Miracle-dz/UniFAR-FTUs huggingface dataset:
GSK‐3 mediates the okadaic acid‐induced modification of collapsin response mediator protein‐2 in human SK‐N‐SH neuroblastoma cells

Collapsin response mediator protein‐2 (CRMP‐2), a phosphoprotein involved in axonal outgrowth and microtubule dynamics, is aberrantly phosphorylated in Alzheimer's disease (AD) brain. Alteration of glycogen synthase kinase‐3 (GSK‐3) activity is associated with the pathogenesis of AD. Here, we show that CRMP‐2 is one of the major substrates for GSK‐3 in pig brain extracts. Both GSK‐3α and 3β phosphorylate purified pig brain CRMP‐2 and significantly alter its mobility in SDS‐gels, resembling the CRMP‐2 modification observed in AD brain. Interestingly, this modification can be detected in SK‐N‐SH neuroblastoma cells treated with a phosphatase inhibitor, okadaic acid (OA), and GSK‐3 inhibitors completely block this OA‐induced event. Knockdown of both GSK‐3α and 3β, but not either kinase alone, impairs OA‐induced modification of CRMP‐2. Mutation of Ser‐518 or Ser‐522 of CRMP‐2, which are highly phosphorylated in AD brain, to Ala blocks the OA‐induced modification of CRMP‐2 in SK‐N‐SH cells. Ser‐522 prephosphorylated by Cdk5 is required for subsequent GSK‐3α‐mediated phosphorylation of CRMP‐2 in vitro. Collectively, our results demonstrate for the first time that OA can induce phosphorylation of CRMP‐2 in SK‐N‐SH cells at sites aberrantly phosphorylated in AD brain, and both GSK‐3α and 3β and Ser‐522 kinase(s) are involved in this process. J. Cell. Biochem. 103: 1833–1848, 2008. © 2007 Wiley‐Liss, Inc.
Examining Regulatory Capture: Evidence from the NHL

Regulatory capture has garnered significant attention, but poses a difficult empirical exercise since most relationships between regulators and regulated parties occur behind closed doors. In this research, we overcome this problem by analyzing an environment where the behavior of both the regulator and regulated parties are publicly available. Specifically, we utilize data from the National Hockey League (NHL) to examine the impact of general experience as a referee as well as experience refereeing a particular team on the assignation of penalties. We find that gaining general experience as a referee significantly reduces the number of penalties that a referee assigns. However, as a referee gains experience refereeing a specific team, they significantly reduce the number of penalties assessed to this team relative to teams that they have less experience refereeing, confirming that regulatory capture is observed among referees and teams in the NHL. (JEL G18, L51, K42)
Decreased Vδ2 γδ T cells associated with liver damage by regulation of Th17 response in patients with chronic hepatitis B.

BACKGROUND γδ T cells comprise a small subset of T cells and play a protective role against cancer and viral infections; however, their precise role in patients with chronic hepatitis B remains unclear. METHODS Flow cytometry and immunofunctional assays were performed to analyze the impact of Vδ2 γδ (Vδ2) T cells in 64 immune-activated patients, 22 immune-tolerant carriers, and 30 healthy controls. RESULTS The frequencies of peripheral and hepatic Vδ2 T cells decreased with disease progression from immune tolerant to immune activated. In the latter group of patients, the decreases in peripheral and intrahepatic frequencies of Vδ2 T cells reversely correlated with alanine aminotransferase levels and histological activity index. These activated terminally differentiated memory phenotypic Vδ2 T cells exhibited impaired abilities in proliferation and chemotaxis, while maintained a relative intact interferon (IFN) γ production. Importantly, Vδ2 T cells, in vitro, significantly suppressed the production of cytokines associated with interleukin 17-producing CD4+ T (Th17) cells through both cell contact-dependent and IFN-γ-dependent mechanisms. CONCLUSIONS Inflammatory microenvironment in IA patients result in decreased numbers of Vδ2 T cells, which play a novel role by regulating the pathogenic Th17 response to protect the liver in patients with chronic hepatitis B.
[Phase II clinical trial of h-R3 combined radiotherapy for locoregionally advanced nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies are easily to produce human anti-murine antibody response at present clinical use. This may influence therapeutic effect. This study was to evaluate the short-term and long-term efficacy and toxicity of the humanized anti-EGFR monoclonal antibody h-R3 in combination with radiotherapy for locoregionally advanced nasopharyngeal carcinoma (NPC). METHODS Patients with newly diagnosed stage III-IVb (UICC 1997) NPC, who had moderate or strong EGFR expression, were randomized into radiotherapy alone group or radiotherapy combined h-R3 group. Similar dosage and technique of radiotherapy was administered in both groups. The combination group received weekly intravenous infusion of 100 mg h-R3 during radiotherapy. The short-term efficacy was evaluated according to WHO criteria. The survival was analyzed by Kaplan-Meier method. RESULTS A total of 35 patients were enrolled, 17 in radiotherapy alone group and 18 in combination group. During treatment, only 1 patient withdrew from the combination group. The overall complete remission (CR) rates at the end of treatment, 5 and 17 weeks after treatment were significantly higher in combination group than in radiotherapy alone group (72.2% vs. 35.3%, 83.3% vs. 41.2%, and 83.3% vs. 47.1%, P<0.05). Median follow-up time was 31.9 months (range, 4.2-40.7 months). No significant differences in 3-year locoregional control, distant metastasis-free survival and overall survival rates between the 2 groups were found. Except for 1 patient suffered from grade 2 vomiting, no patient developed other adverse events in combination group. No significant differences in radiotherapy-related adverse events between the 2 groups were observed. CONCLUSIONS h-R3 is a safe drug which may enhance the response of advanced NPC patients to radiotherapy. However, h-R3 seems not to significantly affect the long-term outcomes.
Collective memory and reputational politics of national heroes and villains

The politics of memory plays an important role in the ways certain figures are evaluated and remembered, as they can be rehabilitated or vilified, or both, as these processes are contested. We explore these issues using a transition society, Georgia, as a case study. Who are the heroes and villains in Georgian collective memory? What factors influence who is seen as a hero or a villain and why? How do these selections correlate with Georgian national identity? We attempt to answer these research questions using a newly generated data set of contemporary Georgian perspectives on recent history. Our survey results show that according to a representative sample of the Georgian population, the main heroes from the beginning of the twentieth century include Zviad Gamsakhurdia, Ilia Chavchavadze, and Patriarch Ilia II. Eduard Shevardnadze, Sergo Ordzhonikidze, and Vladimir Putin represent the main villains, and those that appear on both lists are Mikheil Saakashvili and Joseph Stalin. We highlight two clusters of attitudes that are indicative of how people think about Georgian national identity, mirroring civic and ethnic conceptions of nationalism. How Georgians understand national identity impacts not only who they choose as heroes or villains, but also whether they provide an answer at all.
Adherence to protease inhibitors, HIV-1 viral load, and development of drug resistance in an indigent population

ObjectiveTo examine the relationship between adherence, viral suppression and antiretroviral resistance in HIV-infected homeless and marginally housed people on protease inhibitor (PI) therapy. Design and settingA cross-sectional analysis of subjects in an observational prospective cohort systematically sampled from free meal lines, homeless shelters and low-income, single-room occupancy (SRO) hotels. ParticipantsThirty-four HIV-infected people with a median of 12 months of PI therapy. Main outcomesAdherence measured by periodic unannounced pill counts, electronic medication monitoring, and self-report; HIV RNA viral load; and HIV-1 genotypic changes associated with drug resistance. ResultsMedian adherence was 89, 73, and 67% by self-report, pill count, and electronic medication monitor, respectively. Thirty-eight per cent of the population had over 90% adherence by pill count. Depending on the measure, adherence explained 36–65% of the variation in concurrent HIV RNA levels. The three adherence measures were closely related. Of 20 genotyped patients who received a new reverse transcriptase inhibitor (RTI) when starting a PI, three had primary protease gene substitutions. Of 12 genotyped patients who received a PI without a new RTI, six had primary protease gene substitutions (P < 0.03). ConclusionA substantial proportion of homeless and marginally housed individuals had good adherence to PI therapy. A strong relationship was found between independent methods of measuring adherence and concurrent viral suppression. PI resistance was more closely related to the failure to change RTI when starting a PI than to the level of adherence.
Parameter Estimation for Differential Equation Models Using a Framework of Measurement Error in Regression Models

Differential equation (DE) models are widely used in many scientific fields, including engineering, physics, and biomedical sciences. The so-called “forward problem,” the problem of simulations and predictions of state variables for given parameter values in the DE models, has been extensively studied by mathematicians, physicists, engineers, and other scientists. However, the “inverse problem,” the problem of parameter estimation based on the measurements of output variables, has not been well explored using modern statistical methods, although some least squares–based approaches have been proposed and studied. In this article we propose parameter estimation methods for ordinary differential equation (ODE) models based on the local smoothing approach and a pseudo–least squares (PsLS) principle under a framework of measurement error in regression models. The asymptotic properties of the proposed PsLS estimator are established. We also compare the PsLS method to the corresponding simulation-extrapolation (SIMEX) method and evaluate their finite-sample performances via simulation studies. We illustrate the proposed approach using an application example from an HIV dynamic study.
What Drives Private Saving in Botswana

This study examines the determinants of private saving in Botswana for the period covering 19942009. We use quarterly time series data to evaluate the magnitude and direction of the effects of key policy and non-policy variables on private saving. The variables examined are inflation, real interest rates, real gross national disposable income, degree of financial depth and dependency ratio. The dependency ratio is included in order to capture the effect of demographic influence on private savings. The stated determinants of savings are articulated in the context of the life cycle hypothesis. We investigate the short and long run behavior of the variables using an ARDL-ECM. The results suggest that there is a positive relationship between household income and their savings. The dependency ratio exerts a negative impact on private savings which supports the Lifecycle Hypothesis. The results also suggest that financial sector development has induced a positive impact on private savings in Botswana. Interest rates have a positive relationship with private savings; and, lastly, inflation has a negative relationship with private savings. Financial depth and real interest rates are the core policy instruments that the government can use to encourage savings in Botswana.
Generalized atrophic benign epidermolysis bullosa. Either 180-kd bullous pemphigoid antigen or laminin-5 deficiency.

BACKGROUND Generalized atrophic benign epidermolysis bullosa (GABEB) is a form of nonlethal junctional epidermolysis bullosa, clinically characterized by generalized blistering after birth, atrophic healing, and incomplete universal atrophic alopecia with onset in childhood. Recently, we discovered a deficiency of the 180-kd bullous pemphigoid antigen (BP180) and a reduced amount of BP180 messenger RNA in three patients with GABEB. It is not yet clear, however, whether GABEB is invariably caused by BP180 deficiency. RESULTS We examined 18 patients with nonlethal junctional epidermolysis bullosa from unrelated families; nine of these individuals presented with the clinical characteristics of GABEB. Specimens of clinically normal skin obtained from the patients were stained by immunofluorescence with monoclonal antibodies to BP180 and laminin-5. The BP180 epitopes were not expressed in eight patients, all of whom were sharing the typical clinical features of GABEB. In one of the nine patients with GABEB, the BP180 level was sufficient, but the laminin-5 level was reduced. Among the nine patients with junctional epidermolysis bullosa without atrophic alopecia, laminin-5 level was not expressed in one patient, while in the other patients both antigens were normally expressed. CONCLUSIONS Not all patients with GABEB are deficient in BP180, since some individuals with GABEB only exhibit reduction of the laminin-5 expression. The BP180 deficiency in the skin invariably seems to result in GABEB. Immunofluorescence analysis using monoclonal antibodies against BP180 (and laminin-5) may allow early subtyping, which is of prognostic significance, in children born with junctional epidermolysis bullosa.
Optical chemo-sensor based on long period gratings coated with /spl delta/ form syndiotactic polystyrene

In this work, a long period grating (LPG) is coated with a thin film of syndiotactic polystyrene (sPS) in the nanoporous crystalline /spl delta/ form in order to obtain a species-specific chemical sensor. The combination of the intrinsic and high refractive index sensitivity of the LPGs with the high sorption properties toward chlorinated and aromatic compounds of sPS /spl delta/ form allows detecting very low concentrations (in the range of few parts per million) of chloroform in water. Chemical detection is carried out by measuring the wavelength shift and the amplitude changes in the attenuation band of the LPG due to analyte sorption.
Risk analysis: a guiding force in the improvement of testing

The authors propose a state-based risk assessment methodology at the analysis and design stage of Software Development Life Cycle. First, a method is proposed to estimate the risk for various states of a component within a scenario and then, the risk for the whole scenario is estimated. The key data needed for risk assessment are complexity and severity. An Inter-Component State-Dependence Graph is introduced to estimate the complexity for a state of a component within a system. The severity for a component within a scenario is decided based on three hazard techniques: Functional Failure Analysis, Software Failure Mode and Effect Analysis and Software Fault Tree Analysis. The risk for a scenario is estimated based on the risk of interacting components in various states within the scenario and State COllaboration TEst Model of the scenario. Finally, the system risk is estimated based on two inputs: scenarios risks and Interaction Overview Diagram of the system. The methodology is applied on a Library Management System case study. An experimental comparative analysis is performed and observed that the testing team guided by our state-based risk assessment approach achieves high test efficiency compared with it with an existing component-based risk assessment approach.
Examining Pretreatment Differences Between Veterans in Residential Versus Outpatient Treatment for Alcohol Use Disorder and Comorbid Combat-Related PTSD

ABSTRACT Objective: Veterans with alcohol use disorder (AUD) and co-occurring posttraumatic stress disorder (PTSD) have access to various residential and outpatient treatment programs through the VA Healthcare System. There is a need to better understand the characteristics and needs of veterans who engage in residential versus outpatient treatment in order to help inform veteran care and decisions about treatment services. Methods: The present study examined whether veterans with both AUD and combat-related PTSD who were enrolled in residential (n = 103) or outpatient treatment programs (n = 76) differed on pretreatment psychiatric symptoms, substance use and associated problems/behaviors, or demographics. Veterans completed self-report measures (which referenced symptoms in the past 30 days or 2 weeks) within the first week of PTSD/AUD treatment. Results: Veterans in residential treatment had slightly worse PTSD symptoms compared to outpatient veterans; the groups reported similar levels of depression symptoms. Residential veterans had higher frequency of drug use, were more confident in their ability to be abstinent, attended more self-help meetings, spent more time around risky people or places, were more satisfied with their progress toward recovery goals, were more bothered by arguments with family/friends, and spent fewer days at work or school compared to outpatient veterans; the groups did not differ on drinking (frequency of use, binge drinking) or cravings. With respect to demographics, residential veterans were more likely to be married and non-Hispanic Caucasian (rather than minority races/ethnicities) compared to outpatient veterans. Conclusions: The finding that PTSD symptoms were more severe among veterans in residential substance use treatment highlights the importance of taking advantage of this crucial opportunity to engage veterans in evidence-based PTSD treatment. Consistent with other research, findings also indicated that individuals entering residential care have a higher level of impairment than those beginning outpatient care.
Secure Composition of PKIs with Public Key Protocols

We use symbolic formal models to study the composition of public key-based protocols with public key infrastructures (PKIs). We put forth a minimal set of requirements which a PKI should satisfy and then identify several reasons why composition may fail. Our main results are positive and offer various trade-offs which align the guarantees provided by the PKI with those required by the analysis of protocol with which they are composed. We consider both the case of ideally distributed keys but also the case of more realistic PKIs. ,,Our theorems are broadly applicable. Protocols are not limited to specific primitives and compositionality asks only for minimal requirements on shared ones. Secure composition holds with respect to arbitrary trace properties that can be specified within a reasonably powerful logic. For instance, secrecy and various forms of authentication can be expressed in this logic. Finally, our results alleviate the common yet demanding assumption that protocols are fully tagged.
Whakatipu rawa ma ngā uri whakatipu: optimising the “Māori” in Māori economic development

One of the great challenges for indigenous and non-indigenous entrepreneurs in the twenty-first century is to move beyond profit maximisation as an acceptable modality for doing business and gravitate towards the concept of socially optimal outcomes, where maximising community well-being and minimising externalities to the natural environment and social justice are paramount. We present findings from a case-study analysis of Māori enterprises that demonstrate a wealth of successfully kaupapa Māori (Māori ideology)-attuned strategy and policy. The case studies provide practical examples of the incorporation and expression of kaupapa Māori values into strategy and policy of Māori enterprises. We also identify the numerous challenges to implementing kaupapa Māori in the management of Māori Asset Holding Institutions and offer a way forward. Although the case studies are context specific, they provide some key principles and learning that can guide the greater uptake of kaupapa Māori entrepreneurship.
Altruistic and Selfish Motivations of Charitable Giving: Case of the Hometown Tax Donation System

In Japan’s hometown tax donation system, people can donate to municipalities where they are not resident and in return receive reciprocal gifts from the local governments of those municipalities. A large part of the donated amount can be deducted from their income and residence taxes. This study examined altruistic and selfish motivations in donating money to municipalities where people are not resident through that donation system; we did so using panel data of local governments for 2008–2015. We made the following key findings. (1) The Great East Japan earthquake increased the amount of money donated through that system for local governments with disaster victims. We considered that motivation altruistic. (2) A 1% increase in expenditure for gifts to donors led to a 0.61% increase in donations. We considered that motivation selfish. (3) Compared with donors not receiving gifts, providing gifts to donors led to a reduction in altruistic donations by almost 300%.
Game of Loans: The Rhetoric and Reality of Student Debt

College tuition and student debt levels have been rising at an alarming pace for at least two decades. These trends, coupled with an economy weakened by a major recession, have raised serious questions about whether we are headed for a major crisis, with borrowers defaulting on their loans in unprecedented numbers and taxpayers being forced to foot the bill. Game of Loans draws on new evidence to explain why such fears are misplaced—and how the popular myth of a looming crisis has obscured the real problems facing student lending in America. Bringing needed clarity to an issue that concerns all of us, Beth Akers and Matthew Chingos cut through the sensationalism and misleading rhetoric to make the compelling case that college remains a good investment for most students. They show how, in fact, typical borrowers face affordable debt burdens, and argue that the truly serious cases of financial hardship portrayed in the media are less common than the popular narrative would have us believe. But there are more troubling problems with student loans that don’t receive the same attention. They include high rates of avoidable defaults by students who take on loans but don’t finish college—the riskiest segment of borrowers—and a dysfunctional market where competition among colleges drives tuition costs up instead of down. Persuasive and compelling, Game of Loans moves beyond the emotionally charged and politicized talk surrounding student debt, and offers a set of sensible policy proposals that can solve the real problems in student lending.
To Act or Not To Act? Factors Influencing the General Public’s Decision about Whether to Take Protective Action against Severe Weather

AbstractResearch suggests that providing weather forecast end users with additional information about the forecast uncertainty of a possible event can enhance the preparation of mitigation measures. But not all users have the same threshold for taking action. This paper focuses on the question of whether there are influencing factors that determine decision thresholds for numerical weather forecast information beginning at which the general public would start to take protective action.In spring 2014, 1342 residents of Berlin, Germany participated in a survey. Questions related to the following topics: perception of and prior experience with severe weather, trustworthiness of forecasters and confidence in weather forecasts, and sociodemographic and socioeconomic characteristics. Within the questionnaire a scenario was created in order to determine individual decision thresholds and see whether subgroups of the sample lead to different thresholds.Results show that people’s willingness to act tends to be hig.