Miracle-dz/UniFAR-FTUs huggingface dataset:
Temporal Genetic Modifications after Controlled Cortical Impact—Understanding Traumatic Brain Injury through a Systematic Network Approach

Traumatic brain injury (TBI) is a primary injury caused by external physical force and also a secondary injury caused by biological processes such as metabolic, cellular, and other molecular events that eventually lead to brain cell death, tissue and nerve damage, and atrophy. It is a common disease process (as opposed to an event) that causes disabilities and high death rates. In order to treat all the repercussions of this injury, treatment becomes increasingly complex and difficult throughout the evolution of a TBI. Using high-throughput microarray data, we developed a systems biology approach to explore potential molecular mechanisms at four time points post-TBI (4, 8, 24, and 72 h), using a controlled cortical impact (CCI) model. We identified 27, 50, 48, and 59 significant proteins as network biomarkers at these four time points, respectively. We present their network structures to illustrate the protein–protein interactions (PPIs). We also identified UBC (Ubiquitin C), SUMO1, CDKN1A (cyclindependent kinase inhibitor 1A), and MYC as the core network biomarkers at the four time points, respectively. Using the functional analytical tool MetaCore™, we explored regulatory mechanisms and biological processes and conducted a statistical analysis of the four networks. The analytical results support some recent findings regarding TBI and provide additional guidance and directions for future research.
Assessing knowledge assets: a review of the models used to measure intellectual capital

This paper reviews the literature pertaining to the assessment of knowledge assets. Since knowledge assets are at the crux of sustainable competitive advantage, the burgeoning field of intellectual capital is an exciting area for both researchers and practitioners. Unfortunately, the measurement of such intangible assets is difficult. A variety of models have surfaced in an attempt to measure IC and this paper aims to highlight their strengths, weaknesses and operationalizations.
Abnormal Balance in the Angiopoietin-Tie2 System in Human Brain Arteriovenous Malformations

Brain arteriovenous malformations (BAVMs) are congenital vascular lesions that often present as cerebral hemorrhage in young adults. The variable nature of the clinical course, especially with respect to spontaneous hemorrhage, recurrence, growth, and regression, suggests that BAVMs are lesions with active angiogenesis and vascular remodeling. We examined mRNA and protein expression of angiopoietin 1 (Ang1) and Ang2 by semiquantitative reverse transcriptase–polymerase chain reaction, in situ hybridization, and Western blot in BAVMs and control brains obtained from temporal lobectomy for medically intractable seizures. Although Ang1 mRNA levels were similar in BAVMs and controls, Ang1 protein levels were 30% lower in BAVMs than in controls. Ang2 mRNA levels were 40% higher and Ang2 protein levels were 8-fold higher in BAVMs than in controls. In situ hybridization showed that the Ang2 mRNA was localized to the perivascular area in BAVMs. This abnormal balance in the Ang-Tie2 system may, in part, explain the aberrant vascular phenotype in BAVMs.
Reconstruction of relief objects from line drawings

This paper addresses the problem of automatic reconstruction of a 3D relief from a line drawing on top of a given base object. Reconstruction is challenging due to four reasons–the sparsity of the strokes, their ambiguity, their large number, and their inter-relations. Our approach is able to reconstruct a model from a complex drawing that consists of many inter-related strokes. Rather than viewing the inter-dependencies as a problem, we show how they can be exploited to automatically generate a good initial interpretation of the line drawing. Then, given a base and an interpretation, we propose an algorithm for reconstructing a consistent surface. The strength of our approach is demonstrated in the reconstruction of archaeological artifacts from drawings. These drawings are highly challenging, since artists created very complex and detailed descriptions of artifacts regardless of any considerations concerning their future use for shape reconstruction.
How “Paternalistic” Is Spatial Perception? Why Wearing a Heavy Backpack Doesn’t—and Couldn’t—Make Hills Look Steeper

A chief goal of perception is to help us navigate our environment. According to a rich and ambitious theory of spatial perception, the visual system achieves this goal not by aiming to accurately depict the external world, but instead by actively distorting the environment’s perceived spatial layout to bias action selection toward favorable outcomes. Scores of experimental results have supported this view—including, famously, a report that wearing a heavy backpack makes hills look steeper. This perspective portrays the visual system as unapologetically paternalistic: Backpacks make hills harder to climb, so vision steepens them to discourage ascent. The “paternalistic” theory of spatial perception has, understandably, attracted controversy; if true, it would radically revise our understanding of how and why we see. Here, this view is subjected to a kind and degree of scrutiny it has yet to face. After characterizing and motivating the case for paternalistic vision, I expose several unexplored defects in its theoretical framework, arguing that extant accounts of how and why spatial perception is ability-sensitive are deeply problematic and that perceptual phenomenology belies the view’s claims. The paternalistic account of spatial perception not only isn’t true—it couldn’t be true, even if its empirical findings were accepted at face value.
Tempo Tracking with a Single Oscillator

I describe a simple on-line tempo tracker, based on phase and period locking a single oscillator to performance event timings. The tracker parameters are optimized on a corpus of solo piano performances by twelve musicians. The tracker is then tested on a second corpus of performances, played by the same twelve musicians. The performance of this tracker is compared to previously published results for a tempo tracker based on combining a tempogram and Kalman filter.
Cu2+ toxicity inhibition of mitochondrial dehydrogenases in vitro and in vivo

Wilson's disease results from mutations in the P‐type Cu2+‐ATPase causing Cu2+ toxicity. We previously demonstrated that exposure of mixed neuronal/glial cultures to 20μM Cu2+ induced ATP loss and death that were attenuated by mitochondrial substrates, activators, and cofactors. Here, we show differential cellular sensitivity to Cu2+ that was equalized to 5 μM in the presence of the copper exchanger/ionophore, disulfiram. Because Cu2+ facilitates formation of oxygen radicals (ROS) which inhibit pyruvate dehydrogenase (PDH) and alpha‐ketoglutarate dehydrogenase (KGDH), we hypothesized that their inhibition contributed to Cu2+‐induced death. Toxic CU2+ exposure was accompanied by early inhibition of neuronal and hepatocellular PDH and KGDH activities, followed by reduced mitochondrial transmembrane potential, ΔΨM. Thiamine (1–6mM), and dihydrolipoic acid (LA, 50μM), required cofactors for PDH and KGDH, attenuated this enzymatic inhibition and subsequent death in all cell types. Furthermore, liver PDH and KGDH activities were reduced in the Atp7b mouse model of Wilson's disease prior to liver damage, and were partially restored by oral thiamine supplementation. These data support our hypothesis that Cu2+‐induced ROS may inhibit PDH and KGDH resulting in neuronal and hepatocellular death. Therefore, thiamine or lipoic acid may constitute potential therapeutic agents for Wilson's disease.
mTOR activates the VPS34–UVRAG complex to regulate autolysosomal tubulation and cell survival

Lysosomes are essential organelles that function to degrade and recycle unwanted, damaged and toxic biological components. Lysosomes also act as signalling platforms in activating the nutrient‐sensing kinase mTOR. mTOR regulates cellular growth, but it also helps to maintain lysosome identity by initiating lysosomal tubulation through a process termed autophagosome‐lysosome reformation (ALR). Here we identify a lysosomal pool of phosphatidylinositol 3‐phosphate that, when depleted by specific inhibition of the class III phosphoinositide 3‐kinase VPS34, results in prolonged lysosomal tubulation. This tubulation requires mTOR activity, and we identified two direct mTOR phosphorylation sites on UVRAG (S550 and S571) that activate VPS34. Loss of these phosphorylation sites reduced VPS34 lipid kinase activity and resulted in an increase in number and length of lysosomal tubules. In cells in which phosphorylation at these UVRAG sites is disrupted, the result of impaired lysosomal tubulation alongside ALR activation is massive cell death. Our data imply that ALR is critical for cell survival under nutrient stress and that VPS34 is an essential regulatory element in this process.
Reassessing the biogenicity of Earth’s oldest trace fossil with implications for biosignatures in the search for early life

Significance It has been argued that Archean subseafloor pillow lava sequences provide an environment in which to seek evidence for the earliest traces of life. Candidate titanite biosignatures of microbial activity have been reported in ∼3.45-Ga metavolcanic glass from the Barberton greenstone belt of South Africa. In this paper we present new in situ U–Pb age data, metamorphic constraints, and morphological observations on these titanite microtextures. Our data challenges a biological origin for these oldest purported trace fossils, with implications for the ecological niches where life may have first emerged. We therefore suggest alternative biosignatures and approaches should be considered in the search for subsurface life on early Earth and in extraterrestrial mafic–ultramafic rocks, for example, in martian basalts. Microtextures in metavolcanic pillow lavas from the Barberton greenstone belt of South Africa have been argued to represent Earth’s oldest trace fossil, preserving evidence for microbial life in the Paleoarchean subseafloor. In this study we present new in situ U–Pb age, metamorphic, and morphological data on these titanite microtextures from fresh drill cores intercepting the type locality. A filamentous microtexture representing a candidate biosignature yields a U–Pb titanite age of 2.819 ± 0.2 Ga. In the same drill core hornfelsic-textured titanite discovered adjacent to a local mafic sill records an indistinguishable U–Pb age of 2.913 ± 0.31 Ga, overlapping with the estimated age of intrusion. Quantitative microscale compositional mapping, combined with chlorite thermodynamic modeling, reveals that the titanite filaments are best developed in relatively low-temperature microdomains of the chlorite matrix. We find that the microtextures exhibit a morphological continuum that bears no similarity to candidate biotextures found in the modern oceanic crust. These new findings indicate that the titanite formed during late Archean ca. 2.9 Ga thermal contact metamorphism and not in an early ca. 3.45 Ga subseafloor environment. We therefore question the syngenicity and biogenicity of these purported trace fossils. It is argued herein that the titanite microtextures are more likely abiotic porphyroblasts of thermal contact metamorphic origin that record late-stage retrograde cooling in the pillow lava country rock. A full characterization of low-temperature metamorphic events and alternative biosignatures in greenstone belt pillow lavas is thus required before candidate traces of life can be confirmed in Archean subseafloor environments.
Sparse differential resultant

In this paper, the concept of sparse differential resultant for a differentially essential system of differential polynomials is introduced and its properties are proved. In particular, a degree bound for the sparse differential resultant is given. Based on the degree bound, an algorithm to compute the sparse differential resultant is proposed, which is single exponential in terms of the order, the number of variables, and the size of the differentially essential system.
Extended Interferon-Alpha Therapy Accelerates Telomere Length Loss in Human Peripheral Blood T Lymphocytes

Background Type I interferons have pleiotropic effects on host cells, including inhibiting telomerase in lymphocytes and antiviral activity. We tested the hypothesis that long-term interferon treatment would result in significant reduction in average telomere length in peripheral blood T lymphocytes. Methods/Principal Findings Using a flow cytometry-based telomere length assay on peripheral blood mononuclear cell samples from the Hepatitis-C Antiviral Long-term Treatment against Cirrhosis (HALT-C) study, we measured T cell telomere lengths at screening and at months 21 and 45 in 29 Hepatitis-C virus infected subjects. These subjects had failed to achieve a sustained virologic response following 24 weeks of pegylated-interferon-alpha plus ribavirin treatment and were subsequently randomized to either a no additional therapy group or a maintenance dose pegylated-IFNα group for an additional 3.5 years. Significant telomere loss in naïve T cells occurred in the first 21 months in the interferon-alpha group. Telomere losses were similar in both groups during the final two years. Expansion of CD8+CD45RA+CD57+ memory T cells and an inverse correlation of alanine aminotransferase levels with naïve CD8+ T cell telomere loss were observed in the control group but not in the interferon-alpha group. Telomere length at screening inversely correlated with Hepatitis-C viral load and body mass index. Conclusions/Significance Sustained interferon-alpha treatment increased telomere loss in naïve T cells, and inhibited the accumulation of T cell memory expansions. The durability of this effect and consequences for immune senescence need to be defined.
Sex steroid metabolism in human peripheral blood mononuclear cells changes with aging.

CONTEXT Dehydroepiandrosterone (DHEA) mainly exerts indirect action via downstream conversion toward sex steroids within peripheral target cells including immune cells. In vitro DHEA has been shown to enhance IL-2 release from T lymphocytes, whereas it inhibits IL-6 secretion. Conversely, aging is associated with a decline in both DHEA and IL-2, whereas IL-6 increases. OBJECTIVE The objective of the study was to investigate age-related differences in expression and functional activity of steroidogenic enzymes involved in downstream conversion of DHEA in peripheral blood mononuclear cells (PBMCs). DESIGN This study was cross-sectional. PARTICIPANTS/SETTING Healthy young men (n = 8; age range, 23-29 yr) and healthy middle-aged men (n = 8; age range, 52-66 yr) were studied in an academic setting. MEASURES mRNA expression of steroidogenic enzymes in PBMCs was measured by qualitative and quantitative RT-PCR analysis and enzyme activity assays after incubation of PBMCs with radiolabeled DHEA, 4-androstene-3,17-dione (androstenedione), and testosterone. RESULTS RT-PCR analysis showed expression of all enzymes required for DHEA conversion toward active androgens and to the immune-stimulatory metabolite androstenediol. Steroid conversion patterns indicated a particularly increased activity of 17beta-hydroxysteroid dehydrogenase type 5 (17beta-HSD5) in the older men, demonstrated by significantly higher conversion rates of DHEA to androstenediol and of androstenedione to testosterone (all P < 0.05). By contrast, conversion of DHEA to androstenedione via 3beta-HSD occurred at a similar rate. Quantitative RT-PCR analysis revealed increased expression of 17beta-HSD 5 mRNA in PBMCs from the older men. CONCLUSIONS Our results provide evidence for significant changes in sex steroid metabolism by human PBMCs with aging, which may represent an endocrine link to immune senescence.
EphB2 as a Therapeutic Antibody Drug Target for the Treatment of Colorectal Cancer

Analysis of human colorectal cancer specimens revealed overexpression of the EphB2 receptor tyrosine kinase. Monoclonal antibodies (MAbs) to extracellular sequence of EphB2 were raised and tested for activity against colorectal cancer cells. One of the MAbs, 2H9, effectively blocked the interaction of ephB2 with ephrin ligands and inhibited the resulting autophosphorylation of the receptor. However, this antibody did not affect the proliferation of cancer cells expressing ephB2. Immunocytochemical analysis revealed rapid internalization of the MAb 2H9 on binding ephB2, suggesting that target-dependent cell killing could be achieved with an antibody-drug conjugate. When MAb 2H9 was conjugated to monomethylauristatin E through a cathepsin B-cleavable linker, it specifically killed ephB2-expressing cancer cells in vitro and in vivo. Our results suggest that ephB2 is an attractive target for immunoconjugate cancer therapy.
Hydrophobic substances induce water stress in microbial cells

Ubiquitous noxious hydrophobic substances, such as hydrocarbons, pesticides and diverse industrial chemicals, stress biological systems and thereby affect their ability to mediate biosphere functions like element and energy cycling vital to biosphere health. Such chemically diverse compounds may have distinct toxic activities for cellular systems; they may also share a common mechanism of stress induction mediated by their hydrophobicity. We hypothesized that the stressful effects of, and cellular adaptations to, hydrophobic stressors operate at the level of water : macromolecule interactions. Here, we present evidence that: (i) hydrocarbons reduce structural interactions within and between cellular macromolecules, (ii) organic compatible solutes – metabolites that protect against osmotic and chaotrope‐induced stresses – ameliorate this effect, (iii) toxic hydrophobic substances induce a potent form of water stress in macromolecular and cellular systems, and (iv) the stress mechanism of, and cellular responses to, hydrophobic substances are remarkably similar to those associated with chaotrope‐induced water stress. These findings suggest that it may be possible to devise new interventions for microbial processes in both natural environments and industrial reactors to expand microbial tolerance of hydrophobic substances, and hence the biotic windows for such processes.
Exfoliation syndrome in black South Africans.

BACKGROUND Data on exfoliation syndrome (XFS) in Africans are scarce. OBJECTIVE To determine the prevalence and clinical features of XFS among black South Africans. DESIGN Random cross-sectional samples of the black population aged 40 years or older from 2 districts in South Africa: Hlabisa, in northern KwaZulu-Natal Province, and Temba, North West Province. METHODS Standardized examination, including slitlamp biomicroscopy with pupil dilatation, gonioscopy, pachymetry, tonometry, binocular indirect ophthalmoscopy, and visual field testing. RESULTS Among 1840 participants, the prevalence of XFS was 7.7% (95% confidence interval, 5.4%-10.5%) in Hlabisa and 6.0% (95% confidence interval, 4.1%-8.4%) in Temba. The prevalence increased with age, with 18.9% (Hlabisa) and 16.5% (Temba) of those 70 or older affected. The clinical appearance was similar to that reported in other ethnic groups. Exfoliative glaucoma accounted for approximately one fourth of open-angle glaucoma cases (OAG). Open-angle glaucoma was associated with XFS; the age-adjusted and sex-adjusted odds ratios were 2.3 (95% confidence interval, 1.0-5.2) and 2.8 (95% confidence interval, 1.2-6.3) for Hlabisa and Temba, respectively. The relationship with OAG was absent when adjusting for intraocular pressure. Exfoliative glaucoma was characterized in this predominantly untreated population by high intraocular pressure and severe visual loss. Among subjects with XFS and OAG, 16 of 18 were blind in 1 or both eyes. CONCLUSIONS Exfoliation syndrome occurs at a high prevalence among black South Africans and incurs a moderate increase in risk of glaucoma. In this untreated population, this increased risk was dependent on raised intraocular pressure. Open-angle glaucoma in association with XFS appears to be associated with a poor prognosis.
Pathways through the nose for nasal intubation: a comparison of three endotracheal tubes.

BACKGROUND In nasotracheal intubation, there are two main pathways in the nostril through which the endotracheal tube may pass. The lower pathway lies along the floor of the nose underneath the inferior turbinate. The upper pathway lies above the inferior turbinate, just below the middle turbinate. The lower pathway may be considered to be the safer route as it is located away from the middle turbinate and cribiform plate. METHODS We conducted a randomized controlled trial comparing the frequency with which preformed, reinforced, and thermosoftened preformed tubes pass through upper and lower pathways. Ninety-two maxillofacial patients requiring nasotracheal intubation as part of their anaesthetic management were studied. Two patients were excluded from the study at endoscopy because of atypical nasal anatomy. After the induction of general anaesthesia, a standardized traditional nasal intubation was performed with a Macintosh laryngoscope, the operators endeavouring to direct the tube along the floor of the nose. Fibreoptic nasendoscopy was then performed by passing the tip of the fibrescope 2-3 cm into the nasal cavity above and below the tube, to identify the pathway taken. RESULTS Data were analysed on 30 patients in each group. Five (16.7%) preformed tubes, 17 (56.7%) reinforced tubes, and 6 (20%) thermosoftened preformed tubes passed through the lower pathway. Significantly more reinforced tubes took the preferred pathway (P=0.001). Tubes passing through the upper pathway caused significantly more epistaxis than tubes passing through the lower pathway (P=0.003). CONCLUSIONS Endotracheal tubes, particularly preformed tubes, frequently take the less favourable pathway during nasotracheal intubation, in spite of specific attempts to avoid this.
A Functional Polymorphism in the Promoter Region of the Monoamine Oxidase A Gene Is Associated with the Cigarette Smoking Quantity in Alcohol-Dependent Heavy Smokers

Tobacco smoking represents a leading cause of morbidity and mortality with a strong dose-response relation between the amount of smoking and the risks of tobacco-related diseases and death. The quantity that is smoked is determined predominantly by genetic factors. The present study examined whether there is an association between the quantity of cigarettes smoked and length variation of a functional 30-bp repeat polymorphism in the promoter region of the monoamine oxidase A (MAO-A) gene. The number of 30-bp repeats, which is associated with enzyme activity was assessed in 121 Caucasian men suffering from both alcohol and tobacco dependence. Analysis revealed that the highly active long allele (4 repeat) is associated with a significantly greater amount of cigarette smoking in comparison with the less active short allele (3 repeat). In a logistic regression model (dichotomized), smoking quantity was significantly predicted by MAO-A genotype while no other variable (age, height, body weight, frequency of smoking, quantity and frequency of alcohol consumption) met the significance level. Since tobacco smoke is a potent inhibitor of MAO-A, this result could be regarded as a genotype-related dosage effect. Taken together, in alcohol-dependent heavily smoking men there is evidence for a MAO-A gene-associated effect on the quantity that is smoked as reflected by the daily number of cigarettes consumed.