Miracle-dz/UniFAR-FTUs huggingface dataset:
Complement Protein Isoforms in CSF as Possible Biomarkers for Neurodegenerative Disease

It has been suggested that the activation of the complement system is involved in the pathogenesis of several neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS). Here, the CSF expression levels of complement proteins C3b, C4b, factor B, and factor H were compared between normal subjects and patients diagnosed with AD, PD, MS, and neurosyphilis. The CSF proteins were initially separated using two-dimensional gel electrophoresis, which allowed the comparison of some of the individual complement isoforms. Patients with AD, PD, and MS all showed more than one complement isoform with a significant change (p < 0.05) in CSF expression level compared to normal subjects. PD patients were found to have the greatest number of significantly changed isoforms, all showing a decreased expression level in PD CSF. The complement isoforms examined were able to distinguish between some, but not all, of the diseases studied. The data suggest that when investigating a protein as a possible biomarker, it may be useful to compare individual protein isoform expression levels in addition to the more commonly measured total protein expression level.
Correlation of environmental carbaryl measurements with serum and urinary 1-naphthol measurements in a farmer applicator and his family.

In exposure or risk assessments, both environmental and biological measurements are often used. Environmental measurements are an excellent means for evaluating regulatory compliance, but the models used to estimate body burden from these measurements are complex. Unless all possible routes of exposure (i.e., inhalation, dermal absorption, ingestion) are evaluated, exposure to a toxicant can be underestimated. To circumvent this problem, measurements of the internal dose of a toxicant in blood, serum, urine, or tissues can be used singularly or in combination with environmental data for exposure assessment. In three separate laboratories, carbaryl or its primary metabolite, 1-naphthol, was measured in personal air, dermal samples, blood serum, and urine from farmer applicators and their families. The usefulness of both environmental and biological data has been demonstrated. For the farmer applicator, the environmental levels of carbaryl would have been sufficient to determine that an exposure had occurred. However, biological measurements were necessary to determine the absorbed dose of each member of the applicator's family. In addition, a correlation between serum and urinary 1-naphthol measurements has been shown; therefore, either matrix can be used to accurately evaluate occupational carbaryl exposure. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5. AFigure 5. B
Targeted mutagenesis of simian virus 40 DNA mediated by a triple helix-forming oligonucleotide

Triple-helical DNA can be formed by oligonucleotides that bind as third strands of DNA in a sequence-specific manner in the major groove in homopurine/homopyrimidine stretches in duplex DNA. Such triple helix-forming oligonucleotides have been used to inhibit gene expression by blocking transcription factor access to promoter sites in transient expression assays. In an alternative approach to genetic manipulation using triplex DNA, we show that triplex-forming oligonucleotides can be used to produce site-specific, targeted mutations in a viral genome in order to achieve a permanent, heritable effect on gene function and expression. We use a triplex-forming oligonucleotide linked to a psoralen derivative at its 5' end to achieve targeted mutagenesis in a simian virus 40 (SV40) vector genome. Site-specific triplex formation delivers the psoralen to the targeted site in the SV40 DNA. Photoactivation of the psoralen yields adducts and thereby mutations at that site. Mutations were produced in the target gene in over 6% of the viral genomes. DNA sequence analysis of the mutations in the target gene showed that all were in the targeted region, and 55% were found to be the same T:A-to-A:T transversion precisely at the targeted base pair. In control experiments, no mutagenesis above the background frequency in the assay was produced by a non-triplex-forming, psoralen-linked oligonucleotide unless a vast excess of this oligonucleotide was used, demonstrating the specificity of the targeted mutagenesis. This frequency of targeted mutagenesis of SV40 in monkey cells represents a 30-fold increase relative to similar experiments using lambda phage in bacteria, suggesting that fixation of the triplex-directed lesion into a mutation occurs more efficiently in mammalian cells. If the ability to reproducibly and predictably target mutations to sites in viral DNA in vitro by using modified oligonucleotides can be extended to DNA in vivo, this approach may prove useful as a technique for gene therapy, as a strategy for antiviral therapeutics, and as a tool for genetic engineering.
Phased LSTM: Accelerating Recurrent Network Training for Long or Event-based Sequences

Recurrent Neural Networks (RNNs) have become the state-of-the-art choice for extracting patterns from temporal sequences. Current RNN models are ill suited to process irregularly sampled data triggered by events generated in continuous time by sensors or other neurons. Such data can occur, for example, when the input comes from novel event-driven artificial sensors which generate sparse, asynchronous streams of events or from multiple conventional sensors with different update intervals. In this work, we introduce the Phased LSTM model, which extends the LSTM unit by adding a new time gate. This gate is controlled by a parametrized oscillation with a frequency range which require updates of the memory cell only during a small percentage of the cycle. Even with the sparse updates imposed by the oscillation, the Phased LSTM network achieves faster convergence than regular LSTMs on tasks which require learning of long sequences. The model naturally integrates inputs from sensors of arbitrary sampling rates, thereby opening new areas of investigation for processing asynchronous sensory events that carry timing information. It also greatly improves the performance of LSTMs in standard RNN applications, and does so with an order-of-magnitude fewer computes.
Effect of Dual-Tasking on Postural Control in Subjects With Nonspecific Low Back Pain

Study Design. Three factors mixed-design with 1 between-subject and 2 within-subject factors. Objective. To compare the main effects and interactions of postural and cognitive difficulty on quiet stance between subjects with and without nonspecific low back pain (LBP). Summary of Background Data. The interference between postural control and cognitive tasks depends on factors such as sensorimotor/cognitive integrity. Changes in peripheral sensory and muscular systems as well as cognitive processes have been observed in LBP patients. It was hypothesized that the effect of cognitive task on postural performance might be different in subjects with nonspecific LBP as compared with healthy individuals. To the authors’ knowledge this has not been investigated before. Methods. Postural stability was measured by center of pressure parameters while nonspecific LBP (n = 22) and healthy (n = 22) subjects randomly performed quiet standing task with 3 levels of difficulty (rigid-surface eyes open, rigid-surface eyes-closed, and foam-surface eyes-closed) in isolation or concurrently with an easy or difficult digits backward cognitive task. Results. Subjects with nonspecific LBP had less postural sway than healthy subjects, while postural sway decreased with increase in the level of cognitive difficulty. Nonspecific LBP and healthy subjects had larger postural sway at more difficult sensory conditions such as rigid-surface eyes-closed and foam-surface eyes-closed. The response to dual-tasking was not significantly different between the 2 groups. Conclusion. The dual-tasking did not change the postural performance of nonspecific LBP subjects with low level of pain and disability differently compared to healthy subjects.
Die Filling Characteristics of Metal Powders

Conclusions d'un groupe de travail ISO forme pour la recherche de procedures adequates en vue de la normalisation internationale de la determination des caracteristiques de remplissage des matrices par des poudres. Expose de deux methodes fournissant des evaluations utiles, mais pour un groupe limite de poudres metalliques
Targeting DNA-PKcs and ATM with miR-101 Sensitizes Tumors to Radiation

Background Radiotherapy kills tumor-cells by inducing DNA double strand breaks (DSBs). However, the efficient repair of tumors frequently prevents successful treatment. Therefore, identifying new practical sensitizers is an essential step towards successful radiotherapy. In this study, we tested the new hypothesis: identifying the miRNAs to target DNA DSB repair genes could be a new way for sensitizing tumors to ionizing radiation. Principal Findings Here, we chose two genes: DNA-PKcs (an essential factor for non-homologous end-joining repair) and ATM (an important checkpoint regulator for promoting homologous recombination repair) as the targets to search their regulating miRNAs. By combining the database search and the bench work, we picked out miR-101. We identified that miR-101 could efficiently target DNA-PKcs and ATM via binding to the 3′- UTR of DNA-PKcs or ATM mRNA. Up-regulating miR-101 efficiently reduced the protein levels of DNA-PKcs and ATM in these tumor cells and most importantly, sensitized the tumor cells to radiation in vitro and in vivo. Conclusions These data demonstrate for the first time that miRNAs could be used to target DNA repair genes and thus sensitize tumors to radiation. These results provide a new way for improving tumor radiotherapy.
Ursolic Acid-Induced Elevation of Serum Irisin Augments Muscle Strength During Resistance Training in Men

Ursolic acid (UA), a type of pentacyclic triterpenoid carboxylic acid purified from natural plants, can promote skeletal muscle development. We measured the effect of resistance training (RT) with/without UA on skeletal muscle development and related factors in men. Sixteen healthy male participants (age, 29.37±5.14 years; body mass index=27.13±2.16 kg/m2) were randomly assigned to RT (n=7) or RT with UA (RT+UA, n=9) groups. Both groups completed 8 weeks of intervention consisting of 5 sets of 26 exercises, with 10~15 repetitions at 60~80% of 1 repetition maximum and a 60~90-s rest interval between sets, performed 6 times/week. UA or placebo was orally ingested as 1 capsule 3 times/day for 8 weeks. The following factors were measured pre-and post-intervention: body composition, insulin, insulin-like growth factor-1 (IGF-1), irisin, and skeletal muscle strength. Body fat percentage was significantly decreased (p<0.001) in the RT+UA group, despite body weight, body mass index, lean body mass, glucose, and insulin levels remaining unchanged. IGF-1 and irisin were significantly increased compared with baseline levels in the RT+UA group (p<0.05). Maximal right and left extension (p<0.01), right flexion (p<0.05), and left flexion (p<0.001) were significantly increased compared with baseline levels in the RT+UA group. These findings suggest that UA-induced elevation of serum irisin may be useful as an agent for the enhancement of skeletal muscle strength during RT.
Role of Combination Chemotherapy with 5-Fluorouracil, Cisplatin and Paclitaxel for Advanced Gall Bladder Cancer

Aim: The prognosis for patients with advanced Gallbladder carcinoma is poor. Due to unresectability and relatively ineffective chemotherapy available, a need exists for effective chemotherapeutic regimen. The aim of this study was to determine the efficacy and safety profile of 5-fluorouracil, cisplatin and paclitaxel in patients with advanced Gallbladder cancer. Material and Methods: From January 2002 to July 2004, 40 patients of advanced carcinoma Gallbladder received 5-fluorouracil, cisplatin and paclitaxel. On day 1, paclitaxel was given (150 mg/m2), cisplatin was given on day 2 (50 mg/m2) and 5-fluorouracil was given from day 1 to day 3 (500 mg/m2). This cycle was repeated every three weeks and patient assessment was done. Results: Forty patients were enrolled in this study. Thirty-five were assessed for response. Five patients were lost in follow up. There were thirty females and ten males. A median of three cycles of treatment (range one to seven) was administered. Two patients achieved complete response and eleven had partial responses giving an overall response rate of 32.5% in the intention-to-treat population (95% confidence interval 11.1% to 46.5%). The median response duration was 5.3 months. The median time to progression and overall survival was 4.1 months and 11.2 months, respectively. The most common grade 3 adverse effects were neutropenia (30%), nausea (20%), vomiting (15%), diarrhea (10%), stomatitis (5%), and peripheral neuropathy (5%). Only one case had febrile neutropenia. There was no treatment related death. Conclusions: The combination of 5-fluorouracil, cisplatin and paclitaxel has promising anti-tumor activity and is well tolerated in patients with advanced and metastatic Gallbladder cancer.
MicroRNA expression profiles predictive of human renal allograft status

Immune rejection of organ transplants is a life-threatening complication and is exemplified by alterations in the expression of protein-encoding genes. Because microRNAs (miRNAs) regulate the expression of genes implicated in adaptive immunity, we investigated whether acute rejection (AR) is associated with alterations in miRNA expression within allografts and whether expression profiles are diagnostic of AR and predict allograft function. Seven of 33 renal allograft biopsies (12 AR and 21 normal) were profiled using microfluidic cards containing 365 mature human miRNAs (training set), and a subset of differentially expressed miRNAs were quantified in the remaining 26 allograft biopsies (validation set). We found a strong association between intragraft expression of miRNAs and messenger RNAs (mRNAs), and that AR, and renal allograft function, could be predicted with a high level of precision using intragraft levels of miRNAs. Our investigation of miRNA expression in normal human peripheral blood mononuclear cells (PBMCs) showed that miRNAs (miR-142–5p, -155, and -223) overexpressed in AR biopsies are highly expressed in PBMCs, and that stimulation with the mitogen phytohaemagglutinin results in an increase in the abundance of miR-155 and a decrease in miR-223 and let-7c. Quantification of miRNAs in primary cultures of human renal epithelial cells (HRECs) showed that miR-30a-3p, -10b, and let-7c are highly expressed in HRECs, and that stimulation results in a decreased expression of miR-30a-3p. Our studies, in addition to suggesting a cellular basis for the altered intragraft expression of miRNAs, propose that miRNA expression patterns may serve as biomarkers of human renal allograft status.
Protective Effect of the Energy Precursor Creatine Against Toxicity of Glutamate and β‐Amyloid in Rat Hippocampal Neurons

Abstract: The loss of ATP, which is needed for ionic homeostasis, is an early event in the neurotoxicity of glutamate and β‐amyloid (Aβ). We hypothesize that cells supplemented with the precursor creatine make more phosphocreatine (PCr) and create large energy reserves with consequent neuroprotection against stressors. In serum‐free cultures, glutamate at 0.5‐1 mM was toxic to embryonic hippocampal neurons. Creatine at >0.1 mM greatly reduced glutamate toxicity. Creatine (1 mM) could be added as late as 2 h after glutamate to achieve protection at 24 h. In association with neurotoxic protection by creatine during the first 4 h, PCr levels remained constant, and PCr/ATP ratios increased. Morphologically, creatine protected against glutamate‐induced dendritic pruning. Toxicity in embryonic neurons exposed to Aβ (25‐35) for 48 h was partially prevented by creatine as well. During the first 6 h of treatment with Aβ plus creatine, the molar ratio of PCr/ATP in neurons increased from 15 to 60. Neurons from adult rats were also partially protected from a 24‐h exposure to Aβ (25‐35) by creatine, but protection was reduced in neurons from old animals. These results suggest that fortified energy reserves are able to protect neurons against important cytotoxic agents. The oral availability of creatine may benefit patients with neurodegenerative diseases.
Effect of endometriosis on the protein expression pattern of follicular fluid from patients submitted to controlled ovarian hyperstimulation for in vitro fertilization.

BACKGROUND The aim of this study was to evaluate protein expression profile and quantify the proteins present in follicular fluid (FF) samples from women with endometriosis and pregnant women without endometriosis. METHODS A prospective case-control study was carried out including women with Stage III or IV endometriosis (Group I) and pregnant women without endometriosis (Group II), both at the maximum age of 35 years. Women were submitted to controlled ovarian stimulation for in vitro fertilization, and FF was collected after ultrasound-guided ovarian aspiration. FF from both ovaries was pooled, and patient samples were pooled according to Group I or II. Pooled protein samples were separated and analyzed by MudPIT (multidimensional protein identification technology followed by Expression(E) and label-free quantification with ProteinLynxGlobalServer 2.4v, Identity(E) and Expression(E) software). RESULTS A total of 416 proteins or randomic sequence were identified, 62 proteins differentially expressed between Groups I and II. One (1.6%) was expressed at a higher level and 36 (58.1%) were uniquely expressed in Group I, whereas 8 (12.9%) were expressed at a higher level and 17 (27.4%) were uniquely expressed in Group II. Of all these, 15 (24.2%) are related to binding, 1 (1.6%) to immune response, 8 (12.9%) to cell division, 3 (4.8%) to cellular metabolism, 16 (25.8%) to general function and 19 (30.6%) do not yet present an identified function. CONCLUSIONS Protein expression profiles of patients with and without endometriosis identified at least 64 proteins differentially expressed, which may be related to the physiopathology of endometriosis. These proteins may additionally be useful in determining potential biomarkers for diagnostics, as well as for therapeutic intervention in women with infertility due to endometriosis.
The Effect of Criticism on Functional Brain Connectivity and Associations with Neuroticism

Neuroticism is a robust personality trait that constitutes a risk factor for psychopathology, especially anxiety disorders and depression. High neurotic individuals tend to be more self-critical and are overly sensitive to criticism by others. Hence, we used a novel resting-state paradigm to investigate the effect of criticism on functional brain connectivity and associations with neuroticism. Forty-eight participants completed the NEO Personality Inventory Revised (NEO-PI-R) to assess neuroticism. Next, we recorded resting state functional magnetic resonance imaging (rsfMRI) during two sessions. We manipulated the second session before scanning by presenting three standardized critical remarks through headphones, in which the subject was urged to please lie still in the scanner. A seed-based functional connectivity method and subsequent clustering were used to analyse the resting state data. Based on the reviewed literature related to criticism, we selected brain regions associated with self-reflective processing and stress-regulation as regions of interest. The findings showed enhanced functional connectivity between the clustered seed regions and brain areas involved in emotion processing and social cognition during the processing of criticism. Concurrently, functional connectivity was reduced between these clusters and brain structures related to the default mode network and higher-order cognitive control. Furthermore, individuals scoring higher on neuroticism showed altered functional connectivity between the clustered seed regions and brain areas involved in the appraisal, expression and regulation of negative emotions. These results may suggest that the criticized person is attempting to understand the beliefs, perceptions and feelings of the critic in order to facilitate flexible and adaptive social behavior. Furthermore, multiple aspects of emotion processing were found to be affected in individuals scoring higher on neuroticism during the processing of criticism, which may increase their sensitivity to negative social-evaluation.
Police Powers, Regulatory Takings and the Efficient Compensation of Domestic and Foreign Investors

Modern international investment agreements have challenged the customary exclusion of public good regulations from being considered government ‘takings’ subject to compensation rules. Full compensation for regulatory takings can, however, lead to over-investment and excessive entry in risky industries. An alternative is to ‘carve-out’ apparently efficient regulation from compensation requirements. We design a carve-out/compensation rule that induces efficient regulation and firm-level investment even when the regulator suffers fiscal illusion and has private information about the social benefit from regulation. We also show that a carve-out reduces the subsidy to risky industry implicit in compensation rules, and thus mitigates the entry problem.
A comparison of the therapeutic efficacy and tolerability of etoricoxib and diclofenac in patients with osteoarthritis

SUMMARY Objective: To evaluate and compare the efficacy and tolerability of etoricoxib and diclofenac in patients with osteoarthritis of the knee or hip. Methods: In this 6-week double-blind, active comparator controlled, parallel-group study eligible osteoarthritis patients were randomised to receive either etoricoxib 60 mg once daily (n = 256) or diclofenac 50 mg three times daily (n = 260). The primary study endpoint was the Western Ontario McMaster osteoarthritis index (WOMAC) pain subscale. Other endpoints included were the WOMAC stiffness and physical function subscales, and the Patient's Global Assessment of Response to Therapy (PGART) questionnaire. Early efficacy was evaluated using WOMAC first question (pain walking on a flat surface) and PGART 4 h after the morning dose of each drug on days 1 and 2. Rescue medication (paracetamol) used was also recorded. The study was designed to show comparable efficacy between etoricoxib 60 mg once daily and diclofenac 50 mg three times daily with respect to the primary endpoint and was conducted outside the United States at 67 centres in 29 countries. Results: Etoricoxib (60 mg once daily) was comparable in efficacy to diclofenac (150 mg daily) on all the above parameters. The one exception was in the assessment of early efficacy where etoricoxib demonstrated significantly greater benefit within 4 h of taking the first dose on the first day of therapy (p = 0.007) as evaluated by the percentage of patients with good or excellent (PGART) responses. The treatment effects of both drugs were similar by the time day 2 was reached and were sustained throughout the 6 weeks of therapy. Both treatments were generally well tolerated. Conclusions: Etoricoxib is clinically effective in the therapy of osteoarthritis providing a magnitude of effect comparable to that of the maximum recommended daily dose of diclofenac. The onset of clinical benefit with etoricoxib on day one is more rapid than that of diclofenac. Both drugs were generally well tolerated.