Miracle-dz/UniFAR-FTUs huggingface dataset:
TSPAN8 Expression Distinguishes Spermatogonial Stem Cells in the Prepubertal Mouse Testis

ABSTRACT Precise separation of spermatogonial stem cells (SSCs) from progenitor spermatogonia that lack stem cell activity and are committed to differentiation remains a challenge. To distinguish between these spermatogonial subtypes, we identified genes that exhibited bimodal mRNA levels at the single-cell level among undifferentiated spermatogonia from Postnatal Day 6 mouse testes, including Tspan8, Epha2, and Pvr, each of which encode cell surface proteins useful for cell selection. Transplantation studies provided definitive evidence that a TSPAN8-high subpopulation is enriched for SSCs. RNA-seq analyses identified genes differentially expressed between TSPAN8-high and -low subpopulations that clustered into multiple biological pathways potentially involved in SSC renewal or differentiation, respectively. Methyl-seq analysis identified hypomethylated domains in the promoters of these genes in both subpopulations that colocalized with peaks of histone modifications defined by ChIP-seq analysis. Taken together, these results demonstrate functional heterogeneity among mouse undifferentiated spermatogonia and point to key biological characteristics that distinguish SSCs from progenitor spermatogonia.
International Journal of Copd Dovepress Copd Exacerbations by Disease Severity in England

hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms Objectives: Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with accelerated disease progression and are important drivers of health care resource utilization. The study aimed to quantify the rates of COPD exacerbations in England and assess health care resource utilization by severity categories according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2013. Methods: Data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics were used to identify patients with a COPD diagnosis aged $40 years. Those with complete spirometric, modified Medical Research Council Dyspnea Scale information, and exacerbation history 12 months prior to January 1, 2011 (index date) were classified into GOLD severity groups. Study outcomes over follow-up (up to December 31, 2013) were exacerbation rates and resource utilization (general practitioner visits, hospital admissions). Mean age at diagnosis was 66 years and 52.0% were male. Annual exacerbation rates per person-year increased with severity, from 0.83 (95% confidence interval [CI]: 0.81–0.85) for GOLD A to 2.51 (95% CI: 2.47–2.55) for GOLD D. General practitioner visit rates per person-year also increased with severity, from 4.82 (95% CI: 4.74–4.93) for GOLD A to 7.44 (95% CI: 7.31–7.61) for GOLD D. COPD-related hospitalization rates per person-year increased from less symptoms (GOLD Conclusion: Patients in the most severe category (GOLD D) experienced nearly three times the number of exacerbations and COPD-related hospitalizations as those in the least severe category (GOLD A), in addition to increased general practitioner visits. Better patient management to stabilize the disease progression could allow for an improvement in exacerbation frequency and a reduction in health care resource utilization.
Infection Salmonella Subsets During Acute Differential Involvement of Dendritic Cell

2 Within murine CD11c 1 dendritic cells (DC), CD8 a 1 , CD8 a 2 CD4 1 , and CD8 a 2 CD4 2 subsets are deﬁned. This study charac-terized the localization, number, and function of these subsets during acute Salmonella typhimurium infection. Immunohistochemical and ﬂow cytometric analyses of spleens from mice orally infected with virulent S. typhimurium revealed that in situ redistribution and alteration in the absolute number and function of DC occurred in a subset-speciﬁc manner during infection. CD8 a 2 CD4 1 DC present at B cell follicle borders in the spleen of naive mice were absent 5 days post- Salmonella infection, despite no overall change in the absolute number of CD8 a 2 CD4 1 splenic DC. CD8 a 1 and CD8 a 2 CD4 2 DC were prominently associated with the red pulp, and the frequency of these cells increased strikingly 5 days post- Salmonella infection. Signiﬁcant quantitative increases in both CD8 a 1 and CD8 a 2 CD4 2 subsets were associated with the in situ redistribution. Examination of Salmonella infected TAP1 2 / 2 / b 2 -microglobulin 2 / 2 mice, which lack CD8 a 1 T cells, conﬁrmed the differential subset-speciﬁc modulations in the DC populations both in situ and quantitatively. Ex vivo intracellular cytokine analysis showed signiﬁcantly increased frequencies of CD8 a 1 DC producing TNF- a at days 2 and 5 postinfection. In contrast, CD4 1 DC producing TNF- a were transiently increased followed by a signiﬁcant reduction. No signiﬁcant increase in IL-12p40 or IL-10 production by splenic DC was detected during the ﬁrst 5 days post- S. typhimurium infection. Together these data reveal differential modulation of splenic DC subsets with regard to organization, number, and cytokine production during the course and 7AAD were included in all stainings. Cells were then ﬁxed with 2% paraformaldehyde in PBS and washed in permeabilization buffer (HBSS containing 0.5% saponin and 0.5% BSA (Sigma)). Intracellular cytokines were detected by addition of biotinylated mAbs followed by streptavidin-allophycocyanin diluted in permeabiliza- tion buffer. After ﬁnal washes, cells were resuspended in wash buffer and analyzed by four-color ﬂow cytometry. In some samples, the ﬂuoro- chromes used to detect surface markers and cytokines were reversed to conﬁrm the integrity of the detection and acquisition. All samples were acquired using a FACSCalibur ﬂow cytometer (Bec-ton Dickinson, Mountain View, CA) and were analyzed using CellQuest software (Becton Dickinson). In surface phenotype studies at least 15,000 viable CD11c 1 events were collected per sample. For intracellular cyto- kine analysis at least 10,000 viable CD11c 1 events were collected per sample.
No significant improvement in the outcome of patients with Waldenström's macroglobulinemia treated over the last 25 years

The treatment of Waldenström's macroglobulinemia (WM) has changed over the last decades, mainly because of the introduction of nucleoside analogues and of rituximab while novel agents such as bortezomib have been recently introduced. We performed an analysis to investigate whether the outcome of patients with WM has improved over the last years, compared to that of patients who started treatment before new drugs became widely available, especially as part of the frontline treatment. We analyzed 345 symptomatic patients with WM: 130 who initiated treatment before and 215 who started treatment after January 1, 2000. Patients who started treatment in the latter group were older and had more often elevated beta2‐microglobulin but the other characteristics were similar between the two groups. Most patients who started treatment before January 1, 2000 were treated upfront with alkylating agent‐based regimens and most patients who started treatment after January 1, 2000 received rituximab‐based regimens as initial treatment. Objective response (63 and 59%, respectively) and median overall survival, OS, (106.5 months for Group A and is estimated at 94 months for Group B, P = 0.327) were similar. There was also no difference regarding OS or cause specific survival (CSS) in each risk group according to IPSSWM. Our observation may be explained by the indolent course of WM in several patients and by the lack of profound cytoreduction in patients with high‐risk disease. Possible differences in the 15‐ or 20‐year survival rate between the two groups may be detected with further follow‐up of these patients. Am. J. Hematol. 2011. © 2011 Wiley‐Liss, Inc.
Metformin powder formulation compared to metformin tablets on glycemic control and on treatment satisfaction in subjects with type 2 diabetes mellitus

The aim of this study was to evaluate if the new metformin powder formulation improves the treatment satisfaction in patients with type 2 diabetes, in a case‐control clinical trial. We enrolled 602 subjects in therapy with metformin in tablets formulation and instructed them to take the same dose of metformin in the new powder formulation. At baseline, and after 6 months since the assumption of metformin powder, each patient answered the following questionnaires: the SF‐36 Health Survey, the Diabetes Quality Of Life questionnaire Modified (DQOL/Mod), and the Diabetes Treatment Satisfaction Questionnaire (DTSQ). We also assessed the following at baseline, at 3 and 6 months: fasting plasma glucose (FPG) and postprandial glucose (PPG), glycated hemoglobin (HbA1c), fasting plasma insulin (FPI), and homeostasis model assessment index of insulin resistance (HOMA‐IR). We observed a statistically significant reduction in HbA1c, FPG, PPG, FPI, and HOMA‐IR (P < .05 for all) with metformin powder. The DTSQ questionnaire showed a higher level of satisfaction linked to the assumption of metformin powder compared to the tablets formulation. In conclusion, metformin powder formulation seems to be more appropriate for the treatment of diabetic patients. The improvement of glycemic control suggests a better adherence to the powder formulation.
Peak-to-average power ratio in high-order OFDM

The problem of peak-to-average power ratio (PAPR) of high-order orthogonal frequency-division modulation (OFDM) is considered. Using results on level crossing of random processes, an upper bound on the probability that the PAPR of an OFDM signal will exceed a given value is derived. Numerical computations are used to show that this bound is tight for low-pass OFDM systems. The central limit theorem is used to find an asymptotic expression for the bound when the number of carriers N grows to infinity. The central limit theorem is also used to find an asymptotic expression for another bound that is based on the envelope of the OFDM signal, and is tighter for bandpass systems. It is shown that, effectively, the PAPR grows as 2lnN and not linearly with N, and by developing a lower bound on the probability that the PAPR of an OFDM signal will exceed a given value, it is shown that asymptotically most OFDM symbols have a PAPR close to 2lnN. Some approaches to coping with the PAPR problem are discussed in light of the obtained results.
Experiences from Applying WCET Analysis in Industrial Settings

Knowing the program timing characteristics is fundamental to the successful design and execution of real-time systems. Today, measurement-based timing analysis tools such as in-circuit emulators, logic analyzers and oscilloscopes, are used in industry. A critical timing measure is the worst-case execution time (WCET) of a program. Recently, tools for deriving WCET estimates, mostly based on static program analysis, have reached the market. In this article, we summarize experiences from five different industrial case-studies. The studies were made on typical industrial systems, in close cooperation with the system developers, using both static and measurement-based tools. The primary purpose was to investigate the difficulties involved in applying current timing analysis methods to industrial code. We were also interested how WCET estimates can be derived by different methods, how labor-intensive the methods are, and the accuracy of obtained results. As a result, we provide observations on the benefits and drawbacks of the different timing analysis methods used and specify general conditions when a particular method should be most beneficial. We also show the benefits of having several types of timing analysis tools available
Genetic variability in natural populations of Arabidopsis thaliana in northern Europe

Ten populations of the model plant Arabidopsis thaliana were collected along a north–south gradient in Norway and screened for microsatellite polymorphisms in 25 loci and variability in quantitative traits. Overall, the average levels of genetic diversity were found to be relatively high in these populations, compared to previously published surveys of within population variability. Six of the populations were polymorphic at microsatellite loci, resulting in an overall proportion of polymorphic loci of 18%, and a relatively high gene diversity for a selfing species (HE = 0.06). Of the overall variability, 12% was found within populations. Two of six polymorphic populations contained heterozygous individuals. Both FST and phylogenetic analyses showed no correlation between geographical and genetic distances. Haplotypic diversity patterns suggested postglacial colonization of Scandinavia from a number of different sources. Heritable variation was observed for many of the studied quantitative traits, with all populations showing variability in at least some traits, even populations with no microsatellite variability. There was a positive association between variability in quantitative traits and microsatellites within populations. Several quantitative traits exhibited QST values significantly less than FST, suggesting that selection may be acting to retard differentiation for these traits.
A REGIONAL EXAMINATION OF FORECLOSURES IN WISCONSIN

Foreclosures and their causes and remedies, are being discussed and fiercely debated across our nation. Although there has been some examination of the causes of foreclosures, the current research has devoted most of its attention to examining what factors change the probability that an individual will go into foreclosure. By examining Wisconsin counties over eight years this paper makes a contribution to the literature by taking a regional approach to examining the causes of foreclosures. This regional approach has greater policy applications since policy is often based on regional not individual factors. A spatial econometric model along with several other empirical models are estimated and there are consistent results that greater unemployment, a lower median age, larger families in rental units, and a smaller percentage of Asian or Native Americans leads to more foreclosures in a county. There is also evidence that education seems to affect foreclosures in a nonmonotonic way; higher percentage of the population with a high school degree vs. non high school graduates increases foreclosures, but there is a negative impact or no significant difference between bachelors degree and no high school degree.
TopicFlow: Visualizing topic alignment of Twitter data over time

Social media, particularly Twitter, provides an abundance of real-time data. To account for this volume, researchers often use automated analysis and visualization techniques to produce a high-level overview of a Twitter stream. Existing techniques for understanding Twitter data make use of hashtags or word-pairs and may ignore the complex trends in discussions over time. To remedy this, we present an application of statistical topic modeling and alignment (binned topic models) to group related tweets into automatically generated topics and TopicFlow, an interactive tool to visualize the evolution of these topics. The effectiveness of this visualization for reasoning about large data sets is demonstrated by a usability study with 18 participants.
Speedy: a novel cell cycle regulator of the G2/M transition

Stage VI Xenopus oocytes are suspended at the G2/M transition of meiosis I, and represent an excellent system for the identification and examination of cell cycle regulatory proteins. Essential cell cycle regulators such as MAPK, cyclins and mos have the ability to induce oocyte maturation, causing the resumption of the cell cycle from its arrested state. We have identified the product of a novel Xenopus gene, Speedy or Spy1, which is able to induce rapid maturation of Xenopus oocytes, resulting in the induction of germinal vesicle breakdown (GVBD) and activation of M‐phasepromoting factor (MPF). Spy1 activates the MAPK pathway in oocytes, and its ability to induce maturation is dependent upon this pathway. Spy1‐induced maturation occurs much more rapidly than maturation induced by other cell cycle regulators including progesterone, mos or Ras, and does not require any of these proteins or hormones, indicating that Spy1‐induced maturation proceeds through a novel regulatory pathway. In addition, we have shown that Spy1 physically interacts with cdk2, and prematurely activates cdk2 kinase activity. Spy1 therefore represents a novel cell cycle regulatory protein, inducing maturation through the activation of MAPK and MPF, and also leading to the premature activation of cdk2.
Licensed under Creative Commons Attribution Cc by Dynamic Heterogeneity-aware Resource Provisioning in the Cloud

Data centers consume tremendous amounts of energy in terms of power distribution and cooling. Dynamic capacity provisioning is a promising approach for reducing energy consumption by dynamically adjusting the number of active machines to match resource demands. However, despite extensive studies of the problem, existing solutions have not fully considered the heterogeneity of both workload and machine hardware found in production environments. In particular, production data centers often comprise heterogeneous machines with different capacities and energy consumption characteristics. Meanwhile, the production cloud workloads typically consist of diverse applications with different priorities, performance and resource requirements. Failure to consider the heterogeneity of both machines and workloads will lead to both sub-optimal energy-savings and long scheduling delays, due to incompatibility between workload requirements and the resources offered by the provisioned machines. To address this limitation, the Harmony, a Heterogeneity-Aware dynamic capacity provisioning scheme for cloud data centers is introduced. Specifically, use the K-means clustering algorithm to divide workload into distinct task classes with similar characteristics in terms of resource and performance requirements. A technique that dynamically adjusting the number of machines to minimize total energy consumption and scheduling delay. Simulations using traces from a Google's compute cluster demonstrate Harmony (Heterogeneity-Aware Resource Monitoring and management system) can reduce energy by 28 percent compared to heterogeneity-oblivious solutions.
Chromatin conformation and salt-induced compaction: three-dimensional structural information from cryoelectron microscopy

Cryoelectron microscopy has been used to examine the three-dimensional (3-D) conformation of small oligonucleosomes from chicken erythrocyte nuclei after vitrification in solutions of differing ionic strength. From tilt pairs of micrographs, the 3-D location and orientation of the nucleosomal disks, and the paths of segments of exposed linker can be obtained. In "low-salt" conditions (5 mM NaCl, 1 mM EDTA, pH 7.5), the average trinucleosome assumes the shape of an equilateral triangle, with nucleosomes at the vertices, and a length of exposed linker DNA between consecutive nucleosomes equivalent to approximately 46 bp. The two linker DNA segments converge at the central nucleosome. Removal of histones H1 and H5 results in a much more variable trinucleosome morphology, and the two linker DNA segments usually join the central nucleosome at different locations. Trinucleosomes vitrified in 20 mM NaCl, 1 mM EDTA, (the salt concentration producing the maximal increase in sedimentation), reveal that compaction occurs by a reduction in the included angle made by the linker DNA segments at the central nucleosome, and does not involve a reduction in the distance between consecutive nucleosomes. Frequently, there is also a change in morphology at the linker entry-exit site. At 40 mM NaCl, there is no further change in trinucleosome morphology, but polynucleosomes are appreciably more compact. Nevertheless, the 3-D zig-zag conformation observed in polynucleosomes at low salt is retained at 40 mM NaCl, and individual nucleosome disks remain separated from each other. There is no evidence for the formation of solenoidal arrangements within polynucleosomes. Comparison of the solution conformation of individual oligonucleosomes with data from physical measurements on bulk chromatin samples suggests that the latter should be reinterpreted. The new data support the concept of an irregular zig-zag chromatin conformation in solution over a range of ionic strengths, in agreement with other in situ (McDowall, A.W., J.M. Smith, and J. Dubochet. 1986, EMBO (Eur. Mol. Biol. Organ.) J.5: 1395-1402; Horowitz, R.A. , D.A. Agard, J.W. Sedat, and C.L. Woodcock, 1994. J. Cell Biol. 125:1-10), and in vitro conclusions (van Holde, K., and J. Zlatanova. 1995. J. Biol. Chem. 270:8373-8376). Cryoelectron microscopy also provides a way to determine the 3-D conformation of naturally occurring chromatins in which precise nucleosome positioning plays a role in transcriptional regulation.
A probabilistic analysis of the average consensus algorithm with quantized communication

Abstract In the average consensus problem the states of a set of agents, linked according to a directed graph, have to be driven to their average. When the communication between neighbors is uniformly quantized, such a problem can not be exactly solved by a linear time-invariant algorithm. In this work, we propose a probabilistic estimate of the error from the agreement, in terms of the eigenvalues of the evolution matrix describing the algorithm.
Understanding e-learning continuance intention: a negative critical incidents perspective

This study develops a model to examine the key drivers of users' continuance intention of e-learning, based on negative critical incidents (NCIs) standpoints. The developed research model is tested empirically using a field survey of 230 users. This study finds that users' past service encounters (NCIs), belief (perceived ease of use and usefulness), satisfaction (quality attributes cumulative satisfaction and overall satisfaction) and attitude are key antecedents of continued usage intention. Four dimensions of both NCIs and quality attributes in e-learning (administration procedures, e-learning system functionality, instructional process and human interaction) are explored in this study. Results indicate that NCIs in teaching and administration are comparatively more important in determining user satisfaction and continuance intention. Further analysis finds that the recorded lecture content and the response time to users are the most critical problems in teaching and administration. In practice, this model can identify the key problems of satisfaction and continuance intention to help managers and teachers react promptly or make right decisions about how to better achieve higher user retention rates.
Proliferative activity, angiogenesis, and necrosis in peripheral nerve sheath tumors: a quantitative evaluation for prognosis.

Malignant peripheral nerve sheath tumors (MPNSTs) are distinguished from a control group of typical benign schwannomas and neurofibromas on the basis of a set of quantitatively evaluated parameters, i.e., the cell density; the number of mitoses and apoptotic bodies; the nuclear area and shape; the number and absolute and relative areas of silver-staining nucleolar organizer regions; necrosis; and angiogenesis. Only the extent of tumor necrosis, the mitotic rate, and the parameters related to silver-staining nucleolar organizer regions discriminate between less aggressive MPNSTs (disease-free patients after 4 years of follow-up) and more aggressive MPNSTs (with recurrences or metastases during the first 4 years of follow-up).