Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of intestinal M cells and follicle-associated epithelium is regulated by TRAF6-mediated NF-κB signaling

M cells are located in the follicle-associated epithelium (FAE) that covers Peyer’s patches (PPs) and are responsible for the uptake of intestinal antigens. The differentiation of M cells is initiated by receptor activator of NF-&kgr;B. However, the intracellular pathways involved in M cell differentiation are still elusive. In this study, we demonstrate that the NF-&kgr;B pathway activated by RANK is essential for M cell differentiation using in vitro organoid culture. Overexpression of NF-&kgr;B transcription factors enhances the expression of M cell–associated molecules but is not sufficient to complete M cell differentiation. Furthermore, we evaluated the requirement for tumor necrosis factor receptor–associated factor 6 (TRAF6). Conditional deletion of TRAF6 in the intestinal epithelium causes a complete loss of M cells in PPs, resulting in impaired antigen uptake into PPs. In addition, the expression of FAE-associated genes is almost silenced in TRAF6-deficient mice. This study thus demonstrates the crucial role of TRAF6-mediated NF-&kgr;B signaling in the development of M cells and FAE.
Characteristics of the human isoplanatic patch and implications for adaptive optics retinal imaging.

Conventional adaptive optics enables correction of high-order aberrations of the eye, but only for a single retinal point. When imaging extended regions of the retina, aberrations increase away from this point and degrade image quality. The zone over which aberrations do not change significantly is called the "isoplanatic patch. " Literature concerning the human isoplanatic patch is incomplete. We determine foveal isoplanatic patch characteristics by performing Hartmann-Shack aberrometry in 1 deg increments in 8 directions on 7 human eyes. Using these measurements, we establish the correction quality required to yield at least 80% of the potential patch size for a given eye. Single-point correction systems (conventional adaptive optics) and multiple-point correction systems (multiconjugate adaptive optics) are simulated. Results are compared to a model eye. Using the Marechal criterion for 555-nm light, average isoplanatic patch diameter for our subjects is 0.80+/-0.10 deg. The required order of aberration correction depends on desired image quality over the patch. For the more realistically achievable criterion of 0.1 mum root mean square (rms) wavefront error over a 6.0-mm pupil, correction to at least sixth order is recommended for all adaptive optics systems. The most important aberrations to target for a multiconjugate correction are defocus, astigmatism, and coma.
Morphometric analysis of neuronal and glial cell pathology in the caudate nucleus in late-life depression.

OBJECTIVE To assess glial and neuronal density and neuronal volume in two areas of the caudate nucleus in late-life major depression. DESIGN A postmortem study using the disector and nucleator methods to estimate neuronal density and volume and glial density of cells from human brain tissue from the anterior portion (dorsolateral and ventromedial aspects) of the caudate nucleus. SETTING Brain tissues were obtained from the Newcastle Brain Tissue Resource at Newcastle University, UK. PARTICIPANTS The study group consisted of 13 subjects with late-life major depression and nine comparison subjects of similar age. RESULTS Evidence of moderate reductions in neuronal density was found in the depressed group in both the dorsolateral and ventromedial areas of the caudate nucleus. There were no significant changes in glial density or neuronal volume in either area nor was there any evidence of differences in depression in early and late-onset subgroups. CONCLUSIONS Neuroimaging abnormalities in frontal and subcortical areas including ischemic hyperintensities and a reduction in volume and metabolism in the caudate nucleus have been reported in late-life depression, and previous morphometric studies have reported neuronal changes in prefrontal cortical areas. The findings in this study extend these morphometric investigations in late-life depression to the caudate nucleus, suggesting that neuronal abnormalities are present in this subcortical nucleus as well as in these related prefrontal areas.
Hospitalization-associated disability in older adults with valvular heart disease: incidence, risk factors and its association with care processes

Abstract Background: The aim of this study was to determine the incidence and recovery of hospitalisation-associated disability (HAD), the associated risk factors, and the link with care processes in patients aged 70 years or older hospitalised with valvular heart disease (VHD). Methods: Prospective cohort study performed on the cardiology and cardiac surgery units of University Hospitals Leuven, Belgium. HAD was defined as the loss of independence to complete one of the Activities of Daily Living (ADLs) between hospital admission and discharge. Recovery of HAD at 30 days post hospital discharge was achieved when patients recovered their baseline ADL status (2 weeks before hospital admission) (ClinicalTrials.gov: NCT02572999). Results: Eighty patients were enrolled in the study, 77 completed the assessment at discharge and 62 responded at 30 days follow-up. Forty patients (51.9%) developed HAD; 18 of them (45.0%) recovered their baseline ADL status. The risk of HAD increased when patients were physically restrained (relative risk (RR) 1.73, 95% confidence interval (CI) 1.20–2.49), had indwelling catheters (RR 1.80, 95% CI 0.85–3.80) and received preventive pressure ulcer measures (RR 1.71, 95% CI 1.07–2.74). Patients with HAD had longer hospital stays (+3 days, p = .011) and longer use of indwelling catheters (+2 days, p = .024). Conclusion: Half of the older adults with VHD developed HAD. The results indicate a potential association between HAD and care processes, which could be used as quality measures and intervention targets. Validation in larger cohort studies is recommended.
What happened in 1953? The Big Flood in the Netherlands in retrospect

During the weekend of Saturday 31 January to Sunday 1 February 1953, a storm tide raged across the northwest European shelf and flooded the low-lying coastal areas of the countries around the North Sea. The peak high waters occurred during the night and the storm surprised many people in their sleep. The resulting disaster in terms of loss of life and damage to infrastructure was enormous. In the Netherlands, 1836 people fell victim to the flood; in the UK and Belgium, the casualities were 307 and 22, respectively. The large number of fatalities in the Netherlands was related to the fact that much of the affected area is below sea-level. This paper focuses on the case of the Netherlands. It discusses the history of land reclamation, and the fact that living in low-lying areas protected by dykes, often below sea-level, is an accepted fact of life in the Netherlands. The historical approach to dyke maintenance is then outlined, and the state of the dykes in the early twentieth century and after the war is discussed. The characteristics of the storm and the flood are discussed, along with people's experiences of the first hours and days following the flood. The impact of this human stress has often been lasting—many survivors continue to live with daily memories of the flood. Attention is given to the large-scale rescue and relief efforts, the closure of the dykes during the following nine months and the concept of the Delta Plan, designed to prevent such a large-scale disaster ever happening again. Although the 1953 storm was indeed a low probability event leading to very high storm-induced water-levels, and occurred in combination with spring tide, several arguments are presented that explain why this flood turned into a disaster of such a large scale. Equally, the question is raised whether the disaster could have been prevented. The paper concludes by noting the importance of awareness and preparedness in order to prevent a future storm threat of this scale turning into a disaster of the scope of the Big Flood of 1953.
Preparedness of Americans for the Affordable Care Act

Significance The ultimate success of the Affordable Care Act (ACA) depends on how well the health insurance exchanges can bring the benefits of private competition to individuals in the form of lower premiums. Doing so requires that individuals, when shopping for health insurance, correctly weigh the benefits and costs of various insurance options. Our work suggests that the overall population, and even more so those most likely affected by the ACA, is not well equipped to do so. We documented low levels of ACA and health insurance knowledge in the month preceding the introduction of the exchanges. We propose that simplified options, decision aids, and health insurance product design to address the limited understanding of health insurance contracts will be crucial for ACA’s success. This paper investigates whether individuals are sufficiently informed to make reasonable choices in the health insurance exchanges established by the Affordable Care Act (ACA). We document knowledge of health reform, health insurance literacy, and expected changes in healthcare using a nationally representative survey of the US population in the 5 wk before the introduction of the exchanges, with special attention to subgroups most likely to be affected by the ACA. Results suggest that a substantial share of the population is unprepared to navigate the new exchanges. One-half of the respondents did not know about the exchanges, and 42% could not correctly describe a deductible. Those earning 100–250% of federal poverty level (FPL) correctly answered, on average, 4 out of 11 questions about health reform and 4.6 out of 7 questions about health insurance. This compares with 6.1 and 5.9 correct answers, respectively, for those in the top income category (400% of FPL or more). Even after controlling for potential confounders, a low-income person is 31% less likely to score above the median on ACA knowledge questions, and 54% less likely to score above the median on health insurance knowledge than a person in the top income category. Uninsured respondents scored lower on health insurance knowledge, but their knowledge of ACA is similar to the overall population. We propose that simplified options, decision aids, and health insurance product design to address the limited understanding of health insurance contracts will be crucial for ACA’s success.
Validation approach for a fast and simple targeted screening method for 75 antibiotics in meat and aquaculture products using LC-MS/MS

ABSTRACT An approach is described to validate a fast and simple targeted screening method for antibiotic analysis in meat and aquaculture products by LC-MS/MS. The strategy of validation was applied for a panel of 75 antibiotics belonging to different families, i.e., penicillins, cephalosporins, sulfonamides, macrolides, quinolones and phenicols. The samples were extracted once with acetonitrile, concentrated by evaporation and injected into the LC-MS/MS system. The approach chosen for the validation was based on the Community Reference Laboratory (CRL) guidelines for the validation of screening qualitative methods. The aim of the validation was to prove sufficient sensitivity of the method to detect all the targeted antibiotics at the level of interest, generally the maximum residue limit (MRL). A robustness study was also performed to test the influence of different factors. The validation showed that the method is valid to detect and identify 73 antibiotics of the 75 antibiotics studied in meat and aquaculture products at the validation levels.
Glucocorticoid Receptor Activation Inhibits p53-induced Apoptosis of MCF10Amyc Cells via Induction of Protein Kinase Cϵ*

Background: Glucocorticoid receptor (GR) activation can inhibit apoptosis through mechanisms not fully clarified. Results: GR activation induced PKCϵ expression and protected MCF10A-myc cells from p53-dependent apoptosis. PKCϵ silencing reversed the protective effect of GR. Conclusion: Activated GR can inhibit p53-dependent apoptosis through induction of PKCϵ. Significance: The results demonstrate PKCϵ plays an important role in the signaling pathway activated during GR-induced inhibition of apoptosis. Glucocorticoid receptor (GR) is a ligand-dependent transcription factor that can promote apoptosis or survival in a cell-specific manner. Activated GR has been reported to inhibit apoptosis in mammary epithelial cells and breast cancer cells by increasing pro-survival gene expression. In this study, activated GR inhibited p53-dependent apoptosis in MCF10A cells and human mammary epithelial cells that overexpress the MYC oncogene. Specifically, GR agonists hydrocortisone or dexamethasone inhibited p53-dependent apoptosis induced by cisplatin, ionizing radiation, or the MDM2 antagonist Nutlin-3. In contrast, the GR antagonist RU486 sensitized the cells to apoptosis by these agents. Apoptosis inhibition was associated with maintenance of mitochondrial membrane potential, diminished caspase-3 and -7 activation, and increased expression at both the mRNA and protein level of the anti-apoptotic PKC family member PKCϵ. Knockdown of PKCϵ via siRNA targeting reversed the protective effect of dexamethasone and restored apoptosis sensitivity. These data provide evidence that activated GR can inhibit p53-dependent apoptosis through induction of the anti-apoptotic factor PKCϵ.
The Journal Impact Factor: don't expect its demise any time soon

Abstract Much emphasis continues to be placed on the Journal Impact Factor (IF), a measure of journal article citation rates, and typically used as a surrogate marker of quality of both the article and journal. The IF is both revered and reviled, and is neither a perfect nor comprehensive measure, having several limitations and being subject to easy manipulation. The IF holds ‘power’ for journals because it can influence their future success. Furthermore, the perceived utility of the IF has grown way beyond that of its original and still popular use as a surrogate marker of publication ‘quality’. The IF is increasingly being used (i) to objectively evaluate the scientific and academic value of scientists across a wide variety of disciplines, (ii) to short-list research projects for future financial support, (iii) to short-list or select applicants for academic promotion, and (iv) by researchers to measure the success of research institutes, research funding, or even entire countries. Accordingly, despite our love-hate relationship with the IF, don't expect its demise any time soon. Clin Chem Lab Med 2009;47:1319–24.
Cordyceps militaris Enhances Cell-Mediated Immunity in Healthy Korean Men.

Cordyceps militaris is a mushroom traditionally used for diverse pharmaceutical purposes in East Asia, including China, and has been found to be effective for enhancing immunity through various types of animal testing. The aim of this study is to determine the efficacy of C. militaris for enhancing cell-mediated immunity and its safety in healthy male adults. Healthy male adults were divided into the experimental group (n = 39), given 1.5 g/day of ethanol treated C. militaris in capsules, and the control group (n = 40), given the same number of identical placebo capsules filled with microcrystalline cellulose and lactose for 4 weeks from February 13 to March 14, 2012; the natural killer (NK) cell activity, lymphocyte proliferation index (PI), and T-helper cell 1 (Th1) cytokine cluster (interferon [IFN]-γ, interleukin [IL]-12, IL-2, and tumor necrosis factor [TNF]-α) were measured, along with stability test, at weeks 0, 2, and 4. The C. militaris group showed a statistically significant greater increase in NK200 (P = .0010), lymphocyte PI (P ≤ .0001), IL-2 (P = .0096), and IFN-γ (P = .0126), compared with the basal level, than the placebo group. There was no statistically significant adverse reaction. C. militaris enhanced the NK cell activity and lymphocyte proliferation and partially increased Th1 cytokine secretion. Therefore, C. militaris is safe and effective for enhancing cell-mediated immunity of healthy male adults.
Phosphorylation of Extracellular Matrix Tenascin-X Detected by Differential Mass Tagging Followed by NanoLC-MALDI-TOF/TOF-MS/MS Using ProteinPilot Software

Reversible protein phosphorylation represents a major mechanism of signal transduction in a variety of cellular functions. An understanding of proteome-wide phosphorylation dynamics is important to obtain an overview of the whole signal transduction network. However, a systematic analysis for differentially expressed phosphoproteins under serum-stimulated response is lacking. Here, an easy and fast approach for the identification of differentially expressed phosphoproteins was used. After enrichment of phosphoproteins from serum-stimulated cell lysates by immobilized metal affinity chromatography, a quantitative proteomic approach with isobaric tag for absolute and relative quantitation labeling in combination with nanoLC-MALDI-TOF/TOF-MS/MS followed by ProteinPilot analysis was used. Consequently, 506 differentially expressed phosphoproteins were identified. Among them, 22 proteins that had a reproducible phosphorylation site at Ser or Thr were identified. Out of these 22 phosphoproteins, 7 are mainly involved in splicing. Among the 22 proteins, it was found that extracellular matrix tenascin-X is phosphorylated, although there is little quantitative change by the serum stimulation. MS/MS analysis revealed a novel phosphorylation site of tenascin-X, Thr1841, located in the loop region between the 10th and 11th fibronectin type III repeats. The phosphorylation of tenascin-X would be considered in clarifying its function in the future.
[The Marburg Rating Scale for Asperger's Syndrome (MBAS)--a screening instrument for high-functioning autistic disorders].

OBJECTIVES Asperger's Syndrome is a disorder of uncertain nosological validity, which is difficult to differentiate from high-functioning autism. Even today these disorders are unfortunately diagnosed very late, often in the wake of earlier, different diagnoses. The purpose of this study is to present a screening instrument (MBAS), which is sensitive to these disorders. METHODS The instrument was tested among a total of 91 probands (44 of whom had been diagnosed as autistic, and 47 of whom had been diagnosed with a non-autistic disorder). RESULTS The items on the MBAS were of average difficulty; generally, the all item-total correlation was good. The total scale has an internal consistency of Cronbach's alpha = . 91 and the convergent validity of the MBAS and the ADI-R reached r = . 61 (p = .001). The total score of the questionnaire discriminated highly significantly between the group with autism and that without. At a sensitivity of 95.5% and a specificity of 95.7% the number of misclassifications is low. False negative classifications occurred only in the case of very young children. CONCLUSIONS The MBAS is a reliable and valid instrument for screening and generating tentative diagnoses of high-functioning autism. The questionnaire is well suited for the selection and generation of tentative diagnoses of autism on a high-functioning level.
Idiosyncratic risk and the cross-section of European real estate equity returns

Purpose – This study is the first to examine the role of idiosyncratic risk in the pricing of European real estate equities. The capital asset pricing model predicts that in equilibrium, investors should hold the market portfolio. As a result, investors should only be rewarded for carrying undiversifiable systematic risk and not for diversifiable idiosyncratic risk. The study is adding to the growing body of countering studies by first examining time trends of idiosyncratic risk and subsequently the pricing of idiosyncratic risk in European real estate equities. The paper aims to discuss these issues. Design/methodology/approach – The study analyses 293 real estate equities from 16 European capital markets over the 1991-2011 period. The framework of Fama and MacBeth is employed. Regressions of the cross-section of expected equity excess returns on idiosyncratic risk and other firm characteristics such as beta, size, book-to-market equity (BE/ME), momentum, liquidity and co-skewness are performed. Due to r.
Shrinkage Estimators for Covariance Matrices

Summary. Estimation of covariance matrices in small samples has been studied by many authors. Standard estimators, like the unstructured maximum likelihood estimator (ML) or restricted maximum likelihood (REML) estimator, can be very unstable with the smallest estimated eigenvalues being too small and the largest too big. A standard approach to more stably estimating the matrix in small samples is to compute the ML or REML estimator under some simple structure that involves estimation of fewer parameters, such as compound symmetry or independence. However, these estimators will not be consistent unless the hypothesized structure is correct. If interest focuses on estimation of regression coefficients with correlated (or longitudinal) data, a sandwich estimator of the covariance matrix may be used to provide standard errors for the estimated coefficients that are robust in the sense that they remain consistent under misspecification of the covariance structure. With large matrices, however, the inefficiency of the sandwich estimator becomes worrisome. We consider here two general shrinkage approaches to estimating the covariance matrix and regression coefficients. The first involves shrinking the eigenvalues of the unstructured ML or REML estimator. The second involves shrinking an unstructured estimator toward a structured estimator. For both cases, the data determine the amount of shrinkage. These estimators are consistent and give consistent and asymptotically efficient estimates for regression coefficients. Simulations show the improved operating characteristics of the shrinkage estimators of the covariance matrix and the regression coefficients in finite samples. The final estimator chosen includes a combination of both shrinkage approaches, i.e., shrinking the eigenvalues and then shrinking toward structure. We illustrate our approach on a sleep EEG study that requires estimation of a 24 x 24 covariance matrix and for which inferences on mean parameters critically depend on the covariance estimator chosen. We recommend making inference using a particular shrinkage estimator that provides a reasonable compromise between structured and unstructured estimators.
Phosphinothricin Tripeptide Synthetases in Streptomyces viridochromogenes Tü494

ABSTRACT The tripeptide backbone of phosphinothricin (PT) tripeptide (PTT), a compound with herbicidal activity from Streptomyces viridochromogenes, is assembled by three stand-alone peptide synthetase modules. The enzyme PhsA (66 kDa) recruits the PT-precursor N-acetyl-demethylphosphinothricin (N-Ac-DMPT), whereas the two alanine residues of PTT are assembled by the enzymes PhsB and PhsC (129 and 119 kDa, respectively). During or after assembly, the N-Ac-DMPT residue in the peptide is converted to PT by methylation and deacetylation. Both phsB and phsC appear to be cotranscribed together with two other genes from a single promoter and they are located at a distance of 20 kb from the gene phsA, encoding PhsA, in the PTT biosynthesis gene cluster of S. viridochromogenes. PhsB and PhsC represent single nonribosomal peptide synthetase elongation modules lacking a thioesterase domain. Gene inactivations, genetic complementations, determinations of substrate specificity of the heterologously produced proteins, and comparison of PhsC sequence with the amino terminus of the alanine-activating nonribosomal peptide synthetase PTTSII from S. viridochromogenes confirmed the role of the two genes in the bialanylation of Ac-DMPT. The lack of an integral thioesterase domain in the PTT assembly system points to product release possibly involving two type II thioesterase genes (the1 and the2) located in the PTT gene cluster alone or in conjunction with an as yet unknown mechanism of product release.