Miracle-dz/UniFAR-FTUs huggingface dataset:
Asymptomatic reactivation of JC virus in patients treated with natalizumab.

n engl j med 361;25 nejm.org december 17, 2009 2487 nificant, but the clinical meaning would not be obvious. We disagree that hazard ratios can be misleading for clinicians if such ratios are interpreted properly as an average effect across the entire study period and population.1 Medians and rates can be more misleading, since these measures are a “snapshot” at one point in a study. We agree with Takano that crossover to the comparator treatment would be expected in the first-line setting and that such crossover can confound analysis of overall survival. That is why progression-free survival was our primary outcome. Similar outcomes for progression-free survival among patients with EGFR mutations have recently been reported in three other phase 3 studies comparing first-line gefitinib with doublet chemotherapy.2-4 In conclusion, since the effect was different for patients with EGFR mutations and those without EGFR mutations, our overall results should be interpreted as a combination from two very different subgroups. Tony S. Mok, M.D.
An Adaptive Framework for Improving Quality of Service in Industrial Systems

Limited memory bandwidth is considered as the major bottleneck in multimedia cloud computing for more and more virtual machines (VMs) of multimedia processing requiring high memory bandwidth simultaneously. Moreover, contending memory bandwidth among parallel running VMs leads to poor quality of service (QoS) of the multimedia applications, missing the deadlines of these soft real-time multimedia applications. In this paper, we present an adaptive framework, Service Maximization Optimization (SMO), which is designed to improve the QoS of the soft real-time multimedia applications in multimedia cloud computing. The framework consists of an automatic detection mechanism and an adaptive memory bandwidth control mechanism. With the automatic detection mechanism, the critical section to the multimedia application performance in the VMs is detected. Then, our adaptive memory bandwidth control mechanism adjusts the memory access rates of all the parallel running VMs to protect the QoS of the soft real-time multimedia applications. From the case studies with real-world multimedia applications, our SMO significantly improves the QoS of the soft real-time multimedia applications with a negligible penalty on system throughput.
ERK regulates strain‐induced migration and proliferation from different subcellular locations

Repetitive deformation like that engendered by peristalsis or villous motility stimulates intestinal epithelial proliferation on collagenous substrates and motility across fibronectin, each requiring ERK. We hypothesized that ERK acts differently at different intracellular sites. We stably transfected Caco‐2 cells with ERK decoy expression vectors that permit ERK activation but interfere with its downstream signaling. Targeting sequences constrained the decoy inside or outside the nucleus. We assayed proliferation by cell counting and migration by circular wound closure with or without 10% repetitive deformation at 10 cycles/min. Confocal microscopy confirmed localization of the fusion proteins. Inhibition of phosphorylation of cytoplasmic RSK or nuclear Elk confirmed functionality. Both the nuclear‐localized and cytosolic‐localized ERK decoys prevented deformation‐induced proliferation on collagen. Deformation‐induced migration on fibronectin was prevented by constraining the decoy in the nucleus but not in the cytosol. Like the nuclear‐localized ERK decoy, a Sef‐overexpressing adenovirus that sequesters ERK in the cytoplasm also blocked the motogenic and mitogenic effects of strain. Inhibiting RSK or reducing Elk ablated both the mitogenic and motogenic effects of strain. RSK isoform reduction revealed isoform specificity. These results suggest that ERK must translocate to the nucleus to stimulate cell motility while ERK must act in both the cytosol and the nucleus to stimulate proliferation in response to strain. Selectively targeting ERK within different subcellular compartments may modulate or replace physical force effects on the intestinal mucosa to maintain the intestinal mucosal barrier in settings when peristalsis or villous motility are altered and fibronectin is deposited into injured tissue. J. Cell. Biochem. 109: 711–725, 2010. Published in 2010 Wiley‐Liss, Inc.
Spatial translational motions of base pairs in DNA molecules: Application of the extended matrix generator method

We have used the elementary generator matrices outlined in the preceding paper to examine the conformational plasticity of the nucleic acid double helix. Here we investigate kinked DNA structures made up of alternating B‐ and A‐type helices and intrinsically curved duplexes perturbed by the intercalation of ligands. We model the B‐to‐A transition by the lateral translation of adjacent base pairs, and the intercalation of ligands by the vertical displacement of neighboring residues. We report a complete set of average configuration‐dependent parameters, ranging from scalars (i.e., persistence lengths) to first‐ and second‐order tensor parameters (i.e., average second moments of inertia), as well as approximations of the associated spatial distributions of the DNA and their angular correlations. The average structures of short chains (of lengths less than 100 base pairs) with local kinks or intrinsically curved sequences are essentially rigid rods. At the smallest chain lengths (10 base pairs), the kinked and curved chains exhibit similar average properties, although they are structurally perturbed compared to the standard B‐DNA duplex. In contrast, at lengths of 200 base pairs, the curved and kinked chains are more compact on average and are located in a different space from the standard B‐ or A‐DNA helix. While A‐DNA is shorter and thicker than B‐DNA in x‐ray models, the long flexible A‐DNA helix is thinner and more extended on average than its B‐DNA counterpart because of more limited fluctuations in local structure. Curved polymers of 50 base pairs or longer also show significantly greater asymmetry than other DNAs (in terms of the distribution of base pairs with respect to the center of gravity of the chain). The intercalation of drugs in the curved DNA straightens and extends the smoothly deformed template. The dimensions of the average ellipsoidal boundaries defining the configurations of the intercalated polymers are roughly double those of the intrinsically curved chain. The altered proportions and orientations of these density functions reflect the changing shape and flexibility of the double helix. The calculations shed new light on the possible structural role of short A‐DNA fragments in long B‐type duplexes and also offer a model for understanding how GC‐specific intercalative ligands can straighten naturally curved DNA. The mechanism is not immediately obvious from current models of DNA curvature, which attribute the bending of the chain to a perturbed structure in repeating tracts of A · T base pairs. © 1994 John Wiley & Sons, Inc.
Trends in cardiovascular disease risk factor clustering in eastern Finland: results of 15-year follow-up of the North Karelia Project.

BACKGROUND The study describes 15-year cardiovascular disease risk factor clustering trends in eastern Finland and assesses the degree to which high levels of the risk factors are clustering in the same individuals. METHODS Four independent cross-sectional surveys in randomly selected population samples (in 1972, 1977, 1982, and 1987) have been carried out in two provinces in eastern Finland (North Karelia and Kuopio) to assess the level of cardiovascular disease risk factors and the impact of a community-based prevention program. Each survey included a self-administered questionnaire, blood pressure measurements, and determination of serum cholesterol. Blood pressure and serum cholesterol values were dichotomized. All subjects were classified as either current smokers or nonsmokers. The total sample size was 30,118 and the participation rate varied between 77 and 94%. The common age range in all four surveys was 30 to 59 years. RESULTS The proportion of individuals with a combination of two or three risk factors decreased markedly during the survey period. However, smoking tended to cluster increasingly with the other risk factors in 1987 compared with that seen in 1972. Among men, the proportion of smokers having either high blood pressure or high serum cholesterol levels, or both, is still high. CONCLUSIONS The observed clustering of cardiovascular disease risk factors, particularly among men, underlines the importance of assessing other risk factors in persons with a high level of one risk factor and the need for a multifactorial approach in primary prevention. It is possible that high-risk behaviors, like smoking and high consumption of saturated fat and salt, were normal in 1972, but in 1987 they were declining, though they remained clustered among a particular segment of the population.
Modelado de entornos mediante infrarrojos: Aplicación al guiado de robots móviles

El trabajo realizado en esta tesis consiste en la utilizacion de una emision de infrarrojos, a partir de un diodo laser, para detectar y modelar los obstaculos existentes en entornos desconocidos y cambiantes, permitiendo a robots moviles modificar su trayectoria de movimiento y alcanzar el destino sin riesgo de colision, El sistema sensorial desarrollado se basa en la emision de un haz infrarrojo, la captura de su reflexion en un detector CCD y la obtencion de distancias de los puntos del entorno mediante la tecnica de triangulacion. Las caracteristicas del sistema de captura permiten visualizar campos amplios a distancias reducidas, lo que facilita los movimientos.
Differential Affection of Intestinal Immune Cell Populations after Cerebral Ischemia in Mice

Background/Aims: Infections cause a major clinical problem within the first days after cerebral stroke. In a mouse model we have recently demonstrated that stroke leads to immunodepression facilitating spontaneous bacterial pneumonia and bacteremia. So far, it has been unknown whether poststroke immunomodulation impairs local intestinal immune populations which may promote gut barrier dysfunction leading to translocation of intestinal microorganisms and microbial products. In this study, we investigated changes in intestinal intraepithelial, lamina propria and Peyer’s patch immune cell populations after experimental stroke. Methods: 129SV mice were subjected to experimental stroke by filament occlusion of the middle cerebral artery or sham operation. After 24 h, animals were sacrificed, and intraepithelial lymphocytes, lamina propria lymphocytes and Peyer’s patches were isolated and leukocyte subpopulations analyzed by flow cytometry. Results: Peyer’s patches revealed a significant reduction of T and B cell counts after cerebral ischemia, while no differences in natural killer cells and macrophages were observed. In contrast, no significant changes in intraepithelial and lamina propria lymphocyte subsets were observed in middle cerebral artery animals compared to controls. Conclusion: Cerebral ischemia has differential effects on cellularity of gut-associated lymphoid tissue. Further studies on the mechanisms involved in quantitative changes of gut immune cells as well as on the function of these cells are needed to better understand the consequences of stroke-induced alterations of the local intestinal immune compartment for the enhanced susceptibility to infections after stroke.
Maintenance Contract With Imperfect Preventive Maintenance

In this paper, we study performance based maintenance contracts for heavy equipment operated in a mining industry. A performance based service contract uses an attractive incentives to motivate the agent to increase the maintenance effort such that the resulting equipment’s performance is well above the target. This will in turn give benefits for both the owner of the trucks and the Agent of service contract. In this paper, we study performance based maintenance service contracts for the equipment sold with warranty and the perfomances considered includes availability and safety measures. We find the optimal strategy (i.e. price of each contract and maintenance effort) for the agent and the optimal option for the owner using a non-cooperative game formulation
Investment and Dividend Policy of Oil and Gas and other Russian Companies: Financial Aspect

Abstract: In the article features of formation of investment and dividend policy of oil and gas and other the Russian companies are presented: financial aspect, existing problems are revealed and the corresponding recommendations are offered. The extensive world practice and its invaluable experience in the field of formation of effective investment and dividend policy can help to solve a number of problems to the Russian public joint-stock companies. The analysis, systematization and generalization of the theory and practice of payment of dividends by Russian joint-stock companies are carried out, forecasts are made.
Workshop Report: Governance of Emerging Nanotechnology Risks in the Semiconductor Industry

Assessment of risk in the field of nanotechnology requires an integrated multidisciplinary approach due to the complex and cross-disciplinary framework for materials and activities at the nanoscale. The present paper summarizes the workshop “Governance of emerging nano-risk in the semiconductor industry” held on April 26, 2018 in Brussels, Belgium. The event targeted representatives of stakeholder communities involved in the risk assessment and governance of the engineered nanomaterials. Nanoelectronics was selected as an impactful use case for risk assessment approaches and comparison to bottom-up nanofabrication. The workshop outlined key data gaps impeding successful assessment of risks associated with nanoparticle use in the industry, using the semiconductor industry as an example. The workshop outlined mitigation strategies informing future regulatory decisions and identified some directions for future efforts.
Photosynthesis in a Changing Global Climate: Scaling Up and Scaling Down in Crops

Photosynthesis is the major process leading to primary production in the Biosphere. There is a total of 7000bn tons of CO2 in the atmosphere and photosynthesis fixes more than 100bn tons annually. The CO2 assimilated by the photosynthetic apparatus is the basis of crop production and, therefore, of animal and human food. This has led to a renewed interest in photosynthesis as a target to increase plant production and there is now increasing evidence showing that the strategy of improving photosynthetic traits can increase plant yield. However, photosynthesis and the photosynthetic apparatus are both conditioned by environmental variables such as water availability, temperature, [CO2], salinity, and ozone. The “omics” revolution has allowed a better understanding of the genetic mechanisms regulating stress responses including the identification of genes and proteins involved in the regulation, acclimation, and adaptation of processes that impact photosynthesis. The development of novel non-destructive high-throughput phenotyping techniques has been important to monitor crop photosynthetic responses to changing environmental conditions. This wealth of data is being incorporated into new modeling algorithms to predict plant growth and development under specific environmental constraints. This review gives a multi-perspective description of the impact of changing environmental conditions on photosynthetic performance and consequently plant growth by briefly highlighting how major technological advances including omics, high-throughput photosynthetic measurements, metabolic engineering, and whole plant photosynthetic modeling have helped to improve our understanding of how the photosynthetic machinery can be modified by different abiotic stresses and thus impact crop production.
Impact of Inoculation Protocols, Salinity, and pH on the Degradation of Polycyclic Aromatic Hydrocarbons (PAHs) and Survival of PAH-Degrading Bacteria Introduced into Soil

ABSTRACT Degradation of polycyclic aromatic hydrocarbons (PAHs) and survival of bacteria in soil was investigated by applying different inoculation protocols. The soil was inoculated with Sphingomonas paucimobilis BA 2 and strain BP 9, which are able to degrade anthracene and pyrene, respectively. CFU of soil bacteria and of the introduced bacteria were monitored in native and sterilized soil at different pHs. Introduction with mineral medium inhibited PAH degradation by the autochthonous microflora and by the strains tested. After introduction with water (without increase of the pore water salinity), no inhibition of the autochthonous microflora was observed and both strains exhibited PAH degradation.
Identification and characterization of a stress‐responsive promoter in the macromolecular synthesis operon of Bacillus subtilis

Bacillus subtilis DB1005 is a temperature‐sensitive (Ts) sigA mutant. Induction of σA has been observed exclusively in this mutant harbouring extra copies of the plasmid‐borne Ts sigA gene transcriptionally controlled by the P1P2 promoters of the B. subtilis macromolecular synthesis (MMS; rpoD or sigA) operon. Investigation of the mechanisms leading to the induction has allowed us to identify a σB‐type promoter, P7, in the MMS operon for the first time. Therefore, at least seven promoters in total are responsible for the regulation of the B. subtilis MMS operon, including the four known σA‐ and σH‐type promoters, as well as two incompletely defined promoters. The P7 promoter was activated in B. subtilis after the imposition of heat, ethanol and salt stresses, indicating that the MMS operon of B. subtilis is subjected to the control of general stress. The significant heat induction of P7 in B. subtilis DB1005 harbouring a plasmid‐borne Ts sigA gene can be explained by a model of competition between σA and σB for core binding; very probably, the σB factor binds more efficiently to core RNA polymerase under heat shock. This mechanism may provide a means for the expression of the B. subtilis MMS operon when σA becomes defective in core binding.
Neural Network Approach for Fault Detection in Substations

This paper presents a fault detection algorithm for substations. The algorithm was based on neural network approach. The neural network was trained with Levenberg-Marquardt backpropagation algorithm and the training set was formed from the input-output pairs (generator currents, load currents) generated by the substation physical model which was modeled in SIMULINK® by an ideal generator, a three phase transformer and a resistive load. Then under the no-fault condition, the substation neural network model outputs were compared to the substation physical model outputs and maximum errors were computed for each phase(A,B and C). The simulation of the fault detection algorithm consisted of comparing, for each phase, the squared errors between the substation neural network model outputs and the substation physical model outputs; provided that for the fault condition, they would exceed the square of maximum errors previously computed. The simulation results show that the fault detection algorithm is valid and that it can be improved by increasing the size of the training set and by choosing the right neural network architecture.
Neuroinflammation and Oxidation/Nitration of α-Synuclein Linked to Dopaminergic Neurodegeneration

α-Synuclein (SYN) is the major component of Lewy bodies, the neuropathological hallmarks of Parkinson's disease (PD). Missense mutations and multiplications of the SYN gene cause autosomal dominant inherited PD. Thus, SYN is implicated in the pathogenesis of PD. However, the mechanism whereby SYN promotes neurodegeneration remains unclear. Familial PD with SYN gene mutations are rare because the majority of PD is sporadic and emerging evidence indicates that sporadic PD may result from genetic and environmental risk factors including neuroinflammation. Hence, we examined the relationship between SYN dysfunction and neuroinflammation in mediating dopaminergic neurodegeneration in mice and dopaminergic neuronal cultures derived from wild-type SYN and mutant A53T SYN transgenic mice in a murine SYN-null (SYNKO) background (M7KO and M83KO, respectively). Stereotaxic injection of an inflammagen, lipopolysaccharide, into substantia nigra of these SYN genetically engineered mice induced similar inflammatory reactions. In M7KO and M83KO, but not in SYNKO mice, the neuroinflammation was associated with dopaminergic neuronal death and the accumulation of insoluble aggregated SYN as cytoplasmic inclusions in nigral neurons. Nitrated/oxidized SYN was detected in these inclusions and abatement of microglia-derived nitric oxide and superoxide provided significant neuroprotection in neuron–glia cultures from M7KO mice. These data suggest that nitric oxide and superoxide released by activated microglia may be mediators that link inflammation and abnormal SYN in mechanisms of PD neurodegeneration. This study advances understanding of the role of neuroinflammation and abnormal SYN in the pathogenesis of PD and opens new avenues for the discovery of more effective therapies for PD.
Fat metabolism in exercise – with special reference to training and growth hormone administration

Despite abundance of fat, exclusive dependency on fat oxidation can only sustain a metabolic rate corresponding to 50–60% of VO2max in humans. This puzzling finding has been subject to intense research for many years. Lately, it has gained renewed interest as a consequence of increased obesity and physical inactivity imposed by Western lifestyle. Why are humans so poor at metabolizing fat? Can fat metabolism be manipulated by exercise, training, diet and hormones? And why is fat stored in specialized adipose tissue and not just as lipid droplets inside muscle cells?
Evaluation of brimonidine-timolol fixed combination in patients of primary open-angle glaucoma

The aim of present study was to compare the efficacy and safety of fixed combination of brimonidine and timolol with individual components used as monotherapy in patients of primary open angle glaucoma. Patients were randomly assigned to receive brimonidine or timolol or brimonidine-timolol fixed combination, with 30 patients in each group. The mean reduction in intraocular pressure in brimonidine, timolol, and brimonidine-timolol group were 4.29 ± 1.97 mm Hg, 4.34 ± 1.21 mm Hg, and 5.54 ± 1.87 mm Hg respectively at 2 weeks and 4.86 ± 1.16 mm Hg, 5.42 ± 1.50 mm Hg, and 7.36 ± 2.58 mm Hg respectively at 6 weeks. When values of mean reduction in intraocular pressure were compared between brimonidine-timolol fixed combination with brimonidine and timolol, it was found to be statistically significant (P < 0.05) at 2 weeks and highly significant (0.001) at 6 weeks. The overall frequency of adverse effects was similar in all three groups.
MEASLES IMMUNIZATION WITH KILLED VIRUS VACCINE. SERUM ANTIBODY TITERS AND EXPERIENCE WITH EXPOSURE TO MEASLES EPIDEMIC.

MANY of the previous reports of children immunized with killed measles vaccine 1-5 have covered fairly short periods of observation, and the exposure of patients to a measles epidemic (wild virus infections) has been limited. In this study, the children who received the vaccine were followed for 2 to 2½ years in respect to the antibody levels in their blood sera and their clinical response to exposure to measles which occurred in epidemic proportions in the community. The objectives of the study were (1) the measurement of effectiveness of killed attenuated measles vaccine in producing antibodies against the disease in susceptible children and (2) observation of the effectiveness of the vaccine in protecting the patients when they were exposed to the actual disease. A surprising development was the occurrence of atypical forms of measles in patients who had received vaccine and were subsequently exposed to epidemic clinical measles. Procedure Early