Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of dose-rate on induction of neoplastic transformation in vitro by low doses of 232 MeV protons

Purpose: To determine the effect of dose-rate on induction of neoplastic transformation in vitro by low doses of 232 MeV protons. Materials and methods: The experimental system used was the human hybrid cell assay. The dose-rates examined were 50 cGy/min and 20 cGy/h. The dose-rate 20 cGy/h was chosen as this is in the range of the maximum dose-rate that can be experienced in an unshielded space environment following a solar flare. At low dose-rate (LDR), doses from 0.5–100 cGy were studied. At high dose rate (HDR), the dose range was 0.5–200 cGy. Results: The data indicated no significant differences between the two dose-rates at doses up to 100 cGy. Conclusion: For the endpoint of neoplastic transformation in vitro, high dose-rate data may be sufficient to estimate low dose-rate effects (20 cGy/h) in the dose range up to 100 cGy from 232 MeV protons. The data are of relevance to risk estimation for space travel.
Proximity prominent news value for online publication

This case study examines how editors select stories for a Chinese-language publication’s WeChat public account. Results of a content analysis between May and August 2014 indicate that editors do not strictly rely on established news values to select WeChat stories. News categories better predict story decisions. Furthermore, news-category priorities identified in interviews with editors closely match what readers want to see.
The moving junction of apicomplexan parasites: a key structure for invasion

Most Apicomplexa are obligate intracellular parasites and many are important pathogens of human and domestic animals. For a successful cell invasion, they rely on their own motility and on a firm anchorage to their host cell, depending on the secretion of proteins and the establishment of a structure called the moving junction (MJ). The MJ moves from the apical to the posterior end of the parasite, leading to the internalization of the parasite into a parasitophorous vacuole. Based on recent data obtained in Plasmodium and Toxoplasma, an emerging model emphasizes a cooperative role of secreted parasitic proteins in building the MJ and driving this crucial invasive process. More precisely, the parasite exports the microneme protein AMA1 to its own surface and the rhoptry neck RON2 protein as a receptor inserted into the host cell together with other RON partners. Ongoing and future research will certainly help refining the model by characterizing the molecular organization within the MJ and its interactions with both host and parasite cytoskeleton for anchoring of the complex.
Ozone Exposure and Mortality: An Empiric Bayes Metaregression Analysis

Background: Results from time-series epidemiologic studies evaluating the relationship between ambient ozone concentrations and premature mortality vary in their conclusions about the magnitude of this relationship, if any, making it difficult to estimate public health benefits of air pollution control measures. We conducted an empiric Bayes metaregression to estimate the ozone effect on mortality, and to assess whether this effect varies as a function of hypothesized confounders or effect modifiers. Methods: We gathered 71 time-series studies relating ozone to all-cause mortality, and we selected 48 estimates from 28 studies for the metaregression. Metaregression covariates included the relationship between ozone concentrations and concentrations of other air pollutants, proxies for personal exposure–ambient concentration relationships, and the statistical methods used in the studies. For our metaregression, we applied a hierarchical linear model with known level-1 variances. Results: We estimated a grand mean of a 0.21% increase (95% confidence interval = 0.16–0.26%) in mortality per 10-μg/m3 increase of 1-hour maximum ozone (0.41% increase per 10 ppb) without controlling for other air pollutants. In the metaregression, air-conditioning prevalence and lag time were the strongest predictors of between-study variability. Air pollution covariates yielded inconsistent findings in regression models, although correlation analyses indicated a potential influence of summertime PM2.5. Conclusions: These findings, coupled with a greater relative risk of ozone in the summer versus the winter, demonstrate that geographic and seasonal heterogeneity in ozone relative risk should be anticipated, but that the observed relationship between ozone and mortality should be considered for future regulatory impact analyses.
Risk factors for relapse after remission with repetitive transcranial magnetic stimulation for the treatment of depression

Background: Several studies have shown that repetitive transcranial magnetic stimulation (rTMS) treatment is associated with a significant antidepressant effect that can last for several months. Methods: To investigate the mean remission time and the predictors associated with its duration; we performed a large retrospective, naturalistic study with 204 patients who underwent treatment with rTMS. During the periods from 2000 to 2006, we identified and collected the data on 204 patients who underwent rTMS treatment for major depression and who remitted their depression (defined as Hamilton Depression Rating Scores less or equal to 7). Patients were followed up to 6 months after this therapy. Results: Event‐free remission with the end point defined as relapse (Hamilton Depression Rating Scores higher than 8) was 75.3% (73.7) at 2 months, 60.0% (74.5) at 3 months, 42.7% (74.8) at 4 months, and 22.6% (74.5) at 6 months. According to a multivariate analysis, only the age and number of sessions were independent predictors of outcome. Although depression severity and use of tricyclics also showed a significant relationship with remission duration, the model including these variables was not adequate to explain our data. Conclusions: The results of this study suggest that young age and additional rTMS sessions are associated with a ong duration of rTMS effects and therefore future trials investigating the effects of maintenance rTMS treatment need to explore further the implication of these factors for depression remission. Depression and Anxiety, 2009. © 2009 Wiley‐Liss, Inc.
Calorie restriction limits the generation but not the progression of mitochondrial abnormalities in aging skeletal muscle

The effect of early‐onset calorie restriction and aging on the accumulation of electron transport system (ETS) abnormalities was studied in rat skeletal muscle. Rectus femoris and vastus lateralis muscle fibers were analyzed for cytochrome c oxidase (COX) and succinate dehydrogenase (SDH) enzyme activities. Fibers displaying COX negative and SDH hyper reactive (COX–/SDH++) phenotype were followed through 1000–2000 micrometers to determine the frequency and length of these abnormalities as well as the physiological impact on fiber structure. Calorie restricted rats had fewer ETS abnormal muscle fibers. The mean length of ETS abnormal regions in ad libitum rat muscle fibers was similar to calorie restricted rat muscles. ETS abnormal fibers from both diet groups exhibited intra‐fiber atrophy. A negative correlation between ETS abnormality length and fiber cross‐sectional area (CSA) ratio was observed in both ad libitum and calorie‐ restricted rats. Although calorie restriction reduced the number of ETS abnormalities, it did not affect the length or associated fiber atrophy of ETS abnormal regions once the abnormality was established. Thus, calorie restriction affects the onset but not the progression of electron transport system abnormalities, thereby, limiting a process that ultimately results in fiber breakage and fiber loss.
Chloroplast Genome Evolution in Early Diverged Leptosporangiate Ferns

In this study, the chloroplast (cp) genome sequences from three early diverged leptosporangiate ferns were completed and analyzed in order to understand the evolution of the genome of the fern lineages. The complete cp genome sequence of Osmunda cinnamomea (Osmundales) was 142,812 base pairs (bp). The cp genome structure was similar to that of eusporangiate ferns. The gene/intron losses that frequently occurred in the cp genome of leptosporangiate ferns were not found in the cp genome of O. cinnamomea. In addition, putative RNA editing sites in the cp genome were rare in O. cinnamomea, even though the sites were frequently predicted to be present in leptosporangiate ferns. The complete cp genome sequence of Diplopterygium glaucum (Gleicheniales) was 151,007 bp and has a 9.7 kb inversion between the trnL-CAA and trnV-GCA genes when compared to O. cinnamomea. Several repeated sequences were detected around the inversion break points. The complete cp genome sequence of Lygodium japonicum (Schizaeales) was 157,142 bp and a deletion of the rpoC1 intron was detected. This intron loss was shared by all of the studied species of the genus Lygodium. The GC contents and the effective numbers of co-dons (ENCs) in ferns varied significantly when compared to seed plants. The ENC values of the early diverged leptosporangiate ferns showed intermediate levels between eusporangiate and core leptosporangiate ferns. However, our phylogenetic tree based on all of the cp gene sequences clearly indicated that the cp genome similarity between O. cinnamomea (Osmundales) and eusporangiate ferns are symplesiomorphies, rather than synapomorphies. Therefore, our data is in agreement with the view that Osmundales is a distinct early diverged lineage in the leptosporangiate ferns.
Regional differences in the expression of nitric oxide synthase and specific receptors in the vascular tissues of control and diabetic rabbits: a pilot study.

BACKGROUND Atherosclerosis can influence the expression of endothelial nitric oxide synthase (eNOS) as well as endothelin-1 (ET-1) and 5-hydroxytryptamine (5HT; serotonin) receptors. Diabetes has an effect on the onset, severity and pattern of atherosclerosis with a predilection for more distal arteries. We aimed to identify regional differences in the distribution of eNOS activity, ET-1 and 5HT receptors in vascular tissues obtained from control and diabetic rabbits. MATERIALS AND METHODS The mid abdominal aorta, right renal and right femoral arteries were harvested from 12 adult rabbits (6 months old, 3-3.9 kg); 8 controls and 4 diabetic (induced using alloxan 7 months previously). Samples were stored in liquid nitrogen for Western immunoblotting for eNOS as well as ET-1 and 5HT receptors. RESULTS Significant differences were found in the distribution of eNOS, ET-1 and 5HT between the aorta, renal and femoral arteries in the controls. The number of ET-1 receptors was significantly higher (aorta; p=0.016, renal; p=0.004, femoral; p=0.05,) whereas, the expression of eNOS was significantly lower (aorta; p =0.004, renal; p =0.004, femoral; p =0.008) when comparing arteries from normal rabbits with these from diabetics ones. The number of 5HT receptors was higher in arteries from diabetic rabbits but this was not statistically significantly. CONCLUSION The "regional" distribution of eNOS activity as well as ET-1 and 5HT receptors in control rabbits varies significantly according to the vessel assessed. Further studies are needed to evaluate the effect of blocking these receptors (e.g. on the risk of re-stenosis). Regional receptor differences may explain why diabetes is linked with a predilection for atherosclerosis (and possibly calcification) in distal arteries.
Transitions from alpha to pi helix observed in molecular dynamics simulations of synthetic peptides.

Molecular dynamics simulations were carried out for three 13-residue peptides of the form AcNH-A-A-E-X-A-E-A-H-A-A-E-K-A-CONH(2) with X = A, F, and W. All three peptides exhibited unexpected dynamical behavior, undergoing a transition from an alpha-helical to a pi-helical structure in the course of 5-ns trajectories in aqueous solution. Analysis of peptide length, accessible surface, interaction energies, hydrogen bonding, and dihedral angles was consistent with alpha --> pi transitions at 2800, 500, and 800 ps for X = A, F and W, respectively. The transitions occurred sequentially and cooperatively, propagating from the C- to the N-terminus for X = A and W and from the center toward both termini for X = F. The time scale of the overall transition ranged from 300 to 500 ps. For all three peptides the backbone structural transition was accompanied by a concerted rearrangement of the charged side chains, including a 3 A increase in the distance between carboxylate groups of Glu-3 and Glu-6. During the transition the peptide backbone hydrogen-bonding patterns were disrupted at the interface between the alpha-helical and nascent pi-helical regions, with peptide groups forming water-bridged hydrogen bonds. The peptide structures exhibited significant fluidity, with individual residues sampling alpha-, pi-, and 3(10)-helical conformations, as well as a "coil" state, without any intramolecular hydrogen bonds. The studied peptides have been designed to form alpha-helices when incorporated in novel hemoprotein model compounds, peptide-sandwiched mesohemes, which consist of two identical peptides covalently attached to an Fe(III) mesoporphyrin [Liu, D. , Williamson, D. A. , Kennedy, M. L. , Williams, T. D. , Morton, M. M. , and Benson, D. R. (1999) J. Am. Chem. Soc. 121, 11798-11812]. The possibility of adopting pi-helical structures by the constituent peptides may influence the properties of the hemoprotein models.
Catching-up with supermajors: the technology factor in building the competitive power of national oil companies from developing economies

Abstract The paper investigates the role of technology in the growing competitive potential of state-controlled national oil companies (NOCs) from developing countries. The technological development of NOCs is analyzed in the context of their increasing rivalry with supermajors, which have dominated the global oil and gas industry for decades. The author reveals the main features of NOCs’ catch-up development amid the dynamic changes in the competitive landscape of the global oil industry. These trends were analyzed against the background of the current phase of the oil industry’s technological evolution. The paper concludes that although rapid technological growth did become a key strategic priority of many NOCs, only very small group of them managed to achieve equal footing with traditional industry leaders. For the majority of the remaining NOCs, the existing limitations related to the policy of their home state did not allow them to narrow the technological gap with global supermajors.
Six Centuries of Real Wages in France from Louis IX to Napoleon III: 1250–1860

Evidence of an early modern “Little divergence” in real wages between northwestern Europe and the rest of the continent is mostly based on the comparative study of a sample of leading European cities. Focusing on France and England this study reassesses the debate from a country-level perspective. The findings challenge the notion of an early modern divergence pointing to the coexistence of both divergence and convergence phases until the eighteenth century. Results also suggest that the real wages of a significant share of the French male labor force were broadly on par with the levels prevailing in England before c.1750.
Matrix Approach to Model Matching of Asynchronous Sequential Machines

In this note, we propose a matrix-based approach for asynchronous sequential machines. Using semi-tensor product of matrices, we convert an asynchronous machine into a discrete-time bilinear system, and study its dynamics by investigating its structure matrices. We give simple algorithms for cycle detection and reachability analysis, and moreover, provide a control design method for the model matching of two input/state machines.
Cell cycle analysis of E2F in primary human T cells reveals novel E2F complexes and biochemically distinct forms of free E2F

The transcription factor E2F activates the expression of multiple genes involved in cell proliferation, such as c-myc and the dihydrofolate reductase gene. Regulation of E2F involves its interactions with other cellular proteins, including the retinoblastoma protein (Rb), the Rb-related protein p107, cyclin A, and cdk2. We undertook a detailed analysis of E2F DNA-binding activities and their cell cycle behavior in primary human T cells. Three E2F DNA-binding activities were identified in resting (G0) T cells with mobilities in gel shift assays distinct from those of previously defined E2F complexes. One of these activities was found to be a novel, less abundant, Rb-E2F complex. The most prominent E2F activity in resting T cells (termed complex X) was abundant in both G0 and G1 but disappeared as cells entered S phase, suggesting a possible role in negatively regulating E2F function. Complex X could be dissociated by adenovirus E1A with a requirement for an intact E1A conserved region 2. However, X failed to react with a variety of antibodies against Rb or p107, implicating the involvement of an E1A-binding protein other than Rb or p107. In addition to these novel E2F complexes, three distinct forms of unbound (free) E2F were resolved in gel shift experiments. These species showed different cell cycle kinetics. UV cross-linking experiments suggested that a distinct E2F DNA-binding protein is uniquely associated with the S-phase p107 complex and is not associated with Rb. Together, these results suggest that E2F consists of multiple, biochemically distinct DNA-binding proteins which function at different points in the cell cycle.
The WW Domain of Dystrophin Requires EF-Hands Region to Interact with β-Dystroglycan

Abstract Skeletal muscle dystrophin is a 427 kDa protein thought to act as a link between the actin cytoskeleton and the extracellular matrix. Perturbations of the dystrophin-associated complex, for example, between dystrophin and the transmembrane glycoprotein β-dystroglycan, may lead to muscular dystrophy. Previously, the cysteine-rich region and first half of the carboxy-terminal domain of dystrophin were shown to interact with β-dystroglycan through a stretch of fifteen amino acids at the carboxy-terminus of β-dystroglycan. This region of dystrophin implicated in binding β-dystroglycan contains four modular protein domains: a WW domain, two putative Ca2+-binding EF-hand motifs, and a putative zinc finger ZZ domain. The WW domain is a globular domain of 38–40 amino acids with two highly conserved tryptophan residues spaced 20–22 amino acids apart. A subset of WW domains was shown to bind ligands that contain a Pro-Pro-x-Tyr core motif (where x is any amino acid). Here we elucidate the role of the WW domain of dystrophin and surrounding sequence in binding β-dystroglycan. We show that the WW domain of dystrophin along with the EF-hand motifs binds to the carboxy-terminus of β-dystroglycan. Through site-specific mutagenesis and in vitro binding assays, we demonstrate that binding of dystrophin to the carboxyterminus of β-dystroglycan occurs via a β-dystroglycan Pro-Pro-x-Tyr core motif. Targeted mutagenesis of conserved WW domain residues reveals that the dystrophin/β-dystroglycan interaction occurs primarily through the WW domain of dystrophin. Precise mapping of this interaction could aid in therapeutic design.
Complement-Dependent Enhancement of CD8+ T Cell Immunity to Lymphocytic Choriomeningitis Virus Infection in Decay-Accelerating Factor-Deficient Mice1

Decay-accelerating factor (DAF, CD55) is a GPI-anchored membrane protein that regulates complement activation on autologous cells. In addition to protecting host tissues from complement attack, DAF has been shown to inhibit CD4+ T cell immunity in the setting of model Ag immunization. However, whether DAF regulates natural T cell immune response during pathogenic infection is not known. We describe in this study a striking regulatory effect of DAF on the CD8+ T cell response to lymphocytic choriomeningitis virus (LCMV) infection. Compared with wild-type mice, DAF knockout (Daf-1−/−) mice had markedly increased expansion in the spleen of total and viral Ag-specific CD8+ T cells after acute or chronic LCMV infection. Splenocytes from LCMV-infected Daf-1−/− mice also displayed significantly higher killing activity than cells from wild-type mice toward viral Ag-loaded target cells, and Daf-1−/− mice cleared LCMV more efficiently. Importantly, deletion of the complement protein C3 or the receptor for the anaphylatoxin C5a (C5aR) from Daf-1−/− mice reversed the enhanced CD8+ T cell immunity phenotype. These results demonstrate that DAF is an important regulator of CD8+ T cell immunity in viral infection and that it fulfills this role by acting as a complement inhibitor to prevent virus-triggered complement activation and C5aR signaling. This mode of action of DAF contrasts with that of CD59 in viral infection and suggests that GPI-anchored membrane complement inhibitors can regulate T cell immunity to viral infection via either a complement-dependent or -independent mechanism.
E-bike trials’ potential to promote sustained changes in car owners mobility habits

Modal shifts hold considerable potential to mitigate carbon emissions. Electric bikes (e-bikes) represent a promising energy- and carbon-efficient alternative to cars. However, as mobility behaviour is highly habitual, convincing people to switch from cars to e-bikes is challenging. One strategy to accomplish this is the disruption of existing habits—a key idea behind an annual e-bike promotion programme in Switzerland, in which car owners can try out an e-bike for free over a two-week period in exchange for their car keys. By means of a longitudinal survey, we measured the long-term effects of this trial on mobility-related habitual associations. After one year, participants’ habitual association with car use had weakened significantly. This finding was valid both for participants who bought an e-bike after the trial and those who did not. Our findings contrast the results of other studies who find that the effect of interventions to induce modal shifts wears off over time. We conclude that an e-bike trial has the potential to break mobility habits and motivate car owners to use more sustainable means of transport.
Governance of Biomedical Research Commons to Advance Clinical Translation: Lessons from the Mouse Model Community

The translation of laboratory and clinical research into interventions that improve individual and population health is an iterative process with systemic directionality from basic research through preclinical research, clinical research, clinical implementation, and population health outcomes research (National Center for Advancing Translational Sciences 2015). Engaged in translation are patients and patient advocacy organizations, researchers from public and private sectors and from multiple disciplinary backgrounds, clinical practitioners, as well as a myriad of ancillary support professionals, from business executives, accountants, and marketing/sales staff to venture capitalists and public and philanthropic fund administrators to health and safety regulators. New models of collaboration within this complex ecosystem are required to overcome waste and inefficiencies in current research and development (R&D)