Miracle-dz/UniFAR-FTUs huggingface dataset:
Risk of leukemia after treatment with pituitary growth hormone.

OBJECTIVE To determine whether pituitary-derived human growth hormone treatment increases the subsequent risk of developing leukemia and lymphoma. DESIGN Cohort study. SETTING United States. PARTICIPANTS A total of 6284 recipients of pituitary-derived human growth hormone distributed by the National Hormone and Pituitary Program between 1963 and 1985. MAIN OUTCOME MEASURES Leukemia and lymphoma. RESULTS Three cases of leukemia occurred in 59,736 patient-years of follow-up from the start of growth hormone therapy to case ascertainment at interview; this number was not significantly higher (P = .23) than the 1.66 cases expected in the US age-, race-, and gender-matched general population. Three additional cases, found in an extended follow-up that provided 83,917 person-years of risk, yielded a minimum rate of leukemia that was significantly increased (six cases found, 2.26 expected; P = .028). The relative risk of leukemia in pituitary growth hormone recipients compared with the general population was 1.8 (90% confidence interval [CI], 0.82 to 7.5) for the defined follow-up and 2.6 (90% CI, 1.2 to 5.2) for the extended follow-up. Five of the six subjects who developed leukemia had antecedent cranial tumors (four craniopharyngioma, one astrocytoma) as the cause of growth hormone deficiency, and four had received radiotherapy. There was no increase in leukemia in patients with idiopathic growth hormone deficiency. The association of leukemia and craniopharyngioma was significant (P < .001). There was no excess of lymphoma in the cohort. CONCLUSIONS This cohort of growth hormone recipients had a significantly increased rate of leukemia compared with the age-, race-, and gender-matched general population. However, the upper bound CI of the relative risk in our population (5.2) is well below the other estimates (7.6). Compared with the general population, our study population had more possible risk factors for leukemia (radiation, tumor) that may have contributed to the excess observed. The clustering of cases of leukemia in craniopharyngioma patients should be further evaluated.
Optimal buffer sharing

Addresses the problem of designing optimal buffer management policies in shared memory switches when packets already accepted in the switch can be dropped (pushed-out). The goal is to maximize the overall throughput, or equivalently to minimize the overall loss probability in the system. For a system with two output ports, the authors prove that the optimal policy is of pushout with threshold type (POT). The same result holds if the optimality criterion is the weighted sum of the port loss probabilities. For this system, the authors also give an approximate method for the calculation of the optimal threshold, which they conjecture to be asymptotically correct. For the N-ported system, the optimal policy is not known in general, but it is shown that for a symmetric system (equal traffic on all ports) it consists of always accepting arrivals when the buffer is not full, and dropping one from the longest queue to accommodate the new arrival when the buffer is full. Numerical investigations show that under the optimal POT policy the loss probability of a port is insensitive to traffic fluctuations in the other port.
Bile Acids Up-regulate Death Receptor 5/TRAIL-receptor 2 Expression via a c-Jun N-terminal Kinase-dependent Pathway Involving Sp1*

Bile acids up-regulate death receptor 5 (DR5)/TRAIL-receptor 2 (TRAIL-R2) expression thereby sensitizing hepatocytes to TRAIL-mediated apoptosis. However, the precise mechanism by which bile acids enhance DR5/TRAIL-R2 expression is unknown. Although several bile acids enhanced DR5/TRAIL-R2 expression, deoxycholic acid (DCA) was the most potent. DCA stimulated JNK activation and the JNK inhibitor SP600125 blocked DCA-induced DR5/TRAIL-R2 mRNA and protein expression. Reporter gene analysis identified a 5′-flanking region containing two Sp1 binding sites within the DR5/TRAIL-R2 promoter as bile acid responsive. Sp1 binding to one of the two sites was enhanced by DCA treatment as evaluated by electrophoretic mobility shift assays and chromatin immunoprecipitation studies. JNK inhibition with SP600125 also blocked binding of Sp1 to the DR5/TRAIL-R2 promoter. Finally, point mutations of the Sp1 binding site attenuated promoter activity. In conclusion, Sp1 is a bile acid-responsive transcription factor that mediates DR5/TRAIL-R2 gene expression downstream of JNK.
Cyclin D3 deficiency inhibits skin tumor development, but does not affect normal keratinocyte proliferation

Rearrangement and amplification of the D-type cyclin genes have been reported in human cancer. Previous studies have demonstrated that Ras-mediated skin tumorigenesis depends on pathways that act through cyclin D1 and D2; however, the role of cyclin D3 remains unknown. The present study demonstrates that cyclin D3 ablation does not affect keratinocyte proliferation, but instead increases apoptosis levels in the bulge region of the hair follicle. Consequently, cyclin D3 ablation reduces skin papilloma development in a Ras-dependent carcinogenesis model. Previous results revealed that cyclin D3 preferentially binds to cyclin-dependent kinase 6 (CDK6) in mouse keratinocytes and transgenic expression of CDK6 (K5CDK6 mice) inhibits skin tumor development. Thus, we hypothesized that the inhibitory effect of CDK6 is dependent on cyclin D3 expression. To test this hypothesis, a mouse model that overexpresses CDK6 and does not express cyclin D3 (K5CDK6/cyclin D3-/− compound mouse) was developed. Biochemical analysis of the epidermis of K5CDK6/cyclin D3-/− mice revealed that cyclin D3 ablation resulted in increased expression of cyclin D1 protein, with a consequent elevation in the level of CDK6/cyclin D1 and CDK4/cyclin D1 complexes. These findings were concurrent with the increase skin papilloma malignant progression observed in K5CDK6/cyclin D3-/− mice. In summary the absence of cyclin D3 led to fewer number of papillomas in cyclin D3-ablated mice than in the wild-type owing to increased apoptosis, suggesting that alterations in cell survival are a crucial mechanism for crippling cellular defense against neoplasia. The results of the current study also suggest that although cyclin D3 expression does not alter the tumor suppressive role of CDK6 in skin carcinogenesis, the compensatory increase in cyclin D1 can shift the balance towards malignant progression.
Estimation of Whole Plant Photosynthetic Rate of Irwin Mango under Artificial and Natural Lights Using a Three-Dimensional Plant Model and Ray-Tracing

Photosynthesis is an important physiological response for determination of CO2 fertilization in greenhouses and estimation of crop growth. In order to estimate the whole plant photosynthetic rate, it is necessary to investigate how light interception by crops changes with environmental and morphological factors. The objectives of this study were to analyze plant light interception using a three-dimensional (3D) plant model and ray-tracing, determine the spatial distribution of the photosynthetic rate, and estimate the whole plant photosynthetic rate of Irwin mango (Mangifera indica L. cv. Irwin) grown in greenhouses. In the case of mangoes, it is difficult to measure actual light interception at the canopy level due to their vase shape. A two-year-old Irwin mango tree was used to measure the whole plant photosynthetic rate. Light interception and whole plant photosynthetic rate were measured under artificial and natural light conditions using a closed chamber (1 × 1 × 2 m). A 3D plant model was constructed and ray-tracing simulation was conducted for calculating the photosynthetic rate with a two-variable leaf photosynthetic rate model of the plant. Under artificial light, the estimated photosynthetic rate increased from 2.0 to 2.9 μmolCO2·m−2·s−1 with increasing CO2 concentration. On the other hand, under natural light, the photosynthetic rate increased from 0.2 μmolCO2·m−2·s−1 at 06:00 to a maximum of 7.3 μmolCO2·m−2·s−1 at 09:00, then gradually decreased to −1.0 μmolCO2·m−2·s−1 at 18:00. In validation, simulation results showed good agreement with measured results with R2 = 0.79 and RMSE = 0.263. The results suggest that this method could accurately estimate the whole plant photosynthetic rate and be useful for pruning and adequate CO2 fertilization.
Professional practice Teaching impact assessment : results of an international survey

University teachers of impact assessment (IA) at both undergraduate and graduate levels were surveyed during IAIA conferences in 2008 and 2009. A total of 32 questionnaires were returned, with respondents teaching in 18 countries. IA teaching encompasses both theory and practice. It is supported by textbooks — a sign the IA is a consolidated field — but also by case studies, government or legal guidance and guest lectures. A vast majority of lecturers (94%) also use peer-reviewed papers, indicating that knowledge obtained from research is an important input to teaching. Formal lectures, case studies and group discussions are favorite teaching approaches, and field visits are used by 38% of respondents. Environmental impact assessment is the most frequent type of IA taught, with strategic environmental assessment ranking second. Despite IA teaching being positioned within different university disciplines, there is a great similarity in course contents, suggesting the existence of core topics internationally relevant for IA education and potential for viable teacher and student exchanges.
Are Exports and Imports Cointegrated? Evidence from Nigeria

his study examined the long-run relationship between Nigerian exports and imports between 1960 and 2014. Exports and imports were disaggregated into oil and non-oil components. The application of the Johansen, Bound testing and the Hansen parameter instability test cointegration techniques revealed that Nigerian exports and imports at the aggregate and disaggregated level are cointegrated with the cointegrating coefficient very close to unity. This indicated that Nigeria's macroeconomic policies have been effective in the long run and suggested that Nigeria is not in violation of its international budget constraint. The result is however sensitive to the choice of the dependent variable between exports and imports. Utilizing the Toda and Yamamoto granger non-causality tests, we also report bi-directional causality between aggregate exports and imports, but uni-directional causality from oil exports to oil imports and from non-oil imports to non-oil exports.
Comparing Terrain and Roadside Chipping in Mediterranean Pine Salvage Cuts

Nacrtak In central Italy, the increasing demand for fuel chips and the epidemic spread of maritime pine bast scale have favored the development of large-scale industrial logging operations. After years of extensive commercial trials, local operators have developed their own industrial harvesting systems, through a wise mix of Scandinavian and North American methods. The result is original and effective, and allows keeping harvesting cost below 20 gt–1. The study compared terrain chipping with roadside chipping, as applied to the coastal pine stands of Tuscany. Under the conditions of our study, roadside chipping was over four times more productive than terrain chipping, and it allowed reducing harvesting cost by one third (12.3 vs. 18.3 gt–1). Despite the intense use of diesel, total fossil energy inputs accounted for less than 3% of the potential energy in the wood chips. Terrain chipping and roadside chipping yielded 36 and 47 times the energy they used, respectively. The coexistence of the two systems was most interesting. The harvesting systems described in the study perform best in clear-cuts, but they can also work in partial cuts, including thinning operations. They are actually used in thinnings in the same Regional Park of San Rossore, although their productivity is lower than in clear-cuts.
AGGRESSION, DENSITY, AND SEXUAL DIMORPHISM IN CHERNETID PSEUDOSCORPIONS (ARACHNIDA: PSEUDOSCORPIONIDA)

The determinants of sexual dimorphism in a family of false scorpions (Pseudoscorpionida: Chernetidae) were investigated experimentally and with a literature analysis of comparative morphometric and habitat data. Species vary in the extent to which males and females differ in size of the pedipalps, and, in particular, in size of the pedipalpal chelae. A statistical analysis of dimorphism patterns within the Chernetidae suggests that dimorphism is a highly variable condition, relatively unconstrained by phylogenetic influences. The evolution of species with enlarged male pedipalps appears to be associated with a change from nonpairing to pairing sperm‐transfer behavior and with aggressive mate acquisition by males. Experiments with Dinocheirus arizonensis demonstrate a strong correlation between male combat ability and chela size. Manipulations also suggest that superior combat ability of large males results in increased mating success only under high‐density conditions. The greater success in spermatophore transfer among large males can be attributed to increased opportunity at high density for large males to interrupt matings and aggressively displace smaller males. Comparative analysis showed a positive correlation between density and enlarged male chela size across chernetid species.
Relationship between glycated hemoglobin and circulating 25-hydroxyvitamin D concentration in African American and Caucasian American men.

OBJECTIVES To examine whether (1) serum 25-hydroxyvitamin D level (25[OH]D) is a risk factor for hyperglycemia, as assessed by glycated hemoglobin (HbA1c), in African American men (AAM) and (2) 25(OH)D is a predictor of HbA1c in AAM and Caucasian American men (CAM). METHODS We prospectively assessed 25(OH)D and HbA1c in 1,074 men, outpatients with and without diabetes, at an urban Veteran Administration Medical Center (66.8% AAM, 26.4% CAM, 6% Hispanic, 0.4% Asian, and 0.4% Native American men). Multivariate regression analyzed the determinants of HbA1c after accounting for potential confounders. RESULTS We found high prevalence of low (< 30 ng/mL) 25(OH)D (81%) and elevated (≥5.7%) HbA1c (53.5%). The 25(OH)D was inversely associated with HbA1c in all men (r = -0.12, P<.001), in AAM (r = -0.11, P = .003), and in CAM (r = -0.15, P = .01). In the entire group the independent determinants of HbA1c included body mass index (BMI), age, 25(OH)D levels, systolic blood pressure (BP), triglycerides, high-density lipoprotein (HDL), and current alcohol use (P<.0001, .013, .009, .01, .008, .034, and .048, respectively) while glomerular filtration rate (GFR) and marital status showed borderline significance (P = .08 and .09, respectively). In AAM these determinants included BMI, 25(OH)D levels, systolic BP, and current alcohol use (P<.0001, .01, .02, and .03, respectively), while age had borderline significance (P = .06). In CAM, these included BMI, age, and triglycerides (P = .01, .03, and .004, respectively) but not 25(OH)D levels (P = .50). CONCLUSION Circulating low 25(OH)D is a risk factor for hyperglycemia, as assessed by HbA1c, in AAM. The 25(OH)D level is an independent determinant of HbA1c in AAM, but not in CAM, including men with and without diabetes.
Biological Actions of Insulin Are Differentially Regulated by Glucose and Insulin in Primary Cultured Adipocytes: Chronic Ability to Increase Glycogen Synthase Activity

We have shown previously that prolonged exposure to insulin and glucose impairs the insulin-responsive glucose transport system in primary cultured adipocytes. To assess the ability of insulin and glucose to regulate other cellular insulin actions, epididymal rat adipocytes were cultured in media containing 0–15 mM D-glucose and with or without insulin (50 ng/ml). After 24 h, cells were washed and basal and maximally insulin-stimulated rates of 2-deoxy-D-glucose uptake, L-leucine incorporation into protein, glucose oxidation to CO2, glucose incorporation into lipids, and glycogen synthase activity were measured. The results confirmed that glucose potentiates insulin's chronic ability to decrease basal and maximal glucose transport rates by ∼ 50% at 5 mM glucose and by ∼70% at 15 mM glucose compared with control cells. However, neither glucose nor insulin, alone or in combination, affected rates of leucine incorporation into protein. In addition, basal and maximal rates of glucose oxidation and of glucose incorporation into lipids were not regulated by glucose, and maximal responses declined ∼50% over 24 h only when insulin was not present during preincubation (i.e., chronic insulin exposure was necessary to maintain full maximal responses). Glycogen synthase activity was measured in a cell-free system (0.5 mM UDP-glucose, with 10 or 0.01 mM glucose-6-phosphate) after exposing intact cells to glucose and insulin. Both short-term (1 h) and long-term (24 h) exposure to glucose alone led a dose-dependent increase in I-form and D-form glycogen synthase activity. Chronic exposure to insulin also increased total glycogen synthase activity (I- plus D-form) but did not affect absolute rates of maximally stimulated I-form activity. Glucose (but not insulin) increased the cellular content of immunoreactive glycogen synthase by 70% after 1 h. These results show that 1) chronic exposure to glucose and insulin impairs insulin responsiveness of the glucose transport system but does not affect rates of amino acid incorporation into protein; 2) the chronic presence of insulin is necessary for the maintenance of normal maximally stimulated rates of glucose oxidation and of glucose incorporation into lipids in cultured cells; and 3) glucose increases both D-form and I-form glycogen synthase activity, in part by increasing the amount of synthase protein, whereas chronic insulin exposure increases total glycogen synthase activity without altering maximal absolute rates of I-form activity. In conclusion, glucose and insulin differentially regulate the multiple biological actions of insulin in cultured adipocytes, indicating that underlying mechanisms involve the hormone effector systems or components of signal transduction unique to individual action pathways. In NIDDM, defects in glucose transport but not other insulin actions may be acquired as a result of high circulating blood glucose and insulin concentrations.
The mannose 6‐phosphate/insulin‐like growth factor II receptor restricts the tumourigenicity and invasiveness of squamous cell carcinoma cells

The mannose 6‐phosphate/insulin‐like growth factor II receptor (M6P/IGF2R) mediates biosynthetic sorting and endocytosis of various factors that impinge on the proliferation, migration and invasiveness of tumour cells. The gene encoding M6P/IGF2R is frequently lost or mutated in a wide range of malignant tumours including squamous cell carcinomas. We have previously shown that M6P/IGF2R‐deficient SCC‐VII murine squamous cell carcinoma cells secrete large amounts of pro‐invasive lysosomal proteinases. Furthermore, the formation of mature lysosomes is impaired in SCC‐VII cells. To assess the link between M6P/IGF2R status and tumour invasion, we have now generated SCC‐VII lines stably transfected with human M6P/IGF2R cDNA. Reconstitution of functional M6P/IGF2R expression in SCC‐VII cells strongly improves the intracellular retention of lysosomal proteinases and restores the formation of mature lysosomes. In addition, the presence of heterologous M6P/IGF2R compromises the growth of SCC‐VII cells both in vitro and in vivo. Remarkably, M6P/IGF2R expression also reduces the invasive capacity of SCC‐VII cells in response to various chemoattractants. These results indicate that the M6P/IGF2R status influences the metastatic propensity of squamous cell carcinomas. © 2008 Wiley‐Liss, Inc.
Adenoviral gene transfer of the endogenous inhibitor IkappaBalpha into human osteoarthritis synovial fibroblasts demonstrates that several matrix metalloproteinases and aggrecanases are nuclear factor-kappaB-dependent.

OBJECTIVE To investigate the role of the transcription factor nuclear factor-kB (NF-kappaB) in promoting inflammatory and destructive responses in human osteoarthritis (OA) synovial fibroblasts, by assessing the effect of NF-kappaB blockade on the production of cytokines and destructive enzymes. METHODS Infection with adenoviruses transferring the beta-galactosidase gene was used to ascertain that the OA fibroblasts could be infected (> 95%). Using an adenovirus transferring the inhibitory subunit IkappaBa, effective inhibition of NF-kappaB was achieved. The expression and production of several pro- and antiinflammatory cytokines and mediators, the major matrix metalloproteinases (MMP 1, 3, and 13), their main inhibitor tissue inhibitor of metalloproteinase-1 (TIMP-1), and the aggrecanases (ADAMTS4 and ADAMTS5) were measured by ELISA and/or reverse transcription-polymerase chain reaction, and their dependence on NF-kappaB evaluated. RESULTS The production of interleukin 6 (IL-6), monocyte chemoattractant protein-1, and RANTES was potently inhibited by IkBa overexpression, irrespective of stimulus, but IL-8 was unaffected. The p55 soluble tumor necrosis factor (TNF) receptor was unaffected, but the p75 soluble TNF receptor was potently inhibited by IkBa overexpression. MMP-1, MMP-3, and MMP-13 were inhibited by IkappaBa overexpression, at both the mRNA and protein levels, whereas TIMP-1 was unaffected. The mRNA gene expression of ADAMTS4 was also inhibited by IkappaBa overexpression, particularly in IL-1-stimulated cells, but ADAMTS5 was unaffected. CONCLUSION In OA synovial fibroblasts, inhibition of NF-kappaB has a beneficial effect on the balance between the expression of proinflammatory cytokines and antiinflammatory mediators. Inhibition of this transcription factor also results in the decreased expression of several destructive metalloproteinases and also the ADAMTS4 aggrecanase.