julilili42/papers huggingface dataset:
Search for TeV Gamma-ray Emission from GRB 100621A, an extremely bright GRB in X-rays, with H.E.S.S.
2014-03-20

The long gamma-ray burst (GRB) 100621A, at the time the brightest X-ray transient ever detected by Swift-XRT in the 0:3–10 keV range, has&#13;\\nbeen observed with the H.E.S.S. imaging air Cherenkov telescope array, sensitive to gamma radiation in the very-high-energy (VHE, &gt;100 GeV)&#13;\\nregime. Due to its relatively small redshift of z ~ 0:5, the favourable position in the southern sky and the relatively short follow-up time (&lt;700 s&#13;\\nafter the satellite trigger) of the H.E.S.S. observations, this GRB could be within the sensitivity reach of the H.E.S.S. instrument. The analysis of&#13;\\nthe H.E.S.S. data shows no indication of emission and yields an integral flux upper limit above ~380 GeV of 4:2X10-12 cm-2 s-1 (95% confidence&#13;\\nlevel), assuming a simple Band function extension model. A comparison to a spectral-temporal model, normalised to the prompt flux at sub-MeV&#13;\\nenergies, constraints the existence of a temporally extended and strong additional hard power law, as has been observed in the other bright X-ray&#13;\\nGRB 130427A. A comparison between the H.E.S.S. upper limit and the contemporaneous energy output in X-rays constrains the ratio between&#13;\\nthe X-ray and VHE gamma-ray fluxes to be greater than 0.4. This value is an important quantity for modelling the afterglow and can constrain&#13;\\nleptonic emission scenarios, where leptons are responsible for the X-ray emission and might produce VHE gamma rays
Crystallographic and Glycan Microarray Analysis of Human Polyomavirus 9 VP1 Identifies N -Glycolyl Neuraminic Acid as a Receptor Candidate
2014-03-20

ABSTRACT Human polyomavirus 9 (HPyV9) is a closely related homologue of simian B-lymphotropic polyomavirus (LPyV). In order to define the architecture and receptor binding properties of HPyV9, we solved high-resolution crystal structures of its major capsid protein, VP1, in complex with three putative oligosaccharide receptors identified by glycan microarray screening. Comparison of the properties of HPyV9 VP1 with the known structure and glycan-binding properties of LPyV VP1 revealed that both viruses engage short sialylated oligosaccharides, but small yet important differences in specificity were detected. Surprisingly, HPyV9 VP1 preferentially binds sialyllactosamine compounds terminating in 5- N -glycolyl neuraminic acid (Neu5Gc) over those terminating in 5- N -acetyl neuraminic acid (Neu5Ac), whereas LPyV does not exhibit such a preference. The structural analysis demonstrated that HPyV9 makes specific contacts, via hydrogen bonds, with the extra hydroxyl group present in Neu5Gc. An equivalent hydrogen bond cannot be formed by LPyV VP1. IMPORTANCE The most common sialic acid in humans is 5- N -acetyl neuraminic acid (Neu5Ac), but various modifications give rise to more than 50 different sialic acid variants that decorate the cell surface. Unlike most mammals, humans cannot synthesize the sialic acid variant 5- N -glycolyl neuraminic acid (Neu5Gc) due to a gene defect. Humans can, however, still acquire this compound from dietary sources. The role of Neu5Gc in receptor engagement and in defining viral tropism is only beginning to emerge, and structural analyses defining the differences in specificity for Neu5Ac and Neu5Gc are still rare. Using glycan microarray screening and high-resolution protein crystallography, we have examined the receptor specificity of a recently discovered human polyomavirus, HPyV9, and compared it to that of the closely related simian polyomavirus LPyV. Our study highlights critical differences in the specificities of both viruses, contributing to an enhanced understanding of the principles that underlie pathogen selectivity for modified sialic acids.
Discovery of a Novel Series of Tetrahydro‐β‐carbolines Inducing Autophagic Cell Death in Human Metastatic Melanoma
2014-03-20

Herein, we report the synthesis of novel tetrahydro‐β‐carbolines that induce cell death via the autophagic pathway. Five of the new compounds induced cell death in a panel of patient‐derived human metastatic melanoma cells. The autophagic pathway was confirmed using LC3 autophagosome markers; the involvement of ATG7 and Beclin 1 autophagy regulating genes was confirmed using infection with short hairpin RNA (shRNA) to silence Beclin 1 and ATG7. Compound VIII (IC 50 = 2.34–5.15 μM) displayed activities greater than cisplatin against a panel of patient‐derived human metastatic melanoma cell lines. The structure–activity relationship (SAR) of this class and the role of the absolute stereochemistry and geometrical isomerism are evaluated.
Risks and benefits of hormone therapy: has medical dogma now been overturned?
2014-03-21

Over-interpretation and misrepresentation of the WHI findings have damaged the health and well-being of menopausal women by convincing them and their health professionals that the risks of HT outweigh the benefits.
Simultaneous subependymomas in monozygotic female twins: further evidence for a common genetic or developmental disorder background
2014-03-21

In this paper, a rare case of subependymoma of the fourth ventricle in identical female twins is reported. Magnetic resonance imaging and CT showed nearly identical locations of the tumors in the fourth ventricle and similar growth patterns of the tumors in both sisters. Likewise, postoperative histopathological analysis of both tumors revealed the typical histological appearance of subependymomas. Subependymoma is a rare, low-grade glioma of the CNS, slowly growing and usually asymptomatic. If symptomatic, a subependymoma can in some cases lead to sudden death caused by pressure on the brainstem or decompensated secondary hydrocephalus. This case demonstrates the importance of detecting tumors early and thereby preventing symptoms arising from increasing intracranial pressure, and optimizing therapy options.
Enzyme assays
2014-03-23

The essential requirements for enzyme assays are described and frequently occurring errors and pitfalls as well as their avoidance are discussed. The main factors, which must be considered for assaying enzymes, are temperature, pH, ionic strength and the proper concentrations of the essential components like substrates and enzymes. Standardization of these parameters would be desirable, but the diversity of the features of different enzymes prevents unification of assay conditions. Nevertheless, many enzymes, especially those from mammalian sources, possess a pH optimum near the physiological pH of 7.5, and the body temperature of about 37 °C can serve as assay temperature, although because of experimental reasons frequently 25 °C is preferred. But in many cases the particular features of the individual enzyme dictate special assay conditions, which can deviate considerably from recommended conditions.\\nIn addition, exact values for the concentrations of assay components such as substrates and enzymes cannot be given, unless general rules depending on the relative degree of saturation can be stated. Rules for performing the enzyme assay, appropriate handling, methodical aspects, preparation of assay mixtures and blanks, choice of the assay time, are discussed and suggestions to avoid frequent and trivial errors are given. Particularities of more complex enzyme assays, including reversible reactions and coupled tests are considered.\\nFinally the treatment of experimental data to estimate the enzyme activity is described. The procedure for determining the initial enzyme velocity and its transformation into defined enzyme units as well as suggestions for documentation of the results are presented.
Polarized hadron pair production from electron-positron annihilation
2014-03-24

We study the production of two almost back-to-back hadrons from the\\nannihilation of an electron and a positron, allowing for the polarization of\\nall particles involved. In particular, we conduct a general (model-independent)\\nstructure function decomposition of the cross section for the case . Moreover, using the parton model we calculate the\\nrelevant structure functions in terms of twist-2 transverse momentum dependent\\n(TMD) fragmentation functions (FFs). We also give results for the situation\\n (including - interference) within this\\nmodel. This is the first time a complete framework has been presented for the\\nexamination of TMD FFs within . We also specify certain\\nparts of our analysis that hold for the triple-polarized semi-inclusive\\ndeep-inelastic scattering process and for di-hadron fragmentation. Furthermore,\\nwe give an explicit prescription of how our work can be translated to the\\nDrell-Yan reaction, which provides for the first time full results for\\ndouble-polarized Drell-Yan that include electroweak effects. We further discuss\\nthe relevance of our results for future experiments at\\n machines.\\n
ST2 Deficiency Does Not Impair Type 2 Immune Responses during Chronic Filarial Infection but Leads to an Increased Microfilaremia Due to an Impaired Splenic Microfilarial Clearance
2014-03-24

Our findings suggest that the absence of ST2 does not impair the establishment of adult L. sigmodontis worms, but is important for the splenic clearance of microfilariae from peripheral blood. Thus, ST2 interactions may be important for therapies that intend to block the transmission of filarial disease.
The applicability of probabilistic methods to the online recognition of fixations and saccades in dynamic scenes
2014-03-24

In many applications involving scanpath analysis, especially when dynamic scenes are viewed, consecutive fixations and saccades, have to be identified and extracted from raw eye-tracking data in an online fashion. Since probabilistic methods can adapt not only to the individual viewing behavior, but also to changes in the scene, they are best suited for such tasks.
SubsMatch
2014-03-24

The analysis of visual scanpaths, i.e., series of fixations and saccades, in complex dynamic scenarios is highly challenging and usually performed manually. We propose SubsMatch, a scanpath comparison algorithm for dynamic, interactive scenarios based on the frequency of repeated gaze patterns. Instead of measuring the gaze duration towards a semantic target object (which would be hard to label in dynamic scenes), we examine the frequency of attention shifts and exploratory eye movements. SubsMatch was evaluated on highly dynamic data from a driving experiment to identify differences between scanpaths of subjects who failed a driving test and subjects who passed.
Efficacy of antifungal PACT in an in vitro model of onychomycosis
2014-03-24

Abstract Background The difficulty of antifungal substances to penetrate keratin and slow nail growth limit the efficacy of topical therapy in onychomycosis. One promising alternative is photodynamic antimicrobial chemotherapy, or PACT : an irradiated photosensitizer creates singlet oxygen molecules which destroy pathogens without damaging human cells. Objective As PACT has demonstrated strong antifungal capabilities, we wanted to investigate its efficacy in an in vitro model of onychomycosis. Methods PACT was tested in a microdilution assay, in an in vitro onychomycosis model as well as in a patient. Results PACT inhibited fungal growth in the microdilution assay with no colonies of T. rubrum detectable. Fungal growth was also inhibited in an onychomycosis model, after 30 min of LED irradiation. Subsequently, a patient with distolateral onychomycosis was treated on three consecutive days and showed significant and durable improvement of nail morphology 6 months after. Conclusion PACT appears to be an effective treatment of onychomycosis in vitro . The promising results need to be validated by clinical trials.
Freedom and necessity: the transition to the logic of the concept in Hegel'sScience of Logic
2014-03-24

Whether freedom and causal necessity can coexist in the same world remains a contested question. In this article, I seek to show that Hegel's analysis of the category of causality, which concludes in the transition from the logic of essence to the logic of the concept, can help to elucidate this question itself. Starting with a short characterization of the positions in Kant's account of the ‘antinomy of freedom’ in his Critique of Pure Reason , I reconstruct the main sections of Hegel's account of causality in his Science of Logic . Holding the two accounts together shows that both proponent and opponent in the ‘antinomy of freedom’ are misled in that there are not two different kinds of causality at issue but rather two intrinsically connected moments of causality as such.
Adaptive Gene Regulation in the Striatum of RGS9-Deficient Mice
2014-03-24

Identified signaling components may represent novel targets in antidyskinetic therapy. The long splice variant of the regulator of G-protein signaling 9 (RGS9-2) is enriched in striatal medium spiny neurons and dampens dopamine D2 receptor signaling. Lack of RGS9-2 can promote while its overexpression prevents drug-induced dyskinesia. Other animal models of drug-induced dyskinesia rather pointed towards overactivity of dopamine receptor-mediated signaling. To evaluate changes in signaling pathways mRNA expression levels were determined and compared in wild-type and RGS9-deficient mice. Unexpectedly, expression levels of dopamine receptors were unchanged in RGS9-deficient mice, while several genes related to Ca2+ signaling and long-term depression were differentially expressed when compared to wild type animals. Detailed investigations at the protein level revealed hyperphosphorylation of DARPP32 at Thr34 and of ERK1/2 in striata of RGS9-deficient mice. Whole cell patch clamp recordings showed that spontaneous synaptic events are increased (frequency and size) in RGS9-deficient mice while long-term depression is reduced in acute brain slices. These changes are compatible with a Ca2+-induced potentiation of dopamine receptor signaling which may contribute to the drug-induced dyskinesia in RGS9-deficient mice.
Gaze guidance for the visually impaired
2014-03-24

Visual perception is perhaps the most important sensory input. During driving, about 90% of the relevant information is related to the visual input [Taylor 1982]. However, the quality of visual perception decreases with age, mainly related to a reduce in the visual acuity or in consequence of diseases affecting the visual system. Amongst the most severe types of visual impairments are visual field defects (areas of reduced perception in the visual field), which occur as a consequence of diseases affecting the brain, e.g., stroke, brain injury, trauma, or diseases affecting the optic nerve, e.g., glaucoma. Due to demographic aging, the number of people with such visual impairments is expected to rise [Kasneci 2013]. Since persons suffering from visual impairments may overlook hazardous objects, they are prohibited from driving. This, however, leads to a decrease in quality of life, mobility, and participation in social life. Several studies have shown that some patients show a safe driving behavior despite their visual impairment by performing effective visual exploration, i.e., adequate eye and head movements (e.g., towards their visual field defect [Kasneci et al. 2014b]). Thus, a better understanding of visual perception mechanisms, i.e., of why and how we attend certain parts of our environment while "ignoring" others, is a key question to helping visually impaired persons in complex, real-life tasks, such as driving a car.
Assessing local outcomes in heterogeneous gliomas
2014-03-24

Tumours are known to be heterogeneous, yet typical treatment plans consider them as a single unit. This may influence treatment outcomes. However, treatment cannot be customised to intra-tumour variation without a method to establish outcomes at an intra-tumour scale. This work proposes a method to both assess and measure outcomes locally within tumours. Methods: Four patients were scanned at two post-surgery time points using contrast enhanced MRI and 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (18F-DOPA) PET. The shell of active tumour tissue is divided into a set of small subregions at both time points. Local outcome is measured from changes in subregion volume over time. The utility of the proposed approach is evaluated by measuring the correlation between PET uptake and documented growth. Correlation with overall survival time was also examined. Results: Local outcomes were heterogeneous and evidence of a positive correlation between local 18F-DOPA uptake and local progression was observed. Conclusions: Given that intra-tumour outcomes are heterogeneous the consistently positive correlation between FDOPA uptake and progression, local analysis of tumours could prove useful for treatment planning.
Contribution of FDOPA PET to radiotherapy planning for advanced glioma
2014-03-24

Despite radical treatment with surgery, radiotherapy and chemotherapy, advanced gliomas recur within months. Geographic misses in radiotherapy planning may play a role in this seemingly ineluctable recurrence. Planning is typically performed on post-contrast MRIs, which are known to underreport tumour volume relative to FDOPA PET scans. FDOPA PET fused with contrast enhanced MRI has demonstrated greater sensitivity and specificity than MRI alone. One sign of potential misses would be differences between gross target volumes (GTVs) defined using MRI alone and when fused with PET. This work examined whether such a discrepancy may occur. Materials and Methods: For six patients, a 75 minute PET scan using 3,4-dihydroxy-6-18F-fluoro-L-phynel-alanine (18F-FDOPA) was taken within 2 days of gadolinium enhanced MRI scans. In addition to standard radiotherapy planning by an experienced radiotherapy oncologist, a second gross target volume (GTV) was defined by an experienced nuclear medicine specialist for fused PET and MRI, while blinded to the radiotherapy plans. The volumes from standard radiotherapy planning were compared to the PET defined GTV. Results: The comparison indicated radiotherapy planning would change in several cases if FDOPA PET data was available. PET-defined contours were external to 95% prescribed dose for several patients. However, due to the radiotherapy margins, the discrepancies were relatively small in size and all received a dose of 50 Gray or more. Conclusions: Given the limited size of the discrepancies it is uncertain that geographic misses played a major role in patient outcome. Even so, the existence of discrepancies indicates that FDOPA PET could assist in better defining margins when planning radiotherapy for advanced glioma, which could be important for highly conformal radiotherapy plans.
Dacarbazine with or without oblimersen (a Bcl-2 antisense oligonucleotide) in chemotherapy-naive patients with advanced melanoma and low–normal serum lactate dehydrogenase
2014-03-25

In a previous large randomized, open-label study, retrospective subset analysis revealed that the addition of the Bcl-2 antisense oligonucleotide oblimersen to dacarbazine (Dac) significantly improved overall survival, progression-free survival, and the response rate in chemotherapy-naive patients with advanced melanoma and normal baseline serum lactate dehydrogenase (LDH) levels. To confirm and expand on this observation, we conducted a prospective double-blind, placebo-controlled study to determine whether oblimersen augmented the efficacy of Dac in advanced melanoma patients with low-normal baseline LDH levels. A total of 314 chemotherapy-naive patients were randomly assigned to receive Dac (1000 mg/m(2)) preceded by a 5-day continuous intravenous infusion of either oblimersen sodium (7 mg/kg/day) or placebo every 21 days for less than eight cycles. Co-primary efficacy endpoints were overall survival and progression-free survival. Response and progression of the disease were assessed by independent blinded review of computed tomography scan images. No difference in overall nor progression-free survival was observed between the Dac-oblimersen and Dac-placebo groups. Although the overall (17.2 vs. 12.1%) and durable (10.8 vs. 7.6%) response rates numerically favored Dac-oblimersen over Dac-placebo, they did not differ significantly (P=0.19 and 0.32, respectively). The incidence of hematologic adverse events, particularly thrombocytopenia and neutropenia, was higher in the Dac-oblimersen group than in the Dac-placebo group. Withdrawals from the study because of treatment-related adverse events were low (i.e. <2.5%) in both groups. The addition of oblimersen to Dac did not significantly improve overall survival nor progression-free survival in patients with advanced melanoma and low-normal levels of LDH at baseline.
New Poteintial Serum Biomarkers in Multiple Sclerosis Identified by Proteomic Strategies
2014-03-25

Proteome analysis of body fluids is a powerful tool to identify biomarkers of neurological disorders. Multiple sclerosis (MScl) is a chronic disabling disorder of central nervous system (CNS) and is regarded as an autoimmune disease to myelin components. Clinical subtypes of MScl differ in course, prognosis and response to available therapy. There is evidence of a different pattern of CNS lesions in subtypes, suggesting different immunological mechanisms are relevant in inflammatory demyelination. In order to elucidate proteome signatures, we used two-dimensional differential gel electrophoresis (2D-DIGE) to compare the protein expression profile in serum of different clinical subtypes of MScl patients and of healthy volunteers, resp. controls. Significant expression differences were detected by 2D-DIGE for 241 serum proteins, and transthyretin, zinc-alpha-2-glycoprotein, alpha-1-antitrypsin, immunoglobulin and complement factors (C4, C6 and C8) were identified as potential disease signatures for MScl patients. Three highly-expressed proteins were selected for further evaluation in individual patients by independent immunoassays, and the up-regulation of transthyretin, zinc alpha-2-glycoprotein and immunoglobulin kappa light chain was validated in sera of relapsing-remitting (CIS and RRMScl) patients, when compared to healthy donors. To present significant expression differences in PPMScl, analysis with a larger patient population is required.
Light-front quark model consistent with Drell-Yan-West duality and quark counting rules
2014-03-26

We propose a phenomenological light-front wave function for hadrons with\\narbitrary twist-dimension (mesons, baryons and multiquark states), which gives\\nthe correct scaling behavior of structure functions (parton distributions) and\\nform factors for pions and nucleons. For other hadronic states the proposed\\nwave function produces form factors consistent with quark counting rules, and\\ngives predictions for structure functions (parton distributions). As an\\napplication we build a light-front quark model for nucleons based on the\\nproposed wave function.\\n