Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Expression of Carnitine/Organic Cation Transporter OCTN1/SLC22A4 in Mouse Small Intestine and Liver

Carnitine/organic cation transporter (OCTN1/SLC22A4) accepts various therapeutic agents as substrates in vitro and is expressed ubiquitously, although its function in most organs has not yet been examined. The purpose of the present study was to evaluate functional expression of OCTN1 in small intestine and liver, using octn1 gene knockout [octn1(−/−)] mice. After oral administration of [3H]ergothioneine ([3H]ERGO), a typical substrate of OCTN1, the amount of [3H]ERGO remaining in the small intestinal lumen was much higher in octn1(−/−) mice than in wild-type mice. In addition, uptake of [3H]ERGO by human embryonic kidney 293 cells heterologously expressing OCTN1 gene product and uptake of [3H]ERGO at the apical surface of intestinal everted sacs from wild-type mice were inhibited by OCTN1 substrates, tetraethylammonium and verapamil. Immunohistochemical analysis revealed that OCTN1 is localized on the apical surface of small intestine in mice and humans. These results suggest that OCTN1 is responsible for small intestinal absorption of [3H]ERGO. However, the plasma concentration of [3H]ERGO after oral administration was higher in octn1(−/−) mice than in wild-type mice, despite the lower absorption in octn1(−/−) mice. This was probably because of efficient hepatic uptake of [3H]ERGO, as revealed by integration plot analysis; the uptake clearance was close to the hepatic plasma flow rate. The uptake of [3H]ERGO by isolated hepatocytes was minimal, whereas [3H]ERGO uptake was observed in isolated nonparenchymal cells. This finding is consistent with immunostaining of OCTN1 in liver sinusoids. Thus, our results indicate that OCTN1 is functionally expressed in nonparenchymal liver cells.
Investigating the Effects of Loading Factors on the In Vitro Pharmaceutical Performance of Mesoporous Materials as Drug Carriers for Ibuprofen

The aim of the study was to investigate the effects of the loading factors, i.e., the initial drug loading concentration and the ratio of the drug to carriers, on the in vitro pharmaceutical performance of drug-loaded mesoporous systems. Ibuprofen (IBU) was used as a model drug, and two non-ordered mesoporous materials of commercial silica Syloid® 244FP (S244FP) and Neusilin® US2 (NS2) were selected in the study. The IBU-loaded mesoporous samples were prepared by a solvent immersion method with a rotary evaporation drying technique and characterized by polarized light microscopy (PLM), Fourier transform infrared (FTIR) spectroscopy, X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). Dissolution experiments were performed in simulated gastric media at 37 °C under non-sink conditions. The concentration of IBU in solution was determined by HPLC. The study showed that the dissolution rate of IBU can be improved significantly using the mesoporous S224FP carriers due to the conversion of crystalline IBU into the amorphous form. Both of the loading factors affected the IBU dissolution kinetics. Due to the molecular interaction between the IBU and NS2 carriers, the loading factors had little effects on the drug release kinetics with incomplete drug desorption recovery and insignificant dissolution enhancement. Care and extensive evaluation must therefore be taken when mesoporous materials are chosen as carrier delivery systems.
The effect of process conditions on mechanical properties of laser‐sintered nylon

Purpose – The purpose of this paper is to measure the effect of process conditions on mechanical properties of laser‐sintered nylon 12 (Duraform®) and to determine the range of conditions that provide consistent mechanical performance for additive manufacturing.Design/methodology/approach – Tensile test specimens were fabricated over a range of well‐characterized process conditions including laser power, laser speed, scan spacing, layer thickness, build orientation, and build position. Tensile modulus, yield strength, ultimate tensile strength and elongation‐at‐fracture were measured and related to process parameters.Findings – Tensile properties are strongly related to the amount of energy deposited during scanning. Strength and modulus approach their maximum values as the energy deposited exceeds the amount needed to fully melt the applied powder. Elongation‐at‐fracture does not reach its maximum until higher energy‐melt ratio. Performance of blends with reused powder matches that of virgin powder when .
Mohr-Coulomb Model Considering Variation of Elastic Modulus and Its Application

Mohr-Coulomb model is a perfect elastoplastic model. It only considers the variation of material strength with lateral compressive stress, but doesn’t consider the variation of elastic modulus with lateral compressive stress and stress level and this is accordant with the true characteristic of geological material. The elasticity modulus in Mohr-Coulomb model was modified by employing the processing method of tangential modulus in Duncan-Chang nonlinear elastic model. In modified model, the stress-strain curve in elastic phrase behaves as hyperbola. In order to embed the modified model in FLAC3D program (Fast Lagrangian Analysis of Continua in 3 Dimensions), a preprocessing program was written and was employed to analyze numerically the bearing capacity of rigid piles loaded laterally.
Extended Property Paths: Writing More SPARQL Queries in a Succinct Way

We introduce Extended Property Paths (EPPs), a significant enhancement of SPARQL property paths. EPPs allow to capture in a succinct way a larger class of navigational queries than property paths. We present the syntax and formal semantics of EPPs and introduce two different evaluation strategies. The first is based on an algorithm implemented in a custom query processor. The second strategy leverages a translation algorithm of EPPs into SPARQL queries that can be executed on existing SPARQL processors. We compare the two evaluation strategies on real data to highlight their pros and cons.
Cognitive evaluation of neurologically asymptomatic boys with X-linked adrenoleukodystrophy.

BACKGROUND Various studies have demonstrated abnormal neuropsychological function in boys with the childhood cerebral phenotype of X-linked adrenoleukodystrophy. Not much is known about the cognitive function of neurologically asymptomatic boys with X-linked adrenoleukodystrophy who have normal brain magnetic resonance imaging results. OBJECTIVE To describe the cognitive profile of 52 neurologically asymptomatic boys with X-linked adrenoleukodystrophy (mean +/- SD age, 6.7 +/- 3.6 years). METHODS Neuropsychological tests included evaluation of IQ (full-scale IQ, verbal IQ, and performance IQ), 5 major cognitive domains (language, visuospatial skills, perception, visuomotor or graphomotor skills, memory, and attention or executive function), adaptive skills, and academic achievement. Standardized z scores relative to age-appropriate published norms were generated. Association between age and cognitive performance was evaluated using nonparametric Spearman rank correlation and robust median regression adjusting for full-scale IQ and socioeconomic status. RESULTS All but 4 patients had normal cognitive function. There was a negative correlation between age and visual perception as well as age and visuomotor skills after adjustment for full-scale IQ and socioeconomic status. CONCLUSIONS This study provides, to our knowledge, the first evidence of overall normal cognitive function in neurologically and radiologically normal boys with X-linked adrenoleukodystrophy, indicating no evidence of neurodevelopmental abnormalities despite the inherent ABCD1 mutation. Subtle deterioration with age was observed in some functional domains. This suggests that prevention and timely institution of therapy can potentially preserve cognitive function seen in patients with the cerebral X-linked adrenoleukodystrophy phenotype. X-linked adrenoleukodystrophy should be considered a candidate disorder for neonatal screening.
Reef calcifiers are adapted to episodic heat stress but vulnerable to sustained warming

Shallow marine ecosystems naturally experience fluctuating physicochemical conditions across spatial and temporal scales. Widespread coral-bleaching events, induced by prolonged heat stress, highlight the importance of how the duration and frequency of thermal stress influence the adaptive physiology of photosymbiotic calcifiers. Large benthic foraminifera harboring algal endosymbionts are major tropical carbonate producers and bioindicators of ecosystem health. Like corals, they are sensitive to thermal stress and bleach at temperatures temporarily occurring in their natural habitat and projected to happen more frequently. However, their thermal tolerance has been studied so far only by chronic exposure, so how they respond under more realistic episodic heat-event scenarios remains unknown. Here, we determined the physiological responses of Amphistegina gibbosa, an abundant western Atlantic foraminifera, to four different treatments––control, single, episodic, and chronic exposure to the same thermal stress (32°C)––in controlled laboratory cultures. Exposure to chronic thermal stress reduced motility and growth, while antioxidant capacity was elevated, and photosymbiont variables (coloration, oxygen-production rates, chlorophyll a concentration) indicated extensive bleaching. In contrast, single- and episodic-stress treatments were associated with higher motility and growth, while photosymbiont variables remained stable. The effects of single and episodic heat events were similar, except for the presumable occurrence of reproduction, which seemed to be suppressed by both episodic and chronic stress. The otherwise different responses between treatments with thermal fluctuations and chronic stress indicate adaptation to thermal peaks, but not to chronic exposure expected to ensue when baseline temperatures are elevated by climate change. This firstly implies that marine habitats with a history of fluctuating thermal stress potentially support resilient physiological mechanisms among photosymbiotic organisms. Secondly, there seem to be temporal constraints related to heat events among coral reef environments and reinforces the importance of temporal fluctuations in stress exposure in global-change studies and projections.
qSVA framework for RNA quality correction in differential expression analysis

Significance Many studies use measurements of gene expression in human postmortem and ex vivo tissues like brain and blood to characterize genomic correlates of illness. However, molecular analyses of these tissues can be susceptible to a wide range of confounders that may be difficult to measure and remove. In this article, we describe an analysis framework for identifying and removing previously uncharacterized quality biases in measurements of RNA. Our paper critically highlights the shortcomings of standard RNA quality correction approaches, such as statistically adjusting for RNA integrity numbers. We show that the our framework removes residual confounding by RNA quality and greatly improves replication of significant differentially expressed genes across independent datasets by more than threefold compared with previous approaches. RNA sequencing (RNA-seq) is a powerful approach for measuring gene expression levels in cells and tissues, but it relies on high-quality RNA. We demonstrate here that statistical adjustment using existing quality measures largely fails to remove the effects of RNA degradation when RNA quality associates with the outcome of interest. Using RNA-seq data from molecular degradation experiments of human primary tissues, we introduce a method—quality surrogate variable analysis (qSVA)—as a framework for estimating and removing the confounding effect of RNA quality in differential expression analysis. We show that this approach results in greatly improved replication rates (>3×) across two large independent postmortem human brain studies of schizophrenia and also removes potential RNA quality biases in earlier published work that compared expression levels of different brain regions and other diagnostic groups. Our approach can therefore improve the interpretation of differential expression analysis of transcriptomic data from human tissue.
Identifying synergistic regulation involving c-Myc and sp1 in human tissues

Combinatorial gene regulation largely contributes to phenotypic versatility in higher eukaryotes. Genome-wide chromatin immuno-precipitation (ChIP) combined with expression profiling can dissect regulatory circuits around transcriptional regulators. Here, we integrate tiling array measurements of DNA-binding sites for c-Myc, sp1, TFIID and modified histones with a tissue expression atlas to establish the functional correspondence between physical binding, promoter activity and transcriptional regulation. For this we develop SLM, a methodology to map c-Myc and sp1-binding sites and then classify sites as sp1-only, c-Myc-only or dual. Dual sites show several distinct features compared to the single regulator sites: specifically, they exhibit overall higher degree of conservation between human and rodents, stronger correlation with TFIID-bound promoters, and preference for permissive chromatin state. By applying regression models to an expression atlas we identified a functionally distinct signature for strong dual c-Myc/sp1 sites. Namely, the correlation with c-Myc expression in promoters harboring dual-sites is increased for stronger sp1 sites by strong sp1 binding and the effect is largest in proliferating tissues. Our approach shows how integrated functional analyses can uncover tissue-specific and combinatorial regulatory dependencies in mammals.
Roots in space: a spatially explicit model for below-ground competition in plants

Game theory provides an untapped framework for predicting how below-ground competition will influence root proliferation in a spatially explicit environment. We model root competition for space as an evolutionary game. In response to nutrient competition between plants, an individual's optimal strategy (the spatial distribution of root proliferation) depends on the rooting strategies of neighbouring plants. The model defines and predicts the fundamental (in the absence of competition) and realized (in the presence of competition) root space of an individual plant. Overlapping fundamental root spaces guarantee smaller, yet still overlapping, realized root spaces as individuals concede some but not all space to a neighbour's roots. Root overlap becomes an intentional consequence of the neighbouring plants playing a nutrient foraging game. Root proliferation and regions of root overlap should increase with soil fertility, decline with the distance cost of root production (e.g. soil compactness) and shift with competitive asymmetries. Seemingly erratic patterns of root proliferation and root overlap become the expected outcome of nutrient foraging games played in soils with small-scale heterogeneities in nutrient availability.
Genetic moderation of the effects of cannabis: Catechol-O-methyltransferase (COMT) affects the impact of Δ9-tetrahydrocannabinol (THC) on working memory performance but not on the occurrence of psychotic experiences

Cannabis use can induce cognitive impairments and psychotic experiences. A functional polymorphism in the catechol-O-methyltransferase (COMT) gene (Val158Met) appears to influence the immediate cognitive and psychotic effects of cannabis, or ∆9-tetrahydrocannabinol (THC), its primary psychoactive ingredient. This study investigated the moderation of the impact of experimentally administered THC by COMT. Cognitive performance and psychotic experiences were studied in participants without a psychiatric diagnosis, using a between-subjects design (THC vs. placebo). The effect of COMT Val158Met genotype on the cognitive and psychotic effects of THC, administered intravenously in a double-blind, placebo-controlled manner to 78 participants who were vulnerable to paranoia, was examined. The results showed interactive effects of genotype and drug group (THC or placebo) on working memory, assayed using the Digit Span Backwards task. Specifically, THC impaired performance in COMT Val/Val, but not Met, carriers. In contrast, the effect of THC on psychotic experiences, measured using the Community Assessment of Psychic Experiences (CAPE) positive dimension, was unaffected by COMT genotype. This study is the largest to date examining the impact of COMT genotype on response to experimentally administered THC, and the first using a purely non-clinical cohort. The data suggest that COMT genotype moderates the cognitive, but not the psychotic, effects of acutely administered THC.
Staphylococcus aureus biofilm removal by targeting biofilm-associated extracellular proteins

Aim Among cell surface proteins, biofilm-associated protein promotes biofilm development in Staphylococcus aureus strains. Aim of this study was to investigate proteinase-mediated biofilm dispersion in different isolates of S. aureus. Methods and Results Microtitre plate based biofilm assay showed that 2 μg/mL proteinase K significantly inhibited biofilm development in bap-positive S. aureus V329 as well as other S. aureus strains, i.e. SA7, SA10, SA33, SA352 and but not in bap-mutant M556 and SA392 (a weak biofilm producing strain). However, proteinase K treatment on S. aureus planktonic cells showed that there was no inhibition of planktonic growth at any concentration of proteinase K when tested up to 32 μg/mL. This observation ruled out the possibility of S. aureus biofilm inhibition by altering the cell viability. Proteinase K treatment upon 24 h old preformed biofilms showed an enhanced dispersion of bap-positive V329 and SA7, SA10, SA33 and SA352 biofilms, however, proteinase K did not affect the bap-mutant S. aureus M556 and SA392 biofilms. Biofilm compositions study before and after proteinase K treatment indicated that Bap might also be involved in eDNA retention in the biofilm matrix that aid in biofilm stability. When proteinase K was used in combination with antibiotics, a synergistic effect in antibiotic efficacy was observed against all biofilm forming S. aureus strains. Conclusion Proteinase K inhibited biofilms growth in S. aureus bovine mastitis isolates but did not affect their planktonic growth. An enhanced dispersion of preformed S. aureus biofilms was observed upon proteinase K treatment. Proteinase K treatment with antibiotics showed a synergistic effect against S. aureus biofilms. Significance of the study The study suggests that dispersing S. aureus by protease can be of use while devising strategies against S. aureus biofilms. Proteinase K treatment has a wider scope for control of S. aureus biofilms.
NDT80, a meiosis-specific gene required for exit from pachytene in Saccharomyces cerevisiae

We describe the identification of a new meiosis-specific gene of Saccharomyces cerevisiae, NDT80. The ndt80 null and point mutants arrest at the pachytene stage of meiosis, with homologs connected by full-length synaptonemal complexes and spindle pole bodies duplicated but unseparated. Meiotic recombination in an ndt80 delta mutant is relatively normal, although commitment to heteroallelic recombination is elevated two- to threefold and crossing over is decreased twofold compared with those of the wild type. ndt80 arrest is not alleviated by mutations in early recombination genes, e.g., SPO11 or RAD50, and thus cannot be attributed to an intermediate block in prophase chromosome metabolism like that observed in several other mutants. The ndt80 mutant phenotype during meiosis most closely resembles that of a cdc28 mutant, which contains a thermolabile p34, the catalytic subunit of maturation-promoting factor. Cloning and molecular analysis reveal that the NDT80 gene maps on the right arm of chromosome VIII between EPT1 and a Phe-tRNA gene, encodes a 627-amino-acid protein which exhibits no significant homology to other known proteins, and is transcribed specifically during middle meiotic prophase. The NDT80 gene product could be a component of the cell cycle regulatory machinery involved in the transition out of pachytene, a participant in an unknown aspect of meiosis sensed by a pachytene checkpoint, or a SPO11- and RAD50-independent component of meiotic chromosomes that is the target of cell cycle signaling.
Thyroid Hormone Levels in the Developing Obese-Hyperglycemic Syndrome

Examination of the thyroid hormone levels of C57BL/6J ob/ob mice and their lean littermates between the ages of 6 days and 22 weeks revealed that obese mice have significantly reduced hormone concentrations between 10 and 21 days of age. Thereafter, the values remained equal to, or above those or their lean littermates. The present data indicate that the hypometabolism and abnormal thermal regulation of weanling mice could be a result of diminished thyroid hormone levels, but that other mechanisms must be responsible for the persistence of these abnormalities in adult ob/ob mice.
Geometric and algebraic properties of discrete structures

In the thesis we study two dimensional simplicial complexes and linear codes. We say that a linear code C over a field F is triangular representable if there exists a two dimensional simplicial complex ∆ such that C is a punctured code of the kernel ker∆ of the incidence matrix of ∆ over F and dim C = dimker∆. We call this simplicial complex a geometric representation of C. We show that every linear code C over a primefield is triangular representable. In the case of finite primefields we construct a geometric representation such that the weight enumerator of C is obtained by a simple formula from the weight enumerator of the cycle space of ∆. Thus the geometric representation of C carries its weight enumerator. Our motivation comes from the theory of Pfaffian orientations of graphs which provides a polynomial algorithm for weight enumerator of the cut space of a graph of bounded genus. This algorithm uses geometric properties of an embedding of the graph into an orientable Riemann surface. Viewing the cut space of a graph as a linear code, the graph is thus a useful geometric representation of this linear code. We study embeddability of the geometric representations into Euclidean spaces. We show that every binary linear code has a geometric representation that can be embedded into R. We characterize binary linear codes that have a geometric representation embeddable into R. We further show that the weight enumerator of any binary linear code is polynomial reducible to the permanent of a non-negative three dimensional matrix. We give some applications of our results to statistical physics, by studying the Pfaffian three dimensional matrices.