Miracle-dz/UniFAR-FTUs huggingface dataset:
Leader of the Capsid Protein in Feline Calicivirus Promotes Replication of Norwalk Virus in Cell Culture

ABSTRACT The inability to grow human noroviruses in cell culture has greatly impeded the studies of their pathogenesis and immunity. Vesiviruses, in the family Caliciviridae, grow efficiently in cell culture and encode a unique protein in the subgenomic region designated as leader of the capsid protein (LC). We hypothesized that LC might be associated with the efficient replication of vesiviruses in cell culture and promote the replication of human norovirus in cells. To test this hypothesis, a recombinant plasmid was engineered in which the LC region of feline calicivirus (FCV) was placed under the control of the cytomegalovirus promoter (pCI-LC) so that the LC protein could be provided in trans to replicating calicivirus genomes bearing a reporter gene. We constructed pNV-GFP, a recombinant plasmid containing a full-length NV genome with a green fluorescent protein (GFP) in the place of VP1. The transfection of pNV-GFP in MVA-T7-infected cells produced few GFP-positive cells detected by fluorescence microscopy and flow cytometry analysis. When pNV-GFP was cotransfected with pCI-LC in MVA-T7-infected cells, we observed an increase in the number of GFP-positive cells (ca. 3% of the whole-cell population). Using this cotransfection method with mutagenesis study, we identified potential cis-acting elements at the start of subgenomic RNA and the 3′ end of NV genome for the virus replication. We conclude that LC may be a viral factor which promotes the replication of NV in cells, which could provide a clue to growing the fastidious human noroviruses in cell culture.
Efficient Targeting of Protein Antigen to the Dendritic Cell Receptor DEC-205 in the Steady State Leads to Antigen Presentation on Major Histocompatibility Complex Class I Products and Peripheral CD8+ T Cell Tolerance

To identify endocytic receptors that allow dendritic cells (DCs) to capture and present antigens on major histocompatibility complex (MHC) class I products in vivo, we evaluated DEC-205, which is abundant on DCs in lymphoid tissues. Ovalbumin (OVA) protein, when chemically coupled to monoclonal αDEC-205 antibody, was presented by CD11c+ lymph node DCs, but not by CD11c− cells, to OVA-specific, CD4+ and CD8+ T cells. Receptor-mediated presentation was at least 400 times more efficient than unconjugated OVA and, for MHC class I, the DCs had to express transporter of antigenic peptides (TAP) transporters. When αDEC-205:OVA was injected subcutaneously, OVA protein was identified over a 4–48 h period in DCs, primarily in the lymph nodes draining the injection site. In vivo, the OVA protein was selectively presented by DCs to TCR transgenic CD8+ cells, again at least 400 times more effectively than soluble OVA and in a TAP-dependent fashion. Targeting of αDEC-205:OVA to DCs in the steady state initially induced 4–7 cycles of T cell division, but the T cells were then deleted and the mice became specifically unresponsive to rechallenge with OVA in complete Freund's adjuvant. In contrast, simultaneous delivery of a DC maturation stimulus via CD40, together with αDEC-205:OVA, induced strong immunity. The CD8+ T cells responding in the presence of agonistic αCD40 antibody produced large amounts of interleukin 2 and interferon γ, acquired cytolytic function in vivo, emigrated in large numbers to the lung, and responded vigorously to OVA rechallenge. Therefore, DEC-205 provides an efficient receptor-based mechanism for DCs to process proteins for MHC class I presentation in vivo, leading to tolerance in the steady state and immunity after DC maturation.
Does routine pain assessment result in better care?

BACKGROUND Although a variety of national organizations such as the Canadian Pain Society, the American Pain Society and the Joint Commission on Accreditation of Health Care Organizations have advanced the idea that pain should be assessed on a routine basis, there is little evidence that systematic pain assessment information is used routinely by clinicians even when it is readily available. OBJECTIVE To determine whether systematic pain assessment information alters medical practitioners' clinical practices. METHODS A population of seniors with complex medical problems who were evaluated by case coordinators was studied. Case coordinators were assigned to either an experimental or control patient assessment condition. Control condition patients were assessed as usual. In the experimental condition, a psychometrically valid pain assessment battery as well as the Geriatric Depression Scale - Short Form (because depression and chronic pain are frequently comorbid) were integrated into the routine case coordination assessment. A summary of the results of the depression and pain assessments was subsequently sent to physicians via mail and fax. Patients were also given copies of the assessment summaries and were asked to discuss these with their physicians. Physicians' medication prescriptions were monitored over time through the database of the provincial ministry of health. RESULTS At the end of the study, no significant differences between experimental and control patients were found with respect to medications prescribed or patient self-reports of pain. Nonetheless, there was a significant relationship between Geriatric Depression Scale -- Short Form scores and pain medications prescribed for patients in the experimental condition. Moreover, indexes of overall pain intensity did not change significantly over time. CONCLUSIONS The findings do not support the idea that the availability of systematic pain assessment information leads to change in clinician's medication practices. As such, educational interventions and public policy initiatives are needed to ensure that treatment providers do not only gather but also use pain assessment information.
Quantitative Phosphoproteomic Study of Pressure-Overloaded Mouse Heart Reveals Dynamin-Related Protein 1 as a Modulator of Cardiac Hypertrophy*

Pressure-overload stress to the heart causes pathological cardiac hypertrophy, which increases the risk of cardiac morbidity and mortality. However, the detailed signaling pathways induced by pressure overload remain unclear. Here we used phosphoproteomics to delineate signaling pathways in the myocardium responding to acute pressure overload and chronic hypertrophy in mice. Myocardial samples at 4 time points (10, 30, 60 min and 2 weeks) after transverse aortic banding (TAB) in mice underwent quantitative phosphoproteomics assay. Temporal phosphoproteomics profiles showed 360 phosphorylation sites with significant regulation after TAB. Multiple mechanical stress sensors were activated after acute pressure overload. Gene ontology analysis revealed differential phosphorylation between hearts with acute pressure overload and chronic hypertrophy. Most interestingly, analysis of the cardiac hypertrophy pathway revealed phosphorylation of the mitochondrial fission protein dynamin-related protein 1 (DRP1) by prohypertrophic kinases. Phosphorylation of DRP1 S622 was confirmed in TAB-treated mouse hearts and phenylephrine (PE)-treated rat neonatal cardiomyocytes. TAB-treated mouse hearts showed phosphorylation-mediated mitochondrial translocation of DRP1. Inhibition of DRP1 with the small-molecule inhibitor mdivi-1 reduced the TAB-induced hypertrophic responses. Mdivi-1 also prevented PE-induced hypertrophic growth and oxygen consumption in rat neonatal cardiomyocytes. We reveal the signaling responses of the heart to pressure stress in vivo and in vitro. DRP1 may be important in the development of cardiac hypertrophy.
Plasma hepcidin concentrations significantly predict interindividual variation in iron absorption in healthy men.

BACKGROUND Iron absorption is proposed to be regulated by circulating hepcidin, but, to date, little data are available to evaluate this relation in humans. OBJECTIVE Stored samples from a human iron absorption study were used to test the hypothesis that differences in plasma hepcidin explain interindividual variation in iron absorption. DESIGN Hepcidin-25 concentrations were measured in fasting samples from men aged > or = 40 y (n = 33) recruited to a study investigating the relation between the HFE genotype, iron absorption, and iron status. RESULTS Log iron absorption was negatively correlated with serum ferritin (r = -0.59, P < 0.001) and with plasma hepcidin (r = -0.55, P < 0.001) but was unaffected by genotype. There was a positive correlation (r = 0.82, P < 0.001) between hepcidin (mean: 2.3; range: 0.1-7.8 nmol/L) and ferritin (mean: 70; range: 9-208 microg/L). Multiple linear regression models showed that plasma hepcidin in isolation significantly predicted 36% of the interindividual variation in iron absorption. CONCLUSIONS Plasma hepcidin and serum ferritin concentrations are highly correlated, and, in the normal range of plasma hepcidin values, 36% of interindividual differences in iron absorption are explained by differences in circulating plasma hepcidin.
Alteration of swing leg work and power during human accelerated sprinting

ABSTRACT This study investigated changes in lower-extremity joint work and power during the swing phase in a maximal accelerated sprinting. Twelve male sprinters performed 60 m maximal sprints while motion data was recorded. Lower-extremity joint work and power during the swing phase of each stride for both legs were calculated. Positive hip and negative knee work (≈4.3 and ≈−2.9 J kg−1) and mean power (≈13.4 and ≈−8.7 W kg−1) during the entire swing phase stabilized or decreased after the 26.2±1.1 (9.69±0.25 m s−1) or 34.3±1.5 m mark (9.97±0.26 m s−1) during the acceleration phase. In contrast, the hip negative work and mean power during the early swing phase (≈7-fold and ≈3.7-fold increase in total), as well as the knee negative work and power during the terminal swing phase (≈1.85-fold and ≈2-fold increase in total), increased until maximal speed. Moreover, only the magnitudes of increases in negative work and mean power at hip and knee joints during the swing phase were positively associated with the increment of running speed from the middle of acceleration phase. These findings indicate that the roles of energy generation and absorption at the hip and knee joints shift around the middle of the acceleration phase as energy generation and absorption at the hip during the late swing phase and at the knee during early swing phase are generally maintained or decreased, and negative work and power at hip during the early swing phase and at knee during the terminal swing phase may be responsible for increasing running speed when approaching maximal speed. Summary: The roles of respective swing leg joints intricately change with increases in running speed during accelerated sprinting.
Impaired Retrieval Inhibition of Threat Material in Generalized Anxiety Disorder

Generalized anxiety disorder (GAD) is characterized by cognitive biases toward threat-relevant information, but the underlying mechanisms are unclear. We translated a retrieval-practice paradigm from cognitive science to investigate impaired inhibition of threat information as one such mechanism. Participants diagnosed with GAD and never-disordered control participants learned a series of cue–target pairs; whereas some cues were associated only with neutral targets, others were associated with both neutral and threat targets. Next, participants practiced retrieving neutral targets, which typically suppresses the subsequent recall of unpracticed associated targets (retrieval-induced forgetting; RIF). Finally, participants were tested on their recall of all targets. Despite showing intact RIF of neutral targets, the GAD group failed to exhibit RIF of threat targets. Furthermore, within the GAD group, less RIF of threat targets correlated with greater pervasiveness of worry. Deficits in inhibitory control over threat-relevant information may underlie the cognitive pathology of GAD, which has important treatment implications.
Large Scale Cosmological Anomalies and Inhomogeneous Dark Energy

A wide range of large scale observations hint towards possible modifications on the standard cosmological model which is based on a homogeneous and isotropic universe with a small cosmological constant and matter. These observations, also known as “cosmic anomalies” include unexpected Cosmic Microwave Background perturbations on large angular scales, large dipolar peculiar velocity flows of galaxies (“bulk flows”), the measurement of inhomogenous values of the fine structure constant on cosmological scales (“alpha dipole”) and other effects. The presence of the observational anomalies could either be a large statistical fluctuation in the context of ΛCDM or it could indicate a non-trivial departure from the cosmological principle on Hubble scales. Such a departure is very much constrained by cosmological observations for matter. For dark energy however there are no significant observational constraints for Hubble scale inhomogeneities. In this brief review I discuss some of the theoretical models that can naturally lead to inhomogeneous dark energy, their observational constraints and their potential to explain the large scale cosmic anomalies.
Routine rectal retroflexion during colonoscopy has a low yield for neoplasia.

AIM To investigate the value of retroflexion in detecting neoplasia in the distal rectum. METHODS This was a prospective observational study performed in an academic endoscopy unit. Consecutive patients undergoing colonoscopy had careful forward viewing of the distal rectum by retroflexion. Of 1502 procedures, 1076 (72%) procedures were performed with a 140 degrees angle of view colonoscope and 426 (28%) were performed with a 170 degrees angle of view colonoscope. The outcome measurement was the yield of neoplasia in the distal rectum detected by forward viewing vs retroflexion. RESULTS A total of 1502 patients, including 767 (51%) females and 735 (49%) males, with mean age of 58.8 +/- 12.5 years were enrolled. Retroflexion was successful in 1411 (93.9%) patients, unsuccessful or not performed because the rectum appeared narrow in 91 (6.1%). Forty patients had a polyp detected in the distal rectal mucosa. Thirty-three were visible in both the forward and retroflexed view (25 hyperplastic, 8 adenomatous). Seven polyps were visualized only by retroflexion (6 hyperplastic sessile polyps, one 4 mm sessile tubular adenoma). There was no significant difference in information added by retroflexion with 140 degrees vs 170 degrees angle of view instrument. CONCLUSION To our knowledge, this is the largest reported evaluation of retroflexion in the rectum. Routine rectal retroflexion did not detect clinically important neoplasia after a careful forward examination of the rectum to the dentate line. Since retroflexion has risks and may cause discomfort, the use of routine retroflexion should be at the discretion of the endoscopist.
Sunitinib-Induced Systemic Vasoconstriction in Swine Is Endothelin Mediated and Does Not Involve Nitric Oxide or Oxidative Stress

Angiogenesis inhibition with agents targeting tyrosine kinases of vascular endothelial growth factor receptors is an established anticancer treatment, but is, unfortunately, frequently accompanied by systemic hypertension and cardiac toxicity. Whether vascular endothelial growth factor receptor antagonism also has adverse effects on the pulmonary and coronary circulations is presently unknown. In chronically instrumented awake swine, the effects of the vascular endothelial growth factor receptor antagonist sunitinib on the systemic, pulmonary, and coronary circulation were studied. One week after sunitinib (50 mg PO daily), mean aortic blood pressure (MABP) had increased from 83±5 mm Hg at baseline to 97±6 mm Hg (P<0.05) because of a 57±20% increase in systemic vascular resistance as cardiac output decreased. In contrast, sunitinib had no discernible effects on pulmonary and coronary hemodynamics or cardiac function. We subsequently investigated the mechanisms underlying the sunitinib-induced systemic hypertension. Intravenous administration of NO synthase inhibitor NG-nitro-L-arginine increased MABP by 24±1 mm Hg under baseline conditions, whereas it increased MABP even further after sunitinib administration (32±3 mm Hg; P<0.05). Reactive oxygen species scavenging with a mixture of antioxidants lowered MABP by 13±2 mm Hg before but only by 5±2 mm Hg (P<0.05) after sunitinib administration. However, intravenous administration of the dual endothelin A/endothelin B receptor blocker tezosentan, which did not lower MABP at baseline, completely reversed MABP to presunitinib values. These findings indicate that sunitinib produces vasoconstriction selectively in the systemic vascular bed, without affecting pulmonary or coronary circulations. The sunitinib-mediated systemic hypertension is principally attributed to an increased vasoconstrictor influence of endothelin, with no apparent contributions of a loss of NO bioavailability or increased oxidative stress.
Drosophila synaptotagmin I null mutants survive to early adulthood

Summary: Synaptotagmin is a synaptic vesicle protein required for efficient neurotransmitter release, yet its exact role in the synaptic vesicle cycle is unclear. Drosophila presents an ideal organism for studies aimed at determining the in vivo functions of proteins. However, synaptotagmin studies have been limited by the early (embryonic or first instar) lethality previously reported for Drosophila synaptotagmin I null (sytnull) mutants. Here we report a new culturing technique that enhances survival of severely uncoordinated mutants thereby permitting Drosophila sytnull mutants to survive through early adulthood. We examined synapses in sytnull third instar larvae by electrophysiology and found that they exhibit severely decreased and asynchronous evoked neurotransmitter release, as well as an increased rate of spontaneous neurotransmitter release, as previously seen in first instar sytnull larvae. The ability to examine severe synaptotagmin mutants as third instar larvae, a stage where electrophysiological and morphological analyses are more easily accomplished, will facilitate structure/function studies. genesis 31:30–36, 2001. © 2001 Wiley‐Liss, Inc.
Hyperbolic metrics, measured foliations and pants decompositions for non-orientable surfaces

We provide analogues for non-orientable surfaces with or without boundary or punctures of several basic theorems in the setting of the Thurston theory of surfaces which were developed so far only in the case of orientable surfaces. Namely, we provide natural analogues for non-orientable surfaces of the Fenchel-Nielsen theorem on the parametrization of the Teichm\"uller space of the surface, the Dehn-Thurston theorem on the parametrization of measured foliations in the surface, and the Hatcher-Thurston theorem, which gives a complete minimal set of moves between pair of pants decompositions of the surface. For the former two theorems, one in effect drops the twisting number for any curve in a pants decomposition which is 1-sided, and for the latter, new elementary moves on pants decompositions are introduced.
Analysis of the Channel Energy Capture in Ultra-Wideband Transmitted Reference Systems

In this letter, we analyze the expected value of the channel energy capture as a function of the integration interval of the correlator in a transmitted reference system. A modified Saleh-Valenzuela channel model is employed. We observe that for the system specifications (such as channel model, data rate, and signal-to-noise ratio) considered here, an integration interval that captures approximately 84%-89% of the expected value of the channel energy provides a bit-error probability close to the minimum one.
Modelling Growth and Form of the Scleractinian Coral Pocillopora verrucosa and the Influence of Hydrodynamics

The growth of scleractinian corals is strongly influenced by the effect of water motion. Corals are known to have a high level of phenotypic variation and exhibit a diverse range of growth forms, which often contain a high level of geometric complexity. Due to their complex shape, simulation models represent an important option to complement experimental studies of growth and flow. In this work, we analyzed the impact of flow on coral's morphology by an accretive growth model coupled with advection-diffusion equations. We performed simulations under no-flow and uni-directional flow setup with the Reynolds number constant. The relevant importance of diffusion to advection was investigated by varying the diffusion coefficient, rather than the flow speed in Péclet number. The flow and transport equations were coupled and solved using COMSOL Multiphysics. We then compared the simulated morphologies with a series of Computed Tomography (CT) scans of scleractinian corals Pocillopora verrucosa exposed to various flow conditions in the in situ controlled flume setup. As a result, we found a similar trend associated with the increasing Péclet for both simulated forms and in situ corals; that is uni-directional current tends to facilitate asymmetrical growth response resulting in colonies with branches predominantly developed in the upstream direction. A closer look at the morphological traits yielded an interesting property about colony symmetry and plasticity induced by uni-directional flow. Both simulated and in situ corals exhibit a tendency where the degree of symmetry decreases and compactification increases in conjunction with the augmented Péclet thus indicates the significant importance of hydrodynamics.
High-Stress Abrasion and Impact-Abrasion Testing of Wear Resistant Steels

Energy can be saved by enhancing the service life of machinery and by designing lighter units. These design changes enable, for example, lower fuel consumption and larger payloads. The implementation of this kind of solutions, however, requires development of better wear resistant materials. In this study, the wear resistance of a structural steel and three grades of wear resistant steel was evaluated with granite abrasive in tests simulating the conditions in heavy machinery in mining and transportation. Two high-stress abrasion and one impact-abrasion wear testing methods were used. In all tests, higher hardness led to decreased mass loss, but in impact-abrasion the hardness dependence was smaller than in the heavy abrasion tests. This may, however, at least partly result from deformation of softer materials over the sample edges, which is not shown as mass loss. Wear surfaces of structural steel samples exhibited the highest degree of plastic deformation due to their lower hardness and higher ductility compared to the wear resistant steels. On the other hand, in harder materials the scratches were more visible, indicating a change in wear mechanism. Both differences and similarities in the behavior and wear mechanisms of the selected steels were observed in the applied conditions.