Miracle-dz/UniFAR-FTUs huggingface dataset:
Hypertrophic Cardiomyopathy Is Predominantly a Disease of Left Ventricular Outflow Tract Obstruction

Background— Nonobstructive hypertrophic cardiomyopathy (HCM) has been regarded as the predominant hemodynamic form of the disease on the basis of assessment of outflow gradient under resting conditions. We sought to prospectively define the prevalence, clinical profile, and significance of left ventricular (LV) outflow tract obstruction under resting conditions and with physiological exercise in a large HCM cohort. Methods and Results— We prospectively analyzed 320 consecutive HCM patients (age, 47±17 years), measuring LV outflow gradient at rest, with Valsalva maneuver, and with exercise echocardiography. LV outflow obstruction was present at rest and/or with exercise in 225 patients (70%); 119 had rest gradients ≥50 mm Hg and were not exercised. Of the other 201 patients with gradients <50 mm Hg at rest (average, 4±9 mm Hg), 106 developed mechanical obstruction to LV outflow resulting from mitral valve–septal contact after exercise (80±43 mm Hg), including 76 with marked gradients ≥50 mm Hg and 46 with heart failure symptoms. The remaining 95 patients (30%) had no or small gradients (<30 mm Hg) both at rest and with exercise. Valsalva maneuver underestimated the presence and magnitude of exercise-induced obstruction. Conclusions— Among those patients who come to clinical evaluation, HCM is a predominantly obstructive disease in which LV outflow gradients, frequently associated with heart failure symptoms and often identified only with exercise, are evident in most patients (ie, 70%). Identification of LV outflow obstruction with exercise echocardiography may broaden management options in HCM by identifying symptomatic patients not otherwise regarded as potential candidates for septal reduction therapy. Assessment of subaortic gradients with exercise should be a routine component of the evaluation of HCM patients without outflow obstruction under resting conditions.
A Statistical Framework for Online Arabic Character Recognition

ABSTRACT The widely-used PDAs, touch screens, tablet-PCs are alternatives to keyboards with the advantages of being more friendly, easy, and natural. A framework for Arabic online character recognition is developed. The framework integrates the different phases of online Arabic text recognition. The used data poses several challenges such as delayed strokes handling, connectivity problems, variability, and style change of text. We process the delayed strokes at the different phases differently to improve the overall performance. This work includes feature extraction of many features, including several novel statistical features. Experimental results on challenging online Arabic characters show encouraging results.
Isolation of Genetically Diverse Marburg Viruses from Egyptian Fruit Bats

In July and September 2007, miners working in Kitaka Cave, Uganda, were diagnosed with Marburg hemorrhagic fever. The likely source of infection in the cave was Egyptian fruit bats (Rousettus aegyptiacus) based on detection of Marburg virus RNA in 31/611 (5.1%) bats, virus-specific antibody in bat sera, and isolation of genetically diverse virus from bat tissues. The virus isolates were collected nine months apart, demonstrating long-term virus circulation. The bat colony was estimated to be over 100,000 animals using mark and re-capture methods, predicting the presence of over 5,000 virus-infected bats. The genetically diverse virus genome sequences from bats and miners closely matched. These data indicate common Egyptian fruit bats can represent a major natural reservoir and source of Marburg virus with potential for spillover into humans.
Pulmonary Neuroendocrine Cell Hyperplasia Associated with Surfactant Protein C Gene Mutation

Familial interstitial lung disease (ILD) is defined as presence of ILD in 2 or more family members. Surfactant protein C (SFTPC) gene mutations are rare, but well-known cause of familial ILD. We reported a 20-year-old male, who was referred for lung transplantation. He was symptomatic at age 3 and underwent surgical lung biopsy at age 6, which revealed a nonspecific interstitial pneumonia (NSIP) pattern. Genetic workup revealed a novel SFTPC mutation in the first intron with a C to A transversion. At age 21, he underwent bilateral lung transplantation. Explanted lung histology suggested NSIP. In addition there was pulmonary neuroendocrine cell (PNEC) hyperplasia and carcinoid tumorlets. His mother had undergone lung transplantation several years earlier, and her explanted lung showed similar pathology. SFTPC mutations are inherited in an autosomal dominant pattern. Various types of ILD have been associated with SFTPC mutation including NSIP, usual interstitial pneumonia (UIP), and desquamative interstitial pneumonia (DIP). PNEC hyperplasia has been described to occur in association with lung inflammation but has not been previously described with familial ILD associated with SFTPC mutation.
Chicken major histocompatibility complex congenic lines differ in the percentages of lymphocytes bearing CD4 and CD8 antigens.

In the experiments to be described two congenic inbred lines CB and CC and two recombinant lines CB.R1 and CC.R1 were used. All four lines differ only in regard to the major histocompatibility complex (MHC). To determine the percentage distributions of the two cell subsets in peripheral blood lymphocytes (PBL) in these lines, monoclonal antibodies to these two antigens were used. By FACScan there were more CD4+PBL in CB and CB.R1 lines (share B-F/B-L region, controlling class I/class II antigens with line CB) than CC and CC.R1, while the reverse was true with CD8+ subsets. There were more CD8+ PBL in the CC and CC.R1 lines and less in CB and CB.R1 lines. The ratio of CD4+ to CD8+ in CB chickens was 3.4 +/- 0.2 and in CC chickens 1.6 +/- 0.1.
Coupling or decoupling for KNN search on road networks?: a hybrid framework on user query patterns

We explore in this paper a new KNN algorithm, called the SQUARE algorithm, for searching spatial objects on road networks. Recent works in the literature discussed the necessity to support object updates for promising location-based services. Among them, the decoupling spatial search algorithms, which separate the handle of the network traversal and the object lookup, has been recognized as the most effective approach to cut the maintenance overhead from updates. However, the queue-based network traversal needs to be performed from scratch for each KNN query until the KNN objects are exactly identified, indicating that the query complexity is in proportion to the number of visited network nodes. The query efficiency is concerned for online LBS applications since they only allow lightweight operations for minimizing the query latency. To improve the query scalability while supporting data updates, SQUARE constructs the network index similar to the way used in decoupling models, and meanwhile exploit the coupling idea to maintain the KNN information relative to hot regions in the network index. The hot region denotes the area with frequent queries discovered in the query history. Inspired from the prevalently observed 80-20 rule, SQUARE can maximize the query throughput by returning KNN results in the quasi-constant time for 80% queries that are roughly issued within 20% area (hot regions). As validated in our experimental results, SQUARE outperforms previous works and achieves the significant performance improvement without sacrifice on the maintenance overhead for object updates.
Mechanism of monofunctional and bifunctional alkylation of DNA by mitomycin C.

The relative amounts of monofunctional and bifunctional alkylation products of DNA with mitomycin C (MC) depend on whether one or both masked alkylating functions of MC are activated reductively; adduct 8 is the result of one function and adducts 7 and 9, formed as a pair, are the result of both functions being activated [Tomasz, M. , Lipman, R. , Chowdary, C. , Pawlak, J., Verdine, G. L. , & Nakanishi, K. (1987) Science (Washington, D.C.) 235, 1204-1208]. To determine the mechanism governing this differential reactivity of MC with DNA, MC-Micrococcus luteus DNA complexes formed under varying conditions in vitro were digested to nucleosides and adducts. Adduct distribution, analyzed by high-performance liquid chromatography, served as the measure of monofunctional and bifunctional activation. H2/PtO2 and xanthine oxidase/reduced nicotinamide adenine dinucleotide (NADH) activated MC mostly monofunctionally, and Na2S2O4 activated the drug bifunctionally under comparable conditions. Excess MC selectively suppressed, but excess PtO2 selectively promoted, bifunctional activation by H2/PtO2; excess xanthine oxidase and/or NADH also had promoting effects. O2 tested in the Na2S2O4 system was inhibitory. 10-Decarbamoyl-MC acted strictly monofunctionally under all conditions. Monoadducts bound to DNA were converted to bis adducts upon rereduction. A mechanism with the following features was derived: (i) Activation of MC at C-1 and C-10 is sequential (C-1 first). (ii) A one-time reduction is sufficient for both. (iii) Activation of the second function may be selectively inhibited by kinetic factors or O2. (iv) 7 and 9 are coproducts of bifunctional activation; their ratio depends on the DNA base sequence. (v) Activation of the second function involves an iminium intermediate. Direct applications to the action of MC in vivo are discussed.
Building Large Storage Based On Flash Disks

Flash SSDs are a technology that has the potential of drastically changing the architecture of a DBMS. In this paper we examine the properties of a storage space built on SSDs with RAID and how these affect data intensive systems. While we observed the expected performance improvements of one to two orders of magnitude of SSD-only storage over HDD storage, RAID-SSD systems showed interesting effects and large performance degradation: (a) the SSD read-write asymmetry and the write behavior are amplified due to RAID; (b) scalability issues in a RAID-based storage system appear because of inadequate controllers; (c) fragmentation and distribution issues affect performance much more than expected.
Mobility aware virtual network embedding

Over the last years, network virtualization has become one of the most promising solutions for sustainability towards the ongoing increase of data demand in mobile networks. The problem of efficiently forming a virtual network has been studied extensively during the past years and many different solutions have been proposed but these studies have mainly focused on wired networks. The main purpose of this paper is to provide an optimization framework for optimal virtual network embedding by explicitly considering the effect of the actual user mobility, assuming a Distributed Mobility Management (DMM) scheme. In addition, service differentiation is introduced, giving higher priority to time-critical over-the-top (OTT) services compared to elastic Internet applications. The performance of the proposed framework is compared to greedy heuristics algorithms that are mobility agnostic and numerical investigations reveal that the effect of mobility has an important role to play in the design of virtual networks. Additionally, the mobility aware scheme can provide tangible gains in the overall performance compared with the previous proposed schemes that do not take into account the effect of user mobility.
Salivation and Saliva Control in Children , More than Just Drooling

Welcome to our 4th year! I want to thank all those resubscribers for your support and welcome new readers. We have a jam packed issue this quarter with articles by some of the experts in the field! Joan Sheppard Ph.D. writes about saliva control, Lynn Wolf MOT, OTR and colleague Nan Street PT discuss a personal GI experience, and Betsy Clawson Ph.D. provides an interesting case and explanation of the psychologists role in feeding management. Hope you enjoy. Feel free to contact me with suggestions or comments at Kbracket@unch.unc. edu .
Complications, Failure to Rescue, and Mortality With Major Inpatient Surgery in Medicare Patients

Objective:We sought to determine whether hospital variations in surgical mortality were due to differences in complication rates or failure to rescue rates (ie, case-fatality rates in patients with a complication). Background:Wide variations in mortality after major surgery are becoming increasingly apparent. The clinical mechanisms underling these variations are largely unexplored. Methods:We studied all Medicare beneficiaries undergoing 6 major operations in 2005 to 2006: pancreatectomy, esophagectomy, abdominal aortic aneurysm repair, coronary artery bypass grafting, aortic valve replacement, and mitral valve replacement. We ranked hospitals according to risk-adjusted mortality and divided them into 5 equal groups. We then compared the incidence of complications and rates of failure to rescue between the top 20% of hospitals (“best”) and bottom 20% of hospitals (“worst”). Analyses were conducted for all operations combined and for each individual procedure. Results:For all 6 operations combined, the worst hospitals had mortality rates 2.5-fold higher than the best hospitals (8.0% vs. 3.0%). However, complication rates were similar at worst and best hospitals (36.4% vs. 32.7%). In contrast, failure to rescue rates were much higher at the worst compared with the best hospitals (16.7% vs. 6.8%). These findings persisted in analyses with individual operations and specific complications. Conclusions:Reducing variations in mortality will require strategies to improve the ability of high-mortality hospitals to manage postoperative complications.
Stability and Function of Mammalian Lethal Giant Larvae-1 Oncoprotein Are Regulated by the Scaffolding Protein RanBPM*

The evolutionarily conserved lethal giant larvae (Lgl) tumor suppressor gene has an essential role in establishing apical-basal cell polarity, cell proliferation, differentiation, and tissue organization. However, the precise molecular mechanism by which the Lgl carries out its function remains obscure. In the current study, we have identified Ran-binding protein M (RanBPM) as a novel binding partner of Mgl-1, a mammalian homolog of Drosophila tumor suppressor protein lethal (2) giant larvae (L(2)gl) by yeast two-hybrid screening. RanBPM seems to act as a scaffolding protein with a modulatory function with respect to Mgl-1. The Mgl-1 and RanBPM association was confirmed by co-immunoprecipitation and GST pull-down experiments. Additionally, expression of RanBPM resulted in inhibition of Mgl-1 degradation, and thereby extended the half-life of Mgl-1. Furthermore, the ability of Mgl-1 activity in cell migration and colony formation assay was enhanced by RanBPM. Taken together, our findings reveal that RanBPM plays a novel role in regulating Mgl-1 stability and contributes to its biological function as a tumor suppressor.
Characterization of monoclonal antibodies raised against the latent nuclear antigen (LNA) of human herpesvirus-8

'Characterization of monoclonal antibodies raised against the latent nuclear antigen (LNA) of human herpesvirus-8' Journal of Virology, vol 73, pp. 5149-55. General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact openaccess@ed.ac. uk providing details, and we will remove access to the work immediately and investigate your claim.
Stochastic induction of persister cells by HipA through (p)ppGpp-mediated activation of mRNA endonucleases

Significance Bacteria produce persister cells that are tolerant to multiple antibiotics because they are hibernating in a dormant state in which the antibiotics cannot eradicate them. Persisters can thus survive after drug treatment of infections and cause relapse of disease. The formation of persister cells depends on the ubiquitous bacterial regulatory nucleotides tetra and penta-guanosine phosphate [(p)ppGpp] that activate inhibitors of cell growth. One such inhibitor, HipA (high persister protein A), is an enzyme that halts translation by inhibiting glutamyl tRNA synthetase, an essential tRNA charging enzyme. Here we show that, surprisingly, HipA-induced persistence depends on (p)ppGpp-mediated activation of yet other inhibitors of translation that catalytically degrade messenger RNA. This discovery expands our mechanistic insight into the common and important phenomenon of bacterial multidrug tolerance. The model organism Escherichia coli codes for at least 11 type II toxin–antitoxin (TA) modules, all implicated in bacterial persistence (multidrug tolerance). Ten of these encode messenger RNA endonucleases (mRNases) inhibiting translation by catalytic degradation of mRNA, and the 11th module, hipBA, encodes HipA (high persister protein A) kinase, which inhibits glutamyl tRNA synthetase (GltX). In turn, inhibition of GltX inhibits translation and induces the stringent response and persistence. Previously, we presented strong support for a model proposing (p)ppGpp (guanosine tetra and penta-phosphate) as the master regulator of persistence. Stochastic variation of [(p)ppGpp] in single cells induced TA-encoded mRNases via a pathway involving polyphosphate and Lon protease. Polyphosphate activated Lon to degrade all known type II antitoxins of E. coli. In turn, the activated mRNases induced persistence and multidrug tolerance. However, even though it was known that activation of HipA stimulated (p)ppGpp synthesis, our model did not explain how hipBA induced persistence. Here we show that, in support of and consistent with our initial model, HipA-induced persistence depends not only on (p)ppGpp but also on the 10 mRNase-encoding TA modules, Lon protease, and polyphosphate. Importantly, observations with single cells convincingly show that the high level of (p)ppGpp caused by activation of HipA does not induce persistence in the absence of TA-encoded mRNases. Thus, slow growth per se does not induce persistence in the absence of TA-encoded toxins, placing these genes as central effectors of bacterial persistence.
Balancing Speed and Quality in Online Learning to Rank for Information Retrieval

In Online Learning to Rank (OLTR) the aim is to find an optimal ranking model by interacting with users. When learning from user behavior, systems must interact with users while simultaneously learning from those interactions. Unlike other Learning to Rank (LTR) settings, existing research in this field has been limited to linear models. This is due to the speed-quality tradeoff that arises when selecting models: complex models are more expressive and can find the best rankings but need more user interactions to do so, a requirement that risks frustrating users during training. Conversely, simpler models can be optimized on fewer interactions and thus provide a better user experience, but they will converge towards suboptimal rankings. This tradeoff creates a deadlock, since novel models will not be able to improve either the user experience or the final convergence point, without sacrificing the other. Our contribution is twofold. First, we introduce a fast OLTR model called Sim-MGD that addresses the speed aspect of the speed-quality tradeoff. Sim-MGD ranks documents based on similarities with reference documents. It converges rapidly and, hence, gives a better user experience but it does not converge towards the optimal rankings. Second, we contribute Cascading Multileave Gradient De- scent (C-MGD) for OLTR that directly addresses the speed-quality tradeoff by using a cascade that enables combinations of the best of two worlds: fast learning and high quality final convergence. C-MGD can provide the better user experience of Sim-MGD while maintaining the same convergence as the state-of-the-art MGD model. This opens the door for future work to design new models for OLTR without having to deal with the speed-quality tradeoff.
Genetic Variation Predicting Cisplatin Cytotoxicity Associated with Overall Survival in Lung Cancer Patients Receiving Platinum-Based Chemotherapy

Purpose: Inherited variability in the prognosis of lung cancer patients treated with platinum-based chemotherapy has been widely investigated. However, the overall contribution of genetic variation to platinum response is not well established. To identify novel candidate single nucleotide polymorphisms (SNP)/genes, we carried out a genome-wide association study (GWAS) for cisplatin cytotoxicity by using lymphoblastoid cell lines (LCL), followed by an association study of selected SNPs from the GWAS with overall survival (OS) in lung cancer patients. Experimental Design: A GWAS for cisplatin was conducted with 283 ethnically diverse LCLs. A total of 168 top SNPs were genotyped in 222 small cell lung cancer (SCLC) and 961 non-SCLC (NSCLC) patients treated with platinum-based therapy. Association of the SNPs with OS was determined by using the Cox regression model. Selected candidate genes were functionally validated by siRNA knockdown in human lung cancer cells. Results: Among 157 successfully genotyped SNPs, 9 and 10 SNPs were top SNPs associated with OS for patients with NSCLC and SCLC, respectively, although they were not significant after adjusting for multiple testing. Fifteen genes, including 7 located within 200 kb up or downstream of the 4 top SNPs and 8 genes for which expression was correlated with 3 SNPs in LCLs were selected for siRNA screening. Knockdown of DAPK3 and METTL6, for which expression levels were correlated with the rs11169748 and rs2440915 SNPs, significantly decreased cisplatin sensitivity in lung cancer cells. Conclusions: This series of clinical and complementary laboratory-based functional studies identified several candidate genes/SNPs that might help predict treatment outcomes for platinum-based therapy of lung cancer. Clin Cancer Res; 17(17); 5801–11. ©2011 AACR.
IL‐22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis

IL‐22 is an IFN–IL‐10 cytokine family member, which is produced by activated Th1 and NK cells and acts primarily on epithelial cells. Here we demonstrate that IL‐22, in contrast to its relative IFN‐γ, regulates the expression of only a few genes in keratinocytes. This is due to varied signal transduction. Gene expressions regulated by IL‐22 should enhance antimicrobial defense [psoriasin (S100A7), calgranulin A (S100A8), calgranulin B (S100A9)], inhibit cellular differentiation (e.g., profilaggrin, keratins 1 and 10, kallikrein 7), and increase cellular mobility [e.g., matrix metalloproteinease 1 (MMP1, collagenase 1), MMP3 (stromelysin 1), desmocollin 1]. In contrast, IFN‐γ favored the expression of MHC pathway molecules, adhesion molecules, cytokines, chemokines, and their receptors. The IL‐22 effects were transcriptional and either independent of protein synthesis and secretion, or mediated by a secreted protein. Inflammatory conditions, but not keratinocyte differentiation, amplified the IL‐22 effects. IL‐22 application in mice enhanced cutaneous S100A9 and MMP1 expression. High IL‐22 levels in psoriatic skin were associated with strongly up‐regulated cutaneous S100A7, S100A8, S100A9, and MMP1 expression. Psoriatic patients showed strongly elevated IL‐22 plasma levels, which correlated with the disease severity. Expression of IL‐22 and IL‐22‐regulated genes was reduced by anti‐psoriatic therapy. In summary, despite similarities, IFN‐γ primarily amplifies inflammation, while IL‐22 may be important in the innate immunity and reorganization of epithelia.