julilili42/papers huggingface dataset:
Antihyperglycaemic therapies and cancer risk
2014-09-17

Aims: This review is aimed at highlighting the potential mitogenic/tumour growth–promoting or antimitogenic/tumour growth–inhibiting effects of the main antihyperglycaemic drug classes. Methods: We review and discuss the most current studies evaluating the association between antidiabetic medications used in clinical practice and malignancies as described so far. Results: Metformin seems to be the only antidiabetic drug to exert protective effects both on monotherapy and also when combined with other oral antidiabetic drugs or insulins in several site-specific cancers. In contrast, several other drug classes may increase cancer risk. Some reason for concern remains regarding sulphonylureas and also the incretin-based therapies regarding pancreas and thyroid cancers and the sodium glucose cotransporter-2 inhibitors as well as pioglitazone regarding bladder cancer. The majority of meta-analyses suggest that there is no evidence for a causal relationship between insulin glargine and elevated cancer risk, although the studies have been controversially discussed. For α-glucosidase inhibitors and glinides, neutral or only few data upon cancer risk exist. Conclusion: Although the molecular mechanisms are not fully understood, a potential risk of mitogenicity and tumour growth promotion cannot be excluded in case of several antidiabetic drug classes. However, more large-scale, randomized, well-designed clinical studies with especially long follow-up time periods are needed to get reliable answers to these safety issues.
High lipid order of Arabidopsis cell‐plate membranes mediated by sterol and DYNAMIN‐RELATED PROTEIN1A function
2014-09-18

Summary Membranes of eukaryotic cells contain high lipid‐order sterol‐rich domains that are thought to mediate temporal and spatial organization of cellular processes. Sterols are crucial for execution of cytokinesis, the last stage of cell division, in diverse eukaryotes. The cell plate of higher‐plant cells is the membrane structure that separates daughter cells during somatic cytokinesis. Cell‐plate formation in Arabidopsis relies on sterol‐ and DYNAMIN‐RELATED PROTEIN1A (DRP1A)‐dependent endocytosis. However, functional relationships between lipid membrane order or lipid packing and endocytic machinery components during eukaryotic cytokinesis have not been elucidated. Using ratiometric live imaging of lipid order‐sensitive fluorescent probes, we show that the cell plate of Arabidopsis thaliana represents a dynamic, high lipid‐order membrane domain. The cell‐plate lipid order was found to be sensitive to pharmacological and genetic alterations of sterol composition. Sterols co‐localize with DRP1A at the cell plate, and DRP1A accumulates in detergent‐resistant membrane fractions. Modifications of sterol concentration or composition reduce cell‐plate membrane order and affect DRP1A localization. Strikingly, DRP1A function itself is essential for high lipid order at the cell plate. Our findings provide evidence that the cell plate represents a high lipid‐order domain, and pave the way to explore potential feedback between lipid order and function of dynamin‐related proteins during cytokinesis.
Effects of Personalized Banner Ads on Visual Attention and Recognition Memory
2014-09-18

Summary Internet companies collect a vast amount of data about their users in order to personalize banner ads. However, very little is known about the effects of personalized banners on attention and memory. In the present study, 48 subjects performed search tasks on web pages containing personalized or nonpersonalized banners. Overt attention was measured by an eye‐tracker, and recognition of banner and task‐relevant information was subsequently examined. The entropy of fixations served as a measure for the overall exploration of web pages. Results confirm the hypotheses that personalization enhances recognition for the content of banners while the effect on attention was weaker and partially nonsignificant. In contrast, overall exploration of web pages and recognition of task‐relevant information was not influenced. The temporal course of fixations revealed that visual exploration of banners typically proceeds from the picture to the logo and finally to the slogan. We discuss theoretical and practical implications. Copyright © 2014 John Wiley &amp; Sons, Ltd.
Vacuum-assisted breast biopsy with 7-gauge, 8-gauge, 9-gauge, 10-gauge, and 11-gauge needles: how many specimens are necessary?
2014-09-18

Background Published national and international guidelines and consensus meetings on the use of vacuum-assisted biopsy (VAB) give different recommendations regarding the required numbers of tissue specimens depending on needle size and imaging method. Purpose To evaluate the weights of specimens obtained with different VAB needles to facilitate the translation of the required number of specimens between different breast biopsy systems and needle sizes, respectively. Material and Methods Five different VAB systems and seven different needle sizes were used: Mammotome® (11-gauge (G), 8-G), Vacora® (10-G), ATEC SapphireTM (9-G), 8-G Mammotome® RevolveTM, and EnCor Enspire® (10-G, 7-G). We took 24 (11-G) or 20 (7–10-G) tissue cores from a turkey breast phantom. The mean weight of a single tissue core was calculated for each needle size. A matrix, which allows the translation of the required number of tissue cores for different needle sizes, was generated. Results were compared to the true cumulative tissue weights of consecutively harvested tissue cores. Results The mean tissue weights obtained with the 11-G / 10-G Vacora® / 10-G Enspire® / 9-G / 8-G Original / 8-G RevolveTM / 7-G needles were 0.084 g / 0.142 g / 0.221 g / 0.121 g / 0.192 g / 0.334 g / 0.363 g, respectively. The calculated required numbers of VAB tissue cores for each needle size build the matrix. For example, the minimum calculated number of required cores according to the current German S3 guideline is 20 / 12 / 8 / 14 / 9 / 5 / 5 for needles of 11-G / 10-G Vacora® / 10-G Enspire® / 9-G / 8-G Original / 8-G RevolveTM / 7-G size. These numbers agree with the true cumulative tissue weights. Conclusion The presented matrix facilitates the translation of the required number of VAB specimens between different needle sizes and thereby eases the implementation of current guidelines and consensus recommendations into clinical practice.
Sphingosine kinase 1 (Sphk1) negatively regulates platelet activation and thrombus formation
2014-09-18

Sphingosine 1-phosphate (S1P) is a powerful regulator of platelet formation. Enzymes generating S1P include sphingosine kinase 1. The present study thus explored the role of sphingosine kinase 1 in platelet formation and function. Activation-dependent platelet integrin α IIb β 3 activation and secretion of platelets lacking functional sphingosine kinase 1 ( sphk1 −/− ) and of wild-type platelets ( sphk1 +/+ ) were determined utilizing flow cytometry and chronolume luciferin assay. Cytosolic Ca 2+ activity ([Ca 2+ ] i ) and aggregation were measured using fura-2 fluorescence and aggregometry, respectively. In vitro platelet adhesion and thrombus formation were evaluated using a flow chamber with shear rates of 1,700 s −1 . Activation-dependent increase of [Ca 2+ ] i , degranulation (release of alpha and dense granules), integrin α IIb β 3 activation, and aggregation were all significantly increased in sphk1 −/− platelets compared with sphk1 +/+ platelets. Moreover, while platelet adhesion and thrombus formation under arterial shear rates were significantly augmented in Sphk1-deficient platelets, bleeding time and blood count were unaffected in sphk1 −/− mice. In conclusion, sphingosine kinase 1 is a powerful negative regulator of platelet function counteracting degranulation, aggregation, and thrombus formation.
Synchronization patterns suggest different functional organization in parietal reach region and dorsal premotor cortex
2014-09-18

The parietal reach region (PRR) and dorsal premotor cortex (PMd) form part of the fronto-parietal reach network. While neural selectivity profiles of single-cell activity in these areas can be remarkably similar, other data suggest that both areas serve different computational functions in visually guided reaching. Here we test the hypothesis that different neural functional organizations characterized by different neural synchronization patterns might be underlying the putatively different functional roles. We use cross-correlation analysis on single-unit activity (SUA) and multiunit activity (MUA) to determine the prevalence of synchronized neural ensembles within each area. First, we reliably find synchronization in PRR but not in PMd. Second, we demonstrate that synchronization in PRR is present in different cognitive states, including “idle” states prior to task-relevant instructions and without neural tuning. Third, we show that local field potentials (LFPs) in PRR but not PMd are characterized by an increased power and spike field coherence in the beta frequency range (12–30 Hz), further indicating stronger synchrony in PRR compared with PMd. Finally, we show that neurons with similar tuning properties tend to be correlated in their random spike rate fluctuations in PRR but not in PMd. Our data support the idea that PRR and PMd, despite striking similarity in single-cell tuning properties, are characterized by unequal local functional organization, which likely reflects different network architectures to support different functional roles within the fronto-parietal reach network.
WIPI β-propellers at the crossroads of autophagosome and lipid droplet dynamics
2014-09-18

Macroautophagy (autophagy hereafter) is an evolutionarily highly conserved catabolic process activated by eukaryotes in order to counteract cellular starvation. Autophagy leads to bulk degradation of cytoplasmic content in the lysosomal compartment, thereby clearing the cytoplasm and generating nutrients and energy. Upon autophagy initiation, cytoplasmic material becomes sequestered in newly formed double-membrane vesicles termed ‘autophagosomes’ that subsequently acquire acidic hydrolases for content destruction. The de novo biogenesis of autophagosomes often occurs at the endoplasmic reticulum (ER) and, in many cases, in close proximity to lipid droplets (LDs), intracellular neutral lipid storage reservoirs. LDs are targets of autophagic destruction, but have recently also been shown to contribute to autophagosome formation. In fact, some autophagy-related (Atg) proteins, such as microtubule-associated protein light chain 3 (LC3), Atg2 and Atg14L, functionally contribute to both LD and autophagosome biogenesis. In the present paper, we discuss Atg proteins, including members of the human WD-repeat protein interacting with phosphoinositides (WIPI) family that co-localize prominently with LC3, Atg2 and Atg14L to conceivably integrate LD and autophagosome dynamics.
In Vitro Sensitization of Erythrocytes to Programmed Cell Death Following Baicalein Treatment
2014-09-18

The polyphenolic flavonoid Baicalein has been shown to trigger suicidal death or apoptosis of tumor cells and is thus considered for the prevention and treatment of malignancy. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include increase of cytosolic Ca2+-activity ([Ca2+]i) and ceramide. The present study explored whether Baicalein stimulates eryptosis. To this end, forward scatter was taken for measurement of cell volume, annexin-V-binding for phosphatidylserine-exposure, Fluo3 fluorescence for [Ca2+]i and fluorescent antibodies for ceramide abundance. As a result, a 48 h exposure of human erythrocytes to Baicalein was followed by significant decrease of forward scatter (≥10 μM), significant increase of the percentage of annexin-V-binding cells (≥25 μM), significant increase of [Ca2+]i (50 μM) and significant increase of ceramide abundance (50 μM). The effect of Baicalein (50 μM) on annexin-V-binding was significantly blunted but not abrogated by removal of extracellular Ca2+. In conclusion, at the concentrations employed, Baicalein stimulates suicidal erythrocyte death or eryptosis, an effect at least in part due to the combined effects of Ca2+ entry and ceramide formation.
A Mechatronic System for Robot-Mediated Hand Telerehabilitation
2014-09-19

This paper presents a novel mechatronics master-slave setup for hand telerehabilitation. The system consists of a sensorized glove acting as a remote master and a powered hand exoskeleton acting as a slave. The proposed architecture presents three main innovative solutions. First, it provides the therapist with an intuitive interface (a sensorized wearable glove) for conducting the rehabilitation exercises. Second, the patient can benefit from a robot-aided physical rehabilitation in which the slave hand robotic exoskeleton can provide an effective treatment outside the clinical environment without the physical presence of the therapist. Third, the mechatronics setup is integrated with a sensorized object, which allows for the execution of manipulation exercises and the recording of patient's improvements. In this paper, we also present the results of the experimental characterization carried out to verify the system usability of the proposed architecture with healthy volunteers.
Dynamin-related Protein 1 (Drp1) Promotes Structural Intermediates of Membrane Division
2014-09-19

Drp1 is a dynamin-like GTPase that mediates mitochondrial and peroxisomal division in a process dependent on self-assembly and coupled to GTP hydrolysis. Despite the link between Drp1 malfunction and human disease, the molecular details of its membrane activity remain poorly understood. Here we reconstituted and directly visualized Drp1 activity in giant unilamellar vesicles. We quantified the effect of lipid composition and GTP on membrane binding and remodeling activity by fluorescence confocal microscopy and flow cytometry. In contrast to other dynamin relatives, Drp1 bound to both curved and flat membranes even in the absence of nucleotides. We also found that Drp1 induced membrane tubulation that was stimulated by cardiolipin. Moreover, Drp1 promoted membrane tethering dependent on the intrinsic curvature of the membrane lipids and on GTP. Interestingly, Drp1 concentrated at membrane contact surfaces and, in the presence of GTP, formed discrete clusters on the vesicles. Our findings support a role of Drp1 not only in the formation of lipid tubes but also on the stabilization of tightly apposed membranes, which are intermediate states in the process of mitochondrial fission.
Comparative analysis of bacterial community composition in bulk tank raw milk by culture-dependent and culture-independent methods using the viability dye propidium monoazide
2014-09-19

Microbial diversity of 3 raw milk samples after 72 h of storage at 4 °C in a bulk tank was analyzed by culture-dependent and -independent methods. The culture-dependent approach was based on the isolation of bacteria on complex and selective media, chemotaxonomic differentiation of isolates, and subsequent identification by 16S rRNA gene sequencing. The culture-independent approach included the treatment of raw milk with the dye propidium monoazide before direct DNA extraction by mechanic and enzymatic cell lysis approaches, and cloning and sequencing of the 16S rRNA genes. The selective detection of viable bacteria improved the comparability between bacterial compositions of raw milk based on culture-dependent and -independent methods, which was the major objective of this study. Several bacterial species of the phyla Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria were detected by the culture-dependent method, whereas mainly bacteria of the phylum Proteobacteria as well as low proportions of the phyla Bacteroidetes and Actinobacteria were detected by the culture-independent method. This led to the conclusion that the phylum Firmicutes was strongly discriminated by the culture-independent approach. Generally, species richness detected by the culture-dependent method was higher than that detected by the culture-independent method for all samples. However, few taxa could be detected solely by the direct DNA-based method. In conclusion, the combination of culture-dependent and -independent methods led to the detection of the highest bacterial diversity for the raw milk samples analyzed. It was shown that DNA extraction from raw milk as the essential step in culture-independent methods causes the discrimination of taxa by incomplete cell lysis. Treatment of raw milk with the viability dye propidium monoazide was optimized for the application in raw milk without former removal of milk ingredients and proved to be a suitable tool to ensure comparability of bacterial diversity depicted by both methods.
Dependable Multicore Architectures at Nanoscale: The View From Europe
2014-09-19

This article presented a survey of dependability issues faced by multi-core architectures at nanoscale technology nodes. Existing solutions against these challenges were also discussed, describing their scope of application, from technology level methodologies, to design approaches to the metrics required to evaluate the overall dependability of a system. In the future, the constant reduction of the feature size of the devices will exacerbate the issues related to aging and soft errors. This will create further challenges and at design level, an integrated design approach that will cope with the occurrence of faults at any time of their occurrence i.e., at manufacturing (thus increasing yield) and in the field (thus increasing reliability) will become more and more important to obtain economically viable and dependable systems. Dependability assessment will also need an integrated approach for cross-layer, pre- and post-silicon techniques for “just right”dependability assessment in order to avoid “overdesign”for dependability using classic guard-banding methodologies.
Computer‐assisted navigation is beneficial both in primary and revision surgery with modular rotating‐hinge knee arthroplasty
2014-09-19

Abstract Purpose The objective of the present study was to explore the effect of navigation on the reconstruction of the mechanical leg axis, implant positioning and the restoration of the joint line in hinged knee arthroplasty in vivo. We present the first 1‐ to 3‐year clinical and radiological results following computer‐navigated implantation of the EnduRo modular rotating‐hinge knee arthroplasty system (Aesculap AG, Tuttlingen, Germany) as a primary or revision implant. Methods Thirty‐one patients were analysed retrospectively. Indication was revision surgery in 18 patients and complex primary surgery in 13. The clinical and radiological results of 31 patients with a minimum follow‐up of 12 months (mean 22.2 ± 6.2 months) were recorded. Age at follow‐up was 55.2 ± 9.9 years. Results The absolute varus‐valgus deviation from the neutral mechanical leg axis was determined at 5.1° ± 5.1° preoperatively and 2.1° ± 1.4° postoperatively. No intraoperative complications or problems with the navigation system were observed. At latest follow‐up, no component loosening was detected. Based on the Knee Society Score, a knee score of 64.9 ± 17.7 points and a function score of 67.2 ± 27.3 points were achieved. Conclusions Encouraging short‐term clinical and radiological results with the computer‐navigated implantation of the modular rotating‐hinge EnduRo knee arthroplasty system were found in both primary and revision surgery. The navigation facilitated the reconstruction of the leg axis, implant positioning and the restoration of the joint line. Level of evidence IV.
10.1063/1.4896063.1
2014-09-19

Robust bubble-free priming of complex microfluidic chips represents a critical, yet often unmet prerequisite to enable their practical and widespread application. Towards this end, the usage of a network of capillary stop valves as a generic design feature is proposed. Design principles, numerical simulations, and their application in the development of a microfluidic cell culture device are presented. This chip comprises eight parallel chambers for the assembly and cultivation of human hepatocytes and endothelial cells. The inlet channel divides into cell chambers, after which the flows are reunited to a single chip outlet. Dimensions and geometry of channels and cell chambers are designed to yield capillary burst pressures sequentially increasing towards the chip outlet. Thus, progress of liquid flow through the device is predefined by design and enclosure of air bubbles inside the microfluidic structures is efficiently avoided. Capillary stop valves were designed using numerical simulations. Devices were fabricated in cyclic olefin polymer. Pressure during filling was determined experimentally and is in good agreement with data obtained from simulation.
Bi2Sr2CaCu2O8 intrinsic Josephson junction stacks with improved cooling: Coherent emission above 1 THz
2014-09-22

We report on Bi2Sr2CaCu2O8 (BSCCO) intrinsic Josephson junction stacks with improved cooling, allowing for a remarkable increase in emission frequency compared to the previous designs. We started with a BSCCO stack embedded between two gold layers. When mounted in the standard way to a single substrate, the stack emits in the range of 0.43–0.82 THz. We then glued a second, thermally anchored substrate onto the sample surface. The maximum voltage of this better cooled and dimension-unchanged sample was increased and, accordingly, both the emission frequencies and the tunable frequency range were significantly increased up to 1.05 THz and to 0.71 THz, respectively. This double sided cooling may also be useful for other “hot” devices, e.g., quantum cascade lasers.
DISCOVERY OF THE HARD SPECTRUM VHE γ-RAY SOURCE HESS J1641–463
2014-09-22

This letter reports the discovery of a remarkably hard spectrum source, HESS\\nJ1641-463, by the High Energy Stereoscopic System (H.E.S.S.) in the very-high\\nenergy (VHE) domain. HESS J1641-463 remained unnoticed by the usual analysis\\ntechniques due to confusion with the bright nearby source HESS J1640-465. It\\nemerged at a significance level of 8.5 standard deviations after restricting\\nthe analysis to events with energies above 4 TeV. It shows a moderate flux\\nlevel of F(E &gt; 1 TeV) = (3.64 +/- 0.44_stat +/- 0.73_sys) x 10^-13 cm^-2s-1,\\ncorresponding to 1.8% of the Crab Nebula flux above the same energy, and a hard\\nspectrum with a photon index of Gamma = 2.07 +/- 0.11_stat +/- 0.20_sys. It is\\na point-like source, although an extension up to Gaussian width of sigma = 3\\narcmin cannot be discounted due to uncertainties in the H.E.S.S. PSF. The VHE\\ngamma-ray flux of HESS J1641-463 is found to be constant over the observed\\nperiod when checking time binnings from year-by-year to the 28 min exposures\\ntimescales. HESS J1641-463 is positionally coincident with the radio supernova\\nremnant SNR G338.5+0.1. No X-ray candidate stands out as a clear association,\\nhowever Chandra and XMM-Newton data reveal some potential weak counterparts.\\nVarious VHE gamma-ray production scenarios are discussed. If the emission from\\nHESS J1641-463 is produced by cosmic ray protons colliding with the ambient\\ngas, then their spectrum must extend close to 1 PeV. This object may represent\\na source population contributing significantly to the galactic cosmic ray flux\\naround the knee.\\n