julilili42/papers huggingface dataset:
Amelanotic Esophageal Malignant Melanoma: Case Report and Short Review of the Literature
2008-07-09

Malignant melanoma in the esophagus is a rare condition which has been described only occasionally in case reports or in larger series of patients with esophageal disease. We describe here the very rare case of a patient who presented initially with a 2-month history of dysphagia and weight loss which led to the endoscopic diagnosis of an unclear lesion in the distal esophagus. Biopsies were taken revealing positive immunohistochemical staining against HMB-45. As there were no signs of skin melanoma and there was an absence of pigmentation, a diagnosis of primary amelanotic malignant melanoma was made. Primary staging of the lesion was completed with computed tomography (CT), which revealed a locally advanced tumor with lymph node metastases at the lesser curvature of the stomach and celiac trunk. As there is still a lack of potential protocols for multimodal neoadjuvant treatment for this rare tumor entity, a palliative abdominothoracic esophagectomy with systemic lymphadenectomy and intrathoracic anastomosis was carried out. Due to an intraoperative R2 situation, clip marking was performed to allow postoperative radiotherapy. Two months postoperatively, the planning CT scan for radiotherapy revealed progression of the retroperitoneal tumor mass, which was enclosing the celiac trunk, renal vein, and superior mesenteric artery. Multiple new liver and lung metastases were also found. During the following weeks, the patient developed acute renal failure and was admitted for dialysis, and the planned radiotherapy was deferred. At the end of May 2007, 4 months after the primary diagnosis, the patient died due to acute renal failure.
Asymptotic expansions and attractive invariant manifolds of strongly damped mechanical systems
2008-07-10

Abstract We study analytical properties of strongly damped mechanical systems, for which the equations of motion form a singular singularly perturbed system. We show that slow solutions can be represented by an asymptotic expansion in powers of the reciprocal of the damping parameter. Further it is shown that the strong damping forces the motion to run into an invariant manifold at an exponential rate.
Aldosterone increases KCa1.1 (BK) channel‐mediated colonic K+ secretion
2008-07-11

Mammalian K + homeostasis results from highly regulated renal and intestinal absorption and secretion, which balances the unregulated K + intake. Aldosterone is known to enhance both renal and colonic K + secretion. In mouse distal colon K + secretion occurs exclusively via luminal K Ca 1.1 (BK) channels. Here we investigate if aldosterone stimulates colonic K + secretion via BK channels. Luminal Ba 2+ and iberiotoxin (IBTX)‐sensitive electrogenic K + secretion was measured in Ussing chambers. In vivo aldosterone was augmented via a high K + diet. High K + diet led to a 2‐fold increase of luminal Ba 2+ and IBTX‐sensitive short‐circuit current in distal mouse colonic mucosa. This effect was absent in BK α‐subunit‐deficient (BK −/− ) mice. The resting and diet‐induced K + secretion was stimulated by luminal ionomycin. In BK −/− mice luminal ionomycin did not stimulate K + secretion. In vitro addition of aldosterone likewise triggered a 2‐fold increase in K + secretion, which was inhibited by the mineralocorticoid receptor antagonist spironolactone and the BK channel blocker IBTX. Semi‐quantification of mRNA from colonic crypts showed up‐regulation of BK α‐ and β 2 ‐subunits in high K + diet mice. The BK channel could be detected luminally in colonic crypt cells by immunohistochemistry. The expression level of the channel in the luminal membrane was strongly up‐regulated in K + ‐loaded animals. Taken together, these data strongly suggest that aldosterone‐induced K + secretion occurs via increased expression of luminal BK channels.
ChemInform Abstract: Reaction of N‐Nonaflyl and N‐Cyano‐benzotriazoles with Enamines.
2008-07-11

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Molecular orientation in diindenoperylene thin films deposited on polycrystalline gold
2008-07-14

We present x-ray photoemission spectroscopy (XPS) and near-edge x-ray absorption fine structure spectroscopy measurements taken on diindenoperylene (DIP) thin films of different thicknesses deposited on polycrystalline gold. Our investigations show that DIP films present flat lying molecules in the first layer, while the angle between the molecular axis and the surface increases with thickness. By using XPS, we find evidence for Stranski–Krastanov growth mode.
Centennial‐scale evolution of Dansgaard‐Oeschger events in the northeast Atlantic Ocean between 39.5 and 56.5 ka B.P.
2008-07-15

There is much uncertainty surrounding the mechanisms that forced the abrupt climate fluctuations found in many palaeoclimate records during Marine Isotope Stage (MIS)‐3. One of the processes thought to be involved in these events is the Atlantic Meridional Overturning Circulation (MOC), which exhibited large changes in its dominant mode throughout the last glacial period. Giant piston core MD95‐2006 from the northeast Atlantic Ocean records a suite of palaeoceanographic proxies related to the activity of both surface and deep water masses through a period of MIS‐3 when abrupt climate fluctuations were extremely pronounced. A two‐stage progression of surface water warming during interstadial warm events is proposed, with initial warming related to the northward advection of a thin warm surface layer within the North Atlantic Current, which only extended into deeper surface layers as the interstadial progressed. Benthic foraminifera isotope data also show millennial‐scale oscillations but of a different structure to the abrupt surface water changes. These changes are argued to partly be related to the influence of low‐salinity deepwater brines. The influence of deepwater brines over the site of MD95‐2006 reached a maximum at times of rapid warming of surface waters. This observation supports the suggestion that brine formation may have helped to destabilize the accumulation of warm, saline surface waters at low latitudes, helping to force the MOC into a warm mode of operation. The contribution of deepwater brines relative to other mechanisms proposed to alter the state of the MOC needs to be examined further in future studies.
Plasma Fetuin-A Levels and the Risk of Type 2 Diabetes
2008-07-16

OBJECTIVE—The liver-secreted protein fetuin-A induces insulin resistance in animals, and circulating fetuin-A is elevated in insulin resistance and fatty liver in humans. We investigated whether plasma fetuin-A levels predict the incidence of type 2 diabetes in a large prospective, population-based study. RESEARCH DESIGN AND METHODS—A case-cohort study within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study comprising 27,548 subjects was designed. We randomly selected a subcohort of 2,500 individuals of whom 2,164 were diabetes free at baseline and had anamnestic, anthropometrical, and metabolic data for analysis. Of the 849 incident diabetic case subjects identified in the full cohort during 7 years of follow-up, 703 remained for analyses after similar exclusions. RESULTS—Plasma fetuin-A levels were positively associated with diabetes risk after adjustment for age (relative risk [RR] for extreme quintiles 1.75 [95% CI 1.32–2.31]; RR for 10 μg/ml 1.04 [1.03–1.06]). The association remained significant after adjustment for sex, BMI, waist circumference, and lifestyle risk factors (RR for 10 μg/ml 1.03 [1.01–1.06]). Adjustment for glucose, triglycerides, HDL cholesterol, A1C, γ-glutamyltransferase, or high-sensitivity C-reactive protein or mutual adjustment for these biomarkers did not appreciably change this result (RR for 10 μg/ml full adjusted model 1.05 [1.02–1.07]). Furthermore, fetuin-A was associated with increased diabetes risk particularly in individuals with elevated plasma glucose. CONCLUSIONS—Our data suggest that fetuin-A is an independent risk factor of type 2 diabetes.
MetaRoute: fast search for relevant metabolic routes for interactive network navigation and visualization
2008-07-16

Abstract Summary: We present MetaRoute, an efficient search algorithm based on atom mapping rules and path weighting schemes that returns relevant or textbook-like routes between a source and a product metabolite within seconds for genome-scale networks. Its speed allows the algorithm to be used interactively through a web interface to visualize relevant routes and local networks for one or multiple organisms based on data from KEGG. Availability: http://www-bs.informatik.uni-tuebingen.de/Services/MetaRoute. Contact: blum@informatik.uni-tuebingen.de Supplementary information: Supplementary details are available at http://www-bs.informatik.uni-tuebingen.de/Services/MetaRoute
Amygdaloid metabotropic glutamate receptor subtype 7 is involved in the acquisition of conditioned fear
2008-07-16

The metabotropic glutamate receptor subtype 7 (mGluR7) is presynaptically located and modulates transmitter release. An earlier study from our group demonstrated that systemic administration of N,N'-dibenzyhydryl-ethane-1,2-diamine dihydrochloride (AMN082), a selective allosteric mGluR7 agonist, attenuates the acquisition of conditioned fear measured by fear-potentiated startle. Aim of this study was to explore whether this effect is mediated by the basolateral amygdala, a crucial brain structure for acquisition of conditioned fear. Therefore, AMN082 was locally injected into the basolateral amygdala of rats and the effects of these injections on the acquisition of conditioned fear was measured. Our data clearly show that intra-amygdala injection of AMN082 impairs fear acquisition. This finding demonstrates that amygdaloid mGluR7 controls the learning of conditioned fear.
Anti-Fungal Innate Immunity in C. elegans Is Enhanced by Evolutionary Diversification of Antimicrobial Peptides
2008-07-17

Encounters with pathogens provoke changes in gene transcription that are an integral part of host innate immune responses. In recent years, studies with invertebrate model organisms have given insights into the origin, function, and evolution of innate immunity. Here, we use genome-wide transcriptome analysis to characterize the consequence of natural fungal infection in Caenorhabditis elegans. We identify several families of genes encoding putative antimicrobial peptides (AMPs) and proteins that are transcriptionally up-regulated upon infection. Many are located in small genomic clusters. We focus on the nlp-29 cluster of six AMP genes and show that it enhances pathogen resistance in vivo. The same cluster has a different structure in two other Caenorhabditis species. A phylogenetic analysis indicates that the evolutionary diversification of this cluster, especially in cases of intra-genomic gene duplications, is driven by natural selection. We further show that upon osmotic stress, two genes of the nlp-29 cluster are strongly induced. In contrast to fungus-induced nlp expression, this response is independent of the p38 MAP kinase cascade. At the same time, both involve the epidermal GATA factor ELT-3. Our results suggest that selective pressure from pathogens influences intra-genomic diversification of AMPs and reveal an unexpected complexity in AMP regulation as part of the invertebrate innate immune response.
Comparison of insulin analogue regimens in people with type 2 diabetes mellitus in the PREFER Study: a randomized controlled trial
2008-07-17

Aims: Insulin analogues are widely used but few data exist comparing different analogue regimens. We compared two such regimens in type 2 diabetes mellitus (T2DM) uncontrolled by oral antidiabetic agents (OADs) with or without basal insulin. Methods: In a 26‐week multinational, multicentre, randomized treat‐to‐target trial, OADs were discontinued and subjects randomized to analogue basal–bolus therapy (insulin detemir once daily and insulin aspart mealtimes) or biphasic insulin aspart 30 (30% rapid‐acting insulin aspart), twice daily. Insulin was titrated to targets for fasting, predinner and postprandial plasma glucose (PG), as appropriate. Results: Of 719 subjects, 92% completed the study; 58% achieved haemoglobin fraction A 1c (HbA 1c ) ≤7.0%, with reductions of 1.56% (to 6.96%) with basal–bolus therapy and 1.23% (to 7.17%) with biphasic insulin aspart. Reduction with basal–bolus therapy was superior in the overall population by 0.23% (p = 0.0052), with no difference between regimens in insulin‐naive patients. Major hypoglycaemia occurred in five basal–bolus patients (0.9%) and in no patients with biphasic insulin aspart. Incidence of minor hypoglycaemia was similar in both groups. All insulin doses increased during titration, with increase in lunchtime insulin aspart dose and equal distribution of breakfast and dinner biphasic insulin aspart doses. Insulin detemir remained once daily in 87% of patients. Conclusions: Modern insulin analogue regimens, adjusted to PG targets, enable a majority of people with T2DM to reach HbA 1c ≤7.0% after failure of OADs and OAD‐basal insulin therapy. Insulin‐treated patients may benefit more from transfer to analogue basal–bolus therapy, while insulin‐naive individuals benefit equally well from the more convenient biphasic analogue regimen.
Whole-grain consumption and transcription factor-7-like 2 (TCF7L2) rs7903146: gene–diet interaction in modulating type 2 diabetes risk
2008-07-17

Whole grains are known to influence postprandial glucose response and insulin demand and are inversely associated with diabetes risk. Genetic variation of the transcription factor-7-like 2 encoding gene ( TCF7L2 ) is assumed to promote an early insulin secretory defect and has been consistently attributed to the risk of developing type 2 diabetes. The present study examined the hypothesis that the protective effect of whole grains might be attenuated in the presence of the rs7903146 risk-conferring T-allele. We employed a case–cohort study of 2318 randomised individuals and 724 incident type 2 diabetes cases from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort. Multivariate Cox regression was used to estimate relative risks of diabetes including product terms testing for the genotype-specific effect modification of dietary whole grain. Dietary intake of whole grains was assessed by a validated FFQ. The TCF7L2 rs7903146 T-allele was associated with type 2 diabetes (hazard ratio = 1·51; 95 % CI 1·21, 1·87) and modified the inverse association between whole-grain intake and diabetes risk ( P = 0·016 for interaction). While whole-grain intake was inversely associated with diabetes risk among rs7903146 CC homozygote carriers (hazard ratio for 50 g portion per d = 0·86; 95 % CI 0·75, 0·99), the T-allele negated the protective effect of whole-grain intake (hazard ratio among T-allele carriers for 50 g portion per d = 1·08; 95 % CI 0·96, 1·23). These data provide evidence that the beneficial effect of whole-grain intake on diabetes risk is modified by TCF7L2 rs7903146.
Thymidine Kinase Sequence Analysis of Herpes Simplex Virus Type 1 Strains Present in Different Compartments in an Atypical Impetiginous Rash on the Lesional Skin of a Burn Patient
2008-07-17

ABSTRACT We report the case of a 23-year-old male burn patient with an unusual herpes simplex virus (HSV) skin manifestation. The clinical symptoms and results of HSV type 1 (HSV-1) UL23 polymorphism analysis from saliva and lesional skin underscores the need for performing molecular analysis of HSV-1 infections in burned patients presenting unusual skin lesions.
Complexity and exact algorithms for multicut
2008-07-17

Abstract. The Multicut problem is defined as: given an undirected graph and a collection of pairs of terminal vertices, find a minimum set of edges or vertices whose removal disconnects each pair. We mainly focus on the case of removing vertices, where we distinguish between allowing or disallowing the removal of terminal vertices. Complementing and refining previous results from the literature, we provide several NP-completeness and (fixed-parameter) tractability results for restricted classes of graphs such as trees, interval graphs, and graphs of bounded treewidth. 1
Planetary Migration in Resonance : The Question of the Eccentricities
2008-07-17

\\n \\nThe formation of resonant planets pairs in exoplanetary systems\\ninvolves planetary migration inside the protoplanetary disc: an\\ninwards migrating outer planet captures in Mean Motion Resonance an\\ninner planet. During the migration of the resonant pair of planets,\\nthe eccentricities are expected to rise excessively, if no damping\\nmechanism is applied on the inner planet. We express the required\\ndamping action to match the observations, and we show that the inner\\ndisk can play this role. This result applies for instance to the\\nsystem GJ 876: we reproduce the observed orbital elements through a\\nfully hydrodynamical simulation of the evolution of the resonant\\nplanets.\\n\\n
A novel upstream regulator of WRKY53 transcription during leaf senescence in Arabidopsis thaliana
2008-07-18

Abstract Arabidopsis WRKY proteins comprise a family of zinc finger‐type transcription factors involved in the regulation of gene expression during pathogen defence, wounding, trichome development and senescence. To better understand the regulatory role of the senescence‐related WRKY53 factor, we identified upstream regulatory factors using the yeast one‐hybrid system. Among others, we identified a DNA‐binding protein with a so far unknown function that contains a transcriptional activation domain and a kinase domain with similarities to HPT kinases. In vitro studies revealed that this activation domain protein (AD protein) can phosphorylate itself and that phosphorylation increases its DNA‐binding activity to the WRKY53 promoter region. Using the yeast two‐hybrid system, an interaction with proteins that were previously shown to bind to the WRKY53 promoter was tested. The AD protein interacted with MEKK1. The interaction with MEKK1 was confirmed in vivo by bimolecular fluorescence complementation (BiFC); however, the AD protein was not phosphorylated by MEKK1 in vitro and vice versa . This indicates that there may be competition between WRKY53 and AD protein for binding of MEKK1 at the WRKY53 promoter. Overexpression and knockout of the respective gene resulted in changes in transcription levels of WRKY53 , indicating that AD protein is a positive regulator of WRKY53 expression. Expression of the AD protein gene can be induced by hydrogen peroxide treatment and reduced by jasmonic acid treatment, as previously shown for WRKY53.
Functional Chimeras of the Phosphodiesterase 5 and 10 Tandem GAF Domains
2008-07-18

The tandem GAF domain of hPDE10A uses cAMP as an allosteric ligand (Gross-Langenhoff, M., Hofbauer, K., Weber, J., Schultz, A., and Schultz, J. E. (2006) J. Biol. Chem. 281, 2841-2846). We used a two-pronged approach to study how discrimination of ligand is achieved in human (h)PDE10A and how domain selection in the phosphodiesterase GAF tandems is determined. First, we examined which functional groups of cAMP are responsible for purine ring discrimination. Changes at the C-6 ring position (removal of the amino group; chloride substitution) and at the N-1 ring position reduced stimulation efficacy by 80%, i.e. marking those positions as decisive for nucleotide discrimination. Second, we generated a GAF tandem chimera that consisted of the cGMP-binding GAF-A unit from hPDE5A1, which signals through cGMP in PDE5, and the GAF-B from hPDE10A1, which signals through cAMP in PDE10. Stimulation of the reporter enzyme exclusively was through the GAF-B domain of hPDE10A1 (EC(50) = 7 microm cAMP) as shown by respective point mutations. The PDE5 GAF-A domain in the chimera did not signal, and its function was reduced to a strictly structural role. Signaling was independent of the origin of the N terminus. Generating 10 additional PDE5/10 tandem GAF chimeras surprisingly demonstrated that the length-conserved linker in GAF tandems between GAF-A and GAF-B played an unforeseen decisive role in intramolecular signaling. Swapping the linker sections between PDE5 and PDE10 GAF tandem domains abrogated signaling completely pointing to specific domain interactions within GAF tandems, which are not visible in the available crystal structures with bound ligands.
Tectonic implications of new U–Pb zircon ages of the Ladakh batholith, Indus suture zone, northwest Himalaya, India
2008-07-21

Abstract We determined U–Pb ages on zircons from Ladakh granitoid samples of three previously undated plutons and deduced four distinct age groups between c. 67 and c. 45 Ma (66.6 ± 2.1, 57.6 ± 1.4, 53.4 ± 1.8, 52.50 ± 0.53 and 45.27 ± 0.56 Ma). This suggests that the Ladakh batholith grew by addition of at least four distinct subduction‐related magma pulses at c . 67, 58, 53 and 45 Ma, thus indicating that the belt was continuously active throughout the Palaeocene and the Middle Eocene (Lutetian). The 45.27 ± 0.56 Ma pluton at Daah‐Hanu is the last major calcalkaline arc magmatic pulse in the Ladakh batholith. Thereafter, the subduction‐related major plutonism gradually waned. The earlier estimate for the youngest pluton within the Ladakh batholith is 49.8 ± 0.8 Ma for the Leh pluton ( J. Geol ., 2000, 108 , 303 ).
The ambiguous use of language in the paradigms of QUAN and QUAL
2008-07-21

Whether they teach or apply quantitative (QUAN) or qualitative (QUAL) methodology, textbooks as well as research reports often use ambiguous language in the sense that many formulations cannot be assigned unequivocally to one of the main methodological orientations. An analysis of research reports on the linguistic level shows that QUAN and QUAL paradigms cannot be separated strictly on the level of language. The use of language consolidates the strands of research activities and, therefore, the logic and hidden meanings behind scientific conclusions are revealed. QUAL studies often quantify at least their findings, and QUAN approaches implicitly introduce concepts, ideas and strategies from the field of QUAN. Examples from empirical research and the teaching of statistics demonstrate this ambiguity. Supposing that both approaches actually do not represent isolated paradigms but rather more or less clearly identified steps in the research process, we compare the essential criteria of quality in the domain...