Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of novel T-cell epitopes on 65 kDa and 67 kDa glutamic acid decarboxylase relevant in autoimmune responses in NOD mice.

It has recently been shown that the T-cell mediated immune responses to glutamic acid decarboxylase (GAD) play an important role in insulin-dependent diabetes mellitus (IDDM) in NOD mice. However, specific epitopes responsible for eliciting these responses remain unresolved. In this study, the T-cell epitopes involved in GAD-specific immune responses in NOD mice were characterized. By priming NOD mice with GAD65, three new GAD65 epitopes (GAD65 78-97, GAD65 202-221, GAD65 217-236) distinct from those previously reported were found. Furthermore, our investigations into the fine determinant specificity of GAD67 revealed two additional GAD67-specific peptide epitopes (GAD67 28-47, GAD67 42-61). Two of the GAD65 epitopes (GAD65 202-221 and GAD65 217-236) are shared between GAD65 and GAD67. Spontaneous immune responses to these peptides were found in pre-diabetic and diabetic mice and differential patterns of responses to these peptides were observed depending on the age of the mice, disease status, or if the mice were protected from diabetes by adjuvant immunotherapy. Characterization of these new epitopes will help in the elucidation of autoimmune responses to GAD in IDDM.
Characteristics of Self-Focusing of a Gaussian Laser Pulse Under Lateral and Axial Plasma Density Variations

In this paper, we present a paraxial description of relativistic self-focusing of a Gaussian laser beam in a plasma channel with the density distribution as a function of radial and axial variations. We have derived the nonlinear dielectric permittivity of plasma due to ponderomotive force and relativistic effects. The effect of different conditions of the inhomogeneous plasma and the laser pulse on self-focusing and defocusing of Gaussian laser beam propagation in the plasma is studied. We find that with an increase in the value of intensity of the beam, self-focusing enhances and shifts toward lower values of normalized propagation distance. The self-focusing length also increases with an increase in channel width. When the density rapidly increases along the propagation distance, the nonlinearity increases and gives self-focusing at shorter values of z.
Tinbergen Institute The Tinbergen Institute is the institute for economic research of the Erasmus Universiteit

We develop an isotone recursive approach to the problem of existence, computation, and characterization of nonsymmetric locally Lipschitz continuous (and, therefore, Clarke-di¤erentible) Markovian equilibrium for a class of in nite horizon multiagent competitive equilibrium models with capital, aggregate risk, public policy, externalities, one sector production, and incomplete markets. The class of models we consider is large, and examples have been studied extensively in the applied literature in public economics, macroeconomics, and nancial economics. We provide su¢ cient conditions that distinguish between economies with isotone Lipschitizian Markov equilibrium decision processes (MEDPs) and those that have only locally Lipschitzian (but not necessarily isotone) MEDPs. As our xed point operators are based upon order continuous and compact nonlinear operators, we are able to provide su¢ cient conditions under which isotone iterative xed point constructions converge to extremal MEDPs via successive approximation. We develop a rst application of a new method for computing MEDPs in a system of Euler inequalities using isotone xed point theory even when MEDPs are not necessarily isotone. The method is a special case of a more general mixed monotone recursive approach. We show MEDPs are unique only under very restrictive conditions. Finally, we prove monotone comparison theorems in Veinotts strong set order on the space of public policy parameters and distorted production functions.
Short-Term Effect of Muscle Energy Technique on Pain in Individuals with Non-Specific Lumbopelvic Pain: A Pilot Study

Abstract Muscle energy technique (MET) is a form of manual therapy frequently used to correct lumbopelvic pain (LPP), herein the patient voluntarily contracts specific muscles against the resistance of the clinician. Studies on MET regarding magnitude and duration of effectiveness are limited. This study was a randomized controlled trial in which 20 subjects with self-reported LPP were randomized into two groups (MET or control) after magnitude of pain was determined. MET of the hamstrings and iliopsoas consisted of four 5-second hold/relax periods, while the control group received a sham treatment. Tests for current and worst pain, and pain with provocation were administered at baseline, immediately following intervention and 24 hours after intervention. Separate 2x3 ANOVAs were used to assess results as change scores. Visual analog score (VAS) for worst pain reported in the past 24 hours decreased for the MET group (4.3mm±19.9, p=.03) and increased for the sham (control) group (17.1mm±21.2, p=.03). Subjects receiving MET demonstrated a decrease in VAS worst pain over the past 24 hours, thereby suggesting that MET may be useful to decrease LPP over 24 hours.
The impact of globalization on the composition of government expenditures: Evidence from panel data

Abstract According to the disciplining hypothesis, globalization restrains governments by inducing increased budgetary pressure. As a consequence, governments may attempt to curtail the welfare state, which is often seen as a drag on international competitiveness, by reducing especially their expenditures on transfers and subsidies. This globalization-induced welfare state retrenchment is potentially mitigated by citizens’ preferences to be compensated for the risks of globalization (“compensation hypothesis”). Employing two different datasets and various measures of globalization, we analyze whether globalization has indeed influenced the composition of government expenditures. For a sample of 60 countries, we examine the development of four broad expenditure categories for the period 1971–2001: capital expenditures, expenditures for goods and services, interest payments, and subsidies and other current transfers. A second dataset provides a much more detailed classification: public expenditures, expenditures for defence, order, economic affairs, environment, housing, health, recreation, education, and social expenditures. However, this second data set is only available since 1990—and only for OECD countries. Our results show that globalization did not influence the composition of government expenditures in a notable way.
Corporate Governance in Transitional Economies: Lessons from the Prewar Japanese Cotton Textile Industry

Observers of the formerly communist economies urge firms there to obtain funds from a relatively few sources. They note the problems the firms face: dysfunctional courts, markets, and statutes. Because these firms cannot rely on the courts to discipline managers, they predict that firms will do best if they raise their capital only from a few sources. Firms in Japan at the close of the nineteenth century similarly faced dysfunctional courts, markets, and statutes. Yet the firms that succeeded in Japan were not the ones that took the tack proposed by modern observers. They were the ones that used little debt and raised their equity from a large number of investors. In this article we outline how concentrated finance can introduce problems potentially as severe as the ones it mitigates and discuss why dispersed equity did not reduce firm efficiency in late‐nineteenth‐century Japan.
Sales Force Sizing and Deployment Using a Decision Calculus Model at Syntex Laboratories

A series of subjectively parameterized models was developed and implemented, beginning in 1982, to aid Syntex Laboratories in deciding how large their sales force should be, and how it should be deployed. The response functions of the models were estimated by a team of knowledgeable managers and salespeople using a modified Delphi technique. The model structure and parameter estimation techniques were developed in response to constraints unique to Syntex Laboratories and its available data. The original response functions were significantly better predictors of the sales of each Syntex product for two years in the future than were the existing forecasts. Use of the models helped the corporation to decide to significantly increase its sales force size and to try to change its deployment. This decision resulted in a documented continuing $25,000,000, eight percent annual sales increase. The model had important impacts on the strategic direction of the firm, helping to change its focus to product markets wit.
Relationship between skeletal muscle lipoprotein lipase activity and 24-hour macronutrient oxidation.

A low ratio of whole-body 24-h fat/carbohydrate (CHO) oxidation has been shown to be a predictor of subsequent body weight gain. We tested the hypothesis that the variability of this ratio may be related to differences in skeletal muscle metabolism. Since lipoprotein lipase (LPL) plays a pivotal role in partitioning lipoprotein-borne triglycerides to adipose (storage) and skeletal muscle (mostly oxidation), we postulated that a low ratio of fat/CHO oxidation was associated with a low skeletal muscle LPL (SMLPL) activity. As an index of substrate oxidation, 24-h RQ was measured under sedentary and eucaloric conditions in 16 healthy nondiabetic Pima males. During a 6-h euglycemic, hyperinsulinemic clamp, muscle biopsies were obtained at baseline, 3, and 6 h. Heparin-elutable SMLPL activity was 2.92 +/- 0.56 nmol free fatty acids/g.min (mean +/- SD) at baseline, was unchanged (2.91 +/- 0.51) at the third hour, and increased significantly (P < 0.05) to 3.13 +/- 0.57 at the sixth hour of the clamp. The mean (of baseline and 3-h) SMLPL activity correlated inversely with 24-h RQ (r = 0.57, P < 0.03) but not with body size, body composition, or insulin-mediated glucose uptake. Since SMLPL activity is related to the ratio of whole body fat/CHO oxidation rate, a decreased muscle LPL activity may, therefore, predispose to obesity.
European Prospective Investigation into Cancer and Nutrition (EPIC): study populations and data collection

Abstract The European Prospective Investigation into Cancer and Nutrition (EPIC) is an ongoing multi-centre prospective cohort study designed to investigate the relationship between nutrition and cancer, with the potential for studying other diseases as well. The study currently includes 519 978 participants (366 521 women and 153 457 men, mostly aged 35–70 years) in 23 centres located in 10 European countries, to be followed for cancer incidence and cause-specific mortality for several decades. At enrolment, which took place between 1992 and 2000 at each of the different centres, information was collected through a non-dietary questionnaire on lifestyle variables and through a dietary questionnaire addressing usual diet. Anthropometric measurements were performed and blood samples taken, from which plasma, serum, red cells and buffy coat fractions were separated and aliquoted for long-term storage, mostly in liquid nitrogen. To calibrate dietary measurements, a standardised, computer-assisted 24-hour dietary recall was implemented at each centre on stratified random samples of the participants, for a total of 36 900 subjects. EPIC represents the largest single resource available today world-wide for prospective investigations on the aetiology of cancers (and other diseases) that can integrate questionnaire data on lifestyle and diet, biomarkers of diet and of endogenous metabolism (e.g. hormones and growth factors) and genetic polymorphisms. First results of case–control studies nested within the cohort are expected early in 2003. The present paper provides a description of the EPIC study, with the aim of simplifying reference to it in future papers reporting substantive or methodological studies carried out in the EPIC cohort.
Doctor Behaviour Under a Pay for Performance Contract: Treating, Cheating and Case Finding?

The UK National Health Service introduced a pay for performance scheme for primary care providers in 2004/5. The scheme rewarded providers for the proportion of eligible patients who received appropriate treatment. Eligible patients were those who had been reported by the provider as having the relevant disease minus those they exception reported as not suitable for treatment. Using rich provider level data, we find that differences in reported disease rates between providers, and differences in exception rates both between and within providers, suggest gaming. Faced with ratio performance indicators, providers acted on denominators as well as numerators.
Role of Speculative Short Sales in Price Formation: The Case of the Weekend Effect

We argue that short sellers affect prices in a significant and systematic manner. In particular, we contend that speculative short sales contribute to the weekend effect: The inability to trade over the weekend is likely to cause these short sellers to close their speculative positions on Fridays and reestablish new short positions on Mondays causing stock prices to rise on Fridays and fall on Mondays. We find evidence in support of this hypothesis based on a comparison of high short-interest stocks and low short-interest stocks, stocks with and without actively traded options, IPOs, zero short-interest stocks, and highly volatile stocks. Copyright 2003 by the American Finance Association.
High-growth firms in the Swedish ERP industry

This paper analyses growth patterns in three high‐growth Swedish firms (Intentia, IBS, and in the enterprise resource planning (ERP) industry. A multi‐theoretical framework is developed and used to analyse the firms’ growth. It is concluded that growth is a complex phenomenon that has to be viewed from different theoretical angles to be understood. It is shown that entrepreneurs’ intentions, international growth strategies, organic organisations, industry structure and networks, and national cultures are all factors that influence firms’ growth.
A Stochastic Investment Model for Actuarial Use

1.1. The purpose of this paper is to present to the actuarial profession a stochastic investment model which can be used for simulations of “possible futures” extending for many years ahead. The ideas were first developed for the Maturity Guarantees Working Party (MGWP) whose report was published in 1980. The ideas were further developed in my own paper “Indexing Long Term Financial Contracts” (1981). However, these two papers restricted themselves to a consideration of ordinary shares and of inflation respectively, whereas in this paper I shall present what seems to me to be the minimum model that might be used to describe the total investments of a life office or pension fund.
A Spatial Analysis of Supplemental Nutrition Assistance Program and Economic Conditions in the Applachian Region

Supplemental Nutrition Assistance Program (SNAP) helps low income people and families buy food they need for good health. The main objective of this study is to examine the effects of changes in the economic conditions and welfare on SNAP participation in the Appalachian region. The study employs county level data to capture variation in SNAP participation. Spatial econometric models are developed to examine the relationship among the economic and business cycle conditions, changes in welfare reforms, demographic and household attributes, institutional factors, and SNAP participation. The findings from this study could be helpful in improving welfare programs in this region.
Real-Time Digital Timing in Positron Emission Tomography

Positron emission tomography (PET) requires accurate timing of scintillation events to properly discriminate between coincident and noncoincident pairs. The traditional solution to timing is based on custom application specific integrated circuits (ASIC) designs, whose cost may not be justified in the design of experimental small animal PET scanners. The new generation of PET scanners introduces the idea of continuous sampling of the detected scintillation pulse, replacing event-triggered acquisition front-ends. This approach enables new options to the timing procedure based on digital processing of the sampled pulse signal. This work proposes a time stamping algorithm based on the optically matched filter and compares the potential performance benefits of this approach versus other FIR-based timing algorithms, some of which have been already implemented by different authors. Results show that the coincidence timing resolution may be as low as 1.5 ns without the need of expensive high-speed converters when the proper signal processing is applied.
Healthy lifestyle and risk of kidney disease progression, atherosclerotic events, and death in CKD: findings from the Chronic Renal Insufficiency Cohort (CRIC) Study.

BACKGROUND In general populations, healthy lifestyle is associated with fewer adverse outcomes. We estimated the degree to which adherence to a healthy lifestyle decreases the risk of renal and cardiovascular events among adults with chronic kidney disease (CKD). STUDY DESIGN Prospective cohort. SETTING & PARTICIPANTS 3,006 adults enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. PREDICTORS 4 lifestyle factors (regular physical activity, body mass index [BMI] of 20-<25kg/m(2), nonsmoking, and "healthy diet"), individually and in combination. OUTCOMES CKD progression (50% decrease in estimated glomerular filtration rate or end-stage renal disease), atherosclerotic events (myocardial infarction, stroke, or peripheral arterial disease), and all-cause mortality. MEASUREMENTS Multivariable-adjusted Cox proportional hazards. RESULTS During a median follow-up of 4 years, we observed 726 CKD progression events, 355 atherosclerotic events, and 437 deaths. BMI≥25kg/m(2) and nonsmoking were associated with reduced risk of CKD progression (HRs of 0.75 [95% CI, 0.58-0.97] and 0.61 [95% CI, 0.45-0.82] for BMIs of 25 to <30 and ≥30kg/m(2), respectively, versus 20 to <25kg/m(2); HR for nonsmoking of 0.68 [95% CI, 0.55-0.84] compared to the current smoker reference group) and reduced risk of atherosclerotic events (HRs of 0.67 [95% CI, 0.46-0.96] for BMI of 25-<30 vs 20-<25kg/m(2) and 0.55 [95% CI, 0.40-0.75] vs current smoker). Factors associated with reduced all-cause mortality were regular physical activity (HR, 0.64 [95% CI, 0.52-0.79] vs inactive), BMI≥30kg/m(2) (HR, 0.64 [95% CI, 0.43-0.96] vs 20-<25kg/m(2)), and nonsmoking (HR, 0.45 [95% CI, 0.34-0.60] vs current smoker). BMI<20kg/m(2) was associated with increased all-cause mortality risk (HR, 2.11 [95% CI, 1.13-3.93] vs 20-<25kg/m(2)). Adherence to all 4 lifestyle factors was associated with a 68% lower risk of all-cause mortality compared to adherence to no lifestyle factors (HR, 0.32; 95% CI, 0.11-0.89). LIMITATIONS Lifestyle factors were measured only once. CONCLUSIONS Regular physical activity, nonsmoking, and BMI≥25kg/m(2) were associated with lower risk of adverse outcomes in this cohort of individuals with CKD.
Are Multiple Directorships Beneficial in East Asia?

type="main" xml:id="acfi12008-abs-0001"> We posit that the benefits and costs of multiple directorships are conditional on firm characteristics. We find firm valuation is positively associated with multiple directorships in (i) firms with high advising needs and (ii) firms with high external financing needs. These beneficial effects of multiple directorships are generally stronger in countries with weak shareholder rights and in firms that are widely held. However, when controlling shareholder hold high voting-rights to cash-flow rights, multiple directorships reduce firm valuation, especially in countries with weak shareholder rights and in closely held firms. As multiple directorships increases, cash holdings (capital expenditures) contribute less to shareholder value. The negative association between value of cash (capital expenditure) and busy boards is mitigated in firms with (i) high advising needs, (ii) high external financing needs and (iii) less entrenched ownership structures.
Physiological and pathological angiogenesis in the endocrine system

Formation of new blood vessels occurs in many physiological states (during development of the embryo, cycling changes of the female reproductive tract), as well as in pathological processes (such as diabetic retinopathy and wound healing). Angiogenesis has been shown to be related to tumor formation, prognosis, and response to treatment in many tumor types. Intratumoral microvessels can be related to tumor behavior or hormone secretion in different endocrine tumors. For example, invasive prolactinomas are more vascular than noninvasive adenomas; a surgical approach is more successful in macroprolactinomas with lower microvessel density. A higher number of microvessels have been found in papillary thyroid carcinomas during recurrences. A correlation between microvessel count and prognosis in papillary and medullary thyroid carcinomas has been suggested. Several stimulating and inhibiting factors involved in the regulation of angiogenesis have been identified. Among them, vascular endothelial growth factor (VEGF) has been shown to be critically involved in angiogenesis and also in the neovascularization of solid tumors. Dopamine agonists (already in clinical use for prolactinomas) have potent inhibitory actions on VEGF signaling, and thus may be a new tool in antiangiogenic therapy. Secretion of VEGF in the great majority of human pituitary adenomas is inhibited by dexamethasone. This suggests that glucocorticoids can be considered in the treatment of certain pituitary tumors. The cyclic nature of angiogenesis in the female reproductive tract indicates that stimulation or inhibition of paracrine angiogenic factors may lead to new approaches for being able to influence reproductive endocrine disorders. Experimental and clinical aspects of interactions between angiogenic factors and tumor growth of the endocrine system are also discussed. Microsc. Res. Tech. 60:98–106, 2003. © 2002 Wiley‐Liss, Inc.
EGFR Mutations and ALK Rearrangements Are Associated with Low Response Rates to PD-1 Pathway Blockade in Non–Small Cell Lung Cancer: A Retrospective Analysis

Purpose: PD-1 inhibitors are established agents in the management of non–small cell lung cancer (NSCLC); however, only a subset of patients derives clinical benefit. To determine the activity of PD-1/PD-L1 inhibitors within clinically relevant molecular subgroups, we retrospectively evaluated response patterns among EGFR-mutant, anaplastic lymphoma kinase (ALK)-positive, and EGFR wild-type/ALK-negative patients. Experimental Design: We identified 58 patients treated with PD-1/PD-L1 inhibitors. Objective response rates (ORR) were assessed using RECIST v1.1. PD-L1 expression and CD8+ tumor-infiltrating lymphocytes (TIL) were evaluated by IHC. Results: Objective responses were observed in 1 of 28 (3.6%) EGFR-mutant or ALK-positive patients versus 7 of 30 (23.3%) EGFR wild-type and ALK-negative/unknown patients (P = 0.053). The ORR among never- or light- (≤10 pack years) smokers was 4.2% versus 20.6% among heavy smokers (P = 0.123). In an independent cohort of advanced EGFR-mutant (N = 68) and ALK-positive (N = 27) patients, PD-L1 expression was observed in 24%/16%/11% and 63%/47%/26% of pre–tyrosine kinase inhibitor (TKI) biopsies using cutoffs of ≥1%, ≥5%, and ≥50% tumor cell staining, respectively. Among EGFR-mutant patients with paired, pre- and post-TKI–resistant biopsies (N = 57), PD-L1 expression levels changed after resistance in 16 (28%) patients. Concurrent PD-L1 expression (≥5%) and high levels of CD8+ TILs (grade ≥2) were observed in only 1 pretreatment (2.1%) and 5 resistant (11.6%) EGFR-mutant specimens and was not observed in any ALK-positive, pre- or post-TKI specimens. Conclusions: NSCLCs harboring EGFR mutations or ALK rearrangements are associated with low ORRs to PD-1/PD-L1 inhibitors. Low rates of concurrent PD-L1 expression and CD8+ TILs within the tumor microenvironment may underlie these clinical observations. Clin Cancer Res; 22(18); 4585–93. ©2016 AACR. See related commentary by Gettinger and Politi, p. 4539