julilili42/papers huggingface dataset:
Same Same, but Different: Word and Sentence Reading in German and English
2016-02-06

The current study compared eye fixation patterns during word and sentence processing in a consistent and an inconsistent alphabetic orthography. German and English children as well as adults matched on word reading ability read matched sentences while their eye fixation behavior was recorded. Results indicated that German children read in a more small-unit plodder-like style with more diligent first-pass reading and less rereading. In contrast, English children read in a more large-unit explorer-like style with a greater tendency to skip words, and more regressions. It is important that these cross-linguistic processing differences largely persisted in the adult readers. Orthographic consistency thus influences both local word recognition and global sentence processing in developing and skilled readers.
Chemokine receptor patterns in lymphocytes mirror metastatic spreading in melanoma
2016-02-07

Melanoma prognosis is dictated by tumor-infiltrating lymphocytes, the migratory and functional behavior of which is guided by chemokine or cytokine gradients. Here, we retrospectively analyzed the expression patterns of 9 homing receptors (CCR/CXCR) in naive and memory CD4+ and CD8+ T lymphocytes in 57 patients with metastatic melanoma (MMel) with various sites of metastases to evaluate whether T cell CCR/CXCR expression correlates with intratumoral accumulation, metastatic progression, and/or overall survival (OS). Homing receptor expression on lymphocytes strongly correlated with MMel dissemination. Loss of CCR6 or CXCR3, but not cutaneous lymphocyte antigen (CLA), on circulating T cell subsets was associated with skin or lymph node metastases, loss of CXCR4, CXCR5, and CCR9 corresponded with lung involvement, and a rise in CCR10 or CD103 was associated with widespread dissemination. High frequencies of CD8+CCR9+ naive T cells correlated with prolonged OS, while neutralizing the CCR9/CCL25 axis in mice stimulated tumor progression. The expansion of CLA-expressing effector memory CD8+ T cells in response to a single administration of CTLA4 blockade predicted disease control at 3 months in 47 patients with MMel. Thus, specific CCR/CXCR expression patterns on circulating T lymphocytes may guide potential diagnostic and therapeutic approaches.
An Electrochemical Sensing Platform Based on Liquid–Liquid Microinterface Arrays Formed in Laser-Ablated Glass Membranes
2016-02-07

Arrays of microscale interfaces between two immiscible electrolyte solutions (μITIES) were formed using glass membranes perforated with microscale pores by laser ablation. Square arrays of 100 micropores in 130 μm thick borosilicate glass coverslips were functionalized with trichloro(1H,1H,2H,2H-perfluorooctyl)silane on one side, to render the surface hydrophobic and support the formation of aqueous-organic liquid-liquid microinterfaces. The pores show a conical shape, with larger radii at the laser entry side (26.5 μm) than at the laser exit side (11.5 μm). The modified surfaces were characterized by contact angle measurements and X-ray photoelectron spectroscopy. The organic phase was placed on the hydrophobic side of the membrane, enabling the array of μITIES to be located at either the wider or narrower pore mouth. The electrochemical behavior of the μITIES arrays were investigated by tetrapropylammonium ion transfer across water-1,6-dichlorohexane interfaces together with finite element computational simulations. The data suggest that the smallest microinterfaces (formed on the laser exit side) were located at the mouth of the pore in hemispherical geometry, while the larger microinterfaces (formed on the laser entry side) were flatter in shape but exhibited more instability due to the significant roughness of the glass around the pore mouths. The glass membrane-supported μITIES arrays presented here provide a new platform for chemical and biochemical sensing systems. © 2016 American Chemical Society.
Aberrant Activity in Degenerated Retinas Revealed by Electrical Imaging
2016-02-08

In this review, I present and discuss the current understanding of aberrant electrical activity found in the ganglion cell layer (GCL) of rod-degenerated (rd) mouse retinas. The reported electrophysiological properties revealed by electrical imaging using high-density microelectrode arrays can be subdivided between spiking activity originating from retinal ganglion cells (RGCs) and local field potentials (LFPs) reflecting strong trans-membrane currents within the GCL. RGCs in rd retinas show increased and rhythmic spiking compared to age-matched wild-type retinas. Fundamental spiking frequencies range from 5 to 15 Hz in various mouse models. The rhythmic RGC spiking is driven by a presynaptic network comprising AII amacrine and bipolar cells. In the healthy retina this rhythm-generating circuit is inhibited by photoreceptor input. A unique physiological feature of rd retinas is rhythmic LFP manifested as spatially-restricted low-frequency (5-15 Hz) voltage changes. Their spatiotemporal characterization revealed propagation and correlation with RGC spiking. LFPs rely on gap-junctional coupling and are shaped by glycinergic and by GABAergic transmission. The aberrant RGC spiking and LFPs provide a simple readout of the functionality of the remaining retinal circuitry which can be used in the development of improved vision restoration strategies.
Hereditary spastic paraplegia: Clinicogenetic lessons from 608 patients
2016-02-09

Objective Hereditary spastic paraplegias (HSPs) are genetically driven disorders with the hallmark of progressive spastic gait disturbance. To investigate the phenotypic spectrum, prognostic factors, and genotype‐specific differences, we analyzed baseline data from a continuous, prospective cohort. Methods We recruited 608 HSP cases from 519 families of mostly German origin. Clinical severity was assessed by the Spastic Paraplegia Rating Scale. Complicating symptoms were recorded by a standardized inventory. Results Family history indicated dominant (43%), recessive (10%), and simplex (47%) disease. We observed a significant male predominance, particularly in simplex cases without a genetic diagnosis. Disease severity increased with disease duration. Earlier disease onset was associated with less severe disease. Specific complicating features including cognitive impairment, extrapyramidal or peripheral motor involvement, and ataxia were associated with worse disease severity. Disease severity also depended on the genotype. HSP cases maintained the ability to walk independently for a median disease duration of 22 years. Early onset cases were able to maintain free walking significantly longer and were at less risk to become wheelchair dependent. Interpretation This cross‐sectional cohort study provides the first large‐scale data on disease manifestation, progression, and modifying factors, with relevance for counseling of HSP families and planning of future cross‐sectional and natural history studies. Later age of onset, specific complicating features, and the SPG11 genotype are strongly associated with more severe disease. Future interventional studies will require stratification for modifiers of disease progression identified in this study. Prospective longitudinal studies will verify progression rates calculated in this baseline analysis. Ann Neurol 2016;79:646–658
Seasonal Variation in Shell Calcification of Planktonic Foraminifera in the NE Atlantic Reveals Species-Specific Response to Temperature, Productivity, and Optimum Growth Conditions
2016-02-09

Using shells collected from a sediment trap series in the Madeira Basin, we investigate the effects of seasonal variation of temperature, productivity, and optimum growth conditions on calcification in three species of planktonic Foraminifera. The series covers an entire seasonal cycle and reflects conditions at the edge of the distribution of the studied species, manifesting more suitable growth conditions during different parts of the year. The seasonal variation in seawater carbonate saturation at the studied site is negligible compared to other oceanic regions, allowing us to assess the effect of parameters other than carbonate saturation. Shell calcification is quantified using weight and size of individual shells. The size-weight scaling within each species is robust against changes in environmental parameters, but differs among species. An analysis of the variation in calcification intensity (size-normalized weight) reveals species-specific response patterns. In Globigerinoides ruber (white) and Globigerinoides elongatus, calcification intensity is correlated with temperature (positive) and productivity (negative), whilst in Globigerina bulloides no environmental forcing is observed. The size-weight scaling, calcification intensity, and response of calcification intensity to environmental change differed between G. ruber (white) and G. elongatus, implying that patterns extracted from pooled analyses of these species may reflect their changing proportions in the samples. Using shell flux as a measure of optimum growth conditions, we observe significant positive correlation with calcification intensity in G. elongatus, but negative correlation in G. bulloides. The lack of a consistent response of calcification intensity to optimum growth conditions is mirrored by the results of shell size analyses. We conclude that calcification intensity in planktonic Foraminifera is affected by factors other than carbonate saturation. These factors include temperature, productivity, and optimum growth conditions, but the strength and sign of the relationships differ among species, potentially complicating interpretations of calcification data from the fossil record.
VraH Is the Third Component of the Staphylococcus aureus VraDEH System Involved in Gallidermin and Daptomycin Resistance and Pathogenicity
2016-02-09

ABSTRACT In bacteria, extracellular signals are transduced into the cell predominantly by two-component systems (TCSs) comprising a regulatory unit triggered by a specific signal. Some of the TCSs control executing units such as ABC transporters involved in antibiotic resistance. For instance, in Staphylococcus aureus , activation of BraSR leads to the upregulation of vraDE expression that encodes an ABC transporter playing a role in bacitracin and nisin resistance. In this study, we show that the small staphylococcal transmembrane protein VraH forms, together with VraDE, a three-component system. Although the expression of vraH in the absence of vraDE was sufficient to mediate low-level resistance, only this VraDEH entity conferred high-level resistance against daptomycin and gallidermin. In most staphylococcal genomes, vraH is located immediately downstream of vraDE , forming an operon, whereas in some species it is localized differently. In an invertebrate infection model, VraDEH significantly enhanced S. aureus pathogenicity. In analogy to the TCS connectors, VraH can be regarded as an ABC connector that modulates the activity of ABC transporters involved in antibiotic resistance.
New Middle Palaeolithic sites from the Mani Peninsula, Southern Greece
2016-02-09

We here report the first results from a systematic research project in Mani (Southern Greece), which includes survey and test excavations. Forty-six caves, rockshelters and open-air sites in lowland settings were surveyed. Geomorphological data were collected in order to assess how geological processes affect the preservation of sites and bias site distribution patterns. Artifacts manufactured from non-local rock indicate potential raw material transfers and suggest links among the different regions of Mani, related to mobility patterns. Our research in the Mani has nearly doubled the number of known Middle Palaeolithic sites from the region and confirmed that the peninsula has the strongest ‘Neanderthal signal’ identified to date in Greece. Almost all sites are located at coastal areas. Despite the influence of Pleistocene landscape dynamics, this distribution emerges as a persistent pattern, perhaps indicating a preference for coastal locations. The Neanderthal occupation of Mani can illuminate importan...
A New Tool for Transbronchial Cryobiopsies in the Lung: An Experimental Feasibility ex-vivo Study
2016-02-09

Background: Transbronchial cryobiopsy (TBCB) is a minimally invasive procedure to establish a diagnosis in interstitial lung diseases (ILDs) though with the disadvantages of a rigid intubation and the extraction of the samples together with the whole bronchoscope.
Open-label, randomized study of individualized, pharmacokinetically (PK)-guided dosing of paclitaxel combined with carboplatin in advanced Non-Small Cell Lung Cancer (NSCLC) patient
2016-02-09

Background: Variability of chemotherapy exposure may cause severe toxicity or lack of efficacy. Paclitaxel (PTX) exposure (time above a plasma concentration of 0.05mM, Tc > 0.05) has been shown to predict toxicity. Whereas carboplatin dose is adapted to kidney function, PTX dosing only accounts for body-surface area. We developed a PTX dosing algorithm for avoidance of supra- or subtherapeutic PTX exposure based on Tc > 0.05 determined from a single blood sample drawn 18 – 30 hours after starting PTX infusion. This study was initiated to validate PK-guided PTX dosing in advanced NSCLC patients.
Pooled Safety Analysis Of Adjudicated Serious Adverse Events With The Fixed-Dose Combination Of Tiotropium + Olodaterol
2016-02-09

Rationale: The objective of this analysis was to obtain a comprehensive and objective safety assessment of the fixed-dose combination of tiotropium with olodaterol (T+O FDC) in patients (pts) with moderate to very severe COPD.
The Dokounta of the Platonic Dialectician. On Plato’s distinction between the insufficient "present discussion" and a satisfactory future one
2016-02-09

It is a recurring pattern in Plato ́s dialogues that the dialectician leads the discussion to a certain point where he identifies further, more fundamental problems, on which he claims to have his own view (to emoi dokoun, vel sim.), which he does not communicate. Such passages are briefly analyzed from five dialogues (Timaeus, Sophist, Politicus, Parmenides, Republic). It is shown that this seemingly strange behaviour of the dialectician corresponds exactly to the way a philosopher should behave according to the Phaedrus. The recurring cases of reticence of the leading figure in dialogue have to be understood as Plato ́s written reference to his own unwritten philosophy.
Plato’s Unwritten Doctrine
2016-02-09

With the late Author’s (†24.04.2015) kind permission, the present text is published here in a somewhat abbreviated and modified translation that has been given appropriate subheadings and supplemented with an extensive bibliography. Its German original from 1996 has been translated into French (1998) and English (2012). The purpose of the present translation is to make the Polish reader acquainted with the important and innovative account of Plato’s philosophy that has been put forward by the Tübingen School whose one of the most prominent co-founders was Hans Joachim Krämer. While this text is devoted to Plato’s critique of writing, it also presents Plato’s agrapha dogmata as an important supplement to the written dialogues. A fuller overview of the major assumptions of this new interpretation is to be found in the recently published Gesammelte Ansätze zu Platon (2014).
Improving the informed consent process in international collaborative rare disease research: effective consent for effective research
2016-02-10

The increased international sharing of data in research consortia and the introduction of new technologies for sequencing challenge the informed consent (IC) process, adding complexities that require coordination between research centres worldwide. Rare disease consortia present special challenges since available data and samples may be very limited. Thus, it is especially relevant to ensure the best use of available resources but at the same time protect patients' right to integrity. To achieve this aim, there is an ethical duty to plan in advance the best possible consent procedure in order to address possible ethical and legal hurdles that could hamper research in the future. Therefore, it is especially important to identify key core elements (CEs) to be addressed in the IC documents for international collaborative research in two different situations: (1) new research collections (biobanks and registries) for which information documents can be created according to current guidelines and (2) established collections obtained without IC or with a previous consent that does not cover all CEs. We propose here a strategy to deal with consent in these situations. The principles have been applied and are in current practice within the RD-Connect consortia â a global research infrastructure funded by the European Commission Seventh Framework program but forward looking in terms of issues addressed. However, the principles established, the lessons learned and the implications for future research are of direct relevance to all internationally collaborative rare-disease projects.
Why Was Silcrete Heat-Treated in the Middle Stone Age? An Early Transformative Technology in the Context of Raw Material Use at Mertenhof Rock Shelter, South Africa
2016-02-11

People heat treated silcrete during the Middle Stone Age (MSA) in southern Africa but the spatial and temporal variability of this practice remains poorly documented. This paucity of data in turn makes it difficult to interrogate the motive factors underlying the application of this technique. In this paper we present data on heat treatment of silcrete through the Howiesons Poort and post-Howiesons Poort of the rock shelter site Mertenhof, located in the Western Cape of South Africa. In contrast to other sites where heat treatment has been documented, distance to rock source at Mertenhof can be reasonably well estimated, and the site is known to contain high proportions of a diversity of fine grained rocks including silcrete, hornfels and chert at various points through the sequence. Our results suggest the prevalence of heat treatment is variable through the sequence but that it is largely unaffected by the relative abundance of silcrete prevalence. Instead there is a strong inverse correlation between frequency of heat treatment in silcrete and prevalence of chert in the assemblage, and a generally positive correlation with the proportion of locally available rock. While it is difficult to separate individual factors we suggest that, at Mertenhof at least, heat treatment may have been used to improve the fracture properties of silcrete at times when other finer grained rocks were less readily available. As such, heat treatment appears to have been a component of the MSA behavioural repertoire that was flexibly deployed in ways sensitive to other elements of technological organisation.
Standardized Assessment of Hereditary Ataxia Patients in Clinical Studies
2016-02-11

Abstract Background Hereditary ataxias are a heterogeneous group of degenerative diseases of the cerebellum, brainstem, and spinal cord. They may present with isolated ataxia or with additional symptoms going beyond cerebellar deficits. There are an increasing number of clinical studies with the goal to define the natural history of these disorders, develop biomarkers, and investigate therapeutic interventions. Especially, early and preclinical disease stages are currently of particular interest. Methods and Results Evidence‐based, we review standards for sampling and storage of biomaterials, clinical and neuropsychological assessment, as well as neurophysiology and neuroimaging and recommendations for standardized assessment of ataxia patients in multicenter studies. Conclusions DNA , RNA , serum, and, if possible, cerebrospinal fluid samples should be processed following established standards. Clinical assessment in ataxia studies must include use of a validated clinical ataxia scale. There are several validated clinical ataxia scales available. There are no instruments that were specifically designed for assessing neuropsychological and psychiatric symptoms in ataxia disorders. We provide a list of tests that may prove valuable. Quantitative performance tests have the potential to supplement clinical scales. They provide additional objective and quantitative information. Posturography and quantitative movement analysis—despite valid approaches—require standardization before implemented in multicenter studies. Standardization of neurophysiological tools, as required for multicenter interventional trials, is still lacking. Future multicenter neuroimaging studies in ataxias should implement quality assurance measures as defined by the ADNI or other consortia. MRI protocols should allow morphometric analyses.
Particle creation and annihilation at interior boundaries: one-dimensional models
2016-02-11

We describe creation and annihilation of particles at external sources in one\\nspatial dimension in terms of interior-boundary conditions (IBCs). We derive\\nexplicit solutions for spectra, (generalised) eigenfunctions, as well as Green\\nfunctions, spectral determinants, and integrated spectral densities. Moreover,\\nwe introduce a quantum graph version of IBC-Hamiltonians.\\n
Intramyocellular lipids and their dynamics assessed by 1H magnetic resonance spectroscopy
2016-02-11

Summary This report provides an overview on the present knowledge on intramyocellular lipids ( IMCL ) and their dynamics in the course of interventions with physical activity of variable type and intensity in different population groups, as accessible by examinations using non‐invasive volume‐selective 1 H magnetic resonance spectroscopy ( 1 H MRS ). IMCL serve as energy source in skeletal muscle for fat oxidation in the mitochondria and became intensively studied after discovery of their relation with insulin sensitivity. While baseline levels of IMCL concentration have been shown to be mainly dependent on the metabolic status (insulin sensitivity), on the level of training and on fibre composition in the muscles, studies applying different physical activity protocols revealed the dynamic of their depletion and replenishment. From the findings in human studies, it can be concluded that IMCL levels are potentially useful markers for monitoring metabolic adaptation of skeletal muscle to sportive activities and training.
Perception of light source distance from shading patterns
2016-02-11

Varying the distance of a light source from an object alters both the intensity and spatial distribution of surface shading patterns. We tested whether observers can use such cues to infer light source distance. Participants viewed stereoscopic renderings of rough objects with diffuse and glossy surfaces, which were illuminated by a point source at a range of distances. In one task, they adjusted the position of a small probe dot in three dimensions to report the apparent location of the light in the scene. In a second task, they adjusted the shading on one object (by moving an invisible light source) until it appeared to be illuminated from the same distance as another object. Participants' responses increased linearly with the true light source distance, suggesting that they have clear intuitions about how light source distance affects shading patterns for a variety of different surfaces. However, there were also systematic errors: Subjects overestimated light source distance in the probe adjustment task, and in both experiments, roughness and glossiness affected responses. We find the pattern of results is predicted surprisingly well by a simplistic model based only on the area of the image that exceeds a certain intensity threshold. Thus, although subjects can report light source distance, they may rely on simple--sometimes erroneous--heuristics to do so.