Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of methylcobalamin (vitamin B12) on in vitro cytokine production of peripheral blood mononuclear cells.

Recently in Japan, one form of vitamin B12, methylcobalamin also known as methyl B12, has attracted the attention of physicians as a therapy for patients with rheumatoid arthritis. However, its immunological actions in vivo are still unknown. In this study, we induced the in vitro production of such cytokines as interleukin-6 (IL-6), interferon-gamma (IFN-gamma), and interleukin-1 beta (IL-1 beta) by adding various mitogens (phytohemagglutinin:PHA, concanavalin A: ConA, or pokeweed mitogen:PWM) as well as recombinant interleukin-2, and we investigated the effects of methyl B12 (final concentration, 8-8,000 ng/ml) on the production of these cytokines by peripheral mononuclear cells. As compared to the controls, IL-6 production induced by PHA and ConA on Day 4 of the culture was suppressed by an average 60-70% when methyl B12 (80-8,000 ng/ml) was added to the medium. IFN-gamma production decreased dose-dependently with methyl B12, i.e., it decreased to 46% of the control when this production was induced by rIL-2, and decreased to 56-66% when it was induced by mitogens. The effect of methyl B12 on IL-1 beta production on Day I of the culture was small. These findings indicate that methyl B12 suppresses mainly the cytokine production of T lymphocytes. Such suppressive effects as shown in the in vitro situation are expected to be expressed also in vivo in patients with rheumatoid arthritis, especially at articulation lesion sites.
Recent developments in the assessment of the multiply injured trauma patient

Purpose of reviewTo provide an update on the recent developments and controversies in the assessment of the traumatically injured patient. Recent findingsRecent literature suggests that: whole-body computed tomography (CT) is an effective strategy in more severely injured blunt trauma patients; 64-slice CT scanning now provides an effective noninvasive screening method for blunt cerebrovascular injury; the need for MRI imaging, in addition to CT, for the diagnosis of occult ligamentous injury of the cervical spine remains an unresolved controversy; point-of-care testing has made significant improvements in our ability to predict which patients will need a massive transfusion; and thromboelastography has enhanced our ability to tailor a hemostatic resuscitation more accurately. SummaryThe recent advances in the assessment of the multiply injured patient allow clinicians to more efficiently diagnose a patient's injuries and implement treatment in a more timely manner.
All-trans-retinal shuts down rod cyclic nucleotide-gated ion channels: A novel role for photoreceptor retinoids in the response to bright light?

In retinal rods, light-induced isomerization of 11-cis-retinal to all-trans-retinal within rhodopsin triggers an enzyme cascade that lowers the concentration of cGMP. Consequently, cyclic nucleotide-gated (CNG) ion channels close, generating the first electrical response to light. After isomerization, all-trans-retinal dissociates from rhodopsin. We now show that all-trans-retinal directly and markedly inhibits cloned rod CNG channels in excised patches. 11-cis-retinal and all-trans-retinol also inhibited the channels, but at somewhat higher concentrations. Single-channel analysis suggests that all-trans-retinal reduces average open probability of rod CNG channels by inactivating channels for seconds at a time. At physiological cGMP levels, all-trans-retinal inhibited in the nanomolar range. Our results suggest that all-trans-retinal may be a potent regulator of the channel in rods during the response to bright light, when there is a large surge in the concentration of all-trans-retinal.
THE PHENOTYPIC VARIANCE WITHIN PLASTIC TRAITS UNDER MIGRATION‐MUTATION‐SELECTION BALANCE

Abstract How phenotypic variances of quantitative traits are influenced by the heterogeneity in environment is an important problem in evolutionary biology. In this study, both genetic and environmental variances in a plastic trait under migration‐mutation‐stabilizing selection are investigated. For this, a linear reaction norm is used to approximate the mapping from genotype to phenotype, and a population of clonal inheritance is assumed to live in a habitat consisting of many patches in which environmental conditions vary among patches and generations. The life cycle is assumed to be selection‐reproduction‐mutation‐migration. Analysis shows that phenotypic plasticity is adaptive if correlations between the optimal phenotype and environment have become established in both space and/or time, and it is thus possible to maintain environmental variance (VE) in the plastic trait. Under the special situation of no mutation but maximum migration such that separate patches form an effective single‐site habitat, the genotype that maximizes the geometric mean fitness will come to fixation and thus genetic variance (VG) cannot be maintained. With mutation and/or restricted migration, VG can be maintained and it increases with mutation rate but decreases with migration rate; whereas VE is little affected by them. Temporal variation in environmental quality increases VG while its spatial variance decreases VG. Variation in environmental conditions may decrease the environmental variance in the plastic trait.
Domains of glycoprotein H of herpes simplex virus type 1 involved in complex formation with glycoprotein L.

The complex formation between glycoproteins H (gH) and L (gL) of herpes simplex virus type 1 (HSV-1) was studied by using five recombinant baculoviruses expressing open reading frames that contain deletions in the coding region of the extracellular domain of gH. In addition, the gH-deletion mutants contained a C-terminal tag. Complex formation of gL and the gH-deletion mutants was studied by immunoprecipitations with anti-tag monoclonal antibody (MAb) A16 and with the gH-specific MAbs 37S, 46S, and 52S. All gH-deletion mutants were complexed to gL when analyzed by MAb A16. MAb 37S precipitated complexes between gL and the two gH-deletion mutants that contain the epitope of this MAb. When the gH conformation-dependent MAbs 46S and 52S were used, gL was coprecipitated together with the gH-deletion mutant lacking amino acids 31-299, but gL was not coprecipitated with the gH-deletion mutant lacking amino acids 31-473. The data from the precipitation studies do allow at least two interpretations. There is either one site for gL binding on gH (residue 300-473) or gL contacts multiple regions of gH. We were unable to demonstrate gL-dependent cell surface expression of either of the gH-deletion mutants. This suggests that the coassociation of gH with gL is necessary but not sufficient for transport of gH to the cell surface.
Threshold modulation in error diffusion

A theoretical analysis of threshold modulation in error diffusion is given. It is shown that spatial modulation of the threshold is mathematically identical to processing an equivalent input image with the standard error diffusion algorithm. The equivalent input is the sum of the original image with a high-pass-filtered version of the threshold spatial modulation. The filter is a function only of the weights used to distribute the errors. This result can be used to explain the several published observed effects of threshold modulation, such as edge enhancement and the effects of adding noise to the threshold.
The reliability of the Pelli‐Robson contrast sensitivity chart

Normative contrast sensitivity (CS) data were obtained using the commercially available Pelli‐Robson chart from the dominant eye of 30 young (mean (±SD) age 22.5 ± 4.3 years) and 42 older (mean (±SD) age 70.2 ± 6.7 years) subjects with normal healthy eyes. The majority of young subjects were found to have a CS of 1.80 log units or above. The majority of the older subjects were found to have a CS of 1.65 log units or above. CS results were obtained using both sides (A and B) of the Pelli‐Robson chart from 30 (15 young and 15 older) of these subjects. These measurements were repeated under identical conditions, 2 weeks later. There was no significant difference between the results from sides A and B of the chart. The CS scores were shown to be repeatable to within ±0.15 log units or ±1 step. Therefore a significant change in CS score is +2 steps or 0.30 log units. Slight improvements in reliability could be obtained by more careful permutation of letters on each step and a smaller step size. The restriction against these changes is the ensuing increased chart size.
Vector quantized radial basis function neural network with embedded multiple local linear models for financial prediction

In this paper, a model is proposed which combines multiple local linear models with a novel modified probabilistic neural network (MPNN). The proposed model is developed to approximate multiple nonlinear model with reduced computational requirement. The proposed model shows to provide both low bias and variance with reduced computations by utilizing semiparametric local linear approximation and efficient vector quantization of data space. The proposed model is shown to provide comparable performance to other state-of-the-art models in terms of bias, variance and computational requirement in short-term financial prediction.
Preventing injuries in female youth football – a cluster‐randomized controlled trial

A set of exercises – the “11”– have been selected to prevent football injuries. The purpose of this cluster‐randomized controlled trial was to investigate the effect of the “11” on injury risk in female youth football. Teams were randomized to an intervention (n=59 teams, 1091 players) or a control group (n=54 teams, 1001 players). The intervention group was taught the “11,” exercises for core stability, lower extremity strength, neuromuscular control and agility, to be used as a 15‐min warm‐up program for football training over an 8‐month season. A total of 396 players (20%) sustained 483 injuries. No difference was observed in the overall injury rate between the intervention (3.6 injuries/1000 h, confidence interval (CI) 3.2–4.1) and control group (3.7, CI 3.2–4.1; RR=1.0, CI 0.8–1.2; P=0.94) nor in the incidence for any type of injury. During the first 4 months of the season, the training program was used during 60% of the football training sessions, but only 14 out of 58 intervention teams completed more than 20 prevention training sessions. In conclusion, we observed no effect of the injury prevention program on the injury rate, most likely because the compliance with the program was low.
Institutional Reform and Decision-Making Efficiency in the European Union

tional reform. ince the 1970s, legislative activity of the European Union (EU) has expanded greatly in both scale and scope. ' The number of legislative acts adopted by the EU per year increased from less than 300 in the mid-1970s to more than 500 in the mid-1980s. At the same time, the EU gradually extended its competencies to issue areas not explicitly covered by the Treaties of Rome, such as consumer protection, research and development, and the environment. This continuous expansion of EU legislative activity has been accompanied by periodic changes of the EU's institutional framework. The Single European Act (1987) introduced qualified majority voting for a number of policy areas and provided the European Parliament with the ability to influence legislative outcomes. The Treaty on European Union (1993) extended the use of qualified majority voting and strengthened the role of the Parliament in the legislative process. In this article, we analyze whether institutional reform has enabled the EU to deal efficiently with an expanding legislative agenda. A common theme in the literature is that the efficiency of the EU decision-making process has deteriorated considerably as EU legislative activity has increased over the past two decades. A number of studies suggest that the Council is unable to cope with the Commission's legislative output (Scharpf 1988; Sbragia 1993; Dehousse 1995). Other studies point to a dilution in the substantive content of EU legislation (Van den Bos 1994; Heritier 1996; Scharpf 1997). The most common suggestion is that the EU decisionmaking process has become inordinately slow, suffering from an excessive
Proteomics of Arabidopsis Seed Germination. A Comparative Study of Wild-Type and Gibberellin-Deficient Seeds1

We examined the role of gibberellins (GAs) in germination of Arabidopsis seeds by a proteomic approach. For that purpose, we used two systems. The first system consisted of seeds of the GA-deficient ga1 mutant, and the second corresponded to wild-type seeds incubated in paclobutrazol, a specific GA biosynthesis inhibitor. With both systems, radicle protrusion was strictly dependent on exogenous GAs. The proteomic analysis indicated that GAs do not participate in many processes involved in germination sensu stricto (prior to radicle protrusion), as, for example, the initial mobilization of seed protein and lipid reserves. Out of 46 protein changes detected during germination sensu stricto (1 d of incubation on water), only one, corresponding to the cytoskeleton component α-2,4 tubulin, appeared to depend on the action of GAs. An increase in this protein spot was noted for the wild-type seeds but not for thega1 seeds incubated for 1 d on water. In contrast, GAs appeared to be involved, directly or indirectly, in controlling the abundance of several proteins associated with radicle protrusion. This is the case for two isoforms of S-adenosyl-methionine (Ado-Met) synthetase, which catalyzes the formation of Ado-Met from Met and ATP. Owing to the housekeeping functions of Ado-Met, this event is presumably required for germination and seedling establishment, and might represent a major metabolic control of seedling establishment. GAs can also play a role in controlling the abundance of a β-glucosidase, which might be involved in the embryo cell wall loosening needed for cell elongation and radicle extension.
Biomarkers and endosalpingiosis in the ovarian and tubal microenvironment of women at high-risk for pelvic serous carcinoma.

INTRODUCTION BRCA mutations increase the risk for development of high-grade pelvic serous carcinomas. Tissue biomarkers distinguishing women at high-risk (HR) for ovarian cancer from those at low-risk (LR) may provide insights into tumor initiation pathways. METHODS A prospective study of 47 HR women (40% BRCA carriers) undergoing risk-reducing salpingo-oophorectomy and 48 LR controls undergoing salpingo-oophorectomy was performed. Ovarian/tubal tissues were harvested. Immunohistochemical analysis of candidate proteins CSF-1, CSF-1R, ErbB4 is presented, with scores separately analyzed in epithelium and stroma, in ampulla, fimbria, ovary, and ovarian endosalpingiosis (ES). Comparison was performed between HR and LR groups. RESULTS Elevated levels of CSF-1 (p=0.005) or ErbB4 (p=0.005) in the ovarian epithelium, or ErbB4 (p=0.005) in the ovarian stroma, were significantly associated with both the HR status and carrying a BRCA mutation, as was nuclear ErbB4 staining. Ovarian ES, an entity which likely derives from the tubal mucosal epithelium, was also associated with HR (p=0.038) and BRCA mutation status (p=0.011). Among the BRCA carriers only, markers also found association when present in the tube as well as in ovarian ES (p < 0.05). ROCs were generated including in the regression model both CSF-1 and ErbB4 expression levels. A model including CSF-1 in ovarian epithelium, ErbB4 in ovarian stroma, and younger age achieves AUC=0.87 (73% sensitivity, 93% specificity) of detection of the HR status. In BRCA carriers, CSF-1 in ovarian epithelium alone achieves AUC=0.85. CONCLUSIONS Our data suggest that elevated levels of CSF-1/ErbB4 in the adnexae correlate with HR/BRCA carrier status. CSF-1/CSF-1R signaling is active in ovarian cancer progression; our data suggests a role in its initiation. ErbB4, in particular nuclear ErbB4, may have a role in tumor initiation as well. Ovarian ES, an entity which may represent a latent precursor to low-grade pelvic serous carcinomas, was surprisingly associated with both HR status and the BRCA carrier cohort. In line with these findings, both ErbB4 and CSF-1R expression in ovarian ES correlated with carrying a BRCA mutation. This analysis, which needs to be validated, indirectly suggests a potential link between ovarian ES and the development of pelvic serous carcinoma in women who are BRCA mutation carriers.
Understanding the genetic basis of invasiveness

Invasive species provide excellent study systems to evaluate the ecological and evolutionary processes that contribute to the colonization of novel environments. While the ecological processes that contribute to the successful establishment of invasive plants have been studied in detail, investigation of the evolutionary processes involved in successful invasions has only recently received attention. In particular, studies investigating the genomic and gene expression differences between native and introduced populations of invasive species are just beginning and are required if we are to understand how plants become invasive. In the current issue of Molecular Ecology, Hodgins et al. ( ) tackle this unresolved question, by examining gene expression differences between native and introduced populations of annual ragweed, Ambrosia artemisiifolia. The study identifies a number of potential candidate genes based on gene expression differences that may be responsible for the success of annual ragweed in its introduced range. Furthermore, genes involved in stress response are over‐represented in the differentially expressed gene set. Future experiments could use functional studies to test whether changes in gene expression at these candidate genes do in fact underlie changes in growth characteristics and reproductive output observed in this and other invasive species.
Different Perforin Expression in Peripheral Blood and Prostate Tissue in Patients with Benign Prostatic Hyperplasia and Prostate Cancer

Perforin (P) is a prototypical cytotoxic molecule involved in cell‐mediated immunity against various pathogens, alloantigens and particularly different tumours. The purpose of this study was to determine P expression in different lymphocyte subpopulations isolated from peripheral blood and prostate tissue of patients with benign prostatic hyperplasia (BPH) and prostate cancer (PCa) and compare it with the P expression found in the control group. Twenty subjects were recruited in each of the groups. Prostate mononuclear cells of the BPH and PCa tissues were isolated by enzymatic digestion and gradient density centrifugation, whereas peripheral blood mononuclear cells were isolated by gradient density centrifugation alone. Cells and tissue samples were labelled using monoclonal antibodies against P and different surface antigens (CD3, CD4, CD8 and CD56) and analysed by immunofluorescence and flow cytometry. Total P expression in peripheral blood lymphocytes did not differ significantly between BPH/PCa patients and control group, although the BPH and PCa tissue showed lower P expression level. A negative correlation between prostate‐specific antigen levels and the overall percentage of P+, CD3+CD56−P+, and CD3−CD56+P+ cells in the prostate tissue was observed only in patients with PCa. Our findings indicate that the low frequency of P+ lymphocytes, including T, NKT and NK cells, in the prostate tissue of patients with BPH and, particularly, PCa could be the consequence of local tissue microenvironment and one of the mechanisms involved in the pathogenesis of prostate hyperplasia following malignant alteration.
Molecular Studies of an Impetigo Bullosa Epidemic in Full-Term Infants

Background: Carriers ofStaphylococcus aureus strains can be the source of epidemic infection for patients. Objectives: A molecular epidemiological analysis of an impetigo bullosa outbreak in a neonatal ward was performed in order to determine a potential source of the infection and possible routes of subsequent spreading of the epidemic strain. Methods: The genetic relatedness of S. aureus strains isolated from 6 neonates with epidermal lesions and from 21 staff members was verified by the pulsed field gel electrophoresis (PFGE) method. Additionally, detection of eta and etb genes of S. aureus strains using PCR was performed. Results: None of the infected newborns’ mothers was a carrier. Seven strains, 6 isolated from the newborns and 1 taken from a midwife, showed the same restriction pattern, i.e. type A. In the other 20 health care workers colonized with S. aureus, 3 genetic types could be distinguished, i.e. B (2), C (7) and D (2), as well as 9 strains with unique PFGE patterns. The eta gene detected in 7 strains belonged to the genetic type A; there was no etb gene in any of the 27 S. aureus isolates. Conclusions: The presence of the same genetic type A of S. aureus in the infected newborns is a factor which indicates that the impetigo bullosa was a hospital infection. A probable source of the infection was a midwife who was colonized with the same S. aureus type. She was present at the birth of the first infected newborn. Today, molecular methods are essential for prompt recognition of an epidemic and implementation of appropriate infection control strategies.
Brushing Abrasion of Eroded Bovine Enamel Pretreated with Topical Fluorides

Topical fluorides have been proposed for the prevention of erosive dental wear. This study evaluated the in vitro effect of a single professional application of 4% titanium tetrafluoride (TiF4), 1% amine fluoride (AmF) and 0.1% difluorosilane varnish (FV) in preventing wear due to combined erosion and brushing abrasion. One hundred and eight bovine enamel samples were used. Control groups were not pretreated with any product (C), pretreated with a fluoride-free varnish (FV-bl) or pretreated with fluoride varnish and subsequently submitted to varnish removal (FV-r). Wear was modeled by submitting the fluoride-treated and control groups to 3 cycles of the following regimens: erosion/remineralization (er/remin), abrasion/remineralization (abr/remin) or erosion/abrasion/remineralization (er/abr/remin). Erosion was simulated by immersion of the samples for 10 min in citric acid 50 mM (pH 3). Abrasion was carried out for 1 min (200 strokes, load 150 g) in a wear device. Remineralization (2 h artificial saliva) took place between the cycles. Two-way ANOVA showed that there was a significant interaction (p ≤ 0.001) between the fluoride treatments and the wear regimens. Under er/remin a significant wear protective effect was found for the FV, FV-r and FV-bl groups. Abr/remin resulted in some enamel loss for the TiF4 and AmF groups, but the amounts lost were not statistically significant (p = 0.185 and p = 1.000, respectively). Under er/abr/remin all products showed a significant protective effect, except for TiF4. It was concluded that FV and AmF protected bovine enamel against erosion followed by brushing abrasion in vitro.