Miracle-dz/UniFAR-FTUs huggingface dataset:
(1S,2R)-D-erythro-2-(N-Myristoylamino)-1-phenyl-1-propanol as an Inhibitor of Ceramidase (*)

In this study, we have examined the cellular and biochemical activities of the ceramide analog (1S,2R)-Derythro-2-(N-myristoylamino)-1-phenyl-1-propanol (Derythro-MAPP). Addition of 5 μMD-e-MAPP to HL-60 human promyelocytic leukemia cells resulted in a concentration- and time-dependent growth suppression accompanied by an arrest in the G/G phase of the cell cycle; thus mimicking the action of exogenous ceramides. Its enantiomer L-e-MAPP was without effect. Two lines of evidence suggested that D-e-MAPP may not function as a direct analog of ceramide. First, D-e-MAPP possesses a stereochemical configuration opposite to that of D-erythro-ceramide. Second, D-e-MAPP failed to activate ceramide-activated protein phosphatase in vitro. Therefore, we examined if D-e-MAPP functioned indirectly by modulating endogenous ceramide levels. The addition of D-e-MAPP to cells, but not L-e-MAPP, caused a time- and concentration-dependent elevation in endogenous ceramide levels reaching greater than 3-fold over baseline following 24 h of treatment. Both D-e-MAPP and L-e-MAPP underwent similar uptake by HL-60 cells. D-e-MAPP was poorly metabolized, and remained intact in cells, whereas L-e-MAPP underwent a time- and concentration-dependent metabolism; primarily through N-deacylation. In vitro, L-e-MAPP was metabolized by alkaline ceramidase to an extent similar to that seen with C-ceramide. D-e-MAPP was not metabolized. Instead, D-e-MAPP inhibited alkaline ceramidase activity in vitro with an IC of 1-5 μM. D-e-MAPP did not modulate the activity of other ceramide metabolizing enzymes in vitro or in cells, and it was a poor inhibitor of acid ceramidase (IC > 500 μM). Finally, D-e-MAPP inhibited the metabolism of L-e-MAPP in cells. These studies demonstrate that D-e-MAPP functions as an inhibitor of alkaline ceramidase in vitro and in cells resulting in elevation in endogenous levels of ceramide with the consequent biologic effects of growth suppression and cell cycle arrest. These studies point to an important role for ceramidases in the regulation of endogenous levels of ceramide.
Dominant Negative Mutants of TRAF3 Reveal an Important Role for the Coiled Coil Domains in Cell Death Signaling by the Lymphotoxin-β Receptor*

Ligation of the lymphotoxin-β receptor (LTβR) recruits tumor necrosis factor receptor-associated factor-3 (TRAF3) and initiates cell death in HT29 adenocarcinoma cells. The minimal receptor binding domain (TRAF-C) defined by two hybrid analyses is not sufficient for direct recruitment to the ligated receptor. A series of TRAF3 deletion mutants reveal that a subregion of the coiled coil motif is required for efficient recruitment to the LTβR. Furthermore, the ability of TRAF3 to self-associate maps to an adjacent subregion. A TRAF3 deletion mutant that lacks the N-terminal zinc RING and zinc finger motifs, but retains the coiled coil and TRAF-C motifs, competitively displaces endogenous TRAF3 from the LTβR. A second TRAF3 mutant that lacks the receptor binding domain, yet contains the TRAF3 self-association domain, prevents TRAF3 homodimers from being recruited to the LTβR. Both of these mutants have a dominant negative effect on cell death and demonstrate that the recruitment of TRAF3 oligomers is necessary to initiate signal transduction that activates the cell death pathway.
Entrepreneurial Motivation and Destination Evolution

ABSTRACT This study aims to understand the small tourism business owner’s entrepreneurial motivation in different stages of destination development. Using a qualitative approach, 46 entrepreneurs who owned guesthouses in the Old Town of Lijiang, China, were interviewed. The findings suggest that business orientation was dominant in the predevelopment stage and that the livelihood motivation was a main cause of business orientation, whereas lifestyle orientation was obvious in the early development stage and most of the lifestyle-oriented owners had been tourists who enjoyed the place. However, the percentage of business orientation increased when the tourism area entered into a rapid growth stage, as more entrepreneurial investments were established. Therefore, this study identifies a pattern of small tourism business owners’ entrepreneurial motivation in different stages of destination development. An interactive view that connects tourism entrepreneurship and destination evolution is applied.
Measuring antenna noise parameters using a set of Wheeler caps

The noise correlation matrix and noise parameters are parameters of interest for antennas, and antenna arrays, particularly in the radio-astronomy context. For a passive network, such as an antenna, 2-port scattering parameters can be used to establish a noise correlation matrix and consequently the antenna noise parameters. In this paper we show how the 2-port scattering parameters of an antenna can be completely determined by measuring its reflection coefficient inside two specifically sized Wheeler caps, in addition to a free space measurement. We use the measurement to determine the noise correlation matrices and noise parameters of an antenna.
A Comparison of Cognitive and Everyday Functional Performance Among Older Adults With and Without Hypertension

Secondary data analyses examined the differences in cognitive and instrumental activities of daily living (IADL) performance among hypertensive individuals taking one of four classes of antihypertensive medications, hypertensive individuals not taking any antihypertensive medications, and normotensive individuals (N = 770). After adjusting for covariates, significant group differences were evident on all measures (speed of processing, motor speed, reaction time, p < .05) except memory and timed IADL (p > .05). Follow-up a priori planned comparisons compared hypertensive individuals not on medications to each of the four antihypertensive medication groups. Results indicated that only those on beta-blockers were significantly slower in speed of processing (p < .05). A priori planned comparisons also revealed that normotensive individuals had better cognitive performance on measures of processing speed, motor speed, and reaction time than hypertensive individuals regardless of antihypertensive medication use. Additionally, normotensive individuals performed significantly better on memory (digit and spatial span) than individuals with hypertension on medications. No differences were found between groups on memory (Hopkins Verbal Learning Test) or timed IADL performance. With regard to antihypertensive medications, the use of beta blockers was associated with slowed processing speed. These analyses provide empirical evidence that hypertension primarily impacts speed of processing, but not severe enough to affect IADL performance. Given the contribution of processing speed to memory and executive function performance, this is an important finding. Clinicians need to take into consideration the potential negative impact that beta blockers may have on cognition when determining the best treatment of hypertension among older adult patients.
Predicting non-familial major physical violent crime perpetration in the US Army from administrative data

Background. Although interventions exist to reduce violent crime, optimal implementation requires accurate targeting. We report the results of an attempt to develop an actuarial model using machine learning methods to predict future violent crimes among US Army soldiers. Method. A consolidated administrative database for all 975 057 soldiers in the US Army in 2004–2009 was created in the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS). Of these soldiers, 5771 committed a first founded major physical violent crime (murder-manslaughter, kidnapping, aggravated arson, aggravated assault, robbery) over that time period. Temporally prior administrative records measuring socio-demographic, Army career, criminal justice, medical/pharmacy, and contextual variables were used to build an actuarial model for these crimes separately among men and women using machine learning methods (cross-validated stepwise regression, random forests, penalized regressions). The model was then validated in an independent 2011–2013 sample. Results. Key predictors were indicators of disadvantaged social/socioeconomic status, early career stage, prior crime, and mental disorder treatment. Area under the receiver-operating characteristic curve was 0.80–0.82 in 2004–2009 and 0.77 in the 2011–2013 validation sample. Of all administratively recorded crimes, 36.2–33.1% (male-female) were committed by the 5% of soldiers having the highest predicted risk in 2004–2009 and an even higher proportion (50.5%) in the 2011–2013 validation sample. Conclusions. Although these results suggest that the models could be used to target soldiers at high risk of violent crime perpetration for preventive interventions, final implementation decisions would require further validation and weighing of predicted effectiveness against intervention costs and competing risks.
Report on a Patient with a 12q24.31 Microdeletion Inherited from an Insulin-Dependent Diabetes Mellitus Father

We report a 2.3-year-old female patient with global developmental delay, infantile spasms, hypotonia, microcephaly, flat face, full cheeks, macroglossia, highly arched palate, retro-gnathia, narrow ear orifices, and café-au-lait spots. Molecular karyotyping revealed approximately a 1-Mb interstitial deletion of the long arm of one chromosome 12, del(12)(q24.31). The same deletion was identified in her father who presents insulin-dependent diabetes mellitus (IDDM) diagnosed at 14 years. Only one other patient with a similar de novo deletion has been reported previously [Mol Syndromol 2010;1:42-45]. A phenotype-genotype correlation is discussed, and the description of a novel rare microdeletion entity is raised.
Isolation by distance within a river system: genetic population structuring of Atlantic salmon, Salmo salar, in tributaries of the Varzuga River in northwest Russia

An important issue for designing any conservation programme aimed at preserving genetic diversity is estimation of the scale at which genetic structuring occurs. Additional relevant factors include distinguishing whether or not population structuring is expected to be stable as predicted by the member‐vagrant hypothesis, or alternatively, whether populations are more prone to local extinction–recolonization processes, as predicted by the metapopulation evolutionary model. In this study, the population genetic structure of Atlantic salmon from 11 locations within or nearby the Varzuga River tributary system was assessed using 17 microsatellites. Mantel tests and spatial autocorrelation analyses revealed a significant isolation‐by‐distance signal within the tributary system as well as a negative association between the level of genetic diversity and waterway distance from the river mouth, indicating that dispersal is less likely to occur to populations deep in the tributary system. Individual‐level spatial autocorrelation analyses indicated that the majority of migration occurred between populations situated within 20 km of each other. The relatively high level of genetic structuring and significant isolation‐by‐distance signal observed in the Varzuga tributaries are concordant with the predictions of the member‐vagrant evolutionary model. However, one subpopulation in particular revealed signs of instability which may be due to its location in the tidal zone, or due to the fact that it is more affected by human impacts. The results suggest that preservation of a number of spawning sites spaced throughout the tributary system is recommendable for ensuring sustainable fishing tourism in the river.
On the biologically effective dose (BED)—using convolution for calculating the effects of repair: I. Analytical considerations

This work presents a new mathematical formulation of biologically effective dose (BED) for radiation therapy where effects of repair need to be considered. The formulation is based on the observation that the effects of repair, both during protracted irradiation and of incomplete repair between fractions, can be written using a convolution, i.e. where T is the total irradiation time, RT(t) is the absorbed dose rate as a function of time t and I(t) is the function describing repair. To validate this formulation, the previously published expressions for instant and protracted irradiation are first summarized. Then, by analytical derivation, it is shown that the new formulation gives identical results. The calculation of BED can thus be treated within one single mathematical framework, applicable in external beam therapy, brachytherapy, radionuclide therapy, or a combination of these treatment modalities. Moreover, the new formulation allows for a straightforward incorporation of different repair models and has the advantage of being numerically applicable.
Elevation of large‐T antigen production by sodium butyrate treatment of SV40‐transformed WI‐38 fibroblasts

The effects of sodium butyrate on simian virus 40 early gene expression were determined in SV40‐transformed human embryonic lung fibroblasts (SVWI‐38). Northern blot analysis and nuclear run‐off transcription studies revealed that treatment of cells with millimolar concentrations of sodium butyrate (2.5 to 10 mM) resulted in increased levels of SV40 early gene transcripts, with a concomitant increase in their corresponding proteins (large‐T and small‐t antigens). Although sodium butyrate treatment enhanced the expression of the early genes, it was associated with a reduction in cell growth and total protein synthesis, as measured by cell number and incorporation of 3H‐leucine into macromolecules, respectively. Immunoprecipitation of 35S‐labelled cellular proteins with anti‐p53 and anti‐T antibodies revealed that the level of the cellular protein, p53, declined markedly in the presence of sodium butyrate. Furthermore, in control cells only 30% of the p53 was complexed with large‐T antigen, whereas in butyrate‐treated cells all the p53 was complexed with large‐T antigen. The increased early gene expression was not due to altered methylation patterns, gene amplification, or rearrangement of the integrated SV40 genome. Sodium butyrate treatment did, however, result in the appearance of a new nuclear protein which bound specifically to a SV40 promoter fragment containing large‐T antigen binding sites I and II.
Toward A Theory Of Stakeholder Identification And Salience

Stakeholder TheoryStakeholder TheoryStakeholder Theory and Organizational EthicsToward a New Theory of the FirmThe SAGE Encyclopedia of Business Ethics and SocietyWhat's at Stake? Capitalism at the CrossoadsThe Corporation and Its StakeholdersSustainability, Stakeholder Governance, and Corporate Social ResponsibilityThe Cambridge Handbook of Stakeholder TheoryA Stakeholder Approach to Corporate Social ResponsibilityThe Dynamism of Stakeholder EngagementPublic Governance and the Classical-Liberal PerspectiveStakeholder ManagementStrategic ManagementThe Routledge Companion to Family BusinessThe Power of AndTowards the E-SocietyStakeholder TheoryLimits to Stakeholder InfluenceStakeholder ManagementSocial EntrepreneurshipUnderstanding Stakeholder ThinkingManaging Organizational ResponsivenessManaging for StakeholdersStakeholder TheoryCapitalism, Corporations and the Social ContractCertification in Public Health (CPH) Q&A Exam ReviewGlobal Stakeholder Relationships GovernanceEfficiency and LogisticsToward a Contingency Theory of Stakeholder Relevance and the Stakeholder Mapping ProcessResponsibility, Ethics and Legitimacy of CorporationsThe Rules of Project Risk ManagementBusiness EthicsTowards Zero WasteStakeholder Thinking in MarketingBusiness EthicsStakeholder Engagement: Clinical Research CasesSocial Movements, Stakeholders and Non-Market StrategyRedefining the Corporation
Substance Abuse Treatment Duration for Medicaid Versus Commercial Clients in a Health Maintenance Organization

Background:As Medicaid clients have come to be enrolled in managed care, concerns have arisen about the ability of private sector systems to meet the needs of enrollees with substance abuse problems. Objectives:This project describes treatment initiation and duration for Medicaid and commercial substance abuse treatment clients in a large health maintenance organization (HMO). Research Design:This study was a prospective secondary analysis of information from HMO databases. Subjects were 641 adult Medicaid clients who contacted the HMO's addiction medicine department in 1996 or 1997 and commercial HMO addiction medicine patients (n = 447). First contact with addiction medicine during the study period was the index event. Measures:Chief dependent variables were initiation and duration of substance abuse treatment after the index event. Results:Logistic regression showed that longer HMO enrollment predicted treatment initiation after substance abuse assessment, but Medicaid status was not a significant predictor. A competing risks analysis using Cox proportional hazards models indicated that once subjects had initiated, Medicaid was not significantly related to exit from substance abuse treatment. Analysis of health plan disenrollment by Medicaid clients indicated that the most common reason was loss of Medicaid eligibility. Conclusions:These results raise the possibility that state Medicaid policies may make it difficult for clients to obtain suitable chemical dependency treatment services.
Efficacy and Safety of Twice-Daily versus Three-Times Daily Saquinavir Soft Gelatin Capsules as Part of Triple Combination Therapy for HIV-1 Infection

Objective The objective of this study was to determine whether a triple therapy regimen incorporating twice-daily saquinavir is as effective as a three-times daily regimen. Methods This was an open-label, Phase III, multicentre, 48-week study involving 837 HIV-1-infected patients randomised to one of the following: saquinavir soft gel capsule (SGC) 1200 mg three-times daily, plus two nucleoside reverse transcriptase inhibitors (NRTIs) (arm A); saquinavir SGC 1600 mg twice-daily, plus two NRTIs (arm B); saquinavir SGC 1200 mg twice-daily and nelfinavir 1250 mg twice-daily, plus a single NRTI (arm C). The primary outcome measure was the virological response in arm A versus B and in arm A versus C with respect to the percentage of patients whose plasma HIV-1 RNA levels fell below the level of quantification for the Amplicor assay (<400 copies/ml) at weeks 24 and 48. Results At 48 weeks, the percentage of patients with plasma HIV-1 RNA levels <400 copies/ml was 47.1% (arm A), 45.3% (arm B) and 42.7% (arm C) in the intention-to-treat analysis. The treatment difference between arm B–arm A was -1.8% (95% confidence intervals -10.1, 6.5) and for arm C–arm A was -4.5% (95% confidence intervals -12.7, 3.7) in the intention-to-treat analysis. These differences fell within the maximum allowable difference (±12%) for arm B compared with arm A. At week 24, the percentage of patients with HIV-1 RNA levels <400 copies/ml was 59.6% (arm A), 57.6% (arm B) and 51.3% (arm C). Conclusions A twice-daily triple therapy regimen incorporating saquinavir SGC plus two NRTIs was of equivalent efficacy to the three-times daily regimen studied. All regimens were generally well tolerated.
Reproductive factors and breast cancer.

Early age at menarche, late age at menopause, and late age at first full-term pregnancy are linked to a modest increase in the risk of developing breast cancer. Some evidence suggests that the earlier the full-term pregnancy, the earlier the period of decreased susceptibility of breast tissue changes begins. Nulliparity is related to an increased risk for breast cancer diagnosed after 40 years old. Multiple full-term pregnancies decrease the risk of breast cancers diagnosed after 40 years regardless of the age at first birth. On the other hand, they may increase the risk for breast cancers diagnosed before 40 years old. Surgical removal of the ovaries protects against breast cancer. Breast feeding apparently protects against breast cancer in China, but a protective effect has not been established in the US. Other than shorter intervals between menstrual periods, which tend to increase the risk, research has not yet made clear the etiologic roles of menstrual cycle characteristics. Other unclear etiologic roles include increased intervals between births, spontaneous and induced abortion, infertility, multiple births at last pregnancy, and hypertension during pregnancy. Researchers tend to accept a mechanism to explain the epidemiologic characteristics of menstrual activity and the increased risk of breast cancer, but no mechanisms have emerged for the other likely risk factors. Greater exposure to estrogen and progesterone simultaneously are linked to early age at menarche, late age at menopause, and shorter menstrual cycle length. So far, data show that long-term combined estrogen/progestin hormone replacement therapy and long-term use of oral contraceptives increase the risk of breast cancer. Moderately increased risks linked to longterm estrogen replacement therapy and obesity in postmenopausal women indicate that estrogen alone influences breast cancer risk. Since much of the research on breast cancer risk factors are inconclusive, more research is needed, especially research examining the probability of prolonged exposure to both estrogens and progesterone concurrently.
Can community land trusts slow gentrification?

ABSTRACT Gentrification has become one of the most widely discussed phenomena in urban affairs due to its prevalence around the world. However, most discussions remain at the theoretical level or are limited to case studies of a few metropolitan cities. Furthermore, there is little research on the relationship between gentrification and community land trusts (CLTs)—to our knowledge, no studies have examined their connection. Our investigation seeks to address this research gap by evaluating whether and how CLTs affect gentrification. Can CLTs counteract the negative effects of gentrification? Using a data set detailing the locations of CLT units at the national level, we employed a binomial logistic regression to examine whether CLTs influence gentrification, as well as a paired t-test with 9 relevant indicators to understand how CLTs affect gentrification. The findings suggest that CLTs may function as appropriate tools for stabilizing neighborhoods at risk of gentrification.