Miracle-dz/UniFAR-FTUs huggingface dataset:
BASIC CONCEPTS IN CARDIOLOGY Quantitative Structural Analysis of the Myocardium During Physiologic Growth and Induced Cardiac Hypertrophy: A Review

The quantitative structural properties of the ventricular myocardium during postnatal physiologic growth are compared with those accompanying an increased load in the adult rat heart to determine whether induced cardiac hypertrophy is a pathologic condition or simply a form of well compensated accelerated growth. The expansion of the ventricular myocardium during matu• ration shows a remarkable degree of well balanced com• pensatory response, because the capillary microvas• culature, parenchymal cells and subcellular components of myocytes all grow in proportion to the increase in cardiac mass. In contrast, the increases in myocyte di• ameter and length caused by pressure hypertrophy, vol• ume hypertrophy and infarction-induced hypertrophy are consistent with concentric, eccentric and a combi• nation of concentric and eccentric hypertrophic growth of the whole ventricle, respectively. These cellular shape changes may represent a com• pensatory response of the myocardium at the cellular level of organization that tends to minimize the effects of an increased pressure or volume load, or both, on the heart. Cardiac hypertrophy, however, may also show alterations affecting capillary luminal volume and sur• face and the mitochondrial to myofibril volume ratio, which indicate an inadequate growth adaptation of the component structures responsible for tissue oxygenation and energy production. Thus, hypertrophy of the adult heart differs from that during physiologic growth, and the hypertrophied myocardium may exhibit structural abnormalities that can be expected to increase its vul• nerability to ischemia.
Neuroprotection and Neurodegeneration in Alzheimer's Disease: Role of Cardiovascular Disease Risk Factors, Implications for Dementia Rates, and Prevention with Aerobic Exercise in African Americans

Prevalence of Alzheimer's disease (AD) will reach epidemic proportions in the United States and worldwide in the coming decades, and with substantially higher rates in African Americans (AAs) than in Whites. Older age, family history, low levels of education, and ɛ4 allele of the apolipoprotein E (APOE) gene are recognized risk factors for the neurodegeneration in AD and related disorders. In AAs, the contributions of APOE gene to AD risk continue to engender a considerable debate. In addition to the established role of cardiovascular disease (CVD) risk in vascular dementia, it is now believed that CVD risk and its endophenotype may directly comediate AD phenotype. Given the pleiotropic effects of APOE on CVD and AD risks, the higher rates of CVD risks in AAs than in Whites, it is likely that CVD risks contribute to the disproportionately higher rates of AD in AAs. Though the advantageous effects of aerobic exercise on cognition is increasingly recognized, this evidence is hardly definitive, and data on AAs is lacking. In this paper, we will discuss the roles of CVD risk factors in the development of AD and related dementias, the susceptibility of these risk factors to physiologic adaptation, and fitness-related improvements in cognitive function. Its relevance to AD prevention in AAs is emphasized.
Long-term performance HDPE geomembrane seams in MSW leachate

The effect of a synthetic municipal solid waste leachate on the long-term performance of dual-wedge welds in a 1.5 mm thick high-density polyethylene geomembrane (GMB) is reported based on 4 years of testing at 40, 65, 75, and 85 °C. The effect of leachate on the GMB well away from the weld, in the heat-affected zone (HAZ) beside the weld, and in the welded zone are investigated. The slowest antioxidant depletion rate was in the weld itself and the fastest rate for the HAZ adjacent to the weld. The shear break and peel break properties started to decrease after the standard oxidative induction time had depleted to residual, but before the high-pressure oxidative induction time had reached residual. Failures occured at the HAZ adjacent to weld in both the shear and peel tests. No failure of the seam itself was observed. The times to nominal failure of the GMB in the critical HAZ are predicted. The rate of degradation in the weld and sheet are compared.
Microfludic Device for Creating Ionic Strength Gradients over DNA Microarrays for Efficient DNA Melting Studies and Assay Development

The development of DNA microarray assays is hampered by two important aspects: processing of the microarrays is done under a single stringency condition, and characteristics such as melting temperature are difficult to predict for immobilized probes. A technical solution to these limitations is to use a thermal gradient and information from melting curves, for instance to score genotypes. However, application of temperature gradients normally requires complicated equipment, and the size of the arrays that can be investigated is restricted due to heat dissipation. Here we present a simple microfluidic device that creates a gradient comprising zones of defined ionic strength over a glass slide, in which each zone corresponds to a subarray. Using this device, we demonstrated that ionic strength gradients function in a similar fashion as corresponding thermal gradients in assay development. More specifically, we noted that (i) the two stringency modulators generated melting curves that could be compared, (ii) both led to increased assay robustness, and (iii) both were associated with difficulties in genotyping the same mutation. These findings demonstrate that ionic strength stringency buffers can be used instead of thermal gradients. Given the flexibility of design of ionic gradients, these can be created over all types of arrays, and encompass an attractive alternative to temperature gradients, avoiding curtailment of the size or spacing of subarrays on slides associated with temperature gradients.
Changes in the first-pass success rate with the GlideScope video laryngoscope and direct laryngoscope: a ten-year observational study in two academic emergency departments

Objective The aim of this study was to assess the success rate of the GlideScope video laryngoscope (GVL) and direct laryngoscope (DL) over ten years in two academic emergency departments. Methods We used adult intubation data using DL and GVL collected from airway management registries at two academic emergency departments. We analyzed changes in first-pass success (FPS) rate by device and operator training level. We conducted a multivariate logistic regression analysis to predict the FPS according to time period. Results Over the study period (2006 to 2010, season I; 2013-2015, season II) the DL usage rate dropped from 91.6% to 45.0% while the GVL usage rate increased from 8.4% to 55.4%. The FPS rate using DL also declined from 90.8% in 2007 to 75.5% in 2015. On the other hand, the FPS rate using GVL increased from 87.8% to 95.2%. With DL, all operators’ FPS rate declined by approximately 10% in season II compared to season I. The FPS rate with GVL was significantly higher in the providers of postgraduate year over 3 years (P=0.043). Multivariate logistic regression analysis revealed an adjusted odds ratio for GVL FPS of 0.799 during season I (P=0.274). However, the adjusted odds ratio for GVL FPS was 3.744 during season II (P<0.001). Conclusion We found that the FPS rates of GVL have slightly increased but DL’s FPS rate has significantly decreased during the last ten years.
Theory of Passive Permeability through Lipid Bilayers

Recently measured water permeability through bilayers of different lipids is most strongly correlated with the area per lipid A rather than with other structural quantities such as the thickness. This paper presents a simple three-layer theory that incorporates the area dependence in a physically realistic way and also includes the thickness as a secondary modulating parameter. The theory also includes the well-known strong correlation of permeability upon the partition coefficients of general solutes in hydrocarbon environments (Overton's rule). Two mathematical treatments of the theory are given; one model uses discrete chemical kinetics and one model uses the Nernst-Planck continuum equation. The theory is fit to the recent experiments on water permeability in the accompanying paper.
Nature Genetics Advance Online Publication Meta-analysis of 375,000 Individuals Identifies 38 Susceptibility Loci for Migraine

A r t i c l e s vascular changes representing downstream effects that are not themselves causative of migraine 4,5. However, genetic evidence favoring one theory over the other is lacking. At the phenotype level, migraine is defined by diagnostic criteria from the International Headache Society 6. There are two prevalent subforms: migraine without aura, which is characterized by recurrent attacks of moderate or severe headache associated with nausea or hypersensitivity to light and Migraine is a debilitating neurological disorder affecting around one in seven people worldwide, but its molecular mechanisms remain poorly understood. There is some debate about whether migraine is a disease of vascular dysfunction or a result of neuronal dysfunction with secondary vascular changes. Genome-wide association (GWA) studies have thus far identified 3 independent loci associated with migraine. To identify new susceptibility loci, we carried out a genetic study of migraine on 59,674 affected subjects and 36,078 controls from 22 GWA studies. We identified 44 independent single-nucleotide polymorphisms (SNPs) significantly associated with migraine risk (P < 5 × 0 −8) that mapped to 38 distinct genomic loci, including 28 loci not previously reported and a locus that to our knowledge is the first to be identified on chromosome X. In subsequent computational analyses, the identified loci showed enrichment for genes expressed in vascular and smooth muscle tissues, consistent with a predominant theory of migraine that highlights vascular etiologies. Migraine is the third most common disease worldwide, with a lifetime prevalence of 15–20%, affecting up to 1 billion people across the globe 1,2. It ranks as the seventh most disabling disease worldwide (and the most disabling neurological disease) in terms of years of life lost to disability 1 , and it is the third most costly neurological disorder, after dementia and stroke 3. There is debate about whether migraine is a disease of vascular dysfunction or of neuronal dysfunction with
Smoking cessation: the potential role of risk assessment tools as motivational triggers

Smoking is the most important and preventable cause of morbidity and premature mortality in developed and developing countries. To date, efforts to reduce the burden of smoking have focused on non-personalised strategies. Anxiety about ill health, especially lung cancer and emphysema, is the foremost concern for smokers and a major reason for quitting. Recent efforts in cessation management focus on behaviour change and pharmacotherapy. The ‘3 Ts’ (tension, trigger, treatment) model of behaviour change proposes that at any one time a smoker experiences varying degrees of motivational tension, which in the presence of a trigger may initiate or enhance quitting. Smokers' optimistic bias (ie, denial of one's own vulnerability) sustains continued smoking, while increasing motivational tension (eg, illness) favours quitting. The 1 year quit rates achieved when smokers encounter a life threatening event, such as a heart attack or lung cancer, are as much as 50–60%. Utilising tests of lung function and/or genetic susceptibility personalises the risk and have been reported to achieve 1 year quit rates of 25%. This is comparable to quit rates achieved among healthy motivated smokers using smoking cessation drug therapy. In this paper we review existing evidence and propose that identifying those smokers at increased risk of an adverse smoking related disease may be a useful motivational tool, and enhance existing public health strategies directed at smoking cessation.
The E 3 ligase synoviolin controls body weight and mitochondrial biogenesis through negative regulation of PGC-1 b

Obesity is a major global public health problem, and understanding its pathogenesis is critical for identifying a cure. In this study, a gene knockout strategy was used in post-neonatal mice to delete synoviolin (Syvn)1/Hrd1/Der3, an ER-resident E3 ubiquitin ligase with known roles in homeostasis maintenance. Syvn1 deficiency resulted in weight loss and lower accumulation of white adipose tissue in otherwise wild-type animals as well as in genetically obese (ob/ob and db/db) and adipose tissue-specific knockout mice as compared to control animals. SYVN1 interacted with and ubiquitinated the thermogenic coactivator peroxisome proliferatoractivated receptor coactivator (PGC)-1b, and Syvn1 mutants showed upregulation of PGC-1b target genes and increase in mitochondrion number, respiration, and basal energy expenditure in adipose tissue relative to control animals. Moreover, the selective SYVN1 inhibitor LS-102 abolished the negative regulation of PGC-1b by SYVN1 and prevented weight gain in mice. Thus, SYVN1 is a novel post-translational regulator of PGC-1b and a potential therapeutic target in obesity treatment.
The G516T CYP2B6 Germline Polymorphism Affects the Risk of Acute Myeloid Leukemia and Is Associated with Specific Chromosomal Abnormalities

The etiology of acute myeloid leukemia (AML) underlies the influence of genetic variants in candidate genes. The CYP2B6 enzyme detoxifies many genotoxic xenobiotics, protecting cells from oxidative damage. The CYP2B6 gene is subjected to a single-nucleotide polymorphism (G516T) with heterozygotes (GT) and homozygotes (TT) presenting decreased enzymatic activity. This case-control study aimed to investigate the association of CYP2B6 G516T polymorphism with the susceptibility of AML and its cytogenetic and clinical characteristics. Genotyping was performed on 619 AML patients and 430 healthy individuals using RCR-RFLP and a novel LightSNip assay. The major finding was a statistically higher frequency of the variant genotypes (GT and TT) in patients compared to the controls (GT:38.8% vs 29.8% and TT:9.3% vs 5.3% respectively) (p<0.001). More specifically, a significantly higher frequency of GT+TT genotypes in de novo AML patients (46.6%) and an immensely high frequency of TT in secondary AML (s-AML) (20.5%) were observed. The statistical analysis showed that the variant T allele was approximately 1.5-fold and 2.4-fold higher in de novo and s-AML respectively than controls. Concerning FAB subtypes, the T allele presented an almost 2-fold increased in AML-M2. Interestingly, a higher incidence of the TT genotype was observed in patients with abnormal karyotypes. In particular, positive correlations of the mutant allele were found in patients carrying specific chromosomal aberrations [-7/del(7q), -5/del(5q), +8, +21 or t(8;21)], complex or monosomal karyotypes. Finally, a strikingly higher frequency of TT genotype was also observed in patients stratified to the poor risk group. In conclusion, our results provide evidence for the involvement of the CYP2B6 polymorphism in AML susceptibility and suggest a possible role of the CYP2B6 genetic background on the development of specific chromosomal aberrations.
Xenoestrogens Alter Estrogen Receptor (ER) α Intracellular Levels

17β-estradiol (E2)-dependent estrogen receptor (ER) α intracellular concentration is a well recognized critical step in the pleiotropic effects elicited by E2 in several target tissues. Beside E2, a class of synthetic and plant-derived chemicals collectively named endocrine disruptors (EDs) or xenoestrogens bind to and modify both nuclear and extra-nuclear ERα activities. However, at the present no information is available on the ability of EDs to hamper ERα intracellular concentration. Here, the effects of bisphenol A (BPA) and naringenin (Nar), prototypes of synthetic and plant-derived ERα ligands, have been evaluated on ERα levels in MCF-7 cells. Both EDs mimic E2 in triggering ERα Ser118 phosphorylation and gene transcription. However, only E2 or BPA induce an increase of cell proliferation; whereas 24 hrs after Nar stimulation a dose-dependent decrease in cell number is reported. E2 or BPA treatment reduces ERα protein and mRNA levels after 24 hrs. Contrarily, Nar stimulation does not alter ERα content but reduces ERα mRNA levels like other ligands. Co-stimulation experiments indicate that 48 hrs of Nar treatment prevents the E2-induced ERα degradation and hijacks the physiological ability of E2:ERα complex to regulate gene transcription. Mechanistically, Nar induces ERα protein accumulation by preventing proteasomal receptor degradation via persistent activation of p38/MAPK pathway. As a whole these data demonstrate that ERα intracellular concentration is an important target through which EDs hamper the hormonal milieu of E2 target cells driving cells to different outcomes or mimicking E2 even in the absence of the hormone.
A 3.1 Gb/s 8 $\,\times\,$ 8 Sorting Reduced K-Best Detector With Lattice Reduction and QR Decomposition

This paper presents the VLSI implementation of a lattice-reduction-aided (LRA) detection system. The proposed system includes a QR decomposition, lattice reduction (LR) processor, and sorting-reduced (SR) K-best detector for 8 × 8 multiple-input multiple-output (MIMO) systems. The bit error rate of the proposed MIMO detection system only incurs approximately 3 dB of implementation loss compared with optimal maximum likelihood detection with 64-quadratic-amplitude modulation. The proposed processor can also support different throughput requirements by adjusting the stage number of LR. The SR K-best detector can achieve 3.1 Gb/s throughput with 0.24-ns latency. The throughput of the system reaches 585 Mb/s if one channel preprocessing can support 72 symbol detections. The corresponding energy per bit is 63 pJ/bit, which is the smallest value achieved to date. This paper presents the first VLSI implementation of a complete LRA K-best detector with an 8 × 8 dimension.
Optimal Design of Passenger Car Suspension for Ride and Road

The primary function of a vehicle suspension system is to isolate the road excitations experienced by the tyres from being transmitted to the passengers. In this paper, a suitable optimizing technique is applied at design stage to obtain the suspension parameters of a passive suspension and active suspension for a passenger car which satisfies the performance as per ISO 2631 standards. A number of objectives such as maximum bouncing acceleration of seat and sprung mass, root mean square (RMS) weighted acceleration of seat and sprung mass as per ISO2631 standards, jerk, suspension travel, road holding and tyre deflection are minimized subjected to a number of constraints. The constraints arise from the practical kinetic and comfortability considerations, such as limits of the maximum vertical acceleration of the passenger seat, tyre displacement and the suspension working space. The genetic algorithm (GA) is used to solve the problem and results were compared to those obtained by simulated annealing (SA) technique and found to yields similar performance measures. Both the passive and active suspension systems are compared in time domain analyses subjected to sinusoidal road input. Results show passenger bounce, passenger acceleration, and tyre displacement are reduced by 74.2%, 88.72% and 28.5% respectively, indicating active suspension system has better potential to improve both comfort and road holding. Keywords: ride comfort, road holding, LQR control, genetic algorithm, simulated annealing
Unsteady force production on a flat plate wing by large transverse gusts and plunging maneuvers

Title of dissertation: Unsteady force production on a flat plate wing by large transverse gusts and plunging maneuvers Gino M. Perrotta, Doctor of Philosophy, 2017 Dissertation directed by: Professor Anya Jones Department of Aerospace Engineering The transient forces produced by large-amplitude transverse gust encounters and plunge maneuvers were studied experimentally in a water-filled towing tank. Forces were measured as a flat plate wing with an aspect ratio of four was towed through a fluid gust and as the same wing performed plunge maneuvers which matched the shape of the gust velocity profile. The transient velocity in each case conformed to the sine-squared profile, and the peak transient velocities were of the same order of magnitude as the steady towing velocities. In most cases, the wing pitch angle was high enough to cause constant flow separation. Even at low wing pitch angles, the increase in flow incidence angle by the transverse gust or plunge velocity was enough to cause flow separation. Transient force magnitudes were shown to increase with increasing stream-normal velocity for both the gust encounters and plunge maneuvers. Transient forces varied with increasing wing pitch angle during gust encounters but not during plunge maneuvers. Force histories in each case were compared to predictions made by existing small-perturbation force models, and adaptations were made to those models based on physical interpretation of the observed characteristics. Measured forces in both the gust encounters and the plunge maneuvers were found to correspond more closely to predictions made based on attached flow than on separated flow, which supports the suggestion that the presence of a leading edge vortex significantly augments the transient lift. Additionally, a large trailing edge vortex forms at the end of the gust encounter which temporarily reduces the force production below the steady-state values. This was not observed in the plunge maneuver force histories, which were much closer to quasi-steady than were the gust encounter force histories. This analysis contributes to the understanding of unsteady force production in large-amplitude events, and in particular in conditions with separated flow, the behaviors of which are not adequately captured by existing small-perturbation models. Unsteady force production on a flat plate wing by large transverse gusts and plunging maneuvers