Miracle-dz/UniFAR-FTUs huggingface dataset:
Kinase Promotes in Both Mice and Humans in a Sex-Specific Manner.

Liver Pyruvate NAFLD/NASH In both mice and humans, high levels of liver pyruvate kinase (L-PK) are strongly associated with NAFLD severity only in males. Mechanistically, L-PK regulates mitochondrial pyruvate ﬂ ux and its incorporation into citrate, thereby affecting de novo lipogenesis accompanied by mitochondrial dysfunction/maladaptation. BACKGROUND AIMS: The etiology of nonalcoholic fatty liver disease (NAFLD) is poorly understood, with males and certain populations exhibiting markedly increased susceptibility. Using a systems genetics approach involving multi-omic pyruvate ﬂ ux and its incorporation into citrate, and this, in turn, increased liver triglycerides via up-regulated de novo lipogenesis and increased PNPLA3 levels accompanied by mitochondrial dysfunction. Also, L-PK increased plasma cholesterol levels via increased PCSK9 levels. On the other hand, L-PK silencing reduced de novo lipogenesis and PNPLA3 and PCSK9 levels and improved mitochondrial function. Finally, in ﬁ brosis model, we demonstrate that L-PK silencing in male mice reduced both liver steatosis and ﬁ brosis, accompanied by reduced de novo lipogenesis and improved mitochondrial function. CONCLUSIONS: L-PK acts in a male-speci ﬁ c manner in the development of liver steatosis and ﬁ brosis. Because NAFLD/ nonalcoholic steatohepatitis exhibit sexual dimorphism, our results have important implications for the development of personalized therapeutics. (Cell Mol Gastroenterol Hepatol 2021;11:389 – 406; https://doi.org/10.1016/j.jcmgh.2020.09.004)
Small Samples and Ordered Logistic Regression

The logistic regression proportional odds model is popular for analyzing studies with an ordered categorical outcome. In contingency table analysis, from a Type I error perspective, it is often thought best to collapse categories with sparse cell counts to improve asymptotic approximations used for testing hypotheses. Moreover, in the proportional odds model, it is natural to collapse adjacent categories of outcome since the slope parameter remains unchanged. This article asks the question: Is it really beneficial to do so? Using simulations, we show that in small samples collapsing categories produces Wald tests that are too conservative. Our simulations indicate that this is mainly due to stochastic dependence between the numerator and the denominator of the Wald statistic.
EXPERIMENTAL ANALYSES OF ANTIOXIDANT CAPACITY OF A COMMON ANTIDEPRESSANT DRUG

individuals suffering from different diseases that favour generation of free radicals show oxidative stress due to decrease in the antioxidant levels. [5] Antioxidants may be divided into two groups enzymatic and non-enzymatic. Flavonoids are regarded as non-enzymatic antioxidants apart from the vitamins C, E and the carotenoids, since flavonoids can offer protection against oxidative stress. [6] Flavonoids are polyphenolic compounds possessing 15 carbon atoms, two benzene rings which are joined by a linear three carbon atom chain. Many fruits vegetables, olive oil, tea and red wine are known to contain the flavonoid quercetin. [7] Presence of quercetin in different parts of plants has been reported by several researchers during the past few years. [8-13] Arsenic induced oxidation in experimental animals could be fully driven out by quercetin. [14] In this background the antidepressant drug imipramine was selected to determine its antioxidant potentiality since imipramine possesses a close structural similarity with quarcetin. ABSTRACT Severe damages may be produced in the bio-molecules of human system by free radicals that may ultimately lead to cardiovascular, neurodegenerative and autoimmune diseases. The adverse effects of free radicals may be reduced to a great extent by synthetic and naturally available antioxidants. The flavonoid quercetin present in many plants has been identified as a potent antioxidant. The pharmaceutical compound imipramine, prescribed for patients suffering from depression and psychosis, is structurally similar to quercetin and was therefore selected to determine its antioxidant potentiality. For this purpose highly recognised and standardised procedures were followed. In the FRAP assay and phosphomolybdenum assay imipramine revealed much greater antioxidant value than the control ascorbic acid. In CUPRAC assay and in determination of ferrous ion chelating property imipramine produced positive antioxidant capacity in a gradually increasing dose dependent manner, although the values were less than the control. Imipramine failed to show nitric oxide scavenging activity. This study opens up an important positive side of therapy for patients suffering from depression or psychosis, who have to take imipramine on a regular basis for a long period of time. The antioxidant property of imipramine would most likely place such patients in a much more advantageous position.
A Study of a Wide-Angle Scanning Phased Array Based on a High-Impedance Surface Ground Plane

This paper presents a two-dimensional infinite dipole array system with a mushroom-like high-impedance surface (HIS) ground plane with wide-angle scanning capability in the E-plane. The unit cell of the proposed antenna array consists of a dipole antenna and a four-by-four HIS ground. The simulation results show that the proposed antenna array can achieve a wide scanning angle of up to 65° in the E-plane with an excellent impedance match and a small S11. Floquet mode analysis is utilized to analyze the active impedance and the reflection coefficient. Good agreement is obtained between the theoretical results and the simulations. Using numerical and theoretical analyses, we reveal the mechanism of such excellent wide scanning properties. For the range of small scanning angles, these excellent properties result mainly from the special reflection phase of the HIS ground, which can cause the mutual coupling between the elements of the real array to be compensated by the mutual coupling effect between the real array and the mirror array. For the range of large scanning angles, since the surface wave (SW) mode could be resonantly excited by a high-order Floquet mode TM−1,0 from the array and since the SW mode could be converted into a leaky wave (LW) mode by the scattering of the array, the radiation field from the LW mode is nearly in phase with the direct radiating field from the array. Therefore, with help from the special reflection phase of the HIS and the designed LW mode of the HIS ground, the antenna array with an HIS ground can achieve a wide-angle scanning performance.
Advanced Glycation End Products Are Direct Modulators of b -Cell Function

OBJECTIVE — Excess accumulation of advanced glycation end products (AGEs) contributes to aging and chronic diseases. We aimed to obtain evidence that exposure to AGEs plays a role in the development of type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS — The effect of AGEs was examined on insulin secretion by MIN6N8 cells and mouse islets and in vivo in three separate rodent models: AGE-injected or high AGE – fed Sprague-Dawley rats and nonobese diabetic (NODLt) mice. Rodents were also treated with the AGE-lowering agent alagebrium. RESULTS — b -Cells exposed to AGEs displayed acute glucose- stimulated insulin secretory defects, mitochondrial abnormalities including excess superoxide generation, a decline in ATP con- tent, loss of MnSOD activity, reduced calcium ﬂ ux, and increased glucose uptake, all of which were improved with alagebrium treatment or with MnSOD adenoviral overexpression. Isolated mouse islets exposed to AGEs had decreased glucose-stimulated insulin secretion, increased mitochondrial superoxide production, and depletion of ATP content, which were improved with alagebrium or with MnTBAP, an SOD mimetic. In rats, transient or chronic exposure to AGEs caused progressive insulin secre- tory defects, superoxide generation, and b -cell death, ameliorated with alagebrium. NODLt mice had increased circulating AGEs in association with an increase in islet mitochondrial superoxide generation, which was prevented by alagebrium, which also reduced the incidence of autoimmune diabetes. Finally, at-risk children who progressed to T1D had higher AGE concentra- tions than matched nonprogressors. CONCLUSIONS These ﬁ ndings demonstrate that AGEs di- rectly cause insulin secretory defects, most likely by impairing mitochondrial function, which may contribute to the develop- ment of T1D. Diabetes 60:2523 2532,
IDENTIFICATION AND MAPPING OF ANTHRACNOSE RESISTANCE GENES IN SORGHUM [SORGHUM BICOLOR (L.) MOENCH]

Xu, Xiaochen. Ph.D., Purdue University, December 2019. Identification and Mapping of Anthracnose Resistance Genes in Sorghum [Sorghum bicolor (L.) Moench]. Major Professor: Gebisa Ejeta. Colletotrichum sublineolum is the causal agent of sorghum anthracnose, a very common and destructive fungal disease in warm and humid areas, especially in West and Central Africa. Use of host plant resistance is considered as the most important and effective control option for sorghum diseases. To achieve this goal, identification and mapping resistance genes is essential. In this study, we used an isolate of C. sublineolum, CsGL1, to screen our sorghum germplasm and identified a resistant inbred line, P9830. We developed a mapping population from a cross between P9830 and a susceptible line, TAM428, for this research. The population was advanced to the F6 generation. Progenies were phenotyped at F2, F3 and F6 generations for disease resistance against the pathogen, CsGL1. In the F2 generation, 460 individuals showed resistance and 149 individuals showed susceptibility to CsGL1. This result fits the 3:1 segregation pattern expected for resistance controlled by a single gene. Bulked segregant analysis with next generation sequencing was used on selected F6 recombinant inbred lines. A significant peak containing 153 SNPs was observed on the distal end of the long arm of chromosome 8. To verify resistance to CsGL1 was controlled by genes in this region, indel and SNP markers were used between 59.4Mbp and 60.6Mbp on chromosome 8 to fine map the resistance locus. One SNP marker located in the gene Sobic.008G166400 co-segregated with resistance, and another two indel markers were discovered to be tightly linked to the resistance locus. These three PCR-based SNP markers would be useful for marker-assisted selection for improving anthracnose resistance against CsGL1. Two candidate genes, Sobic.008G166400 and Sobic.008G166550, were found in the locus. Both of the genes encode LRR proteins implicated in plant disease defense response. The identity of DNA sequence between these two candidate genes is 94.1%, possibly the result of tandem duplication. Another
Structural and Genetic Characterization of Enterohemorrhagic Escherichia coli O145 O Antigen and Development of an O145 Serogroup-Speciﬁc PCR Assay†

Enterohemorrhagic Escherichia coli O145 strains are emerging as causes of hemorrhagic colitis and hemolytic uremic syndrome. In this study, we present the structure of the E. coli O145 O antigen and the sequence of its gene cluster. The O145 antigen has repeat units containing three monosaccharide residues: 2-acetamido- 2-deoxy-D -glucose (GlcNAc), 2-acetamidoylamino-2,6-dideoxy- L -galactose, and N -acetylneuraminic acid. It is very closely related to Salmonella enterica serovar Touera and S. enterica subsp . arizonae O21 antigen. The E. coli O145
CaM kinase II (cid:1) 2 -dependent regulation of vascular smooth muscle cell polarization and migration

kinase II 2 -dependent regulation of vascular smooth muscle cell polarization and migration. studies indicate involvement of the multifunctional Ca 2 (cid:2) /calmodulin-depen-dent protein kinase II (CaMKII) in vascular smooth muscle (VSM) cell migration. In the present study, molecular loss-of-function studies were used speciﬁcally to assess the role of the predominant CaMKII (cid:1) 2 isoform on VSM cell migration using a scratch wound healing assay. Targeted CaMKII (cid:1) 2 knockdown using siRNA or inhibition of activity by overexpressing a kinase-negative mutant resulted in attenuation of VSM cell migration. Temporal and spatial assessments of kinase autophosphorylation indicated rapid and transient activation in response to wounding, in addition to a sustained activation in the leading edge of migrating and spreading cells. Furthermore, siRNA-mediated suppression of CaMKII (cid:1) 2 resulted in the inhibition of wound-induced Rac activation and Golgi reorganization, and disruption of leading edge morphology, indicating an important function for CaMKII (cid:1) 2 in regulating VSM cell polarization. Numerous previous reports link activation of CaMKII to ERK1/2 signaling in VSM. Wound-induced ERK1/2 activation was also found to be dependent on CaMKII; however, ERK activity did not account for effects of CaMKII in regulating Golgi polarization, indicating alternative mechanisms by which CaMKII affects the complex events involved in cell migration. Wounding a VSM cell monolayer results in CaMKII (cid:1) 2 activation, which positively regulates VSM cell polarization and downstream signaling, including Rac and ERK1/2 activation, leading to cell migration.
Antibacterial Efﬁcacy of Phages against Pseudomonas aeruginosa Infections in Mice and Drosophila melanogaster (cid:1)

Phage therapy against Pseudomonas aeruginosa infections has received renewed attention owing to the increasing prevalence of antibiotic resistance in this bacterium. Here, we isolated and characterized two new potentially lytic bacteriophages (MPK1 and MPK6), which produced large and clear plaques on P. aeruginosa strain PAO1. Based on their morphology, MPK1 belongs to the Myoviridae , while MPK6 belongs to the Podoviridae . The group B polysaccharide of lipopolysaccharide was required for infection, suggesting that their host spectra are associated with the serotypes of P. aeruginosa strains. Intramuscular and intraperitoneal administration of MPK1 and, to a lesser extent, MPK6 signiﬁcantly protected mice from mortality caused by PAO1-induced peritonitis-sepsis ( P < 0.01). Mice treated with either phage also had lower bacterial burdens in their livers, lungs, and spleens. The antibacterial efﬁcacy of MPK1 and MPK6 was also evaluated based on Drosophila melanogaster systemic infection caused by P. aeruginosa , for which phages were administered by feeding. Both phages signiﬁcantly delayed the PAO1-induced killing of D. melanogaster ( P < 0.001), although MPK1 persisted longer than MPK6 in uninfected D. melanogaster tissue samples. These results suggest that a mini-scale experiment using D. melanogaster infection is valid for evaluating the antibacterial efﬁcacy of phage therapy against P. aeruginosa infections.
Parallelization of the AVL FIRE Benchmark with SVM-Fortran

This article outlines the parallelization of an irregular grid application with SVM-Fortran. It describes the di(cid:11)erent optimizations and their e(cid:11)ectiveness. The parallelization was much simpli(cid:12)ed by the performance analysis tool OPAL, a source code based tool for requesting and analyzing runtime performance data. Although shared memory parallelization is easier than distributed memory parallelization, understand-ing and eliminating the overhead from page faults is impossible without such a tool. It relates the page faults to the arrays and to the location in the source code. An area which is not supported by OPAL but where supporting tools are highly desirable, is the performance degradation due to low utilization of the on-chip cache.
FORMULATION AND EVALUATION OF CHRONOMODULATED DRUG DELIVERY SYSTEM CONTAINING CAPTOPRIL AND HYDROCHLOROTHIAZIDE

B lood pressures displays circadian rhythm. The objective of present study was to develop chronomodulated drug delivery system containing Captopril and Hydrochlorothiazide to achieve extended retention in upper gastro intestinal tract to enhance absorption and bioavailability. Captopril mucoadhesive microspheres were prepared by emulsification method using sodium alginate and guar gum polymers whereas Hydrochlorothiazide floating microspheres were prepared by non-aqueous solvent evaporation method using ethyl cellulose and hydroxyl propyl methyl cellulose K15 polymers in various ratios. Fourier-transform infrared spectroscopy study showed that drug and polymers were compatible with each other. The effects of polymer concentration on drug release profile were investigated. From the drug and excipients compatibility studies it was confirmed that the drug and excipients used weren’t have any interactions. Microspheres obtained were evaluated for percentage yield, micromeritics studies, percentage mucoadhesion, percentage buoyancy, percentage entrapment efficiency, in-vitro percentage drug release after 10 hours, in-vitro kinetic release studies and surface morphology. Formulation M3 (1:3, sodium alginate) showed highest drug entrapment efficiency 72.54 %, 93.09 % mucoadhesion and 74.38 % drug release after 10 hours. Formulation F12 (1:4, ethyl cellulose and hydroxyl propyl methyl cellulose K15) showed higher drug entrapment efficiency 85.75 %, percentage buoyancy 80.42 % and 61.02 % drug release after 10 hours. Scanning electron microscopy showed that microspheres were spherical in shape. In-vitro release studies showed that formulation observed Zero-order and Peppas (Case II transport) pattern. Better results were observed, thereby improving the bioavailability and treating hypertension effectively due to prolong release of drug in stomach.
MiR-423-5p may regulates ovarian response to ovulation induction via CSF1 CURRENT

Background We have previously shown that hsa-miR-423-5p expression in ovarian granulosa cells is decreased in high ovarian response populations. The objective of the present study was to find the target gene and mechanism for miR-423-5p involved in ovarian response regulation. Methods (a) TargetScan was used to predict the target gene of hsa-miR-423-5p. (b) A model for hsa-miR-423-5p overexpression or inhibition was constructed by transfecting KGN cells with lentivirus. CSF1 mRNA and protein expression and luciferase activity were measured. (c) The cell cycles of control and lentivirus treated KGN cells were analyzed. Western blot was used to measure the expression of CDKN1A in KGN cells. (d) The concentration of E 2 in KGN cell culture medium were measured. Results (a) TargetScan revealed that the 3′ un-translated region of CSF1 matched 11 bases at the 5′ end of miR-423-5p, making it a likely target gene. (b) Overexpression or inhibition of miR-423-5p were associated with respective decreases or increases in CSF1 expression (both mRNA and protein) (p < 0.05) and luciferase activity (p < 0.05). (c) When miR-423-5p expression increased, the number of G0/G1 phase cells and the expression of CDKN1A protein increased while estradiol concentrations in the cell culture solution decreased (p<0.05). However, when miR-423-5p expression decreased, the number of S phase cells increased and E2 concentrations increased while the expression of CDKN1A protein decreased (p < 0.05). and of E 2 bound to the streptavidin-coated magnetic microparticles was measured using a photomultiplier tube. The concentration of E 2 in the sample specimen was extrapolated from the emission intensity of a calibrator operating in the same manner. CSF1 is a target gene of hsa-miR-423-5p. Moreover, we demonstrated that hsa-miRNA-423-5p could influence cycle proliferation of KGN cells, and this effect may be achieved by affecting the expression of CDKN1A. Through measuring the E 2 concentration of cell culture medium, we show that the secretion of E2 in KGN cells affected by hsa-miR-423-5p. These results suggest that the altered expression of hsa-miR-423-5p and its target gene CSF1 in ovarian granulosa cells maybe the reason of high ovarian response to exogenous gonadotropins. analysis of miRNAs with altered expression in ovarian hyperresponders revealed that the target genes of differential miRNAs were enriched in pathways such as cell-cycle regulation. In this study, we found that increased hsa-miR-423-5p can cause a large number of KGN cells to arrest in the G0/G1 phase, with the number of cells in S phase increased when hsa-miR-423-5p expression was inhibited. This result indicates that the expression level of hsa-miR-11
Comment on The Identi(cid:133)cation Power in Games by A. Aradillas-Lopez and E. Tamer:

The paper by Andres Aradillas-Lopez and Elie Tamer clari(cid:133)es how identi(cid:133)cation can be obtained in games and provides techniques to do so. In other words, it o⁄ers constructive ways of analyzing either point or set identi(cid:133)cation of parameters governing the preferences and beliefs of players in di⁄erent games. In this short comment, I am trying to highlight the key issues that are brought out by the paper.
Fractional Order Adaptive Feed‐Forward Cancellation for Periodic Disturbances

In this paper, a fractional order adaptive feed‐forward cancellation (FO‐AFC) scheme is proposed to cancel periodic disturbances. This FO‐AFC offers one more tuning knob, the fractional order, for the performance improvement of the periodic disturbance cancellation, according to the interests of the users. The equivalence of the fractional order internal model principle (FO‐IMP) scheme is derived for FO‐AFC. So, the FO‐IMP equivalence can be used to analyze the performance of the cancellation for the target periodic disturbance and the suppression for the harmonics and noise. Two FO‐AFC cases, fractional order α ∈ (0, 1) and α ∈ (1, 2), are discussed for the performance analysis. FO‐AFC with additional tuning knob α ∈ (0, 2) has many advantages, and it is much more flexible than the integer order adaptive feed‐forward cancellation (IO‐AFC) with only α = 1. Experimental results are presented to validate the performance analysis of FO‐AFC compared with IO‐AFC.
Unusual C (cid:2) / D (cid:2) motifs enable box C / D snoRNPs to modify multiple sites in the same rRNA target region

Eukaryotic box C / D small nucleolar (sno)RNPs catal-yse the site-speciﬁc 2 (cid:2) -O-methylation of ribosomal RNA. The RNA component (snoRNA) contains guide regions that base-pair with the target site to select the single nucleotide to be modiﬁed. The terminal C / D and internal C (cid:2) / D (cid:2) motifs in the snoRNA, adjacent to the guide region, function as binding sites for the snoRNP proteins including the enzymatic subunit ﬁbrillarin / Nop1. Four yeast snoRNAs are unusual in that they are predicted to methylate two nucleotides in a single target region. In each case, the internal C (cid:2) / D (cid:2) motifs from these snoRNAs differ from the consensus. Our data indicate that the C (cid:2) / D (cid:2) motifs in snR13, snR48 and U18 form two alternative structures that lead to differences in the position of the proteins bound to this motif. We propose that each snoRNA forms two different snoRNPs, subtly different in how the proteins are bound to the C (cid:2) / D (cid:2) motif, leading to 2 (cid:2) -O-methylation of different nucleotides in the target region. For snR48 and U18, the unusual C (cid:2) / D (cid:2) alone is enough for the modiﬁcation of two nucleotides.