julilili42/papers huggingface dataset:
The hallmarks of Parkinson's disease
2013-05-11

Since the discovery of dopamine as a neurotransmitter in the 1950s, P arkinson's disease ( PD ) research has generated a rich and complex body of knowledge, revealing PD to be an age‐related multifactorial disease, influenced by both genetic and environmental factors. The tremendous complexity of the disease is increased by a nonlinear progression of the pathogenesis between molecular, cellular and organic systems. In this minireview, we explore the complexity of PD and propose a systems‐based approach, organizing the available information around cellular disease hallmarks. We encourage our peers to adopt this cell‐based view with the aim of improving communication in interdisciplinary research endeavors targeting the molecular events, modulatory cell‐to‐cell signaling pathways and emerging clinical phenotypes related to PD .
One night of total sleep deprivation promotes a state of generalized hyperalgesia: A surrogate pain model to study the relationship of insomnia and pain
2013-05-11

Sleep disturbances are highly prevalent in chronic pain patients. Understanding their relationship has become an important research topic since poor sleep and pain are assumed to closely interact. To date, human experimental studies exploring the impact of sleep disruption/deprivation on pain perception have yielded conflicting results. This inconsistency may be due to the large heterogeneity of study populations and study protocols previously used. In addition, none of the previous studies investigated the entire spectrum of nociceptive modalities. To address these shortcomings, a standardized comprehensive quantitative sensory protocol was used in order to compare the somatosensory profile of 14 healthy subjects (6 female, 8 male, 23.5 ± 4.1 year; mean ± SD) after a night of total sleep deprivation (TSD) and a night of habitual sleep in a cross-over design. One night of TSD significantly increased the level of sleepiness (P<0.001) and resulted in higher scores of the State Anxiety Inventory (P<0.01). In addition to previously reported hyperalgesia to heat (P<0.05) and blunt pressure (P<0.05), study participants developed hyperalgesia to cold (P<0.01) and increased mechanical pain sensitivity to pinprick stimuli (P<0.05) but no changes in temporal summation. Paradoxical heat sensations or dynamic mechanical allodynia were absent. TSD selectively modulated nociception, since detection thresholds of non-nociceptive modalities remained unchanged. Our findings show that a single night of TSD is able to induce generalized hyperalgesia and to increase State Anxiety scores. In the future, TSD may serve as a translational pain model to elucidate the pathomechanisms underlying the hyperalgesic effect of sleep disturbances.
International migration, remittances, and the human capital formation of Egyptian children
2013-05-11

We study the roles that migration and remittances play in the human capital formation of children in Egypt. Our estimations reveal a significant association between remittances and human capital formation: the higher the probability of receipt of remittances, the higher the probability of school enrollment, and the older the age at which children enter the labor force. Although, with regard to the likelihood of school enrollment and the age of the first participation in the labor force, the family disruption effect of migration dominates the income effect of remittances, the likelihood of labor force participation decreases even in households from which both parents migrated.
Role of the ubiquitin ligase E6AP/UBE3A in controlling levels of the synaptic protein Arc
2013-05-13

Inactivation of the ubiquitin ligase E6 associated protein (E6AP) encoded by the UBE3A gene has been associated with development of the Angelman syndrome. Recently, it was reported that in mice, loss of E6AP expression results in increased levels of the synaptic protein Arc and a concomitant impaired synaptic function, providing an explanation for some phenotypic features of Angelman syndrome patients. Accordingly, E6AP has been shown to negatively regulate activity-regulated cytoskeleton-associated protein (Arc) and it has been suggested that E6AP targets Arc for ubiquitination and degradation. In our study, we provide evidence that Arc is not a direct substrate for E6AP and binds only weakly to E6AP, if at all. Furthermore, we show that down-regulation of E6AP expression stimulates estradiol-induced transcription of the Arc gene. Thus, we propose that Arc protein levels are controlled by E6AP at the transcriptional rather than at the posttranslational level.
Preference for point-light human biological motion in newborns: Contribution of translational displacement.
2013-05-13

In human newborns, spontaneous visual preference for biological motion is reported to occur at birth, but the factors underpinning this preference are still in debate. Using a standard visual preferential looking paradigm, 4 experiments were carried out in 3-day-old human newborns to assess the influence of translational displacement on perception of human locomotion. Experiment 1 shows that human newborns prefer a point-light walker display representing human locomotion as if on a treadmill over random motion. However, no preference for biological movement is observed in Experiment 2 when both biological and random motion displays are presented with translational displacement. Experiments 3 and 4 show that newborns exhibit preference for translated biological motion (Experiment 3) and random motion (Experiment 4) displays over the same configurations moving without translation. These findings reveal that human newborns have a preference for the translational component of movement independently of the presence of biological kinematics. The outcome suggests that translation constitutes the first step in development of visual preference for biological motion.
In vivobiocompatibility and biodegradation of a novel thin and mechanically stable collagen scaffold
2013-05-13

Abstract The demand for scaffolds comprised of natural materials such as collagen has increased in recent years. However, many scaffolds rely on chemical or physical modifications in order to comply with the necessary requirements for biomedical engineering. We evaluated the in vivo biocompatibility and biodegradation of a novel, thin, mechanically stable, and chemically non‐crosslinked collagen cell carrier (CCC). CCC was implanted subcutaneously into 25 adult Lewis rats and biopsies were taken on days 7, 14, 21, 42, and 84 after surgery. For histological analysis, paraffin sections of implanted skin were immunolabeled for CD68 and stained by hematoxylin–eosin and Masson–Goldner's trichrome method. Macroscopic analysis of skin surface during wound healing process showed a normal physiological reaction. Biodegradation of CCC was completed 42 days after subcutaneous implantation. Histological evaluation revealed no evidence of encapsulation, scar formation, or long‐term vascularization and inflammation. The collagen type I based biomaterial demonstrated a high in vivo biocompatibility, low irritability, complete resorption, and replacement by autologous tissue. The in vivo biocompatibility and degradation behavior encourage for further evaluation of CCC in surgical applications and regenerative medicine. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 1173–1179, 2014.
Nb nano superconducting quantum interference devices with high spin sensitivity for operation in magnetic fields up to 0.5 T
2013-05-13

We investigate electric transport and noise properties of microstrip-type submicron direct current superconducting quantum interference devices (dc SQUIDs) based on Nb thin films and overdamped Josephson junctions with a HfTi barrier. The SQUIDs were designed for optimal spin sensitivity Sμ1/2 upon operation in intermediate magnetic fields B (tens of mT), applied perpendicular to the substrate plane. Our, so far, best SQUID can be continuously operated in fields up to B≈±50 mT with rms flux noise SΦ,w1/2≤250 nΦ0/Hz1/2 in the white noise regime and spin sensitivity Sμ1/2≤29 μB/Hz1/2. Furthermore, we demonstrate operation in B = 0.5 T with high sensitivity in flux SΦ,w1/2≈680 nΦ0/Hz1/2 and in electron spin Sμ1/2≈79 μB/Hz1/2. We discuss strategies to further improve the nanoSQUID performance.
The reliability of approximate radiation transport methods for irradiated disk studies
2013-05-13

\\n Context. Dynamical studies of irradiated circumstellar disks require an\\n accurate treatment of radiation transport to, for example, properly determine cooling and\\n fragmentation properties. At the same time the radiation transport algorithm should be as\\n fast as the (magneto-) hydrodynamics to allow for an efficient usage of computing\\n resources. Such fast radiation transport methods imply the acceptance of far-reaching\\n approximations. \\n Aims. We check the reliability of fast, approximate radiation transport\\n methods for circumstellar disk studies by comparing their accuracy to previous standard\\n radiation benchmark test results. \\n Methods. We use different approximate radiation transport methods and\\n compute the equilibrium temperature distribution in a setup of a central star and a\\n slightly flared circumstellar disk, which is embedded in an optically thin envelope. We\\n perform simulations for a wide range of optical depths of the disk’s midplane from\\n τ550 nm = 0.1 up to\\n τ810 nm = 1.22 × 10+6. We check the accuracy of\\n the gray flux-limited diffusion (FLD) approximation and the gray and frequency-dependent\\n hybrid approximation. In the hybrid method, the stellar irradiation is computed via a gray\\n or frequency-dependent ray-tracing (RT) step and the thermal (re-)emission by dust grains\\n is shifted to a gray FLD solver. \\n Results. 1. For moderate optical depths, a gray approximation of the\\n stellar irradiation yields a slightly hotter inner rim and a slightly cooler midplane of\\n the disk at larger radii, but is otherwise in agreement with the frequency-dependent\\n treatment. 2. The gray FLD approximation fails to compute an appropriate temperature\\n profile in all regimes of optical depth; the maximum deviations to the comparison runs are\\n 50% in the optically thin and up to 280% in the optically thick limit. For low optical\\n depth, the isotropic assumption within the FLD method yields a too steep decrease of the\\n radial temperature slope. For higher optical depths, the FLD approximation does not\\n reproduce the shadow behind the optically thick inner rim of the circumstellar disk,\\n yielding artificial heating at larger disk radii. 3. The frequency-dependent RT + gray FLD\\n approximation yields remarkable accuracy for the whole range of optical depths. \\n Conclusions. The high accuracy of the frequency-dependent hybrid\\n radiation transport algorithm makes this method ideally suited for (magneto-)\\n hydrodynamical studies of irradiated circumstellar disks. \\n
Model Complexity Needed for Quantitative Analysis of High Resolution Isotope and Concentration Data from a Toluene-Pulse Experiment
2013-05-13

Separating microbial- and physical-induced effects on the isotope signals of contaminants has been identified as a challenge in interpreting compound-specific isotope data. In contrast to simple analytical tools, such as the Rayleigh equation, reactive-transport models can account for complex interactions of different fractionating processes. The question arises how complex such models must be to reproduce the data while the model parameters remain identifiable. In this study, we reanalyze the high-resolution data set of toluene concentration and toluene-specific δ(13)C from the toluene-pulse experiment performed by Qiu et al. (this issue). We apply five reactive-transport models, differing in their degree of complexity. We uniquely quantify degradation and sorption properties of the system for each model, estimate the contributions of biodegradation-induced, sorption-induced, and transverse-dispersion-induced isotope fractionation to the overall isotope signal, and investigate the error introduced in the interpretation of the data when individual processes are neglected. Our results show that highly resolved data of both concentration and isotope ratios are needed for unique process identification facilitating reliable model calibration. Combined analysis of these highly resolved data demands reactive transport models accounting for nonlinear degradation kinetics and isotope fractionation by both reactive and physical processes such as sorption and transverse dispersion.
The benefit of using CT-perfusion imaging for reliable response monitoring in patients with gastrointestinal stromal tumor (GIST) undergoing treatment with novel targeted agents
2013-05-13

Solely size-based response criteria may be unreliable in patients with gastrointestinal stromal tumors (GIST) treated with tyrosine kinase inhibitors, because they typically underestimate responses to treatment. As GISTs are generally hypervascularized and novel targeted drugs knowingly affect angiogenic signaling pathways, perfusion measurements are expected to deliver important information about their efficacy. This pictorial essay illustrates the benefit of using complementary CT-perfusion-based measurements for more accurate evaluation of response to therapy in GIST.
Reply to Honjo et al.: Functional relevant expression of Toso on granulocytes
2013-05-13

Functional relevant expression of Toso on granulocytes. (A) Toso expression. Splenocytes from WT and Toso−/− mice were immunostained with anti-CD19 (B cells) and anti-Gr1 (granulocytes) antibody in combination with DAPI and anti-Toso antibody after pretreatment with Fc receptor block. One representative staining of cells gated on Gr1hi DAPI− cells (Left) or CD19+ DAPI− cells is shown (Right). (B) Quantification of FACS stainings derived from A (n = 4/group). (C–E) WT recipient mice were irradiated and reconstituted with BM from WT mice (CD45.1; group 1), Toso−/− mice (CD45.2; group 2), or a 1:1 mixture of WT and Toso−/− BM (group 3). At 30 d posttransplantation, peripheral blood cells were stimulated with different concentrations of fMLP (Formyl-Methionyl-Leucyl-Phenylalanine) and granulocytes (Gr1+ cells) were analyzed after 30 min for CD45.1 expression (anti-CD45.1), CD45.2 expression (anti-CD45.2), reactive oxygen species production (dihydrorhodamine staining), and degranulation (side scatter). Representative FACS ...
The heterogeneous costs of disclosure and the propensity to patent
2013-05-13

This article explores whether the heterogeneous costs of disclosure induced by patenting can serve as an explanation for the empirically observed heterogeneity of the propensity to patent across firms. A theoretical model identifies the interplay between market entry barriers and the usefulness of the information disclosed through patenting for competitors as a crucial factor driving the extent of disclosure costs that a patenting firm faces. High costs of disclosure may outweigh the merits of patenting, leading innovators to rely on alternative protection strategies, such as secrecy. An empirical investigation using the German part of the CIS data provides evidence for these theoretical predictions. Copyright 2013 Oxford University Press 2013 All rights reserved, Oxford University Press.
Optimal caliper placement: manual vs automated methods
2013-05-13

ABSTRACT Objective To examine the inter‐ and intraoperator repeatability of manual placement of calipers in the assessment of basic fetal biometric measurements and to compare the results with those of an automated caliper placement system . Methods We used stored ultrasound images of 95 normal fetuses between 19 and 25 weeks' gestation. Five operators (two experts, one resident and two students) were asked to measure the biparietal diameter ( BPD ), occiptofrontal diameter ( OFD ), abdominal circumference ( AC ) and femur length ( FL ) twice manually and twice automatically. For each operator, the repeatability of manual and automated measurements was assessed using intraoperator SD . For the assessment of interoperator repeatability, the mean of the four manual measurements by the two experts for each fetus was used as the gold standard. The relative bias of the manual measurements of the three non‐expert operators and the operator‐independent automated measurement were compared with the gold standard measurement by mean and 95% CI . Results In 89.5% of the 95 cases, the automated measurement algorithm was able to obtain appropriate measurements of BPD , OFD , AC and FL . Intraoperator SDs for the manual measurements ranged between 0.15 and 1.56, irrespective of the experience of the operator. For the automated biometric measurement system, there was no difference between the measurements of each operator. Regarding interoperator repeatability, the mean difference between the manual measurements of the two students, the resident and the gold standard was between −0.10 and 2.53 mm. The automated measurements tended to be closer to the gold standard, but the difference in bias in automated vs manual measurements did not reach statistical significance . Conclusion In about 90% of cases, it was possible to obtain basic biometric measurements with an automated system. The use of automated measurements resulted in a significant improvement in intraoperator repeatability, but measurements were not significantly closer to the gold standard of expert examiners. Copyright © 2013 ISUOG. Published by John Wiley &amp; Sons Ltd .
Direct Experimental Evidence of Non-first Order Degradation Kinetics and Sorption-Induced Isotopic Fractionation in a Mesoscale Aquifer: 13C/12C Analysis of a Transient Toluene Pulse
2013-05-13

The injection of a mixed toluene and D2O (conservative tracer) pulse into a pristine mesoscale aquifer enabled a first direct experimental comparison of contaminant-specific isotopic fractionation from sorption versus biodegradation and transverse dispersion on a relevant scale. Water samples were taken from two vertically resolved sampling ports at 4.2 m distance. Analysis of deuterium and toluene concentrations allowed quantifying the extent of sorption (R = 1.25) and biodegradation (37% and 44% of initial toluene at the two sampling ports). Sorption and biodegradation were found to directly affect toluene (13)C/(12)C breakthrough curves. In particular, isotope trends demonstrated that biodegradation underwent Michaelis-Menten kinetics rather than first-order kinetics. Carbon isotope enrichment factors obtained from an optimized reactive transport model (Eckert et al., this issue) including a possible isotope fractionation of transverse dispersion were ε(equ)(sorption) = -0.31 ‰, ε(kin)(transverse-dispersion) = -0.82 ‰, and ε(kin)(biodegradation) = -2.15 ‰. Extrapolation of our results to the scenario of a continuous injection predicted that (i) the bias in isotope fractionation from sorption, but not transverse dispersion, may be avoided when the plume reaches steady-state; and (ii) the relevance from both processes is expected to decrease at longer flow distances when isotope fractionation of degradation increasingly dominates.
Anti-Vascular endothelial growth factor therapy impairs endothelial function of retinal microcirculation in colon cancer patients – an observational study
2013-05-13

Abstract Background To assess acute effects of bevacizumab (anti-VEGF therapy) on cerebral microvessels and systemic cardiovascular regulation. Design and subjects 20 consecutive patients with colorectal cancer (median age: 60.4 years, range 45.5-73.9 years) received bevacizumab intravenously (5 mg/kg) uncoupled of chemotherapy. Prior to and within the first 24 hours after bevacizumab infusion, patients were investigated for retinal endothelial function. A series of a triple 24-hour ambulatory blood pressure measurement was conducted. Retinal endothelial function was determined as flicker light-induced vasodilation. The integrity of baroreflex arc and autonomic cardiovascular control was examined by stimulatory manoeuvres. Results Bevacizumab therapy significantly reduced the vasodilatory capacity of retinal arterioles in response to flicker light. A slight decrease in diastolic pressure and heart rate was observed after bevacizumab infusion but this was unrelated to changes in retinal function. The pressure response upon nitroglycerin was largely preserved after bevacizumab infusion. The proportion of patients with abnormal nocturnal blood pressure regulation increased under anti-angiogenic therapy. Autonomic blood pressure control was not affected by bevacizumab treatment. Conclusions Bevacizumab acutely impairs microvascular function independent of blood pressure changes. Imaging of the retinal microcirculation seems a valuable tool for monitoring pharmacodynamic effects of bevacizumab. Trial registration NCT ID: NCT00740168
cyp51A -Based Mechanisms of Aspergillus fumigatus Azole Drug Resistance Present in Clinical Samples from Germany
2013-05-14

ABSTRACT Since the mid-1990s, a steady increase in the occurrence of itraconazole-resistant Aspergillus fumigatus isolates has been observed in clinical contexts, leading to therapeutic failure in the treatment of aspergillosis. This increase has been predominantly linked to a single allele of the cyp51A gene, termed TR/L98H, which is thought to have arisen through the use of agricultural azoles. Here, we investigated the current epidemiology of triazole-resistant A. fumigatus and underlying cyp51A mutations in clinical samples in Germany. From a total of 527 samples, 17 (3.2%) showed elevated MIC 0 values (the lowest concentrations with no visible growth) for at least one of the three substances (itraconazole, voriconazole, and posaconazole) tested. The highest prevalence of resistant isolates was observed in cystic fibrosis patients (5.2%). Among resistant isolates, the TR/L98H mutation in cyp51A was the most prevalent, but isolates with the G54W and M220I substitutions and the novel F219C substitution were also found. The isolate with the G54W substitution was highly resistant to both itraconazole and posaconazole, while all others showed high-level resistance only to itraconazole. For the remaining six isolates, no mutations in cyp51A were found, indicating the presence of other mechanisms. With the exception of the strains carrying the F219C and M220I substitutions, many itraconazole-resistant strains also showed cross-resistance to voriconazole and posaconazole with moderately increased MIC 0 values. In conclusion, the prevalence of azole-resistant A. fumigatus in our clinical test set is lower than that previously reported for other countries. Although the TR/L98H mutation frequently occurs among triazole-resistant strains in Germany, it is not the only resistance mechanism present.