Miracle-dz/UniFAR-FTUs huggingface dataset:
Acetate Dissimilation and Assimilation in Mycobacterium tuberculosis Depend on Carbon Availability

ABSTRACT Mycobacterium tuberculosis persists inside granulomas in the human lung. Analysis of the metabolic composition of granulomas from guinea pigs revealed that one of the organic acids accumulating in the course of infection is acetate (B. S. Somashekar, A. G. Amin, C. D. Rithner, J. Troudt, R. Basaraba, A. Izzo, D. C. Crick, and D. Chatterjee, J Proteome Res 10:4186–4195, 2011, doi:http://dx.doi.org/10.1021/pr2003352), which might result either from metabolism of the pathogen or might be provided by the host itself. Our studies characterize a metabolic pathway by which M. tuberculosis generates acetate in the cause of fatty acid catabolism. The acetate formation depends on the enzymatic activities of Pta and AckA. Using actyl coenzyme A (acetyl-CoA) as a substrate, acetyl-phosphate is generated and finally dephosphorylated to acetate, which is secreted into the medium. Knockout mutants lacking either the pta or ackA gene showed significantly reduced acetate production when grown on fatty acids. This effect is even more pronounced when the glyoxylate shunt is blocked, resulting in higher acetate levels released to the medium. The secretion of acetate was followed by an assimilation of the metabolite when other carbon substrates became limiting. Our data indicate that during acetate assimilation, the Pta-AckA pathway acts in concert with another enzymatic reaction, namely, the acetyl-CoA synthetase (Acs) reaction. Thus, acetate metabolism might possess a dual function, mediating an overflow reaction to release excess carbon units and resumption of acetate as a carbon substrate. IMPORTANCE During infection, host-derived lipid components present the major carbon source at the infection site. β-Oxidation of fatty acids results in the formation of acetyl-CoA. In this study, we demonstrate that consumption of fatty acids by Mycobacterium tuberculosis activates an overflow mechanism, causing the pathogen to release excess carbon intermediates as acetate. The Pta-AckA pathway mediating acetate formation proved to be reversible, enabling M. tuberculosis to reutilize the previously secreted acetate as a carbon substrate for metabolism.
Reproductive health and the environment: Counseling patients about risks

Endocrine-disrupting chemicals (EDCs) are associated with reproductive complications such as infertility, pregnancy complications, poor birth outcomes, and child developmental abnormalities, although not all chemicals of concern are EDCs. Pregnant patients and women of childbearing age need reasonable advice about environmental contaminants and reproductive health. Endocrine-disrupting chemicals are ubiquitous and affect multiple pathways. The precautionary principle should apply.
Evaluating forum discussions as collaborative learning tool via information retrieval techniques

Asynchronous discussion forum may be considered as a key tool in sharing learners' knowledge and handling communications in an eLearning environment. The huge number of messages makes it hard for participants to find their related topics and make an efficient contribution. Current research investigates the relevance of discussion posts to their containing forums, as well as extracting each learner's most frequent topics, via utilizing some information retrieval techniques. Results have retrieved a large number of posts irrelevant to their related forums. In addition, there are some weak contributions. In order to make learners contribution more informative and beneficial, this paper has proposed a new approach which emphasizes on training participants, and evaluating their related activities. The proposed approach has been applied in some academic courses in University of Tehran, department of Electrical and Computer Engineering. The results have revealed some considerable improvements in comparison to the traditional forums. Research outcomes may be used in building learners profiles more precise and providing forums discussions with more valuable learners' contributions.
Prefrontal Cortex and the Bridging of Temporal Gaps in the Perception‐Action Cycle

Normal behavior is characterized by a constant circular flow of influences from sensory receptors to motor effectors, to the physical environment, back to sensory receptors, and so on. This cybernetic cycle of influences (the perception-action cycle) governs all sequences of behavior to make them adaptive and goal directed. In the primate (including the human primate), considerable evidence indicates that dorsolateral prefrontal cortex is essential for the bridging of temporal gaps in the perception-action cycle, in other words, for mediating cross-temporal contingencies of behavior. This chapter summarizes some neuropsychological and neurophysiological evidence in support of this conclusion. The evidence has been obtained from monkeys performing delay tasks, which epitomize the principle of cross-temporal contingency.
QSAR analysis of nicotinamidic compounds and design of potential Bruton’s tyrosine kinase (Btk) inhibitors

Bruton’s tyrosine kinase (Btk) is an important enzyme in B-lymphocyte development and differentiation. Furthermore, Btk expression is considered essential for the proliferation and survival of these cells. Btk inhibition has become an attractive strategy for treating autoimmune diseases, B-cell leukemia, and lymphomas. With the objective of proposing new candidates for Btk inhibitors, we applied receptor-dependent four-dimensional quantitative structure–activity relationship (QSAR) methodology to a series of 96 nicotinamide analogs useful as Btk modulators. The QSAR models were developed using 71 compounds, the training set, and externally validated using 25 compounds, the test set. The conformations obtained by molecular dynamics simulation were overlapped in a virtual three-dimensional cubic box comprised of 2 and 5 Å cells, according to the six trial alignments. The models were generated by combining genetic function approximation and partial least squares regression technique. The analyses suggest that Model 1a yields the best results. The best equation shows , r2 = . 743, RMSEC = . 831, RMSECV = . 879. Given the importance of the Tyr551, this residue could become a strategic target for the design of novel Btk inhibitors with improved potency. In addition, the good potency predicted for the proposed M2 compound indicates this compound as a potential Btk inhibitor candidate.
Efficacy of quadriceps vastus medialis dry needling in a rehabilitation protocol after surgical reconstruction of complete anterior cruciate ligament rupture

Background: Several new rehabilitation modalities have been proposed after anterior cruciate ligament (ACL) reconstruction. Among these, trigger point dry needling (TrP-DN) might be useful in the treatment of myofascial pain syndrome associated with ACL reconstruction to reduce pain intensity, increase knee flexion range and modify the mechanical properties of the quadriceps muscle during late-stage rehabilitation. To date, this is the first randomized clinical trial to support the use of TrP-DN in the early rehabilitation process after ACL reconstruction. The aim of this study was to determine the pain intensity, range of motion (ROM), stability, and functionality improvements by adding quadriceps vastus medialis TrP-DN to the rehabilitation protocol (Rh) provided to subacute ACL reconstructed patients. Methods: This randomized, single-blinded, clinical trial (NCT02699411) included 44 subacute patients with surgical reconstruction of complete ACL rupture. The patients were randomized into 2 intervention groups: Rh (n = 22) or Rh + TrP-DN (n = 22). Pain intensity, ROM, stability, and functionality were measured at baseline (A0) and immediately (A1), 24 hours (A2), 1 week (A3), and 5 weeks (A4) after the first treatment. Results: Comparing statistically significant differences (P ⩽ .001; Eta2 = 0.198–0.360) between both groups, pain intensity (at A1), ROM (at A1, A2, and A3), and functionality (at A2, A3, and A4) were increased. Nevertheless, the rest of measurements did not show significant differences (P > .05). Conclusion: Quadriceps vastus medialis TrP-DN in conjunction with a rehabilitation protocol in subacute patients with surgical reconstruction of complete ACL rupture increases ROM (short-term) and functionality (short- to mid-term). Although there was an increase in pain intensity with the addition of TrP-DN, this was not detected beyond immediately after the first treatment. Furthermore, stability does not seem to be modified after TrP-DN.
Assessing Psychiatric Impairment in Primary Care with the Sheehan Disability Scale

Objective: Several recent studies have documented that substantial functional impairment is associated with many of the mental disorders seen in primary care. However, brief measures of mental health-related functional impairment are not commonly applied in primary care settings. The Sheehan Disability Scale (SDS), a three-item instrument for assessing such impairment, is evaluated in this study. Method: A psychometric analysis of the SDS was conducted with a sample of 1001 primary care patients at Kaiser Permanente in Oakland, California. The SDS and the Symptom Driven Diagnostic System for Primary Care assessments were completed. Results: The internal consistency reliability of the SDS is high, with coefficient alpha of 0.89. The construct validity was substantiated in two ways. A one-factor model fit the data quite well. Furthermore, patients with each of six psychiatric disorders had significantly higher impairment scores than those who did not. Finally, over 80 percent of the patients with mental disorder diagnoses had an elevated SDS score and nearly 50 percent of those with elevated SDS scores had at least one disorder. Conclusions: The psychometric properties of the SDS were evaluated in primary care. The internal consistency reliability was high. The analyses also lend empirical support for the construct validity. The scale is a sensitive tool for identifying primary care patients with mental health-related functional impairment, who would warrant a diagnostically-oriented mental health assessment.
Profiles Matching in Social Networks Based on Semantic Similarities and Common Relationships

Social networks have experienced an explosion in both the number of users and shared data. Users of social network sites are constantly troubled by information overload as there are too many people to interact with and too much content to consult. So, helping users to find new relationships and relevant content is becoming a major challenge for these sites. The most popular social networks now offer tools to search content, people, pages, etc. but also recommend items of interest to the user. We cite as an example the famous phrase used by Facebook "People you may know" followed by a list of people who often belong to the user's environment (friends of friends), working or having worked in the same company, etc. This type of recommendation explores the links between users and few simple attributes (work company, address, .) but neglects the published content. In this article, we propose a new persons' recommendation approach based on profiles matching by integrating both semantic similarities and common relationships between users. We conducted an experimental study, on real data from Twitter, that compares our approach with lexical and semantic matching methods.
GRAPPA: A Semantical Framework for Graph-Based Argument Processing

Graphical models are widely used in argumentation to visualize relationships among propositions or arguments. The intuitive meaning of the links in the graphs is typically expressed using labels of various kinds. In this paper we introduce a general semantical framework for assigning a precise meaning to labelled argument graphs which makes them suitable for automatic evaluation. Our approach rests on the notion of explicit acceptance conditions, as first studied in Abstract Dialectical Frameworks (ADFs). The acceptance conditions used here are functions from multisets of labels to truth values. We define various Dung style semantics for argument graphs. We also introduce a pattern language for specifying acceptance functions. Moreover, we show how argument graphs can be compiled to ADFs, thus providing an automatic evaluation tool via existing ADF implementations. Finally, we also discuss complexity issues.
THE ROLE OF DELETERIOUS MUTATIONS IN ALLOPATRIC SPECIATION

Abstract Allopatric speciation is often assumed to occur as a consequence of adaptive divergence between two isolated populations. However, there are some scenarios in which reproductive isolation can be favored due to accumulated unconditionally deleterious mutations. If deleterious mutations have synergistic epistatic effects, it is shown here that the average fitness of recombinants between two parental lines with a given number of fixed mutations is lower than that of the parents in both the F1 and F2 generations. If individual mutations are only slightly deleterious, then they will tend to fixation at a high enough rate to cause lower hybrid fitness. If the fitness effects of mutation give rise to antagonistic epistasis, the hybrids tend to have a higher average fitness than the parental lines, suggesting a possible scenario for the origin of hybrid vigor. The other model of deleterious mutations investigated is the accumulation of knockout mutants in a duplicated gene family. While neutral in the parental lines, upon contact the F1 and later generations have a significant probability of carrying double knockouts. Under this scenario, selection may also favor reproductive isolation between the two lines. Even when the selection coefficients generated are too low to drive speciation, epistatic interactions between deleterious mutations offer a possible explanation for both outbreeding depression and hybrid vigor.
Novel low cost integration of through chip interconnection and application to CMOS image sensor

If vertical interconnections could be fabricated at low cost, it would bring about many advantages, such as miniaturization and lower a height of the package. Our through-chip via (TCV) technology to fabricate vertical interconnections consists of a first via drilling by laser ablation (silicon drilling), followed by dielectric film lamination, a second via drilling by laser ablation (dielectric film drilling) and pattern plating of Cu. Our technology, being based on the printed-circuit-board fabrication process, has no need for expensive wafer fabrication techniques such as RIE, CVD and CMP. Thus, it enables the realization of the fabrication of through-chip vertical interconnections at low cost. In this paper, we describe the details of our process and its application in the fabrication of CMOS image sensor
Role of LDL Receptors in the In Vitro Uptake and Degradation of LDL in the Media of Rabbit Thoracic Aorta

The possible role of plasma low-density protein (LDL) receptors in the uptake and degradation of LDL in the whole arterial wall was investigated by comparison of the in vitro uptake of I25l-native LDL (nLDL) and 131l-methylated LDL (mLDL) by the media of deendothelialized rabbit thoracic aorta excised at in vivo length and pressurized to 70 mm Hg, taking the advantage that mLDL is not recognized by the LDL receptor. The distribution of the relative concentrations of nLDL (C± and mLDL (Cm) across the wall was obtained using a serial frozen sectioning technique. The aorta was incubated under three different conditions for varying periods of incubation in order to analyze separately the processes of binding, binding-internalization, and degradation. At 39°C, in which binding-internalization and degradation occurred, Cn was significantly higher than Cm at each position across the media. The mean medial Cn/Cm ratio was 1.36±0.15 (n=5) after 1 hour of incubation, and decreased to 1.23±0.22 (n=7) after 2 hours of incubation and to 1.13±0.11 (n=5) after 4 hours of incubation. At 4°C, in which internalization and degradation were blocked, the Cn/Cm ratio reflected the surface nLDL binding alone; the CnCm ratio was 1.47±0.20 (n=5) after 4 hours of incubation, higher than the value obtained at 39°C. To investigate whether degradation of nLDL occurred after receptor binding, the interstitial LDL was washed out by an LDL-free solution after 2-hour incubation at 39°C. After 30 minutes of washout, the Cn/Cm ratio decreased to 1.06±0.20 (n=5) in the inner media and was unchanged in the outer media. After 1 hour of washout, the ratio declined to 0.57±0.18 (n=7) in the inner part of the media and increased progressively to 1 at the media-adventitia boundary. The CnCm ratio, at 0.67±0.12 (n=5), was practically constant throughout the media after 2 hours of washout. The nLDL degradation rate across the media was obtained from the comparison of nLDL and mLDL before and after the washout. A steep decreasing gradient hi nLDL degradation rate was observed from the luminal to the external surface. The mean medial nLDL degradation rate value was 9.6±4.5 μl/cm3 wet tissue/hr. We concluded that functional LDL receptors participate in the uptake and degradation of LDL in the whole aorta.
Epigenetic Mutation of RAV6 Affects Leaf Angle and Seed Size in Rice1[OPEN]

Epigenetic modification of a B3 transcription factor alters rice leaf angle via modulation of brassinosteroid homeostasis. Heritable epigenetic variants of genes, termed epialleles, can broaden genetic and phenotypic diversity in eukaryotes. Epialleles may also provide a new source of beneficial traits for crop breeding, but very few epialleles related to agricultural traits have been identified in crops. Here, we identified Epi-rav6, a gain-of-function epiallele of rice (Oryza sativa) RELATED TO ABSCISIC ACID INSENSITIVE3 (ABI3)/VIVIPAROUS1 (VP1) 6 (RAV6), which encodes a B3 DNA-binding domain-containing protein. The Epi-rav6 plants show larger lamina inclination and smaller grain size; these agronomically important phenotypes are inherited in a semidominant manner. We did not find nucleotide sequence variation of RAV6. Instead, we found hypomethylation in the promoter region of RAV6, which caused ectopic expression of RAV6 in Epi-rav6 plants. Bisulfite analysis revealed that cytosine methylation of four CG and two CNG loci within a continuous 96-bp region plays essential roles in regulating RAV6 expression; this region contains a conserved miniature inverted repeat transposable element transposon insertion in cultivated rice genomes. Overexpression of RAV6 in the wild type phenocopied the Epi-rav6 phenotype. The brassinosteroid (BR) receptor BR INSENSITIVE1 and BR biosynthetic genes EBISU DWARF, DWARF11, and BR-DEFICIENT DWARF1 were ectopically expressed in Epi-rav6 plants. Also, treatment with a BR biosynthesis inhibitor restored the leaf angle defects of Epi-rav6 plants. This indicates that RAV6 affects rice leaf angle by modulating BR homeostasis and demonstrates an essential regulatory role of epigenetic modification on a key gene controlling important agricultural traits. Thus, our work identifies a unique rice epiallele, which may represent a common phenomenon in complex crop genomes.
Defective NK Cells in Acute Myeloid Leukemia Patients at Diagnosis Are Associated with Blast Transcriptional Signatures of Immune Evasion

Acute myeloid leukemia (AML) is a heterogeneous group of malignancies that may be sensitive to the NK cell antitumor response. However, NK cells are frequently defective in AML. In this study, we found in an exploratory cohort (n = 46) that NK cell status at diagnosis of AML separated patients in two groups with a different clinical outcome. Patients with a deficient NK cell profile, including reduced expression of some activating NK receptors (e.g., DNAX accessory molecule-1, NKp46, and NKG2D) and decreased IFN-γ production, had a significantly higher risk of relapse (p = 0.03) independently of cytogenetic classification in multivariate analysis. Patients with defective NK cells showed a profound gene expression decrease in AML blasts for cytokine and chemokine signaling (e.g., IL15, IFNGR1, IFNGR2, and CXCR4), Ag processing (e.g., HLA-DRA, HLA-DRB1, and CD74) and adhesion molecule pathways (e.g., PVR and ICAM1). A set of 388 leukemic classifier genes defined in the exploratory cohort was independently validated in a multicentric cohort of 194 AML patients. In total, these data evidenced the interplay between NK cells and AML blasts at diagnosis allowing an immune-based stratification of AML patients independently of clinical classifications.
Bromidotricarbonyl[4-iodo-N-(pyridin-2-ylmethylidene)aniline-κ2 N,N′]rhenium(I)

In the title compound, [ReBr(C12H9IN2)(CO)3], the coordination geometry of the ReI ion is a distorted fac-ReC3BrN2 octahedron, arising from the N,N′-bidentate ligand, a bromide ion and a facial arrangement of three carbonyl ligands. The dihedral angle between the aromatic rings in the 4-iodo-N-(pyridin-2-ylmethylidene)aniline ligand is 46.2 (3)°. The bromide ion and its corresponding trans CO molecule are disordered over two sets of sites in a 0.966 (3):0.034 (3) ratio.
Augmented cytotoxicity of hydroxycamptothecin-loaded nanoparticles in lung and colon cancer cells by chemosensitizing pharmaceutical excipients

Abstract The aim of this was to investigate and compare the chemosensitizing effect of some pharmaceutical excipients (TPGS, Pluronic P85 and chitosan) by evaluating the cytotoxicity of the chemotherapeutic drug Hydroxy Camptothecin (HCPT) loaded into PLGA nanoparticles. Different nanoparticles formulations were developed and evaluated for size, zeta potential, morphology, loading and encapsulation efficiency as well as in vitro drug release. The cytotoxicity of the nanoparticles was evaluated by MTT assay in A549 (human lung carcinoma cell line) and HT29 (human colon carcinoma cell line) whereas their cellular uptake was determined by confocal laser scanning microscopy and microfluorimetry assay. The results revealed that nanoparticles possessed a desirable nanometric size (revealed by dynamic light scattering measurements and TEM) with appreciable HCPT encapsulation (>48%) and negative surface charge that was switched to positive upon coating with chitosan. The nanoparticles adopted a sustained release phase preceded by initial burst of HCPT that was reduced by chitosan coating. The cytotoxicity of the nanoparticles in A549 and HT29 cells was significantly augmented compared to simple drug solution and basic nanoparticles without excipients. The excipients could be ranked according to their IC50 lowering effect in the following order [TPGS (sixfold lower IC50) > Pluronic P85 > Chitosan]. The augmented cytotoxicity and chemosensitizing effect might be attributed to overcoming drug efflux (in case of TPGS 1000 or Pluronic P85) and/or maximizing internalization by cancer cells (chitosan coating). Acting as chemopotentiators, the studied excipients could have potential in reducing therapeutic HCPT doses and minimizing adverse effects in lung and colon chemotherapy.