Miracle-dz/UniFAR-FTUs huggingface dataset:
Ser1292 Autophosphorylation Is an Indicator of LRRK2 Kinase Activity and Contributes to the Cellular Effects of PD Mutations

LRRK2 autophosphorylation on Ser1292 may be a useful indicator of kinase activity, providing a readout for screening candidate LRRK2 inhibitors. LRRK2 Inhibitor Heralds a Happier Song Genetic polymorphisms in the leucine-rich repeat kinase 2 (LRRK2) are the most common causes of familial Parkinson’s disease (PD) and are also linked to idiopathic PD. The most prevalent LRRK2 PD mutation G2019S imbues the kinase with a gain of function, suggesting that blocking LRRK2 activity may be a therapeutic strategy for reversing the pathogenic effects of LRRK2 mutations in PD. However, the mechanistic link between LRRK2 kinase activity and the cellular effects of PD mutations remains elusive, and there has been no reliable way to monitor LRRK2 kinase activity in vivo. Using quantitative mass spectrometry and subsequent phospho-specific antibody approaches, Sheng et al. now report that LRRK2 phosphorylates itself on Ser1292 in vitro and in vivo (Ser1292 autophosphorylation). Five of the six confirmed familial LRRK2 PD mutations increased Ser1292 autophosphorylation when transiently expressed in heterologous cells, suggesting increased Ser1292 autophosphorylation as a common feature of LRRK2 PD mutations. Elimination of the Ser1292 autophosphorylation site abrogated the defects on neurite outgrowth caused by LRRK2 PD mutations in cultured rat embryonic neurons. Using Ser1292 autophosphorylation as the readout of kinase activity, Sheng et al. developed assays to monitor LRRK2 kinase activity in cultured cells and rodents. These assays were used to profile the potencies of hundreds of LRRK2 kinase inhibitors derived from high-throughput compound screening. A potent and selective compound that effectively inhibited LRRK2 kinase activity in mouse brains and reversed cellular effects of LRRK2 PD mutations in cultured primary neurons was identified. Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of familial Parkinson’s disease (PD). Although biochemical studies have shown that certain PD mutations confer elevated kinase activity in vitro on LRRK2, there are no methods available to directly monitor LRRK2 kinase activity in vivo. We demonstrate that LRRK2 autophosphorylation on Ser1292 occurs in vivo and is enhanced by several familial PD mutations including N1437H, R1441G/C, G2019S, and I2020T. Combining two PD mutations together further increases Ser1292 autophosphorylation. Mutation of Ser1292 to alanine (S1292A) ameliorates the effects of LRRK2 PD mutations on neurite outgrowth in cultured rat embryonic primary neurons. Using cell-based and pharmacodynamic assays with phosphorylated Ser1292 as the readout, we developed a brain-penetrating LRRK2 kinase inhibitor that blocks Ser1292 autophosphorylation in vivo and attenuates the cellular consequences of LRRK2 PD mutations in vitro. These data suggest that Ser1292 autophosphorylation may be a useful indicator of LRRK2 kinase activity in vivo and may contribute to the cellular effects of certain PD mutations.
Minimum Wages and Earnings Inequality in Urban Mexico

This paper analyzes the contribution of the minimum wage to the well documented rise in earnings inequality in Mexico between the late 1980s and the early 2000s. We find that a substantial part of the growth in inequality, and essentially all the growth in inequality in the bottom end, is due to the steep decline in the real value of the minimum wage.
Institutional Determinants of Sectoral FDI in Eastern European and Central Asian Countries: The Role of Investment Climate and Democracy

We study the determinants of the sectoral distribution of foreign direct investment (FDI) in Eastern Europe and Central Asia, focusing on the investment climate and state of democracy. Using a dynamic system generalized method of moments estimator, we examine twenty-one countries for the period 1994-2008. We find that when human capital is controlled for, the host country investment profile has a positive effect on agricultural FDI and the host country state of democracy positively affects agricultural and manufacturing FDI. In addition, services FDI is attracted by educated labor, whereas FDI to other sectors is attracted by cheap labor. Moreover, natural resource endowments have a positive impact on FDI in the sectors of agriculture and manufacturing.
Quality choice in models of vertical differentiation

In this paper, we consider a duopoly model of vertical product differentiation. Firms choose simultanously the quality of the product they sell and then compete in prices simultaneously. We offer the complete characterization of quality choices for this model and thereby give a precise content to the " principle of differentiation " in models of vertical product differentiation.
Single and multiple motion control of autonomous robotic vehicles

The past few decades have witnessed a significant research effort in the area of motion control for autonomous robotic vehicles. This paper presents a brief survey related to two topics in this area: i) the design of control systems to drive a vehicle to track a time-parameterized trajectory (trajectory tracking), or to follow a geometric path (path-following); and ii) the problem of making a group of autonomous robotic vehicles follow desired geometric paths while keeping a specified formation pattern (cooperative path-following). From a theoretical standpoint, special attention is given to a number of challenging problems that include the complex and nonlinear vehicle dynamics, uncertainty, disturbances, and when in cooperation, the problem of communication constraints. Illustrative examples using Lyapunov based techniques for motion control design will be presented for wheeled mobile robots, autonomous underwater vehicles, and unmanned aerial vehicles.
The Effectiveness of International Financial Reporting Standards Adoption on Cost of Equity Capital: A Vector Error Correction Model

The purpose of this paper was to determine empirically whether adopting the International Financial Reporting Standards by Jordanian companies listed on the Amman Stock Exchange influenced its cost of equity capital over the period 1996-2000 using a Vector Error Correction Model. Expected return, extent of disclosure, financial leverage, and company size used as a proxy for cost of equity capital, disclosure, financial risk, and business risk, respectively. Moreover, Dickey-Fuller and Johansen Cointegartion tests were applied. Another tools used were the variance decomposition and Granger Causality tests. Results indicate that none of the independent variables significantly influenced the cost of equity capital.
Comparing Asset Pricing Models

A Bayesian asset-pricing test is derived that is easily computed in closed-form from the standard F-statistic. Given a set of candidate traded factors, we develop a related test procedure that permits an analysis of model comparison, i.e., the computation of model probabilities for the collection of all possible pricing models that are based on subsets of the given factors. We find that the recent models of Hou, Xue and Zhang (2015a,b) and Fama and French (2015a,b) are both dominated by five and six-factor models that include a momentum factor, along with value and profitability factors that are updated monthly.
Genome Sequence of the Anaerobic Bacterium Clostridium arbusti SL206T

ABSTRACT A new Clostridium species has been isolated from pear orchard soil in Daejeon, Republic of Korea. The isolate, Clostridium arbusti SL206T (KCTC 5449T), showed a nitrogenase activity as well as an organic acid production. Here we first report the draft genome sequence of a novel species in the genus Clostridium within the largest Gram-positive group.
Phosphatidylinositol turnover and transformation of cells by Abelson murine leukaemia virus.

The transforming protein of the Abelson murine leukaemia virus encodes a protein‐tyrosine kinase. Previously, we have shown that in Abelson‐transformed cells, the Abelson kinase regulates the phosphoserine content of ribosomal protein S6. Phorbol 12‐myristate 13‐acetate (TPA), which activates protein kinase C, induces the phosphorylation of S6 at the same five phosphopeptides as found in S6 isolated from Abelson‐transformed cells. We have investigated three models whereby the Abelson kinase might regulate S6 phosphorylation via the activation of protein kinase C. First, the Abelson kinase could phosphorylate protein kinase C on tyrosine. However, we do not detect significant amounts of phosphotyrosine in protein kinase C in vivo. Second, it has been suggested that protein‐tyrosine kinases might phosphorylate phosphatidylinositol. This could increase the intracellular levels of diacylglycerol and thereby activate protein kinase C. Our data strongly suggest that direct phosphorylation of phosphatidylinositol by the Abelson protein‐tyrosine kinase has no physiological role. Third, an indirect activation of protein kinase C may occur via an increase in the rate of phosphoinositide breakdown. We have found that phosphoinositide breakdown appears to be constitutively activated in Abelson‐transformed cells. The implications of these observations are discussed with regard to S6 phosphorylation and the mechanism of Abelson‐induced transformation.
Ceremonies of the whole: does social participation moderate the mood consequences of neuroticism?

BACKGROUND The aim of this research was to test whether social participation is associated with improvements in mood and well-being, and in particular to test whether social participation might moderate the chronic distress associated with high levels of neuroticism (N). METHOD A rural Australian sample of 394 adults (54.3% female) completed questionnaires and participated in follow-up interviews. Social participation was indexed by community group membership, and operationalised for analysis in two forms: extent (number of group memberships) and presence (zero vs. one or more memberships). Mood was measured as Positive Affect (PA) and Negative Affect (NA) as rated on the Positive and Negative Affect Schedule and well-being was measured with Diener's Satisfaction with Life (SWL) questionnaire. Items from Goldberg's International Personality Item Pool were used to measure N. RESULTS The extent of social participation was significantly associated with all three mood/well-being variables in bivariate analyses, and remained as a significant net predictor of PA and NA (beta = 0.11, P < 0.05, beta = -0.13, P < 0.05) when modeled with age, gender and income. In parallel, categorical social participation was found to be significantly associated with PA, NA and SWL in bivariate analyses and in multivariate analyses controlling for age, gender and income (beta = 0.11, P < 0.05, beta = -0.15, P < 0.01 and beta = 0.11, P < 0.05, respectively). The interaction term N*Social interaction was significantly correlated with NA in bivariate analyses involving both continuous (r = -0.14, P < 0.01) and categorical (r = -0.13, P < 0.01) measures of social participation, and in its continuous form remained a significant net predictor of NA after controlling for the main effects of N and Social participation (beta = -0.09, P < 0.05). CONCLUSIONS The present findings extend upon existing evidence that social participation tends to be positively associated with mental health by demonstrating the predicted effect across a comprehensive set of mood/well-being variables. Preliminary evidence was also obtained that social participation may serve as a moderator of the chronic distress associated with N. It is concluded that further research seeking to confirm the causal direction of the identified pathways is warranted.
Generalized Channel-Aware Power Control Scheme for Random Access with Multi-Packet Reception

This paper develops a generalized channel-aware power control scheme to enhance the multi-packet reception (MPR) capability for random access. In the proposed scheme, each user randomly selects its transmit power with a probability in accordance with a distribution function based on its own channel state. For two-user systems, we show that the optimal power distribution function has a simple discrete structure, based on which the optimal random access strategy can be efficiently computed. Leveraging the relevant insights, we further propose a decentralized binary power control scheme for general K-user systems. It is established that such a simple scheme can asymptotically approach the performance of the optimal centralized scheme, as the system load grows large. Numerical results show that the proposed schemes obtain noticeable performance improvement over the existing alternatives.
Oms 1 associates with cytochrome c oxidase assembly intermediates to stabilize newly synthesized

The mitochondrial cytochrome c oxidase assembles in the inner membrane from subunits of dual genetic origin. The assembly process of the enzyme is initiated by membrane insertion of the mitochondria-encoded Cox1 subunit. During complex maturation, transient assembly intermediates, consisting of structural subunits and specialized chaperone-like assembly factors, are formed. In addition, cofactors such as heme and copper have to be inserted into the nascent complex. To regulate the assembly process, the availability of Cox1 is under control of a regulatory feedback cycle in which translation of COX1 mRNA is stalled when assembly intermediates of Cox1 accumulate through inactivation of the translational activator Mss51. Here we isolate a cytochrome c oxidase assembly intermediate in preparatory scale from coa1Δ mutant cells, using Mss51 as bait. We demonstrate that at this stage of assembly, the complex has not yet incorporated the heme a cofactors. Using quantitative mass spectrometry, we define the protein composition of the assembly intermediate and unexpectedly identify the putative methyltransferase Oms1 as a constituent. Our analyses show that Oms1 participates in cytochrome c oxidase assembly by stabilizing newly
An economic history of London, 1800-1914

Part I: Economics and Urban History 1. This City 2. Economic Theory and London's History Part II: London's Economy and People 3. Population and Migration 4. Work and Industry 5. Wealth, Living Standards and Poverty Part III: The Transformation of London 6. Retailing and the New Mass Market 7. Leisure and Pleasure 8. Suburbanisation and Housing Part IV: Infrastructure 9. To and From the Capital 10. Moving Round London 11. Utilities, Communications and Markets Part V: Industrial and Commercial Change 12. Manufacturing 13. Domestic, Professional and Clerical Services 14. Financial Services and the City Part VI: Welfare and Government 15. Welfare and Social Policy 16. The Government of London Part VII: An Assessment 17. Conclusions
Alliance Dynamics for Entrepreneurial Firms

Small firms are thought to encounter various difficulties implementing strategic alliances. Due to these problems, they may be less able to reap the benefits of alliance adaptation, and the changes that do occur in alliances may not coincide with a small firm's interests. The evidence we present on contractual renegotiations in alliances suggests that small firms are no more or less likely to adjust their alliances contracts in general. However, small firms tend to bear inefficiencies of two kinds in their collaborations. First, they are less likely to adapt alliances in the presence of governance misalignments. Second, our sampled small firms were more prone to make transaction-specific investments, which can stimulate ex post hold-up in the form of contractual renegotiations.
Mutual transformation and the development of European policy spaces. The case of medicines licensing

This article aims to come to grips with the complexity of the intertwined processes that explain the formation of European policy spaces. Three observations, covered by the ‘mutual transformation’ notion, guide the analysis: (1) influence among the levels composing the Union runs simultaneously from ‘Brussels’ to the lower levels, from the lower levels to the EU authorities, and from country to country; (2) sources of change are both exogenous and endogenous; (3) the nature of the policies under study and the issues and interests associated with them evolve over time, affecting the different level actors and their ties. The case of the formation of a European medicines licensing system here illustrates the usefulness of exploring this mutual transformation. We emphasize the role played in this sector by three closely interrelated social mechanisms: competition, co-operation, and the transformation of relations between expertise and policy-making.
Risk, safety and culture in Brazil and Argentina: the case of TransInc Corporation

Purpose – The purpose of this paper is to show how employees' work cultural values in three cities of two different South American countries (Buenos Aires, Sao Paolo, and Rio de Janeiro) differ, and how these differences are related to the manner in which people perceive risk and construe the meaning of danger.Design/methodology/approach – A total of 220 line employees of a multinational enterprise in Rio de Janeiro, Sao Paulo and Buenos Aires participated in this study. The paper compared the means of reported job satisfaction and cultural values among the cities. Furthermore, regressions are used for cultural values on perceptions of risks from job hazards.Findings – There are different cultural values across the cities. These cultural values are associated with the manner people understand risk and respond to risk management programs. This could eventually influence the success of the implementation of safety management programs.Research limitations/implications – This is a study carried out in a singl.
Repeated Signaling and Firm Dynamics∗

As an alternative to the pecking-order, we develop a dynamic calibratable model where the firm avoids mispricing via signaling. The model is rich, featuring endogenous investment, debt, default, dividends, equity flotations, and share repurchases. In equilibrium, firms with negative private information have negative leverage, issue equity, and overinvest. Firms signal positive information by substituting debt for equity. Default costs induce such firms to underinvest. Model simulations reveal that repeated signaling can account for: countercyclical leverage; leverage persistence; volatile procylical investment; and correlation between size and leverage. The ∗We thank seminar participants at Columbia, Dartmouth College, NYU, LBS, LSE, Bank of England, HEC Lausanne, Minnesota, University of Vienna, Washington University, Chicago GSB, Stanford (SITE), SED (Prague), CEPR (Norway), the 2006 Lone Star Conference, the 2007 WFA Meetings, and the CMU Hansen-Singleton Conference. We owe special thanks to Sudipto Bhattacharya, Peter DeMarzo, Andrea Eisfeldt, and Neng Wang who served as discussants on this paper. This paper was previously circulated under a different title. †London Business School, Regent’s Park, London NW1 4SA, United Kingdom. Tel: +44 (0)20 7000 8285; e-mail: chennessy@london.edu. ‡Finance Group, Haas School of Business, University of California, Berkeley, S545 Student Services Building #1900, Berkeley, CA 94720. Tel: (510) 642-4733; e-mail: livdan@haas.berkeley. edu. §Countrywide Bank.
Measuring Positive Externalities from Unobservable Victim Precaution: An Empirical Analysis of Lojack

Private expenditures on crime reduction have potentially important externalities. Observable measures such as barbed-wire fences and deadbolt locks may shift crime to those who are unprotected, imposing a negative externality. Unobservable precautions, on the other hand, may provide positive externalities since criminals cannot determine a priori who is protected. Focusing on one specific form of victim precaution, Lojack, we provide the first thorough empirical analysis of the magnitude of such externalities. Because installing Lojack does not reduce the likelihood that an individual car will be stolen, any decrease in the aggregate crime rates due to Lojack is an externality from the perspective of the individual Lojack purchaser. We find that the presence of Lojack is associated with a sharp fall in auto theft in central cities and a more modest decline in the remainder of the state. Rates of other crimes do not change appreciably. Our estimates suggest that, at least historically, the marginal social benefit of an additional unit of Lojack has been as much as 15 times greater than the marginal social cost in high crime areas. Those who install Lojack in their cars, however, obtain less than ten percent of the total social benefits of Lojack, causing Lojack to be undersupplied by the free market. Current insurance subsidies for the installation of Lojack appear to be well below the socially optimal level.
Benzylpenicillin skin testing is still important in diagnosing immediate hypersensitivity reactions to penicillins

Background: The fact that both Hollister‐Stier and Allergopharma ceased the production of penicilloyl‐polylysine (PPL) and minor determinant mixture (MDM) in 2004 is severely hampering the diagnosis of β‐lactam hypersensitivity and may produce negative consequences.
Average dwell-time approach to H∞ control of time-varying delay switched systems

This work investigates the problem of state controller synthesis of switched system with time-varying delay. Based on Lyapunov-krasovskii technique and the average dwell time approach (ADTA), a switched state feedback controller is created such that the system is exponentially stable and a weighted La-gain is accomplished. By solving a set of linear matrix inequalities (LMIs), controller parameters and the tolerable switching sequence, subject to the disposed average dwell time, can be taken. Two illustrative examples are proposed to demonstrate validity of the introduced method.
An electromagnetic model for the Lundell alternator with switched-mode rectifier

An electromagnetic model for Lundell alternator switched-mode rectifier system including the main parameters is presented. The purpose of the study that underlies this paper was to create a simple model, capable of providing a satisfactory description of the machine¿s magnetic properties by considering of the saturation and the saliency. The paper deals with an approach using both analytic and experimental techniques. The mutual inductance between field and armature windings is modeled as a saturated harmonic function which depends on rotor position and magnetizing curve equation. The reaction inductance model is defined by the total phase inductance which depends solely on the phase angle between current and back emf phasors.