Miracle-dz/UniFAR-FTUs huggingface dataset:
Flow Cytometry Enables Multiplexed Measurements of Genetically Encoded Intramolecular FRET Sensors Suitable for Screening

Genetically encoded sensors based on intramolecular FRET between CFP and YFP are used extensively in cell biology research. Flow cytometry has been shown to offer a means to measure CFP-YFP FRET; we suspected it would provide a unique way to conduct multiplexed measurements from cells expressing different FRET sensors, which is difficult to do with microscopy, and that this could be used for screening. We confirmed that flow cytometry accurately measures FRET signals using cells transiently transfected with an ERK activity reporter, comparing responses measured with imaging and cytometry. We created polyclonal long-term transfectant lines, each expressing a different intramolecular FRET sensor, and devised a way to bar-code four distinct populations of cells. We demonstrated the feasibility of multiplexed measurements and determined that robust multiplexed measurements can be conducted in plate format. To validate the suitability of the method for screening, we measured responses from a plate of bacterial extracts that in unrelated experiments we had determined contained the protein kinase C (PKC)–activating compound teleocidin A-1. The multiplexed assay correctly identifying the teleocidin A-1-containing well. We propose that multiplexed cytometric FRET measurements will be useful for analyzing cellular function and for screening compound collections.
N-(3,4-Dimethylphenyl)maleamic acid

The title compound, C12H13NO3, crystallizes with four independent molecules in the asymmetric unit. The N—H bond and the C=O bond in the amide segment are anti to each other. The C=C double bond is cis configured and an intramolecular O—H⋯O hydrogen bond is formed in each molecule. The mean planes through the aromatic ring and the amide group –NHCO– are inclined at angles of 17.4 (3), 20.8 (2), 16.2 (2) and 11.2 (3)° in the four molecules. In the crystal, intermolecular N—H⋯O hydrogen bonds link the molecules into ribbons along the b axis.
The 3 mm skin prick test (SPT) threshold criterion is not reliable for Tyrophagus putrescentiae: the re‐evaluation of SPT criterion to dust mites

Background: The mean wheal diameter ≥ 3 mm is the usual criterion for positive skin prick test (SPT) reaction to dust mites. The study assessed the accuracy of this SPT criterion with respect to specific IgE values of above 0.35 kUA/l (+ sIgE).
Localization of Atypical Protein Kinase C Isoforms into Lysosome-Targeted Endosomes through Interaction with p62

ABSTRACT An increasing number of independent studies indicate that the atypical protein kinase C (PKC) isoforms (aPKCs) are critically involved in the control of cell proliferation and survival. The aPKCs are targets of important lipid mediators such as ceramide and the products of the PI 3-kinase. In addition, the aPKCs have been shown to interact with Ras and with two novel proteins, LIP (lambda-interacting protein; a selective activator of λ/ιPKC) and the product ofpar-4 (a gene induced during apoptosis), which is an inhibitor of both λ/ιPKC and ζPKC. LIP and Par-4 interact with the zinc finger domain of the aPKCs where the lipid mediators have been shown to bind. Here we report the identification of p62, a previously described phosphotyrosine-independent p56 lck SH2-interacting protein, as a molecule that interacts potently with the V1 domain of λ/ιPKC and, albeit with lower affinity, with ζPKC. We also show in this study that ectopically expressed p62 colocalizes perfectly with both λ/ιPKC and ζPKC. Interestingly, the endogenous p62, like the ectopically expressed protein, displays a punctate vesicular pattern and clearly colocalizes with endogenous λ/ιPKC and endogenous ζPKC. P62 colocalizes with Rab7 and partially with lamp-1 and limp-II as well as with the epidermal growth factor (EGF) receptor in activated cells, but not with Rab5 or the transferrin receptor. Of functional relevance, expression of dominant negative λ/ιPKC, but not of the wild-type enzyme, severely impairs the endocytic membrane transport of the EGF receptor with no effect on the transferrin receptor. These findings strongly suggest that the aPKCs are anchored by p62 in the lysosome-targeted endosomal compartment, which seems critical for the control of the growth factor receptor trafficking. This is particularly relevant in light of the role played by the aPKCs in mitogenic cell signaling events.
The Quality of Goverment

We investigate empirically the determinants of the quality of governments in a large cross-section of countries. We assess government performance using measures of government intervention, public sector efficiency, public good provision, size of government, and political freedom. We find that countries that are poor, close to the equator, ethnolinguistically heterogeneous, use French of socialist laws, or have high proportions of Catholics or Muslims exhibit inferior government performance. We also find that the larger governments tend to be the better performing ones. The importance of historical factors in explaining the variation in government performance across countries sheds light on the economic, political, and cultural theories of institutions.
Developing Effective Strategies for Tackling Seasonality in the Tourism Industry

Seasonality is a key aspect for the performance of the majority of tourism enterprises and a central theme for policy makers. The usual practice of strategy formulation in this area, whilst often involving a sound analysis of objective performance data, largely ignores the perceptions which the businesses concerned have of the seasonality issue. This paper demonstrates that the heterogeneity of attitudes and perceptions in the sector need to be recognised when developing effective strategies for tackling seasonality. An empirical quantitative approach is applied using occupancy data of the serviced accommodation sector in addition to a survey of owner/managers. The findings indicate that an insufficiently detailed level of segmentation of the business sector concerned may lead to ill-focused broad-brush strategies and consequent misallocations of resources. The paper contends that policy makers in this area need information beyond what can be obtained from the usual performance measurement systems.
A Coupled Theory of Tropical Climatology: Warm Pool, Cold Tongue, and Walker Circulation

Abstract Based on results from analytic and general circulation models, the authors propose a theory for the coupled warm pool, cold tongue, and Walker circulation system. The intensity of the coupled system is determined by the coupling strength, the local equilibrium time, and latitudinal differential heating. Most importantly, this intensity is strongly regulated in the coupled system, with a saturation level that can be reached at a modest coupling strength. The saturation west–east sea surface temperature difference (and the associated Walker circulation) corresponds to about one-quarter of the latitudinal differential equilibrium temperature. This regulation is caused primarily by the decoupling of the SST gradient from a strong ocean current. The author’s estimate suggests that the present Pacific is near the saturation state. Furthermore, the much weaker Walker circulation system in the Atlantic Ocean is interpreted as being the result of the influence of the adjacent land, which is able to extend.
Oleate Promotes the Proliferation of Breast Cancer Cells via the G Protein-coupled Receptor GPR40*

Evidence from epidemiological studies and animal models suggests a link between high levels of dietary fat intake and risk of breast cancer. In addition, obesity, in which circulating lipids are elevated, is associated with increased risk of various cancers. Relative to this point, we previously showed that oleate stimulates the proliferation of breast cancer cells and that phosphatidylinositol 3-kinase plays a role in this process. Nonetheless, questions remain regarding the precise mechanism(s) by which oleate promotes breast cancer cell growth. Pharmacological inhibitors of the GTP-binding proteins Gi/Go, phospholipase C, Src, and mitogenic-extracellular signal-regulated kinase 1/2 (MEK 1/2) decreased oleate-induced [3H]thymidine incorporation in the breast cancer cell line MDA-MB-231. In addition, oleate caused a rapid and transient rise in cytosolic Ca2+ and an increase in protein kinase B phosphorylation. Overexpressing in these cells the G protein-coupled receptor GPR40, a fatty acid receptor, amplified oleate-induced proliferation, whereas silencing the GPR40 gene using RNA interference decreased it. Overexpressing GPR40 in T47D and MCF-7 breast cancer cells that are poorly responsive to oleate allowed a robust proliferative action of oleate. The data indicate that the phospholipase C, MEK 1/2, Src, and phosphatidylinositol 3-kinase/protein kinase B signaling pathways are implicated in the proliferative signal induced by oleate and that these effects are mediated at least in part via the G protein-coupled receptor GPR40. The results suggest that GPR40 is implicated in the control of breast cancer cell growth by fatty acids and that GPR40 may provide a link between fat and cancer.
“It’s as if you don’t know, because you don’t do anything about it”: gender and violence in El Salvador

This paper explores how gendered violence in El Salvador contin- ues to be minimized within public and private discourse. Through an examination of social understandings and reactions to violence, based on qualitative research, the paper argues that gendered violence remains an issue sidelined from mainstream social and political debates. In a society where the threshold for tolerating violence is very high, gendered violence stands out as an issue which, to a great degree, has become normalized as a central element of gender relations. This is borne out by the scant attention paid to issues of gender in both policy proposals and debates on violence.
Role of ancillary studies in fine‐needle aspiration from selected tumors

The routine use of ancillary studies is reshaping the practice of cytopathology. Currently, most cytopathologists recognize the importance of immunocytochemistry and molecular techniques as adjuncts to morphology to achieve a precise diagnosis. Cytopathologists also are expected to include specific prognostic and predictive information in their reports. The objective of this review was to address the use of immunocytochemistry and molecular techniques to refine the preoperative diagnosis and classification of lung cancer, thyroid cancer, kidney cancer, gastrointestinal cancer, and soft tissue tumors. Fine‐needle aspiration also offers a suitable alternative to biopsy in a variety of clinical settings, in particular, when it may be useful to obtain material to study prognostic and predictive markers. This is particularly relevant to obtain material from metastatic sites. The study of KRAS in colon cancer, CKIT in gastrointestinal stromal tumors, and epidermal growth factor receptor mutational status in lung cancer also are addressed particularly in this report. Cancer (Cancer Cytopathol) 2012;. © 2012 American Cancer Society.
TQM and service quality: a survey of commercial banking industry in Malaysia

The objective of this paper is to examine the association between Total Quality Management (TQM) practices and service quality in Malaysia's commercial banking industry. This study is based on empirical data collected from a survey of 101 middle management employees of 20 commercial banks in Malaysia. Multiple regression analysis was used to examine the relationship between the dimensions of TQM and service quality. The results revealed that TQM dimensions such as leadership, strategic planning, information analysis and human resource management are significantly and positively associated with service quality. The human resource management, a perceived dominant TQM practice for improving service quality levels, was found to be significant. The results of this study can be used by banking industry to prioritise the adoption of the dimensions of TQM practices. For instance, those practices that were found to have positive association with service quality can be recommended to senior management so that appropriate resources are allocated to further enhance these practices, and more importantly, to achieve higher quality of service.
Structural Factor-Augmented VARs (SFAVARs) and the Effects of Monetary Policy

Factor-augmented VARs (FAVARs) have combined standard VARs with factor analysis to exploit large data sets in the study of monetary policy. FAVARs enjoy a number of advantages over VARs: they allow a better identification of the monetary policy shock; they avoid the use of a single variable to proxy theoretical constructs; they allow researchers to compute impulse responses for hundreds of variables. Their shortcoming, however, is that the factors are not identified and lack an economic interpretation.This paper seeks to provide an interpretation to the factors. We propose a novel Structural Factor-Augmented VAR (SFAVAR) model, where the factors have a clear meaning: Real Activity factor, Inflation factor, Financial Market factor, Credit factor, Expectations factor, and so forth. The paper employs a Bayesian approach to jointly estimate the factors and the dynamic model. This framework is then used to study the effects of monetary policy on a wide range of macroeconomic variables.
Happy Environments: Bhutan, Interdependence and the West

There is a growing trend to understand economic and environmental policies in terms of multiple dimensions and “interdependence. ” Bhutan is increasingly seen as an operational model with its Gross National Happiness (GNH) strategy. GNH, which is rooted in Mahayana Buddhism, is a framework and set of policy tools that conceptualizes sustainability as interdependent ecological, economic, social, cultural and good governance concerns. Bhutan’s practical GNH experience illustrates a significant ability to positively couple economic growth with a healthy environment. Can the “West”—with its legacy of either/or economics—learn anything from Bhutan’s multidimensional policy experiment? At first, it would seem not. It is questionable whether the West can replicate Bhutan’s unorthodox policy tools as we do not have a balancing set of Buddhist values rooted in mainstream culture. We are not equipped to respond to the many unintended consequences of interdependent policy because we do not yet understand what “interdependence” actually entails. There is hope, but much of it exists in the grey literature of ecological economics. This literature is in urgent need of greater exposure if we are to imagine and enact sustainability policy tools that are truly sensitive to interdependence, and thus follow Bhutan on its perilous but necessary journey.
Relation between Top Executive Compensation Structure and Corporate Governance: Evidence from Japanese Public Disclosed Data

Manuscript Type. Empirical. Research Question/Issue. This paper explores the incentive structure of executive compensation in Japan in 2010, when Japanese individual executive compensation data for those receiving more than 100 million Japanese yen were made public for the first time. This public disclosure enables investigation of the relation between cash‐based and stock‐based individual incentive compensation and corporate governance mechanisms in Japan. Research Findings/Insights. Results show that 1) the bank ties do not substitute for incentive compensation, unlike in the 1990s in Japan, when they were effective for solving agency conflicts; and 2) the role of incentive compensation is found to be effective for firms with a higher degree of foreign ownership. We also examine the role of the new internal control mechanism of firms with a committee system which includes a compensation committee for facilitating incentive compensation. However results show that internal control systems of firms with committees only facilitate short‐term incentive packages because they fall into short‐termism as a result of their short duration of a single year. Theoretical/Academic Implications. Theoretically, bank ties do not contribute as a substitute for incentive compensation to align management and shareholder interests under a Japanese relationship‐oriented system. This implies that Japanese relationship‐oriented systems would have been weakened by solving agency conflicts. Furthermore, firms with committee systems can no longer provide managerial incentives because of the short‐termism of committee members. Practitioner/Policy Implications. This study provides insights for practitioners and policymakers interested in executive compensation structures in any country where corporate governance is reformed to introduce Anglo‐American mechanisms.
IS TRAVEL DEMAND INSATIABLE? A STUDY OF CHANGES IN STRUCTURAL RELATIONSHIPS UNDERLYING TRAVEL

Stability in travel over time is examined in this study, and the source of observed instability is decomposed into: change in socio-demographic and other contributing factors, and change in structural relationships underlying travel. As a tool for this analysis, simultaneous equations model systems are developed to describe urban residents' activity-travel patterns. The models are estimated using repeated cross-sectional data from the Kyoto-Osaka-Kobe metropolitan area of Japan, collected in 1980, 1990 and 2000. The results of statistical analysis indicate that the structural relationships are instable, that changes in non-workers' travel patterns are largely due to the instability in the structural relations while changes in demographic and socio-economic factors play relatively minor roles, and that urban residents' travel has the tendency to expand over time.
CEO Risk‐Taking Incentives and Bank Loan Syndicate Structure

This paper investigates the effects of a borrowing firm's CEO risk-taking incentives on the structure of the firm's syndicated loans. When CEO risk-taking incentives are high, syndicates are structured to facilitate better due diligence and monitoring efforts. These syndicates have a smaller number of total lenders and are more concentrated, and lead arrangers will retain a greater portion of the loan. Moreover, CEO risk-taking incentives have a lesser effect on the syndicate structure when lead arrangers have a good reputation and a prior lending relationship with a borrowing firm, while they have a greater effect on the syndicate structure when borrowing firms have low information transparency, are financially distressed or have low growth prospects.
Stock versus Mutual Ownership Structures: The Risk Implications

This article provides empirical tests of the risk differences between two types of ownership structure in the property-liability insurance industry. Empirical evidence is provided that suggests stock insurers have more risk than mutuals where the risk inherent in future cash flows is proxied by the variance of the loss ratio. Further evidence suggests that stock insurers write relatively more business than do mutuals in lines and states having higher risk. Copyright 1993 by University of Chicago Press.
How Big Is the Random Walk in GNP?

This paper presents a measure of the persistence of fluctuations in GNP based on the variance of its long differences. That measure finds little long-term persistence in GNP. Previous research on this question found a great deal of persistence in GNP, suggesting models such as a random walk. A reconciliation of this paper's results with previous research shows that conventional criteria for time-series model building can produce misleading estimates of persistence.
The Forward Premium Anomaly: Statistical Artefact or Economic Puzzle? New Evidence from Robust Tests

Recent literature has questioned statistical inference in predictive regressi on with persistent regressors, suggesting a possible explanation for puzzles suc h as the forward premium anomaly. We therefore revisit this puzzle using three a lternative econometric methods known to provide reliable inference in the presen ce of persistent conditioning variables. While they provide less evidence agains t forward rate unbiasedness than traditional predictive regression tests, we sti ll reject using at least one method for all six currencies. Thus, while the econ ometric problems inherent in predictive regression likely play a role in this an omaly, we are left with an economic puzzle even after accounting for their influence.
Age-Related Lipid Metabolic Signature in Human LMNA-Lipodystrophic Stem Cell-Derived Adipocytes.

CONTEXT Lamin A (LMNA)-linked lipodystrophies belong to a group of clinical disorders characterized by a redistribution of adipose tissue with a variable range of metabolic complications. The leading cause of these disorders is the nonphysiological accumulation of the lamin A precursor, prelamin A. However, the molecular mechanisms by which prelamin A induces the pathology remain unclear. OBJECTIVE The aim of this study is to use an experimental LMNA-lipodystrophy model based on human mesenchymal stem cell (hMSC)-derived adipocytes that accumulate prelamin A to gain deeper insights into the mechanisms governing these diseases. DESIGN/SETTING/PARTICIPANTS Prelamin A-induced or -noninduced hMSC-derived adipocytes were obtained from healthy donors. The study was performed at the Biocruces Health Research Institute. MAIN OUTCOME MEASURES Lipolytic activity was determined by the measurement of glycerol and free fatty acids. Ultrastructural analysis was performed by electron microscopy. Flow cytometry was used to assess mitochondrial membrane potential, and ultra-performance liquid chromatography coupled to mass spectrometry was used to explore lipid profiles. RESULTS Prelamin A accumulating hMSC-derived adipocytes revealed increased lipolysis, mitochondrial dysfunction, and endoplasmic reticulum stress. Accumulation of prelamin A induces an altered lipid profile characterized by reduced diacylglyceride content, a higher ratio of monounsaturated over polyunsaturated fatty acids, and decreased stearoyl-coenzyme A desaturase-1 activity. In contrast, the ratio of diacylglycerophosphatidylcholine over diacylglycerophosphatidylethanolamine and the activity of phosphatidylethanolamine-methyltransferase were increased. CONCLUSIONS Prelamin A accumulation causes mitochondrial dysfunction, endoplasmic reticulum stress, and altered lipid metabolism resembling a premature aging phenotype.
Toward a Framework for Improving Health Care Financing for an Aging Population: The Case of Israel

The conventional wisdom is that because at any time the aged cost more than the young, there is a positive relationship between aging and health care spending. It is hard, however, to find evidence that aging correlates positively with such spending. Intrigued by the puzzle, we account for the factors that contribute to changes of the age distribution of medical costs and their potential effect on aggregate cost. As changes in costs are not age neutral, the health system needs to facilitate a dynamic shift of resources from those whose relative cost rise less -- the young -- to those whose relative costs rise more -- the old. As there is an apparent market failure associated with uncertainty about growth in longevity (no market for 'death insurance'), the private market does not seem to effectively facilitate this shift. Aging, and its known correlates and antecedents produce a complex picture about the potential effect of aging on total cost of medical care in Israel. Shifting morbidity and mortality to older age can lower cost of care, all other things equal. Growth in incomes and insurance coverage are likely to increase use of care particularly amongst the old. Rising levels of education would have the opposite effect, but among the relatively young. The effect of a key element, technology, remains unknown. The Israeli experience also points to the advantages of a unified publicly financed health system with a timely allocation mechanism.