Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of insulin domains important for binding to and degradation by endosomal acidic insulinase.

The endosomal compartment of hepatic parenchymal cells contains an acidic endopeptidase, endosomal acidic insulinase (EAI), which hydrolyzes internalized insulin at a limited number of sites. Although the positions of these cleavages are partially known, the residues of insulin important in its binding to and proteolysis by EAI have not been defined. To this end, we have studied the degradation over time of native human insulin and three insulin-analog peptides using a soluble endosomal extract from rat liver parenchyma followed by purification of the products by HPLC and determination of their structure by mass spectrometry. We found variable rates of ligand processing, i.e. high ([Asp(B10)]- and [Glu(A13),Glu(B10)]-insulin), moderate (insulin) and low (the H2-analog). On the basis of IC(50) values, competition studies revealed that human and mutant insulins display nearly equivalent affinity for the EAI. Proteolysis of human and mutant insulins by EAI resulted in eight cleavages in the B-chain which occurred in the central region (Glu(B13)-Leu(B17)) and at the C-terminus (Arg(B22)-Thr(B27)), the latter region comprising the initial cleavages at Phe(B24)-Phe(B25) (major pathway) and Phe(B25)-Tyr(B26) (minor pathway) bonds. Except for the [Glu(A13),Glu(B10)]-insulin mutant, only one cleavage on the A-chain was observed at residues Gln(A15)-Leu(A16). Analysis of the nine cleavage sites showed a preference for hydrophobic and aromatic amino acid residues on both the carboxyl and amino sides of a cleaved peptide bond. Using the B-chain alone as a substrate resulted in a 30-fold increase in affinity for EAI and a 6-fold increase in the rate of hydrolysis compared with native insulin. A similar role for the C-terminal region of the B-chain of insulin in the high-affinity recognition of EAI was supported by the use of the corresponding B(22)-B(30) peptide, which displayed an increase in EAI affinity similar to the entire B-chain vs. wild-type insulin. Thus, we have identified a highly specific molecular interaction of insulin with EAI at the aromatic locus Phe(B24)-Phe(B25)-Tyr(B26). Analytical subfractionation of a postmitochondrial supernatant fraction showed that a pulse of internalized [(125)I]Tyr(A14)-H2-analog, a protease-resistant insulin analog, undergoes a greater lysosomal transfer and lesser degradation than [(125)I]Tyr(A14)-insulin, confirming that endosomal sorting is regulated directly or indirectly by endosomal proteolysis.
Monetary Integration in the Ex-Soviet Union: A 'Union of Four'?

The governments of four ex-Soviet countries recently discussed forming a currency union. To examine the economic feasibility of this proposition, we use conventional techniques and show that the arrangement is likely to find it difficult to handle the lack of structural symmetry, the asymmetric pattern of shocks, and the lack of market flexibility among the potential participants. Moreover, the union would be a unilateral one. It would require an unusual degree of political commitment to survive. Nonetheless, there are some subtleties in the timing and pattern of mutual dependence between Russia and Kazakhstan, and to a lesser extent in Belarus, which may reduce the strain from a currency union in those countries. Otherwise, the black market will have to provide the necessary market flexibility.
Global gene expression response of a population exposed to benzene: A pilot study exploring the use of RNA‐sequencing technology

The mechanism of toxicity of the leukemogen benzene is not entirely known. This pilot study used RNA‐sequencing (RNA‐seq) technology to examine the effect of benzene exposure on gene expression in peripheral blood mononuclear cells obtained from 10 workers occupationally exposed to high levels of benzene (≥5 ppm) in air and 10 matched unexposed control workers, from a large study (n = 125) in which gene expression was previously measured by microarray. RNA‐seq is more sensitive and has a wider dynamic range for the quantification of gene expression. Further, it has the ability to detect novel transcripts and alternative splice variants. The main conclusions from our analysis of the 20 workers by RNA‐seq are as follows: The Pearson correlation between the two technical replicates for the RNA‐seq experiments was 0.98 and the correlation between RNA‐seq and microarray signals for the 20 subjects was around 0.6. 60% of the transcripts with detected reads from the RNA‐seq experiments did not have corresponding probes on the microarrays. Fifty‐three percent of the transcripts detected by RNA‐seq and 99% of those with probes on the microarray were protein‐coding. There was a significant overlap (P < 0.05) in transcripts declared differentially expressed due to benzene exposure using the two technologies. About 20% of the transcripts declared differentially expressed using the RNA‐seq data were non‐coding transcripts. Six transcripts were determined (false‐discovery rate < 0.05) to be alternatively spliced as a result of benzene exposure. Overall, this pilot study shows that RNA‐seq can complement the information obtained by microarray in the analysis of changes in transcript expression from chemical exposures. Environ. Mol. Mutagen. 54:566‐573, 2013. © 2013 Wiley Periodicals, Inc.
How Leadership Matters: The Effects of Leadership Alignment on Strategic Execution

Leadership has been a central, and sometimes controversial, topic in the study of organizations. In spite of claims to the contrary, there is substantial evidence that leadership is positively related to a variety of individual and organizational outcomes. While research has confirmed that leadership-performance associations exist, less attention has been paid to how senior leaders ensure that their strategic decisions are implemented. In this study, we investigated one mechanism of action, exploring how the consistency of leadership effectiveness across hierarchical levels enhanced or impeded influenced the implementation of a strategic initiative in a large health care system. We found that medical department performance was not affected by any one leader's (CEO, medical center leader, department leader) effectiveness but rather, it was only when leadership effectiveness at different levels were considered in the aggregate that significant performance improvement occurred. We discuss the implications of these findings for leadership research, specifically, that leaders at various levels should be considered collectively to understand how leadership influences strategic change.
The Social Value of Transparency and Accountability: Experimental Evidence from Asymmetric Public Good Games

Transparency and accountability are often regarded as crucial for good governance and the efficient organization of public affairs. To systematically explore the impact of transparency and accountability on cooperation, we conduct a series of laboratory experiments on a variation of the public good game with agents that differ in their action space. While some agents may only contribute to the public good, one (special) agent has the additional option to exploit the existing public good stock. In the absence of a sanction mechanism, we identify a surprising, yet intuitive effect: transparency backfires as special agents extract significantly more resources. Introducing a peer punishment mechanism sustains contributions to the public good if types or actions of agents are made transparent. When actions are not known we however identify a stigmatization effect for the special agent as he receives substantially more peer punishment while contributions by other agents do not change. Finally full transparency of all agents actions creates full accountability as it allows targeted punishment and thereby increases contributions by all agents.
EEG Operant Conditioning for Control of Epilepsy

Summary: We report the results of 23 severely epileptic patients who were given EEG feedback training. The paradigm reinforced the patients' 18 Hz activity over the scalp approximation of their focus while suppressing temporalis EMG and low frequency EEG activity. In contrast to other studies using EEG feedback, only 43% of patients showed significant changes in seizure occurrence and a lesser number were felt to have benefited clinically. None of our neuropsychological test parameters were helpful in identifying (prospectively or retrospectively) patients most likely to respond to this treatment. Although a few patients were significantly helped by this training, the mechanism for this effect is unclear.
Risk factors for respiratory tract infections in children aged 2-5 years.

OBJECTIVE To study risk factors for respiratory tract infections (RTIs) in children aged 2-5 years. DESIGN A questionnaire was used to chart the number of visits to doctors and the number of antibiotics courses because of RTIs during a 1-year period. The risk factors studied were age, sex, birth weight, breastfeeding, atopy, siblings, smoking and childcare. SETTING The catchment area of Oxie health centre in southern Sweden. SUBJECTS 190 pre-school children. MAIN OUTCOME MEASURES Number of visits to doctors and number of antibiotics courses. RESULTS The risk of having to consult a doctor, as well as the risk of receiving treatment with antibiotics, because of RTIs was greater among children at daycare centres than among children who were mostly at home (adjusted OR 2.78 (95% CI 1.34-5.78) and 2.73 (1.38-5.43), respectively). CONCLUSION Attending a daycare centre is the most important risk factor for RTIs in children aged 2-5 years.
Information and the Coase Theorem

Abstract Some economists think the Coase theorem implies a lot about the proper scope of government intervention in the economy and about the welfare consequences of laissez-faire. Others see it as a mere tautology: that if people negotiate efficiently then every outcome will be efficient. The Coase theorem is important only if we believe that efficient negotiation is likely. Of course we can attribute inefficiencies to “bargaining imperfection,” but it may not be useful to do so. Such attitudes sometimes seem to depend more on ideology than on reason. This article gives one economist's reasoned view. It discusses the Coase Theorem as a decentralization result and why decentralization results are interesting. It considers mechanism design for revealing private information, and describes the problems of centralization. Should the Coase theorem should be viewed as a second-best result—property rights are more efficient than some reasonable alternative? Does the Coase theorem recommend an institution or make.
Industrial alliances and firm location behaviour: some evidence from the US semiconductor industry

This study uses a log-linear model in order to analyse data on interfirm strategic alliances within the US semiconductor industry. The findings suggest that although the finding that the intensity of information transaction between firms is directly associated with geographical proximity, this effect is much less localized than would be usually expected. The results cast doubt on much of the existing qualitative literature on the nature of agglomeration externalities.
Fads and the Crash of '87

This paper examines changes in return-generating processes before and after the crash of '87. We find that the process for daily returns of size-sorted portfolios changed from an ARMA (1, 2) in the pre-crash period to a MA(1) in the post-crash period. The change is explained by a "fads" model similar to that proposed by Poterba and Summers. The analysis suggests that the crash may have been related to speculative fads that prevailed prior to the crash. The fads component in stock prices then disappeared after the crash. Other possible explanations are also discussed. Copyright 1993 by MIT Press.
Warning from Nagano: increase of vulvar hematoma and/or lacerated injury caused by snowboarding.

BACKGROUND On the basis of the number of women snowboarders whose vulvar injuries we have recently treated, we believe that the cases of vulvar hematoma and lacerated injuries caused by snowboarding have been increasing. To analyze the causal relation between snowboarding and vulvar injuries, we investigated how women were injured during snowboarding. METHODS During the last three ski-ing seasons at the five hospitals near the ski resorts in Nagano Prefecture, Japan, the clinical charts of all patients with vulvar injuries during snowboarding were reviewed for the number of patients treated, the condition of the patients at diagnosis, and the characteristics of vulvar injuries. All patients were also asked by phone about how their vulvar injury was caused during snowboarding. RESULTS The number of patients with vulvar injuries during the last three seasons was 16, 14, and 35, respectively. The types of vulvar injuries included hematoma in 33 (51%) patients, hematoma with lacerated injury in 17 (26%), and lacerated injury in the remaining 15 (23%). Of the 65 patients, 45 (69%) needed surgical treatment. Characteristically, 54 (88%) patients were injured when they tumbled onto the binding of the snowboard at the same time that one foot was left off the board and the binding was not turned down but left erect. CONCLUSION It is important for women snowboarders to realize that in snowboarding there are dangers that may cause vulvar injuries. The prevention of such injuries requires that the binding should be turned down when the foot is left off the board and that snowboarders should try not to tumble onto the board.
The Regional Economy, Spatial Structure and Regional Urban Systems

Parr J. B. The regional economy, spatial structure and regional urban systems, Regional Studies. In approaching the concept of the regional urban system, attention is initially drawn to the better-known types of economic region. The distinctive nature of the regional economy is next examined, and it is argued that its spatial structure represents an important dimension. Spatial structure can be characterized in a variety of ways, the most comprehensive of which employs the perspective of an urban system. This is examined firstly in terms of particular models from location theory, which provide important points of reference, and then within the setting of the present-day city-region.
Human capital use, innovation, patent protection, and economic growth in multiple regions

We provide the first theoretical analysis of the effects of human capital use, innovative activity, and patent protection, on economic growth in a model with many regions. In each region, consumers have constant relative risk-aversion preferences, there is no human capital growth, and there are three kinds of manufacturing activities involving the production of blueprints for inputs (machines), the inputs themselves, and a single final consumption good. Our analysis generates four results. For any given region, we first describe the balanced growth path (BGP) equilibrium and show that the BGP growth rate depends negatively on the rate at which patents expire. Second, we characterize the transitional dynamics in our model. Third, we determine the value of the patent expiry rate that maximizes the equilibrium growth rate of a region. Finally, we show that a policy of offering perpetual patent protection does not necessarily maximize social welfare in a region.
Comparative study of core values of excellence models vis‐à‐vis human values

Purpose – This paper sets out to present a comparative study of the core values of 16 excellence models vis‐a‐vis human values enshrined in ancient religious philosophies and identified by social scientists as a spiritual way of working.Design/methodology/approach – Contemporary excellence models (EMs) are considered as role models to attain success, and thus it is appropriate to review the effectiveness of their core values. The core values of 16 EMs are identified through a literature review and are studied comparatively. Further, common human values enshrined in various religious philosophies and also advocated by research as success strategies are identified for the comparative study.Findings – The paper identifies and compares the core values of 16 contemporary excellence models. By and large, the focus of core values in EMs is similar. However, the Deming Prize has a uniqueness and different focus in comparison with other models. Some of the common values are customer focus, continuous learning, inn.
Brainstem Acoustic Areas in the Marine Catfish, Arius felis

The marine catfish Arius felis produces low frequency sounds for communication and obstacle detection. It was hypothesized that the utriculus of the inner ear might play an important role in these behaviors. In the current study, brainstem acoustic areas were studied to reveal possible neuroanatomical specializations in utricular processing areas. The first-order octaval nuclei in Arius were identical in number, anatomical characteristics, and organization of saccular, lagenar, and utricular inputs to previous reports of these features in Ictalurus, a closely related species of catfish that does not exhibit the specialized acoustic behaviors present in Arius. Similarly, injections of neural tracer in the acoustic midbrain (nucleus centralis) of Arius revealed afferent and retrograde pathways almost identical to those previously reported in Ictalurus. It is suggested that areas within the primary and higher-order octaval nuclei that utilize utricular input in acoustic processing are likely identical in Arius and Ictalurus. Two sets of higher-order connections in Arius differ from those in Ictalurus. First, Arius apparently lacks the direct input from the anterior octaval nucleus to nucleus centralis reported in Ictalurus. Second, in Arius nucleus centralis projects bilaterally to a strip of neurons positioned ventral to the ventral boundary of the torus semicircularis. This projection is apparently absent in Ictalurus and in the related species Carassius (goldfish), but has been previously reported in Porichthyes, a sound-producing species belonging to a different teleost taxon.
Campaign Finance Reform as Institutional Choice

If the Bipartisan Campaign Reform Act (BCRA) of 2002 banned the use of soft money—the only source of funds in which Democrats approached parity with Republicans—why did the Republican congressional leadership revile the bill and the Democratic congressional leadership embrace it? We address this puzzle by modeling competing electoral, partisan, and policy motives that guided members’ decision making on the vote for final passage of this bill. Our solution lies in the fact that members believed that BCRA would reduce the role of the national parties in congressional elections. Although the parties may behave similarly under a fixed electoral regime, we find that the BCRA vote is consistent with two parties that prefer different sets of electoral rules. Specifically, Democrats appear more sympathetic to changes that enhance the role of candidates and outside groups, whereas Republicans appear to prefer stronger national parties.
The Efficiency of Sponsor and Participant Portfolio Choices in 401(K) Plans

Portfolio performance in 401(k) plans depends on both the investment menu made available by plan sponsors and participants portfolio decisions. We use a unique dataset of nearly 1 million participants in one thousand pension plans to identify key portfolio inefficiencies in 401(k) plans,attributing them either to the sponsor's menu design or to participants' own portfolio choices. We show that most sponsors offer efficient investment menus. However, many participants fail to construct efficient portfolios, leading to retirement wealth that could be one-fifth lower due to poor portfolio decisions. Because participants are the main source of inefficient DC portfolio choices, strategies targeting their portfolio choices, such as improved default investment strategies or advice programs, may help. Also, in sponsors' design of 401(k) menus, the number of options offered is less important than the range of funds provided.
Paracetamol use and risk of ovarian cancer: a meta-analysis.

AIM Ovarian cancer remains the most fatal gynaecological malignancy. Several observational studies have examined paracetamol as a potential chemopreventive agent. The nonconclusive nature of the epidemiological evidence prompted us to conduct a detailed meta-analysis of the studies published on the subject in peer-reviewed literature. METHODS A comprehensive search for articles published up to 2004 was performed, reviews of each study were conducted and data were abstracted. Prior to meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk estimates (RR) and 95% confidence intervals (CIs) were calculated using the random and the fixed-effects models. RESULTS Eight studies (four case-control and four cohort studies), published between 1998 and 2004, were included. We found no evidence of publication bias or heterogeneity among the studies. The analysis revealed an inverse association between paracetamol use and ovarian cancer risk. This association was marginally significant assuming a random-effects model (RR=0.84, 95% CI 0.70, 1.00), but not statistically significant assuming a fixed-effects model (RR=0.90, 95% CI 0.80, 1.01). When the analysis was stratified into subgroups according to study design, the association was inverse in both case-control and cohort studies, but only in the former was it statistically significant. The sensitivity analysis strengthened our confidence in the validity of this association. Furthermore, our results provided evidence for a dose effect; 'regular use' was associated with a statistically significant 30% reduction in the risk of developing ovarian cancer compared with non-use (RR=0.70, 95% CI 0.51, 0.95). CONCLUSIONS Our meta-analysis supports a protective association between paracetamol use and ovarian cancer, and provides evidence for a dose effect. However, the question of paracetamol's potential association with ovarian cancer deserves further verification, since proof of chemoprevention would represent a major public health advance.