Miracle-dz/UniFAR-FTUs huggingface dataset:
Airway Basal Cells, Protectors of Epithelial Walls in Health and Respiratory Diseases

The airway epithelium provides a critical barrier to the outside environment. When its integrity is impaired, epithelial cells and residing immune cells collaborate to exclude pathogens and to heal tissue damage. Healing is achieved through tissue-specific stem cells: the airway basal cells. Positioned near the basal membrane, airway basal cells sense and respond to changes in tissue health by initiating a pro-inflammatory response and tissue repair via complex crosstalks with nearby fibroblasts and specialized immune cells. In addition, basal cells have the capacity to learn from previous encounters with the environment. Inflammation can indeed imprint a certain memory on basal cells by epigenetic changes so that sensitized tissues may respond differently to future assaults and the epithelium becomes better equipped to respond faster and more robustly to barrier defects. This memory can, however, be lost in diseased states. In this review, we discuss airway basal cells in respiratory diseases, the communication network between airway basal cells and tissue-resident and/or recruited immune cells, and how basal cell adaptation to environmental triggers occurs.
Predicted and measured retinal nerve fiber layer thickness from time-domain optical coherence tomography compared with spectral-domain optical coherence tomography.

IMPORTANCE New methods are needed to compare peripapillary retinal nerve fiber layer thickness (pRNFLT) measurements taken from time-domain optical coherence tomography (TD-OCT) and spectral-domain OCT (SD-OCT). OBJECTIVE To compare the agreement of measured and predicted pRNFLT using different equations based on pRNFLT measurements obtained by TD-OCT and SD-OCT. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional single-center study that took place at the Department of Ophthalmology, University of Erlangen-Nuremberg from November 16, 2005, to June 3, 2015, and included 138 eyes of control participants, 126 eyes of patients with ocular hypertension, 128 eyes of patients with preperimetric glaucoma, and 160 eyes of patients with perimetric glaucoma. All participants had standard clinical examinations to obtain TD-OCT (via Stratus OCT) and SD-OCT (via Spectralis OCT) measurements of pRNFLT. Two groups were matched for diagnostic subgroup, eye side, sex, and age. The TD-OCT measurements of the first group were used to predict the mean SD-OCT and 6-sector vertical-split pRNFLT measurements of the second group and vice versa. The agreement between the predicted pRNFLT calculations of conversion equations and measured pRNFLT of the second group was evaluated by intraclass correlation coefficients and Bland-Altman plots. MAIN OUTCOMES AND MEASURES Mean and sectoral pRNFLT measurements obtained by TD-OCT and SD-OCT as well as the agreement between measured and predicted pRNFLT. RESULTS The agreement for all investigated equations to predict mean pRNFLT measurements with intraclass correlation coeffecients ranged from 0.937 to 0.939. Bland-Altman plots demonstrated systemic biases between -0.7 μm and +1.1 μm for measured and predicted mean pRNFLT measurements. The ratio method demonstrated an intraclass correlation coefficient of 0.969 for the temporal-inferior sector. The best color-code agreement between both OCT devices was achieved by the no conversion method, with κ = 0.731 (95% CI, 0.656-0.806) for the mean pRNFLT. CONCLUSIONS AND RELEVANCE These data suggest that the prediction of mean pRNFLT values by equations derived from TD-OCT and SD-OCT can be conducted with high levels of agreement. In individual cases and singular sectors, high prediction errors may occur. When longitudinal imaging data from both TD-OCT and SD-OCT are available, conversion equations may provide longitudinal comparability.
Past physical activity, current physical activity, and risk of coronary heart disease.

PURPOSE Middle-aged and older women who are physically active have decreased risk of coronary heart disease (CHD); however, little is known about how physical activity during young adulthood influences activity during middle age and older, and CHD risk. We examined the relationship between 1) physical activity during young adulthood and middle age, and 2) physical activity during each time period and CHD occurring in middle age or older. METHODS Cohort study of 39,876 healthy U.S. female health professionals, age > or = 45 yr, in the Women's Health Study. Physical activity was reported at baseline. Additionally, physical activity in high school and age 18-22 yr was reported on the 24-month follow-up survey. Women were followed for an average of 9 yr, after the 24-month survey, for CHD occurrence (N = 477). RESULTS Among 37,169 eligible participants at baseline, the most active women (vigorous physical activity 10-12 months x yr) during high school and age 18-22 yr were more than twice as likely to meet physical activity recommendations at baseline than the least active women (no vigorous activity) during high school and age 18-22 yr (multivariate-adjusted odds ratio = 2.43; 95% C.I. 2.24, 2.63). At baseline, the most active women (> or = 1500 kcal x wk(-1)) had a 39% lower risk of CHD during follow-up than the least active (<200 kcal x wk(-1)) (multivariate-adjusted relative risk = 0.61; 95% C.I. 0.46, 0.81). However, physical activity during young adulthood was not associated with risk of CHD occurring during middle age and older. CONCLUSION Women who are physically active during young adulthood are more likely to be active when middle-aged and older, when rates of CHD increase, and physical activity during middle-age predicts lower risk of CHD.
Antigen Nonspecific Suppression of T Cell Responses by Activated Stimulation-Refractory CD4+ T Cells 1

Several classes of anergic T cells are capable of suppressing naive T cell proliferation and thereby limiting immune responses. Activated T cells, although not anergic, are transiently refractory to restimulation with Ag. We examine in this study whether activated refractory murine T cells can also suppress naive T cell responses. We find that they can, and that they exhibit many of the suppressive properties of anergic T cells. The activated cells strongly diminish Ag-mediated T cell proliferation, an activity that correlates with their refractory period. Suppression is independent of APC numbers and requires cell contact or proximity. Naive T cells stimulated in the presence of activated refractory cells up-regulate CD25 and CD69, but fail to produce IL-2. The addition of IL-2 to culture medium, however, does not prevent the suppression, which is therefore not solely due to the absence of this growth factor. Persistence of the suppressor cells is also not essential. T cells stimulated in their presence and then isolated from them and cultured do not divide. The suppressive cells, however, do not confer a refractory or anergic state on the target T lymphocytes, which can fully respond to antigenic stimulation if removed from the suppressors. Our results therefore provide evidence that activated T cells act as transient suppressor cells, severely constraining bystander T cell stimulation and thereby restricting their response. These results have potentially broad implications for the development and regulation of immune responses.
Persistent signaling by thyrotropin‐releasing hormone receptors correlates with G‐protein and receptor levels

G‐protein‐coupled receptors with dissociable agonists for thyrotropin, parathyroid hormone, and sphingosine‐1‐phosphate were found to signal persistently hours after agonist withdrawal. Here we show that mouse thyrotropin‐releasing hormone (TRH) receptors, subtypes 2 and 1(TRH‐R2 and TRH‐R1), can signal persistently in HEK‐EM293 cells under appropriate conditions, but TRH‐R2 exhibits higher persistent signaling activity. Both receptors couple primarily to Gαq/11. To gain insight into the mechanism of persistent signaling, we compared proximal steps of inositolmonophosphate (IP1) signaling by TRH‐Rs. Persistent signaling was not caused by slower dissociation of TRH from TRH‐R2 (t1/2=77±8.1 min) compared with TRH‐R1 (t1/2=82±12 min) and was independent of internalization, as inhibition of internalization did not affect persistent signaling (115% of control), but required continuously activated receptors, as an inverse agonist decreased persistent signaling by 60%. Gαq/11 knockdown decreased persistent signaling by TRH‐R2 by 82%, and overexpression of Gαq/11 induced persistent signaling in cells expressing TRH‐R1. Lastly, persistent signaling was induced in cells expressing high levels of TRH‐R1. We suggest that persistent signaling by TRHRs is exhibited when sufficient levels of agonist/receptor/G‐protein complexes are established and maintained and that TRH‐R2 forms and maintains these complexes more efficiently than TRH‐R1. —Boutin, A. , Allen, M. D. , Neumann, S. , Gershengorn, M. C. Persistent signaling by thyrotropin‐releasing hormone receptors correlates with G‐protein and receptor levels. FASEB J. 26, 3473–3482 (2012). www.fasebj. org
Effects of Low Temperature Proton Irradiation on a Large Area CCD for Astrometric Applications

Charge transfer and dark current effects are compared for regions of a large area 4500 × 1966 pixel CCD irradiated with 7.4 MeV protons at -130°C and at room temperature. Post-annealing measurements were also performed. Although there are differences in the concentration of individual defects following warm and -130°C irradiation and after subsequent annealing steps, these differences were less than a factor 3.5 (and in most cases a factor 2)-with the room temperature irradiation giving a good estimate of the effects except for traps with emission time constant ~4 ms.
MOVING TO OPPORTUNITY: A SYMPOSIUM Neighborhood Effects on Economic Self- Sufficiency: A Reconsideration of the Moving to Opportunity Experiment 1

This article revisits the Moving to Opportunity housing mobility experiment, which heretofore has not provided strong evidence to support the hypothesis of neighborhood effects on economic selfsufficiency among adults. The authors undertake a conceptual and empirical analysis of the study’s design and implementation to gain a better understanding of the selection processes that occur within the study. The article shows that the study is potentially affected by selectivity at several junctures: in determining who complied with the program’s requirements, who entered integrated versus segregated neighborhoods, and who left neighborhoods after initial relocation. Furthermore, previous researchers have not found an experimental treatment effect on adult economic self-sufficiency, relative to controls. The authors propose an alternative approach that involves measuring the cumulative amount of time spent in different neighborhood environments. With this method, they find evidence that neighborhood is associated with outcomes such as employment, earnings, TANF receipt, and use of food stamps.
Do Foreign Multinationals' Tax Incentives Influence Their U.S. Income Reporting and Debt Policy?

Using a matched sample of financial data on foreign multinationals and confidential income tax return data on U.S. foreign-controlled corporations (FCCs) during 1987-1996, we examine whether the tax incentives of foreign multinationals influence their U.S. tax reporting. We find that foreign multinationals with relatively low average foreign tax rates report less taxable income and use more debt in their FCCs than those with relatively high average foreign tax rates. Our findings provide insights regarding the complex reporting behavior of FCCs and have implications for U.S. tax policy.
Paradox Lost

Simpatía is a cultural script that characterizes Hispanics as agreeable, friendly, sympathetic, and polite. However, on self-reports Hispanics score lower on Simpatía/Agreeableness than do non-Hispanics. This study reveals that it is the modesty within Simpatía that accounts for these paradoxical findings by driving down scores on Hispanics' self-reports. To test this idea, this study assesses Simpatía/Agreeableness in Mexican American bilinguals using (a) self-reports of Simpatía in English and Spanish and (b) behavioral manifestations of Simpatía in a social interaction task conducted in English and Spanish. As predicted, on self-reports bilinguals score lower on Simpatía when the assessment is in Spanish than when it is in English, but they show more Simpatía-related behaviors in the social interaction task in Spanish than in English. Follow-up analyses show that the results cannot be explained by translation artifacts on the questionnaire, response-style biases, or reference-group effects. The paradox sheds light on the complex interplay between culture and language.
The CXCL12/CXCR4 Signaling Axis Retains Neutrophils at Inflammatory Sites in Zebrafish

The inappropriate retention of neutrophils at inflammatory sites is a major driver of the excessive tissue damage characteristic of respiratory inflammatory diseases including COPD, ARDS, and cystic fibrosis. The molecular programmes which orchestrate neutrophil recruitment to inflammatory sites through chemotactic guidance have been well-studied. However, how neutrophil sensitivity to these cues is modulated during inflammation resolution is not understood. The identification of neutrophil reverse migration as a mechanism of inflammation resolution and the ability to modulate this therapeutically has identified a new target to treat inflammatory disease. Here we investigate the role of the CXCL12/CXCR4 signaling axis in modulating neutrophil retention at inflammatory sites. We used an in vivo tissue injury model to study neutrophilic inflammation using transgenic zebrafish larvae. Expression of cxcl12a and cxcr4b during the tissue damage response was assessed using in situ hybridization and analysis of RNA sequencing data. CRISPR/Cas9 was used to knockdown cxcl12a and cxcr4b in zebrafish larvae. The CXCR4 antagonist AMD3100 was used to block the Cxcl12/Cxcr4 signaling axis pharmacologically. We identified that cxcr4b and cxcl12a are expressed at the wound site in zebrafish larvae during the inflammatory response. Following tail-fin transection, removal of neutrophils from inflammatory sites is significantly increased in cxcr4b and cxcl12a CRISPR knockdown larvae. Pharmacological inhibition of the Cxcl12/Cxcr4 signaling axis accelerated resolution of the neutrophil component of inflammation, an effect caused by an increase in neutrophil reverse migration. The findings of this study suggest that CXCR4/CXCL12 signaling may play an important role in neutrophil retention at inflammatory sites, identifying a potential new target for the therapeutic removal of neutrophils from the lung in chronic inflammatory disease.
Export Growth, Export Potential and Export Resistance: A Case Study of Laos

This study applies a stochastic frontier gravity model to examine Laos’ export potential as well as factors hindering its export growth. This article uses a panel data of thirty-four importing countries from 2001 to 2011. Three main export growth factors are analysed in the model: (i) core factors (income per capita, population, and distance); (ii) implicit behind-the-border constraints; and (iii) implicit beyond-the-border constraints. The findings show that only half of the country’s export potential has been realized to date and export losses can primarily be attributed to implicit behind-the-border constraints. At the same time, these constraints have been reduced during the last decade. This article identifies border trade, a common language, income per capita and the Generalized System of Preferences scheme as important factors for export growth. Conversely, it finds that an appreciating real exchange rate is a signal of a slowdown in export growth.
Analysis of Serological Biomarkers of SARS-CoV-2 Infection in Convalescent Samples From Severe, Moderate and Mild COVID-19 Cases

Precision monitoring of antibody responses during the COVID-19 pandemic is increasingly important during large scale vaccine rollout and rise in prevalence of Severe Acute Respiratory Syndrome-related Coronavirus-2 (SARS-CoV-2) variants of concern (VOC). Equally important is defining Correlates of Protection (CoP) for SARS-CoV-2 infection and COVID-19 disease. Data from epidemiological studies and vaccine trials identified virus neutralising antibodies (Nab) and SARS-CoV-2 antigen-specific (notably RBD and S) binding antibodies as candidate CoP. In this study, we used the World Health Organisation (WHO) international standard to benchmark neutralising antibody responses and a large panel of binding antibody assays to compare convalescent sera obtained from: a) COVID-19 patients; b) SARS-CoV-2 seropositive healthcare workers (HCW) and c) seronegative HCW. The ultimate aim of this study is to identify biomarkers of humoral immunity that could be used to differentiate severe from mild or asymptomatic SARS-CoV-2 infections. Some of these biomarkers could be used to define CoP in further serological studies using samples from vaccination breakthrough and/or re-infection cases. Whenever suitable, the antibody levels of the samples studied were expressed in International Units (IU) for virus neutralisation assays or in Binding Antibody Units (BAU) for ELISA tests. In this work we used commercial and non-commercial antibody binding assays; a lateral flow test for detection of SARS-CoV-2-specific IgG/IgM; a high throughput multiplexed particle flow cytometry assay for SARS-CoV-2 Spike (S), Nucleocapsid (N) and Receptor Binding Domain (RBD) proteins); a multiplex antigen semi-automated immuno-blotting assay measuring IgM, IgA and IgG; a pseudotyped microneutralisation test (pMN) and an electroporation-dependent neutralisation assay (EDNA). Our results indicate that overall, severe COVID-19 patients showed statistically significantly higher levels of SARS-CoV-2-specific neutralising antibodies (average 1029 IU/ml) than those observed in seropositive HCW with mild or asymptomatic infections (379 IU/ml) and that clinical severity scoring, based on WHO guidelines was tightly correlated with neutralisation and RBD/S antibodies. In addition, there was a positive correlation between severity, N-antibody assays and intracellular virus neutralisation.
Assessing the Quality of Municipal Government Web Sites

MUNICIPAL GOVERNMENTS have a reputation for quickly adopting new technologies to engage and serve constituents (Gronlund 2001). Web sites, one of the latest of these technologies, are key tools for communication and service provision to multiple constituencies. A recent International City/County Management Association (ICMA) survey of more than 4,000 local governments in the United States found that over 85 percent of the responding municipalities had active Web sites (Moon 2002). More recent research shows that the number of people who access government Web sites in the United States tripled between 2001 and 2003 (Horrigan 2004). Many policymakers, e-government service providers, and scholars argue that the World Wide Web offers unprecedented potential for governments to improve effi ciency and effectiveness, and ultimately strengthen democracy and public trust (see Accenture 2004; Caldow 2004; Fountain 2001). 1 This potential seems particularly important at local levels at which the most basic public services are provided and citizens are most connected to government. With few exceptions (see Kaylor, Deshazo, and Van Eck 2001; Scott, forthcoming; The E-Government Institute 2003; West 2002; Musso, Weare, and Hale 2001), research rarely examines the content of local government Web sites.2 In fact, no offi cial standards or guidelines of service quality are available to guide the development of U.S. municipal government Web sites.3 More research is needed to assess the effects of local government Web sites on citizen involvement, democratic practice, and public trust. Research is also needed on how the dynamic, competitive Web culture affects citizen (and other user) demands for e-service quality, e-security, privacy, and accountability. As Web content and use continues to increase, municipal governments must regularly monitor and enhance the quality of their sites to attract and satisfy users. This article proposes a set of quantifi able quality indicators for use in assessing this process and reports how 100 municipal government Web sites measure against the indicators. The study draws on a review of quality standards applied in commercial or other high-traffi c Web sites and on data collected from a recent content analysis of municipal government Web sites (Scott, forthcoming). First, the research problem is presented in light of recent trends. Second, fi ve quality standards for local government Web sites are proposed based on previous research and emerging best practices. The research design, which applies these standards to 100 U.S. municipal governPRACTITIONER’S CORNER
Biological markers of drug use in the club setting.

OBJECTIVE The prevalence of drug and alcohol use among patrons of clubs featuring electronic music dance events was determined by using biological assays at entrance and exit. METHOD Using a portal methodology that randomly selects groups of patrons on arrival at clubs, oral assays for determining level and type of drug use and level of alcohol use were obtained anonymously. Patrons provided self-reported data on their personal characteristics. A total of 362 patrons were interviewed at entrance and provided oral assay data, and 277 provided data at both entrance and exit. RESULTS Overall, one quarter of all patrons surveyed at entrance were positive for some type of drug use. Based on our exit sample, one quarter of the sample was positive at exit. Individual drugs most prevalent at entrance or exit included cocaine, marijuana, and amphetamines/stimulants. Only the amphetamine/stimulant category increased significantly from entrance to exit. Drug-using patrons arrive at the club already using drugs; few patrons arrive with no drug use and leave with detectable levels of drug use. Clubs vary widely in drug-user prevalence at entrance and exit, suggesting that both events and club policies and practices may attract different types of patrons. Approximately one half of the total entrance sample arrived with detectable alcohol use, and nearly one fifth arrived with an estimated blood alcohol concentration of . 08 or greater. Based on our exit sample data, one third of patrons were intoxicated, and slightly less than one fifth were using both drugs and alcohol at exit. Clubs attract a wide array of emerging adults, with both genders and all ethnicities well represented. Clubs also attract emerging adults who are not in college and who are working full time. CONCLUSIONS At clubs featuring electronic music dance events, drug use and/or high levels of alcohol use were detected using biological assays from patrons at entrance and exit from the clubs. Thus, these clubs present a potentially important location for prevention strategies designed to reduce the risks associated with drug and alcohol use for young people. Combined substance use may prove particularly important for prevention efforts designed to increase safety at clubs. Personal characteristics do not identify drug users, suggesting that environmental strategies for club safety may offer more promise for promoting health and safety.