Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Hypoxia-response Element in the Human Endothelial Nitric-oxide Synthase Gene Promoter*

The human endothelial nitric-oxide synthase gene (heNOS) is constitutively expressed in endothelial cells, and its expression is induced under hypoxia. The goal of this study was to search for regulatory elements of the endothelial nitric-oxide synthase (eNOS) gene responsive to hypoxia. Levels of eNOS mRNA, measured by real time reverse transcriptase-PCR analysis, were increased, and heNOS promoter activity was enhanced by hypoxia as compared with normoxia control experiments. Promoter truncation followed by footprint analysis allowed the mapping and identification of the hypoxia-responsive elements at position –5375 to –5366, closely related to hypoxia-inducible factor (HIF)-responsive element (HRE). To test whether known HIF-1 and HIF-2 are involved in hypoxia-induced heNOS promoter activation, HMEC-1 and HUVEC were transiently transfected with HIF-1α and HIF-1β or HIF-2α and HIF-1β expression vectors. Exogenous HIF-2 markedly increased luciferase reporter activity driven by the heNOS promoter in its native location. The induction of luciferase was conserved with the antisense construct and was increased in cotransfection experiments when this fragment was cloned 5′ to the proximal 785-bp fragment of the eNOS promoter. Deletion analysis and site-directed mutagenesis demonstrated that the two contiguous HIF consensus binding sites spanning bp –5375 to –5366 relative to the transcription start site were both functional for heNOS promoter activity induction by hypoxia and by HIF-2 overexpression. In conclusion, we demonstrate that heNOS is a hypoxia-inducible gene, whose transcription is stimulated through HIF-2 interaction with two contiguous HRE sites located at –5375 to –5366 of the heNOS promoter.
A 48-week, randomized, double-blind, double-observer, placebo-controlled multicenter trial of combination methotrexate and intramuscular gold therapy in rheumatoid arthritis: results of the METGO study.

OBJECTIVE To evaluate the efficacy and safety of adding intramuscular (IM) gold to the treatment regimen of patients with rheumatoid arthritis (RA) who have a suboptimal response to methotrexate (MTX). METHODS A randomized, double-blind, double-observer, placebo-controlled multicenter trial of 48 weeks was conducted. Sixty-five RA patients who had a suboptimal response to >/=12 weeks of MTX therapy were randomly assigned to receive weekly IM gold or placebo in addition to MTX. Gold was administered according to a standard protocol developed for the study. The primary outcome measure was the percentage of patients who met the American College of Rheumatology (ACR) 20% improvement criteria (achieved an ACR20 response) at week 48. Secondary outcomes included the percentages of patients achieving ACR50 and ACR70 responses, the individual criteria that make up the primary outcome, quality of life, direct and indirect health care costs, intraarticular steroid use, and adverse events, among other measures. Statistical analyses were based on an intent-to-treat strategy. RESULTS Sixty-one percent of patients receiving gold achieved an ACR20 response compared with 30% of patients receiving placebo (chi(2) = 6.04, P = 0.014; logistic regression odds ratio 3.64 [95% confidence interval 1.3, 10.4], P = 0.016). Twenty-six percent of patients receiving gold achieved an ACR50 response compared with 4% of patients receiving placebo (P = 0.017), and 21% of patients receiving gold achieved an ACR70 response compared with 0% of patients receiving placebo (P = 0.011). From both clinical and cost-effectiveness perspectives, gold was the preferred and dominant strategy. Study treatment was discontinued in 23 patients (14 in the placebo group compared with 9 in the gold group; P = 0.022) due to loss to followup, adverse events, or lack of efficacy. CONCLUSION In RA patients with a suboptimal response to MTX, adding weekly IM gold causes significant clinical improvement. Adverse events were minor, and IM gold-related adverse events led to discontinuation in only 11% of the gold group over 48 weeks.
Visceral leishmaniasis in the BALB/c mouse: a comparison of the in vivo activity of five non-ionic surfactant vesicle preparations of sodium stibogluconate.

Five non-ionic surfactants (Surfactants V-IX) were screened for their ability to produce vesicles for the delivery of sodium stibogluconate. Mean vesicle diameter and antimony content were determined prior to in vivo assessment of antiparasitic activity in a mouse model of acute visceral leishmaniasis. V/D suspensions (i.e. stibogluconate loaded vesicles kept in the hydrating drug solution) were more effective against spleen, liver and bone marrow parasites than drug loaded vesicle suspensions that had unentrapped drug removed. A Surfactant IX V/D suspension was the most active antileishmanial preparation causing 74 +/- 10%, 99 +/- 1% and 38 +/- 8% suppression of liver, spleen and bone marrow parasite burdens respectively. Contrary to previous findings, a reduction in splenic and bone marrow parasite burdens was achieved using large vesicles (mean diameter > 800nm). The significance of these results is discussed.
Giant cell glioblastoma and pleomorphic xanthoastrocytoma show different immunohistochemical profiles for neuronal antigens and p53 but share reactivity for class III beta-tubulin.

CONTEXT Giant cell glioblastoma multiforme (GCGBM) and pleomorphic xanthoastrocytoma (PXA) are clinically, radiographically, and histologically distinct tumors of the central nervous system. However, they share features of gross circumscription, reticulin deposition, lymphocytic infiltrates, and prominent populations of tumor giant cells. Neuronal antigens have been detected in the neoplastic cells of PXAs, but to our knowledge have not been studied previously in GCGBMs. While TP53 is mutated in most GCGBMs, a feature usually paralleled by strong immunostaining of the protein, the expression pattern of PXAs has not been extensively studied. OBJECTIVES To compare the immunoprofiles of GCGBM and PXA with regard to neuronal antigens and p53 and to evaluate the potential diagnostic utility of such a panel. DESIGN Archival paraffin sections of 9 GCGBMs and 9 PXAs were immunostained for class III beta-tubulin, neuronal nuclear antigen, neurofilament protein, synaptophysin, glial fibrillary acidic protein, and p53. RESULTS Giant cell glioblastomas were strongly immunoreactive for class III beta-tubulin and glial fibrillary acidic protein, but showed only rare staining for the other neuronal polypeptides. In contrast, PXAs usually showed at least focal staining of individual tumor cells for most of the neuronal antigens tested. Tubulin was strongly positive in tumor giant cells and in smaller neoplastic cells of both tumor types. Double-immunolabeling revealed distinct populations of tumor cells that expressed either glial fibrillary acidic protein or tubulin and dual-labeling of individual cells in GCGBM and PXA. Strong p53 staining was observed in many tumor cells in 5 of 8 GCGBMs tested, while staining for this antigen was negative or focally positive in 6 of 8 PXAs examined. CONCLUSIONS Giant cell glioblastoma multiforme and PXA show distinct patterns of immunoreactivity for neuronal antigens and p53 that may be useful diagnostically in difficult cases or in limited samples. These results provide further evidence of neuronal antigen expression by PXA.
Cloning and characterization of SRP1, a suppressor of temperature-sensitive RNA polymerase I mutations, in Saccharomyces cerevisiae

The SRP1-1 mutation is an allele-specific dominant suppressor of temperature-sensitive mutations in the zinc-binding domain of the A190 subunit of Saccharomyces cerevisiae RNA polymerase I (Pol I). We found that it also suppresses temperature-sensitive mutations in the zinc-binding domain of the Pol I A135 subunit. This domain had been suggested to be in physical proximity to the A190 zinc-binding domain. We have cloned the SRP1 gene and determined its nucleotide sequence. The gene encodes a protein of 542 amino acids consisting of three domains: the central domain, which is composed of eight (degenerate) 42-amino-acid contiguous tandem repeats, and the surrounding N-terminal and C-terminal domains, both of which contain clusters of acidic and basic amino acids and are very hydrophilic. The mutational alteration (P219Q) responsible for the suppression was found to be in the central domain. Using antibody against the SRP1 protein, we have found that SRP1 is mainly localized at the periphery of the nucleus, apparently more concentrated in certain regions, as suggested by a punctate pattern in immunofluorescence microscopy. We suggest that SRP1 is a component of a larger macromolecular complex associated with the nuclear envelope and interacts with Pol I either directly or indirectly through other components in the structure containing SRP1.
Cervical cerclage complications: eight years of experience

Objective: The aim of this study is to analyze cervical cerclage cases in our clinic retrospectively and to evaluate the complications asso- ciated with the procedure. Methods: The patients who undergone cervical cerclage opera- tion between April 2004 and December 2012 at Suleymaniye Training and Research Hospital were included in the study. The data of patients, complications of the procedure, week of gestation at delivery, delivery type and postnatal complications were ana- lyzed retrospectively. Results: Cervical cerclage suture was applied to 100 patients. While the rate of emergency cases was 8.0% (n=8), the rate of elective cases was 68% (n=68) and the rate of prophylactic cases was 24% (n=24). Mean week of gestation was 33.55±6.06. While 31% (n=31) of the deliveries were preterm, 69% (n=69) of them were term. Mean delivery week was 27.8±7.9 in emergency group, 33.9±5.8 in elective group and 34.2±5.1 in prophylactic group. The membranes were ruptured (PPROM) after cerclage in 10 (10%) patients. While preg- nancy was lost in nine patients at the early period after the rupture of membrane, pregnancy was lost in one patient after three weeks. One of these patients developed fever and chorioamnionitis. When the complications were analyzed, it was seen that the rate of compli- cations in emergency group was statistically and significantly higher than two other groups. (p=0.005 and p<0.1). Conclusion: The rates of preterm labor were relatively higher in our cases, and other complications were seen rarely (chorioamnioni- tis, fever, cervical laceration). Compared to elective and prophylac- tic cerclage groups, the rate of preterm labor and complications were significantly higher in the emergency cerclage group.
Decrease in the number of deaths from secondary amyloidosis in patients with juvenile rheumatoid arthritis.

OBJECTIVE The analysis of the mortality rate and causes of death of all Finnish patients with juvenile rheumatoid arthritis (JRA) in 1969-1979 and 1980-1990. METHODS Cases with JRA and deaths at the age of 24 years or younger were identified by using the nationwide register of persons entitled to free medication because of rheumatoid arthritis and allied diseases. Causes of death are based on autopsy in all but 4 of 47 cases. RESULTS There were 24 deaths during 1969-1979 and 23 during 1980-1990. The expected numbers of deaths were 8.9 and 9.5, giving a standardized mortality rate of 2.7 and 2.4, respectively. Secondary amyloidosis was the direct cause of death in 10 patients during the earlier period and in 4 patients during the later period. CONCLUSIONS The decrease in amyloidosis as a cause of death may be explained by an increased use of cytotoxic drug treatment for severe JRA in the early 1980s. Deaths from violence have increased.
Two years of clinical experience with biliopancreatic bypass for obesity.

Most complications of jejunoileal bypass for morbid obesity (1-3) may be referred to two main defects ofthe classic operation. The first defect is the mechanism of malabsorption itself, based on the short bowel and on the interruption of enterohepatic bile salt circulation. The result is an indiscriminate malabsorption, with loss of great amounts of bile acids into the colon and, consequently, diarrhea, electrolyte imbalance, urinary and biliary calculi and, perhaps, liver injury. The second defect is the presence of a long section of excluded intestinal tract, with the risk of intussusception and the consequences of peptic ulcer due to gastric hypersecretion and, perhaps, of polyarthritis and of liver injury. Complications of jejunoileal bypass then should not occur after an operation that, without leaving any blind intestinal loop and without interfering with enterohepatic bile salt circulation, can induce a malabsorption selective for foodstuffs with caloric value. Bilio-pancreatic bypass is carried out by performing a two-thirds distal gastrectomy and dividing the small bowel at a certain distance from the ligament of Treitz. A gastroenteroanastomosis is then made by using the distal end of the transected bowel, while the proximal end is anastomosed to the side of the distal ileum (Fig. 1).
Effects of morphine, butorphanol, buprenorphine, and U50488H on the minimum alveolar concentration of isoflurane in cats.

OBJECTIVE To determine whether opioids with varying interactions at receptors induce a reduction in minimum alveolar concentration (MAC) of isoflurane in cats. ANIMALS 12 healthy, female, spayed cats. PROCEDURE Cats were anesthetized with isoflurane and instrumented to allow collection of arterial blood and measurement of arterial blood pressure. Each drug was studied separately, and for each drug cats were randomly allocated to receive 2 doses. The drugs studied were morphine (0.1 or 1.0 mg/kg), butorphanol (0.08 or 0.8 mg/kg), buprenorphine (0.005 and 0.05 mg/kg), and U50488H (0.02 and 0.2 mg/kg). All drugs were diluted in 5 ml of saline (0.9% NaCl) solution and infused IV for 5 minutes. The MAC of isoflurane was determined in triplicate, the drug administered, and the MAC of isoflurane redetermined for a period of 3 hours. RESULTS All drugs had a significant effect on MAC over time. With morphine only, the effect on MAC over time was different between doses. The greatest mean (+/- SD) reductions in MAC of isoflurane in response to morphine, butorphanol, buprenorphine, and U50488H administration were 28 +/- 9, 19 +/- 3, 14 +/- 7, and 11 +/- 7%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Morphine (1.0 mg/kg) and butorphanol (0.08 and 0.8 mg/kg) induced significant reductions in MAC of isoflurane that were considered clinically important. Although significant, reductions in MAC of isoflurane induced by morphine (0.1 mg/kg), buprenorphine (0.005 and 0.05 mg/kg), and U50488H (0.02 and 0.2 mg/kg) were not considered clinically relevant because they fell within the error of the measurement technique. Administration of morphine or butorphanol decreases the need for potent inhalant anesthetics in cats and could potentially be beneficial in combination with inhalants.
Randomized Trials on Consider This, a Tailored, Internet-Delivered Smoking Prevention Program for Adolescents

The Internet may be an effective medium for delivering smoking prevention to children. Consider This, an Internet-based program, was hypothesized to reduce expectations concerning smoking and smoking prevalence. Group-randomized pretest-posttest controlled trials were conducted in Australia (n = 2,077) and the United States (n = 1,234) in schools containing Grades 6 through 9. Australian children using Consider This reported reduced 30-day smoking prevalence. This reduction was mediated by decreased subjective norms. The amount of program exposure was low in many classes, but program use displayed a dose-response relationship with reduced smoking prevalence. American children only reported lower expectations for smoking in the future. Intervening to prevent smoking is a challenge, and this data suggest small benefits from an Internet-based program that are unlikely to be of practical significance unless increased by improved implementation. Implementation remains the major challenge to delivering interventions via the Internet, both for health educators and researchers.
Proprioception after total knee arthroplasty: A comparison with clinical outcome

We determined proprioception in replaced and unreplaced arthrotic knees by measuring threshold levels for the perception of passive knee motion. In addition, results of these proprioception measurements were compared with the clinical outcomes in patients with a total knee arthroplasty. Threshold detection levels were significantly higher in the replaced than in the unreplaced knees. Moreover, detection-failure rates were significantly higher in the replaced knees as well. In contrast to this diminished movement sense in the replaced knees, clinical examination of these knees showed good or excellent outcome in all cases. A correlation between the clinical outcome and the ability to perceive passive motion in either patient group could not be found. We hypothesize that our findings may be due to the operative removal of intraarticular receptor-rich tissue that is affected by arthrosis. This would not only contribute to marked clinical improvements but also to a significant decrease in proprioception.
NBTI lifetime prediction in SiON p-MOSFETs by H/H2 Reaction-Diffusion(RD) and dispersive hole trapping model

IDLIN shift due to NBTI is measured using UF-OTF IDLIN method in PNO, RTNO and RTNO+PN SiON p-MOSFETs having a wide range of EOT and %N. Time evolution of IDLIN shift at different stress EOX and T is modeled from ultra-short to long stress time using non-dispersive H/H<inf>2</inf> RD model governed N<inf>IT</inf> and dispersive N<inf>h</inf> components. N<inf>IT</inf> and N<inf>h</inf> model parameters show consistent E<inf>OX</inf> and T dependent behavior across all devices. Finally, extrapolated tt<inf>F</inf> values are obtained for different E<inf>OX</inf> from conventional power-law fit and the proposed model, and are compared across different measurement delay. Inconsistencies associated with conventional power-law fit extrapolation method are highlighted, which justifies the use of proposed model.
Disparity, Diversity, and Duplications in the Caryophyllales

The role whole genome duplication (WGD) plays in the history of lineages is actively debated. WGDs have been associated with advantages including superior colonization, various adaptations, and increased effective population size. However, the lack of a comprehensive mapping of WGDs within a major plant clade has led to uncertainty regarding the potential association of WGDs and higher diversification rates. Using seven chloroplast and nuclear ribosomal genes, we constructed a phylogeny of 5,036 species of Caryophyllales, representing nearly half of the extant species. We phylogenetically mapped putative WGDs as identified from analyses on transcriptomic and genomic data and analyzed these in conjunction with shifts in climatic niche and lineage diversification rate. Thirteen putative WGDs and twenty-seven diversification shifts could be mapped onto the phylogeny. Of these, four WGDs were concurrent with diversification shifts, with other diversification shifts occurring at more recent nodes than WGDs. Five WGDs were associated with shifts to colder climatic niches. While we find that many diversification shifts occur after WGDs it is difficult to consider diversification and duplication to be tightly correlated. Our findings suggest that duplications may often occur along with shifts in either diversification rate, climatic niche, or rate of evolution.
The Regulatory/Cytotoxic Graft-Infiltrating T Cells Differentiate Renal Allograft Borderline Change From Acute Rejection

The interpretation of cellular infiltrate from renal transplant recipients with borderline (BL) changes is still a challenging problem. To analyze the immune phenotype of such infiltrate, we quantified the mRNA expression of Foxp3 and interleukinL-10 and granzyme B (GB) in 15 kidney biopsies with BL changes. Controls were patients presenting type IA acute rejection and nonrejecting patients. Only levels of GB mRNA correlated significantly with response to antirejection therapy. Levels of Foxp3 mRNA in BL changes were intermediate between type IA acute rejection and nonrejecting controls. To determine the balance of alloagressive to graft-protecting T cells, we quantified the Foxp3/GB ratio. BL changes T cells infiltrate expressed a significantly higher Foxp3/GB ratio than that in IA acute rejection. These results suggest that T cell infiltrate from BL change exhibit a tolerogenic rather than a cytotoxic phenotype.
Goblet Cell Types in Intestine of Tiger Barb and Black Tetra (Cyprinidae, Characidae: Teleostei)

Histochemical properties of goblet cells in intestine of a stomach‐less teleost, tiger barb (Puntius tetrazona), and a stomach‐containing teleost, black tetra (Gymnocorymbus ternetzi), are described and compared. The intestine goblet cells were mostly wide in both species, but in tiger barb, some of them were markedly thinner. In black tetra, all the intestine goblet cells displayed magenta colour after PAS, whereas in the tiger barb, only the thinner goblet cells displayed such affinity. The latter cell type was coloured strongly magenta when the tissue was treated with alcian blue (pH 2.5) followed by PAS, whereas the wide goblet cells in tiger barb and all goblet cells in black tetra displayed mainly a blue colour after such treatment. Further, the goblet cells in both species were coloured cleanly blue after high iron diamine followed by alcian blue (pH 2.5). The intestine goblet cells in both species displayed a moderate affinity to WGA and concanavalin A lectins and no affinity to DBA. Most of the goblet cells displayed no affinity to PNA, but some of them in the tiger barb displayed a moderate or strong affinity to this lectin. The affinity to WGA was somewhat strengthened after pre‐treatment with neuraminidase. These results suggest that tiger barb contains two types or variants of intestinal goblet cells: high numbers of wide cells filled by acidic, non‐sulphated mucin and some thinner cells filled by neutral mucin. The intestine goblet cells in black tetra were filled by variable amounts of neutral and acidic mucin, but the total number of such cells is much less than in tiger barb. The present lectin and neuraminidase results suggest that the intestinal mucins in both species contain significant amounts of N‐acetylglucosamine, sialic acid and glucose/mannose, but seem to lack N‐acetylgalactosamine. However, some of these cells in tiger barb contain moderate to large amounts of galactose. Together, these results suggest significant species‐specific features of the intestine goblet cells and mucin types in tiger barb and black tetra. In conclusion, the present results suggest that the diet and feeding habits in stomach‐less teleosts compared with stomach‐containing teleosts, greatly influence the number of intestine goblet cells and type of mucin in these cells.