julilili42/papers huggingface dataset:
Mice Can Use Second-Order, Contrast-Modulated Stimuli to Guide Visual Perception
2016-04-20

Visual processing along the primate ventral stream takes place in a hierarchy of areas, characterized by an increase in both complexity of neuronal preferences and invariance to changes of low-level stimulus attributes. A basic type of invariance is form-cue invariance, where neurons have similar preferences in response to first-order stimuli, defined by changes in luminance, and global features of second-order stimuli, defined by changes in texture or contrast. Whether in mice, a now popular model system for early visual processing, visual perception can be guided by second-order stimuli is currently unknown. Here, we probed mouse visual perception and neural responses in areas V1 and LM using various types of second-order, contrast-modulated gratings with static noise carriers. These gratings differ in their spatial frequency composition and thus in their ability to invoke first-order mechanisms exploiting local luminance features. We show that mice can transfer learning of a coarse orientation discrimination task involving first-order, luminance-modulated gratings to the contrast-modulated gratings, albeit with markedly reduced discrimination performance. Consistent with these behavioral results, we demonstrate that neurons in area V1 and LM are less responsive and less selective to contrast-modulated than to luminance-modulated gratings, but respond with broadly similar preferred orientations. We conclude that mice can, at least in a rudimentary form, use second-order stimuli to guide visual perception. SIGNIFICANCE STATEMENT To extract object boundaries in natural scenes, the primate visual system does not only rely on differences in local luminance but can also take into account differences in texture or contrast. Whether the mouse, which has a much simpler visual system, can use such second-order information to guide visual perception is unknown. Here we tested mouse perception of second-order, contrast-defined stimuli and measured their neural representations in two areas of visual cortex. We find that mice can use contrast-defined stimuli to guide visual perception, although behavioral performance and neural representations were less robust than for luminance-defined stimuli. These findings shed light on basic steps of feature extraction along the mouse visual cortical hierarchy, which may ultimately lead to object recognition.
Continued decay in the cyclotron line energy in Hercules X-1
2016-04-20

The centroid energy E_(cyc) of the cyclotron line in the spectrum of the binary X-ray pulsar Her X-1 has been found to decrease with time on a time scale of a few tens of years – surprisingly short in astrophysical terms. This was found for the pulse phase-averaged line centroid energy using observational data from various X-ray satellites over the time period 1996 to 2012, establishing a reduction of ~4 keV. Here we report on the result of a new observation by NuSTAR performed in August 2015. The earlier results are confirmed and strengthened with respect to both the dependence of E_(cyc) on flux (it is still present after 2006) and the dependence on time: the long-term decay continued with the same rate, corresponding to a reduction of ~5 keV in 20 yr.
Expression of RANK‐L and in part of PD‐1 on blasts in patients with acute myeloid leukemia correlates with prognosis
2016-04-20

Abstract Background Co‐stimulatory receptor ( COR ) and ligand ( COL ) expression on immune effectors are known to be relevant for immunological interactions and might be of prognostic relevance if expressed on acute myeloid leukemia ( AML ) blasts as reported for receptors of the tumor necrosis factor receptor family. Aim and methods Antigen expression profiling of COR ( RANK , PD ‐1), COL ( RANK ‐L, PD ‐1L), and HLA ‐ ABC ‐antigens on blasts from 90 AML ‐patients at first diagnosis was performed by flow cytometry ( SFI ‐Level characterization) and findings were correlated with clinical parameters. Results RANK expression was higher in immature compared to mature FAB groups ( P = 0.08). As a monocytic marker, we identified HLA ‐ ABC ( P = 0.07). Prognostic analysis revealed a higher probability of overall survival in cases with lower RANK ‐L expression (&lt;1.6 and ≥1.6, 15.6 vs. 12.2 months, P = 0.008, hazard ratio 0.36, P = 0.008). No significant impact of PD ‐1/L expression for patients’(pts) survival was seen but a correlation of PD ‐1 with a secondary AML ( P = 0.03). Prolonged disease‐free survival however correlated with higher PD ‐1 expression (≥1.1 vs. &lt;1.1, 31.4 vs. 12.7 months; P = 0.03). Conclusion Our study revealed that RANK ‐L is a promising marker to forecast pts’ prognosis in AML . Immune checkpoint receptor PD ‐1/L as well as RANK and HLA ‐ ABC did not show an impact on pts’ survival.
Selective di- and monochlorination of pyridazine-annelated bis(imidazolium) salts
2016-04-20

Abstract A synthetic route for the selective di- and monochlorination of pyridazine annelated bis(imidazolium) salts at the formamidinium moieties with trichloroisocyanuric acid (TCCA) is presented. Due to the steric hindrance, the molecular structure of the dichlorobis(imidazolium) salt shows a pronounced torsion from planarity as well as a deviation of the C–Cl bond vectors from the ideal bisecting line of the respective NCN angles such as to avoid each other. The monochlorinated bis(imidazolium) salt is free of steric hindrance and therefore shows less deviation from the parent bis(imidazolium) salt. In the presence of acetate the chloroimidazolium salt acts as a chlorination agent for acetate leading to formation of acetyl chloride and the respective urea.
Radiological Findings in Children and Adolescents with Homonymous Visual Field Defects: Types of Lesion and Frequency
2016-04-20

Background: Severe visual impairment in children is often caused by cerebral lesions. Suprachiasmal lesions typically lead to homonymous visual field defects. In adults these are mostly caused by ischemic lesions of the visual cortex. Studies in children are rare.
Multimodal Assessment Reveals Late-Onset Hemispheric Shift of Language in a Child with Meningocerebral Dysplasia
2016-04-20

Background: We report on a girl with progressive left frontal tissue destruction starting at almost 8 years of age. She manifested acutely with epileptic seizures accompanied by Broca aphasia as well as transient right hemiparesis. Due to refractory epilepsy developing over the next years which originated from the left frontal lobe, the decision was made to proceed to epilepsy surgery. By then, her language functions had recovered despite progressive left frontal tissue destruction, raising the possibility of a hemispheric shift of language.
Response Assessment in Neuro-Oncology working group and European Association for Neuro-Oncology recommendations for the clinical use of PET imaging in gliomas
2016-04-21

This guideline provides recommendations for the use of PET imaging in gliomas. The review examines established clinical benefit in glioma patients of PET using glucose ((18)F-FDG) and amino acid tracers ((11)C-MET, (18)F-FET, and (18)F-FDOPA). An increasing number of studies have been published on PET imaging in the setting of diagnosis, biopsy, and resection as well radiotherapy planning, treatment monitoring, and response assessment. Recommendations are based on evidence generated from studies which validated PET findings by histology or clinical course. This guideline emphasizes the clinical value of PET imaging with superiority of amino acid PET over glucose PET and provides a framework for the use of PET to assist in the management of patients with gliomas.
Spindle activity phase-locked to sleep slow oscillations
2016-04-21

The <1Hz slow oscillation (SO) and spindles are hallmarks of mammalian non-rapid eye movement and slow wave sleep. Spindle activity occurring phase-locked to the SO is considered a candidate mediator of memory consolidation during sleep. We used source localization of magnetoencephalographic (MEG) and electroencephalographic (EEG) recordings from 11 sleeping human subjects for an in-depth analysis of the temporal and spatial properties of sleep spindles co-occurring with SOs. Slow oscillations and spindles were identified in the EEG and related to the MEG signal, providing enhanced spatial resolution. In the temporal domain, we confirmed a phase-locking of classical 12-15Hz fast spindle activity to the depolarizing SO up-state and of 9-12Hz slow spindle activity to the up-to-down-state transition of the SO. In the spatial domain, we show a broad spread of spindle activity, with less distinct anterior-posterior separation of fast and slow spindles than commonly seen in the EEG. We further tested a prediction of current memory consolidation models, namely the existence of a spatial bias of SOs over sleep spindles as a mechanism to promote localized neuronal synchronization and plasticity. In contrast to that prediction, a comparison of SOs dominating over the left vs. right hemisphere did not reveal any signs of a concurrent lateralization of spindle activity co-occurring with these SOs. Our data are consistent with the concept of the neocortical SO exerting top-down control over thalamic spindle generation. However, they call into question the notion that SOs locally coordinate spindles and thereby inform spindle-related memory processing.
Equation of state constraints for the cold dense matter inside neutron stars using the cooling tail method
2016-04-21

The cooling phase of thermonuclear (type-I) X-ray bursts can be used to constrain the neutron star (NS) compactness by comparing the observed cooling tracks of bursts to accurate theoretical atmosphere model calculations. By applying the so-called cooling tail method, where the information from the whole cooling track is used, we constrain the mass, radius, and distance for three different NSs in low-mass X-ray binaries 4U 1702-429, 4U 1724-307, and SAX J1810.8-260. Care is taken to only use the hard state bursts where it is thought that only the NS surface alone is emitting. We then utilize a Markov chain Monte Carlo algorithm within a Bayesian framework to obtain a parameterized equation of state (EoS) of cold dense matter from our initial mass and radius constraints. This allows us to set limits on various nuclear parameters and to constrain an empirical pressure-density relation for the dense matter. Our predicted EoS results in NS radius between 10.5-12.8 km (95% confidence limits) for a mass of 1.4 . Due to systematic errors and uncertainty in the composition these results should be interpreted as lower limits for the radius.
Sex-specific effects of TLR9 promoter variants on spontaneous clearance of HCV infection
2016-04-21

<i>TLR9</i> promoter SNPs are associated with the natural course of HCV infection and show higher transcriptional activities. Our results imply the DNA sensor TLR9 in natural immunity against the RNA virus, HCV.
mRNA-Mediated Gene Supplementation of Toll-Like Receptors as Treatment Strategy for Asthma In Vivo
2016-04-21

Asthma is the most common chronic disease in childhood. Although several therapeutic options are currently available to control the symptoms, many drugs have significant side effects and asthma remains an incurable disease. Microbial exposure in early life reduces the risk of asthma and several studies have suggested protective effects of Toll-like receptor (TLR) activation. We showed previously that modified mRNA provides a safe and efficient therapeutic tool for in vivo gene supplementation. Since current asthma drugs do not take patient specific immune and TLR backgrounds into consideration, treatment with tailored mRNA could be an attractive approach to account for the patient's individual asthma phenotype. Therefore, we investigated the effect of a preventative treatment with combinations of Tlr1, Tlr2 and Tlr6 mRNA in a House Dust Mite-induced mouse model of asthma. We used chemically modified mRNA which is-in contrast to conventional viral vectors-non-integrating and highly efficient in gene transfer. In our study, we found that treatment with either Tlr1/2 mRNA or Tlr2/6 mRNA, but not Tlr2 mRNA alone, resulted in better lung function as well as reduced airway inflammation in vivo. The present results point to a potentially protective effect of TLR heterodimers in asthma pathogenesis.
Compound-Specific Stable Isotope Fractionation of Pesticides and Pharmaceuticals in a Mesoscale Aquifer Model
2016-04-21

Compound-specific isotope analysis (CSIA) receives increasing interest for its ability to detect natural degradation of pesticides and pharmaceuticals. Despite recent laboratory studies, CSIA investigations of such micropollutants in the environment are still rare. To explore the certainty of information obtainable by CSIA in a near-environmental setting, a pulse of the pesticide bentazone, the pesticide metabolite 2,6-dichlorobenzamide (BAM), and the pharmaceuticals diclofenac and ibuprofen was released into a mesoscale aquifer with quasi-two-dimensional flow. Concentration breakthrough curves (BTC) of BAM and ibuprofen demonstrated neither degradation nor sorption. Bentazone was transformed but did not sorb significantly, whereas diclofenac showed both degradation and sorption. Carbon and nitrogen CSIA could be accomplished in similar concentrations as for "traditional" priority pollutants (low μg/L range), however, at the cost of uncertainties (0.4-0.5‰ (carbon), 1‰ (nitrogen)). Nonetheless, invariant carbon and nitrogen isotope values confirmed that BAM was neither degraded nor sorbed, while significant enrichment of (13)C and in particular (15)N corroborated transformation of diclofenac and bentazone. Retardation of diclofenac was reflected in additional (15)N sorption isotope effects, whereas isotope fractionation of transverse dispersion could not be identified. These results provide a benchmark on the performance of CSIA to monitor the reactivity of micropollutants in aquifers and may guide future efforts to accomplish CSIA at even lower concentrations (ng/L range).
Reply
2016-04-21

Elena Gardella, S, andor Beniczky, Rikke S. Møller, Felicitas Becker, Johannes R. Lemke, Steffen Syrbe, Hans Eiberg, Thomas Bast, Bernhard Steinhoff, Peter N, urnberg, Pia Gellert, Hans Atli Dahl, Sarah Weckhuysen, Sarah E. Heron, Leanne M. Dibbens, Helle Hjalgrim, Holger Lerche, Yvonne G. Weber
Association of transketolase polymorphisms with measures of polyneuropathy in patients with recently diagnosed diabetes
2016-04-22

Abstract Background Shunting of glycolytic intermediates into the pentose phosphate pathway has been suggested to protect from hyperglycaemia‐induced microvascular damage. We hypothesized that genetic variability in the gene encoding transketolase, a key pentose phosphate pathway enzyme, contributes to early nerve dysfunction in recent‐onset diabetes. Methods In this cross‐sectional study, we assessed nine single nucleotide polymorphisms (SNPs) in the transketolase gene, plasma methylglyoxal concentrations, and clinical and quantitative measures of peripheral nerve function in 165 type 1 and 373 type 2 diabetic patients with a diabetes duration up to 1 year. Results The Total Symptom Score was associated with transketolase SNPs rs7648309, rs62255988, and rs7633966, while peroneal motor nerve conduction velocity (MNCV) correlated only with rs7648309 ( P &lt; 0.01). Cold thermal detection threshold (TDT) (foot) was associated with transketolase SNPs rs11130362 and rs7648309, while warm TDT (hand) correlated with rs62255988 and rs7648309 ( P &lt; 0.01). After Bonferroni correction, the correlations of transketolase SNP rs7648309 with Total Symptom Score and rs62255988 with warm TDT (hand) remained statistically significant. Among subgroups, men with type 2 diabetes showed the strongest associations. No associations were observed between each of the nine tagged transketolase SNPs and plasma methylglyoxal concentrations. Conclusions The observed associations of genetic variation in transketolase enzyme with neuropathic symptoms and reduced thermal sensation in recent‐onset diabetes suggest a role of pathways metabolizing glycolytic intermediates in early diabetic neuropathy. Copyright © 2016 John Wiley &amp; Sons, Ltd.
Alchemical Free Energy Calculations and Isothermal Titration Calorimetry Measurements of Aminoadamantanes Bound to the Closed State of Influenza A/M2TM
2016-04-22

Adamantane derivatives, such as amantadine and rimantadine, have been reported to block the transmembrane domain (TM) of the M2 protein of influenza A virus (A/M2) but their clinical use has been discontinued due to evolved resistance in humans. Although experiments and simulations have provided adequate information about the binding interaction of amantadine or rimantadine to the M2 protein, methods for predicting binding affinities of whole series of M2 inhibitors have so far been scarcely applied. Such methods could assist in the development of novel potent inhibitors that overcome A/M2 resistance. Here we show that alchemical free energy calculations of ligand binding using the Bennett acceptance ratio (BAR) method are valuable for determining the relative binding potency of A/M2 inhibitors of the aminoadamantane type covering a binding affinity range of only ∼2 kcal mol(-1). Their binding affinities measured by isothermal titration calorimetry (ITC) against the A/M2TM tetramer from the Udorn strain in its closed form at pH 8 were used as experimental probes. The binding constants of rimantadine enantiomers against M2TMUdorn were measured for the first time and found to be equal. Two series of alchemical free energy calculations were performed using 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipids to mimic the membrane environment. A fair correlation was found for DPPC that was significantly improved using DMPC, which resembles more closely the DPC lipids used in the ITC experiments. This demonstrates that binding free energy calculations by the BAR approach can be used to predict relative binding affinities of aminoadamantane derivatives toward M2TM with good accuracy.
The Pulsation Modes Of The Pre-White Dwarf PG 1159-035
2016-04-22

Context. PG 1159-035, a pre-white dwarf with T&lt;SUB&gt;eff&lt;/SUB&gt; ≃ 140000 K, is the prototype of both two classes: the PG 1159 spectroscopic class and the DOV pulsating class. Previous studies of PG 1159-035 photometric data obtained with the Whole Earth Telescope (WET) showed a rich frequency spectrum allowing the identification of 122 pulsation modes. Analyzing the periods of pulsation, it is possible to measure the stellar mass, the rotational period and the inclination of the rotation axis, to estimate an upper limit for the magnetic field, and even to obtain information about the inner stratification of the star. Aims. We have three principal aims: to increase the number of detected and identified pulsation modes in PG 1159-035, study trapping of the star's pulsation modes, and to improve or constrain the determination of stellar parameters. Methods. We used all available WET photometric data from 1983, 1985, 1989. 1993 and 2002 to identify the pulsation periods. Results. We identified 76 additional pulsation modes, increasing to 198 the number of known pulsation modes in PG 1159-035, the largest number of modes detected in any star besides the Sun. From the period spacing we estimated a mass M/M⊙= 0.59 ±0.02 for PG 1159-035, with the uncertainty dominated by the models, not the observation. Deviations in the regular period spacing suggest that some of the pulsation modes are trapped, even though the star is a pre-white dwarf and the gravitational settling is ongoing. The position of the transition zone that causes the mode trapping was calculated at r&lt;SUB&gt;c&lt;/SUB&gt;/R&lt;SUB&gt;*&lt;/SUB&gt; = 0.83 ± 0.05. From the multiplet splitting, we calculated the rotational period P&lt;SUB&gt;rot&lt;/SUB&gt; = 1.3920 ± 0.0008 days and an upper limit for the magnetic field, B &lt; 2000 G. The total power of the pulsation modes at the stellar surface changed less than 30% for l = 1 modes and less than 50% for l = 2 modes. We find no evidence of linear combinations between the 198 pulsation mode frequencies. PG 1159-035 models have not significative convection zones, supporting the hypothesis that nonlinearity arises in the convection zones in cooler pulsating white dwarf stars.
HDAC inhibition protects degenerating cone photoreceptorsin vivo
2016-04-22

Abstract Retinal diseases caused by cone photoreceptor cell death are devastating as the patients are experiencing loss of accurate and color vision. Understanding the mechanisms of cone cell death and the identification of key players therein could provide new treatment options. We studied the neuroprotective effects of a histone deacetylase inhibitor, Trichostatin A (TSA), in a mouse model of inherited, primary cone degeneration ( cpfl1 ). We show that HDAC inhibition protects cones in vitro , in retinal explant cultures. More importantly, in vivo a single TSA injection increased cone survival for up to 10 days post-injection. In addition, the abnormal, incomplete cone migration pattern in the cpfl1 retina was significantly improved by HDAC inhibition. These findings suggest a crucial role for HDAC activity in primary cone degeneration and highlight a new avenue for future therapy developments for cone dystrophies and diseases associated with impaired cone migration.
Cerebral autoregulation in acute SAH
2016-04-23

Regulation of cerebral blood flow serves to protect the brain in the face of changing perfusion pressure. In acute subarachnoid hemorrhage (SAH), this autoregulation faces challenges both from reduced local cerebral perfusion pressure caused by cerebral vasospasm and from reductions in global cerebral perfusion pressure due to hydrocephalus. Early impairment of cerebral autoregulation plays a major role for development of delayed cerebral ischemia (DCI) in SAH patients.1 The mechanism of cerebral autoregulation itself involves myogenic and neurogenic (sympathetic or cholinergic) mechanisms. Impairment of these mechanisms in acute SAH may differentially contribute to early brain damage through DCI with territorial infarctions due to severe vasospasm, DCI with watershed infarctions due to microvascular dysfunction, or both. Understanding the pathophysiology of impaired vasoregulation in acute SAH and the potentially different roles in clinical complications would constitute an important step forward in development of specific treatments to improve autoregulation and outcomes in SAH.
Effect of surface modification of zirconia on cell adhesion, metabolic activity and proliferation of human osteoblasts
2016-04-24

Abstract Titanium dental implants with sandblasted and/or acid-etched surfaces have shown clinical superiority in comparison to their smooth, machined counterparts, and are now state of the art. Sandblasting of finished, sintered zirconia implants, however, will damage the surface structure and affect the mechanical properties. To improve osseointegration of zirconia dental implants without impairing the original mechanical strength by crack initiation and partial phase transformation from tetragonal to monoclinic, roughening of the zirconia surface by sandblasting before the final sintering step was employed. Impact of the treatments on cellular reactions of SAOS-2 human osteoblast-like cells was investigated. Sandblasting of Yttrium-stabilized zirconia (Y-TZP) with 120 μm and 250 μm Al