Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficient in vivo deletion of a large imprinted lncRNA by CRISPR/Cas9

Recent genome-wide studies have revealed that the majority of the mouse genome is transcribed as non-coding RNAs (ncRNAs) and growing evidence supports the importance of ncRNAs in regulating gene expression and epigenetic processes. However, the low efficiency of conventional gene targeting strategies has hindered the functional study of ncRNAs in vivo, particularly in generating large fragment deletions of long non-coding RNAs (lncRNAs) with multiple expression variants. The bacterial clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system has recently been applied as an efficient tool for engineering site-specific mutations of protein-coding genes in the genome. In this study, we explored the potential of using the CRISPR/Cas9 system to generate large genomic deletions of lncRNAs in mice. We developed an efficient one-step strategy to target the maternally expressed lncRNA, Rian, on chromosome 12 in mice. We showed that paired sgRNAs can precisely generate large deletions up to 23kb and the deletion efficiency can be further improved up to 33% by combining multiple sgRNAs. The deletion successfully abolished the expression of Rian from the maternally inherited allele, validating the biological relevance of the mutations in studying an imprinted locus. Mutation of Rian has differential effects on expression of nearby genes in different somatic tissues. Taken together, we have established a robust one-step method to engineer large deletions to knockout lncRNA genes with the CRISPR/Cas9 system. Our work will facilitate future functional studies of other lncRNAs in vivo.
In Vitro Antiviral Characteristics of HIV-1 Attachment Inhibitor BMS-626529, the Active Component of the Prodrug BMS-663068

ABSTRACT BMS-663068 is the phosphonooxymethyl prodrug of BMS-626529, a novel small-molecule attachment inhibitor that targets HIV-1 gp120 and prevents its binding to CD4+ T cells. The activity of BMS-626529 is virus dependent, due to heterogeneity within gp120. In order to better understand the anti-HIV-1 spectrum of BMS-626529 against HIV-1, in vitro activities against a wide variety of laboratory strains and clinical isolates were determined. BMS-626529 had half-maximal effective concentration (EC50) values of <10 nM against the vast majority of viral isolates; however, susceptibility varied by >6 log10, with half-maximal effective concentration values in the low pM range against the most susceptible viruses. The in vitro antiviral activity of BMS-626529 was generally not associated with either tropism or subtype, with few exceptions. Measurement of the binding affinity of BMS-626529 for purified gp120 suggests that a contributory factor to its inhibitory potency may be a relatively long dissociative half-life. Finally, in two-drug combination studies, BMS-626529 demonstrated additive or synergistic interactions with antiretroviral drugs of different mechanistic classes. These results suggest that BMS-626529 should be active against the majority of HIV-1 viruses and support the continued clinical development of the compound.
Preserved CD4 T-cell telomere length during long-lasting HIV-2 infection

HIV-2 infection features a much slower course than HIV-1 infection, often asymptomatic for over 20 years, without antiretroviral therapy (ART). Nevertheless, CD4 T cells progressively decline, in direct correlation with immune activation and cell cycling. We report, for the first time, preserved telomere length within naive and memory CD4 subsets in prolonged HIV-2 infection despite the increased CD4 turnover.
Role of the Nitric Oxide Pathway in κ-Opioid-Induced Hypothermia in Rats

The effect of central and peripheral administration of a nitric oxide synthase inhibitor,N-nitro-l-arginine methyl ester (l-NAME), on the hypothermia induced by the selective κ-opioid receptor agonisttrans-(±)3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]-cyclohexyl)-benzeneacetamide methane sulfate (U50,488H) was studied in male Sprague-Dawley rats. In the first series of experiments, we examined the effect of subcutaneous (s.c.) administration of l-NAME on the hypothermia induced by s.c. injection of U50,488H. l-NAME, at a dose of 50 mg/kg s.c. , had no influence on body temperature (Tb). Coadministration of l-NAME (50 mg/kg, s.c.) with U50,488H (10 mg/kg, s.c.) blocked the hypothermia induced by U50,488H. In the second series of experiments, we investigated the effect of intracerebroventricular (i.c.v.) administration of l-NAME on the hypothermia induced by s.c. injection of U50,488H. l-NAME itself, given i.c. v. at a dose of 1 mg/rat, did not evoke any change in Tb. Administration of l-NAME (1 mg/rat, i.c.v.) caused a significant suppression of U50,488H hypothermia. The results indicate that either central or peripheral nitric oxide synthesis is required for the production of hypothermia induced by U50,488H.
The Hitchhiking Effect on Linkage Disequilibrium Between Linked Neutral Loci

We analyzed a three-locus model of genetic hitchhiking with one locus experiencing positive directional selection and two partially linked neutral loci. Following the original hitchhiking approach by Maynard Smith and Haigh, our analysis is purely deterministic. In the first half of the selected phase after a favored mutation has entered the population, hitchhiking may lead to a strong increase of linkage disequilibrium (LD) between the two neutral sites if both are <0.1s away from the selected site (where s is the selection coefficient). In the second half of the selected phase, the main effect of hitchhiking is to destroy LD. This occurs very quickly (before the end of the selected phase) when the selected site is between both neutral loci. This pattern cannot be attributed to the well-known variation-reducing effect of hitchhiking but is a consequence of secondary hitchhiking effects on the recombinants created in the selected phase. When the selected site is outside the neutral loci (which are, say, <0.1s apart), however, a fast decay of LD is observed only if the selected site is in the immediate neighborhood of one of the neutral sites (i.e., if the recombination rate r between the selected site and one of the neutral sites satisfies \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(r{\ll}0.1s\) \end{document}). If the selected site is far away from the neutral sites (say, r > 0.3s), the decay rate of LD approaches that of neutrality. Averaging over a uniform distribution of initial gamete frequencies shows that the expected LD at the end of the hitchhiking phase is driven toward zero, while the variance is increased when the selected site is well outside the two neutral sites. When the direction of LD is polarized with respect to the more common allele at each neutral site, hitchhiking creates more positive than negative linkage disequilibrium. Thus, hitchhiking may have a distinctively patterned LD-reducing effect, in particular near the target of selection.
Robot-based Tele-Echography: the TER system

This paper presents a master-slave robotized system enabling a remote echographic diagnosis. The expert holds a virtual probe placed on a haptic device; he moves this virtual probe in order to control the motion of the real probe positioned on the body of the patient located remotely. The real probe is placed on a lightweight and user-friendly slave robot and moved by it. The contact force between the probe and the patient is fed back to the operator allowing him to have a haptic virtual environment. The aim of this haptic control is to preserve the medical expert proprioception in order to the facilitate hand-eye coordination necessary to echographic examination. In this paper we present the architecture of the system and experimental results.
Quantifying the common computational problems in contemporary applications

Selecting, for each application, the top five functions for manual code inspection resulted in analyzing a portion of the source code accounting for 77% of the total run time. Figure 2 shows the fraction of the analyzed run time covered by the 16 identified CPs (some are condensed in one slice for clarity.)
Spatial and temporal online charging/discharging coordination for mobile PEVs

Coordinated charging is an effective charging plan for PEVs to improve the overall system energy utilization and prevent the overload of an electric power grid. On the other hand, PEVs, which have energy storage and controllable loads, can be discharged to help the grid to smooth the fluctuations, for example, introduced by distributed generators (DGs). Either to prevent overloading or to regulate the power grid, most existing charging/discharging plans focus on temporal charging/discharging coordination for parked vehicles. However, for moving vehicles, spatial coordination can also bring benefits to the grid. For spatial coordination, the range anxiety problem should be carefully handled, since PEVs cannot reach some charging stations due to the limited battery levels. In this article, by exploiting both spatial and temporal coordinations, we introduce an online PEV charging/discharging strategy considering range anxieties. To collect real-time information for the proposed online strategy, a heterogeneous wireless infrastructure is proposed by integrating cellular networks with vehicular ad-hoc networks (VANETs). Challenging issues are discussed in terms of modeling PEV mobility, network selection for real-time information delivery, balancing the trade-off between the grid power utilization and drivers' preferences, and modeling business revenues for charging/discharging. Case studies demonstrate that joint spatial and temporal charging coordination can effectively improve power utilization and avoid overloading the power grid.
Making Sense of Spiritual Media: An Audience Study of "The Secret" DVD, book and website.

This paper considers The Secret DVD, together with the accompanying book and website, by means of analyzing an active audience seeking spiritual meaning and results. This study hypothesizes that many of those who have adopted The Secret ’s spiritual framework have done so by adhering to beliefs and practices just as one would when they commit to an organized religion. Evidence of individuals adopting the set of beliefs as outlined in The Secret is analyzed by means of audience members’ narratives published on the DVD and the book’s complimentary website ( www.thesecret.tv ). This investigation considers the audience – or believers – of The Secret by means of a uses-and-gratifications theoretical framework. A “grounded” theoretical approach (Charmaz, 2006) is employed to analyze the audience and its narratives. Finally, particular attention is paid to how the audience/believers “use” The Secret , as well as references to traditional spiritual practices such as prayer, belief, and references to God.
Complex evolutionary history of the pallid dotted‐blue butterfly (Lycaenidae: Euphilotes pallescens) in the Great Basin of western North America

The aim of this study was to investigate patterns of genetic isolation associated with populations in discrete habitat patches in a North American cold desert through analysis of the pallid dotted‐blue butterfly, Euphilotes pallescens. This small butterfly is largely restricted to low‐elevation habitats across the Great Basin. The apparent geographical isolation and reported morphological variation among E. pallescens populations makes this species an ideal candidate with which to investigate patterns of genetic isolation and diversification in this arid region.
Mobile Robot Navigation Modulated by Artificial Emotions

For artificial intelligence research to progress beyond the highly specialized task-dependent implementations achievable today, researchers may need to incorporate aspects of biological behavior that have not traditionally been associated with intelligence. Affective processes such as emotions may be crucial to the generalized intelligence possessed by humans and animals. A number of robots and autonomous agents have been created that can emulate human emotions, but the majority of this research focuses on the social domain. In contrast, we have developed a hybrid reactive/deliberative architecture that incorporates artificial emotions to improve the general adaptive performance of a mobile robot for a navigation task. Emotions are active on multiple architectural levels, modulating the robot's decisions and actions to suit the context of its situation. Reactive emotions interact with the robot's control system, altering its parameters in response to appraisals from short-term sensor data. Deliberative emotions are learned associations that bias path planning in response to eliciting objects or events. Quantitative results are presented that demonstrate situations in which each artificial emotion can be beneficial to performance.
Reparixin, an Inhibitor of CXCR2 Function, Attenuates Inflammatory Responses and Promotes Recovery of Function after Traumatic Lesion to the Spinal Cord

It has been shown that the blockade of CXCR1 and CXCR2 receptors prevents ischemia/reperfusion damage in several types of vascular beds. Reparixin is a recently described inhibitor of human CXCR1/R2 and rat CXCR2 receptor activation. We applied reparixin in rats following traumatic spinal cord injury and determined therapeutic temporal and dosages windows. Treatment with reparixin significantly counteracts secondary degeneration by reducing oligodendrocyte apoptosis, migration to the injury site of neutrophils and ED-1-positive cells. The observed preservation of the white matter might also be secondary to the enhanced proliferation of NG2-positive cells. The expression of macrophage-inflammatory protein-2, tumor necrosis factor-α, interleukin (IL)-6, and IL-1β was also counteracted, and the proliferation of glial fibrillary acidic protein-positive cells was markedly reduced. These effects resulted in a smaller post-traumatic cavity and in a significantly improved recovery of hind limb function. The best beneficial outcome of reparixin treatment required 7-day administration either by i.p. route (15 mg/kg) or subcutaneous infusion via osmotic pumps (10 mg/kg), reaching a steady blood level of 8 μg/ml. Methylprednisolone was used as a reference drug; such treatment reduced cytokine production but failed to affect the rate of hind limb recovery.
Visual acuity test for isolated words using speech recognition

Visual acuity tests are performed by doctors to assess a patient's visual acuity. Health practitioners carry out this test manually on daily basis. This proposed technique aims at the ease of accurately testing vision anywhere instead of planning a visit to a practitioner. In this interactive method, a user utters isolated words as a guess input to the system from a table of selected words. The system accepts user's utterance in the form of speech and performs processing in two steps i.e. extraction of salient features or speech vectors from the speech signal sufficient enough to represent the utterance and application to compare the speech vectors extracted. The system will identify the correct and wrong guesses in parallel with each isolated word uttered by the user. Isolated words are determined by the system as part of the test. The feature sets extracted from the isolated words database includes mel frequency cepstral coefficients and computation of perceptual parameters which are classified by optimum class boundaries using Support Vector Machine. Challenging findings and evaluations are discussed.
Diarrheal Illness and Healthcare Seeking Behavior among a Population at High Risk for Diarrhea in Dhaka, Bangladesh

Diarrhea remains one of the major causes of death in Bangladesh. We studied diarrheal disease risk and healthcare seeking behavior among populations at high risk for diarrhea in Dhaka, Bangladesh. Data were obtained from a cross-sectional survey conducted during April and September 2010. The prevalence of diarrhea was calculated by age-group and sex. A generalized estimating equation with logit link function was used to predict diarrheal disease risk and seeking care from a professional healthcare provider. Of 316,766 individuals, 10% were young children (<5 years). The prevalence of diarrhea was 16 per 1000 persons among all ages; young children accounted for 44 per 1000 persons. Prevalence of diarrhea was significantly higher (p=.003) among younger males (<15 years) compared to that among younger females. In contrast, prevalence of diarrhea was significantly higher (p<.0001) among older females (≥15 years) compared to that among older males. An increased risk for diarrhea was observed in young children, males, and those staying in rented houses, lower family members in the house, using non-sanitary toilets, living in the area for short times, living in a community with less educated persons, living in a community with less use of safe water source for drinking, or living close to the hospital. About 80% of those with diarrhea sought care initially from a non-professional healthcare provider. Choice of the professional healthcare provider was driven by age of the patient, educational status of the household head, and hygienic practices by the household. The study reaffirms that young children are at greater risk for diarrhea. Like other developing countries most people in this impoverished setting of Dhaka are less likely to seek care from a professional healthcare provider than from a non-professional healthcare provider, which could be attributed to a higher number of diarrheal deaths among young children in Bangladesh. Dissemination of information on health education, increasing the supply of skilled healthcare providers, and low-cost and quality healthcare services may encourage more people to seek care from professional healthcare providers, thus may help reduce child mortality in the country. Further studies are warranted to validate the results.
Context-dependent deterministic plus stochastic model

This article proposes a method to improve the performance of deterministic plus stochastic model (DSM-) based feature extraction by integrating the contextual information. One precious advantage of speech synthesis over speech recognition is that in both training and testing phases of synthesis, contextual information is available. However, similar to recognition, this invaluable knowledge has been forgotten during acoustic feature extraction of speech synthesis. DSM expresses the residual of Mel-cepstral analysis through a summation of two components, namely deterministic and stochastic. This study proposes to model the deterministic component through a novel context-dependent principal component analysis (CD-PCA), and the stochastic component through the conventional high-pass filtered noise. Furthermore, due to the high dependency of the proposed feature extraction on state boundaries, the feature analysis and HMM-based modeling are performed in an iterative manner. Subjective evaluations conducted on a Persian speech database confirm the effectiveness of the proposed synthesis system.
The fate of osseointegrated implants in patients following oral cancer surgery and mandibular reconstruction

The feasibility of implant treatment in patients after oral ablative tumor surgery and defect reconstruction has not yet been investigated in terms of the requisite high standards of success assessment. A report on this topic must address not only implant survival but implant health, bone response, soft tissue health, failure pattern, and time of failure, as well.
Reperfusion delay in patients with high-risk ST-segment elevation myocardial infarction: every minute counts, much more than suspected

Study director Karl H. Scholz, corresponding author Thomas Meyer, and their co-authors are publishing very important findings on the impact of treatment delays on mortality in ST-segement elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI) in the environment of a fully developed Emergency Medical Service (EMS). The data have been collected in the context of the ongoing FITTSTEMI trial (NCT 00794001) in Germany, a prospective, observational, registry-based study involving a consortium of nearly 50 hospital systems committing to enrol prospectively all STEMI patients presenting within <24 h after onset of symptoms. The study started in October 2007 and is planned to continue until December 2021 after enrolment of 50 000þ patients. Key strategies for reducing door to balloon (D2B) time and standard quality indicators were endorsed by all participating hospitals. Phase I evaluates whether formal data collection and regular feedback can improve first medical contact (FMC) to PCI treatment delays. Phase II investigates whether survival can be improved by behavioural changes triggered by quarterly feedback data analysis with cardiology, emergency department, and EMS staff. Outcome measures are the contact to balloon (C2B) time and mortality at various time intervals up to 1 year (NCT 00794001).
The Role of Social and Cognitive Factors in the Emergence of Communication: Experiments in Evolutionary Robotics

Evolutionary robotics is a biologically inspired approach to robotics that is advantageous to studying the evolution of language. A new model for the evolution of language is presented. This model is used to investigate the interrelationships between communication abilities, namely linguistic production and comprehension, and other behavioral skills. For example, the model supports the hypothesis that the ability to form categories from direct interaction with an environment constitutes the ground for subsequent evolution of communication and language. A variety of experiments, based on the role of social and evolutionary variables in the emergence of communication, are described.
Text localization in natural scene images by mean-shift clustering and parallel edge feature

A new text localization method using the parallel edge feature of text strokes is proposed, based on the observation that text-stroke consists of two edges in parallel. First, mean-shift clustering is employed to group similar pixels into clusters. The connected components in each cluster are considered as candidates for text strokes. Then, parallel edges are detected to verify whether the connected components are text strokes. The contribution of this paper is the presentation of a new feature of parallel edges along the stroke, providing structural information for the text localization. The performance, evaluated on ICDAR2003 image database, shows that the proposed algorithm works successfully with most of the text images.
Dynamic Redeployment to Counter Congestion or Starvation in Vehicle Sharing Systems

Extensive usage of private vehicles has led to increased traffic congestion, carbon emissions, and usage of non-renewable resources. These concerns have led to the wide adoption of vehicle sharing (ex: bike sharing, car sharing) systems in many cities of the world. In vehicle-sharing systems, base stations (ex: docking stations for bikes) are strategically placed throughout a city and each of the base stations contain a pre-determined number of vehicles at the beginning of each day. Due to the stochastic and individualistic movement of customers,there is typically either congestion (more than required)or starvation (fewer than required) of vehicles at certain base stations. As demonstrated in our experimental results, this happens often and can cause a significant loss in demand. We propose to dynamically redeploy idle vehicles using carriers so as to minimize lost de-mand or alternatively maximize revenue for the vehicle sharing company. To that end, we contribute an optimization formulation to jointly address the redeploy-ment (of vehicles) and routing (of carriers) problemsand provide two approaches that rely on decomposability and abstraction of problem domains to reduce the computation time significantly. Finally, we demonstrate the utility of our approaches on two real world data sets of bike-sharing companies.