Miracle-dz/UniFAR-FTUs huggingface dataset:
Yeast Homologues of Three BLOC‐1 Subunits Highlight KxDL Proteins As Conserved Interactors of BLOC‐1

Biogenesis of lysosome‐related organelle complex‐1 (BLOC‐1) is one of the four multi‐subunit complexes implicated in sorting cargo to lysosome‐related organelles, as loss of function of any of these complexes causes Hermansky–Pudlak syndrome. Eight subunits of BLOC‐1 interact with each other and with many other proteins. Identifying new interactors of BLOC‐1 will increase understanding of its mechanism of action, and studies in model organisms are useful for finding such interactors. PSI‐BLAST searches identify homologues in diverse model organisms, but there are significant gaps for BLOC‐1, with none of its eight subunits found in Saccharomyces cerevisiae. Here we use more sensitive searches to identify distant homologues for three BLOC‐1 subunits in S. cerevisiae: Blos1, snapin and cappuccino (cno). Published data on protein interactions show that in yeast these are likely to form a complex with three other proteins. One of these is the yeast homologue of the previously uncharacterized KxDL protein, which also interacts with Blos1 and cno in higher eukaryotes, suggesting that KxDL proteins are key interactors with BLOC‐1.
Day-to-day measurement of patient-reported outcomes in exacerbations of chronic obstructive pulmonary disease

Background Exacerbations of chronic obstructive pulmonary disease (COPD) are a major burden to patients and to society. Little is known about the possible role of day-to-day patient-reported outcomes during an exacerbation. This study aims to describe the day-to-day course of patient-reported health status during exacerbations of COPD and to assess its value in predicting clinical outcomes. Methods Data from two randomized controlled COPD exacerbation trials (n = 210 and n = 45 patients) were used to describe both the feasibility of daily collection of and the day-to-day course of patient-reported outcomes during outpatient treatment or admission to hospital. In addition to clinical parameters, the BORG dyspnea score, the Clinical COPD Questionnaire (CCQ), and the St George’s Respiratory Questionnaire were used in Cox regression models to predict treatment failure, time to next exacerbation, and mortality in the hospital study. Results All patient-reported outcomes showed a distinct pattern of improvement. In the multivariate models, absence of improvement in CCQ symptom score and impaired lung function were independent predictors of treatment failure. Health status and gender predicted time to next exacerbation. Five-year mortality was predicted by age, forced expiratory flow in one second % predicted, smoking status, and CCQ score. In outpatient management of exacerbations, health status was found to be less impaired than in hospitalized patients, while the rate and pattern of recovery was remarkably similar. Conclusion Daily health status measurements were found to predict treatment failure, which could help decision-making for patients hospitalized due to an exacerbation of COPD.
Do Realized Skewness and Kurtosis Predict the Cross-Section of Equity Returns?

Yes. We use intraday data to compute weekly realized variance, skewness and kurtosis for individual equities and assess whether this week? s realized moments predict next week? s stock returns in the cross-section. We sort stocks each week according to their past realized moments, form decile portfolios and analyze subsequent weekly returns. We ? nd a very strong negative relationship between realized skewness and next week? s stock returns, and a positive relationship between realized kurtosis and next week? s stock returns. We do not ? nd a strong relationship between realized volatility and stock returns. A trading strategy that buys stocks in the lowest realized skewness decile and sells stocks in the highest realized skewness decile generates an average weekly return of 43 basis points with a t-statistic of 8:91. A similar strategy that buys stocks with high realized kurtosis and sells stocks with low realized kurtosis produces a weekly return of 16 basis points with a t-statistic of 2:98. Our results are robust across sample periods, portfolio weightings, and proxies for ? rm characteristics, and they are not captured by the Fama-French and Carhart factors.
The Ratio of Monocytes to Lymphocytes in Peripheral Blood Correlates with Increased Susceptibility to Clinical Malaria in Kenyan Children

Background Plasmodium falciparum malaria remains a major cause of illness and death in sub-Saharan Africa. Young children bear the brunt of the disease and though older children and adults suffer relatively fewer clinical attacks, they remain susceptible to asymptomatic P. falciparum infection. A better understanding of the host factors associated with immunity to clinical malaria and the ability to sustain asymptomatic P. falciparum infection will aid the development of improved strategies for disease prevention. Methods and Findings Here we investigate whether full differential blood counts can predict susceptibility to clinical malaria among Kenyan children sampled at five annual cross-sectional surveys. We find that the ratio of monocytes to lymphocytes, measured in peripheral blood at the time of survey, directly correlates with risk of clinical malaria during follow-up. This association is evident among children with asymptomatic P. falciparum infection at the time the cell counts are measured (Hazard ratio (HR) = 2.7 (95% CI 1.42, 5.01, P = 0.002) but not in those without detectable parasitaemia (HR = 1.0 (95% CI 0.74, 1.42, P = 0.9). Conclusions We propose that the monocyte to lymphocyte ratio, which is easily derived from routine full differential blood counts, reflects an individual's capacity to mount an effective immune response to P. falciparum infection.
Activation of signal transducer and activator of transcription 3 correlates with cell proliferation and renal injury in human glomerulonephritis.

BACKGROUND Signal transducer and activator of transcription (STAT) 3 plays an important role in the regulation of cell proliferation. However, the mechanism of STAT3 activation in human glomerulonephritis is unclear. METHODS STAT3 activation was determined using immunohistochemistry for phosphorylated STAT3 (p-STAT3) in normal human kidney and various types of glomerulonephritis. We also identified the cell exhibiting activated p-STAT3 expression in human glomerulonephritis and correlated STAT3 activation with renal function and histologic injury. RESULTS p-STAT3 staining was identified in glomeruli and some tubules in normal human kidney. p-STAT3 positive glomerular cells were significantly increased in lupus nephritis, IgA nephropathy and vasculitis compared with normal kidney. p-STAT3 positive tubulointerstitial cells were significantly increased in IgA nephropathy and vasculitis compared with normal kidney. Glomerular and tubulointerstitial p-STAT3 staining was significantly decreased after steroid therapy. There was a significant correlation between the number of p-STAT3 positive cells and the number of PCNA positive glomerular and tubulointerstitial cells in all cases of glomerulonephritis. Furthermore, renal function inversely correlated with the number of p-STAT3 positive glomerular and tubulointerstitial cells in all cases of glomerulonephritis. CONCLUSIONS The present study has identified STAT3 activation in normal human kidney and a marked increase in STAT3 activation in many forms of glomerulonephritis. The correlation of STAT3 activation with clinical and histologic parameters suggests that this pathway plays an important role in the pathogenesis of kidney disease. Furthermore, localization of STAT3 activation to individual cell types suggests that this pathway may play a pivotal role in promoting renal inflammation and fibrosis.
Appendix C : Analysis with the Median Forecasts from the MS and the SPF

This paper examines the nexus between news coverage on inflation and households’inflation expectations. In doing so, we test the epidemiology of inflation expectations (Carroll, 2003, 2006). We use both aggregate and household-level data from the Survey Research Center at the University of Michigan. We highlight a fundamental disconnection between news on inflation, consumers’frequency of expectation updating and the accuracy of their expectations. Our evidence provides at best weak support to the epidemiological framework, as most of the consumers who update their expectations do not revise them towards professional forecasters’mean forecast. JEL classification: C53, D84, E31
Strategies for Spectral Profile Inversion Using Artificial Neural Networks

This paper explores three different strategies for the inversion of spectral lines (and their Stokes profiles) using artificial neural networks. It is shown that a straightforward approach in which the network is trained with synthetic spectra from a simplified model leads to considerable errors in the inversion of real observations. This problem can be overcome in at least two different ways that are studied here in detail. The first method makes use of an additional preprocessing autoassociative neural network to project the observed profile into the theoretical model subspace. The second method considers a suitable regularization of the neural network used for the inversion. These new techniques are shown to be robust and reliable when applied to the inversion of both synthetic and observed data.
How personal experience modulates the neural circuitry of memories of September 11

Brown and Kulik [Brown R, Kulik J (1977) Cognition 5:73–99] introduced the term “flashbulb memory” to describe the recall of shocking, consequential events such as hearing news of a presidential assassination. They proposed that the vivid detail of such memories results from the action of a unique neural mechanism. In the present study of personal recollections of the terrorist attacks of September 11, 2001 (9/11) in New York City, we combine behavioral and brain imaging techniques, with two goals: (i) to explore the neural basis of such memories and (ii) to clarify the characteristics of the emotional events that may give rise to them. Three years after the terrorist attacks, participants were asked to retrieve memories of 9/11, as well as memories of personally selected control events from 2001. At the time of the attacks, some participants were in Downtown Manhattan, close to the World Trade Center; others were in Midtown, a few miles away. The Downtown participants exhibited selective activation of the amygdala as they recalled events from 9/11, but not while they recalled control events. This was not the case for the Midtown participants. Moreover, only the Downtown participants reported emotionally enhanced recollective experiences while recalling events from 9/11, as compared with control events. These results suggest that close personal experience may be critical in engaging the neural mechanisms that underlie the emotional modulation of memory and thus in producing the vivid recollections to which the term flashbulb memory is often applied.
Comparative Risk for Angioedema Associated with the Use of Drugs That Target the Renin-angiotensin-aldosterone System

Background: Although certain drugs that target the re-nin-angiotensin-aldosterone system are linked to an increased risk for angioedema, data on their absolute and comparative risks are limited to the use of most drugs that target the system. We assessed the risk for angio-edema associated with the use of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and the direct renin inhibitor aliskiren.
No clear support for a role for vitamin D in Parkinson's disease: A Mendelian randomization study

Observational studies have found that relative to healthy controls, patients with Parkinson's disease have lower circulating concentrations of 25‐hydroxyvitamin D, a clinical biomarker of vitamin D status. However, the causality of this association is uncertain. We undertook a Mendelian randomization study to investigate whether genetically decreased 25‐hydroxyvitamin D concentrations are associated with PD to minimize confounding and prevent bias because of reverse causation.
Dynamic optimization of a system with input-dependant time delays

This paper studies one example of dynamic optimisation of systems subject to hydraulic transportation delays. Properly taking into account the variability of the delay in optimisation is a challenging problem, of importance in several applications. While stationary conditions have been derived in earlier works, here we investigate practical numerical aspects and propose a direct resolution method using an orthogonal collocation approach and a state of the art interior point solver. On the basis of the benchmark process considered here, we compute optimal solutions, discuss their surprisingly rich structure and explore the relevance of different numerical schemes.
Characterization and simulation of SiGe HBT degradation induced by electromagnetic field stress

A new reliability study in SiGe Heterojunction Bipolar Transistors (HBTs) is investigated resulting from electromagnetic field aggression. We demonstrate experimental evidence of current gain degradation during electromagnetic stress. The device degradation is due to the Hot Carrier (HC) injected into the emitter- base spacer oxide, which induces Generation/Recombination trap centers, and leads to excess non-ideal base currents. Two-dimensional simulations, based on the HBT cross section, have been used to help understand the device physics associated with this degradation mechanism. As a consequence of introducing the surface recombination centers at the emitter-base spacer oxide, a non-ideal base current arises in agreement with the experimental data extracted. Simulation results show a strong correlation between stress time and recombination rate induced by the Si/SiO2 interface damage.
A CFH12K Survey of Red Giant Stars in the M81 Group

We present the preliminary results of a wide-field photometric survey of individual red giant branch (RGB) and asymptotic giant branch (AGB) stars in the M81 group, performed with the CFH12K mosaic camera of the CFHT. We use deep VI images of 0.65 sq. deg. of sky to map out the two-dimensional distribution of intragroup stars and to search for stars associated with the many HI tidal tails in the group. We place an upper limit on the presence of metal-poor RGB stars in a field located 50-80 kpc from M81, and derive an `intragroup' fraction of <2%. In a field sampling the M81-NGC3077 HI tidal tail, we find blue stars associated with some of the tidal features, including 2 clumps which we tentatively describe as tidal dwarf candidates. These objects are ~1 kpc in size, and, based on their color-magnitude diagrams, have formed stars as recently as ~30-70 Myr ago, long after the group's most recent interactions.
Airborne LiDAR and Terrestrial Laser Scanning Derived Vegetation Obstruction Factors for Visibility Models

Research presented here explores the feasibility of leveraging vegetation data derived from airborne light detection and ranging (LiDAR) and terrestrial laser scanning (TLS) for visibility modeling. Using LiDAR and TLS datasets of a lodgepole pine (Pinus contorta) dominant ecosystem, tree canopy and trunk obstructions were isolated relevant to a discrete visibility beam in a short‐range line‐of‐sight model. Cumulative obstruction factors from vegetation were compared with reference visibility values from digital photographs along sightline paths. LiDAR‐derived tree factors were augmented with single‐scan TLS data for obstruction prediction. Good correlation between datasets was found up to 10 m from the terrestrial scanner, but fine scale visibility modeling was problematic at longer distances. Analysis of correlation and regression results reveal the influence of obstruction shadowing inherent to discrete LiDAR and TLS, potentially limiting the feasibility of modeling visibility over large areas with similar technology. However, the results support the potential for TLS‐derived subcanopy metrics for augmenting large amounts of aerial LiDAR data to significantly improve models of forest structure. Subtle LiDAR processing improvements, including more accurate tree delineation through higher point density aerial data, combined with better vegetation quantification processes for TLS data, will advance the feasibility and accuracy of data integration.
Cloud migration: Planning guidelines and execution framework

Cloud computing is becoming increasingly popular because it offers valuable benefits, such as on-demand services, resource pooling, rapid elasticity, measured service, etc. However, recent studies indicate that many enterprises still hesitate to adopt cloud services due to various security concerns and implementation obstacles. Particularly, there is little research devoted to exploring the influences on cloud migration execution. To bridge this gap, our study derived some comprehensive cloud migration execution influences by interview approach, based on the technology-organization-environment (TOE) theory. We posit that system configuration (the technological aspect, which consists of complexity and compatibility), organizational fit (the organizational aspect, which consists of member reflection and operation process), and external support (the environmental aspect, which affects the migration execution of cloud computing). The findings in this paper can help enterprises facilitate various cloud migration activities, achieve their goals of migrating applicable legacy applications to the cloud environment, and realize the benefits provided by the cloud computing paradigm.
Scott A. Smolka Research Statement

The primary focus of my research is the computer-aided verification and validation of computer systems, including concurrent and distributed systems; security, network and wireless protocols; software systems; biological systems; and safety-critical and embedded systems. Throughout my career I have been interested in both the computational complexity and algorithmica of verification, striving to provide e.g. NPand PSPACEhardness proofs for those verification problems that are computationally intractable, and efficient (and sometimes parallel) algorithms for those that are not.
Structure and Assembly of a Trans-Periplasmic Channel for Type IV Pili in Neisseria meningitidis

Type IV pili are polymeric fibers which protrude from the cell surface and play a critical role in adhesion and invasion by pathogenic bacteria. The secretion of pili across the periplasm and outer membrane is mediated by a specialized secretin protein, PilQ, but the way in which this large channel is formed is unknown. Using NMR, we derived the structures of the periplasmic domains from N. meningitidis PilQ: the N-terminus is shown to consist of two β-domains, which are unique to the type IV pilus-dependent secretins. The structure of the second β-domain revealed an eight-stranded β-sandwich structure which is a novel variant of the HSP20-like fold. The central part of PilQ consists of two α/β fold domains: the structure of the first of these is similar to domains from other secretins, but with an additional α-helix which links it to the second α/β domain. We also determined the structure of the entire PilQ dodecamer by cryoelectron microscopy: it forms a cage-like structure, enclosing a cavity which is approximately 55 Å in internal diameter at its largest extent. Specific regions were identified in the density map which corresponded to the individual PilQ domains: this allowed us to dock them into the cryoelectron microscopy density map, and hence reconstruct the entire PilQ assembly which spans the periplasm. We also show that the C-terminal domain from the lipoprotein PilP, which is essential for pilus assembly, binds specifically to the first α/β domain in PilQ and use NMR chemical shift mapping to generate a model for the PilP:PilQ complex. We conclude that passage of the pilus fiber requires disassembly of both the membrane-spanning and the β-domain regions in PilQ, and that PilP plays an important role in stabilising the PilQ assembly during secretion, through its anchorage in the inner membrane.
Understanding and assessing intercultural competence: A summary of theory, research, and practice (Technical report for the Foreign Language Program Evaluation Project)

In its broadest sense, intercultural competence ca n be defined following Fantini (2006) as “a complex of abilities needed to perform effectively and appropriately when interacting with others who are linguistically and culturally different fro m oneself” (p. 12, emphasis in original). Throughout the literature, researchers and theoreti cians use a range of more or less related terms to discuss and describe intercultural competence , including intercultural communicative competence (ICC) , transcultural communication, cross-cultural adapt ation , and intercultural sensitivity, among others (Fantini, 2006). What all of these te rms attempt to account for is the ability to step beyond one’s own culture and functi on with other individuals from linguistically and culturally diverse backgrounds. College foreign language and study abroad programs play a unique role in offering students the opportunity to develop their intercultural competencies. The acquisition of such competencies may be important not only for individual enrichment and communicative proficiency but also for providing fu ture educators, professionals, and leaders with the capabilities necessary for promoting succe ssful collaboration across cultures. In this report we summarize theory and research on intercultural competence, paying particular attention to existing approaches and too ls for its assessment. We also review examples of the assessment of intercultural competence in th e specific contexts of general education and college foreign language and study abroad programs. It is our hope that these resources will provide a useful basis to foreign language (and oth er) educators as they seek to understand and improve the intercultural competencies of their stu dents.
Estimating the Future Impact of a Multi-Pronged Intervention Strategy on Ocular Disease Sequelae Caused by Trachoma: A Modeling Study

Abstract Purpose: Trachoma control programs are underway in endemic regions worldwide. They are based on the SAFE strategy (Surgery for trichiasis, Antibiotic distribution, Facial cleanliness, and Environmental improvement). Although much is known about the effect of community-wide treatment with antibiotics on the prevalence of Chlamydia trachomatis, the impact of the SAFE strategy on severe ocular disease sequelae (the main focus of the Global Elimination of blinding Trachoma by 2020 program) remains largely unknown. Methods: We use a mathematical model to explore the impact of each of the components of the SAFE strategy, individually and together, on disease sequelae, arising from repeat infection and subsequent conjunctival scarring. We ask whether two elimination goals, to reduce the prevalence of trachomatous trichiasis to 1 per 1000 persons, and the incidence of corneal opacity to 1 per 10,000 persons per annum, are achievable, and which combinations of interventions have the greatest impact on these indicators. Results: In high prevalence communities (here, >20% infection of children aged 1–9 years), a combination of efforts is needed to bring down sustainably the prevalence and incidence of ocular disease sequelae. Conclusion: The mass delivery of antibiotics is highly beneficial for the clearance of infection, inflammation and prevention of subsequent scarring, but needs to be supplemented with sustained reductions in transmission and surgery to consider realistically the elimination of blindness by the year 2020.