Miracle-dz/UniFAR-FTUs huggingface dataset:
Amino acid losses during hemodialysis with polyacrylonitrile membranes: effect of intradialytic amino acid supplementation on plasma amino acid concentrations and nutritional variables in nondiabetic patients.

BACKGROUND Malnutrition is highly prevalent in hemodialysis patients. Amino acid (AA) losses during the dialysis procedure may be a contributing factor. OBJECTIVES The objectives of this study were 1) to prospectively evaluate AA losses and their effect on plasma AA concentrations during dialysis with polyacrylonitrile at baseline and after administration of AAs by intradialysis and 2) to investigate the effects of intradialytic AA supplementation on nutritional status. DESIGN Seventeen stable patients without diabetes who were receiving hemodialysis were studied. In the first phase, AA losses were evaluated over 2 wk in 10 patients randomly assigned to receive AA supplementation. AA losses were analyzed during the first week without supplementation and during the second week with AA administration. In the second phase, the patients' nutritional status was investigated after 3 mo of AA supplementation and was compared with those in 7 patients not receiving AAs. RESULTS Mean +/- SD) AA losses during a 4-h dialysis session were 12 +/- 2 g; there was a significant decrease in plasma AA concentrations (386 +/- 298 micromol/L for essential and 902 +/- 735 micromol/L for nonessential AAs). After administration of AAs, the losses increased to 28 +/- 4 g. However, this procedure produced a positive net balance of AAs (10.6 +/- 5.6 g for total AAs), preventing a reduction in plasma concentrations. After 3 mo of AA administration, there was a significant increase in protein catabolic rate and serum albumin and transferrin. This improvement occurred without any change in the dialysis dose, ruling out the possibility that an increase in dialysis efficiency played a role. CONCLUSIONS Intradialysis adequately provides AA supplements, prevents reductions in plasma AA concentrations, and favorably affects the nutritional status of patients receiving hemodialysis.
Dengue virus inhibits interferon-α signaling by reducing STAT 2 expression

DDRC, Queen Mary’s School of Medicine and Dentistry, Newark Street, London E1 2AD, UK; Department of Pathology and Microbiology, University of Bristol, University Walk, Bristol BS8 1TD, UK; Department of Gastroenterology and Hepatology, University Hospital of Essen, Hufelandstr. 55, 45122 Essen, Germany; Centre for Hepatology, Royal Free & University College Medical School, Rowland Hill Street, London NW3 2PF, UK.
Association of Plasma Small-Molecule Intermediate Metabolites With Age and Body Mass Index Across Six Diverse Study Populations.

BACKGROUND Older age and obesity are associated with metabolic dysregulation; the mechanism by which these factors impact metabolism across the lifespan is important, but relatively unknown. We evaluated a panel of amino acids (AAs) and acylcarnitines (ACs) to identify effects of age and adiposity (body mass index) on circulating small-molecule metabolites in a meta-analysis of six diverse study populations. METHODS Targeted metabolic profiling was performed in six independent studies, representing 739 subjects with a broad range of age, body mass index, health states, and ethnic origin. Principal components analysis was performed on log-normalized values for AAs and ACs separately, generating one AC factor and two AA factors for each study. A common AC factor consisted primarily of acetylcarnitine, medium-chain AC, and several long-chain AC. AA Factor 1 consisted primarily of large neutral AAs. Glycine was its own factor. RESULTS Metabolic profiling and factor analysis identified clusters of related metabolites of lipid and AA metabolism that were consistently associated with age and body mass in a series of studies with a broad range of age, body mass index, and health status. An inverse association of glycine with body mass index and male gender supports its role as a marker of favorable metabolic health. CONCLUSIONS An important focus of future investigations should be to determine whether these clusters of metabolic intermediates are possible early predictors of health outcomes associated with body mass; are involved with accelerated aging; are involved in the causative pathway of aging; and how modification of these metabolic pathways impact the biology of aging.
Homocysteine concentration, related B vitamins, and betaine in pregnant women recruited to the Seychelles Child Development Study.

BACKGROUND Both folate and betaine are important predictors of total homocysteine (tHcy) during pregnancy. However, studies to date have only been undertaken in populations with Western dietary patterns. OBJECTIVE We investigated the predictors of tHcy in pregnant women recruited in the Seychelles, a population where access to fortified foods is limited and where women habitually consume diets rich in fish, eggs, rice, and fruit. DESIGN Pregnant women (n = 226) provided blood samples at enrollment, at week 28 of gestation, and at delivery. Cord blood was obtained from a subset of participants (n = 135). RESULTS As in other studies, maternal tHcy was lower during pregnancy than at delivery, whereas folate and vitamin B-12 status declined significantly to delivery. Despite low maternal folate status at delivery (median: 9.0 nmol/L), with 35% of women in the deficient range (serum folate: <6.8 nmol/L), cord blood folate status (median: 40.2 nmol/L) was similar to concentrations reported in Western populations. Folate was a significant predictor of tHcy at all time points (P < 0.001). In contrast with previous studies, betaine was only a significant predictor of maternal tHcy (P < 0.001) when the essential amino acid methionine was low. CONCLUSIONS The current study reports 2 important findings. First, fetal requirements for folate are paramount, such that cord blood folate status is maintained, even when maternal status is low. Second, betaine is a significant predictor of tHcy in pregnant women with low serum folate and low serum methionine concentrations.
Efficacy of boron neutron capture synovectomy in an animal model

Boron Neutron Capture Synovectomy (BNCS) proposes to use the 10B(n,(X) 7Li nuclear reaction to destroy inflamed synovium (a tissue lining articular joints) in Rheumatoid Arthritis patients. In a treatment, a boronated compound would be injected into the joint space and taken up by synovial cells. The joint would be irradiated with neutrons, inducing the boron neutron capture reaction with the potential of inducing cellular death in boron-loaded cells. The major goal of this thesis was to experimentally determine whether BNCS is effective in the ablation of arthritic synovium. This entailed neutron beam development and boron uptake characterization. Practical acceleratorbased neutron sources were designed to deliver a target dose of 10,000 RBE-cGy to the synovium in under 30 minutes. The highest in vivo synovial boron uptake was achieved after intra-articular injection of 150,000 ppm of '0B as K2B12H12; an average synovial boron concentration of 19,000 ppm for 30 minutes post-injection was obtained. In vivo uptake results were consistent with results from in vitro and ex vivo studies. Animal irradiations were performed using the tandem electrostatic accelerator at MIT LABA and a newly constructed target and beamline assembly. Synovial target doses ranging from 1,400 to 140,000 RBE-cGy were delivered to the knee joints of antigen-induced-arthritic rabbits. Synovial necrosis was observed at doses approximately 10,000 RBE-cGy and above. The delivery of doses below 10,000 RBE-cGy resulted in decreased synovial inflammation in all cases except one where necrosis was also observed. Thus, BNCS was demonstrated to be an effective means for the experimental ablation of synovial tissue. Lastly, a boron compound screening method, based on in vivo prompt gamma neutron activation analysis, was evaluated experimentally and via simulation. Thesis Supervisor: Jacquelyn C. Yanch Title: Associate Professor, Department of Nuclear Engineering Thesis Reader: Sonya Shortkroff Title: Research Associate, Harvard Medical School
Lead-free organic–inorganic tin halide perovskites for photovoltaic applications

Already exhibiting solar to electrical power conversion efficiencies of over 17%, organic–inorganic lead halide perovskite solar cells are one of the most promising emerging contenders in the drive to provide a cheap and clean source of energy. One concern however, is the potential toxicology issue of lead, a key component in the archetypical material. The most likely substitute is tin, which like lead, is also a group 14 metal. While organic–inorganic tin halide perovskites have shown good semiconducting behaviour, the instability of tin in its 2+ oxidation state has thus far proved to be an overwhelming challenge. Here, we report the first completely lead-free, CH3NH3SnI3 perovskite solar cell processed on a mesoporous TiO2 scaffold, reaching efficiencies of over 6% under 1 sun illumination. Remarkably, we achieve open circuit voltages over 0.88 V from a material which has a 1.23 eV band gap.
Structural and functional connectivity in children and adolescents with and without attention deficit/hyperactivity disorder

BACKGROUND Attention deficit/hyperactivity disorder (ADHD) has frequently been associated with changes in resting-state functional connectivity, and decreased white matter (WM) integrity. In the current study, we investigated functional connectivity within Default Mode and frontal control resting-state networks (RSNs) in children with and without ADHD. We hypothesized the RSNs of interest would show a pattern of impaired functional integration and segregation and corresponding changes in WM structure. METHODS Resting-state fMRI and diffusion-weighted imaging data were acquired from 35 participants with ADHD and 36 matched typically developing peers, aged 6 through 18 years. Functional connectivity was assessed using independent component analysis. Network topology and WM connectivity were further investigated using graph theoretical measures and tract-based spatial statistics (TBSS). RESULTS Resting-state fMRI analyses showed increased functional connectivity in right inferior frontal gyrus (IFG), and bilateral medial prefrontal cortex (mPFC) within the Default Mode and frontal control networks. Furthermore, a more diffuse spatial pattern of functional connectivity was found in children with ADHD. We found no group differences in structural connectivity as assessed with TBSS or graph theoretical measures. CONCLUSIONS Resting-state networks show a more diffuse pattern of connectivity in children with ADHD. The increases in functional connectivity in right IFG and bilateral mPFC in children with ADHD may reflect reduced or delayed functional segregation of prefrontal brain regions. As these functional changes were not accompanied by changes in WM, they may precede the development of the frequently reported changes in WM structure.
Molecular cross‐talk of IL‐6 in tumors and new progress in combined therapy

IL‐6, a cytokine activated by type I interferons (IFNs), is encoded by the IL‐6 gene, and secreted by T cells and macrophages. It serves many purposes in the human body and is significant to pathological and physiological activities, such as acute inflammatory responses, autoimmune diseases, and tumor formation. The wide range of IL‐6 actions on tumors rely on more than one specific pathway. Advances in modern research have determined that to fulfill its complex physiological functions, IL‐6 must be involved in cross‐talk with a number of other molecular pathways. Therefore, it is important to clarify the comprehensive pathway network associated with IL‐6 activity and to explore the mechanisms to inhibit its pathological activity in order to develop corresponding treatment plans. This study is a simple review of the pathological and physiological actions of IL‐6 on the human body. It explains in detail the molecular pathways involved in cross‐talk between IL‐6 and tumors, summarizing and discussing the latest progress made in IL‐6‐related internal medicine treatments in recent years, including chemotherapies, targeted therapies, and immunotherapies. Our results provide new insight into the treatment of tumors.
Creation of a Rodent Model of Abdominal Aortic Aneurysm by Blocking Adventitial Vasa Vasorum Perfusion

The adventitial vasa vasorum (VV) provides oxygen and nourishment to the aortic wall. Hypoxia in the aortic wall can cause enlarged abdominal aortic aneurysms (AAAs). This article introduces and describes a standard protocol used to induce AAAs through adventitial VV hypoperfusion created with a combination of polyurethane catheter insertion into the aortic lumen and suture ligation of the infrarenal abdominal aorta. The protocol involves the use of male rats weighing 300-400 g, which are provided food and water ad libitum. After laparotomy with a ventral midline abdominal incision, exfoliation of the aorta is performed, which blocks blood flow from the perivascular tissue. Aortotomy involving a small incision adjacent to the renal artery branches is performed, and a polyurethane catheter is inserted using an 18-gauge indwelling needle. After repairing the incision, tight ligation of the aorta over the catheter blocks VV blood flow from the proximal direction through the aortic wall without disturbing the aortic blood flow. This technique can induce an AAA with progressive aortic dilatation. The greatest benefit of this model is that VV hypoperfusion causes tissue hypoxia and the development of an infrarenal AAA, which has morphological and pathological characteristics similar to those of a human AAA.
Functional Characterization of Two M42 Aminopeptidases Erroneously Annotated as Cellulases

Several aminopeptidases of the M42 family have been described as tetrahedral-shaped dodecameric (TET) aminopeptidases. A current hypothesis suggests that these enzymes are involved, along with the tricorn peptidase, in degrading peptides produced by the proteasome. Yet the M42 family remains ill defined, as some members have been annotated as cellulases because of their homology with CelM, formerly described as an endoglucanase of Clostridium thermocellum. Here we describe the catalytic functions and substrate profiles CelM and of TmPep1050, the latter having been annotated as an endoglucanase of Thermotoga maritima. Both enzymes were shown to catalyze hydrolysis of nonpolar aliphatic L-amino acid-pNA substrates, the L-leucine derivative appearing as the best substrate. No significant endoglucanase activity was measured, either for TmPep1050 or CelM. Addition of cobalt ions enhanced the activity of both enzymes significantly, while both the chelating agent EDTA and bestatin, a specific inhibitor of metalloaminopeptidases, proved inhibitory. Our results strongly suggest that one should avoid annotating members of the M42 aminopeptidase family as cellulases. In an updated assessment of the distribution of M42 aminopeptidases, we found TET aminopeptidases to be distributed widely amongst archaea and bacteria. We additionally observed that several phyla lack both TET and tricorn. This suggests that other complexes may act downstream from the proteasome.
Cannabis use and adherence to antipsychotic medication: a systematic review and meta-analysis

Background Substance use may increase the risk of non-adherence to antipsychotics, resulting in negative outcomes in patients with psychosis. Method We aimed to quantitatively summarize evidence regarding the effect of cannabis use, the most commonly used illicit drug amongst those with psychosis, on adherence to antipsychotic medication. Studies were identified through a systematic database search. Adopting random-effects models, pooled odds ratios (OR) for risk of non-adherence to antipsychotic medications were calculated comparing: cannabis-users at baseline v. non-users at baseline; non users v. continued cannabis users at follow-up; non-users v. former users at follow-up; former users v. current users. Results Fifteen observational studies (n = 3678) were included. Increased risk of non-adherence was observed for cannabis users compared to non-users (OR 2.46, n = 3055). At follow-up, increased risk of non-adherence was observed for current users compared to non-users (OR 5.79, n = 175) and former users (OR 5.5, n = 192), while there was no difference between former users and non-users (OR 1.12, n = 187). Conclusions Cannabis use increases the risk of non-adherence and quitting cannabis use may help adherence to antipsychotics. Thus, cannabis use may represent a potential target for intervention to improve medication adherence in those with psychosis.
Gaps in the Cloud Cover? Comparing Extinction Measures in Spiral Disks

Dust in galaxies can be mapped either by the FIR/submillimeter emission, the optical or infrared reddening of starlight, or the extinction of a known background source. We compare two dust extinction measurements for a set of 15 sections in 13 nearby galaxies to determine the scale of the dusty interstellar medium (ISM) responsible for disk opacity: one using stellar reddening and the other a known background source. In our earlier papers, we presented extinction measurements of 29 galaxies, based on calibrated counts of distant background objects identified though foreground disks in Hubble Space Telescope WFPC2 images. For the 13 galaxies that overlap with the Spitzer Infrared Nearby Galaxies Survey, we now compare these results with those obtained from an I - L color map. Our goal is to determine whether or not a detected distant galaxy indicates a gap in the dusty ISM, and hence to better understand the nature and geometry of the disk extinction. We find that distant galaxies are predominantly in low-extinction sections marked by the color maps, indicating that their number depends both on the cloud cover of Spitzer-resolved dust structures, mostly the spiral arms, and a diffuse, unresolved underlying disk. We note that our infrared color map [E(I - L)] underestimates the overall dust presence in these disks severely because it implicitly assumes the presence of a dust screen in front of the stellar distribution.
Immunoglobulin A Protease Variants Facilitate Intracellular Survival in Epithelial Cells By Nontypeable Haemophilus influenzae That Persist in the Human Respiratory Tract in Chronic Obstructive Pulmonary Disease

Background Nontypeable Haemophilus influenzae (NTHi) persists in the airways in chronic obstructive pulmonary disease (COPD). NTHi expresses 4 immunoglobulin (Ig)A protease variants (A1, A2, B1, B2) with distinct cleavage specificities for human IgA1. Little is known about the different roles of IgA protease variants in NTHi infection. Methods Twenty-six NTHi isolates from a 20-year longitudinal study of COPD were analyzed for IgA protease expression, survival in human respiratory epithelial cells, and cleavage of lysosomal-associated membrane protein 1 (LAMP1). Results IgA protease B1 and B2-expressing strains showed greater intracellular survival in host epithelial cells than strains expressing no IgA protease (P < .001) or IgA protease A1 or A2 (P < .001). Strains that lost IgA protease expression showed reduced survival in host cells compared with the same strain that expressed IgA protease B1 (P = .006) or B2 (P = .015). IgA proteases B1 and B2 cleave LAMP1. Passage of strains through host cells selected for expression of IgA proteases B1 and B2 but not A1. Conclusions IgA proteases B1 and B2 cleave LAMP1 and mediate intracellular survival in respiratory epithelial cells. Intracellular persistence of NTHi selects for expression of IgA proteases B1 and B2. The variants of NTHi IgA proteases play distinct roles in pathogenesis of infection.
Neural dedifferentiation in relation to risk for Alzheimer's disease

NEURAL DEDIFFERENTIATION IN RELATION TO RISK FOR ALZHEIMER’S DISEASE Nathan C. Hantke, B.A. Marquette University, 2010 Functional magnetic resonance imaging (fMRI) research indicates that as an individual’s age increases, the task-related spatial extent of neural activation increases. This decrease in neural specificity, or dedifferentiation, is often demonstrated by older adults during challenging cognitive tasks. Cognitively intact individuals at-risk for Alzheimer’s disease (AD), as deemed by having an apolipoprotein-E e4 allele or a family history of AD, demonstrate increased fMRI activation as compared to individuals at lower risk. Using a low effort, high accuracy eventrelated semantic memory task involving the presentation of famous and non-famous names, we examined spatial neural specificity through a measure of dedifferentiation using fMRI. In particular, the goal was to look at degree of dedifferentiation between older healthy subjects with or without risk factors for AD. Our results indicated that while there was not a significant difference between the two groups on the total amount of neural dedifferentiation, there was a significant interaction between stimulus type and risk group. Individuals at-risk for AD displayed greater dedifferentiation for non-famous names yet greater differentiation (i.e., less dedifferentiation) for famous names as compared to the low-risk group. These findings may reflect disturbances in memory formation for individuals at-risk for AD.
Protein kinase CK2 and protein kinase D are associated with the COP9 signalosome

The COP9 signalosome (CSN) purified from human erythrocytes possesses kinase activity that phosphoryl ates proteins such as c‐Jun and p53 with consequence for their ubiquitin (Ub)‐dependent degradation. Here we show that protein kinase CK2 (CK2) and protein kinase D (PKD) co‐purify with CSN. Immunoprecipi tation and far‐western blots reveal that CK2 and PKD are in fact associated with CSN. As indicated by electron microscopy with gold‐labeled ATP, at least 10% of CSN particles are associated with kinases. Kinase activity, most likely due to CK2 and PKD, co‐immuno precipitates with CSN from HeLa cells. CK2 binds to ΔCSN3(111–403) and CSN7, whereas PKD interacts with full‐length CSN3. CK2 phosphorylates CSN2 and CSN7, and PKD modifies CSN7. Both CK2 and PKD phosphorylate c‐Jun as well as p53. CK2 phosphoryl ates Thr155, which targets p53 to degradation by the Ub system. Curcumin, emodin, DRB and resveratrol block CSN‐associated kinases and induce degradation of c‐Jun in HeLa cells. Curcumin treatment results in elevated amounts of c‐Jun–Ub conjugates. We conclude that CK2 and PKD are recruited by CSN in order to regulate Ub conjugate formation.
A tabletop instrument for manipulation of sound morphologies with hands, fingertips and upper-body

We present a musical instrument, named the Embodied Musical Instrument (EMI) which allows musicians to perform free gestures with the upper--body including hands and fingers thanks to 3D vision sensors, arranged around the tabletop. 3D interactive spaces delimit the boundaries in which the player performs metaphorical gestures in order to play with sound synthesis engines. A physical-based sound synthesis engine and a sampler have been integrated in the system in order to manipulate sound morphologies in the context of electro-acoustic and electronic composition.
Enhanced atrazine degradation is widespread across the United States.

BACKGROUND Atrazine (ATZ) has been a key herbicide for annual weed control in corn, with both a soil and post-emergence vegetation application period. Although enhanced ATZ degradation in soil with a history of ATZ use has been reported, the extent and rate of degradation in the US Corn Belt is uncertain. We show that enhanced ATZ degradation exists across much of the country. RESULTS Soils from 15 of 16 surveyed states had enhanced ATZ degradation. The average ATZ half-life was only 2.3 days in ATZ history soils, compared with an average 14.5 days in soils with no previous ATZ use, meaning that ATZ degrades an average 6 times faster in soils with previous ATZ use. CONCLUSION When ATZ is used for several years, enhanced degradation will undoubtedly change the way ATZ is used in agronomic crops and also its ultimate environmental fate. © 2017 Society of Chemical Industry.