Miracle-dz/UniFAR-FTUs huggingface dataset:
NF-IL6 represses early gene expression of human papillomavirus type 16 through binding to the noncoding region

The expression of human papillomavirus type 16 (HPV16) early genes, including E6 and E7 transforming genes, is regulated by several cellular factors binding to the noncoding region (NCR), such as the glucocorticoid receptor, NF-I, and AP1, all of which are positive regulators. We demonstrated that the nuclear factor for interleukin 6 expression (NF-IL6) specifically binds to the HPV16 NCR ranging from nucleotides 7007 to 7766 and represses the early gene expression of HPV16. The responsive element in HPV16 NCR was determined within the region ranging from nucleotides 7454 to 7766. In this region, many binding sites for other cellular transactivators, such as NF-I and AP1, have been detected. Interestingly, three of seven binding sites for NF-I and two of two binding sites for AP1 in this region overlap with the putative NF-IL6 binding sites identified by computer analysis. Competition experiments with the oligonucleotides containing such NF-I or AP1 sites indicated that NF-IL6 certainly binds to them. Furthermore, in a chloramphenicol acetyltransferase assay using mutant NF-IL6 expression vectors, the DNA binding domain of NF-IL6 was shown to be necessary for repression, whereas the functional domain was not. These findings indicate that repression may be caused by competition with other transcriptional activators, such as NF-I and AP1. Thus, NF-IL6 may play a significant role in the regulation of viral transcription as a part of the host's resistance to viral infection.
Correcting an Evident Error: A Plea to Revise Jesner v. Arab Bank, PLC

In Jesner v. Arab Bank, PLC, the Supreme Court held that foreign corporations are not subject to lawsuits under the Alien Tort Statute (“ATS”). Written by Justice Kennedy, the highly fractured opinion offered several reasons for its holding. Commentators have already criticized various aspects of Justice Kennedy’s opinion. But, one aspect of the opinion has not received any consideration and merits immediate correction by the Court. While interpreting the ATS, Justice Kennedy attached significance to the placement of the Torture Victim Protection Act (“TVPA”) as a statutory note to the ATS in the U.S. Code. In so doing, he disregarded long-standing practice and black letter law that the placement of a statutory note in the U.S. Code does not have any substantive impact on the law’s meaning, interpretation, or application. This error merits correction by the Court for several reasons. While it undoubtedly influenced Justice Kennedy’s interpretation of the ATS in Jesner, it may affect future ATS and TVPA cases. And, more broadly, it raises uncertainty over the status of the countless statutory notes that populate the federal code.
A review of awareness interventions in brain injury rehabilitation

Unawareness related to brain injury has implications for participation in rehabilitation, functional outcomes, and the emotional well-being of clients. Addressing disorders of awareness is an integral component of many rehabilitation programmes, and a review of the literature identified a range of awareness interventions that include holistic milieu-oriented neuropsychological programmes, psychotherapy, compensatory and facilitatory approaches, structured experiences, direct feedback, videotaped feedback, confrontational techniques, cognitive therapy, group therapy, game formats and behavioural intervention. These approaches are examined in terms of their theoretical bases and research evidence. A distinction is made between intervention approaches for unawareness due to neurocognitive factors and approaches for unawareness due to psychological factors. The socio-cultural context of unawareness is a third factor presented in a biopsychosocial framework to guide clinical decisions about awareness interventions. The ethical and methodological concerns associated with research on awareness interventions are discussed. The main considerations relate to the embedded nature of awareness interventions within rehabilitation programmes, the need for individually tailored interventions, differing responses according to the nature of unawareness, and the risk of eliciting emotional distress in some clients.
Ligand-induced Dimer-Tetramer Transition during the Activation of the Cell Surface Epidermal Growth Factor Receptor-A Multidimensional Microscopy Analysis*

The epidermal growth factor receptor (EGFR) is a member of the erbB tyrosine kinase family of receptors. For many years it has been believed that receptor activation occurs via a monomer-dimer transition that is associated with a conformational change to activate the kinase. However, little is known about the quaternary state of the receptor at normal levels of expression (<105 receptors/cell). We employed multidimensional microscopy techniques to gain insight into the state of association of the human EGFR, in the absence and presence of ligand, on the surface of intact BaF/3 cells (50,000 receptors/cell). Image correlation microscopy of an EGFR-enhanced green fluorescent protein chimera was used to establish an average degree of aggregation on the submicron scale of 2.2 receptors/cluster in the absence of ligand increasing to 3.7 receptors/cluster in the presence of ligand. Energy transfer measurements between mixtures of fluorescein isothiocyanate-EGF and Alexa 555-EGF were performed using fluorescence lifetime imaging microscopy as a function of the donor: acceptor labeling ratio to gain insight into the spatial disposition of EGFR ligand binding sites on the nanometer scale. In the context of a two-state Förster resonance energy transfer (FRET)/non-FRET model, the data are consistent with a minimum transfer efficiency of 75% in the FRET population. The microscopy data are related to biophysical data on the EGFR in the A431 cell line and the three-dimensional structure of the ligated EGFR extracellular domain. In the context of a monomer-dimer-oligomer model, the biophysical data are consistent with a significant fraction of ligated EGFR tetramers comprising two dimers juxtaposed in a side-by-side (or slightly staggered) arrangement. Our data are consistent with a specific higher order association of the ligand-bound EGFR on the nanometer scale and indicate the existence of distinct signaling entities beyond the level of the EGFR dimer which could play an important role in receptor transactivation.
Occupational allergy to birds within the population of Polish bird keepers employed in zoo gardens

ObjectivesTo evaluate the risk factors for the development of occupational allergy to birds among Polish zoo garden keepers.MethodsA total of 200 bird zookeepers employed in the Polish zoo gardens in KLódź, Warsaw, Gdańsk, Chorzów and Płock and exposed occupationally to bird allergens were examined using a questionnaire, skin prick tests (SPTs) to common allergens and bird allergens, spirometry and cytograms of nasal swab. The level of total IgE in serum and serum-specific IgE to parrot, canary, pigeon feathers and serum were also evaluated.ResultsEight percent of bird zookeepers were sensitized to at least one of the bird allergens. The most frequent allergens yielding positive SPT results were D. farinae — 32 cases (16%), D. pteronyssinus — 30 cases (15%) and grass pollens (16.5%). In the studied group, allergen-specific IgE against bird allergens occurred with the following frequency: 87 (43.5%) against canary feathers and/or serum, 80 (40%) against parrot feathers and/or serum and 82 (41%) against pigeon feathers and/or serum. Occupational allergy was diagnosed in 39 (26.5%) cases, occupational rhinitis was present in 22 (15%) cases, occupational asthma in 20 (13.6%) subjects, occupational conjunctivitis in 18 (12.2%) cases, whereas occupational skin diseases in 11 (7.5%) cases. More eosinophils were found in nose swab cytograms among bird zookeepers with occupational airway allergy.ConclusionsThe findings indicate that occupational allergy to birds is an important health problem among zoo bird keepers in Poland.
The Great Divide: Unequal Societies and What We Can Do About Them

In The Great Divide, Joseph E. Stiglitz expands on the diagnosis he offered in his best-selling book The Price of Inequality and suggests ways to counter America's growing problem. With his signature blend of clarity and passion, Stiglitz argues that inequality is a choice-the cumulative result of unjust policies and misguided priorities. Gathering his writings for popular outlets including Vanity Fair and the New York Times, Stiglitz exposes in full America's inequality: its dimensions, its causes, and its consequences for the nation and for the world. From Reagan-era to the Great Recession and its long aftermath, Stiglitz delves into the irresponsible policies-deregulation, tax cuts, and tax breaks for the 1 percent-that are leaving many Americans farther and farther beyond and turning the American dream into an ever more unachievable myth. With formidable yet accessible economic insight, he urges us to embrace real solutions: increasing taxes on corporations and the wealthy; offering more help to the children of the poor; investing in education, science, and infrastructure; helping out homeowners instead of banks; and, most importantly, doing more to restore the economy to full employment. Stiglitz also draws lessons from Scandinavia, Singapore, and Japan, and he argues against the tide of unnecessary, destructive austerity that is sweeping across Europe. Ultimately, Stiglitz believes our choice is not between growth and fairness; with the right policies, we can choose both. His complaint is not so much about capitalism as such, but how twenty-first-century capitalism has been perverted. His is a call to confront America's economic inequality as the political and moral issue that it is. If we reinvest in people and pursue the other policies that he describes, America can live up to the shared dream of a more prosperous, more equal society.
Stimulus-Dependent Regulation of Serum and Glucocorticoid Inducible Protein Kinase (SGK) Transcription, Subcellular Localization and Enzymatic Activity

We originally discovered the serum and glucocorticoid inducible protein kinase, SGK, as a novel protein kinase that is under acute transcriptional control by serum and glucocorticoids. An expanding set of cell surface receptor, nuclear receptor, and cellular stress pathways has been shown to target SGK, which has implicated this regulated signaling molecule in a variety of biological functions. Compared to most other protein kinases, a distinguishing feature of SGK is the stringent stimulus-dependent regulation of its transcription, subcellular localization and enzymatic activity. In addition, SGK expression is regulated during discrete developmental stages, and during normal and abnormal physiological function. An analysis of the SGK promoter reveals many potential transcription factor sites that potentially account for the stimulus-dependent changes in SGK transcript expression observed in a variety of cell systems, although, the direct stimulus regulation of SGK promoter activity has been established only for glucocorticoids, p53 tumor suppressor protein, hyperosmotic stress and follicle stimulating hormone. In the systems tested to date, hormones, growth factors and environmental cues induce expression of a catalytically active SGK. It is now well established that the enzymatic activity of SGK is controlled by the PI 3-kinase cascade which produces a hyperphosphorylated active SGK. A critical third level of regulation is the stimulus-dependent control of SGK subcellular localization. The nuclear-cytoplasmic shuttling of SGK is regulated by a nuclear localization signal (NLS) that binds to the importin-alpha nuclear import receptor. Modeling of the 3-D structure of the central region of SGK that includes the kinase domain predicts that the NLS is located at an external surface of the molecule. Thus, multiple signal transduction pathways converge on SGK to control its availability, function and access to its substrates and non-substrate targets.
Un modelo Fay-Herriot espacial para estimar la tasa de embarazo adolescente en Colombia

Lograr estimaciones a un mayor nivel de desagregacion hace que los modelos de estimacion de areas pequenas adquieran gran relevancia en el analisis de datos que provienen de encuestas con alcances menores. El presente documento se constituye en un ejercicio de investigacion cuyo objetivo es garantizar que las estimaciones de la tasa de embarazo adolescente en los departamentos de Colombia que producidas por la Encuesta Nacional de Demografia y Salud de Colombia del 2015 puedan ser extrapolables a todos los municipios del pais. Para tal fin, se utilizara una adaptacion del modelo de Fay-Herriot Espacial que incorpora informacion a nivel municipal de la tasa de embarazo e informacion administrativa de las caracteristicas de los municipios del pais. Las estimaciones obtenidas se compararon con las derivadas de las estimaciones directas en el mismo grado de agregacion de cada fuente de datos, observandose mejoria en terminos de precision.
Gamma delta T cells from HIV+ donors can be expanded in vitro by zoledronate/interleukin-2 to become cytotoxic effectors for antibody-dependent cellular cytotoxicity.

BACKGROUND AIMS Immunotherapy using γδ T cells capable of mediating antibody-dependent cellular cytotoxicity (ADCC) is a promising anti-human immunodeficiency virus (HIV) strategy. Approved aminobispohsphonate drugs, for example zoledronate (Zometa), stimulate γδ T cells in cancer patients, where they may promote direct tumor killing. Knowing that γδ T cells are modulated during HIV disease, documenting their responses and potential for controlling HIV is important. We investigated whether zoledronate/interleukin (IL)-2 could expand cytotoxic Vδ2 cells from HIV+ donors and whether these cells functioned in ADCC. METHODS Peripheral blood mononuclear cells from uninfected controls and HIV+ individuals receiving anti-retroviral therapy were treated with isopentenyl pyrophosphate (IPP) or zoledronate plus IL-2 to expand the Vδ2+ subset. Immunophenotyping and functional analyzes (cytotoxicity or cytokine expression) allowed us to compare cell properties from individual donors and to compare the responses to each stimulating agent. RESULTS Zoledronate stimulated a greater expansion of Vδ2 cells in HIV+ individuals compared with phosphoantigen IPP, and these cells expressed CD16. CD56 expression (a marker for cytotoxic cells) was lower on zoledronate-expanded cells, consistent with significantly lower cytotoxicity against the Daudi tumor cell line. Cells expanded with either zoledronate or IPP were active in ADCC, were similar in terms of interferon (IFN)-γ and tumor necrosis factor (TNF)-α expression, and degranulated in response to Fc receptor cross-linking. CONCLUSIONS Zoledronate causes ex vivo expansion of Vδ2 cells from HIV+ individuals. Despite lower expression of CD56 and decreased direct cytotoxicity, these effectors were potent in ADCC. Zoledronate/IL-2- expanded cells have potential for immunotherapy to activate Vδ2 cells in HIV patients and enhance ADCC.
Vulnerability of Islets in the Immediate Posttransplantation Period: Dynamic Changes in Structure and Function

To learn more about islet vulnerability in the immediate posttransplant period, 400 syngeneic islets were transplanted under the kidney capsule of B6AF1 mice. Three groups of recipients were used: normal mice (normal), streptozotocin (STZ)-diabetic (diabetic), and STZ-diabetic kept hypo- or normoglycemic with insulin pellets (diabetic-normalized). Normoglycemia was achieved in all three groups 14 days after transplantation; however, in the diabetic and diabetic-normalized groups, blood glucose levels throughout the posttransplantation period were respectively higher and lower than in the normal group. Grafts were harvested 1, 3, 7, and 14 days after transplantation and analyzed for morphology, β-cell death, β-cell mass, insulin content, and insulin mRNA expression. In all groups, substantial damage in islet grafts was found on days 1 and 3 with apoptotic nuclei and necrotic cores; on day 3, β-cell death was significantly higher in the diabetic group than in the other groups. Tissue remodeling occurred in all groups with stable graft appearance on day 14; the actual β-cell mass of the grafts was lowest in the diabetic group. Graft insulin content decreased in all groups on day 1 and fell even further on days 3 and 7. Insulin mRNA levels of grafts retrieved from both the diabetic and diabetic-normalized group were lower than those from the normal group already by day 1 and remained lower on day 14. In conclusion, the first few days of islet transplantation, even under the most advantageous circumstances of excellent metabolic control, are characterized by dynamic changes, with substantial islet cell dysfunction and death followed by tissue remodeling and then stable engraftment.
Incidence of symptomatic venous thromboembolism after different elective or urgent surgical procedures

Summary There have been no comprehensive studies that have compared the incidence of symptomatic VTE over a spectrum of different urgent or elective surgical procedures. In this study we determined the incidence of symptomatic venous thromboembolic events (VTE) within a 3 month period after 76 different surgical procedures. Using a large administrative data-base, we analyzed 1,653,275 cases that underwent one of 76 selected surgical procedures between January 1, 1992 and September 30, 1996. The principal outcomes were venous thrombosis or pulmonary embolism, during either the initial hospitalization or a re-hospitalization for VTE within 91 days of the date of surgery. Predictors of VTE were analyzed using logistic regression. Overall, VTE was diagnosed in 13,533 cases (0.8%, 95% CI = 0.7-0.9%) and of these, 5049 (37%, 95% CI = 36-38%) had pulmonary embolism. Predictors of VTE included: advancing age (OR=1.1 per 5 year increment in age, 95% CI =1.1-1.1), Latino ethnicity (OR = 0.9, 95% CI =0.8-0.9), Asian/Pacific Islander ethnicity (OR = 0.5, 95% CI = 0.4-0.6), presence of a malignancy (OR = 1.7, 95% CI = 1.6-1.8) and prior VTE (OR = 6.2, 95% CI = 5.5-7.0). High-risk procedures that had an incidence of symptomatic VTE of approximately 2 to 3% included invasive neurosurgery, total hip arthroplasty, major vascular surgery and radical cystectomy. Fifty-six percent of all VTE events diagnosed within 91 days of surgery occurred after discharge. The findings of this study provide a basis for categorizing different surgical procedures as low, intermediate, high and very high risk for VTE. Because of the high incidence of VTE diagnosed after hospital discharge, further studies of extended thromboprophylaxis appear warranted.
Circadian Cycling of a PERIOD-β-galactosidase Fusion Protein in Drosophila: Evidence for Cyclical Degradation

The authors analyzed circadian features of two period-lacZ (per-lacZ) fusion genes in transgenic strains of Drosophila. Both genes manifest circadian fluctuations of mRNA levels, but fluctuations of only the larger chimeric protein are apparent. Fusion protein cycling is indistinguishable from the behavior of wild-type per protein (PER), including apparent temporal regulation of phosphorylation state. Several arguments indicate that the difference in the two constructs is proper regulation at the level of protein turnover: the smaller protein has much higher levels; a β-galactosidase degradation product is visible in both strains but fails to manifest cycling, presumably due to a long half-life; and only the noncycling proteins accumulate as a function of adult age. The large cycling fusion protein also undergoes modest cycling in an arrhythmic per01 background. This is light dependent, resembles the regulation of the timeless protein (TIM) by light, and reflects a documented fusion protein-TIM interaction. The results are discussed with respect to the posttranscriptional regulation that is necessary for proper cycling of both PER and TIM as well as for clock function.
Serum Levels of Calcitonin Gene-Related Peptide and Substance P are Decreased in Patients with Diabetes Mellitus and Coronary Artery Disease

OBJECTIVE: This study evaluated serum levels of the neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP) in coronary artery disease (CAD) patients with and without a history of diabetes mellitus (DM). METHODS: Patients undergoing coronary angiography for suspected myocardial ischaemia were divided into four groups depending on their clinical status: control group (no CAD or DM; n = 44), DM group (DM without CAD; n = 46), CAD group (stable CAD without DM; n = 44) and DM + CAD group (stable CAD with DM; n = 50). Serum levels of CGRP and SP were determined using radioimmunoassays. RESULTS: CGRP and SP levels in the DM and CAD groups were significantly lower than in the control group. The lowest levels of CGRP and SP were observed in the DM + CAD group. There were no significant differences in CGRP and SP levels between the DM group and the CAD group. CONCLUSION: CGRP and SP may have a role in the pathogenesis of CAD in patients with diabetes.
One step forward toward characterization: some important material properties to distinguish biochars.

Terra Preta research gave evidence for the positive influence of charred organic material (biochar) on infertile tropical soils. Facing global challenges such as land degradation, fossil energy decline, water shortage, and climate change, the use of biochar as a soil amendment embedded into regional matter cycles seems to provide an all-round solution. However, little is known about biochar effects on individual ecosystem processes. Besides, the term is used for a variety of charred products. Therefore, the aim of this study was to investigate principal material properties of different chars to establish a minimum set of analytical properties and thresholds for biochar identification. For this purpose, chars from different production processes (traditional charcoal stack, rotary kiln, Pyreg reactor, wood gasifier, and hydrothermal carbonization) were analyzed for physical and chemical properties such as surface area, black carbon, polycyclic aromatic hydrocarbons, and elemental composition. Our results showed a significant influence of production processes on biochar properties. Based on our results, to identify biochar suitable for soil amendment and carbon sequestration, we recommend using variables with the following thresholds: O/C ratio <0.4, H/C ratio <0.6, black carbon >15% C, polyaromatic hydrocarbons lower than soil background values, and a surface area >100 m g.