Prognostic utility of ADAMTS13 activity for the atypical hemolytic uremic syndrome (aHUS) and comparison of complement serology between aHUS and thrombotic thrombocytopenic purpura

Background Atypical hemolytic uremic syndrome (aHUS) involves dysregulation of the complement system, but whether this also occurs in thrombotic thrombocytopenic purpura (TTP) remains unclear. Although these conditions are difficult to differentiate clinically, TTP can be distinguished by low (<10%) ADAMTS13 activity. The aim was to identify the differences in complement activation products between TTP and aHUS and investigate ADAMTS13 activity as a prognostic factor in aHUS. Methods We analyzed patients with thrombotic microangiopathy diagnosed as TTP (N=48) or aHUS (N=50), selected from a Korean registry (N=551). Complement activation products in the plasma samples collected from the patients prior to treatment and in 40 healthy controls were measured by ELISA. Results The levels of generalized (C3a), alternate (factor Bb), and terminal (C5a and C5b-9) markers were significantly higher (all P<0.01) in the patients than in the healthy controls. Only the factor Bb levels significantly differed (P=0.008) between the two disease groups. In aHUS patients, high normal ADAMTS13 activity (≥77%) was associated with improved treatment response (OR, 6.769; 95% CI, 1.605–28.542; P=0.005), remission (OR, 6.000; 95% CI, 1.693–21.262; P=0.004), exacerbation (OR, 0.242; 95% CI, 0.064–0.916; P=0.031), and disease-associated mortality rates (OR, 0.155; 95% CI, 0.029–0.813; P=0.017). Conclusion These data suggest that complement biomarkers, except factor Bb, are similarly activated in TTP and aHUS patients, and ADAMTS13 activity can predict the treatment response and outcome in aHUS patients

Precision Measurement of the Proton Flux in Primary Cosmic Rays from Rigidity 1 GV to 1.8 TV with the Alpha Magnetic Spectrometer on the International Space Station

A precise measurement of the proton flux in primary cosmic rays with rigidity (momentum/charge) from 1 GV to 1.8 TV is presented based on 300 million events. Knowledge of the rigidity dependence of the proton flux is important in understanding the origin, acceleration, and propagation of cosmic rays. We present the detailed variation with rigidity of the flux spectral index for the first time. The spectral index progressively hardens at high rigidities.</p

Observation of intermediate bands feeding the positive-parity yrast band in 155^{155}Gd

High-spin states of $^{155}$Gd were populated by using the $^{154}$Sm($\alpha$,3n$\gamma$)$^{155}$Gd reaction at $E_{\alpha}$ = 33 MeV. $\gamma-\gamma$ coincidence, $E_{\gamma}$ singles, excitation function, and the DCO ratios were measured. we have identified three intermediate bands with $\Delta I = 2$ feeding the positive yrast band. The bands are interpreted as such candidate bands that are mixed with the negative-parity ground state band. This observation can provide a plausible explanation for unusually large population of the positive-parity yrast band observed in a recent Coulomb excitation

Prioritizing climate change adaptation options: Application of multi-criteria decision-making (MCDM) with stakeholder participation in water resources management

The complexity and uncertainty of climate change and differing stakeholder interests present substantial challenges to prioritization in adaptation strategies. Given that priorities can vary widely based on stakeholder composition and the selected adaptation measures, decision-making methodologies must possess the flexibility to accommodate these differences. With its multidisciplinary nature and diverse stakeholder involvement, water resources management requires comprehensive and integrated methods for rational priority-setting. This study assembled expert groups, including municipalities and civic organizations, to form a governance system. Trustworthy adaptation policy priorities were subsequently derived from this governance system's evaluation results. Recognizing that priority outcomes may differ across groups, we applied the Technique for Order Preference by Similarity to Ideal Solution (TOPSIS), a Multi-Criteria Decision-Making (MCDM) method. The application of TOPSIS within governance offers a variety of flexible priority options, surpassing the limitations of a single top priority, and allows decision-makers to adapt their choices to both national and local contexts. While survey-derived priorities may differ based on stakeholder composition, this approach allows for developing plans that reflect the urgency of regionally tailored policies. Our findings offer a foundation for understanding each priority's significance

PIASy-mediated sumoylation of SREBP1c regulates hepatic lipid metabolism upon fasting signaling

SREBP1c is a key transcription factor that regulates de novo lipogenesis during anabolic periods. However, the molecular mechanisms involved in the suppression of SREBP1c under nutritional deprivation are largely unknown. In this study, we demonstrate that the small ubiquitin-related modifier (SUMO) E3 ligase, a protein inhibitor of activated STAT Y (PIASy), sumoylates SREBP1c at Lys98, leading to suppression of the hepatic lipogenic program upon fasting-induced signals. In primary hepatocytes, ablation of PIASy stimulated intracellular lipid accumulation through the induction of SREBP1c and its target genes. Given that protein kinase A (PKA) plays important roles in catabolic responses, activated PKA enhances the sumoylation of SREBP1c and potentiates the interaction between SREBP1c and PIASy. Notably, overexpression of PIASy in obese db/db mice ameliorated hepatic steatosis, while suppression of PIASy in lean (wild-type) mice stimulated hepatic lipogenesis with increased expression of SREBP1c target genes. Furthermore, PKA-mediated SREBP1c phosphorylation augmented SREBP1c sumoylation, subsequently leading to degradation of SREBP1c via ubiquitination. Together, these data suggest that PKA-induced SREBP1c sumoylation by PIASy is a key regulatory mechanism to turn off hepatic lipogenesis during nutritional deprivation. © 2014, American Society for Microbiology.11Ysciescopu

Discontinuous pn-heterojunction for organic thin film transistors

Utilization of discontinuous pn-oragnic heterojunction is introduced as a versatile method to improve charge transport in organic thin film transistors (OTFTs). The method is demonstrated by depositing n-type dioctyl perylene tetracarboxylic diimide (PTCDI-C8) discontinuously onto base p-type pentacene OTFTs. A more pronounced impact of the discontinuous upper layer is obtained on the transistor performances when thinner base layers are employed; a >100-fold enhancement in hole mobility and a >20 V shift in threshold voltage are achieved after applying PTCDI-C8 discontinuously onto 2 nm thick pentacene thin films. Local surface potential measurements (Kelvin-probe force microscopy) and temperature-dependent transport measurements (77-300 K) reveal that the interfacial dipole formed at the pn-heterostructures effectively dopes the base pentacene films p-type and leads to a reduction in transport activation energy. cop. 2014 American Chemical Society

Smad4 expression in gastric adenoma and adenocarcinoma: Frequent loss of expression in diffuse type of gastric adenocarcinoma

Smads are signal transducers for the members of the TGF-ß superfamily. Of these Smads, Smad4 is essential for TGF-ß signaling. The purpose of this study was to elucidate Smad4 expression and localization in 65 gastric adenomas, 49 intestinal-type and 39 diffuse type of gastric adenocarcinomas (including 12 cases of fresh frozen tissue) using Realtime RT-PCR and immunohistochemistry. Real-time RTPCR showed that intestinal type gastric adenocarcinomas have higher Smad4 mRNA expression than diffuse type gastric adenocarcinomas. Immunohistochemical stain for Smad4 revealed that expression of Smad4 was significantly lower in diffusetype gastric adenocarcinoma than intestinal-type gastric adenocarcinomas. Also, higher Smad4 protein expression in intestinal type gastric adenocarcinomas than overall gastric adenoma was noted. The rate of reduced Smad4 expression was higher in advanced gastric cancer than early gastric cancer. These results suggest that Smad4 might play different roles in human gastric carcinogenesis, especially between intestinal type and diffuse type of gastric adenocarcinoma