Miracle-dz/UniFAR-FTUs huggingface dataset:
Cardiovascular pharmacogenetics: a promise for genomically‐guided therapy and personalized medicine

Cardiovascular disease (CVD) is the leading cause of death worldwide. The basic causes of CVD are not fully understood yet. Substantial evidence suggests that genetic predisposition plays a vital role in the physiopathology of this complex disease. Hence, identification of genetic contributors to CVD will likely add diagnostic accuracy and better prediction of an individual's risk. With high‐throughput genetics and genomics technology and newer genome‐wide study approaches, a number of genetic variations across the human genome were uncovered. Evidence suggests that genetic defects could influence CVD development and inter‐individual responses to widely used cardiovascular drugs like clopidogrel, aspirin, warfarin, and statins, and therefore, they may be integrated into clinical practice. If clinically validated, better understanding of these genetic variations may provide new opportunities for personalized diagnostic, pharmacogenetic‐based drug selection and best treatment in personalized medicine. However, numerous gaps remain unsolved due to the lack of underlying pathological mechanisms for how genetic predisposition could contribute to CVD. This review provides an overview of the extraordinary scientific progress in our understanding of genetic and genomic basis of CVD as well as the development of relevant genetic biomarkers for this disease. Some of the actual limitations to the promise of these markers and their translation for the benefit of patients will be discussed.
Neurodevelopmental abnormalities in schizophrenia: Insights from neuropathology

Growing epidemiological, genetic, and clinical neurobiological evidence indicates that abnormalities in brain development play determining roles in the pathobiology of schizophrenia. Neuropathological research has made significant progress in delineating cellular and molecular abnormalities in schizophrenia that have relevance to neurodevelopment. This paper reviews the neurodevelopmental processes of neurogenesis, neuronal migration, differentiation, synaptogenesis, neuron and synaptic pruning, and myelination and the reported neuropathological findings in schizophrenia that may be a consequence of disturbances in these processes. While many neuropathological findings in schizophrenia are controversial or await confirmation, reported abnormalities in neuron density, number and morphology, cytoarchitecture, dendritic arbors and spines, synapse-related proteins, and the well-established absence of gliosis or any other evidence of neurodegeneration or neural injury all provide support for the neurodevelopmental model of schizophrenia.
How far an evolutionary approach can go for protocol state analysis and discovery

Securing todays computer networks requires numerous technologies to constantly be developed, refined and challenged. One area of research aiding in this process is that of protocol analysis, the study of the methods with which networks communicate. Our specific area of interest, the interaction with different protocol implementations, is a crucial component of this domain. Our work aims to identify and highlight a protocols states and state transitions, while minimizing the required a priori knowledge known about the protocol and its different versions (implementations). To this end, our approach uses a Genetic Programming (GP) based technique in order to analyze a client or a server of a given protocol via interacting with it with minimum a priori information. We evaluate our system against another well-known system from the literature on two different protocols, namely Dynamic Host Configuration Protocol (DHCP) and File Transfer Protocol (FTP). We measure the performances of these two systems in terms of the similarities and differences seen in the state diagrams produced for the protocols under testing. Results show that, by using our approach, it is possible to identify the different versions of a given protocol.
New topics in bradykinin research

To cite this article: Maurer M, Bader M, Bas M, Bossi F, Cicardi M, Cugno M, Howarth P, Kaplan A, Kojda G, Leeb‐Lundberg F, Lötvall J, Magerl M. New topics in bradykinin research. Allergy 2011; 66: 1397–1406.
Revenue-Maximising or Revenue-Sacrificing Government? Property Tax in Pakistan

ABSTRACT The idea that states seek to maximise their revenue collection has occupied a significant place in contemporary political economy analysis of taxation, and has helped us understand the history of state formation. It is, however, very much at variance with the daily experience of tax policy and practice. Governments are frequently revenue-sacrificers: they fail to use the functioning, legitimate tax collection systems they have available to actually collect much revenue. This paper details the case of property tax collection in Pakistan, and concludes that governments tend to maximise rule before they maximise revenue.
Prevalence of Vertebral Compression Fractures and Associated Factors in Children and Adolescents with Severe Juvenile Idiopathic Arthritis

Objective. Vertebral fractures occur in patients with juvenile idiopathic arthritis (JIA), but data on their frequency and causes are scarce. Our cross-sectional study evaluated prevalence of compression fractures and associated factors in a high-risk pediatric population with severe JIA. Methods. Children and adolescents with a history of treatment-resistant polyarticular-course JIA for ≥ 5 years or systemic arthritis for ≥ 3 years were recruited. Clinical examination, dietary recall, laboratory measurements, bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry, and spinal radiography were performed. Results. Our study included 50 patients (41 girls), of whom 6 (12%) had systemic arthritis, with a median age of 14.8 years (range 7.0–18.7 yrs) and median disease duration of 10.2 years (range 3.9–16.8 years). Ninety-four percent had used systemic glucocorticoids (GC); the median total duration of GC treatment was 7.1 years (range 0–15.5 yrs). The median weight-adjusted cumulative GC dose for the preceding 3 years was 72 mg/kg (range 0–911 mg/kg). The median bone age-corrected lumbar spine and whole-body areal BMD Z-scores were −0.8 and −1.0, respectively. Twenty-two percent had vertebral fractures, mostly thoracic. Compression fractures were associated with high disease activity, high body mass index (BMI), and high recent cumulative GC dose, but not with disease duration or BMD. Thirty percent had sustained at least 1 peripheral low energy fracture. Twenty-six percent were deemed to have significantly compromised bone health. Conclusion. Severe JIA is associated with a significant risk of vertebral compression fractures. Associated factors include high disease activity, high BMI, and high recent GC exposure. Further studies are needed to establish optimal prevention and treatment guidelines.
Quality of Science Teaching in Public Secondary Schools in Rivers State: The Journey So Far

The study seeks to explore certain variables necessary for the provision of quality science learning in Rivers State. Two sets of questionnaires tagged; “Questionnaire on Quality Science Teaching in Secondary Schools (QQSTSS) and Science Laboratory Apparatus Observational Checklist (SLAOC) were utilized as the research instruments. Ex-post facto and Survey research design were adopted for the study. The sample size consisted of 68 science teachers randomly selected from three (3) Local Government Areas in Rivers Original Research Article British Journal of Education, Society & Behavioural Science, 4(12): 1737-1749, 2014 1738 State. Using the Pearson Product Moment Correlation Coefficient method for calculating reliability, a reliability index of 0.82. Data were analysed using frequency count, percentage and modified four-point Likert scale statistical analysis. The findings of the study amongst others revealed that teacher-students ratio in some Local Government Areas is not in line with the stipulated National Policy on Education of 1:40; there are insufficient science laboratory apparatus in the secondary schools and the allocation of period for science subject teaching is insufficient. Recommendations were posited based on the findings in Rivers State, Nigeria.
Keratocyte Phenotype Mediates Proteoglycan Structure

In pathological corneas, accumulation of fibrotic extracellular matrix is characterized by proteoglycans with altered glycosaminoglycans that contribute to the reduced transparency of scarred tissue. During wound healing, keratocytes in the corneal stroma transdifferentiate into fibroblasts and myofibroblasts. In this study, molecular markers were developed to identify keratocyte, fibroblast, and myofibroblast phenotypes in primary cultures of corneal stromal cells and the structure of glycosaminoglycans secreted by these cells was characterized. Quiescent primary keratocytes expressed abundant protein and mRNA for keratocan and aldehyde dehydrogenase class 3 and secreted proteoglycans containing macromolecular keratan sulfate. Expression of these marker compounds was reduced in fibroblasts and also in transforming growth factor-β-induced myofibroblasts, which expressed high levels of α-smooth muscle actin, biglycan, and the extra domain A (EDA or EIIIA) form of cellular fibronectin. Collagen types I and III mRNAs were elevated in both fibroblasts and in myofibroblasts. Expression of these molecular markers clearly distinguishes the phenotypic states of stromal cells in vitro. Glycosaminoglycans secreted by fibroblasts and myofibroblasts were qualitatively similar to and differed from those of keratocytes. Chondroitin/dermatan sulfate abundance, chain length, and sulfation were increased as keratocytes became fibroblasts and myofibroblasts. Fluorophore-assisted carbohydrate electrophoresis analysis demonstrated increased N-acetylgalactosamine sulfation at both 4- and 6-carbons. Hyaluronan, absent in keratocytes, was secreted by fibroblasts and myofibroblasts. Keratan sulfate biosynthesis, chain length, and sulfation were significantly reduced in both fibroblasts and myofibroblasts. The qualitatively similar expression of glycosaminoglycans shared by fibroblasts and myofibroblasts suggests a role for fibroblasts in deposition of non-transparent fibrotic tissue in pathological corneas.
Consequences of a De fi cit in Vitamin B 6 Biosynthesis de Novo for Hormone Homeostasis and Root Development in Arabidopsis 1 [ OPEN ]

Vitamin B6 (pyridoxal 59-phosphate) is an essential cofactor of many metabolic enzymes. Plants biosynthesize the vitamin de novo employing two enzymes, pyridoxine synthase1 (PDX1) and PDX2. In Arabidopsis (Arabidopsis thaliana), there are two catalytically active paralogs of PDX1 (PDX1.1 and PDX1.3) producing the vitamin at comparable rates. Since single mutants are viable but the pdx1.1 pdx1.3 double mutant is lethal, the corresponding enzymes seem redundant. However, the single mutants exhibit substantial phenotypic differences, particularly at the level of root development, with pdx1.3 being more impaired than pdx1.1. Here, we investigate the differential regulation of PDX1.1 and PDX1.3 by identifying factors involved in their disparate phenotypes. Swapped-promoter experiments clarify the presence of distinct regulatory elements in the upstream regions of both genes. Exogenous sucrose (Suc) triggers impaired ethylene production in both mutants but is more severe in pdx1.3 than in pdx1.1. Interestingly, Suc specifically represses PDX1.1 expression, accounting for the stronger vitamin B6 deficit in pdx1.3 compared with pdx1.1. Surprisingly, Suc enhances auxin levels in pdx1.1, whereas the levels are diminished in pdx1.3. In the case of pdx1.3, the previously reported reduced meristem activity combined with the impaired ethylene and auxin levels manifest the specific root developmental defects. Moreover, it is the deficit in ethylene production and/or signaling that triggers this outcome. On the other hand, we hypothesize that it is the increased auxin content of pdx1.1 that is responsible for the root developmental defects observed therein. We conclude that PDX1.1 and PDX1.3 play partially nonredundant roles and are differentially regulated as manifested in disparate root growth impairment morphologies.
Cointegration and Relative Value Arbitrage

This paper examines a new method of identifying close economic substitutes in the context of relative value arbitrage. We show that close economic substitutes correspond to a special case of cointegration whereby individual prices have approximately the same exposure to a common stochastic factor, or the cointegrating relation is approximately one-to-one. Empirical analysis of cointegration-based pairs trading shows that a metric of closeness constructed from the cointegrating relation strongly predicts the probability of convergence and profitability of pairs trades. Over period 1962-2013, a strategy that trades cointegrated pairs of near-parity generates average returns of 58 bps per month after trading costs, experiences 71% probability of convergence and outperform pairs that are selected using the conventional method of minimizing price distance. When extending to triplets trading, the predictability of the metric of closeness remains, however trading of cointegrated baskets of three stocks is less profitable due to smaller mispricings.
Somatosensory thalamus of a prosimian primate (Galago senegalensis). I. Configuration of nuclei and termination of spinothalamic fibers

The configuration of somatosensory relay nuclei and termination of spinothalamic fibers were studied in the dorsal thalamus of a prosimian primate (Galago senegalensis) using Nissl, Klüver and Barrera ('53), Weil ('45), and Fink and Heimer ('67) methods. The ventral posterolateral nucleus (VPL) is divided into medial and lateral parts (VPLm and VPLl, respectively) by a sheet‐like lamina of fibers. Spinothalamic input to Galago VPL is somatopically arranged; input from the forelimb terminates in VPLm and that from hindlimb in VPLl. In addition, preterminal debris in caudal VPL is dense and organized into “parcellated bursts” (terminology of Mehler, '69). Consequently, the nature of the spinothalamic debris in VPL of Galago is similar to that reported for higher primates (Mehler et al., '60). Located dorsomedial to the rostral extension of VPL is a zone of large, deeply staining cells designated as the ventral intermediate nucleus (Vim). Following hemisection at either cervical or lumbar spinal cord levels, preterminal debris, independent of that coursing into VPL, enters the Vim. This substantiates the presence of an intermediate nucleus (i.e., Vim) between VPL and the more rostral ventral lateral nucleus.
Psychophysical Localization of the Human Visual Streak

In a topographical study of the human retina, Curcio and Allen documented the presence of the human visual streak, which they described as a prominent nasotemporal asymmetry in ganglion cell density. This asymmetry could also be expected to be measurable in any visual function limited by ganglion cell density. By using an interferometer we sought to test the hypothesis of Thibos et al. that peripheral resolution acuity is limited by the spacing of ganglion cells and should therefore reflect the anatomical asymmetry of the visual streak, once the attenuating effects of the eye's optics have been removed. This proved to be the case and differences predicted by a ganglion cell density of 2:1 were easily measurable. This study has potential clinical implications for the detection of disease or abnormalities of the visual system that cause death or dysfunction of retinal ganglion cells.
Development and characterization of a Versatile Engineered Nanomaterial Generation System (VENGES) suitable for toxicological studies

A novel system for generation of engineered nanomaterials (ENMs) suitable for in situ toxicological characterization within biological matrices was developed. This Versatile Engineered Nanomaterial Generation System (VENGES) is based on industry-relevant, flame spray pyrolysis aerosol reactors that can scaleably produce ENMs with controlled primary and aggregate particle size, crystallinity, and morphology. ENMs are produced continuously in the gas phase, allowing their continuous transfer to inhalation chambers, without altering their state of agglomeration. Freshly generated ENMs are also collected on Teflon filters for subsequent physicochemical and morphological characterization and for in vitro toxicological studies. The ability of the VENGES system to generate families of ENMs of pure and selected mixtures of iron oxide, silica, and nanosilver with controlled physicochemical properties was demonstrated using a range of state-of-the-art-techniques. Specific surface area was measured by nitrogen adsorption using the Brunauer–Emmett–Teller method, and crystallinity was characterized by X-ray diffraction. Particle morphology and size were evaluated by scanning and transmission electron microscopy. The suitability of the VENGES system for toxicological studies was also shown in both in vivo and in vitro studies involving Sprague–Dawley rats and human alveolar-like monocyte derived macrophages, respectively. We demonstrated linkage between physicochemical ENM properties and potential toxicity.
Inferring genetic interactions from comparative fitness data

Darwinian fitness is a central concept in evolutionary biology. In practice, however, it is hardly possible to measure fitness for all genotypes in a natural population. Here, we present quantitative tools to make inferences about epistatic gene interactions when the fitness landscape is only incompletely determined due to imprecise measurements or missing observations. We demonstrate that genetic interactions can often be inferred from fitness rank orders, where all genotypes are ordered according to fitness, and even from partial fitness orders. We provide a complete characterization of rank orders that imply higher order epistasis. Our theory applies to all common types of gene interactions and facilitates comprehensive investigations of diverse genetic interactions. We analyzed various genetic systems comprising HIV-1, the malaria-causing parasite Plasmodium vivax, the fungus Aspergillus niger, and the TEM-family of β-lactamase associated with antibiotic resistance. For all systems, our approach revealed higher order interactions among mutations.
In vivo effect of pinosylvin and pterostilbene in the animal model of adjuvant arthritis.

OBJECTIVE The aim of this study was to evaluate the effects of pinosylvin (PIN) and pterostilbene (PTE), natural substances from the stilbenoid group, on the development of adjuvant arthritis in rats. METHODS Adjuvant arthritis (AA) was induced by a single intradermal injection of Mycobacterium butyricum in incomplete Freund's adjuvant in male Lewis rats. Our experiments included healthy intact animals as reference controls, arthritic animals without any drug administration, and arthritic animals with administration of PIN and PTE in the oral daily dose of 30 mg/kg b.w. The treatment involved administration of the substances tested from day 0, i.e. the day of immunization, to the experimental day 28. The following parameters were monitored: change of the hind paw volume (HPV) on day 14, 21 and 28, luminol-enhanced chemiluminescence (CL) of the joint and myeloperoxidase (MPO) activity in hind paw joint homogenates (day 28). RESULTS Arthritic animals treated with PIN showed a decrease in HPV, significantly on days 14 and 28. PIN decreased CL of the joint as well as MPO activity of the joint homogenate, in comparison with untreated animals. PTE had no effect on HPV and MPO activity in hind paw joint homogenates and exerted only a partial effect on luminol-enhanced CL. CONCLUSIONS On the basis of our results we conclude that the effect of PTE on CL was only partial. PIN, on the other hand, had a beneficial anti-inflammatory and antioxidant effect on oxidative stress induced biochemical changes occurring in AA, as determined by all three functional parameters.
Potential of Spartina maritima in Restored Salt Marshes for Phytoremediation of Metals in a Highly Polluted Estuary

Sedimentary abiotic environment, and concentration and stock of nine metals were analyzed in vegetation and sediments to evaluate the phytoremediation capacity of restored Spartina maritima prairies in the highly polluted Odiel Marshes (SW Iberian Peninsula). Samples were collected in two 10 –m long rows parallel to the tidal line at two sediments depths (0–2 cm and 2–20 cm). Metal concentrations were measured by inductively coupled plasma spectroscopy. Iron, aluminum, copper, and zinc were the most concentrated metals. Every metal, except nickel, showed higher concentration in the root zone than at the sediment surface, with values as high as ca. 70 g Fe kg–1. The highest metal concentrations in S. maritima tissues were recorded in its roots (maximum for iron in Spartina roots: 4160.2 ± 945.3 mg kg–1). Concentrations of aluminum and iron in leaves and roots were higher than in superficial sediments. Rhizosediments showed higher concentrations of every metal than plant tissues, except for nickel. Sediment metal stock in the first 20 cm deep was ca. 170.89 t ha–1. Restored S. maritima prairies, with relative cover of 62 ± 6%, accumulated ca. 22 kg metals ha–1. Our results show S. maritima to be an useful biotool for phytoremediation projects in European salt marshes.
Inter-hemispheric coupling changes associate with motor improvements after robotic stroke rehabilitation.

PURPOSE In the chronic phase of stroke brain plasticity plays a crucial role for further motor control improvements. This study aims to assess the brain plastic reorganizations and their association with clinical progresses induced by a robot-aided rehabilitation program in chronic stroke patients. METHODS 7 stroke patients with an upper limb motor impairment in chronic phase underwent a multi-modal evaluation before starting and at the end of a 12-week upper-limb neurorehabilitation program. Fugl-Meyer Assessment (FMA) Scale scores and performance indices of hand movement performance (isometric pinch monitored through a visual feedback) were collected. Cerebral reorganizations were characterized by 32-channel electroencephalography (EEG) focusing on ipsilesional and contralesional resting state properties investigating both bipolar derivations overlying the middle cerebral artery territory and the primary somatosensory sources (S1) obtained through the Functional Source Separation (FSS) method. Power Spectral Density (PSD) and interhemispheric coherence (IHCoh) at rest were measured and correlated with clinical and hand control robot-induced improvements. RESULTS After the robotic rehabilitation we found an improvement of FMAS scores and hand motor control performance and changes of brain connectivity in high frequency rhythms (24-90 Hz). In particular, the improvement of motor performance correlated with the modulation of the interhemispheric S1 coherence in the high beta band (24-33 Hz). CONCLUSIONS Recently it has been shown that an upper limb robot-based rehabilitation improves motor performance in stroke patients. We confirm this potential and demonstrate that a robot-aided rehabilitation program induces brain reorganizations. Specifically, interhemispheric connectivity between primary somatosensory areas got closer to a 'physiological level' in parallel with the acquisition of more accurate hand control.