julilili42/papers huggingface dataset:
Genome‐wide linkage meta‐analysis identifies susceptibility loci at 2q34 and 13q31.3 for genetic generalized epilepsies
2012-01-13

Summary Purpose: Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% with heritability estimates of 80%. A considerable proportion of families with siblings affected by GGEs presumably display an oligogenic inheritance. The present genome‐wide linkage meta‐analysis aimed to map: (1) susceptibility loci shared by a broad spectrum of GGEs, and (2) seizure type–related genetic factors preferentially predisposing to either typical absence or myoclonic seizures, respectively. Methods: Meta‐analysis of three genome‐wide linkage datasets was carried out in 379 GGE‐multiplex families of European ancestry including 982 relatives with GGEs. To dissect out seizure type–related susceptibility genes, two family subgroups were stratified comprising 235 families with predominantly genetic absence epilepsies (GAEs) and 118 families with an aggregation of juvenile myoclonic epilepsy (JME). To map shared and seizure type–related susceptibility loci, both nonparametric loci (NPL) and parametric linkage analyses were performed for a broad trait model (GGEs) in the entire set of GGE‐multiplex families and a narrow trait model (typical absence or myoclonic seizures) in the subgroups of JME and GAE families. Key Findings: For the entire set of 379 GGE‐multiplex families, linkage analysis revealed six loci achieving suggestive evidence for linkage at 1p36.22, 3p14.2, 5q34, 13q12.12, 13q31.3, and 19q13.42. The linkage finding at 5q34 was consistently supported by both NPL and parametric linkage results across all three family groups. A genome‐wide significant nonparametric logarithm of odds score of 3.43 was obtained at 2q34 in 118 JME families. Significant parametric linkage to 13q31.3 was found in 235 GAE families assuming recessive inheritance (heterogeneity logarithm of odds = 5.02). Significance: Our linkage results support an oligogenic predisposition of familial GGE syndromes. The genetic risk factor at 5q34 confers risk to a broad spectrum of familial GGE syndromes, whereas susceptibility loci at 2q34 and 13q31.3 preferentially predispose to myoclonic seizures or absence seizures, respectively. Phenotype– genotype strategies applying narrow trait definitions in phenotypic homogeneous subgroups of families improve the prospects of disentangling the genetic basis of common familial GGE syndromes.
Global structure of magnetorotationally turbulent protoplanetary discs
2012-01-13

The aim of the present paper is to investigate the spatial structure of a protoplanetary disc whose dynamics is governed by magnetorotational turbulence. We perform a series of local 3D chemo-radiative MHD simulations located at different radii of a disc which is twice as massive as the standard minimum mass solar nebula of Hayashi (1981). The ionisation state of the disc is calculated by including collisional ionisation, stellar X-rays, cosmic rays and the decay of radionuclides as ionisation sources, and by solving a simplified chemical network which includes the effect of the absorption of free charges by {\\mu}m-sized dust grains. In the region where the ionisation is too low to assure good coupling between matter and magnetic fields, a non-turbulent central "dead zone" forms, which ranges approximately from a distance of 2 AU to 4 AU from the central star. The approach taken in the present work allows for the first time to derive the global spatial structure of a protoplanetary disc from a set of physically realistic numerical simulations.
Deterministic Josephson vortex ratchet with a load
2012-01-13

We investigate experimentally a deterministic underdamped Josephson vortex ratchet-a fluxon particle moving along a Josephson junction in an asymmetric periodic potential. By applying a sinusoidal driving current, one can compel the vortex to move in a certain direction, producing an average dc voltage across the junction. Being in such a rectification regime, we also load the ratchet, i.e., apply an additional dc bias current I(dc) (counterforce) which tilts the potential so that the fluxon climbs uphill due to the ratchet effect. The value of the bias current at which the fluxon stops climbing up defines the strength of the ratchet effect and is determined experimentally. This allows us to estimate the loading capability of the ratchet, the output power, and the efficiency. For the quasistatic regime we present a simple model which delivers straightforward analytic expressions for the above-mentioned figures of merit.
On the fluid‐tissue contrast behavior of high‐resolution steady‐state sequences
2012-01-13

Abstract In general, MR image contrast is expected to be resolution independent, but a pronounced loss of contrast is observed between fluids and tissues with contemporary musculoskeletal protocols (typical inplane resolution &lt;&lt; 1 mm) using nonbalanced steady‐state free precession, such as double echo steady state. For nonbalanced steady‐state free precession, diffusion sensitivity increases with increasing spoiler moments which increase with decreasing voxel size, suggesting diffusion damping as the major cause for the observed contrast variation. This is confirmed by simulations and measurements indicating that for fluids, diffusion effects become apparent already for resolutions Δ x &lt; 1 mm, whereas tissues typically require Δ x &lt; 200 μm. Gradient spoiling, however, is generically not minimized but frequently applied along the readout direction. For anisotropic steady‐state free precession scans, the loss of contrast between fluids and tissues from diffusion can thus be minimized by simply moving the spoiler gradients to the lowest resolution direction. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
Diene Dissolution of the Heavier Alkaline Earth Metals
2012-01-13

Abstract Alkaline and alkaline earth metals are efficiently activated in the presence of aromatic hydrocarbons (“potassium–naphthalene”, “magnesium–anthracene”) or (substituted) 1,3‐dienes to produce well‐defined organometallic complexes. In this study, mononuclear diene complexes of calcium, strontium, and barium have been synthesized by utilizing tailor‐made 1,3‐dienes. Complexes [M(2,3‐dimethyl‐1,4‐ditolyl‐1,3‐butadiene)(thf) 4 ] (M = Ca, Sr), [Ca(2,3‐dimethyl‐1,4‐dinaphthyl‐1,3‐butadiene)(thf) 4 ], and {Ba[2,3‐dimethyl‐1,4‐bis(2,4‐dimethylphenyl)‐1,3‐butadiene](thf) 4 } were isolated and fully characterized including X‐ray structure analyses. Whereas the calcium– and strontium–dienes show an approximate metallacylo‐3‐pentene coordination, barium(II) as the largest nonradioactive metal(II) cation reveals metallacyclo‐2,4‐heptadiene bonding in the solid state. It is further shown that barium(II) can accommodate eight thf molecules as evidenced in the dicationic complex {[Ba(thf) 8 ][B(C 6 F 5 ) 4 ] 2 }, obtained from the reaction of barium–diene with trityl borate.
Optimization of Autologous Stem Cell Transplantation for Systemic Sclerosis — A Single-center Longterm Experience in 26 Patients with Severe Organ Manifestations
2012-01-15

Objective. Autologous stem cell transplantation (aSCT) for systemic sclerosis (SSc) has been shown to be effective in recent reports. This aggressive approach and the disease itself are associated with a high mortality. We report our experiences in 26 consecutive patients. Methods. Between 1997 and 2009, 26 patients were scheduled for aSCT. Our standard transplant regimen consists of cyclophosphamide (CYC) and granulocyte colony-stimulating factor (GCSF) for mobilization and CYC plus antithymocyte globulin for conditioning before the retransfusion of CD34 selected stem cells. The major outcome variable was the response to treatment [reduction of modified Rodnan skin score (mRSS) by 25%] at Month 6. Secondary endpoints were the transplant-related mortality and the progression-free survival. Results. Significant skin and lung function improvement of the mRSS was achieved in 78.3% of patients at Month 6. The overall response rate was 91%, as some patients improved even after Month 6. Three patients died between mobilization and conditioning treatment, 2 due to severe disease progression and 1 whose death was considered treatment-related (i.e., GCSF or CYC toxicity). Depending on definitions, transplant-related mortality was 4% and treatment-related mortality 11%. Seven patients experienced a relapse during the 4.4 years of followup. The progression-free survival was 74%. Four patients died during followup and the most frequent causes of death were pulmonary and cardiac complications of SSc. Conclusion. aSCT led to significant improvement in most patients with SSc. The procedure requires further optimization; hence we are modifying our screening and treatment strategy. To minimize infectious complications, CYC for mobilization and GCSF were reduced. We intensified our screening for cardiac involvement and modified our conditioning regimen in case of cardiac involvement.
Reversal of Cardiovascular Risk Factors in Patients with End-Stage-Renal-Disease
2012-01-15

Patients with end-stage-renal disease (ESRD) experience a high cardiovascular mortality and cardiovascular risk factors such as obesity, hyperlipidemia and hypertension are very common. Recent epidemiological research has revealed that the association between mortality and traditional cardiovascular risk factors has been altered and inverted in ESRD patients in a sense that a low bodymass-index, a low blood pressure or low plasma cholesterol concentrations are associated with an increased mortality. In addition, low plasma creatinine, homocysteine, uric acid, advanced glycation end products, leptin and adiponectin concentrations are indicators of a high mortality instead of the lower mortality seen in the normal population. These findings have been referred to as reverse epidemiology in the literature and the underlying causes are multifactorial comprising the malnutritioninflammation-syndrome, timing of competitive risk factors, altered pathophysiology and the impact of multiple selection biases of the studies. In the presence of reverse epidemiology, the approach to the patients and the definition of target values for therapy are difficult. In this article an attempt is made to enlighten the concept of reverse epidemiology and to review the current available literature. KeY WORDs: Cardiovascular, Risk, Dialysis, Reverse, Epidemiology doi: 10.5262/tndt.2012.1001.03 Yazisma Adresi: Ferruh ARtuNC Tubingen Universitesi Dahiliye Klinigi, Nefroloji ve Hipertansiyoloji Alt Bilim Dali, Tubingen, Almanya Tel : +4970712982711 E-posta : ferruh.artunc@med.uni-tuebingen.de Gelis Tarihi : 04.02.2011 Kabul Tarihi : 30.04.2011
A novel approach to probabilistic biomarker‐based classification using functional near‐infrared spectroscopy
2012-01-16

Abstract Pattern recognition approaches to the analysis of neuroimaging data have brought new applications such as the classification of patients and healthy controls within reach. In our view, the reliance on expensive neuroimaging techniques which are not well tolerated by many patient groups and the inability of most current biomarker algorithms to accommodate information about prior class frequencies (such as a disorder's prevalence in the general population) are key factors limiting practical application. To overcome both limitations, we propose a probabilistic pattern recognition approach based on cheap and easy‐to‐use multi‐channel near‐infrared spectroscopy (fNIRS) measurements. We show the validity of our method by applying it to data from healthy controls ( n = 14) enabling differentiation between the conditions of a visual checkerboard task. Second, we show that high‐accuracy single subject classification of patients with schizophrenia ( n = 40) and healthy controls ( n = 40) is possible based on temporal patterns of fNIRS data measured during a working memory task. For classification, we integrate spatial and temporal information at each channel to estimate overall classification accuracy. This yields an overall accuracy of 76% which is comparable to the highest ever achieved in biomarker‐based classification of patients with schizophrenia. In summary, the proposed algorithm in combination with fNIRS measurements enables the analysis of sub‐second, multivariate temporal patterns of BOLD responses and high‐accuracy predictions based on low‐cost, easy‐to‐use fNIRS patterns. In addition, our approach can easily compensate for variable class priors, which is highly advantageous in making predictions in a wide range of clinical neuroimaging applications. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.
Measurement invariance of big-five factors over the life span: ESEM tests of gender, age, plasticity, maturity, and la dolce vita effects.
2012-01-17

This substantive-methodological synergy applies evolving approaches to factor analysis to substantively important developmental issues of how five-factor-approach (FFA) personality measures vary with gender, age, and their interaction. Confirmatory factor analyses (CFAs) conducted at the item level often do not support a priori FFA structures, due in part to the overly restrictive assumptions of CFA models. Here we demonstrate that exploratory structural equation modeling (ESEM), an integration of CFA and exploratory factor analysis, overcomes these problems with the 15-item Big Five Inventory administered as part of the nationally representative British Household Panel Study (N = 14,021; age: 15-99 years, Mage = 47.1). ESEM fitted the data substantially better and resulted in much more differentiated (less correlated) factors than did CFA. Methodologically, we extended ESEM (introducing ESEM-within-CFA models and a hybrid of multiple groups and multiple indicators multiple causes models), evaluating full measurement invariance and latent mean differences over age, gender, and their interaction. Substantively the results showed that women had higher latent scores for all Big Five factors except for Openness and that these gender differences were consistent over the entire life span. Substantial nonlinear age effects led to the rejection of the plaster hypothesis and the maturity principle but did support a newly proposed la dolce vita effect in old age. In later years, individuals become happier (more agreeable and less neurotic), more self-content and self-centered (less extroverted and open), more laid back and satisfied with what they have (less conscientious, open, outgoing and extroverted), and less preoccupied with productivity.
Cyclin D1-negative Blastoid Mantle Cell Lymphoma Identified by SOX11 Expression
2012-01-17

SOX11 expression has been recently shown to be useful in the diagnosis of mantle cell lymphoma (MCL), including cyclin D1-negative MCL with typical morphology. We evaluated SOX11 expression pattern in B-cell non-Hodgkin lymphoma (B-NHL) subtypes to confirm specificity and used it as a feature to identify the first reported cases of cyclin D1-negative blastoid MCL. SOX11 expression was evaluated by immunohistochemistry in 140 cases of mature B-NHL, including 4 cases of suspected blastoid MCL that lacked cyclin D1 expression and 8 cases of CD5-positive diffuse large B-cell lymphoma (DLBL). In addition, 5 cases of B or T lymphoblastic lymphoma were included. Nuclear expression of SOX11 was found in cyclin D1-positive MCL (30/30, 100%) and in a case of cyclin D1-negative MCL with typical morphology. SOX11 was also expressed in Burkitt lymphoma (1/5, 20%) and lymphoblastic lymphoma (2/3 T-LBLs, 2/2 B-LBLs, overall 4/5, 80%), whereas all cases of DLBL (including CD5 DLBL) and other small B-NHL were negative. The 4 suspected cases of blastoid MCL were also SOX11. These cases had a complex karyotype that included 12p abnormalities. We confirmed prior reports that stated that SOX11 nuclear expression was a specific marker for MCL, including cyclin D1-negative MCL with typical morphology. To our knowledge, this is the first report regarding its use in identifying cases of cyclin D1-negative blastoid MCL. Routine use of SOX11 in cases of suspected CD5 DLBL might help identify additional cases of cyclin D1-negative blastoid MCL.
MAPK and PI3K/AKT mediated YB‐1 activation promotes melanoma cell proliferation which is counteracted by an autoregulatory loop
2012-01-17

Abstract: Y‐box binding protein 1 (YB‐1) is an oncogenic transcription and translation factor and is overexpressed in several types of cancer. Our previous data showed that YB‐1 is upregulated and translocated to the nucleus during melanoma progression and that YB‐1 is an important transcription factor regulating proliferation, survival, migration, invasion and chemosensitivity of melanoma cells. It has been suggested that YB‐1 is activated and translocated to the nucleus after S102‐phosphorylation in the DNA binding domain. In this study, we show that activation of YB‐1 by S102‐phosphorylation and nuclear translocation is increased during melanoma progression using a human tissue microarray with 100 melanocytic lesions. Furthermore, we analysed the mechanisms governing the expression and activity of YB‐1 in melanoma cells. We show that the PI3K/AKT and p53 signalling, growth factors and chemotherapeutic agents increase YB‐1 promoter activity. This, however, resulted in no or only modest increase in YB‐1 protein expression. We show that the MAPK and PI3K/AKT signalling pathways, both activated in melanoma cells, as well as p53 overexpression increase YB‐1 S102‐phosphorylation, whereas NFκB signalling inhibits phosphorylation. Overexpression of YB‐1 in melanoma cells inhibits translation efficiency and by this proliferation and survival of melanoma cells indicating that there is an autoregulatory loop restricting YB‐1 protein expression. These data suggest that there is a tightly regulated feedback mechanism regulating YB‐1 expression and activation, necessary for proper cell cycle progression of melanoma cells.
Genome‐scale metabolic representation of Amycolatopsis balhimycina
2012-01-17

Abstract Infection caused by methicillin‐resistant Staphylococcus aureus (MRSA) is an increasing societal problem. Typically, glycopeptide antibiotics are used in the treatment of these infections. The most comprehensively studied glycopeptide antibiotic biosynthetic pathway is that of balhimycin biosynthesis in Amycolatopsis balhimycina . The balhimycin yield obtained by A. balhimycina is, however, low and there is therefore a need to improve balhimycin production. In this study, we performed genome sequencing, assembly and annotation analysis of A. balhimycina and further used these annotated data to reconstruct a genome‐scale metabolic model for the organism. Here we generated an almost complete A. balhimycina genome sequence comprising 10,562,587 base pairs assembled into 2,153 contigs. The high GC‐genome (∼69%) includes 8,585 open reading frames (ORFs). We used our integrative toolbox called SEQTOR for functional annotation and then integrated annotated data with biochemical and physiological information available for this organism to reconstruct a genome‐scale metabolic model of A. balhimycina . The resulting metabolic model contains 583 ORFs as protein encoding genes (7% of the predicted 8,585 ORFs), 407 EC numbers, 647 metabolites and 1,363 metabolic reactions. During the analysis of the metabolic model, linear, quadratic and evolutionary programming algorithms using flux balance analysis (FBA), minimization of metabolic adjustment (MOMA), and OptGene, respectively were applied as well as phenotypic behavior and improved balhimycin production were simulated. The A. balhimycina model shows a good agreement between in silico data and experimental data and also identifies key reactions associated with increased balhimycin production. The reconstruction of the genome‐scale metabolic model of A. balhimycina serves as a basis for physiological characterization. The model allows a rational design of engineering strategies for increasing balhimycin production in A. balhimycina and glycopeptide production in general. Biotechnol. Bioeng. 2012; 109:1798–1807. © 2012 Wiley Periodicals, Inc.
Straightforward Synthesis of Dipyrido‐Annelated NHC‐Palladium(II) Complexes by Oxidative Addition
2012-01-17

Abstract A straightforward synthesis method for mixed phosphane dipyrido‐annelated N‐heterocyclic carbene (dipiy) palladium(II) complexes is presented. The key step is the oxidative addition of 6‐bromodipyridoimidazolium bromides that can be prepared easily from dipyridine in a two step reaction. This new procedure avoids any generation of the free carbene as well as any transmetallation step.
Unfavourable consequences of chronic cardiac HIF-1α stabilization
2012-01-18

Changes induced with transgenic cardiac HIF-1α possibly mediate beneficial effects in the short term; however, with increased mechanical load and ageing they become detrimental for cardiac function. Together with the finding of increased HIF-1α protein levels in samples from human patients with cardiomyopathy, these data indicate that chronic HIF-1α stabilization drives autonomous pathways that add to disease progression.
Location, existence, and possession: A constructional-typological exploration
2012-01-18

The semantic space location–existence–possession has been investigated from different perspectives since Lyons 1967. In this paper it is first accurately redefined (Section 2) so that it constitutes an operative onomasiological grid for lexical and constructional typological research. Patterns of joint expression of categories and of clear distinction of categories are examined over significant subparts of the relevant semantic space (Sections 2.3/3.1: possession corresponding e.g., to E. The boy had a book; thematic location: E. The book was on the table; rhematic location: E. There was a book on the table; bounded existence: E. There are many lions in Africa; (generic) existence: E. There are many unhappy people). This research is conducted on the basis of an initial 19-language sample (Section 3.2 and Appendix B), which, despite its bias towards Europe and Africa, yields very interesting observations concerning crosslinguistic tendencies and the effects of genetic affiliation and areal proximity. Since for the typology of this field it is not only the verbal lexical item that counts, but the whole construction (in some languages even with zero copula), adequate tools for a constructional typology have to be developed in terms of inheritance links inspired by Construction Grammar (Section 4). In the central sections of the paper, crosslinguistic patterns of inheritance and of clear distinction of categories within the semantic space are analyzed with respect to the target concepts possession (Section 5), location (Section 6), and existence (Section 7). On the semantic level the relevant links are all metonymic or at least contiguity-based. From the detailed analyses several interesting crosslinguistic, but also areal tendencies can be gathered (Section 8.1). A general hypothesis about the domain location + existence emerges: languages either opt for informational salience, opposing thematic location to the (rhematic) rest, or for propositional salience, opposing (generic) location to existence, or they dismiss both types of salience, linking (generic) location and existence directly to each other. As a conclusion, three interesting methodological and theoretical issues are addressed: the non-necessary congruence between synchronic patterns and diachronic paths (Section 8.2.1), problems of the conceptual grid in the realm rhematic existence/rhematic location (Section 8.2.2), and the utility of an account in terms of constructional typology (8.2.3).