The role of SARS-CoV-2 ORF8 protein ARKS motif on novobiocin binding

The discovery of the SARS-CoV-2 virus during the COVID-19 pandemic required scientists to develop medical solutions to reduce infectivity, severity of symptoms, and death. Although vaccines and drugs provided urgent assistance, the need to continue developing better drugs is necessary long term, and understanding the structure of the virus and finding potential inhibitors would prove vital to discovering solutions to this worldwide health problem. This experimental project focuses on targeting the unique accessory protein, Open Reading Frame 8 (ORF8) in SARS-CoV-2 through studying its interactions with a repurposable drug, novobiocin. Importantly, ORF8 specializes in helping evade immune system checks by downregulating major histocompatibility complex I (MHC-I) after infection, and is also involved in inflammatory responses from the cytokine storm, the most prominent cause of fatalities from the virus. Additionally, the ORF8 protein has been proposed to act as a histone mimic at the histone-H3 ARKS motif that causes post-translational changes in chromatin, further worsening these problems through gene transcription. Previous in silico and in vitro work from our lab has shown that novobiocin [Kd = 54.5 ± 3.14 μM] and three other computationally verified ligands (iohexol [Kd = 1185 ± 193 μM], kaempferol-7-O-glucoside [Kd = 135 ± 10.9 μM] & lercanidipine hydrochloride [Kd = 52.7 ± 5.71 μM]) bind to. To probe the role of Arg in the histone-H3 ARKS motif, specific mutation was done in position 52 from Arg to Met, Glu and Leu respectively. The above results in drastic changes in intermolecular forces such as opposing charge, polarity and different sizes of these side chains that negatively affect novobiocin’s ability to bind to the ORF8 pocket , which this research aims to experimentally prove this hypothesis. In silico analyses for the mutagenic ORF8 were initially found to require more energy to bind novobiocin to the ARKS motif than wild-type, but was still possible to dock according to Swissdock. Primers for the ORF8 R52 mutants were then designed and mutagenic plasmids were constructed and sequence verified. Each of the mutant ORF8 proteins was overexpressed, purified, and Kd values for binding to novobiocin were determined via intrinsic fluorescence spectroscopy and compared with wild-type binding. This data will help further understand the role of SARS-CoV-2 ORF8 protein ARKS motif and how its interactions affected novobiocin binding, potentially benefitting future studies attempting to repurpose novobiocin and other ligands for treatment of the spreading virus

Trends and Variations of Ocean Surface Latent Heat Flux: Results from GSSTF2c Data Set

Trends and variations of Goddard Satellite-based Surface Turbulent Fluxes (GSSTF) version 2c (GSSTF2c) latent heat flux (LHF) are examined. This version of LHF takes account of the correction in Earth incidence angle. The trend of global mean LHF for GSSTF2c is much reduced relative to GSSTF version 2b Set 1 and Set 2 for the same period 1988-2008. Temporal increase of GSSTF2c LHF in the two decades is 11.0%, in which 3.1%, 5.8%, and 2.1% are attributed to the increase in wind, the increase in sea surface saturated air humidity, and the decrease in near-surface air humidity, respectively. The first empirical orthogonal function of LHF is a conventional El Nino Southern Oscillation (ENSO) mode. However, the trends in LHF are independent of conventional ENSO phenomena. After removing ENSO signal, the pattern of LHF trends is primarily determined by the pattern of air-sea humidity difference trends

Poemas chineses

Apresentamos aqui três versões de dois poemas de Li Po. Durante o trabalho, deparamo-nos com a delicada tarefa de transpor a estrutura sintética dos poemas, o que nos levou à extrema concisão no processo de tradução. A visualidade ideogrâmica e a riqueza imagética da poesia chinesa foram aspectos fundamentais que exigiram bastante cuidado de nossa parte, incluindo o próprio universo cifrado e simbólico dos poemas

A Multirate MAC Protocol for Reliable Multicast in Multihop Wireless Networks

Many multicast applications, such as audio/video streaming, file sharing or emergency reporting, are becoming quite common in wireless mobile environment, through the widespread deployment of 802.11-based wirelessnetworks. However, despite the growing interest in the above applications, the current IEEE 802.11 standard does not offer any medium access control (MAC) layer support to the efficient and reliable provision of multicast services. It does not provide any MAC-layer recovery mechanism for unsuccessful multicast transmissions. Consequently, lost frames cannot be detected, hence retransmitted, causing a significant quality of service degradation. In addition, 802.11 multicast traffic is sent at the basic data rate, often resulting in severe throughput reduction. In this work, we address these issues by presenting areliablemulticastMACprotocol for wirelessmultihopnetworks, which is coupled with a lightweight rate adaptation scheme. Simulation results show that our schemes provide high packet delivery ratio and when compared with other state-of-the-art solutions, they also provide reduced control overhead and data delivery dela

Differential Emphases on Modernity and Confucian Values in Social Categorization: The Case of Hong Kong Adolescents in Political Transition

This study investigated if modernity and Confucian values were ingroup's positively valued distinctiveness for Hong Kong adolescents with different social identities. Participants (236 Hong Kong adolescents) filled out a questionnaire which tapped social identity and intergroup perception. They also participated in a card-sorting activity in which they decided if any of 20 attributes (e.g., advanced, respecting collective will) could be used to characterize a specific ethnic-social group (e.g., mainland Chinese, Hongkongers, Americans). Multidimensional scaling performed on the card-sorting data resulted in a two-dimensional solution. Emphasis on Dimension I (modernity) correlated with positive perception of Hong Kong and Hong Kong people while emphasis on Dimension 2 (Confucian values) correlated with positive perception of China and Chinese. In addition, compared to adolescents who identified themselves as Chinese or Chinese-Hongkongers, those who identified themselves as Hongkongers or Hongkonger-Chinese placed more emphasis on modernity and less on Confucian values. The results were discussed with reference to Tajfel's theory of social identity. (C) 1999 Elsevier Science Ltd. All rights reserved

Ki67 Antigen as a Predictive Factor for Prognosis of Sinonasal Mucosal Melanoma

ObjectivesSinonasal mucosal melanoma is a rare and aggressive disease. The aim of this study was to analyze the clinical features of patients with sinonasal mucosal melanoma and to determine the role of Ki67 antigen as a predictor of prognosis in sinonasal mucosal melanoma.MethodsThis was a retrospective case-series study at a single institution, an academic tertiary referral center. From 1995 to 2007, 27 patients with sinonasal mucosal melanoma were reviewed retrospectively, and the expression of Ki67 antigen was assessed by immunohistochemistry.ResultsThe overall 5-yr survival rate was 33.9%. No significant differences were observed in 5-yr survival according to age, sex, stage, or the presence of melanin. The rates of local failure, regional failure, and distant failure were 37.0%, 14.8%, and 11.1%, respectively. Patients with spindle or mixed cell types had better prognoses than those with other cell types. At a cut-off value of 35%, patients with lower Ki67 scores showed better survival than those with higher Ki67 scores.ConclusionThe presence of spindle or mixed cell types may indicate a better prognosis than other cell types. Ki67 immunostaining may be a useful predictor of prognosis in patients with mucosal malignant melanoma of the sinonasal tract

Wireless body sensor design for intra-vaginal temperature monitoring

Sensor nodes are small devices able to collect and retrieve sensorial data. The use of these sensors for medical purposes offers valuable contributions to improve patients’ healthcare, both for diagnosis and therapeutics monitoring. An important and common parameter used on healthcare diagnosis is the body temperature. It is monitored on several matters related with gynecological and obstetrics issues but, usually it is measure at the skin surface. Then, this paper proposes the design concepts of a new intra-body sensor for long-term intra-vaginal temperature collection. The embedded IEEE 802.15.4 communication module allows the integration of this sensor in wireless sensor networks for remote data access and monitoring. It is presented the sensor architecture, the construction of the corresponding testbed, and its performance evaluation. This sensor may be used on several applications, including fertile and ovulation period detection, and preterm labor prevention

Prescribing patterns of antidepressants, antipsychotics and mood stabilizers in bipolar patients misdiagnosed with major depressive disorder in China

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94515/1/hup2262.pd

Prescribing patterns of low doses of antipsychotic medications in older Asian patients with schizophrenia, 2001-2009

Background: This study examined the use of low doses of antipsychotic medications (300mg/day CPZeq or less) in older Asian patients with schizophrenia and its demographic and clinical correlates. Methods: Information on hospitalized patients with schizophrenia, aged 55 years or older, was extracted from the database of the Research on Asian Psychotropic Prescription Patterns (REAP) study (2001-2009). Data on 1,452 patients in eight Asian countries and territories including China, Hong Kong, Japan, Korea, Singapore, Taiwan, India, and Malaysia were analyzed. Sociodemographic and clinical characteristics and antipsychotic prescriptions were recorded using a standardized protocol and data collection procedure. Results: The prescription frequency for low doses of antipsychotic medications was 40.9% in the pooled sample. Multiple logistic regression analysis of the whole sample showed that patients on low doses of antipsychotic medications were more likely to be female, have an older age, a shorter length of illness, and less positive symptoms. Of patients in the six countries and territories that participated in all the surveys between 2001 and 2009, those in Japan were less likely to receive low doses of antipsychotics. Conclusion: Low doses of antipsychotic medications were only applied in less than half of older Asian patients with schizophreni