Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel Polymorphisms Associated With Tacrolimus Trough Concentrations: Results From a Multicenter Kidney Transplant Consortium

Background. The CYP4503A5*1 genotype is associated with lower tacrolimus concentrations. Although its effect is important, it incompletely explains the variability in tacrolimus concentrations and has a relatively low minor allele frequency in whites relative to African Americans (AA). Methods. We studied clinical and recipient genetic correlates of dose-normalized tacrolimus troughs (n=12,277) in the first 6 months posttransplant using a customized single-nucleotide polymorphism chip with 2722 variants in a large, ethnically diverse (144 AA and 551 non-AA) adult kidney transplant population through a seven-center consortium. Results. During the 6-month study, AAs had consistently lower median (interquartile range) troughs than non-AAs, 6.2 (4.4–8.4) ng/mL vs. 8.3 (6.4–10.4) ng/mL (P<0.0001), despite 60% higher daily doses, 8 (5–10) mg vs. 5 (4–7) mg (P<0.0001). The median tacrolimus trough concentration in week 1 posttransplant was particularly low in AAs (2.1 [1.2–3.5] ng/mL) compared with non-AAs (5.0 [3.1–8.2] ng/mL) (P<0.0001), despite similar initial doses. In single-variant analysis, CYP3A5*3 (rs776746) was the top variant (P=2.4×10−33) associated with troughs. After adjustment for CYP3A5*3, clinical factors and race, 35 additional variants were identified (P<0.01, not significant at false discovery rate 20%). In the final multivariant, regression models beginning with these variants and clinical factors, seven variants were identified in the non-AA and seven variants in the AA group towards the first trough concentrations. Rs776746 (CYP3A5), rs2239393 (COMT) and diabetes were the only factors common in both populations. Conclusion. We identified variants beyond CYP3A5*3, which may further explain pharmacokinetic variability of tacrolimus and demonstrated that important variants differ by race.
Role of calcium-dependent protease(s) in globulization of isolated rat lens cortical fiber cells.

PURPOSE To investigate the role of calcium-activated proteases in calcium-dependent disintegrative globulization of isolated rat lens cortex fiber cells. METHODS Rat lens fiber cells were isolated and plated on coverslips at the bottom of a temperature-controlled chamber. The fiber cells were incubated with 10 microM protease substrate, (t-butoxycarbonyl-leu-met-7-amino-4-chloromethylcoumarin:BOC-Leu-M et- CMAC) and the proteolytic activity in the fiber cells was determined by observing the increase in fluorescence, using an excitation wavelength of 360 nm, and measuring emission at 410 nm. Free intracellular calcium was measured using the cell-permeable calcium indicator Fluo-3-AM, and the globulization time (T(g)) was determined using image analysis. RESULTS T:(g) of fiber cells superfused with Ringer's solution containing 2 x 10(-)(3) M, 10(-)(6) M, and 10(-)(8) M [Ca(2+)](o) were: 24.7 +/- 1.3, 53.0 +/- 2.8, and more than 120 minutes, respectively. A significant increase in T:(g) ( approximately 95 minutes) was observed when the fibers were preincubated with acetoxymethyl ester of 1,2-bis (2-amino-phenoxy) ethane N:, N:, N:, N:-tetra-acetic acid (BAPTA-AM) to buffer changes in [Ca(2+)](i), or the protease substrate to competitively inhibit degradation of cellular proteins. In the presence of Ringer's solution containing 2 x 10(-)(3) M [Ca(2+)](o) and 0.5 mM of the cysteine protease inhibitor, leupeptin, T:(g) increased to 100 minutes, without affecting [Ca(2+)](i). The proteolytic activity of fiber cells in Ringer's solution containing 10(-)(6) M and 2 x 10(-)(3) M [Ca(2+)](o) increased by approximately 7- and 12-fold, respectively, compared with sucrose-EDTA solution or Ringer's solution containing 10(-)(8) M [Ca(2+)](o). This increase in proteolytic activity was inhibited by leupeptin. CONCLUSIONS Elevation of calcium in the medium results in a proportionate increase in [Ca(2+)](i) and the proteolytic activity in isolated lens fiber cells. The increase in the proteolytic activity is accompanied by an increase in the rate of globulization of the fiber cells. Inhibition of the proteolytic activity by leupeptin increases T:(g) without affecting the gain in [Ca(2+)](i). These results suggest that globulization of isolated fiber cells in physiological salt solutions is mediated by Ca(2+)-activated protease(s).
Design of ZF and MMSE filter-banks in relay networks with average and peak power constraints

In this paper we consider the design of jointly optimal filter-banks for transmission over frequency selective MIMO relay channels. Utilising block processing we present designs that maximise signal to noise ratio under the zero forcing constraint and minimise the mean square error. Both designs targetted in this paper assume limited power resource at the relaying stage of the network and we resort to techniques from convex optimisation theory to obtain the solutions to the constrained design problems.
Temporary Contracts – the new European inequality ? Comparing men and women in West Germany and France

This paper seeks to reveal whether temporary contracts are the new European inequality and does so in a comparative analysis of two countries typically regarded as eurosclerotic: Germany and France. We compare the wages, wage growth and labour market outcomes of fixed-term contract workers relative to a matched sample of permanent workers with similar characteristics. Using seven waves of the ECHP we find evidence of wage penalties, increased exposure to unemployment and repeat spells of temporary employment. However, these tendencies vary significantly by country and by gender. The main finding of this paper is the extent to which temporary contract employment is of considerable disadvantage for French women. This is important, as previous research on female employment in the United-Kingdom and in West-Germany (Booth et al 2002; Giesecke and Gross 2003), two countries with intermittent female employment, did not find evidence of temporary worker disadvantage. Our findings, however, suggest that in countries where female employment tends to be full-time and continuous, women will experience disadvantage on the introduction of temporary contracts. The impact of temporary contract employment was not as damaging for our matched male sample, however, and contrary to our expectations, we found a slight tendency for greater male disadvantage in West Germany relative to France. Correspondence: Vanessa Gash, Max Planck Institute for Human Development, Lentzealle 94, D-14195 Berlin. Email: gash@mpibberlin.mpg. de or Frances McGinnity, Economic and Social Research Institute, Dublin 4. email: fran.mcginnity@esri.ie
Estimating societal preferences for the allocation of healthcare resources using stated preference methods

Most governments in the world provide some publicly funded healthcare to their citizens, but given the scarcity of resources relative to potential demand, some form of rationing or priority setting is required, and some patients must be denied effective treatment. The thesis took the position that an explicit approach based on maximising the value that society derives from healthcare is the preferred way to address this rationing problem. Conventional health economic practice proposes that value should be equated with quality-adjusted life years (QALYs), leading to a policy of QALY maximisation, but, it is argued, not necessarily value maximisation. A more inclusive approach to defining value, based on societal preferences, may maximise overall well-being and be associated with greater trust and legitimacy in the priority setting process. The thesis identified patient and program characteristics that appeared to have empirical evidence of public support as well as a defensible ethical justification in determining the strength of a patient’s claim to societal healthcare resources. The relative strength of preferences for these characteristics, or the equity-efficiency trade-off, was estimated using stated preference methods. Two different methods, discrete choice experiments and constant-sum paired comparisons, were used and the response behaviours of the two elicitations were compared to identify a preferred method for eliciting societal preferences in the context of healthcare. Both methods found a statistically significant equity-efficiency trade-off in an age and sex representative sample of the Canadian public as well as a convenience sample of decision-making agents. This suggested that society would be willing to sacrifice some degree of efficiency in maximising individual life year gains in order to prioritise other characteristics consistent with the promotion of equity or distributive justice in the allocation of healthcare resources. However, differences between the results of the two elicitation methods suggested some systematic procedural variance.
Modeling Variable Emission Lines in Active Galactic Nuclei: Method and Application to NGC 5548

We present a new scheme for modeling the broad-line region in active galactic nuclei (AGNs). It involves photoionization calculations of a large number of clouds, in several predetermined geometries, and a comparison of the calculated line intensities with observed emission-line light curves. Fitting several observed light curves simultaneously provides strong constraints on model parameters such as the run of density and column density across the nucleus, the shape of the ionizing continuum, and the radial distribution of the emission-line clouds. When applying the model to the Seyfert 1 galaxy NGC 5548, we were able to reconstruct the light curves of four ultraviolet emission lines in time and in absolute flux. This has not been achieved by any previous work. We argue that the Balmer line light curves, and possibly also the Mg II λ2798 light curve, cannot be tested in this scheme because of the limitations of present-day photoionization codes. Our fitting procedure can be used to rule out models in which the particle density scales as r-2, where r is the distance from the central source. The best models are those in which the density scales as r-1 or r-1.5. We can place a lower limit on the column density at a distance of 1 lt-day of Ncol(r = 1) ≳ 1023 cm-2 and limit the particle density to be in the range of 1012.5 > N(r = 1) > 1011 cm-3. We have also tested the idea that the spectral energy distribution (SED) of the ionizing continuum is changing with continuum luminosity. None of the variable-shape SEDs tried resulted in real improvement over a constant-SED case, although models with harder continuum during phases of higher luminosity seem to better fit the observed spectrum. Reddening and/or different composition seem to play a minor role, at least to the extent tested in this work.
Combining Multiple Artificial Neural Networks Using Random Committee to Decide upon Electrical Disturbance Classification

An ANN-based automatic classifier for power system disturbance waveforms was developed. Actual voltage waveforms were applied in the training process. Signals were processed in two steps: i) decomposition through wavelet transformation up to the 5th decomposition level; ii) the resultant wavelet coefficients are processed via PCA, reducing the input space of the classifier to a much lower dimension. The classification was carried out using a combination of six MLPs with different architectures: five representing the first to fifth-level details, and one representing the fifth-level approximation. The RPROP algorithm was applied for training the networks. Network combination was formed using random committee which builds an ensemble of randomized base classifiers. Experimental results with real data indicate that the random committee is clearly an effective way to improve disturbance classification accuracy when compared with the simple average and the individual models.
Do Gravity Waves Transport Angular Momentum Away From Tropical Cyclones

Previous studies have suggested that gravity waves can transport a significantly large amount of angular momentum away from tropical cyclones, as much as 10% of the core angular momentum per hour. These previous studies used the shallow-water equations to model gravity waves radiating outward from rapidly rotating inner-core asymmetries. This issue is reinvestigated with a three-dimensional, nonhydrostatic, linear model of the vortex-anelastic equations. The response of balanced, axisymmetric vortices modeled after tropical cyclones to rotating asymmetric heat sources is examined to assess angular momentum transport by gravity waves radiating away from the core region of the vortices. Calculations show that gravity waves do transportangularmomentumawayfromthevortexcore;however,theamounttransportedisseveralordersof magnitude smaller than recent estimates.
omega-Conotoxin block of N-type calcium channels in frog and rat sympathetic neurons

Block of N-type Ca channels by omega-conotoxin GVIA (CgTx) was studied in freshly dissociated bullfrog and rat sympathetic neurons. With 2–5 mM Ba as charge carrier, CgTx blocked almost all of the high-threshold Ca channel current recorded in the presence of nimodipine (3 microM) to block L-type Ca channels. Toxin block reversed slowly (time constant approximately 1 hr) in frog cells and even more slowly in rat cells. CgTx block was faster and more potent in rat cells than frog cells. The rate of block was proportional to CgTx concentration, consistent with 1:1 binding of CgTx to channels. When the external Ba concentration was increased, the development of block was slower, consistent with competition between CgTx and Ba for a binding site. The recovery from block was somewhat faster in higher external Ba. Some cells had significant current remaining in saturating concentrations of nimodipine and CgTx, especially with high Ba concentrations in the external solution. The current resistant to nimodipine and CgTx was activated at lower depolarizations than the CgTx-sensitive current and had faster activation and inactivation kinetics, but unlike low- threshold T-type current, the resistant current had rapidly decaying tail currents.
Imaging Brain Plasticity: Conceptual and Methodological Issues— A Theoretical Review

The neural plasticity associated with learning and development is increasingly being studied using functional neuroimaging methods such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). In this paper I outline a set of conceptual and methodological issues that are particularly relevant for the study of neural plasticity. A number of confounds, related to changes in performance and the inherently temporal nature of learning and development, must be addressed when imaging plasticity. The interpretation of changes in imaging signals is greatly underdetermined, suggesting that hypothesis-driven research approaches may be most fruitful. Finally, I argue that the imaging of learning-related and developmental plasticity can enhance the ability of functional neuroimaging to identify and characterize the underlying neural basis of cognition.
Folic Acid and Coenzyme Q10 Ameliorate Cognitive Dysfunction in the Rats with Intracerebroventricular Injection of Streptozotocin

Objective(s) The present study aimed to investigate the effects of a fat soluble antioxidant, coenzyme Q10 (CoQ10) and folic acid on learning and memory in the rats with intracerebroventricular injection of streptozotocin (ICV-STZ), an animal model of sporadic type of Alzheimer's disease. Materials and Methods The lesion groups were injected bilaterally with ICV-STZ (1.5 mg/kg b.wt., in normal saline). In the treated groups, rats received folic acid (4 mg/kg; i.p.) or CoQ10 (10 mg/kg; i.p.), either alone or together, for 21 days. Passive avoidance learning test was used for evaluation of learning and memory. Results The results showed that learning and memory performance was significantly impaired in the rats with ICV-STZ (P< 0.001), however CoQ10 and folic acid, either alone or together, prevented impairments significantly (P< 0.001), as there was not any significant difference between these treated lesion groups and control group. Conclusion The present results suggest that CoQ10 and folic acid have therapeutic and preventive effects on cognitive impairments in Alzheimer’s disease.
Uses and Misuses of Bronfenbrenner's Bioecological Theory of Human Development

This paper evaluates the application of Bronfenbrenner’s bioecological theory as it is represented in empirical work on families and their relationships. We describe the ‘‘mature’’ form of bioecological theory of the mid-1990s and beyond, with its focus on proximal processes at the center of the Process-Person-Context-Time model. We then examine 25 papers published since 2001, all explicitly described as being based on Bronfenbrenner’s theory, and show that all but 4 rely on outmoded versions of the theory, resulting in conceptual confusion and inadequate testing of the theory.
Islamic Political Culture, Democracy, and Human Rights: A Comparative Study

Preface Introduction The Need for a New Approach How and Why Islam Should Influence Politics? Egypt and Jordan Syria and Tunisia Saudi Arabia and Morocco Algeria and Iran Islam and Democracy: Cross-National Analysis Islam and Individual Rights Does Culture Matter? Appendix I: The Islamic Political Culture Variable Appendix II: Country Abbreviations and Islamic Political Culture Scores Appendix III: Islamic Ideologies Bibliography Index
Thermal and Structural Behavior of Dioctadecyldimethylammonium Bromide Dispersions Studied by Differential Scanning Calorimetry and X-Ray Scattering

Dioctadecyldimethylammonium bromide (DODAB) is a double chain cationic lipid, which assembles as bilayer structures in aqueous solution. The precise structures formed depend on, e.g., lipid concentration and temperature. We here combine differential scanning calorimetry (DSC) and X-ray scattering (SAXS and WAXS) to investigate the thermal and structural behavior of up to 120 mM DODAB in water within the temperature range 1–70°C. Below 1 mM, this system is dominated by unilamellar vesicles (ULVs). Between 1 and 65 mM, ULVs and multilamellar structures (MLSs) co-exist, while above 65 mM, the MLSs are the preferred structure. Depending on temperature, DSC and X-ray data show that the vesicles can be either in the subgel (SG), gel, or liquid crystalline (LC) state, while the MLSs (with lattice distance d = 36.7 Å) consist of interdigitated lamellae in the SG state, and ULVs in the LC state (no Bragg peak). Critical temperatures related to the thermal transitions of these bilayer structures obtained in the heating and cooling modes are reported, together with the corresponding transition enthalpies.
The pioneer factor PBX1 is a novel driver of metastatic progression in ERα-positive breast cancer

Over 30% of ERα breast cancer patients develop relapses and progress to metastatic disease despite treatment with endocrine therapies. The pioneer factor PBX1 translates epigenetic cues and mediates estrogen induced ERα binding. Here we demonstrate that PBX1 plays a central role in regulating the ERα transcriptional response to epidermal growth factor (EGF) signaling. PBX1 regulates a subset of EGF-ERα genes highly expressed in aggressive breast tumours. Retrospective stratification of luminal patients using PBX1 protein levels in primary cancer further demonstrates that elevated PBX1 protein levels correlate with earlier metastatic progression. In agreement, PBX1 protein levels are significantly upregulated during metastatic progression in ERα-positive breast cancer patients. Finally we reveal that PBX1 upregulation in aggressive tumours is partly mediated by genomic amplification of the PBX1 locus. Correspondingly, ERα-positive breast cancer patients carrying PBX1 amplification are characterized by poor survival. Notably, we demonstrate that PBX1 amplification can be identified in tumor derived-circulating free DNA of ERα-positive metastatic patients. Metastatic patients with PBX1 amplification are also characterized by shorter relapse-free survival. Our data identifies PBX1 amplification as a functional hallmark of aggressive ERα-positive breast cancers. Mechanistically, PBX1 amplification impinges on several critical pathways associated with aggressive ERα-positive breast cancer.
Why do we play the games? Exploring institutional and political motivations

Purpose – The purpose of this paper is to explore why digital games based learning (DGBL) is spreading rapidly in all educational settings, when the literature does not provide clear empirical evidence of the pedagogical benefits. The paper seeks to understand why DGBL is constantly developing despite this lack of consensus about the learning outcomes. Design/methodology/approach – In order to identify the motivations for DGBL adoption and implementation beyond pedagogical ones, the authors use organizational theories to propose a three-dimensional framework in which pedagogical motivation is articulated with political (linked to local characteristics) and institutional (linked to the macro-environment) motivations. They then study the respective importance the three kinds of motivation in the adoption decisions and the implementation process of DGBL. To this end, they conducted a retrospective analysis of four embedded case studies in European business schools. Findings – The authors find that institutional motivation plays a major role in adoption decisions while political motivations can contribute to the decision but are not necessarily present. Isomorphic pressure is essentially mimetic for early adopters and combined with coercive elements for late adopters. Practical implications – During the implementation phase customization is mainly driven by political objectives while institutionalized ideas about the best way to implement the game are not typically influential. Originality/value – The study shows that pedagogical benefits are a prerequisite rather than the core motivation for adoption or implementation. Second, the study is a call for both academics and practitioners not to over-rationalize or under-rationalize DGBL and, more broadly, pedagogical innovations and adoption decisions.
Polynomial optimization with applications to stability analysis and control - Alternatives to sum of squares

In this paper, we explore the merits of various algorithms for solving polynomial optimization and optimization of polynomials, focusing on alternatives to sum of squares programming. While we refer to advantages and disadvantages of Quantifier Elimination, Reformulation Linear Techniques, Blossoming and Groebner basis methods, our main focus is on algorithms defined by Polya's theorem, Bernstein's theorem and Handelman's theorem. We first formulate polynomial optimization problems as verifying the feasibility of semi-algebraic sets. Then, we discuss how Polya's algorithm, Bernstein's algorithm and Handelman's algorithm reduce the intractable problem of feasibility of semi-algebraic sets to linear and/or semi-definite programming. We apply these algorithms to different problems in robust stability analysis and stability of nonlinear dynamical systems. As one contribution of this paper, we apply Polya's algorithm to the problem of $H_\infty$ control of systems with parametric uncertainty. Numerical examples are provided to compare the accuracy of these algorithms with other polynomial optimization algorithms in the literature.
Shrinking Fish By

Fisheries scientist David Conover, dean and director of the Marine Sciences Research Center at SUNY Stony Brook, is leading the most extensive laboratory study to date on the effects of size-selective harvesting in fish stocks. As described in Scientific American magazine, he and his team mimicked fishing by removing 90 percent of the largest fish from a lab population of Atlantic Siversides (Menidia menidia), a small marine fish. In another experimental group they removed 90 percent of the smallest fish, and in a control group they removed the same amount of fish, but without regard to size.