Miracle-dz/UniFAR-FTUs huggingface dataset:
Thyroid hormone receptor β mutants: Dominant negative regulators of peroxisome proliferator-activated receptor γ action

Thyroid hormone (T3) and peroxisome proliferators have overlapping metabolic effects in the maintenance of lipid homeostasis. Their actions are mediated by their respective receptors: thyroid hormone receptors (TR) and peroxisome proliferator-activated receptors (PPAR). We recently found that a dominantly negative TRbeta mutant (PV) that causes a genetic disease, resistance to thyroid hormone, acts to repress the ligand (troglitazone)-mediated transcriptional activity of PPARgamma in cultured thyroid cells. This finding suggests that TRbeta mutants could crosstalk with PPARgamma-signaling pathways. The present study explored the molecular mechanisms by which PV represses the PPARgamma transcriptional activity. Gel-shift assays show that the PV, similar to wild-type TRbeta, bound to the peroxisome proliferator response element (PPRE) as homodimers and heterodimers with PPARgamma or the retinoid X receptor (RXR), thereby competing with PPARgamma for binding to PPRE and for sequestering RXR. Association of PPRE-bound PV with corepressors [e.g., nuclear receptor corepressor (NCoR)] that led to transcriptional repression was independent of T3 and troglitazone. Chromatin immunoprecipitation assay further demonstrated that, despite the presence of ligands, NCoR was recruited to PPRE-bound PV on a PPARgamma-target gene, the lipoprotein lipase, in vivo, suggesting the dominant action of PV on PPARgamma-mediated transcriptional activity. Thus, the dominant negative action of PV is not limited on the wild-type TRs. The findings that TRbeta mutants affect PPARgamma functions through dominant negative action provide insights into the molecular mechanisms by which TR regulates the PPARgamma-target genes involved in metabolic pathways, lipid homeostasis, and carcinogenesis.
Characterization of a major aromatic DNA adduct detected in human breast tissues

A bulky DNA adduct (Spot 1) was previously detected in normal adjacent breast tissues of 41% (36/87) of women with breast cancer and in none (0/29) of the noncancer controls by 32P‐postlabeling. To characterize this adduct, it was chromatographically compared with DNA adduct profiles generated in several in vitro and in vivo experimental systems. First, MCF‐7 cells were exposed to a number of chemical carcinogens, that is, benzo[a]pyrene (B[a]P), 4‐OH‐B[a]P, 9‐OH‐B[a]P, 11‐OH‐B[a]P, B[a]P‐trans‐4,5‐dihydrodiol, 1‐nitropyrene, 6‐nitrochrysene, dibenzo[a,l]pyrene, benzo[c]phenanthrene, dibenzo[a,h]anthracene, 3‐methylcholanthrene, and 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine. Spot 1 was detected as a minor adduct in cells treated with B[a]P but not other compounds. Second, to determine whether Spot 1 is derived from lipid peroxidation products or estrogen metabolites, it was compared with adduct profiles of cells or DNAs exposed to 17β‐estradiol, 4‐hydroxy estradiol, 4‐hydroxynonenal, or oxidized oat oil. Spot 1 was not detectable in these samples. In addition, Spot 1 did not comigrate with the 1,N2‐ethenodeoxyguanosine adduct standard. Third, to explore the mechanism of Spot 1 formation, it was compared with adduct profiles detected in DNA or mononucleotides reacted with BPDE, 1‐OH‐7,8‐dihydrodiol of B[a]P, and 3‐OH‐7,8‐dihydrodiol of B[a]P as well as in rats orally treated with B[a]P. Spot 1 comigrated with a minor adduct in BPDE‐treated DNA during anion exchange rechromatography but these two adducts were separated by partition chromatography. Spot 1 also behaved in a manner that was very similar to that of the polar B[a]P adducts detected in rat liver, but the two adducts were separated by HPLC. Fourth, Spot 1 was compared with CD1 mice exposed to 7H‐benzo[c]fluorene (B[c]F). Spot 1 from some patients comigrated with a major adduct induced by B[c]F. Finally, we found that the presence of Spot 1 in human breast tissues was not related to smoking status but, rather, with CYP1A1 MspI polymorphism. The CYP1A1 mutant carriers had a significantly higher frequency of this adduct than did the wild‐type genotypes. Furthermore, individuals with Spot 1 had a significantly higher staining intensity for BPDE–PAH adducts in their tissue sections than those without it. These results demonstrate that this major bulky DNA adduct detected in human breast tissues is related to PAH exposure. Environ. Mol. Mutagen. 39:193–200, 2002. © 2002 Wiley‐Liss, Inc.
Nondestructive DNA extraction from blackflies (Diptera: Simuliidae): retaining voucher specimens for DNA barcoding projects

A nondestructive, chemical‐free method is presented for the extraction of DNA from small insects. Blackflies were submerged in sterile, distilled water and sonicated for varying lengths of time to provide DNA which was assessed in terms of quantity, purity and amplification efficiency. A verified DNA barcode was produced from DNA extracted from blackfly larvae, pupae and adult specimens. A 60‐second sonication period was found to release the highest quality and quantity of DNA although the amplification efficiency was found to be similar regardless of sonication time. Overall, a 66% amplification efficiency was observed. Examination of post‐sonicated material confirmed retention of morphological characters. Sonication was found to be a reliable DNA extraction approach for barcoding, providing sufficient quality template for polymerase chain reaction amplification as well as retaining the voucher specimen for post‐barcoding morphological evaluation.
Intcal04 Terrestrial Radiocarbon Age Calibration, 0–26 Cal Kyr BP

A new calibration curve for the conversion of radiocarbon ages to calibrated (cal) ages has been constructed and internationally ratified to replace IntCal98, which extended from 0–24 cal kyr BP (Before Present, 0 cal BP = AD 1950). The new calibration data set for terrestrial samples extends from 0–26 cal kyr BP, but with much higher resolution beyond 11.4 cal kyr BP than IntCal98. Dendrochronologically-dated tree-ring samples cover the period from 0–12.4 cal kyr BP. Beyond the end of the tree rings, data from marine records (corals and foraminifera) are converted to the atmospheric equivalent with a site-specific marine reservoir correction to provide terrestrial calibration from 12.4–26.0 cal kyr B P. A substantial enhancement relative to IntCal98 is the introduction of a coherent statistical approach based on a random walk model, which takes into account the uncertainty in both the calendar age and the 14C age to calculate the underlying calibration curve (Buck and Blackwell, this issue). The tree-ring data sets, sources of uncertainty, and regional offsets are discussed here. The marine data sets and calibration curve for marine samples from the surface mixed layer (Marine04) are discussed in brief, but details are presented in Hughen et al. (this issue a). We do not make a recommendation for calibration beyond 26 cal kyr BP at this time; however, potential calibration data sets are compared in another paper (van der Plicht et al., this issue).
Testosterone Concentrations and Sirolimus in Male Renal Transplant Patients

Sirolimus damages the testes in animals; however, human data are sparse. We conducted a case‐control study to obtain further insight into this issue and compared testosterone, follicle‐stimulating hormone (FSH), luteinizing hormone (LH), and prolactin concentrations in matched renal transplant patients who did or did not receive sirolimus. We found that testosterone values were lower (11.2 ± 6.3 nmol/L vs. 15.5 ± 7.7 nmol/L, p < 0.05), in 28 sirolimus‐treated patients, compared to 28 non‐sirolimus‐treated controls. Furthermore, these patients more commonly had testosterone concentrations that were below our reference value for normal men. In contrast, FSH and LH concentrations were higher while prolactin levels were not different. These data are consistent with sirolimus‐related testosterone suppression and suggest a need for further studies.
What people study when they study Tumblr: Classifying Tumblr-related academic research

Purpose Since its launch in 2007, research has been carried out on the popular social networking website Tumblr. The purpose of this paper is to identify published Tumblr-based research, classify it to understand approaches and methods, and provide methodological recommendations for others. Design/methodology/approach Research regarding Tumblr was identified. Following a review of the literature, a classification scheme was adapted and applied, to understand research focus. Papers were quantitatively classified using open coded content analysis of method, subject, approach, and topic. Findings The majority of published work relating to Tumblr concentrates on conceptual issues, followed by aspects of the messages sent. This has evolved over time. Perceived benefits are the platform’s long-form text posts, ability to track tags, and the multimodal nature of the platform. Severe research limitations are caused by the lack of demographic, geo-spatial, and temporal metadata attached to individual posts, the limited Advanced Programming Interface, restricted access to data, and the large amounts of ephemeral posts on the site. Research limitations/implications This study focusses on Tumblr: the applicability of the approach to other media is not considered. The authors focus on published research and conference papers: there will be book content which was not found using the method. Tumblr as a platform has falling user numbers which may be of concern to researchers. Practical implications The authors identify practical barriers to research on the Tumblr platform including lack of metadata and access to big data, explaining why Tumblr is not as popular as Twitter in academic studies. Social implications This paper highlights the breadth of topics covered by social media researchers, which allows us to understand popular online platforms. Originality/value There has not yet been an overarching study to look at the methods and purpose of those who study Tumblr. The authors identify Tumblr-related research papers from the first appearing in 2011 July until 2015 July. The classification derived here provides a framework that can be used to analyse social media research, and in which to position Tumblr-related work, with recommendations on benefits and limitations of the platform for researchers.
Pathology of Avian Pox in Wild Red‐Legged Partridges (Alectoris rufa) in Spain

Abstract: The diagnosis and pathology of an avian pox outbreak in free‐living red‐legged partridges in Cádiz, Southern Spain, is described. Diagnosis of the disease was based on histopathology, ultrastructural examination of, and virus isolation from lesions of necropsied animals. Lesions were present mainly in juvenile partridges (41%), and were observed primarily on the dorsal part of the digits or on the hock joint. The lesions ranged from small wartlike nodules to large tumor‐like lesions. The presence of acute lesions of any grade as opposed to absence of lesions or healed lesions adversely affected body condition of the partridges (P < .01). Further investigations on the epidemiology of the disease and on the relation of the isolated strains to other avian poxviruses are under way.
Census from Heaven: An Estimate of Global Electricity Demand 'If Everyone Lived Like in OECD'

How much electricity does the world really need? Economic theory suggests that electricity demand depends on a number of factors such as per capita income, economic output, supply and cost of electricity. However, formal electricity demand models based on Gross Domestic Product (GDP), population growth and efficiency improvement assumptions may not capture the appropriate variables for responses at high geographical resolution level and, as a result, may be quite wrong about the prospective electricity need.This study proposed a method and then implemented it for the question of whether luminosity (measures of nighttime lights visible from space) could be used to improve estimates of electricity prospective demand in non-OECD countries at the high geographical resolution. Further, we investigated whether luminosity may serve as a proxy for electricity consumption. Luminosity data has an advantage over other proxies as night lights data are available over time and all space, but data on electricity consumption are unavailable for many lower income countries and generally are unavailable for most countries at sub-national levels. To the extent that luminosity is a good proxy for electricity consumption, we evaluated how much electricity the world would likely demand “if everyone lived like in OECD countries. ”
BerEp4, cytokeratin 14, and cytokeratin 17 immunohistochemical staining aid in differentiation of basaloid squamous cell carcinoma from basal cell carcinoma with squamous metaplasia.

CONTEXT Basaloid squamous cell carcinoma (bSCC) is an uncommon variant of squamous cell carcinoma, which may overlap histologically with basal cell carcinoma with squamous metaplasia (BCCm). OBJECTIVE To aid in the differentiation of these neoplasms using immunohistochemical staining because of the worse prognosis associated with bSCC. DESIGN Using immunohistochemical techniques, we investigated BerEp4, cytokeratin 17 (CK17), and cytokeratin 14 (CK14) protein expression in 25 cases of bSCC (8 cutaneous [32%], 12 aerodigestive tract [48%], and 5 lymph node metastases [20%]) and 43 cases of BCCm (39 cutaneous [91%], and 4 metastases [9%]). An immunoreactivity score was assigned using the percentage of tumor cells staining and the pattern of expression. Interobserver agreement for 2 independent pathologists was assessed using a κ coefficient. RESULTS The mean percentage of staining was significantly higher in BCCm, compared with bSCC (BerEp4, P = .006; CK17, P < .001; CK14, P < .001; unpaired t test), with 58% of BCCm cases (25 of 43) displaying diffuse staining for all markers, and nearly all (98%; 42 of 43) displaying diffuse staining for CK17 and CK14. In contrast, no bSCC cases (0%) displayed diffuse staining for all 3 markers, and only 8% (2 of 25) displayed diffuse staining for CK17 and CK14. High interobserver agreement was determined. CONCLUSIONS BerEp4 alone is unreliable for differentiation between BCCm and bSCC, and the addition of either CK14 or CK17 will augment the sensitivity and negative predictive value of BerEp4 staining in BCCm and bSCC diagnosis.
Seeing is Believing : The Impact of Local Economic Conditions on Firm Expectations , Employment and Investment

I show that managers overweight observations of local economic conditions at firm headquarters (HQ) when forming their macroeconomic expectations. This implies that HQ local economic conditions have an excessive impact on firm investment and employment growth. Using an empirical strategy identifying the impact of local economic conditions at HQ on employment outside the HQ, I find that a 1 percentage point (p.p.) higher local unemployment rate at HQ leads to 2 p.p. lower employment growth at non-HQ establishments. I consider a number of alternative explanations such as internal capital markets reallocation or local financing, and rule these out using placebo tests and by testing the key implications of the explanations. Then, I present evidence that HQ local conditions are overweighted in managers’ expectations. Worse HQ local conditions lead to more pessimistic sales forecasts and more negative macroeconomic sentiment. These findings, along with results from tests comparing firms with different sensitivities to the macroeconomic cycle, support the notion that local economic conditions bias managers’ macroeconomic expectations. Finally, I show that this bias can explain differences in county economic outcomes and may lead to significant investment misallocation. ∗Harvard University, Department of Economics. Email: bchen@fas.harvard. edu. I am indebted to Jeremy Stein, Andrei Shleifer, Sam Hanson and David Scharfstein for their encouragement, guidance, and support. I thank Malcolm Baker, Laura Blattner, John Campbell, Gabriel Chodorow-Reich, David Choi, Lauren Cohen, Benjamin Friedman, Xavier Gabaix, Robin Greenwood, Larry Katz, Nihar Shah, Larry Summers, Adi Sunderam, David Thesmar, Peter Tu, and seminar participants at Harvard finance and macroeconomics lunch for helpful discussions and suggestions. I thank Jim Davis for assistance with the Census microdata. Any opinions and conclusions expressed herein are those of the author and do not necessarily represent the views of the U.S. Census Bureau. All results have been reviewed to ensure that no confidential information is disclosed.
Small-scale spatial variability of food partitioning between cultivated oysters and associated suspension-feeding species, as revealed by stable isotopes

Oyster culture structures support a host of epibionts belonging to the same suspension- feeding guild, which are considered to be potential competitors for food with cultivated oysters. In an intertidal shellfish ecosystem on the northern French coast, an approach based on stable isotopes ( 13 C and 15 N) was used to investigate intra- and interspecific food resource partitioning among culti- vated oysters and the main associated wild sessile epibionts such as polychaetes, barnacles, mussels and ascidians. The main objective of the present study was to determine inter- and intraspecific food partitioning, along with small-scale spatial variability, within the guild of suspension feeders. We demonstrated that interspecific competition was limited among co-occurring suspension-feeders (ascidians, serpulid and terebellid polychaetes, bivalves and barnacles). None of the studied species had similar δ 13 C and δ 15 N signatures, indicating that relative contributions of organic matter sources may differ for each suspension-feeding species. Spatial variability was investigated both from the view of intra- and interspecific variability. Intraspecific variability was examined with regard to spe- cies' feeding biology and the trophic plasticity of co-occurring suspension-feeders. Mantel tests indi- cated that spatial heterogeneity resulted not only from environmental conditions, such as elevation above sea level (a.s.l.) and sediment features, but also from the inherent spatial structure of isotopic signatures. Our results show that isotopic approaches that are limited to sampling in one area and at one time are at risk of mistaking trophic interactions.
What is the most effective way to reduce incidence of amputation in the diabetic foot?

Approximately 40–60% of all amputations of the lower extremity are performed in patients with diabetes. More than 85% of these amputations are precipitated by a foot ulcer deteriorating to deep infection or gangrene. The prevalence of diabetic foot ulcers has been estimated to be 3–8%. The complexity of these ulcers necessitates a multifactorial approach in which aggressive management of infection and ischemia is of major importance. For the same reason, a process‐oriented approach in the evaluation of prevention and management of the diabetic foot is essential. Healing rates of foot ulcers are unknown with the exception of specialised centres where it is between 80–90%. The negative consequences of diabetic foot ulcers on quality of life include not only morbidity but also disability and premature mortality. Costs for healing ulcers are high and even higher for ulcers resulting in amputation, due to prolonged hospitalisation, rehabilitation, and need for home care and social service for disabled patients. Therefore, one of the most important steps to reduce cost in the management of the diabetic foot is to avoid amputations. A cost‐effective management should not only be focused on the short‐term cost until healing but also on the long‐term cost, since foot ulcer and especially amputation are related to increased re‐ulceration rate and lifelong disability. A multidisciplinary approach including preventive strategy, patient and staff education, and multifactorial treatment of foot ulcers has been reported to reduce the amputation rate by more than 50%. Copyright © 2000 John Wiley & Sons, Ltd.
Determinants of Waterpipe and Cigarette Smoking Progression among a School Based Sample of Adolescents in Irbid, Jordan: A Three-Year Longitudinal Study (2008-2011)

BACKGROUND: Based on anecdotal evidence, waterpipe may provide gateway to cigarette smoking onset among youth. This hypothesis is yet to be examined using appropriate study design and a theoretical model of behavioral change. AIM: To compare the risk of cigarette smoking initiation for waterpipe-only and never-smokers among a school-based sample of adolescents from Irbid, Jordan. METHODS: A total of 1454 cigarette naive participants were drawn from the Irbid longitudinal study of smoking behavior out of 1781 seventh-graders who were enrolled at baseline (2008) and completed the study questionnaire of smoking behavior annually through 2011. Grouped-time survival analysis was used to compare the risk of a subsequent initiation of cigarette smoking between waterpipe smokers (n=298) and never smokers (n=1156) using Adjusted Hazard Ratio [AHR] and 95% Confidence Interval [95%CI]. RESULTS: Risk of cigarette initiation among waterpipe smokers was significantly higher than never-smokers after adjusting for potential confounders (AHR: 1.67; [95% CI: 1.46-1.92]). The association between waterpipe and cigarette smoking initiation was dose dependent. As frequency of waterpipe smoking increased, the probability of cigarette initiation increased (P for linear trend < 0.001). CONCLUSIONS: Waterpipe smoking temporally predicted cigarette initiation among this cohort of Jordanian adolescents and this effect was dose-dependent.
Elder Abuse and Neglect in a Population Offering Care by a Primary Health Care Center in Izmir, Turkey

The objective of this study is to investigate the prevalence of abuse and neglect of the elderly aged 65 years and older, living with their relative in a primary health care center area and affecting factors. A descriptive study included 331 people aged 65 years. The most frequent type of abuse was psychological abuse and the least frequent was sexual abuse. Female gender, low education levels, living with spouses and children, and perception of familial relationships as average or below average significantly increased abuse. The nurses providing primary health care should be able to identify and observe the elderly at risk of abuse and conduct programs preventing abuse.