Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification and HLA-Tetramer-Validation of Human CD4+ and CD8+ T Cell Responses against HCMV Proteins IE1 and IE2

Human cytomegalovirus (HCMV) is an important human pathogen. It is a leading cause of congenital infection and a leading infectious threat to recipients of solid organ transplants as well as of allogeneic hematopoietic cell transplants. Moreover, it has recently been suggested that HCMV may promote tumor development. Both CD4+ and CD8+ T cell responses are important for long-term control of the virus, and adoptive transfer of HCMV-specific T cells has led to protection from reactivation and HCMV disease. Identification of HCMV-specific T cell epitopes has primarily focused on CD8+ T cell responses against the pp65 phosphoprotein. In this study, we have focused on CD4+ and CD8+ T cell responses against the immediate early 1 and 2 proteins (IE1 and IE2). Using overlapping peptides spanning the entire IE1 and IE2 sequences, peripheral blood mononuclear cells from 16 healthy, HLA-typed, donors were screened by ex vivo IFN-γ ELISpot and in vitro intracellular cytokine secretion assays. The specificities of CD4+ and CD8+ T cell responses were identified and validated by HLA class II and I tetramers, respectively. Eighty-one CD4+ and 44 CD8+ T cell responses were identified representing at least seven different CD4 epitopes and 14 CD8 epitopes restricted by seven and 11 different HLA class II and I molecules, respectively, in total covering 91 and 98% of the Caucasian population, respectively. Presented in the context of several different HLA class II molecules, two epitope areas in IE1 and IE2 were recognized in about half of the analyzed donors. These data may be used to design a versatile anti-HCMV vaccine and/or immunotherapy strategy.
Using Proteomics to Understand How Leishmania Parasites Survive inside the Host and Establish Infection

Leishmania is a protozoan parasite that causes a wide range of different clinical manifestations in mammalian hosts. It is a major public health risk on different continents and represents one of the most important neglected diseases. Due to the high toxicity of the drugs currently used, and in the light of increasing drug resistance, there is a critical need to develop new drugs and vaccines to control Leishmania infection. Over the past few years, proteomics has become an important tool to understand the underlying biology of Leishmania parasites and host interaction. The large-scale study of proteins, both in parasites and within the host in response to infection, can accelerate the discovery of new therapeutic targets. By studying the proteomes of host cells and tissues infected with Leishmania, as well as changes in protein profiles among promastigotes and amastigotes, scientists hope to better understand the biology involved in the parasite survival and the host-parasite interaction. This review demonstrates the feasibility of proteomics as an approach to identify new proteins involved in Leishmania differentiation and intracellular survival.
Use of Linked Data to enhance Open Educational Resources

Open Educational Resources (OER) are freely accessible, openly licensed documents and media that are useful for teaching, learning, research, and assessing. OER are usually conceptualized as Learning Objects (LO). While there is a big abundance of OER available today, finding, querying, and integrating/interlinking these resources, to say the least, is difficult. On the other hand, Linked Data is a mechanism to tackle the issues related to publishing and to exploring data on the Internet. Linked Data allows a person or machine to explore the Web of Data. In the last years, many efforts have been carried out using Linked Data in different domains. However, Linked Data has not been used extensively to publish and explore OER. In this paper, we review the current status of use of Linked Data to manage OER and we propose the use of Linked Data to enhance the use of OER. Linked Data offers a mechanism where OER can be most easily found to use, reuse, sharing and remix.
Portfolio Credit Risk Models with Interacting Default Intensities: a Markovian Approach

We consider reduced­form models for portfolio credit risk with interacting default intensities. In this class of models the impact of default of some firm on the default intensities of surviving firms is exogenously specified and the dependence structure of the default times is endogenously determined. We construct and study the model using Markov process techniques. We analyze in detail a model where the interaction between firms is of the mean­field type. Moreover, we discuss the pricing of portfolio related credit products such as basket default swaps and CDOs in our model.
A Survey of Outlier Detection Methods in Network Anomaly Identification

The detection of outliers has gained considerable interest in data mining with the realization that outliers can be the key discovery to be made from very large databases. Outliers arise due to various reasons such as mechanical faults, changes in system behavior, fraudulent behavior, human error and instrument error. Indeed, for many applications the discovery of outliers leads to more interesting and useful results than the discovery of inliers. Detection of outliers can lead to identification of system faults so that administrators can take preventive measures before they escalate. It is possible that anomaly detection may enable detection of new attacks. Outlier detection is an important anomaly detection approach. In this paper, we present a comprehensive survey of well-known distance-based, density-based and other techniques for outlier detection and compare them. We provide definitions of outliers and discuss their detection based on supervised and unsupervised learning in the context of network anomaly detection.
The Atopic March: Progression from Atopic Dermatitis to Allergic Rhinitis and Asthma

Atopic dermatitis (AD) is an inflammatory disease characterized by pruritic skin lesions. The pathogenesis of AD may include disrupted epidermal barrier function, immunodysregulation, and IgE-mediated sensitization to food and environmental allergens. AD is also part of a process called the atopic march, a progression from AD to allergic rhinitis and asthma. This has been supported by multiple cross-sectional and longitudinal studies and experimental data. Research on the mechanisms of AD has been centered on the adaptive immune system with an emphasis on the T-helper 1 (Th1)-Th2 paradigm. Recently, the conceptual focus has largely shifted to include a primary defect in the epithelial barrier as an initial event in AD providing a significant insight into the disease initiation and pointing to a complex secondary interplay of environmental and immunological sequelae with barrier disruption. Further understanding of AD will help the development of more effective treatment for AD and ultimately, preventative algorithms for the atopic march. In this review we highlight recent advances in our understanding of the pathogenesis of AD and the atopic march.
Self-Injury and Suicide Attempt in Relation with Trauma and Dissociation among Adolescents with Dissociative and Non-Dissociative Disorders

Objective To explore the role of trauma and dissociation over self-injurious behaviors (SIB) and suicide attempts (SA) in adolescents. Methods A total of 207 adolescents participated in the study. After conducting diagnostic interview, participants were divided into five groups as subjects with dissociative disorders (DD), attention deficit hyperactivity disorder (ADHD), major depressive disorder (MDD) and anxiety disorders (AD), and a control group (CG) without any psychiatric disorder. ADHD, MDD and AD groups were considered as non-dissociative disorders (non-DD group) in the present study. Results There is no significant difference between groups in terms of number and age of the subjects (p>0.05). Among all participants SIB was reported in 32.2% of females (n=37) and 25% of males (n=23) while SA was reported in 29.6% of females (n=34) and 4.4% of males (n=4). Adolescents with DD were found to experience higher rates of SIB and SA than the other groups. Dissociation was the most important variable contributing to SIB and female gender was the most efficient variable for SA. Total trauma scores were also found to be significantly higher in DD group followed by non-DD and CG respectively. Conclusion SIB and SA are complex behavioral problems which may be associated with many psychiatric factors. However higher level dissociation seems as an important mediating factor, even regardless of psychiatric diagnosis, in the development of SIB and SA. More research is needed to further explore the factors effective over SIB and SA in adolescents.
ESSAYS ON INNOVATION, HUMAN CAPITAL, AND ECONOMIC INSTABILITY

This thesis represents a contribution to the empirical literature on the relation between technological progress and development. In its first chapter, the functional form properties of the relationship between national aggregate R&D expenditure and innovation outputs are investigated. A non-parametric estimation of such relationship demonstrates the existence of important non-linearities. Firstly, a critical mass effect is represented by a delayed onset of positive returns to R&D spending. Secondly, diminishing returns to the accumulation of R&D are uncovered. A disaggregation of R&D by funding source reveals that it is the privately funded R&D component the driving force behind such pattern. The second chapter investigates the channels through which institutional and macroeconomic instability hinder innovative investment undertakings financed by the domestic private sector. The analysis is based on a sample of 44 countries representing all levels of development and considers a number of instability dimensions. The results suggest a negative impact of real, monetary and political instability on the aggregate level of national R&D financed by the business sector. Thus, they highlight the desirability of stable macro-institutional environments in preventing avoidance or abandonment of private innovation undertakings.The third chapter investigates the impact of institutional and macroeconomic instability on the skill premium, in a 69-country panel. The results suggest a negative effect of both types of instability on the skill premium, defined as the ratio of unskilled to skilled wages. An interpretation of such findings in light of the results of chapter two indicates that low skilled wages are associated with lagging R&D investment, as a result of reduced skilled labour productivity and less demand for skilled workers. These findings stress again the importance of stable environments, as a way of preventing the shrinkage of the skill premium, and, thereby, sub-optimal human capital accumulation or brain drain.Overall, the thesis provides empirical evidence regarding the accumulation path of technological development, and how such accumulation may be disrupted in the presence of economic instability.
A General Noise Resolution Model for Parking Occupancy Sensors

In this paper the authors address a challenging problem of predicting on-street parking occupancy based on sensors with occasionally missing data. These missing values are most likely not missing at random. However, the exact process behind it is unknown at the outset. For example, an entry in the data stream might read: “at time t, blockface b, which has capacity 20, has 18 working sensors, and of those working sensors 10 indicate that a parking space is occupied. ” The challenge is to infer as accurately as possible the actual occupancy of blockface b, i.e. the occupancy of all parking spaces, including the ones with inoperative sensors. The fact that sensors are inoperative only occasionally allows us to learn a demand model and a sensor noise model jointly, and use this to “fill in the blanks” in the best possible way. The authors introduce a series of sensor noise models of increasing complexity that are suited for several sensor characteristics. Cross-validation allows the selection of the suitable model for a particular application. The sensor noise models introduced are flexible and can be combined with any probabilistic model for demand and hence have a very wide applicability. In our demonstration application the authors find that sensors are more likely to be inoperative when parking spaces are empty, in particular during busy traffic periods. This supports the hypothesis that drive-by-traffic is an important source of noise for the sensor. Compared to baseline methods based on a missing-at-random assumption our method gives better predictive performance and avoids a systematic bias in the inferred occupancies.
The spectral reflectance of ship wakes between 400 and 900 nanometers

This technical note describes the use of an airborne hyperspectral imaging sensor (HICO - Hyperspectral Imager of the Coastal Ocean) to record the spectral reflectance characteristics of centerline ship wakes in the 400 to 900 nm wavelength region. Data were collected for a target of known provenance (the United States Coast Guard Cutter Kittiwake) off the Wai'anae coast of O'ahu, Hawai'i, on 8 April 2010. HICO acquired data in 60 spectral bands by flying along the long axis of the wake while the vessel travelled at three speeds (~3.6 m s-1 or 7 knots; ~7.2 m s-1 or 14 knots; and ~11.2 m s-1 or 21 knots). A flying altitude of ~1500 m yielded a spatial resolution of ~1.5 m. Spectral profiles along and across the wake axes are presented which show how the spectral reflectance of the centerline wake varies spatially and temporally as a function of vessel speed. Length (and to a lesser extent, width) vary in proportion to speed. In common with previous studies and model predictions, the wakes show a pronounced greening of the wake (i.e. enhanced reflectance at ~550 nm), with evidence for elevated reflectance at 750-800 nm. Resampling the data from its raw 1.5 m spatial resolution yields insights into how the turbulent wake becomes spectrally inseparable from the background water as spatial resolution decreases (i.e. becomes increasingly coarse). Using a simple statistical test, the wake becomes spectrally similar to the background ocean as the resolution approaches 60 m.
Effect of Calcium Hydroxide on the Push-out Bond Strength of Endodontic Biomaterials in Simulated Furcation Perforations

Introduction: The aim of this in vitro study was to evaluate the effect of calcium hydroxide (CH) on push-out bond strength of white mineral trioxide aggregate (WMTA) and calcium-enriched mixture (CEM) cement in simulated furcation perforations. Methods and Materials: Furcation perforations, measuring 1.3 mm in diameter and 2 mm in height, were created in 80 human mandibular first molars. The teeth were then divided into 4 groups (n=20). In groups 1 and 3 CH was placed in the perforation for one week, before placement of WMTA and CEM. In groups 2 and 4 perforations were repaired without placement of CH. In groups 1 and 2 the perforation sites were repaired with WMTA and CEM cement was used in groups 3 and 4. After 7 days, the push-out test was carried out using a universal testing machine. Data were analyzed with two-way ANOVA. The level of significance was set at 0.05. Results: The maximum and minimum bond strength values were recorded in the WMTA/CH (13.08±1.8 MPa) and CEM cement groups (8.03±0.98 MPa), respectively. There were significant differences in resistance to dislodgement between the WMTA/CH and other groups (P<0.05). Conclusion: Placement of CH before placement of WMTA in furcation perforation improves the push-out bond strength of this material.
Inositol Hexakisphosphate Kinase-3 Regulates the Morphology and Synapse Formation of Cerebellar Purkinje Cells via Spectrin/Adducin

The inositol hexakisphosphate kinases (IP6Ks) are the principal enzymes that generate inositol pyrophosphates. There are three IP6Ks (IP6K1, 2, and 3). Functions of IP6K1 and IP6K2 have been substantially delineated, but little is known of IP6K3's role in normal physiology, especially in the brain. To elucidate functions of IP6K3, we generated mice with targeted deletion of IP6K3. We demonstrate that IP6K3 is highly concentrated in the brain in cerebellar Purkinje cells. IP6K3 physiologically binds to the cytoskeletal proteins adducin and spectrin, whose mutual interactions are perturbed in IP6K3-null mutants. Consequently, IP6K3 knock-out cerebella manifest abnormalities in Purkinje cell structure and synapse number, and the mutant mice display deficits in motor learning and coordination. Thus, IP6K3 is a major determinant of cytoskeletal disposition and function of cerebellar Purkinje cells. SIGNIFICANCE STATEMENT We identified and cloned a family of three inositol hexakisphosphate kinases (IP6Ks) that generate the inositol pyrophosphates, most notably 5-diphosphoinositol pentakisphosphate (IP7). Of these, IP6K3 has been least characterized. In the present study we generated IP6K3 knock-out mice and show that IP6K3 is highly expressed in cerebellar Purkinje cells. IP6K3-deleted mice display defects of motor learning and coordination. IP6K3-null mice manifest aberrations of Purkinje cells with a diminished number of synapses. IP6K3 interacts with the cytoskeletal proteins spectrin and adducin whose altered disposition in IP6K3 knock-out mice may mediate phenotypic features of the mutant mice. These findings afford molecular/cytoskeletal mechanisms by which the inositol polyphosphate system impacts brain function.
Maize systems under climate change in sub-Saharan Africa

Purpose – The purpose of this study is to examine the biophysical and socioeconomic impacts of climate change on maize production and food security in sub-Saharan Africa (SSA) using adapted improved maize varieties and well-calibrated and validated bioeconomic models. Design/methodology/approach – Using the past climate (1950-2000) as a baseline, the study estimated the biophysical impacts of climate change in 2050 (2040-2069) and 2080 (2070-2099) under the A1B emission scenario and three nitrogen levels, and the socioeconomic impacts in 2050. Findings – Climate change will affect maize yields across SSA in 2050 and 2080, and the extent of the impact at a given period will vary considerably between input levels, regions and maize mega environments (MMEs). Greater relative yield reductions may occur under medium and high-input intensification than under low intensification, in Western and Southern Africa than in Eastern and Central Africa and in lowland and dry mid-altitude than in highland and wet mid-alt.
Cardiovascular and Mortality Risk of Apparent Resistant Hypertension in Women With Suspected Myocardial Ischemia: A Report From the NHLBI‐Sponsored WISE Study

Background Women are more likely than men to develop resistant hypertension, which is associated with excess risk of major adverse outcomes; however, the impact of resistant hypertension in women with ischemia has not been explicitly studied. In this Women's Ischemia Syndrome Evaluation (WISE) analysis, we assessed long‐term adverse outcomes associated with apparent treatment‐resistant hypertension (aTRH) among women with suspected myocardial ischemia referred for coronary angiography. Methods and Results Women (n=927) were grouped according to baseline blood pressure (BP): normotensive (no hypertension history, BP <140/90 mm Hg, no antihypertensive drugs); controlled (BP <140/90 mm Hg and a hypertension diagnosis or on 1 to 3 drugs); uncontrolled (BP ≥140/90 mm Hg on ≤2 drugs); or aTRH (BP ≥140/90 mm Hg on 3 drugs or anyone on ≥4 drugs). Adverse outcomes (first occurrence of death [any cause], nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure or angina) were collected over 10 years of follow‐up. Apparent treatment‐resistant hypertension prevalence was 10.4% among those with hypertension. Women with aTRH had a greater incidence of adverse outcomes, compared with normotensive women (adjusted hazard ratio [HR], 3.25; 95% confidence interval [CI], 1.94 to 5.43), and women with controlled (HR, 1.77; 95% CI, 1.26 to 2.49) and uncontrolled (HR, 1.62; 95% CI, 1.15 to 2.27) hypertension; outcome differences were evident early in follow‐up. Risk of all‐cause death was greater in the aTRH group, compared to the normotensive women and women with controlled and uncontrolled hypertension. Conclusions In this cohort of women with evidence of ischemia, aTRH was associated with a profoundly increased long‐term risk of major adverse events, including death, that emerged early during follow‐up.
Electron and positron collisions with polar molecules: studies with the benchmark water molecule

It is difficult to measure low-energy cross sections for collisions of charged particles with strongly dipolar systems since the magnitude of such cross sections is completely dominated by collisions in the forward direction. Theoretically, it is possible to account for the strong forward scattering using the Born approximation but the procedure for combining Born ‘top-up’ with the more sophisticated treatments required to treat the scattering in other directions is not unique. This comment describes recent progress in describing both electron and positron collisions with polar molecules taking the important water molecule as a benchmark. Previous calculations on electron water at collision energies below 7 eV are compared with new experiments. Positron water studies up to 10 eV are re-analysed based on given experimental acceptance profiles, which depend on the details of the apparatus and method used in the measurements. It is suggested that theory is capable of giving reliable results for elastic and rotationally inelastic electron/positron collisions with strongly dipolar species.
On estimation and identifiability issues of sex-linked inheritance with a case study of pigmentation in Swiss barn owl (Tyto alba)

Genetic evaluation using animal models or pedigree-based models generally assume only autosomal inheritance. Bayesian animal models provide a flexible framework for genetic evaluation, and we show how the model readily can accommodate situations where the trait of interest is influenced by both autosomal and sex-linked inheritance. This allows for simultaneous calculation of autosomal and sex-chromosomal additive genetic effects. Inferences were performed using integrated nested Laplace approximations (INLA), a nonsampling-based Bayesian inference methodology. We provide a detailed description of how to calculate the inverse of the X- or Z-chromosomal additive genetic relationship matrix, needed for inference. The case study of eumelanic spot diameter in a Swiss barn owl (Tyto alba) population shows that this trait is substantially influenced by variation in genes on the Z-chromosome ( and ). Further, a simulation study for this study system shows that the animal model accounting for both autosomal and sex-chromosome-linked inheritance is identifiable, that is, the two effects can be distinguished, and provides accurate inference on the variance components.
Atomic persistence for SCM with a non-intrusive backend controller

Non-volatile byte-addressable memory has the potential to revolutionize system architecture by providing instruction-grained direct access to vast amounts of persistent data. We describe a non-intrusive memory controller that uses backend operations for achieving lightweight failure atomicity. By moving synchronous persistent memory operations to the background, the performance overheads are minimized. Our solution avoids costly software intervention by decoupling isolation and concurrency-driven atomicity from failure atomicity and durability, and does not require changes to the front-end cache hierarchy. Two implementation alternatives - one using a hardware structure, and the other extending the memory controller with a firmware managed volatile space - are described. Our results show the performance is significantly better than traditional approaches.