Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of ERK activation in growth and erythroid differentiation of K562 cells.

Inhibition of signaling through Ras in BCR-ABL-positive pluripotent K562 cells leads to apoptosis and spontaneous differentiation. However, Ras-induced activation of the mitogen-activated protein kinase ERK has been suggested to play a critical role in either growth or differentiation in different model systems. We studied the role of ERK activation in the growth-promoting and anti-apoptotic effect of Ras and its involvement in hemin-induced nonterminal erythroid differentiation using the BCR-ABL-positive K562 cell line as a model. K562 cells were stably transfected with ERK1 or the dominant inhibitory mutant of ERK1 (ERK1-KR). Overexpression of ERK1-KR inhibited cell growth with an approximately fourfold increase in doubling time and induced apoptosis in K562 cells. Incubation with the MEK1 inhibitor UO126 inhibited cell growth and induced apoptosis in K562 cells in a dose-dependent manner as well. In the presence of exogenously added hemin, K562 cells differentiate into erythroblasts, as indicated by the production of large amounts of fetal hemoglobin. We examined the activation of MAP kinases during hemin-induced differentiation. The ERK1 and 2 activity increased within 2 h post hemin treatment and remained elevated for 24-48 h. During this time, fetal hemoglobin synthesis also increases from 0.8 to 10 pg/cell. There was no activation of JNK or p38 protein kinases. The hemin-induced accumulation of hemoglobin was inhibited in ERK1-KR overexpressing cells and was enhanced in the wild-type ERK1 transfectants. Our results suggest that ERK activation is involved in both growth and hemin-induced erythroid differentiation in the BCR-ABL-positive K562 cell line.
Nutrient Metabolism Chlorogenic Acid Bioavailability Largely Depends on Its Metabolism by the Gut Microflora in Rats 1

Chlorogenic acid, the ester of caffeic acid with quinic acid, is one of the most abundant polyphenols in the human diet with coffee, fruits and vegetables as its major sources. Its antioxidant and anticarcinogenic properties have been well established in animal studies. However, little is known about its gut absorption and metabolism. In the present work, four groups of rats (n 8) were fed a diet supplemented with chlorogenic, caffeic or quinic acids (250 mol/d) or an unsupplemented diet for 8 d. Parent compounds and their metabolites were estimated in urine (24-h collection) and plasma by HPLC-electrospray ionization-tandem mass spectrometry. Significant differences in their levels were observed among the groups. The recovery of chlorogenic acid in urine was low (0.8%, mol/mol), and the total urinary excretion of caffeic acid liberated by hydrolysis of chlorogenic acid and its tissular methylated metabolites (ferulic and isoferulic acids) did not account for 0.5% (mol/mol) of the dose ingested. On the other hand, the metabolites of microbial origin, namely, m-coumaric acid and derivatives of phenylpropionic, benzoic and hippuric acids, represented the major compounds in both urine and plasma. Hippuric acid largely originated from the transformation of the quinic acid moiety, and all other metabolites from the caffeic acid moiety. These microbial metabolites accounted for 57.4% (mol/mol) of the chlorogenic acid intake. Such a high abundance of microbial metabolites shows that the bioavailability of chlorogenic acid depends largely on its metabolism by the gut microflora. Their potential importance in explaining the biological effects of dietary polyphenols is emphasized. J. Nutr. 133: 1853–1859, 2003.
Endoneurial blood flow in rat sciatic nerve during development.

1. Endoneurial blood flow (EBF) in the sciatic nerve of rats aged 2‐12 weeks was studied using microelectrode H2 polarography. 2. EBF is highest in 2‐week‐old rats and progressively declines during development. Mean arterial pressure (MAP) is low at 2 weeks of age, gradually increases through the next 4 weeks, and is relatively constant thereafter. The decrease in EBF, in spite of an increase in MAP, occurs because the endoneurial vascular resistance is increasing faster than the MAP. 3. The higher EBF in younger rats is not due to the smaller diameter of their nerves. Sural and tibial nerves of 12‐week‐old rats, with diameters comparable to that of the sciatic nerve of a 3‐week‐old rat, have EBFs similar to that of the sciatic nerve of a 12‐week‐old rat. 4. There was no compelling evidence of autoregulation of EBF in 3‐week‐old rats over a MAP range from ‐40 to +30 mmHg of the normal value. 5. The increase of nerve vascular resistance with maturation is probably due to a decrease in capillary density and, to a lesser extent, to an increase in plasma viscosity and haematocrit. 6. The higher EBF in immature rats is likely to be a developmentally adaptive mechanism which permits greater blood‐nerve exchange of material to accommodate the greater metabolic needs of rapidly elongating and myelinating axons and proliferating Schwann cells.
Childhood cancer frequency in the center of Tunisia.

OBJECTIVE In this paper, we analyzed the frequency of childhood cancer in the Center of Tunisia during 1993-2006. DESIGN The different types of cancer were grouped according to the International Classification for Cancer in Children. The general and specific frequencies by age and by sex were analyzed. RESULTS A total of 727 new cases of childhood cancer were registered, with a male to-female sex ratio of 1.7/1. Leukemias had the highest frequency (27%) and, of these, lymphoid leukemias were the most prevalent (73.5%). Thereafter, in descending order of frequency, were lymphomas (25.7%), tumors of the central nervous system (CNS, 9.2%), neuroblastomas (7.7%), sarcomas (6.9%), carcinomas (6.3%), bone tumors (5.8%), nephroblastomas (5.5%), and germinal cell tumors (2.6%). The highest frequency of cancer was found at age 10-14 years (34.9%). Leukemias were the most frequent in age groups 1-4 and 5-9 years, whereas, neuroblastomas and lymphomas were the most frequent at age under one year and 10-14 years, respectively. Of those cases of solid tumors, 55.8% were diagnosed as having advanced stages of the disease. CONCLUSION Leukemias, lymphomas, and CNS tumors were the principal cancers in the Center of Tunisia. A childhood cancer registry with high-resolution data collection is advocated for in-depth analysis of pediatric malignancies.
L A New Wireless Indoor Localization Algorithm

In the recent years, the advances in localization based technologies and the increasing importance of ubiquitous computing and context-dependent information have led to a growing business interest in location-based applications and services. There are many applications like security, healthcare, location based services, and social networking use wireless indoor localization to locate or track of physical belongings inside buildings. In the art of wireless indoor localization, a lot of research works have been done, mostly classified into two categories, namely, fingerprinting-based and model-based. To take advantage of their strengths and overcome their limitations, we propose a new algorithm which can not only determine position of a device without training stage but also in-depend on hardware configurations. By using mathematical formulation analysis, we demonstrate its advantages than the other techniques.
Esomeprazole 40 mg and 20 mg is efficacious in the long-term management of patients with endoscopy-negative gastro-oesophageal reflux disease: a placebo-controlled trial of on-demand therapy for 6 months

Background On-demand therapy may offer an effective approach to the long-term management of gastro-oesophageal reflux disease (GORD) without oesophagitis. Aim To examine the efficacy of the novel proton pump inhibitor esomeprazole as on-demand therapy in endoscopy-negative GORD. Patients and methods Endoscopy-negative GORD patients who achieved complete resolution of heartburn after short-term esomeprazole or omeprazole treatment (n = 721) were randomized to esomeprazole 20 mg (n = 282), 40 mg (n = 293) or placebo (n = 146) on demand (maximum one dose/day) for 6 months. The primary and secondary efficacy endpoints were time to study discontinuation due to (i) unwillingness to continue and (ii) inadequate control of heartburn, respectively. Results Both doses of esomeprazole were more effective than placebo. During the 6-month period, 42% of placebo recipients discontinued treatment due to unwillingness to continue, compared with 8% and 11% of esomeprazole 20 mg and 40 mg recipients, respectively. Overall, more patients treated with esomeprazole were free from gastrointestinal symptoms after 6 months of on-demand therapy. Conclusions Esomeprazole 20 mg was superior to placebo for on-demand treatment of GORD; a higher dose did not confer additional clinical benefit. Over 90% of patients were willing to continue on-demand treatment with esomeprazole 20 mg over a 6-month period.
In Vitro and In Vivo Activities of 1,3,4-Thiadiazole-2-Arylhydrazone Derivatives of Megazol against Trypanosoma cruzi

ABSTRACT From a series of 1,3,4-thiadiazole-2-arylhydrazone derivatives of megazol screened in vitro against Trypanosoma cruzi, eight (S1 to S8) were selected for in vivo screening by single-dose oral administration (200 mg/kg of body weight) to infected mice at 5 days postinfection (dpi). Based on significant decreases in both parasitemia levels and mortality rates, S2 and S3 were selected for further assays. Despite having no in vivo effect, S1 was included since it was 2-fold more potent against trypomastigotes than megazol in vitro. Trypomastigotes treated with S1, S2, or S3 showed alterations of the flagellar structure and of the nuclear envelope. When assayed on intracellular amastigotes, the selectivity index (SI) for macrophages was in the range of >27 to >63 and for cardiac cells was >32 for S1 and >48 for megazol. In noninfected mice, S1 did not alter the levels of glutamic oxalacetic transaminase (GOT), glutamate pyruvate transaminase (GPT), or urea. S2 led to an increase in GOT, S3 to increases in GOT and GPT, and megazol to an increase in GOT. Infected mice were treated with each derivative at 50 and 100 mg/kg from dpi 6 to 15: S1 did not interfere with the course of infection or reduce the number of inflammatory foci in the cardiac tissue, S2 led to a significant decrease of parasitemia, and S3 decreased mortality. There was no direct correlation between the in vitro effect on trypomastigotes and amastigotes and the results of the treatment in experimental models, as S1 showed a high potency in vitro while, in two different schemes of in vivo treatment, no decrease of parasitemia or mortality was observed.
Combined p53 and Retinoblastoma Protein Detection Identifies Persistent and Regressive Cervical High-Grade Squamous Intraepithelial Lesions

Most cervical high-grade squamous intraepithelial lesions (HSILs) persist, but approximately one third regress (ie, no HSIL in follow-up biopsies). To identify factors related to histologic proven persistence or regression. Twenty-eight small histologic (marker) biopsies with adequate follow-up were analyzed for human papillomavirus (HPV) genotypes and different immunoquantitative proliferation, cell cycle regulation, and differentiation markers. All cases had a biopsy-interval between the marker and first follow-up biopsy of at least 100 days (median, 8.2 months; range, 3.4-22.5 months). Follow-up was classified as regression or persistence. All lesions were high-risk (hr) HPV and p16 positive, 63% for HPV-16 or HPV-16 mixed with other hr genotypes, while 37% had other hrHPV types. The marker biopsies of the persistent HSILs had lower p53 and retinoblastoma protein (pRb) detected in the deep half of the epithelium (P = 0.001 and 0.02, respectively) than nonpersistent HSILs. The degree of positivity of p16, Ki-67, cyclin D1, lesion extent, positivity of the resection margins, and patient age were all unrelated to persistence or regression. Lesions with HPV-16 or mixed-16 genotypes had a significantly lower percentage of pRb (P = 0.02), p53 (P = 0.02), and cyclin D (P = 0.04) positive nuclei in the deep epithelial layers. In agreement with this, type-16 positive HSILs had a lower regression percentage than those with other HPV types, but the difference was not significant. HSILs with combined negativity/low positivity for p53 and pRb protein in small histologic biopsies are highly likely to persist, contrasting those in which one of these cell cycle regulators is strongly positive (p53 > 15%; pRb > 40%).
THE COOLING POWER OF THE PIGEON HEAD

Resting pigeons preheated to a stable core temperature of 43.2 °C, which is within the range of body temperatures recorded during flight, were able to cool their body at high rates if their head and upper neck were exposed to an air stream at 23.5 °C. The heat dissipation capacity of the head and neck, estimated from measurements made at a wind speed (100 km h-1) corresponding to fast flight, was 9.8 W, or 4.5 times the resting heat production. Since the greater part of this capacity, about 8 W, was attributable to the inner surfaces of the mouth, ram ventilation of the buccal cavity appears to be an important mechanism for increasing evaporative heat loss during flight. Accordingly, wind-assisted mouth cooling should be utilized by resting pigeons, since exposure to a slight breeze (approximately 10 km h-1) could augment their dissipating power by an amount equivalent to their resting metabolic rate. It is concluded that beak opening, together with a source of convection other than panting and gular flutter, is required to exploit fully the heat dissipation capacity of the buccopharyngeal mucosa of birds.
Fluid flow stimulates rapid and continuous release of nitric oxide in osteoblasts.

Interstitial fluid flow may mediate skeletal remodeling in response to mechanical loading. Because nitric oxide (NO) has been shown to be an osteoblast mitogen and inhibitor of osteoclastic resorption, we investigated and characterized the role of fluid shear on the release of NO in osteoblasts. Rat calvarial cells in a stationary culture produced undetectable levels of NO. Fluid shear stress (6 dyn/cm2) rapidly increased NO release rate to 9.8 nmol.h-1.mg protein-1 and sustained this production for 12 h of exposure to flow. Cytokine treatment also induced NO synthesis after a 12-h lag phase of zero production, followed by a production rate of 0.6 nmol.h-1.mg protein-1. Flow-induced NO production was blocked by the NO synthase (NOS) inhibitor NG-amino-L-arginine, but not by dexamethasone, which suggests that the flow stimulated a constitutive NOS isoform. This is the first time that a functional constitutively present NOS isoform has been identified in osteoblasts. Moreover, fluid flow represents the most potent stimulus of NO release in osteoblasts reported to date. Fluid flow-induced NO production may therefore play a primary role in bone maintenance and remodeling.
Impact of substance use disorders on recovery from episodes of depression in bipolar disorder patients: prospective data from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).

OBJECTIVE Bipolar disorder is highly comorbid with substance use disorders, and this comorbidity may be associated with a more severe course of illness, but the impact of comorbid substance abuse on recovery from major depressive episodes in these patients has not been adequately examined. The authors hypothesized that comorbid drug and alcohol use disorders would be associated with longer time to recovery in patients with bipolar disorder. METHOD Subjects (N=3,750) with bipolar I or bipolar II disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) were followed prospectively for up to 2 years. Prospectively observed depressive episodes were identified for this analysis. Subjects with a past or current drug or alcohol use disorder were compared with those with no history of drug or alcohol use disorders on time to recovery from depression and time until switch to a manic, hypomanic, or mixed episode. RESULTS During follow up, 2,154 subjects developed a new-onset major depressive episode; of these, 457 subjects switched to a manic, hypomanic, or mixed episode prior to recovery. Past or current substance use disorder did not predict time to recovery from a depressive episode relative to no substance use comorbidity. However, those with current or past substance use disorder were more likely to experience switch from depression directly to a manic, hypomanic, or mixed state. CONCLUSIONS Current or past substance use disorders were not associated with longer time to recovery from depression but may contribute to greater risk of switch into manic, mixed, or hypomanic states. The mechanism conferring this increased risk merits further study.
Liking a Sexual Character Affects Willingness to Have Casual Sex

Abstract. The aim of the present study was to investigate individual differences in the influence of the likability of a sexual female main character on women’s willingness to have casual sex with a stranger. Specifically, we studied the moderating role of relationship status (Experiments 1 and 2) and satisfaction with one’s relationship or with being single (Experiment 2). Women (aged 18–30), who were single or in a relationship, watched an erotic scene with a likable or unlikable sexual female main character who had casual sex. In both experiments, women in a relationship were less willing to have casual sex than single women, after they had seen a likable sexual female character. However, an unpredicted effect was found in Experiment 2. After seeing an unlikable sexual female character, women who were dissatisfied with their relationship or with being single were more willing to have casual sex than their satisfied counterparts.
Management of severe acute malnutrition in low-income and middle-income countries

Kwashiorkor and marasmus, collectively termed severe acute malnutrition (SAM), account for at least 10% of all deaths among children under 5 years of age worldwide, virtually all of them in low-income and middle-income countries. A number of risk factors, including seasonal food insecurity, environmental enteropathy, poor complementary feeding practices, and chronic and acute infections, contribute to the development of SAM. Careful anthropometry is key to making an accurate diagnosis of SAM and can be performed by village health workers or even laypeople in rural areas. The majority of children can be treated at home with ready-to-use therapeutic food under the community-based management of acute malnutrition model with recovery rates of approximately 90% under optimal conditions. A small percentage of children, often those with HIV, tuberculosis or other comorbidities, will still require inpatient therapy using fortified milk-based foods.
Principais aspectos da obesidade em cães.

Nos ultimos anos, problemas de obesidade em caes vem crescendo de forma drastica, assim como as doencas associadas a ela. A Obesidade e considerada um processo inflamatorio, e tem como resultado o aumento dos niveis de citocina e proteinas circulantes na fase aguda da inflamacao. O estilo de vida sedentario e a superalimentacao dos caes os levam a um estresse fisiologico e ambiental, o que contribui para a diminuicao da expectativa de vida o que aumenta sua vulnerabilidade as doencas, como diabetes mellitus, doencas articulares e locomotoras, alteracoes cardiacas, pulmonares, endocrinas alem de tornar os animais mais vulneraveis as infeccoes, aumentando com isso os riscos de complicacoes cirurgicas podendo leva-los a morte. A Obesidade pode afetar todos os tipos de animais, sendo as femeas castradas mais acometidas. O objetivo desse estudo e realizar uma revisao bibliografica e abordar os principais aspectos da obesidade em caes, destacando a prevencao dessa doenca, o correto diagnostico e o tratamento que devem ser instituidos, fazendo com que os animais tenham maior expectativa e qualidade de vida.
Secondary alveolar bone grafting: Radiographic and clinical evaluation

Introduction: Secondary bone grafting of maxilla and residual alveolar clefts at the stage of transitional dentition was first introduced by Boyne and Sands. The aim of this prospective case control study was to clinically and radiologically evaluate the success rate of anterior iliac crest graft in primary alveolar cleft. Methods and Material: In this study we evaluated 10 patients who underwent secondary alveolar bone grafting for various types of cleft palate with autologous iliac crest graft. Type of septum measured radiologically was taken as the outcome measure. Results: Postoperative radiographic evaluation revealed Type I inter alveolar septum in 7 cases (87.5%), with complete unilateral cleft lip, palate and alveolus. Non-eruption of canine occurred in 5 patients (50%). Periodontal Examination revealed presence of pocket formation (less than 4 mm) and Grade II mobility in 2 cases (20%). Conclusions: In conclusion, secondary alveolar bone grafting done during the time of transitional dentition, before the eruption of permanent canine is an excellent treatment modality.
Towards Merging Context-Aware, Mobile and Grid Computing

ISAM is a proposal directed to supporting physical and logical mobility, context-awareness, dynamic adaptation and the execution of large-scale distributed applications. In order to achieve its goals, ISAM uses, as strategy, an integrated environment that provides: (a) a programming language; (b) an execution environment; (c) a context recognition server. The integration is accomplished through an adaptation process that uses a multilevel collaborative model, in which both the system and the application contribute for that. In this paper we discuss the main components used to implement the ISAM features, and we also present a distributed application that explores some of this features.
Pharmacokinetics of (-)-2'-3'-dideoxy-3'-thiacytidine in woodchucks

The woodchuck (Marmota monax) has proven to be a suitable animal model for studying hepatitis B virus (HBV) infection owing to similarities in the course of infection between woodchuck hepatitis virus (WHV) in woodchucks and HBV in humans. (-)-beta-L-2',3'-Dideoxy-3'-thiacytidine (3TC; lamivudine) is a nucleoside analog which has demonstrated antiviral activity against HBV as well as human immunodeficiency virus (HIV). The purpose of the present investigation was to characterize the pharmacokinetics of 3TC following intravenous and oral administration of 20 mg of 3TC per kg of body weight to woodchucks. Following intravenous administration, the concentrations of 3TC in plasma declined, with a terminal half-life of 2.84 +/- 0.85 h (mean +/- standard deviation). The systemic clearance and steady-state volume of distribution of 3TC were 0.22 +/- 0.078 liters/h/kg and 0.75 +/- 0.13 liters/kg, respectively. The renal clearance of the nucleoside analog was 0.063 +/- 0.016 liters/h/kg. The oral bioavailability of 3TC ranged from 18 to 54%. Allometric relationships between pharmacokinetic parameters and body weight developed by Hussey et al. (E.K. Hussey, K.H. Donn, M.J. Daniel, S.T. Hall, A.J. Harker, and G.L. Evans, J. Clin. Pharmacol. 34:975-977, 1994) were augmented by including data from woodchucks, monkeys (S.M. Blaney, M.J. Daniel, A.J. Harker, K. Godwin, and F.M. Balis, Antimicrob. Agents Chemother. 39:2779-2782, 1995), and additional data from rats (P. Rajagopalan, L. Moore, C.K. Chu, R.F. Schinazi, and F.D. Boudinot, submitted for publication). Interspecies scaling of the pharmacokinetic parameters of 3TC demonstrated a good correlation between clearance (0.74 . W0.76 [where W is body weight]; r = 0.93; P < 0.025), apparent volume of distribution (1.62 . W0.81; r = 0.98; P < 0.005), and steady-state volume of distribution (1.09 . W0.94; r = 0.99; P < 0.05) and species body weight. The allometric relationships for clearance and volume of distribution at steady state predicted the observed pharmacokinetic parameters in humans quite well; however, the apparent volume of distribution was underestimated in humans. Thus, the pharmacokinetic data obtained with the woodchuck HBV animal model should be useful for designing clinical trials.