Journal articles on the topic 'Additive combinatory'
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1
Bimbó, Katalin. "The Church-Rosser property in dual combinatory logic." Journal of Symbolic Logic 68, no. 1 (March 2003): 132–52. http://dx.doi.org/10.2178/jsl/1045861508.
Abstract:
AbstractDual combinators emerge from the aim of assigning formulas containing ← as types to combinators. This paper investigates formally some of the properties of combinatory systems that include both combinators and dual combinators. Although the addition of dual combinators to a combinatory system does not affect the unique decomposition of terms, it turns out that some terms might be redexes in two ways (with a combinator as its head, and with a dual combinator as its head). We prove a general theorem stating that no dual combinatory system possesses the Church-Rosser property. Although the lack of confluence might be problematic in some cases, it is not a problem per se. In particular, we show that no damage is inflicted upon the structurally free logics, the system in which dual combinators first appeared.
2
Erdmann, Kati, Jessica Ringel, Silke Hampel, Manfred P. Wirth, and Susanne Fuessel. "Carbon nanomaterials sensitize prostate cancer cells to docetaxel and mitomycin C via induction of apoptosis and inhibition of proliferation." Beilstein Journal of Nanotechnology 8 (June 23, 2017): 1307–17. http://dx.doi.org/10.3762/bjnano.8.132.
Abstract:
We have previously shown that carbon nanofibers (CNFs) and carbon nanotubes (CNTs) can sensitize prostate cancer (PCa) cells to platinum-based chemotherapeutics. In order to further verify this concept and to avoid a bias, the present study investigates the chemosensitizing potential of CNFs and CNTs to the conventional chemotherapeutics docetaxel (DTX) and mitomycin C (MMC), which have different molecular structures and mechanisms of action than platinum-based chemotherapeutics. DU-145 PCa cells were treated with DTX and MMC alone or in combination with the carbon nanomaterials. The impact of the monotreatments and the combinatory treatments on cellular function was then systematically analyzed by using different experimental approaches (viability, short-term and long-term proliferation, cell death rate). DTX and MMC alone reduced the viability of PCa cells to 94% and 68%, respectively, whereas a combined treatment with CNFs led to less than 30% remaining viable cells. Up to 17- and 7-fold higher DTX and MMC concentrations were needed in order to evoke a similar inhibition of viability as mediated by the combinatory treatments. In contrast, the dose of platinum-based chemotherapeutics could only be reduced by up to 3-fold by combination with carbon nanomaterials. Furthermore, combinatory treatments with CNFs led mostly to an additive inhibition of short- and long-term proliferation compared to the individual treatments. Also, higher cell death rates were observed in combinatory treatments than in monotreatments, e.g., a combination of MMC and CNFs more than doubled the cell death rate mediated by apoptosis. Combinations with CNTs showed a similar, but less pronounced impact on cellular functions. In summary, carbon nanomaterials in combination with DTX and MMC evoked additive to partly synergistic anti-tumor effects. CNFs and CNTs possess the ability to sensitize cancer cells to a wide range of structurally diverse chemotherapeutics and thus represent an interesting option for the development of multimodal cancer therapies. Co-administration of chemotherapeutics with carbon nanomaterials could result in a reduction of the chemotherapeutic dosage and thus limit systemic side effects.
3
Netopilova, Marie, Marketa Houdkova, Klara Urbanova, Johana Rondevaldova, and Ladislav Kokoska. "Validation of Qualitative Broth Volatilization Checkerboard Method for Testing of Essential Oils: Dual-Column GC–FID/MS Analysis and In Vitro Combinatory Antimicrobial Effect of Origanum vulgare and Thymus vulgaris against Staphylococcus aureus in Liquid and Vapor Phases." Plants 10, no. 2 (February 18, 2021): 393. http://dx.doi.org/10.3390/plants10020393.
Abstract:
Combinatory action of antimicrobial agents such as essential oils (EOs) show to be an effective strategy to overcome the problem with increasing antibiotic resistance of microorganisms, including Staphylococcus aureus. The objective of this study was to evaluate in vitro antimicrobial interactions between Origanum vulgare and Thymus vulgaris EOs against various S.aureus strains in both liquid and vapor phases using the broth volatilization checkerboard method. Fractional inhibitory concentrations (FICs) were determined for both liquid and vapor phases, and the composition of EOs was analyzed by gas chromatography-mass spectrometry using dual-column/dual-detector gas chromatograph. Results of oregano and thyme EOs combination showed additive effects against all S. aureus strains in both phases. In several cases, sums of FICs were lower than 0.6, which can be considered a strong additive interaction. The lowest FICs obtained were 0.53 in the liquid phase and 0.59 in the gaseous phase. Chemical analysis showed that both EOs were composed of many compounds, including carvacrol, thymol, γ-terpinene, and p-cymene. This is the first report on oregano and thyme EOs interactions against S. aureus in the vapor phase. It also confirms the accuracy of the broth volatilization checkerboard method for the evaluation of combinatory antimicrobial effects of EOs in the vapor phase.
4
Yang, Shun-Kai, Khatijah Yusoff, Chun-Wai Mai, Wei-Meng Lim, Wai-Sum Yap, Swee-Hua Lim, and Kok-Song Lai. "Additivity vs Synergism: Investigation of the Additive Interaction of Cinnamon Bark Oil and Meropenem in Combinatory Therapy." Molecules 22, no. 11 (November 4, 2017): 1733. http://dx.doi.org/10.3390/molecules22111733.
5
Dotti Sani, Giulia Maria, and Mario Quaranta. "A Mixed Approach to the Work-Motherhood Relation: An Application of Fuzzy Set Qualitative Comparative Analysis and Generalized Linear Models." Comparative Sociology 12, no. 1 (2013): 31–65. http://dx.doi.org/10.1163/15691330-12341251.
Abstract:
Abstract Female labor force participation and total fertility rates have been negatively correlated until the early ’80s. By the end of that decade, however, the relationship changed sign. Scholars have suggested a close link between individual reproductive behavior, labor market participation and institutional contexts, but we still lack clear evidence of the underlying micro-level mechanism. We propose the use of complementary techniques, fuzzy set Qualitative Comparative Analysis and Generalized Linear Models, as the different assumptions underlying the two, combinatory vs. additive, may lead to new insights on how the combination of institutional features can produce different outcomes in terms of the work-motherhood relationship.
6
Bhattamisra, Subrat Kumar, Chew Hui Kuean, Lee Boon Chieh, Vivian Lee Yean Yan, Chin Koh Lee, Lee Peng Hooi, Lai Pei Shyan, Yun Khoon Liew, Mayuren Candasamy, and Priyadarshi Soumyaranjan Sahu. "Antibacterial Activity of Geraniol in Combination with Standard Antibiotics against Staphylococcus aureus, Escherichia coli and Helicobacter pylori." Natural Product Communications 13, no. 7 (July 2018): 1934578X1801300. http://dx.doi.org/10.1177/1934578x1801300701.
Abstract:
The antibacterial activity of geraniol and its effect in combination with ampicillin, amoxicillin and clarithromycin against Staphylococcus aureus, Escherichia coli and Helicobacter pylori was tested. The minimum inhibitory concentrations (MICs) and combinatory effects of geraniol against the bacteria were assessed by using the modified broth microdilution and checkerboard assay, respectively. The combinatory effect is expressed as fractional inhibitory concentration index (FICI). The MIC of geraniol against S. aureus, E. coli and H. pylori was found to be 11200, 5600, and 7325 μg/mL, respectively. A significant synergistic effect was observed with geraniol and ampicillin against S. aureus with FICI in the range 0.19 to 0.32. Geraniol and ampicillin exhibited a partial synergistic effect against E. coli. A similar effect was observed with geraniol and clarithromycin against S. aureus. A partial synergistic effect was observed with clarithromycin and geraniol against H. pylori with the FICI value in the range 0.86 to 0.89. An additive effect was observed with geraniol and amoxicillin combination against H. pylori. However, the amoxicillin and clarithromycin dose was reduced by thirty-two fold when combined with geraniol against H. pylori. The anti- H. pylori effect of geraniol with clarithromycin and amoxicillin could be of potential interest in the treatment of H. pylori infection and associated ulcers in humans. Further, geraniol, in combination with other antibiotics, has substantial therapeutic potential against S. aureus and E.coli infection.
7
Sakaue, Saori, Masato Akiyama, Makoto Hirata, Koichi Matsuda, Yoshinori Murakami, Michiaki Kubo, Yoichiro Kamatani, and Yukinori Okada. "Functional variants in ADH1B and ALDH2 are non-additively associated with all-cause mortality in Japanese population." European Journal of Human Genetics 28, no. 3 (September 26, 2019): 378–82. http://dx.doi.org/10.1038/s41431-019-0518-y.
Abstract:
Abstract The functional variants involved in alcohol metabolism, the A allele of rs1229984:A > G in ADH1B and the A allele of rs671:G > A in ALDH2, are specifically prevalent among East Asian population. They are shown to be under recent positive selection, but the reasons for the selection are unknown. To test whether these positively selected variants have beneficial effects on survival in modern population, we performed the survival analyses using the large-scale Japanese cohort (n = 135,974) with genotype and follow-up survival data. The rs671-A allele was significantly associated with the better survival in the additive model (HR for mortality = 0.960, P = 1.7 × 10−5), and the rs1229984-A had both additive and non-additive effects (HR = 0.962, P = 0.0016 and HR = 0.958, P = 0.0066, respectively), which was consistent with the positive selection. The favorable effects of these alleles on survival were independent of the habit of alcohol consumption itself. The heterogenous combinatory effect between rs1229984 and rs671 genotype was also observed (HRs for AA genotype at rs671 were 1.03, 0.80, and 0.90 for GG, GA, and AA genotype at rs1229984, respectively), supposedly reflecting the synergistic effects on survival.
8
Villalobos-González, Antonio, Ignacio Benítez-Riquelme, Fernando Castillo-González, Ma del Carmen Mendoza-Castillo, and Alejandro Espinosa-Calderón. "Genetic Parameters in Mesocotyl Elongation and Principal Components for Corn in High Valleys, Mexico." Seeds 3, no. 1 (March 13, 2024): 149–68. http://dx.doi.org/10.3390/seeds3010012.
Abstract:
Corn germplasm with different mesocotyl elongation was characterized for High Valleys in Mexico by estimating the general combinatory aptitude (GCA), specific combinatory aptitude (SCA), heterosis (H), inbreeding depression (ID) and principal component aptitude (PCA), with the purpose of directing the improvement for deep sowing. The hypothesis was that the parents and crosses of mesocotyl present variability in seedling and adult plant traits based on deep sowing. The 36 F1 and F2 crosses—derived from nine parents, three with short mesocotyl (S), three medium (M) and three long (L), obtained through Griffing diallel II—plus the parents were planted in sand beds and polyethylene bags in a greenhouse during the spring–summer cycles of 2021 and 2022. The following traits were measured: length of mesocotyl (LM), length of coleoptile, total seedling dry matter and 10 cob traits in addition to total dry matter. In 11 of the 14 traits, there was a positive and significant correlation (p ≤ 0.05) between the GCA of the parents and their LM. The highest SCA, H and ID (p ≤ 0.05) were for crosses L × L for all the traits measured. When comparing the GCA/SCA proportions, this relation varied from 0.76 to 0.97, which points to practically equal additive effects with those of dominance; however, in parents and L × L crosses, this relation was on average 0.94, 1.07 in M × M, 0.22 in S × S and 0.36 in L × S. In both F1 and F2, the variation was explained by two principal components: 89.5% for GCA and 73.4% for SCA. In both generations, the parents with higher GCA were H-48, HS-2 and Promesa, the three with long mesocotyl, while those with the highest GCA were crosses between these three hybrids.
9
Miklasińska-Majdanik, Maria, Małgorzata Kępa, Tomasz J. Wąsik, Karolina Zapletal-Pudełko, Magdalena Klim, and Robert D. Wojtyczka. "The Direction of the Antibacterial Effect of Rutin Hydrate and Amikacin." Antibiotics 12, no. 9 (September 21, 2023): 1469. http://dx.doi.org/10.3390/antibiotics12091469.
Abstract:
The aim of the presented study was to examine the in vitro antimicrobial activity of rutin hydrate (RH) alone and in combination with amikacin against 12 reference strains of Gram-positive and Gram-negative bacteria. The antibacterial activity assay was evaluated in the concentration range of 2–2048 µg/mL. A serial microdilution method was used to determine the minimal inhibitory concentration (MIC) of the examined compound against reference strains. RH showed varying potential against the tested strains with MICs ranging from 128 to 1024 µg/mL. In order to examine the combinatory profile of RH and amikacin, the fractional inhibitory concentrations (FICs) were determined. The RH–amikacin combination was more active against Gram-negative bacteria where four synergism and two additive interactions were noted. For four out of six Gram-positive isolates, an indifferent effect of RH and amikacin was demonstrated, and for two strains, the tested combination had an additive effect. The results of this study showed that RH possesses antimicrobial potential in vitro towards the tested reference isolates. Moreover, it shows a promising combined effect with amikacin against Gram-negative bacteria.
10
Muñoz Romero, Luis Ángel, Enrique Navarro Guerrero, Manuel De la Rosa Ibarra, Luis Pérez Romero, and Ángel Enrique Caamal Dzul. "Estimación de varianzas genéticas en ocho variedades criollas de maíz para el Bajío mexicano." Agronomía Mesoamericana 28, no. 2 (April 30, 2017): 455. http://dx.doi.org/10.15517/ma.v28i2.21801.
Abstract:
The aim of this work was to estimate the combinatory aptitude, genetic variance and heterosis of eight creole corn varieties. The research work was carried in Irapuato, Guanajuato, México, during 2008 and 2009. A randomized complete block design with three replications was used to evaluate the twenty-eight crosses under method 4 Griffing (1956). Each experimental plot included four rows five meters long with a separation of 0,75 m. The general combing ability and specific (ACG and ACE) were highly significant (P<0.01) for all traits except flowering days. The dominance variance (σ2D) was larger and more important than additive variance (σ2A) for most of the traits, indicating that non- additive genetic genes were important on the expression of those traits on crosses. It was observed that varieties P6 (creole #5), P7 (creole #2) and P8 (creole San Antonio) had larger variance effects (σ2ACE) for long cob, number of rows per cob, total cob number, and grain yield. Some outstanding crosses were identified for their high grain yield as well as heterosis, mainly those that included germoplasm of creole #5, #2 and San Antonio. According to the aforementioned we recommend to draw lines from the above populations and cross them to produce hybrids.
11
Sayed, Hesham M., Ashraf S. Awaad, Fatma El-Zahraa S. Abdel Rahman, M. Al-Dossari, N. S. Abd El-Gawaad, and Osama M. Ahmed. "Combinatory Effect and Modes of Action of Chrysin and Bone Marrow-Derived Mesenchymal Stem Cells on Streptozotocin/Nicotinamide-Induced Diabetic Rats." Pharmaceuticals 16, no. 1 (December 27, 2022): 34. http://dx.doi.org/10.3390/ph16010034.
Abstract:
The purpose of this study was to see how chrysin and/or bone marrow-derived mesenchymal stem cells (BM-MSCs) affected streptozotocin (STZ)/nicotinamide (NA)-induced diabetic rats as an animal model of type 2 diabetes mellitus (T2DM). Male Wistar rats were given a single intraperitoneal (i.p.) injection of 60 mg STZ/kg bodyweight (bw) 15 min after an i.p. injection of NA (120 mg/kg bw) to induce T2DM. The diabetic rats were given chrysin orally at a dose of 100 mg/kg bw every other day, BM-MSCs intravenously at a dose of 1 × 106 cells/rat/week, and their combination for 30 days after diabetes induction. The rats in the diabetic group displayed impaired oral glucose tolerance and a decrease in liver glycogen content and in serum insulin, C-peptide, and IL-13 levels. They also had significantly upregulated activities in terms of liver glucose-6-phosphatase and glycogen phosphorylase and elevated levels of serum free fatty acids, IL-1β, and TNF-α. In addition, the diabetic rats exhibited a significant elevation in the adipose tissue resistin protein expression level and a significant decrease in the expression of adiponectin, insulin receptor-beta subunit, insulin receptor substrate-1, and insulin receptor substrate-2, which were associated with a decrease in the size of the pancreatic islets and in the number of β-cells and insulin granules in the islets. The treatment of diabetic rats with chrysin and/or BM-MSCs significantly improved the previously deteriorated alterations, with chrysin combined with BM-MSCs being the most effective. Based on these findings, it can be concluded that combining chrysin with BM-MSCs produced greater additive therapeutic value than using them separately in NA/STZ-induced T2DM rats.
12
Milczarek, Małgorzata, Tomasz Cierpiał, Piotr Kiełbasiński, Milena Małecka-Giełdowska, Marta Świtalska, Joanna Wietrzyk, Maciej Mazur, and Katarzyna Wiktorska. "An Organofluorine Isoselenocyanate Analogue of Sulforaphane Affects Antimetabolite 5-Fluorouracil’s Anticancer Activity: A Perspective for New Combinatory Therapy in Triple-Negative Breast Cancer." Molecules 28, no. 15 (August 1, 2023): 5808. http://dx.doi.org/10.3390/molecules28155808.
Abstract:
Antimetabolites, especially 5-fluorouracil, are commonly used clinically to treat breast, colon, and other cancers. However, their side effects and inefficiency in monotherapy have prompted further searches for new combinations. Thus, the anticancer effect of 5-fluorouracil (5-FU) and the sulforaphane analogue, 4-isoselenocyanato-1-butyl 4′-fluorobenzyl sulfoxide (ISC), were tested in in vitro and in vivo models of triple-negative breast cancer (TNBC) as a new option for this treatment-resistant and aggressive type of breast cancer. A synergic interaction between 5-FU and ISC was observed in the TNBC in vitro model MDA-MB-231 cell line, which led to enhanced antiproliferative effects. The results of in vitro studies were confirmed by in vivo tests, which demonstrated stronger tumor growth inhibition and additive interactions between 5-FU and ISC in the murine TNBC model. Moreover, the results of the body mass and blood analysis showed the safety of the tested combination. The mechanistic study revealed that the combined treatment triggered apoptosis and necrosis, as well as inhibited cell migration.
13
Karabulut, Gözde, and Nurhayat Barlas. "The possible effects of mono butyl phthalate (MBP) and mono (2-ethylhexyl) phthalate (MEHP) on INS-1 pancreatic beta cells." Toxicology Research 10, no. 3 (May 2021): 601–12. http://dx.doi.org/10.1093/toxres/tfab045.
Abstract:
Abstract Mono-2-ethyhexyl phthalate (MEHP), an environmental xenoestrogen, is widely used in the production of polyvinyl chloride materials and can be easily accumulated in human body. MBP is the active monoester metabolite of di butyl phthalate that is widely used as plasticizer in many products such as plastic toys, food packaging, personal care products, as well as an additive in lubricants, eliminating foams, and lotions. The presented in-vitro cytotoxicity study focused on time-dependent and combinatory exposure scenarios. We chose these phthalates because they are posed a considerable interest because of their contribution to insulin resistance, type-2 diabetes and obesity. All experiments performed in INS-1 pancreatic beta cells show moderate cytotoxicity with a time-dependent increase in effectiveness. INS-1 cells were treated with 0.001, 0.01, 0.1, 1, or 10-μM MEHP and MBP for 24, 48, and 72 h. Our results showed that cell viability was decreased and total oxidant levels were increased. Also, mRNA expression levels with asscociated beta cells were measured and for MBP dose groups, all mRNA expression levels were decreased. In conclusion, these findings suggest that, MEHP and MBP are have a negative and distruptor role on pancreatic beta cells and it will be linked with insulin resistance and type 2 diabetes.
14
Isa, Reiko, Mano Horinaka, Taku Tsukamoto, Kentaro Mizuhara, Yuto Fujibayashi, Yoko Taminishi-Katsuragawa, Haruya Okamoto, et al. "The Rationale for the Dual-Targeting Therapy for RSK2 and AKT in Multiple Myeloma." International Journal of Molecular Sciences 23, no. 6 (March 8, 2022): 2919. http://dx.doi.org/10.3390/ijms23062919.
Abstract:
Multiple myeloma (MM) is characterized by remarkable cytogenetic/molecular heterogeneity among patients and intraclonal diversity even in a single patient. We previously demonstrated that PDPK1, the master kinase of series of AGC kinases, is universally active in MM, and plays pivotal roles in cell proliferation and cell survival of myeloma cells regardless of the profiles of cytogenetic and genetic abnormalities. This study investigated the therapeutic efficacy and mechanism of action of dual blockade of two major PDPK1 substrates, RSK2 and AKT, in MM. The combinatory treatment of BI-D1870, an inhibitor for N-terminal kinase domain (NTKD) of RSK2, and ipatasertib, an inhibitor for AKT, showed the additive to synergistic anti-tumor effect on human MM-derived cell lines (HMCLs) with active RSK2-NTKD and AKT, by enhancing apoptotic induction with BIM and BID activation. Moreover, the dual blockade of RSK2 and AKT exerted robust molecular effects on critical gene sets associated with myeloma pathophysiologies, such as those with MYC, mTOR, STK33, ribosomal biogenesis, or cell-extrinsic stimuli of soluble factors, in HMCLs. These results provide the biological and molecular rationales for the dual-targeting strategy for RSK2 and AKT, which may overcome the therapeutic difficulty due to cytogenetic/molecular heterogeneity in MM.
15
Kvich, Lasse, Mads H. Christensen, Malgorzata K. Pierchala, Konstantin Astafiev, Rasmus Lou-Moeller, and Thomas Bjarnsholt. "The Combination of Low-Frequency Ultrasound and Antibiotics Improves the Killing of In Vitro Staphylococcus aureus and Pseudomonas aeruginosa Biofilms." Antibiotics 11, no. 11 (October 28, 2022): 1494. http://dx.doi.org/10.3390/antibiotics11111494.
Abstract:
Due to an increase in underlying predisposing factors, chronic wounds have become an increasing burden on healthcare systems worldwide. Chronic infections often contain biofilm-forming bacteria, which are challenging to eradicate due to increased antibiotic tolerance; thus, new and improved therapeutic strategies are warranted. One such strategy is the combination of ultrasound and antibiotics. Therefore, this study aimed to investigate the combinatory effects of low-frequency (50 kHz) ultrasound delivered by specially designed ultrasound patches using flexible piezoelectric material, PiezoPaint™, in combination with antibiotics against biofilms with Staphylococcus aureus and Pseudomonas aeruginosa. The reduction in viable cells in S. aureus and P. aeruginosa biofilms was evaluated post-treatment with fusidic acid, clindamycin, ciprofloxacin, and colistin in combination with ultrasound treatment. Two-hour ultrasound treatment significantly increased the bactericidal effect of all four antibiotics, resulting in a 96–98% and 90–93% reduction in P. aeruginosa and S. aureus, respectively. In addition, an additive effect was observed when extending treatment to 4 h, resulting in >99% and 95–97% reduction in P. aeruginosa and S. aureus, respectively. These results contrasted the lack of effect observed when treating filter-biofilms with antibiotics alone. The combined effect of ultrasound and antibiotic treatment resulted in a synergistic effect, reducing the viability of the clinically relevant pathogens S. aureus and P. aeruginosa. The modularity of the specially designed patches intended for topical treatment holds promising applications as a supplement in chronic wound therapy. Further studies are warranted with clinically isolated strains and other clinically relevant antibiotics before proceeding to studies where safety and applicability are investigated.
16
Fremy, J. M., I. Alassane-Kpembi, I. P. Oswald, B. Cottrill, and H. P. Van Egmond. "A review on combined effects of moniliformin and co-occurring Fusarium toxins in farm animals." World Mycotoxin Journal 12, no. 3 (July 1, 2019): 281–91. http://dx.doi.org/10.3920/wmj2018.2405.
Abstract:
Co-occurrence of mycotoxins in food and feed represents the rule rather than the exception. Information about combinatory toxic effects of co-occurring mycotoxins is scarce, in particular the effects that mixtures of mycotoxins in feed may have on farm animals. This review focusses on studies on the combined effects of moniliformin and co-occurring mycotoxins in feed on farm animals. Moniliformin is a mycotoxin of emerging scientific interest, which may co-occur with many other mycotoxins, especially Fusarium mycotoxins. Oral exposure to moniliformin reduces feed consumption and body weight gain in poultry, in pigs and catfish, and induces cardiotoxic effects and/or alterations in serum biochemical and haematological parameters. In this review only experiments comparing effects as a result of the exposure to a combination of mycotoxins with effects due to the exposure to single mycotoxins were considered. Identified published studies on combined toxicity have been limited to combinations of moniliformin with either fumonisin B1 or deoxynivalenol, and were performed with poultry, pigs, and catfish. Most of the moniliformin/fumonisin B1 investigations involved poultry and focussed on adverse effects on feed intake, weight gain and immune response, as well as organ lesions. These studies mainly reported an interactive toxicity of moniliformin and fumonisin B1 but did not allow identification of the type of interaction. Likewise, no indication could be given for the interaction detected for both mycotoxins on weight gains of catfish. For the moniliformin/deoxynivalenol combination, only one study with broiler chickens was found relevant. This study concluded additive or less than additive toxicity, using kidney lesions and renal tubular epithelial degeneration as endpoints. While possible interactions between moniliformin and fumonisin B1 or deoxynivalenol were identified, the conclusions are based on limited studies and experimental designs. Further studies on the combined toxicity of moniliformin with other mycotoxins and other animal species would be needed.
17
Wu, Wen-Sheng, Chin-Hsien Ling, Ming-Che Lee, Chuan-Chu Cheng, Rui-Fang Chen, Chen-Fang Lin, Ren-In You, and Yen-Cheng Chen. "Targeting Src-Hic-5 Signal Cascade for Preventing Migration of Cholangiocarcinoma Cell HuCCT1." Biomedicines 10, no. 5 (April 28, 2022): 1022. http://dx.doi.org/10.3390/biomedicines10051022.
Abstract:
Cholangiocarcinoma (CCA) is the second most common primary liver cancer with poor prognosis. The deregulation of a lot of oncogenic signaling molecules, such as receptor tyrosine kinases (RTKs), has been found to be associated with CCA progression. However, RTKs-based target therapy showed limited improvement suggesting a need to search for alternative targets for preventing CCA progression. To address this issue, we screened the oncogenic signal molecules upregulated in surgical tissues of CCAs. Interestingly, over-expression of hydrogen peroxide inducible clone-5 (Hic-5) coupled with over-activation of Src, AKT, JNK were observed in 50% of the cholangiocarcinoma with metastatic potential. To investigate whether these molecules may work together to trigger metastatic signaling, their up-and-down relationship was examined in a well-established cholangiocarcinoma cell line, HuCCT1. Src inhibitors PP1 (IC50, 13.4 μM) and dasatinib (IC50, 0.1 μM) significantly decreased both phosphorylated AKT (phosphor-AKT Thr450) and Hic-5 in HuCCT1. In addition, a knockdown of Hic-5 effectively suppressed activation of Src, JNK, and AKT. These implicated a positive cross-talk occurred between Hic-5 and Src for triggering AKT activation. Further, depletion of Hic-5 and inhibition of Src suppressed HuccT1 cell migration in a dose-dependent manner. Remarkably, prior transfection of Hic-5 siRNA for 24 h followed by treatment with PP1 or dasatinib for 24 h resulted in additive suppression of HuCCT1 migration. This suggested that a promising combinatory efficacy can be achieved by depletion of Hic-5 coupled with inhibition of Src. In the future, target therapy against CCA progression by co-targeting Hic-5 and Src may be successfully developed in vivo.
18
Mishra, Rudra, and Pasupathi Rathinasabapathi. "Antibiotics Susceptibility Profile and Synergistic Effects of Flavonoids with Antibiotics against Resistant Staphylococcus aureus from Asymptomatic Individuals." Journal of Pure and Applied Microbiology 14, no. 4 (December 2, 2020): 2669–76. http://dx.doi.org/10.22207/jpam.14.4.44.
Abstract:
Staphylococcus aureus exhibits resistance to most of the commonly used antibiotics. Although antibiotics suceptibility studies have been performed on the pathogen isolated from the patient samples, only limited information is available about that of S. aureus isolated from asymptomatic individuals. In this study, S. aureus was isolated from the skin microbiota of the asymptomatic individuals, and susceptibility of the pathogen against different antibiotics and plant flavonoids was compared to drug-sensitive strain. The minimum inhibitory concentration (MIC) value and IC50 of the pathogen were calculated against the antibiotics and flavonoids. The susceptibility pattern of the isolated strain showed higher resistance against erythromycin (100 μg mL-1) and vancomycin (25 μg mL-1). Based on the fractional inhibitory concentration index (FICI) values, the combinatory effects of antibiotics and flavonoids were categorized into synergistic, additive, and indifferent. The combination of rutin and erythromycin showed a synergistic effect with the concentrations of 31.25 μg mL-1 and 1.562 μg mL-1 against drug-sensitive strains of S. aureus. Similarly, the same combination showed synergistic effects against isolated strains at the concentration of 625 μg mL-1 and 12.5 μg mL-1.We observed an increase in drug resistance in the isolated strain of S. aureus in comparison to the drug-sensitive strain. To the best of our knowledge, this was the first study reporting increase in antimicrobial resistance of S. aureus present on asymptomatic individuals than the sensitive strain.
19
Reye, Gina, Xuan Huang, Kara L. Britt, Christoph Meinert, Tony Blick, Yannan Xu, Konstantin I. Momot, et al. "RASSF1A Suppression as a Potential Regulator of Mechano-Pathobiology Associated with Mammographic Density in BRCA Mutation Carriers." Cancers 13, no. 13 (June 29, 2021): 3251. http://dx.doi.org/10.3390/cancers13133251.
Abstract:
High mammographic density (MD) increases breast cancer (BC) risk and creates a stiff tissue environment. BC risk is also increased in BRCA1/2 gene mutation carriers, which may be in part due to genetic disruption of the tumour suppressor gene Ras association domain family member 1 (RASSF1A), a gene that is also directly regulated by tissue stiffness. High MD combined with BRCA1/2 mutations further increase breast cancer risk, yet BRCA1/2 mutations alone or in combination do not increase MD. The molecular basis for this additive effect therefore remains unclear. We studied the interplay between MD, stiffness, and BRCA1/2 mutation status in human mammary tissue obtained after prophylactic mastectomy from women at risk of developing BC. Our results demonstrate that RASSF1A expression increased in MCF10DCIS.com cell cultures with matrix stiffness up until ranges corresponding with BiRADs 4 stiffnesses (~16 kPa), but decreased in higher stiffnesses approaching malignancy levels (>50 kPa). Similarly, higher RASSF1A protein was seen in these cells when co-cultivated with high MD tissue in murine biochambers. Conversely, local stiffness, as measured by collagen I versus III abundance, repressed RASSF1A protein expression in BRCA1, but not BRCA2 gene mutated tissues; regional density as measured radiographically repressed RASSF1A in both BRCA1/2 mutated tissues. The combinatory effect of high MD and BRCA mutations on breast cancer risk may be due to RASSF1A gene repression in regions of increased tissue stiffness.
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Franson, Andrea, Cassie Kline, Annette Molinaro, Yalan Zhang, Kelly Hitchner, Nalin Gupta, Carl Koschmann, Michael Prados, Javad Nazarian, and Sabine Mueller. "CTNI-09. DIFFUSE MIDLINE GLIOMA-ADAPTIVE COMBINATORY TRIAL (DMG-ACT): A COMBINATION PLATFORM TRIAL IN PEDIATRIC AND YOUNG ADULT PATIENTS WITH DIFFUSE MIDLINE GLIOMA." Neuro-Oncology 24, Supplement_7 (November 1, 2022): vii71—vii72. http://dx.doi.org/10.1093/neuonc/noac209.275.
Abstract:
Abstract Despite advances in understanding the biology of diffuse midline gliomas (DMGs), clinical outcomes have not significantly improved. Therapy development is limited by: lack of preclinical data across multiple models and laboratories, limited knowledge about blood-brain barrier penetrance, and lack of multi-agent therapeutic approaches. We aimed to address these limitations by designing and implementing an innovative platform clinical trial (DMG-ACT). DMG-ACT is an open-label, multi-institutional, international trial of combination therapy for patients with DMG between 2 and 39 years of age. This study utilizes a novel Bayesian drug combination platform design with adaptive shrinkage (ComPAS). ComPAS allows for ongoing assessment of therapy efficacy with data borrowing across arms and the ability to eliminate ineffective drug combinations and add new promising combinations throughout the trial. The current treatment arms include ONC201 in combination with paxalisib. Patients enter one of three cohorts: newly-diagnosed (Cohort 1), post-radiation (Cohort 2), and relapsed/progressive (Cohort 3). Each cohort offers a target validation phase for patients who have not yet undergone biopsy to assess intratumoral pharmacokinetics/pharmacodynamics of pre-biopsy, single-agent dosing. Cohorts 1 and 3 offer radiation (Cohort 1) or re-irradiation (Cohort 3) with concomitant single-agent therapy followed by maintenance with combination therapy. The primary efficacy endpoints are median progression-free survival at 6 months (Cohorts 1 and 2) and overall survival at 7 months (Cohort 3). Exploratory endpoints include intratumoral drug concentrations; toxicity profile of combination therapy during radiation; toxicity profile and efficacy of combination therapy; CSF, ctDNA, stool, and flow cytometry biomarker analyses; and health related quality of life, cognitive, and patient/proxy-reported outcome measures. Additional therapy combinations that have shown additive or synergistic benefit in preclinical testing will be incorporated in future trial iterations and several are currently in development. The trial was launched in October 2021, with a total of 21 patients enrolled as of May 2022.
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Żyrek, Dawid, Andrzej Wajda, Paulina Czechowicz, Joanna Nowicka, Maciej Jaśkiewicz, Damian Neubauer, and Wojciech Kamysz. "The Antimicrobial Activity of Omiganan Alone and In Combination against Candida Isolated from Vulvovaginal Candidiasis and Bloodstream Infections." Antibiotics 10, no. 8 (August 19, 2021): 1001. http://dx.doi.org/10.3390/antibiotics10081001.
Abstract:
Fungi from the Candida genus are widespread commensals and, at the same time, are the leading cause of fungal infections worldwide. For instance, vulvovaginal candidiasis (VVC) affects approximately 75% of women at least once in their lifetime, remaining the second most common gynecological infection. On the contrary, hospital-acquired fungal bloodstream infections (BSIs), although less frequent, are characterized by a high mortality rate. Undoubtedly, the main reason for this situation are virulence factors that these yeast-like fungi can produce, and the ability to form a biofilm is one of the most important of them. Due to the low effectiveness of classic antimycotics against Candida biofilms, an intense search for new drugs capable of eradicating this structure is highly demanded. One of the most promising groups of compounds exhibiting such properties are antimicrobial peptides (AMPs). This study focuses on a comparison of the efficacy of Omiganan and fluconazole alone and in combination against Candida strains isolated from BSIs. The obtained results are consistent with our previous reports on the effectiveness of Omiganan against clinical strains isolated from VVC. This is also the first report on the combinatory application of Omiganan in the context of fungal BSI. The majority of combinations with fluconazole showed an additive effect, as well as a synergistic effect in the range of certain concentrations. Importantly, such effects are visible at concentrations much lower than for those compounds used individually. Potentially, this entails the possibility of limiting the adverse effects (e.g., toxicity) of Omiganan and fluconazole applied in vivo, thus improving the safety profile of this particular antifungal therapy.
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Franson, Andrea, Cassie Kline, Annette Molinaro, Yalan Zhang, Kelly Hitchner, Carl Koschmann, Javad Nazarian, and Sabine Mueller. "DIPG-09. Diffuse Midline Glioma-Adaptive Combinatory Trial (DMG-ACT): A biology-driven platform trial in pediatric and young adult patients with diffuse midline glioma." Neuro-Oncology 24, Supplement_1 (June 1, 2022): i19. http://dx.doi.org/10.1093/neuonc/noac079.066.
Abstract:
Abstract BACKGROUND: Despite advances in our understanding of the biology of diffuse midline gliomas (DMGs), little progress has been made in improving outcomes. Therapy development is limited by lack of preclinical data across multiple model systems and laboratories; limited knowledge about blood-brain barrier penetrance; and lack of multi-agent therapies. We aim to address these issues through DMG-ACT, where we translate robust preclinical data using ONC201 as the therapy backbone in a multi-arm, combination strategy within an innovative trial design. DESIGN: DMG-ACT is an open-label, multi-institutional trial of combination therapy for patients with DMG between 2 and 39 years of age. The trial utilizes a novel Bayesian drug combination platform design with adaptive shrinkage (ComPAS). ComPAS allows ongoing assessment of therapy efficacy with borrowing of data across different arms and the ability to eliminate ineffective drug combinations and add new promising combinations throughout the trial. ONC201 is the backbone therapy in each arm and given in combination with other agents that show additive or synergistic benefit in preclinical testing. Patients enter into one of three cohorts: newly diagnosed (Cohort 1), post-radiation (Cohort 2), and relapsed/progressive (Cohort 3). The cohorts offer a target validation option to assess intratumoral pharmacokinetics and pharmacodynamics of drug given prior to tumor biopsy. Cohort 1 and 3 offer radiation or re-irradiation with concomitant single agent therapy followed by maintenance combination therapy. The primary efficacy endpoints are median progression-free survival at 6 months (Cohort 1 and 2) and overall survival at 7 months (Cohort 3). Exploratory endpoints include intratumoral drug concentration, toxicity profile of combination therapy during radiation therapy, toxicity profile and efficacy of combination therapy, CSF and ctDNA analysis, and health related quality of life, cognitive, and patient/proxy-reported outcome measures. This trial was successfully launched in November 2021 with updates to be presented at the meeting.
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Jibira, Yakubu, Elizabeth Cudjoe, Frederick M. Tei-Maya, Benjamin Ayensu, and Linda E. Amoah. "The Effectiveness of Varying Combination Ratios of A. cordifolia and M. indica against Field and Laboratory Strains of P. falciparum In Vitro." Journal of Parasitology Research 2020 (November 18, 2020): 1–6. http://dx.doi.org/10.1155/2020/8836771.
Abstract:
Background. Drug resistance in malaria is a global problem, with reports of Plasmodium parasites resistant to the current first-line antimalarial drug, artemisinin, expanding from Southeast Asia to Africa. There is therefore an urgent need to identify new drug candidates that will be effective against the existing malaria parasites. Drug combination therapy presents a myriad of advantages over monotherapy including delayed onset of resistance, potentiation, and synergism. This present study explored the effectiveness of combinations of aqueous extracts of Alchornea cordifolia (A. cordifolia) and Mangifera indica (M. indica) at clearing both laboratory and field isolates of P. falciparum. Methods. Synchronized ring stage cultures of field (FA08) and laboratory strains (NF54 and CamWT_C580Y) of P. falciparum were subjected to combinations of different concentrations and ratios of aqueous extracts of A. cordifolia and M. indica. The growth inhibition of the individual plant extracts and their combinatory effects were studied in vitro using SYBR Green I drug assay. Results. The A. cordifolia extract exhibited 50% inhibitory concentration (IC50) of 2.71, 7.80, and 3.56 μg/mL against the NF54, CamWT_C580Y, and FA08 parasite strains, respectively. Mangifera indica exhibited IC50 of 18.11, 20.08, and 10.23 μg/mL against the NF54, CamWT_C580Y, and FA08 parasite strains, respectively. Additive, synergistic and antagonistic interactions were observed at different combinations of A. cordifolia and M. indica extracts. Conclusion. A combination product containing A. cordifolia and M. indica has the potential to serve as an effective antimalarial as majority of the tested combinations of aqueous extracts of A. cordifolia and M. indica extracts exhibited synergistic effects in vitro against the NF54, CamWT_C580Y, and FA08 P. falciparum strains.
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GHANI, NEIL, and PATRICIA JOHANN. "Monadic augment and generalised short cut fusion." Journal of Functional Programming 17, no. 6 (November 2007): 731–76. http://dx.doi.org/10.1017/s0956796807006314.
Abstract:
AbstractMonads are commonplace programming devices that are used to uniformly structure computations; in particular, they are often used to mimic the effects of impure features such as state, error handling, and I/O. This paper further develops the monadic programming paradigm by investigating the extent to which monadic computations can be optimised by using generalisations of short cut fusion to eliminate monadic structures whose sole purpose is to “glue together” monadic program components. Ghani, Uustalu, and Vene have recently shown that every inductive type has an associated build combinator and an associated short cut fusion law. They have also used the notion of a parameterised monad to describe those monads that give rise to inductive types, and have shown that the standard augment combinators and cata/augment fusion rules for algebraic data types can be generalised to fixed points of all parameterised monads. We revisit these augment combinators and generalised short cut fusion rules for such types but consider them from a functional programming perspective, rather than a categorical one. In addition to making the category-theoretic ideas of Ghani, Uustalu, and Vene more easily accessible to a wider audience of functional programmers, we demonstrate their practical applicability by developing nontrivial application programs and performing modest benchmarking on them. We also show how the cata/augment rules can serve as the basis for deriving additional generic fusion laws, thus opening the way for an algebra of fusion. Finally, we offer deep theoretical insights, arguing that the augment combinators are monadic in nature, and thus that the cata/build and cata/augment rules are arguably the best generally applicable fusion rules obtainable.
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GUSEVA, S. A., O. S. NOSCO, S. P. KUDRYASHOV, and V. N. CHEKHONIN. "STUDYING THE INITIAL MATERIAL OF SUNFLOWER VARIETIES ON THE TRAIT “BASKET`S AREA” UNDER THE CONDITIONS OF THE LOWER VOLGA REGION." Izvestiâ Timirâzevskoj selʹskohozâjstvennoj akademii, no. 3 (2023): 87–99. http://dx.doi.org/10.26897/0021-342x-2023-3-87-99.
Abstract:
The article presents the results of a three-year study of the combinatory ability of sunflower (HelianthusannuusL.) varieties on the trait “basket’s area” by the topcross method. The experiment was conducted in 2016–2018 in the fields of Russian Research, Design and Technology Institute of Sorghum and Corn. The experiment was repeated three times. The plant density was 4.5 plants per m2. The area of the plots was 7.7 m2 (two rows 5.5 m long; row spacing was 70 cm). The initial material for the study consisted of 43 samples of domestic and foreign selection. Three sterile lines (KSP232, KSP228, SE16b) were used as testers. The meteorological conditions in the years of the experiment were different. The hydrothermal coefficient (May-August) was 0.481 in 2016, 0.975 in 2017, and 0.521 in 2018. Sunflower varieties with high effects of common combining ability (CCA) were identified: 2016 for Veydelevsky, Melin, Krepysh, Fortimi; 2017 – Patriot, Fortimi; 2018 – Sholohovsky, Fortimi. Relatively stable high effects of CCA were found for the Fortimi genotype. The variety Lubo had the highest dispersion of specific combining ability (SCA) for three years of the experiment, and the Fortimi genotype had relatively high and stable indicators. These varieties can serve as a basis to create hybrids with high heterosis. Among the testers, a high effect of CCA was observed in YuV16b, and a high variance in KSP228. The effects of SCA of experimental hybrids varied from year to year. The cross KSP232/Lubo showed high values in years with higher humidity at the beginning of vegetation. The F1 hybrid KSP228/Lyubo demonstrated high effects of SCA during the years of contrasting moisture availability (2017 and 2018). The experimental hybrids KSP228/Krepysh, YuV16b/Svetlana, KSP232/Stepnoy 81, KSP228/Patriot, YuV16b/Fortimi, KSP228/YuVS3 and YuV16b/YuVS3 showed low but consistently positive values under different environmental conditions. According to the ratio of the mean squares of the deviations of the CCA/SCA, the additive effects of the genes predominated over the dominant ones.
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Smolewski, Piotr, Markus Duechler, Anna Linke, Barbara Cebula, Olga Grzybowska-Izydorczyk, Medhat Shehata, and Tadeusz Robak. "Anti-CD20 and Anti-CD52 Monoclonal Antibodies Enhance Cytotoxicity of Bortezomib Against Chronic Lymphocytic Leukemia Cells." Blood 106, no. 11 (November 16, 2005): 2972. http://dx.doi.org/10.1182/blood.v106.11.2972.2972.
Abstract:
Abstract Background: Inhibitor of proteasome, bortezomib (BOR), has high in vitro cytotoxic activity in chronic lymphocytic leukemia (CLL). However, first clinical trials showed low efficacy of BOR used alone in CLL patients. One way to increase the efficacy of BOR in vivo may be its combinatory use with other agents active in CLL, what can bring also benefit from lowering their doses. Indeed, there is some evidence, that efficacy of BOR may be increased by its combination with other agents active in CLL. Aim: To assess in vitro cytotoxic effects exerted by BOR in concomitant treatment with monoclonal antibodies anti-CD20 (rituximab, RIT) or anti-CD52 (alemtuzumab, ALT), agents with confirmed activity in CLL. Additionally, we investigated mechanisms responsible for observed interactions. Methods: The study was performed on cells isolated from 61 untreated CLL patients. Cell viability was evaluated by propydium iodide and MTT assays. Proapoptotic effects were measured by detection of active caspase-3, collapse of mitochondrial transmembrane potential (Mitotracker Red dye) and annexin V flow cytometry assays. Additionally, expression of several promoters of apoptosis (Bid, Bax, Bak, Bcl-w) and anti-apoptotic proteins (Bcl-2, Mcl-1, XIAP and FLIP) was measured. BOR concentration varied in different experiments between 1,25nM and 5nM. Based on preliminarily performed experiments RIT and ALT were used at final doses 10 μg/ml and 20 μg/ml, respectively. Cells were cultured for 24 hours in following sets of samples: 1/untreated control, 2/BOR alone, 3/RIT alone, 4/ALT alone, 5/BOR+RIT and 6/BOR+ALT. Moreover, all those sets of cultures were either done in RPMI 1640 medium supplemented with 5% human serum as a source of complement or in the presence of 20 μg/ml anti-human IgG crosslinking antibodies. Finally, in additional series of experiments cells were pretreated for 24 hours with RIT or ALT, and then BOR was added for the next 24 hours of incubation. Results: Combinations of BOR+RIT and BOR+ALT showed additive cytotoxicity, especially when 24-hour incubation with the antibodies crosslinked with anti-IgG preceded BOR administration (combination index 1.07 and 0.83, respectively). In these settings both combinations, BOR+RIT and BOR+ALT, significantly increased caspase-3 activation. Interestingly, addition of complement enhanced significantly only cell death mediated by ALT. Caspase-3 activation correlated with collapse of mitochondrial potential in samples treated with BOR+RIT (R= 0.71; p<0.02). Upregulation of Bax and downregulation of Bcl-2 or Mcl-1 were found after BOR+RIT treatment (p<0.005 and p<0.01, respectively). ALT+BOR triggered significant downregulation of Bcl-2 (p<0.005) and XIAP (p<0.01) proteins in CLL cells. For both combinations, significant increase in Bax/Bcl-2 ratio was shown (p<0.001). Conclusions: We found additive cytotoxic effects of both combinations, BOR+RIT and BOR+ALT. Upregulation of Bax and downregulation of Bcl-2 and Mcl-1 proteins were main mechanisms of additive interaction of BOR+RIT. The BOR+ALT combination significantly increased Bid and p53 expression and downregulated Bcl-2 and XIAP proteins. These data indicate feasibility of treatment combining proteasome inhibition with the use of RIT or CAM monoclonal antibodies in CLL.
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Feng, Shao-Wei, Pei-Chi Chang, Hsuan-Yu Chen, Dueng-Yuan Hueng, Yao-Feng Li, and Shih-Ming Huang. "Exploring the Mechanism of Adjuvant Treatment of Glioblastoma Using Temozolomide and Metformin." International Journal of Molecular Sciences 23, no. 15 (July 25, 2022): 8171. http://dx.doi.org/10.3390/ijms23158171.
Abstract:
Glioblastoma is the most frequent and lethal primary central nervous system tumor in adults, accounting for around 15% of intracranial neoplasms and 40–50% of all primary malignant brain tumors, with an annual incidence of 3–6 cases per 100,000 population. Despite maximum treatment, patients only have a median survival time of 15 months. Metformin is a biguanide drug utilized as the first-line medication in treating type 2 diabetes. Recently, researchers have noticed that metformin can contribute to antineoplastic activity. The objective of this study is to investigate the mechanism of metformin as a potential adjuvant treatment drug in glioblastoma. Glioblastoma cell lines U87MG, LNZ308, and LN229 were treated with metformin, and several cellular functions and metabolic states were evaluated. First, the proliferation capability was investigated using the MTS assay and BrdU assay, while cell apoptosis was evaluated using the annexin V assay. Next, a wound-healing assay and mesenchymal biomarkers (N-cadherin, vimentin, and Twist) were used to detect the cell migration ability and epithelial–mesenchymal transition (EMT) status of tumor cells. Gene set enrichment analysis (GSEA) was applied to the transcriptome of the metformin-treated glioblastoma cell line. Then, DCFH-DA and MitoSOX Red dyes were used to quantify reactive oxygen species (ROS) in the cytosol and mitochondria. JC-1 dye and Western blotting analysis were used to evaluate mitochondrial membrane potential and biogenesis. In addition, the combinatory effect of temozolomide (TMZ) with metformin treatment was assessed by combination index analysis. Metformin could decrease cell viability, proliferation, and migration, increase cell apoptosis, and disrupt EMT in all three glioblastoma cell lines. The GSEA study highlighted increased ROS and hypoxia in the metformin-treated glioblastoma cells. Metformin increased ROS production, impaired mitochondrial membrane potential, and reduced mitochondrial biogenesis. The combined treatment of metformin and TMZ had U87 as synergistic, LNZ308 as antagonistic, and LN229 as additive. Metformin alone or combined with TMZ could suppress mitochondrial transcription factor A, Twist, and O6-methylguanine-DNA methyltransferase (MGMT) proteins in TMZ-resistant LN229 cells. In conclusion, our study showed that metformin decreased metabolic activity, proliferation, migration, mitochondrial biogenesis, and mitochondrial membrane potential and increased apoptosis and ROS in some glioblastoma cells. The sensitivity of the TMZ-resistant glioblastoma cell line to metformin might be mediated via the suppression of mitochondrial biogenesis, EMT, and MGMT expression. Our work provides new insights into the choice of adjuvant agents in TMZ-resistant GBM therapy.
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MacLennan, Bruce. "A Formal Model of Universal Algorithmic Assembly and Molecular Computation." International Journal of Nanotechnology and Molecular Computation 2, no. 3 (July 2010): 55–68. http://dx.doi.org/10.4018/jnmc.2010070104.
Abstract:
In this paper, the author describes a systematic and general approach to nanostructure synthesis and control through autonomous molecular combinatory computing. Combinatory computing is based on simple network (graph) substitution operations, deriving from combinatory logic (Curry, Feys, & Craig, 1958), which are sufficient for any computation. When these operations are implemented by autonomous molecular processes, they provide a means for computing within supramolecular networks, which may be used to assemble these networks or control their behavior. Further, the Church-Rosser Theorem (Curry, Feys, & Craig, 1958) proves that substitutions may be performed in any order or in parallel without affecting the computational result; this is a very advantageous property for autonomous molecular computation. In addition to the theoretical foundations of molecular combinatory computing, the author discusses possible molecular implementations as well as accomplishments in the (simulated) synthesis of membranes, channels, nanotubes, and other nanostructures.
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Roversi, Fernanda Marconi, Fernando Vieira Pericole, Adriana da Silva Santos Duarte, Karla Priscila Ferro, Flávia Adolfo Corrocher, Bruna Palodetto, Ana Leda Longhini, Maurizio Botta, and Sara T. Olalla Saad. "Knockdown of HCK Reduces Cell Death and Erythroid Differentiation in Human CD34+ Hematopoietic Progenitor Cells." Blood 126, no. 23 (December 3, 2015): 2860. http://dx.doi.org/10.1182/blood.v126.23.2860.2860.
Abstract:
Abstract Myelodysplastic syndromes (MDS) are clonal disorders characterized by ineffective hematopoiesis and increased risk of transformation to acute myeloid leukemia (AML). The identification of genes and cellular pathways active in leukemia cells but not in normal hematopoietic stem/progenitor cells (HSC) may help to understand the key steps in the MDS and AML pathogenesis and lead to new approaches to further enhance the treatment of both diseases, considered incurable with non-transplantation therapy. Src kinase family (SFK) is a central mediator in multiple oncogenic signaling pathways and some SFK members (Hck, Lyn, Fgr, Fyn) had previously been described as overexpressed or activated in leukemic cells. However, to this moment, the role of hematopoietic cell kinase (HCK), the unique SFK member restricted expressed in hematopoietic cells, had not been characterized in MDS and AML pathogenesis as well as in HSC. In order to better understand the HCK importance in hematopoiesis, we used lentiviral shRNA vectors to knockdown the HCK expression in primary human CD34+ HSC. The HCK levels were reduced in approximately 70-80% (shHCK) compared to the control lentiviral shRNA (shControl-GFP). To promote erythroid differentiation, human CD34+ transduced cells were grown in methylcellulose for 7 days and in liquid media for another 6 days. During this experiment, shHCK cells showed decreased cell viability (fold change compared to shControl-GFP = 0.55, P<.0001, n=3) combined with an increase in CD71+ expression (fold change compared to shControl-GFP = 3, P<.01, n=3), indicating a delay in erythroid differentiation. As expected, shControl-GFP cells showed a decreased GATA1 expression during erythroid differentiation. Meanwhile, shHCK cells did not modulate GATA1 expression. Interestingly, without any stimulus, HCK knockdown in CD34+ cells significantly decreased apoptosis (AnnexinV+ cells) compared to shControl-GFP (fold change = 0.52, P<.01, n=4). Attempts have been made to overexpress HCK in CD34+ HSC, however more than 80% cells were apoptotic and further assays were not possible. Thus, in HSC, HCK participates of erythroid differentiation and apoptosis signaling. According to the HCK importance on HSC and that SFK inhibitors are undergoing early phase clinical testing, a specific inhibitory activity compound for HCK, named iHCK-37, had been developed by Dr Maurizzio Botta. We tested this compound on primary normal human CD34+ cells originated from healthy donors bone marrow samples and also from cord blood units. The iHCK-37 treatment did not change proliferation, survival and death of these normal CD34+ cells. Conversely, MDS and AML CD34+ cells treated with the same drug exhibited a dose-dependent growth inhibition. Likewise, following iHCK-37 treatment of MDS and AML total bone marrow mononuclear cells, the BFU-E and CFUs colony numbers were significantly decreased compared to untreated cells (vehicle). We also observed a potent in vitro antiproliferative activity of iHCK-37 against a panel of leukemia cell lines, with uM IC50 values in AML (5.0 - 5.8uM) and chronic myeloid leukemia (9.1 - 19.2uM). In addition, the combinatory in vitro treatment of iHCK-37 and 5-Azacitidine (Aza) also demonstrated additive effects relative to either drug alone. Interestingly, iHCK-37 or iHCK-37 plus Aza treatments of dysplastic and leukemia cells enhanced apoptosis and resulted in increased BAX and reduced BCL-XL protein levels. This result could be clinically relevant for MDS, as Aza is the only treatment available for higher-risk MDS, but with low response rates and frequent induced resistance and refractoriness over time. In summary, we herein have shown that HCK mRNA knockdown of normal CD34+ cells resulted in growth inhibition, decreased cell death and reduced erythroid differentiation, suggesting that HCK is essential for normal hematopoiesis. We presume that the deregulation of HCK pathway in leukemic cells might be crucial for MDS and AML pathogenesis. On the other hand, the inhibition of HCK protein activity with a specific inhibitor was able to restore the apoptotic pathways of leukemic cells, acting on cancer cells without alter any signaling of normal cells. Moreover, the specific inhibitor may have antineoplastic effect that can even be additive to current available drugs. Our study adds new insights to the role of HCK in MDS and AML as well as into potential new anticancer treatment strategies. Disclosures No relevant conflicts of interest to declare.
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LIN, LEI, XIAOLONG WANG, and DANIEL YEUNG. "COMBINING MULTIPLE CLASSIFIERS BASED ON A STATISTICAL METHOD FOR HANDWRITTEN CHINESE CHARACTER RECOGNITION." International Journal of Pattern Recognition and Artificial Intelligence 19, no. 08 (December 2005): 1027–40. http://dx.doi.org/10.1142/s0218001405004459.
Abstract:
Combining multiple classifiers is a new method that achieves a substantial gain in performance in many areas of pattern recognition. This paper demonstrates a novel method (based on statistics) of combining multiple classifiers to address the task of recognizing handwritten Chinese characters. Fusion strategies are discussed to provide a basis for the architecture of the combined classifiers. The weights of these fusion strategies are assigned via a genetic algorithm (GA). These fusion strategies are then tested using our online system for handwritten Chinese character recognition. In addition, different combinatory approaches are tested for comparison purposes. These include the conventional approach that is based on the Bayesian principle and the improved weighted combination, employing shared and distinct representations. Our experimental results demonstrate the effectiveness of these combinatory approaches.
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Kim, Daeyeoul, Kwangchul Lee, and Gyeong-Sig Seo. "A study of approximate normal distribution derived from combinatoric convolution sums of divisor functions." Filomat 30, no. 7 (2016): 1811–21. http://dx.doi.org/10.2298/fil1607811k.
Abstract:
In this paper, we consider the relations between Bernoulli polynomials, Legendre polynomials and combinatoric convolution sums of divisor functions. In addition, we give examples of approximate normal distribution derived from combinatoric convolution sums of divisor functions.
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Mella, Piero. "The unexpected cybernetics life of collectivities: the combinatory systems approach." Kybernetes 46, no. 7 (August 7, 2017): 1086–111. http://dx.doi.org/10.1108/k-02-2017-0058.
Abstract:
Purpose The purpose of this study is to show how simple “collectivities” of non-interconnected similar agents, which the author has termed “combinatory systems” and which produce analogous micro behaviors, reveal very interesting forms of micro and macro behaviors and effects attributable to a cybernetic mechanism the author shall call “micro-macro feedback”. On the one hand, the macro behavior of the system as a whole derives from the “combination” of the analogous micro behaviors or effects of the agents, and on the other hand, the macro behavior determines, conditions or directs the subsequent micro behavior, thereby creating observable effects and patterns in the collectivity. Design/methodology/approach This paper proposes a new combinatory system theory (CSysT) by constructing a formal model that explains a vast group of phenomena produced by the cybernetic behavior of the collectivity as if an internal organizer were regulating the micro dynamics of agents, producing self-organization, synchronization, path dependence and chaos. Findings In addition to illustrating the CSysT, this study also proposes a new and powerful tool to simulate combinatory systems: the “combinatory automaton”. This is composed of a lattice, each of whose cells contains a variable representing the state of an agent. The value of each cell at each time depends on a synthetic global variable whose values derive from some operations carried out on the values of the cells and that represents the synthetic state of the automaton. The micro-macro feedback connects the analytical values of the cells and the synthetic state of the automaton. Practical implications The CSysT suggests how to control combinatory systems through external actions aimed at making the macro and micro behaviors conform to the desired behaviors. The control is carried out through suitable strengthening or weakening actions, which operate by acting directly on the macro behavior – the author will define this as macro or external control – or by influencing the micro behaviors; in this case, the control will be called micro or internal control. The macro-level control is achieved through strengthening or weakening actions aimed at modifying some recombining factor. Instead, the micro-level control acts on the necessitating factors. Originality/value The CSysT is original and represents an effective tool for observing collective behavior. Combinatory systems are not easily recognizable; nevertheless, they are widely diffused and produce most of the social and economic collective phenomena involving the accumulation of objects, the spread of features or information, the pursuit of a limit and the achievement of general progress as the consequence of the individual pursuit of particular interests.
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Purwati, Andang Miatmoko, Nasronudin, Eryk Hendrianto, Deya Karsari, Aristika Dinaryanti, Nora Ertanti, et al. "An in vitro study of dual drug combinations of anti-viral agents, antibiotics, and/or hydroxychloroquine against the SARS-CoV-2 virus isolated from hospitalized patients in Surabaya, Indonesia." PLOS ONE 16, no. 6 (June 18, 2021): e0252302. http://dx.doi.org/10.1371/journal.pone.0252302.
Abstract:
A potent therapy for the infectious coronavirus disease COVID-19 is urgently required with, at the time of writing, research in this area still ongoing. This study aims to evaluate the in vitro anti-viral activities of combinations of certain commercially available drugs that have recently formed part of COVID-19 therapy. Dual combinatory drugs, namely; Lopinavir-Ritonavir (LOPIRITO)-Clarithromycin (CLA), LOPIRITO-Azithromycin (AZI), LOPIRITO-Doxycycline (DOXY), Hydroxychloroquine (HCQ)-AZI, HCQ-DOXY, Favipiravir (FAVI)-AZI, HCQ-FAVI, and HCQ-LOPIRITO, were prepared. These drugs were mixed at specific ratios and evaluated for their safe use based on the cytotoxicity concentration (CC50) values of human umbilical cord mesenchymal stem cells. The anti-viral efficacy of these combinations in relation to Vero cells infected with SARS-CoV-2 virus isolated from a patient in Universitas Airlangga hospital, Surabaya, Indonesia and evaluated for IC50 24, 48, and 72 hours after viral inoculation was subsequently determined. Observation of the viral load in qRT-PCR was undertaken, the results of which indicated the absence of high levels of cytotoxicity in any samples and that dual combinatory drugs produced lower cytotoxicity than single drugs. In addition, these combinations demonstrated considerable effectiveness in reducing the copy number of the virus at 48 and 72 hours, while even at 24 hours, post-drug incubation resulted in low IC50 values. Most combination drugs reduced pro-inflammatory markers, i.e. IL-6 and TNF-α, while increasing the anti-inflammatory response of IL-10. According to these results, the descending order of effective dual combinatory drugs is one of LOPIRITO-AZI>LOPIRITO-DOXY>HCQ-AZI>HCQ-FAVI>LOPIRITO-CLA>HCQ-DOX. It can be suggested that dual combinatory drugs, e.g. LOPIRITO-AZI, can potentially be used in the treatment of COVID-19 infectious diseases.
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Ha, Ji-Hui, and Young-Jin Kim. "Photodynamic and Cold Atmospheric Plasma Combination Therapy Using Polymeric Nanoparticles for the Synergistic Treatment of Cervical Cancer." International Journal of Molecular Sciences 22, no. 3 (January 25, 2021): 1172. http://dx.doi.org/10.3390/ijms22031172.
Abstract:
Integrating multi-modal therapies into one platform could show great promise in overcoming the drawbacks of conventional single-modal therapy and achieving improved therapeutic efficacy in cancer. In this study, we prepared pheophorbide a (Pheo a)/targeting ligand (epitope analog of oncoprotein E7, EAE7)-conjugated poly(γ-glutamic acid) (γ-PGA)/poly(lactide-co-glycolide)-block-poly(ethylene glycol) methyl ether (MPEG-PLGA)/hyaluronic acid (PPHE) polymeric nanoparticles via self-assembly and encapsulation method for the photodynamic therapy (PDT)/cold atmospheric plasma (CAP) combinatory treatment of human papillomavirus (HPV)-positive cervical cancer, thereby enhancing the therapeutic efficacy. The synthesized PPHE polymeric nanoparticles exhibited a quasi-spherical shape with an average diameter of 80.5 ± 17.6 nm in an aqueous solution. The results from the in vitro PDT efficacy assays demonstrated that PPHE has a superior PDT activity on CaSki cells due to the enhanced targeting ability. In addition, the PDT/CAP combinatory treatment more effectively inhibited the growth of cervical cancer cells by causing elevated intracellular reactive oxygen species generation and apoptotic cell death. Moreover, the three-dimensional cell culture model clearly confirmed the synergistic therapeutic efficacy of the PDT and the CAP combination therapy using PPHE on CaSki cells. Overall, these results indicate that the PDT/CAP combinatory treatment using PPHE is a highly effective new therapeutic modality for cervical cancer.
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Rastogi, Aayush, Rong Qiu, and Neelu Puri. "Abstract 3290: FTO mediates tumor growth and resistance to erlotinib in NSCLC." Cancer Research 84, no. 6_Supplement (March 22, 2024): 3290. http://dx.doi.org/10.1158/1538-7445.am2024-3290.
Abstract:
Abstract Lung cancer, among the most common cancer types, ranks first in cancer associated deaths. Nearly 85% of the lung cancer cases are non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR), an established marker for NSCLC, is frequently overexpressed on the cell surface. Amplifying mutations often render these receptors activated in a ligand independent manner, therefore, therapies such as erlotinib, an EGFR tyrosine kinase inhibitor (EGFR-TKI), target these activating mutations and inhibit tumor growth. Nevertheless, patients acquire resistance to EGFR TKI within 9-14 months of treatment. Recent studies show that fat mass and obesity- associated (FTO) gene, initially identified to increase the body mass index, plays a major role in cancer development and acquired therapy resistance in several cancer types. FTO demethylates m6A mRNA and modulates tumorigenesis, and drug resistance. In this study, we explored the functions of FTO in EGFR TKI resistance in NSCLC. To study the expression of FTO in erlotinib resistant cells, we used wildtype-EGFR NSCLC cell lines (H2170, H358) and mutant EGFR NSCLC cell lines (H1975, PC9) that were rendered resistant to erlotinib. Our RT-qPCR results demonstrated that FTO was upregulated by 1.7-3.0 fold in erlotinib resistant H2170, H358, PC9 and H1975 cells. FTO protein was upregulated by 1.3-1.6 fold as seen by western blotting, and by 1.7 to 2.6 fold in the nucleus of erlotinib resistant H1975, H2170 and PC9 cell lines by immunofluorescence. Furthermore, we investigated FTO inhibition with Dac51 (FTOi) on cell viability and cell migration properties. MTT cell viability assay showed a 9-17% decrease in cell viability when treated with a combination of Dac51 and erlotinib compared to Dac51 alone in erlotinib resistant H2170 and PC9 cells, respectively. The combinatory treatment showed an additive effect compared to the Dac51 and erlotinib treatments alone. Wound healing assay revealed an 18% open wound area after 48-hour treatment with both Dac51 and erlotinib compared to 0.1% after treatment with erlotinib alone in erlotinib resistant H2170 cells. To evaluate the effect of siRNA mediated FTO (siFTO) knockdown on cell viability and energy metabolism, MTT and luciferase assays were performed. MTT assay showed a 21-28% decrease in viability in erlotinib resistant H1975, H2170, PC9 cells, demonstrating increase in the erlotinib efficacy, as compared to the mock siRNA treatment. Luciferase assay showed an inverse relationship between the FTO and ATP, where the latter was upregulated by 1.3 to 3.4 folds in erlotinib resistant H1975, H2170 and PC9 cells, when treated with siFTO, suggesting its involvement in the energy requirements of the NSCLC cells. In conclusion, our study suggests FTO was upregulated in erlotinib resistant NSCLC cells on both the gene and protein levels. FTO could mediate resistance to EGFR TKI possibly through cell proliferation and migration and help with prognosis of NSCLC patients. Citation Format: Aayush Rastogi, Rong Qiu, Neelu Puri. FTO mediates tumor growth and resistance to erlotinib in NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3290.
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Longo, Brunetti, Gnoni, Licchetta, Delcuratolo, Memeo, Solimando, and Argentiero. "Emerging role of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma." Medicina 55, no. 10 (October 17, 2019): 698. http://dx.doi.org/10.3390/medicina55100698.
Abstract:
Hepatocellular carcinoma is the most common primary liver cancer and the fourth leading cause of cancer death worldwide. A total of 70–80% of patients are diagnosed at an advanced stage with a dismal prognosis. Sorafenib had been the standardcare for almost a decade until 2018 when the Food and Drug Administration approved an alternative first-line agent namely lenvatinib. Cabozantinib, regorafenib, and ramucirumab also displayed promising results in second line settings. FOLFOX4, however, results inan alternative first-line treatment for the Chineseclinical oncology guidelines. Moreover,nivolumab and pembrolizumab,two therapeutics against the Programmed death (PD)-ligand 1 (PD-L1)/PD1 axis have been recently approvedfor subsequent-line therapy. However, similar to other solid tumors, the response rate of single agent targeting PD-L1/PD1 axis is low. Therefore, a lot of combinatory approaches are under investigation, including the combination of different immune checkpoint inhibitors (ICIs), the addition of ICIs after resection or during loco-regional therapy, ICIs in addition to kinase inhibitors, anti-angiogenic therapeutics, and others. This review focuses on the use of ICIs for the hepatocellular carcinoma with a careful assessmentof new ICIs-based combinatory approaches.
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Sáfrán, György, Péter Petrik, Noémi Szász, Dániel Olasz, Nguyen Quang Chinh, and Miklós Serényi. "Review on High-Throughput Micro-Combinatorial Characterization of Binary and Ternary Layers towards Databases." Materials 16, no. 8 (April 10, 2023): 3005. http://dx.doi.org/10.3390/ma16083005.
Abstract:
The novel, single-sample concept combinatorial method, the so-called micro-combinatory technique, has been shown to be suitable for the high-throughput and complex characterization of multicomponent thin films over an entire composition range. This review focuses on recent results regarding the characteristics of different binary and ternary films prepared by direct current (DC) and radiofrequency (RF) sputtering using the micro-combinatorial technique. In addition to the 3 mm diameter TEM grid used for microstructural analysis, by scaling up the substrate size to 10 × 25 mm, this novel approach has allowed for a comprehensive study of the properties of the materials as a function of their composition, which has been determined via transmission electron microscopy (TEM), scanning electron microscopy (SEM), Rutherford backscattering spectrometry (RBS), X-ray diffraction analysis (XRD), atomic force microscopy (AFM), spectroscopic ellipsometry, and nanoindentation studies. Thanks to the micro-combinatory technique, the characterization of multicomponent layers can be studied in greater detail and efficiency than before, which is beneficial for both research and practical applications. In addition to new scientific advances, we will briefly explore the potential for innovation with respect to this new high-throughput concept, including the creation of two- and three-component thin film databases.
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Castañón, Guillermo, Dan Jeffers, and Héctor Hidalgo. "Aptitud combinatoria de líneas de maíz tropical con diferente capacidad para tolerar el achaparramiento." Agronomía Mesoamericana 11, no. 1 (January 1, 2006): 77. http://dx.doi.org/10.15517/am.v11i1.17354.
Abstract:
This research was carried out to evaluated seven parents and theirs F1’s progenies. The objective was to study the response of the hybrids and parents to infection with the bushy stunt, trasmited for Dalbulus maydis. The results showed that additive effects (GCA) were more important that no-additives effects (SCA). It was found that to grain yield (GY) the best cros ses, were between one resistant ( R) line x susceptible (S) line. The lowest yield grain crosses were observed between R X R or S x S parents or lines. The lines three and five, were the material values of GCA to yield grain. The estimated values for SCA had important role in the hybrid genetic structure. The line two, was the parental that in hybrid combination presented highest SCA values. Lines one and seven, were the lowest materials to GCA.
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THIEMANN, PETER. "A typed representation for HTML and XML documents in Haskell." Journal of Functional Programming 12, no. 4-5 (July 2002): 435–68. http://dx.doi.org/10.1017/s0956796802004392.
Abstract:
We define a family of embedded domain specific languages for generating HTML and XML documents. Each language is implemented as a combinator library in Haskell. The generated HTML/XML documents are guaranteed to be well-formed. In addition, each library can guarantee that the generated documents are valid XML documents to a certain extent (for HTML only a weaker guarantee is possible). On top of the libraries, Haskell serves as a meta language to define parameterized documents, to map structured documents to HTML/XML, to define conditional content, or to define entire web sites. The combinator libraries support element-transforming style, a programming style that allows programs to have a visual appearance similar to HTML/XML documents, without modifying the syntax of Haskell.
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Youf, Raphaëlle, Max Müller, Ali Balasini, Franck Thétiot, Mareike Müller, Alizé Hascoët, Ulrich Jonas, et al. "Antimicrobial Photodynamic Therapy: Latest Developments with a Focus on Combinatory Strategies." Pharmaceutics 13, no. 12 (November 24, 2021): 1995. http://dx.doi.org/10.3390/pharmaceutics13121995.
Abstract:
Antimicrobial photodynamic therapy (aPDT) has become a fundamental tool in modern therapeutics, notably due to the expanding versatility of photosensitizers (PSs) and the numerous possibilities to combine aPDT with other antimicrobial treatments to combat localized infections. After revisiting the basic principles of aPDT, this review first highlights the current state of the art of curative or preventive aPDT applications with relevant clinical trials. In addition, the most recent developments in photochemistry and photophysics as well as advanced carrier systems in the context of aPDT are provided, with a focus on the latest generations of efficient and versatile PSs and the progress towards hybrid-multicomponent systems. In particular, deeper insight into combinatory aPDT approaches is afforded, involving non-radiative or other light-based modalities. Selected aPDT perspectives are outlined, pointing out new strategies to target and treat microorganisms. Finally, the review works out the evolution of the conceptually simple PDT methodology towards a much more sophisticated, integrated, and innovative technology as an important element of potent antimicrobial strategies.
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Ding, Longjiang, Sili Han, Kun Wang, Sainan Zheng, Wenyue Zheng, Xiu Peng, Yumei Niu, Wei Li, and Linglin Zhang. "Remineralization of enamel caries by an amelogenin-derived peptide and fluoride in vitro." Regenerative Biomaterials 7, no. 3 (March 3, 2020): 283–92. http://dx.doi.org/10.1093/rb/rbaa003.
Abstract:
Abstract Dental caries is one of the most common oral diseases in the world. This study was tantamount to investigate the combinatory effects of an amelogenin-derived peptide (called QP5) and fluoride on the remineralization of artificial enamel caries. The peptide QP5 was synthesized and characterized, and the binding capability of the peptide on hydroxyapatite (HA) and demineralized tooth enamel surface was analysed. Then, the mineralization function of the peptide and fluoride was studied through the spontaneous mineralization testing and remineralization on enamel caries in vitro. First, the novel peptide QP5 could bind on the hydroxyapatite and demineralized tooth enamel surfaces. Second, QP5 can transitorily stabilize the formation of amorphous calcium phosphate and direct the transformation into hydroxyapatite crystals alone and in combination with fluoride. In addition, compared to blocks treated by peptide QP5 alone or fluoride, the sample blocks showed significantly higher surface microhardness, lower mineral loss and shallower lesion depth after treatment with a combination of QP5 and fluoride at high or low concentrations. The peptide QP5 could control the crystallization of hydroxyapatite, and combinatory application of peptide QP5 and fluoride had a potential synergistic effect on the remineralization of enamel caries.
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Lovska, A., O. Fomin, D. Skurikhin, and V. Bondarenko. "COMBINATORY APPROACH TO FAILURE FINDING IN PASSENGER CAR ELECTRICAL EQUIPMENT SYSTEM." Collection of scientific works of the State University of Infrastructure and Technologies series "Transport Systems and Technologies" 1, no. 38 (December 24, 2021): 185–93. http://dx.doi.org/10.32703/2617-9040-2021-38-182-17.
Abstract:
Maintaining a high level of maintenance of electrical equipment in passenger cars requires research in the field of improving methods and means of technical diagnostics. Electronic devices for automatic control and protection, which are located in the switchboard of the car, are one of the most critical elements in the electrical equipment system, ensuring its reliable, efficient and safe operation. If the automatic adjustment and protection devices are out of regulation during operation, the voltage and current in the electrical equipment network may exceed the permissible level, which leads to the failure of electricity consumers, a battery and a generator. In addition, the semiconductor devices themselves are very sensitive to short-term overloads, in which, even with minor overloads, a breakdown or breakage of the conductive layer occurs. Modern trends in the development of passenger car fleet indicate a sharp increase in the complexity of the element base of cars. This mainly concerns the electrical systems of cars, where all the functions of control, monitoring and diagnostics are performed by electronics. Maintaining a high level of service for such systems requires research in the field of improving methods and means of technical diagnostics. For these purposes, the authors have developed a method for constructing optimal control and diagnostic tests, which is based on a combinatorial approach. The method is easily implemented on a computer.
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Douloudi, Marilina, Eleni Nikoli, Theodora Katsika, Michalis Vardavoulias, and Michael Arkas. "Dendritic Polymers as Promising Additives for the Manufacturing of Hybrid Organoceramic Nanocomposites with Ameliorated Properties Suitable for an Extensive Diversity of Applications." Nanomaterials 11, no. 1 (December 24, 2020): 19. http://dx.doi.org/10.3390/nano11010019.
Abstract:
As the field of nanoscience is rapidly evolving, interest in novel, upgraded nanomaterials with combinatory features is also inevitably increasing. Hybrid composites, offer simple, budget-conscious and environmental-friendly solutions that can cater multiple needs at the same time and be applicable in many nanotechnology-related and interdisciplinary studies. The physicochemical idiocrasies of dendritic polymers have inspired their implementation as sorbents, active ingredient carriers and templates for complex composites. Ceramics are distinguished for their mechanical superiority and absorption potential that render them ideal substrates for separation and catalysis technologies. The integration of dendritic compounds to these inorganic hosts can be achieved through chemical attachment of the organic moiety onto functionalized surfaces, impregnation and absorption inside the pores, conventional sol-gel reactions or via biomimetic mediation of dendritic matrices, inducing the formation of usually spherical hybrid nanoparticles. Alternatively, dendritic polymers can propagate from ceramic scaffolds. All these variants are covered in detail. Optimization techniques as well as established and prospected applications are also presented.
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Schreiber, André, Benjamin Ambrosy, Oliver Planz, Sebastian Schloer, Ursula Rescher, and Stephan Ludwig. "The MEK1/2 Inhibitor ATR-002 (Zapnometinib) Synergistically Potentiates the Antiviral Effect of Direct-Acting Anti-SARS-CoV-2 Drugs." Pharmaceutics 14, no. 9 (August 25, 2022): 1776. http://dx.doi.org/10.3390/pharmaceutics14091776.
Abstract:
The coronavirus disease 2019 (COVID-19) represents a global public health burden. In addition to vaccination, safe and efficient antiviral treatment strategies to restrict the viral spread within the patient are urgently needed. An alternative approach to a single-drug therapy is the combinatory use of virus- and host-targeted antivirals, leading to a synergistic boost of the drugs’ impact. In this study, we investigated the property of the MEK1/2 inhibitor ATR-002’s (zapnometinib) ability to potentiate the effect of direct-acting antivirals (DAA) against SARS-CoV-2 on viral replication. Treatment combinations of ATR-002 with nucleoside inhibitors Molnupiravir and Remdesivir or 3C-like protease inhibitors Nirmatrelvir and Ritonavir, the ingredients of the drug Paxlovid, were examined in Calu-3 cells to evaluate the advantage of their combinatory use against a SARS-CoV-2 infection. Synergistic effects could be observed for all tested combinations of ATR-002 with DAAs, as calculated by four different reference models in a concentration range that was very well-tolerated by the cells. Our results show that ATR-002 has the potential to act synergistically in combination with direct-acting antivirals, allowing for a reduction in the effective concentrations of the individual drugs and reducing side effects.
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Cha, Dong H., Dominick Skabeikis, Bong-Soo Kim, Jana C. Lee, and Man-yeon Choi. "Insecticidal Properties of Erythritol on Four Tropical Tephritid Fruit Flies, Zeugodacus cucurbitae, Ceratitis capitata, Bactrocera dorsalis, and B. latifrons (Diptera: Tephritidae)." Insects 14, no. 5 (May 16, 2023): 472. http://dx.doi.org/10.3390/insects14050472.
Abstract:
Tephritid fruit flies are among the most destructive agricultural pests of fruits and vegetables worldwide and can impose trade barriers against the movement of fresh tropical commodities. Primary pre-harvest control methods for these flies rely on the spraying of conventional chemical insecticides or bait sprays. However, resistance to these control methods has been reported in fruit flies. Erythritol is a non-nutritive sugar alternative for human consumption, which has been tested and confirmed for its insecticidal properties against various insect pest species. In this study, using laboratory bioassays, we evaluated the insecticidal effect of erythritol alone or various erythritol formulations containing sucrose and/or protein on four tropical fruit fly species established in Hawaii (e.g., melon fly, Mediterranean fruit fly, oriental fruit fly, and Malaysian fruit fly). In addition, the effects of other non-nutritive hexose and pentose sugar alcohols, such as sorbitol, mannitol, and xylitol, were tested. Among the different standalone and combinatory treatments tested, 1M erythritol and a combinatory formulation of 2M erythritol + 0.5M sucrose appeared to be the most detrimental to the survival of all four species of tested flies, suggesting the potential of using erythritol as a non-toxic management tool for the control of tropical tephritid fruit flies.
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Cantini, Andrea. "Extending the first-order theory of combinators with self-referential truth." Journal of Symbolic Logic 58, no. 2 (June 1993): 477–513. http://dx.doi.org/10.2307/2275216.
Abstract:
AbstractThe aim of this paper is to introduce a formal system STW of self-referential truth, which extends the classical first-order theory of pure combinators with a truth predicate and certain approximation axioms. STW naturally embodies the mechanisms of generalpredicate application/abstractionona par withfunction application/abstraction; in addition, it allows non-trivial constructions, inspired by generalized recursion theory. As a consequence, STW provides a smooth inner model for Myhill's systems with levels of implication.
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Li, Rui, Wingman Chan, Waikin Mat, Yiucheong Ho, Rigil K. Yeung, Shuiying Tsang, and Hong Xue. "Antiaging and Anxiolytic Effects of Combinatory Formulas Based on Four Medicinal Herbs." Evidence-Based Complementary and Alternative Medicine 2017 (2017): 1–15. http://dx.doi.org/10.1155/2017/4624069.
Abstract:
The objective of the present study was to search for medicinal-herb combinations based on RadixBupleurum chinenseDC (“B”), RhizomaCorydalis yanhusuoWT Wang (“Y”), CaulisPolygonum multiflorumThunb (“P”), and FlosAlbizia julibrissinDurazz (“A”) for antiaging, anxiolytic, and sedative effects. Application of theD-galactose induced accelerated-aging model employing male ICR mice showed that oral administration of some combinations of B, Y, P, and A significantly improved spatial memory in Y-maze test and reduced brain levels of tumor necrosis factor-αand interleukin-6 based on immunoassays and oxidative stress marker malondialdehyde, based on the thiobarbituric acid test, and the loss of whiskers, indicating antiaging and antineurodegeneration effects. In addition, some of the combinatory formulas induced anxiolysis measured using the elevated plus-maze test and/or sedative effects measured using the hole-board test. Over the range of dosages examined, all possible combinations of the four herbs were devoid of any significant side effects in the form of altered locomotor activity, decreased muscle coordination, or anterograde amnesia assessed using the photobeam and rotarod and step-through passive avoidance methods, respectively. The results suggest that various combinations of the B, Y, P, and A herbs could be useful as nonsedative, antiaging and/or antineurodegenerative agents, or anxiolytic agents.
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Jia, Peilin, Guangsheng Pei, and Zhongming Zhao. "CNet: a multi-omics approach to detecting clinically associated, combinatory genomic signatures." Bioinformatics 35, no. 24 (May 28, 2019): 5207–15. http://dx.doi.org/10.1093/bioinformatics/btz441.
Abstract:
Abstract Motivation Genome-wide multi-omics profiling of complex diseases provides valuable resources and opportunities to discover associations between various measures of genes and diseases. Currently, a pressing challenge is how to effectively detect functional genes associated with or causing phenotypic outcomes. We developed CNet to identify groups of genomic signatures whose combinatory effect is significantly associated with clinical and phenotypical outcomes. Results CNet builds on a generalized sequential feedforward method, augmented by a down-sampling bootstrap strategy to reduce random hitchhiking signatures. It further applies a dynamic trimming procedure to remove relatively less informative signatures at every step. CNet can manage heterogeneous genomic signature profiles simultaneously and select the best signature to represent a specific gene. To deal with various forms of clinical and phenotypical measurements, we introduced four models to deal with continuous, categorical and censored data. We tested CNet using drug-response data, multidimensional cancer genomics data and genome-wide association study data for multiple traits. Our results demonstrated that in various scenarios, CNet could effectively identify signatures that are associated with the outcomes. In addition, we applied CNet to identify likely disease-causing chains involving somatic mutations, pathway activities and patient outcomes. With appropriate setting, CNet can be applied in many biological conditions. Availability and implementation CNet can be downloaded at https://github.com/bsml320/CNet. Supplementary information Supplementary data are available at Bioinformatics online.
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Ortiz, José Richard, and Pedro Comalat Rodes. "Habilidad combinatoria de 8 líneas élites dominicanas de maíz (Zea Mays L.)." Agronomía Mesoamericana 4 (June 21, 2016): 65. http://dx.doi.org/10.15517/am.v4i0.25169.
Abstract:
Twenty eight inter-crosses from a diallel set of 8 Dominican inbred lines of maize were evaluated in 1990. The specific objectives were to determine general(gca) and specific (SCA) combining ability and to predict the best two and three-way hybrids. The inheritance of yield was determined by diaIlel analysis. General and specific (sca) combining ability and specific mean squares were statistically significant in yield, being the additive genetic variation much larger than the non additive variation. The parental T66 and NO3 showed the highest gca values and DK12xT66 (9.02 t/ha),NO2xNO3 (8.57t/ha) and DK12xT66 (8.36 t/ha) the best sca values. The results partially agree with previous studies. The best three and two way hybrids predictions were (NO3xT66)x NO3 and(NO2xT66) (NO3xDK14) with grain yield of 8.80 and 8.30 t/ha.
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Sui, Hongshu, Ningxia Ma, Ying Wang, Hui Li, Xiaoming Liu, Yanping Su, and Jiali Yang. "Anti-PD-1/PD-L1 Therapy for Non-Small-Cell Lung Cancer: Toward Personalized Medicine and Combination Strategies." Journal of Immunology Research 2018 (August 8, 2018): 1–17. http://dx.doi.org/10.1155/2018/6984948.
Abstract:
Lung cancer remains a leading cause of cancer-related mortality worldwide with the poor prognosis. Encouragingly, immune checkpoint blockade targeting programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) has dramatically changed the landscape for treatments in patients with non-small-cell lung cancer (NSCLC). However, only a small proportion of NSCLC patients responded to monotherapy of anti-PD-1/PDL1 agents; together, the development of resistance to anti-PD-1/PD-L1 therapy that leads to failure of anti-PD-1/PD-L1 therapy has significantly limited a broad applicability of the findings in clinical practices. Nowadays, several companion diagnostic assays for PDL1 expression have been introduced for identifying patients who may benefit the immunotherapy. In addition, results from clinical trials explored combinatory therapeutic strategies with conventional and/or targeted therapy reported a higher efficacy with an acceptable safety profile in NSCLC treatments, as compared to the monotherapy of these agents alone. In this review article, we summarized several anti-PD-1/PD-L1 agents licensed for NSCLC treatment, with a focus on predictive biomarkers and companion diagnostic assays for identification of NSCLC patients for immunotherapy anti-PD-1/PDL1 antibodies. Of a great interest, potentials of the combinatory therapy of anti-PD-1/PDL1 therapy with a conventional or targeted therapy, or other immunotherapy such as CAR-T cell therapy were emphasized in the article.