Miracle-dz/UniFAR-FTUs huggingface dataset:
MicroRNA-Dependent Transcriptional Silencing of Transposable Elements in Drosophila Follicle Cells

RNA interference-related silencing mechanisms concern very diverse and distinct biological processes, from gene regulation (via the microRNA pathway) to defense against molecular parasites (through the small interfering RNA and the Piwi-interacting RNA pathways). Small non-coding RNAs serve as specificity factors that guide effector proteins to ribonucleic acid targets via base-pairing interactions, to achieve transcriptional or post-transcriptional regulation. Because of the small sequence complementarity required for microRNA-dependent post-transcriptional regulation, thousands of microRNA (miRNA) putative targets have been annotated in Drosophila. In Drosophila somatic ovarian cells, genomic parasites, such as transposable elements (TEs), are transcriptionally repressed by chromatin changes induced by Piwi-interacting RNAs (piRNAs) that prevent them from invading the germinal genome. Here we show, for the first time, that a functional miRNA pathway is required for the piRNA-mediated transcriptional silencing of TEs in this tissue. Global miRNA depletion, caused by tissue- and stage-specific knock down of drosha (involved in miRNA biogenesis), AGO1 or gawky (both responsible for miRNA activity), resulted in loss of TE-derived piRNAs and chromatin-mediated transcriptional de-silencing of TEs. This specific TE de-repression was also observed upon individual titration (by expression of the complementary miRNA sponge) of two miRNAs (miR-14 and miR-34) as well as in a miR-14 loss-of-function mutant background. Interestingly, the miRNA defects differentially affected TE- and 3' UTR-derived piRNAs. To our knowledge, this is the first indication of possible differences in the biogenesis or stability of TE- and 3' UTR-derived piRNAs. This work is one of the examples of detectable phenotypes caused by loss of individual miRNAs in Drosophila and the first genetic evidence that miRNAs have a role in the maintenance of genome stability via piRNA-mediated TE repression.
On the Island of Misfit Toys

The performance of compute hardware varies: running the same software repeatedly on the same system, on the same system at a later date, or on supposedly-identical systems produces performance results that differ. This fact has important implications for the reproducibility of systems research and the ability to quantitatively compare the performance of different systems. It also has implications for commercial computing, such as in the quantification and measurement of SLAs. Over a period of 10 months, we conducted a largescale study capturing performance samples from 835 servers, comprising nearly 900,000 data points. We examine this data from two perspectives: from that of a service provider wishing to offer a consistent environment, and that of a systems researcher user who must understand how variability necessarily affects their results. From this examination, we draw a number of lessons about the types and magnitudes of performance variability, and explore effects on confidence in experiment results. We also create a statistical model that can be used to understand how representative an individual server is of the general population. We have made the full dataset and analysis tools publicly available, and have built a system to interactively explore the data and make recommendations for experiment parameters based on rigorous statistics.
In vitro and in vivo antimycobacterial activities of ketone and amide derivatives of quinoxaline 1,4-di-N-oxide.

OBJECTIVES To evaluate a novel series of quinoxaline 1,4-di-N-oxides for in vitro activity against Mycobacterium tuberculosis and for efficacy in a mouse model of tuberculosis (TB). METHODS Ketone and amide derivatives of quinoxaline 1,4-di-N-oxide were evaluated in in vitro and in vivo tests including: (i) activity against M. tuberculosis resistant to currently used antitubercular drugs including multidrug-resistant strains (MDR-TB resistant to isoniazid and rifampicin); (ii) activity against non-replicating persistent (NRP) bacteria; (iii) MBC; (iv) maximum tolerated dose, oral bioavailability and in vivo efficacy in mice; and (v) potential for cross-resistance with another bioreduced drug, PA-824. RESULTS Ten compounds were tested on single drug-resistant M. tuberculosis. In general, all compounds were active with ratios of MICs against resistant and non-resistant strains of <or=4.00. One compound, 5, was orally active in a murine model of TB, bactericidal, active against NRP bacteria and active on MDR-TB and poly drug-resistant clinical isolates (resistant to 3-5 antitubercular drugs). CONCLUSIONS Quinoxaline 1,4-di-N-oxides represent a new class of orally active antitubercular drugs. They are likely bioreduced to an active metabolite, but the pathway of bacterial activation was different from PA-824, a bioreducible nitroimidazole in clinical trials. Compound 5 was bactericidal and active on NRP organisms indicating that activation occurred in both growing and non-replicating bacteria leading to cell death. The presence of NRP bacteria is believed to be a major factor responsible for the prolonged nature of antitubercular therapy. If the bactericidal activity and activity on non-replicating bacteria in vitro translate to in vivo conditions, quinoxaline 1,4-di-N-oxides may offer a path to shortened therapy.
How Stock of Origin Affects Performance of Individuals across a Meta-Ecosystem: An Example from Sockeye Salmon

Connectivity among diverse habitats can buffer populations from adverse environmental conditions, influence the functioning of meta-ecosystems, and ultimately affect the reliability of ecosystem services. This stabilizing effect on populations is proposed to derive from complementarity in growth and survival conditions experienced by individuals in the different habitats that comprise meta-ecosystems. Here we use the fine scale differentiation of salmon populations between diverse lake habitats to assess how rearing habitat and stock of origin affect the body condition of juvenile sockeye salmon. We use genetic markers (single nucleotide polymorphisms) to assign individuals of unknown origin to stock group and in turn characterize ecologically relevant attributes across habitats and stocks. Our analyses show that the body condition of juvenile salmon is related to the productivity of alternative habitats across the watershed, irrespective of their stock of origin. Emigrants and residents with genetic origins in the high productivity lake were also differentiated by their body condition, poor and high respectively. These emigrants represented a substantial proportion of juvenile sockeye salmon rearing in the lower productivity lake habitat. Despite emigrants originating from the more productive lake, they did not differ in body condition from the individuals spawned in the lower productivity, recipient habitat. Genetic tools allowed us to assess the performance of different stocks groups across the diverse habitats comprising their meta-ecosystem. The ability to characterize the ecological consequences of meta-ecosystem connectivity can help develop strategies to protect and restore ecosystems and the services they provide to humans.
Exploration in POMDPs

In recent work, Bayesian methods for exploration in Markov decision processes (MDPs) and for solving known partially-observable Markov decision processes (POMDPs) have been proposed. In this paper we review the similarities and differences between those two domains and propose methods to deal with them simultaneously. This enables us to attack the Bayes-optimal reinforcement learning problem in POMDPs.
Childhood socioeconomic status and adult health

Socioeconomic status (SES) exposures during childhood are powerful predictors of adult cardiovascular morbidity, cardiovascular mortality, all‐cause mortality, and mortality due to a range of specific causes. However, we still know little about when childhood SES exposures matter most, how long they need to last, what behavioral, psychological, or physiological pathways link the childhood SES experience to adult health, and which specific adult health outcomes are vulnerable to childhood SES exposures. Here, we discuss the evidence supporting the link between childhood and adolescent SES and adult health, and explore different environmental, behavioral, and physiological pathways that might explain how early SES would influence adult health. We also address the ages when SES exposures matter most for setting adult health trajectories as well as the role of exposure duration in SES influences on later health. While early childhood exposures seem to be potent predictors of a range of health outcomes, we emphasize that later childhood and adolescent exposures are risks for other health outcomes.
Towards artistic minimal rendering

Many nonphotorealistic rendering techniques exist to produce artistic effects from given images. Inspired by various artistic work such as Warhol's, interesting artistic effects can be produced by using a minimal rendering, where the minimum refers to the number of tones as well as the number and complexity of the primitives used for rendering. To achieve this goal, based on various computer vision techniques, our method uses a combination of refined lines and blocks, as well as a small number of tones, to produce abstracted artistic rendering with sufficient elements from the original image. There is always a trade-off between reducing the amount of information and the ability to represent the shape and details of the original images. Judging the level of abstraction is semantic-based, so we believe that giving users this flexibility is probably a good choice. By changing some intuitive parameters, a wide range of visually pleasing results can be produced. Our method is usually fully automatic, but a small amount of user interaction can optionally be incorporated to obtain selective abstraction.
The Effect of Viral Suppression on Cross-Sectional Incidence Testing in the Johns Hopkins Hospital Emergency Department

Objective(s):To determine the effect of viral suppression on cross-sectional incidence testing. Methods:In 2001 and 2003, patients entering the Johns Hopkins Hospital (JHH) Emergency Department (ED) were enrolled into an interview-based identity-unlinked serosurvey. All HIV-positive samples were tested by the Vironostika-less sensitive (LS) enzyme immunoassay (EIA) (Organon-Teknika, Charteston, SC) and an avidity assay to determine recent HIV infection. Additionally 16 samples from 8 previously characterized elite suppressors (ES) were tested by cross-sectional incidence assays. Results:HIV prevalence was 12% for the 2001 survey and 11% for the 2003 survey. Of the HIV-infected subjects, 18% did not know they were infected. The Vironostika-LS EIA determined that 6% (11 of 183) and 7% (17 of 243) of HIV-positive individuals in 2001and 2003, respectively, were recently infected. Avidity testing confirmed that 6 of 11 in 2001 and 5 of 17 in 2003 were newly infected, leaving 17 discrepant samples. All 17 discrepant samples were Western blot-positive and viral load undetectable, and 7 of 17 had antiretroviral drugs (ARVs) in their serum. Ten individuals were virally suppressed without ARVs and seemed incident by the Vironostika-LS EIA but chronic by avidity testing. These 10 subjects had similar testing profiles to the known 16 ES samples, because 9 of 16 were incident by the Vironostika-LS EIA and 0 of 16 were incident by avidity testing. Conclusions:By removing the viral load-negative individuals and confirming the initial Vironostika-LS EIA results by avidity testing, the incidence estimate was lowered from 1.73% to 0.94% per year in 2001 and from 1.90% to 0.56% per year in 2003. Viral suppression affects the performance of the cross-sectional incidence tests, which rely on antibody titer. In addition, 2% (10 of 426) of all HIV-infected individuals who use the JHH ED for medical care seem to suppress HIV to undetectable levels without ARVs.
A Genome‐Wide Association Study for Venous Thromboembolism: The Extended Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium

Venous thromboembolism (VTE) is a common, heritable disease resulting in high rates of hospitalization and mortality. Yet few associations between VTE and genetic variants, all in the coagulation pathway, have been established. To identify additional genetic determinants of VTE, we conducted a two‐stage genome‐wide association study (GWAS) among individuals of European ancestry in the extended cohorts for heart and aging research in genomic epidemiology (CHARGE) VTE consortium. The discovery GWAS comprised 1,618 incident VTE cases out of 44,499 participants from six community‐based studies. Genotypes for genome‐wide single‐nucleotide polymorphisms (SNPs) were imputed to approximately 2.5 million SNPs in HapMap and association with VTE assessed using study‐design appropriate regression methods. Meta‐analysis of these results identified two known loci, in F5 and ABO. Top 1,047 tag SNPs (P ≤ 0.0016) from the discovery GWAS were tested for association in an additional 3,231 cases and 3,536 controls from three case‐control studies. In the combined data from these two stages, additional genome‐wide significant associations were observed on 4q35 at F11 (top SNP rs4253399, intronic to F11) and on 4q28 at FGG (rs6536024, 9.7 kb from FGG; P < 5.0 × 10−13 for both). The associations at the FGG locus were not completely explained by previously reported variants. Loci at or near SUSD1 and OTUD7A showed borderline yet novel associations (P < 5.0 × 10−6) and constitute new candidate genes. In conclusion, this large GWAS replicated key genetic associations in F5 and ABO, and confirmed the importance of F11 and FGG loci for VTE. Future studies are warranted to better characterize the associations with F11 and FGG and to replicate the new candidate associations.
Sparse Local Submap Joining Filter for Building Large-Scale Maps

This paper presents a novel local submap joining algorithm for building large-scale feature-based maps: sparse local submap joining filter (SLSJF). The input to the filter is a sequence of local submaps. Each local submap is represented in a coordinate frame defined by the robot pose at which the map is initiated. The local submap state vector consists of the positions of all the local features and the final robot pose within the submap. The output of the filter is a global map containing the global positions of all the features as well as all the robot start/end poses of the local submaps. Use of an extended information filter (EIF) for fusing submaps makes the information matrix associated with SLSJF exactly sparse. The sparse structure together with a novel state vector and covariance submatrix recovery technique makes the SLSJF computationally very efficient. The SLSJF is a canonical and efficient submap joining solution for large-scale simultaneous localization and mapping (SLAM) problems that makes use of consistent local submaps generated by any reliable SLAM algorithm. The effectiveness and efficiency of the new algorithm is verified through computer simulations and experiments.
Games and Mechanism Design in Machine Scheduling—An Introduction

We survey different models, techniques, and some recent results to tackle machine scheduling problems within a distributed setting. In traditional optimization, a central authority is asked to solve a (computationally hard) optimization problem. In contrast, in distributed settings there are several agents, possibly equipped with private information that is not publicly known, and these agents must interact to derive a solution to the problem. Usually the agents have their individual preferences, which induces them to behave strategically to manipulate the resulting solution. Nevertheless, one is often interested in the global performance of such systems. The analysis of such distributed settings requires techniques from classical optimization, game theory, and economic theory. The paper therefore briefly introduces the most important of the underlying concepts and gives a selection of typical research questions and recent results, focusing on applications to machine scheduling problems. This includes the study of the so‐called price of anarchy for settings where the agents do not possess private information, as well as the design and analysis of (truthful) mechanisms in settings where the agents do possess private information.
Simple Behavioral Assessment of Mouse Olfaction

This unit presents two basic protocols that offer rapid assessments of anosmia (the absence of a sense of smell) in mice. The buried food test is used to check for the ability to smell volatile odors. The olfactory habituation/dishabituation test is used to test whether the animal can detect and differentiate different odors, including both nonsocial and social odors. A non‐contact method of odor presentation, along with a general method for collecting urine samples, is given as an alternate protocol. The tests described in this unit only require simple equipment and can be adopted readily by most laboratories.Curr. Protoc. Neurosci. 48:8.24. 1‐8.24. 12. © 2009 by John Wiley & Sons, Inc.
False positives and false negatives in functional near-infrared spectroscopy: issues, challenges, and the way forward

Abstract. We highlight a significant problem that needs to be considered and addressed when performing functional near-infrared spectroscopy (fNIRS) studies, namely the possibility of inadvertently measuring fNIRS hemodynamic responses that are not due to neurovascular coupling. These can be misinterpreted as brain activity, i.e., “false positives” (errors caused by wrongly assigning a detected hemodynamic response to functional brain activity), or mask brain activity, i.e., “false negatives” (errors caused by wrongly assigning a not observed hemodynamic response in the presence of functional brain activity). Here, we summarize the possible physiological origins of these issues and suggest ways to avoid and remove them.
A prospective study of the rate of progression in compensated, histologically advanced chronic hepatitis C

The incidence of liver disease progression among subjects with histologically advanced but compensated chronic hepatitis C is incomplete. The Hepatitis C Antiviral Long‐term Treatment against Cirrhosis Trial was a randomized study of 3.5 years of maintenance peginterferon treatment on liver disease progression among patients who had not cleared virus on peginterferon and ribavirin therapy. Patients were followed subsequently off therapy. Because maintenance peginterferon treatment did not alter liver disease progression, we analyzed treated and control patients together. Among 1,050 subjects (60% advanced fibrosis, 40% cirrhosis), we determined the rate of progression to cirrhosis over 4 years and of clinical outcomes over 8 years. Among patients with fibrosis, the incidence of cirrhosis was 9.9% per year. Six hundred seventy‐nine clinical outcomes occurred among 329 subjects. Initial clinical outcomes occurred more frequently among subjects with cirrhosis (7.5% per year) than subjects with fibrosis (3.3% per year) (P < 0.0001). Child‐Turcotte‐Pugh (CTP) score ≥7 was the most common first outcome, followed by hepatocellular carcinoma. Following occurrence of a CTP score ≥7, the rate of subsequent events increased to 12.9% per year, including a death rate of 10% per year. Age and sex did not influence outcome rates. Baseline platelet count was a strong predictor of all clinical outcomes. During the 8 years of follow‐up, death or liver transplantation occurred among 12.2% of patients with advanced fibrosis and 31.5% of those with cirrhosis. Conclusion: Among patients with advanced hepatitis C who failed peginterferon and ribavirin therapy, the rate of liver‐related outcomes, including death and liver transplantation, is high, especially once the CTP score reaches at least 7. (HEPATOLOGY 2011)
Governance, Legitimation, Commons: A Public Sphere Framework and Research Agenda for the Public Library Sector

Abstract Public libraries continually struggle to define their social value, and economic or educational rationales are commonly submitted to this end. In contrast to these approaches, public sphere theory emphasizes the political and social justice aspects of public libraries. Existing library literature has established strong associations between public sphere theory and public libraries, and a tentative model of the public sphere in public libraries has been developed. It is not yet clear, however, how a public sphere model of public libraries might benefit the profession. This paper therefore explains how a conceptual model of the public sphere in public libraries can serve as a potential framework and research agenda for the public library sector. A model of the public sphere in public libraries contains three main arenas of discourse: governance, legitimation, and commons. Each of the arenas represents values that are central to public librarianship. Practitioners and scholars in the public library sector can use the public sphere model to orient research and practice. This paper explains each arena in detail and discusses the model’s relevance as a philosophy and research agenda.
EVAULATING THE ACCURACY OF A PREDICTIVE MODEL IN SURVIVAL ANALYSIS

Background. Risk prediction models can be used as an aid when determining patient management. Because incorrect predictions could have substantial consequences, it is very important to evaluate the predictive accuracy of a model. When the risk prediction model is the result of a survival analysis where the outcomes are potentially censored, there is no standard way of evaluating predictive accuracy. There have been many different measures proposed for this purpose, but they all have limitations. The most frequently used measure in practical applications is the concordance index (c-index) proposed by Harrell et al. (1982). The c-index, however, is biased when the data are censored, a problem that does not appear to be widely recognized. The purpose of this poster is to highlight and explore this bias.
Entrapment efficiency of pyridoxine hydrochloride in unilamellar liposomes: experimental versus model-generated data

Abstract The present study investigates the effect of the preparation method (four methods) and formulation additives (propylene glycol (PG) and cholesterol (CH)) on the entrapment efficiency (EE) of pyridoxine hydrochloride (vitamin B6 (VB6)), representing hydrophilic water-soluble low permeable vitamins, in unilamellar liposomes. The main aim is to compare determined EE with predicted values generated using a web-published, computational model. Results showed that among the different preparation methods, modified film hydration showed significantly higher EE (p < 0.05). With regard to formulation additives, PG (5% w/v) produced smaller vesicles size with narrow size distribution. Agreement between determined and model-generated EE values was more evident in formulae with narrow size distribution (polydispersity index (PdI) below 0.23). Formulae containing PG showed slightly higher determined than predicted EE values indicating vitamin–phospholipid bilayer interaction. Meanwhile, agreement between determined and predicted EE was limited to VB6-to-phospholipid ratio below (1.2:2). The comparison provided further insight into the usefulness of the prediction model factors affecting agreement between determined and predicted EE data.