Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of paramyosin as a binding protein for calgranulin C in experimental helminthic keratitis.

PURPOSE Calgranulin C (CaGC) is a protein released by activated neutrophils and involved in host defense against filarial infections. This study involved the identification of binding protein(s) of the helminth Brugia malayi to CaGC and the ability of binding complexes to induce keratitis. METHODS Parasitic extracts prepared from B. malayi microfilariae and adult worms were incubated with recombinant CaGC protein. Parasite binding protein-CaGC complex was isolated by affinity chromatography. A B. malayi microfilariae cDNA library was immunoscreened with antisera from rats immunized with the isolated parasitic CaGC-binding protein. All positive clones contained paramyosin sequences. Paramyosin was thus considered the major CaGC-binding protein in the parasite. To delineate the binding of CaGC to native and recombinant paramyosin, 125I-CaGC was used as a binding tracer in SDS-PAGE analysis to identify a CaGC-binding complex. To determine whether the complex of CaGC and its binding protein could induce keratitis mimicking the onchocercal human corneal disease, BALB/c mice preimmunized with the binding complex were challenged with intracorneal binding complex or live Brugia microfilariae. In addition, splenocytes harvested from the same animals were assessed for their ability to elicit cellular immune responses to the binding complex by [3H]thymidine assay. RESULTS In vitro binding of CaGC to paramyosin was confirmed using recombinant paramyosin and 125I-CaGC. Test animals showed development of severe keratitis that mimicked, clinically and histopathologically, the human onchocercal corneal disease, demonstrating the antigenic specificity of the paramyosin-CaGG-binding complex. CONCLUSIONS Paramyosin is identified as a CaGC-binding protein in B. malayi.
Structure of an RNA Polymerase II–TFIIB Complex and the Transcription Initiation Mechanism

Dissecting TFIIB Mechanics Eukaryotic RNA polymerase II (Pol II) requires five protein cofactors for promoter recognition and initiation of transcription. The factor TFIIB is implicated in start site selection and stabilization of the initial transcript. The co-crystal structure of Pol II and TFIIB showed an N-terminal “finger” region located in the RNA exit channel, but the core C-terminal region of TFIIB was disordered. Now Liu et al. (p. 206; published online 12 November) present a structure of the same complex determined under different conditions in which the C-terminal structure is well localized but the finger is disordered. Docking DNA into the structure suggests that the C-terminal region stabilizes initial promoter melting. After transcription of a few bases, TFIIB probably switches to the alternate conformation where the C-terminal region is released and the finger region stabilizes the initial transcript. X-ray structures provide more details on the initiation of transcription. Previous x-ray crystal structures have given insight into the mechanism of transcription and the role of general transcription factors in the initiation of the process. A structure of an RNA polymerase II–general transcription factor TFIIB complex at 4.5 angstrom resolution revealed the amino-terminal region of TFIIB, including a loop termed the “B finger,” reaching into the active center of the polymerase where it may interact with both DNA and RNA, but this structure showed little of the carboxyl-terminal region. A new crystal structure of the same complex at 3.8 angstrom resolution obtained under different solution conditions is complementary with the previous one, revealing the carboxyl-terminal region of TFIIB, located above the polymerase active center cleft, but showing none of the B finger. In the new structure, the linker between the amino- and carboxyl-terminal regions can also be seen, snaking down from above the cleft toward the active center. The two structures, taken together with others previously obtained, dispel long-standing mysteries of the transcription initiation process.
Risk-treatment mismatch in the pharmacotherapy of heart failure.

CONTEXT Patients with heart failure have a wide spectrum of mortality risks. To maximize the benefit of available pharmacotherapies, patients with high mortality risk should receive high rates of drug therapy. OBJECTIVE To examine patterns of drug therapy and underlying mortality risk in patients with heart failure. DESIGN, SETTING, AND PATIENTS In the Enhanced Feedback for Effective Cardiac Treatment (EFFECT) population-based cohort (1999-2001) of 9942 patients with heart failure hospitalized in Ontario, Canada, we evaluated 1418 patients with documented left ventricular ejection fraction of 40% or less and aged 79 years or younger with low-, average-, and high-predicted risk of death within 1 year; all patients survived to hospital discharge. Administration of angiotensin-converting enzyme (ACE) inhibitors, ACE inhibitors or angiotensin II receptor blockers (ARBs), and beta-adrenoreceptor antagonists was evaluated according to predicted risk of death. MAIN OUTCOME MEASURE Heart failure drug administration rates at time of discharge and 90 days after hospital discharge. RESULTS At hospital discharge, prescription rates for patients in the low-, average-, and high-risk groups were 81%, 73%, 60%, respectively, for ACE inhibitors; 86%, 80%, 65%, respectively, for ACE inhibitors or ARBs; and 40%, 33%, 24%, respectively, for beta-adrenoreceptor antagonists (all P<.001 for trend). Within 90 days following hospital discharge, the rates were 83%, 76%, and 61% for ACE inhibitors; 89%, 83%, and 67% for ACE inhibitors or ARBs; and 43%, 36%, and 28% for beta-adrenoreceptor antagonists for the 3 risk groups, respectively (all P<.001 for trend). The pattern of lower rates of drug administration in those patients at increasing risk was maintained up to 1 year postdischarge (P<.001). After accounting for varying survival time and potential contraindications to therapy, low-risk patients were more likely to receive ACE inhibitors or ARBs (adjusted hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.49-1.74) and beta-adrenoreceptor antagonists (HR, 1.80; 95% CI, 1.60-2.01) compared with high-risk patients (both P<.001). CONCLUSIONS Patients with heart failure at greatest risk of death are least likely to receive ACE inhibitors, ACE inhibitors or ARBs, and beta-adrenoreceptor antagonists. Understanding the reasons underlying this mismatch may facilitate improvements in care and outcomes for patients with heart failure.
Effects of Partial and Acute Total Sleep Deprivation on Performance across Cognitive Domains, Individuals and Circadian Phase

Background Cognitive performance deteriorates during extended wakefulness and circadian phase misalignment, and some individuals are more affected than others. Whether performance is affected similarly across cognitive domains, or whether cognitive processes involving Executive Functions are more sensitive to sleep and circadian misalignment than Alertness and Sustained Attention, is a matter of debate. Methodology/Principal Findings We conducted a 2 × 12-day laboratory protocol to characterize the interaction of repeated partial and acute total sleep deprivation and circadian phase on performance across seven cognitive domains in 36 individuals (18 males; mean ± SD of age = 27.6±4.0 years). The sample was stratified for the rs57875989 polymorphism in PER3, which confers cognitive susceptibility to total sleep deprivation. We observed a deterioration of performance during both repeated partial and acute total sleep deprivation. Furthermore, prior partial sleep deprivation led to poorer cognitive performance in a subsequent total sleep deprivation period, but its effect was modulated by circadian phase such that it was virtually absent in the evening wake maintenance zone, and most prominent during early morning hours. A significant effect of PER3 genotype was observed for Subjective Alertness during partial sleep deprivation and on n-back tasks with a high executive load when assessed in the morning hours during total sleep deprivation after partial sleep loss. Overall, however, Subjective Alertness and Sustained Attention were more affected by both partial and total sleep deprivation than other cognitive domains and tasks including n-back tasks of Working Memory, even when implemented with a high executive load. Conclusions/Significance Sleep loss has a primary effect on Sleepiness and Sustained Attention with much smaller effects on challenging Working Memory tasks. These findings have implications for understanding how sleep debt and circadian rhythmicity interact to determine waking performance across cognitive domains and individuals.
Flow visualization for turbomachinery design

Visualization of CFD data for turbomachinery design poses some special requirements which are often not addressed by standard flow visualization systems. The authors discuss the issues involved with this particular application and its requirements with respect to flow visualization. Aiming at a feature-based visualization for this task, they examine various existing techniques to locate vortices. The specific flow conditions for turbomachines demonstrate limitations of current methods. Visualization of turbomachinery flow thus raises some challenges and research topics, particularly regarding feature extraction.
The Diabetes Surgery Summit Consensus Conference: Recommendations for the Evaluation and Use of Gastrointestinal Surgery to Treat Type 2 Diabetes Mellitus

Objectives:To develop guidelines for the use of gastrointestinal surgery to treat type 2 diabetes and to craft an agenda for further research. Background:Increasing evidence demonstrates that bariatric surgery can dramatically ameliorate type 2 diabetes. Not surprisingly, gastrointestinal operations are now being used throughout the world to treat diabetes in association with obesity, and increasingly, for diabetes alone. However, the role for surgery in diabetes treatment is not clearly defined and there are neither clear guidelines for these practices nor sufficient plans for clinical trials to evaluate the risks and benefits of such “diabetes surgery. ” Methods:A multidisciplinary group of 50 voting delegates from around the world gathered in Rome, Italy for the first International Conference on Gastrointestinal Surgery to Treat Type 2 Diabetes–(the “Diabetes Surgery Summit”). During the meeting, available scientific evidence was examined and critiqued by the entire group to assess the strength of evidence and to draft consensus statements. Through an iterative process, draft statements were then serially discussed, debated, edited, reassessed, and finally presented for formal voting. After the Rome meeting, statements that achieved consensus were summarized and distributed to all voting delegates for further input and final approval. These statements were then formally critiqued by representatives of several sientific societies at the 1st World Congress on Interventional Therapies for T2DM (New York, Sept 2008). Input from this discussion was used to generate the current position statement. Results:A Diabetes Surgery Summit (DSS) Position Statement consists of recommendations for clinical and research issues, as well as general concepts and definitions in diabetes surgery. The DSS recognizes the legitimacy of surgical approaches to treat diabetes in carefully selected patients. For example, gastric bypass was deemed a reasonable treatment option for patients with poorly controlled diabetes and a body mass index ≥30 kg/m2. Clinical trials to investigate the exact role of surgery in patients with less severe obesity and diabetes are considered a priority. Furthermore, investigations on the mechanisms of surgical control of diabetes are strongly encouraged, as they may help advance the understanding of diabetes pathophysiology. Conclusions:The DSS consensus document embodies the foundations of “diabetes surgery,” and represents a timely attempt by leading scholars to improve access to surgical options supported by sound evidence, while also preventing harm from inappropriate use of unproven procedures.
Zika Virus: An Emerging Worldwide Threat

ZIKA virus (ZIKV) poses a severe threat to the world. Recent outbreaks of ZIKV after 2007 along with its quick transmission have made this virus a matter of international concern. The virus shows symptoms that are similar to those caused in the wake of dengue virus (DENV) and other flaviviruses, which makes it difficult to discern the viral infection. Diagnosis is further complicated as the virus cross-reacts with antibodies of other viruses. Currently, molecular diagnosis of the virus is being performed by RT-PCR and IgM-captured enzyme-linked immunosorbent assay (MAC-ELISA). The real brunt of the virus is, however, borne by children and adults alike. Case studies of the ZIKV outbreaks in the French Polynesia and other places have suggested that there is a close link between the ZIKV and Gullian-Barre syndrome (GBS). The GBS has closely followed in areas facing ZIKV outbreaks. Although solid evidence is yet to emerge, clinical data integration has revealed a large number of ZIKV patients having GBS. Moreover, the amniotic fluids, blood cord, and miscarriage tissues of mothers have been detected with ZIKV, which indicates that the virus either gets transferred from mother to fetus or seeks direct entry in the fetus, causing microcephaly and other brain anomalies in the newborn babies. Studies on mice have confirmed the link between the ZIKV infection during pregnancy and microcephaly in babies. Reports have highlighted the sexual transmission of the ZIKV, as it has been detected in the semen and saliva of affected persons. The intensity with which the ZIKA is spreading can collapse the health sector of several countries, which are poor. A comprehensive strategy is a need of an hour to combat this virus so as to prevent its transmission and avert the looming threat. At the same time, more research on the cure of the ZIKV is imperative.
Effects of Neutron-Induced Well Potential Perturbation for Multiple Cell Upset of Flip-Flops in 65 nm

We measure and investigate the relationship between well potential perturbation and multiple cell upsets (MCUs) by neutron irradiation. Area-efficient cell-based perturbation detectors are placed adjacent to FFs (Flip-Flops). They can measure duration time of perturbation with 5 μm spatial resolution at two voltage levels. The measurement results by neutron irradiation on a 65-nm bulk CMOS show that 95% of MCUs occur simultaneously with well-potential perturbation, while there is very weak relationship between single event upsets (SEUs) and the perturbation.
Characterization of Shear-Sensitive Genes in the Normal Rat Aorta Identifies Hand2 as a Major Flow-Responsive Transcription Factor

Objective Shear forces play a key role in the maintenance of vessel wall integrity. Current understanding regarding shear-dependent gene expression is mainly based on in vitro or in vivo observations with experimentally deranged shear, hence reflecting acute molecular events in relation to flow. Our objective was to combine computational fluid dynamic (CFD) simulations with global microarray analysis to study flow-dependent vessel wall biology in the aortic wall under physiological conditions. Methods and Results Male Wistar rats were used. Animal-specific wall shear stress (WSS) magnitude and vector direction were estimated using CFD based on aortic geometry and flow information acquired by magnetic resonance imaging. Two distinct flow pattern regions were identified in the normal rat aortic arch; the distal part of the lesser curvature being exposed to low WSS and a non-uniform vector direction, and a region along the greater curvature being subjected to markedly higher levels of WSS and a uniform vector direction. Microarray analysis identified numerous novel mechanosensitive genes, including Trpc4 and Fgf12, and confirmed well-known ones, e.g. Klf2 and Nrf2. Gene ontology analysis revealed an over-representation of genes involved in transcriptional regulation. The most differentially expressed gene, Hand2, is a transcription factor previously shown to be involved in extracellular matrix remodeling. HAND2 protein was endothelial specific and showed higher expression in the regions exposed to low WSS with disturbed flow. Conclusions Microarray analysis validated the CFD-defined WSS regions in the rat aortic arch, and identified numerous novel shear-sensitive genes. Defining the functional importance of these genes in relation to atherosusceptibility may provide important insight into the understanding of vascular pathology.
Quantum Computation over Continuous Variables

This paper provides necessary and sufficient conditions for constructing a universal quantum computer over continuous variables. As an example, it is shown how a universal quantum computer for the amplitudes of the electromagnetic field might be constructed using simple linear devices such as beam splitters and phase shifters, together with squeezers and nonlinear devices such as Kerr-effect fibers and atoms in optical cavities. Such a device could in principle perform “floating point” computations. Problems of noise, finite precision, and error correction are discussed.
How state counter-industry campaigns help prime perceptions of tobacco industry practices to promote reductions in youth smoking

Objective: This study assessed the impact of state media campaigns that prominently feature counter-industry messages on youth cigarette smoking, beyond the effects of price, secular trends, tobacco control efforts, and the national truth® campaign. Methods: Rates of youth smoking were compared in three groups of states: (1) those with long funded counter-industry campaigns (California, Florida, and Massachusetts); (2) states with more recently funded counter-industry media campaigns (Indiana, Minnesota, Mississippi, and New Jersey); and (3) other states. An analysis was performed for a series of national telephone surveys of 12–17 year olds between 1999 and 2002, controlling for differences in demographic background, the price of cigarettes, and exposure to the national truth® campaign. Results: Between 1999 and 2002, rates of current smoking and established smoking decreased significantly faster in states with established or more newly funded counter-industry campaigns than in other states. State counter-industry campaigns appear to prime, or make more salient, negative perceptions about tobacco industry practices. Conclusion: Results highlight the value of continued state counter-industry campaigns.
Elevated Akt Activity Protects the Prostate Cancer Cell Line LNCaP from TRAIL-induced Apoptosis*

We find that the prostate cancer cell lines ALVA-31, PC-3, and DU 145 are highly sensitive to apoptosis induced by TRAIL (tumor-necrosis factor-relatedapoptosis-inducing ligand), while the cell lines TSU-Pr1 and JCA-1 are moderately sensitive, and the LNCaP cell line is resistant. LNCaP cells lack active lipid phosphatase PTEN, a negative regulator of the phosphatidylinositol (PI) 3-kinase/Akt pathway, and demonstrate a high constitutive Akt activity. Inhibition of PI 3-kinase using wortmannin and LY-294002 suppressed constitutive Akt activity and sensitized LNCaP cells to TRAIL. Treatment of LNCaP cells with TRAIL alone induced cleavage of the caspase 8 and XIAP proteins. However, processing of BID, mitochondrial release of cytochrome c, activation of caspases 7 and 9, and apoptosis did not occur unless TRAIL was combined with either wortmannin, LY-294002, or cycloheximide. Blocking cytochromec release by Bcl-2 overexpression rendered LNCaP cells resistant to TRAIL plus wortmannin treatment but did not affect caspase 8 or BID processing. This indicates that in these cells mitochondria are required for the propagation rather than the initiation of the apoptotic cascade. Infection of LNCaP cells with an adenovirus expressing a constitutively active Akt reversed the ability of wortmannin to potentiate TRAIL-induced BID cleavage. Thus, the PI 3-kinase-dependent blockage of TRAIL-induced apoptosis in LNCaP cells appears to be mediated by Akt through the inhibition of BID cleavage.
MPEG-H 3D Audio—The New Standard for Coding of Immersive Spatial Audio

The science and art of Spatial Audio is concerned with the capture, production, transmission, and reproduction of an immersive sound experience. Recently, a new generation of spatial audio technology has been introduced that employs elevated and lowered loudspeakers and thus surpasses previous `surround sound' technology without such speakers in terms of listener immersion and potential for spatial realism. In this context, the ISO/MPEG standardization group has started the MPEG-H 3D Audio development effort to facilitate high-quality bitrate-efficient production, transmission and reproduction of such immersive audio material. The underlying format is designed to provide universal means for carriage of channel-based, object-based and Higher Order Ambisonics based input. High quality reproduction is provided for many output formats from 22.2 and beyond down to 5.1, stereo and binaural reproduction-independently of the original encoding format, thus overcoming the incompatibility between various 3D formats. This paper provides an overview of the MPEG-H 3D Audio project and technology and an assessment of the system capabilities and performance.
SWI/SNF Enzymes Promote SOX10- Mediated Activation of Myelin Gene Expression

SOX10 is a Sry-related high mobility (HMG)-box transcriptional regulator that promotes differentiation of neural crest precursors into Schwann cells, oligodendrocytes, and melanocytes. Myelin, formed by Schwann cells in the peripheral nervous system, is essential for propagation of nerve impulses. SWI/SNF complexes are ATP dependent chromatin remodeling enzymes that are critical for cellular differentiation. It was recently demonstrated that the BRG1 subunit of SWI/SNF complexes activates SOX10 expression and also interacts with SOX10 to activate expression of OCT6 and KROX20, two transcriptional regulators of Schwann cell differentiation. To determine the requirement for SWI/SNF enzymes in the regulation of genes that encode components of myelin, which are downstream of these transcriptional regulators, we introduced SOX10 into fibroblasts that inducibly express dominant negative versions of the SWI/SNF ATPases, BRM or BRG1. Dominant negative BRM and BRG1 have mutations in the ATP binding site and inhibit gene activation events that require SWI/SNF function. Ectopic expression of SOX10 in cells derived from NIH 3T3 fibroblasts led to the activation of the endogenous Schwann cell specific gene, myelin protein zero (MPZ) and the gene that encodes myelin basic protein (MBP). Thus, SOX10 reprogrammed these cells into myelin gene expressing cells. Ectopic expression of KROX20 was not sufficient for activation of these myelin genes. However, KROX20 together with SOX10 synergistically activated MPZ and MBP expression. Dominant negative BRM and BRG1 abrogated SOX10 mediated activation of MPZ and MBP and synergistic activation of these genes by SOX10 and KROX20. SOX10 was required to recruit BRG1 to the MPZ locus. Similarly, in immortalized Schwann cells, BRG1 recruitment to SOX10 binding sites at the MPZ locus was dependent on SOX10 and expression of dominant negative BRG1 inhibited expression of MPZ and MBP in these cells. Thus, SWI/SNF enzymes cooperate with SOX10 to directly activate genes that encode components of peripheral myelin.