Miracle-dz/UniFAR-FTUs huggingface dataset:
Computational model of sphingolipids metabolism: a case study of Alzheimer's disease

Background: Sphingolipids - as suggested by the prefix in their name - are mysterious molecules, which play surprisingly various roles in opposable cellular processes, like autophagy, apoptosis, proliferation and differentiation. Recently they have been also recognized as important messengers in cellular signalling pathways. More importantly, sphingolipid metabolism disorders were observed in various pathological conditions such as cancer and neurodegeneration. Results: Existing formal models of sphingolipids metabolism concentrates mostly on de novo ceramide synthesis or restrict their focus to biochemical transformations of a particular subspecies. We propose first comprehensive computational model of sphingolipid metabolism in human tissue. In contrast to previous approaches we explicitly model compartmentalization what allows emphasizing the differences among individual organelles. Conclusions: Presented here model was validated by means of recently proposed model analysis technics allowing for detection of most sensitive and experimentally non-identifiable parameters and determination of main sources of model variance. Moreover, we demonstrate the utility of the model for the study of molecular processes underlying Alzheimer's disease.
Three essays in fiscal policy

This thesis presents three papers on fiscal policy. The first paper "Macroeconomic impacts of fiscal policy shocks in UK; a DSGE analysis" (joint with Keshab Bhattarai) uses an estimated new-Keynesian dynamic stochastic general equilibrium (DSGE) model to analyse the effects of fiscal policy in the UK. We show that positive shocks in government consumption and investment result in the highest stimulus in the short term, whereas the capital tax cut and the positive public investment shock in the longer horizon. On the government’s expenditure side public investment remains the most stimulating instrument even if we allow for a constant elasticity of substitution index of private and public consumption in utility. We also find that, the nominal and real frictions present in the model tend to influence stronger the level of labour and capital tax multipliers and less public expenditure multipliers. The second paper "Credit constraints, the housing market, and fiscal policy" investigates the effects of fiscal policy in an estimated new-Keynesian open-economy DSGE model with a housing market and indebted households. We show that house prices drop following a negative shock to government transfers, and a positive shock to public spending, public investment and taxes. The results reveal that the financial deregulation increases the sensitivity of fundamentals to fiscal policy. In particular, in the case of a stimulus, the financial deregulation contributes to a weakening of multipliers in the case of government consumption and investment and tends to improve multipliers for public transfers and tax cuts. The third paper "Who is afraid of austerity? The redistributive impact of fiscal policy in a DSGE framework" (joint with Richard McManus and Gulcin Ozkan) explores the distributional consequences of fiscal austerity using a medium scale new-Keynesian DSGE model with a richly specified fiscal sector. We show that agents who are credit constrained are most exposed to austerity in contrast to agents with full access to financial markets. This is particularly true in the case of rises in taxes on labour income and cuts in transfers. In general, tax based consolidations exhibit more conflict than spending based ones. Our results also reveal that the distributive impacts of fiscal consolidations are amplified the longer the austerity persists; the slower the policy reversal and when monetary policy reaches its zero lower bound.
Deliberate self harm: systematic review of efficacy of psychosocial and pharmacological treatments in preventing repetition

Abstract Objective: To identify and synthesise the findings from all randomised controlled trials that have examined the effectiveness of treatments of patients who have deliberately harmed themselves. Design: Systematic review of randomised controlled trials of psychosocial and physical treatments. Studies categorised according to type of treatment. When there was more than one investigation in a particular category a summary odds ratio was estimated with the Mantel-Haenszel method. Setting: Randomised trials available in electronic databases in 1996, in the Cochrane Controlled Trials Register in 1997, and from hand searching of journals to 1997. Subjects: Patients who had deliberately harmed themselves shortly before entry into the trials with information on repetition of behaviour. The included trials comprised 2452 randomised participants with outcome data. Main outcome measure: Repetition of self harm. Results: 20 trials reported repetition of self harm as an outcome variable, classified into 10 categories. Summary odds ratio (all for comparison with standard aftercare) indicated reduced repetition for problem solving therapy (0.73; 95% confidence interval 0.45 to 1.18) and for provision of an emergency contact card in addition to standard care (0.45; 0.19 to 1.07). The summary odds ratios were 0.83 (0.61 to 1.14) for trials of intensive aftercare plus outreach and 1.19 (0.53 to 2.67) for antidepressant treatment compared with placebo. Significantly reduced rates of further self harm were observed for depot flupenthixol versus placebo in multiple repeaters (0.09; 0.02 to 0.50) and for dialectical behaviour therapy versus standard aftercare (0.24; 0.06 to 0.93). Conclusion: There remains considerable uncertainty about which forms of psychosocial and physical treatments of patients who harm themselves are most effective. Further larger trials of treatments are needed. Key messages A systematic review of the effectiveness of psychosocial and drug treatments of patients who deliberately harm themselves identified 20 randomised controlled trials in which repetition of self harm was reported as an outcome Promising results were found for problem solving therapy, provision of a card to allow patients to make emergency contact with services, depot flupenthixol for recurrent self harm, and long term psychological therapy for female patients with borderline personality disorder and recurrent self harm Assertive outreach can help to keep patients in treatment Nearly all the trials included too few patients to detect clinically significant differences in repetition of self harm, and even synthesis of results by meta-analysis did not have the power to detect such differences There is an urgent need for large trials of promising therapies for this substantial clinical population
Habitat-based models of cetacean density and distribution in the central North Pacific

The central North Pacific Ocean includes diverse temperate and tropical pelagic habitats. Studies of the abundance and distribution of cetaceans within these dynamic marine ecosystems have generally been patchy or conducted at coarse spatial and temporal scales, limiting their utility for pelagic conservation planning. Habitat-based density models provide a tool for identifying pelagic areas of importance to cetaceans, because model predictions are spatially explicit. In this study, we present habitat-based models of cetacean density that were developed and validated for the central North Pacific. Spatial predictions of cetacean densities and measures of uncertainty were derived based on data collected during 15 large-scale shipboard cetacean and ecosystem assessment surveys conducted from 1997 to 2012. We developed generalized additive models using static and remotely sensed dynamic habitat variables, including distance to land, sea-surface temperature (SST), standard deviation of SST, surface chlorophyll concentration, seasurface height (SSH), and SSH root-mean-square variation. The resulting models, developed using new grid-based prediction methods, provide finer scale information on the distribution and density of cetaceans than previously available. Habitat-based abundance estimates around Hawaii are similar to those derived from standard line-transect analyses of the same data and provide enhanced spatial resolution to inform management and conservation of pelagic cetacean species.
Organic Cation Transporters Modulate the Uptake and Cytotoxicity of Picoplatin, a Third-Generation Platinum Analogue

Picoplatin, a third-generation platinum agent, is efficacious against lung cancers that are otherwise resistant or become refractory during platinum treatment. This effort was aimed at the determination of the influence of organic cation transporters 1, 2, and 3 (OCT1, OCT2, and OCT3) and their genetic variants on cellular uptake of picoplatin and on the individual components of the ensuing cytotoxicity such as DNA adduct formation. The effect of OCT1 on picoplatin pharmacokinetics and antitumor efficacy was determined using OCT knockout mice and HEK293 xenografts stably expressing OCT1. The uptake and DNA adduct formation of picoplatin were found to be significantly enhanced by the expression of the OCTs. Expression of OCT1 and OCT2, but not OCT3, significantly enhanced picoplatin cytotoxicity, which was reduced in the presence of an OCT inhibitor. Common reduced functional variants of OCT1 and OCT2 led to reduction in uptake and DNA adduct formation of picoplatin in comparison with the reference OCT1 and OCT2. Pharmacokinetic parameters of picoplatin in Oct1−/− and Oct1+/+ mice were not significantly different, suggesting that the transporters do not influence the disposition of the drug. In contrast, the volume of OCT1-expressing xenografts in mice was significantly reduced by picoplatin treatment, suggesting that OCT1 may enhance the antitumor efficacy of picoplatin. These studies provide a basis for follow-up clinical studies that would seek to examine the relationship between the anticancer efficacy of picoplatin and expression levels of OCTs and their genetic variants in tumors. Mol Cancer Ther; 9(4); 1058–69. ©2010 AACR.
The Fed's Preference for Policy Rate Smoothing: Overestimation Due to Misspecification?

The federal funds rate is featured by frequent, small changes in the same direction and infrequent reversals. How to replicate the observed smooth behavior of the federal funds rate with a small scale macroeconomic model? This paper compares the descriptive performance of an empirical fully backward looking model with that of an empirical new-Keynesian hybrid framework. It turns out that the Feds monetary policy conduct can be very well described with a framework allowing for the presence of a small but positive fraction of forward looking agents in the IS curve. This element remarkably reduces the large interest rate smoothing weight otherwise needed to track the observed macroeconomic series.
Physical activity, cognitive activity, and cognitive decline in a biracial community population.

BACKGROUND Findings from studies investigating whether physical activity reduces the risk of cognitive decline in old age have been inconsistent. OBJECTIVE To examine whether participation in physical activity by older adults reduces the rate of cognitive decline after accounting for participation in cognitively stimulating activities. DESIGN A prospective population study conducted from August 1993 to January 2003, with an average follow-up of 6.4 years. SETTING A biracial community population on the south side of Chicago. PARTICIPANTS Participants were 4055 community-dwelling adults 65 years and older who were able to walk across a small room and had participated in at least 2 of the 3 follow-up assessments. MAIN OUTCOME MEASURE Annual rate of cognitive change as measured by a global cognitive score, which consisted of averaged standardized scores from 4 cognitive tests. RESULTS In a mixed model adjusted for age, sex, race, and education, each additional physical activity hour per week was associated with a slower rate of cognitive decline by 0.0007 U/y (P = .04). However, with further adjustments (1) for participation in cognitive activities (beta = .0006, P = .10), (2) for depression and vascular diseases (beta = .0005, P = .19), and (3) by excluding participants whose global cognitive score at baseline was at or below the 10th percentile (beta = .0002, P = .45), the coefficients were smaller and no longer statistically significant. CONCLUSION These data do not support the hypothesis that physical activity alone protects against cognitive decline among older adults.
Characterization and modelling of 40 nm mHEMT process up to 110 GHz

An extensive measurement campaign, including DC curves, S-parameters and noise factor has been carried out on a new 40 nm gate length GaAs mHEMT technology under development by OMMIC. For the first time this technology is presented. A scalable equivalent-circuit model, also equipped with noise parameters according to Pospieszalski's approach, has been extracted for the 2 finger family devices. In order to accomplish accurate characterizations of active devices up to very high frequencies, a coplanar TRL calibration kit was specifically designed to be realized on the same substrate as the devices.
Bioenergy from the forest – a source of conflict between forestry and nature conservation?

Bioenergy from the forest has been heavily debated in Sweden for several decades due to the interest of society to decrease dependence upon fossil fuels and limit the effects of climate change. The actual use of bioenergy from the forest has shifted over the years but increased during the last decades. Private actors within forest and nature conservation sectors play an important role for the development of bioenergy from the forest as well as for the debate and the implementation of political goals. Forestry in Sweden is characterised by ‘freedom under responsibility’ for private actors and the perspective of governance is valuable for studying actors and discourses. Actors have their own interests and goals and the study focuses on three key actors representing ownership, industrial and environmental interests respectively. The aim of the study is to describe how the key actor’s positions concerning bioenergy from the forest have developed between years 2000-2010. Positions and dominating discourses were identified by text analysis. All the key actors in the study agree that the Swedish forest has to contribute more to the energy supply. The key actors however continue to have opposing positions regarding the implementation and the main conflicts are regulations and restrictions. The results of the study confirm earlier scientific findings that representatives of the forest industries and forest owners might argue in a new way but they are still mostly interested in power and the freedom to control the forest resource. At the same time, for large parts of the environmental movement, the profitability and production factors cannot motivate risking the protection of the ecosystem and biodiversity. For decision makers there are limited possibilities of finding synergies and practical solutions concerning the realization of the potential and the increased extraction of biomass from the forest for energy purposes.
Exchange Rate Volatility and Export Margins

This paper examines the effect of real exchange rate volatility on the intensive margin and the extensive margin of exports. Using highly disaggregated U.S. import data by product and country of origin, and a methodology that takes into account the possible endogeneity of volatility to trade, this paper finds that exchange rate volatility hinders trade by reducing the number of goods exported by countries. This result suggests that exchange rate volatility can make countries more dependent on a narrower set of export goods, particularly in developing economies with export concentration. Policy makers should take this effect into account when deciding their exchange rate regimes.
Vibrissal sensitivity in a harbor seal (Phoca vitulina)

ABSTRACT Prior efforts to characterize the capabilities of the vibrissal system in seals have yielded conflicting results. Here, we measured the sensitivity of the vibrissal system of a harbor seal (Phoca vitulina) to directly coupled sinusoidal stimuli delivered by a vibrating plate. A trained seal was tested in a psychophysical paradigm to determine the smallest velocity that was detectable at nine frequencies ranging from 10 to 1000 Hz. The stimulus plate was driven by a vibration shaker and the velocity of the plate at each frequency–amplitude combination was calibrated with a laser vibrometer. To prevent cueing from other sensory stimuli, the seal was fitted with a blindfold and headphones playing broadband masking noise. The seal was sensitive to vibrations across the range of frequencies tested, with best sensitivity of 0.09 mm s−1 at 80 Hz. Velocity thresholds as a function of frequency showed a characteristic U-shaped curve with decreasing sensitivity below 20 Hz and above 250 Hz. To ground-truth the experimental setup, four human subjects were tested in the same paradigm using their thumb to contact the vibrating plate. Threshold measurements for the humans were similar to those of the seal, demonstrating comparable tactile sensitivity for their structurally different mechanoreceptive systems. The thresholds measured for the harbor seal in this study were about 100 times more sensitive than previous in-air measures of vibrissal sensitivity for this species. The results were similar to those reported by others for the detection of waterborne vibrations, but show an extended range of frequency sensitivity. Summary: Psychophysical testing of vibration detection in the harbor seal demonstrates acute sensitivity of the vibrissal system.
Complete Genome Analysis of Three Acinetobacter baumannii Clinical Isolates in China for Insight into the Diversification of Drug Resistance Elements

Background The emergence and rapid spreading of multidrug-resistant Acinetobacter baumannii strains has become a major health threat worldwide. To better understand the genetic recombination related with the acquisition of drug-resistant elements during bacterial infection, we performed complete genome analysis on three newly isolated multidrug-resistant A. baumannii strains from Beijing using next-generation sequencing technology. Methodologies/Principal Findings Whole genome comparison revealed that all 3 strains share some common drug resistant elements including carbapenem-resistant bla OXA-23 and tetracycline (tet) resistance islands, but the genome structures are diversified among strains. Various genomic islands intersperse on the genome with transposons and insertions, reflecting the recombination flexibility during the acquisition of the resistant elements. The blood-isolated BJAB07104 and ascites-isolated BJAB0868 exhibit high similarity on their genome structure with most of the global clone II strains, suggesting these two strains belong to the dominant outbreak strains prevalent worldwide. A large resistance island (RI) of about 121-kb, carrying a cluster of resistance-related genes, was inserted into the ATPase gene on BJAB07104 and BJAB0868 genomes. A 78-kb insertion element carrying tra-locus and bla OXA-23 island, can be either inserted into one of the tniB gene in the 121-kb RI on the chromosome, or transformed to conjugative plasmid in the two BJAB strains. The third strains of this study, BJAB0715, which was isolated from spinal fluid, exhibit much more divergence compared with above two strains. It harbors multiple drug-resistance elements including a truncated AbaR-22-like RI on its genome. One of the unique features of this strain is that it carries both bla OXA-23 and bla OXA-58 genes on its genome. Besides, an Acinetobacter lwoffii adeABC efflux element was found inserted into the ATPase position in BJAB0715. Conclusions Our comparative analysis on currently completed Acinetobacter baumannii genomes revealed extensive and dynamic genome organizations, which may facilitate the bacteria to acquire drug-resistance elements into their genomes.
Detecting Gunshots Using Wearable Accelerometers

Gun violence continues to be a staggering and seemingly intractable issue in many communities. The prevalence of gun violence among the sub-population of individuals under court-ordered community supervision provides an opportunity for intervention using remote monitoring technology. Existing monitoring systems rely heavily on location-based monitoring methods, which have incomplete geographic coverage and do not provide information on illegal firearm use. This paper presents the first results demonstrating the feasibility of using wearable inertial sensors to recognize wrist movements and other signals corresponding to firearm usage. Data were collected from accelerometers worn on the wrists of subjects shooting a number of different firearms, conducting routine daily activities, and participating in activities and tasks that could be potentially confused with firearm discharges. A training sample was used to construct a combined detector and classifier for individual gunshots, which achieved a classification accuracy of 99.4 percent when tested against a hold-out sample of observations. These results suggest the feasibility of using inexpensive wearable sensors to detect firearm discharges.
High Rate of Viral Identification and Coinfections in Infants with Acute Bronchiolitis

OBJECTIVES: To determine the viruses and risk factors associated with hospital and intensive care unit (ICU) admissions in infants with acute bronchiolitis. INTRODUCTION: Bronchiolitis is a major cause of morbidity in infants. Widespread use of molecular-based methods has yielded new insights about its etiology, but the impact of viral etiologies on early outcomes is still unclear. METHODS: Seventy-seven infants with bronchiolitis who were under two years of age and visited an emergency unit were included. Using molecular-based methods, samples were tested for 12 different respiratory viruses. Logistic regression models were used to identify clinical and virological variables associated with the main endpoints: hospital admission and ICU admission. RESULTS: We identified at least one virus in 93.5% of patients, and coinfections were found in nearly 40% of patients. RSV was the most common pathogen (63.6%), followed by rhinovirus (39%). Identification of RSV was only associated with an increased risk of hospital admission in the univariate model. Younger age and enterovirus infection were associated with an increased risk of hospital admission, while atopy of a first-degree relative showed a protective effect. Prematurity was associated with an increased risk of admission to the ICU. Coinfections were not associated with worse outcomes. CONCLUSIONS: Molecular-based methods resulted in high rates of viral identification but did not change the significant role of RSV in acute bronchiolitis. Younger age and enterovirus infection were risk factors for hospital admission, while prematurity appeared to be a significant risk factor for admission to the ICU in acute viral bronchiolitis.
Inferring Hidden Causes

One of the important aspects of human causal reasoning is that from the time we are young children we reason about unobserved causes. How can we learn about unobserved causes from information about observed events? Causal Bayes nets provide a formal account of how causal structure is learned from a combination of associations and interventions. This formalism makes specific predictions about the conditions under which learners postulate hidden causes. In this study adult learners were shown a pattern of associations and interventions on a novel causal system. We found that they were able to infer hidden causes as predicted by the Bayes net formalism, and were able to distinguish between one hidden common cause and two hidden independent causes of the observed events.