Miracle-dz/UniFAR-FTUs huggingface dataset:
Divergent signalling via APO‐1/Fas and the TNF receptor, two homologous molecules involved in physiological cell death.

Tumor necrosis factor receptor (TNF‐R) and APO‐1/Fas (CD95) are members of the tumor necrosis factor/nerve growth factor receptor superfamily involved in various forms of physiological cell death. Due to the structural homology between these receptors and their ligands, it has been suggested that APO‐1/Fas and TNF‐R kill cells by similar mechanisms. Here, we compared the killing pathways mediated by each receptor molecule in TNF‐sensitive L929 cells stably transfected with APO‐1/Fas cDNA. Morphological analysis revealed that TNF‐induced cell death resembles necrosis, while APO‐1/Fas‐mediated cell killing shows an apoptotic pattern, evident by the appearance of membrane blebbing, nuclear condensation and non‐random DNA degradation. Studies with inhibitors of several intracellular pathways further demonstrate that the mechanisms of TNF‐ and APO‐1/Fas‐mediated cell killing are substantially different. TNF cytotoxicity is mediated by reactive oxygen intermediates generated during mitochondrial respiration. However, these mediators are not involved in APO‐1/Fas‐mediated cell death as neither mitochondrial inhibitors nor antioxidants exert a protecting effect. Moreover, several inhibitors of calcium metabolism, ADP ribosylation and phospholipase action suppress TNF cytotoxicity, but not APO‐1/Fas‐mediated apoptosis. Additional differences between the two molecules were observed at the transcriptional level. Whereas transcription factor NF‐kappa B was readily activated by TNF, activation was not induced by triggering APO‐1/Fas. These data suggest that the two molecules, though structurally related, utilize distinct signal transduction pathways, even in a single cell type. Hence, cells may undergo different programs of cell death depending on the activating stimulus.
Use of mechanistic data in IARC evaluations

Consideration of mechanistic data has the potential to improve the analysis of both epidemiologic studies and cancer bioassays. IARC has a classification system in which mechanistic data can play a pivotal role. Since 1991, IARC has allowed an agent to be classified as carcinogenic to humans (Group 1) when there is less than sufficient evidence in humans but there is sufficient evidence in experimental animals and “strong evidence in exposed humans that the agent acts through a relevant mechanism of carcinogenicity. ” Mechanistic evidence can also substitute for conventional cancer bioassays when there is less than sufficient evidence in experimental animals, just as mechanistic evidence can substitute for conventional epidemiologic studies when there is less than sufficient evidence in humans. The IARC Monographs have used mechanistic data to raise or lower a classification that would be otherwise based on epidemiologic studies and cancer bioassays only. Recently, the IARC Monographs have evaluated several agents where mechanistic data were pivotal to the overall evaluation: benzo[a]pyrene, carbon black and other poorly soluble particles, ingested nitrates and nitrites, and microcystin‐LR. In evaluating mechanistic data, it is important to consider alternative mechanistic hypotheses, because an agent may induce tumors through multiple mechanisms. Environ. Mol. Mutagen. , 2008. © 2008 Wiley‐Liss, Inc.
Evidence Supporting Radiation Hormesis in Atomic Bomb Survivor Cancer Mortality Data

A recent update on the atomic bomb survivor cancer mortality data has concluded that excess relative risk (ERR) for solid cancers increases linearly with dose and that zero dose is the best estimate for the threshold, apparently validating the present use of the linear no threshold (LNT) model for estimating the cancer risk from low dose radiation. A major flaw in the standard ERR formalism for estimating cancer risk from radiation (and other carcinogens) is that it ignores the potential for a large systematic bias in the measured baseline cancer mortality rate, which can have a major effect on the ERR values. Cancer rates are highly variable from year to year and between adjacent regions and so the likelihood of such a bias is high. Calculations show that a correction for such a bias can lower the ERRs in the atomic bomb survivor data to negative values for intermediate doses. This is consistent with the phenomenon of radiation hormesis, providing a rational explanation for the decreased risk of cancer observed at intermediate doses for which there is no explanation based on the LNT model. The recent atomic bomb survivor data provides additional evidence for radiation hormesis in humans.
Increased mortality after anterior shoulder dislocation: 255 patients aged 12–40 years followed for 25 years

Background No data exist regarding mortality rate in young patients with a first–time anterior shoulder dislocation. A cohort of 255 patients aged 12–40 years had a primary anterior shoulder dislocation during the years 1978 and 1979. After 10 years, 9 of the patients had died—which is a high figure for this cohort of patients. The question thus arose as to whether these patients had an increased mortality rate. In this study we have examined the mortality rate in these patients 25 years after the primary dislocation, relative to that of the Swedish population in general. Patients and methods In 1978 and 1979, 255 patients aged 12–40 years (257 shoulders) with first–time anterior shoulder dislocation were treated with or without immobilization. During 2003 and 2004, a follow-up of all patients who were alive was undertaken and the certificates of causes of death of 27 deceased patients were also analyzed. Results The mortality rate (SMR) for the patients in this study was more than double that of the general Swedish population (p < 0.001). A higher proportion of the deceased patients had etiology other than sportsrelated activity as a cause of their initial dislocation (p = 0.04). 11 of the 27 who were deceased had died from injury or intoxication (S00–T98, ICD10), which was more than expected relative to the causes of death for the general Swedish population in 2003 and 2004 (p < 0.001) Interpretation The doubled mortality rate in our cohort of patients is most probably explained by the inclusion of a disproportionate number of patients with alcoholic behavior, which may affect the long-term outcome in trauma series.
Choline: High-Affinity Uptake by Rat Brain Synaptosomes

Synaptosomes from rat brain accumulate choline by two kinetically distinct processes, a high-affinity uptake system [Michaelis constant (Km) = 1 x 10-6M], and a low-affinity system (Km = 9 x 10-5M). The high-affinity uptake system requires sodium, and is associated with considerable formation of acetylcholine. The low-affinity uptake system is less dependent on sodium, and does not appear to be associated with a marked degree of acetylcholine formation. The high-affinity choline uptake appears to represent selective choline accumulation by cholinergic neurons.
Iodine Supply in Children From Different European Areas: The Euro‐Growth Study

In many areas of Europe iodine deficiency disorders still exist. Urinary iodine excretion is a valuable tool in characterizing the iodine supply of a population. However, there is a continuing discussion on the most appropriate parameter to measure urinary iodine excretion.In 247 children (ages 3–5 years) from six European centers, spot urine samples were analyzed for urinary iodine concentration and urinary iodine‐creatinine ratio. : The median values of urinary iodine concentration from the six centers were very similar (90–106 μg/l) corresponding to a normal or marginal iodine supply according to the criteria of the World Health Organization. However, the median values of the urinary iodine‐creatinine ratio from the six centers differed significantly (143–445 μg/g, P < 0.001). The different results of the two urinary parameters to assess urinary iodine supply were due to large significant differences in the urinary creatinine concentration reported by the various centers, which probably reflect marked differences in water intake.Iodine deficiency is still a significant health problem in many European countries. In comparable and homogeneous population subgroups (even from different countries), the urinary iodine‐creatinine ratio appears to be a much better parameter for assessing iodine supply than urinary iodine concentration.
Ethics and the HPV Vaccine: Considerations for School Nurses

School nurses are at the forefront of health care providers for many families of junior high and high school students and are used as primary sources of information and guidance about recommended student vaccinations. In the case of the relatively new vaccine for human papillomavirus (HPV), school nurses must be both knowledgeable about the infection itself and unbiased when asked to give students and families information about the vaccine. This article explores the development and current status of HPV and the HPV vaccine and the ethical principles of autonomy, utilitarianism, beneficence, nonmaleficence, justice, and cultural and religious issues as they relate to discussions with students and families about HPV vaccinations. School nurses are advocates for the health of students. Therefore, they must critically evaluate the application of these ethical principles when providing information and recommendations about the HPV vaccination.
Modulation of antigen expression in B‐cell precursor acute lymphoblastic leukemia during induction therapy is partly transient: Evidence for a drug‐induced regulatory phenomenon. Results of the AIEOP‐BFM‐ALL‐FLOW‐MRD‐Study Group

Background: Changes of antigen expression on residual blast cells of acute lymphoblastic leukemia (ALL) occur during induction treatment. Many markers used for phenotyping and minimal residual disease (MRD) monitoring are affected. Glucocorticoid (GC)‐induced expression modulation has been causally suspected, however, subclone selection may also cause the phenomenon.
Chlamydia trachomatis Induces Remodeling of the Actin Cytoskeleton during Attachment and Entry into HeLa Cells

ABSTRACT To elucidate the host cell machinery utilized by Chlamydia trachomatis to invade epithelial cells, we examined the role of the actin cytoskeleton in the internalization of chlamydial elementary bodies (EBs). Treatment of HeLa cells with cytochalasin D markedly inhibited the internalization of C. trachomatis serovar L2 and D EBs. Association of EBs with HeLa cells induced localized actin polymerization at the site of attachment, as visualized by either phalloidin staining of fixed cells or the active recruitment of GFP-actin in viable infected cells. The recruitment of actin to the specific site of attachment was accompanied by dramatic changes in the morphology of cell surface microvilli. Ultrastructural studies revealed a transient microvillar hypertrophy that was dependent upon C. trachomatis attachment, mediated by structural components on the EBs, and cytochalasin D sensitive. In addition, a mutant CHO cell line that does not support entry of C. trachomatis serovar L2 did not display such microvillar hypertrophy following exposure to L2 EBs, which is in contrast to infection with serovar D, to which it is susceptible. We propose that C. trachomatis entry is facilitated by an active actin remodeling process that is induced by the attachment of this pathogen, resulting in distinct microvillar reorganization throughout the cell surface and the formation of a pedestal-like structure at the immediate site of attachment and entry.
c-Raf/MEK/ERK Pathway Controls Protein Kinase C-mediated p70S6K Activation in Adult Cardiac Muscle Cells*

p70S6 kinase (S6K1) plays a pivotal role in hypertrophic cardiac growth via ribosomal biogenesis. In pressure-overloaded myocardium, we show S6K1 activation accompanied by activation of protein kinase C (PKC), c-Raf, and mitogen-activated protein kinases (MAPKs). To explore the importance of the c-Raf/MAPK kinase (MEK)/MAPK pathway, we stimulated adult feline cardiomyocytes with 12-O-tetradecanoylphorbol-13-acetate (TPA), insulin, or forskolin to activate PKC, phosphatidylinositol-3-OH kinase, or protein kinase A (PKA), respectively. These treatments resulted in S6K1 activation with Thr-389 phosphorylation as well as mammalian target of rapamycin (mTOR) and S6 protein phosphorylation. Thr-421/Ser-424 phosphorylation of S6K1 was observed predominantly in TPA-treated cells. Dominant negative c-Raf expression or a MEK1/2 inhibitor (U0126) treatment showed a profound blocking effect only on the TPA-stimulated phosphorylation of S6K1 and mTOR. Whereas p38 MAPK inhibitors exhibited only partial effect, MAPK-phosphatase-3 expression significantly blocked the TPA-stimulated S6K1 and mTOR phosphorylation. Inhibition of mTOR with rapamycin blocked the Thr-389 but not the Thr-421/Ser-424 phosphorylation of S6K1. Therefore, during PKC activation, the c-Raf/MEK/extracellular signal-regulated kinase-1/2 (ERK1/2) pathway mediates both the Thr-421/Ser-424 and the Thr-389 phosphorylation in an mTOR-independent and -dependent manner, respectively. Together, our in vivo and in vitro studies indicate that the PKC/c-Raf/MEK/ERK pathway plays a major role in the S6K1 activation in hypertrophic cardiac growth.
Subclinical disability in valued life activities among individuals with rheumatoid arthritis.

OBJECTIVE Subclinical disability, the need for modifications in task performance or frequency without reported difficulty with the task, has been identified as a stage along the disability continuum. We estimated the prevalence of subclinical disability in valued life activities (VLAs) among individuals with rheumatoid arthritis (RA), identified characteristics of individuals with VLA subclinical disability, and estimated the ability of VLA subclinical disability to predict later decrements in functioning. METHODS Data were from 3 years of a longitudinal panel study of individuals with RA, for which annual structured telephone interviews are conducted (n=508 in year 1, n=442 in year 3). Respondents rated difficulty in VLAs and then reported whether they used any of 4 behavioral modifications (limitations, extra time, help, or equipment) for each. Subclinical disability was defined for each VLA as no reported difficulty with use of any modification. Multiple regression analyses identified predictors of subclinical disability in year 1 and the role of year 1 subclinical disability in development of overt disability between year 1 and year 3. RESULTS Almost three-quarters of the subjects exhibited subclinical disability in at least 1 VLA in year 1. Duration of RA was consistently associated with subclinical disability. Individuals with subclinical disability at baseline were significantly more likely to experience increases in functional limitations (odds ratio [OR] 1.09, 95% confidence interval [95% CI] 1.01-1.18) and VLA disability (OR 1.14, 95% CI 1.06-1.23) over a prospective 2-year period. CONCLUSION Subclinical disability may be a valuable marker of individuals in a disability transition phase who are particularly susceptible to intervention that would enable them to maintain functioning.
Selecting the power electronic interface for a supercapattery based energy storage system

This paper presents the initial investigations in selecting the topology of the power electronic interface for an energy storage system for power levelling applications based on a novel storage device, the supercapattery. The particularities of the supercapattery device are summarized leading to a multistage power converter structure. A review of the two stage DC/DC converter structure to interface with the supercapattery and of various DC/AC inverters and conversion techniques suitable for connection to a medium voltage and high power AC grid, is given. Simulation results prove the capability of the power electronic interface to control independently and fast the active and reactive power flow which are vital in power peak leveling and power grid stabilization.
Actual experience on the short-term wind power forecasting at Penghu — From an island perspective

Wind power is expected to contribute significantly to the renewable energy targets owing to advancements in wind technologies, falling capital costs, abundance of free resource and commercial viability. However, it also brings into a lot of new challenges for the power network planning and operation. The predictability of wind power in managing load and generation balance is very important. If the fluctuations of wind were perfectly predictable, the additional cost of operating the system with a large penetration of wind power would be reduced. Therefore, accurate and reliable forecasting systems for wind power are widely recognized as a major contribution for increasing wind penetration. The target of this paper is to investigate the state-of-the-art wind power forecast technologies all over the world and predict wind power generated by the Penghu Jhong-tun wind farm. The short termand very short term forecasts, including ten-minute-ahead, one-hour-ahead, and one-day-ahead predictions, have been taken into account respectively. This prediction module will be developed with statistical models and Artificial Intelligence (AI) technologies respectively to capture the relations between input variables, i.e., online measurement data and numerical weather prediction (NWP) based on meteorological information, and the output valuable, such as future total wind farm power. Furthermore, the significance of NWP values on wind power forecasting has been highlighted in this paper by using a real example at the Penghu Jhong-tun wind farm.
Sociality, Tempo & Flow: Learning from Namibian Ridesharing

Ridesharing has become a hot topic in research and in the media, largely because of the recent rise of platforms like Lyft and Uber. Yet shared taxis and paratransit services have played central roles in many African countries' transport systems for years. We conducted an ethnographic study of shared taxis in Windhoek, Namibia, to understand how ridesharing is achieved in this setting, including the drivers' orientations, concerns and practices, and their consequences for their passengers. Our findings lead us to suggest designing a different sort of ridesharing system to support the drivers' agency and tempo, which enables drivers to locate customers in a more ad hoc way than established digital ridesharing platforms. This contributes to a growing body of research on designing for ridesharing.
Intestinal microbiota influence the early postnatal development of the enteric nervous system

Normal gastrointestinal function depends on an intact and coordinated enteric nervous system (ENS). While the ENS is formed during fetal life, plasticity persists in the postnatal period during which the gastrointestinal tract is colonized by bacteria. We tested the hypothesis that colonization of the bowel by intestinal microbiota influences the postnatal development of the ENS.
New cytostatic drugs in ovarian cancer.

BACKGROUND Many ovarian cancer patients will after treatment of the recurrence with cisplatin based therapy enter phase I or II studies with new drugs. Lately, some new agents have shown activity. MATERIALS AND METHODS The review is based on phase II studies mainly and focuses on paclitaxel (taxol). RESULTS A Canadian/European study of high (175 mg/m2) versus low dose (135 mg/m2), and short (3 hours) versus long (24 hours) infusion confirms the reported activity of paclitaxel in previously treated patients. The preliminary overall response rate in 286 evaluable patients is 18.5%. A dose effect exists regarding neuropathy and neutropenia, and a longer infusion duration results in a higher frequency of grade 4 neutropenia. In a phase III study comparing cisplatin 75 mg/m2 plus cyclophosphamide (750 mg/m2) or plus paclitaxel 135 mg/m2 over 24 hours, the paclitaxel-based combination gave a superior response rate (54% versus 33%) and statistically significant longer progression-free interval. The semisynthetic docetaxel (taxotere) gives an overall response rate of 32% (95% confidence interval 23%-43%). Skin toxicity and edema are dose-limiting factors. Gemcitabine has also shown activity in platinum-resistant patients with an overall response rate of 23% (95% CI 10%-40%). CONCLUSIONS The role of new drugs in first-line therapy remains to be seen. Further development of experimental work for screening and evaluation of new agents is needed.
A new half-bridge based inverter with the reduced-capacity DC capacitors for DC micro-grid

This paper proposes a new half-bridge based inverter for the DC micro-grid. The proposed topology consists of a three-leg inverter, which can be constructed by an intelligent power module (IPM). Using the IPM gives cost-effective inverters for the dc micro-grid. In the proposed half-bridge based topology with a three-leg inverter, two legs are used for two single-phase half-bridge inverters, where the neutral line is grounded. The third leg performs a power de-coupler balancing the mean value of two dc capacitor voltages. This power de-coupler exchanges the energies between two dc capacitors connected to two single-phase half-bridge inverters. Thus the capacity of the dc capacitors of the half-bridge inverters can be dramatically reduced as compared to those of the previously proposed half-bridge inverters for the dc micro-grid. The basic principle of the proposed half-bridge based inverter is discussed in detail, and then confirmed by digital computer simulation using PSIM software. Simulation results demonstrate that the capacity of the dc capacitors is reduced by one fortieth as compared to those of the previously proposed half-bridge based inverter used in the dc micro-grid.
Evolving assortativity and social conventions

This paper considers a stochastic evolutionary model in which agents can vote for different policies through majority voting that induce different assortative matching patterns. We find that in coordination games, agents either vote for complete segregation policy or maximal integration policy. The Pareto-dominant social convention is always stochastically stable and it is possible that both risk-dominant and Pareto-dominant social conventions are stochastically stable. This contrasts to risk-dominant social convention being uniquely stochastically stable predicted in conventional stochastic stability analysis where matching is uniformly random.
Effects of room reverberation on time-delay estimation performance

Previously, time-delay estimation (TDE) between two or more microphones has been proposed as a means for the passive localization of a talker in an audio-conference room. The authors present a simulation study of the effects of room reverberation on the performance of the maximum likelihood (ML) estimator of the time delay, which is obtained by maximizing the output of a generalized cross-correlator. To this end, synthetic microphone signals are generated with the image model technique and are used to evaluate the bias, variance and probability of anomaly of the ML estimator as a function of the room reflection coefficients and other external parameters of interest. The results clearly demonstrate the adverse effects of room reverberation on MLTDE performance. Qualitative and quantitative explanations of these effects are provided. <<ETX>>