Miracle-dz/UniFAR-FTUs huggingface dataset:
Insulin-like Growth Factor-I Inhibits Transcriptional Responses of Transforming Growth Factor-β by Phosphatidylinositol 3-Kinase/Akt-dependent Suppression of the Activation of Smad3 but Not Smad2*

Insulin-like growth factor-I (IGF-I) and transforming growth factor-β (TGF-β) have been shown to be oncogenic and tumor suppressive, respectively, on prostate epithelial cells. Here we show that IGF-I inhibits the ability of TGF-β to regulate expression of several genes in the non-tumorigenic rat prostatic epithelial line, NRP-152. In these cells, IGF-I also inhibits TGF-β-induced transcriptional responses, as shown by several promoter reporter constructs, suggesting that IGF-I intercepts an early step in TGF-β signaling. We show that IGF-I does not down-regulate TGF-β receptor levels, as determined by both receptor cross-linking and Western blot analyses. However, Western blot analysis reveals that IGF-I selectively inhibits the TGF-β-triggered activation Smad3 but not Smad2, while not altering expression of total Smads 2, 3, or 4. The phosphatidylinositol 3-kinase (PI3K) inhibitor, LY29004 reverses the ability of IGF-I to inhibit TGF-β-induced transcriptional responses and the activation of Smad3, suggesting that the suppression of TGF-β signaling by IGF-I is mediated through activation of PI3K. Moreover, we show that enforced expression of dominant-negative PI3K (DN-p85α) or phosphatidylinositol 3-phosphate-phosphatase, PTEN, also reverse the suppressive effect of IGF-I on TGF-β-induced 3TP-luciferase reporter activity, whereas constitutively active PI3K (p110αCAAX) completely blocks TGF-β-induced 3TP-luciferase reporter activity. Further transfection experiments including expression of constitutively active and dominant-negative Akt and rapamycin treatment suggest that suppression of TGF-β signaling/Smad3 activation by IGF-I occurs downstream of Akt and through mammalian target of rapamycin activation. In summary, our data suggest that IGF-I inhibits TGF-β transcriptional responses through selective suppression of Smad3 activation via a PI3K/Akt-dependent pathway.
Monitoring systemic risk in the hedge fund sector

We propose measures for systemic risk generated through intra-sectorial interdependencies in the hedge fund sector. These measures are based on variations in the average cross-effects of funds showing significant interdependency between their individual returns and the moments of the sector’s return distribution. The proposed measures display a high ability to identify periods of financial distress, are robust to modifications in the underlying econometric model and are consistent with intuitive interpretation of the results.
Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial.

PURPOSE Nasopharyngeal carcinoma (NPC) is highly sensitive to both radiotherapy (RT) and chemotherapy. This randomized phase III trial compared concurrent cisplatin-RT (CRT) with RT alone in patients with locoregionally advanced NPC. PATIENTS AND METHODS Patients with Ho's N2 or N3 stage or N1 stage with nodal size > or = 4 cm were randomized to receive cisplatin 40 mg/m(2) weekly up to 8 weeks concurrently with radical RT (CRT) or RT alone. The primary end point was progression-free survival (PFS). RESULTS Three hundred fifty eligible patients were randomized. Baseline patient characteristics were comparable in both arms. There were significantly more toxicities, including mucositis, myelosuppression, and weight loss in the CRT arm. There were no treatment-related deaths in the CRT arm, and one patient died during treatment in the RT-alone arm. At a median follow-up of 2.71 years, the 2-year PFS was 76% in the CRT arm and 69% in the RT-alone arm (P =.10) with a hazards ratio of 1.367 (95% confidence interval [CI], 0.93 to 2.00). The treatment effect had a significant covariate interaction with tumor stage, and a subgroup analysis demonstrated a highly significant difference in favor of the CRT arm in Ho's stage T3 (P =.0075) with a hazards ratio of 2.328 (95% CI, 1.26 to 4.28). For T3 stage, the time to first distant failure was statistically significantly different in favor of the CRT arm (P =.016). CONCLUSION Concurrent CRT is well tolerated in patients with advanced NPC in endemic areas. Although PFS was not significantly different between the concurrent CRT arm and the RT-alone arm in the overall comparison, PFS was significantly prolonged in patients with advanced tumor and node stages.
New Approaches in Social and Humanistic Sciences Tobit Regression Model to Determine the Dividend Yield in Iraq

In the model of linear regression, the values of variables are known. The sample is limited by censoring limited restriction point where the approved variable is (Threshold point). Censoring occurs at the observation of the independent variables for the entire sample and the censored regression model is considered adequate when the data has to be censored from left at censored point equal to zero. After this, the Tobit regression model can be applied. In this paper we will identify the determinants of the Distribution of Profits between some competing companies on the Iraq Stock Exchange. The profit distribution in the shareholding companies determines the profits which are distributed to the shareholders and the part that is held. The retained profits are a major source of investment in the companies. Although expansion is desirable, profit distribution is as well. The study examines the determinants of the dividend yield, by using the Tobit regression model. The study will use a data set for some companies that traded on the Iraqi Stock Exchange between 2005 and 2015.The results of the analysis of tables use data on Market capitalization, Earnings per share, Market price to book value ratio and debt-equity ratio affect the distribution of profits paid, in some companies traded by Iraq Stock Exchange.
Modulation of mitogen-activated protein kinase activation and cell cycle regulators by the potent skin cancer preventive agent silymarin.

Recently we showed that the skin cancer preventive effect of silymarin involves inhibition of erbB1 activation. Here we assessed the effect of silymarin on cytoplasmic and nuclear signals employing human epidermoid carcinoma A431 cells. Silymarin treatment of cells resulted in a significant inhibition of mitogen-activated protein kinase (MAPK)/ERK1/2 activation only at lower doses, whereas higher doses activated MAPK/JNK1. These differential responses of silymarin were accompanied by its growth inhibitory and apoptotic cell death effects at low and high doses, respectively. Silymarin-caused growth inhibition was via both G2-M and G1 arrests due to a significant decrease in the kinase activity and protein levels of CDKs and cyclins. In other studies, only low doses of silymarin also showed an induction of Cip1/p21 and Kip1/p27. Together, these results identify distinct signaling pathways for the antiproliferative and apoptotic effects of silymarin and form a basis for developing strategies targeted to ERK and JNK pathways for the prevention and intervention of malignancies by silymarin.
Role of Layer 6 of V2 Visual Cortex in Object-Recognition Memory

Modulating Visual Memory Layer 3 of the secondary visual cortical area V2 plays a role in visual information processing. However, in contrast to layer 3, layer 6 of visual cortex is composed of many types of neurons and their response to visual stimuli is more complex. The importance of layer 6 in visual information processing remains an enigma. López-Aranda et al. (p. 87; see the Perspective by Saksida) investigated its role in the rat visual cortex in the processing of both short- and long-term visual memory. Elimination of neurons from layer 6 of area V2 led to complete loss of normal memory. However, overexpression of a protein called RGS-14 in the same area boosted the visual memory capacity in such a way that the animals retained the visual information for many months, rather than the normal 45 minutes. Experiments reveal the localization of short- and long-term visual memory encoding in the rat visual cortex. Cellular responses in the V2 secondary visual cortex to simple as well as complex visual stimuli have been well studied. However, the role of area V2 in visual memory remains unexplored. We found that layer 6 neurons of V2 are crucial for the processing of object-recognition memory (ORM). Using the protein regulator of G protein signaling–14 (RGS-14) as a tool, we found that the expression of this protein into layer 6 neurons of rat-brain area V2 promoted the conversion of a normal short-term ORM that normally lasts for 45 minutes into long-term memory detectable even after many months. Furthermore, elimination of the same-layer neurons by means of injection of a selective cytotoxin resulted in the complete loss of normal as well as protein-mediated enhanced ORM.
Influence of stocking rate and steroidal implants on growth rate of steers grazing toxic tall fescue and subsequent physiological responses.

An 84-d grazing experiment was conducted in 2 growing seasons to evaluate interactions of stocking rate and steroidal implants with BW gain and symptoms of toxicosis in yearling steers grazing endemic endophyte-infected (E+) tall fescue (Festuca arundinacea Schreb.). A 4 x 2 factoral design was used to evaluate 4 stocking rates (3.0, 4.0, 5.0, and 6.0 steers/ ha) with or without steroidal implants (200 mg of progesterone + 20 mg of estradiol benzoate). Treatment combinations were randomly assigned to eight 1-ha pastures of E+ Kentucky-31 tall fescue (i.e., treatments were not replicated). Treatment effects were analyzed for ADG, total BW gain per hectare, forage availability, and hair coat ratings. At the conclusion of grazing in the second year (22 June), steers were placed on a bermudagrass [Cynodon dactylon (L.) Pers. ] pasture, and rectal temperatures and serum prolactin concentrations were monitored for 10 d to assess carryover effects of stocking rate and steroidal implants on recovery from toxicosis-related heat stress. Forage availability differed (P < 0.001) between years, but there were no year x treatment interactions (P > 0.10). There was an implant x stocking rate interaction (P < 0.05) on ADG. Differences between the slopes in the regression equations indicated that ADG responded to implantation when stocking rates were low, but the response diminished as stocking rate increased. Stocking rate did not influence (P = 0.89) postgraze rectal temperature, but the regression intercept for implanted steers was 0.4 degrees C greater (P < 0.05) than for nonimplanted steers, and the difference was consistent across the entire 10-d fescue-free grazing period. Concentrations of prolactin increased during the 10-d fescue-free grazing period, but trends differed due to an implantation x stocking rate interaction (P < 0.05). Results indicate that implantation with progesterone + estradiol benzoate increases ADG with lower stocking rates, but the effect diminishes with increased grazing intensity. Implantation with steroid hormones increased rectal temperatures, but during a fescue-free grazing period rectal temperatures and serum prolactins for implanted and nonimplanted steers returned to values indicative of a stable and healthy status in a 192- to 240-h (i.e., an 8- to 10-d) period. However, because the treatments used in this study were not replicated, these observations need to be confirmed with replicated studies.
Vertical transitions in low temperature co-fired ceramics for LMDS applications

To realize the advantages of low temperature co-fired ceramics (LTCC), such as highly integrated and low cost microwave packages, a library of repeatable and low loss vertical transitions is necessary. This paper presents measured results of three LTCC vertical transitions: stripline to coplanar waveguide (CPW), CPW to CPW, and CPW to microstrip. A novel grounding structure for intermediate ground planes is presented and discussed. The measured results demonstrate vertical transitions with good performance across the LMDS range.
Impact of a Supervised Worksite Exercise Program on Back and Core Muscular Endurance in Firefighters

Purpose. Low back pain is a leading cause of disability in firefighters and is related to poor muscular endurance. This study examined the impact of supervised worksite exercise on back and core muscular endurance in firefighters. Design. A cluster randomized controlled trial was used for this study Setting. The study occurred in fire stations of a municipal fire department (Tampa, Florida). Subjects. Subjects were 96 full-duty career firefighters who were randomly assigned by fire station to exercise (n = 54) or control (n = 42) groups. Intervention. Exercise group participants completed a supervised exercise targeting the back and core muscles while on duty, two times per week for 24 weeks, in addition to their usual fitness regimen. Control group participants continued their usual fitness regimen. Measures. Back and core muscular endurance was assessed with the Biering-Sorensen test and plank test, respectively. Analysis. Changes in back and core muscular endurance from baseline to 24 weeks were compared between groups using analysis of covariance and linear mixed effects models. Results. After 24 weeks, the exercise group had 12% greater (p = .021) back muscular endurance and 21% greater (p= .0006) core muscular endurance than did the control group. The exercise intervention did not disrupt operations or job performance. Conclusion. A supervised worksite exercise program was safe and effective in improving back and core muscular endurance in firefighters, which could protect against future low back pain.
Can British terminology in cervical cytology survive liquid‐based cytology?

The recent guidance from the National Institute for Clinical Excellence (NICE) on liquidbased cytology (LBC) is optimistic but realistically cautious. In particular, the guidance notes that, despite widespread enthusiasm for the technique, no randomized controlled trial has yet assessed the eects of LBC on cervical cancer morbidity and mortality. Furthermore, in order to establish its potential contribution to the NHS Cervical Screening Programme (NHSCSP), pilot implementation projects are recommended.
Molecular analysis of VP4, VP7, and NSP4 genes of P[6]G2 rotavirus genotype strains recovered from neonates admitted to hospital in Belém, Brazil

This investigation describes the molecular characterization of P[6]G2 rotavirus strains from hospitalized neonates with community‐acquired diarrhea (CAD), nosocomial diarrhea (ND), and asymptomatic nosocomial infection (ANI) in Belém, Brazil. Twenty‐six rotavirus strains with P[6]G2 genotype were sequenced to genes coding for VP4, VP7, and NSP4 proteins. Phylogenetic analysis of the VP4 gene, including prototype strains RV3, ST3, M37, and U1205, showed that local P[6]G2 strains clustered forming a distinct lineage (bootstrap of 99%). Brazilian P[6]G2 strains had the highest homology (ranging from 96.0%–98.3%) with the African strain GR1107, G4P[6]. Phylogenetic tree for VP7 gene was constructed including old and new G2 African strains SA3958GR/97, SA356PT/96, SA514GR/87, SA4476PT/97, BF3676/99, GH1803/99, and representative strains of G1, G3, G4, G5, G8, and G9 genotypes. The Brazilian P[6]G2 samples fell into a distinct group (bootstrap value of 97%) and showed homology rates ranging from 92.1% to 93.5% with P[6]G2 African strains BF3676/99, GH1803/99, and SA3958GR/97. Nucleotide sequence analysis of the NSP4 gene, including human prototype strains S2, KUN, DS‐1, RV5, RV3 and ST3, and animal prototype OSU, showed that all neonatal isolates fell into genotype A and clustered with a bootstrap value of 100%, with in‐group similarities ranging from 99.3% to 100%. In this study no significant differences in nucleotide sequences of the VP4, VP7, and NSP4 genes could be observed when comparing diarrheic (CAD and ND) and non‐diarrheic (ANI) babies. Monitoring of rotavirus strains in hospital environments is of particular importance, since it is claimed currently that an efficacious rotavirus vaccine, when available for routine use, will determine an impact on hospital‐acquired rotavirus disease. J. Med. Virol. 78:281–289, 2006. © 2005 Wiley‐Liss, Inc.
Stent under‐expansion on the procedure day, a predictive factor for poor oral intake after metallic stenting for gastric outlet obstruction

Self‐expandable metallic stents (SEMS) have been widely accepted as palliation therapy for malignant gastric outlet obstruction (GOO). However, the factors predictive of poor oral intake after SEMS placement have not been elucidated sufficiently. We aimed to clarify both the patient and stent‐related predictive factors.
Increased coronary-artery atherosclerosis in rheumatoid arthritis: relationship to disease duration and cardiovascular risk factors.

OBJECTIVE To compare the prevalence and severity of coronary-artery atherosclerosis in patients with early and established rheumatoid arthritis (RA) and controls. METHODS Electron-beam computed tomography was used to measure the extent of coronary-artery calcification in 227 subjects, of whom 70 had early RA, 71 had established RA, and 86 were controls. Coronary-artery calcification calculated according to the Agatston calcium score was compared in patients and controls, and its relationship to clinical characteristics was examined. Adjusted odds ratios (ORs) were obtained with the use of proportional odds logistic regression models to determine independent associations of early and established RA and coronary-artery calcification. RESULTS Calcium scores were higher in patients with established RA (median 40.2, interquartile range [IQR] 0-358.8) compared with those with early disease (median 0, IQR 0-42.6) and controls (median 0, IQR 0-19.2) (P = 0.001). Coronary-artery calcification occurred more frequently in patients with established RA (60.6%) than in patients with early RA (42.9%) and control subjects (38.4%) (P = 0.016) The OR for the likelihood of having more severe coronary-artery calcification (defined as an Agatston score >109) in patients with established disease was 3.42 (P = 0.002) after adjusting for cardiovascular risk factors. Among patients with RA, smoking (OR 1.02, P = 0.04) and an elevated erythrocyte sedimentation rate (OR 1.02, P = 0.05) were associated with more severe coronary-artery calcification after adjustment for age and sex. CONCLUSION The prevalence and severity of coronary calcification is increased in patients with established RA and is related, in part, to smoking and an increased erythrocyte sedimentation rate.
Associations of periodontal damage and tooth loss with atherogenic factors among patients with type 2 diabetes mellitus.

OBJECTIVE To clarify the associations of periodontal damage and tooth loss with atherogenic factors among diabetic patients. METHODS We examined the correlations of age, sex, smoking, oral hygiene score, blood pressure, body mass index, and blood chemical data with the mean depth of periodontal pockets or the number of remaining teeth. PATIENTS One hundred outpatients with type 2 diabetes aged 29 to 77 years. RESULTS The mean depth of periodontal pockets was significantly associated with smoking, oral hygiene score, and HbA1c; the Spearman correlation coefficients (r) were 0.220, 0.417, and 0.260, respectively. Age, oral hygiene score, and HbA1c were inversely correlated with the number of remaining teeth (r=-0.306, -0.287, and -0.275, respectively). Serum total cholesterol was significantly correlated with the mean depth of pockets after adjustment for smoking, oral hygiene score, and HbA1c (r=0.211; P=0.044), while serum HDL cholesterol tended to be negatively associated with depth (r=-0.202; P=0.055). Serum HDL cholesterol was also associated with an increased number of teeth, which remained significant after adjustment for age, oral hygiene score, and HbA1c (r=0.202; P=0.048). The estimated glomerular filtration rate was significantly and positively correlated with the number of teeth in the univariate analysis, although consideration of the potential confounding factors somewhat weakened the association (r=0.186; P=0.069). CONCLUSIONS We may expect better management of oral health in diabetic patients with control of dyslipidemia in addition to blood glucose.
Protein Phosphatase 2A Negatively Regulates Insulin's Metabolic Signaling Pathway by Inhibiting Akt (Protein Kinase B) Activity in 3T3-L1 Adipocytes

ABSTRACT Protein phosphatase 2A (PP2A) is a multimeric serine/threonine phosphatase which has multiple functions, including inhibition of the mitogen-activated protein (MAP) kinase pathway. Simian virus 40 small t antigen specifically inhibits PP2A function by binding to the PP2A regulatory subunit, interfering with the ability of PP2A to associate with its cellular substrates. We have reported that the expression of small t antigen inhibits PP2A association with Shc, leading to augmentation of insulin and epidermal growth factor-induced Shc phosphorylation with enhanced activation of the Ras/MAP kinase pathway. However, the potential involvement of PP2A in insulin's metabolic signaling pathway is presently unknown. To assess this, we overexpressed small t antigen in 3T3-L1 adipocytes by adenovirus-mediated gene transfer and found that the phosphorylation of Akt and its downstream target, glycogen synthase kinase 3β, were enhanced both in the absence and in the presence of insulin. Furthermore, protein kinase C λ (PKC λ) activity was also augmented in small-t-antigen-expressing 3T3-L1 adipocytes. Consistent with this result, both basal and insulin-stimulated glucose uptake were enhanced in these cells. In support of this result, when inhibitory anti-PP2A antibody was microinjected into 3T3-L1 adipocytes, we found a twofold increase in GLUT4 translocation in the absence of insulin. The small-t-antigen-induced increase in Akt and PKC λ activities was not inhibited by wortmannin, while the ability of small t antigen to enhance glucose transport was inhibited by dominant negative Akt (DN-Akt) expression and Akt small interfering RNA (siRNA) but not by DN-PKC λ expression or PKC λ siRNA. We conclude that PP2A is a negative regulator of insulin's metabolic signaling pathway by promoting dephosphorylation and inactivation of Akt and PKC λ and that most of the effects of PP2A to inhibit glucose transport are mediated through Akt.