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Zhang-Liu, Yiran, Rolf Müller, Jens-Uwe Grooß, Sabine Robrecht, Bärbel Vogel, Abdul Mannan Zafar und Ralph Lehmann. „The impact of dehydration and extremely low HCl values in the Antarctic stratospheric vortex in mid-winter on ozone loss in spring“. Atmospheric Chemistry and Physics 24, Nr. 22 (14.11.2024): 12557–74. http://dx.doi.org/10.5194/acp-24-12557-2024.
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Abstract. Simulations of Antarctic chlorine and ozone chemistry in previous work show that in the core of the Antarctic vortex (16–18 km, 85–55 hPa, 390–430 K) HCl null cycles (initiated by reactions of Cl with CH4 and CH2O) are effective. These HCl null cycles cause both HCl molar mixing ratios to remain very low throughout Antarctic winter and spring. They cause ozone-destroying chlorine (ClOx) to remain enhanced so that rapid ozone depletion proceeds. Here we investigate the impact of the observed dehydration in Antarctica, which strongly reduces ice formation and the uptake of HNO3 from the gas phase; however the efficacy of HCl null cycles is not affected. Moreover, also when using the observed very low HCl molar mixing ratios in Antarctic winter as an initial value, HCl null cycles are efficient in maintaining low HCl (and high ClOx) throughout winter and spring. Further, the reaction CH3O2+ClO is important for the efficacy of the HCl null cycle initiated by the reaction CH4+Cl. Using the current kinetic recommendations instead of earlier ones has very little impact on the simulations. All simulations presented here for the core of the Antarctic vortex show extremely low minimum ozone values (below 50 ppb) in late September to early October in agreement with observations.
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Rezaee, Zabihollah, Phil Malone und Ghassem Homaifar. „An Assessment Of Event Study Methodologies Using Daily Stock Returns“. Journal of Applied Business Research (JABR) 8, Nr. 1 (18.10.2011): 78. http://dx.doi.org/10.19030/jabr.v8i1.6186.
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This paper examines Multinational Stock Price reactions to foreign currency translation, using three alternative residual methodologies. The results reveal that when a crude measure such as Mean Adjusted Return, which makes not explicit risk adjustments is used, the null hypothesis of zero abnormal return is rejected in three out of six events. However, market and risk adjusted residual returns reveal that the null hypothesis of zero abnormal return cannot be rejected.
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Klčová, Lenka, Daniela Mikulíková, Štefan Masár und Alžbeta Žofajová. „Evaluation Of Slovak Winter Wheat Quality In Terms Of Puroindoline Genes“. Agriculture (Polnohospodárstvo) 61, Nr. 3 (01.09.2015): 88–96. http://dx.doi.org/10.1515/agri-2015-0014.
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Abstract The grain hardness of 100 current and 24 old superior Slovak winter wheat cultivars was studied at molecular level. Using polymerase chain reactions (PCRs), normal and null alleles of both puroindoline Pina and Pinb genes were identified. Three different genotypes were found: 1) normal allele of both genes (dominant wild type with soft endosperm) − Pina-D1a/Pinb-D1a; 2) normal allele of the Pina gene and null allele of the Pinb gene – Pina-D1a/Pinb-D1b; and 3) null allele of the Pina gene and normal allele of the Pinb gene Pina-D1b/Pinb-D1a. No Slovak current as well as old wheat cultivar had together null allele of both puroindoline genes. The frequencies of wild-type Pinb-D1a and null Pinb-D1b allele in current cultivars were 62.0% and 38.0%, respectively, whilst in old cultivars, 8.3% and 91.7%, respectively. Regarding null allele Pina-D1b of puroindoline Pina gene, only in Rheia current cultivar, one was found. All other cultivars had wild-type Pina-D1a allele. Alacris, Alana, Axis, Balada, Blava, Bona Dea, Bruta, Charger, Hana, Ilona, IS Karpatia, Ludwig and Sulamit current cultivars were selected as donors of the null Pinb-D1b allele for molecular breeding in order to improve the grain hardness as important wheat quality trait. Statistically significant correlations between null Pinb-D1b allele and grain size as well as colour were found. In comparison with wild type, cultivars with this null allele have paler and longer grain with higher length-to-width ratio and lighter grain colour.
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Stenger, Drake C., Roy French und Frederick E. Gildow. „Complete Deletion of Wheat Streak Mosaic Virus HC-Pro: a Null Mutant Is Viable for Systemic Infection“. Journal of Virology 79, Nr. 18 (15.09.2005): 12077–80. http://dx.doi.org/10.1128/jvi.79.18.12077-12080.2005.
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ABSTRACT A Wheat streak mosaic virus (WSMV) genome lacking HC-Pro was constructed and confirmed by reverse transcription-PCR to systemically infect wheat, oat, and corn. Coupled in vitro transcription/translation reactions indicated that WSMV P1 proteinase cleaved the polyprotein at the P1/P3 junction of the HC-Pro null mutant. The WSMV HC-Pro null mutant was competent for virion formation, but the virus titer was reduced 4.5-fold relative to that of the wild type. Collectively, these results indicate that WSMV HC-Pro is dispensable for replication and movement, two essential processes that are disrupted by point and small-insertion mutations introduced into potyvirus HC-Pro.
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Moore, Angus K., und Darryl E. Granger. „Technical note: Altitude scaling of 36Cl production from Fe“. Geochronology 6, Nr. 4 (18.10.2024): 541–52. http://dx.doi.org/10.5194/gchron-6-541-2024.
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Abstract. Cosmogenic nuclide production rates depend on the excitation functions of the underlying nuclear reactions and the intensity and energy spectrum of the cosmic-ray flux. The cosmic-ray energy spectrum shifts towards lower average energies with decreasing altitude (increasing atmospheric depth), so production rate scaling will differ for production reactions that have different energy sensitivities. Here, we assess the possibility of the unique scaling of 36Cl production from Fe by modeling changes in the 36ClFe/36ClK and 36ClFe/10Beqtz production ratios with altitude. We evaluate model predictions against measured 36Cl concentrations in magnetite and K-feldspar and 10Be concentrations in quartz from granitic rocks exposed across an elevation transect (ca. 1700–4300 ma.s.l.) in western North America. The data are broadly consistent with model predictions. The null hypothesis that 36ClFe/10Beqtz and 36ClFe/36ClK production ratios are invariant with altitude can be rejected at the 90 % confidence level. Thus, reaction-specific scaling factors will likely yield more accurate results than non-reaction-specific scaling factors when scaling 36Cl production in Fe-rich rocks and minerals.
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Kim, Sang-Heon, Sang-Hoon Kim, Ho Joo Yoon, Dong Ho Shin, Sung Soo Park, Youn-Seup Kim, Jae-Seuk Park und Young Koo Jee. „GSTT1 and GSTM1 null mutations and adverse reactions induced by antituberculosis drugs in Koreans“. Tuberculosis 90, Nr. 1 (Januar 2010): 39–43. http://dx.doi.org/10.1016/j.tube.2009.12.001.
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Doming, Luis R., und Mar Ríos-Gutiérrez. „A Useful Classification of Organic Reactions Based on the Flux of the Electron Density“. Scientiae Radices 2, Nr. 1 (14.02.2023): 1–24. http://dx.doi.org/10.58332/scirad2023v2i1a01.
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A useful classification of polar organic reactions in Forward Electron Density Flux (FEDF) and Reverse Electron Density Flux (REDF), based on the unambiguously analysis of the direction of the flux of the global electron density transfer (GEDT) at the transition state structures (TSs), has been recently proposed (RSC Adv. 2020, 10, 15394) within the Molecular Electron Density Theory. Further, non-polar reactions have been classified as Null Electron Density Flux (NEDF) (Eur. J. Org. Chem. 2020, 5938). This classification allows characterizing the nucleophilic/electrophilic species participating in polar reactions. Analysis of the electronic chemical potential m, and the electrophilicity w and nucleophilicity N indices, defined within Conceptual DFT, at the ground state (GS) of the reagents also permits to establish this classification of polar reactions.
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Economopoulos, Konstantinos P., Theodoros N. Sergentanis und Nikos F. Vlahos. „Glutathione S-transferase M1, T1, and P1 Polymorphisms and Ovarian Cancer Risk: A Meta-Analysis“. International Journal of Gynecologic Cancer 20, Nr. 5 (Juni 2010): 732–37. http://dx.doi.org/10.1111/igc.0b013e3181dedeb5.
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Introduction:Cytosolic glutathione S-transferase (GST) comprises multiple isoenzymes that catalyze reactions between glutathione and lipophilic compounds with electrophilic centers, resulting in the neutralization of toxic compounds, xenobiotics, and products of oxidative stress. Several studies have examined whether GST polymorphisms (GSTM1 null/present genotype, GSTT1 null/present genotype, and GSTP1 Ile105Val) represent risk factors for ovarian cancer, as they all may denote reduced enzyme activity. This meta-analysis aimed to examine the associations between the aforementioned polymorphisms and ovarian cancer risk.Methods:The MEDLINE database was searched up to September 2009 using the appropriate terms. Case-control studies with no mutually overlapping populations were selected. Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random-effects models. Meta-regression with publication year was also performed.Results:Eight studies regarding GSTM1 null polymorphism status (2357 cases and 3044 controls), 6 studies concerning GSTT1 null polymorphism (1923 cases and 2759 controls), and 3 studies on GSTP1 Ile105Val were included in the meta-analysis. The GSTM1 null genotype was not associated with an increased risk for ovarian cancer (pooled OR, 1.031; 95% confidence interval, 0.867-1.226; random effects). The GSTT1 null genotype was not associated with an increased ovarian cancer risk (pooled OR, 0.934; 95% confidence interval, 0.804-1.086; random effects); similarly, no significant associations were demonstrated for GSTP1 Ile105Val.Conclusions:The examined GSTM1, GSTT1, and GSTP1 genotype polymorphisms do not seem to confer any additional risk for ovarian cancer. Given that the studies included in this meta-analysis involve mainly white populations, these results cannot be extrapolated on other populations, and additional data are needed for future race-specific analyses.
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Zhang, Weifeng, Xueling Chen, Xingxing Chen, Jirui Li, Hui Wang, Xiaomiao Yan, Han Zha et al. „Fc–Fc interactions and immune inhibitory effects of IgG4: implications for anti-PD-1 immunotherapies“. Journal for ImmunoTherapy of Cancer 12, Nr. 6 (Juni 2024): e009034. http://dx.doi.org/10.1136/jitc-2024-009034.
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BackgroundThe majority of anti-programmed cell-death 1 (PD-1) monoclonal antibodies (mAbs) use S228P mutation IgG4 as the structural basis to avoid the activation of immune cells or complement. However, little attention has been paid to the Fc–Fc interactions between IgG4 and other IgG Fc fragments that could result in adverse effects. Fc-null IgG1 framework is a potential safer alternative to avoid the undesirable Fc–Fc interactions and Fc receptor binding derived effects observed with IgG4. This study provides a comprehensive evaluation of anti-PD-1 mAbs of these two frameworks.MethodsTrastuzumab and rituximab (both IgG1), wildtype IgG1 and IgG4 were immobilized on nitrocellulose membranes, coated to microplates and biosensor chips, and bound to tumor cells as targets for Fc–Fc interactions. Wildtype IgG1 and IgG4, anti-PD-1 mAb nivolumab (IgG4 S228P), penpulimab (Fc-null IgG1), and tislelizumab (Fc-null IgG4 S228P-R409K) were assessed for their binding reactions to the immobilized IgG proteins and quantitative kinetic data were obtained. To evaluate the effects of the two anti-PD-1 mAbs on immune responses mediated by trastuzumab and rituximab in the context of combination therapy, we employed classic immune models for antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and complement dependent cytotoxicity. Tumor-bearing mouse models, both wildtype and humanized, were used for in vivo investigation. Furthermore, we also examined the effects of IgG1 and IgG4 on diverse immune cell populationsResultsExperiments demonstrated that wildtype IgG4 and nivolumab bound to immobilized IgG through Fc–Fc interactions, diminishing antibody-dependent cell-mediated cytotoxicity and phagocytosis reactions. Quantitative analysis of kinetic parameters suggests that nivolumab and wildtype IgG4 exhibit comparable binding affinities to immobilized IgG1 in both non-denatured and denatured states. IgG4 exerted inhibitory effects on various immune cell types. Wildtype IgG4 and nivolumab both promoted tumor growth in wildtype mouse models. Conversely, wildtype IgG1, penpulimab, and tislelizumab did not show similar adverse effects.ConclusionsFc-null IgG1 represents a safer choice for anti-PD-1 immunotherapies by avoiding both the adverse Fc–Fc interactions and Fc-related immune inhibitory effects of IgG4. Fc-null IgG4 S228P-R409K and Fc-null IgG1 displayed similar structural properties and benefits. This study contributes to the understanding of immunotherapy resistance and the advancement of safer immune therapies for cancer.
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Jaramillo-Valverde, Luis, Kelly S. Levano, David D. Tarazona, Andres Vasquez-Dominguez, Anel Toledo-Nauto, Silvia Capristano, Cesar Sanchez, Eduardo Tarazona-Santos, Cesar Ugarte-Gil und Heinner Guio. „GSTT1/GSTM1 Genotype and Anti-Tuberculosis Drug-Induced Hepatotoxicity in Peruvian Patients“. International Journal of Molecular Sciences 23, Nr. 19 (20.09.2022): 11028. http://dx.doi.org/10.3390/ijms231911028.
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In Peru, 24,581 people were diagnosed with tuberculosis (TB) in 2020. Although TB treatments are effective, 3.4–13% are associated with significant adverse drug reactions (ADRs), with drug-induced liver injury (DILI) considered the most predominant. Among the first-line antituberculosis drugs, isoniazid (INH) is the main drug responsible for the appearance of DILI. In the liver, INH is metabolized by the enzymes N-acetyltransferase-2 (NAT2), cytochrome P450 2E1 (CYP2E1), and glutathione S-transferase (GST) with two isoforms, GSTT1 and GSTM1. Based on previous studies, we hypothesized that interactions between the GSTT1 and GSTM1 null genotypes induce DILI in TB patients. In this cross-sectional study of 377 participants who completed their anti-TB treatment, we genotyped by revealing the presence or absence of 215- and 480-bp bands of GSTM1 and GSTT1, respectively. We found that the prevalence of the GSTM1 genotype was 52.79% and 47.21% for presence and null, respectively, and for GSTT1 it was 69.76% and 30.24% for presence and null, respectively. Neither genotype was prevalent in the patients who developed DILI (n = 16). We did not confirm our hypothesis; however, we found that the combination of GSTM1 present genotype, GSTT1 null genotype, fast NAT2 acetylators, and CYP2E1 c1/c1 genotype had a significant risk for the development of ADR (OR 11; p = 0.017; 95% CI: (0.54–186.35)). We propose that the presence of the GSTM1 present genotype, GSTT1 null genotype, fast NAT2 acetylators, and CYP2E1 c1/c1 genotype in the Peruvian population could be considered a risk factor for the development of ADR due to therapeutic drug intake.
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Aguilera, Jaime, Johannes P. Van Dijken, Johannes H. De Winde und Jack T. Pronk. „Carbonic anhydrase (Nce103p): an essential biosynthetic enzyme for growth of Saccharomyces cerevisiae at atmospheric carbon dioxide pressure“. Biochemical Journal 391, Nr. 2 (10.10.2005): 311–16. http://dx.doi.org/10.1042/bj20050556.
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The NCE103 gene of the yeast Saccharomyces cerevisiae encodes a CA (carbonic anhydrase) that catalyses the interconversion of CO2 and bicarbonate. It has previously been reported that nce103 null mutants require elevated CO2 concentrations for growth in batch cultures. To discriminate between ‘sparking’ effects of CO2 and a CO2 requirement for steady-state fermentative growth, we switched glucose-limited anaerobic chemostat cultures of an nce103 null mutant from sparging with pure CO2 to sparging with nitrogen gas. This switch resulted in wash-out of the biomass, demonstrating that elevated CO2 concentrations are required even under conditions where CO2 is produced at high rates by fermentative sugar metabolism. Nutritional analysis of the nce103 null mutant demonstrated that growth on glucose under a non-CO2-enriched nitrogen atmosphere was possible when the culture medium was provided with L-aspartate, fatty acids, uracil and L-argininine. Thus the main physiological role of CA during growth of S. cerevisiae on glucose-ammonium salts media is the provision of inorganic carbon for the bicarbonate-dependent carboxylation reactions catalysed by pyruvate carboxylase, acetyl-CoA carboxylase and CPSase (carbamoyl-phosphate synthetase). To our knowledge, the present study represents the first full determination of the nutritional requirements of a CA-negative organism to date.
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Letkin, Alexander Ilyich, Alexander Sergeevich Zenkin, Vadim Vladimirovich Fedoskin, Daniel Evgenyevich Yavkin, Tatyana Alexandrovna Batyaeva und Natalia Vladimirovna Letkina. „ASSESSMENT OF CORRELATION OF BIOCHEMICAL PARAMETERS OF BLOOD SERUM OF LAYING HENS AT DIFFERENT LEVELS OF PLANTING DENSITY“. SCIENTIFIC LIFE 19, Nr. 2 (2024): 300–307. http://dx.doi.org/10.35679/1991-9476-2024-19-2-300-307.
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With the cellular technology of keeping laying hens, their mobility is limited. This can lead to various negative consequences due to the development of a protective and adaptive reaction in the body of an agricultural bird. One of the approaches to the early diagnosis of stress reactions in poultry is the study of biochemical parameters of blood serum. Biochemical indicators can provide information about the general condition of the bird, changes in its body and stress levels. In particular, the study of biochemical parameters of blood serum of laying hens at different levels of planting density can help to identify the relationship between the conditions of poultry keeping and its stress response. Mathematical calculations of the estimation of the correlation dependence of biochemical parameters of blood serum of laying hens depending on different levels of planting density with cellular content are important in the interpretation of the data obtained. Fischer's F-criterion (F-distribution) was used for mathematical processing of the research results. The results obtained allow us to conclude that the indicators of cholesterol and total protein in laying hens do not depend on the planting density. Alkaline phosphatase, phosphorus, calcium, ACTH depend on the density of laying hens (the null hypothesis is refuted at 1% significance level). Blood glucose and cortisol levels are also dependent on planting density. Here, the null hypothesis is refuted at the 5% significance level. The results of the study of the levels of alkaline phosphatase, glucose, phosphorus, calcium, adrenocorticotropic hormone (ACTH) and cortisol at different levels of planting density indicate the development of a stress reaction in laying hens and are important diagnostic markers when exposed to technological stresses.
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SCHUSTER, STEFAN, und CLAUS HILGETAG. „ON ELEMENTARY FLUX MODES IN BIOCHEMICAL REACTION SYSTEMS AT STEADY STATE“. Journal of Biological Systems 02, Nr. 02 (Juni 1994): 165–82. http://dx.doi.org/10.1142/s0218339094000131.
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A mathematical definition of the concept of elementary mode is given so as to apply to biochemical reaction systems subsisting at steady state. This definition relates to existing concepts of null-space vectors and includes a condition of simplicity. It is shown that for systems in which all fluxes have fixed signs, all elementary modes are given by the generating vectors of a convex cone and can, thus, be computed by an existing algorithm. The present analysis allows for the more general case that some reactions can proceed in either direction. Basic ideas on how to compute the complete set of elementary modes in this situation are outlined and verified by way of several examples, with one of them representing glycolysis and gluconeogenesis. These examples show that the elementary modes can be interpreted in terms of the particular biochemical functions of the network. The relationships to (futile) substrate cycles are elucidated.
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Jones, D., A. Mehlert und M. A. J. Ferguson. „The N-glycan glucosidase system in Trypanosoma brucei“. Biochemical Society Transactions 32, Nr. 5 (26.10.2004): 766–68. http://dx.doi.org/10.1042/bst0320766.
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Reactions involving removal and addition of glucose to N-glycans in the ER (endoplasmic reticulum) are performed in higher eukaryotes by glucosidases I and II and the UDP-glucose:glycoprotein glucosyltransferase respectively. Monoglucosylated N-glycan structures have been implicated in glycoprotein folding or ER quality control. Components of the system appear across a range of organisms; however, the precise combination differs between organisms. We have identified putative components of the system in the protozoal organism Trypanosoma brucei by local alignment searching. The function of one of these components, a glucosidase II α-subunit homologue, has been confirmed by phenotyping a null mutant, and an ectopic expression cell line. A combination of MS, methylation linkage analysis, exoglycosidase digestion and partial acetolysis have been used to characterize three novel N-glycan structures on the variant surface glycoprotein of the null mutant. On the basis of our results, we propose that two N-glycan precursors are available for transfer to variant surface glycoprotein (variant 221) in the ER of T. brucei; only one of these precursors is glucosylated after transfer.
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Nagamitsu, Teruyoshi, Takayuki Kawahara und Ayako Kanazashi. „Inference of allelic dosages and inheritance modes in tetraploids: a case study in Betula apoiensis with a putative hybrid origin“. Silvae Genetica 63, Nr. 1-6 (01.12.2014): 159–68. http://dx.doi.org/10.1515/sg-2014-0021.
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Abstract In tetraploids, inference of allelic dosages and inheritance modes is difficult due to the ambiguous number of allele copies and the variation between disomic and tetrasomic patterns. Considering the biases of amplification and the overlaps of stutter products in polymerase chain reactions, we inferred tetraploid genotypes at three nuclear microsatellite loci in progeny arrays from six reciprocal crosses among three parents of Betula apoiensis with a putative hybrid origin. In each cross, we assigned diploid genotypes to gametes on the basis of the tetraploid genotypes of the parents and their progeny and observed the frequencies of the gamete genotypes. Segregation patterns of the observed gamete genotypes indicated few null alleles in the progeny arrays and tetrasomic inheritance with rare double reduction. This mode of inheritance was consistent between genders and between mates in the crosses. This result suggests that our method to infer tetraploid genotypes in nuclear microsatellites is successful in family samples with few null alleles when the amplification biases and the stutter-product overlaps are accessed properly.
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Guarini, Jean-Marc, Jennifer Coston-Guarini, Tim Deprez und Laurent Chauvaud. „An inference procedure for behavioural studies combining numerical simulations, statistics and experimental results“. Journal of the Marine Biological Association of the United Kingdom 99, Nr. 1 (08.11.2017): 1–7. http://dx.doi.org/10.1017/s0025315417001783.
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The technical difficulties of performing underwater observation mean that marine ecologists have long relied on behavioural experiments to study reactions of marine organisms. In this article, we examine the underlying complexity of assumptions made in raceway experiments and we propose a statistical inference procedure tailored to this type of experimental protocol. As an example, experiments were performed to test if light of two different intensities affects the proximal behaviour (i.e. direct, local and immediate) of two species of crustaceans, the hermit crab (Pagurus bernhardus), and the green crab (Carcinus maenas). Individuals were collected in the vicinity of the Sven Loven Marine Center in Tjarnö (Sweden). Their movements in raceways were recorded and the statistical distance between the resulting experimental distribution and a simulated null distribution was used to compare their behaviour in two situations: dim (when they were expected to feed) and bright light (when they were expected to shelter). Initial tests indicated no differences of behaviour between dim and bright light for the two species. However, when compared with the reference state (here, a null distribution) the behaviour in dim light deviates significantly from the null distribution suggesting non-random behaviour. Our results suggest that efforts should be made to understand the behaviours of the individuals of these two species to establish a comprehensive reference state as a basis for comparison. This fundamental information should be a prerequisite before implementing experiments testing how potential disturbances affect individual organisms in behavioural ecology.
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LU, Biao, Yan J. JIANG, Yaling ZHOU, Fred Y. XU, Grant M. HATCH und Patrick C. CHOY. „Cloning and characterization of murine 1-acyl-sn-glycerol 3-phosphate acyltransferases and their regulation by PPARα in murine heart“. Biochemical Journal 385, Nr. 2 (07.01.2005): 469–77. http://dx.doi.org/10.1042/bj20041348.
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AGPAT (1-acyl-sn-glycerol 3-phosphate acyltransferase) exists in at least five isoforms in humans, termed as AGPAT1, AGPAT2, AGPAT3, AGPAT4 and AGPAT5. Although they catalyse the same biochemical reaction, their relative function, tissue expression and regulation are poorly understood. Linkage studies in humans have revealed that AGPAT2 contributes to glycerolipid synthesis and plays an important role in regulating lipid metabolism. We report the molecular cloning, tissue distribution, and enzyme characterization of mAGPATs (murine AGPATs) and regulation of cardiac mAGPATs by PPARα (peroxisome-proliferator-activated receptor α). mAGPATs demonstrated differential tissue expression profiles: mAGPAT1 and mAGPAT3 were ubiquitously expressed in most tissues, whereas mAGPAT2, mAGPAT4 and mAGPAT5 were expressed in a tissue-specific manner. mAGPAT2 expressed in in vitro transcription and translation reactions and in transfected COS-1 cells exhibited specificity for 1-acyl-sn-glycerol 3-phosphate. When amino acid sequences of five mAGPATs were compared, three highly conserved motifs were identified, including one novel motif/pattern KX2LX6GX12R. Cardiac mAGPAT activities were 25% lower (P<0.05) in PPARα null mice compared with wild-type. In addition, cardiac mAGPAT activities were 50% lower (P<0.05) in PPARα null mice fed clofibrate compared with clofibrate fed wild-type animals. This modulation of AGPAT activity was accompanied by significant enhancement/reduction of the mRNA levels of mAGPAT3/mAGPAT2 respectively. Finally, mRNA expression of cardiac mAGPAT3 appeared to be regulated by PPARα activation. We conclude that cardiac mAGPAT activity may be regulated by both the composition of mAGPAT isoforms and the levels of each isoform.
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Leonard, Nwafor Chimuanya, und A. U. Nwanekezi. „Effects of Guided Inquiry and Task Hierarchy Analysis Model in Cooperative Learning Strategy on Chemistry Students’ Performance in Imo State“. European Scientific Journal, ESJ 14, Nr. 25 (30.09.2018): 54. http://dx.doi.org/10.19044/esj.2018.v14n25p54.
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The study investigated the effects of guided inquiry and task hierarchy analysis model in cooperative learning strategy on Chemistry students’ performance in Nwangele Local Government Area, Imo State. The study adopted Pretest Posttest non-equivalent quasi-experimental design. One hundred and sixty-three Chemistry students from six public schools purposively selected participated in the study. Chemistry Performance Test on Acid-Base Reactions (CPTABR) which also tested retention with a reliability index of 0.75 was developed, validated and used for data collection. Research questions were answered using mean and Standard deviation, while the null hypotheses were tested using Analysis of Covariance at 0.05 significance level. The result revealed that Guided Inquiry Learning Strategy (GILS) and Task Hierarchy Analysis Model (THAM) in Cooperative Learning Strategy (CLS) proved to be more effective than lecture method (LM) in understanding of Acid-Base Reactions. It was recommended that Guided Inquiry Learning Strategy (GILS) and Task Hierarchy Analysis Model (THAM) in Cooperative Learning Strategy (CLS) should be used by Chemistry teachers to teach Acid- Base Reactions to enhance students’ performance and retention in Chemistry.
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Bouanaka, Fouzi, Saida Rebiaï, Hanene Bahouh und Salah Sahli. „PIC-MC Simulation Method of DC Discharge Plasmas“. Advanced Materials Research 227 (April 2011): 121–24. http://dx.doi.org/10.4028/www.scientific.net/amr.227.121.
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We propose in this paper a numerical particle type model PIC-MC (Particle-In-Cell Monte Carlo) for modeling plasma reactors in the case of DC discharge used for various industrial applications. The model is developed in the case of argon plasma at low pressure, generated in a reactor consisting of two flat electrodes parallel and spaced 3 cm. The collisions treatment is based on the “null collision” method. PIC-MC model can provide the plasma characteristics (potential, field and charge density) in inter-electrodes space, for all reactions in addition to collisions that may occur.
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Qi, Gong-jin, Chang-rui Zhang und Hai-feng Hu. „Embrittlement Behaviour and Mechanism of Silica Fibres with Polymer-Derived Silicon Nitride Coatings“. Advanced Composites Letters 14, Nr. 6 (November 2005): 096369350501400. http://dx.doi.org/10.1177/096369350501400602.
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Silicon nitride coatings were prepared on silica fibres using two polysilazanes, respectively, by dip coating with subsequent pyrolysis at 873 K in ammonia atmosphere. The silica fibres with polyhydridomethylsilazane derived coatings exhibited a residual tensile breaking force about 3.87% of the original fibres, while the fibres with perhydropolysilazane derived coatings showed a lower strength with the tensile breaking force approaching null. Besides the intrinsic degradation of silica fibres, the chemical reactions between the hydroxyl groups on silica fibres and the active radicals in polysilazanes probably played an important role in the embrittlement of silicon nitride-coated fibres.
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Ha, Son Tung, Thi Hong Hanh Pham und Thi Nguyet Anh Nguyen. „Stock Market Reactions to the Comprehensive and Progressive Agreement for Trans-Pacific Partnership’s Approval: Evidence from Vietnam“. Journal of Economic Integration 36, Nr. 3 (15.09.2021): 462–90. http://dx.doi.org/10.11130/jei.2021.36.3.462.
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We examine the stock market performance of Vietnam’s listed firms in response to the country’s approval of the Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CPTPP). Employing an event study methodology, we first calculate the abnormal returns of all listed Vietnamese firms around the CPTPP’s approval date. Then, we attempt to link these abnormal returns to firms’ characteristics. We find evidence that the announcement of the CPTPP’s approval is associated with positive abnormal returns for Vietnam’s listed firms. We also find considerable heterogeneity in the magnitude and pace of the impacts of the CPTPP’s approval on market returns across Vietnam’s two stock exchanges. However, we fail to reject the null hypothesis that the market did not react to the CPTPP’s approval at the sectoral level.
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Simić, Tatjana, Ana Savić-Radojević, Marija Plješa-Ercegovac, Marija Matić, Tatjana Sašić, Dejan Dragičević und Jasmina Mimić-Oka. „The Role of Glutathione S-Transferases in Urinary Tract Tumors“. Journal of Medical Biochemistry 27, Nr. 3 (01.07.2008): 360–66. http://dx.doi.org/10.2478/v10011-008-0016-1.
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The Role of Glutathione S-Transferases in Urinary Tract Tumors Exposure to potential carcinogens is among the etiological factors for renal cell carcinoma (RCC) and transitional cell carcinoma (TCC) of the urinary bladder. RCC is very resistant, while TCC exhibits a high recurrence rate and multifocality. Cytosolic glutathione S-transferases (GST) are a superfamily of enzymes which protect normal cells by catalyzing conjugation reactions between electrophylic compounds, including carcinogens, and glutathione. Some GST enzymes posses hydroperoxidase activity. The most well characterized classes have been named Alpha (GSTA), Mu (GSTM), Pi (GSTP) and Theta (GSTT) and each of these classes contains several different isoenzymes. Several types of allelic variation have been identified within classes, among which GSTM1-null and GSTT1-null confer impaired catalytic activity. Individuals with the GSTM1-null genotype carry a substantially higher risk for bladder carcinogenesis. The effects of glutathione S-transferase T1 polymorphism on the increased susceptibility to RCC and TCC of urinary bladder depend on the presence of specific chemical exposures to compounds metabolized via the GSTT1-1 pathway. In the process of kidney cancerisation expression of GST alpha isoenzymes tends to decrease, consequently favoring a prooxidant environment necessary for the growth of RCC. GST pi enzyme activities are generally retained in RCC and might contribute to the chemotherapy resistance of RCC. In the malignant phenotype of TCC of the urinary bladder up regulation of various GST classes occurs. Up regulation of GSTT1-1 and GSTP1-1 might have important consequences on the tumor growth, by providing a reduced environment and inhibition of apoptotic pathways.
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Ring, H. Z., und J. T. Lis. „The SR protein B52/SRp55 is essential for Drosophila development“. Molecular and Cellular Biology 14, Nr. 11 (November 1994): 7499–506. http://dx.doi.org/10.1128/mcb.14.11.7499-7506.1994.
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B52, also called SRp55, is a 52-kDa member of the Drosophila SR protein family of general splicing factors. Escherichia coli-produced B52 is capable of both activating splicing and affecting the alternative splice site choice in human in vitro splicing reactions. Here we report the isolation of a B52 null mutant generated by remobilizing a P element residing near the B52 gene. The resulting deletion, B52(28), is confined to the B52 gene and its neighbor the Hrb87F gene. Second-instar larvae homozygous for the deletion are deficient in both B52 mRNA and protein. The B52 null mutant is lethal at the first- and second-instar larval stages. Germ line transformation of Drosophila flies with B52 genomic DNA rescues this lethality. Thus, B52 is an essential gene and has a critical role in Drosophila development. Larvae deficient in B52 are still capable of splicing the five endogenous pre-mRNAs tested here, including both constitutively and alternatively spliced genes. Therefore, B52 is not required for all splicing in vivo. This is the first in vivo deficiency analysis of a member of the SR protein family.
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Ring, H. Z., und J. T. Lis. „The SR protein B52/SRp55 is essential for Drosophila development.“ Molecular and Cellular Biology 14, Nr. 11 (November 1994): 7499–506. http://dx.doi.org/10.1128/mcb.14.11.7499.
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B52, also called SRp55, is a 52-kDa member of the Drosophila SR protein family of general splicing factors. Escherichia coli-produced B52 is capable of both activating splicing and affecting the alternative splice site choice in human in vitro splicing reactions. Here we report the isolation of a B52 null mutant generated by remobilizing a P element residing near the B52 gene. The resulting deletion, B52(28), is confined to the B52 gene and its neighbor the Hrb87F gene. Second-instar larvae homozygous for the deletion are deficient in both B52 mRNA and protein. The B52 null mutant is lethal at the first- and second-instar larval stages. Germ line transformation of Drosophila flies with B52 genomic DNA rescues this lethality. Thus, B52 is an essential gene and has a critical role in Drosophila development. Larvae deficient in B52 are still capable of splicing the five endogenous pre-mRNAs tested here, including both constitutively and alternatively spliced genes. Therefore, B52 is not required for all splicing in vivo. This is the first in vivo deficiency analysis of a member of the SR protein family.
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Mukhopadhyay, Chandrani, Aleata Triplett, Tom Bargar, Carol Heckman, Kay-Uwe Wagner und Mayumi Naramura. „Casitas B-cell lymphoma (Cbl) proteins protect mammary epithelial cells from proteotoxicity of active c-Src accumulation“. Proceedings of the National Academy of Sciences 113, Nr. 51 (05.12.2016): E8228—E8237. http://dx.doi.org/10.1073/pnas.1615677113.
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Casitas B-cell lymphoma (Cbl) family ubiquitin ligases negatively regulate tyrosine kinase-dependent signal transduction by promoting degradation of active kinases. We and others previously reported that loss of Cbl functions caused hyperproliferation in lymphoid and hematopoietic systems. Unexpectedly, Cbl deletion in Cbl-b–null, Cbl-c–null primary mouse mammary epithelial cells (MECs) (Cbl triple-deficiency) induced rapid cell death despite enhanced MAP kinase and AKT activation. Acute Cbl triple-deficiency elicited distinct transcriptional and biochemical responses with partial overlap with previously described cellular reactions to unfolded proteins and oxidative stress. Although the levels of reactive oxygen species were comparable, detergent-insoluble protein aggregates containing phosphorylated c-Src accumulated in Cbl triple-deficient MECs. Treatment with a broad-spectrum kinase inhibitor dasatinib blocked protein aggregate accumulation and restored in vitro organoid formation. This effect is most likely mediated through c-Src because Cbl triple-deficient MECs were able to form organoids upon shRNA-mediated c-Src knockdown. Taking these data together, the present study demonstrates that Cbl family proteins are required to protect MECs from proteotoxic stress-induced cell death by promoting turnover of active c-Src.
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Кulieva, Sona, Rejhan Agaeva und Asif Mamedov. „Investigation of the interaction and composition of vapor in Bi: X(S, Se, Te): Br = 1: 1: 1 systems“. High Temperatures-High Pressures 50, Nr. 3 (2021): 233–41. http://dx.doi.org/10.32908/hthp.v50.1017.
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The vapor pressure in Bi: X (S, Se, Te): Br = 1: 1: 1 systems was measured by the static method using a membrane null manometer in the temperature range 300–1220 K and pressures 1–900 mm Hg. In the Bi-S-Br and Bi-Se-Br systems, the chemical interaction between the components begins at room temperature, and in the Bi-Te-Br system at 170 C. However, the formation of BiXBr ternary compounds going on only in the range of 350–400 C as a result of the interaction bismuth with chalcogen bromides according to the scheme X2Br2 (l) + 2Bi(s) → 2BiXBr (s). When heated above 400 C in the Bi-Te-Br system, above 420 and 460 C in the Bi-S-Br and Bi-Se-Br systems, the dissociation of ternary compounds going on according to the scheme 3BiXBr (l) → BiBr3 (vapor) + Bi2X3 (s). Based on the temperature dependences of the equilibrium constant of the reaction, the enthalpies and entropies of dissociation reactions are determined. The composition of the vapor after dissociation processes was defined.
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Strozzi, A., und G. Monegato. „On the incompatibility between the equivalent shear force concept and the integral formulation of contact problems between Kirchhoff plates and irregular linear supports“. Proceedings of the Institution of Mechanical Engineers, Part C: Journal of Mechanical Engineering Science 222, Nr. 7 (01.07.2008): 1149–63. http://dx.doi.org/10.1243/09544062jmes801.
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It is shown that, when employing the integral formulation to describe contact problems between Kirchhoff plates and irregular linear supports, the equivalent shear force concept may be incompatible with the integral approach. In such circumstances the equivalent shear force concept has to be abandoned in favour of an equivalent twisting moment approach. A classical example of an infinite plate resting on a linear central segment is revisited in the light of the equivalent twisting moment concept, where all the computations are carried out in exact form. An additional example is developed to show that the usefulness of an integral approach based upon the equivalent twisting moment concept remains valid even when the equivalent twisting moment is applied at a plate border along which the twisting moment must be null, as it occurs in a partially clamped border. The reaction singularity at the endpoints of a linear support is examined with the Williams asymptotic method. Finally, a physical interpretation is proposed for the adoption of a distributed twisting moment among the contact reactions.
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Lu, Q., und B. D. Shur. „Sperm from beta 1,4-galactosyltransferase-null mice are refractory to ZP3-induced acrosome reactions and penetrate the zona pellucida poorly“. Development 124, Nr. 20 (15.10.1997): 4121–31. http://dx.doi.org/10.1242/dev.124.20.4121.
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A variety of sperm surface components have been suggested to mediate gamete recognition by binding to glycoside ligands on the egg coat glycoprotein ZP3. The function of each of these candidate receptors is based upon varying degrees of circumstantial and direct evidence; however, the effects on fertilization of targeted mutations in any of these candidate receptors have not yet been reported. In this paper, we describe the effects of targeted mutations in beta1,4-galactosyltransferase, the best studied of the candidate receptors for ZP3. Surprisingly, galactosyltransferase-null (gt[−/−]) males are fertile; however, sperm from gt(−/−) males bind less radiolabeled ZP3 than wild-type sperm, and are unable to undergo the acrosome reaction in response to either ZP3 or anti-galactosyltransferase antibodies, as do wild-type sperm. In contrast, gt(−/−) sperm undergo the acrosome reaction normally in response to calcium ionophore, which bypasses the requirement for ZP3 binding. The inability of gt(−/−) sperm to undergo a ZP3-induced acrosome reaction renders them physiologically inferior to wild-type sperm, as assayed by their relative inability to penetrate the egg coat and fertilize the oocyte in vitro. Thus, although ZP3 binding and subsequent induction of the acrosome reaction are dispensable for fertilization, they impart a physiological advantage to the fertilizing sperm. A second strain of mice was created that is characterized by a loss of of the long galactosyltransferase isoform responsible for ZP3-dependent signal transduction, but which maintains normal levels of Golgi galactosylation. Sperm from these mice show that the defective sperm-egg interactions in gt(−/−) mice are due directly to a loss of the long galactosyltransferase isoform from the sperm surface and are independent of the state of intracellular galactosylation during spermatogenesis.
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Le Balc’h, Kévin. „Local controllability of reaction-diffusion systems around nonnegative stationary states“. ESAIM: Control, Optimisation and Calculus of Variations 26 (2020): 55. http://dx.doi.org/10.1051/cocv/2019033.
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We consider a n × n nonlinear reaction-diffusion system posed on a smooth bounded domain Ω of ℝN. This system models reversible chemical reactions. We act on the system through m controls (1 ≤ m < n), localized in some arbitrary nonempty open subset ω of the domain Ω. We prove the local exact controllability to nonnegative (constant) stationary states in any time T > 0. A specificity of this control system is the existence of some invariant quantities in the nonlinear dynamics that prevents controllability from happening in the whole space L∞(Ω)n. The proof relies on several ingredients. First, an adequate affine change of variables transforms the system into a cascade system with second order coupling terms. Secondly, we establish a new null-controllability result for the linearized system thanks to a spectral inequality for finite sums of eigenfunctions of the Neumann Laplacian operator, due to David Jerison, Gilles Lebeau and Luc Robbiano and precise observability inequalities for a family of finite dimensional systems. Thirdly, the source term method, introduced by Yuning Liu, Takéo Takahashi and Marius Tucsnak, is revisited in a L∞-context. Finally, an appropriate inverse mapping theorem in suitable spaces enables to go back to the nonlinear reaction-diffusion system.
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RADID, Atika, und Karim RHOFIR. „Improvement of a nonnegative preserved efficient solver for atmospheric chemical kinetic equations“. International Journal of Engineering & Technology 7, Nr. 3 (06.07.2018): 6657. http://dx.doi.org/10.14419/ijet.v7i4.24694.
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Generally, chemical reactions from atmospheric chemistry models are described by a strongly coupled, stiff and nonlinear system of ordinary differential equations, which requires a good numerical solver. Several articles published about the solvers of chemical equations, during the numerical simulation, indicate that one renders the concentration null when it becomes negative. In order to preserve the positivity of the exact solutions, recent works have proposed a new solver called Modified-Backward-Euler (MBE). To improve this solver, we propose in this paper an iterative numerical scheme witch is better fitted to stiff problems. This new approach, called Iterative-Modified-Backward-Euler (IMBE), is based on iterative solution of the P-L structure of the implicit nonlinear ordinary differential equations on each time step. The efficiency of the iteration process is increased by using the Gauss and Successive-Over-Relaxation (SOR). In the case of fast/slow chemical kinetic reactions, we proposed an other variant called Iterative-Quasi-Steady-State-Approximation (IQSSA). The numerical exploration of stiff test problem shows clearly that this formalism is applicable to a wide range of chemical kinetics problems and give a good approximation compared to the recent solver. The numerical procedures give reasonable accurate solutions when compared to exact solution.Generally, chemical reactions from atmospheric chemistry models are described by a strongly coupled, stiff and nonlinear system of ordinary differential equations, which requires a good numerical solver. Several articles published about the solvers of chemical equations, during the numerical simulation, indicate that one renders the concentration null when it becomes negative. In order to preserve the positivity of the exact solutions, recent works have proposed a new solver called Modified-Backward-Euler (MBE). To improve this solver, we propose in this paper an iterative numerical scheme witch is better fitted to stiff problems. This new approach, called Iterative-Modified-Backward-Euler (IMBE), is based on iterative solution of the P-L structure of the implicit nonlinear ordinary differential equations on each time step. The efficiency of the iteration process is increased by using the Gauss and Successive-Over-Relaxation (SOR). In the case of fast/slow chemical kinetic reactions, we proposed an other variant called Iterative-Quasi-Steady-State-Approximation (IQSSA). The numerical exploration of stiff test problem shows clearly that this formalism is applicable to a wide range of chemical kinetics problems and give a good approximation compared to the recent solver. The numerical procedures give reasonable accurate solutions when compared to exact solution.
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Yuan, Changqing, Raghavendra Pralhada Rao, Nahid Jesmin, Takeshi Bamba, Kunio Nagashima, Alberto Pascual, Thomas Preat, Eiichiro Fukusaki, Usha Acharya und Jairaj K. Acharya. „CDase is a pan-ceramidase in Drosophila“. Molecular Biology of the Cell 22, Nr. 1 (Januar 2011): 33–43. http://dx.doi.org/10.1091/mbc.e10-05-0453.
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Ceramidases catalyze the conversion of ceramide to sphingosine. They are acylaminohydrolases that catalyze the deacylation of the amide-linked saturated fatty acid from ceramide to generate sphingosine. They also catalyze the reverse reaction of ceramide biosynthesis using sphingosine and fatty acid. In mammals, different proteins catalyze these reactions while individually exhibiting optimal activity over a narrow pH range and have been accordingly called acid, neutral, and alkaline ceramidases. Several genes encode for variants of alkaline ceramidase in mammals. Brainwashing (Bwa) is the only putative alkaline ceramidase homologue present in Drosophila. In this study we have demonstrated that BWA does not exhibit ceramidase activity and that bwa null mutants display no loss of ceramidase activity. Instead, the neutral ceramidase gene CDase encodes the protein that is responsible for all measurable ceramidase activity in Drosophila. Our studies show strong genetic interaction of Bwa with CDase and the Drosophila ceramide kinase gene (DCERK). We show that, although BWA is unlikely to be a ceramidase, it is a regulator of sphingolipid flux in Drosophila. Bwa exhibits strong genetic interaction with other genes coding for ceramide-metabolizing enzymes. This interaction might partly explain its original identification as a ceramidase.
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PHAN, Hao Duy, und Lan Ngoc NGUYEN. „The South China Sea Arbitration: Bindingness, Finality, and Compliance with UNCLOS Dispute Settlement Decisions“. Asian Journal of International Law 8, Nr. 1 (06.12.2017): 36–50. http://dx.doi.org/10.1017/s2044251317000121.
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AbstractOn 12 July 2016, the Tribunal in theSouth China Seaarbitration issued its final award. China rejected the ruling as “null and void”. The Philippines dismissed it as “a piece of paper” after initially hailing the ruling a “milestone decision”. The reactions of the parties concerned raise important questions about the bindingness, finality, and state compliance with UNCLOS dispute settlement decisions. This paper addresses these questions by dissecting China’s arguments that the award “has no binding force” and by examining the options available for promoting compliance with the award. The paper also considers the broader question of how states generally comply with UNCLOS dispute settlement decisions and evaluates the significance of UNCLOS dispute settlement mechanisms, including theSouth China Seaarbitration, in the absence of external enforcement.
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Hata, Daisuke, Yuko Kawakami, Naoki Inagaki, Chris S. Lantz, Toshio Kitamura, Wasif N. Khan, Mari Maeda-Yamamoto et al. „Involvement of Bruton's Tyrosine Kinase in FcεRI-dependent Mast Cell Degranulation and Cytokine Production“. Journal of Experimental Medicine 187, Nr. 8 (20.04.1998): 1235–47. http://dx.doi.org/10.1084/jem.187.8.1235.
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We investigated the role of Bruton's tyrosine kinase (Btk) in FcεRI-dependent activation of mouse mast cells, using xid and btk null mutant mice. Unlike B cell development, mast cell development is apparently normal in these btk mutant mice. However, mast cells derived from these mice exhibited significant abnormalities in FcεRI-dependent function. xid mice primed with anti-dinitrophenyl monoclonal IgE antibody exhibited mildly diminished early-phase and severely blunted late-phase anaphylactic reactions in response to antigen challenge in vivo. Consistent with this finding, cultured mast cells derived from the bone marrow cells of xid or btk null mice exhibited mild impairments in degranulation, and more profound defects in the production of several cytokines, upon FcεRI cross-linking. Moreover, the transcriptional activities of these cytokine genes were severely reduced in FcεRI-stimulated btk mutant mast cells. The specificity of these effects of btk mutations was confirmed by the improvement in the ability of btk mutant mast cells to degranulate and to secrete cytokines after the retroviral transfer of wild-type btk cDNA, but not of vector or kinase-dead btk cDNA. Retroviral transfer of Emt (= Itk/Tsk), Btk's closest relative, also partially improved the ability of btk mutant mast cells to secrete mediators. Taken together, these results demonstrate an important role for Btk in the full expression of FcεRI signal transduction in mast cells.
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Voso, Maria Teresa, Francesco D'Alo', Rossana Putzulu, Luca Mele, Alessandra Scardocci, Patrizia Chiusolo, Roberto Latagliata et al. „Negative prognostic value of glutathione S-transferase(GSTM1 and GSTT1) deletions in adult acute myeloid leukemia“. Blood 100, Nr. 8 (15.10.2002): 2703–7. http://dx.doi.org/10.1182/blood.v100.8.2703.
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Glutathione S-transferases (GSTs) are enzymes involved in the detoxification of several environmental mutagens, carcinogens, and anticancer drugs. GST polymorphisms resulting in decreased enzymatic activity have been associated with several types of solid tumors. We determined the prognostic significance of the deletion of 2 GST subfamilies genes, M1 and T1, in patients with acute myeloid leukemia (AML). Using polymerase chain reactions, we analyzed theGSTM1 and GSTT1 genotype in 106 patients with AML (median age, 60.5 years; range, 19-76 years). The relevance ofGSTM1 and GSTT1 homozygous deletions was studied with respect to patient characteristics, response to therapy, and survival. Homozygous deletions resulting in null genotypes at theGSTM1 and GSTT1 loci were detected in 45 (42%) and 30 (28%) patients, respectively. The double-null genotype was present in 19 patients (18%). GST deletions predicted poor response to chemotherapy (P = .04) and shorter survival (P = .04). The presence of at least one GST deletion proved to be an independent prognostic risk factor for response to induction treatment and overall survival in a multivariate analysis including age and karyotype (P = .02). GST genotyping was of particular prognostic value in the cytogenetically defined intermediate-risk group (P = .003). In conclusion, individuals with GSTM1 or GSTT1 deletions (or deletions of both) may have an enhanced resistance to chemotherapy and a shorter survival.
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Parmagnani, Ambra S., Giuseppe Mannino und Massimo E. Maffei. „Transcriptomics and Metabolomics of Reactive Oxygen Species Modulation in Near-Null Magnetic Field-Induced Arabidopsis thaliana“. Biomolecules 12, Nr. 12 (06.12.2022): 1824. http://dx.doi.org/10.3390/biom12121824.
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The geomagnetic field (GMF) is a natural component of Earth’s biosphere. GMF reduction to near-null values (NNMF) induces gene expression modulation that generates biomolecular, morphological, and developmental changes. Here, we evaluate the effect of NNMF on gene expression and reactive oxygen species (ROS) production in time-course experiments on Arabidopsis thaliana. Plants exposed to NNMF in a triaxial Helmholtz coils system were sampled from 10 min to 96 h to evaluate differentially expressed genes (DEGs) of oxidative stress responses by gene microarray. In 24–96 h developing stages, H2O2 and polyphenols were also analyzed from roots and shoots. A total of 194 DEGs involved in oxidative reactions were selected, many of which showed a fold change ≥±2 in at least one timing point. Heatmap clustering showed DEGs both between roots/shoots and among the different time points. NNMF induced a lower H2O2 than GMF, in agreement with the expression of ROS-related genes. Forty-four polyphenols were identified, the content of which progressively decreased during NNMF exposition time. The comparison between polyphenols content and DEGs showed overlapping patterns. These results indicate that GMF reduction induces metabolomic and transcriptomic modulation of ROS-scavenging enzymes and H2O2 production in A. thaliana, which is paralleled by the regulation of antioxidant polyphenols.
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Chanet, R., M. Heude, A. Adjiri, L. Maloisel und F. Fabre. „Semidominant mutations in the yeast Rad51 protein and their relationships with the Srs2 helicase.“ Molecular and Cellular Biology 16, Nr. 9 (September 1996): 4782–89. http://dx.doi.org/10.1128/mcb.16.9.4782.
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Suppressors of the methyl methanesulfonate sensitivity of Saccharomyces cerevisiae diploids lacking the Srs2 helicase turned out to contain semidominant mutations in Rad5l, a homolog of the bacterial RecA protein. The nature of these mutations was determined by direct sequencing. The 26 mutations characterized were single base substitutions leading to amino acid replacements at 18 different sites. The great majority of these sites (75%) are conserved in the family of RecA-like proteins, and 10 of them affect sites corresponding to amino acids in RecA that are probably directly involved in ATP reactions, binding, and/or hydrolysis. Six mutations are in domains thought to be involved in interaction between monomers; they may also affect ATP reactions. By themselves, all the alleles confer a rad5l null phenotype. When heterozygous, however, they are, to varying degrees, negative semidominant for radiation sensitivity; presumably the mutant proteins are coassembled with wild-type Rad51 and poison the resulting nucleofilaments or recombination complexes. This negative effect is partially suppressed by an SRS2 deletion, which supports the hypothesis that Srs2 reverses recombination structures that contain either mutated proteins or numerous DNA lesions.
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Koduru, Suresh, Lalit Kumar, Esra Ozcan, Michiko Oyoshi, Michel Massaad, Severine Le Bras, Narayanaswamy Ramesh et al. „Impaired T cell homing and transendothelial migration in CIP4 null mice caused by defective integrin-mediated adhesion (44.1)“. Journal of Immunology 184, Nr. 1_Supplement (01.04.2010): 44.1. http://dx.doi.org/10.4049/jimmunol.184.supp.44.1.
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Abstract The F-BAR domain-containing protein CIP4 interacts with Cdc42 and WASP/N-WASP and is thought to participate in the assembly of filamentous actin. CIP4-/- mice had normal T and B lymphocyte development but impaired T cell-dependent antibody production, IgG antibody affinity maturation, and germinal center formation, despite intact CD40L-CD40 axis. CIP4-/- T cells, but not B cells, homed poorly to lymphoid organs. CIP4-/- mice had impaired contact hypersensitivity (CHS) and their T cells failed to adoptively transfer CHS. CD4+ effector T cells from CIP4-/-/OT-II mice migrated poorly to antigen challenged skin. CIP4-/- T cells exhibited normal rolling on endothelial selectins and chemotaxis to SDF-1α, but impaired adhesion and polarization on immobilized VCAM-1 and ICAM-1, and defective arrest and transmigration across murine endothelial cells under shear flow conditions. These results demonstrate an important role for CIP4 in integrin-mediated T cell adhesive events that are essential for normal recruitment to lymphoid organs and sites of antigen driven immune reactions.
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Upmacis, Rita K., Mark J. Crabtree, Ruba S. Deeb, Hao Shen, Paul B. Lane, Lea Esther S. Benguigui, Nobuyo Maeda, David P. Hajjar und Steven S. Gross. „Profound biopterin oxidation and protein tyrosine nitration in tissues of ApoE-null mice on an atherogenic diet: contribution of inducible nitric oxide synthase“. American Journal of Physiology-Heart and Circulatory Physiology 293, Nr. 5 (November 2007): H2878—H2887. http://dx.doi.org/10.1152/ajpheart.01144.2006.
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Diminished nitric oxide (NO) bioactivity and enhanced peroxynitrite formation have been implicated as major contributors to atherosclerotic vascular dysfunctions. Hallmark reactions of peroxynitrite include the accumulation of 3-nitrotyrosine (3-NT) in proteins and oxidation of the NO synthase (NOS) cofactor, tetrahydrobiopterin (BH4). The present study sought to 1) quantify the extent to which 3-NT accumulates and BH4 becomes oxidized in organs of apolipoprotein E-deficient (ApoE−/−) atherosclerotic mice and 2) determine the specific contribution of inducible NOS (iNOS) to these processes. Whereas protein 3-NT and oxidized BH4 were undetected or near the detection limit in heart, lung, and kidney of 3-wk-old ApoE−/− mice or ApoE−/− mice fed a regular chow diet for 24 wk, robust accumulation was evident after 24 wk on a Western (atherogenic) diet. Since 3-NT accumulation was diminished 3- to 20-fold in heart, lung, and liver in ApoE−/− mice missing iNOS, iNOS-derived species are involved in this reaction. In contrast, iNOS-derived species did not contribute to elevated protein 3-NT formation in kidney or brain. iNOS deletion also afforded marked protection against BH4 oxidation in heart, lung, and kidney of atherogenic ApoE−/− mice but not in brain or liver. These findings demonstrate that iNOS-derived species are increased during atherogenesis in ApoE−/− mice and that these species differentially contribute to protein 3-NT accumulation and BH4 oxidation in a tissue-selective manner. Since BH4 oxidation can switch the predominant NOS product from NO to superoxide, we predict that progressive NOS uncoupling is likely to drive atherogenic vascular dysfunctions.
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Alghamdi, Mansour, Afnan Al-Hunaiti, Sharif Arar, Mamdouh Khoder, Ahmad Abdelmaksoud, Hisham Al-Jeelani, Heikki Lihavainen et al. „A Predictive Model for Steady State Ozone Concentration at an Urban-Coastal Site“. International Journal of Environmental Research and Public Health 16, Nr. 2 (17.01.2019): 258. http://dx.doi.org/10.3390/ijerph16020258.
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Ground level ozone (O3) plays an important role in controlling the oxidation budget in the boundary layer and thus affects the environment and causes severe health disorders. Ozone gas, being one of the well-known greenhouse gases, although present in small quantities, contributes to global warming. In this study, we present a predictive model for the steady-state ozone concentrations during daytime (13:00–17:00) and nighttime (01:00–05:00) at an urban coastal site. The model is based on a modified approach of the null cycle of O3 and NOx and was evaluated against a one-year data-base of O3 and nitrogen oxides (NO and NO2) measured at an urban coastal site in Jeddah, on the west coast of Saudi Arabia. The model for daytime concentrations was found to be linearly dependent on the concentration ratio of NO2 to NO whereas that for the nighttime period was suggested to be inversely proportional to NO2 concentrations. Knowing that reactions involved in tropospheric O3 formation are very complex, this proposed model provides reasonable predictions for the daytime and nighttime concentrations. Since the current description of the model is solely based on the null cycle of O3 and NOx, other precursors could be considered in future development of this model. This study will serve as basis for future studies that might introduce informing strategies to control ground level O3 concentrations, as well as its precursors’ emissions.
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Chiabrando, Deborah, Sonia Mercurio, Samuele Marro, Sharmila Fagoonee, Erika Messana, Emilia Turco, Lorenzo Silengo, Fiorella Altruda und Emanuela Tolosano. „FLVCRb: a Mitochondrial FLVCR Isoform Important for Erythropoiesis“. Blood 116, Nr. 21 (19.11.2010): 4243. http://dx.doi.org/10.1182/blood.v116.21.4243.4243.
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Abstract Abstract 4243 Feline Leukemia Virus subgroup C Receptor (FLVCR) was originally identified and cloned as a cell-surface protein receptor for feline leukemia virus subgroup C, causing pure red blood cell aplasia in cats. Recent studies have demonstrated that FLVCR is a heme exporter which is essential for erythropoiesis. The heme efflux via FLVCR was shown to be essential for erythroid differentiation in K562 cells as well as in CD34+ precursors cells1. Moreover, Keel and co-authors have reported that Flvcr-null mice die in utero due to the failure of fetal erythropoiesis; also post-natal mice lacking FLVCR showed severe anemia. In addition to the erythroid defect, Flvcr-null embryos display defective growth and developmental anomalies2. We have identified an alternative transcription start site giving rise to a novel FLVCR isoform (FLVCRb). Flvcr-b transcript completely lacks the first exon of the canonical isoform (FLVCRa) and code for a putative 6 transmembrane domain containing protein ubiquitously expressed. In vitro over-expression of FLVCRa and FLVCRb showed that the two proteins display different subcellular localization. As expected, FLVCRa is localized at the cell membrane while FLVCRb is in the mitochondrial compartment. The mitochondrial localization of this novel isoform is further confirmed by the identification of a N-terminal mitochondrial sorting presequence. The mitochondrion is the site in which heme biosynthesis occurs. Although all the enzymatic reactions involved in heme synthesis are well characterized, how heme is exported to the cytosol is largely unknown. Because of FLVCRa is a heme exporter at the cell membrane, we hypothesized that FLVCRb could be the mitochondrial heme exporter. According to this hypothesis, FLVCRb expression increased following the stimulation of heme biosynthesis in vitro, in correlation with the increase in hemoglobin production. The ability of FLVCRb to bind and export heme out of the mitochondria is still under investigation. To gain insights into the specific roles of the two isoforms, we have generated Flvcr mutant mice different from those previously reported2. Keel and co-author generated a mouse model in which both FLVCRa and FLVCRb have been deleted. In our mouse model, FLVCRa has been specifically deleted while FLVCRb is still expressed (FLVCRa-null mice). Flvcr-a +/− mice were grossly normal, fertile and indistinguishable from their wild-type littermates. When Flvcr-a +/− mice were intercrossed, no Flvcr-a homozygous knock-out newborns were obtained. The analysis of the embryos from timed Flvcr-a +/− intercrosses showed that the Flvcr-a homozygous knock-out genotype was lethal between E14.5 and the birth. E13.5 Flvcr-a-null embryos showed multifocal and extended hemorrhages, visible in the limbs, head and throughout the body wall, as well as subcutaneous edema. Imcomplete vasculogenesis in the Flvcr-a-null embryos was observed at E11.5, a developmental stage in which hemorrhages were not still evident. This suggests that hemorrhages arise from a defect in the development of embryonic vasculature. Moreover, FLVCRa-null embryos showed skeletal abnormalities as demonstrated by Alcian blue-alizarin red staining. Skeletal malformations were evident in the limb where digits did not form properly and in the head where Meckel's cartilage was incomplete. It is interesting to note that this kind of malformations also occurs in Diamond Blackfan Anemia (DBA) patients. Surprisingly, flow cytometric analyses of E14.5 fetal liver cells double-stained for Ter119 (erythroid-specific antigen) and CD71 (transferrin receptor) showed normal erythropoiesis in Flvcr-a-null embryos, in opposition to what occurs in the previously reported Flvcr-null mice2. Taken together, these data demonstrated that FLVCRb is sufficient to support fetal erythropoiesis when the expression of FLVCRa is loss, likely exporting heme out of the mithocondrion for hemoglobin synthesis. Moreover, the loss of FLVCRa leads to incomplete vasculogenesis, hemorrhages and skeletal malformations highlighting new roles of FLVCRa in these processes. 1. Quigley JG et al. Identification of a human heme exporter that is essential for erythropoiesis. Cell 2004 2. Keel SB et al. A heme export protein is required for red blood cell differentiation and iron homeostasis. Science 2008. Disclosures: No relevant conflicts of interest to declare.
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Zhang, Chenggang, Pengrui Ou und Pengfei Guo. „Does Public Health Emergency Experience Have an Impact on Individual Reactions during COVID-19?“ Healthcare 11, Nr. 9 (24.04.2023): 1212. http://dx.doi.org/10.3390/healthcare11091212.
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Local historical experience in public health emergencies has been perceived to largely affect COVID-19’s social influence. Specifically, individuals’ personal experience in public health emergencies would likely have an impact on their reactions to the next similar event. Herein, we combined life course and risk analysis frameworks to explore how individuals’ experiences influence current risk perception and protective behaviors. We collected 1000 questionnaires of random network samples in six Chinese provinces of different risk levels from 29 April to 8 May 2020, and used the propensity score matching (PSM) model and multivariable linear regression to process the data. We categorized individual public emergency experience into three patterns: (1) having ever witnessed a public health emergency, (2) having ever experienced a public health emergency, and (3) currently experiencing a public health emergency. The study indicates that individuals’ experiences had significant positive effects on protective behaviors against COVID-19. The average effects of the three patterns on behaviors were 0.371 (p < 0.001), 0.898 (p < 0.001) and 0.319 (p < 0.05), respectively. The study also shows that for those experiencing any one pattern, the effect of risk perception on protective behaviors appeared null in the early stage of the pandemic. We propose the potential interactive mechanism of risk factors in the life course at the individual level. Academically, this study develops the risk theory of perception and behavior and expands the application of the life course approach in the public health arena. Practically, our research indicates that public health emergency experiences are valuable for responding to a future pandemic and normalizing prevention policies.
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Achong, Gypsy R., Ana M. Rodriguez und Alfred M. Spormann. „Benzylsuccinate Synthase of Azoarcussp. Strain T: Cloning, Sequencing, Transcriptional Organization, and Its Role in Anaerobic Toluene and m-Xylene Mineralization“. Journal of Bacteriology 183, Nr. 23 (01.12.2001): 6763–70. http://dx.doi.org/10.1128/jb.183.23.6763-6770.2001.
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ABSTRACT Biochemical studies in Azoarcus sp. strain T have demonstrated that anaerobic oxidation of both toluene andm-xylene is initiated by addition of the aromatic hydrocarbon to fumarate, forming benzylsuccinate and 3-methyl benzylsuccinate, respectively. Partially purified benzylsuccinate synthase was previously shown to catalyze both of these addition reactions. In this study, we identified and sequenced the genes encoding benzylsuccinate synthase from Azoarcus sp. strain T and examined the role of this enzyme in both anaerobic toluene and m-xylene mineralization. Based on reverse transcription-PCR experiments and transcriptional start site mapping, we found that the structural genes encoding benzylsuccinate synthase,bssCAB, together with two additional genes,bssD and bssE, were organized in an operon in the order bssDCABE. bssD is believed to encode an activating enzyme, similar in function to pyruvate formate-lyase activase. bssE shows homology to tutHfrom Thauera aromatica strain T1, whose function is currently unknown. A second operon that is upstream ofbssDCABE and divergently transcribed contains two genes,tdiS and tdiR. The predicted amino acid sequences show similarity to sensor kinase and response regulator proteins of prokaryotic two-component regulatory systems. A chromosomal null bssA mutant was constructed (the bssAgene encodes the α-subunit of benzylsuccinate synthase). ThisbssA null mutant strain was unable to grow under denitrifying conditions on either toluene or m-xylene, while growth on benzoate was unaffected. The growth phenotype of the ΔbssA mutant could be rescued by reintroducingbssA in trans. These results demonstrate that benzylsuccinate synthase catalyzes the first step in anaerobic mineralization of both toluene and m-xylene.
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Hatagima, Ana, Maria Nazaré Klautau-Guimarães, Felizardo Penalva da Silva und Pedro Hernan Cabello. „Glutathione S-transferase M1 (GSTM1) polymorphism in two Brazilian populations“. Genetics and Molecular Biology 23, Nr. 4 (Dezember 2000): 709–13. http://dx.doi.org/10.1590/s1415-47572000000400003.
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The distribution of GSTM1 phenotype frequencies was studied in two Brazilian samples composed of healthy and unrelated blood donors of both sexes ranging in age from 18 to 61 years. The first sample consisted of 658 individuals from Rio de Janeiro, and the second included 179 individuals from Brasília. The GSTM1 phenotypes were detected using PCR reactions and subsequent digestion by the restriction enzyme HaeII. The GSTM1 null phenotype frequency was 46% and 49% for Rio de Janeiro and Brasília samples, respectively. The GSTM1 phenotype distributions were not in agreement with Hardy-Weinberg equilibrium in either sample, chi²1 = 11.49 (P < 0.001) for Rio de Janeiro and chi²1 = 6.77 (P < 0.01) for Brasília. This deviation from Hardy-Weinberg equilibrium may be due to factors such as selection, errors in the phenotype determination or incomplete panmixia of the Brazilian population, whose main racial components are Caucasians, Africans and Indians.
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Flores-Rivera, Ciro-Filemon. „Modeling and Behavior Analysis of a Membraneless Fuel Cell“. ISRN Applied Mathematics 2012 (09.02.2012): 1–24. http://dx.doi.org/10.5402/2012/695167.
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Membraneless fuel cells are examples of microelectromechanical systems (MEMSs) that can be considered as alternate energy sources. Applications include microfluidic-based devices like miniaturized laboratories, sensors, or actuators to be used in medicine or agronomy. This paper presents a mathematical model for this type of cells based on the governing physical laws. It includes fluid dynamics, electric charge distribution and electrostatics modeled by the Navier-Stokes, Nernst-Planck, and Poisson equations, respectively. A robust numerical algorithm is proposed to solve the model. Two cases are discussed: allowing electrochemical reactions on one of the electrodes and the simpler situation of null exchange current density. An initial characterization for the behavior of membraneless fuel cells is achieved concerning to prevalence of velocity and electric field, use of non-Newtonian fluids, relationship to initial conditions for some variables, general profile for conductivity and electric density, and linear dependence on current density under specific conditions.
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Yang, Wenqiang, Tyler M. Wittkopp, Xiaobo Li, Jaruswan Warakanont, Alexandra Dubini, Claudia Catalanotti, Rick G. Kim et al. „Critical role ofChlamydomonas reinhardtiiferredoxin-5 in maintaining membrane structure and dark metabolism“. Proceedings of the National Academy of Sciences 112, Nr. 48 (16.11.2015): 14978–83. http://dx.doi.org/10.1073/pnas.1515240112.
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Photosynthetic microorganisms typically have multiple isoforms of the electron transfer protein ferredoxin, although we know little about their exact functions. Surprisingly, aChlamydomonas reinhardtiimutant null for the ferredoxin-5 gene (FDX5) completely ceased growth in the dark, with both photosynthetic and respiratory functions severely compromised; growth in the light was unaffected. Thylakoid membranes in dark-maintainedfdx5mutant cells became severely disorganized concomitant with a marked decrease in the ratio of monogalactosyldiacylglycerol to digalactosyldiacylglycerol, major lipids in photosynthetic membranes, and the accumulation of triacylglycerol. Furthermore, FDX5 was shown to physically interact with the fatty acid desaturases CrΔ4FAD and CrFAD6, likely donating electrons for the desaturation of fatty acids that stabilize monogalactosyldiacylglycerol. Our results suggest that in photosynthetic organisms, specific redox reactions sustain dark metabolism, with little impact on daytime growth, likely reflecting the tailoring of electron carriers to unique intracellular metabolic circuits under these two very distinct redox conditions.
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Dykstra, Josiah, Kelly Shortridge, Jamie Met und Douglas Hough. „Opportunity Cost of Action Bias in Cybersecurity Incident Response“. Proceedings of the Human Factors and Ergonomics Society Annual Meeting 66, Nr. 1 (September 2022): 1116–20. http://dx.doi.org/10.1177/1071181322661490.
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The hours and days immediately following the discovery of a cyber intrusion can be stressful and chaotic for victims. Without a documented and well-rehearsed incident response plan, people are prone to costly fear-based reactions. Action bias is the human tendency to favor action over inaction. It feels better for victims to do something even if rushed decisions are suboptimal to thoughtful, careful alternatives. Furthermore, the null baseline of doing nothing or watchful waiting can sometimes be advantageous. This paper describes an application of opportunity cost to action bias. While these insights are not yet backed by empirical data, this is the first work to examine the intersection of opportunity cost with action bias in cybersecurity incident response. Using Sony Pictures Entertainment as a case study, we discuss the implications of opportunity costs from acting prematurely and, conversely, the opportunity costs of waiting to act.
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Oliveira, Cleiton Lourenço de, Natália Souza Oliveira, Márcia Souza de Oliveira, Vicente Paulo Campos, Wilson Roberto Maluf und Luiz Antônio Augusto Gomes. „Reaction of common bean to Meloidogyne incognita race 1 and Meloidogyne javanica“. Revista Ceres 65, Nr. 4 (August 2018): 321–28. http://dx.doi.org/10.1590/0034-737x201865040004.
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ABSTRACT Identification of common bean genotypes resistant to the root-knot nematodes may be useful for bean breeding programs. The objective of this study was to evaluate the reaction of bean genotypes to M. incognita race 1 and M. javanica. Two independent trials to assess resistance to both root-knot nematodes were carried out with fifty-eight common bean genotypes and six snap bean genotypes. The experiments were arranged in a randomized block design, with three replications and two plants per plot. A total of 10,000 nematode eggs were inoculated per plant 15 days after germination. At forty-five days after inoculation, the root system of each plant was harvested and the nematode eggs were extracted. The number of eggs per gram of root was counted and the Reproduction Factor and the Reduction of the Reproduction Factor were calculated. The performance of the genotypes differed between the trials, indicating different resistance reactions to the nematode species evaluated. The genotypes VP-25 and BRS Valente were resistant to M. incognita race 1. The genotypes Aporé, Ouro Vermelho, Radiante, and CNFP 10793 showed good resistance to both M. incognita race 1 and M. javanica, with potential as source of resistance in breeding programs. There was a significant correlation between root mass and number of eggs. The correlation between nematode reproduction and shoot mass was null.
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Drukier, A. K., Ch Cantor, M. Chonofsky, G. M. Church, R. L. Fagaly, K. Freese, A. Lopez, T. Sano, C. Savage und W. P. Wong. „New class of biological detectors for WIMPs“. International Journal of Modern Physics A 29, Nr. 19 (30.07.2014): 1443007. http://dx.doi.org/10.1142/s0217751x14430076.
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Weakly Interacting Massive Particles (WIMPs) may constitute a large fraction of the matter in the Universe. There are excess events in the data of DAMA/LIBRA, CoGeNT, CRESST-II, and recently CDMS-Si, which could be consistent with WIMP masses of approximately 10 GeV /c2. However, for M DM > 10 GeV /c2 null results of the CDMS-Ge, XENON, and LUX detectors may be in tension with the potential detections for certain dark matter scenarios and assuming a certain light response. We propose the use of a new class of biological dark matter (DM) detectors to further examine this light dark matter hypothesis, taking advantage of new signatures with low atomic number targets. Two types of biological DM detectors are discussed here: DNA-based detectors and enzymatic reactions (ER) based detectors. In the case of DNA-based detectors, we discuss a new implementation. In the case of ER detectors, there are four crucial phases of the detection process: (a) change of state due to energy deposited by a particle; (b) amplification due to the release of energy derived from the action of an enzyme on its substrate; (c) sustainable but nonexplosive enzymatic reaction; (d) self-termination due to the denaturation of the enzyme, when the temperature is raised. This paper provides information of how to design as well as optimize these four processes.
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Franzoso, Guido, Louise Carlson, Ljiljana Poljak, Elizabeth W. Shores, Suzanne Epstein, Antonio Leonardi, Alex Grinberg et al. „Mice Deficient in Nuclear Factor (NF)-κB/p52 Present with Defects in Humoral Responses, Germinal Center Reactions, and Splenic Microarchitecture“. Journal of Experimental Medicine 187, Nr. 2 (19.01.1998): 147–59. http://dx.doi.org/10.1084/jem.187.2.147.
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p52 is a subunit of nuclear factor (NF)-κB transcription factors, most closely related to p50. Previously, we have shown that p52, but not p50 homodimers can form transactivating complexes when associated with Bcl-3, an unusual member of the IκB family. To determine nonredundant physiologic roles of p52, we generated mice deficient in p52. Null mutant mice were impaired in their ability to generate antibodies to T-dependent antigens, consistent with an absence of B cell follicles and follicular dendritic cell networks in secondary lymphoid organs, and an inability to form germinal centers. Furthermore, the splenic marginal zone was disrupted. These phenotypes are largely overlapping with those observed in Bcl-3 knockout animals, but distinct from those of p50 knockouts, supporting the notion of a physiologically relevant complex of p52 homodimers and Bcl-3. Adoptive transfer experiments further suggest that such a complex may be critical in accessory cell functions during antigen-specific immune reactions. Possible roles of p52 and Bcl-3 are discussed that may underlie the oncogenic potential of these proteins, as evidenced by recurrent chromosomal translocations of their genes in lymphoid tumors.
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Taketomi, Yoshitaka, Yuki Endo, Takayoshi Higashi, Remi Murase, Tomio Ono, Choji Taya, Tetsuyuki Kobayashi und Makoto Murakami. „Mast Cell-Specific Deletion of Group III Secreted Phospholipase A2 Impairs Mast Cell Maturation and Functions“. Cells 10, Nr. 7 (04.07.2021): 1691. http://dx.doi.org/10.3390/cells10071691.
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Tissue-resident mast cells (MCs) have important roles in IgE-associated and -independent allergic reactions. Although microenvironmental alterations in MC phenotypes affect the susceptibility to allergy, understanding of the regulation of MC maturation is still incomplete. We previously reported that group III secreted phospholipase A2 (sPLA2-III) released from immature MCs is functionally coupled with lipocalin-type prostaglandin D2 (PGD2) synthase in neighboring fibroblasts to supply a microenvironmental pool of PGD2, which in turn acts on the PGD2 receptor DP1 on MCs to promote their proper maturation. In the present study, we reevaluated the role of sPLA2-III in MCs using a newly generated MC-specific Pla2g3-deficient mouse strain. Mice lacking sPLA2-III specifically in MCs, like those lacking the enzyme in all tissues, had immature MCs and displayed reduced local and systemic anaphylactic responses. Furthermore, MC-specific Pla2g3-deficient mice, as well as MC-deficient KitW-sh mice reconstituted with MCs prepared from global Pla2g3-null mice, displayed a significant reduction in irritant contact dermatitis (ICD) and an aggravation of contact hypersensitivity (CHS). The increased CHS response by Pla2g3 deficiency depended at least partly on the reduced expression of hematopoietic PGD2 synthase and thereby reduced production of PGD2 due to immaturity of MCs. Overall, our present study has confirmed that MC-secreted sPLA2-III promotes MC maturation, thereby facilitating acute anaphylactic and ICD reactions and limiting delayed CHS response.