M. Nazrul Islam, and Nazmul Hoque. "Consequences of use of fenpropathrin compared to other fish toxicants in commercial aquaculture." Asian-Australasian Journal of Food Safety and Security 3, no. 1 (May 30, 2019): 27–37. http://dx.doi.org/10.3329/aajfss.v3i1.55924.

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Анотація:
Use of fish toxicants is an important management tool in inland commercial aquaculture. In entrepreneurial fishery in northwest Bangladesh where pond ownership (using rights due to lease) changes frequently (every few years) use of fish toxicants is very routine and more crucial. Along with some traditional fish toxicants (rotenone and aluminium phosphide), unconventional and insecticides like fenpropathrin (not approved for aquaculture use) are being used by fish farm owners in northwest Bangladesh. The study was conducted to understand the consequences of use of fenpropathrin compared to other traditional fish toxicants in commercial aquaculture for harvesting of food fish. Of all the toxicants, fenpropathrin’ s impact was lowest on zooplankton and aquatic insect population, while rotenone had the lowest impact on benthos population in terms of killing and quick recovery time for the population, primarily due to the high turbidity (suspended soil particle) of the pond water (under this study) by which both fenpropathrin and rotenone got affected. Aluminium phosphide found to be more damaging in terms of killing and relatively longer recovery time for zooplankton, aquatic insect and benthos population. Using convenience, quick killing, cheaper price, short duration of toxicity and no potential long-term damage of the waterbody contributes positively for fenpropathrin as fish toxicant except the severe potential public health concern from eating of fish killed by fenpropathrin due to very high bioconcentration factor of fenpropathrin; hence, demands regulation of fenpropathrin’ s use as fish toxicants for food fish. Asian Australas. J. Food Saf. Secur. 2019, 3(1), 27-37
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4

Hayashi, Masayuki, Masashi Nomura, and Daisuke Kageyama. "Rapid comeback of males: evolution of male-killer suppression in a green lacewing population." Proceedings of the Royal Society B: Biological Sciences 285, no. 1877 (April 18, 2018): 20180369. http://dx.doi.org/10.1098/rspb.2018.0369.

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Анотація:
Evolutionary theory predicts that the spread of cytoplasmic sex ratio distorters leads to the evolution of host nuclear suppressors, although there are extremely few empirical observations of this phenomenon. Here, we demonstrate that a nuclear suppressor of a cytoplasmic male killer has spread rapidly in a population of the green lacewing Mallada desjardinsi . An M. desjardinsi population, which was strongly female-biased in 2011 because of a high prevalence of the male-killing Spiroplasma endosymbiont, had a sex ratio near parity in 2016, despite a consistent Spiroplasma prevalence. Most of the offspring derived from individuals collected in 2016 had 1 : 1 sex ratios in subsequent generations. Contrastingly, all-female or female-biased broods appeared frequently from crossings of these female offspring with males derived from a laboratory line founded by individuals collected in 2011. These results suggest near-fixation of a nuclear suppressor against male killing in 2016 and reject the notion that a non-male-killing Spiroplasma variant has spread in the population. Consistently, no significant difference was detected in mitochondrial haplotype variation between 2011 and 2016. These findings, and earlier findings in the butterfly Hypolimnas bolina in Samoa, suggest that these quick events of male recovery occur more commonly than is generally appreciated.
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5

Beyerchen, Alan. "Rational Means and Irrational Ends: Thoughts on the Technology of Racism in the Third Reich." Central European History 30, no. 3 (September 1997): 386–402. http://dx.doi.org/10.1017/s0008938900014497.

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Анотація:
Among the most haunting features of the culture of murder created by the Nazis are the ruthless efficiency and sheer scale of their success in killing millions of human beings. There are those who link both to the earlier efficiency and scale of death in the titanic and grinding battles of the Great War. And there are others who would associate both with the alternatives of quick or lingering death promised by nuclear war. Efficiency and scale seem common to the mass death produced or proposed in the twentieth century, and many observers view both as attributes of the process of modernity.
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6

Campbell, MH, and RD Murison. "Effect of mixtures of tetrapion and 2,2-DPA on the control of serrated tussock (Nassella trichotoma)." Australian Journal of Experimental Agriculture 25, no. 3 (1985): 672. http://dx.doi.org/10.1071/ea9850672.

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Анотація:
Mixtures of tetrapion (sodium 2,2,3,3-tetrafluoropropionate) and 2,2-DPA (sodium 2,2-dichloropropionate) at rates of 1.125 + 5.2 and 0.75 + 10.4 kg/ha a.i. were applied to serrated tussock on six occasions between 1980 and 1983 and were equal to or superior to the recommended rate of tetrapion alone (1.5 kg/ha a.i.) or 2,2-DPA alone (20.8 kg/ ha a.i.) in killing serrated tussock. Although the mixtures of tetrapion and 2,2-DPA produced a much faster phytotoxic effect on serrated tussock than tetrapion alone, establishment of surfaces own pasture species was not improved by using the mixtures. The reasons for this result are discussed. Mixtures of tetrapion and 2,2-DPA may be useful on soils where residual effects of tetrapion remain for long periods, when quick phytotoxic effects will stop serrated tussock flowering or allow re-spraying to be carried out after 6 weeks rather than after 9-12 weeks with tetrapion alone, and where improved effectiveness on annual grass weeds is required. Establishment of surface-sown pasture species after use of tetrapion, 2,2-DPA, or the mixtures applied before the autumn break, was improved by killing annual weeds with glyphosate application 1 week before sowing in late autumn or early winter.
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7

Jay, Chourasia. "The Engineered CRISPR-CAS System is a Beneficial Biological Tool for Detecting and Combating Antibiotic Resistance Microbes." BOHR International Journal of Biocomputing and Nano Technology 1, no. 1 (2021): 40–41. http://dx.doi.org/10.54646/bijbnt.08.

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Анотація:
Nowadays, the quick detection of antibiotic resistance bacteria causes a major problem in the field of the development of new antibiotics against the resistant bacteria. To overcome this problem, genome editing tools like clustered regularly interspaced short palindromic repeats (CRISPR) can be used. The CRISPR-CAS system is useful for targeting and killing antibiotic-resistant bacteria by cleaving resistance genes. It is also used to detect antibioticresistant bacteria. CRISPR is made up of a single guide RNA and the CAS 9 protein. The single guide RNA is used to guide toward the target sequence, and the CAS 9 protein is an enzyme that cuts DNA and is used in conjunction with the guide RNA. This modified sgRNA contains a complementary sequence to that of the target resistance gene and recognizes the target resistance sequence; therefore, it is cleaved by CAS-9 protein, and the removal of the resistance gene turns bacteria into antibiotic-sensitive ones. One of the delivery systems of CRISPR into bacteria is via bacteriophage.
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8

Proulx, Gilbert, Stephen R. Cook, and Morley W. Barrett. "Assessment and preliminary development of the rotating-jaw Conibear 120 trap to effectively kill marten (Martes americana)." Canadian Journal of Zoology 67, no. 4 (April 1, 1989): 1074–79. http://dx.doi.org/10.1139/z89-149.

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Анотація:
Testing and development of the commercially available rotating-jaw Conibear 120 (C120) trap were conducted from January to June 1986 with wild marten (Martes americana) in simulated natural environments. Minimizing the pain and suffering of animals was a primary concern throughout the entire investigation. Through a series of approach tests involving traps wired in the set position, a pitch-fork style trigger was developed which enabled the trap to consistently strike animals in the head and neck region. The ability of the C120 to effectively kill marten was first assessed in preselection tests in which anaesthetized animals were placed in the trap in a position that duplicated the finding of the approach tests. Five out of six animals were rendered unconscious within 3 min. Thereafter, the ability of the C120 to effectively kill unanaesthetized marten was tested against that of a prototype, the C120 Mark IV, a more powerful modified version of the original model. The C120 failed to render unconscious at least five out of six unanaesthetized marten within 3 min and, by protocol, was rejected as an effective killing trap. The C120 Mark IV, with a metal bar welded on the top striking jaw, rendered five out of six marten unconscious within 3 min and qualified for further testing as a potentially effective trap to kill marten. Despite its wide use as a quick-kill trap, the C120 did not meet the performance criteria of this study. The mechanically upgraded C120 Mark IV outperformed the C120 but further improvements are needed to ensure consistently quick kills with marten.
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9

Amrane, Dyhia, Christophe-Sébastien Arnold, Sébastien Hutter, Julen Sanz-Serrano, Miguel Collia, Amaya Azqueta, Lucie Paloque, et al. "2-Phenoxy-3-Trichloromethylquinoxalines Are Antiplasmodial Derivatives with Activity against the Apicoplast of Plasmodium falciparum." Pharmaceuticals 14, no. 8 (July 26, 2021): 724. http://dx.doi.org/10.3390/ph14080724.

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Анотація:
The malaria parasite harbors a relict plastid called the apicoplast. Although not photosynthetic, the apicoplast retains unusual, non-mammalian metabolic pathways that are essential to the parasite, opening up a new perspective for the development of novel antimalarials which display a new mechanism of action. Based on the previous antiplasmodial hit-molecules identified in the 2-trichloromethylquinoxaline series, we report herein a structure–activity relationship (SAR) study at position two of the quinoxaline ring by synthesizing 20 new compounds. The biological evaluation highlighted a hit compound (3i) with a potent PfK1 EC50 value of 0.2 µM and a HepG2 CC50 value of 32 µM (Selectivity index = 160). Nitro-containing (3i) was not genotoxic, both in the Ames test and in vitro comet assay. Activity cliffs were observed when the 2-CCl3 group was replaced, showing that it played a key role in the antiplasmodial activity. Investigation of the mechanism of action showed that 3i presents a drug response by targeting the apicoplast and a quick-killing mechanism acting on another target site.
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10

de Jong, Irene. "De ring van Polycrates (Herodotus, Historiën 3.39-43)." Lampas 52, no. 1 (March 1, 2019): 3–15. http://dx.doi.org/10.5117/lam2019.1.002.dejo.

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Анотація:
Summary This paper offers a narratological close reading of one of Herodotus’ most celebrated stories. Special attention is paid to the recurrent Herodotean themes and story-patterns which shape it and thus can help to interpret it. For once the advice of a warner is heeded, but the return of the ring shows that Polycrates’ fate is already sealed and cannot be averted anymore. His great good fortune has brought Polycrates the envy of the gods, a concept which must be looked at in terms of the contemporary Ionian interest in ‘balance’ (of the bodily humours, of climate, of good fortune): the gods watch over the balance of the kosmos and when mortals threaten to disturb it (because of excessive power, riches or good fortune), these mortals are brought down. Most of the times these ‘excessive’ mortals also ‘earn’ their fate by committing crimes or making grave mistakes, and the quick account of Polycrates’ earlier career showed him killing one of his brothers and abusing the unwritten law of ξεινίη. When he faithfully executes Amasis’ advice and throws away his precious ring it is already too late and, as Amasis concludes, his fate cannot be changed anymore.
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11

Sweeney, Esther, Akshay Sabnis, Andrew M. Edwards, and Freya Harrison. "Effect of host-mimicking medium and biofilm growth on the ability of colistin to kill Pseudomonas aeruginosa." Microbiology 166, no. 12 (December 1, 2020): 1171–80. http://dx.doi.org/10.1099/mic.0.000995.

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In vivo biofilms cause recalcitrant infections with extensive and unpredictable antibiotic tolerance. Here, we demonstrate increased tolerance of colistin by Pseudomonas aeruginosa when grown in medium that mimics cystic fibrosis (CF) sputum versus standard medium in in vitro biofilm assays, and drastically increased tolerance when grown in an ex vivo CF model versus the in vitro assay. We used colistin conjugated to the fluorescent dye BODIPY to assess the penetration of the antibiotic into ex vivo biofilms and showed that poor penetration partly explains the high doses of drug necessary to kill bacteria in these biofilms. The ability of antibiotics to penetrate the biofilm matrix is key to their clinical success, but hard to measure. Our results demonstrate both the importance of reduced entry into the matrix in in vivo-like biofilm, and the tractability of using a fluorescent tag and benchtop fluorimeter to assess antibiotic entry into biofilms. This method could be a relatively quick, cheap and useful addition to diagnostic and drug development pipelines, allowing the assessment of drug entry into biofilms, in in vivo-like conditions, prior to more detailed tests of biofilm killing.
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12

Tanaka, M., T. Suda, T. Yatomi, N. Nakamura, and S. Nagata. "Lethal effect of recombinant human Fas ligand in mice pretreated with Propionibacterium acnes." Journal of Immunology 158, no. 5 (March 1, 1997): 2303–9. http://dx.doi.org/10.4049/jimmunol.158.5.2303.

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Abstract Fas ligand (FasL) is a type II membrane protein. Binding of FasL to its receptor, Fas, induces apoptosis. Matrix metalloproteinase cleaves the membrane-bound human FasL to yield the active soluble form. Here, we have produced a large amount of human soluble rFasL using the yeast, Pichia pastoris. The purified rFasL was found to be glycosylated and to exist as a trimer. The rFasL was effective in inducing apoptosis in a Fas-expressing T cell or a fibroblast cell line. The ID50 of rFasL for mouse Fas-expressing T cells was about 0.5 ng/ml. The killing process with rFasL was quick. That is, >80% Fas-expressing mouse cells were killed within 1 h by a saturation concentration of human rFasL. Intravenous administration of 500 microg of human rFasL had a lethal effect in mice. When the mice were pretreated with Propionibacterium acnes, the subsequent injection of 30 microg of human rFasL induced hepatic failure and killed the mice within 24 h. These results indicated that the soluble human FasL is active in inducing apoptosis in vitro and in vivo, and its deleterious effect may be strengthened in patients who are suffering from bacterial infection.
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13

Sakamoto, Hironori, and Koichi Goka. "Acute toxicity of typical ant control agents to the red imported fire ant, Solenopsis invicta (Hymenoptera: Formicidae)." Applied Entomology and Zoology 56, no. 2 (February 23, 2021): 217–24. http://dx.doi.org/10.1007/s13355-021-00728-8.

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Анотація:
AbstractThe red imported fire ant Solenopsis invicta Buren (Hymenoptera: Formicidae), is a serious invasive alien ant around the world and has expanded its invasive range to the Pacific Rim since the early 2000s. It was first reported in Japan in 2017, and its entry through cargo has been reported numerous times in many ports. Colonies have been found in Tokyo Port since 2019, and now it is an urgent issue to prevent further invasion and establishment. Chemical control is the best tested method of insect control, but we have little information on the efficacy of insecticides against S. invicta in Japan. Here, we conducted acute toxicity assays of six quick-acting pyrethroids (transfluthrin, prallethrin, phenothrin, permethrin, metofluthrin, and pyrethrin) for killing adults and five new-type insecticides (fipronil, thiamethoxam, indoxacarb, imidacloprid, and hydramethylnon) for controlling colonies with toxic baits. We found that the LD50 from six pyrethroids were comparable to each other. The ED50 causing abnormal behaviors were smaller than LD50, but some ants recovered from paralysis within 12 h. Fipronil showed the lowest LD50 suggesting this chemical is the most promising agent for controlling S. invicta. Our results promise to develop a method for the chemical control of S. invicta.
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14

Zhang, Yuan, Pingping Luo, Shuangfeng Zhao, Shuxin Kang, Pengbo Wang, Meimei Zhou, and Jiqiang Lyu. "Control and remediation methods for eutrophic lakes in the past 30 years." Water Science and Technology 81, no. 6 (March 15, 2020): 1099–113. http://dx.doi.org/10.2166/wst.2020.218.

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Анотація:
Abstract Accelerated eutrophication, which is harmful and difficult to repair, is one of the most obvious and pervasive water pollution problems in the world. In the past three decades, the management of eutrophication has undergone a transformation from simple directed algal killing, reducing endogenous nutrient concentration to multiple technologies for the restoration of lake ecosystems. This article describes the development and revolution of three remediation methods in application, namely physical, chemical, and biological methods, and it outlines their possible improvements and future directions. Physical and chemical methods have obvious and quick effects to purify water in the short term and are more suitable for small-scale lakes. However, these two methods cannot fundamentally solve the eutrophic water phenomenon due to costly and incomplete removal results. Without a sound treatment system, the chemical method easily produces secondary pollution and residues and is usually used for emergency situations. The biological method is cost-effective and sustainable, but needs a long-term period. A combination of these three management techniques can be used to synthesize short-term and long-term management strategies that control current cyanobacterial blooms and restore the ecosystem. In addition, the development and application of new technologies, such as big data and machine learning, are promising approaches.
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15

Pauter, Katarzyna, Małgorzata Szultka-Młyńska, and Bogusław Buszewski. "Determination and Identification of Antibiotic Drugs and Bacterial Strains in Biological Samples." Molecules 25, no. 11 (May 31, 2020): 2556. http://dx.doi.org/10.3390/molecules25112556.

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Анотація:
Antibiotics were initially natural substances. However, nowadays, they also include synthetic drugs, which show their activity against bacteria, killing or inhibiting their growth and division. Thanks to these properties, many antibiotics have quickly found practical application in the fight against infectious diseases such as tuberculosis, syphilis, gastrointestinal infections, pneumonia, bronchitis, meningitis and septicemia. Antibiotic resistance is currently a detrimental problem; therefore, in addition to the improvement of antibiotic therapy, attention should also be paid to active metabolites in the body, which may play an important role in exacerbating the existing problem. Taking into account the clinical, cognitive and diagnostic purposes of drug monitoring, it is important to select an appropriate analytical method that meets all the requirements. The detection and identification of the microorganism responsible for the infection is also an essential factor in the implementation of appropriate antibiotic therapy. In recent years, clinical microbiology laboratories have experienced revolutionary changes in the way microorganisms are identified. The MALDI-TOF MS technique may be interesting, especially in some areas where a quick analysis is required, as is the case with clinical microbiology. This method is not targeted, which means that no prior knowledge of the infectious agent is required, since identification is based on a database match.
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16

Hussain, Saghir, Noorulain Khakwani, Yasir Faiz, Sonia Zulfiqar, Zahid Shafiq, Faisal Faiz, Abeer Elhakem, et al. "Green Production and Interaction of Carboxylated CNTs/Biogenic ZnO Composite for Antibacterial Activity." Bioengineering 9, no. 9 (September 4, 2022): 437. http://dx.doi.org/10.3390/bioengineering9090437.

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Using biomolecule-rich plant extracts, the conversion of metal ions to metal oxide nanoparticles via abiogenic approach is highly intriguing, environmentally friendly, and quick. The inherent inclination of plant extracts function as capping agents in the insitu synthesis. In this study, biogenic zinc oxide nanoparticles (ZnO−NPs) were synthesized using an aqueous leaf extract from Moringaoleifera. The ZnO−NPs were then mixed with carboxylated carbon nanotubes (CNTs) to create a carboxylated CNTs/biogenic ZnO composite using asol–gel method. The CNTs/ZnO composite displayed 18 mm, 16 mm, and 17 mm zones of inhibition (ZOI) against Bacillus cereus, Pseudomonas aeruginosa, and Escherichia coli, respectively. In contrast with ZnO−NPs, the produced carboxylated CNTs/ZnO composite demonstrated a 13 percent elevation in ZOI as antibacterial activity against Bacillus cereus ATCC 19659, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853. The characterization of ZnO−NPs and the carboxylated CNTs/ZnO composite were performed via FTIR, UV/Vis spectroscopy, SEM, and XRD. The XRD pattern depicted a nano−sized crystalline structure (Wurtzite) of ZnO−NPs and a carboxylated CNTs/ZnO composite. The current work comprehends a valuable green technique for killing pathogenic bacteria, and gives fresh insights into the manufacture of metal oxide composites for future research.
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17

Lamontagne, Maurice, Denis Demers, and Florin Savopol. "Description et analyse du glissement de terrain meurtrier du 25 octobre 1870 dans le rang des Lahaie, Sainte-Geneviève-de-Batiscan, Québec." Canadian Journal of Earth Sciences 44, no. 7 (July 1, 2007): 947–60. http://dx.doi.org/10.1139/e07-001.

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Анотація:
This study presents and analyses a deadly landslide that occurred in October 1870 on a clay slope of the Champlain River at Sainte-Geneviève-de-Batiscan, Quebec. Based on contemporary newspapers and a coroner's report, we can now determine the time of origin, the number and the names of the casualties, and the circumstances of their death. The landslide occurred on 25 October 1870, killing three people instantly while mortally wounding a fourth one. Correlating information with land ownership, we determined that the landslide was located in the rang des Lahaie, in Sainte-Geneviève-de-Batiscan. A number of factors could have lead to the triggering of the landslide : vibrations from the magnitude 6 ½ Charlevoix earthquake of 20 October 1870 or its aftershocks, rainfall, riverbank erosion, or local natural gas sources. Results from recent geotechnical borings indicate that the landslide has occurred in homogeneous clay sequences that should not liquefy under seismic vibrations. We infer that the enhanced fall season water infiltration, possibly coupled with river bank erosion, may have favoured the triggering of this event. The geotechnical properties of the clay, the morphology of the landslide scar, together with the description of a witness all suggest that the event was a quick clay landslide, typical of many others identified along the Champlain River.
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18

Kanayama, Masashi, Makoto Inoue, You-Wen He та Mari Shinohara. "Autophagy enhances NFκB activity and boosts early anti-fungal immunity (INM8P.447)". Journal of Immunology 192, № 1_Supplement (1 травня 2014): 124.13. http://dx.doi.org/10.4049/jimmunol.192.supp.124.13.

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Анотація:
Abstract To avoid excessive inflammation, molecular signaling that triggers immune responses has to be well restrained by various cellular and molecular regulatory mechanisms. However, in infections, such restraints must be removed to exert quick and efficient anti-microbial responses. Here, we report a novel role of autophagy in systemic Candida infection by enhancing early immune responses through increased nuclear factor kappa B (NFκB) activity. First, we found that Atg7 conditional knockout (CKO) mice with LysM-Cre were susceptible to Candida infection. Our ex vivo experiments showed that autophagy did not affect Candida-phagocytosis and inhibition of Candida expansion by macrophages and neutrophils. We also found that phagocytosed conidia were not contained in LC3-positive vesicles. The data suggested that it is unlikely that autophagy played a role in “direct” Candida killing by myeloid cells. Unexpectedly, instead, enhancement of NFκB activation was observed in a certain macrophage subset. Enhancement of NFκB activation was achieved by autophagy-mediated sequestration of an NFκB inhibitor. This allows the macrophages to release chemokines to effectively attract neutrophils to infected sites, resulting in better resistance to Candida in wild-type mice compared to Atg7 CKO mice. Thus, autophagy protects mice from systemic Candida infection by a mechanism distinct from those that protect mice from bacteria and viruses.
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19

M'Homa Soudja, Saidi, Ceena Chandrabos, Mike Veenstra, Anne L. Ruiz, Marie Julien, and Gregoire Lauvau. "Switching on memory CD8+ T cells for enlarged pathogen-specific protection (P4375)." Journal of Immunology 190, no. 1_Supplement (May 1, 2013): 183.23. http://dx.doi.org/10.4049/jimmunol.190.supp.183.23.

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Анотація:
Abstract Memory CD8+ T cells induced upon immunization exhibit improved functional features that contribute to protection of immunized hosts. Although both cognate antigen recognition and inflammation are important for memory CD8+ T cell reactivation, the relative contribution of these factors and the cell types providing these signals in vivo are poorly defined. In recent work, we have shown that Ly6C+CCR2+ inflammatory monocytes, a subset of monocytes, largely orchestrate memory CD8+ T and NK lymphocytes to become potent effector cells by sensing IL-18 and IL-15-derived inflammatory cytokines from monocytes independently of their cognate antigen. Like NK cells, they underwent rapid mobilization, upregulated intense and sustained effector functions during bacterial, viral and parasitic infections, and contributed to innate responses and protection in vivo. In our most recent experiments, we investigate further the molecular mechanisms of cross-talk between activated memory T cells and innate immune effector cells that allow for pathogen-specific protective immunity. Our results unravel a novel and unexpected level of antigen-dependent spatio-temporal tissue organization that is essential to achieve quick and efficient pathogen confinement and killing. This mechanism depends on memory T cell-derived IFN-γ and chemotactic cues, and on effector monocytes. We will present and discuss these data.
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20

E. Baker, Sandra, Stephanie A. Maw, Paul J. Johnson, and David W. Macdonald. "Not in My Backyard: Public Perceptions of Wildlife and ‘Pest Control’ in and around UK Homes, and Local Authority ‘Pest Control’." Animals 10, no. 2 (January 30, 2020): 222. http://dx.doi.org/10.3390/ani10020222.

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Human–wildlife conflict occurs globally. Attempts to control ‘pest’ wildlife involve killing and harming the welfare of animals on a vast scale. We examined public perceptions of 10 wildlife species/groups and wildlife management, in and around UK homes, and public authority ‘pest control’ provision, in an effort to identify ethical, welfare-friendly ways to reduce conflict. Most people reported never having problems with each of the 10 species, and reported problems for some species were largely tolerated. Wasps, mice, and rats were the most frequently problematic species, the least tolerated, and those for which local authorities most often offered pest control services. Do-It-Yourself pest control was preferred over professional control, except for with wasps. People wanted control to be quick, lasting, and safe for people and non-target animals. Where people accepted lethal control, they were nevertheless concerned for animal welfare. Drivers of pest status were complex, while drivers of demand for control were fewer and species-specific. Local authority pest control provision increased over the four years studied, but only half of councils offered advice on preventing/deterring wildlife; this advice was patchy and variable in quality. Greater focus is required on preventing/deterring rather than controlling wildlife problems. Councils should provide standardised, comprehensive advice on prevention/deterrence and prevention/deterrence services.
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Masali, Hajra Tasneem, Aparna Takpere, and Praveen Shahapur. "A Comparative Study of Ziehl-Neelsen Stain and Fluorescent Stain Microscopy in the Diagnosis of Pulmonary Tuberculosis." Journal of Pure and Applied Microbiology 15, no. 4 (October 13, 2021): 2027–33. http://dx.doi.org/10.22207/jpam.15.4.24.

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Tuberculosis remains a global disease, killing over 2 million people each year. India accounts for two-third of the global total i.e. 26%. A good, fast, and economical test to diagnose a disease is urgently needed so that effective treatment can begin as soon as possible. Various investigations can be done for TB diagnosis and these include clinical suspicion, Chest imaging, acid-fast bacilli staining, MTB culture, serological methods and Assays for amplification of nucleic acids. For developing countries like India due to the enormous number of patients and budget restrictions, the assessment of a quick and low-cost diagnostic procedure is critical. A present prospective study was undertaken to compare Ziehl-Neelsen stain with Fluorescent stain microscopy in detecting of Mycobacterium tuberculosis in TB patient’s sputum samples. Among 274 sputum samples collected from suspected TB cases, 50 (18.2%) were positive by ZN and 116 (42.3%) were positive by fluorescent microscopy. The sensitivity, specificity, Positive predictive value (PPV) & Negative predictive value (NPV) of FM microscopy was 98%, 70%, 42%, and 99% respectively. FM microscopy was superior to ZN microscopy in detecting pulmonary tuberculosis cases as it could detect 24.1% more positive cases than ZN staining. Fluorescence staining provides better sensitivity and specificity and can detect accurately more paucibacillary cases hence is of diagnostic value and can help in the early treatment of pulmonary tuberculosis.
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Tahir, Rabia, Aftab Ahmed Anjum, Khushi Muhammad, Asfa Rasool, and Farah Khan. "AVIAN INFLUENZA AND ITS MASS DEPOPULATION STRATEGIES IN INFECTED POULTRY BIRDS." Taiwan Veterinary Journal 41, no. 02 (June 2015): 51–57. http://dx.doi.org/10.1142/s1682648515300026.

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Avian influenza (AI) is a highly contagious and zoonotic viral disease that affects several animal species. It causes heavy economic losses in the domestic poultry. A quick response is always desired in the event of any disease outbreak. The principal approach to control a contagious disease involves the killing of diseased animals along with the bio containment of infectious agent. Mass depopulation of the infected birds plays an important role in the eradication of the disease. The possible strategies for mass depopulation include maceration, electrocution, cervical dislocation, gassing and foaming. All of these procedures are much intensive and time consuming because it involves a lot of man power, biosecurity risks, applicability for all house types and suitability for large-scale emergency implementation. The basic objectives of these strategies include (1) To reduce pain and suffering to the birds, (2) To minimize disease spread and (3) To ensure of protection to human operators from potential biohazards. A suitable depopulation technique can only be suggested keeping in view the species and type of bird involved, and differences in husbandry practices like management, housing and stocking density. Mass depopulation is an important tool to control the spread of any disease but the selection of procedure depends upon the prevailing circumstances. In this paper, various mass depopulation strategies and their selection in different conditions is reviewed and discussed.
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NISHIGUCHI, SHUHEI, TAKASHI FUKUDA, MASASHI ANDO, and YASUYUKI TSUKAMASA. "Effects of temperature treatment before thawing on NAD+ and ATP concentrations in frozen fish meats prepared by instant killing and quick freezing and on pH after thawing." NIPPON SUISAN GAKKAISHI 86, no. 6 (November 15, 2020): 494–501. http://dx.doi.org/10.2331/suisan.20-00030.

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Ma, Yurong, Yingyi Zhu, Benzhi Liu, Guixiang Quan, and Liqiang Cui. "Colorimetric Determination of Hypochlorite Based on the Oxidative Leaching of Gold Nanorods." Materials 11, no. 9 (September 6, 2018): 1629. http://dx.doi.org/10.3390/ma11091629.

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Анотація:
Hypochlorite plays a critical role in killing microorganisms in the water. However, it can also cause cardiovascular diseases, neuron degeneration, and cancer to humans. Although traditional methods feature excellent sensitivity and reliability in detecting hypochlorite, the expensive instruments and strict determination conditions have limited their application in environmental analysis to some extent. Thus, it is necessary and urgent to propose a cheap, facile, and quick analytical assay for hypochlorite. This paper proposes a colorimetric assay for hypochlorite utilizing gold nanorods (AuNRs) as the nanoreactor and color reader. The AuNRs were acquired via a reported seed-mediated method. NaClO with strong oxidation property can cause the etching of gold from the longitudinal tips of AuNRs, which could shorten the aspect ratio of AuNRs, decrease the absorption in the UV–Vis spectrum and also induce the solution color changing from red to pale yellow. Thus, according to the solution color change and the absorbance of longitudinal surface plasmon resonance of AuNRs, we established the calibration curve of NaClO within 0.08 μM to 125 μM (∆Abs = 0.0547 + 0.004 CNaClO, R2 = 0.9631). Compared to traditional method, we obtained the conversion formula between the concentration of residual-chlorine in tap water and the concentration of hypochlorite detected by the proposed colorimetric assay, which is Cresidual-chlorine = 0.24 CNaClO. Finally, the real application of the colorimetric assay in tap water was successfully performed, and the accuracy of the colorimetric method can reach from −6.78% to +8.53%.
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Martini, C., A. Hammerer-Lercher, M. Zuck, A. Jekle, D. Debabov, M. Anderson, and M. Nagl. "Antimicrobial and Anticoagulant Activities ofN-Chlorotaurine,N,N-Dichloro-2,2-Dimethyltaurine, andN-Monochloro-2,2-Dimethyltaurine in Human Blood." Antimicrobial Agents and Chemotherapy 56, no. 4 (January 17, 2012): 1979–84. http://dx.doi.org/10.1128/aac.05685-11.

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ABSTRACTThe aim of this study was to determine the potential application ofN-chlorotaurine (NCT),N,N-dichloro-2,2-dimethyltaurine (NVC-422), andN-monochloro-2,2-dimethyltaurine (NVC-612) as catheter lock solutions for the prevention of catheter blockage and catheter-related bloodstream infections by testing their anticoagulant and broad-spectrum antimicrobial activities in human blood. NCT, NVC-422, NVC-612, and control compounds were serially diluted in fresh human blood to evaluate the effects on prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, and direct thrombin inhibition. Quantitative killing assays against pathogens, including methicillin-resistantStaphylococcus aureus,Escherichia coli, andCandida albicans, were performed in the presence of heparin and human blood. NCT and NVC-612 (1.38 mM each) and 1.02 mM NVC-422 prolonged prothrombin time (Quick value, 17 to 30%), activated partial thromboplastin time 3- to 4-fold to 76 to 125 s, and thrombin time 2- to 4-fold to 34 to 68 s. Fibrinogen decreased from 258 to 283 mg/dl (range of controls) to <40 mg/dl. No direct thrombin inhibition was observed by NVC-422 or NVC-612. Heparin did not influence the bactericidal activity of NCT. The microbicidal activities of NCT, NVC-422, and NVC-612 were maintained in diluted human blood. NCT, NVC-612, and NVC-422 have broad-spectrum antimicrobial activity in blood and anticoagulant activity targeting both intrinsic and extrinsic pathways of the coagulation system. These properties support their application as catheter lock solutions.
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Acharya, T. D., S. C. Mainali, I. T. Yang, and D. H. Lee. "ANALYSIS OF JURE LANDSLIDE DAM, SINDHUPALCHOWK USING GIS AND REMOTE SENSING." ISPRS - International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences XLI-B6 (June 17, 2016): 201–3. http://dx.doi.org/10.5194/isprs-archives-xli-b6-201-2016.

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Анотація:
On 2<sup>nd</sup> August 2014, a rainfall-induced massive landslide hit Jure village, Sindhupalchowk killing 156 people at a distance of 70 km North-East of Kathmandu, Nepal. The landslide was a typical slope failure with massive rock fragments, sand and soil. A total of estimated 6 million cubic meters debris raised more than 100 m from the water level and affected opposite side of the bank. The landslide blocked the Sunkoshi River completely forming an estimated 8 million cubic meter lake of 3km length and 300-350m width upstream. It took nearly 12 hour to fill the lake and overflow the debris dam. The lake affected five Village Development Committees (VDC) including highway, school, health post, postal service, police station, VDC office and temple upstream. The bottom of the dam was composed of highly cemented material and the derbies affected Sunkoshi hydropower downstream. Moreover, it caused the potential threat of Lake Outburst Flood. The lake was released by blasting off part of the landslide blockade and facilitated release of water from the lake. With the help of Remote Sensing (RS), series satellite images were used to identified, compared with previous state and quick estimation of potential treat was analysed. Using geographic information System (GIS) technology, estimation of volume, affected households, service centres, parcels etc. in the area was possible. In such hilly regions where disaster are very frequent, using GIS and RS technology comes very handy for immediate planning and response.
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Acharya, T. D., S. C. Mainali, I. T. Yang, and D. H. Lee. "ANALYSIS OF JURE LANDSLIDE DAM, SINDHUPALCHOWK USING GIS AND REMOTE SENSING." ISPRS - International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences XLI-B6 (June 17, 2016): 201–3. http://dx.doi.org/10.5194/isprsarchives-xli-b6-201-2016.

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Анотація:
On 2&lt;sup&gt;nd&lt;/sup&gt; August 2014, a rainfall-induced massive landslide hit Jure village, Sindhupalchowk killing 156 people at a distance of 70 km North-East of Kathmandu, Nepal. The landslide was a typical slope failure with massive rock fragments, sand and soil. A total of estimated 6 million cubic meters debris raised more than 100 m from the water level and affected opposite side of the bank. The landslide blocked the Sunkoshi River completely forming an estimated 8 million cubic meter lake of 3km length and 300-350m width upstream. It took nearly 12 hour to fill the lake and overflow the debris dam. The lake affected five Village Development Committees (VDC) including highway, school, health post, postal service, police station, VDC office and temple upstream. The bottom of the dam was composed of highly cemented material and the derbies affected Sunkoshi hydropower downstream. Moreover, it caused the potential threat of Lake Outburst Flood. The lake was released by blasting off part of the landslide blockade and facilitated release of water from the lake. With the help of Remote Sensing (RS), series satellite images were used to identified, compared with previous state and quick estimation of potential treat was analysed. Using geographic information System (GIS) technology, estimation of volume, affected households, service centres, parcels etc. in the area was possible. In such hilly regions where disaster are very frequent, using GIS and RS technology comes very handy for immediate planning and response.
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28

Costa, M. A. F., F. T. G. Rodrigues, B. C. A. Chagas, C. M. F. Rezende, A. M. Goes, and R. A. P. Nagem. "Preliminary crystallographic studies of aSchistosoma mansoniantigen (Sm21.7) dynein light-chain (DLC) domain." Acta Crystallographica Section F Structural Biology Communications 70, no. 6 (May 24, 2014): 803–7. http://dx.doi.org/10.1107/s2053230x14009273.

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Schistosomiasis is an inflammatory chronic disease that represents a major health problem in tropical and subtropical countries. The drug of choice for treatment, praziquantel, is effective in killing adult worms but fails to kill immature forms and prevent reinfection. One prominent antigen candidate for an anti-schistosomiasis vaccine is the protein Sm21.7 (184 amino-acid residues) fromSchistosoma mansoni, a tegumental protein capable of reducing the worm burden in a murine immunization model. In the present work, the Sm21.7 gene was cloned and expressed inEscherichia coliand the full-length protein was purified to homogeneity. Crystals of recombinant Sm21.7 suitable for X-ray diffraction were obtained using PEG monomethyl ether 2000 as a precipitant. X-ray diffraction images of a native crystal (at 2.05 Å resolution) and a quick-cryosoaked NaI derivative (at 1.95 Å resolution) were collected on the W01B-MX2 beamline at the Laboratório Nacional de Luz Síncrotron (LNLS, Brazilian Synchrotron Light Laboratory/MCT). Both crystals belonged to the hexagonal space groupP6122, with similar unit-cell parametersa=b= 108.5,c= 55.8 Å. SIRAS-derived phases were used to generate the first electron-density map, from which a partial three-dimensional model of Sm21.7 (from Gln89 to Asn184) was automatically constructed. Anaysis of dissolved crystals by SDS–PAGE confirmed that the protein was cleaved in the crystallization drop and only the Sm21.7 C-terminal domain was crystallized. The structure of the Sm21.7 C-terminal domain will help in the localization of the epitopes responsible for its protective immune responses, constituting important progress in the development of an anti-schistosomiasis vaccine.
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Avci, Edibe, Yeliz Z. Akkaya-Ulum, Digdem Yoyen-Ermis, Gunes Esendagli, and Banu Balci-Peynircioglu. "A method for high-purity isolation of neutrophil granulocytes for functional cell migration assays." Turkish Journal of Biochemistry 44, no. 6 (December 18, 2019): 810–21. http://dx.doi.org/10.1515/tjb-2019-0089.

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Abstract Background Neutrophil-mediated killing of pathogens is one of the most significant functions of the primary defense of the host. Neutrophil activity and migration play a key role in inflammatory conditions. To gain insights into the interactions between neutrophils and neutrophil migration-related disorders, a large number of sophisticated methods have been developed. The technical limitations of isolating highly purified neutrophil populations, minimizing both cell death and activation during the isolation process, and the short lifespan of neutrophils present challenges for studying specific functions of neutrophils in vitro. In this study, we aimed to evaluate a separation medium-based density gradient method to obtain highly purified neutrophil populations and combined this protocol with a model for studying neutrophil migration in-vitro. Materials and methods Human granulocytes were isolated using Lympholyte-poly solution. The purity and viability of isolated neutrophils were assessed by flow cytometry and morphological analysis. Neutrophil activation was confirmed by immunocytochemistry. Lastly, filter assay was performed to measure neutrophil chemotaxis. Results and discussion All validation experiments revealed that this method was capable of generating a highly purified neutrophil population for further functional in-vitro assays. Consequently, this study demonstrates a quick, cost effective, and easy-to-follow model, and may be a significant alternative to isolation methods that need extra subsequent steps such as flow cytometry-based cell sorting for reaching highly purified neutrophil population. Conclusion The suggested combination of methods for the isolation and cell migration analysis of human neutrophils is highly recommended to use for disease models involving neutrophil migration such as autoinflammatory disorders.
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Humelnicu, Andra-Cristina, Petrișor Samoilă, Corneliu Cojocaru, Raluca Dumitriu, Andra-Cristina Bostănaru, Mihai Mareș, Valeria Harabagiu, and Bogdan C. Simionescu. "Chitosan-Based Therapeutic Systems for Superficial Candidiasis Treatment. Synergetic Activity of Nystatin and Propolis." Polymers 14, no. 4 (February 11, 2022): 689. http://dx.doi.org/10.3390/polym14040689.

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The paper deals with new approaches to chitosan (CS)-based antifungal therapeutic formulations designed to fulfill the requirements of specific applications. Gel-like formulations were prepared by mixing CS dissolved in aqueous lactic acid (LA) solution with nystatin (NYS) powder and/or propolis (PRO) aqueous solution dispersed in glycerin, followed by water evaporation to yield flexible mesoporous (pore widths of 2–4 nm) films of high specific surfaces between 1 × 103 and 1.7 × 103 m2/g. Morphological evaluation of the antifungal films showed uniform dispersion and downsizing of NYS crystallites (with initial sizes up to 50 μm). Their mechanical properties were found to be close to those of soft tissues (Young’s modulus values between 0.044–0.025 MPa). The films presented hydration capacities in physiological condition depending on their composition, i.e., higher for NYS-charged (628%), as compared with PRO loaded films (118–129%). All NYS charged films presented a quick release for the first 10 min followed by a progressive increase of the release efficiency at 48.6%, for the samples containing NYS alone and decreasing values with increasing amount of PRO to 45.9% and 42.8% after 5 h. By in vitro analysis, the hydrogels with acidic pH values around 3.8 were proven to be active against Candida albicans and Candida glabrata species. The time-killing assay performed during 24 h on Candida albicans in synthetic vagina-simulative medium showed that the hydrogel formulations containing both NYS and PRO presented the faster slowing down of the fungal growth, from colony-forming unit (CFU)/mL of 1.24 × 107 to CFU/mL < 10 (starting from the first 6 h).
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Bodansky, Daniel, Nina Naske, and Georg Nolte. "“Aerial Security Law.” Case No. 1 BvR 357/05. 115 BVerfGE 118." American Journal of International Law 101, no. 2 (April 2007): 466–71. http://dx.doi.org/10.1017/s0002930000030190.

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“Aerial Security Law.” Case No. 1 BvR 357/05. 115 BVerfGE 118. Available at <http://www.bundesverfassungsgericht.de>.Bundesverfassungsgericht (Federal Constitutional Court of Germany), February 15, 2006.On February 15,2006, the Federal Constitutional Court of Germany (Bundesverfassungsgericht) held the Aerial Security Act to be unconstitutional. This act authorized the use of military force against any aircraft intended to be used for the killing of human beings, if the use of such force was the only means to avert an immediate danger. The Court based its ruling on two grounds: first, that the federal level of government had no legislative power to enact such a law, and second, that the act's authorization of military force infringed upon the guarantee of human dignity as embodied in Article 1(1) of the German Constitution, or Basic Law (Grundgesetz).On January 5, 2003, a small airplane circled over the Frankfurt banking district. For a few moments people saw themselves confronted with a terror attack, recalling 9/11 and the pictures of the burning World Trade Center. The police evacuated several buildings and two Air Force fighter jets arrived before it was established that the pilot was not a terrorist but merely a mentally confused person. A year later, in January 2004, the federal government proposed a draft federal Aerial Security Act. The government argued that the attacks of 9/11, along with the Frankfurt incident, made clear that in order to protect against such attacks, it was necessary to clarify the roles of the federal and state (Länder) governments. “This draft is meant to achieve that aim … and to establish quick and efficient mechanisms for information gathering and decision.”
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Keith, L., L. Sugiyama, and M. Nagao. "Macadamia Quick Decline Caused by Phytophthora tropicalis is Associated with Sap Bleeding, Frass, and Nectria in Hawaii." Plant Disease 94, no. 1 (January 2010): 128. http://dx.doi.org/10.1094/pdis-94-1-0128b.

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Анотація:
Macadamia quick decline (MQD) has been a persistent problem since 1986 when it started killing productive 14- to 36-year-old macadamia trees in the Hilo, HI area. Fungi including Nectria regulosa, Xylaria arbuscula, Phellinus gilvus, and Acremonium recifei have been attributed to MQD and could kill twigs on healthy macadamia trees after artificial inoculation (3). The oomycete originally called Phytophthora capsici and later reclassified as P. tropicalis was also considered to be involved in the MQD complex (3). However, the primary causal agent has never been determined and the issue continues to perplex the industry. Between 2005 and 2006, a mature macadamia field on the Waiakea Experiment Station planted with cv. HAES 333 began to experience a high frequency of MQD. Trees exhibiting dull green, yellow, or brown leaves within the tree canopy were observed. Sap bleeding from the trunk, Ambrosia beetles, and Nectria fruiting bodies were consistently associated with MQD. Disease incidence was 22%. Of 21 infected trees, 53% died within an average period of 6.8 months. Four branch samples were collected from four trees showing browning of leaves, sap bleeding, Ambrosia beetles, and Nectria, and seven P. tropicalis isolates were recovered from diseased tissue on water agar or V8 agar media. No other microorganisms were isolated from diseased branches. On the basis of the morphological characteristics described by Aragaki and Uchida (1), the isolates were identified as P. tropicalis. The morphological identification was confirmed by molecular analysis of the 5.8S subunit and flanking internal transcribed spacers (ITS1 and ITS2) of rDNA amplified from DNA extracted from single-zoospore cultures with the ITS1/ITS4 primers (2,4) and sequenced (GenBank No. FJ849839). Pathogenicity tests were conducted on four 12-year-old macadamia trees in the field. A 4 × 104 zoospore/ml suspension of P. tropicalis isolate L1 was injected into branches of cv. HAES 344 to incite MQD signs and symptoms. Branches inoculated with P. tropicalis started showing the initial sign of MQD, excessive sap bleeding, within 36 days postinoculation (dpi). The presence of Ambrosia beetle frass and the appearance of orange fruiting bodies of Nectria were visible within 110 dpi. No symptoms were noted on the four control tree branches inoculated by the same method but with sterilized distilled water. P. tropicalis was reisolated from the symptomatic macadamia branches, fulfilling Koch's postulates. To our knowledge, this is the first report of P. tropicalis as the primary causal agent of MQD and its association with sap bleeding, Ambrosia beetles, and a saprotrophic species of Nectria. After completion of our research, Ko (3) reported that the MQD P. capsici was P. tropicalis, supporting our finding in this study. Quick decline of macadamia trees continues to be a serious problem in Hawaii. Minimizing tree loss in mature orchards is critical for maintaining the economic viability of Hawaii's macadamia industry. Understanding the biology of this pathosystem will enable the development of control and prevention strategies. References: (1) M. Aragaki and J. Y. Uchida. Mycologia 93:137, 2001. (2) G. Caetano-Annolles et al. Curr. Genet. 39:346, 2001. (3) W.-H. Ko. Bot. Stud. 50:1, 2009. (4) T. J. White et al. PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, CA, 1990.
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N., Prashanth V., and Sneha . "Shock index as a predictor of vasopressor use in patients with sepsis." International Journal of Advances in Medicine 6, no. 5 (September 23, 2019): 1488. http://dx.doi.org/10.18203/2349-3933.ijam20193624.

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Анотація:
Background: Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis and septic shock are major healthcare problems affecting millions of people around the world each year and killing as many as one in four. The documented incidence of sepsis worldwide is 1.8 million each year with mortality rate of almost 30%. Sepsis is the 10th leading cause of death in the United States. Shock index (SI) is defined as “Heart rate divided by Systolic blood pressure (HR/SBP)”. Normal range is 0.5 to 0.7 in healthy adults.Methods: A Prospective study was conducted between August 2018 to March 2019 comprising of 100 consecutive patients presenting to emergency department and ICU with sepsis. Subjects were identified by having evidence of infection presenting with cardiovascular collapse or organ failure with help of q-SOFA(quick- sepsis related organ failure assessment ) and SOFA scores (sequential organ failure assessment score).Cases with clear alternative diagnosis were excluded. Vital signs were recorded, and Shock index was calculated. Primary outcome, which was use of Vasopressor therapy was analysed. Results : A Total of 100 cases were studied, of which 70 patients were males and 30 females with mean age of 48.5 ±16.2 yrs. Most of the cases were between 35 to 60 years. Patients were classified into 3 categories based on shock index:1. <0.8 (normal, n=16) 2. 0.8 to <1.2 (n=29) 3. >1.2 (n=55). The use of vasopressor therapy within first 24 hours for each group was 18%, 34%, and 78%. This difference was statistically significant (p=<0.05).Conclusion : In patients with sepsis an elevated shock index was indicator of early vasopressor therapy in the first 24hours. It is a simple bedside tool to identify septic patients in need for early vasopressor therapy thereby preventing further clinical deterioration.
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Obande-Ogbuinya, Nkiru Edith, Lois Nnenna Omaka-Amari, Jude N. Nwafor, Chinenye B. Omeje, Maria-lauretta Chito Orji, Chihurumnanya Alo, Patricia C. Ngwakwe, et al. "Review of COVID-19 Re-Infection among Recovered Patients and Its Implication for Lung Health." Global Journal of Health Science 12, no. 12 (October 19, 2020): 64. http://dx.doi.org/10.5539/gjhs.v12n12p64.

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Анотація:
COVID-19 infection has continued to pose a very serious health threat to mankind globally despite all efforts geared toward curbing its spread. More worrisome recently is the report from different parts of the world on the re-infection of those treated and recovered with COVID -19 patients thus making containment of the virus even more difficult. Of more worrisome is the fact that the lung, a vital human organ is a major site being attacked by the virus even on re-infection cases. If quick action is not taken early enough, it may lead to the outright death of the patient. A lung infection, (Pneumonia) caused by COVID-19 has been discovered to be having a stunning effect on hospital systems and killing COVID-19 patients silently and it occurs even as the patient is asymptomatic. This paper examines the reasons for re-infection, Lacuna in the reviewed literature with regards to PCR test results, the effect of re-infection on the lungs, and implication for patients&rsquo; lung health. The papers summarized and concluded that it&rsquo;s a fact that re-infection occurs among patients accompanied by mild or severe symptoms having far-reaching implications for the patient&rsquo;s lung health. The paper recommends that the government at all levels should collaborate with WHO, CDC, and health policymakers to legally mandating, that every recovered patient should stay an additional 2weeks in the hospital for early detection of re-infection in order to avert any invasion and damage to the lungs thus ensuring lung health. Also, proper health education should be availed to the recovered patients to avoid any exposures or habits (different from the index disease) such as smoking that can pose dangers to the already fatigued lungs.
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Al-alwani, Safa, and Aseel Almashaleh. "Silver Nanoparticles' Therapeutic Antibacterial, Antiproliferative, and Toxicological Effects." Journal of Basic and Applied Research in Biomedicine 8, no. 1 (October 30, 2022): 8–15. http://dx.doi.org/10.51152/jbarbiomed.v8i1.217.

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Анотація:
Silver nanoparticles, among others, have broad-spectrum antimicrobial properties. Silver nanoparticles have suppressed dangerous microorganisms in medical and agricultural settings in several studies. Chemicals are harmful to humans and the environment, raising awareness of bioactive synthetic methods. These methods produce nanoparticles with better physicochemical qualities, stability, and toxicity. Biogenic nanoparticles can be made from bacterial and fungal byproducts that reduce and stabilize. Encapsulating these nanoparticles with biomolecules from the producing organisms may boost stability and biological activity. Nanoparticles' quick, clean, cheap, and ecological biologic manufacturing technique increases biocompatibility. Silver nanoparticles affect fish, algae, cell-based in vitro procedures, and microbes. Even though most of these studies were done quickly in well-regulated labs with much higher silver ion concentrations than in real life. Many silver types undergo long-term chemical transformation at extremely low levels (ng/L to g/L) in aquatic ecosystems. Thus, silver nanoparticles' environmental and health hazards need additional investigation. Recently detected antimicrobial silver at 10102 μg/mL. Multiple processes make silver nanoparticles dangerous. Basic (Ag0) and monovalent (Ag+) silver are most poisonous. Silver framework free ions affect silver toxicity. ROS damage DNA when elemental or zero-valent silver penetrates tissues. Packaged foods, contaminated water, swimming pools, antifouling, nasal and throat medicines, and other pharmaceuticals include silver nanoparticles. Consumption accumulates silver ions in subcutaneous fat. Prolonged exposure causes argyria-blue-gray skin. Silver inhibits Na+ and Cl absorption, disrupting electrolytes. Airborne silver nanoparticles may influence chronic pulmonary disease patients. Silver ions oxidize enzyme thiols, hindering electron transport and DNA replication. Ag+ rapidly damages DNA and RNA. Silver nanoparticle breakdown into silver ions creates germ-killing ROS. Silver nanoparticles are more hazardous than silver ions in the same atmosphere.
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Yang, Lili, Zuhuang Wen, Yijuan Long, Ning Huang, Yuan Cheng, Li Zhao, and Huzhi Zheng. "A H+-triggered bubble-generating nanosystem for killing cancer cells." Chemical Communications 52, no. 72 (2016): 10838–41. http://dx.doi.org/10.1039/c6cc04511a.

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37

Kramer, Anne Marijn, Sara Ghorashian, Gordon Weng-Kit Cheung, Winston Vetharoy, Dale Moulding, Leila Mekkaoui, Shimobi Onuoha, Persis J. Amrolia, and Martin A. Pule. "Construction and Pre-Clinical Evaluation of a New Anti-CD19 Chimeric Antigen Receptor." Blood 128, no. 22 (December 2, 2016): 1627. http://dx.doi.org/10.1182/blood.v128.22.1627.1627.

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Abstract Relapsed and refractory B-lineage acute lymphoblastic leukemia remain the leading cause of cancer related death in children and young adults. Clinical studies of adoptive cell immunotherapy, re-directing T cells against CD19 by endowing them with a chimeric antigen receptor (CAR), have shown considerable clinical responses. To date, 3 different binding domains (scFv) targeting CD19 have been used in CARs taken forward in clinical trials and we have constructed a new CD19-CAR, derived from a different anti-human CD19 antibody, clone CAT. Whether different binding affinities of the CD19 targeting domain, when significantly different, could affect CAR-mediated T cell functionality has not been evaluated in depth. We therefore investigated the impact of scFv affinity on CAR-mediated T cell function in vitro, as well as on anti-tumour efficacy in vivo. We have generated 3 CD19-CARs only differing in their scFv, which were derived from 3 anti-human CD19 antibodies (Clones FMC63, 4G7 & CAT) respectively. All other structural variables of the CAR and the use of the 4-1BB endodomain were identical. The Kd values obtained by Biacore Surface Plasmon resonance (SPR) analysis ranged from 8.8 x 10-10 to 1.1 x 10-7. Differences in affinity were predominantly determined by the off-rates, leading to significantly quicker dissociation from its target in CAT scFv compared to FMC63 and 4G7. CAT-CAR transduced T-cells showed enhanced cytotoxic responses to the CD19+ cell line SUPT1-CD19 in 51Cr release assays (p<0.001) compared to 4G7 and FMC63. Moreover, CAT+ T-cells demonstrate an increased proliferative capacity following antigen specific stimulation and an increased capacity to produce IL-2 and TNFα (p<0.001). A quick dissociation rate has been described to be of particular importance when targeting cells with low levels of antigen expression, as T cell functional avidity can be detrimentally affected when dissociation is prolonged (Thomas et al, Blood 2011). We therefore investigated cytotoxicity of CAR transduced T cells against a cell line engineered to express CD19 at very low levels. This demonstrated increased cytotoxicity by CAT+ T-cells as well as greater CD107a degranulation in response to low CD19 expressing targets compared to FMC63 or 4G7-transduced T cells. Similarly, CAT+ T-cells showed greater killing of NALM 6 cells at very low effector:target ratios, reflecting the ability of serial killing by CAT+ T-cells by virtue of their rapid dissociation from target cells. Live cell imaging studies by confocal microscopy analysis confirmed a higher number of serial engagements by CAT+ T-cells (p<0.001), as well as greater motility (p<0.001). We are now studying the relative potency in a xenogeneic model of ALL, using a CAR-T cell dose that is purposefully lowered to a suboptimal range to study kinetic differences and tumor clearance. Preliminary data suggests that, transferred after exposure to leukemia, CAT+ T cells have a less exhausted phenotype and higher effector:target ratios 2 weeks after infusion. Further experiments, in which recipient mice are re-challenged with the same tumor, will assess differences in the ability of adoptively-transferred CAR T cells to form memory. In conclusion, we have developed a novel CD19-CAR which confers enhanced cytotoxicity and proliferative responses compared to existing CD19-CARs. Our work indicates that the scFv binding kinetics impacts the functional avidity of CAR-transduced T cells, providing important implications for the design of future CARs, especially when tumour cells expressing low levels of antigen are targeted. Disclosures Onuoha: Autolus Ltd: Employment, Research Funding. Pule:Autolus Ltd: Employment, Equity Ownership, Research Funding; UCL Business: Patents & Royalties; Amgen: Honoraria; Roche: Honoraria.
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Jain, Kanika, Ian C. Henrich, Laura Nicole Quick, Robert A. Young, and Margaret M. Chou. "Abstract 3147: Natural killer cells mediate tumor-inhibitory functions of USP6 in Ewing sarcoma." Cancer Research 82, no. 12_Supplement (June 15, 2022): 3147. http://dx.doi.org/10.1158/1538-7445.am2022-3147.

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Abstract INTRODUCTION: Understanding how Natural Killer (NK) cell activity is regulated by cancer cells is critical for developing NK-cell based immunotherapies. Our studies show that the deubiquitinating enzyme ubiquitin-specific protease-6 (USP6) can induce an immune-stimulatory hot tumor microenvironment in Ewing sarcoma (ES), the 2nd most common pediatric bone cancer. High USP6 expression in ES is associated with significantly improved overall and progression-free survival. We found that USP6 expression in ES cells inhibits xenograft growth in nude mice, but not NSG mice, implicating a role for the innate immune system, particularly cytotoxic NK cells. Notably, USP6 expression enhanced intra-tumoral abundance, activation, and proliferative capacity of NK cells. In vitro cytotoxicity assays confirm that USP6 can directly augment the ability of ES cells to activate NK cells. Based on these observations, we hypothesize that NK cells are essential for USP6-mediated tumor suppression and seek to determine the mechanism by which their cytolytic function is activated by USP6. METHOD: We used ES cell lines A673 and RD-ES expressing USP6 in a doxycycline (dox)-inducible manner, the immortalized human NK cell line NK-92, and primary human and mouse NK cells. Athymic nude or RAG2-/- mice were xenografted subcutaneously with ES cell lines and fed dox-infused water to induce USP6. Immune cell abundance and activation were monitored both in tumors and peripheral blood by flow cytometry. For in vivo depletion of NK cells, 300ug of anti-NK1.1 (PK136) ab was injected i.p. into RAG2-/- mice one day prior to ES xenografting, then once weekly thereafter. RESULTS: USP6 induces in ES cells the surface expression of multiple NK activating ligands, as well as receptors for the apoptotic factor TRAIL (DR5) and Type I/II interferons (IFNAR1 and IFNGR1), both in vitro and in vivo. This leads to enhanced NK activation and renders ES cells hypersensitive to NK-mediated cytotoxicity. IFNy released by activated NK cells feeds back on the USP6-expressing ES cells, inducing synergistic expression of multiple IFNy-inducible genes, including chemokines CXCL9/10 (chemoattractants for NK cells) and ICAM-1 (essential for immunological synapse formation between NK cells and their targets). A potent feed forward loop for NK activation/ES cell killing is thus generated. Concordantly, in RAG2-/- mice, USP6 induces increased intratumoral infiltration and activation of NK cells, and also, strikingly, systemic activation of NK cells. Depletion of NK cells using anti-NK1.1(PK136) completely abrogates USP6-mediated inhibition of ES xenograft growth. CONCLUSION: NK cells are essential for mediating the tumor inhibitory functions of USP6 in ES. We posit that USP6’s ability to activate NK cells both intratumorally and systemically underlies its association with improved ES patient prognosis, which we seek to exploit for therapeutic benefit in future studies. Citation Format: Kanika Jain, Ian C. Henrich, Laura Nicole Quick, Robert A. Young, Margaret M. Chou. Natural killer cells mediate tumor-inhibitory functions of USP6 in Ewing sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3147.
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Gómez-Hoyos, Diego A., Rocío Seisdedos-de-Vergara, Fernando Castañeda, Jan Schipper, Ronit Amit, and José F. González-Maya. "SHORT-TERM MEASURES TO AVOID RETALIATORY KILLING OF A TAPIR (Tapirus bairdii ) DURING A CASE OF HUMAN CONFLICT AT LA AMISTAD BIOSPHERE RESERVE, COSTA RICA." Revista Mexicana de Mastozoología (Nueva Epoca) 10, no. 1 (July 15, 2020): 52. http://dx.doi.org/10.22201/ie.20074484e.2020.10.1.300.

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AbstractThe increase in human tapir conflict and lack of management options is worrying and has been identified as a research priority in previous conservation planning reviews for the group. Crop-raiding by Baird’s tapir was reported on a private farm within the La Amistad Biosphere Reserve, Costa Rica. We conducted an open interview with the owner and baited the tapir out of the damaged area using an artificial salt-lick. The measures taken (quick response, assistance on alternative solutions, and the decision to use of salt-licks) were successful short-term measures to avoid lethal retaliatory control of tapirs.Key words: conservation, crop-raiding, hunting, interview, salt-lick, tapir.ResumenEl aumento en los conflictos humano-tapir y la falta de opciones de manejo es preocupante, por lo que han sido identificados como una prioridad de investigación en revisiones previas de planeación para la conservación del grupo. En una finca privada ubicada dentro de la Reserva de la Biósfera La Amistad, Costa Rica, se reportó el daño a cultivos de un tapir centroamericano. Se realizó una entrevista abierta con el propietario y se atrajo al tapir fuera del área afectada usando un saladero artificial. Las medidas a corto plazo tomadas (respuesta rápida, asistencia en soluciones alternativas y la decisión del uso de saladeros) al parecer fueron exitosas para evitar el control letal retaliativo de tapires.Palabras clave: asalto de cultivos, cacería, conservación, entrevistas, saladeros, tapir.
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Nie, Lei, Yang Liu, Yuxuan Che, Yijing Li, Wei Wang, Jingling Jin, Qingsong Cai, et al. "Establishment of Patient-Derived Organoid Culture Platform of Mantle Cell Lymphoma." Blood 138, Supplement 1 (November 5, 2021): 3508. http://dx.doi.org/10.1182/blood-2021-152994.

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Abstract Background Mantle Cell Lymphoma (MCL) is a rare incurable non-Hodgkin's lymphoma despite remarkable recent therapeutic innovations such as CAR T cell therapies. Drug sensitivity and immunotherapy efficacy assays using preclinical tumor models are important in new therapy development. As for preclinical tumor models, in addition to the commonly used mouse model such as patient-derived xenograft (PDX) and genetically engineered mouse models, a 3 rd tumor model, the patient-derived organoid (PDO) in 3D culture model has been established in many types of solid tumors. However, no PDO models have been generated from MCL yet. We have established MCL PDO model by optimizing cell isolation, culture add-ons, spatial and temporal conditions. Our protocol presents a versatile MCL PDO platform, suitable for quick drug screens and applicable for rapid immunotherapy evaluation. For proof of concept demonstration, we tested the therapeutic efficacy of CD19-targeted CAR T-cell in MCL-specific PDOs. The established PDO procedures can be used for diverse biopsies including whole blood, apheresis, bone marrow, lymph node and previously established PDX tumors. Methods For human blood, bone marrow and apheresis biospecimens, we first eliminated red blood cells using RBC lysis buffer. The cells were then spun down and cell pellets were resuspended in culture medium and aliquoted and spun-down into V-shaped 96-well plates at 1-6´10 6 cells per well. After overnight incubation, the cell culture medium was replaced by 60 ml of precooled 60% Matrigel per well. The 3D formed aggregates were gently transferred into 24-well plate and feed the solidified domes with the medium containing an in-house cytokine cocktail. The developed organoids reach the drug screening optimal phase within 3-6 days or it can be further expanded for future use. For PDX tumor and human lymph node biospecimens, we first sliced tumor tissue using surgical scalpel blade, which resulted in small tissue pieces that were then resuspended in HBSS. Debris (&gt;100 mm) were removed by brief gravity sedimentation. The resultant tissue pieces were then resuspended in 60% Matrigel in culture medium and dispensed onto pre-warmed 24-well plates. The primary tumor organoids were observed for 3-5 days before drug testing on processed for further expansion. For organoid passaging, primary organoids were extracted in pre-cooled medium by mechanically breaking the gel domes. The extracted organoids were digested by collagenase/dispase. The resultant MCL and stromal cells were enforced to aggregate in V-shape wells as described in the apheresis procedure. Organoid cell composition was examined using FACS. Drug sensitivity and T-cell activity against the MCL organoids were assessed using CellTiter-Glo 3D kit. Results We have successfully established and optimized the PDO procedure from diverse MCL biopsies (Fig. 1A). The success rate of MCL organoid from apheresis was &gt; 80% with even higher success rates when using PDX tumors, lymph node and bone marrow samples (&gt; 90%). One critical step for processing the biopsies is preserving the original stromal cells. FACS analysis showed that although &lt;5% of total cell population is composed of macrophages, circulating fibroblast, epithelial and endothelial cells and they are indispensable for organoid formation and expansion. Addition of hematopoietic cytokines in culture medium significantly improved the organoid formation and expansion from diverse biopsies. FACS with lineage markers revealed that the cell populations of the primary and secondary organoids were not significantly different (Fig. 1B). Tumor-killing activity of the CD19-targeting CAR T cells was assessed by co-culturing the CAR T cells with MCL organoids. Conclusion We have established an MCL PDO platform which is time-efficient, labor-saving, cost-effective and highly reproducible. This platform provides a rapid approach for immune cell activity assays and drug screening. The organoids have been successfully used to generate PDX models. This platform can also be used for investigating the mechanism of drug resistance in the context of different TMEs. Figure 1 Figure 1. Disclosures Wang: Acerta Pharma: Consultancy, Honoraria, Research Funding; BioInvent: Research Funding; Pharmacyclics: Consultancy, Research Funding; Lilly: Research Funding; CStone: Consultancy; Oncternal: Consultancy, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; Genentech: Consultancy; OMI: Honoraria; Newbridge Pharmaceuticals: Honoraria; Hebei Cancer Prevention Federation: Honoraria; Moffit Cancer Center: Honoraria; Molecular Templates: Research Funding; Physicians Education Resources (PER): Honoraria; Mumbai Hematology Group: Honoraria; InnoCare: Consultancy, Research Funding; Anticancer Association: Honoraria; VelosBio: Consultancy, Research Funding; Loxo Oncology: Consultancy, Research Funding; DTRM Biopharma (Cayman) Limited: Consultancy; Juno: Consultancy, Research Funding; Epizyme: Consultancy, Honoraria; Bayer Healthcare: Consultancy; CAHON: Honoraria; BeiGene: Consultancy, Honoraria, Research Funding; Celgene: Research Funding; Imedex: Honoraria; Kite Pharma: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Scripps: Honoraria; Dava Oncology: Honoraria; The First Afflicted Hospital of Zhejiang University: Honoraria; Clinical Care Options: Honoraria; Chinese Medical Association: Honoraria; BGICS: Honoraria; Miltenyi Biomedicine GmbH: Consultancy, Honoraria.
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Pylypchuk, Oleh, Oleh Strelko, and Yulia Berdnychenko. "PREFACE." History of science and technology 10, no. 1(16) (June 5, 2020): 7–9. http://dx.doi.org/10.32703/2415-7422-2020-10-1(16)-7-9.

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This issue of the journal “History of Science and Technology” has been prepared in difficult conditions. In difficult conditions for authors… In difficult conditions for reviewers ... In difficult conditions for the editorial board… In difficult conditions for the whole world in general!!! This issue contains ten articles. The first of these articles came in late 2019, when the world did not know yet these terrible words: Corona virus disease 2019 (COVID-19); severe acute respiratory syndrome Corona virus 2 (SARS-CoV-2)… COVID-19 was first identified in December 2019 in Wuhan, China, and has since spread worldwide, resulting in an ongoing pandemic. As on May 29, 2020, when these lines were written, more than 5 800 000 cases were recorded in 188 countries, killing more than 359 000 people. We hope that humanity will invent a vaccine as soon as possible, and these horrific death statistics will first stop growing and then stop altogether. For this, many events and activities are important, as history shows. Including the history of the development of science and technology, that is the subject area of our publication. In many sources on the history of electric power production the evolution of electric power production was studied both in developed and developing countries and its impact on economy. The growing demand for electric power became the most problem that stood before the power sector of Ghana. This issue begins with an article examining activities that in many ways helped to create a sustainable electricity supply for households and industries in Ghana, especially in the cities of Accra and Kumasi, between 1900 and 1960. Scientific-technical borrowings are one of those types of scientific support for the work of industrial sectors, whose role in the conditions of exiting the crisis to acquiring the particular importance. Since the mid-1920s, they have become the main way of scientific support for the organization of the development of Ukrainian electric machine-building industry in the context of large-scale electrification of the country. That was due to the need for a quick withdrawal of this industry from the previous crisis in the absence in the Ukrainian SSR of its own scientific support system for the electric machine engineering. An example of this measure, which was considered in the study, was an attempt to achieve the fastest possible increase in productivity of the Kharkiv Electromechanical Plant at minimal financial cost. The next article analyzes the activities of the mining industry in the south of the Russian Empire, of which Ukraine was a part of that time. An analysis of the so-called “coal crisis” and the role of large miners in collusion has been made. Market monopolization has been considered. Emphasis is made on the customs policy of the tsarist government, speculation on temporary fuel difficulties. The study shows that in the last quarter of the nineteenth century there was a consolidation and monopolization of the mining industry in the south of the Russian Empire. In the 21st century, every reputable journal also has an online version, which makes the dissemination of scientific information almost instantaneous. We are so accustomed to the conveniences of the information age that it is difficult for us to imagine the difficulties that scientists faced a little over 150 years ago. The genesis of science launched the process of forming branch of scientific communities and demanded stable ways of communication for productive and effective development of the branch. Scientific journals have become an ideal means of disseminating information, and a scientific article has been transformed from an ordinary letter into a modern form and has taken on an ideal form. The importance of international communication between scientists, on the example of consideration of the activities of Valerian Mykolaiovych Lihin, is discussed in the following study. He became the first Russian-speaking member of one of the oldest Mathematical Societies in Europe - the French. V. Lihin broke the tradition of “isolated” science when discoveries in the Russian Empire (and later in the USSR) were made separately from the rest of the world. In the next article an attempt to investigate in a chronological order the historical circumstances on the formation and development of the mainline electric locomotives engineering at the Luhansk diesel locomotives engineering plant (1957–2014) has been made. Historical and biographical research is continued by the article, which considers the factors shaping the scientific worldview of Mykola Pavlovych Petrov - an outstanding scientist and engineer against the background of his initiative and organizational efforts to develop the domestic scientific and technical space of the late nineteenth - early twentieth The article devoted to highlighting the contribution of academician Mariia Vasylivna Pavlova (Gortynska) in the development of palaeozoology science at the end of the XIX – the first third of the XX centuries continues the cycle of historical and biographical researches. We hope that our readers will be interested in scientific work, examining the research of Russian women in the field of human genetics in 1920-1930. The main task of the article was to determine the contribution of women scientists to the development of different fields of human genetics. Particular attention was given to reconstructing women’s geneticists’ research work, reviewing the content of their publications, and analyzing the theoretical and methodological approaches they employed in solving various scientific problems. In the history of Ukrainian archeology, there are many names of outstanding researchers who have devoted their lives to the study of our antiquity. Among them is Yulian Kulakovskyi, a well-known domestic historian and archeologist. In 1883 Yu. A. Kulakovskyi joined the Nestor Chronicler Historical Society. Since that time, his life and career have been closely linked to this scientific union. The analysis of the results of researches in the field of late antique archeology of the Crimea, published on the pages of “Readings of the Historical Society of Nestor the Chronicler”, is discussed in the next article. The development of the spread of COVID-19 shows that in the fight against it in the first place are such measures and actions as unrestricted access to information on methods of combating the spread of the virus; exchange of data at the international level on treatment methods of the disease; communication between scientists from different countries; timely quarantine measures, etc. In this sense, it is important to study the historical experience of mankind in the fight against pandemics. This issue of the journal History of Science and Technology concludes with an article on a critical analysis of nineteenth-century military interventions as the main cause of the spread of infectious diseases internationally. Emerging problems and solutions obtained as a result of a critical analysis of the materials of the International Sanitary Conferences reveal the history of the spread of infectious diseases and the methods of early statistics used for epidemiological purposes. Concluding this Preface, we emphasize once again the importance of a comprehensive study of international historical experience in the development of science and technology. Not limited to any one field or field of science, we are ready to provide the pages of our journal for the opportunity to exchange views with the international scientific community. Let peace and health be with everyone in these hard times!
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Burns, Amy L., Brad E. Sleebs, Maria Gancheva, Kimberley T. McLean, Ghizal Siddiqui, Henrietta Venter, James G. Beeson, et al. "Targeting malaria parasites with novel derivatives of azithromycin." Frontiers in Cellular and Infection Microbiology 12 (November 30, 2022). http://dx.doi.org/10.3389/fcimb.2022.1063407.

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IntroductionThe spread of artemisinin resistant Plasmodium falciparum parasites is of global concern and highlights the need to identify new antimalarials for future treatments. Azithromycin, a macrolide antibiotic used clinically against malaria, kills parasites via two mechanisms: ‘delayed death’ by inhibiting the bacterium-like ribosomes of the apicoplast, and ‘quick-killing’ that kills rapidly across the entire blood stage development.MethodsHere, 22 azithromycin analogues were explored for delayed death and quick-killing activities against P. falciparum (the most virulent human malaria) and P. knowlesi (a monkey parasite that frequently infects humans).ResultsSeventeen analogues showed improved quick-killing against both Plasmodium species, with up to 38 to 20-fold higher potency over azithromycin after less than 48 or 28 hours of treatment for P. falciparum and P. knowlesi, respectively. Quick-killing analogues maintained activity throughout the blood stage lifecycle, including ring stages of P. falciparum parasites (&lt;12 hrs treatment) and were &gt;5-fold more selective against P. falciparum than human cells. Isopentenyl pyrophosphate supplemented parasites that lacked an apicoplast were equally sensitive to quick-killing analogues, confirming that the quick killing activity of these drugs was not directed at the apicoplast. Further, activity against the related apicoplast containing parasite Toxoplasma gondii and the gram-positive bacterium Streptococcus pneumoniae did not show improvement over azithromycin, highlighting the specific improvement in antimalarial quick-killing activity. Metabolomic profiling of parasites subjected to the most potent compound showed a build-up of non-haemoglobin derived peptides that was similar to chloroquine, while also exhibiting accumulation of haemoglobin-derived peptides that was absent for chloroquine treatment.DiscussionThe azithromycin analogues characterised in this study expand the structural diversity over previously reported quick-killing compounds and provide new starting points to develop azithromycin analogues with quick-killing antimalarial activity.
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Burns, Amy L., Brad E. Sleebs, Ghizal Siddiqui, Amanda E. De Paoli, Dovile Anderson, Benjamin Liffner, Richard Harvey, et al. "Retargeting azithromycin analogues to have dual-modality antimalarial activity." BMC Biology 18, no. 1 (September 29, 2020). http://dx.doi.org/10.1186/s12915-020-00859-4.

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Abstract Background Resistance to front-line antimalarials (artemisinin combination therapies) is spreading, and development of new drug treatment strategies to rapidly kill Plasmodium spp. malaria parasites is urgently needed. Azithromycin is a clinically used macrolide antibiotic proposed as a partner drug for combination therapy in malaria, which has also been tested as monotherapy. However, its slow-killing ‘delayed-death’ activity against the parasite’s apicoplast organelle and suboptimal activity as monotherapy limit its application as a potential malaria treatment. Here, we explore a panel of azithromycin analogues and demonstrate that chemical modifications can be used to greatly improve the speed and potency of antimalarial action. Results Investigation of 84 azithromycin analogues revealed nanomolar quick-killing potency directed against the very earliest stage of parasite development within red blood cells. Indeed, the best analogue exhibited 1600-fold higher potency than azithromycin with less than 48 hrs treatment in vitro. Analogues were effective against zoonotic Plasmodium knowlesi malaria parasites and against both multi-drug and artemisinin-resistant Plasmodium falciparum lines. Metabolomic profiles of azithromycin analogue-treated parasites suggested activity in the parasite food vacuole and mitochondria were disrupted. Moreover, unlike the food vacuole-targeting drug chloroquine, azithromycin and analogues were active across blood-stage development, including merozoite invasion, suggesting that these macrolides have a multi-factorial mechanism of quick-killing activity. The positioning of functional groups added to azithromycin and its quick-killing analogues altered their activity against bacterial-like ribosomes but had minimal change on ‘quick-killing’ activity. Apicoplast minus parasites remained susceptible to both azithromycin and its analogues, further demonstrating that quick-killing is independent of apicoplast-targeting, delayed-death activity. Conclusion We show that azithromycin and analogues can rapidly kill malaria parasite asexual blood stages via a fast action mechanism. Development of azithromycin and analogues as antimalarials offers the possibility of targeting parasites through both a quick-killing and delayed-death mechanism of action in a single, multifactorial chemotype.
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"Humane Killing of Livestock using Firearms." Animal Welfare 9, no. 1 (February 2000): 88–89. http://dx.doi.org/10.1017/s0962728600022314.

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With the correct equipment and technique, shooting is a quick and humane method of despatch and it has particular application in the humane destruction of casualty animals. This booklet published by the Humane Slaughter Association describes the principles and practice of using free-bullet firearms for the humane killing of large farm animals. It provides a very valuable source of information for veterinarians, slaughtermen, police firearms officers, and others who may be directly or indirectly involved in humane killing of livestock. After sections on anatomical considerations, physical principles (eg the calculation of muzzle energy) and the physiological effects of shooting including clear information on the signs of an effective shot, brief reviews are provided on types of firearm and ammunition with guidance as to their suitability for various purposes. There are then four pages describing the correct shooting positions (location and angle of entry) for humane despatch of cattle, deer, horses, sheep, pigs and goats. These are clearly illustrated, using photographs of midline sections through heads, to show the position and size of the brain in relation to external features. The booklet also contains information on the selection of appropriate firearms and ammunition, safety aspects, carcase disposal and routine maintenance of equipment. It is written clearly and concisely in handbook style and is well illustrated. With the exception of the information on legislation (which deals specifically with UK law), the subjects covered are relevant to humane despatch of livestock anywhere in the world and the booklet is highly recommended for all who may be involved in this work.
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Selter, Felicitas, Kirsten Persson, Johanna Risse, Peter Kunzmann, and Gerald Neitzke. "Dying like a dog: the convergence of concepts of a good death in human and veterinary medicine." Medicine, Health Care and Philosophy, September 15, 2021. http://dx.doi.org/10.1007/s11019-021-10050-3.

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AbstractStandard views of good death in human and veterinary medicine considerably differ from one another. Whereas the good death ideal in palliative medicine emphasizes the positive aspects of non-induced dying, veterinarians typically promote a quick and painless killing with the aim to end suffering. Recent developments suggest a convergence of both professions and professional attitudes, however. Palliative physicians are confronted with patients wishing to be ‘put to sleep’, while veterinarians have begun to integrate principles and practices from hospice care. We will argue that the discourses on good human and animal deaths are not distinct, but that they interact and influence each other. On the one hand, veterinary medicine adapts techniques like chemotherapy or sedation from palliative end-of-life care. On the other hand, philosophers, veterinarians, pet owners, patients and the general public alike make certain assumptions about the (dis)analogy of human and animal dying or killing. Unfortunately, these interactions have only scarcely been reflected normatively, especially on the part of human medicine. Conflicts and misattributions with potential serious negative consequences for the (animal and human) patients’ wellbeing are provoked. For these reasons, palliative physicians and veterinarians are invited to engage in the debate around human and animal end-of-life care.
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Fang, Zhixiang, Jihang Chen, Jiangxia Pan, Guoqiang Liu, and Chen Zhao. "The Development Tendency of 3D-Printed Bioceramic Scaffolds for Applications Ranging From Bone Tissue Regeneration to Bone Tumor Therapy." Frontiers in Bioengineering and Biotechnology 9 (December 20, 2021). http://dx.doi.org/10.3389/fbioe.2021.754266.

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Three-dimensional (3D) printing concept has been successfully employed in regenerative medicine to achieve individualized therapy due to its benefit of a rapid, accurate, and predictable production process. Traditional biocomposites scaffolds (SCF) are primarily utilised for bone tissue engineering; nevertheless, over the last few years, there has already been a dramatic shift in the applications of bioceramic (BCR) SCF. As a direct consequence, this study focused on the structural, degeneration, permeation, and physiological activity of 3D-printed BCR (3DP-B) SCF with various conformations and work systems (macros, micros, and nanos ranges), as well as their impacts on the mechanical, degeneration, porosity, and physiological activities. In addition, 3DP-B SCF are highlighted in this study for potential uses applied from bone tissue engineering (BTE) to bone tumor treatment. The study focused on significant advances in practical 3DP-B SCF that can be utilized for tumor treatment as well as bone tissue regeneration (BTR). Given the difficulties in treating bone tumors, these operational BCR SCF offer a lot of promise in mending bone defects caused by surgery and killing any remaining tumor cells to accomplish bone tumor treatment. Furthermore, a quick assessment of future developments in this subject was presented. The study not only summarizes recent advances in BCR engineering, but it also proposes a new therapeutic strategy focused on the extension of conventional ceramics’ multifunction to a particular diagnosis.
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Leinberger, Charles Francis. "An Austrian in Hollywood." Journal of Film Music, March 8, 2021. http://dx.doi.org/10.1558/jfm.19071.

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When interviewed about film music, John Williams is often quick to credit Max Steiner as the originator of the leitmotif technique in film music. Steiner brought with him to the U.S. the compositional techniques he learned as a child prodigy in Europe, including the leitmotif technique. This paper will discuss Steiner’s use of leitmotifs in his Academy Award winning score to the 1942 Warner Bros. film Now, Voyager. Film musicologists disagree on the relevance of themes being heard in different keys throughout a film score and their possible effect on the audience. I intend to demonstrate that, although the significance of these key relationships may only exist on a subconscious level, they do contribute in a meaningful way to the viewing/listening experience. To demonstrate this, I will use examples of “Charlotte’s Theme,” also known as the “Love Theme,” which appears in various keys throughout the film. The key relationships are clearly intentional and well thought out by Steiner. This theme, which is almost always in triple meter, was recorded in 1943 by Allen Miller and his Orchestra as a pop tune, in quadruple meter, with the title “It Can’t Be Wrong.” Steiner plagiarizes himself when this instrumental version is heard as source music in the 1945 Warner Bros. film Mildred Pierce. Vocal versions, including one recorded by Frank Sinatra, include lyrics by Kim Gannon. This version was also sung in the Star Trek: Voyager episode “The Killing Game, Part 1.”
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48

Xia, Yushan, Yuding Weng, Congjuan Xu, Dan Wang, Xiaolei Pan, Zhenyang Tian, Bin Xia, et al. "Endoribonuclease YbeY Is Essential for RNA Processing and Virulence in Pseudomonas aeruginosa." mBio 11, no. 3 (June 30, 2020). http://dx.doi.org/10.1128/mbio.00659-20.

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ABSTRACT Posttranscriptional regulation plays an essential role in the quick adaptation of pathogenic bacteria to host environments, and RNases play key roles in this process by modifying small RNAs and mRNAs. We find that the Pseudomonas aeruginosa endonuclease YbeY is required for rRNA processing and the bacterial virulence in a murine acute pneumonia model. Transcriptomic analyses reveal that knocking out the ybeY gene results in downregulation of oxidative stress response genes, including the catalase genes katA and katB. Consistently, the ybeY mutant is more susceptible to H2O2 and neutrophil-mediated killing. Overexpression of katA restores the bacterial tolerance to H2O2 and neutrophil killing as well as virulence. We further find that the downregulation of the oxidative stress response genes is due to defective expression of the stationary-phase sigma factor RpoS. We demonstrate an autoregulatory mechanism of RpoS and find that ybeY mutation increases the level of a small RNA, ReaL, which directly represses the translation of rpoS through the 5′ UTR of its mRNA and subsequently reduces the expression of the oxidative stress response genes. In vitro assays demonstrate direct degradation of ReaL by YbeY. Deletion of reaL or overexpression of rpoS in the ybeY mutant restores the bacterial tolerance to oxidative stress and the virulence. We also demonstrate that YbeZ binds to YbeY and is involved in the 16S rRNA processing and regulation of reaL and rpoS as well as the bacterial virulence. Overall, our results reveal pleiotropic roles of YbeY and the YbeY-mediated regulation of rpoS through ReaL. IMPORTANCE The increasing bacterial antibiotic resistance imposes a severe threat to human health. For the development of effective treatment and prevention strategies, it is critical to understand the mechanisms employed by bacteria to grow in the human body. Posttranscriptional regulation plays an important role in bacterial adaptation to environmental changes. RNases and small RNAs are key players in this regulation. In this study, we demonstrate critical roles of the RNase YbeY in the virulence of the pathogenic bacterium Pseudomonas aeruginosa. We further identify the small RNA ReaL as the direct target of YbeY and elucidate the YbeY-regulated pathway on the expression of bacterial virulence factors. Our results shed light on the complex regulatory network of P. aeruginosa and indicate that inference with the YbeY-mediated regulatory pathway might be a valid strategy for the development of a novel treatment strategy.
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49

Ejeh, Stephen, Adamu Uzairu, Gideon A. Shallangwa, Stephen E. Abechi, and Muhammad Tukur Ibrahim. "In silico design and pharmacokinetics investigation of some novel hepatitis C virus NS5B inhibitors: pharmacoinformatics approach." Bulletin of the National Research Centre 46, no. 1 (April 15, 2022). http://dx.doi.org/10.1186/s42269-022-00796-y.

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Abstract Background Hepatitis C virus (HCV) is a contagious disease that damages the liver over time, eventually leading to cirrhosis and death. Chronic HCV infection is regarded as a serious health problem worldwide, impacting up to 3% of the populace and killing over 300,000 people annually. Quick reproduction driven by non-structural protein 5B (NS5B), which is a possible target spot for the development of anti-HCV vaccines, causes genomic diversity. Sofosbuvir, a new oral NS5B inhibitor, was recently licensed by the US Food and Drug Administration for the cure of HCV. Unfortunately, it has received a lot of attention due to its financial concerns and adverse effects. As a result, there is a pressing need to explore alternative HCV treatments that are both cost-effective and free of adverse effects. In this study, we used a Pharmacoinformatics-based strategy to identify and design bioactive molecules that are anti-HCV NS5B. The simulation outcomes are compared to Sofosbuvir simulation outcomes. Results Based on docking simulation, the proposed molecules have high-binding energies at the range of − 41.71 to − 39.90 kcal/mol against − 30.34 kcal/mol of Sofosbuvir. Furthermore, when compared to Sofosbuvir, which has a drug score of 0.31 (31% performance), the ADMET analysis of the lead compound demonstrates superior performance with a drug score of 0.88 (88% performance). Conclusions The findings revealed that alternative bioactive molecules vary substantially in docking rankings at a range of − 41.71 to − 39.90 kcal/mol against − 30.34 kcal/mol of Sofosbuvir, the FDA-approved NS5B enzyme inhibitor, and when compared to Sofosbuvir, which has a drug score of 0.31, the ADMET analysis of the chosen compound (1c) demonstrates superior performance with a drug score of 0.88.
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50

Servienė, Elena, Juliana Lukša, Iglė Vepštaitė-Monstavičė, and Jaunius Urbonavičius. "A quick and reliable method for genome-wide host factor screening of Saccharomyces cerevisiae killer toxins." Biologija 62, no. 4 (January 5, 2017). http://dx.doi.org/10.6001/biologija.v62i4.3413.

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Numerous yeasts produce toxic compounds to fight the competitors. Such compounds include small molecules (like antibiotics), antibiotic peptides, and also larger proteins, including killer toxins. Their ability to affect the cell depends on the host factors modulating the killing activity. Here we describe a robotics-based method to advance the genome-wide screening for the host factors affecting sensitivity of budding yeast to the killer toxins using the K2 system as the model. We demonstrate that arraying the mutant library on the agar plates containing the K2 killer toxinproducing strain and/or purified toxin (“survival” assay) increases the sensitivity and speed of the screen and decreases the costs compared to the traditional “killer” assay. We show the applicability of a new screening method of searching for the host factors using a killer strain isolated from agricultural plant environment. In addition, the “survival” assay allows identification of previously undetected factors that could be the “missing links” in the pathways of toxininduced cellular responses.
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