Miracle-dz/UniFAR-FTUs huggingface dataset:
Meta-Analysis of Expression of Hepatic Organic Anion–Transporting Polypeptide (OATP) Transporters in Cellular Systems Relative to Human Liver Tissue

Organic anion–transporting polypeptide (OATP)1B1, OATP1B3, and OATP2B1 transporters play an important role in hepatic drug disposition. Recently, an increasing number of studies have reported proteomic expression data for OATP transporters. However, systematic analysis and understanding of the actual differences in OATP expression between liver tissue and commonly used cellular systems is lacking. In the current study, meta-analysis was performed to assess the protein expression of OATP transporters reported in hepatocytes relative to liver tissue and to identify any potential correlations in transporter expression levels in the same individual. OATP1B1 was identified as the most abundant uptake transporter at 5.9 ± 8.3, 5.8 ± 3.3, and 4.2 ± 1.7 fmol/μg protein in liver tissue, sandwich-cultured human hepatocytes (SCHH), and cryopreserved suspended hepatocytes, respectively. The rank order in average expression in liver tissue and cellular systems was OATP1B1 > OATP1B3 ≈ OATP2B1. Abundance levels of the OATP transporters investigated were not significantly different between liver and cellular systems, with the exception of OATP2B1 expression in SCHH relative to liver tissue. Analysis of OATP1B1, OATP1B3, and OATP2B1 liver expression data in the same individuals (n = 86) identified weak (OATP1B1-OATP2B1) to moderately (OATP1B3-OATP2B1) significant correlations. A significant weak correlation was noted between OATP1B1 abundance and age of human donors, whereas expression of the OATPs investigated was independent of sex. Implications of the current analysis on the in vitro–in vivo extrapolation of transporter-mediated drug disposition using physiologically based pharmacokinetic models are discussed.
Time Spent per delta PASI (TSdP) among psoriasis patients undergoing UVB-therapy – A pilot study

Abstract Background: Psoriasis often poses a significant challenge to treat. Ultraviolet light band (UVB) treatment is widely used and well recognized. However, the frequent visits to the dermatologist may indirectly present an impediment to many of the patients’ careers and every day life due to the vast time burden with subsequent lost work earnings. We investigated the cost-effectiveness of the psoriasis UVB treatment from a patient’s point of view using time as a surrogate measure. Method: Twenty-five patients participated (17 males and 8 females) in the study. We registered the number of UVB treatments per patient as well as the patients PASI (psoriasis area and severity index) score at each treatment session. The time spent in relation to each treatment session was reported in a questionnaire given to the patient. Time Spent per delta PASI (TSdP) was defined as number of minutes to reduce the PASI score by one. Results: Seventeen (68%) of the participants needed less than 300 min to lower the PASI with one score. The rest (n = 7 (32%)) used more than 300 min to lower the PASI score by one. Thus, the TSdP distribution displayed two peaks; ><300 min/dPASI. Log-transformed linear regression model showed that the expected TSdP would decrease with 42% for each time the start PASI was doubled, i.e. the higher the PASI level at the beginning of the treatment, the lower the TSdP. Conclusion: The level of reduction in psoriasis severity compared with the amount of lost work time/earnings may pose a much higher impact for patients and society than what is currently recognized.
Labour-market institutions, (un)employment, wages, and growth: theory and data

ABSTRACT We analyse the implications of labour-market institutions on wage inequality in favour of skilled labour, on relative unemployment of unskilled labour, and on the economic growth rate in two clusters resulting from 27 OECD countries: Cluster 1, closely related with the Anglo-Saxon model, and Cluster 2, dominated by the Continental-European model. By linking the unskilled wage to the skilled one in Cluster 2, due to the indexation of social benefits to per-capita income, we accommodate the observed paths of the three variables in both clusters between 1991 and 2008: Cluster 1 presents a higher wage inequality in favour of skilled labour, a lower unemployment of the unskilled labour, and a better economic growth rate.
Hyperglycemia Inhibits Anesthetic-induced Postconditioning in the Rabbit Heart via Modulation of Phosphatidylinositol-3-kinase/Akt and Endothelial Nitric Oxide Synthase Signaling

Hyperglycemia is known to inhibit ischemic and anesthetic preconditioning. We tested whether hyperglycemia inhibits anesthetic postconditioning with isoflurane and whether this effect is mediated via phosphatidylinositol-3-kinase/Akt and nitric oxide signaling. New Zealand white rabbits subjected to 40 minutes of myocardial ischemia, followed by 3 hours of reperfusion were assigned to the following groups: ischemia and reperfusion (I/R), isoflurane (1 minimal alveolar concentration) postconditioning, and isoflurane postconditioning with hyperglycemia (15% dextrose in water infusion). A control group of hyperglycemia + I/R was also included. Levels of MB fraction of creatine kinase (CK-MB) were assessed as an indicator of myocardial damage, and infarct size was evaluated. Akt, iNOS, and endothelial nitric oxide synthase (eNOS) expression was assessed by immunoblotting. Determination of nitrite and nitrate levels in the myocardium was also performed. Isoflurane postconditioning reduced infarct size compared with the I/R group: 25% ± 4% versus 49% ± 5% (P < 0.01). CK-MB concentrations in the postconditioned animals (124% ± 14% above baseline levels) were lower than those in the I/R group (236% ± 9% above baseline levels; P < 0.01). Hyperglycemia inhibited the cardioprotective effect of isoflurane: myocardial infarction size was 46% ± 4% and CK-MB increased to 241% ± 11% above baseline. Phosphorylated Akt and eNOS protein expression increased after isoflurane postconditioning compared with the I/R group. These effects were also inhibited by hyperglycemia. iNOS expression, however, did not change significantly within the various experimental groups. There were increased tissue levels of nitrite and nitrate (NOx) in the postconditioning group. This was also blocked by hyperglycemia. Our results suggest that hyperglycemia inhibits cardioprotection provided by isoflurane postconditioning. This effect seems to be mediated via modulation Akt and eNOS.
A simple macroscopic model for the diffusion and adsorption kinetics of r‐adenovirus

The diffusion of viruses toward cells is a limiting step of the infection process. To be modeled correctly, this step must be evaluated in combination with the adsorption of the virus to the cell surface, which is a rapid but reversible step. In this paper, the recombinant adenovirus (rAd) diffusion and its adsorption to 293S cells in suspension were both measured and modeled. First, equilibrium experiments permitted to determine the number of receptors on the surface of 293S (RT = 3,500 cell−1) and the association constant (KA = 1.9 × 1011 M−1) for rAd on these cells based on a simple monovalent adsorption model. Non‐specific binding of the virus to the cell surface was not found to be significant. Second, total virus particle degradation rates between 5.2 × 10−3 and 4.0 × 10−2 min−1 were measured at 37°C in culture medium, but no significant virus degradation was observed at 4°C. Third, free viral particle disappearance rates from a mixed suspension of virus and cells were measured at different virus concentrations. Experimental data were compared to a phenomenological dynamic model comprising both the diffusion and the adsorption steps. The diffusion to adsorption ratio, a fitted parameter, confirmed that the contact process of a virus with a cell is indeed diffusion controlled. However, the characteristic diffusion time constants obtained, based on a reversible adsorption model, were eightfolds smaller than those reported in the literature, based on diffusion models that assume irreversible adsorption. Biotechnol. Bioeng. 2007; 98: 239–251. © 2007 Wiley Periodicals, Inc.
The TCN/AACN 2005 “Salary Survey”: Professional Practices, Beliefs, and Incomes of U.S. Neuropsychologists

Doctoral-level members of Division 40 (Clinical Neuropsychology) of the American Psychological Association and other neuropsychologists were invited to participate in a web-based survey in early 2005. Response rate was estimated to be between 28.5 and 31.3%. The range of years postdoctorate was 1–51. Demonstrating the substantial proportional change in gender taking place in the field, 7 of 10 postdoctoral residents were women. Whereas the median age of APA members has been over 50 since the early 1990s, the current median age of clinical neuropsychologists is 47 and has essentially remained unchanged since 1994, indicating substantial entrance of young psychologists into the field. Use of testing assistants remains commonplace. The “flexible battery” approach has increased in popularity and predominates, whereas endorsement of the “standardized battery” approach continues to decline. More than 90% of respondents are engaged in full-time or full-time plus part-time employment. Incomes from 2004 vary considerably by years of clinical practice, work setting, amount of forensic practice, and region of country. Job satisfaction has little relationship to income and is comparable across most variables (e.g., work setting, professional identity, amount of forensic activity), whereas income satisfaction has a stronger relationship to actual income, at least at the higher income levels. Job satisfaction of neuropsychologists in general is higher than reported for other U.S. jobs. Fewer than one in five respondents is considering changing job position and very few individuals are considering leaving neuropsychology or psychology for a different field. More than 8 of 10 respondents experienced an income increase in the last five years, whereas fewer than 1 in 10 experienced a decrease. While higher than reported by other types of psychologists, neuropsychology incomes have lagged behind inflation when compared to 1992 data. Numerous breakdowns related to income and professional activities are provided.
Disruption of a Structurally Important Extracellular Element in the Glycine Receptor Leads to Decreased Synaptic Integration and Signaling Resulting in Severe Startle Disease

Functional impairments or trafficking defects of inhibitory glycine receptors (GlyRs) have been linked to human hyperekplexia/startle disease and autism spectrum disorders. We found that a lack of synaptic integration of GlyRs, together with disrupted receptor function, is responsible for a lethal startle phenotype in a novel spontaneous mouse mutant shaky, caused by a missense mutation, Q177K, located in the extracellular β8–β9 loop of the GlyR α1 subunit. Recently, structural data provided evidence that the flexibility of the β8–β9 loop is crucial for conformational transitions during opening and closing of the ion channel and represents a novel allosteric binding site in Cys-loop receptors. We identified the underlying neuropathological mechanisms in male and female shaky mice through a combination of protein biochemistry, immunocytochemistry, and both in vivo and in vitro electrophysiology. Increased expression of the mutant GlyR α1Q177K subunit in vivo was not sufficient to compensate for a decrease in synaptic integration of α1Q177Kβ GlyRs. The remaining synaptic heteromeric α1Q177Kβ GlyRs had decreased current amplitudes with significantly faster decay times. This functional disruption reveals an important role for the GlyR α1 subunit β8–β9 loop in initiating rearrangements within the extracellular–transmembrane GlyR interface and that this structural element is vital for inhibitory GlyR function, signaling, and synaptic clustering. SIGNIFICANCE STATEMENT GlyR dysfunction underlies neuromotor deficits in startle disease and autism spectrum disorders. We describe an extracellular GlyR α1 subunit mutation (Q177K) in a novel mouse startle disease mutant shaky. Structural data suggest that during signal transduction, large transitions of the β8–β9 loop occur in response to neurotransmitter binding. Disruption of the β8–β9 loop by the Q177K mutation results in a disruption of hydrogen bonds between Q177 and the ligand-binding residue R65. Functionally, the Q177K change resulted in decreased current amplitudes, altered desensitization decay time constants, and reduced GlyR clustering and synaptic strength. The GlyR β8–β9 loop is therefore an essential regulator of conformational rearrangements during ion channel opening and closing.
The Welfare State and Socioeconomic Inequalities in Women’s Health Dynamics: A Comparative Study of Four OECD Countries

While it is known that social policies influence the organization of employment and family life, this knowledge is rarely used to understand women's health. The current study uses feminist welfare state theory to examine socioeconomic inequalities in women's health dynamics in countries differing by the extent to which their social policies encourage male breadwinning and female caring/homemaking. The pathways underlying these inequalities are also investigated. Socioeconomic inequalities in health are hypothesized to be largest in strong male-breadwinner states (Britain/Germany), smallest in weak male-breadwinner welfare states (Denmark), and intermediate in modified male-breadwinner states (France). Further, family and income will explain more of health inequalities in strong and modified versus weak male-breadwinner
Prior belief and polarity in multicue learning

We report two experiments in which participants are trained using a multicue probability learning (MCPL) task, which attempts to simulate the acquisition of expert judgement by experience in the real world. Participants were asked to predict performance in certain occupations given a profile of personality test results with trial-by-trial outcome feedback. Only some cues were relevant, and the polarity of the cues (positive or negative predictors) was unspecified. In addition, 25% of random noise was added to the feedback to simulate real world uncertainty. The main factor of interest was that the role of prior belief (determined in a separate study of stereotypes) interfered with the learning process. Experiment 1 failed to find any influence of prior belief in the cues that were irrelevant to the criterion being trained. However, in Experiment 2 people learned to use the relevant cues better when their effect conformed with rather than conflicted with prior belief. Both experiments showed strong effects of cue polarity, with positive predictors much more easily learned. The results are discussed with reference to the cognitive processes involved in MCPL and closely related tasks.
Polynomial estimation of the smoothing splines for the new Finnish reference values for spirometry

Abstract Background Discontinuity of spirometry reference values from childhood into adulthood has been a problem with traditional reference values, thus modern modelling approaches using smoothing spline functions to better depict the transition during growth and ageing have been recently introduced. Following the publication of the new international Global Lung Initiative (GLI2012) reference values also new national Finnish reference values have been calculated using similar GAMLSS-modelling, with spline estimates for mean (Mspline) and standard deviation (Sspline) provided in tables. The aim of this study was to produce polynomial estimates for these spline functions to use in lieu of lookup tables and to assess their validity in the reference population of healthy non-smokers. Methods Linear regression modelling was used to approximate the estimated values for Mspline and Sspline using similar polynomial functions as in the international GLI2012 reference values. Estimated values were compared to original calculations in absolute values, the derived predicted mean and individually calculated z-scores using both values. Results Polynomial functions were estimated for all 10 spirometry variables. The agreement between original lookup table-produced values and polynomial estimates was very good, with no significant differences found. The variation slightly increased in larger predicted volumes, but a range of −0.018 to +0.022 litres of FEV1 representing ± 0.4% of maximum difference in predicted mean. Conclusions Polynomial approximations were very close to the original lookup tables and are recommended for use in clinical practice to facilitate the use of new reference values.
The Impact of a Building Implosion on Airborne Particulate Matter in an Urban Community

Abstract In response to community concerns, the air quality impact of imploding a 22-story building in east Baltimore, MD, was studied. Time- and space-resolved concentrations of indoor and outdoor particulate matter (PM) (nominally 0.5–10 µm) were measured using a portable nephelometer at seven and four locations, respectively. PM10 levels varied in time and space; there was no measurable effect observed upwind of the implosion. The downwind peak PM10 levels varied with distance (54,000–589 µg/m3) exceeding pre-implosion levels for sites 100 and 1130 m 3000- and 20-fold, respectively. Estimated outdoor 24-hr integrated mass concentrations varied from 15 to 72 µg/m3. The implosion did not result in the U.S. Environmental Protection Agency (EPA) National Ambient Air Quality Standard (NAAQS) for PM10 being exceeded. X-ray fluorescence analysis indicated that the elemental composition was dominated by crustal elements: calcium (57%), silicon (23%), aluminum (7.6%), and iron (6.1%). Lead was above background but at a low level (0.17 µg/m3). Peak PM10 concentrations were short-lived; most sites returned to background within 15 min. No increase in indoor PM10 was observed even at the most proximate 250 m location. These results demonstrate that a building implosion can have a severe but short-lived impact on community air quality. Effective protection is offered by being indoors or upwind.
Clinical trial risk in Non-Hodgkin's lymphoma: endpoint and target selection.

PURPOSE To quantify the clinical trial risk of new drug development in Non-Hodgkin's lymphoma (NHL). Risk estimates for this disease have not been reported before. METHODS We undertook a retrospective review of clinical trials in (NHL) in four subtypes to compare the success rate with the industry average. Our inclusion criteria required that a drug must initiate its phase I trial in one of the four NHL subtypes between 1998 and June 2008 in the US. In addition, clinical trials of new drug candidates that pertain to four subtypes of NHL were retrieved from clinicaltrial.gov. Drug candidates that did not meet these criteria were excluded from the study. RESULTS The overall success rate (8-11%) was significantly lower than the industry standard (17%). Overall survival (OS) as a secondary outcome appeared more predictive than primary endpoints that were surrogate, of overall success. Further, targeted therapies appear more successful in these lymphoma sub-types than broad acting drugs. CONCLUSION Clinical trial risk in NHL, with an 89% failure rate reported here, may be reduced by basing decisions on OS secondary endpoints and biologic drugs.
Human serum albumin cysteinylation is increased in end stage renal disease patients and reduced by hemodialysis: mass spectrometry studies

Abstract The aim of the present work was to monitor the covalent modifications of human serum albumin (HSA) in end stage renal diseases (ESRD) non-diabetic patients, before and after hemodialysis (HD), by direct infusion electrospray mass spectrometry (ESI-MS). Human serum samples were collected from healthy subjects (n = 10, 20–60 yr) and age-matched ESRD patients (n = 8) before and after HD, purified by affinity chromatography and analyzed by a triple-quadrupole mass spectrometer. The deconvoluted spectra from healthy subjects were all characterized by three peaks attributed to non-glycated mercaptoalbumin (HSA-SH) and to the corresponding adducts with cysteine (HSA-Cys) and glucose (HSA-Glc); relative contents: mercaptoalbumin in both glycated and non-glycated form, HSA-SHt (74 ± 6%), HSA-Cys (26 ± 5%) and HSA-Glc (24 ± 3%). HSA isolated from ESRD patients before HD was characterized by a significant reduction of HSA-SHt (42 ± 7%), and by a concomitant increase of the HSA-Cys adduct (58 ± 7%). Hemodialysis significantly reduced the cysteinylated form (37 ± 7%) and restored HSA-SHt (63 ± 8%) in all the ESRD patients. The mechanism of thiol oxidation and cysteinylation was then studied by mass spectrometry, using LQQCPF as a model peptide and H2O2 as an oxidizing agent.
Representative systems and policy punctuations

ABSTRACT This article examines how the characteristics of political institutions impact the extensiveness of budget punctuations. We develop a theory based on an adaptive systems framework from policy process studies of budgeting, and posit that institutional factors that impede democratic responsiveness lead to inefficiencies that cause policy changes to become more punctuated. Based on previous research on policy responsiveness, we hypothesize that national budgets become more punctuated with increases in federalism, electoral proportionality and executive dominance. We test our theory using Eurostat and International Monetary Fund (COFOG) budget data from 24 countries over the period 1996–2011. Our results strongly support the proposition that more federalized systems produce more budget punctuations, but provide only weak support for the propositions that proportional systems and those with dominant executives do so. The general proposition that institutions can impede the efficient processing of information receives some support, and warrants further investigation.
Equity Risk Premium in ASEAN: Empirical Analysis on Its Puzzle and Impact of 2008 Financial Crisis

This paper aims to mainly investigate equity risk premium of the six major members of ASEAN countries such as Indonesia, Malaysia, Philippines, Singapore, Thailand and Vietnam which have been chosen based on their stock market development and data availability. It has focused on the two main issues of the equity risk premium such as the intriguing issue on the existence of equity premium puzzle and the analysis on the impact of the 2008 financial crisis on the trend of the equity risk premium and their potential contribution on the risk aversion's attitude of the ASEAN investors. Three methods are utilized to test this phenomenon (1) basic model consumption of Mehra and Prescott (1985) and simplified model by Ni (2006); (2) calibration (Campbell, 2003) and (3) GMM estimation (Hansen, 1982). The calibration method results suggest that the puzzle exists in Indonesia.It has determined that the puzzle seems lying on the negative covariance between the consumption growth rate and the average real stock return. After applying GMM as method of the three sub-sample analyses for before, after and excluding 2008, it shows that financial crisis didn't affect much the value of risk aversion, but it cannot deny the fact that it has profound effect on the behavior of the equity risk premium. It can also be inferred that after crisis, ASEAN investors are likely tend to become more decreasing relative risk averse and prefer to have happiness tomorrow than today.