Miracle-dz/UniFAR-FTUs huggingface dataset:
Tacrolimus Dosing in Pediatric Heart Transplant Patients is Related to CYP3A5 and MDR1 Gene Polymorphisms

Tacrolimus is a substrate for P‐glycoprotein (P‐gp) and cytochrome (CYP) P4503A. P‐gp is encoded by the multiple drug resistance gene MDR1 and CYP3A is the major enzyme responsible for tacrolimus metabolism. Both MDR1 and CYP3A5 genes have multiple single nucleotide polymorphisms. The objective of this study was to evaluate whether the MDR1 exon21 and exon26 polymorphisms and the CYP3A5 polymorphism are associated with tacrolimus disposition in pediatric heart transplant patients. At 3, 6 and 12 months post transplantation, a significant difference in tacrolimus blood level per dose/kg/day was found between the CYP3A5 *1/*3 (CYP3A5 expressor) vs. *3/*3 (nonexpressor) genotypes with the *1/*3 patients requiring a larger tacrolimus dose to maintain the same blood concentration. There were no significant differences in tacrolimus blood level per dose/kg/day between MDR1 exon21 G2677T and exon 26 C3435T at 3 months, but both were found to have a significant association with tacrolimus blood level per dose/kg/day at 6 and 12 months. We conclude that specific genotypes of MDR1 and CYP3A5 in pediatric heart transplant patients require larger tacrolimus doses to maintain their tacrolimus blood concentration, and that this information could be used prospectively to manage patient's immunosuppressive therapy.
MASSIVE BLACK HOLE PAIRS IN CLUMPY, SELF-GRAVITATING CIRCUMNUCLEAR DISKS: STOCHASTIC ORBITAL DECAY

We study the dynamics of massive black hole pairs in clumpy gaseous circumnuclear disks. We track the orbital decay of the light, secondary black hole M•2 orbiting around the more massive primary at the center of the disk, using N-body/smoothed particle hydrodynamic simulations. We find that the gravitational interaction of M•2 with massive clumps Mcl erratically perturbs the otherwise smooth orbital decay. In close encounters with massive clumps, gravitational slingshots can kick the secondary black hole out of the disk plane. The black hole moving on an inclined orbit then experiences the weaker dynamical friction of the stellar background, resulting in a longer orbital decay timescale. Interactions between clumps can also favor orbital decay when the black hole is captured by a massive clump that is segregating toward the center of the disk. The stochastic behavior of the black hole orbit emerges mainly when the ratio M•2/Mcl falls below unity, with decay timescales ranging from ∼1 to ∼50 Myr. This suggests that describing the cold clumpy phase of the interstellar medium in self-consistent simulations of galaxy mergers, albeit so far neglected, is important to predict the black hole dynamics in galaxy merger remnants.
Genetic diversity of the relict moss Rhytidium rugosum (Hypnales) in Europe inferred from the ITS region (nrDNA)

Post-glacial survival, potential migration routes, genetic diversity and phylogeography of the boreal moss species Rhytidium rugosum have been studied. This species is considered to be one of glacial relics of the wide but scattered Holarctic range. According to molecular data sampling from the selected European, American and Asian populations high genetic diversity of this species is present, even if this species is mostly sterile and produced sex organs extremely rarely and spread mostly asexually. Analysing the internal transcribed spacer (ITS) of the nuclear ribosomal DNA, it can be concluded that the populations of this species survived glaciations in various places in Europe and settled and re-settled present range space in various times from various refuges.
Discrete Wavelet Transforms in the Large Time-Frequency Analysis Toolbox for MATLAB/GNU Octave

The discrete wavelet transform module is a recent addition to the Large Time-Frequency Analysis Toolbox (LTFAT). It provides implementations of various generalizations of Mallat's well-known algorithm (iterated filterbank) such that completely general filterbank trees, dual-tree complex wavelet transforms, and wavelet packets can be computed. The resulting transforms can be equivalently represented as filterbanks and analyzed as filterbank frames using fast algorithms.
Ammonia-Oxidizing Bacteria Rather than Ammonia-Oxidizing Archaea were Widely Distributed in Animal Manure Composts from Field-Scale Facilities

The distribution of ammonia-oxidizing archaea (AOA) and bacteria (AOB) in cattle, swine, and chicken manure compost was analyzed. PCR-denaturing gradient gel electrophoresis (DGGE) showed that a Candidatus Nitrososphaera gargensis-like sequence dominated in cattle manure compost, while few AOA were detected in other composts. In the case of AOB, Nitrosomonas-like sequences were detected with higher diversity in cattle and swine manure composts. The relative abundance of ammonia oxidizers by real-time PCR revealed that more AOB was present in compost except in one swine manure compost. Our results indicated that AOB rather than AOA are widely distributed in animal manure compost.
Object Individuation and Physical Reasoning in Infancy: An Integrative Account

Much of the research on object individuation in infancy has used a task in which two different objects emerge in alternation from behind a large screen, which is then removed to reveal either one or two objects. In their seminal work, Xu and Carey (1996) found that it is typically not until the end of the first year that infants detect a violation when a single object is revealed. Since then, a large number of investigations have modified the standard task in various ways and found that young infants succeed with some but not with other modifications, yielding a complex and unwieldy picture. In this article, we argue that this confusing picture can be better understood by bringing to bear insights from a related subfield of infancy research, physical reasoning. By considering how infants reason about object information within and across physical events, we can make sense of apparently inconsistent findings from different object-individuation tasks. In turn, object-individuation findings deepen our understanding of how physical reasoning develops in infancy. Integrating the insights from physical-reasoning and object-individuation investigations thus enriches both subfields and brings about a clearer account of how infants represent objects and events.
A1C Underestimates Glycemia in HIV Infection

OBJECTIVE The objective of this study was to determine the relationship between A1C and glycemia in HIV infection. RESEARCH DESIGN AND METHODS We completed a prospective cross-sectional study of 100 HIV-infected adults with type 2 diabetes (77%) or fasting hyperglycemia (23%) with measured glucose, A1C, mean corpuscular volume (MCV), and fructosamine. A total of 200 HIV-uninfected type 2 diabetic subjects matched for key demographic characteristics served as control subjects. RESULTS Relative to the control subjects, A1C underestimated glucose by 29 ± 4 mg/dl in the HIV-infected subjects. Current nucleoside reverse transcriptase inhibitors (NRTIs), higher MCV and hemoglobin, and lower HIV RNA and haptoglobin were associated with greater A1C-glucose discordance. However, only MCV and current NTRI use, in particular abacavir, remained significant predictors in multivariate analyses. Fructosamine more closely reflected glycemia in the HIV-infected subjects. CONCLUSIONS A1C underestimates glycemia in HIV-infected patients and is related to NRTI use. Use of abacavir and increased MCV were key correlates in multivariate analyses. Fructosamine may be more appropriate in this setting.
Current of Injury Predicts Acute Performance of Catheter‐Delivered Active Fixation Pacing Leads

Background: During pacemaker lead (PPML) implantation, the implanter must assess lead stability (fixation) and pacing threshold adequacy. Implanters rely principally on lead impedance (IMP) and pacing threshold measurements after fixation of the PPML to determine adequacy of pacing sites. Continuously monitoring lead parameters during fixation might better identify predictors of acute lead stability and performance.
Optimal Regression for Reasoning about Knowledge and Actions

We show how in the propositional case both Reiter's and Scherl & Levesque's solutions to the frame problem can be modelled in dynamic epistemic logic (DEL), and provide an optimal regression algorithm for the latter. Our method is as follows: we extend Reiter's framework by integrating observation actions and modal operators of knowledge, and encode the resulting formalism in DEL with announcement and assignment operators. By extending Lutz' recent satisfiability-preserving reduction to our logic, we establish optimal decision procedures for both Reiter's and Scherl & Levesque's approaches: satisfiability is NP-complete for one agent, PSPACE-complete for multiple agents and EXPTIME-complete when common knowledge is involved.
Play and Social Interactions Between Children with Developmental Disabilities and Their Siblings

A systematic literature review identified fourteen studies published between 1980 and 2002 that addressed the reciprocal nature of sibling interaction when one sibling presents with a developmental disability. Variables of birth order, chronological age, age gap, sex composition, gender, and type and/or degree of disability were studied as possible contributing factors to difference in interactional patterns among siblings. This research found that the primary difference between siblings, frequency of role symmetry and social reciprocity, is influenced primarily by the presence of a sibling with a disability rather than any other variable studied. Suggested methods of increasing the frequency of sibling role symmetry and social reciprocity as a family-centered intervention are given.
Use of Geospatial Modeling to Predict Schistosoma mansoni Prevalence in Nyanza Province, Kenya

Background Schistosomiasis, a parasitic disease that affects over 200 million people, can lead to significant morbidity and mortality; distribution of single dose preventative chemotherapy significantly reduces disease burden. Implementation of control programs is dictated by disease prevalence rates, which are determined by costly and labor intensive screening of stool samples. Because ecological and human factors are known to contribute to the focal distribution of schistosomiasis, we sought to determine if specific environmental and geographic factors could be used to accurately predict Schistosoma mansoni prevalence in Nyanza Province, Kenya. Methodology/Principal Findings A spatial mixed model was fit to assess associations with S. mansoni prevalence in schools. Data on S. mansoni prevalence and GPS location of the school were obtained from 457 primary schools. Environmental and geographic data layers were obtained from publicly available sources. Spatial models were constructed using ArcGIS 10 and R 2.13. 0. Lower S.mansoni prevalence was associated with further distance (km) to Lake Victoria, higher day land surface temperature (LST), and higher monthly rainfall totals. Altitude, night LST, human influence index, normalized difference vegetation index, soil pH, soil texture, soil bulk density, soil water capacity, population, and land use variables were not significantly associated with S. mansoni prevalence. Conclusions Our model suggests that there are specific environmental and geographic factors that influence S. mansoni prevalence rates in Nyanza Province, Kenya. Validation and use of schistosomiasis prevalence maps will allow control programs to plan and prioritize efficient control campaigns to decrease schistosomiasis burden.
DNA methylation regulates neuronal glutamatergic synaptic scaling

Epigenetically mediated changes in postsynaptic glutamate receptor expression enable neurons to adjust responsiveness to their environment. DNA demethylation ramps up synaptic reception To prevent overstimulation, neurons decrease the abundance of postsynaptic receptors to reduce the strength of incoming excitatory currents. Conversely, in periods of low activity, neurons increase the abundance of receptors to increase receptiveness. This adjustment is called synaptic scaling and is critical for maintaining neuronal function. Using cultured primary rat cortical neurons, Meadows et al. found that synaptic upscaling—adjustments that increase excitatory responses—involved a decrease in DNA methylation that promoted the expression of genes encoding glutamate receptors and the proteins that deliver the receptors to the synaptic membrane. The findings have implications not only for understanding homeostatic regulation of neuronal activity but also for understanding such cognitive processes as learning and memory. Enhanced receptiveness at all synapses on a neuron that receive glutamatergic input is called cell-wide synaptic upscaling. We hypothesize that this type of synaptic plasticity may be critical for long-term memory storage within cortical circuits, a process that may also depend on epigenetic mechanisms, such as covalent chemical modification of DNA. We found that DNA cytosine demethylation mediates multiplicative synaptic upscaling of glutamatergic synaptic strength in cultured cortical neurons. Inhibiting neuronal activity with tetrodotoxin (TTX) decreased the cytosine methylation of and increased the expression of genes encoding glutamate receptors and trafficking proteins, in turn increasing the amplitude but not frequency of miniature excitatory postsynaptic currents (mEPSCs), indicating synaptic upscaling rather than increased spontaneous activity. Inhibiting DNA methyltransferase (DNMT) activity, either by using the small-molecule inhibitor RG108 or by knocking down Dnmt1 and Dnmt3a, induced synaptic upscaling to a similar magnitude as exposure to TTX. Moreover, upscaling induced by DNMT inhibition required transcription; the RNA polymerase inhibitor actinomycin D blocked upscaling induced by DNMT inhibition. Knocking down the cytosine demethylase TET1 also blocked the upscaling effects of RG108. DNMT inhibition induced a multiplicative increase in mEPSC amplitude, indicating that the alterations in glutamate receptor abundance occurred in a coordinated manner throughout a neuron and were not limited to individual active synapses. Our data suggest that DNA methylation status controls transcription-dependent regulation of glutamatergic synaptic homeostasis. Furthermore, covalent DNA modifications may contribute to synaptic plasticity events that underlie the formation and stabilization of memories.
Mutation in Spike Protein Cleavage Site and Pathogenesis of Feline Coronavirus

Feline coronaviruses (FCoV) exist as 2 biotypes: feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV). FECV causes subclinical infections; FIPV causes feline infectious peritonitis (FIP), a systemic and fatal disease. It is thought that mutations in FECV enable infection of macrophages, causing FIP. However, the molecular basis for this biotype switch is unknown. We examined a furin cleavage site in the region between receptor-binding (S1) and fusion (S2) domains of the spike of serotype 1 FCoV. FECV sequences were compared with FIPV sequences. All FECVs had a conserved furin cleavage motif. For FIPV, there was a correlation with the disease and >1 substitution in the S1/S2 motif. Fluorogenic peptide assays confirmed that the substitutions modulate furin cleavage. We document a functionally relevant S1/S2 mutation that arises when FIP develops in a cat. These insights into FIP pathogenesis may be useful in development of diagnostic, prevention, and treatment measures against coronaviruses.
Investigating the origin of candidate lava channels on Mercury with MESSENGER data: Theory and observations

Volcanic plains identified on Mercury are morphologically similar to lunar mare plains but lack constructional and erosional features that are prevalent on other terrestrial planetary bodies. We analyzed images acquired by the MESSENGER spacecraft to identify features on Mercury that may have formed by lava erosion. We used analytical models to estimate eruption flux, erosion rate, and eruption duration to characterize the formation of candidate erosional features, and we compared results with analyses of similar features observed on Earth, the Moon, and Mars. Results suggest that lava erupting at high effusion rates similar to those required to form the Teepee Butte Member of the Columbia River flood basalts (0.1–1.2 × 106 m3 s–1) would have been necessary to form wide valleys (>15 km wide) observed in Mercury's northern hemisphere, first by mechanical erosion to remove an upper regolith layer, then by thermal erosion once a lower rigid layer was encountered. Alternatively, results suggest that lava erupting at lower effusion rates similar to those predicted to have formed Rima Prinz on the Moon (4400 m3 s–1) would have been required to form, via thermal erosion, narrower channels (<7 km wide) observed on Mercury. Although these results indicate how erosion might have occurred on Mercury, the observed features may have formed by other processes, including lava flooding terrain sculpted during the formation of the Caloris basin in the case of the wide valleys, or impact melt carving channels into impact ejecta in the case of the narrower channels.
Influence of Perilla frutescens var. acuta Water Extract on the Shelf Life and Physicochemical Qualities of Cooked Beef Patties

This study investigated the effects of Perilla frutescens var. acuta water extract (WEP) on the shelf life and physicochemical qualities of cooked beef patties. The WEP contained phenolic compounds (80.65 mg gallic acid equivalents/g) and had half-maximal effective concentrations of 0.437 and 4.509 mg/mL for scavenging of DPPH and ABTS+ radicals, respectively. Treatment with 0.6% WEP inhibited the growth of Escherichia coli O157:H7 (p<0.05). Based on the result of the antioxidative potential and antimicrobial potential of WEP, beef patties were prepared with three treatment groups: (1) beef patties without added antioxidant (control); (2) beef patties with 0.02% ʟ-ascorbic acid (BAA); and (3) beef patties with 0.6% WEP (BWEP). The pH and cooking loss of BWEP were lower and higher than those in the control, respectively (p<0.05). When cooked beef patties were stored for 21 d at 4℃, the total number of aerobic bacteria in BWEP was lower than those in the control on all days except day 14 (p<0.05). The TBARS values in BWEP were lower than those of controls on days 7, 14, and 21 (p<0.05). Compared to control and BAA, BWEP had lower L* and b* values and higher a* values throughout the storage period (p<0.05). Except on day 0, acceptability was higher in BWEP than in control and BAA (p<0.05). According to results, WEP can be used as a natural ingredient that improves the shelf life and sensorial qualities of meat products.
Signal Peptide Cleavage from GP5 of PRRSV: A Minor Fraction of Molecules Retains the Decoy Epitope, a Presumed Molecular Cause for Viral Persistence

Porcine reproductive and respiratory syndrome virus (PRRSV) is the major pathogen in the pig industry. Variability of the antigens and persistence are the biggest challenges for successful control and elimination of the disease. GP5, the major glycoprotein of PRRSV, is considered an important target of neutralizing antibodies, which however appear only late in infection. This was attributed to the presence of a “decoy epitope” located near a hypervariable region of GP5. This region also harbors the predicted signal peptide cleavage sites and (dependent on the virus strain) a variable number of potential N-glycosylation sites. Molecular processing of GP5 has not been addressed experimentally so far: whether and where the signal peptide is cleaved and (as a consequence) whether the “decoy epitope” is present in virus particles. We show that the signal peptide of GP5 from the American type 2 reference strain VR-2332 is cleaved, both during in vitro translation in the presence of microsomes and in transfected cells. This was found to be independent of neighboring glycosylation sites and occurred in a variety of porcine cells for GP5 sequences derived from various type 2 strains. The exact signal peptide cleavage site was elucidated by mass spectrometry of virus-derived and recombinant GP5. The results revealed that the signal peptide of GP5 is cleaved at two sites. As a result, a mixture of GP5 proteins exists in virus particles, some of which still contain the “decoy epitope” sequence. Heterogeneity was also observed for the use of glycosylation sites in the hypervariable region. Lastly, GP5 mutants were engineered where one of the signal peptide cleavage sites was blocked. Wildtype GP5 exhibited exactly the same SDS-PAGE mobility as the mutant that is cleavable at site 2 only. This indicates that the overwhelming majority of all GP5 molecules does not contain the “decoy epitope”.
THE ISOLATION OF MOUSE HEPATOCYTE GAP JUNCTIONS Preliminary Chemical Characterization and X-Ray Diffraction

A method is reported for isolating a preparation of hepatic gap junctions from the mouse. The method involves a collagenase digestion, treatment with the detergent Sarkosyl NL-97, and ultrasonication, followed by sucrose gradient nltracentrifugadon. A run with 36 animals yields 0.1-0.5 mg protein. Electron microscopy with thin-sectioning and negative staining techniques reveals that the final pellet is a very pure preparation of gap junctions, accompanied by a small amount of amorphous contamination. Polyacrylamide-gel electrophoresis of sodium dodecyl sulfate (SDS)-solubilized material shows one major protein in the junction, with an apparent tool wt of 20,000, and two minor components. Thin-layer chromatography demonstrates one major and one minor phospholipid, and some neutral lipid. Lowangle X-ray diffraction of wet and dried specimens show reflections which index on an 86 A center-to-center hexagonal lattice, corresponding closely to electron microscope data. Dried specimens also show a lamellar diffraction, corresponding to the total profile thickness of the junction (150 A).
WATER ABSORPTION AND TENSILE PROPERTIES OF KENAF BAST FIBER- PLASTICIZED POLY(LACTIC ACID) BIOCOMPOSITES

Increasing awareness on the environmental safety coupled with new rules and regulations has forced manufacturers to consider biodegradable materials for their products.The aim of this work was to investigate tensile properties and water absorption behavior of biocomposites from kenaf bast fiber and poly(lactic acid). The composites were prepared by Haake internal mixer and compression molding. Composites containing fiber loading up to 40 wt% were prepared. PLA is brittle and would result in composites with poor impact properties. Because of this, PLA was plasticized with polyethylene glycol (PEG) at 10 wt%, evaluated as the polymer matrix and referred to as p-PLA. p- PLA/KBF composites exhibited good tensile properties than unfilled p-PLA. The tensile strength and modulus of the composites increased with increasing fiber content due to high fiber-matrix compatibility. Reinforcing effect of KBF was observed when the fiber content exceeded 10 wt%. Scanning electron microscopy (SEM) of the tensile fractured surfaces revealed a very good adhesion between KBF and p-PLA matrix. In addition to fiber pullout, failure by fiber cell wall fibrillation was also observed. Water absorption behavior of p-PLA/KBF composites were studied by immersion in distilled water at room temperature for 60 days. All composites as well as unfilled p-PLA were found to exhibit non-Fickian behavior. The deviation from Fickian water uptake behavior was attributed to the development of microcracks on the surface and inside the composites. In addition to microcracks that occurred along the fiber length, water absorption too caused fiber-matrix debonding. Both were revealed via SEM examination on the surfaces of p- PLA/KBF composites. SEM examination too showed microcracks on the surface of p-PLA. Results suggested that KBF is a potential reinforcement for plasticized poly(lactic acid) composites but possible applications should avoid high humidity environment.