julilili42/papers huggingface dataset:
Association of AHSG Gene Polymorphisms With Fetuin-A Plasma Levels and Cardiovascular Diseases in the EPIC-Potsdam Study
2009-09-07

Background— Elevated circulating levels of fetuin-A in blood have been associated with increased risk of cardiovascular disease. The goal of our study was to prospectively investigate the potential causal nature of the association between fetuin-A levels and myocardial infarction (MI) and ischemic stroke by applying a Mendelian randomization approach. Methods and Results— Five tagging single-nucleotide polymorphisms (rs2248690, rs2070633, rs2070635, rs4917, and rs6787344) capturing the common genetic variation of the fetuin-A coding gene α 2 -Heremans-Schmid glycoprotein ( AHSG ) were genotyped in a case-cohort comprising 214 MI cases, 154 ischemic stroke cases, and 2152 persons who remained free of cardiovascular disease events in the European Prospective Investigation into Cancer and Nutrition-Potsdam study. One single-nucleotide polymorphism (rs6787344) was discarded because of Hardy-Weinberg disequilibrium. All AHSG tagging single-nucleotide polymorphisms were associated with fetuin-A plasma levels ( P &lt;0.0001). AHSG rs4917 C&gt;T showed the strongest association, explaining 21.2% of the phenotypic variance independent of potential confounding factors (+35.5 μg/mL increase per C-allele, P =2�10 −121 ). Furthermore, the rs4917 C-allele showed a significant association with MI (adjusted hazard rate ratio [RR] 1.34, 95% CI 1.05 to 1.70, P =0.02). Based on this association, the expected RR for MI corresponding to 1 SD in fetuin-A was 1.54 and, thus, strikingly matches the previously observed association between fetuin-A plasma levels and MI risk (RR 1.59). Conclusions— These data provide evidence for the causal nature of the recently reported association between fetuin-A plasma levels and MI risk, thereby suggesting an involvement of fetuin-A in the pathogenesis of cardiovascular disease.
Germa‐closo‐dodecaborate: A New Ligand in Transition‐Metal Chemistry with a Strong trans Influence
2009-09-08

Abstract The strong nucleophilic character of germa‐ closo ‐dodecaborate towards late transition metal centres is described. The synthesis and characterisation of the first germa‐ closo ‐dodecaborate complexes are presented, and the solid state structures of the germaborate transition metal complexes were determined by X‐ray crystal structure analyses. The strong trans influence of the new germaborate ligand was determined by IR spectroscopy and NMR coupling constants.
2-[(1-Methyl-1H-pyrrol-2-yl)carbonylmethyl]isoindoline-1,3-dione
2009-09-08

The asymmetric unit of the title compound, C(15)H(12)N(2)O(3), contains two almost identical mol-ecules forming an nearly C(2-)symmetric dimeric pattern. The dihedral angles between the pyrrole ring and the phthalimide unit are 82.95 (8) and 86.57 (8)° for the two mol-ecules. Within such a dimer, the phthalimide units of the two mol-ecules form a dihedral angle of 1.5 (5)°.
Platelet-Derived Transforming Growth Factor-β Down-Regulates NKG2D Thereby Inhibiting Natural Killer Cell Antitumor Reactivity
2009-09-09

Abstract Natural killer (NK) cells play an important role in cancer immunosurveillance and may prevent tumor progression and metastasis due to their ability to mediate direct cellular cytotoxicity and by releasing immunoregulatory cytokines, which shape adaptive immune responses. Their reactivity is governed by various activating and inhibitory molecules expressed on target cells and reciprocal interactions with other hematopoietic cells such as dendritic cells. In mice, thrombocytopenia inhibits metastasis, and this is reversed by NK cell depletion, suggesting that platelets are an important additional player in NK cell-tumor interaction. Moreover, it has been shown that metastasizing tumor cells do not travel through the blood alone but are rapidly coated by platelets. However, the knowledge about the molecular mechanisms by which platelets influence NK cells is fragmentary at best. Here we show that platelet-derived soluble factors, secreted on coating of tumor cells or after stimulation with classic platelet agonists, impair NK cell antitumor reactivity resulting in diminished granule mobilization, cytotoxicity, and IFN-γ production. The impaired NK cell reactivity was not due to induction of apoptosis but mediated by down-regulation of the activating immunoreceptor natural killer group 2, member D (NKG2D) on NK cells by platelet-derived transforming growth factor β (TGF-β). Neutralization of TGF-β in platelet releasate not only prevented NKG2D down-regulation but also restored NK cell antitumor reactivity. Thus, our data elucidate the molecular basis of the previously described influence of platelets on NK cell antitumor reactivity and suggest that therapeutic intervention in tumor cell-platelet interaction and the resulting TGF-β release by platelets may serve to enhance antitumor immunity. [Cancer Res 2009;69(19):7775–83]
Magnetomyographic recording and identification of uterine contractions using Hilbert-wavelet transforms
2009-09-09

We propose a multi-stage approach using Wavelet and Hilbert transforms to identify uterine contraction bursts in magnetomyogram (MMG) signals measured using a 151 magnetic sensor array. In the first stage, we decompose the MMG signals by wavelet analysis into multilevel approximate and detail coefficients. In each level, the signals are reconstructed using the detail coefficients followed by the computation of the Hilbert transform. The Hilbert amplitude of the reconstructed signals from different frequency bands (0.1-1 Hz) is summed up over all the sensors to increase the signal-to-noise ratio. Using a novel clustering technique, affinity propagation, the contractile bursts are distinguished from the noise level. The method is applied on simulated MMG data, using a simple stochastic model to determine its robustness and to seven MMG datasets.
Meson wave function from holographic models
2009-09-10

We consider the light-front wave function for the valence quark state of mesons using the AdS/CFT correspondence, as has been suggested by Brodsky and Teramond. Two kinds of wave functions, obtained in different holographic Soft-Wall models, are discussed.
Circulating melanoma cells in peripheral blood of patients with uveal melanoma before and after different therapies and association with prognostic parameters: a pilot study
2009-09-11

No changes in CMC values were observed before and after different tumour therapies. In the majority of cases therapy does not lead to a shedding of detectable melanoma cells into the systemic circulation.
Area-Feature Boundary Labeling
2009-09-11

Boundary labeling is a relatively new labeling method. It can be useful in automating the production of technical drawings and medical drawings, where it is common to explain certain parts of the drawing with text labels, arranged on its boundary so that other parts of the drawing are not obscured. In boundary labeling, we are given a rectangle R which encloses a set of n sites. Each site s is associated with an axis-parallel rectangular label ls. The labels must be placed in distinct positions on the boundary of R and they must be connected to their corresponding sites with polygonal lines, called leaders, so that the labels are pairwise disjoint and the leaders do not intersect each other. In this paper, we study a version of the boundary labeling problem where the sites can ‘float’ within a polygonal region. We present a polynomial time algorithm, which runs in O(n3) time and produces a labeling of minimum total leader length for labels of uniform size placed in fixed positions on the boundary of rectangle R.
Synthesis and Characterization of Digerma‐closo‐dodecaborate: A Higher Homologue of Icosahedral ortho‐Carborane
2009-09-11

Missing link: Starting from germanium(II) bromide, decaborane, and triethylamine, a dimeric 2,2′-bis(1,2-digerma-closo-dodecaborate) was prepared. Reductive cleavage yielded the monomeric dianion [Ge2B10H10]2−. With alkyl halides, neutral disubstituted species were obtained (see example), which were fully characterized by NMR spectroscopy and X-ray crystallography. The gap in the series of Group 14 di-hetero-closo-dodecaboranes is now closed. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Impaired Mast Cell Activation in Gene-Targeted Mice Lacking the Serum- and Glucocorticoid-Inducible Kinase SGK1
2009-09-12

Abstract The PI3K pathway plays a pivotal role in the stimulation of mast cells. PI3K-dependent kinases include the serum- and glucocorticoid-inducible kinase 1 (SGK1). The present study explored the role of SGK1 in mast cell function. Mast cells were isolated from bone marrow (BMMC) of SGK1 knockout mice (sgk1−/−) and their wild-type littermates (sgk1+/+). The BMMC number as well as CD117, CD34, and FcεRI expression in BMCCs were similar in both genotypes. Upon Ag stimulation of the FcεRI receptor, Ca2+ entry but not Ca2+ release from intracellular stores was markedly impaired in sgk1−/− BMMCs. The currents through Ca2+-activated K+ channels induced by Ag were significantly higher in sgk1+/+ BMMCs than in sgk1−/− BMMCs. Treatment with the Ca2+ ionophore ionomycin (1 μM) led to activation of the K+ channels in both genotypes, indicating that the Ca2+-activated K+ channels are similarly expressed and sensitive to activation by Ca2+ in sgk1+/+ and sgk1−/− BMMCs, and that blunted stimulation of Ca2+-activated K+ channels was secondary to decreased Ca2+ entry. Ag-IgE-induced degranulation and early IL-6 secretion were also significantly blunted in sgk1−/− BMMCs. The decrease in body temperature following Ag treatment, which reflects an anaphylactic reaction, was substantially reduced in sgk1−/− mice, pointing to impaired mast cell function in vivo. Serum histamine levels measured 30 min after induction of an anaphylactic reaction were significantly lower in sgk1−/− than in sgk1+/+mice. The observations reveal a critical role for SGK1 in ion channel regulation and the function of mast cells, and thus disclose a completely novel player in the regulation of allergic reaction.
The mammalian aryl hydrocarbon (Ah) receptor: from mediator of dioxin toxicity toward physiological functions in skin and liver
2009-09-13

Abstract The mammalian Ah receptor (AhR) is a ligand-activated transcription factor with multiple functions in adaptive metabolism, development and dioxin toxicity in a variety of organs and cell systems. Phenotypes observed following sustained activation by dioxin or in AhR-null mice suggest organ-dependent physiological functions. These functions are probably deregulated following exposure to dioxin. We focus on skin and liver to facilitate discussion of mechanisms linking phenotypes and AhR-modulated genotypes. After a brief summary of currently discussed AhR ligand candidates, two groups of direct AhR target genes/proteins and associated functions are highlighted: (i) xenobiotic-metabolizing enzymes which are also involved in homeostasis of endogenous ligands and (ii) proteins controlling cell proliferation/apoptosis, differentiation and inflammation. Homeostatic feedback loops might not only include CYP1A1 but also Phase II enzymes such as UGT1A1 which controls the antioxidant AhR ligand bilirubin. The AhR is involved in extensive crosstalk with other transcription factors and multiple signaling pathways. Efforts elucidating the pathway toward identification of physiological functions of the AhR remain challenging and promising.
Nuclear saturation with low momentum interactions
2009-09-14

Relativistic effects are investigated in nuclear matter calculations employing renormalized low-momentum nucleon-nucleon ( ) interactions. It is demonstrated that the relativistic effects cure a problem of non-relativistic low-momentum interactions, which fail to reproduce saturation of nuclear matter. Including relativistic effects, one already obtains saturation in a Hartree-Fock calculation. Brueckner-Hartree-Fock calculations lead to a further improvement of the saturation properties. The results are rather insensitive to the realistic interaction on which they are based.
Evaluation of nine candidate genes in patients with normal tension glaucoma: a case control study
2009-09-15

Abstract Background Normal tension glaucoma is a major subtype of glaucoma, associated with intraocular pressures that are within the statistically normal range of the population. Monogenic forms following classical inheritance patterns are rare in this glaucoma subtype. Instead, multigenic inheritance is proposed for the majority of cases. The present study tested common sequence variants in candidate genes for association with normal tension glaucoma in the German population. Methods Ninety-eight SNPs were selected to tag the common genetic variation in nine genes, namely OPTN (optineurin), RDX (radixin), SNX16 (sorting nexin 16), OPA1 (optic atrophy 1), MFN1 (mitofusin 1), MFN2 (mitofusin 2), PARL (presenilin associated, rhomboid-like), SOD2 (superoxide dismutase 2, mitochondrial) and CYP1B1 (cytochrome P450, family 1, subfamily B, polypeptide 1). These SNPs were genotyped in 285 cases and 282 fully evaluated matched controls. Statistical analyses comprised single polymorphism association as well as haplogroup based association testing. Results Results suggested that genetic variation in five of the candidate genes (RDX, SNX16, OPA1, SOD2 and CYP1B1) is unlikely to confer major risk to develop normal tension glaucoma in the German population. In contrast, we observed a trend towards association of single SNPs in OPTN, MFN1, MFN2 and PARL. The SNPs of OPTN, MFN2 and PARL were further analysed by multimarker haplotype-based association testing. We identified a risk haplotype being more frequent in patients and a vice versa situation for the complementary protective haplotype in each of the three genes. Conclusion Common variants of OPTN, PARL, MFN1 and MFN2 should be analysed in other cohorts to confirm their involvement in normal tension glaucoma.
New insights into the expanding complexity of the tumor suppressor ASPP2
2009-09-15

Apoptosis Stimulating Protein of p53-2, ASPP2, aka 53BP2L, (encoded by TP53BP2) is a pro-apoptotic member of a family of p53 binding proteins. ASPP2 expression is frequently suppressed in human cancers and numerous studies have consistently demonstrated that ASPP2 inhibits cell growth as well as stimulates apoptosis-at least in part through a p53-mediated pathway. Two independent mouse models have shown that ASPP2 is a haplo-insufficient tumor suppressor and underscore the importance of the role of ASPP2 in human cancer. However, mounting evidence suggests that the mechanism(s) of action for ASPP2 are complex and likely extend beyond stimulation of apoptotic programs. Data highlighting this expanding spectrum of potential ASPP2-mediated pathways is summarized along with new results from recent in vivo models suggesting new avenues for investigation.
Ba2+currents in inner and outer hair cells of mice lacking the voltage-dependent Ca2+channel subunits β3 or β4
2009-09-15

Voltage-activated Ca(2+) channels comprise complexes of a pore-forming Ca(V)alpha(1) and auxiliary subunits Ca(V)beta, Ca(V)alpha(2)delta and sometimes Ca(V)gamma. The intracellular Ca(V)beta subunit assists in trafficking and surface expression of the Ca(V)alpha(1) subunit and can modulate biophysical properties of the Ca(2+) channel. Four genes, Ca(V)beta1-4, exist which confer different properties to Ca(2+) currents through the various Ca(V)alpha(1) subunits. Ca(2+) currents in cochlear inner (IHC) and outer hair cells (OHC) serving synaptic transmission flow predominantly through the L-type Ca(V)alpha(1) subunit Ca(V)1.3, but associated Ca(V)beta subunits are unknown. In the organ of Corti, we found mRNA and protein for all four Ca(V)beta subunits including Ca(V)beta2, but clear assignment of the Ca(V)beta1-4 immunolabelling with hair cells or nerve fibers was difficult. We analyzed Ca(V)beta3 knockout (Ca(V)beta3(-/-)) and Ca(V)beta4 mutant mice (Ca(V)beta4(lh/lh)), which had normal hearing. Recording voltage-activated Ba(2+) currents from hair cells of the two mouse models revealed distinct significant changes of cell size and Ba(2+) current properties compared with their wild-type controls. Neonatal Ca(V)beta4(lh/lh) IHCs showed reduced membrane capacitances and changes in the voltage dependence and kinetics of current activation, whereas mature IHCs had reduced peak currents compared with Ca(V)beta4(wt), altogether indicating the presence of Ca(V)beta4 in IHCs. Ba(2+) currents of Ca(V)beta3(-/-) OHCs showed largely reduced amplitudes, changes in the voltage dependence and kinetics of Ba(2+) current activation, and increased inactivation compared with Ca(V)beta3(wt), pointing to a role of Ca(V)beta3 for OHCs. These results indicate that neither Ca(V)beta3 nor Ca(V)beta4 are indispensable for hair cell Ca(2+) currents but contribute to the overall current properties.
Accuracy of dual-source CT in the characterisation of non-calcified plaque: use of a colour-coded analysis compared with virtual histology intravascular ultrasound
2009-09-16

Non-invasive assessment of plaque volume and composition is important for risk stratification and long-term studies of plaque stabilisation. Our aim was to evaluate dual-source computed tomography (DSCT) and colour-coded analysis in the quantification and classification of coronary atheroma. DSCT and virtual histology intravascular ultrasound (IVUS-VH) were prospectively performed in 14 patients. 22 lesions were compared in terms of plaque volume, maximal per cent vessel stenosis and percentages of fatty, fibrous or calcified components. Plaque characterisation was performed with software that automatically segments luminal or outer vessel boundaries and uses CT attenuation for a colour-coded plaque analysis. Good correlation was found for per cent vessel stenosis in DSCT (53+/-13%) and IVUS (51+/-14%; r(2) = 0.70). Mean volumes for entire plaque and non-calcified atheroma were 68.5+/-33 mm(3) and 56.7+/-30 mm(3), respectively, in DSCT and 60.8+/-29 mm(3) and 55.8+/-26 mm(3), respectively, in IVUS. Mean percentages of fatty, fibrous or calcified components were 28.2+/-6%, 53.2+/-9% and 18.7+/-13%, respectively, in DSCT and 29.9+/-5%, 55.3+/-12% and 14.4+/-9%, respectively, in IVUS-VH. Significant overestimation was present for the entire plaque and the volume of calcified plaque (p = 0.03; p = 0.0004). Although good correlation with IVUS was obtained for the entire plaque (r(2) = 0.76) and non-calcified plaque volume (r(2) = 0.84), correlation proved very poor and insignificant for percentage plaque composition. Interclass correlation coefficients for non-calcified plaque volume and percentages of fatty, fibrous or calcified components were 0.99, 0.99, 0.95 and 0.98, respectively, and intraclass coefficients were 0.98, 0.93, 0.98 and 0.99, respectively. We found that using Hounsfield unit-based analysis, DSCT allows for accurate quantification of non-calcified plaque. Although percentage plaque composition proves highly reproducible, it is not correlated with IVUS-VH.
Normal Spatial Attention But Impaired Saccades and Visual Motion Perception After Lesions of the Monkey Cerebellum
2009-09-16

Lesions of the cerebellum produce deficits in movement and motor learning. Saccadic dysmetria, for example, is caused by lesions of the posterior cerebellar vermis. Monkeys and patients with such lesions are unable to modify the amplitude of saccades. Some have suggested that the effects on eye movements might reflect a more global cognitive deficit caused by the cerebellar lesion. We tested that idea by studying the effects of vermis lesions on attention as well as saccadic eye movements, visual motion perception, and luminance change detection. Lesions in posterior vermis of four monkeys caused the known deficits in saccadic control. Attention tested by examination of acuity threshold changes induced by prior cueing of the location of the targets remained normal after vermis lesions. Luminance change detection was also unaffected by the lesions. In one case, after a lesion restricted to lobulus VIII, the animal had impaired visual motion perception.
Problem‐based training for medical students reduces common prescription errors: a randomised controlled trial
2009-09-16

Context Avoidable drug‐related problems (DRPs) cause substantial morbidity, mortality and costs. As most prescription errors are committed by recently graduated doctors, undergraduate training should specifically address DRPs. Objectives This study set out to investigate whether a DRP teaching module can reduce prescription errors made by advanced medical students in varying clinical contexts. Methods A total of 74 Year 5 medical students (mean age 25 ± 3 years; 24 men, 50 women) participated in a randomised controlled crossover study. Students filled in patients’ prescription charts before and after a special DRP training module and a control intervention. The 1‐week training module comprised a seminar on common prescription errors, a prescribing exercise with a standardised paper case patient, drafting of inoperative prescription charts for real patients and discussions with a lecturer. During the observation points, prescription charts for standardised patient cases in different clinical contexts had to be completed. These prescription charts were subsequently analysed by two independent raters using a checklist for common prescription errors. Results Prior to training, students committed a mean of 69 ± 12% of the potential prescription errors. This decreased to 29 ± 15% after DRP training ( P &lt; 0.001). Conclusions Prescription errors can be significantly reduced in a relatively brief training time by implementing a specific DRP teaching module.
The European Exenatide study of long‐term exenatide vs. glimepiride for type 2 diabetes: rationale and patient characteristics
2009-09-16

Aim : To describe the rationale for the European Exenatide (EUREXA) clinical study and describe the characteristics of the patient cohort. Methods : EUREXA is a multinational study of long‐term effects of add‐on exenatide vs. glimepiride in patients with type 2 diabetes and failure of diet/lifestyle plus metformin monotherapy. Metformin failure was defined as hemoglobin A1c (HbA1c) ≥ 6.5% and patients were overweight/obese (BMI ≥ 25 to &lt; 40 kg/m 2 ). The primary end point is time to failure of combination treatment, defined from HbA1c concentration according to current criteria. At baseline, an oral glucose tolerance test (OGTT) was performed, fasting blood was taken for lipid profile and patients were randomized to add‐on exenatide (5 μg b.i.d. for 4 weeks then 10 μg b.i.d.) or glimepiride (1 mg/day titrated to maximum dose). Results : A total of 1039 patients were entered in the study, with mean (± s.d.) age 57.2 ± 9.6 years, body mass index (BMI) 32.4 ± 4.1 kg/m 2 , duration of diabetes 5.6 ± 4.5 years and HbA1c 7.4 ± 0.7%. A history of cardiovascular disease (CVD) was present for 64.8% of patients overall and duration of diabetes was statistically significantly longer for patients with CVD than without (p = 0.010). Lipid abnormalities were reported for 48.9% of patients and 40.9% were taking at least one lipid‐lowering medication. Conclusion : Patients included in the EUREXA study had early failure of glucose control with metformin and presented typical features of type 2 diabetes: overweight/obesity and high prevalence of lipid abnormalities and CVD. In this population, the effects of exenatide vs. glimepiride will be evaluated over at least 2.5 years.