Characterizing Interdisciplinarity of Researchers and Research Topics Using Web Search Engines

Researchers' networks have been subject to active modeling and analysis. Earlier literature mostly focused on citation or co-authorship networks reconstructed from annotated scientific publication databases, which have several limitations. Recently, general-purpose web search engines have also been utilized to collect information about social networks. Here we reconstructed, using web search engines, a network representing the relatedness of researchers to their peers as well as to various research topics. Relatedness between researchers and research topics was characterized by visibility boost-increase of a researcher's visibility by focusing on a particular topic. It was observed that researchers who had high visibility boosts by the same research topic tended to be close to each other in their network. We calculated correlations between visibility boosts by research topics and researchers' interdisciplinarity at individual level (diversity of topics related to the researcher) and at social level (his/her centrality in the researchers' network). We found that visibility boosts by certain research topics were positively correlated with researchers' individual-level interdisciplinarity despite their negative correlations with the general popularity of researchers. It was also found that visibility boosts by network-related topics had positive correlations with researchers' social-level interdisciplinarity. Research topics' correlations with researchers' individual- and social-level interdisciplinarities were found to be nearly independent from each other. These findings suggest that the notion of "interdisciplinarity" of a researcher should be understood as a multi-dimensional concept that should be evaluated using multiple assessment means.Comment: 20 pages, 7 figures. Accepted for publication in PLoS On

PPAR? Downregulation by TGF in Fibroblast and Impaired Expression and Function in Systemic Sclerosis: A Novel Mechanism for Progressive Fibrogenesis

The nuclear orphan receptor peroxisome proliferator-activated receptor-gamma (PPAR-γ) is expressed in multiple cell types in addition to adipocytes. Upon its activation by natural ligands such as fatty acids and eicosanoids, or by synthetic agonists such as rosiglitazone, PPAR-γ regulates adipogenesis, glucose uptake and inflammatory responses. Recent studies establish a novel role for PPAR-γ signaling as an endogenous mechanism for regulating transforming growth factor-ß (TGF-ß)- dependent fibrogenesis. Here, we sought to characterize PPAR-γ function in the prototypic fibrosing disorder systemic sclerosis (SSc), and delineate the factors governing PPAR-γ expression. We report that PPAR-γ levels were markedly diminished in skin and lung biopsies from patients with SSc, and in fibroblasts explanted from the lesional skin. In normal fibroblasts, treatment with TGF-ß resulted in a time- and dose-dependent down-regulation of PPAR-γ expression. Inhibition occurred at the transcriptional level and was mediated via canonical Smad signal transduction. Genome-wide expression profiling of SSc skin biopsies revealed a marked attenuation of PPAR-γ levels and transcriptional activity in a subset of patients with diffuse cutaneous SSc, which was correlated with the presence of a ''TGF-ß responsive gene signature'' in these biopsies. Together, these results demonstrate that the expression and function of PPAR-γ are impaired in SSc, and reveal the existence of a reciprocal inhibitory cross-talk between TGF-ß activation and PPAR-γ signaling in the context of fibrogenesis. In light of the potent anti-fibrotic effects attributed to PPAR-γ, these observations lead us to propose that excessive TGF-ß activity in SSc accounts for impaired PPAR-γ function, which in turn contributes to unchecked fibroblast activation and progressive fibrosis. © 2010 Wei et al

Ergodic properties of quasi-Markovian generalized Langevin equations with configuration dependent noise and non-conservative force

We discuss the ergodic properties of quasi-Markovian stochastic differential equations, providing general conditions that ensure existence and uniqueness of a smooth invariant distribution and exponential convergence of the evolution operator in suitably weighted $L^{\infty}$ spaces, which implies the validity of central limit theorem for the respective solution processes. The main new result is an ergodicity condition for the generalized Langevin equation with configuration-dependent noise and (non-)conservative force

Prolyl Isomerase Pin1 Regulates Mouse Embryonic Fibroblast Differentiation into Adipose Cells

isomerase, Pin1, regulates insulin signal transduction. Pin1 reduces responses to insulin stimulation by binding CRTC2 (CREB-regulated transcriptional co-activator 2) and PPARγ (peroxisome prolifereator- activated receptor γ), but conversely enhances insulin signaling by binding IRS-1 (insulin receptor substrate-1), Akt kinase, and Smad3. Therefore, it is still unclear whether Pin1 inhibits or enhances adipose cell differentiation. mice was restored by increasing expression of Pin1. We found that Pin1 binds to phosphoThr172- and phosphoSer271-Pro sites in CREB suppress the activity in COS-7 cells.Pin1 enhanced the uptake of triglycerides and the differentiation of MEF cells into adipose cells in response to insulin stimulation. Results of this study suggest that Pin1 down-regulation could be a potential approach in obesity-related dysfunctions, such as high blood pressure, diabetes, non-alcoholic steatohepatitis

Unresectable gastric cancer with gastric outlet obstruction and distant metastasis responding to intraperitoneal and folfox chemotherapy after palliative laparoscopic gastrojejunostomy: report of a case

<p>Abstract</p> <p>Background</p> <p>Gastric outlet obstruction (GOO) caused by unresectable gastric cancer is a challenging aspect of patient care. There have been no reports involving patients with obstructing gastric cancer and several incurable factors curatively treated by multimodal treatments.</p> <p>Case presentation</p> <p>We report a case of 55-year-old man who was diagnosed with a poorly differentiated adenocarcinoma in the pre-pyloric antrum with GOO by gastroscopy. An abdominal computed tomography (CT) scan revealed thickening of the gastric wall and adjacent fat infiltration, and a large amount of food in the stomach suggesting a passage disturbance, enlarged lymph nodes along the common hepatic and left gastric arteries, and multiple hepatic metastases. The serum carcinoembryonic antigen (CEA) level was 343 ng/ml and the carbohydrate antigen (CA) 19-9 level was within normal limits. The patient underwent a laparoscopic gastrojejunostomy for palliation of the GOO. On the 3^rdand 12^thdays after surgery, he received intraperitoneal chemotherapy with 40 mg of docetaxel and 150 mg of carboplatin. Simultaneously, combined chemotherapy with 85 mg/m²of oxaliplatin for the 1^stday and 600 mg/m²of 5-FU for 2 days (FOLFOX regimen) was administered from the 8^thpost-operative day. After completion of nine courses of FOLFOX, the patient achieved a complete response (CR) with complete disappearance of the primary tumor and the metastatic foci. He underwent a radical subtotal gastrectomy with D3 lymph node dissection 4 months after the initial palliative surgery. The pathologic results revealed no residual primary tumor and no lymph node metastasis in 43 dissected lymph nodes. He has maintained a CR for 18 months since the last operation.</p> <p>Conclusion</p> <p>Combination chemotherapy with systemic and intraperitoneal chemotherapy following laparoscopic bypass surgery showed marked efficacy in the treatment for unresectable advanced gastric cancer with GOO.</p

Monoubiquitination of syntaxin 3 leads to retrieval from the basolateral plasma membrane and facilitates cargo recruitment to exosomes

Syntaxin 3 (Stx3), a SNARE protein located and functioning at the apical plasma membrane of epithelial cells, is required for epithelial polarity. A fraction of Stx3 is localized to late endosomes/lysosomes, although how it traffics there and its function in these organelles is unknown. Here we report that Stx3 undergoes monoubiquitination in a conserved polybasic domain. Stx3 present at the basolateral—but not the apical—plasma membrane is rapidly endocytosed, targeted to endosomes, internalized into intraluminal vesicles (ILVs), and excreted in exosomes. A nonubiquitinatable mutant of Stx3 (Stx3-5R) fails to enter this pathway and leads to the inability of the apical exosomal cargo protein GPRC5B to enter the ILV/exosomal pathway. This suggests that ubiquitination of Stx3 leads to removal from the basolateral membrane to achieve apical polarity, that Stx3 plays a role in the recruitment of cargo to exosomes, and that the Stx3-5R mutant acts as a dominant-negative inhibitor. Human cytomegalovirus (HCMV) acquires its membrane in an intracellular compartment and we show that Stx3-5R strongly reduces the number of excreted infectious viral particles. Altogether these results suggest that Stx3 functions in the transport of specific proteins to apical exosomes and that HCMV exploits this pathway for virion excretion

Neural coding in a single sensory neuron controlling opposite seeking behaviours in Caenorhabditis elegans

Unveiling the neural codes for intricate behaviours is a major challenge in neuroscience. The neural circuit for the temperature-seeking behaviour of Caenorhabditis elegans is an ideal system to dissect how neurons encode sensory information for the execution of behavioural output. Here we show that the temperature-sensing neuron AFD transmits both stimulatory and inhibitory neural signals to a single interneuron AIY. In this circuit, a calcium concentration threshold in AFD acts as a switch for opposing neural signals that direct the opposite behaviours. Remote control of AFD activity, using a light-driven ion pump and channel, reveals that diverse reduction levels of AFD activity can generate warm- or cold-seeking behaviour. Calcium imaging shows that AFD uses either stimulatory or inhibitory neuronal signalling onto AIY, depending on the calcium concentration threshold in AFD. Thus, dual neural regulation in opposite directions is directly coupled to behavioural inversion in the simple neural circuit

Diabetes status and post-load plasma glucose concentration in relation to site-specific cancer mortality: findings from the original Whitehall study

ObjectiveWhile several studies have reported on the relation of diabetes status with pancreatic cancer risk, the predictive value of this disorder for other malignancies is unclear. Methods: The Whitehall study, a 25year follow-up for mortality experience of 18,006 men with data on post-challenge blood glucose and self-reported diabetes, allowed us to address these issues. Results: There were 2158 cancer deaths at follow-up. Of the 15 cancer outcomes, diabetes status was positively associated with mortality from carcinoma of the pancreas and liver, while the relationship with lung cancer was inverse, after controlling for a range of potential covariates and mediators which included obesity and socioeconomic position. After excluding deaths occurring in the first 10years of follow-up to examine the effect of reverse causality, the magnitude of the relationships for carcinoma of the pancreas and lung was little altered, while for liver cancer it was markedly attenuated. Conclusions: In the present study, diabetes status was related to pancreatic, liver, and lung cancer risk. Cohorts with serially collected data on blood glucose and covariates are required to further examine this area

STEM nanoanalysis of Au/Pt/Ti-Si3N4 interfacial defects and reactions during local stress of SiGe HBTs

A new insight on the behavior of metal contact-insulating interfaces in SiGe heterojunction bipolar transistor is given by high-performance aberration-corrected scanning transmission electron microscopy (STEM) analysis tools equipped with sub-nanometric probe size. It is demonstrated that the presence of initial defects introduced during technological processes play a major role in the acceleration of degradation mechanisms of the structure during stress. A combination of energy-filtered transmission electron microscopy analysis with high angle annular dark field STEM and energy dispersive spectroscopy provides strong evidence that migration of Au-Pt from the metal contacts to Ti/Si3N4 interface is one of the precursors to species interdiffusion and reactions. High current densities and related local heating effects induce the evolution of the pure Ti initial layer into mixture layer composed of Ti, O, and N. Local contamination of Ti layers by fluorine atoms is also pointed out, as well as rupture of TiN thin barrier layer

Novel autoantigens immunogenic in COPD patients

<p>Abstract</p> <p>Background</p> <p>Chronic obstructive pulmonary disease (COPD) is a respiratory inflammatory condition with autoimmune features including IgG autoantibodies. In this study we analyze the complexity of the autoantibody response and reveal the nature of the antigens that are recognized by autoantibodies in COPD patients.</p> <p>Methods</p> <p>An array of 1827 gridded immunogenic peptide clones was established and screened with 17 sera of COPD patients and 60 healthy controls. Protein arrays were evaluated both by visual inspection and a recently developed computer aided image analysis technique. By this computer aided image analysis technique we computed the intensity values for each peptide clone and each serum and calculated the area under the receiver operator characteristics curve (AUC) for each clone and the separation COPD sera versus control sera.</p> <p>Results</p> <p>By visual evaluation we detected 381 peptide clones that reacted with autoantibodies of COPD patients including 17 clones that reacted with more than 60% of the COPD sera and seven clones that reacted with more than 90% of the COPD sera. The comparison of COPD sera and controls by the automated image analysis system identified 212 peptide clones with informative AUC values. By <it>in silico </it>sequence analysis we found an enrichment of sequence motives previously associated with immunogenicity.</p> <p>Conclusion</p> <p>The identification of a rather complex humoral immune response in COPD patients supports the idea of COPD as a disease with strong autoimmune features. The identification of novel immunogenic antigens is a first step towards a better understanding of the autoimmune component of COPD.</p