Linear β-reduction

Linear head reduction is a key tool for the analysis of reduction machines for lambda-calculus and for game semantics. Its definition requires a notion of redex at a distance named primary redex in the literature. Nevertheless, a clear and complete syntactic analysis of this rule is missing. We present here a general notion of beta-reduction at a distance and of linear reduction (i.e., not restricted to the head variable), and we analyse their relations and properties. This analysis rests on a variant of the so-called sigma-equivalence that is more suitable for the analysis of reduction machines, since the position along the spine of primary redexes is not permuted. We finally show that, in the simply typed case, the proof of strong normalisation of linear reduction can be obtained by a trivial tuning of Gandy's proof for strong normalisation of beta-reduction

The effect of atorvastatin on pancreatic beta cell requirement in women with polycystic ovary syndrome

Background There is an increased risk of developing T2DM in women with polycystic ovary syndrome (PCOS) and there is evidence that statins improve metabolic parameters in these patients. However, there is some data to show that statins increase the risk of incipient diabetes. Material and Methods We have previously shown that 12-weeks of atorvastatin improves insulin resistance when measured using HOMA-IR. This post hoc-analysis was designed to look at the effect of atorvastatin on pancreatic β cell function using HOMA-β in the same study. In this randomised, double blind placebo controlled study, 40 medication naïve patients with PCOS were randomized to either atorvastatin 20 mg daily or placebo for 3 months. A 3-month extension study for both groups of patients was undertaken with metformin 1500 mg daily after completing initial 3 months of atorvastatin or placebo. Results There was a significant reduction in HOMA-β (240±3.2vs.177±2.3; pvalue<0.01) after 12 weeks of atorvastatin treatment which was maintained by metformin in the subsequent 12 weeks. There were no changes in HOMA-β after the placebo or after subsequent metformin treatment. There was no linear correlation between reduction in HOMA-β with improvement of free androgen index (FAI) (r2=0.02;p=0.72), testosterone (r2=0.13;p=0.49), SHBG (r2=0.22;p=0.48), hsCRP (r2=0.19;p=0.64), triglycerides (r2=0.09;p=0.12), total cholesterol (r2=0.11;p=0.32) or LDL-C (r2=0.19;p=0.38). Conclusion Treatment with atorvastatin for 12 weeks in women with PCOS significantly reduced HOMA-β. This could be potentially due to fall in βcell requirement with improvement of insulin resistance rather than a reduction of βcell function

Capturing health and eating status through a nutritional perception screening questionnaire (NPSQ9) in a randomised internet-based personalised nutrition intervention : the Food4Me study

BACKGROUND: National guidelines emphasize healthy eating to promote wellbeing and prevention of non-communicable diseases. The perceived healthiness of food is determined by many factors affecting food intake. A positive perception of healthy eating has been shown to be associated with greater diet quality. Internet-based methodologies allow contact with large populations. Our present study aims to design and evaluate a short nutritional perception questionnaire, to be used as a screening tool for assessing nutritional status, and to predict an optimal level of personalisation in nutritional advice delivered via the Internet. METHODS: Data from all participants who were screened and then enrolled into the Food4Me proof-of-principle study (n = 2369) were used to determine the optimal items for inclusion in a novel screening tool, the Nutritional Perception Screening Questionnaire-9 (NPSQ9). Exploratory and confirmatory factor analyses were performed on anthropometric and biochemical data and on dietary indices acquired from participants who had completed the Food4Me dietary intervention (n = 1153). Baseline and intervention data were analysed using linear regression and linear mixed regression, respectively. RESULTS: A final model with 9 NPSQ items was validated against the dietary intervention data. NPSQ9 scores were inversely associated with BMI (β = -0.181, p < 0.001) and waist circumference (Β = -0.155, p < 0.001), and positively associated with total carotenoids (β = 0.198, p < 0.001), omega-3 fatty acid index (β = 0.155, p < 0.001), Healthy Eating Index (HEI) (β = 0.299, p < 0.001) and Mediterranean Diet Score (MDS) (β = 0. 279, p < 0.001). Findings from the longitudinal intervention study showed a greater reduction in BMI and improved dietary indices among participants with lower NPSQ9 scores. CONCLUSIONS: Healthy eating perceptions and dietary habits captured by the NPSQ9 score, based on nine questionnaire items, were associated with reduced body weight and improved diet quality. Likewise, participants with a lower score achieved greater health improvements than those with higher scores, in response to personalised advice, suggesting that NPSQ9 may be used for early evaluation of nutritional status and to tailor nutritional advice. TRIAL REGISTRATION: NCT01530139 .Peer reviewedFinal Published versio

CSF protein biomarkers predicting longitudinal reduction of CSF β-amyloid42 in cognitively healthy elders.

β-amyloid (Aβ) plaque accumulation is a hallmark of Alzheimer's disease (AD). It is believed to start many years prior to symptoms and is reflected by reduced cerebrospinal fluid (CSF) levels of the peptide Aβ1-42 (Aβ42). Here we tested the hypothesis that baseline levels of CSF proteins involved in microglia activity, synaptic function and Aβ metabolism predict the development of Aβ plaques, assessed by longitudinal CSF Aβ42 decrease in cognitively healthy people. Forty-six healthy people with three to four serial CSF samples were included (mean follow-up 3 years, range 2-4 years). There was an overall reduction in Aβ42 from a mean concentration of 211-195 pg ml(-1) after 4 years. Linear mixed-effects models using longitudinal Aβ42 as the response variable, and baseline proteins as explanatory variables (n=69 proteins potentially relevant for Aβ metabolism, microglia or synaptic/neuronal function), identified 10 proteins with significant effects on longitudinal Aβ42. The most significant proteins were angiotensin-converting enzyme (ACE, P=0.009), Chromogranin A (CgA, P=0.009) and Axl receptor tyrosine kinase (AXL, P=0.009). Receiver-operating characteristic analysis identified 11 proteins with significant effects on longitudinal Aβ42 (largely overlapping with the proteins identified by linear mixed-effects models). Several proteins (including ACE, CgA and AXL) were associated with Aβ42 reduction only in subjects with normal baseline Aβ42, and not in subjects with reduced baseline Aβ42. We conclude that baseline CSF proteins related to Aβ metabolism, microglia activity or synapses predict longitudinal Aβ42 reduction in cognitively healthy elders. The finding that some proteins only predict Aβ42 reduction in subjects with normal baseline Aβ42 suggest that they predict future development of the brain Aβ pathology at the earliest stages of AD, prior to widespread development of Aβ plaques

Bgs1p is responsible for primary septum formation

[EN]Cytokinesis is a crucial event in the cell cycle of all living cells. In fungal cells, it requires coordinated contraction of an actomyosin ring and synthesis of both plasmatic membrane and a septum structure that will constitute the new cell wall end. Schizosaccharomyces pombe contains four essential putative (1,3)β-D-glucan synthase catalytic subunits, Bgs1p to Bgs4p. Here we examined the function of Bgs1p in septation by studying the lethal phenotypes of bgs1 + shut-off and bgs1 Δ cells and demonstrated that Bgs1p is responsible and essential for linear (1,3)β-D-glucan and primary septum formation. bgs1 + shut-off generates a more than 300-fold Bgs1p reduction, but the septa still present large amounts of disorganized linear (1,3)β-D-glucan and partial primary septa. Conversely, both structures are absent in bgs1 Δ cells, where there is no Bgs1p. The septum analysis of bgs1+-repressed cells indicates that linear (1,3)β-D-glucan is necessary but not sufficient for primary septum formation. Linear (1,3)β-D-glucan is the polysaccharide that specifically interacts with the fluorochrome Calcofluor white in fission yeast. We also show that in the absence of Bgs1p abnormal septa are formed, but the cells cannot separate and eventually die

A parametric study on creep-fatigue strength of welded joints using the linear matching method

This paper presents a parametric study on creep-fatigue strength of the steel AISI type 316N(L) weldments of types 1 and 2 according to R5 Vol. 2/3 Procedure classification at 550◦C. The study is implemented using the Linear Matching Method (LMM) and is based upon a latest developed creep-fatigue evaluation procedure considering time fraction rule for creep-damage assessment. Parametric models of geometry and FE-meshes for both types of weldments are developed in this way, which allows variation of parameters governing shape of the weld profile and loading conditions. Five configurations, characterised by individual sets of parameters, and presenting different fabrication cases, are proposed. For each configuration, the total number of cycles to failure N⋆ in creep-fatigue conditions is assessed numerically for different loading cases including normalised bending moment M and dwell period t. The obtained set of N⋆ is extrapolated by the analytic function, which is dependent on M, t and geometrical parameters (α and β). Proposed function for N⋆ shows good agreement with numerical results obtained by the LMM. Thus, it is used for the identification of Fatigue Strength Reduction Factors (FSRFs) intended for design purposes and dependent on t, α, β

З досвіду застосування активного індуктивного моделювання до прогнозування цін

This paper shortly considers the next topics: (1) problem of unstability in linear modelling; (2) factor analysis and stabilization; method of two thresholds (MTT), or (β, γ)-method; (3) stabilization principle; the hypothesis about essence of GMDH; (4) economic criteria of forecast models; (5) active agent models; cycles of absorption and reduction. On some examples we demonstrate the advantage of MTT over known methods GAME and GMDH

Increasing smoking intensity is associated with increased disease activity in axial spondyloarthritis.

A history of ever-smoking appears to be associated with a more severe disease phenotype in axial spondyloarthritis (axSpA). However, evidence is sparse for the effect of increased smoking exposure on disease outcomes or whether smoking reduction or cessation improves outcomes. The aim of this study was to explore whether a dose-response relationship exists between pack-years and disease activity and functional impairment in axSpA. Consecutive patients meeting ASAS criteria for axial SpA were recruited from a spondyloarthritis service. The associations between pack-years of smoking and: (1) disease activity (BASDAI/ASDAS), (2) spinal pain, (3) functional impairment (BASFI) and (4) inflammatory markers were explored using multivariable linear models, adjusted for age, gender and use of TNF inhibition (TNFi) therapy. Pack-years were categorised into four groups (40) and analysed with light smoking (40, β = 2.6 (0.54, 3.56)), higher BASFI (21-40, β = 2.1 (0.42, 4.80); >40, β = 3.2 (0.76, 5.71)), and higher ASDAS (21-40, β = 0.82 (0.14, 1.51)). This cross-sectional study demonstrated that smoking is associated with increased axSpA severity markers in a dose-response manner. Particular effort should be made to restrict smoking exposure early before accruing a significant number of pack-years

The impact of structural integrity and route of administration on the antibody specificity against three cow's milk allergens - a study in Brown Norway rats.

BACKGROUND: Characterisation of the specific antibody response, including the epitope binding pattern, is an essential task for understanding the molecular mechanisms of food allergy. Examination of antibody formation in a controlled environment requires animal models. The purpose of this study was to examine the amount and types of antibodies raised against three cow’s milk allergens; β-lactoglobulin (BLG), α-lactalbumin (ALA) and β-casein upon oral or intraperitoneal (i.p.) administration. A special focus was given to the relative amount of antibodies raised against linear versus conformational epitopes. METHODS: Specific antibodies were raised in Brown Norway (BN) rats. BN rats were dosed either (1) i.p. with the purified native cow’s milk allergens or (2) orally with skimmed milk powder (SMP) alone or together with gluten, without the use of adjuvants. The allergens were denatured by reduction and alkylation, resulting in unfolding of the primary structure and a consequential loss of conformational epitopes. The specific IgG1 and IgE responses were analysed against both the native and denatured form of the three cow’s milk allergens, thus allowing examination of the relative amount of linear versus conformational epitopes. RESULTS: The inherent capacity to induce specific IgG1 and IgE antibodies were rather similar upon i.p. administration for the three cow’s milk allergens, with BLG = ALA > β-casein. Larger differences were found between the allergens upon oral administration, with BLG > ALA > β-casein. Co-administration of SMP and gluten had a great impact on the specific antibody response, resulting in a significant reduced amount of antibodies. Together results indicated that most antibodies were raised against conformational epitopes irrespectively of the administration route, though the relative proportions between linear and conformational epitopes differed remarkably between the allergens. CONCLUSIONS: This study showed that the three-dimensional (3D) structure has a significant impact on the antibodies raised for both systemic and orally administered allergens. A remarkable difference in the antibody binding patterns against linear and conformational epitope was seen between the allergens, indicating that the structural characteristics of proteins may heavily affect the induced antibody response

Pressure-induced insulating state in an organic superconductor

The electronic-transport properties of the quasi-two-dimensional organic superconductor β″–(BEDT-TTF)₂SF₅CH₂CF₂SO₃, where BEDT-TTF stands for bisethylenedithio-tetrathiafulvalene, have been investigated in magnetic fields up to 15 T and under hydrostatic pressure up to about 14 kbars. Shubnikov–de Haas data reveal a nonmonotonic pressure dependence of the holelike Fermi surface, a roughly linear increase of the electron g factor, and an approximately linear decrease of the cyclotron effective mass. By assuming that the latter reflects the pressure-induced reduction of the superconducting coupling parameter λ the rapid reduction of the superconducting transition temperature Tc(p) can be reasonably well described by the modified McMillan equation. Above about 12 kbars the material becomes insulating with an activated resistive behavior. This first-order metal-insulator transition has a hysteresis of about 3 kbars. This unexpected behavior is assumed to be of structural origin, although clear changes of electronic band-structure properties precede the phase transition