Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of poly(adenosine diphosphate-ribose) polymerase activity in erythroleukemic mouse cells during cell cycle and erythropoietic differentiation.

Accumulation of erythroleukemic mouse spleen cells (F4N-Ostertag) in the G-l phase of the cell cycle was achieved in three ways: maintenance of cells 1) at high densities (3 to 5 x 10” cells ml-‘), 2) at low densities (1 x 10” cells ml-‘) in isoleucine-free medium, and 3) in the presence of 1.5 nm butyric acid or 3.8 mu hexamethylene bisacetamide, both potent inducers of erythropoietic differentiation, at these given concentrations in F4N cells. These G-l arrests were documented by microfluorometric determination of the DNA content of single cells. Poly(ADPribose) polymerase activity was followed during the process of G-l accumulation. This enzyme catalyzes the synthesis of poly(ADP-ribose) from NAD. As poly(ADP-ribose) is covalently bound to chromosomal proteins, this system provides a possible means for connecting cellular NAD levels with regulative events in chromatin. Poly(ADP-rihose) polymerase had a fairly constant activity level in logarithmically growing cells and increased 3to 4-fold when G-l accumulation was achieved by either of the three methods. Although increased levels of poly(ADP-ribose) polymerase activity seemed to occur whenever F4N cells accumulated in G-l, it also appeared to be conditional for the expression of the erythroid differentiation program in these cells. For determination of poly(ADP-ribose) polymerase activity we used an in vitro enzyme assay system. Under these conditions two variables which contribute to the enzyme activity could be excluded: fluctuations in nuclear NAD levels and poly(ADP-ribose) degradation. Enzyme concentration and number of polymer attachment sites on chromatin thus are the rate-determining factors.
In vitro and in vivo approaches to characterize transporter-mediated disposition in drug discovery

Introduction: It is becoming increasingly evident that transporters play an important role in the absorption, distribution and elimination of many drugs. Different approaches have been developed and validated to understand the interactions between drugs and transporters, and the in vivo role of drug transporters. These tools are helping to understand the impact of transporters on the pharmacokinetics (PK) of drugs and assess the risk of drug–drug interactions (DDIs) in drug discovery and development. Areas covered: This article provides an overview of different approaches to evaluate the drug transporters involved in intestinal absorption, hepatic and renal clearance, and brain penetration. Specifically, it provides the best practices to evaluate the major uptake and efflux transporters in drug discovery. It also discusses the challenges and gaps in understanding the clinical relevance of drug transporters. Expert opinion: Quantitative prediction of transporter-mediated clearance, tissue exposure, as well as DDIs is still limited. The current challenge is to develop in vitro–in vivo correlations, extrapolate and integrate data from in vitro transporter assays, and preclinical species into humans to quantitatively predict the impact of transporters on drug absorption, disposition, elimination and DDIs. With the development of a variety of novel tools, the ultimate goal is to use high quality in vitro and in vivo data to establish physiologically based PK models, which will improve the capability to predict PK, tissue exposure and DDIs in humans.
Present-Biased Individuals, Optimal Paternalism, and Transfers in Kind

Present-biased preferences cause distortions in consumption that can motivate the use of paternalistic in-kind transfers. Empirically, goods are consumed to different degrees when consumption outlay changes. Economists distinguish between necessary goods and luxury goods. A present-biased individual has an intertemporal distortion of consumption toward the present, which in turn distorts present consumption toward luxury goods. In-kind transfers of necessary goods, such as food stamps, can alleviate the intertemporal distortion and make present-biased transfer recipients better off. Further, transfers in kind are asymmetrical in the sense that they can target present-biased recipients without affecting fully rational recipients.
Electrical Characterization of Coaxial Silicon–Insulator–Silicon Through-Silicon Vias: Theoretical Analysis and Experiments

Coaxial through-silicon via (TSV) provides an effective solution to achieve impedance matching, reduce transmission loss, and suppress interference or noise coupling in 3-D/2.5-D heterointegrated systems. This paper presents a fabrication friendly coaxial TSV configuration based on heavily doped silicon-insulator-silicon (SIS) structure, whose electrical characteristics are studied through deriving analytical solution, performing numerical simulation, and conducting experimental measurement. The distributed resistance-inductance-capacitance-conductance (RLCG) parameters are calculated from electromagnetic theory and semiconductor physics. Wideband S-parameters of the fabricated devices are obtained using on-wafer measurement with deembedding technique, and then compared against 3-D full-wave simulations and analytical solutions, exhibiting good agreement up to 50 GHz. Results show that the proposed coaxial SIS TSV offers flexible impedance control, good matching, and low insertion loss, and supports 30-Gbps data transmission with the simpler structure as well as the lower fabrication cost compared with various coaxial TSV structures reported to date.
Effects of ruminally degradable nitrogen intake and in vitro addition of ammonia and propionate on the metabolic fate of L-[1-14C]alanine and L-[15N]alanine in isolated sheep hepatocytes.

Isolated hepatocytes prepared from sheep fed a basal diet (bromegrass hay-corn, 50:50 wt/ wt, as-fed basis) with or without urea were used to determine the effects of added ammonia (as NH4Cl) and propionate on the partitioning of C from 1.25 mM L-[1-14C]alanine between oxidation and gluconeogenesis, and the flux of 15N from 1.25 mM L-[15N]alanine to [14N15N]urea and [15N15N]urea. Hepatocyte suspensions were incubated with NH4Cl (0, .31, .63, and 1.25 mM) and (or) propionate (0, .31, .63, and 1.25 mM) in the presence of either 1.25 mM L-[15N]alanine or 1.25 mM L-alanine plus 18.5 kBq of L-[1-14C]alanine. Feeding dietary urea did not affect [1-14C]alanine oxidation to 14CO2 (P = .601), or its conversion to [14C]glucose (P = .576) by isolated hepatocytes. Increasing in vitro concentrations of NH4Cl and propionate between 0 and 1.25 mM reduced [1-14C]alanine oxidation to 14CO2 (P < .001). Increasing NH4Cl concentration between 0 and 1.25 mM reduced [1-14C]alanine conversion to [14C]glucose in isolated hepatocytes (P < .001), whereas addition of propionate between 0 and 1.25 mM stimulated production of [14C]glucose from [1-14C]alanine (P < .001). Feeding urea did not affect in vitro rates of total urea production (P = .655) but increased the production of [14N15N]urea and [15N15N]urea (P < .05). Addition of NH4Cl increased total urea, [14N15N]urea, and [15N15N]urea production (P < .001), but reduced 15N isotopic enrichments of [14N15N]urea and [15N15N]urea (P < .001). Increasing propionate concentration between 0 and 1.25 mM reduced total urea production (P < .001), but [14N15N]urea and [15N15N]urea production was reduced only at 1.25 mM propionate (P < .001). We conclude that NH3 detoxification by isolated sheep hepatocytes increases amino acid deamination and this might have implications for nitrogen retention in ruminants consuming diets that promote considerable NH3 absorption from the digestive tract.
Rejoinder to Professors Kadane and Larkey

John C. Harsanyi's rejoinder to comments and replies to Kadane, J. B. , P. D. Larkey. 1982. Subjective probability and the theory of games. Management Sci.28 2 113-120 and Kadane, J. B. , P. D. Larkey. 1982. Reply to Professor Harsanyi. Management Sci.28 2 124.
A VEGF-dependent autocrine loop mediates proliferation and capillarogenesis in bone marrow endothelial cells of patients with multiple myeloma

Summary The expression/function of vascular endothelial growth factor (VEGF) and its receptor 2 (VEGFR-2/KDR) in multiple myeloma (MM)-associated angiogenesis is under scrutiny. We show here that bone marrow endothelial cells (EC) from 16 patients with MM (MMEC) highly expressed VEGF-A (the main VEGF isoform) and VEGFR-2 at both mRNA and protein level, whereas EC from 14 patients with monoclonal gammopathy unassociated/unattributable (MG[u]) (MG[u]EC) and 12 human umbilical veins (HUVEC) expressed very low mRNAs and/or proteins. MMEC showed constitutive autophosphorylation in both VEGFR-2 and the associated extracellular signal-regulated kinase-2 (ERK-2), whereas this was marginal in MG[u]EC and HUVEC. MMEC proliferated rapidly and formed a closely-knit capillary meshwork on Matrigel. These cell functions were reduced in the other EC. Autophosphorylation, proliferation and capillarogenesis were prevented by a neutralizing antiVEGF-A antibody, and more efficaciously by an anti-VEGFR-2 antibody. Both antibodies had no effect or were poorly effective on the other EC. These findings as a whole suggest the existence of an autocrine loop of VEGF in MMEC. Since this is very likely a mechanism for the amplification of VEGF activity in neovascularization, it would constitute an appropriate target for antiangiogenic management in MM.
La competencia electoral y la descentralización partidista en México

SINCE THERE HAVE BEEN SO MANY WORKS STRESSING THE PROCESS OF FISCAL DECENTRALIZATION, VIRTUALLY NO RESEARCH ON MEXICAN POLITICS HAS ANALYZED THE ISSUE OF PARTY DECENTRALIZATION. THIS ARTICLE HOLDS THAT, DUE TO THE INCREASE IN ELECTORAL COMPETITION, SUB-NATIONAL POLITICAL LEADERS HAVE OBTAINED CONTROL OVER SIGNIFICANT POLITICAL RESOURCES, SUCH AS NOMINATIONS, CAMPAIGN FINANCING AND FUTURE JOBS. IN ORDER TO MEASURE THE SCOPE OF THESE CHANGES, THIS ARTICLE USES DATA ON THE POLITICAL CAREERS OF PRI SENATE CANDIDATES, IN ORDER TO ASSESS THE DEGREE OF DECENTRALIZATION OF ONE OF THE MOST HIGHLY CENTRALIZED PARTIES IN THE WORLD.
Peribiliary capillary plexus around interlobular bile ducts in various chronic liver diseases: An immunohistochemical and morphometric study

Peribiliary capillary plexus (PCP) is a network of capillaries which arise from the hepatic artery surrounding the intrahepatic bile ducts. We immunohistochemically investigated the density of PCP around interlobular bile ducts in various chronic liver diseases including primary biliary cirrhosis (PBC) (n = 47), autoimmune hepatitis (AIH) (n = 12), chronic hepatitis B (n = 16), chronic hepatitis C (n = 19), liver cirrhosis due to hepatitis B virus (n = 13), liver cirrhosis due to hepatitis C virus (n = 20), alcoholic hepatitis (n = 20), alcoholic liver cirrhosis (n = 17), using human liver biopsies fixed in formalin and embedded in paraffin wax. PCP was immunohistochemically detected by an endothelial marker, the CD34 antigen. The number of PCP per duct was 1.21 ± 0.18 in normal livers. Compared with normal liver, vasopenia was observed in PBC and AIH, the number in which was 0.93 ± 0.34 (P< 0.0001) and 0.82 ± 0.38 (P< 0.005) per duct, respectively. In contrast, increased number of PCP was observed in liver cirrhosis due to hepatitis B or C virus, alcoholic hepatitis, and alcoholic liver cirrhosis, the number in which were 1.59 ± 0.37 (P< 0.005), 1.55 ± 0.52 (P< 0.02), 1.38 ± 0.23 (P< 0.02) and 1.61 ± 0.33 (P< 0.002) per duct, respectively. These data suggest that PCP may be destroyed in autoimmune liver diseases, including PBC and AIH, but PCP may proliferate in other inflammatory and alcoholic liver diseases.
The performance of micro firms in Kosova: size, age and educational implications

In this paper we aim to measure the performance of micro firms operating in trade sector in Kosova, and to analyse how a firm's size, its age and the entrepreneur's educational background influence the firm performance. In a two-stage analysis we first employ the Data Envelopment Analyses (DEA) technique and afterwards a censored Tobit regression. The results indicate that the firm size negatively influences the efficiency of the firms while the newer the firm is, the better it performs. As expected, the educational background of the entrepreneur positively affects the performance of the micro firm. Considering the results, several policy recommendations were given for entrepreneurs and policymakers.
Two economic perspectives on the IPv6 transition

Purpose – IPv6 is the replacement for the internet's incumbent protocol, IPv4. IPv6 adoption is required to allow the internet to continue to grow; however, there has been almost no uptake since its standardization in the late 1990s. This paper seeks to explain how this non‐adoption may be a consequence of current policies paradoxically intended to promote IPv6.Design/methodology/approach – Economic theories of exhaustible resources and permit markets are used to provide an explanation for the lack of adoption of IPv6.Findings – The current policy approach will not yield a significant adoption of IPv6 until after the IPv4 address space is exhausted and may also constrain internet growth after IPv4 exhaustion occurs.Practical implications – Current policies intended to promote IPv6 diffusion through the internet must be reconsidered. The economics of permit markets in particular can inform discussions about IPv4 address transfer markets.Originality/value – Economic analyses of IPv6 adoption are almost non‐.
Fiscal Policy and Inflation in a Monetary Union

This paper studies optimal fiscal policies in a small open economy within a monetary union. The government has access to nominal non-state contingent debt and distortionary labour taxes to finance exogenous spending. Price levels differ across countries due to consumption home bias; thus fiscal policy influences inflation and the terms of trade. Prices are flexible. We show that, unlike in a country with an independent monetary policy, some variability in labour taxes is optimal. This is true even when the terms-of-trade externality is shut down. While fiscal policy aims at smoothing production distortions, with nominal public debt there is an incentive to use taxes to inflate in bad times when debt levels are high, reminiscent of Chari et al's (1991) optimal monetary policy result.
Modelos condicionais de apreçamento de ativos com prêmios de risco macroeconômicos variantes no tempo

Analisamos a previsibilidade dos retornos mensais de ativos no mercado brasileiro em um período de 10 anos desde o início do plano Real. Para analisarmos a variação cross-section dos retornos e explicarmos estes retornos em função de prêmios de risco variantes no tempo, condicionados a variáveis de estado macroeconômicas, utilizamos um novo modelo de apreçamento de ativos, combinando dois diferentes tipos de modelos econômicos, um modelo de nanças condicional e multifatorial, e um modelo estritamente macroeconômico do tipo Vector Auto Regressive. Veri camos que o modelo com betas condicionais não explica adequadamente os retornos dos ativos, porém o modelo com os prêmios de risco (e não os betas) condicionais, produz resultados com interpretação econômica e estatisticamente satisfatórios.
Perinatal Iron Deficiency Decreases Cytochrome c Oxidase (CytOx) Activity in Selected Regions of Neonatal Rat Brain

Intrauterine growth retardation and diabetes mellitus during human gestation result in significant losses of fetal and neonatal brain iron. Brain iron deficiency is associated with impaired cognitive processes including memory and attention. The regional distribution of iron staining and cytochrome c oxidase (CytOx) activity have not been mapped in the iron-sufficient or -deficient neonatal rat. CytOx is the iron-containing terminal enzyme in oxidative phosphorylation; its activity reflects neuronal metabolism. We hypothesized that neonatal brain iron deficiency differentially decreases iron and CytOx activity in brain regions, with more pronounced losses in structures involved in recognition memory. Pregnant Sprague Dawley rats were fed either an iron-deficient or -fortified diet from gestational d 1 until postnatal d 10. Iron staining and CytOx activity of 20 brain structures were mapped histochemically in 25 rats from each group. Brain iron staining was reduced from 75% to 100% and CytOx staining was decreased from 0% to 42% in the iron-deficient group (p < 0.001). Areas with significantly reduced CytOx activity (p < 0.001) included all measured subareas of the hippocampus (CA1: 42%, CA3ab: 34%, CA3c: 33%, and dentate gyrus: 32%), the piriform cortex (17%), the medial dorsal thalamic nucleus (28%), and the cingulate cortex (41%). In contrast, the anterior thalamic nucleus, the lateral amygdaloid nucleus, and the medial habenula, areas not involved in higher cognitive functions, did not have significantly reduced CytOx activity (0%, 10%, and 16%, respectively). We conclude that perinatal iron deficiency differentially reduces neuronal metabolic activity, specifically targeting areas of the brain involved in memory processing.
Functional organization of mammalian mitochondrial DNA in nucleoids: History, recent developments, and future challenges

Various proteins involved in replication, repair, and the structural organization of mitochondrial DNA (mtDNA) have been characterized in detail over the past 25 or so years. In addition, in recent years, many proteins were identified with a role in the dynamics of the mitochondrial network. Using advanced imaging and an increasing number of cytological techniques, we have begun to realize that an important aspect to mtDNA maintenance, in both health and disease, is its organization within the dynamic mitochondrial network in discrete protein–DNA complexes usually termed nucleoids. Here, I review recent developments in the study of nucleoid dynamics and proteins. I will discuss the implications of the organization of mtDNA in nucleoids in light of DNA replication, repair, gene expression, segregation, and inheritance. © 2009 IUBMB IUBMB Life, 62(1):19–32, 2010
Distortions to Agricultural Incentives in Bangladesh

This is a product of a research project on Distortions to Agricultural Incentives, under the leadership of Kym Anderson of the World Bank’s Development Research Group (www.worldbank.org/agdistortions). The authors are grateful for excellent research support from Marika Krausova, for helpful comments and suggestions from Garry Pursell and workshop participants, and for funding from World Bank Trust Funds provided by the governments of Ireland, Japan, the Netherlands (BNPP) and the United Kingdom (DfID).
Effects of denosumab in patients with bone metastases with and without previous bisphosphonate exposure

Bone metastases place patients at increased risk of skeletal‐related events (SREs), including pathologic fractures, spinal cord compression, severe pain requiring radiotherapy or surgery, and hypercalcemia, because of increased osteoclast‐mediated bone resorption. Denosumab, a fully human monoclonal antibody, decreases bone resorption by inhibiting RANKL, which mediates osteoclast activity. We compared the effects of denosumab in two phase 2 studies in patients with bone metastases naive to intravenous bisphosphonate therapy (IV BP; n = 255) and those with elevated levels of the bone resorption marker urinary N‐telopeptide (uNTX) despite ongoing IV BP treatment (n = 111). Patients were randomized to receive IV BP every 4 weeks or subcutaneous denosumab every 4 weeks (30/120/180 mg) or every 12 weeks (60/180 mg). Patients treated with denosumab experienced a rapid and sustained reduction in bone turnover regardless of prior IV BP exposure. After 25 weeks, the median uNTX reduction was 75% (IV BP‐naive) and 80% (prior IV BP) after denosumab treatment and 71% (IV BP‐naive) and 56% (prior IV BP) in the IV BP arms. Denosumab patients with prior IV BP exposure had marked suppression of the osteoclast marker TRAP‐5b (median reduction: denosumab 73%, IV BP 11%). SRE incidence was low across both studies. In patients previously treated with BPs, the rate of first on‐study SRE was lower in the denosumab groups (8%) than the IV BP group (17%). Denosumab appeared to be well tolerated in both studies. Denosumab suppresses bone resorption markers independently of prior BP treatment, even in patients who appear to respond poorly to BPs. © 2010 American Society for Bone and Mineral Research.
Determination of estrogen receptors in paraffin‐embedded tissue: Techniques and the value in breast cancer treatment

Estrogen receptor (ER) analysis in breast cancer has been used in three clinical situations: to select patients with advanced breast cancer for hormonal therapy, as a prognostic parameter, and for selection of women with early breast cancer to adjuvant hormonal treatment. ER has traditionally been measured using labelled hormone in binding assays--often in dextran-coated charcoal assays (DCC). Monoclonal antibodies to ER has permitted development of a solid phase enzyme immunoassay (ER-EIA) used for quantitative determination of ER in tissue homogenates, and have also been used for determination of ER using an immunohistochemical assay in frozen sections (ER-ICA) or in formalin-fixed, paraffin-embedded tissue (ER-PAR). A large number of studies has compared ER-EIA with ER-DCC assays. There is a good linear correlation between the two types of assay but ER-EIA measure more ER and classify a larger fraction of tumors ER-positive than conventional ER assays. Lack of clinical data makes the significance of this uncertain. Numerous studies have reported on the correlation between ER-ICA and ER-DCC or ER-EIA. There is a good correlation among the assays on classification of ER status with a median 86% concordance, but a somewhat poorer correlation between semiquantified ER of immunohistochemical assays and ER determined by the quantitative methods (median coefficient of correlation 0.67). There is a large variation in the cut-off level for definition of ER-positive in immunohistochemical assays emphasizing the need for quality control studies. The major problem involved in ER analysis in paraffin-embedded tissue is a considerable loss of immunoreactivity compared to sections from frozen tissue. This can partly be overcome by modifications of the immunohistochemical technique using enzyme pretreatment and other amplification systems, but the sensitivity of ER-PAR remains lower than ER-ICA despite these modifications, and the ER status is less reliably determined in tumors with low ER contents (< 100 fmol). The prognostic value of ER-PAR was evaluated with a multivariate analysis. The endpoint was disease-free interval in systemically untreated patients with early breast cancer, and the variables used were: ER-DCC, ER-PAR, age, tumor size, tumor grade, and nodal status. A total of 133 patients from the Danish Breast Cancer Cooperative Group's (DBCG) 77c protocols had a complete set of variables. The analysis showed that only nodal status, ER-DCC, and tumor grade were significant and independent prognostic variables. An overview of larger multivariate studies on mainly node-negative patients failed to show independent prognostic significance of ER-DCC. (ABSTRACT TRUNCATED AT 400 WORDS)