Miracle-dz/UniFAR-FTUs huggingface dataset:
Availability of PSC833, a substrate and inhibitor of P-glycoproteins, in various concentrations of serum.

BACKGROUND P-glycoproteins are membrane-associated transporters that can render cells resistant to a variety of chemotherapeutic drugs. Reversal agents are (preferably nontoxic) drugs that can inhibit these P-glycoproteins and thereby overcome multidrug resistance. PSC833, a cyclosporin A analog, is a reversal agent that has shown potential in in vitro experiments and in clinical trials. We tested PSC833 to determine whether it is a transported substrate of human and murine P-glycoproteins associated with multidrug resistance (encoded by the human MDR1 gene and its murine homolog, mdr1a) and whether it can completely inhibit these P-glycoproteins under simulated in vivo conditions. METHODS Monolayers of polarized LLC-PK1 pig kidney cells transfected with complementary DNA containing either MDR1 or mdr1a sequences were used to measure the directional transport of P-glycoprotein substrates under various serum conditions. RESULTS In contrast to two previous studies, we found that PSC833 is transported by both the MDR1 and the mdr1a P-glycoproteins, albeit at a low rate. PSC833 has a very high affinity for the MDR1 P-glycoprotein, and its Michaelis constant (Km) for transport is 50 nM, fourfold lower than for cyclosporin A. Inhibition of drug transport by PSC833 is approximately eightfold less effective in 100% fetal bovine serum than in tissue culture medium containing 10% serum. The concentration of PSC833 necessary to fully inhibit transport of digoxin and paclitaxel (Taxol) under complete (i.e., 100%) serum conditions is higher than the plasma concentrations achieved in clinical trials. CONCLUSIONS Although PSC833 binds efficiently to the MDR1 P-glycoprotein and is released only sluggishly, the high concentrations of PSC833 necessary to inhibit this P-glycoprotein under complete serum conditions in our in vitro system suggest that it may be difficult for PSC833 alone to produce total inhibition of P-glycoprotein activity in patients.
A bacterial sensor of plant cell contact controls the transcriptional induction of Ralstonia solanacearum pathogenicity genes

The hrp genes of the plant pathogen Ralstonia solanacearum are key pathogenicity determinants; they encode a type III protein secretion machinery involved in the secretion of mediators of the bacterium–plant interaction. These hrp genes are under the genetic control of the hrpB regulatory gene, expression of which is induced when bacteria are co‐cultivated with plant cell suspensions. In this study, we used hrp–gfp transcriptional fusions to demonstrate that the expression of the hrpB and type III secretion genes is specifically induced in response to the bacterium–plant cell contact. This contact‐dependent induction of hrpB gene expression requires the outer membrane protein PrhA, but not a functional type III secretion apparatus. Genetic evidence indicates that PrhA constitutes the first example of a bacterial receptor for a non‐diffusible signal present in the plant cell wall and which triggers the transcriptional activation of bacterial virulence genes.
Sensomotorische Entwicklung im Kindesalter

Zusammenfassung Studien uber die Bedeutung der Musik in der Evolution des Menschen und der Entwicklung musikalischer Fahigkeiten bei Kindern haben sich bislang auf den melodischen Aspekt der Musik konzentriert, wahrend Untersuchungen uber den rhythmischen Aspekt der Musik vergleichsweise wenig Beachtung fanden. Erst in den letzten funfzehn Jahren wurden vermehrt Studien uber die aktive korperliche Rhythmuswahrnehmung und sensomotorischen Synchronisation mit uberraschenden Ergebnissen publiziert: beispielsweise wurde gezeigt, dass bereits Neugeborene Rhythmus wahrnehmen und einen rhythmischen Puls antizipieren konnen. Kleinkinder konnen daruber hinaus aus einem rhythmischen Puls akzentuierte Schlage und somit einen Takt heraushoren, eine erforderliche Voraussetzung, die Kinder zum Tanzen befahigt. Eltern beobachten haufig, dass sich ihre Kinder schon im Kleinkindalter spontan zu einem auseren Rhythmus koordiniert bewegen. Konstanz und Zeitpunkt des Auftretens rhythmischer Bewegungen bei Kleinkindern und die zeitlichen Beziehung zu anderen Indikatoren einer gesunden fruhkindlichen Entwicklung wurden jedoch bislang nicht systematisch untersucht. In einer kulturubergreifenden Studie haben wir Eltern von 1023 gesunden Kindern sowie Eltern von 100 Kindern mit Entwicklungsstorungen mittels eines standardisierten Fragebogens befragt. Ziel war Erkenntnisse uber die Haufigkeit des spontanen individuellen und gemeinschaftlichen Tanzverhaltens, deren zeitlichen Auftretens im Laufe der fruhkindlichen Entwicklung, eventuelle ausere Einflussfaktoren sowie uber Zusammenhange bei Verspatung oder Nicht-Auftreten dieser Fahigkeiten zu gewinnen. Die Ergebnisse unserer Studie belegen fur das untersuchte multi-ethnische Kollektiv, dass sich annahrend (1008 der 1016 auswertbaren Fragebogen [99.21%]) alle gesunden Kinder unabhangig von auseren Einflussfaktoren wie ethnischer Herkunft oder kulturellen Gegebenheiten sehr fruh spontan in Einklang mit einem auseren Rhythmus bewegten. Bei mehr als 63,82% (598/937) der Kinder trat dieses Verhalten sogar vor dem Sprechen des ersten Worts und vor dem Gehen der ersten Schritte auf. Bei Kindern mit Entwicklungsstorungen trat dieses Verhalten durchschnittlich neun Monate spater und in 15% (15/100) uberhaupt nicht auf (gesunde vs. Kinder mit Entwicklungsstorungen; p Die Ergebnisse dieser Arbeit legen nahe, dass das Verhalten sich spontan zu einem Rhythmus zu bewegen bei Kleinkindern angeborenen ist. Das Fehlen oder verspatete Auftreten dieses Verhaltens kann somit hingegen als Warnsignal fur eine mogliche Storung oder Verzogerung der Entwicklung der kindlichen Sensomotorik interpretiert werden.
Expression and localization of translationally controlled tumor protein in rat urinary organs

This study describes the very first assessment of the expression and localization of translationally controlled tumor protein (TCTP) in adult rat urinary organs. TCTP expression levels in kidneys, urinary bladder, and urethra were evaluated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS–PAGE) and Western blotting, and its cellular localization was examined immunohistochemically in paraffin sections of various urinary organs. TCTP was found in all urinary organs. Its expression was high in the urethra and low in the bladder. TCTP was localized in glomerular podocytes, epithelium of proximal and distal renal tubules, in the loop of Henle, and in the transitional epithelium of the bladder and urethra, mostly in basal cell layers). The subcellular localization of TCTP in these urinary organs was cytoplasmic. These findings suggest that TCTP may be involved in urine formation and excretion. Microsc. Res. Tech. 2012. © 2012 Wiley Periodicals, Inc.
HUBUNGAN ANTARA PERAN PENYULUH DAN ADOPSI TEKNOLOGI OLEH PETANI TERHADAP PENINGKATAN PRODUKSI PADI DI KABUPATEN TASIKMALAYA

Saat ini sentra pengembangan produksi padi di jalur pantai utara, namun ke depan ada pemikiran untuk mengembangkan peningkatan produksi padi di daerah selatan, diantaranya adalah di Kabupaten Tasikmalaya. Dalam pelaksanaan tugas, penyuluh pertanian di Tasikmalaya dihadapkan pada masalah kelembagaan, karena belum memiliki Badan Pelaksana Penyuluhan, dan masih bergabung dengan Dinas Pertanian dan Dinas Peternakan. Tujuan yang ingin diperoleh dari penelitian ini adalah: (1) Mengetahui hubungan antara peran penyuluh dengan peningkatan produksi padi, (2) Mengetahui hubungan antara adopsi teknologi oleh petani dengan peningkatan produksi padi, dan (3) Mengetahui peran penyuluh dan adopsi teknologi oleh petani dalam peningkatan produksi padi. Penelitian ini dilaksanakan pada Bulan April sampai dengan September 2009 di Kabupaten Tasikmalaya. Populasi dari penelitian ini adalah petani padi yang telah berusaha tani minimal 2 tahun di Kabupaten Tasikmalaya. Sampel penelitian adalah petani padi sebanyak 30 orang yang dipilih berdasarkan snowball sampling. Variabel dan Indikator Penelitian adalah peran penyuluh (X1), adopsi teknologi oleh petani (X2) dan Peningkatan produksi (Y). Untuk analisis, dilakukan uji korelasi dan regresi terhadap variabel tersebut. Hasil yang diperoleh dari penelitian ini adalah: (1) Peran penyuluh di Kabupaten Tasikmalaya tidak berkontribusi dan tidak berpengaruh terhadap peningkatan produksi padi (2) Adopsi teknologi oleh petani di Kabupaten Tasikmalaya tidak berpengaruh terhadap peningkatan produksi padi, dan (3) Peran penyuluh dan adopsi teknologi di Kabupaten Tasikmalaya secara bersama-sama bersinergi meningkatkan produksi padi.
Sarilumab improves patient-reported outcomes in rheumatoid arthritis patients with inadequate response/intolerance to tumour necrosis factor inhibitors

Objective To evaluate effects of the anti-interleukin-6 receptor monoclonal antibody sarilumab administered with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) on patient-reported outcomes (PROs) in the TARGET trial in patients with rheumatoid arthritis (RA) with inadequate response or intolerance to tumour necrosis factor inhibitors (TNF-IR). Methods 546 patients (81.9% female, mean age 52.9 years) were randomised to placebo, sarilumab 150 or 200 mg subcutaneously every 2 weeks + csDMARDs. PROs included patient global assessment (PtGA); pain and morning stiffness visual analogue scales; Health Assessment Questionnaire Disability Index (HAQ-DI); Short Form-36 Health Survey (SF-36); FACIT-Fatigue (FACIT-F); Work Productivity Survey-Rheumatoid Arthritis (WPS-RA) and Rheumatoid Arthritis Impact of Disease (RAID). Changes from baseline at weeks 12 and 24 were analysed using a mixed model for repeated measures; post hoc analyses included percentages of patients reporting improvements ≥ minimum clinically important differences (MCID) and scores ≥ normative values. Results Sarilumab + csDMARDs doses resulted in improvements from baseline at week 12 vs placebo + csDMARDs in PtGA, pain, HAQ-DI, SF-36 and FACIT-F that were maintained at week 24. Sarilumab improved morning stiffness and reduced the impact of RA on work, family, social/leisure activities participation (WPS-RA) and on patients' lives (RAID). Percentages of patients reporting improvements ≥MCID and ≥ normative scores were greater with sarilumab than placebo. Conclusions In patients with TNF-IR RA, 150 and 200 mg sarilumab + csDMARDs resulted in clinically meaningful patient-reported benefits on pain, fatigue, function, participation and health status at 12 and 24 weeks that exceeded placebo + csDMARDs, and were consistent with the clinical profile previously reported. Trial registration number NCT01709578; Results.
Decreased PM 10 exposure attenuates age-related lung function decline : genetic variants in p 53 , p 21 , and CCND 1 modify this effect

Background: Decreasing exposure to airborne particulates was previously associated with reduced age-related decline in lung function. However, whether the benefit from improved air quality depends on genetic background is not known. Recent evidence points to the involvement of the genes p53 and p21 and of the cell cycle control gene cyclin D1 (CCND1) in the response of bronchial cells to air pollution. Objective: We determined in 4,326 participants of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) whether four single-nucleotide polymorphisms in three genes [CCND1 (rs9344 [P242P], rs667515), p53 (rs1042522 [R72P]), and p21 (rs1801270 [S31R])] modified the previously observed attenuation of the decline in the forced expiratory flow between 25% and 75% of the forced vital capacity (FEF25-75) associated with improved air quality. Methods: Subjects of the prospective population-based SAPALDIA cohort were assessed in 1991 and 2002 by spirometry, questionnaires, and biological sample collection for genotyping. We assigned spatially resolved concentrations of particulate matter with aerodynamic diameter ≤ 10 μm (PM10) to each participant's residential history 12 months before the baseline and follow-up assessments. Results: The effect of diminishing PM10 exposure on FEF25-75 decline appeared to be modified by p53 R72P, CCND1 P242P, and CCND1 rs667515. For example, a 10-μg/m3 decline in average PM10 exposure over an 11-year period attenuated the average annual decline in FEF25-75 by 21.33 mL/year (95% confidence interval, 10.57-32.08) among participants homozygous for the CCND1 (P242P) GG genotype, by 13.72 mL/year (5.38-22.06) among GA genotypes, and by 6.00 mL/year (-4.54 to 16.54) among AA genotypes. Conclusions: Our results suggest that cell cycle control genes may modify the degree to which improved air quality may benefit respiratory function in adults.
Feature Article: Optimization for simulation: Theory vs. Practice

Probably one of the most successful interfaces between operations research and computer science has been the development of discrete-event simulation software. The recent integration of optimization techniques into simulation practice, specically into commercial software, has become nearly ubiquitous, as most discrete-event simulation packages now include some form of ? optimization? routine. The main thesis of this article, how-ever,is that there is a disconnect between research in simulation optimization--which has addressed the stochastic nature of discrete-event simulation by concentratingon theoretical results of convergence and specialized algorithms that are mathematically elegant--and the recent software developments, which implement very general algorithms adopted from techniques in the deterministic optimization metaheuristic literature (e.g., genetic algorithms, tabu search, artificial neural networks). A tutorial exposition that summarizes the approaches found in the research literature is included, as well as a discussion contrasting these approaches with the algorithms implemented in commercial software. The article concludes with the author's speculations on promising research areas and possible future directions in practice.
Determinants of Financial Development

The paper studies effects of country level determinants on the rate of financial development and, in particular, assesses the empirical question whether democracy and political freedom can enhance financial development, as measured by Bank Private Credit to GDP and Liquid Liabilities to GDP. Using Fixed Effects estimation techniques and a panel data for a list of 39 countries over the period 1990 to 2011, we provide evidence that suggests positive link between political openness and financial development. The empirical evidence also confirms financial openness and real per capita income to be positively correlated to financial deepening and in contrast, we find that size of financial sector does not spur the rate of financial development. JEL Classification F12, F43, G28, G29
[Prevalence and risk factors for dyslipidemia in diabetics with overweight or obesity].

OBJECTIVE To explore the prevalence and risk factors for dyslipidemia in diabetics with overweight or obesity. METHODS Diabetics with overweight or obesity were recruited from 62 tertiary and secondary hospitals in Guangdong Province between August 2011 and March 2012. Dyslipidemia was diagnosed as total cholesterol (TC) ≥ 5.7 mmol/L or triglycerides (TG) ≥ 1.7 mmol/L or low-density-lipoprotein cholesterol (LDL-C) ≥ 3.6 mmol/L or high-density-lipoprotein cholesterol (HDL-C) < 1.29 mmol/L in females or HDL-C < 1.03 mmol/L in males. Binary Logistic regression was used to assess the associations between dyslipidemia and associated risk factors. RESULTS Dyslipidemia was detected in 3160/3593 (87.9%) diabetics with overweight or obesity. And the prevalence of hypertriglyceridemia, low blood HDL-C, hypercholesterolemia and high blood LDL-C was 52.5% (1888/3593) , 54.1% (1945/3593), 33.1% (1188/3593) and 27.4% (985/3593) respectively. Among those with dyslipidemia, patients with simple and mixed dyslipidemia accounted for 34.1% and 53.9% respectively. In binary Logistic regression analysis, the presence of dyslipidemia were associated with female gender (OR = 1.593, 95%CI 1.233-2.057), hemoglobinA1c(HbA1c) (OR = 1.120, 95%CI 1.054-1.191), body mass index (OR = 1.084, 95%CI 1.022-1.150), hypertension (OR = 1.331, 95%CI 1.033-1.714), history of diabetes (OR = 1.586, 95%CI 1.186-2.120) and hyperuricacidemia (OR = 2.270, 95%CI 1.642-3.138). CONCLUSIONS The prevalence of dyslipidemia is quite high in diabetics with overweight or obesity. The controls of blood pressure, serum uric acid level, blood glucose and body weight may reduce the prevalence of dyslipidemia, prevent and delay the development of cardiovascular complications and reduce the mortality of diabetics with overweight or obesity.
In vitro study on the immunological effect of bromelain and trypsin on mononuclear cells from humans.

BACKGROUND Proteolytic enzymes such as bromelain and trypsin are used as an adjuvant therapeutic approach in the treatment of chronic inflammatory, malignant and autoimmune diseases. In vitro studies have shown that proteolytic enzymes modulate surface adhesion molecules on T-cells. In this study we analysed the influence of bromelain and trypsin on the cytokine production and proliferation of peripheral blood mononuclear cells (PBMC) from patients with a classical cellular mediated autoimmune disorder, namely encephalomyelitis disseminata (ED) as well as from healthy controls. - METHODS PBMC from patients with ED (n=12) and healthy controls (n=12) were cultured for seven days at 37 degrees C under three different conditions: without antigen, with bromelain and with trypsin (final concentrations 10-1000 microg/ml). Proliferation was determined by superset3H-thymidine incorporation. Secretion of cytokines into the supernatant was measured by a double sandwich ELISA. Intracellular cytokines were determined by flow cytometric analysis. - RESULTS PBMC from patients with ED and healthy controls showed a significantly increased proliferative response to bromelain (ED: 14053+/- 7585 cpm with bromelain vs. spontaneous proliferation of 430+/- 255 cpm; healthy controls: 10689+/- 4607 cpm vs. 327+/-193) but not to trypsin. Bromelain induced in all 24 individuals a significant increase of the macro-phage/monocyte associated cytokines interleukin (IL)-6, granulocyte-macrophage-colony stimulating factor (GM-CSF), tumour necrosis factor alpha (TNFa) (p<0.01) as well as of the type 1 cytokine gamma-interferon (IFNgamma). In contrast, the type 2 cytokines IL-4 and IL-5 were not induced. Flow cytometric analysis revealed a significant increase of IFNgamma-producing CD4+ T-cells. There were no differences in cytokine production between ED patients and healthy controls. - CONCLUSION These results indicate that bromelain - but not trypsin - activates macrophages/monocytes and type 1 cells independently from the underlying disease and may stimulate, therefore, the innate as well as the adaptive immune system.
An IoT Platform for Epilepsy Monitoring and Supervising

Epilepsy is a chronic neurological disorder with several different types of seizures, some of them characterized by involuntary recurrent convulsions, which have a great impact on the everyday life of the patients. Several solutions have been proposed in the literature to detect this type of seizures and to monitor the patient; however, these approaches lack in ergonomic issues and in the suitable integration with the health system. This research makes an in-depth analysis of the main factors that an epileptic detection and monitoring tool should accomplish. Furthermore, we introduce the architecture for a specific epilepsy detection and monitoring platform, fulfilling these factors. Special attention has been given to the part of the system the patient should wear, providing details of this part of the platform. Finally, a partial implementation has been deployed and several tests have been proposed and carried out in order to make some design decisions.
Utilization of Labeled Proteins in Synthesis of Tissue Proteins.∗

Summary Ehrlich ascites cells were incubated in vitro with radioactive amino acids or radioactive ascites proteins prepared biosynthetically. Incubations with free amino acids resulted in accumulation of large amounts of radioactivity in the acid-soluble fraction and in incorporation of radioactivity into the proteins. Incubations with labeled proteins resulted in labeling of cell proteins without significant accumulation of radioactivity in the acid-soluble fraction. Radioactive proteins were isolated from various cell fractions of ascites cells following incubation with labeled free amino acids or proteins. These results suggest that proteins enter ascites cells where they are utilized for synthesis of cellular proteins; free amino acids do not appear to be intermediates in this process.
Reply to treatment decisions and outcome in very elderly patients with diffuse large B‐cell lymphoma

We appreciate the insightful letter by Fabbri et al regarding our article. Because patients aged>80 years have the highest incidence of diffuse large B-cell lymphoma (DLBCL) yet are rarely included in studies, we sought to characterize treatment and survival patterns in this population. We found that in patients with DLBCL who were aged >80 years (1156 patients), treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) was associated with the longest survival, even after controlling for potential confounders such as performance status and comorbidity. Although the data from our study suggested that age alone should not be a contraindication to effective treatment, we agree with Fabbri et al that anthracycline toxicity is a major concern in very elderly patients given their decreased functional and physiologic reserve. Indeed, a recent study found that approximately one-third of elderly patients with DLBCL who received anthracycline-based therapy experienced toxicity requiring treatment modification. As alternatives, Fabbri et al have thoughtfully suggested reduced doses of R-CHOP, non-anthracycline-based regimens, and nonpegylated liposomal doxorubicin in this population. In addition to the aforementioned treatment modifications, radiotherapy also may be beneficial for elderly patients with DLBCL. A recent study revealed that elderly patients with limited-stage DLBCL who were treated with abbreviated R-CHOP and radiotherapy (359 patients) had a decreased risk of second-line therapy and febrile neutropenia compared with patients treated with fullcourse R-CHOP alone (515 patients); overall survival was similar between the 2 groups. These results suggest that abbreviated R-CHOP with radiotherapy may be better tolerated in elderly patients with limited-stage DLBCL, and future studies should further investigate this treatment regimen. In conclusion, we agree with the points raised by Fabbri et al and advocate for further studies examining alternative DLBCL treatment regimens for elderly patients who cannot tolerate standard therapy with R-CHOP.
Psychosocial Risk Factors and Urban/Rural Differences in the Prevalence of Major Depression

The Piedmont Health Survey interviewed 3798 adult community residents in a region of North Carolina. Current major depression was nearly three times more common in the urban than in the rural counties; rural residence decreased the risk of major depression for some, but not all, demographic subgroups. The risk of major depression was decreased for young rural residents, compared with their urban age peers; rural residence was more protective for young women than for young men. Rural residence appears to be a buffer against major depression.