Miracle-dz/UniFAR-FTUs huggingface dataset:
Signal transduction in hypoxic cells: inducible nuclear translocation and recruitment of theCBP/p300 coactivator by the hypoxia‐induciblefactor‐1α

In response to decreased cellular oxygen concentrations the basic helix‐loop‐helix (bHLH)/PAS (Per, Arnt, Sim) hypoxia‐inducible transcription factor, HIF‐1α, mediates activation of networks of target genes involved in angiogenesis, erythropoiesis and glycolysis. Here we demonstrate that the mechanism of activation ofHIF‐1α is a multi‐step process which includes hypoxia‐dependent nuclear import and activation (derepression) of the transactivation domain, resulting in recruitment of the CREB‐binding protein (CBP)/p300 coactivator. Inducible nuclear accumulation was shown to be dependent on a nuclear localization signal (NLS) within the C‐terminal end of HIF‐1α which also harbors the hypoxia‐inducible transactivation domain. Nuclear import of HIF‐1α was inhibited by either deletion or a single amino acid substitution within the NLS sequence motif and, within the context of the full‐length protein, these mutations also resulted in inhibition of the transactivation activity of HIF‐1α and recruitment of CBP. However, nuclear localization per se was not sufficient for transcriptional activation, since fusion of HIF‐1α to the heterologous GAL4 DNA‐binding domain generated a protein which showed constitutive nuclear localization but required hypoxic stimuli for function as a CBP‐dependent transcription factor. Thus, hypoxia‐inducible nuclear import and transactivation by recruitment of CBP can be functionally separated from one another and play critical roles in signal transduction by HIF‐1α.
p53-Independent Endoplasmic Reticulum Stress-Mediated Cytotoxicity of a Newcastle Disease Virus Strain in Tumor Cell Lines

ABSTRACT While Newcastle disease virus (NDV) causes serious infections in birds, it is apparently nonpathogenic in mammalian species, including humans. Previous observations and small-scale clinical trials indicated that NDV exerts oncolytic effects. Isolates of NDV were found to have selective affinity to transformed cells. We previously showed that the attenuated NDV strain MTH-68/H causes apoptotic cell death in cultures of PC12 rat pheochromocytoma cells. The aim of the present study was to extend MTH-68/H cytotoxicity testing with human tumor cell lines and to analyze certain biochemical aspects of its oncolytic effect. MTH-68/H was found to be able to kill a wide range of transformed cells by apoptosis. While caspase-8 and caspase-9 are not involved in MTH-68/H-induced apoptosis, activation of caspase-3 and caspase-12 was detected in virus-infected PC12 cells. A human glioblastoma cell line with repressible expression of the p53 protein did not show any difference in MTH-68/H sensitivity in its p53-expressing and p53-depleted states, indicating that the apoptotic process induced by MTH-68/H does not depend on p53. Apoptosis was accompanied by virus replication in two tumor cell lines tested (PC12 cells and HeLa human cervical cells), and signs of endoplasmic reticulum stress (phosphorylation of protein kinase R-like endoplasmic reticulum kinase and eIF2α) were also detected in transformed cells. In contrast, proliferation of nontransformed mouse and rat fibroblast cell lines and human primary fibroblasts was not affected by MTH-68/H treatment. MTH-68/H thus selectively kills tumor cell cultures by inducing endoplasmic reticulum stress leading to p53-independent apoptotic cell death.
Changes in the Growth-Promoting Activity of Human Milk during Lactation

Summary: We measured the concentrations of protein, insulin, and epidermal growth factor (EGF) in human milk from mothers delivering at term. Samples were obtained from d 1 (colostrum) to d 42 after birth. Human colostrum contains very high concentrations of protein [83.7 ± 7.4 g/1 (SEM)], insulin (3.75 ± 0.88 nM), and EGF (53.9 ± 6.9 nM). Similar concentrations have been measured in prebirth milk. Insulin, EGF, and protein in milk decline rapidly during the first few days of lactation but remain constant thereafter. Although the concentrations of insulin and EGF in mature milk are only 10% of those in colostrum, they are considerably higher than in serum. We also showed that human milk has a growth-promoting activity in cultured cells, causing a stimulation of protein synthesis in L6 myoblasts and 3T3-L1 fibroblasts and an increase in DNA synthesis in L6 cells and T47D breast cancer cells. This mitogenic activity declines as lactation progresses, with a similar time-course to the fall in insulin and EGF; however, the cell lines used here are not responsive to either of these two growth factors in the range of concentrations found in milk. This indicates that human milk also contains high concentrations of additional, unidentified growth factors. The occurrence of high concentrations of growth factors in milk suggests that they may be important for the proliferation and differentiation of infant tissues.
Contact With Health Professionals for the Treatment of Psychiatric and Emotional Problems

This study focuses on predisposing, enabling, and need factors affecting contact with health professionals for the treatment of psychiatric and emotional problems during a 6-month period. Data are from the first wave of the Yale Epidemiologic Catchment Area (ECA) Project. The study confirms the important relationship of psychopathology to both the likelihood of using mental health related services and the quantity of service contacts. Sex, age, race, education, marital status, usual source of medical care, and attitudes toward mental health services were found to exert independent effects on the likelihood of contact with a health professional after controlling for clinical status. Factors affecting the quality of service contacts among utilizers were psychiatric status, usual source of care, and attitudes.
Serum leptin levels and uterine Doppler flow velocimetry at 20 weeks' gestation as markers for the development of pre-eclampsia

Altered Doppler flow velocimetry of the uterine arteries during the second trimester is correlated with the risk of developing pre-eclampsia. Serum levels of leptin, a protein regulating body weight and secreted by the placenta, are higher in women with severe pre-eclampsia. We investigated whether alterations of uterine arteries' Doppler flow velocimetry during the early second-trimester scan were accompanied by changes in leptin levels, and whether these changes might be an early risk factor for pre-eclampsia. We retrospectively selected 50 women with altered uterine artery velocimetry at the second-trimester scan who subsequently developed pre-eclampsia (group A) and 100 women who did not develop pre-eclampsia, divided into two groups: 50 women with normal velocimetry at the second-trimester scan (group B) and 50 women with altered velocimetry at the second-trimester scan (group C). Serum leptin levels during the second and third trimesters and bilateral uterine artery resistance index during the second trimester were evaluated. No differences were observed in serum leptin levels in the second trimester among the three groups. During the third trimester, women in group A showed significantly higher serum leptin levels in comparison with women in groups B and C (p< 0.01). Serum leptin levels do not seem to be a useful early marker for the development of pre-eclampsia in the presence of altered uterine blood flow, and may be a late compensatory mechanism or reflect a generalized response of the trophoblast to hypoxic stimuli.
Child Health, Human Capital and Adult Financial Behavior

In this work, utilizing yearly variation between biological siblings, we test for a correlation between poor child health and adult household financial behavior, i.e. risky asset market participation. Using regression and decomposition techniques, we test if this long reach of child health operates through cognitive and non-cognitive skills. Our results indicate a negative correlation of roughly -4.1 percentage points conditional on demographics and family background. Slightly more than half of this correlation can be explained by differences in cognitive and non-cognitive skills. This work highlights the importance of good child health for adult financial behavior.
Circulating Levels of Adipocytokines as Potential Biomarkers for Early Detection of Colorectal Carcinoma in Egyptian Patients.

BACKGROUND Early detection of various kinds of cancers nowadays is needed including colorectal cancer due to the highly significant effects in improving cancer treatment. The aim of this study was to evaluate the potential value of adiponectin, visfatin and resistin as early biomarkers for colorectal cancer patients. MATERIALS AND METHODS Serum levels of adiponectin, visfatin and resistin were measured by a sandwich-enzyme-linked (ELISA) assay technique in 114 serum samples comprising 34 patients with colorectal cancer (CRC), 27 with colonic polyps (CP), 24 with inflammatory bowel disease (IBD) and 29 healthy controls . The diagnostic accuracy of each serum marker was evaluated using receiver-operating characteristic (ROC) curve analysis. RESULTS The mean concentration of adiponectin was significantly higher in CRC and CP groups than IBD and control groups (P-value <0.05). Also the mean concentration of serum resistin was significantly elevated in the IBD and control groups compared to CRC and CP groups (P-value = 0.014). However, no significant difference was noted in patients of the CRC and CP groups. On the other hand, the mean concentration of visfatin was significantly elevated in CRC and control groups compared to CP and IBD groups (P-value = 0.03). ROC analysis curves for the studied markers revealed that between CRC and IBD groups serum level of adiponectin had a sensitivity of 76.7% and a specificity of 76% at a cut off value of 3940, +LR being 3.2 and -LR 0.31 with AUC 0.852, while serum level of adiponectin between CP and IBD had a sensitivity of 77.8% and a specificity of 75% at a cut off value of 3300, with +LR=3.11 and -LR = 0.3 with AUC 0.852. On the other hand the serum level of visfatin between CRC and CP groups had a sensitivity of 65.5% and a specificity of 66.7 at a cut off value of 2.4, +LR being 1.67 and -LR 0.52 with AUC 0.698. Also the serum level of resistin had a sensitivity of 62.5% and a specificity of 70.3% at a cut off value of 24500, with +LR=2.1 and -LR = 0.53 with AUC 0.685 between control and other groups. On the other hand by comparing control vs CP groups resistin had a sensitivity of 81.8% and a specificity of 70.8% at a cut off value of 17700, with +LR=2.8 and -LR = 0.26 with AUC 0.763 while visfatin had a sensitivity of 68.2% and a specificity of 70.8% at a cut off value of 2.7, with +LR=2.34 and -LR = 0.0. 45 with AUC 0.812. CONCLUSIONS These findings support potential roles of adiponectin, visfatin and resistin in early detection of CRC and discrimination of different groups of CRC, CP or IBD patients from normal healthy individuals.
From meeting presentation to peer-review publication--a UK review.

INTRODUCTION Annual academic surgical meetings provide a forum for the discussion of research. For the wide-spread dissemination of this information, peer-reviewed publication is required. The aim of this study was to compare the amount of presentations which go on to publication from 4 UK-based surgical meetings. MATERIALS AND METHODS We determined whether a presentation had led to a successful publication using PubMed, a median of 28 months following each meeting. We compared the ASGBI publication rate with the meetings of the Vascular Surgical Society (VSSGBI), the Association of Coloproctology of Great Britain and Ireland (ACPGBI) and the British Transplantation Society (BTS). We also compared the median impact factor of journals used. RESULTS The ASGBI and BTS had a similar rate of presentations resulting in publication, with 35% and 36% at 2 years, respectively. The VSS had a significantly greater proportion of presentations resulting in publication (54% at 2 years; P = 0.004), whilst the ACPGBI had significant fewer (24% at 2 years; P = 0.006). There was no difference in the median impact factors of the journals used between the meetings (Kruskal Wallis P = 0.883). CONCLUSIONS There is a significant variation between meetings in terms of turning presentations into publications. However, the majority of abstracts have still not been fully published within 2 years of presentation at the meeting.
Exposure to Mixtures of Metals and Neurodevelopmental Outcomes: A Multidisciplinary Review Using an Adverse Outcome Pathway Framework

Current risk assessment guidance calls for an individual chemical‐by‐chemical approach that fails to capture potential interactive effects of exposure to environmental mixtures and genetic variability. We conducted a review of the literature on relationships between prenatal and early life exposure to mixtures of lead (Pb), arsenic (As), cadmium (Cd), and manganese (Mn) with neurodevelopmental outcomes. We then used an adverse outcome pathway (AOP) framework to integrate lines of evidence from multiple disciplines based on evolving guidance developed by the Organization for Economic Cooperation and Development (OECD). Toxicological evidence suggests a greater than additive effect of combined exposures to As–Pb–Cd and to Mn with any other metal, and several epidemiologic studies also suggest synergistic effects from binary combinations of Pb–As, Pb–Cd, and Pb–Mn. The exposure levels reported in these epidemiologic studies largely fall at the high‐end (e.g., 95th percentile) of biomonitoring data from the National Health and Nutrition Examination Survey (NHANES), suggesting a small but significant potential for high‐end exposures. This review integrates multiple data sources using an AOP framework and provides an initial application of the OECD guidance in the context of potential neurodevelopmental toxicity of several metals, recognizing the evolving nature of regulatory interpretation and acceptance.
Effects of syringe material and temperature and duration of storage on the stability of equine arterial blood gas variables.

OBJECTIVES To evaluate the consistency of partial pressures (P) of arterial oxygen (aO(2)), arterial carbon dioxide (aCO(2)) and pH measurements in equine carotid arterial blood samples taken into syringes made from three different materials and stored at room temperature or placed in iced water for measurement at three different times. STUDY DESIGN Prospective observational study over 19 days. ANIMALS Four clinically normal Thoroughbred or Thoroughbred-cross horses (three geldings, one mare, mean age 6.25 years, range 5-7 years). METHODS Identical blood samples were taken on two separate occasions from the carotid arteries of the four horses into syringes made of glass, plastic and polypropylene. PaO(2), PaCO(2) and pH determinations were performed on blood from each syringe type at 10, 60 and 120 minutes post-sampling with samples stored at room temperature (approximately 20 degrees C) or in iced water (approximately 0 degrees C). Data were analysed by anova and a split plot model fitting syringe within horse X pair and time within temperature within syringe. RESULTS Syringe material, storage temperature and time before analysis all had significant effects on PaO(2) (p < 0.001). PaCO(2) was unaffected by syringe material or storage temperature. However, over 120 minutes, storage duration significantly (p = 0.002) affected values. Temperature of storage and duration prior to analysis both significantly affected pH values (p = 0.005 and p < 0.001, respectively), but syringe material did not. Several significant interactions between these variables were noted. CONCLUSIONS Equine arterial blood gas determination has a different sensitivity to storage conditions compared to other veterinary species. CLINICAL RELEVANCE For accurate equine arterial blood analysis, PaO(2) samples need to be analysed within 10 minutes or taken into glass syringes, stored on ice and analysed at 2 hours post-sampling. PaCO(2) and pH measurements can be performed on samples stored in glass, plastic or polypropylene syringes at room temperature for up to 1 hour post-sampling.
Information technology adoption for sustainable development: green e-books as an example*

ABSTRACT In recent years, due to increasing awareness of the need for environmental protection, there have been significant efforts to improve consumers’ acceptance of green information technology(IT) products for sustainable development. This study first investigated how knowledge about a green IT product (e-books) influences consumers’ planning processes by using the technology acceptance model and the theory of planned behavior. Data from 320 respondents were analyzed using structural equation modeling to examine the hypothesized relationships in the research model. Results show that perceived usefulness, attitudes, subjective norms, and perceived behavioral control have a significant and positive impact on the intention to purchase e-books. Results also show the moderating effect of consumers’ knowledge about the environmental friendliness of e-books on their intention to buy e-books. Finally, important implications of the findings are discussed, and directions for future research are also provided in this paper.
LAS, a novel selective estrogen receptor modulator with chemopreventive and therapeutic activity in the N-nitroso-N-methylurea-induced rat mammary tumor model.

The N-nitroso-N-methylurea-induced rat mammary tumor model was used to conduct two types of studies: a prevention study designed to test the ability of the novel selective estrogen receptor modulator lasofoxifene (LAS) to inhibit the development of mammary tumors, and a treatment study designed to test the inhibitory effect of LAS on the growth of established tumors. The prevention study indicated that LAS markedly delayed the emergence of N-nitroso-N-methylurea-induced tumors to an extent similar to that obtained by the established antiestrogen tamoxifen (TAM). At the highest dose administered, both TAM and LAS reduced tumor incidence by 75% and total tumor number by 90% relative to the controls. LAS also reduced the multiplicity of tumors, i.e., the mean number of tumors per rat, and resulted in substantially smaller total tumor burden. In the treatment study, LAS significantly inhibited tumor growth compared with the controls. In addition, whereas none of the untreated tumors regressed completely over the experimental period, 40% of LAS-treated tumors regressed by >50% at the highest dose (10 mg/kg daily). The results of this study in a rat mammary tumor model indicate that LAS has both chemopreventive and chemotherapeutic effects quantitatively comparable with those of TAM.
Maximum Likelihood Approach for RFID Tag Cardinality Estimation under Capture Effect and Detection Errors

Cardinality estimation schemes of Radio Frequency IDentification (RFID) tags using Framed Slotted ALOHA (FSA) based protocol are studied in this paper. Not as same as previous estimation schemes, we consider tag cardinality estimation problem under not only detection errors but also capture effect, where a tag’s IDentity (ID) might not be detected even in a singleton slot, while it might be identified even in a collision slot due to the fading of wireless channels. Maximum Likelihood (ML) approach is utilized for the estimation of the detection error probability, the capture effect probability, and the tag cardinality. The performance of the proposed method is evaluated under different system parameters via computer simulations to show the method’s effectiveness comparing to other conventional approaches. key words: RFID, Maximum Likelihood (ML), tag cardinality estimation, capture effect, detection errors
Range Size Heritability in Carnivora Is Driven by Geographic Constraints

Range size heritability refers to an intriguing pattern where closely related species occupy geographic ranges of similar extent. Its existence may indicate selection on traits emergent only at the species level, with interesting consequences for evolutionary processes. We explore whether range size heritability may be attributable to the fact that range size is largely driven by the size of geographic domains (i.e., continents, biomes, areas given by species’ climatic tolerance) that tend to be similar in phylogenetically related species. Using a well-resolved phylogeny of carnivorans, we show that range sizes are indeed constrained by geographic domains and that the phylogenetic signal in range sizes diminishes if the domain sizes are accounted for. Moreover, more detailed delimitation of species’ geographic domain leads to a weaker signal in range size heritability, indicating the importance of definition of the null model against which the pattern is tested. Our findings do not reject the hypothesis of range size heritability but rather unravel its underlying mechanisms. Additional analyses imply that evolutionary conservatism in niche breadth delimits the species’ geographic domain, which in turn shapes the species’ range size. Range size heritability patterns thus emerge as a consequence of this interplay between evolutionary and geographic constraints.
Identification of a new coeliac disease subgroup: antiendomysial and anti‐transglutaminase antibodies of IgG class in the absence of selective IgA deficiency

Abstract. Picarelli A, Di Tola M, Sabbatella L, Mastracchio A, Trecca A, Gabrielli F, Di Cello T, Anania MC, Torsoli A (University of Rome “La Sapienza”, Rome, Italy). Identification of a new coeliac disease subgroup: antiendomysial and anti‐transglutaminase antibodies of IgG class in the absence of selective IgA deficiency. J Intern Med 2001; 249: 181–188.
Double Ducted Fan (DDF) as a Novel Ducted Fan Inlet Lip Separation Control Device

This paper describes computational study of a novel ducted fan inlet flow conditioning concept that will significantly improve the performance and controllability of VTOL UAVs and many other ducted fan based systems. The new concept that will significantly reduce the inlet lip separation related performance penalties in the edgewise flight zone is named “DOUBLE DUCTED FAN” (DDF). The current concept uses a secondary stationary duct system to control “inlet lip separation” related momentum deficit at the inlet of the fan rotor typically occurring at elevated edgewise flight velocities. DDF is selfadjusting in a wide edgewise flight velocity range and its corrective aerodynamic influence becomes more pronounced with increasing flight velocity due to its inherent design properties. Most axial flow fans are designed for an inlet flow with zero or minimal inlet flow distortion. The DDF concept is proven to be an effective way of dealing with inlet flow distortions occurring near the lip section of a typical axial flow fan rotor system. In this paper, a conventional baseline duct is compared to two different double ducted fans named DDF CASE-A and DDF CASE-B via 3D, viscous and turbulent flow computational analysis. Both hover and edgewise flight conditions are considered. Significant relative improvements from DDF CASE-A and DDF CASE-B are in the areas of thrust enhancement, nose-up pitching moment control and recovery of fan through-flow mass flow rate. The results clearly show a major reduction of highly 3D and recirculatory inlet lip separation zone when the DDF concept is implemented. The improved uniformity of fan exit flow and reduced differentials between the leading side and trailing side are other performance enhancing features of the novel concept. The local details of the flow near the entrance area of the leading side of the ducted fan are explained via detailed static pressure distributions obtained from 3D computational analysis including a simulated rotor in the duct.