Miracle-dz/UniFAR-FTUs huggingface dataset:
The effects of insulin, transferrin and androgens on rat prostate explants in serum‐free organ culture

A model previously developed in our laboratory to culture rat prostate explants in serum‐free chemically‐defined medium was used to evaluate the direct influence of potential regulators. The aim of the present work was to verify the effects of insulin (I) and transferrin (Tr), two hormones considered as essential in other serum‐free culture systems, and three androgenic hormones, since the prostate is known to be androgen‐dependent. Explants of rat prostate were cultured for five days in serum‐free Leibovitz's L‐15 medium (37°C, 95% air – 5% CO2). The addition of Tr (50 μg/ml) had no effect, but I (5 μg/ml) significantly increased DNA synthesis. This influence was amplified by combination of the two hormones. However, protein synthesis was only slightly stimulated. Testosterone (T) or androstanediol significantly increased DNA synthesis when compared to corresponding control values at five days. In combination with I plus Tr, each hormone showed potentiated effects, particularly T with a twofold increase over day 0 values. When dihydrotestosterone was added singly, the incorporation of 3H‐thymidine was stimulated by 300% over control values at five days, and by 100% over values in uncultured explants. This influence was maximal since it was not improved by I plus Tr. Protein synthesis was increased significantly by the triple combination. In addition, each androgen as well as the combination of I plus Tr had a positive influence on explant morphology. The above conditions optimize the present culture system and establish its usefulness as a valuable tool to study the direct influence of different effectors in prostate metabolism and to eventually identify putative cancer markers.
Regulation, chamber localization, and subtype distribution of angiotensin II receptors in human hearts.

BACKGROUND To assess the chamber localization, subtype distribution, and regulation of human myocardial angiotensin II receptors in heart failure, we determined the binding of angiotensin II, Sar1Ile8-angiotensin II, and the subtype-specific antagonists Dup 753 (AT1-specific) and PD 123319 (AT2-specific) in atria from patients with normal (left ventricular ejection fraction > 55%) or moderately impaired (left ventricular ejection fraction 30% to 55%) cardiac function and in atria and ventricles from explanted end-stage failing hearts. Sarcolemmal and combined fractions, the latter including internalized receptors, were studied. In addition, AT1 mRNA content was analyzed by polymerase chain reaction after reverse transcription. METHODS AND RESULTS The number of angiotensin II binding sites (Bmax) in sarcolemmal fractions was significantly reduced in explanted end-stage failing hearts in comparison with control subjects and moderate heart failure (Bmax 3.9 +/- 0.8 versus 11.2 +/- 1.7 and 9.6 +/- 0.8 fmol/mg protein, respectively). A comparable 65% reduction in receptor numbers was found in combined fractions from end-stage failing hearts, indicating that the loss of binding sites was not due to their internalization. The dissociation constants were comparable in sarcolemmal and combined fractions and in nonfailing and failing hearts, ranging from 0.5 +/- 0.2 to 1.2 +/- 0.5 nmol/L. In nonfailing hearts, 69 +/- 4% of binding sites were blocked by the subtype-2-specific inhibitor PD 123319 and were therefore classified as AT2; 33 +/- 5% were blocked by the subtype-1-specific inhibitor DUP 753 and thus classified as subtype 1. In explanted hearts, comparable ratios of 66 +/- 5% AT2 sites and 34 +/- 5% AT1 sites were found. AT1 cDNA amplification signals by polymerase chain reaction were reduced to about one third of the level in control subjects in end-stage failing hearts. CONCLUSIONS Angiotensin II receptors in human myocardium are present in relatively low numbers, and AT2 is the predominant subtype. A significant loss of angiotensin II receptors occurs in end stage but not in moderate heart failure. The loss of receptors affects both subtypes to a comparable degree. The data suggest that the decrease in receptor density is due to a decrease in steady-state mRNA abundance.
Simulation of Nitrogen Balance in Rice-Wheat Systems of the Indo-Gangetic Plains

Crop growth simulation models provide a means to quantify the effects of climate, soil, and management on crop growth and biogeochemical processes in soil. The Denitrification and Decomposition (DNDC) model was evaluated for its ability to simulate N dynamics and balance in the rice (Oryza saliva L.)-wheat (Triticum aestivum L.) cropping systems in the Indo-Gangetic Plains with various N and water management practices. The observed crop yield, N uptake, and losses of N were in good agreement with the values predicted by the model. In the rice-wheat systems, current annual inputs of N through fertilizer, manure, biological fixation, atmospheric deposition, and irrigation were 98, 37, 17, 8, and 7 kg N ha -1 , respectively, while outputs through uptake, volatilization, leaching, and denitrification were 175, 14, 12, and 4 kg N ha -1 , respectively. The northwestern transects of the Indo-Gangetic Plains (Punjab and Haryana) showed greater yields and N uptake because of a higher amount of N use and more favorable climatic conditions than those in the eastern transects (Uttar Pradesh, Bihar, and West Bengal). Volatilization was the dominant N loss mechanism in Punjab and West Bengal while NO 3 leaching was dominant in Bihar, Uttar Pradesh, and West Bengal. The simulated balance of N was negative in all the states. The largest depletion of soil N was estimated in Bihar, followed by Uttar Pradesh, Haryana, Punjab, and West Bengal. The study suggests that better N management is required to arrest the depletion of soil N.
The Comparative Effect of Subnational and Nationwide Cultural Variation on Subsidiary Ownership Choices: The Role of Spatial Coordination Challenges and Penrosean Growth Constraints

ABSTRACT To shed more light on the spatial determinants of foreign entry mode decisions, I examine the comparative effect of cultural variation inside target countries and target subnational regions on firms’ choices between joint ventures (JVs) and wholly owned subsidiaries. Based on the notions of spatial coordination challenges and Penrosean growth constraints, I argue that foreign entries tend to have a subnational scope, causing ownership mode choices to be more sensitive to target-region cultural variation than to target-country cultural variation. Accordingly, I hypothesize that target-region cultural varation has a more positive effect on the chance of JV selection than target-country cultural variation. I also hypothesize that this will be especially so for initially relatively large subsidiaries and subsidiaries established through acquisitions. An analysis of 170 entries by Dutch firms into 90 regions in 35 countries lends support to my hypotheses and indicates that the dominant effect of subnational cultural variation is not absolute but is confined to subsidiaries with specific establishment characteristics.
Prostate cancer screening in primary care.

BACKGROUND Little is known about the actual frequency with which men have prostate screening in primary care settings, nor are the determinants of screening understood. METHODS We examined the records of 50 consecutive primary care office visits by men aged 50 or older. Men were asked to complete a brief questionnaire outlining their previous use of prostate screening services and the factors that influenced screening. RESULTS Screening in the previous year with digital rectal examination (DRE) and prostate specific antigen (PSA) was reported by 46% and 30% of respondents, respectively. Most respondents (86%) had heard of prostate screening and most (78%) believed it was effective. The only factor predictive of screening with DRE in multivariate analysis was a doctor's discussion of screening (odds ratio, 4.8). Two factors were predictive of PSA screening--knowing someone who had prostate cancer (odds ratio, 12.8) and advancing age (odds ratio [per year], 1.1). CONCLUSIONS Many men are not having annual prostate screening. Men who were older, who reported knowing someone with prostate cancer, and whose doctors discussed screening, were more likely to have been screened in the past year.
Impact on the immune system of undetectable plasma HIV‐1 RNA for more than 2 years

Objective:To investigate the impact of prolonged HIV suppression on the immune system by analysing the expression of several lymphocyte surface markers in a group of HIV-1-infected patients who maintained undetectable HIV-1 RNA levels for more than 24 months. Patients and methods:The study included a highly selected group of nine HIV-1-infected asymptomatic subjects and seven HIV-1-seronegative controls. The inclusion criteria of HIV-1-infected patients was to have plasma HIV-1 RNA levels below 20 (1.3 log10) copies/ml for at least 24 months while under antiretroviral treatment with nucleoside analogues. The patient population was retrospectively taken from a cohort of 1418 treated subjects. Mean initial absolute CD4+ T-cell count and percentage were 468 ± 234 × 106/l (range, 202–935 × 106/l) and 25 ± 6% (range, 16–33%), respectively. Plasma HIV-1 RNA quantification was determined using a standard and ultrasensitive reverse transcriptase polymerase chain reaction assay. Median HIV-1 RNA plasma level before antiretroviral treatment was 3.14 log10 copies/ml (range, 1.74–3.73 log10 copies/ml). Two or three-colour immunophenotyping was performed on whole blood and frozen peripheral blood mononuclear cells by flow cytometry. Results:A significant increase was noted in CD4+ lymphocyte counts at the end of the study in HIV-1-positive patients. In addition, the CD4:CD8 ratio rose significantly with respect to baseline, although it remained lower than in the controls. CD45RA+ and CD45RO+ population percentages did not differ between groups. A significant rise in CD45RA+ T cells was observed. Analysis of T-cell activation measuring the expression of human leukocyte antigen-DR and CD25 did not differ between groups. The proportion of CD8+ lymphocytes that were CD28+ was similar in both groups at the end of the follow-up. T-cell receptor Vβ subfamily analysis showed that an expansion of the T-cell receptor repertoire might occur in these patients. Conclusion:Patients who maintain undetectable viral load for prolonged periods of time with antiretroviral therapy may achieve a partial immune restoration of the immune system. Our results suggest that treatment of patients at early stages of HIV infection is warranted.
Internal validity of attention deficit hyperactivity disorder, oppositional defiant disorder, and overt conduct disorder symptoms in young children: implications from teacher ratings for a dimensional approach to symptom validity.

Uses a dimensional approach to evaluate the internal validity of the attention deficit hyperactivity disorder (ADHD) inattention (I) and hyperactivity/impulsivity (H/I), oppositional defiant disorder (ODD), and overt conduct disorder (CD) symptoms (i.e., whether a symptom has a stronger correlation with its own dimension than the other three dimensions). In Study 1, teachers rated 1,445 children on the DSM-III-R I, H/I, ODD, and overt CD symptoms. In Study 2, teachers rated 1,711 children on the DSM-IV I, H/I, ODD, and overt CD symptoms. All the I symptoms showed internal validity in both studies. In contrast, the H/I symptoms and the ODD symptoms, especially the H/I symptoms, showed weaker internal validity. All the overt CD symptoms showed internal validity except the DSM-IV bullies others symptom, with this symptom being more strongly related to the ODD dimension. Confirmatory factor analysis provided support for a 4-factor model consisting of I, H/I, ODD, and overt CD factors. Finally, the importance of internal validity for the construct validation of the disruptive behavior symptoms is discussed.
Biochemical Characterization of a Membrane-bound Manganese-containing Superoxide Dismutase from the CyanobacteriumAnabaena PCC 7120*

The filamentous cyanobacteriumAnabaena PCC 7120 (now renamed Nostoc PCC 7120) possesses two genes for superoxide dismutase (SOD). One is an iron-containing (FeSOD) whereas the other is a manganese-containing superoxide dismutase (MnSOD). Localization experiments and analysis of the sequence showed that the FeSOD is cytosolic, whereas the MnSOD is a membrane-bound homodimeric protein containing one transmembrane helix, a spacer region, and a soluble catalytic domain. It is localized in both cytoplasmic and thylakoid membranes at the same extent with the catalytic domains positioned either in the periplasm or the thylakoid lumen. A phylogenetic analysis revealed that generally the highly homologous MnSODs of filamentous cyanobacteria are unique in being membrane-bound. Two recombinant variants of Anabaena MnSOD lacking either the hydrophobic region (MnSOD(Δ28)) or the hydrophobic and the linker region (MnSOD(Δ60)) are shown to exhibit the characteristic manganese peak at 480 nm, an almost 100% occupancy of manganese per subunit, a specific activity using the ferricytochrome assay of (660 ± 90) unit mg− 1 protein and a dissociation constant for the inhibitor azide of (0.84 ± 0.05) mm. Using stopped-flow spectroscopy it is shown that the decay of superoxide in the presence of various (MnSOD(Δ28)) or (MnSOD(Δ60)) concentrations is first-order in enzyme concentration allowing the calculation of catalytic rate constants which increase with decreasing pH: 8 × 106 m − 1s− 1 (pH 10) and 6 × 107 m − 1 s− 1(pH 7). The physiological relevance of these findings is discussed with respect to the bioenergetic peculiarities of cyanobacteria.
Comparison of Real-Time PCR Techniques to Cytotoxigenic Culture Methods for Diagnosing Clostridium difficile Infection

ABSTRACT In the past decade, the incidence of Clostridium difficile infections (CDI) with a more severe course has increased in Europe and North America. Assays that are capable of rapidly diagnosing CDI are essential. Two real-time PCRs (LUMC and LvI) targeting C. difficile toxin genes (tcdB, and tcdA and tcdB, respectively) were compared with the BD GeneOhm PCR (targeting the tcdB gene), using cytotoxigenic culture as a gold standard. In addition, a real-time PCR targeting the tcdC frameshift mutation at position 117 (Δ117 PCR) was evaluated for detecting toxigenic C. difficile and the presence of PCR ribotype 027 in stool samples. In total, 526 diarrheal samples were prospectively collected and included in the study. Compared with those for cytotoxigenic culture, sensitivity, specificity, positive predicted value (PPV), and negative predicted value (NPV) were for PCR LUMC 96.0%, 88.0%, 66.0%, and 98.9%, for PCR LvI 100.0%, 89.4%, 69.7%, and 100.0%, for PCR Δ117 98.0%, 90.7%, 71.9%, and 99.5%, and for PCR BD GeneOhm 88.3%, 96.9%, 86.5%, and 97.4%. Compared to those with feces samples cultured positive for C. difficile type 027, the sensitivity, specificity, PPV, and NPV of the Δ117 PCR were 95.2%, 96.2%, 87.0%, and 98.7%. We conclude that all real-time PCRs can be applied as a first screening test in an algorithm for diagnosing CDI. However, the low PPVs hinder the use of the assays as stand-alone tests. Furthermore, the Δ117 PCR may provide valuable information for minimizing the spread of the epidemic C. difficile PCR ribotype 027.
Mixing SABR Models for Negative Rates

In the current low-interest-rate environment, extending option models to negative rates has become an important issue. In our previous paper, we introduced the Free SABR model, which is a natural and an attractive extension to the classical SABR model. In spite of its advantages over the Shifted SABR, the Free SABR option pricing formula is based on an approximation. Although this approximation is very good, it cannot guarantee the absence of arbitrage.In this article, we build on an exact option pricing formula for the normal SABR with a free boundary and an arbitrary correlation. First, we derive this formula in terms of a 1D integral, which is suitable for fast calibration. Next, we apply the formula as a control variate to the Free SABR to improve the accuracy of its approximation, especially for high correlations. Finally, we come up with a Mixture SABR model, which is a weighted sum of the normal and free zero-correlation models. This model is guaranteed to be arbitrage free and has a closed-form solution for option prices. Added degrees of freedom also allow the Mixture SABR model to be calibrated to a broader set of trades, in particular, to a joint set of swaptions and CMS payment. We demonstrate this capability with a wide set of numerical examples.
Faktor-Faktor yang Mempengaruhi Alokasi Pembiayaan Perbankan Syariah Untuk Usaha Mikro Kecil dan Menengah di Indonesia

Tujuan penelitian ini adalah untuk menguji pengaruh Dana Pihak Ketiga (DPK), Capital Adequacy Ratio(CAR), Non Performing Financing (NPF), Return On Asset (ROA) dan Tingkat Inflasi terhadap besarnya pembiayaan yang diberikan perbankan syariah untuk UMKM. Metode analisis yang digunakan untuk menguji hipotesis adalah analaisis regresi linier berganda . Penelitian ini menemukan bukti bahwa dana pihak ketiga mempunyai pengaruh positif signifikan terhadap pembiayaan perbankan syariah untuk UMKM, Capital Adequacy Ratio(CAR) tidak mempunyai pengaruh positif terhadap pembiayaan perbankan syariah, non performing financing mempunyai pengaruh positif terhadap pembiayaan perbankan syariah untuk UMKM, Return on Asset (ROA) tidak mempunyai pengaruh positif terhadap pembiayaan perbankan syariah untuk UMKM, dan tingkat inflasi mempunyai pengaruh positif terhadap pembiayaan perbankan syariah untuk UMKM. Hasil uji F memperlihatkan kelima variabel independen tersebut di atas secara bersama-sama mempunyai pengaruh signifikan terhadap pembiayaan untuk UMKM Kata kunci: Capital Adequacy Ratio , Dana Pihak Ketiga, , Non Performing Financing , Return On Asset, Pembiayaan UMKM dan Tingkat Inflasi
Multicolor time‐resolved Förster resonance energy transfer microscopy reveals the impact of GPCR oligomerization on internalization processes

Identifying the interacting partners and the dynamics of the molecular networks constitutes the key point in understanding cellular processes. Different methods often based on energy transfer strategies have been developed to examine the molecular dynamics of protein complexes. However, these methods suffer a couple of drawbacks: a single complex can be studied at a time, and its localization and tracking cannot generally be investigated. Here, we report a multicolor time‐resolved Förster resonance energy transfer microscopy method that allows the identification of up to 3 different complexes simultaneously, their localization in cells, and their tracking after activation. Using this technique, we studied GPCR oligomerization and internalization in human embryonic kidney 293 cells. We definitively show that receptors can internalize as oligomers and that receptor coexpression deeply impacts oligomer internalization processes. — Faklaris, O. , Cottet, M. , Falco, A. , Villier, B. , Laget, M. , Zwier, J. M. , Trinquet, E. , Mouillac, B. , Pin, J.‐P., Durroux, T. Multicolor time‐resolved Förster resonance energy transfer microscopy reveals the impact of GPCR oligomerization on internalization processes. FASEB J. 29, 2235‐2246 (2015). www.fasebj. org
Who Loses When Prices are Negotiated? An Analysis of the New Car Market

We establish that there are large and persistent differences in final transaction prices for identical new cars, and that demographic characteristics explain at least 20% of the observed variation. Older consumers perform progressively worse in negotiations, and the age premium is greater for women than for men. Our results suggest that the complex nature of vehicle transactions leads to price dispersion in this market, and that the worst performing groups—older women—have the lowest rates of market participation. We conjecture that the results are driven by the sharp increases in women's education and labor force participation in recent decades.
System Design and Modeling of a Time-Varying, Nonlinear Temperature Controller for Microfluidics

We present a custom-made temperature control system for performing sensitive biochemical reactions within a microfluidic platform. The thermoelectric module (TEM)-based system is part of a microfluidic platform for genetic basis of disease diagnosis. Multistage TEMs with individualized control are used to improve the response speeds compared to a single TEM. Currently, there exists neither a mathematical representation to predict the TEMs' response, nor any standardized approach to identify such systems-both of which will greatly assist in effectively controlling the temperature of the TEMs. Hence, we propose here an approach for system identification of these nonlinear elements in a cascade configuration. In this customized TEM configuration, a linear multiple-input-multi-output (MIMO) structure with temperature difference variables as the system outputs is chosen to derive the system model for subsequent controller design. For the application of temperature cycling between different set-points, a group of model-based controllers with switching strategy is designed, and for each set-point region, an internal model-based decentralized controller is implemented. Both simulation and experimental results demonstrate that the switching controller exhibits superior control performance for fast tracking (~ 6°C/s slew rate) and low steady state error (±0.1°C) when compared to a non-switching controller. The controller design approach can easily be extended to further multi-channel modules for wider applicability. Here, the integration of cost-effective and thermally-efficient physical temperature control elements with a switching and decentralized controller is applied to viral detection, which serves as the validation of the system identification-based controller.