P‐13: Photosensitivity of Amorphous IGZO TFTs for Active‐Matrix Flat‐Panel Displays

We studied the optical and electrical properties of the amorphous indium gallium zinc oxide thin‐film transistors (a‐IGZO TFTs). To develop a‐IGZO density‐of‐states model, intrinsic a‐IGZO optical properties such as optical band gap and Urbach energy, and TFT characteristics under illumination are investigated. During the a‐IGZO TFTs illumination with the wavelengths ranging from 460 to 660 nm, the off‐state drain current only slightly increases while a large increase was observed for the wavelength below 400 nm. Threshold voltage and subthreshold swing are also only slightly modified between 460 to 660 nm, while field‐effect mobility is almost unchanged in the investigated photon energy range. The observed results are consistent with the a‐IGZO optical energy band gap of about 3.05 eV. This study suggest that the a‐IGZO TFTs are light sensitive above 3.0 eV and photogenerated electrons are more mobile than holes within device channel region.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92030/1/1.3069354.pd

Proposal of a diagnostic algorithm for intraductal ultrasonography to distinguish between benign and malignant biliary strictures

To reexamine the recognizability of intraductal ultrasonography (IDUS) findings from an imaging database and propose a novel algorithm for clinical application. IDUS images of 102 patients who had undergone IDUS examinations for indeterminate causes of common bile duct dilation were independently reviewed by two endoscopists. The strength of the inter-rater agreement between the endoscopists was analyzed using Cohen's kappa (κ). An algorithm was implemented by arranging the IDUS characteristics according to their recognizability. The proposed algorithm was evaluated by examining the inter-rater agreement and diagnostic accuracy before and after the use of the algorithm. The strength of the inter-rater agreement was good for common bile duct stones with or without acoustic shadowing; intraluminal tumors; or bile duct wall thicknesses of more than or equal to 9 mm (κ > 0.8); followed by intraluminal hypoechoic nodules without common bile duct stone characteristics (κ = 0.771); and finally eccentric wall thickening, outer layer disruption, irregular mucosa, and destructed mural layers (κ: 0.595–0.419). Our algorithm improved the strength of inter-rater agreement with a diagnostic accuracy of 81.4%. We proposed an algorithm according to the recognizability of IDUS characteristics, and it can be used by endoscopists to evaluate such characteristics and determine the cause of biliary obstruction

An investigation of conventional microbial culture for the Naja atra bite wound, and the comparison between culture-based 16S Sanger sequencing and 16S metagenomics of the snake oropharyngeal bacterial microbiota.

Naja atra is a major venomous snake found in Taiwan. The bite of this snake causes extensive wound necrosis or necrotizing soft tissue infection. Conventional microbial culture-based techniques may fail to identify potential human pathogens and render antibiotics ineffective in the management of wound infection. Therefore, we evaluated 16S Sanger sequencing and next-generation sequencing (NGS) to identify bacterial species in the oropharynx of N. atra. Using conventional microbial culture methods and the VITEK 2 system, we isolated nine species from snakebite wounds. On the basis of the 16S Sanger sequencing of bacterial clones from agar plates, we identified 18 bacterial species in the oropharynx of N. atra, including Morganella morganii, Proteus vulgaris, and Proteus mirabilis, which were also present in the infected bite wound. Using NGS of 16S metagenomics, we uncovered more than 286 bacterial species in the oropharynx of N. atra. In addition, the bacterial species identified using 16S Sanger sequencing accounted for only 2% of those identified through NGS of 16S metagenomics. The bacterial microbiota of the oropharynx of N. atra were modeled better using NGS of 16S metagenomics compared to microbial culture-based techniques. Stenotrophomonas maltophilia, Acinetobacter baumannii, and Proteus penneri were also identified in the NGS of 16S metagenomics. Understanding the bacterial microbiota that are native to the oropharynx of N. atra, in addition to the bite wound, may have additional therapeutic implications regarding empiric antibiotic selection for managing N. atra bites

Allosteric Inhibitors of Zika Virus NS2B-NS3 Protease Targeting Protease in “Super-Open” Conformation

The Zika virus (ZIKV), a member of the Flaviviridae family, is considered a major health threat causing multiple cases of microcephaly in newborns and Guillain-Barré syndrome in adults. In this study, we targeted a transient, deep, and hydrophobic pocket of the "super-open" conformation of ZIKV NS2B-NS3 protease to overcome the limitations of the active site pocket. After virtual docking screening of approximately seven million compounds against the novel allosteric site, we selected the top six candidates and assessed them in enzymatic assays. Six candidates inhibited ZIKV NS2B-NS3 protease proteolytic activity at low micromolar concentrations. These six compounds, targeting the selected protease pocket conserved in ZIKV, serve as unique drug candidates and open new opportunities for possible treatment against several flavivirus infections

Diabetes diminishes the portal-systemic collateral vascular response to vasopressin via vasopressin receptor and Gα proteins regulations in cirrhotic rats.

Liver cirrhosis may lead to portal-systemic collateral formation and bleeding. The hemostatic effect is influenced by the response of collateral vessels to vasoconstrictors. Diabetes and glucose also influence vasoresponsiveness, but their net effect on collaterals remains unexplored. This study investigated the impact of diabetes or glucose application on portal-systemic collateral vasoresponsiveness to arginine vasopressin (AVP) in cirrhosis. Spraque-Dawley rats with bile duct ligation (BDL)-induced cirrhosis received vehicle (citrate buffer) or streptozotocin (diabetic, BDL/STZ). The in situ collateral perfusion was done after hemodynamic measurements: Both were perfused with Krebs solution, D-glucose, or D-glucose and NaF, with additional OPC-31260 for the BDL/STZ group. Splenorenal shunt vasopressin receptors and Gα proteins mRNA expressions were evaluated. The survival rate of cirrhotic rats was decreased by STZ injection. The collateral perfusion pressure changes to AVP were lower in STZ-injected groups, which were reversed by OPC-31260 (a V2R antagonist) and overcome by NaF (a G protein activator). The splenorenal shunt V2R mRNA expression was increased while Gα proteins mRNA expressions were decreased in BDL/STZ rats compared to BDL rats. The Gαq and Gα11 mRNA expressions also correlated with the maximal perfusion pressure changes to AVP. Diabetes diminished the portal-systemic collateral vascular response to AVP in rats with BDL-induced cirrhosis, probably via V2 receptor up-regulation and Gα proteins down-regulation

Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital

A B S T R A C T Gastro-oesophageal variceal haemorrhage is one of the most dreadful complications of portal hypertension and can be controlled with vasoconstrictors. Nevertheless, sympathetic tone abnormality and vascular hyporesponsiveness in portal hypertension may impede the haemostatic effects of vasoconstrictors. Propranolol, a β-blocker binding the G-protein-coupled adrenoceptor, is a portal hypotensive agent. However, whether propranolol influences the collateral vasoresponse is unknown. Portal hypertension was induced by PVL (portal vein ligation) in Sprague-Dawley rats. In an acute study with an in situ perfusion model, the collateral responsiveness to AVP (arginine vasopressin) was evaluated with vehicle, propranolol (10 μmol/l), propranolol plus suramin (100 μmol/l, a G α inhibitor) or suramin pre-incubation. G α mRNA expression in the splenorenal shunt, the most prominent intra-abdominal collateral vessel, was measured. In the chronic study, rats received DW (distilled water) or propranolol (10 mg · kg − 1 of body weight · day − 1 ) for 9 days. Then the concentration-response relationship of AVP and G α mRNA expression were assessed. Propranolol pre-incubation elevated the perfusion pressure changes of collaterals in response to AVP, which was inhibited by suramin. The splenorenal shunt G αq and G α11 mRNA expression were enhanced by propranolol. The group treated with propranolol plus suramin had a down-regulation of G α11 as compared with the propranolol group. Chronic propranolol treatment reduced mean arterial pressure, PP (portal pressure) and the perfusion pressure changes of collaterals to AVP. G αs expression was up-regulated. In conclusion, propranolol pre-incubation enhanced the portalsystemic collateral AVP responsiveness in portal hypertensive rats, which was related to G αq and G α11 up-regulation. In contrast, the attenuated AVP responsiveness by chronic propranolol treatment was related to G αs up-regulation. The G α signalling pathway may be a therapeutic target to control variceal bleeding and PP in portal hypertension

Enhancement of NETosis by ACE2-cross-reactive anti-SARS-CoV-2 RBD antibodies in patients with COVID-19.

BACKGROUND: High levels of neutrophil extracellular trap (NET) formation or NETosis and autoantibodies are related to poor prognosis and disease severity of COVID-19 patients. Human angiotensin-converting enzyme 2 (ACE2) cross-reactive anti-severe acute respiratory syndrome coronavirus 2 spike protein receptor-binding domain (SARS-CoV-2 RBD) antibodies (CR Abs) have been reported as one of the sources of anti-ACE2 autoantibodies. However, the pathological implications of CR Abs in NET formation remain unknown. METHODS: In this study, we first assessed the presence of CR Abs in the sera of COVID-19 patients with different severity by serological analysis. Sera and purified IgG from CR Abs positive COVID-19 patients as well as a mouse monoclonal Ab (mAb 127) that can recognize both ACE2 and the RBD were tested for their influence on NETosis and the possible mechanisms involved were studied. RESULTS: An association between CR Abs levels and the severity of COVID-19 in 120 patients was found. The CR Abs-positive sera and IgG from severe COVID-19 patients and mAb 127 significantly activated human leukocytes and triggered NETosis, in the presence of RBD. This NETosis, triggered by the coexistence of CR Abs and RBD, activated thrombus-related cells but was abolished when the interaction between CR Abs and ACE2 or Fc receptors was disrupted. We also revealed that CR Abs-induced NETosis was suppressed in the presence of recombinant ACE2 or the Src family kinase inhibitor, dasatinib. Furthermore, we found that COVID-19 vaccination not only reduced COVID-19 severity but also prevented the production of CR Abs after SARS-CoV-2 infection. CONCLUSIONS: Our findings provide possible pathogenic effects of CR Abs in exacerbating COVID-19 by enhancing NETosis, highlighting ACE2 and dasatinib as potential treatments, and supporting the benefit of vaccination in reducing disease severity and CR Abs production in COVID-19 patients