Miracle-dz/UniFAR-FTUs huggingface dataset:
Methylation Status of Imprinting Centers for H19/IGF2 and SNURF/SNRPN in Primate Embryonic Stem Cells

Embryonic stem cells (ESCs) hold promise for cell and tissue replacement approaches to treating human diseases based on their capacity to differentiate into a wide variety of somatic cells and tissues. However, long‐term in vitro culture and manipulations of ESCs may adversely affect their epigenetic integrity, including imprinting. We have recently reported aberrant biallelic expression of IGF2 and H19 in several rhesus monkey ESC lines, whereas SNRPN and NDN were normally imprinted and expressed predominantly from the paternal allele. The dysregulation of IGF2 and H19 that is associated with tumorigenesis in humans may result from improper maintenance of allele‐specific methylation patterns at an imprinting center (IC) upstream of H19. To test this possibility, we performed methylation analysis of several monkey ESC lines by genomic bisulfite sequencing. We investigated methylation profiles of CpG islands within the IGF2/H19 IC harboring the CTCF‐6 binding site. In addition, the methylation status of the IC within the promoter/exon 1 of SNURF/SNRPN known as the Prader‐Willi syndrome IC was examined. Our results demonstrate abnormal hypermethylation within the IGF2/H19 IC in all analyzed ESC lines, whereas the SNURF/SNRPN IC was differentially methylated, consistent with monoallelic expression.
Accumulation of Wildtype and ALS-Linked Mutated VAPB Impairs Activity of the Proteasome

Cellular homeostasis relies on a tight control of protein synthesis, folding and degradation, in which the endoplasmic reticulum (ER) quality control and the ubiquitin proteasome system (UPS) have an instrumental function. ER stress and aberrant accumulation of misfolded proteins represent a pathological signature of amyotrophic lateral sclerosis (ALS), a fatal paralytic disorder caused by the selective degeneration of motoneurons in the brain and spinal cord. Mutations in the ER-resident protein VAPB have been associated with familial forms of the disease. ALS-linked mutations cause VAPB to form cytoplasmic aggregates. We previously demonstrated that viral-mediated expression of both wildtype and mutant human VAPB (hVAPB) leads to an ER stress response that contributes to the selective death of motoneurons. However, the mechanisms behind ER stress, defective UPS and hVAPB-associated motoneuron degeneration remain elusive. Here, we show that the overexpression of wildtype and mutated hVAPB, which is found to be less stable than the wildtype protein, leads to the abnormal accumulation of ubiquitin and ubiquitin-like protein conjugates in non-human primate cells. We observed that overexpression of both forms of hVAPB elicited an ER stress response. Treatment of wildtype and mutated hVAPB expressing cells with the ER stress inhibitor salubrinal diminished the burden of ubiquitinated proteins, suggesting that ER stress contributes to the impairment of proteasome function. We also found that both wildtype and mutated hVAPB can associate with the 20S proteasome, which was found to accumulate at the ER with wildtype hVAPB or in mutant hVAPB aggregates. Our results suggest that ER stress and corruption of the proteasome function might contribute to the aberrant protein homeostasis associated with hVAPB.
Volumetric Gain of the Liver after Major Hepatectomy in Obese Patients: A Case-Matched Study in 84 Patients

Objective:The objective was to determine the liver volumetric recovering capacity and postoperative course after major hepatectomy in obese patients through a case-matched study. Background:In literature, the impact of obesity on liver recovering has been analyzed only indirectly in terms of morbimortality but never through volumetric assessment. Patients and Method:Between 2005 and 2011, 42 patients with body mass index (BMI) 30 or higher (Ob group) underwent major hepatectomy and were matched with 42 patients with BMI 25 or lower (NonOb group) on the magnitude of resection (number of resected segments ±1, remnant liver volume to total liver volume, RLV/TLV, ±5%). The RLV was measured on computed tomographic slices preoperatively and postoperatively at 1 month (RLV-1M) for all patients and within 3 to 12 months in 42 paired patients (median = 6 months, RLV-6M). Considering hepatomegaly in Ob group, RLV was also normalized to body weight (RLVBWR). The liver volumetric gain was expressed as a relative increase [(RLV-1M − RLV)/RLV] or increase in RLVBWR. Results:The Ob and NonOb groups were comparable regarding clinicopathological data, except for arterial hypertension (48% vs 19%; P = 0.005), mean steatosis (24% vs 10%; P = 0.03), and fibrosis incidence (33% vs 10%; P = 0.008). Ob group showed longer operative time and higher blood losses. There were no intergroup differences in liver failure (both 7.1%) and 90-day morbimortality. Despite comparable RLV/TLV (38.1% vs 37.7%; P = 0.13), the relative liver volumetric gain at 1 month was significantly lower in Ob group (+93% vs +115%; P = 0.002), as well as RLVBWR increase (+0.59% vs +0.79%; P < 0.001). The RLV-1M represented 66.2% of initial TLV in Ob group compared with 73.8% (P = 0.005) in NonOb group. This delay in relative volumetric gain persisted at 6 months (+105.4% vs +137.6%; P = 0.009), the RLV-6M representing 71.2% vs 82.4% of initial TLV (P = 0.014). Conclusions:In a methodologically robust trial in the first cohort reported up to date, the regenerative response in obese patients was comparatively slower based on their initial TLV or body weight.
Community-associated Methicillin-resistant Staphylococcus aureus in Pediatric Patients

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections increased from 2000 to 2003 in hospitalized pediatric patients in Houston. CA-MRSA was associated with greater illness than was infection with methicillin-susceptible strains. Children with CA-MRSA were younger and mostly African American. Of MRSA isolates, 4.5% had the inducible macrolide-lincosamide-streptogramin B phenotype.
Convolution Method for Time-Dependent Beach-Profile Response

A simple analytical solution is presented for approximating the time-dependent beach-profile response to severe storms. This solution is in the form of a convolution integral involving a time-varying erosion-forcing function and an exponential erosion-response function. The erosion-forcing function reflects changes in the nearshore water level and breaking wave height. In this paper, an idealized storm-surge hydrograph is considered from which an analytic solution is obtained for beach and dune erosion associated with severe storms such as hurricanes or northeasters. It is shown that for a given initial beach geometry and sediment size, the peak water level and the incipient breaking wave height determine the maximum erosion potential that would be achieved if the beach were allowed to respond to equilibrium. Because of the assumed exponential erosion rate, beach response obtained from the convolution method is found to lag the erosion forcing in time, and is damped relative to the maximum erosion potential such that only a fraction of the equilibrium response actually occurs.
Costs of Bloodstream Infections Caused by Escherichia coli and Influence of Extended-Spectrum-β-Lactamase Production and Inadequate Initial Antibiotic Therapy

ABSTRACT Escherichia coli is the leading cause of bloodstream infections (BSIs) caused by Gram-negative bacteria. The increasing prevalence of antibiotic-resistant E. coli strains, particularly those producing extended-spectrum β-lactamases (ESBLs), increases the odds that empirically prescribed antimicrobial therapy for these infections will be inadequate, but the economic impact of this risk has not been fully evaluated. In the present retrospective 1-year analysis of 134 consecutive E. coli BSIs in our hospital, we explored the clinical and economic impacts of (i) inadequate initial antimicrobial treatment (IIAT) (i.e., empirical treatment with drugs to which the isolate had displayed in vitro resistance) of these infections and (ii) ESBL production by the bloodstream isolate. Cost data were obtained from the hospital accounting system. Compared with the 107 (79.8%) adequately treated patients, the 27 (20.1%) who received IIAT had a higher proportion of ESBL BSIs (74.0% versus 15.8%), longer (+6 days) and more costly (+EUR 4,322.00) post-BSI-onset hospital stays, and higher 21-day mortality rates (40.7% versus 5.6%). Compared with the 97 non-ESBL infections, the 37 (27.6%) ESBL BSIs were also associated with longer (+7 days) and more costly (+EUR 5,026.00) post-BSI-onset hospital stays and increased 21-day mortality (29.7% versus 6.1%). These findings confirm that the hospital costs and mortality associated with E. coli BSIs are significantly increased by ESBL production and by IIAT.
Risedronate prevents bone loss in breast cancer survivors: a 2-year, randomized, double-blind, placebo-controlled clinical trial.

PURPOSE Limited data are available on the efficacy of oral bisphosphonate therapy in breast cancer survivors. Our goal was to examine prevention of breast cancer-related bone loss in this cohort. PATIENTS AND METHODS Eighty-seven postmenopausal women after chemotherapy for breast cancer were randomly assigned to once-weekly risedronate 35 mg or placebo for 24 months. Outcomes included bone mineral density (BMD) and turnover markers. RESULTS At study initiation, 13% of patients were on an aromatase inhibitor (AI). After 24 months, there were differences of 1.6 to 2.5% (P < .05) at the spine and hip BMD between the placebo and risedronate groups. At study completion, 44% were on an AI. Adjusting for an AI, women on placebo plus AI had a decrease in BMD of (mean +/- SE) 4.8% +/- 0.8% at the spine and 2.8% +/- 0.5% at the total hip (both P < .001). In women on risedronate + AI, the spine decreased by 2.4% +/- 1.1% (P < .05) and was stable at the hip. Women in the placebo group not on an AI, maintained BMD at the spine, and had a 1.2% +/- 0.5% loss at the total hip (P < .05). Women who received risedronate but no AI had the greatest improvement in BMD of 2.2% +/- 0.9% (P < .05) at the total hip. Bone turnover was reduced with risedronate. There were no differences in adverse events between the groups. CONCLUSION We conclude that in postmenopausal women with breast cancer with or without AI therapy, once-weekly oral risedronate was beneficial for spine and hip BMD, reduced bone turnover, and was well tolerated.
Dual-structure Data Center Multicast Using Software Defined Networking

Data center applications use multicast as an effective method to reduce bandwidth cost. However, traditional multicast protocols designed for IP networks are usually bottlenecked by the limited state capacity on switches. In this paper, we propose a scalable multicast solution on fat tree networks based on the observation that data center multicast traffic has strong heterogeneity. We propose to remove the multicast management logic from switches and use the SDN controller to manage multicast groups. The proposed Dual-structure Multicast (DuSM) determines elephant and mice groups according to their traffic amounts and treats them separately. For each elephant group, the controller installs multicast state to maintain multiple shared trees and the group traffic will be balanced evenly among the trees to avoid congestion. For mice groups, the controller applies state-free mutlicast that trades bandwidth capacity for state capacity, such as multicast-to-unicast translation. Our experiments using real multicast traffic data show that the number of groups DuSM supports can be 300% of that of IP multicast. DuSM also achieves traffic balance among links.
Application of wavelet denoising to improve compression efficiency while preserving integrity of digital micrographs

Modern microscopy methods require efficient image compression techniques owing to collection of up to thousands of images per experiment. Current irreversible techniques such as JPEG and JPEG2000 are not optimized to preserve the integrity of the scientific data as required by 21 CFR part 11. Therefore, to construct an irreversible, yet integrity‐preserving compression mechanism, we establish a model of noise as a function of signal in our imaging system. The noise is then removed with a wavelet shrinkage algorithm whose parameters are adapted to local image structure. We ascertain the integrity of the denoised images by measuring changes in spatial and intensity distributions of registered light in the biological images and estimating changes of the effective microscope MTF. We demonstrate that the proposed denoising procedure leads to a decrease in image file size when a reversible JPEG2000 coding is used and provides better fidelity than irreversible JPEG and JPEG2000 at the same compression ratio. We also demonstrate that denoising reduces image artefacts when used as a pre‐filtering step prior to irreversible image coding.
Automated Algorithm for J-Tpeak and Tpeak-Tend Assessment of Drug-Induced Proarrhythmia Risk

Background Prolongation of the heart rate corrected QT (QTc) interval is a sensitive marker of torsade de pointes risk; however it is not specific as QTc prolonging drugs that block inward currents are often not associated with torsade. Recent work demonstrated that separate analysis of the heart rate corrected J-Tpeakc (J-Tpeakc) and Tpeak-Tend intervals can identify QTc prolonging drugs with inward current block and is being proposed as a part of a new cardiac safety paradigm for new drugs (the “CiPA” initiative). Methods In this work, we describe an automated measurement methodology for assessment of the J-Tpeakc and Tpeak-Tend intervals using the vector magnitude lead. The automated measurement methodology was developed using data from one clinical trial and was evaluated using independent data from a second clinical trial. Results Comparison between the automated and the prior semi-automated measurements shows that the automated algorithm reproduces the semi-automated measurements with a mean difference of single-deltas <1 ms and no difference in intra-time point variability (p for all > 0.39). In addition, the time-profile of the baseline and placebo-adjusted changes are within 1 ms for 63% of the time-points (86% within 2 ms). Importantly, the automated results lead to the same conclusions about the electrophysiological mechanisms of the studied drugs. Conclusions We have developed an automated algorithm for assessment of J-Tpeakc and Tpeak-Tend intervals that can be applied in clinical drug trials. Under the CiPA initiative this ECG assessment would determine if there are unexpected ion channel effects in humans compared to preclinical studies. The algorithm is being released as open-source software. Trial Registration NCT02308748 and NCT01873950
FPGA IMPLEMENTATION OF A VEDIC CONVOLUTION ALGORITHM

In digital signal processing convolution is a fundamental computation that is ubiquitous in many application areas. In order to compute convolution of long sequence, Overlap-Add method (OLA) and Overlap-Save method (OLS) methods are employed. In this paper, block convolution process is proposed using a multiplier architecture based on vertical and crosswise algorithm of Ancient Indian Vedic Mathematics and embedding it in OLA method for reducing calculations.And as the vedic multiplier is been used it is named as Vedic convolution algorithm.The coding is done in VHDL (Very High Speed Integrated Circuits Hardware Description Language) for the FPGA , as it is being increasingly used for variety of computationally intensive
Stratigraphic Variations Beneath Lunar Mare Surfaces as Indicated by Ejecta Characteristics of 0.5 to 2 KM Craters

AS INDICATED BY EJECTA CHARACTERISTICS OF 0.5 TO 2 KM CRATERS: R.A. Young, W.J. Brennan, and D.J. Nichols, Department of Geological Sciences, SUNY, Geneseo, New York, 14454. The increasing evidence for the complex volcanic history of the lunar maria (1,2,3) and of the rapid decrease in impact flux prior to and during mare flooding (4) suggests the following: 1) the maria were almost certainly filled by a series of volcanic flows of different thicknesses and dimensions, 2) during this time interval some of the circular maria must have been undergoing tectonic adjustments and may at first have looked much like Mare Orientale, and 3) the rapidly decreasing impact flux probably formed variable thicknesses of regolith and ejecta deposits on each new extrusive sequence. The gradual filling of the lunar maria would have proceeded so that: 1) the lowest depressions within the maria were probably filled first, producing larger, more level, uniform surfaces for younger deposits, and 2) the later stages of filling were characterized, in part, by more extensive, thinner flows which could have covered increasingly wider regions. The filling of initially uneven areas over different time intervals by flows of varying thicknesses and areal dimensions would give rise to basically different stratigraphic sequences in different regions (within or between individual maria). Each mare region must therefore be underlain by a different sequence consisting of layered flows, ejecta from large impacts, and regolith zones formed between episodes of volcanism. Postmare impacts which penetrated these different regional stratigraphic sequences should have produced exposures of layering in crater walls and ejecta deposits characteristic of each subsurface stratigraphic section. It appears that for craters larger than a few kilometers in diameter, the effect of the impact process on the "typical" mare stratigraphic sequence has been to homogenize the ejected debris to the extent that differences between crater ejecta blankets are not always obvious. In addition, the fractured nature of the crater wall materials makes tracing of individual layers for extended distances difficult. The uniformity of the ejecta deposits may be the result of impact penetration through many layers which are thin in comparison with the crater dimensions. Recent Apollo panoramic photography (with resolution approaching 10 meters) provides the first extensive lunar coverage which permits uniform, detailed regional comparisons of crater ejecta characteristics for craters in the 0.5 to 2 km diameter size range (see Figure 1). Since these small craters represent penetrations of a smaller number of subsurface stratigraphic units, their ejecta deposits would be more likely to show differences resulting from excavation of only a few, possibly dissimilar near-surface units.
Analysis of Linear Growth Using a Mathematical Model

ABSTRACT. According to the “ICP‐growth model” (ICP=Infancy, Childhood and Puberty components), linear growth during the first three years of life can be represented mathematically by a combination of a sharply decelerating Infancy component and a slowly decelerating Childhood component. Growth as measured by supine length is analysed for 191 longitudinally followed healthy infants using this model. The main aim is to devise ICP‐based methods for biological and clinical applications. The onset of the Childhood component, which occurs some time between 6 and 12 months of age and is typically abrupt, can be detected on an individual basis. Its starting point probably defines the as yet unknown age at which growth hormone begins to exert a significant influence. The analyses have also revealed some new facets of linear growth. Most infants are found to have a non‐linear decelerating Infancy component, free from seasonal influence. Age at onset of the Childhood component is earlier for girls than for boys and is positively related to the magnitude of the Infancy component. During the second year of life the variation in growth rate of the cohort increases. This fluctuation is found to be seasonal and greater for those with late onset of the Childhood component. During the third year of life the growth pattern is stabilized.
Emergence of gentamicin-resistant bacteremia in hemodialysis patients receiving gentamicin lock catheter prophylaxis.

BACKGROUND AND OBJECTIVES Antibiotic locks in catheter-dependent chronic hemodialysis patients reduce the rate of catheter-related blood stream infections (CRIs), but there are no data regarding the long-term consequences of this practice. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Over a 4-year period, from October 1, 2002, to September 30, 2006, we initiated a gentamicin and heparin lock (GHL) protocol in 1410 chronic hemodialysis patients receiving dialysis through a tunneled catheter in eight outpatient units. RESULTS Within the first year of the GHL protocol, our CRI rate decreased from 17 to 0.83 events per 1000 catheter-days. Beginning 6 months after initiation of the GHL protocol, febrile episodes occurred in 13 patients with coagulase-negative Staphylococcus bacteremia resistant to gentamicin. Over the 4 years of GHL use, an additional 10 patients developed 11 episodes of gentamicin-resistant CRI (including 7 with Enterococcus faecalis), in which there were 4 deaths, 2 cases of septic shock requiring intensive care unit admission, and 4 cases of endocarditis. Because of these events, the GHL protocol was discontinued at the end of 2006. CONCLUSIONS Although the use of GHL effectively lowered the CRI rate in our dialysis population, gentamicin-resistant CRIs emerged within 6 months. Gentamicin-resistant infections are a serious complication of the long-term use of GHLs. Alternative nonantibiotic catheter locks may be preferable to decrease the incidence of CRIs without inducing resistant pathogens.
Hepatitis C Virus RNA Strands Detection in Peripheral Blood Mononuclear Cells Legitimizes Virus Eradication in Negative Serum PCR Naïve and Post-treatment Patients

Abstract Background and Aims: Hepatitis C virus (HCV) hepatotropism is associated with intra-peripheral blood mononuclear cell (PBMC) infection that causes post-treatment relapse in RNA seronegative patients. Our understanding of the association of non-viremic hepatic fibrosis with positive anti-HCV IgG antibodies and active hepatocellular damage might be increased by PBMCs screening for intracellular infection. Thus, the goals of this study included evaluation of PBMCs PCR for diagnosing HCV infection, addressing PBMCs plus serum real-time (SRT) PCR benefits over SRT-PCR alone, studying intra-PBMCs distribution of RNA sense and antisense strands, and identifying treatment feasibility in solitary intracellular infection. Methods: Enzyme-linked immunosorbent assay, SRT-PCR and PBMCs PCR were used to evaluate HCV infection in 401 subjects. The patients were classified into groups of negative controls (n = 30), positive controls (n = 63), non-viremia post-treatment (experienced; n = 166) and naïve (n = 49) cases, and non-viremia positive PBMCs PCR naïve (n = 35) and experienced (n = 58) patients. Results: The diagnosis of true positive and negative by PBMCs PCR and SRT-PCR had 100% and 96.7% compatibility respectively. PBMCs PCR detected intracellular HCV infection in 49 out of 215 non-viremia patients; among them, naïve cirrhotics had significantly higher number of intracellular infection than the naïve non-cirrhotic (p < 0.001) and experienced patients (p < 0.0001). Antisense and sense strands were respectively recognized in naïve and experienced cases (p = 0.01218). Intracellular HCV strands were detected in 18.02% of experienced patients. Recognition of intracellular RNA strands showed significant decline in experienced compared to naïve patients (p < 0.05). Conclusion: PBMCs PCR is a valid diagnostic test that can diagnose intracellular HCV when SRT-PCR is negative. Antisense and sense strands are respectively recognized more often in naïve and experienced patients. The expected overall relapsing rate in our cohort was 18.02%. Intra-PBMC infections are associated with liver cirrhosis in naïve non-viremia patients. Eradication of intracellular strands is recommended to avoid RNA seroconversion. Ethical approval certificate: Registration number 10231.