Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutation spectrum in children with primary hemophagocytic lymphohistiocytosis: molecular and functional analyses of PRF1, UNC13D, STX11, and RAB27A

Familial hemophagocytic lymphohistiocytosis (FHL) is an autosomal‐recessive disease that affects young children. It presents as a severe hyperinflammatory syndrome with activated macrophages and T lymphocytes. Mutations in the perforin 1 gene (PRF1) were found in FHL‐2 in 15–50% of all cases. Defective granule exocytosis caused by mutations in the hMunc13‐4 gene (UNC13D) has been described in FHL‐3. FHL‐4 patients have mutations in STX11, a t‐SNARE involved in intracellular trafficking. We analyzed a large group of 63 unrelated patients with FHL of different geographic origins (Turkey:32; Germany:23; others:8) for mutations in STX11, PRF1, and UNC13D. We identified mutations in 38 samples (20 in PRF1, 12 in UNC13D, and six in STX11). Of 32 patients from Turkey, 14 had mutations in PRF1, six had mutations in UNC13D, and six had mutations in STX11. The mutation Trp374X in PRF1 was found in 12 patients from Turkey and was associated with a very early onset of the disease below the age of 3 months in all cases. In contrast, three of 23 and four of 23 patients from Germany, and three of eight and two of eight from other origins showed mutations in PRF1 and UNC13D, respectively, but none in STX11. Thus, FHL‐2, FHL‐3, and FHL‐4 account for 80% of the HLH cases of Turkish origin, and for 30% of German patients. Furthermore, we identified mutations in RAB27A in three patients with FHL‐related Griscelli syndrome type 2. In functional studies using a mammalian two‐hybrid system we found that missense mutations Ala87Pro in Rab27a and Leu403Pro in hMunc13‐4 each prevented the formation of a stable hMunc13‐4/Rab27a complex in vitro. Our findings demonstrate extensive genetic and allelic heterogeneity in FHL and delineate an approach for functionally characterizing missense mutations in RAB27A and UNC13D. Hum Mutat 27(1),62–68, 2005. © 2005 Wiley‐Liss, Inc.
Technological Innovation, Capital Mobility, and the Product Cycle in North-South Trade

This paper constructs a general equilibrium model of North-South tradein which the North continually introduces new goods. The rate at whichtechnology diffuses to the South is a function of differences in the cost of production in the two regions. The key result of the model is that labor force growth in the South initially increases real wages inthe North (a standard result in classical trade models), but in the long run reduces Northern wages by accelerating the transfer of technology and drawing capital out of the North as well. Copyright 1986 by American Economic Association.
External validation and improvement of LiFe score as a prediction tool in critically ill cirrhosis patients

The LiFe (liver, injury, failure, evaluation) score, calculated according to arterial lactate, total bilirubin, and international normalized ratio (INR), is a novel score for risk prediction in intensive care unit (ICU) patients with cirrhosis. The present study aimed to externally validate and optimize the LiFe score for predicting outcomes in critically ill cirrhosis patients.
A lipid-binding loop of botulinum neurotoxin serotypes B, DC and G is an essential feature to confer their exquisite potency

The exceptional toxicity of botulinum neurotoxins (BoNTs) is mediated by high avidity binding to complex polysialogangliosides and intraluminal segments of synaptic vesicle proteins embedded in the presynaptic membrane. One peculiarity is an exposed hydrophobic loop in the toxin’s cell binding domain HC, which is located between the ganglioside- and protein receptor-binding sites, and that is particularly pronounced in the serotypes BoNT/B, DC, and G sharing synaptotagmin as protein receptor. Here, we provide evidence that this HC loop is a critical component of their tripartite receptor recognition complex. Binding to nanodisc-embedded receptors and toxicity were virtually abolished in BoNT mutants lacking residues at the tip of the HC loop. Surface plasmon resonance experiments revealed that only insertion of the HC loop into the lipid-bilayer compensates for the entropic penalty inflicted by the dual-receptor binding. Our results represent a new paradigm of how BoNT/B, DC, and G employ ternary interactions with a protein, ganglioside, and lipids to mediate their extraordinary neurotoxicity.
Dependency Parsing with Partial Annotations: An Empirical Comparison

This paper describes and compares two straightforward approaches for dependency parsing with partial annotations (PA). The first approach is based on a forest-based training objective for two CRF parsers, i.e., a biaffine neural network graph-based parser (Biaffine) and a traditional log-linear graph-based parser (LLGPar). The second approach is based on the idea of constrained decoding for three parsers, i.e., a traditional linear graph-based parser (LGPar), a globally normalized neural network transition-based parser (GN3Par) and a traditional linear transition-based parser (LTPar). For the test phase, constrained decoding is also used for completing partial trees. We conduct experiments on Penn Treebank under three different settings for simulating PA, i.e., random, most uncertain, and divergent outputs from the five parsers. The results show that LLGPar is most effective in directly learning from PA, and other parsers can achieve best performance when PAs are completed into full trees by LLGPar.
Investment into venture capital funds in Europe: An exploratory study

Abstract Insight into the flow of capital into venture capital (VC) funds is fundamental to our understanding of the overall flow of capital into entrepreneurial ventures. To understand the processes and criteria utilized by limited partners (LPs) in the selection of the VC funds in which they invest we studied 21 European fund-of-fund investment management firms that actively invest in VC funds. We have demonstrated that such LPs utilize structured selection processes and criteria that are comparable to those used by VCs themselves, but with important differences. Notably, we found that LPs build early consensus within the investment team via a stage we have termed ratification. In selecting VCs, quantitative measures of reputation via historical performance are important, consistent with previous findings, but we found that reputation also captures opinions from entrepreneurs, other LPs and other VCs. We found that nurturing informal relationships outside the formal limited partnership agreement is an important component of LPs' decisions to invest and that LPs may pre-allocate capital to VCs with whom a relationship exists already. We conclude that early relationship building with potential LPs is an essential prerequisite for VCs aiming to raise a first fund.
Determinants of new product performance in small firms

Purpose – The purpose of this paper is to explore the determinants of new product performance in small firms; specifically, the impact of customer orientation, competitor orientation, interfunctional co‐ordination, product launch proficiency and product advantage.Design/methodology/approach – Based on previous studies a model was developed addressing determinants of new product and organisational performance (customer orientation, competitor orientation, interfunctional co‐ordination, product advantage, and product launch proficiency). These relationships were explored using data collected from 26 small firms in Ireland.Findings – The results indicate that competitor orientation and product launch proficiency are strongly linked to new product performance and organisational performance in small firms. Additionally, they illustrate a lack of significant relationships between performance and customer orientation, interfunctional coordination and product advantage, thus suggesting that the existing large fir.
ESTIMATING A MARKET EQUILIBRIUM SEARCH MODEL FROM PANEL DATA ON INDIVIDUALS

In this paper, the feasibility of estimating a Nash labor market equilibrium model using only information on workers is demonstrated. The equilibrium model, adapted from Albrecht and Axell (1984), is based on workers who are homogenous in terms of market productivity and heterogeneous in terms of nonmarket productivity, and on firms that are heterogeneous in terms of productive efficiency. The equilibrium model is contrasted with an unrestricted version of the model in terms of its fit to the data. Copyright 1990 by The Econometric Society.
Exchange Rate Regimes and Pass-Through: Evidence from the Turkish Economy

"We seek to demonstrate the variations in the exchange rate pass-through (ERPT) and identify the shift in the price-setting behavior by placing the emphasis on the implemented exchange rate and monetary policy regimes. Having a history of several distinct monetary regimes, Turkey exhibits a genuine laboratory in this respect. Our empirical results reveal that the pass-through from exchange rates to domestic prices has changed dramatically. We detect breaks in the pass-through coefficients at three episodes, all of which coincide with a shift in monetary/exchange rate regime, lending support to the view that monetary and exchange rate regimes might be among the major determinants of the ERPT process". ("JEL" C51, E31, E58) Copyright 2007 Western Economic Association International.
Loss of signal transduction and inhibition of lymphocyte locomotion in a ground-based model of microgravity

SummaryInflammatory adherence to, and locomotion through the interstitium is an improtant component of the immune response. Conditions such as microgravity and modeled microgravity (MMG) severely inhibit lymphocyte locomotion in vitro through gelled type I collagen. We used the NASA rotating wall vessel bioreactor or slow-turning lateral vessel as a prototype for MMG in ground-based experiments. Previous experiments from our laboratory revealed that when lymphocytes (human peripheral blood mononuclear cells [PBMCs]) were first activated with phytohemaglutinin followed by exposure to MMG, locomotory capacity was not affected. In the present study, MMG inhibits lymphocyte locomotion in a manner similar to that observed in microgravity. Phorbol myristate acetate (PMA) treatment of PBMCs restored lost locomotory capacity by a maximum of 87%. Augmentation of cellular calcium flux with ionomycin had no restorative effect. Treatment of lymphocytes with mitomycin C prior to exposure to MMG, followed by PMA, restored locomotion to the same extent as when nonmitomycin C-treated lymphocytes were exposed to MMG (80–87%), suggesting that deoxyribonucleic acid replication is not essential for the restoration of locomotion. Thus, direct activation of protein kinase C (PKC) with PMA was effective in restoring locomotion in MMG comparable to the normal levels seen in 1g cultures. Therefore, in MMG, lymphocyte calcium signaling pathways were functional, with defects occurring at either the level of PKC or upstream of PKC.
Human Capital, Effort, and the Sexual Division of Labor

Increasing returns from specialized human capital is a powerful force creating a division of labor in the allocation of time and investments in human capital between married men and married women. Moreover, since child care and housework are more effort intensive than leisure and other household activities, married women spend less effort on each hour of market work than married men working the same number of hours. Hence, married women have lower hourly earnings than married men with the same market human capital, and they economize on the effort expended on market work by seeking less demanding jobs. The responsibility of married women for child care and housework has major implications for earnings and occupational differences between men and women.
The Inter-institutional Division of Power and Time Allocation in the European Parliament

This paper examines whether the European Parliament strategically adapts to the inter-institutional balance of power by allocating its resources so that it spends more time in those areas of competence where it has the greatest power. Focusing on the legislative area, the authors examine whether differences in the inter-institutional division of power between different legislative procedures affect how long the EP spends on reaching its first reading position. They conduct a large-N analysis of over 3,000 legislative acts and a complementary analysis of treaty articles where the required decision procedure changed. In all analyses, the inter-institutional balance of power has the expected effect. The authors show that the EP spends more time reaching its first reading opinion in co-decision than it does in the consultation procedure where it has less power, even when they control for the characteristics of the files debated and the level of disagreement on the files.
Atg9A Protein, an Autophagy-related Membrane Protein, Is Localized in the Neurons of Mouse Brains

Old and unneeded intracellular macromolecules are delivered through autophagy to lysosomes that degrade macromolecules into bioactive monomers such as amino acids. Autophagy is conserved in eukaryotes and is essential for the maintenance of cellular metabolism. Currently, more than 30 autophagy-related genes (Atgs) have been identified in yeast. Of these genes, the 18 that are essential for autophagosome formation are also conserved in mammalian cells. Atg9 is the only transmembrane Atg protein required for autophagosome formation. Although the subcellular localization of the Atg9A protein (Atg9Ap) has been examined, little is known about its precise cell and tissue distribution. To determine this, we produced an antibody specific to mouse Atg9Ap. The antibody recognized both non-glycosylated and glycosylated Atg9Ap, which have molecular masses of ×94 kDa and 105 kDa, respectively. Although Atg9Ap was ubiquitously detected, it was highly expressed in neurons of the central nervous system. In Purkinje cells, Atg9Ap immunoreactivity was localized in the endoplasmic reticulum (ER), trans-Golgi network (TGN), lysosomes/late endosomes, and in axon terminals. These results suggest that Atg9Ap may be involved in autophagosome formation in the ER and axon terminals of neurons, the TGN, and lysosomes/late endosomes.
Examination of the association of sex and race/ethnicity with appearance concerns: a Scleroderma Patient-centered Intervention Network (SPIN) Cohort study.

OBJECTIVES Appearance concerns are common in systemic sclerosis (SSc) and have been linked to younger age and more severe disease. No study has examined their association with sex or race/ethnicity. METHODS SSc patients were sampled from the Scleroderma Patient-centered Intervention Network Cohort. Presence of appearance concerns was assessed with a single item, and medical and sociodemographic information were collected. RESULTS Of 644 patients, appearance concerns were present in 72%, including 421 of 565 women (75%), 42 of 79 men (53%), 392 of 550 patients who identified as White (71%), 35 of 41 who identified as Black (85%), and 36 of 53 who identified as another race/ethnicity (68%). In multivariate analysis, women had significantly greater odds of reporting appearance concerns than men (odds ratio (OR)=2.97, 95% confidence interval (CI)=1.78-4.95, p<. 001). Black patients had significantly greater odds of appearance concerns than White patients in unadjusted (OR=2.64, 95% CI=1.01-6.34, p=.030), but not multivariate analysis (OR=1.76, 95% CI=0.67-4.60, p=.250). Compared to a general population sample, appearance concerns were substantially more common in SSc, particularly for men across all age groups and for younger women. The most commonly reported features of concern were related to the face and head, followed by the hands and fingers; this did not differ by sex or race/ethnicity. CONCLUSIONS Appearance concerns were common in SSc. Women were substantially more likely than men to have appearance concerns. Although non-significant in multivariate analysis, Black patients were more likely to have concerns than White patients, likely due to more severe changes in appearance.
From image to language and back again

Work in computer vision and natural language processing involving images and text has been experiencing explosive growth over the past decade, with a particular boost coming from the neural network revolution. The present volume brings together five research articles from several different corners of the area: multilingual multimodal image description (Frank et al.), multimodal machine translation (Madhyastha et al., Frank et al.), image caption generation (Madhyastha et al., Tanti et al.), visual scene understanding (Silberer et al.), and multimodal learning of high-level attributes (Sorodoc et al.). In this article, we touch upon all of these topics as we review work involving images and text under the three main headings of image description (Section 2), visually grounded referring expression generation (REG) and comprehension (Section 3), and visual question answering (VQA) (Section 4).
Human Resource Management in Public Service: Paradoxes, Processes, and Problems

Part I: Context and Challenges Chapter 1: The Public Service Heritage A Day in the Life of Maria Hernandez Some Challenges in Getting and Managing the Right People The Structure and Role of Human Resource Departments Historical and Institutional Context Reforming Government in the Clinton, Bush, and Obama Years Human Resource Management Principles Values, Ethics, and Moral Management Summary and Conclusion Chapter 2: Legal Rights and Responsibilities The Foundations of Employment Law The Employment Relationship Balancing Employer, Employee, and Societal Interests Privacy Issues Preemployment Investigations: Truth, Personality, Health, Credit, and Criminal Records Discrimination Summary and Conclusion Part II: Processes and Skills Chapter 3: Recruitment Factors in Recruitment: Employer and Applicant Perspectives Recruitment Steps Planning and Approval Position Announcements Recruitment Strategies Enhancing Recruitment Prospects: The Seeker's Perspective Summary and Conclusion Chapter 4: Selection The Bases and Origin of Selection Criteria in Selecting Selection Tests Selection: Four Screening Phases Initial Reviewing and Testing Interviewing and Reference Checks: Narrowing the Pool General Considerations for Those Conducting Interviews Choosing and Negotiation Postoffer and Hiring Issues Summary and Conclusion Chapter 5: Position Management Three Types of Personnel Strategies The Origins of Position Classification and Management Job Design and Job Analysis Job and Position Descriptions From Jobs to Job Systems Summary and Conclusion Chapter 6: Employee Engagement Pull, Push, or Drive? Human Resource Management and the Climate for Engagement Tools of Engagement Summary and Conclusion Chapter 7: Compensation Equity and Expectancy Theory Pay Determination Philosophy The Great Pay Debate Labor Market Forces: External Competition Job Content: Internal Consistency Individual Considerations: Fairness and Individual Contributions Implications Summary and Conclusion Chapter 8: Employee-Friendly Policies Workforce and Workplace Trends Family/Work Programs Health, Safety, and Wellness Programs Flexible Work Arrangements Keys to Success Traditional Benefits: Not-So-Employee-Friendly Trends Implementation, Assessment, and Evaluation Best Places to Work Summary and Conclusion Chapter 9: Training, Development and Learning General Principles of Learning Training Strategies Organizational Learning Strategies Application: Ethics Training Summary and Conclusion Chapter 10: Appraisal Evolution Appraisal Systems Improving the Process Disciplinary Systems Summary and Conclusion Chapter 11: Unions and the Government Background: Context and Evolution of Employee Relations Differing Views of Unions Paradoxes and Contradictions Trends and Variations Summary and Conclusion Chapter 12: Collective Bargaining Structure, Representation, and Collective Bargaining Strategies and Skills Bargaining-Related Reforms Hostility Versus Harmony Summary and Conclusion
Functional state of the plasma membrane Ca2+ pump in Plasmodium falciparum‐infected human red blood cells

1 The active Ca2+ transport properties of malaria‐infected, intact red blood cells are unknown. We report here the first direct measurements of Ca2+ pump activity in human red cells infected with Plasmodium falciparum, at the mature, late trophozoite stage. 2 Ca2+ pump activity was measured by the Co2+‐exposure method adapted for use in low‐K+ media, optimal for parasitised cells. This required a preliminary study in normal, uninfected red cells of the effects of cell volume, membrane potential and external Na+/K+ concentrations on Ca2+ pump performance. 3 Pump‐mediated Ca2+ extrusion in normal red cells was only slightly lower in low‐K+ media relative to high‐K+ media despite the large differences in membrane potential predicted by the Lew‐Bookchin red cell model. The effect was prevented by clotrimazole, an inhibitor of the Ca2+‐sensitive K+ (KCa) channel, suggesting that it was due to minor cell dehydration. 4 The Ca2+‐saturated Ca2+ extrusion rate through the Ca2+ pump (Vmax) of parasitised red cells was marginally inhibited (2‐27 %) relative to that of both uninfected red cells from the malaria‐infected culture (cohorts), and uninfected red cells from the same donor kept under identical conditions (co‐culture). Thus, Ca2+ pump function is largely conserved in parasitised cells up to the mature, late trophozoite stage. 5 A high proportion of the ionophore‐induced Ca2+ load in parasitised red cells is taken up by cytoplasmic Ca2+ buffers within the parasite. Following pump‐mediated Ca2+ removal from the host, there remained a large residual Ca2+ pool within the parasite which slowly leaked to the host cell, from which it was pumped out.
An Economic Analysis of Tobacco Control in Thailand

Revenue from taxation of tobacco products accounts for more than 5 % of total government revenue in Thailand. The Thai tobacco industry is less significant: in 2000 it employed only 0.67 percent of the total agricultural workforce, and only 0.11 percent of all manufacturing workers. Until 1996, tobacco prices increased more slowly than prices of other consumer goods. After 1996 the trend reversed as tax/price policies were used to discourage smoking. Smoking prevalence is higher among men than women (50 percent and 3 percent respectively) and higher in rural than urban areas (26 percent and 18 percent respectively). Price and income elasticity of tobacco demand are analyzed. They vary across income categories and between urban and rural areas. Overall, price elasticity is -0.39 and income elasticity is 0.70, similar to estimates for many other middle-income countries. Earlier studies that estimated health costs due to tobacco use are reviewed. Two main policy recommendations are made: to continue to use tax policy to reduce tobacco use and future health costs, which will also raise government revenue, and to enforce existing tobacco control measures better.