Miracle-dz/UniFAR-FTUs huggingface dataset:
SR proteins promote the first specific recognition of Pre-mRNA and are present together with the U1 small nuclear ribonucleoprotein particle in a general splicing enhancer complex

We show that addition of SR proteins to in vitro splicing extracts results in a significant increase in assembly of the earliest prespliceosomal complex E and a corresponding decrease in assembly of the heterogeneous nuclear ribonucleoprotein (hnRNP) complex H. In addition, SR proteins promote formation of the E5' and E3' complexes that assemble on RNAs containing only 5' and 3' splice sites, respectively. We conclude that SR proteins promote the earliest specific recognition of both the 5' and 3' splice sites and are limiting for this function in HeLa nuclear extracts. Using UV cross-linking, we demonstrate specific, splice site-dependent RNA-protein interactions of SR proteins in the E, E5', and E3' complexes. SR proteins do not UV cross-link in the H complex, and conversely, hnRNP cross-linking is largely excluded from the E-type complexes. We also show that a discrete complex resembling the E5' complex assembles on both purine-rich and non-purine-rich exonic splicing enhancers. This complex, which we have designated the Enhancer complex, contains U1 small nuclear RNP (snRNP) and is associated with different SR protein family members, depending on the sequence of the enhancer. We propose that both downstream 5' splice site enhancers and exonic enhancers function by establishing a network of pre-mRNA-protein and protein-protein interactions involving U1 snRNP, SR proteins, and U2AF that is similar to the interactions that bring the 5' and 3' splice sites together in the E complex.
Beyond Multiprocessing: Multithreading the SunOS Kernel

Preparing the SunOS/SVR4 kernel for today’s challenges: symmetric multiprocessing, multi-threaded applications, real-time, and multimedia, led to the incorporation of several innovative techniques. In particular, the kernel was re-structured around threads. Threads are used for most asynchronous processing, including interrupts. The resulting kernel is fully preemptible and capable of real-time response. The combination provides a robust base for highly concurrent, responsive operation.
An Overview of Respiratory Syncytial Virus

Respiratory Syncytial Virus (RSV), a member of the Paramyxoviridae family, is the leading cause of lower respiratory tract illness (LRI) in infants. From 1993 to 2008, the total RSV hospitalization rate in the United States across all age groups was 55 per 100,000 person-years, slightly lower than the rate of 64 per 100,000 personyears for influenza viruses [1]. In infants, the hospitalization rate was 2,345 per 100,000 person-years for RSV compared to 151 for influenza, consistent with reports that RSV hospitalizes 1–2% of infants in the US each winter, a staggering statistic [1]. RSV disease is not limited to infants. RSV resulted in more hospitalizations in 1– 4-year-olds than influenza [1]. One in 13 children under the age of five in the US required medical attention for RSV each year, and 60% of office visits were for 2–5-year-olds [2]. RSV remains a significant cause of death. Over all age groups, influenza caused three times as many deaths as RSV in the US from 1990 to 1999, mostly in the elderly [3]. RSV caused 137 deaths per year in the US in children less than 4 years old, compared to 38 per year in this age group for influenza [3]. Globally, RSV was estimated to have caused 66,000 to 199,000 pneumonia deaths in children less than 5 years old in 2005, making RSV the third most important cause of deadly childhood pneumonia after Streptococcus pneumonia and Haemophilus influenza [4]. RSV is increasingly recognized as a global health priority. Other than ribavirin, there are no licensed RSV vaccines or therapeutics. The monoclonal antibody (mAb) palivizumab is a neutralizing mAb against a conserved epitope in the viral fusion (F) surface glycoprotein. Palivizumab is administered prophylactically to high-risk infants, such as those with chronic lung disease of prematurity, congenital heart disease, or premature birth at less than 36 weeks gestational age, but it costs $4,500 per patient treatment course [5].
The aryl hydrocarbon receptor is required for induction of p21cip1/waf1 expression and growth inhibition by SU5416 in hepatoma cells

The aryl hydrocarbon receptor (AhR) is a potential clinical target for cancer and autoimmune dysfunction. Identifying selective AhR modulators that produce desirable clinical outcomes represents an opportunity for developing new anti-cancer agents. Repurposing clinically-used drugs with established safety profiles that activate the AhR represents a good starting place to pursue this goal. In this study, we characterized the AhR-dependent effects of SU5416 (Semaxanib) following its identification in a small-molecule library screen. SU5416 potently activated AhR-dependent reporter genes, induced AhR nuclear localization, facilitated AhR-DNA binding, and increased, expression of its endogenous target genes. SU5416 significantly inhibited proliferation of Hepa1 hepatoma cells in an AhR-dependent manner, but did not induce apoptosis. SU5416 also inhibited the growth of human HepG2 liver cancer cells. The effects of SU5416 correlated with an increased G1 population and increased expression of cell cycle inhibitor p21cip1/waf1 at both the mRNA and protein level. Increased expression of p21cip1/waf1 by SU5416 required expression of both AhR and Arnt. In addition, evidence for long-term activation of the AhR in vivo by a single dose of SU5416 was identified by analyzing published microarray data. Our results provide support for continued investigation of the AhR as therapeutic for cancers such as hepatocellular carcinoma. In addition, our findings raise the possibility that some of the previously observed anti-proliferative effects of SU5416 may be due to activation of the AhR.
Diffusion and fluctuations in a nonequilibrium electron gas with electron-electron collisions.

We investigate the equivalence between the Boltzmann (or field) approach and the particle approach for the definition of the diffusion coefficient in the presence of electron-electron collisions. Accordingly, we introduce a ‘‘model’’ collision operator as well as a ‘‘model’’ electron distribution function which can be used in a one-particle numerical procedure. In this way one can overcome the difficulties connected with the calculation of the diffusion coefficient in the presence of electron-electron collisions within the framework of the particle approach.
Cell-Free Synthesis Meets Antibody Production: A Review

Engineered antibodies are key players in therapy, diagnostics and research. In addition to full size immunoglobulin gamma (IgG) molecules, smaller formats of recombinant antibodies, such as single-chain variable fragments (scFv) and antigen binding fragments (Fab), have emerged as promising alternatives since they possess different advantageous properties. Cell-based production technologies of antibodies and antibody fragments are well-established, allowing researchers to design and manufacture highly specific molecular recognition tools. However, as these technologies are accompanied by the drawbacks of being rather time-consuming and cost-intensive, efficient and powerful cell-free protein synthesis systems have been developed over the last decade as alternatives. So far, prokaryotic cell-free systems have been the focus of interest. Recently, eukaryotic in vitro translation systems have enriched the antibody production pipeline, as these systems are able to mimic the natural pathway of antibody synthesis in eukaryotic cells. This review aims to overview and summarize the advances made in the production of antibodies and antibody fragments in cell-free systems.
SPEK: a storage performance evaluation kernel module for block-level storage systems under faulty conditions

This paper introduces a new benchmark tool, SPEK (storage performance evaluation kernel module), for evaluating the performance of block-level storage systems in the presence of faults as well as under normal operations. SPEK can work on both direct attached storage (DAS) and block level networked storage systems such as storage area networks (SAN). Each SPEK consists of a controller, several workers, one or more probers, and several fault injection modules. Since it runs at kernel level and eliminates skews and overheads caused by file systems, SPEK is highly accurate and efficient. It allows a storage architect to generate configurable workloads to a system under test and to inject different faults into various system components such as network devices, storage devices, and controllers. Available performance measurements under different workloads and faulty conditions are dynamically collected and recorded in SPEK over a spectrum of time. To demonstrate its functionality, we apply SPEK to evaluate the performance of two direct attached storage systems and two typical SANs under Linux with different fault injections. Our experiments show that SPEK is highly efficient and accurate to measure performance for block-level storage systems.
Multi-scale decomposition for remote sensing image processing

Based on image gradients, an alternative image multi-scale decomposition approach for remote sensing image processing is derived through solving a Poisson equation in this paper. First, the image gradients are obtained. Second, the gradients with given magnitudes are attenuated using some operators. Finally, the modified gradients are used to solve a Poisson equation to obtain the smooth base layer and thus the detail layer. This multi-scale decomposition approach is used for remote sensing image enhancement and remote sensing image smoothing, which outperforms the other methods such as bilateral filter (BLF) and weighted least squares based multi-scale decomposition (WLSMD) in edge-preserving image decomposition via experiments.
A Long Time Tracker Based on Self-Correction and Random Selection Strategy

Visual tracking is one of the most active research areas in computer vision, with numerous application including augmented reality, surveillance, weapons-guiding technologies, and object identification. The key question for robust visual tracking is to extract the appearance model features of target appropriately and locate the object exactly. This paper presents a novel nonrigid target tracking algorithm which can track a nonrigid target(such as hand) stably and is real time, and we review on the latter target tracking research direction, which is a very challenging problem in the field of visual tracking. Our algorithm is based on a SCTS (self-correction tracking strategy), then we use a RSHD (random selection HAAR detector) to detect the real target, the final target location is the mixed results of SCTS and RSHD. The proposed algorithm can track hand or some other nonrigid targets reliably even in clutter environments. Finally, we demonstrate the benefits of our approach in contrast to existing methods.
A Molecular Basis for Agonist and Antagonist Actions at GABAC Receptors

We modelled the N‐terminal ligand‐binding domain of the ρ1 GABAC receptor based on the Lymnaea stagnalis acetylcholine‐binding protein (L‐AChBP) crystal structure using comparative modelling and validated using flexible docking guided by known mutagenesis studies. A range of known ρ1 GABAC receptor ligands comprising seven full agonists, 10 partial agonists, 43 antagonists and 12 inactive molecules were used to evaluate and validate the models. Of the 50 models identified, six models that allowed flexible ligand docking in accordance with the experimental data were selected and used to study detailed receptor‐ligand interactions. The most refined model to accommodate all known active ligands featured a cavity comprising of a volume of 488 Å3. A detailed analysis of the interaction between the ρ1 GABAC receptor model and the docked ligands revealed possible H‐bonds and cation‐π interactions between the different ligands and binding site residues. Based on quantum mechanical/molecular mechanical (QM/MM) calculations, the model showed distinctive conformations of loop C that provided a molecular basis for agonist and antagonist actions. Agonists elicit loop C closure, while a more open loop C was observed upon antagonist binding. The model differentiates the role for key residues known to be involved in either binding and/or gating.
Cognitive Variability during Middle-Age: Possible Association with Neurodegeneration and Cognitive Reserve

Objective: Increased variability in cognition with age has been argued as an indication of pathological processes. Focusing on early detection of neurodegenerative disorders, we investigated variability in cognition in healthy middle-aged adults. In order to understand possible determinants of this variability, we also investigated associations with cognitive reserve, neuroimaging markers, subjective memory complaints, depressive symptomatology, and gender. Method: Thirty-one 50 ± 2 years old individuals were investigated as target group and deviation was studied in comparison to a reference younger group of 30 individuals 40 ± 2 years old. Comprehensive neuropsychological and structural imaging protocols were collected. Brain regional volumes and cortical thickness were calculated with FreeSurfer, white matter hyperintensities with CASCADE, and mean diffusivity with FSL. Results: Across-individuals variability showed greater dispersion in lexical access, processing speed, executive functions, and memory. Variability in global cognition correlated with, reduced cortical thickness in the right parietal-temporal-occipital association cortex, and increased mean diffusivity in the cingulum bundle and right inferior fronto-occipital fasciculus. A trend was also observed for the correlation between global cognition and hippocampal volume and female gender. All these associations were influenced by cognitive reserve. No correlations were found with subjective memory complaints, white matter hyperintensities and depressive symptomatology. Across-domains and across-tasks variability was greater in several executive components and cognitive processing speed. Conclusion: Variability in cognition during middle-age is associated with neurodegeneration in the parietal–temporal–occipital association cortex and white matter tracts connecting this to the prefrontal dorsolateral cortex and the hippocampus. Moreover, this effect is influenced by cognitive reserve. Studying variability offers valuable information showing that differences do not occur in the same magnitude and direction across individuals, cognitive domains and tasks. These findings may have important implications for early detection of subtle cognitive impairment and clinical interpretation of deviation from normality.
Face Set Classification using Maximally Probable Mutual Modes

In this paper we consider face recognition from sets of face images and, in particular, recognition invariance to illumination. The main contribution is an algorithm based on the novel concept of maximally probable mutual modes (MMPM). Specifically: (i) we discuss and derive a local manifold illumination invariant and (ii) show how the invariant naturally leads to a formulation of "common modes" of two face appearance distributions. Recognition is then performed by finding the most probable mode, which is shown to be an eigenvalue problem. The effectiveness of the proposed method is demonstrated empirically on a challenging database containing the total of 700 video sequences of 100 individuals
s‐CARBOXYMETHYLCYSTEINE INHIBITS CARBACHOL‐INDUCED CONSTRICTION OF EPITHELIUM‐DENUDED RAT AND HUMAN AIRWAY PREPARATIONS

1 The effects of s‐carboxymethyl‐l‐cysteine (S‐CMC), either administered orally to rats or incubated with tissue preparations from rats and humans, on isometric contractions of tracheal smooth muscle were investigated in the present study using an improved in vitro model of tracheal tube or ring preparations. The involvement of the tracheal epithelium in the observed effects was also investigated. 2 The experimental model permitted selective perfusion of the airway tube, luminal‐IN or serosal–OUT, and measurement of airway smooth muscle contraction or relaxation in preparations with (+) or without (–) epithelium (Ep), excluding direct effects of airway mucus. 3 We found that oral pretreatment of rats with S‐CMC (mixed with water; 200 mg/kg per day for 2 weeks), but not short pre‐incubation of preparations in vitro (10−3 mol/L S‐CMC for 1 h), diminished the sensitivity of –Ep preparations to carbachol compared with controls (EC50 (–log10 mol/L) values: 5.5 ± 0.1 vs 5.8 ± 0.1, respectively, for IN perfusion (P < 0.005); 5.6 ± 0.1 vs 5.9 ± 0.1, respectively, for OUT perfusion (P < 0.005)), whereas the sensitivity of preparations to aminophylline was not affected. Normal sensitivity to carbachol stimulation was re‐established if preparations were pre‐incubated with capsaicin. 4 It was also found that longer pre‐incubation (4 h) of ring‐preparations of human bronchus with S‐CMC (10−5 mol/L) in vitro resulted in a diminished response to carbachol stimulation. 5 In conclusion, S‐CMC had small inhibitory effects on the sensitivity of rat and human airway smooth muscle to carbachol, particularly in endothelium‐denuded preparations. Whether the epithelium was responding to S‐CMC by producing some contracting factor(s) requires further investigation.
Anti-filarial Activity of Antibiotic Therapy Is Due to Extensive Apoptosis after Wolbachia Depletion from Filarial Nematodes

Filarial nematodes maintain a mutualistic relationship with the endosymbiont Wolbachia. Depletion of Wolbachia produces profound defects in nematode development, fertility and viability and thus has great promise as a novel approach for treating filarial diseases. However, little is known concerning the basis for this mutualistic relationship. Here we demonstrate using whole mount confocal microscopy that an immediate response to Wolbachia depletion is extensive apoptosis in the adult germline, and in the somatic cells of the embryos, microfilariae and fourth-stage larvae (L4). Surprisingly, apoptosis occurs in the majority of embryonic cells that had not been infected prior to antibiotic treatment. In addition, no apoptosis occurs in the hypodermal chords, which are populated with large numbers of Wolbachia, although disruption of the hypodermal cytoskeleton occurs following their depletion. Thus, the induction of apoptosis upon Wolbachia depletion is non-cell autonomous and suggests the involvement of factors originating from Wolbachia in the hypodermal chords. The pattern of apoptosis correlates closely with the nematode tissues and processes initially perturbed following depletion of Wolbachia, embryogenesis and long-term sterilization, which are sustained for several months until the premature death of the adult worms. Our observations provide a cellular mechanism to account for the sustained reductions in microfilarial loads and interruption of transmission that occurs prior to macrofilaricidal activity following antibiotic therapy of filarial nematodes.
Performance status and cytoreductive nephrectomy

An Eastern Cooperative Oncology Group performance status (ECOG PS) of 2/3 can quantify cancer patients' well being and may be used to select patients for treatment. The objective of the current study was to investigate the outcomes of cytoreductive nephrectomy (CN) for patients who have an impaired performance status (ECOG PS 2/3).
Constraining application behaviour by generating languages

Writing a platform for reactive applications which enforces operational constraints is difficult, and has been approached in various ways. In this experience report, we detail an approach using an embedded DSL which can be used to specify the structure and permissions of a program in a given application domain. Once the developer has specified which components an application will consist of, and which permissions each one needs, the specification itself evaluates to a new, tailored, language. The final implementation of the application is then written in this specialised environment where precisely the API calls associated with the permissions which have been granted, are made available. Our prototype platform targets the domain of mobile computing, and is implemented using Racket. It demonstrates resource access control (e.g., camera, address book, etc.) and tries to prevent leaking of private data. Racket is shown to be an extremely effective platform for designing new programming languages and their run-time libraries. We demonstrate that this approach allows reuse of an inter-component communication layer, is convenient for the application developer because it provides high-level building blocks to structure the application, and provides increased control to the platform owner, preventing certain classes of errors by the developer.
Potential Impact of Influenza A/H1N1 Pandemic and Hand-Gels on Acute Diarrhea Epidemic in France

Background The 2009 A/H1N1 influenza pandemic has received a great deal of attention from public health authorities. Our study examines whether this pandemic and the resulting public health measures could have impacted acute diarrhea, a prevalent, highly transmissible and historically monitored disease. Methods Using augmentation procedures of national data for the previous five years (2004–2009), we estimated the expected timing and incidence of acute diarrhea in France in 2009–2010 and evaluated differences with the observed. We also reviewed national hand gels for the same period. Findings Number of episodes of acute diarrhea in France in 2009–2010 was significantly lower than expected until the third week of December (−24%, 95% CI [−36%; −9%]), then significantly higher (+40%, 95% CI [22%; 62%]), leading to a surplus of 574,440 episodes. The epidemic was delayed by 5 weeks with a peak 1.3 times higher than expected. Hand-gels sales inversely correlated with incidence of both influenza-like illness and acute diarrheal disease. Among individuals >65 yo, no excess cases of influenza and no excess rebound in acute diarrhea were observed, despite similar delay in the onset of the seasonal diarrheal epidemic. Interpretation Our results suggest that at least one endemic disease had an unexpected behavior in 2009–2010. Acute diarrhea seems to have been controlled during the beginning of the pandemic in all age groups, but later peaked higher than expected in the younger population. The all-age delay in seasonal onset seems partly attributable to hand-gels use, while the differential magnitude of the seasonal epidemic between young and old, concurrent for both influenza and acute diarrhea, is compatible with disease interaction.