Miracle-dz/UniFAR-FTUs huggingface dataset:
Arrest of afferent axon extension by target neurons in vitro is regulated by the NMDA receptor

Cerebellar granule neurons in vitro specifically arrest the extension of their appropriate presynaptic axons, mossy fibers. This “stop- growing signal” may be an essential step in the formation and specificity of synapses. Here, we have tested whether ionotropic glutamate receptors are involved in the stop-growing signal. When explants of basilar pontine nuclei, a mossy fiber source, were cultured on granule neurons, most pontine neurites terminated <200 microm from their explant of origin, a criterion for the stop-growing signal. In contrast, treatment with the NMDA antagonist D(-)-2-amino-5- phosphonopentanoic acid (D-AP5) greatly increased the number of pontine neurites extending beyond 300 microm, whereas treatment with NMDA reduced the number of pontine neurites extending beyond 200 microm. A non-NMDA agonist (AMPA) and antagonist (6-cyano-7-nitroquinoxaline-2,3- dione) did not alter pontine neurite lengths. None of these agents affected neurite outgrowth from pontine explants in the absence of granule neurons, nor did any agent affect the survival of granule neurons. These results indicate that NMDA and D-AP5 specifically perturb an interaction between axons and target cells necessary for the stop-growing signal, and that NMDA receptors are critical for the development of a major cerebellar afferent system. These findings also suggest that NMDA-sensitive refinement of axon arbors during later development may involve the direct regulation of axon extension by target neurons.
Hypoxia‐sensitive pathways in intestinal inflammation

Inflammatory bowel disease (IBD) is a common chronic intestinal disorder characterised by a loss of epithelial barrier function leading to the unregulated movement of luminal antigenic material into mucosal tissue with resultant inflammation. In IBD, multiple components of the inflammatory response lead to tissue hypoxia. Mucosal hypoxia leads to the inactivation of prolyl hydroxylase domain‐containing (PHD) enzymes, which in turn leads to the stabilisation of the hypoxia‐inducible factor (HIF), which induces the expression of barrier protective genes. Furthermore, pharmacological hydroxylase inhibition has been shown to be protective in colitis, at least in part through enhancing intestinal epithelial barrier function through HIF‐1‐dependent barrier‐protective gene expression. Therefore, targeting hypoxia‐sensitive pathways represents a new and promising therapeutic approach in IBD.
Glucose-Induced Changes in Gene Expression in Human Pancreatic Islets: Causes or Consequences of Chronic Hyperglycemia

Dysregulation of gene expression in islets from patients with type 2 diabetes (T2D) might be causally involved in the development of hyperglycemia, or it could develop as a consequence of hyperglycemia (i.e., glucotoxicity). To separate the genes that could be causally involved in pathogenesis from those likely to be secondary to hyperglycemia, we exposed islets from human donors to normal or high glucose concentrations for 24 h and analyzed gene expression. We compared these findings with gene expression in islets from donors with normal glucose tolerance and hyperglycemia (including T2D). The genes whose expression changed in the same direction after short-term glucose exposure, as in T2D, were considered most likely to be a consequence of hyperglycemia. Genes whose expression changed in hyperglycemia but not after short-term glucose exposure, particularly those that also correlated with insulin secretion, were considered the strongest candidates for causal involvement in T2D. For example, ERO1LB, DOCK10, IGSF11, and PRR14L were downregulated in donors with hyperglycemia and correlated positively with insulin secretion, suggesting a protective role, whereas TMEM132C was upregulated in hyperglycemia and correlated negatively with insulin secretion, suggesting a potential pathogenic role. This study provides a catalog of gene expression changes in human pancreatic islets after exposure to glucose.
Alternative investments are mean variance efficient and inflation hedger- fact or fiction?

Using NCRIEF farmland and timberland smoothed indices from the 1st quarter of 1992 to the 3rd quarter of 2012, we explore the mean-variance diversification features of both asset classes and find that farmland and timberland improve the portfolio choice of the investors due to their diversification characteristics. Empirical results from de-smoothed series, generated from smoothed series to overcome the autocorrelation problem, demonstrate a significant meanvariance diversification characteristic of farmland and timberland. During the period of market turmoil and high uncertainty both asset classes have the potential to increase (reduce) the return (risk) of a diversified traditional asset portfolio at a given level of risk (return). During inflationary periods, both asset classes are found to possess inflation hedging characteristics.
Genetics of Parkinson disease and other movement disorders.

PURPOSE OF REVIEW We will review the recent advances in the genetics of Parkinson disease and other movement disorders such as dystonia, essential tremor and restless legs syndrome (RLS). RECENT FINDINGS Mutations in VPS35 were identified as a novel cause of autosomal dominant Parkinson disease using exome sequencing. Next generation sequencing (NGS) was also used to identify PRRT2 mutations as a cause of paroxysmal kinesigenic dyskinesia (DYT10). Using a different technique, that is linkage analysis, mutations in EIF4G1 were implicated as a cause of Parkinson disease and mutations in SLC20A2 as a cause of familial idiopathic basal ganglia calcification. Furthermore, genome-wide association studies (GWAS) and meta-analyses have confirmed known risk genes and identified new risk loci in Parkinson disease, RLS and essential tremor. New models to study genetic forms of Parkinson disease, such as stem cell-derived neurons, have helped to elucidate disease-relevant molecular pathways, such as the molecular link between Gaucher disease and Parkinson disease. SUMMARY New genes have been implicated in Parkinson disease and other movement disorders through the use of NGS. The identification of risk variants has been facilitated by GWAS and meta-analyses. Furthermore, new models are being developed to study the molecular mechanisms involved in the pathogenesis of these diseases.
Targeting of Lectinlike Oxidized Low-Density Lipoprotein Receptor 1 (LOX-1) with 99mTc-Labeled Anti–LOX-1 Antibody: Potential Agent for Imaging of Vulnerable Plaque

Lectinlike oxidized low-density lipoprotein (LDL) receptor 1 (LOX-1), a cell surface receptor for oxidized LDL, has been implicated in vascular cell dysfunction related to plaque instability, which could be a potential target for an atherosclerosis imaging tracer. In this study, we designed and prepared 99mTc-labeled anti–LOX-1 monoclonal IgG and investigated its usefulness as an atherosclerosis imaging agent. Methods: Anti–LOX-1 monoclonal IgG and control mouse IgG2a were labeled with 99mTc after derivatization with 6-hydrazinonicotinic acid to yield 99mTc-LOX-1-mAb and 99mTc-IgG2a, respectively. Myocardial infarction–prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits (atherosclerosis model) and control rabbits were injected intravenously with these probes, and in vivo planar imaging was performed. At 24 h after the injection, the aortas were removed, and radioactivity was measured. Autoradiography and histologic studies were performed with serial aortic sections. Results: The level of 99mTc-LOX-1-mAb accumulation was 2.0-fold higher than the level of 99mTc-IgG2a accumulation in WHHLMI rabbit aortas, and the level of 99mTc-LOX-1-mAb accumulation in WHHLMI rabbit aortas was 10.0-fold higher than the level of 99mTc-LOX-1-mAb accumulation in control rabbit aortas. In vivo imaging clearly visualized the atherosclerotic aortas of WHHLMI rabbits. Autoradiography and histologic studies revealed that regional 99mTc-IgG2a accumulation was independent of the histologic grade of the lesions; however, regional 99mTc-LOX-1-mAb accumulation was significantly correlated with LOX-1 expression density and the vulnerability index. The highest level of 99mTc-LOX-1-mAb accumulation, expressed as {radioactivity in region of interest (Bq/mm2)/[injected radioactivity (Bq)/animal body weight (g)]} × 102, was found in atheromatous lesions (3.8 ± 1.1 [mean ± SD]), followed in decreasing order by fibroatheromatous lesions (2.0 ± 1.0), collagen-rich lesions (1.6 ± 0.8), and neointimal lesions (1.4 ± 0.7). Conclusion: The level of 99mTc-LOX-1-mAb accumulation in grade IV atheroma was higher than that in neointimal lesions or other, more stable lesions. Nuclear imaging of LOX-1 expression with 99mTc-LOX-1-mAb may be a useful means for predicting atheroma at high risk for rupture.
Real-Time Analysis for Memory Access in Media Processing SoCs: A Practical Approach

In shared-memory multi-processor systems on chip for media processing, the access to off-chip memory is often a critical resource. The memory channel is shared by a mix of streams with timing requirements at different levels. The streams are arbitrated in the memory access network. Some streams have to meet a hard deadline for each transaction; other streams have to meet task-level execution-time constraints, where task execution times depend on the service received when performing memory accesses. Earlier work has resulted in arbitration algorithms that provide the necessary balance between the different stream types, allowing aggressive system design with a high utilization of the memory access path. The next challenge is to provide real-time analysis in an early stage of system design. To address this challenge, this paper proposes a practical approach that combines proven analytical methods with fast simulations. The approach provides a design space from which to choose arbiter settings and buffer sizes for memory-communication buffers.
Contrast‐Carrying Liposomes Current Status

Seltzer SE. Contrast‐carrying liposomes: current status. Invest Radiol 1988;23:(Suppl 1):S122‐S125. The goal of recent research has been to encapsulate standard, water‐soluble radiographic contrast media (RCM) into liposomes, in order to direct them to reticuloendothelial tissues. Toward this end several varieties of contrast‐carrying liposomes (CCLs) have been prepared. Each of these has proven effective in opacifying the liver and spleen of animals on computed tomography (CT). The suitability of two new encapsulation techniques: (1) Microemulsification (MELs), and (2) Dehydration Rehydration Vesicles (DRVs), for CCL production has been explored recently. Each of these two new preparative techniques were valuable in the effort to “scale‐up” the CCL production process, leading to “pharmaceutically acceptable” preparation.
Detection of millimeter movements using ultrasonic ranging and precise time synchronization in wireless sensor networks

In this work, we present a wireless sensor network platform that detects two-dimensional movements with sub-millimeter accuracy in a controlled environment. This was achieved through the use of omnidirectional ultrasonic ranging, cross-correlation of ultrasonic pulses, and precise time synchronization between sensor nodes. The synchronization protocol is based on IEEE 1588, and was adapted for implementation in a wireless sensor network. Experiment results show that the sensor nodes can maintain a worst-case synchronization error of 1µs relative to the reference clock. This enables the system to detect movements with sub-millimeter accuracy, at initial distances of up to one meter between sensor nodes.
Management of hospital outbreaks of gastro-enteritis due to small roundstructured viruses.

Small round structured viruses (SRSVs, Norwalk-like viruses, NLVs) are the most common cause of outbreaks of gastro-enteritis in hospitals and also cause outbreaks in other settings such as schools, hotels, nursing homes and cruise ships. Hospital outbreaks often lead to ward closure and major disruption in hospital activity. Outbreaks usually affect both patients and staff, sometimes with attack rates in excess of 50%. For this reason, staff shortages can be severe, particularly if several wards are involved at the same time. SRSVs may be spread by several routes: faecal-oral; vomiting/aerosols; food and water. Viruses may be introduced into the ward environment by any of these routes and then propagated by person-to-person spread. In an outbreak setting, the diagnosis can usually be made rapidly and confidently on clinical and epidemiological grounds, particularly if vomiting is a prominent symptom. By the time an SRSV outbreak has been recognized at ward level, most susceptible individuals will have been exposed to the virus and infection control efforts must prioritize the prevention of spread of infection to other clinical areas bycontainment of infected/exposed individuals (especially the prevention of patient and staff movements to other areas), hand-hygiene and effective environmental decontamination. This report of the Public Health Laboratory Service Viral Gastro-enteritis Working Group reviews the epidemiology of outbreaks of infection due to SRSVs and makes recommendations for their management in the hospital setting. The basic principles which underpin these recommendations will also be applicable to the management of some community-based institutional outbreaks.
Acetaminophen Developmental Pharmacokinetics in Premature Neonates and Infants: A Pooled Population Analysis

Background The aim of this study was to describe acetaminophen developmental pharmacokinetics in premature neonates through infancy to suggest age-appropriate dosing regimens. Methods A population pharmacokinetic analysis of acetaminophen time–concentration profiles in 283 children (124 aged ≤ 6 months) reported in six studies was undertaken using nonlinear mixed-effects models. Neonates and infants were given either single or multiple doses of four different formulations: oral elixir, rectal solution, or triglyceride or capsular suppository. The median postnatal age of children younger than 6 months was 1 day (range, birth to 6 months), median postconception age was 40 weeks (range, 28–64 weeks), and median weight was 3.1 kg (range, 1.2–9.0 kg). Results Population pharmacokinetic parameter estimates and their variability (percent) for a one-compartment model with first-order input, lag time, and first-order elimination were as follows: volume of distribution, 66.6 l (20%); clearance, 12.5 l/h (44%); standardized to a 70-kg person using allometric “1/4 power” models. The volume of distribution decreased exponentially with a maturation half-life of 11.5 weeks from 109.7 l/70 kg at 28 weeks after conception to 72.9 l/70 kg by 60 weeks. Clearance increased from 28 weeks after conception (0.74 l · h−1 · 70 kg−1) with a maturation half-life of 11.3 weeks to reach 10.8 l · h−1 · 70 kg−1 by 60 weeks. The absorption half-life for the oral elixir preparation was 0.21 h (120%) with a lag time of 0.42 h (70%), but absorption was further delayed (2 h) in premature neonates in the first few days of life. Absorption half-life parameters for the triglyceride base and capsule suppositories were 0.80 h (100%) and 1.4 h (57%), respectively. The absorption half-life for the rectal solution was 0.33 h. Absorption lag time was negligible by the rectal route for all three formulations. The bioavailability of the capsule suppository relative to elixir decreased with age from 0.92 (22%) at 28 weeks after conception to 0.86 at 2 yr of age, whereas the triglyceride base decreased from 0.86 (35%) at 28 weeks postconception to 0.5 at 2 yr of age. The relative bioavailability of the rectal solution was 0.66. Conclusions A mean steady state target concentration greater than 10 mg/l at trough can be achieved by an oral dose of 25 mg · kg−1 · d−1 in premature neonates at 30 weeks’ postconception, 45 mg · kg−1 · d−1 at 34 weeks’ gestation, 60 mg · kg−1 · d−1 at term, and 90 mg · kg−1 · d−1 at 6 months of age. The relative rectal bioavailability is formulation dependent and decreases with age. Similar concentrations can be achieved with maintenance rectal doses of 25 (capsule suppository) or 30 (triglyceride suppository) mg · kg−1 · d−1 in premature neonates at 30 weeks’ gestation, increasing to 90 (capsule suppository) or 120 (triglyceride suppository) mg · kg−1 · d−1 at 6 months. These regimens may cause hepatotoxicity in some individuals if used for longer than 2–3 days.
IL‐35: A potential therapeutic target for controlling hepatitis B virus infection

Interleukin (IL)‐35, a recently identified cytokine of the IL‐12 family, is a potent immunosuppressive cytokine secreted by regulatory T (Treg) cells and the newly reported regulatory B (Breg) cells. IL‐35 functions as a crucial immunosuppressive factor in immune‐mediated diseases, and the predominant mechanism of suppression is its ability to suppress T cell proliferation and effector functions. The pathogenic processes of the non‐cytopathic hepatitis B virus (HBV) infection‐related liver diseases are immune‐mediated, including liver damage and viral control. It has been found that IL‐35 is detectable in peripheral CD4+ T cells in chronic HBV‐infected patients, whereas it is undetectable in healthy individuals. There is growing evidence that cytokine‐mediated immune responses play a pivotal role in determining the clinical outcome during HBV infection. It is particularly important to investigate the effects of IL‐35 in the immunopathogenesis of chronic HBV infection. In this study, the recent understanding of this issue is discussed.
IMBALANCE OF MHC CLASS I EXPRESSION IN 3LL TUMOUR CELLS

Cell lines and a clone established from the C57BL/6 (H‐2b) Lewis lung (3LL) tumour were previously characterized with respect to tumour growth and metastatic spread in vivo, and to the expression of a 3LL tumour‐specific antigen (3LL TA) using a monoclonal antibody raised in syngeneic mice immunized with 3LL cells. No correlation was observed between the presence of 3LL TA and the prevention of metastatic spread which suggests that the immune recognition of this tumour antigen requires the presence of a self H‐2 molecule absent from these tumour cells. Indeed, radioimmunoassay (RIA) and cytofluorometric analysis using specific monoclonal antibodies have shown that the H‐2Kb molecule was not expressed at the cell surface of all 3LL cell lines and clones, while the H‐2Db molecule was present at normal levels. This defect, which was not the consequence of a lack Of (32m expression, was accompanied by an absence or a marked reduction of the H‐2K mRNA level (which has been reversed in the M4 cell line by in vitro gamma interferon treatment), while the H‐2D class I gene was normally transcribed. Another defective transcription was also observed for a gene in the Tla region (gene 37). This low‘37’phenotype was corrected by in vitro treatment of the M4 cell line with gamma interferon, which indicates that this class I gene of the Qa/Tla region has an interferon response sequence in the promoter.
Randomized trial of a chlorhexidine mouthwash for alleviation of radiation-induced mucositis.

PURPOSE To determine whether a chlorhexidine mouthwash could alleviate radiation-induced oral mucositis. PATIENTS AND METHODS Patients scheduled to receive radiation therapy to include greater than one third of the oral cavity mucosa were selected for study. Following stratification, they were randomized in a double-blind manner to receive a chlorhexidine mouthwash or a placebo mouthwash. Both groups were then similarly evaluated for mucositis and mouthwash toxicity. RESULTS Twenty-five patients were randomized to receive the chlorhexidine mouthwash, while 27 received the placebo mouthwash. Treatment arms were well balanced. There was a trend for more mucositis and there was substantially more toxicity (eg, mouthwash-induced discomfort, taste alteration, and teeth staining) on the chlorhexidine arm. CONCLUSION In contrast to the prestudy hypothesis that a chlorhexidine mouthwash might provide benefit for patients receiving radiation therapy to the oral mucosa, this study provides strong evidence suggesting that a chlorhexidine mouthwash is detrimental in this clinical situation.
Functional characterization of Kv channel beta‐subunits from rat brain.

1. The potassium channel beta‐subunit from rat brain, Kv beta 1.1, is known to induce inactivation of the delayed rectifier channel Kv1.1 and Kv1.4 delta 1‐110. 2. Kv beta 1.1 was co‐expressed in Xenopus oocytes with various other potassium channel alpha‐subunits. Kv beta 1.1 induced inactivation in members of the Kv1 subfamily with the exception of Kv 1.6; no inactivation of Kv 2.1, Kv 3.4 delta 2‐28 and Kv4.1 channels could be observed. 3. The second member of the beta‐subunit subfamily, Kv beta 2, had a shorter N‐terminal end, accelerated inactivation of the A‐type channel Kv 1.4, but did not induce inactivation when co‐expressed with delayed rectifiers of the Kv1 channel family. 4. To test whether this subunit co‐assembles with Kv alpha‐subunits, the N‐terminal inactivating domains of Kv beta 1.1 and Kv beta 3 were spliced to the N‐terminus of Kv beta 2. The chimaeric beta‐subunits (beta 1/ beta 2 and beta 3/ beta 2) induced fast inactivation of several Kv1 channels, indicating that Kv beta 2 associates with these alpha‐subunits. No inactivation was induced in Kv 1.3, Kv 1.6, Kv2.1 and Kv3.4 delta 2‐28 channels. 5. Kv beta 2 caused a voltage shift in the activation threshold of Kv1.5 of about ‐10 mV, indicating a putative physiological role. Kv beta 2 had a smaller effect on Kv 1.1 channels. 6. Kv beta 2 accelerated the activation time course of Kv1.5 but had no marked effect on channel deactivation.
The toxic and stress responses of cultured human retinal pigment epithelium (ARPE19) and human glial cells (SVG) in the presence of triamcinolone.

PURPOSE To compare the cytotoxic effect of TA on human retinal pigment epithelium (ARPE19) and human glial (SVG) cells over a range of concentrations and durations of exposure. METHODS TA (0.01-1 mg/mL) or vehicle (benzyl alcohol, 0.025%) was added to the ARPE19 and SVG cultures on day 0 and then subsequently for 1, 3, or 5 days. The amount of cell proliferations with or without TA treatment was performed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. All samples were read in triplicate (n = 4 in all cases). c-Fos, c-jun, caspase-3, c-myc, and p53 expression was determined after TA treatments after 0, 10, 20, 30, 40, 50, 60, and 90 minutes. All results were analyzed with ANOVA. RESULTS TA (0.01-1 mg/mL) caused a significant reduction in ARPE19 cells that had been exposed to it for more than 1 day. Significant reductions in the number of SVG cells were observed as early as day 1 at 0.1 and 1 mg/mL TA. In general, the level of remaining SVG cells was less than that of the APRE19 cells over the 5 days. SVG cells appeared more susceptible to TA. Caspase-3 was elevated in both ARPE19 and SVG cells after TA treatment. c-Fos and c-jun expression was also increased in ARPE19 cells but not in SVG. The vehicle of TA had no effect, and there was no change in p53 or c-myc expression. CONCLUSIONS TA was cytotoxic to both SVG and ARPE19 cells, with higher efficacy on SVG. TA caused the activation of the caspase-3 pathway more readily than the cell-protective c-fos and c-jun pathways in SVG cells, making those cells more vulnerable than the ARPE19 cells. The results suggest that TA toxicity in one cell type may not reliably indicate its toxicity in other cells. Different cells within the retina may react to TA differently, or TA may cause changes in the gene expressions differentially with different concentrations of the same stimulus.