Miracle-dz/UniFAR-FTUs huggingface dataset:
MINERALOCORTICOID RECEPTORS

Mineralocorticoid receptors (MR) are found not only in classical aldosterone target tissues (kidney, colon, parotid) but also non-epithelial tissues such as hippocampus. In addition, MR have equivalent affinity for cortisol (in the rat corticosterone) as for aldosterone, which circulates at very much lower levels. Aldosterone occupancy of MR in physiologic target tissues but not hippocampus reflects the activity in these tissues of the enzyme llμ-hydroxysteroid dehydrogenase (11HSD), which converts cortisol and corticosterone to receptor-inactive 11-keto congeners; aldosterone escapes equivalent metabolism as its C11-OH is stably cyclized with the very reactive aldehyde group at C18. Studies currently in progress in this area include (1) characterization of the NAD-dependent 11HSD species (11HSD2) operant in renal distal tubule distinct from the cloned enzyme (11 ESDI) expressed in proximal tubule, testis, liver and lung; (2) exploration of the physiologic roles of ‘MR’ in hippocampus, where they are occupied by cortisol/corticosterone, and function as high-affinity glucocorticoid receptors; (3) recognition of the basis for MR and GR specificity at the transcriptional level, by oncogene product binding and/or response element differences; (4) investigation of the evolutionary basis for non-selective MR by comparative studies on guinea pigs and hamsters, and (5) further studies of the molecular mechanisms underlying the resistance syndrome of pseudohypoaldosteronism, in which independent laboratories have failed to find sequence abnormalities in the coding region of MR cDNA in different kindred with absent receptor binding.
The Fuzzy Frontier between Subjective Memory Complaints and Early Dementia

Background: Mild cognitive decline is frequent in the elderly population. Whether it is related to normal aging or an early phase of evolving dementia is difficult to ascertain with confidence, and accordingly there is a lack of consensus guidelines for diagnosis and therapy in such patients. We assessed the variability with which memory clinics deal with this problem in everyday practice. Methods: We sent three fictitious case histories to all 85 German memory clinics that contained the results of clinical examination and neuropsychological test scores and asked for diagnosis and patient management. Patient 1 presented with complaints of mental decline but normal neuropsychological and neurological evaluation and normal daily living activities. Patient 2 came in as a control subject for a study and had impaired test scores but preserved daily living activities, and patient 3 was brought in by relatives with slight impairment of daily living activities and decline in some neuropsychological test scores but relatively spared memory scores. Results: Most of the 51 respondents agreed in recommending further neuropsychological testing, a basic laboratory work-up, brain imaging, and a re-examination after 3–6 months. Yet, there was a high variability in the diagnostic terms used, in the additional diagnostic procedures proposed, and in the recommendations concerning therapeutic intervention and driving. Conclusions: The results reveal a need of practice guidelines for the use of diagnostic terms, therapeutic interventions and driving recommendations in patients between subjective memory complaints and early dementia.
Method for Reducing Uncertainties of Predictive Range Estimation Algorithms in Electric Vehicles

This paper investigates problems that arise with the availability of trip-based range estimation when displaying it as an alternative or in addition to history-based range estimation data in the vehicle and proposes a method to significantly improve the overall usability and reliability of a comprehensive range display system. It is demonstrated that even with the use of a perfect trip-based energy prediction to a given destination, the displayed range of an electric vehicle can still vary significantly. The main cause for these uncertainties is discussed and a new method to improve the overall performance of a range estimation system by using trip-based energy consumption to virtually preadapt the history-based range estimation algorithm is proposed. The results of multiple simulations are used to illustrate the function of the proposed method and demonstrate the potential for improvements in future range estimation algorithms.
Prevalence and risk factors for lens opacities in Nigeria: results of the national blindness and low vision survey.

PURPOSE Investigate prevalence and risk factors for lens opacities among a nationally representative sample of Nigerians aged ≥ 40 years. METHODS Across 305 clusters, 13,591 adults were examined. Every seventh participant (n = 1722) was sampled systematically and examined in detail, including lens opacity grading. Lenses were examined at the slit-lamp with pupil dilation and graded using the World Health Organization (WHO) system. Significant opacities were defined as nuclear, cortical, or posterior subcapsular opacity of WHO grade >1, or hyper/mature cataract. The category "Any Opacity" included hyper/mature opacity and aphakia/pseudophakia/couching. Data were collected on sociodemographic and environmental factors, including height and weight. RESULTS A total of 1631/1722 (95%) in the normative subsample had their lenses graded. Prevalence of "Any Opacity" was 19.8% (95% confidence interval [CI]: 7.9-21.7) the prevalence of all types increased with age, and was higher in females and those not literate. Prevalence of nuclear, cortical, and posterior subcapsular were 8.8% (95% CI: 7.5-10.1); 11.7% (95% CI: 10.0-13.3); and 2.9% (95% CI: 2.1-3.8), respectively. In multivariate analysis, age was an independent risk factor for all types. Nuclear opacity was also associated with female sex (odds ratio [OR] 2.4; 95% CI: 1.5-3.6); lean body mass index (BMI; OR 2.0; 95% CI: 1.1-3.5); and the Igbo ethnic group (OR 4.4; 95% CI: 2.3-8.4). Cortical opacity was also associated with female sex (OR 2.1; 95% CI: 1.5-3.0) and the Yoruba (OR 0.45; 95% CI: 0.3-0.8), but not with BMI. "Other Lens Opacities," which includes couching, was significantly lower in the Guinea savannah region (OR 0.4; 95% CI: 0.2-0.9), while living in rain forest areas was protective for posterior subcapsular cataracts (OR 0.3; 95% CI: 0.1-0.7). CONCLUSIONS A fifth of Nigerian adults have some degree of lens opacity. Further studies are needed to investigate the role of ethnicity, climate variables, and other risk factors.
[Community effectiveness of vaccines against infectious parotiditis (mumps). Report of cases].

BACKGROUND In our country, there are two types of infectious mumps vaccines available. In recent times, doubts have been raised regarding the overall effectiveness of these vaccines and the comparative effectiveness of the two strains (Rubini strain and Jeryl Lynn strain). In the "East Seville" Primary Care district, 245 cases were reported in 1997 (90.1 cases per 100,000 inhabitants). This study is aimed at taking advantage of the outbreak of cases of mumps to evaluate affected populations and comparative incidence according to type of vaccines given during childhood. METHODS Descriptive analysis of the cases (age, territorial spread, inoculation history') and trend analysis (annual incident rates) within this health care district and the surrounding area. The overall effectiveness of the mumps vaccines. The case incidence rates among those inoculated with Rubini strain and those inoculated with Jeryl Lynn strain are also estimated. RESULTS The highest rates of incidence are found among children in the 1-4 age range. Overall effectiveness rates for these vaccines have been estimated. A significantly higher rate of infection has been found among the children inoculated with Rubini strain than those inoculated with the Jeryl Lynn strain (relative risk of 6.5 with a Confidence Interval of 95% 3.6-11.8). CONCLUSIONS The effectiveness which follows from this study does not seem as good as the theoretical effectiveness anticipated for the mumps vaccines. It thus seems advisable for other case studies to be conducted by types of vaccines used. The data to be furnished by means of sero-epidemiological studies are also of major interest.
Melatonin inhibits expression of the inducible isoform of nitric oxide synthase in murine macrophages: role of inhibition of NFκB activation

The role of melatonin as an immuno‐modulator is well established. Recent reports showed that melatonin exerts protective effects in septic and hemorrhagic shock and in inflammation. The expression of the inducible isoform of nitric oxide synthase (iNOS) makes an important contribution to the pathophysiology of shock and inflammation. We studied, in cultured murine macrophages, the role of melatonin in the regulation of the expression of iNOS and defined the mode of melatonin's action. Our results show that melatonin, at 1 μM‐1 mM, decreased the production of nitrite/nitrate (the breakdown products of NO) as well as the production of 6‐keto‐prostaglandin F1α (the major stable breakdown product of prostacyclin) in macrophages stimulated with bacterial lipopolysaccharide (10 μg/ml). We observed that melatonin reduces iNOS steady‐state mRNA levels and iNOS protein expression in the same concentration range (1 |mM‐1 mM). Melatonin, up to 10 mM, exerted only a slight direct inhibitory effect on iNOS activity. Using iNOS promoter‐luciferase constructs, we found that melatonin inhibits iNOS promoter activation. Inhibition of iNOS expression was associated with inhibition of activation of the transcription factor nuclear factor kappa B (NFκB). We conclude that melatonin inhibits NO production in immunostimulated macrophages mainly by inhibiting the expression of iNOS. This is due to inhibition of iNOS transcription, in part through inhibition of NFκB activation. Inhibition of iNOS‐derived NO production by melatonin may contribute to the anti‐inflammatory effects of this pineal secretory product. —Gilad, Eli, Wong, H. R. , Zingarelli, B. , Virág, L. , O'connor, M. , Salzman, A. L. , Szabó, C. Melatonin inhibits expression of the inducible isoform of nitric oxide synthase in murine macrophages: role of inhibition of NFκB activation. FASEB J. 12, 685–693 (1998)
Sensitive Balance of Suppressing and Activating Effects of Mesenchymal Stem Cells on T-cell Proliferation

The human leukocyte antigen–independent immune-modulatory potential of human mesenchymal stem cells (hMSC) makes them a promising candidate for clinical cell therapy. A better understanding of their “immune-privileged” status is therefore of high priority. Here we used Ki-67-antigen staining to estimate T-cell alloreactivity in mixed lymphocyte cultures in the presence of hMSC as second or third party. We found that the allostimulatory activity of mesenchymal stem cells (MSC) leading to an increased T-cell proliferation and interleukin-2 secretion is measurable only at low MSC/effector ratios (≤0.1:1). Moreover, this stimulating effect could be efficiently suppressed by MSC-conditioned medium. This suggests that the “immune-privileged” status of MSC exists only when MSC-mediated downregulation of immune cell activation can overrule their own allostimulatory potential. Thus the “immune-privileged” state of MSC represents a sensitive balance of suppressing and activating effects, which should be considered in a clinical setting with limited cell amounts.
Interaction of Endogenous Growth Hormone, Cortisol, and Catecholamines with Blood Glucose in Children with Brittle Diabetes Mellitus

Extract: Hormonal balance was studied in eight insulin-treated diabetic children who had excessive glycosuria. Glucose, growth hormone, and cortisol in plasma were determined every 0.5 hr for 48 hr. Total catecholamines and glucose were measured and tests for ketones done in 2-hourly collections of urine.Intermittent hypoglycemia as low as 20 mg/100 ml and swings of the blood sugar curve by 200–300 mg/100 ml within 2–4 hr were documented in most patients.Peaks of growth hormone concentration in plasma (8–78 ng/ml) followed almost every sharp fall in blood glucose; these peaks were usually followed by abrupt rises of glucose and prolonged hyperglycemia.Cortisol concentration was usually within the high normal range; there was no consistent relationship to the concentration of glucose.Urinary excretion of catecholamines in most patients was between 1 and 6 μg/hr; three patients excreted up to 8–23 μg/hr during short periods and up to 190 μg in 24 hr. The causes for the high excretion of catecholamines are unknown and may not have included hypoglycemia.Speculation: Excessive production of growth hormone and possibly other hormonal antagonists of insulin may be provoked by hypoglycemia and other physiologic stresses in diabetic children. The resulting hyperglycemia may prompt the administration of increasing doses of insulin which, in turn, contribute to a vicious cycle of hypoglycemia alternating with hyperglycemia.
Computer Science Security Research and Human Subjects: Emerging Considerations for Research Ethics Boards

This paper explores the growing concerns with computer science research, and in particular, computer security research and its relationship with the committees that review human subjects research. It offers cases that review boards are likely to confront, and provides a context for appropriate consideration of such research, as issues of bots, clouds, and worms enter the discourse of human subjects review.
Incidence and risk factors for stroke in pregnancy and the puerperium.

OBJECTIVE To estimate the incidence, mortality, and risk factors for pregnancy-related stroke in the United States. METHODS The Nationwide Inpatient Sample from the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality, for the years 2000-2001 was queried for International Classification of Diseases, 9th Revision, codes for stroke among all pregnancy-related discharges. RESULTS A total of 2,850 pregnancy-related discharges included a diagnosis of stroke for a rate of 34.2 per 100,000 deliveries. There were 117 deaths or 1.4 per 100,000 deliveries. Twenty-two percent of survivors were discharged to another facility. The risk of stroke increased with age, particularly ages 35 years and older. African-American women were at a higher risk, odds ratio (OR) 1.5 (95% confidence interval [CI] 1.2-1.9). Medical conditions that were strongly associated with stroke included migraine headache, OR 16.9 (CI 9.7-29.5), thrombophilia, OR 16.0 (CI 9.4-27.2), systemic lupus erythematosus, OR 15.2 (CI 7.4-31.2), heart disease, OR 13.2 (CI 10.2-17.0), sickle cell disease, OR 9.1 (CI 3.7-22.2), hypertension, OR 6.1(CI 4.5-8.1) and thrombocytopenia, OR 6.0 (CI 1.5-24.1). Complications of pregnancy that were significant risk factors were postpartum hemorrhage, OR 1.8 (CI 1.2-2.8), preeclampsia and gestational hypertension, OR 4.4 (CI 3.6-5.4), transfusion OR 10.3 (CI 7.1-15.1) and postpartum infection, OR 25.0 (CI 18.3-34.0). CONCLUSION The incidence, mortality and disability from pregnancy related-stroke are higher than previously reported. African-American women are at an increased risk, as are women aged 35 years and older. Risk factors, not previously reported, include lupus, blood transfusion, and migraine headaches. Specific strategies, not currently employed, may be required to reduce the devastation caused by stroke during pregnancy and the puerperium. LEVEL OF EVIDENCE II-2.
Dryocrassin ABBA Induces Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells Through a Caspase-Dependent Mitochondrial Pathway.

BACKGROUND Biological and pharmacological activities of dryocrassin ABBA, a phloroglucinol derivative extracted from Dryopteris crassirhizoma, have attracted attention. In this study, the apoptotic effect of dryocrassin ABBA on human hepatocellular carcinoma HepG2 cells was investigated. MATERIALS AND METHODS We tested the effects of dryocrassin ABBA on HepG2 in vitro by MTT, flow cytometry, real-time PCR, and Western blotting. KM male mice were used to detect the effect of dryocrassin ABBA on H22 cells in vivo. RESULTS Dryocrassin ABBA inhibited the growth of HepG2 cells in a concentration-dependent manner. After treatment with 25, 50, and 75 μg/mL dryocrassin ABBA, the cell viability was 68%, 60% and 49%, respectively. Dryocrassin ABBA was able to induce apoptosis, measured by propidium iodide (PI)/annexin V-FITC double staining. The results of real-time PCR and Western ting showed that dryocrassin ABBA up-regulated p53 and Bax expression and inhibited Bcl-2 expression which led to an activation of caspase-3 and caspase-7 in the cytosol, and then induction of cell apoptosis. In vivo experiments also showed that dryocrassin ABBA treatment significantly suppressed tumor growth, without major side effects. CONCLUSIONS Overall, these findings provide evidence that dryocrassin ABBA may induce apoptosis in human hepatocellular carcinoma cells through a caspase-mediated mitochondrial pathway.
The Multi-Copy Mouse Gene Sycp3-Like Y-Linked (Sly) Encodes an Abundant Spermatid Protein That Interacts with a Histone Acetyltransferase and an Acrosomal Protein1

Abstract Deletion analysis has established that genes on the Y chromosome are essential for normal sperm production in humans, mice, and Drosophila. In mice, long-arm deletions have an impact on spermiogenesis, with the most extensive deletions resulting in severe sperm head malformations and infertility. Intriguingly, smaller deletions are compatible with fertility but result in a distorted sex ratio in favor of females, and recently it was found that Y long-arm deletions are also associated with a marked upregulation of several X-encoded and Y-encoded spermatid-expressed genes. The mouse Y long arm encodes a number of distinct transcripts, each of which derives from multiple gene copies. Of these multicopy genes, the recently described Sly has been favored as the gene underlying the spermiogenic defects associated with Y long-arm deletions. To assess the candidacy of Sly, the expression of this gene was examined in the testis at the transcript and protein levels. Sly is transcribed after the first meiotic division in secondary spermatocytes and round spermatids and encodes two transcript variants, Sly_v1 and Sly_v2 (proteins referred to as SLY1 and SLY2). We raised an antibody against SLY1 which detected the protein in round and early elongating spermatids, where it is predominantly cytoplasmic. Yeast two-hybrid and coimmunoprecipitation studies demonstrated that SLY1 interacts with the acrosomal protein DKKL1, the histone acetyltransferase KAT5 (also known as TIP60), and the microtubule-associated protein APPBP2. Together, these data suggest SLY1 may be involved in multiple processes during spermiogenesis, including the control of gene expression and the development or function of the acrosome.
Room Temperature Si–Si Direct Bonding Technique Using Velcro-Like Surfaces

Si surfaces were functionalized by anodization to create nanoneedles. Such surfaces allow Velcro-like bonding at room temperature with large bond strength for such functionalized surfaces. In addition, Velcro-like bonding has a capability of multiple bonding and debonding of the same surfaces analogous to the Velcro principle. To employ such surfaces and the bonding technique in wafer or chip bonding or in integrated circuit packaging applications, understanding the fabrication and the bonding mechanism between such surfaces is very crucial. This paper presents a simple silicon-based technology to generate Velcro-like surfaces using the anodization of Si wafer in a hydrofluoric acid-based electrolyte, and describes the bond strength between such surfaces using the van der Waals force approach. The capability of the technique and the validity of the proposed van der Waals force model are shown by comparison with the experimental results.
NQO1-Mediated Tumor-Selective Lethality and Radiosensitization for Head and Neck Cancer

Ionizing radiation (IR) is a key therapeutic regimen for many head and neck cancers (HNC). However, the 5-year overall survival rate for locally advanced HNCs is approximately 50% and better therapeutic efficacy is needed. NAD(P)H:quinone oxidoreductase 1 (NQO1) is overexpressed in many cancers, and β-lapachone (β-lap), a unique NQO1 bioactivatable drug, exploits this enzyme to release massive reactive oxygen species (ROS) that synergize with IR to kill by programmed necrosis. β-Lap represents a novel therapeutic opportunity in HNC leading to tumor-selective lethality that will enhance the efficacy of IR. Immunohistochemical staining and Western blot assays were used to assess the expression levels of NQO1 in HNC cells and tumors. Forty-five percent of endogenous HNCs expressed elevated NQO1 levels. In addition, multiple HNC cell lines and tumors demonstrated elevated levels of NQO1 expression and activity and were tested for anticancer lethality and radiosensitization by β-lap using long-term survival assays. The combination of nontoxic β-lap doses and IR significantly enhanced NQO1-dependent tumor cell lethality, increased ROS, TUNEL-positive cells, DNA damage, NAD+, and ATP consumption, and resulted in significant antitumor efficacy and prolonged survival in two xenograft murine HNC models, demonstrating β-lap radiosensitization of HNCs through a NQO1-dependent mechanism. This translational study offers a potential biomarker-driven strategy using NQO1 expression to select tumors susceptible to β-lap–induced radiosensitization. Mol Cancer Ther; 15(7); 1757–67. ©2016 AACR.
Extracellular Matrix Metalloproteinase 2 Levels Are Regulated by the Low Density Lipoprotein-related Scavenger Receptor and Thrombospondin 2*

We have recently shown that the adhesive defect observed in dermal fibroblasts derived from thrombospondin 2 (TSP2)-null mice results from an increase in matrix metalloproteinase 2 (MMP2) levels (Yang, Z., Kyriakides, T. R., and Bornstein, P. (2000) Mol. Biol. Cell 11, 3353–3364). Adhesion was restored by replacement of TSP2 and by inhibitors of MMP2 activity. In pursuing the observation that TSP2 and MMP2 interact, we now demonstrate that this interaction is required for optimal clearance of extracellular MMP2 by fibroblasts. Since TSP2 is known to be endocytosed by the scavenger receptor, low density lipoprotein receptor-related protein (LRP), we determined whether interference with LRP function affected fibroblast adhesion and/or extracellular MMP2 levels. Addition of heparin, which competes for the binding of TSP2 to LRP coreceptor proteoglycans, inhibited adhesion of control but not TSP2-null cells, and a blocking antibody to LRP as well as the LRP inhibitor, receptor-associated protein, also inhibited adhesion and increased MMP2 levels only in control fibroblasts. TSP2 did not inhibit active MMP2 directly and did not inhibit the activation of pro-MMP2. Finally, the internalization of 125I-MMP2 was reduced in TSP2-null compared with control fibroblasts. We propose that clearance of MMP2-TSP2 complexes by LRP is an important mechanism for the regulation of extracellular MMP2 levels in fibroblasts, and perhaps in other cells. Thus, some features of the phenotype of TSP2-null mice, such as abnormal collagen fibrillogenesis, accelerated wound healing, and increased angiogenesis, could result in part from increased MMP2 activity.