Miracle-dz/UniFAR-FTUs huggingface dataset:
Huntingtin Phosphorylation Sites Mapped by Mass Spectrometry

Huntingtin (Htt) is a large protein of 3144 amino acids, whose function and regulation have not been well defined. Polyglutamine (polyQ) expansion in the N terminus of Htt causes the neurodegenerative disorder Huntington disease (HD). The cytotoxicity of mutant Htt is modulated by proteolytic cleavage with caspases and calpains generating N-terminal polyQ-containing fragments. We hypothesized that phosphorylation of Htt may modulate cleavage and cytotoxicity. In the present study, we have mapped the major phosphorylation sites of Htt using cell culture models (293T and PC12 cells) expressing full-length myc-tagged Htt constructs containing 23Q or 148Q repeats. Purified myc-tagged Htt was subjected to mass spectrometric analysis including matrix-assisted laser desorption/ionization mass spectrometry and nano-HPLC tandem mass spectrometry, used in conjunction with on-target alkaline phosphatase and protease digestions. We have identified more than six novel serine phosphorylation sites within Htt, one of which lies in the proteolytic susceptibility domain. Three of the sites have the consensus sequence for ERK1 phosphorylation, and addition of ERK1 inhibitor blocks phosphorylation at those sites. Other observed phosphorylation sites are possibly substrates for CDK5/CDC2 kinases. Mutation of amino acid Ser-536, which is located in the proteolytic susceptibility domain, to aspartic acid, inhibited calpain cleavage and reduced mutant Htt toxicity. The results presented here represent the first detailed mapping of the phosphorylation sites in full-length Htt. Dissection of phosphorylation modifications in Htt may provide clues to Huntington disease pathogenesis and targets for therapeutic development.
The Use of Random Utility in Modeling Rural Health Care Demand: Discussion

that are quality-differentiated, close substitutes. The three papers in this session take advantage of this modeling strategy in the context of health care facility choice, so as to shed light on the impact of rural hospital closings on the welfare of rural populations. Each of the three papers is of interest in its own right, but all three illustrate that many of the same problems that plague recreation demand applications emerge in this new application-albeit sometimes for different rea-
Effects of Childcare Subsidies on Employment and Earnings of Low-Income Mothers

Abstract This study examines how childcare subsidies funded by the Child Care and Development Fund (CCDF – the most widespread childcare subsidy program in the United States) affect the employment status and earnings of low-income mothers. Employing a rich database of administrative records, we compute instrumental variables and control function estimates of the program’s effects. As an exclusion restriction, we take advantage of differences in efficiency levels across administrative agencies that process subsidy applications and payments. CCDF-funded subsidies have short-term effects that are primarily driven by changes in the extensive margin of labor supply. Mothers who are either unemployed or earning closer to the upper cutoff of eligibility benefit the most from participation in this program.
The Variability of Expectations in Hyperinflations

A problem in the use of adaptive expectations as a mechanism for generating expectations of inflation is the assumption that the speed with which individuals revise their expectations is constant. The purpose of this paper is to estimate the Cagan model of the demand for money for six hyperinflation countries allowing the coefficient of expectations (which measures the response to the error between the actual and the expected rate of inflation) to vary with the level and the change in the rate of inflation. The results indicate considerable support for this particular hypothesis.
Application of the enterprise management tools Lean Six Sigma and PMBOK in developing a program of research management.

OBJECTIVE Introduce a program for the management of scientific research in a General Hospital employing the business management tools Lean Six Sigma and PMBOK for project management in this area. METHODS The Lean Six Sigma methodology was used to improve the management of the institution's scientific research through a specific tool (DMAIC) for identification, implementation and posterior analysis based on PMBOK practices of the solutions found. RESULTS We present our solutions for the management of institutional research projects at the Sociedade Beneficente Israelita Brasileira Albert Einstein. The solutions were classified into four headings: people, processes, systems and organizational culture. A preliminary analysis of these solutions showed them to be completely or partially compliant to the processes described in the PMBOK Guide. CONCLUSION In this post facto study, we verified that the solutions drawn from a project using Lean Six Sigma methodology and based on PMBOK enabled the improvement of our processes dealing with the management of scientific research carried out in the institution and constitutes a model to contribute to the search of innovative science management solutions by other institutions dealing with scientific research in Brazil.
Mouse MTH1 Protein with 8-Oxo-7,8-dihydro-2′-deoxyguanosine 5′-Triphosphatase Activity That Prevents Transversion Mutation

8-Oxo-7,8-dihydro-2′-deoxyguanosine 5′-triphosphate (8-oxo-dGTP) is formed in the nucleotide pool of a cell during normal cellular metabolism, and when it is incorporated into DNA causes mutation. Organisms possess 8-oxo-dGTPase, an enzyme that specifically degrades 8-oxo-dGTP to 8-oxo-dGMP. We isolated cDNA for mouse 8-oxo-dGTPase, using as a probe human MTH1 (Escherichia coli mutT homolog) cDNA. The nucleotide sequence of the cDNA revealed that the mouse MTH1 protein (molecular weight of 17,896) comprises 156 amino acid residues. When the cDNA for mouse 8-oxo-dGTPase was expressed in E. coli mutT mutant cells devoid of their own 8-oxo-dGTPase activity, an 18-kDa protein, which is cross-reactive with an anti-human MTH1 antibody, was formed. In such cells, the level of spontaneous mutation frequency that was elevated reverted to normal. High levels of 8-oxo-dGTPase activity were found in liver, thymus, and large intestine, whereas all other organs examined contained smaller amounts of the enzyme. In embryonic stem cells, an exceedingly high level of the enzyme was present.
Frequency Compensation for Multistage Amplifiers Using Active-Feedback Current Buffers

A frequency compensation scheme based on an active-feedback current buffer (AFCB) is presented in this paper. With an active-feedback mechanism, the proposed AFCB offers quite low input impedance across wide frequency spectrum, which greatly reduces the power consumption of AFCB amplifiers employing the AFCB as frequency compensation. The bandwidth and slew rate of the AFCB amplifier are also improved due to the much smaller compensation capacitors. Moreover, the presence of a left-half-plane zero in the AFCB amplifier enhances the stability and settling behavior of the amplifier. A three-stage AFCB amplifier is implemented by a standard 0.18-mum CMOS process. When driving a 120-pF capacitive load, the AFCB amplifier achieves over 100-dB dc gain, 8.5-MHz gain-bandwidth product (GBW), 65deg phase margin, and 3.4-V/mus average slew rate with total 1.2-pF compensation capacitances, while only dissipating 88-muW power at a 1.5-V supply
A Note on Satisfaction with Life, Government and Job: The Case of Eastern Europe

Recent studies on life satisfaction or well-being focus on transition countries. These countries are the Central Eastern European and Baltic states (CEE) and the Commonwealth of Independent States (CIS). The half of the CEE countries are meanwhile members of the European Union (EU). Using the year 2008 of the European Values Study 2010 (EVS), I use simple OLS regressions for life satisfaction, as well as satisfaction with government and the job. Individual characteristics are in line with global well-being results. I find no evidence that Eastern European EU member countries behave different then other transition countries. But there are a some differences between the countries concerning governmental quality and job satisfaction.
Thermal analysis of gold nanorods heated with femtosecond laser pulses

We present an axisymmetric computational model to study the heating processes of gold nanoparticles, specifically nanorods, in aqueous medium by femtosecond laser pulses. We use a two-temperature model for the particle, a heat diffusion equation for the surrounding water to describe the heat transfer processes occurring in the system, and a thermal interface conductance to describe the coupling efficiency at the particle/water interface. We investigate the characteristic time scales of various fundamental processes, including lattice heating and thermal equilibration at the particle/surroundings interface, the effects of multiple laser pulses, and the influence of nanorod orientation relative to the beam polarization on energy absorption. Our results indicate that the thermal equilibration at the particle/water interface takes approximately 500 ps, while the electron–lattice coupling is achieved at approximately 50 ps when a 48 × 14 nm2 gold nanorod is heated to a maximum temperature of 1270 K with the application of a laser pulse having 4.70 J m−2 average fluence. Irradiation by multiple pulses arriving at 12.5 ns time intervals (80 MHz repetition rate) causes a temperature increase of no more than 3 °C during the first few pulses with no substantial changes during the subsequent pulses. We also analyse the degree of the nanorods' heating as a function of their orientation with respect to the polarization of the incident light. Lastly, it is shown that the temperature change of a nanorod can be modelled using its volume-equivalent sphere for femtosecond laser heating within 5–15% accuracy.
Mechanism of action of acetylcholine on calcium current in single cells from frog ventricle.

Ca currents (ICa) were measured by whole‐cell patch clamp in single cells isolated from frog ventricle in which K currents were blocked with intracellular (120 mM) and extracellular (20 mM) Cs. Inward currents elicited by depolarizing voltage steps from a holding potential of ‐80 mV were blocked completely by 0.5 mM‐Cd. The quality of the voltage clamp was assessed using two patch electrodes on a single cell. One electrode was used in the voltage‐clamp mode to measure membrane currents and the other in current‐clamp to measure membrane potential. Ca currents as large as 2 nA were well clamped in cells as long as 210 micron. Acetylcholine (ACh) had no effect on ICa in the absence of beta‐adrenergic stimulation but reduced to control levels ICa elevated by isoprenaline. Nanomolar concentrations of ACh were able to reduce significantly ICa elevated by 2 microM‐isoprenaline. ACh had no effect on the shape of the I‐V curve, on the reactivation (recovery from inactivation), or on the inactivation of ICa. Although isoprenaline increased ICa by an average of 6.5‐fold, it had no effect on the shape of the I‐V curve or on the inactivation at test potentials negative to +40 mV. However, isoprenaline slowed the half‐reactivation time from a control value of 120 +/‐ 10 ms (mean +/‐ S.D.) to 153 +/‐ 12 ms at ‐80 mV. The effect of cyclic AMP on ICa was investigated using two patch electrodes, one filled with cyclic AMP. Maximal effects of cyclic AMP were observed with 5 microM‐cyclic AMP in the pipette. Maximal ICa was recorded several minutes after breaking the patch with the second electrode. After removing the cyclic‐AMP‐containing electrode, ICa declined to control levels after approximately 10 min. 5 microM‐cyclic AMP in the patch electrode increased ICa by an average of 6.9‐fold, but had no effect on the shape of the I‐V curve or on inactivation. Cyclic AMP had a slowing effect on reactivation (half‐reactivation time = 155 +/‐ 24 ms) similar to that of isoprenaline. ACh (1‐10 microM) did not reduce ICa elevated with cyclic AMP (0.1‐20 microM‐cyclic AMP in the pipette). With low concentrations of cyclic AMP in the pipette (0.1 microM), isoprenaline augmented ICa, but with 5 microM‐cyclic AMP in the pipette, isoprenaline was incapable of increasing ICa further. These results suggest that the decrease of ICa produced by ACh can be explained solely by decreases in cyclic AMP levels.
Should the Caribbean Countries Sign an Economic Partnership Agreement with the EU?: Challenges and Strategic Options

Currently, the European Union is negotiating an free trade agreement, called Economic Partnership Agreement (EPA), with Caribbean countries as part of the Cotonou Agreement between the European Union and African, Caribbean and Pacific countries. The paper empirically assesses the impact of the proposed EPA on trade flows and government revenue for Caribbean countries. The results indicate that the decline in import duties due to the preferential tariff elimination might be of some cause for concern in a number of countries, and that complementary fiscal and economic policies have to be implemented before or at the time the EPA comes into force.
Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1 (supplement).

We established a protocol for the prediction of the coding sequences of unidentified human genes based on the double selection and sequence analysis of cDNA clones with inserts carrying unreported 5'-terminal sequences and with insert sizes corresponding to nearly full-length transcripts. By applying the protocol, cDNA clones with inserts longer than 2 kb were isolated from a cDNA library of human immature myeloid cell line KG-1, and the coding sequences of 40 new genes were predicted. A computer search of the sequences indicated that 20 genes contained sequences similar to known genes in the GenBank/EMBL databases. The sequences of the remaining 20 genes were entirely new, and characteristic protein motifs or domains were identified in 32 genes. Other sequence features noted were that the coding sequences of 23 genes were followed by relatively long stretches of 3'-untranslated sequences and that 5 genes contained repetitive sequences in their 3'-untranslated regions. The chromosomal location of these genes has been determined. By increasing the scale of the above analysis, the coding sequences of many unidentified genes can be predicted.
Peritubular capillary C4d staining in late acute renal allograft rejection – is it relevant?

Abstract: Background: In the early post‐transplant period, renal allograft rejection with diffuse peritubular capillary (PTC) C4d deposition predicts poor graft survival. In the late post‐transplant setting, that is, one or more yr after transplantation, the implication of diffuse PTC C4d deposition is still a topic of debate. The purpose of our study was to see if diffuse PTC C4d deposition, in late acute rejection (LAR), occurring more than one yr post‐transplant, has any impact on graft survival and function.
The performance profile: A multi–criteria performance evaluation method for test–based problems

Abstract In test-based problems, solutions produced by search algorithms are typically assessed using average outcomes of interactions with multiple tests. This aggregation leads to information loss, which can render different solutions apparently indifferent and hinder comparison of search algorithms. In this paper we introduce the performance profile, a generic, domain-independent, multi-criteria performance evaluation method that mitigates this problem by characterizing the performance of a solution by a vector of outcomes of interactions with tests of various difficulty. To demonstrate the usefulness of this gauge, we employ it to analyze the behavior of Othello and Iterated Prisoner’s Dilemma players produced by five (co)evolutionary algorithms as well as players known from previous publications. Performance profiles reveal interesting differences between the players, which escape the attention of the scalar performance measure of the expected utility. In particular, they allow us to observe that evolution with random sampling produces players coping well against the mediocre opponents, while the coevolutionary and temporal difference learning strategies play better against the high-grade opponents. We postulate that performance profiles improve our understanding of characteristics of search algorithms applied to arbitrary test-based problems, and can prospectively help design better methods for interactive domains.
Titanium Dioxide (TiO2) Nanoparticles Induce JB6 Cell Apoptosis Through Activation of the Caspase-8/Bid and Mitochondrial Pathways

Titanium dioxide (TiO2), a commercially important material, is used in a wide variety of products. Although TiO2 is generally regarded as nontoxic, the cytotoxicity, pathogenicity, and carcinogenicity of TiO2 nanoparticles have been recently recognized. The present study investigated TiO2 nanoparticle-induced cell apoptosis and molecular mechanisms involved in this process in a mouse epidermal (JB6) cell line. Using the 3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay, TiO2 nanoparticles were found to exhibit higher cytotoxicity than fine particles. YO-PRO-1 iodide (YP) staining demonstrated that both TiO2 nanoparticles and fine particles induced cell death through apoptosis. The signaling pathways involved in TiO2 particle-induced apoptosis were investigated. Western-blot analysis showed an activation of caspase-8, Bid, BAX, and caspase-3 and a decrease of Bcl-2 in JB6 cells treated with TiO2 particles. Time-dependent poly(ADP)ribose polymerase (PARP) cleavage induced by TiO2 nanoparticles was observed. TiO2 particles also induced cytochrome c release from mitochondria to cytosol. Further studies demonstrated that TiO2 nanoparticles induced significant changes in mitochondrial membrane permeability, suggesting the involvement of mitochondria in the apoptotic process. In conclusion, evidence indicated that TiO2 nanoparticles exhibit higher cytotoxicity and apoptotic induction compared to fine particles in JB6 cells. Caspase-8/Bid and mitochondrial signaling may play a major role in TiO2 nanoparticle-induced apoptosis involving the intrinsic mitochondrial pathway. Unraveling the complex mechanisms associated with these events may provide further insights into TiO2 nanoparticle-induced pathogenicity and potential to induce carcinogenicity.
A method for the direct synthesis of cascaded quintuplets

A new lowpass prototype configuration for a cascaded quintuplet is presented. The cascaded quintuplet is a cross-coupled filter structure that is used in microwave filter topologies to realize three finite frequency transmission zeros. The lowpass prototype can be converted into the cascaded quintuplet format using a series of equivalent circuit transformations. The method permits the direct synthesis of an arbitrary number of in-line cascaded quintuplets from the filter impedance function.
A Microwave Ring Resonator Sensor for Early Detection of Breaches in Pipeline Coatings

A planar microwave resonator sensor is designed, customized, and fabricated to detect coating breaches in industrial steel pipelines. The sensor, which utilizes a ring-shaped resonator to maximize the sensitivity at its core, is tuned to 2.5 GHz with a quality factor of 280. In the setup, the sensor is grounded to a piece of steel pipeline with an Epoxy-100 coating, which provides the substrate beneath the microstrip structure. It is demonstrated that any change in the gap height between the substrate layer and the pipeline, from 0 to 3.5 mm, produces a significant resonant frequency variation and bandwidth change in the sensor's response. The sensor structure demonstrates sensitivity and selectivity to air and water penetration to the breach. The sensor structure described in this work is a compact, low-cost solution and has potential for further miniaturization in mobile applications which may serve as a method for pipeline breach detection.
Firm Valuation, Earnings Expectations, and the Exchange‐Rate Exposure Effect

Consistent with previous research, the authors fail to find a significant correlation between the abnormal returns of their sample firms with international activities and changes in the dollar. They investigate the possibility that this failure is due to mispricing. Lagged changes in the dollar are a significant variable in explaining current abnormal returns of the authors' sample firms, suggesting that misprizing does occur. A simple trading strategy based upon these results generates significant abnormal returns. Corroborating evidence from returns around earnings announcements as well as errors in analysts' forecasts of earnings is also provided. Copyright 1994 by American Finance Association.
Modeled insulin sensitivity and interstitial insulin action from a pilot study of dynamic insulin sensitivity tests

An accurate test for insulin resistance can delay or prevent the development of Type 2 diabetes and its complications. The current gold standard test, CLAMP, is too labor intensive to be used in general practice. A recently developed dynamic insulin sensitivity test, DIST, uses a glucose-insulin-C-peptide model to calculate model-based insulin sensitivity, SI. Preliminary results show good correlation to CLAMP. However both CLAMP and DIST ignore saturation in insulin-mediated glucose removal. This study uses the data from 17 patients who underwent multiple DISTs to investigate interstitial insulin action and its influence on modeled insulin sensitivity. The critical parameters influencing interstitial insulin action are saturation in insulin receptor binding, αG, and plasma-interstitial diffusion rate, nI. Very low values of αG and very low values of nI produced the most intra-patient variability in SI. Repeatability in SI is enhanced with modeled insulin receptor saturation. Future parameter study on subjects with varying degree of insulin resistance may provide a better understanding of different contributing factors of insulin resistance.
Differences in cancer incidence among predominantly Muslim and Buddhist subpopulations in Songkhla.

BACKGROUND The population of Songkhla, a province in Southern Thailand, can be divided into a predominantly Muslim subpopulation (PMSP, approximately 70% Muslim) and a predominantly Buddhist subpopulation (PBSP, around 14% Muslim). OBJECTIVES This study was conducted to 1) describe the incidence of various cancers in both PMSP and PBSP, and 2) compare the incidence of various cancers between the two subpopulations. MATERIALS AND METHODS Cancer cases diagnosed between 1990 and 2010 were drawn from the database of Songkhla Cancer Registry. Population denominators were estimated from the 3 population censuses surveyed by the National Statistical Office of Thailand in 1990, 2000, and 2010. RESULTS The age-standardized incidence rates (ASR) of the 5 commonest male cancers among both subpopulations were calculated. In females, a lower incidence of cancers of the cervix and breast in PMSP compared to PBSP, with odds ratios of 0.54 (95% CI: 0.45-0.64) and 0.51 (95% CI: 0.43-0.60) respectively, was observed. In males, the incidence of cancers of the lung, liver, colon-rectum, and some other cancers were significantly different between the two populations in the past, but only prostate cancer showed a lower incidence among males in PMSP in recent years. Independent of sex and year of diagnosis, the incidence of lung, liver, NHL, and colorectal cancers was lower in MPSP compared to BPSP, with odds ratios of 0.75 (95% CI: 0.65-0.85), 0.74 (95% CI: 0.62-0.88), 0.74 (95% CI: 0.60-0.91), and 0.67 (95% CI: 0.56-0.78) respectively. CONCLUSIONS The differences in incidence of some cancers and religion- related culture between the two subpopulations need 2 sets of cancer-control plans and goals to fit the unique population context in deep Southern Thailand. This plan can be used in the 3 southernmost provinces of Thailand where the percentage of Muslims is over 85%.