Miracle-dz/UniFAR-FTUs huggingface dataset:
Transgenic Activation of Ras in Neurons Promotes Hypertrophy and Protects from Lesion-Induced Degeneration

Ras is a universal eukaryotic intracellular protein integrating extracellular signals from multiple receptor types. To investigate its role in the adult central nervous system, constitutively activated V12-Ha-Ras was expressed selectively in neurons of transgenic mice via a synapsin promoter. Ras-transgene protein expression increased postnatally, reaching a four- to fivefold elevation at day 40 and persisting at this level, thereafter. Neuronal Ras was constitutively active and a corresponding activating phosphorylation of mitogen-activated kinase was observed, but there were no changes in the activity of phosphoinositide 3-kinase, the phosphorylation of its target kinase Akt/PKB, or expression of the anti-apoptotic proteins Bcl-2 or Bcl-XL. Neuronal Ras activation did not alter the total number of neurons, but induced cell soma hypertrophy, which resulted in a 14.5% increase of total brain volume. Choline acetyltransferase and tyrosine hydroxylase activities were increased, as well as neuropeptide Y expression. Degeneration of motorneurons was completely prevented after facial nerve lesion in Ras-transgenic mice. Furthermore, neurotoxin-induced degeneration of dopaminergic substantia nigra neurons and their striatal projections was greatly attenuated. Thus, the Ras signaling pathway mimics neurotrophic effects and triggers neuroprotective mechanisms in adult mice. Neuronal Ras activation might become a tool to stabilize donor neurons for neural transplantation and to protect neuronal populations in neurodegenerative diseases.
Characterisation of the creep-fatigue behaviour of a 1CrMoV turbine steel

Abstract This paper concerns the creep-fatigue lifetime assessment of a 1CrMoV steel. A procedure based on the calculation of fatigue and creep damage fractions and their summation according to a non-linear interaction rule is applied for the endurance evaluation of isothermal fatigue and service-like thermo-mechanical fatigue tests performed with plain (uniaxial) and notched testpieces. In order to avoid the uncertainties associated with heat-to-heat variability, testpieces were manufactured from a single heat, for which the fatigue and creep deformation/endurance properties were specifically characterised. With the availability of a reliable constitutive model, finite element calculations could be used to determine the local stress-strain response at the position of crack initiation in each test. The predictive capabilities of the proposed approach for lifetime calculation as well as the suitability of uniaxial fatigue and creep data for the damage assessment of notched components are evaluated.
The Synergistic Enhancing-Memory Effect of Donepezil and S 38093 (a Histamine H3 Antagonist) Is Mediated by Increased Neural Activity in the Septo-hippocampal Circuitry in Middle-Aged Mice

Donepezil, an acetylcholinesterase inhibitor, induces only moderate symptomatic effects on memory in Alzheimer’s disease patients. An alternative strategy for treatment of cognitive symptoms could be to act simultaneously on both histaminergic and cholinergic pathways, to create a synergistic effect. To that aim, 14 month old C57/Bl6 mice were administered per oesophagy during nine consecutive days with Donepezil (at 0.1 and 0.3 mg/kg) and S 38093 (at 0.1, 0.3, and 1.0 mg/kg), a H3 histaminergic antagonist developed by Servier, alone or in combination and tested for memory in a contextual memory task that modelized the age-induced memory dysfunction. The present study shows that the combination of Donepezil and S 38093 induced a dose-dependent synergistic memory-enhancing effect in middle-aged mice with a statistically higher size of effect never obtained with compounds alone and without any pharmacokinetic interaction between both compounds. We demonstrated that the memory-enhancing effect of the S 38093 and Donepezil combination is mediated by its action on the septo-hippocampal circuitry, since it canceled out the reduction of CREB phosphorylation (pCREB) observed in these brain areas in vehicle-treated middle-aged animals. Overall, the effects of drug combinations on pCREB in the hippocampus indicate that the synergistic promnesiant effects of the combination on memory performance in middle-aged mice stem primarily from an enhancement of neural activity in the septo-hippocampal system.
On the Explanation of Factors Affecting E-Commerce Adoption

The Internet has grown at a remarkable pace since the emergence of the World Wide Web in the early 1990s. While electronic commerce (e-Commerce) has become an important issue with the growth of the Internet, there has been insufficient empirical research concerning its adoption by Internet users. In this paper, we propose the e-Commerce Adoption Model (e-CAM), which attempts to examine important factors that predict a consumer’s online purchasing behavior. e-CAM integrates the technology acceptance model with the theories of perceived risk to explain the adoption of e-Commerce. Specifically, we examine the impact of the following factors on the consumer’s purchasing behavior: perceived ease of use, perceived usefulness, perceived risk with products/services, and perceived risk in the context of online transaction. We test the e-CAM model using the structural equation modeling technique. Most of the causal relationships between the constructs postulated by our model are well supported, accounting for 33.4% of the total variance in e-Commerce adoption. In sum, our study finds that all of the antecedent constructs directly and/or indirectly affect the consumer’s adoption of e-Commerce. Therefore, the findings suggest that firms providing products/services through eCommerce should consider these contextual factors in order to facilitate consumers’ adoption behavior.
Letters-31 jan 1998

Editor—Last year Ismail and Carnall highlighted the positive attitude of the British in bringing racism in the NHS to worldwide attention. Similar coverage by Deutsches Ärzteblatt, the medical and political organ of the Bundesärztekammer (the German medical association) in Germany, would be unthinkable. Such discussions on race issues would be embarrassing. I was a target of racial abuse from an overbearing consultant in a hospital in Nordrhein-Westphalia for about two years. He was fully supported by the hospital authorities; I was simply a non-white British citizen blowing a whistle. Hounded and harassed, I approached the Marburger Bund (the hospital doctors’ trade union), of which I was a member; it is the largest association of doctors in Germany. I was told that although I was legally in the right in my attempts to get my fair share of private patients and medical insurance fees, it could not help me. Apparently it did not deal with racism problems. As a member of the BMA, I referred my case to its international department for representation at the Standing Committee of European Doctors in Brussels. I explained the rejection by the Marburger Bund, but it was six months before the BMA replied decisively, in November 1995. It confirmed that the BMA’s legal department was unable to help because “the Marburger Bund would be the appropriate body to do so. ” And so I had to accept that the Marburger Bund is unable to seek redress for racial abuse and legally is not bound by its constitution to proceed to civil cases. I find it a moral scandal that I was ignored by the Marburger Bund and that the BMA’s international department was unable to act. I wonder how the associations’s legal department would respond to complaints of racism in the NHS by a non-white doctor from another country in the European Union—that would, hypothetically, be a similar case to mine. “Equality strategies” in the European Union must be rethought. These become a farce when the union itself does not have antidiscriminatory laws because some hegemonic states do not like them. Britain and Germany should identify ethnicity first; not everything in life is based on race, the criterion on which the BMA and the Marburger Bund betrayed me as their member and as a British/European Union citizen.
A Discontinuous Galerkin Method for Multiphysics Welding Simulations

This paper describes the development of a multiphysics welding simulation model based on the discontinuous Galerkin (DG) finite-element method. Our numerical model implements a classical enthalpy-porosity constitutive law accounting for hydrodynamic and thermal effects occurring during the phase transition from solid to liquid metal. The objective of the study is to present the verification of our numerical framework and explore the applicability of the DG formulation to the simulation of welding processes. Three computational examples of increasing complexity are presented.
Quantitative and qualitative profiles of circulating monocytes may help identifying tuberculosis infection and disease stages

Tuberculosis (TB) is one of the most important cause of morbidity and death among infectious diseases, and continuous efforts are needed to improve diagnostic tools and therapy. Previous published studies showed that the absolute cells number of monocytes or lymphocytes in peripheral blood or yet the ratio of monocytes to lymphocytes displayed the ability to predict the risk of active TB. In the present study we evaluated the ratio of monocytes to lymphocytes variation and we also analyzed the ex-vivo expression of CD64 on monocytes as tools to identify biomarkers for discriminating TB stages. Significant differences were found when the average ratio of monocytes to lymphocytes of active TB patients was compared with latent TB infection (LTBI) subjects, cured TB and healthy donors (HD). By the receiver operator characteristics (ROC) curve analysis the cut-off value of 0.285, allowed the discrimination of active TB from HD, with a sensitivity of 91.04% and a specificity of 93.55% (95% of confidence interval: 0.92–0.99). The ROC curve analysis comparing TB patients and LTBI groups, led to a sensitivity and the specificity of the assay of 85.07% and 85.71%, respectively (95% of confidence interval: 0.85 to 0.96). The upregulation of CD64 expression on circulating monocytes in active TB patients could represent an additional biomarker for diagnosis of active TB. In conclusion, we found that the ML ratio or monocyte absolute count or phenotypic measures show predictive value for active TB.
Determinants of Visceral Leishmaniasis: A Case-Control Study in Gedaref State, Sudan

Background Improving knowledge on local determinants of visceral leishmaniasis (VL) is crucial to guide the development of relevant control strategies. This study aimed to identify individual and household level determinants of primary VL in 24 highly endemic villages of Tabarak Allah hospital’s catchment area, Gedaref State, Sudan. Methods From September 2012 to July 2013, in an unmatched case-control design, 198 patients with primary VL were compared to 801 controls free of VL symptoms and with a negative VL rapid test. Using random spatial sampling, controls were selected with a distribution of age, sex and village of residence proportionate to the distribution of the target population. Data were collected using a structured questionnaire. Results Children and men were at higher risk of VL. Reporting VL patient(s) in the household in the previous year was the strongest VL risk factor. In a multivariate analysis, VL risk increased with household size, sleep location (outside the yard, not in the farm), evening outdoor activities in the rainy season (playing, watching TV, radio listening), use of ground nut oil as animal repellent and of smoke of Acacia seyal as indoor repellent, presence of dogs in the yard at night, Acacia nilotica in the yard’s immediate surroundings and of a forest at eye range. VL risk appeared to decrease with the use of drinking water sources other than the village water tank, a buffer distance from the adjacent house yard, and with the presence of animals other than dogs in the yard at night. In contrast with previous studies, housing factors, mosquito-net use, black cotton soil, ethnicity, socioeconomic index, presence of Balanites aegyptica and Azadirachta indica in the yard were not independent VL determinants. Discussion and conclusion Although these results do not provide evidence of causality, they provide useful suggestions for guiding further intervention studies on VL preventive measures.
Transient expression of human TorsinA enhances secretion of two functionally distinct proteins in cultured Chinese hamster ovary (CHO) cells

Cultured mammalian cells, particularly Chinese hamster ovary (CHO) cells, are widely exploited as hosts for the production of recombinant proteins, but often yields are limiting. Such limitations may be due in part to the misfolding and subsequent degradation of the heterologous proteins. Consequently we have determined whether transiently co‐expressing yeast and/or mammalian chaperones that act to disaggregate proteins, in CHO cell lines, improve the levels of either a cytoplasmic (Fluc) or secreted (Gluc) form of luciferase or an immunoglobulin IgG4 molecule. Over‐expression of the yeast ‘protein disaggregase’ Hsp104 in a CHO cell line increased the levels of Fluc more significantly than for Gluc although levels were not further elevated by over‐expression of the yeast or mammalian Hsp70/40 chaperones. Over‐expression of TorsinA, a mammalian protein related in sequence to yeast Hsp104, but located in the ER, significantly increased the level of secreted Gluc from CHO cells by 2.5‐fold and to a lesser extent the secreted levels of a recombinant IgG4 molecule. These observations indicate that the over‐expression of yeast Hsp104 in mammalian cells can improve recombinant protein yield and that over‐expression of TorsinA in the ER can promote secretion of heterologous proteins from mammalian cells. Biotechnol. Bioeng. 2010; 105: 556–566. © 2009 Wiley Periodicals, Inc.
Childhood Adversities Are Associated with Shorter Telomere Length at Adult Age both in Individuals with an Anxiety Disorder and Controls

Accelerated leukocyte telomere shortening has been previously associated to self-perceived stress and psychiatric disorders, including schizophrenia and mood disorders. We set out to investigate whether telomere length is affected in patients with anxiety disorders in which stress is a known risk factor. We also studied the effects of childhood and recent psychological distress on telomere length. We utilized samples from the nationally representative population-based Health 2000 Survey that was carried out between 2000–2001 in Finland to assess major public health problems and their determinants. We measured the relative telomere length of the peripheral blood cells by quantitative real-time PCR from 321 individuals with DSM-IV anxiety disorder or subthreshold diagnosis and 653 matched controls aged 30–87 years, who all had undergone the Composite International Diagnostic Interview. While telomere length did not differ significantly between cases and controls in the entire cohort, the older half of the anxiety disorder patients (48–87 years) exhibited significantly shorter telomeres than healthy controls of the same age (P = 0.013). Interestingly, shorter telomere length was also associated with a greater number of reported childhood adverse life events, among both the anxiety disorder cases and controls (P = 0.005). Childhood chronic or serious illness was the most significantly associated single event affecting telomere length at the adult age (P = 0.004). Self-reported current psychological distress did not affect telomere length. Our results suggest that childhood stress might lead to accelerated telomere shortening seen at the adult age. This finding has potentially important implications supporting the view that childhood adversities might have a considerable impact on well being later in life.
Influence of meteorology and anthropogenic pollution on chemical flux divergence of the NO–NO2–O3 triad above and within a natural grassland canopy

Abstract. The detailed understanding of surface–atmosphere exchange fluxes of reactive trace gases is a crucial precondition for reliable modelling of processes in atmospheric chemistry. Plant canopies significantly impact the atmospheric budget of trace gases. In the past, many studies focused on taller forest canopies or crops, where the bulk plant material is concentrated in the uppermost canopy layer. However, within grasslands, a land-cover class that globally covers vast terrestrial areas, the canopy structure is fundamentally different, as the main biomass is concentrated in the lowest part of the canopy. This has obvious implications for aerodynamic in-canopy transport, and consequently also impacts on global budgets of key species in atmospheric chemistry such as nitric oxide (NO), nitrogen dioxide (NO2) and ozone (O3). This study presents for the first time a comprehensive data set of directly measured in-canopy transport times and aerodynamic resistances, chemical timescales, Damkohler numbers, trace gas and micrometeorological measurements for a natural grassland canopy (canopy height = 0.6 m). Special attention is paid to the impact of contrasting meteorological and air chemical conditions on in-canopy transport and chemical flux divergence. Our results show that the grassland canopy is decoupled throughout the day. In the lowermost canopy layer, the measured transport times are fastest during nighttime, which is due to convection during nighttime and a stable stratification during daytime in this layer. The inverse was found in the layers above. During periods of low wind speed and high NOx (NO+NO2) levels, the effect of canopy decoupling on trace gas transport was found to be especially distinct. The aerodynamic resistance in the lowermost canopy layer (0.04–0.2 m) was around 1000 s m−1, which is as high as values determined previously for the lowest metre of an Amazonian rain forest canopy. The aerodynamic resistance representing the bulk canopy was found to be more than 3–4 times higher than in forests. Calculated Damkohler numbers (ratio of transport and chemical timescales) suggest a strong flux divergence for the NO–NO2–O3 triad within the canopy during daytime. During that time, the timescale of NO2 uptake by plants ranged from 90 to 160 s and was the fastest relevant timescale, i.e. faster than the reaction of NO and O3. Thus, our results reveal that grassland canopies of similar structure exhibit a strong potential to retain soil-emitted NO due to oxidation and subsequent uptake of NO2 by plants. Furthermore, photo-chemical O3 production was observed above the canopy, which was attributed to a deviation from the NO–NO2–O3 photostationary state by a surplus of NO2 due to oxidation of NO, by e.g. peroxy radicals. The O3 production was one order of magnitude higher during high NOx than during low NOx periods and resulted in an underestimation of the O3 deposition flux measured with the EC method.
Association of previous injury and speed with running style and stride‐to‐stride fluctuations

Running‐related injuries remain problematic among recreational runners. We evaluated the association between having sustained a recent running‐related injury and speed, and the strike index (a measure of footstrike pattern, SI) and spatiotemporal parameters of running. Forty‐four previously injured and 46 previously uninjured runners underwent treadmill running at 80%, 90%, 100%, 110%, and 120% of their preferred running speed. Participants wore a pressure insole device to measure SI, temporal parameters, and stride length (Slength) and stride frequency (Sfrequency) over 2‐min intervals. Coefficient of variation and detrended fluctuation analysis provided information on stride‐to‐stride variability and correlative patterns. Linear mixed models were used to compare differences between groups and changes with speed. Previously injured runners displayed significantly higher stride‐to‐stride correlations of SI than controls (P = 0.046). As speed increased, SI, contact time (Tcontact), stride time (Tstride), and duty factor (DF) decreased (P < 0.001), whereas flight time (Tflight), Slength, and Sfrequency increased (P < 0.001). Stride‐to‐stride variability decreased significantly for SI, Tcontact, Tflight, and DF (P ≤ 0.005), as did correlative patterns for Tcontact, Tstride, DF, Slength, and Sfrequency (P ≤ 0.044). Previous running‐related injury was associated with less stride‐to‐stride randomness of footstrike pattern. Overall, runners became more pronounced rearfoot strikers as running speed increased.
Zoledronic acid and survival in breast cancer patients with bone metastases and elevated markers of osteoclast activity.

OBJECTIVE Most breast cancer patients with bone metastases will receive bisphosphonate treatment. This post hoc analysis investigated whether early normalization of urinary N-telopeptide of type I collagen (NTX) levels during bisphosphonate therapy correlates with a long-term reduction in skeletal-related event (SRE) risk and mortality in patients with breast cancer. METHODS This was a retrospective subset analysis of a phase III randomized trial comparing i.v. zoledronic acid with pamidronate treatment in patients with bone metastases from breast cancer or multiple myeloma. Patients with breast cancer who had NTX assessments at baseline and at months 1 and 3 (n = 342) were classified as normal (NTX < 64 nmol/mmol creatinine) or elevated (NTX > or = 64 nmol/mmol creatinine). The relative risk for an SRE or death was estimated with Cox regression models. RESULTS Among the 328 evaluable patients treated with zoledronic acid, 196 patients (59.7%) had elevated baseline NTX, with 149 of those patients (76.0%) having normalized NTX levels and 31 patients (15.8%) having persistently elevated NTX levels at 3 months. The normalized NTX group had significantly lower risks for a first SRE, a first fracture or surgery to bone, or death than the group that had persistently elevated NTX levels. CONCLUSIONS These results suggest that early normalization of elevated baseline NTX while receiving zoledronic acid is associated with longer event-free and overall survival times compared with persistently elevated NTX. Further analyses in cancer patients with elevated marker levels are warranted to confirm the implications of these findings.
Nanotexturing of poly(dimethylsiloxane) in plasmas for creating robust super-hydrophobic surfaces

A rapid, easy-to-implement, and potentially large-scale production method for fabricating high-aspect-ratio columnar-like nanostructures on poly(dimethylsiloxane) (PDMS) is demonstrated. Plasma treatment of PDMS under appropriate conditions in SF6 gas, followed by plasma-induced fluorocarbon film deposition, results in PDMS surfaces of fully controlled wetting properties, geometrical characteristics leading to robust superhydrophobic surfaces, and transparency. Potential applications to microfluidic devices are outlined.
IEEE 802.11 distributed coordination function (DCF): analysis and enhancement

Being a part of IEEE project 802, the 802.11 medium access control (MAC) is used to support asynchronous and time bounded delivery of radio data packets. It is proposed that a distributed coordination function (DCF), which uses carrier sense multiple access with collision avoidance (CSMA/CA) and binary slotted exponential backoff, be the basis of the IEEE 802.11 WLAN MAC protocols. This paper proposes a throughput enhancement mechanism for DCF by adjusting the contention window (CW) resetting scheme. Moreover, an analytical model based on Markov chain is introduced to compute the enhanced throughput of 802.11 DCF. The accuracy of the model and the enhancement of the proposed scheme are verified by elaborate simulations.