Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of the response oscillator in inverse responses of Halobacterium halobium to weak light stimuli

Under certain conditions Halobacterium halobium organisms respond to a weak attractant light stimulus with a repellent response and to a weak repellent stimulus with an attractant response. The appearance of inverse responses depends on the stimulus strength, on the interval length between spontaneous reversals, and on the moment of stimulation during the interval. Although the cells are absolutely refractory to repellent stimuli for 500 ms after a reversal, repellent responses can be evoked even during that period if they are inverse responses to weak attractant stimuli. Simultaneous attractant and repellent stimuli cancel each other even when one of them leads to an inverse response, indicating that normal cellular signals occur at the site of signal integration. We postulate that the inverse responses are caused by certain properties of a cellular oscillator for which we previously postulated a role in response regulation and sensory control in halobacteria (A. Schimz and E. Hildebrand, Nature [London] 317:641-643, 1985).
Mobilization of CD34+ haematopoietic stem cells is associated with a functional inactivation of the integrin very late antigen 4

The β1 integrin very late antigen 4 (VLA‐4) plays a central role in mobilization and homing of CD34+ cells. In this study, we examined the activation state of VLA‐4 on CD34+ cells from bone marrow (BM) and peripheral blood (PB) by flow cytometry using a vascular cell adhesion molecule I–immunoglobulin (VCAM‐I/IgG) fusion protein as soluble ligand. In an intraindividual analysis, we found a significantly reduced affinity and avidity of the VLA‐4 receptor on CD34+ cells from PB during granulocyte colony‐stimulating factor (G‐CSF)‐enhanced marrow recovery in comparison with steady‐state BM. Moreover, the amount of circulating CD34+ cells during marrow recovery was inversely related to the activation state but not to the expression level of VLA‐4, suggesting that a modulation of the functional state of VLA‐4 is involved in the mobilization of CD34+ cells. Moreover, VLA‐4 function on CD34+ cells from BM was associated with the maturation state of CD34+ cells as high‐affinity VLA‐4 receptors were observed on the vast majority of more primitive CD34+ cells. In addition, we found that Mg2+ ions as well as co‐incubation of CD34+ cells with endothelial cells resulted in an activation of the VLA‐4 receptor. In conclusion, modulation of the functional state of VLA‐4 appears to be of relevance for the mobilization and homing of CD34+ haematopoietic stem cells.
Selection and Evaluation of Empirical Research in Technology Assessment

Technology assessment involves application of the scientific method to the practice of medicine. Finding all of the assessment reports in a given field is not an easy task. Proper evaluation of those assessments requires the conduct of a prospective experiment in which the sources and results are blinded when the choice is made of papers to exclude and to include, and the process should be carried in duplicate. There are several available data bases for carrying out the search, but because of problems they should be supplemented by reference to the bibliographies of pertinent published articles. Clinical trials included in meta-analyses should be graded by quality and thus facilitate sensitivity analyses. Attention must be paid to the possibility of publication bias. Finally, the advent of meta-analysis makes it desirable to begin randomized controlled trials in areas of uncertainty, even when there is no possibility that individual investigators will encounter enough patients to draw valid conclusions.
Climate and atmospheric drivers of historical terrestrial carbon uptake in the province of British Columbia, Canada

The impacts of climate change and increasing atmospheric CO 2 concentration on the terrestrial uptake of carbon dioxide since 1860 in the Canadian province of British Columbia are estimated using the process-based Canadian Terrestrial Ecosystem Model (CTEM). Model simulations show that these two factors yield an enhanced carbon uptake of around 44 gC m −2 yr −1 (or equivalently 63 gC m −2 yr −1 over the province's forested area), during the 1980s and 1990s, and continuing into the 2000s. About three-quarters of the simulated sink enhancement in our study compared to pre-industrial conditions is attributed to changing climate, and the rest is attributed to increase in CO 2 concentration. The model response to changing climate and increasing CO 2 is corroborated by comparing simulated stem wood growth rates with ground-based measurements from inventory plots in coastal British Columbia. The simulated sink is not an estimate of the net carbon balance because the effects of harvesting, insect disturbances and land-use change are not considered.
Shift work, social class, and ischaemic heart disease in middle aged and elderly men; a 22 year follow up in the Copenhagen Male Study.

OBJECTIVES: Shift work has been associated with an increased risk of ischaemic heart disease (IHD). Most published studies have had potential problems with confounding by social class. This study explores shift work as a risk factor for IHD after controlling for social class. METHODS: The Copenhagen male study is a prospective cohort study established in 1970-1 comprising 5249 men aged 40-59. Information obtained included working time, social class, and risk factors for IHD. A second baseline was obtained in 1985-6. The cohort was followed up for 22 years through hospital discharge registers for IHD, and cause of death was recovered from death certificates. RESULTS: One fifth of the cohort was shift working at entry with a significantly larger proportion of shift workers in lower social classes. Risk of IHD and all cause mortality over 22 years, adjusted for age only, for age and social class, and finally for age, social class, smoking, fitness, height, weight, and sleep disturbances, did not differ between shift and day workers. The relative risk of IHD, adjusted for age and social class was 1.0 (95% confidence interval (95% CI) 0.9-1.2). Men being shift workers in both 1971 and 1985 had the same risk as ex-shift workers in an 8 years follow up from the 1985-6 baseline. CONCLUSIONS: The present study questions shift work as an independent risk factor for IHD. The results of the study emphasise the importance of controlling adequately for the interplay of shift work and social class.
Noninvasive prenatal diagnosis of Down syndrome: current knowledge and novel insights

Abstract The noninvasive prenatal diagnosis of trisomy 21 (Down syndrome) is an actively researched area of prenatal medicine, as this is the most common aneuploidy compatible with life and a major cause of mental retardation. The isolation of intact fetal cells, and most importantly, the successful detection of fetal-origin nucleic acids (cell-free fetal DNA and RNA), in maternal plasma even from the early stages of pregnancy has inspired scientists to develop discriminative genetic markers for the prenatal detection of aneuploidy. In the near future, the development of epigenetic fetal-specific markers will possibly allow the universal application of a cell-free fetal DNA-based diagnostic test regardless of the gender of the fetus or its polymorphic status. Other promising approaches rely upon the detection of free placentally derived RNA transcribed from genes located on chromosome 21 and the application of highly sensitive techniques, such as digital polymerase chain reaction and high-throughput shotgun sequencing. However, irrespective of which strategy is selected for isolating or distinguishing fetal genetic material in maternal plasma, the small quantity of fetal origin nucleic acids poses severe technical challenges. In this review article, we present an overview of the current knowledge in the field of noninvasive prenatal assessment of fetuses with Down syndrome and the future perspectives regarding new fetal markers and novel molecular techniques that may eventually be applied in the clinical setting as a valid and safe option for women who opt for noninvasive accurate prenatal diagnosis.
Prediction and Decision Making in Health Care using Data Mining

Tendency for data mining application in healthcare today is great, because healthcare sector is rich with information, and data mining is becoming a necessity. Healthcare organizations produce and collect large volumes of information on daily basis. Use of information technologies allows automatization of processes for extraction of data that help to get interesting knowledge and regularities, which means the elimination of manual tasks and easier extraction of data directly from electronic records, transferring onto secure electronic system of medical records which will save lives and reduce the cost of the healthcare services, as well and early discovery of contagious diseases with the advanced collection of data. Data mining can enable healthcare organizations to predict trends in the patient conditions and their behaviors, which is accomplished by data analysis from different perspectives and discovering connections and relations from seemingly unrelated information. Raw data from healthcare organizations are voluminous and heterogeneous. They need to be collected and stored in the organized forms, and their integration enables forming of hospital information system. Healthcare data mining provides countless possibilities for hidden pattern investigation from these data sets. These patterns can be used by physicians to determine diagnoses, prognoses and treatments for patients in healthcare organizations.
SERUM CHOLESTEROL CONCENTRATION IN GREEK PUPILS AGED 9–18 YEARS. THE EFFECT OF PUBERTY

Of the different risk factors the serum cholesterol (CHI concentration is thought to be the most reliable predictor for the development of coronary artery disease ( 1 ). Genetic and nutritional, factors most likely determine the circulating levels of CH but the relative importance of these determinants at the different age periods is not known. Serum CH levels change with age. The mechanisms responsible for these changes are not apparent. One wonders whether or not hormones have anything to do with these alterations. In studying the effect of puberty, as a prototype of major hormonal changes, on the coronary risk factors, we noted a decline in serum CH levels in boys as puberty progressed. These findings are herein reported. Subjects and Methods. Serum CH was determined after an overnight fast in 531 healthy pupils, aged 9-18 years (322 from Chania, Crete, and 209 from Athens), and in 41 medical students, aged 22-25 years. The method of Richterich ( 2 ) was used for the determination of CH. The interday coefficient of variation for plasma CH level, in a pool
Tendon Transfer Fixation: Comparing a Tendon to Tendon Technique vs. Bioabsorbable Interference-Fit Screw Fixation

Tendon transfer techniques in the foot and ankle are used for tendon ruptures, deformities, and instabilities. This fresh cadaver study compares the tendon fixation strength in 10 paired specimens by performing a tendon to tendon fixation technique or using 7times20–25 mm bioabsorbable interference-fit screw tendon fixation technique. Load at failure of the tendon to tendon fixation method averaged 279N (Standard Deviation 81N) and the bioabsorbable screw 148N (Standard Deviation 72N) [p=0.0008]. Bioabsorbable interference-fit screws in these specimens show decreased fixation strength relative to the traditional fixation technique. However, the mean bioabsorbable screw fixation strength of 148N provides physiologic strength at the tendon-bone interface.
Syndromes Associated with Congenital Facial Paralysis

Thirty-five of 1,488 pediatric otologic cases had congenital facial nerve weakness. A cause was generally not found, but two probably had nuclear dysgenesis; one may have had an intracanalicular lesion; two cases resulted from teratogens, one from poor intrauterine environment, and three from genetic complications. Five had total unilateral paralysis; one had bilateral palsy. Frequent associated anomalies were microtia-atresia, hemifacial microsomia, facial clefts, Moebius syndrome, and congenital conductive sensorineural loss.
No Differences in DNA Damage and Antioxidant Capacity Between Intervention Groups of Healthy, Nonsmoking Men Receiving 2, 5, or 8 Servings/Day of Vegetables and Fruit

The effects of different intake levels of vegetables and fruit (VF) on some cancer-relevant biomarkers such as DNA damage and oxidative stress were investigated. In a randomized controlled trial, 64 nonsmoking male subjects were asked to consume a diet with 2 servings of VF/day for 4 wk. Then subjects were randomly assigned to 1 of 3 groups with either a low (2 servings/day), medium (5 servings/day), or high (8 servings/day) intake level of VF for another 4 wk. At the end of study, the plasma lutein, zeaxanthin, α -carotene, and β-carotene but not cryptoxanthin and lycopene concentrations were significantly higher in subjects consuming 8 servings/day than in those receiving 2 servings/day. Different levels of VF consumption and plasma carotenoid concentrations did not result in differences in the levels of endogenous DNA strand breaks, oxidative DNA damage, antigenotoxic capacity of lymphocytes, plasma markers for lipid peroxidation (malondialdehyde, 8-iso-prostaglandin-F2α) and antioxidant capacity [trolox-equivalent antioxidant capacity assay]. Thus, although consumption of 8 servings vs 2 servings/day of VF for 4 wk significantly increased the carotenoid level in plasma, there were no differences in DNA damage, lipid peroxidation, and antioxidant capacity markers among healthy, well-nourished, nonsmoking men.
Influence of moisture content of forage on ruminal functional specific gravity and passage of digesta.

Four crossbred beef steers (392 kg BW) fitted with ruminal cannulas were used in a 4 x 4 Latin square experiment with treatments arranged in a 2 x 2 factorial to evaluate effects of forage species (F) and reconstitution (R) on apparent digestibility, ruminal kinetics, and digesta functional specific gravity (FSG). Dietary treatments were alfalfa (Medicago sativa L.) and timothy (Phleum pratense L.) hays (90% DM) and the same hays reconstituted with water to 38% DM. Apparent DM digestibility was unaffected by R or F. Proportion of ruminal digesta with a FSG of . 9 to 1.1 or 1.1 to 1.2 decreased linearly (P < .05) after feeding, whereas the proportion with FSG > 1.2 increased linearly (P < .01). Reconstitution decreased (P < .10) the proportion of ruminal digesta with FSG of 1.1 to 1.2 and increased (P < .10) the proportion with a FSG > 1.2 compared with the hay diets. Reconstitution decreased digesta passage rate for timothy forage; no influence on passage rate for alfalfa was detected (F x R, P < .10). Ruminal DM pool was increased by reconstitution (P < .10). Inert particles of 1-mm length passed from the rumen at a faster rate (P < .05) than 3-mm particles. Inert particles with SG of 1.32 passed from the rumen at a faster rate (P < .05) in the reconstituted alfalfa than in the dry alfalfa diet but at a slower rate in the reconstituted timothy than in the dry timothy diet. These results suggest that factors other than SG of the digesta can have a profound effect on passage of forage particles from the rumen.
Cyanobacteria contain a structural homologue of the Hfq protein with altered RNA‐binding properties

Hfq proteins are common in many species of enterobacteria, where they participate in RNA folding and translational regulation through pairing of small RNAs and messenger RNAs. Hfq proteins share the distinctive Sm fold, and form ring‐shaped structures similar to those of the Sm/Lsm proteins regulating mRNA turnover in eukaryotes. However, bacterial Hfq proteins are homohexameric, whereas eukaryotic Sm/Lsm proteins are heteroheptameric. Recently, Hfq proteins with poor sequence conservation were identified in archaea and cyanobacteria. In this article, we describe crystal structures of the Hfq proteins from the cyanobacteria Synechocystis sp. PCC 6803 and Anabaena PCC 7120 at 1.3 and 2.3 Å resolution, respectively, and show that they retain the classic Sm fold despite low sequence conservation. In addition, the intersubunit contacts and RNA‐binding site are divergent, and we show biochemically that the proteins bind very weakly to known Escherichia coli Hfq target RNAs in vitro. Moreover, when expressed in E. coli, the proteins cannot mediate Hfq‐dependent RNA regulation. It therefore appears that the cyanobacterial proteins constitute a specialized subfamily of Hfq proteins that bind relatively weakly to A/U‐rich tracks of regulatory RNAs. The results have implications for our understanding of the evolution of the Sm fold and the Hfq proteins in the bacterial kingdom in general.
Microsatellite instability in Japanese gastric cancer

Background. Recent studies have shown that micro‐satellites are unstable in various types of cancers, and such genetic instability at the microsatellite loci (micro‐satellite instability) has been considered to play an important role in the development of cancer. However, the clinicopathologic significance of microsatellite instability in gastric cancer has not been clarified.
Defective assembly and intracellular transport of mutant paramyxovirus hemagglutinin-neuraminidase proteins containing altered cytoplasmic domains

The hemagglutinin-neuraminidase (HN) integral membrane protein of paramyxoviruses is expressed at the cell surface as a tetramer consisting of a pair of disulfide-linked dimers. HN has a large C-terminal ectodomain, a 19-residue uncleaved signal-anchor domain, and a 17-residue N-terminal cytoplasmic tail. Various mutant HN genes were constructed to examine the role of residues flanking the signal-anchor domain, including the cytoplasmic tail, on assembly and intracellular transport of the HN glycoprotein. Expression of the altered genes showed that by 90 min after synthesis the majority of the mutant HN proteins were in a conformationally mature form as assayed by their reactivity with conformation-specific monoclonal antibodies. However, the mutant proteins showed varied endoplasmic reticulum-to-Golgi apparatus transport rates, ranging from that of wild-type HN (t1/2 approximately 90 min) to slowly transported molecules (t1/2 approximately 5 h) and to molecules in which transport was not detected. Pulse-chase experiments indicated that the altered HN molecules had a specific and transient interaction with the resident endoplasmic reticulum protein GRP78-BiP, and thus the altered HN molecules were not retained in the endoplasmic reticulum by a prolonged interaction with GRP78-BiP. Sucrose density gradient sedimentation analysis of the mutant HN molecules indicated that they all had an oligomeric form that differed from that of wild-type HN; most of the molecules were found as disulfide-linked dimers rather than as tetramers. These data suggest that the HN cytoplasmic tail may function in the assembly of the final transport-competent oligomeric form of HN and that mutant HN molecules with seemingly properly folded ectodomains are retained in the endoplasmic reticulum by an as yet unidentified mechanism. The possible role of the HN cytoplasmic tail as a signal for intracellular transport is discussed.
Antigen‐driven tissue‐specific suppression following oral tolerance: Orally administered myelin basic protein suppresses proteolipid protein‐induced experimental autoimmune encephalomyelitis in the SJL mouse

Immunomodulatory treatment paradigms have been applied to animal models of T cell‐mediated autoimmune diseases in an attempt to develop an immunospecific and non‐toxic form of therapy which can be applied to humans. These treatment paradigms are often directed to T cells with a restricted T cell receptor repertoire or that react with dominant peptide determinants. Experimental data, however, suggests that even if the initial T cell response is restricted to a specific self‐protein in the target organ, spreading autoimmunity may develop with broadening of T cell autoreactivity to additional epitopes of the same autoantigen or to different autoantigens in the target organ. Thus, multiple autoantigens may become targets of the autoimmune response. This makes immunotherapeutic strategies based on suppressing responses to restricted proteins or clones of cells problematic. We have previously shown that suppression of experimental autoimmune encephalomyelitis (EAE) in the Lewis rat by oral myelin basic protein (MBP) is mediated by the release of transforming growth factor‐β after triggering by the oral tolerogen. Here, we report that in the SJL model of EAE oral administration of an autoantigen from the target tissue suppresses disease independent of whether it is or is not the inciting antigen. Thus, orally administered MBP or MBP peptides suppress proteolipid protein (PLP)‐induced EAE, whereas intravenously administered MBP does not. Both oral and intravenous PLP, however, suppressed PLP disease. These findings have important implications for the use of oral tolerance as a therapeutic approach for the treatment of T cell‐mediated inflammatory autoimmune diseases in man in which the inciting autoantigen is unknown or in which there is autoreactivity to multiple autoantigens in the target tissue.
Phase I/II study of transjugular transhepatic peritoneovenous venous shunt, a new procedure to manage refractory ascites in cancer patients: Japan Interventional Radiology in Oncology Study Group 0201.

OBJECTIVE This multicenter phase I/II study evaluated the safety and the efficacy of transjugular transhepatic peritoneovenous shunt (PVS), a new palliative treatment for malignant refractory ascites. SUBJECTS AND METHODS Patients with refractory malignant ascites and patent hepatic veins and vena cava were included in this study. Eligible patients underwent the placement of transjugular transhepatic PVS catheter via the jugular vein into the abdominal cavity through the hepatic vein. In phase I, a step-by-step analysis of the safety was performed. The safety and the efficacy were determined through phases I and II. RESULTS Thirty-three patients were entered in this study, nine in phase I and 24 in phase II. Transjugular transhepatic PVS was technically successful in all patients. No severe adverse events were observed during the placement procedure. After the placement, 22 adverse events (grade 2 or higher) occurred. Frequent adverse events were hypoalbuminemia (24%) and decrease in hemoglobin (18%), which resolved within 1 week without additional treatment. The clinical efficacy rate at 1 week after the procedure was 67%. Occlusion of the catheter due to fibrin sheath was observed in seven patients, and the revision of the system was performed. CONCLUSION Transjugular transhepatic PVS is a safe and feasible procedure for managing refractory ascites in patients with cancer. Sufficient efficacy was observed in our initial experience, but a larger clinical trial is warranted.