Miracle-dz/UniFAR-FTUs huggingface dataset:
Deletion of 30 Murine Cytochrome P450 Genes Results In Viable Mice With Compromised Drug Metabolism s

In humans, 75% of all drugs are metabolized by the cytochrome P450-dependent monooxygenase system. Enzymes encoded by the CYP2C , CYP2D , and CYP3A gene clusters account for ∼ 80% of this activity. There are profound species differences in the multiplicity of cytochrome P450 enzymes, and the use of mouse models to predict pathways of drug metabolism is further complicated by overlapping substrate specificity between enzymes from different gene families. To establish the role of the hepatic and extrahepatic P450 system in drug and foreign chemical disposition, drug efficacy, and toxicity, we created a unique mouse model in which 30 cytochrome P450 genes from the Cyp2c , Cyp2d , and Cyp3a gene clusters have been deleted. Remarkably, despite a wide range of putative important endogenous functions, Cyp2c/2d/3a KO mice were viable and fertile, demonstrating that these genes have evolved primarily as detoxification enzymes. Although there was no overt phenotype, detailed examination showed Cyp2c/2d/3a KO mice had a smaller body size (15%) and larger livers (20%). Changes in hepatic morphology and a decreased blood glucose (30%) were also noted. A five-drug cocktail of cytochrome P450 isozyme probe substrates were used to evaluate changes in drug pharmacokinetics; marked changes were observed in either the pharmacokinetics or metabolites formed from Cyp2c, Cyp2d, and Cyp3a substrates, whereas the metabolism of the Cyp1a substrate caffeine was unchanged. Thus, Cyp2c/2d/3a KO mice provide a powerful model to study the in vivo role of the P450 system in drug metabolism and efficacy, as well as in chemical toxicity.
Effects of Calcium and Nonphytate Phosphorus Concentrations on Phytase Efﬁcacy in Broiler Chicks

Phytase supplementation over a range of different levels of dietary Ca and nonphytate phosphorus (NPP) was investigated by comparing surface response curves from regression equations generated with (experi-ment 1) and without (experiment 2) phytase using various performance and bone quality parameters. Cobb × Cobb broiler chicks were raised from 0 to 16 d in 2 experiments using corn-soybean meal based diets. Experiment 1 used a 4 × 4 factorial arrangement with diets formulated to contain combinations of 4 levels of Ca: 0.38, 0.58, 0.78, and 0.98% and 4 levels of NPP: 0.2, 0.3, 0.4, and 0.5%. Experiment 2 used a composite rotatable design in which rations were formulated to contain dietary Ca levels of 0.38, 0.47, 0.68, 0.89, and 0.98% and NPP levels of 0.20, 0.24, 0.35, 0.46, and 0.50%. An extra point was included in the design to contain the lowest Ca and lowest NPP levels (0.38% Ca and 0.20% NPP). All combinations of Ca
Biological Activity of the G-quadruplex Ligand RHPS4 is Associated with Telomere Capping Alteration

deoxynucleotide transferase [TdT]-mediated dUTP nick-end TRAP, telomeric repeat amplification ITAS, internal TRAP assay standard; TRF, terminal restriction fragment; PI, propidium iodide; SA- β -gal, senescence- β -galactosidase; X-Gal, 5-bromo-4-chloro-3-indolyl- β -D-galactoside; ALT, alternative lenghtening of telomeres. Abstract The goal of this study was two-fold: i) to evaluate the biological effect of the novel methosulfate (RHPS4) on human melanoma lines, possessing long telomeres, and ii) to elucidate the relationship between G-quadruplex-based telomerase inhibitor-induced cellular effects and telomere length/dysfunction. The cellular pharmacological effects of RHPS4 have been evaluated by treating melanoma lines with increasing concentrations of RHPS4. A dose-dependent inhibition of cell proliferation was observed in all the lines during short-term treatment. Flow cytometric analysis demonstrated that RHPS4 induced a dose-dependent accumulation of cells in the S-G 2 /M phase of cell cycle. The RHPS4-induced cell cycle alteration was irreversible even at low doses, and the cells died from apoptosis. At high RHPS4 concentration, apoptosis was accompanied by the induction of a senescence phenotype: large cell size, vacuolated cytoplasm and β -galactosidase activity. The short-term biological activity of RHPS4 was not due to telomere shortening, but it was associated with telomere dysfunction, in terms of presence of telomeric fusions, polynucleated cells, and typical images of telophase bridge. In conclusion, our results demonstrate that the G-quadruplex ligand RHPS4 can function in a telomere length-independent manner through its ability to cause telomere-capping alteration. still remain in the S-G 2 /M compartment. These results suggest that RHPS4 induces a delay in progression through the cell cycle. Moreover, at day 8 the cells treated with RHPS4 show
DPPH Radical Scavenging Assay, Biological Activities, Nutritional Composition and Quality Parameters of Momordica charantia Seeds Grown in District Charsadda, KPK, Pakistan

The nutritional composition, physicochemical characteristics, antimicrobial activity and DPPH free radical scavenging activity of the oil extracted and proximate and elemental composition of seed cake of the local variety of Momordica charantia were examined as per AOAC or elsewhere mentioned procedures. Physicochemical properties of the oil exhibited colour (1.71 R/U, 1.19 Y/U) being reddish brown, the higher iodine value (105.5), saponification value (190.7), low acid value (1.3) and the higher proportion of unsaturated fatty acids (especially the omega-3 fatty acid) as compared to saturated fatty acids of the oil are an indication of its edibility and industrial utility. The oil also showed good inhibitory action against the selected fungal and bacterial strains as well as DPPH free radical scavenging activity. Results of the proximate composition of the seed cake showed it to be good source of total proteins (18. 17%), crude fibre 10.37%, percent oil (38.1%) and elements such as calcium (374.9 mg/100 g), copper (3.01 mg/100 g), iron (39.57 mg/100 g) and zinc (12.04 mg/100 g). It can be concluded from the study that oil and seed cake of the local variety of bitter gourd seed (BGS) oil possesses a good nutritional, antioxidant and antimicrobial
Stocks and cryptocurrencies: Antifragile or robust? A novel antifragility measure of the stock and cryptocurrency markets

In contrast with robust systems that resist noise or fragile systems that break with noise, antifragility is defined as a property of complex systems that benefit from noise or disorder. Here we define and test a simple measure of antifragility for complex dynamical systems. In this work we use our antifragility measure to analyze real data from return prices in the stock and cryptocurrency markets. Our definition of antifragility is the product of the return price and a perturbation. We explore different types of perturbations that typically arise from within the system. Our results suggest that for both the stock market and the cryptocurrency market, the tendency among the ‘top performers’ is to be robust rather than antifragile. It would be important to explore other possible definitions of antifragility to understand its role in financial markets and in complex dynamical systems in general.
FOOD AND FEEDING HABITS OF Oreochromis niloticus IN LAKE GBEDIKERE, BASSA, KOGI STATE.

The food and feeding adaptations of Oreochromis niloticus in Gbedikere Lake, Bassa, Kogi State Nigeria were studied. A total of 146 fish samples were collected between July and December 2008; the stomach contents were analyzed using numerical and frequency of occurrence methods. The result shows that the fish is an omnivore, feeding mainly on plant parts (34.02%), detritus (11.35%), algae (22.68%), insect part (6.16%), crustaceans (7.56%), sand grains (8.51%) unidentified particles (9.71%). The length-weight relationship implied that adult female fish had the highest standard length (19.50cm) followed by the adult male (15.30cm) and the juveniles (5.90cm). The diversity of food substances found in the stomach and their occurrences in the juveniles and adults varied with the water bodies and season.
A parallel analysis of proepicardial cells in transgenic mice with dominant negative inhibition of connexin43 targeted only to neural crest cells

Gap junctions are intercellular junctions containing membrane channels that mediate the movement of ions, metabolites and secondary messengers below 1.2 kDa. They are formed by a protein family of at least 16 members termed connexins (Bruzzone et al., 1996; Condorelli et al., 1998; Itahana et al., 1998; Manthey et al., 1999). Given these properties, gap junctions are thought to have a role in maintaining tissue homeostasis, and regulating cell proliferation and differentiation, and embryonic development (Goodenough et al., 1996; Kumar and Gilula, 1996; Lo, 1999; Newman, 1985). Mutations in connexin genes have been associated with a variety of human diseases, including heart anomalies, cataract, deafness, skin disorders and X-linked Charcot-Marie-Tooth disease (Britz-Cunningham et al., 1995; Kelsell et al., 1997; Richard et al., 1998; Shiels et al., 1998; Xia et al., 1998). The essential role of gap junctions also has been revealed by the analysis of connexin knockout mice (reviewed by White and Paul, 1999; Lo, 1999). Furthermore, connexin knock-in mouse models demonstrated that the phenotypes resulting from eliminating one connexin gene cannot be fully corrected by the replacement of another connexin gene (Plum et al., 2000). This suggests that each connexin isotype may have unique function that is cellor tissue type-specific. The connexin gene known as connexin43 or α1 connexin (referred to as Cx43α 1; Gja1 – Mouse Genome Informatics) plays a crucial role in cardiac development, as Cx43 α1 knockout mice die shortly after birth due to pulmonary outflow obstruction (Reaume et al., 1995). Typically, the Cx43 α1 knockout mouse heart exhibits two prominent pouches at the base of the pulmonary outflow tract, a region known as the infundibulum of the heart. Studies using transgenic mouse models to manipulate Cx43 α1 function indicate that the 2031 Development 129, 2031-2042 (2002) Printed in Great Britain © The Company of Biologists Limited 2002 DEV14518
CIA_A_316064 1563..1571

1New York University Grossman School of Medicine, Department of Population Health, New York, NY, 10016, USA; 2New York University Grossman School of Medicine, Department of Psychiatry, New York, NY, 10016, USA; 3Weill Cornell Medicine, Department of Radiology, New York, NY, 10021, USA Objective: Compared to European Americans, research indicates that African Americans have higher white matter hyperintensity (WMH) load; however, the clinical and biological bases underlying this higher burden are poorly understood. We hypothesize that obesity may explain differences in WMH between African and European Americans. Methods: Participants enrolled in longitudinal brain aging studies (n=292; 61% Female; 92% European American; mean age=69.6±7.7) completed evaluations including medical exams, neuroimaging, and sociodemographic surveys. Overweight/obese status defined as body mass index ≥30 kg/m, and WMH load, captured by FLAIR images, as sum of deep and periventricular volumes, scored using the Fazekas scale (0–6), WMH≥4 considered high. Results: Logistic regression analyses, adjusted for age, sex, hypertension, and smoking history, indicated that age and interaction between race and obesity were significant predictors of WMH, demonstrating that obesity significantly moderated the relationship between race and WMH. Age independently increased the odds of high WMH by 16% (OR=1.16, 95% CI=1.09–1.23, p<0.001). Stratified analysis indicates that older European Americans had increased WMH (OR=1.17, 95% CI=1.09–1.23, p<0.001), while obese African Americans had increased WMH (OR=27.65, 95% CI=1.47–519.13, p<0.05). In a case controlled subgroup matched by age, sex, and education (n=48), African Americans had significantly higher WMH load (27% vs 4%, Χ=5.3, p=0.02). Conclusion: Results denote that age predicted WMH among European Americans, while obesity predicted WMH among African Americans. Matched sample analyses indicate that obesity increases the odds of WMH, though more pronounced in African Americans. These findings suggest that obesity may explain the differential burden of white matter hyperintensity load, signifying public health and clinical importance.
Patient Satisfaction and Wellness During and after Invisalign® Orthodontic Treatment Technology

Background: With its introduction in 1998, the Invisalign® transparent aligner system has become an important Orthodontic protocol. In 2018, Invisalign® refined its precision Orthodontic aligner process and introduced a smartphone mobile application called “My Invisalign® mobile app” to help inform, guide, remind and encourage patients in their healthcare as they improve their smiles. Study Aim: This research aimed to determine if the Invisalign® Orthodontic technology and its associated website and mobile smartphone applications improve patients’ health and wellbeing. The Hypothesis for this research was that the Invisalign® technology protocol (i.e., website, mobile technology, and Invisalign® process) is safe and provides adequate patient information and intuitive support throughout the protocol. Study Methodology and Design: This research model consisted of a) Historical Design (understanding the origin of Invisalign® technology), b) Descriptive Design (understanding through survey responses the decision to use Invisalign®), and c) Evaluation Design (understanding patient acceptability and effectiveness of Invisalign® protocol through observation and surveys). Participants for this research were obtained through cluster / convenience sampling using a SurveyMonkey (Anonymous) National Target Audience (United States) Web-based Survey administered through a SurveyMonkey Account to collect data for specific measures of patient satisfaction and wellbeing during and after the Invisalign® treatment technology. Participants agreed to the informed consent and indicated using or having used the Invisalign® protocol after February 27, 2018 (My Invisalign® Mobile Application Launch). Results: Adult Invisalign® participants surveyed indicated mostly satisfied / very satisfied overall Orthodontic results and showed extensive use of the My Invisalign® mobile application (weekly use of the Calendar with reminders to change aligners most significant). Discussion and Conclusion: Invisalign® Orthodontic technology and its associated website and mobile smartphone applications could improve the participant/patient’s health and wellbeing.
Site-directed Mutagenesis of Histidine 93, Aspartic Acid 180, Glutamic Acid 205, Histidine 290, and Aspartic Acid 291 at the Active Site and Tryptophan 279 at the Raw Starch Binding Site in Barley &-Amylase 1"

The pseudotetrasaccharide acarbose has high affin- ity for the active site = 1 b ~ ) and low affinity for a secondary site (& = 2.3 mM) in barley a-amylase 1, distinguished by inhibition kinetics and spectral perturbation. Mutants of putative catalytic residues, DlSON, E205Q, and D291N, are inactive and display low affinity for acarbose-Sepharose, H93N and H290N mutants, at invariant residues, have kc,JKm for p-nitrophenylmaltoheptaoside of 0.3 and 1.2% of wild- type. A corresponding 370- and 85-fold increased Ki,,,, for acarbose and a lack of shifts in pH activity profiles indicate that these histidines participate in transition state stabilization but not directly in catalysis. This finding agrees with H bonding to OH groups of the valienamine ring of acarbose in the three-dimensional structure. Loss of inhibition above pH 6 supports that acarbose is most
Impact of water hyacinth ( Eichhornia crassipes ) on water quality and phytoplankton community structure in the littoral region of Koka Reservoir, Ethiopia

Invasion of aquatic habitats by non-native species is a global environmental challenge with serious ecological, social and economic consequences demanding urgent action. Water hyacinth’s ( Eichhornia crassipes ) appearance in Koka Reservoir was reported in 1965 and has become a threat to the aquatic ecosystem. Even though there were several limnological and fish related studies, the effects of water hyacinth on water quality and phytoplankton composition and abundance in Koka Reservoir have not been addressed. To assess its effect on water quality, composition and abundance of phytoplankton in the reservoir, samples were collected from three weed-infested and three non-infested sites from March to July 2018. The phytoplankton community, which constituted of 62 species, was dominated by Bacillariophyceae followed by Cyanophyceae and Chlorophyceae at both weed-infested and non-infested sites. The variations in the Physico-chemical parameters, abundance and species richness (d) of phytoplankton between the two sites were significant, with higher mean values in the non-infested sites ( P< 0.05). The existing infestation level of water hyacinth poses a significant effect on water quality, composition, and abundance of phytoplankton. Therefore, continuous monitoring of Physico-chemical and biological water quality parameters and the development of a sustainable management strategy are deemed imperative.
Virus-Induced Demyelinating Disease Theiler's Murine Encephalomyelitis Effect of Anti-B7-1 and Anti-B7-2 mAb on

† We examined the role of B7-1 and B7-2, costimulatory molecules critical to full activation of T cells, in the development of Theiler’s murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). Treatment with mAbs to B7-1 resulted in signiﬁcant suppression of the development of this disease both clinically and histologically. In mice treated with these mAbs, the production of TNF- a and IFN- g in the spleen cells was decreased. The delayed-type hypersensitivity and T cell proliferative response speciﬁc for TMEV were decreased by this treatment. In contrast, treatment with Abs to B7-2, resulted in no effect on TMEV-IDD. These data suggest that B7-1 is critically involved in the pathogenesis of TMEV-IDD and that Abs to B7-1 could be a novel therapeutic approach in the clinical treatment of demyelinating diseases such as human multiple sclerosis. The Journal of Immunology, 1999, 163: 6180–6186.
Income Distribution, Product Quality, and International Trade Please share how this access benefits you. Your story matters

We develop a framework for studying trade in horizontally and vertically differentiated products. In our model, consumers with heterogeneous incomes and tastes purchase a homogeneous good and make a discrete choice of quality and variety of a differentiated product. The distribution of preferences generates a nested-logit demand structure such that the fraction of consumers who buy a higher-quality product rises with income. The model features a home-market effect that helps to explain why richer countries export higher-quality goods. It provides a tractable tool for studying the welfare consequences of trade and trade policy for different income groups in an economy.
The Developments of Cold-rolled TRIP-assisted Multiphase Steels. Low Silicon TRIP-assisted Multiphase Steels

TRIP-assisted multiphase steels are newly developed steels exhibiting an improved balance of strength and ductility very well adapted for the automotive industry. In order to allow the retention of austenite, the steels studied up to now contained high levels of silicon incompatible with the industrial practice. This study shows how the combination of both a composite strengthening effect and the TRIP effect can improve the mechanical properties of a cold-rolled 0.16wt%C–1.3wt%Mn steel containing only 0.4 wt% of silicon. A complete characterisation of the bainite transformation and of the resulting microstructures, tensile properties and mechanical stability of retained austenite has allowed the determination of the factors responsible for the enhanced balance of strength and ductility of this steel well adapted for automotive applications.
E ﬀ ects of Relative Roughness and Particle Size on the Interface Behavior of Concrete Suction Caisson Foundation for O ﬀ shore Wind Turbines

: The interface behavior between a caisson and the surrounding soil plays an important role in the installation of suction caissons as foundations for o ﬀ shore wind turbines. A series of shear tests were carried out using a modiﬁed direct shear apparatus to study the interface shear behavior between sand and concrete. Sand samples with three particle size ranges (0.63–1.25 mm, 1.25–2.5 mm, 2.5–5.0 mm) and concrete plates with di ﬀ erent relative roughness were used to explore the inﬂuence of the relative roughness parameter ( R n ) and mean particle size ( D 50 ) on shear behavior. The responses from the pure sand shear test are also discussed for comparison. Test results show that the higher the relative roughness ( R n ), the greater the maximum shear stress ( τ max ) appeared. The interface shear stress was weaker than that of the pure sand test. Furthermore, the interface friction angle ( ϕ ) of sand–concrete was closely related to the relative roughness of the concrete surface. Under the same conditions, the interface friction angle ( ϕ ) increased with relative roughness due to the e ﬀ ect of sand particles breakage and redistribution. By contrast, the e ﬀ ect of the mean particle size ( D 50 ) on the interface friction angle ( ϕ ) was less signiﬁcant. However, for the pure sand shear test, the friction angle ( ϕ (cid:48) ) obtained from the traditional shear test apparently increased with D 50 , indicating that the friction angle was more a ﬀ ected by D 50 in the pure sand test than in the interface shear test.
Catalysis Today Support effect on the reactivity and stability of Au 25 (SR) 18 and Au 144 (SR) 60 nanoclusters in liquid phase cyclohexane oxidation

Using oxide supported atomically precise gold nanoclusters is an emerging field in heterogeneous catalysis. Such well-defined nanocatalysts represent a rather new model system enabling fundamental insights in catalytic reactions. In the present work, the stability of Au 25 and Au 144 clusters, supported either on TiO 2 or SiO 2 , was examined upon thermal air pretreatment and, for the first time, upon liquid phase oxidation reaction. A pronounced influence of the support (TiO 2 vs. SiO 2 ) and cluster size (Au 25 vs. Au 144 ) was revealed by XAS, DRS and STEM. Upon pretreatment, Au 144 was more stable which may be related to its specific cluster core structure and staple configuration. The catalytic properties in liquid phase cyclohexane oxidation were clearly size dependent, with Au 144 yielding higher TOF values, particularly in the case of SiO 2 supported catalysts. However, with respect to selectivity, TiO 2 supported catalysts led to higher KA production than SiO 2 supported ones. This can be explained by the different reaction pathways, as observed by in situ ATR. HERFD-XAS measurements of Au 144 / TiO 2 catalysts revealed a pronounced cluster structure modification towards bulk gold during the reaction, in contrast to a high stability of Au 144 /SiO 2 . This study demonstrates the important role the support material has on the reactivity and stability of gold nanoclusters, which is key for their catalytic function.