Miracle-dz/UniFAR-FTUs huggingface dataset:
Foxl1‐Cre BAC transgenic mice: a new tool for gene ablation in the gastrointestinal mesenchyme

The use of Cre‐loxP technology for the purpose of cell type‐specific gene ablation has revolutionized developmental biology and biomedicine. Several transgenic mouse lines have been developed for the analysis of gene function in the gastrointestinal tract, but in all of these the expression of Cre is limited to the epithelial cell layer. No Cre‐ expressing transgenic mouse lines (“Cre lines”) exist for the deletion of loxP‐flanked genes specifically in gut mesoderm. To address this deficiency, we have derived a bacterial artificial chromosome based transgenic mouse line in which the Cre gene is controlled by the Foxl1 promoter and enhancer elements. X‐Gal staining of Foxl1‐Cre; Rosa26R bi‐transgenic lines confirm that Foxl1‐Cre results in recombination specifically in the gastrointestinal mesenchyme. The Foxl1‐Cre line will facilitate the dissection of mesenchymal to epithelial signaling that is known to play a major role in the patterning and function of the gastrointestinal tract. genesis 45:518–522, 2007. Published 2007 Wiley‐Liss, Inc.
General practitioners, complementary therapies and evidence-based medicine: the defence of clinical autonomy.

Amidst the substantial change currently gripping primary health care are two developments central to contemporary debate regarding the very nature, territory and identity of general practice - the integration of complementary and alternative medicine (CAM) and the rise of evidence-based medicine (EBM). This paper reports findings from a study based upon 25 in-depth interviews with general practitioners (GPs) personally practising complementary therapies alongside more conventional medicine to treat their NHS patients. The paper outlines the GPs' perceptions of EBM, its relationship to their personal development of CAM, and their notions of good clinical practice more generally. Analysis of the GPs' accounts demonstrates how CAM can be seen as a useful resource with which some GPs defend their clinical autonomy from what they perceive to be the threat of EBM.
The influence of entrepreneur’s personal characteristics on MSEs growth through innovation

ABSTRACT Research in the separate areas of innovation and growth has considerably intensified in recent years. However, little scholarly attention has been paid to the entrepreneurs’ personal characteristics that might explain the growth of micro and small enterprises (MSEs) through innovation. This study examines the key entrepreneurs’ personal characteristics affecting micro and small enterprises (MSEs) upgrading, defined here as substantial growth through innovation. Six major determining types of entrepreneurs’ characteristics were identified from the innovation and the growth literature: education, work experience, gender, motivations, nationality and age. The empirical results which are based on t-tests of the differences between upgraders and non-upgraders, the linear probability model and the logit model, all suggest that work experience and motivations are cornerstones in the likelihood that an MSE will upgrade. The policy implications of this study on promoting MSEs upgrading are also discussed.
Behavior of a brushless doubly-fed induction generator with a rotating power electronic converter during symmetrical voltage sags

Impact of the different magnitudes of symmetrical voltage dip on the performance of a Rotating Power Electronic Brushless Doubly-Fed Induction Generator is presented. This type of topology consists of a doubly-fed induction generator with power electronic converter and an integrated exciter mounted on the shaft and rotating with it. The transient simulation study is carried out in order to investigate the magnitude of the voltage dip the rotor converters can withstand before a protection scheme is needed for Low Voltage Ride Through (LVRT) of the generator. Furthermore, successful LVRT under severe voltage dips is also performed using passive resistive network strategy.
Nucleotide sequence of the Wolinella succinogenes flagellin, which contains in the antigenic domain two conserved regions also present in Campylobacter spp. and Helicobacter pylori

Wolinella succinogenes possesses one polar flagellum, which shows a characteristic surface pattern of parallel lines along the axis of the filament in electron microscopic images. We determined the gene sequence of the Wolinella flagellin, which is, as in most other bacteria, the only structural component of the filament. Sequence comparison with other members of the Proteobacteria revealed two highly conserved regions in the central part of the flagellin molecule among Campylobacter spp. and Helicobacter pylori, an area that had previously been described as highly variable. Similar surface patterns are found in related polarly flagellated bacteria, but not in Escherichia coli and Bacillus subtilis, which also lack these conserved regions.
Morphable Face Models - An Open Framework

In this paper, we present a novel open-source pipeline for face registration based on Gaussian processes as well as an application to face image analysis. Non-rigid registration of faces is significant for many applications in computer vision, such as the construction of 3D Morphable face models (3DMMs). Gaussian Process Morphable Models (GPMMs) unify a variety of non-rigid deformation models with B-splines and PCA models as examples. GPMM separate problem specific requirements from the registration algorithm by incorporating domain-specific adaptions as a prior model. The novelties of this paper are the following: (i) We present a strategy and modeling technique for face registration that considers symmetry, multi-scale and spatially-varying details. The registration is applied to neutral faces and facial expressions. (ii) We release an open-source software framework for registration model-building demonstrated on the publicly available BU3D-FE database. The released pipeline also contains an implementation of an Analysis-by-Synthesis model adaption of 2D face images, tested on the Multi-PIE and LFW database. This enables the community to reproduce, evaluate and compare the individual steps of registration to model-building and 3D/2D model fitting. (iii) Along with the framework release, we publish a new version of the Basel Face Model (BFM-2017) with an improved age distribution and an additional facial expression model.
Medulloblastoma Variants: Age-Dependent Occurrence and Relation to Gorlin Syndrome—A New Clinical Perspective

Purpose: We aimed to test the hypothesis that medulloblastoma (MB) variants show a different age distribution and clinical behavior reflecting their specific biology, and that MB occurring at very young age is associated with cancer predisposition syndromes such as Gorlin syndrome (GS). Experimental Design: We investigated the frequency, age distribution, location, response to treatment, outcome, and association with familial cancer predisposition syndromes in a series of 82 cases of MB in patients ages <14 years diagnosed at the Giannina Gaslini Children's Hospital, Genoa, between 1987 and 2004. Results: Desmoplastic MB and MB with extensive nodularity (MBEN), were present in 22 of 82 cases (27%) and were more frequent in children ages ≤3 years (13 of 25; 52%). In this age group, MBEN was significantly more frequent than desmoplastic MB and classic MB (P < 0.001) and had a good prognosis. MBEN was associated with GS in 5 of 12 cases. Overall, 8 cases occurred in the context of familial tumor predisposition syndromes (5 GS, 1 each NF1, Li-Fraumeni, and Fragile X) and 7 of these patients were ages ≤3 years at diagnosis. Desmoplastic histology and a more intensive treatment represented independent favorable prognostic factors in multivariate analysis (P = 0.003 and P = 0.0139, respectively). Metastasis was a predictor of bad outcome (P = 0.0001). Conclusions: Our data indicate that biologically different MB entities warrant risk-adapted treatment and that MBEN is strongly associated with GS. Patients, ages ≤3 years, with MB and their families should be investigated for tumor predisposition syndromes such as GS.
Deadlines and Matching

Deadlines and fixed end dates are pervasive in matching markets including school choice, the market for new graduates, and even financial markets such as the market for federal funds. Deadlines drive fundamental non-stationarity and complexity in behavior, generating significant departures from the steady-state equilibria usually studied in the search and matching literature. I consider a two-sided matching market with search frictions where vertically differentiated agents attempt to form bilateral matches before a deadline. I give conditions for existence and uniqueness of equilibria, and show that all equilibria exhibit an "anticipation effect" where less attractive agents become increasingly choosy over time, preferring to wait for the opportunity to match with attractive agents who, in turn, become less selective as the deadline approaches. When payoffs accrue after the deadline, or agents do not discount, a sharp characterization is available: at any point in time, the market is segmented into a first class of matching agents and a second class of waiting agents. This points to a different interpretation of unraveling observed in some markets and provides a benchmark for other studies of non-stationary matching. A simple intervention -- a small participation cost -- can dramatically improve efficiency.
Cholera toxin: A paradigm for multi-functional engagement of cellular mechanisms (Review)

Cholera toxin (Ctx) from Vibrio cholerae and its closely related homologue, heat-labile enterotoxin (Etx) from Escherichia coli have become superb tools for illuminating pathways of cellular trafficking and immune cell function. These bacterial protein toxins should be viewed as conglomerates of highly evolved, multi-functional elements equipped to engage the trafficking and signalling machineries of cells. Ctx and Etx are members of a larger family of A-B toxins of bacterial (and plant) origin that are comprised of structurally and functionally distinct enzymatically active A and receptor-binding B sub-units or domains. Intoxication of mammalian cells by Ctx and Etx involves B pentamer-mediated receptor binding and entry into a vesicular pathway, followed by translocation of the enzymatic A1 domain of the A sub-unit into the target cell cytosol, where covalent modification of intracellular targets leads to activation of adenylate cyclase and a sequence of events culminating in life-threatening diarrhoeal disease. Importantly, Ctx and Etx also have the capacity to induce a wide spectrum of remarkable immunological processes. With respect to the latter, it has been found that these toxins activate signalling pathways that modulate the immune system. This review explores the complexities of the cellular interactions that are engaged by these bacterial protein toxins, and highlights some of the new insights to have recently emerged.
Beryllium-10 from the Sun

Beryllium-10 (10Be) in excess of that expected from in situ cosmic ray spallation reactions is present in lunar surface soil 78481; its presence was revealed with a sequential leaching technique. This excess 10Be, representing only 0.7 to 1.1% of the total 10Be inventory, is associated with surface layers (<1 micrometer) of the mineral grains composing 78481. This excess10Be and its association with surficial layers corresponds to (1.9 ± 0.8) × 108 atoms per square centimeter, requiring a 10Be implantation rate of (2.9 ± 1.2) × 10−6 atoms per square centimeter per second on the surface of the Moon. The most likely site for the production of this excess 10Be is the Sun's atmosphere. The 10Be is entrained into the solar wind and transported to the lunar surface.
Enhanced Antiviral Benefit of Combination Therapy with Lamivudine and Alpha Interferon against WHV Replication in Chronic Carrier Woodchucks

Cell culture studies in our laboratory previously demonstrated synergistic antiviral activity for the combinations of lamivudine and a novel recombinant hybrid human alpha B/D interferon (rHuαB/D IFN) against hepatitis B virus (HBV) replication. Based on these results, a study was designed to determine if an enhanced antiviral effect with this drug combination could be demonstrated in vivo using the woodchuck hepatitis virus (WHV)/woodchuck experimental model of chronic HBV infection. Both antiviral agents have been shown to be effective against WHV replication in WHV chronic carriers during previous studies by our laboratories. Two combination treatment regimens were compared to matched monotherapies in a placebo-controlled trial. The first used simultaneous administration of rHuαB/D IFN and lamivudine for 24 weeks. The other combination treatment regimen used a staggered dosing schedule of 12 weeks of administration of lamivudine alone, followed by 12 weeks of simultaneous dosing with both drugs, followed by 12 weeks of therapy with rHuαB/D IFN alone. Both treatment regimens with combinations of lamivudine and rHuαB/D IFN were more effective at reducing WHV replication in chronically infected wood-chucks than the corresponding monotherapies. Both combination treatments produced antiviral effects that were at least equal to that expected for additive activity based on estimations generated by Bliss Independence calculations. The staggered treatment regimen reduced viraemia and intrahepatic WHV replication significantly more than that expected for additive interactions, indicating synergistic antiviral effects. These studies demonstrate that combination therapy of chronic WHV infection has enhanced antiviral benefit over corresponding monotherapies and indicate that combination treatment of chronic HBV infection can be superior to therapies using a single antiviral agent.
Interrelations between fibromyalgia, thyroid autoantibodies, and depression.

OBJECTIVE To detect and quantify the association between fibromyalgia (FM) and thyroid autoimmunity. METHODS This cross-sectional study comprised 146 women with FM and 74 case-controls, all 18 years of age or older. FM was diagnosed according to the American College of Rheumatology 1990 classification criteria. The Mini-International Neuropsychiatric Interview (MINI) was applied for the diagnosis of depression, previously considered as an important confounding factor. Thyroid autoimmunity was defined as the occurrence of detectable antithyroid peroxidase antibodies and/or antithyroglobulin antibodies by the immunometric assay. Cases of diffuse connective tissue diseases and thyroid dysfunctions (hypo or hyperthyroidism) were excluded in both groups. RESULTS Univariate analysis detected an association between FM and thyroid autoimmunity (odds ratio, OR = 3.87, 95% confidence interval, CI = 1.54-10.13), depression (OR = 3.94, 95% CI = 1.97-7.93), and age (OR = 1.04, 95% CI = 1.01-1.07). In the final logistic regression model, after adjustment for depression and age, the association between FM and thyroid autoimmunity was strengthened (OR = 4.52, 95% CI = 1.86-11.0). CONCLUSION Our results suggest an association between FM and thyroid autoimmunity.
CX3CR1+ CD8α+ dendritic cells are a steady-state population related to plasmacytoid dendritic cells

Lymphoid organs are characterized by a complex network of phenotypically distinct dendritic cells (DC) with potentially unique roles in pathogen recognition and immunostimulation. Classical DC (cDC) include two major subsets distinguished in the mouse by the expression of CD8α. Here we describe a subset of CD8α+ DC in lymphoid organs of naïve mice characterized by expression of the CX3CR1 chemokine receptor. CX3CR1+ CD8α+ DC lack hallmarks of classical CD8α+ DC, including IL-12 secretion, the capacity to cross-present antigen, and their developmental dependence on the transcriptional factor BatF3. Gene-expression profiling showed that CX3CR1+ CD8α+ DC resemble CD8α− cDC. The microarray analysis further revealed a unique plasmacytoid DC (PDC) gene signature of CX3CR1+ CD8α+ DC. A PDC relationship of the cells is supported further by the fact that they harbor characteristic D–J Ig gene rearrangements and that development of CX3CR1+ CD8α+ DC requires E2-2, the critical transcriptional regulator of PDC. Thus, CX3CR1+ CD8α+ DC represent a unique DC subset, related to but distinct from PDC. Collectively, the expression-profiling data of this study refine the resolution of previous DC definitions, sharpen the border of classical CD8α+ and CD8α− DC, and should assist the identification of human counterparts of murine DC subsets.
Nickel-pincer cofactor biosynthesis involves LarB-catalyzed pyridinium carboxylation and LarE-dependent sacrificial sulfur insertion

Significance Nicotinic acid is a precursor of the ubiquitous cofactors nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). Previous studies revealed that nicotinic acid is required for lactate racemization, an enzymatic activity that enables microorganisms to produce or use both isomers of lactate. Lactate racemase (Lar) was shown to harbor a nicotinic acid-derived cofactor that coordinates a nickel ion, forming a pincer complex. The biosynthesis of this cofactor requires three accessory proteins: LarB, LarC, and LarE. Here, we describe this biosynthetic pathway by showing that LarB carboxylates and hydrolyzes the NAD precursor nicotinic acid adenine dinucleotide (NaAD) and LarE sacrificially inserts two sulfur atoms into the product of LarB. Finally, LarC inserts the nickel ion to form the mature cofactor. The lactate racemase enzyme (LarA) of Lactobacillus plantarum harbors a (SCS)Ni(II) pincer complex derived from nicotinic acid. Synthesis of the enzyme-bound cofactor requires LarB, LarC, and LarE, which are widely distributed in microorganisms. The functions of the accessory proteins are unknown, but the LarB C terminus resembles aminoimidazole ribonucleotide carboxylase/mutase, LarC binds Ni and could act in Ni delivery or storage, and LarE is a putative ATP-using enzyme of the pyrophosphatase-loop superfamily. Here, we show that LarB carboxylates the pyridinium ring of nicotinic acid adenine dinucleotide (NaAD) and cleaves the phosphoanhydride bond to release AMP. The resulting biscarboxylic acid intermediate is transformed into a bisthiocarboxylic acid species by two single-turnover reactions in which sacrificial desulfurization of LarE converts its conserved Cys176 into dehydroalanine. Our results identify a previously unidentified metabolic pathway from NaAD using unprecedented carboxylase and sulfur transferase reactions to form the organic component of the (SCS)Ni(II) pincer cofactor of LarA. In species where larA is absent, this pathway could be used to generate a pincer complex in other enzymes.
Induction of Necrotic-Like Cell Death by Tumor Necrosis Factor Alpha and Caspase Inhibitors: Novel Mechanism for Killing Virus-Infected Cells

ABSTRACT Induction of apoptotic cell death generally requires the participation of cysteine proteases belonging to the caspase family. However, and similar to most cell types, mouse fibroblasts are normally resistant to tumor necrosis factor alpha (TNF-α)-induced apoptosis. Surprisingly, TNF-α treatment of vaccinia virus-infected mouse fibroblasts resulted in necrotic-like cell death, which was significantly reduced in cells infected with a vaccinia virus mutant lacking the caspase inhibitor B13R. Furthermore, TNF-α also induced necrotic-like cell death of fibroblasts in the presence of peptidyl caspase inhibitors. In both cases, necrosis was accompanied by generation of superoxide species. Caspase inhibitors also sensitized fibroblasts to killing by double-stranded RNA and gamma interferon. In all cases, cell death was efficiently blocked by antioxidants or mitochondrial respiratory chain inhibitors. These results define a new mitochondrion-dependent mechanism which may be important in the killing of cells infected with viruses encoding caspase inhibitors.
DopAmide: Novel, Water‐Soluble, Slow‐Release l‐dihydroxyphenylalanine (l‐DOPA) Precursor Moderates l‐DOPA Conversion to Dopamine and Generates a Sustained Level of Dopamine at Dopaminergic Neurons

Long‐term l‐dihydroxyphenylalanine (l‐DOPA) treatment of Parkinson's disease (PD) is associated with motor complications known as l‐DOPA‐induced dyskinesias (LID) and on/off fluctuations, which are linked to unsteady pulsatile dopaminergic stimulation.
A new general regression-based approach for method comparison studies

Abstract Background: A scatter plot combined with correlation and regression analysis to assess the agreement between analytical methods that measure the same quantity has a long tradition in clinical chemistry. However, only when linearity is absolute this approach may be useful to estimate whether the methods under comparison produce the same errors in measurement. The aim of this study is to provide a new original regression-based tool which does not suffer from the problems of the classical regression/correlation method and that is also easy to use and to interpret. Methods: To evaluate the performance of the new method, the results of some analytical determinations were compared by the new procedure, the Bland-Altman test, Passing-Bablok regression and Mountain plot. Results: All the tests used to compare the data allowed superimposable interpretations, both when methods under comparison were in agreement and in disagreement. Conclusions: The understanding of the new test is truly intuitive and it is reduced to the appraisal of how much the equation of the best-fit line (Y=X) is able to predict the value of the Y. The goodness of this prediction can be evaluated by the coefficient of determination, whose value is closely connected to the differences between the methods under comparison. The result of our simulation is that quite high agreement between the methods occurs for determination coefficient equal or greater than 0.98. Clin Chem Lab Med 2008;46:1046–9.
Altered re‐excitation thresholds and conduction of extrasystolic action potentials contribute to arrhythmogenicity in murine models of long QT syndrome

QT interval prolongation reflecting delayed action potential (AP) repolarization is associated with polymorphic ventricular tachycardia and early after depolarizations potentially initiating extrasystolic APs if of sufficient amplitude. The current experiments explored contributions of altered re‐excitation thresholds for, and conduction of, such extrasystolic APs to arrhythmogenesis in Langendorff‐perfused, normokalaemic, control wild‐type hearts and two experimental groups modelling long QT (LQT). The two LQT groups consisted of genetically modified, Scn5a +/Δ KPQ and hypokalaemic wild‐type murine hearts.
Absenteeism following a workplace intervention for older food industry workers.

BACKGROUND The effects of workplace interventions on sickness absence are poorly understood, in particular in ageing workers. AIMS To analyse the effects of a senior programme on sickness absence among blue-collar food industry workers of a food company in Finland. METHODS We followed up 129 employees aged 55 years or older, who participated in a senior programme (intervention group), and 229 employees of the same age from the same company who did not participate (control group). Total sickness absence days and spells of 1-3, 4-7, 8-21 and >21 days were recorded for the members of the intervention group from the year before joining the programme and for the control group starting at age 54 years. Both groups were followed for up to 6 years. RESULTS The median number of sickness absence days per person-year increased significantly from baseline in both groups during the follow-up. Compared with the control group, the intervention group had increased risk for 1-3 days spells [rate ratio 1.34 (1.21-1.48)] and 4-7 days spells [rate ratio 1.23 (1.07-1.41)], but the risk for >21 days spells was decreased [rate ratio 0.68 (0.53-0.88)] after participation in the senior programme. CONCLUSIONS A programme to enhance individual work well-being in ageing workers may increase short-term but reduce long-term sickness absence.