Miracle-dz/UniFAR-FTUs huggingface dataset:
KCTD5, a putative substrate adaptor for cullin3 ubiquitin ligases

Potassium channel tetramerization domain (KCTD) proteins contain a bric‐a‐brac, tramtrak and broad complex (BTB) domain that is most similar to the tetramerization domain (T1) of voltage‐gated potassium channels. Some BTB‐domain‐containing proteins have been shown recently to participate as substrate‐specific adaptors in multimeric cullin E3 ligase reactions by recruiting proteins for ubiquitination and subsequent degradation by the proteasome. Twenty‐two KCTD proteins have been found in the human genome, but their functions are largely unknown. In this study, we have characterized KCTD5, a new KCTD protein found in the cytosol of cultured cell lines. The expression of KCTD5 was upregulated post‐transcriptionally in peripheral blood lymphocytes stimulated through the T‐cell receptor. KCTD5 interacted specifically with cullin3, bound ubiquitinated proteins, and formed oligomers through its BTB domain. Analysis of the interaction with cullin3 showed that, in addition to the BTB domain, some amino acids in the N‐terminus of KCTD5 are required for binding to cullin3. These findings suggest that KCTD5 is a substrate‐specific adaptor for cullin3‐based E3 ligases.
The Discrete and Differential Impact of Monetary Policy

This study exploits a unique feature of the Australian monetary policy environment to determine whether economic recovery can be stimulated via central bank communications. This study finds that unexpected monetary policy announcements and communications have a significant and comparable impact on the value and volatility of the Australian foreign exchange market, suggesting that they can be used interchangeably to stimulate economic recovery. However, further analysis reveals that the state of the economy influences this impact. Specifically, during poor economic states, monetary policy actions speak louder than words, an adage that in this context provides actionable information for central bank regulators.
Reduced myocilin expression in cultured monkey trabecular meshwork cells induced by a selective glucocorticoid receptor agonist: comparison with steroids.

PURPOSE To assess in vitro myocilin (MYOC) expression in trabecular meshwork (TM) cells exposed to BOL-303242-X, a selective glucocorticoid receptor (GR) agonist (SEGRA), in comparison with dexamethasone (DEX), and prednisolone acetate (PA). METHODS After drug treatment of monkey TM cultures, MYOC protein in conditioned media (CM) was measured by Western blot and densitometry. MYOC mRNA levels were analyzed by qRT-PCR. RU-486 was tested for antagonism of MYOC protein expression induced by DEX and BOL-303242-X. RESULTS Baseline MYOC protein released into CM and MYOC mRNA were detected. DEX or PA elicited dose-dependent increases in MYOC in CM and also in MYOC mRNA. BOL-303242-X effects typified partial agonism, with significantly reduced MYOC protein and mRNA, compared with DEX. Maximum efficacy for BOL-303242-X was 53% of that for DEX. Mean EC(50) across all strains tested was lower, but not significantly different, for BOL-303242-X versus DEX. Compared with DEX, MYOC mRNA levels were significantly lower in BOL-303242-X-treated TM cells at the highest doses tested. EC(50)s for PA were higher than DEX, for both myocilin protein and mRNA. RU-486 displayed a dose-dependent antagonism to drug-induced increases in myocilin levels. CONCLUSIONS In vitro quantitative assays of myocilin expression in TM cells can be used for characterizing anti-inflammatory drugs that are GR ligands. The results suggest that, compared with traditional ocular steroids, therapeutic doses of BOL-303242-X elicit a reduced myocilin expression profile in TM cells by virtue of the partial agonist properties of this compound.
Effects of Paroxetine CR on Depressive and Anxiety Symptoms: In a Community Sample of Adult Hispanic Women with Major Depression or Generalized Anxiety Disorder.

OBJECTIVE Previous research reports higher rates of depression in Hispanic women than Caucasian or African American women. The effectiveness and tolerability of paroxetine CR (controlled release) was examined in women of Hispanic heritage with depression or anxiety. METHODS Thirty-six Hispanic female patients 18 years or older meeting DSM-IV criteria for major depression or generalized anxiety disorder diagnosis with an initial Hamilton Depression Rating scale (17 item) Ž20 or Hamilton Anxiety Rating scale Ž18 measuring no less than 4 on the Clinical Global Impression Severity scale received paroxetine CR (12.5-50mg/day) for 29 weeks of open label treatment. Analysis was conducted using repeated measures methodology. RESULTS Significant symptom reduction was observed on all scales. Mean dose was 31.7mg. The side effect of sexual dysfunction (17%) appeared most frequently but did not cause any patients to cease study participation. CONCLUSIONS Paroxetine CR was an effective and generally well tolerated treatment in this population.
Soft Power Runs into Popular Geopolitics: Western Media Frames Democratic Taiwan

How does the Western media frame Taiwan? Analysing a large set of Western newspaper reports over the past two decades, this article provides the first systematic assessment of global coverage of Taiwan. Seeking to explain why Taiwan has been framed in the way it has, the article reports the views of journalists and editors and puts forward a framework based on popular geopolitics. The article concludes with a discussion of why media framing matters, and the implications for Taiwan’s public diplomacy and ‘soft power’ efforts.
Study on timetable design for Osaka International University by Differential Evolution

Timetabling problem is a kind of combinatorial optimizations. However, it is very difficult to be solved the timetabling problem from the enormous combination total number and the complexity of the limitation condition. In this study, we develop the timetabling algorithm for Osaka International University (OIU). Otherwise, it is difficult to design and solving the problem with many constraints. So, in this paper, we design the reduced model and propose a solution method by Differential Evolution (DE) that a kind of the evolution algorithm. This study is a new trial such as to apply the DE to timetabling problem. During the writing of this manuscript, the experimental results have not been obtained yet. However, we consider that our solution method by DE obtains more effective solutions. We report the results of numerical experiments on the day.
Incidence and Factors Associated with the Switch to the Second Line Antiretroviral Treatment at the Ambulatory Treatment Center (CTA) in Dakar

Introduction: Over the past years, efforts have been made to expand access to antiretroviral combinations (cART) in low-income countries. However, major concerns are noted with drug resistance emergence, as treatment failure result and need to introduce a second line treatment, more expensive and difficult to implement. The objective was to study the incidence of switch to second line, reasons for switch and risk factors using a cohort of people living with HIV in an Ambulatory Treatment Center in Dakar. Methodology: This was a cohort study of people living with HIV under cART from January 2004 to December 2013. Naive patients monitored for at least six months, regardless of their profile and regimen with baseline CD4 counts 3 were included in this study. Results: The median age of the 827 patients included was 44 [IQR = 18 - 78]. The switch to second-line treatment was observed in 72 patients (8.7%) after an average of 38.5 months of follow-up. The overall incidence rate of switch to second line of antiretroviral treatment was 1.59 per 100 persons-years. Most of changes in first-line treatment were motivated by virological failures (n = 60, 83.3%) under treatment with AZT/3TC/NVP (n = 25, 34.7%) or AZT/3TC/EFV21 (29.2%). 9.7% of switch occurred after immunological failure, 1.4% after clinical failure, 4.2% after severe toxicity and 1.4% was not documented. Predictive factors identifying failures at the end of the multivariate analysis were age 3. Conclusions: In total, CTA identified a low incidence rate of treatment failure of the first line of treatment. Associated risk factors were age 3 and high viral load at treatment initiation.
The Influence of Top Management Team on Chinese Firms’ FDI Ambidexterity

ABSTRACT Strategic ambidexterity has been under researched in the context of Chinese outward foreign direct investment (FDI). An ambidextrous FDI, balancing between exploratory and exploitive activities, is strategically desirable but managerially challenging. We examine the role of top management team (TMT) functional diversity in influencing Chinese firms’ degree of FDI ambidexterity, and its boundary conditions in relation to the informal and formal institutional environments within which the TMT operates. Based on a panel of Chinese outward-investing manufacturing firms, our empirical analyses show that a marginal positive effect of TMT functional diversity on a firm's FDI ambidexterity is strengthened by the social faultline presence in the firm's TMT, but is weakened by the development of formal institutions in the firm's external environment.
Proteolytic analysis of domain structure in the beta heavy chain of dynein from sea urchin sperm flagella.

The stability of different regions of the beta heavy chain of dynein has been investigated by examining the perturbing effects of methanol, temperature, salt, and nucleotide on the pattern of tryptic digestion. In standard low-salt medium, tryptic proteolysis cleaves the beta heavy chain into three principal polypeptides of 130, 215, and 110 kDa, with the 215-kDa central peptide containing the ATP binding site as well as the vanadate and iron photocleavage sites (Mocz, G., Tang, W.-J. Y., & Gibbons, I. R. (1988) J. Cell Biol. 106, 1607-1614). The 130-kDa peptide is the most stable, and its susceptibility to trypsin appears unaffected by methanol concentrations up to 25% or temperatures up to 45 degrees C, although a 5-kDa region at one end is lost in the presence of salt (greater than 20 mM NaCl). The 215-kDa tryptic peptide contains two regions of different stability: its 123-kDa portion adjoining the 130-kDa peptide is destabilized by mild heat (37 degrees C) or by 25% methanol and becomes digested away to leave the more stable region of 92 kDa that is located toward the 110-kDa peptide and retains the V1 photocleavage site and most of the ATP binding site. The 110-kDa peptide is the least stable and at 37 degrees C, or in the presence of low concentrations of methanol or salt, it rapidly digested to small peptides. The presence of ATP during digestion of the beta heavy chain retards the formation of the 130- and 215-kDa peptides and also protects the 215-kDa peptide from further digestion at 37 degrees C. (ABSTRACT TRUNCATED AT 250 WORDS)
Contribution of metabolites to the route- and time-dependent hepatic effects of di-(2-ethylhexyl)phthalate in the rat.

The effects of exposure to the plasticizer di-(2-ethyl-hexyl)phthalate (DEHP) and its two primary products of presystemic de-esterification, mono-(2-ethylhexyl)phthalate and 2-ethyl-hexanol, on hepatic microsomal oxidation were investigated in rats. The metabolic clearance of antipyrine was utilized as an in vivo measure of the activity of the hepatic microsomal oxidative enzyme system. Subchronic (7 days) p.o. treatment of rats with DEHP, mono-(2-ethylhexyl)phthalate or 2-ethylhexanol produced a substantial increase in both wet liver weight and antipyrine clearance relative to corn oil-treated controls. In contrast, i.p. administration of DEHP resulted in a minor but statistically significant stimulation of liver growth and antipyrine metabolism. Whereas chronic administration of the plasticizer or its metabolites produced apparent induction of hepatic microsomal oxidative enzymes, administration of a single dose of each compound was associated with immediate inhibition of the metabolism of antipyrine. The present data suggest that the products of deesterification of DEHP are primarily responsible for the stimulation of hepatic metabolism observed after long-term exposure to the plasticizer, whereas the parent compound and both metabolites have the potential to produce acute inhibition of hepatic microsomal oxidation in vivo.
Cognitive functioning in breast cancer patients during and following chemotherapy.

e20571 Background: The development of cognitive difficulties, including memory loss, confusion, and difficulty concentrating following cancer treatment is a significant concern in patients receiving chemotherapy. METHODS This secondary analysis of a study assessing the effects of a RCT of paroxetine on fatigue in cancer patients investigated changes in self-report cognitive functioning over four cycles of chemotherapy and then approximately two years later. Approximately half of the patients were chemotherapy naïve. Questions on 5 point scales anchored by 1 = "absence of" and 5 = "a great deal" evaluating whether patients experienced heavy headedness, muddled thoughts, difficulty thinking, trouble concentrating, and forgetfulness. Each was answered seven days after each treatment and scores from each cycle were summed. RESULTS Fifty-eight of 84 patients completed questionnaires for all four cycles and are included herein. Paired t-tests showed cognitive difficulties were highest following the 1st on-study chemotherapy cycle (mean=7.9) and were significantly improved at the 3rd (mean=6.9) and 4th (mean=6.6) on-study cycles (both, p<0.005). Independent sample t-tests revealed that paroxetine had no effect on cognitive functioning when compared to placebo at all 4 cycles (all, p>0.54). Fifteen participants were reassessed two years after completing treatement. There was an increase in reported cognitive difficulties from the last cycle (mean=5.9) to the follow-up time-point (mean=7.8) that was not significant (p=0.18). Patients with ≥2 point change in score from the last on-study cycle to follow-up were categorized as "better" or "worse". Those with <2 point change in score were classified as "no change". Four (27 %) patients got worse (mean change=9.0), 2 (13 %) got better (mean change=-3.5), and 9 (60%) did not change. CONCLUSIONS These data suggest that self-report cognitive difficulties related to cancer treatment are most pronounced following initial cycles of chemotherapy treatment and improve during the treatment course. Further studies need to include objective neuropsychological examinations and biological correlates of cognitive functioning to understand the extent of cognitive decline due to chemotherapy. FUNDING DOD DA17-96-C-6106, NCI R25CA10618. No significant financial relationships to disclose.
A Thompson sampling approach to channel exploration-exploitation problem in multihop cognitive radio networks

Cognitive radio technology is a promising solution to the exponential growth in bandwidth demand sustained by increasing number of ubiquitous connected devices. The allocated spectrum is opened to the secondary users conditioned on limited interference on the primary owner of the band. A major bottleneck in cognitive radio systems is to find the best available channel quickly from a large accessible set of channels. This work formulates the channel exploration-exploitation dilemma as a multi-arm bandit problem. Existing theoretical solutions to a multi-arm bandit are adapted for cognitive radio and evaluated in an experimental test-bed. It is shown that a Thompson sampling based algorithm efficiently converges to the best channel faster than the existing algorithms and achieves higher asymptotic average throughput. We then propose a multihop extension together with an experimental proof of concept.
Estimating Treatment Effect in the Wild via Differentiated Confounder Balancing

Estimating treatment effect plays an important role on decision making in many fields, such as social marketing, healthcare, and public policy. The key challenge on estimating treatment effect in the wild observational studies is to handle confounding bias induced by imbalance of the confounder distributions between treated and control units. Traditional methods remove confounding bias by re-weighting units with supposedly accurate propensity score estimation under the unconfoundedness assumption. Controlling high-dimensional variables may make the unconfoundedness assumption more plausible, but poses new challenge on accurate propensity score estimation. One strand of recent literature seeks to directly optimize weights to balance confounder distributions, bypassing propensity score estimation. But existing balancing methods fail to do selection and differentiation among the pool of a large number of potential confounders, leading to possible underperformance in many high dimensional settings. In this paper, we propose a data-driven Differentiated Confounder Balancing (DCB) algorithm to jointly select confounders, differentiate weights of confounders and balance confounder distributions for treatment effect estimation in the wild high dimensional settings. The synergistic learning algorithm we proposed is more capable of reducing the confounding bias in many observational studies. To validate the effectiveness of our DCB algorithm, we conduct extensive experiments on both synthetic and real datasets. The experimental results clearly demonstrate that our DCB algorithm outperforms the state-of-the-art methods. We further show that the top features ranked by our algorithm generate accurate prediction of online advertising effect.
Home Rules: The Case for Local Administrative Procedure

Administrative law is critical to the modern practice of governance. Administrative rules fill the gaps in statutes left open by lawmakers, allow agencies to exercise legislative grants of authority and discretion, and give agencies with subject-matter expertise and frontline experience the opportunity to promulgate detailed standards and requirements in their designated issue areas. Adjudication allows an agency to dispose of matters and disputes formally before it, whether under its rules or another source of law. While agencies at every level of government—federal, state, and local— engage in administrative action, legal scholarship on administrative law is almost exclusively focused on the federal realm, which is shaped by the Administrative Procedure Act. States can look to a Model State Administrative Procedure Act drafted by experts at the National Conference of Commissioners on Uniform State Laws, a document that was originally promulgated around the same time as the federal Administrative Procedure Act, for guidance on ordering the activities of their agencies. Local governments, however, have far fewer resources to draw upon. This Note argues that the time has come for localities to embrace the codification of administrative procedures. The governments and agencies of localities have always played a prominent role in the everyday lives of residents, as well as regional and national economic structures, and their work will benefit from procedural statutes. Cities, in particular, have taken on an increasingly central role as political agents and policy entrepreneurs and this shift underscores the need for greater procedural guidance. To make the case, this Note briefly examines the purposes and history of modern administrative law, analyzes approaches taken by exemplar cities, lays out and probes some of arguments for and against more rigorous procedures at the local level, and proposes three methods to help localities and states undertake this project.
Structure, Policy, Services, and Performance in the Business Incubator Industry

Business incubators are one of the newest tools on the enterprise development scene; nearly 400 are now in operation. A business incubator is a facility that provides affordable space, shared office services, and business development assistance in an environment conducive to new venture creation, survival, and early-stage growth. This article is a preliminary examination of the relationships among incubator structure, policy, services, and performance. A value-added continuum model is used to describe various kinds of incubators and aspects of their operations. Managers of 127 incubators were surveyed to examine features of the value-added continuum. Surrogate measures for the concepts that anchor either end of the continuum—property development and business development—are empirically examined. Incubators are found to be poor real estate ventures. Age and size of facility are found to be important determinants of jobs created and firms graduated. Only one other structure, policy, or services variable is important for explaining business development outcomes.
Anxiety disorders and their clinical correlates in multiple sclerosis patients

Objective To assess prevalence rates and clinical correlates of anxiety disorders in patients with multiple sclerosis (MS). Methods Demographic and neurological data were collected on 140 consecutive clinic attendees, and their lifetime and point prevalences of anxiety disorders were determined with the Structured Clinical Interview for DSM-IV disorders (SCID-IV). All subjects completed the self-report Hospital Anxiety and Depression Scale (HADS). Suicidal intent was rated with the Beck Suicide Scale (BSS), psychosocial stressors and supports were quantified with Social Stress and Support Interview (SSSI), and cognition assessed with Neuropsychological Screening Battery for MS. Results The lifetime prevalence of any anxiety disorder was 35.7%, with panic disorder (10%), obsessive compulsive disorder (8.6%), and generalized anxiety disorder (18.6%), the most common diagnoses obtained. Subjects with an anxiety disorder were more likely to be female, have a history of depression, drink to excess, report higher social stress and have contemplated suicide. The diagnosis of an anxiety disorder had been missed in the majority of subjects, therefore, they had not received treatment. A discriminant function analysis identified a series of variables that correctly classified 75% of patients with an anxiety disorder. Conclusion Anxiety disorders are common in patients with MS, but are frequently overlooked and under-treated. Risk factors include being female, a co-morbid diagnosis of depression, and limited social support. Clinicians should evaluate all MS subjects for anxiety disorders, as they represent a treatable cause of disability in MS.