Miracle-dz/UniFAR-FTUs huggingface dataset:
Non-invasive assessment of shear strain in the carotid arterial wall based on ultrasound radiofrequency data

The primary trigger for myocardial infarction and stroke is destabilization of atherosclerotic plaques. It has been hypothesized that the shear strain, induced in the adventitial layer by the pulsating pressure wave and blood flow, initiates and/or stimulates the development of such a plaque into a rupture-prone, vulnerable plaque. The aim of this paper was to experimentally test and validate methods to estimate longitudinal shear strain in arterial vessel walls and to investigate the feasibility of in vivo application. In simulations and in phantoms rf ultrasound data was used to estimate local longitudinal displacements and shear strain. The estimated shear strains were compared with the applied values. Additionally, rf-based estimates of longitudinal shear strain in the adventitia of the carotid artery wall were obtained in a healthy volunteer. In the simulations and phantom experiments, the estimates of longitudinal displacement and shear strain were linearly related to the applied displacement and shear strain (Spearman's rho = 0.879 − 1.00, p ≪ .05). The shear strain estimates in the in vivo experiments were found to be reproducible and the periodicity corresponded well with the cardiac cycle. Noninvasive ultrasound radiofrequency signals appeared to represent an adequate base for measurement of longitudinal shear strain in the adventitia layer of the carotid artery wall.
Sex Hormone Concentrations and the Risk of Breast Cancer Recurrence in Postmenopausal Women without Hot Flashes

Background: We examined if the reduced risk of breast cancer events seen among women without baseline hot flash symptoms in the Women's Healthy Eating and Living (WHEL) dietary intervention trial was related to changes in sex hormone concentrations. Methods: Baseline and year one concentrations of total and bioavailable estradiol, and testosterone and sex hormone-binding globulin (SHBG) were compared by intervention arm among 447 postmenopausal women without hot flashes. Cox proportional hazard models tested interaction terms between study arm and baseline hormone concentrations adjusted for study site, antiestrogen use, positive nodes, tumor size, oophorectomy status, and hormone replacement therapy use. Results: Sex hormone concentrations did not differ by study arm at baseline nor at year one. Twenty-two (9.8%) events occurred in the intervention arm versus 42 (18.9%) in the comparison arm (P = 0.009). Baseline bioavailable testosterone was significantly, positively associated with additional events (HR 1.69, 95% CI: 1.00–2.84; P = 0.049). There were significant interactions between the intervention and total (P = 0.015), and bioavailable (P = 0.050) testosterone: the intervention was more protective among participants with higher baseline total (HR 0.3, 95% CI: 0.2–0.7) or bioavailable (HR 0.4, 95% CI: 0.2–0.7) testosterone than for participants with lower baseline total (HR 0.8, 95% CI: 0.4–1.5) or bioavailable (HR 0.8, 95% CI: 0.4–1.5) testosterone. No significant effects were seen for estradiol or SHBG. Conclusions: The WHEL dietary intervention may have modified other risk factors of recurrence correlated with testosterone. Impact: Sex hormones should be considered as part of a larger biological system related to the risk of breast cancer recurrence. Cancer Epidemiol Biomarkers Prev; 20(5); 939–45. ©2011 AACR.
Anti-Oxidative Effects of Rooibos Tea (Aspalathus linearis) on Immobilization-Induced Oxidative Stress in Rat Brain

Exposure to chronic psychological stress may be related to increased reactive oxygen species (ROS) or free radicals, and thus, long-term exposure to high levels of oxidative stress may cause the accumulation of oxidative damage and eventually lead to many neurodegenerative diseases. Compared with other organs, the brain appears especially susceptible to excessive oxidative stress due to its high demand for oxygen. In the case of excessive ROS production, endogenous defense mechanisms against ROS may not be sufficient to suppress ROS-associated oxidative damage. Dietary antioxidants have been shown to protect neurons against a variety of experimental neurodegenerative conditions. In particular, Rooibos tea might be a good source of antioxidants due to its larger proportion of polyphenolic compounds. An optimal animal model for stress should show the features of a stress response and should be able to mimic natural stress progression. However, most animal models of stress, such as cold-restraint, electric foot shock, and burn shock, usually involve physical abuse in addition to the psychological aspects of stress. Animals subjected to chronic restraint or immobilization are widely believed to be a convenient and reliable model to mimic psychological stress. Therefore, in the present study, we propose that immobilization-induced oxidative stress was significantly attenuated by treatment with Rooibos tea. This conclusion is demonstrated by Rooibos tea’s ability to (i) reverse the increase in stress-related metabolites (5-HIAA and FFA), (ii) prevent lipid peroxidation (LPO), (iii) restore stress-induced protein degradation (PD), (iv) regulate glutathione metabolism (GSH and GSH/GSSG ratio), and (v) modulate changes in the activities of antioxidant enzymes (SOD and CAT).
Quantitative Gait Analysis Using a Motorized Treadmill System Sensitively Detects Motor Abnormalities in Mice Expressing ATPase Defective Spastin

The hereditary spastic paraplegias (HSPs) are genetic conditions in which there is progressive axonal degeneration in the corticospinal tract. Autosomal dominant mutations, including nonsense, frameshift and missense changes, in the gene encoding the microtubule severing ATPase spastin are the most common cause of HSP in North America and northern Europe. In this study we report quantitative gait analysis using a motorized treadmill system, carried out on mice knocked-in for a disease-associated mutation affecting a critical residue in the Walker A motif of the spastin ATPase domain. At 4 months and at one year of age homozygous mutant mice had a number of abnormal gait parameters, including in stride length and stride duration, compared to heterozygous and wild-type littermates. Gait parameters in heterozygous animals did not differ from wild-type littermates. We conclude that quantitative gait analysis using the DigiGait system sensitively detects motor abnormalities in a hereditary spastic paraplegia model, and would be a useful method for analyzing the effects of pharmacological treatments for HSP.
African ancestry allelic variation at the MYH9 gene contributes to increased susceptibility to non-diabetic end-stage kidney disease in Hispanic Americans

Recent studies identified MYH9 as a major susceptibility gene for common forms of non-diabetic end-stage kidney disease (ESKD). A set of African ancestry DNA sequence variants comprising the E-1 haplotype, was significantly associated with ESKD. In order to determine whether African ancestry variants are also associated with disease susceptibility in admixed populations with differing genomic backgrounds, we genotyped a total of 1425 African and Hispanic American subjects comprising dialysis patients with diabetic and non-diabetic ESKD and controls, using 42 single nucleotide polymorphisms (SNPs) within the MYH9 gene and 40 genome-wide and 38 chromosome 22 ancestry informative markers. Following ancestry correction, logistic regression demonstrated that three of the E-1 SNPs are also associated with non-diabetic ESKD in the new sample sets of both African and Hispanic Americans, with a stronger association in Hispanic Americans. We also identified MYH9 SNPs that are even more powerfully associated with the disease phenotype than the E-1 SNPs. These newly associated SNPs, could be divided into those comprising a haplotype termed S-1 whose association was significant under a recessive or additive inheritance mode (rs5750248, OR 4.21, P < 0.01, Hispanic Americans, recessive), and those comprising a haplotype termed F-1 whose association was significant under a dominant or additive inheritance mode (rs11912763, OR 4.59, P < 0.01, Hispanic Americans, dominant). These findings strengthen the contention that a sequence variant of MYH9, common in populations with varying degrees of African ancestry admixture, and in strong linkage disequilibrium with the associated SNPs and haplotypes reported herein, strongly predisposes to non-diabetic ESKD.
Breaking the glass ceiling: hollow OmniGuide fibers

Summary form only given. Telecommunications has continued to push optical fibers towards ever-more demanding applications-such as high bit rates, dense wavelength-division multiplexing (DWDM), and long distances-and in response there has been renewed interest in alternative fiber designs to lift fundamental limitations of silica fibers. A particularly exciting departure from traditional fibers are fibers based on photonic band gaps, forbidden frequency ranges in periodic dielectric structures that can confine light even in low-index or hollow regions. Two main classes of fibers have emerged using photonic band gaps: photonic-crystal "holey" fibers that use a two-dimensional transverse periodicity, and Bragg fibers that use a one-dimensional periodicity of concentric rings. We introduce a novel class of Bragg fibers: "OmniGuide" fibers, which can guide light within a hollow core by concentric multilayer films with the property of omnidirectional reflection.
Evaluation of Subsurface Defects Created During the Finishing of Composites

The objective ofthis study was to test the hypothesis that a degraded subsurface layer containing microcracks is produced in dental composites as a result of finishing procedures. Various composites in the form of rectangular bars were finished with a 12-fluted carbide bur or a fine diamond within minutes of light-curing, and were subsequently stained with silver nitrate. Microscopic evaluation revealed that significant penetration of stain occurred in the unfinished as well as in the finished surfaces. The extent of dye penetration that could be directly attributed to a damaged layer produced by the finishing procedure was less than 10 μm, being greatest for a microfill (Silux Plus) and a hybrid (P-50) composite. There was no difference between the effects of the finishing instruments. SEM analysis of the subsurface showed an absence of any cracks for the composites. However, occasional disruption of the interface between the pre-polymerized resin fillers and the matrix was apparent for the microfill material. The results showed that only a very limited subsurface damage may be created in certain composites during the initial contouring of a restoration.
A Mitosis-specific Phosphorylation of the Gap Junction Protein Connexin43 in Human Vascular Cells: Biochemical Characterization and Localization

Western blotting studies revealed that connexin43 (Cx43), one of the major gap junction proteins in human vascular endothelial cells, is posttranslationally modified during mitosis. This mitosis-specific modification results in a Cx43 species that migrates as a single protein band and was designated Cx43m. Cx43m was shown to be the result of additional Ser/Thr phosphorylation as indicated by: (a) the increased gel mobility induced by both alkaline phosphatase and the Ser/ Thr-specific protein phosphatase-2A (PP2A) and (b) the removal of virtually all 32Pi from Cx43m by PP2A. Immunofluorescent confocal microscopy of mitotic cells revealed that Cx43 is intracellularly located, while in nonmitotic cells Cx43 is located at regions of cell–cell contact. Dye coupling studies revealed that mitotic endothelial cells were uncoupled from each other and from nonmitotic cells. After cytokinesis, sister cells resumed cell coupling independent of de novo protein synthesis. The mitosis-specific phosphorylation of Cx43 correlates with the transient loss of gap junction intercellular communication and redistribution of Cx43, suggesting that a protein kinase that regulates gap junctions is active in M-phase.
Role of p53 in DNA strand break‐induced apoptosis in organotypic slice culture from the mouse cerebellum

Apoptosis occurs not only in mitotic cells but also in postmitotic neuronal cells. We previously suggested that the tumor suppressor gene p53 is required for DNA strand break‐induced apoptosis in dissociated culture of cerebellar granule neurons. In this study, we examined the role of p53 in apoptosis using organotypic slice culture of cerebellum from p53 null and wild‐type mice. Exposure to bleomycin significantly increased the numbers of TUNEL‐, p53‐, and c‐Jun–positive neurons in the wild‐type mouse cerebellar internal granular layer (IGL) and Purkinje cell layer (PL). However, in p53‐deficient mice, these responses were not observed. These results are consistent with our previous observations in dissociated neuronal culture showing that the amount of c‐Jun protein increases significantly after addition of bleomycin in p53 wild‐type cerebellar granule cells. The results presented here also indicate that p53 is involved in DNA strand break‐induced apoptosis of fully postmitotic central nervous system neurons and suggest that c‐Jun expression occurs downstream of p53 expression. J. Neurosci. Res. 4:450–457, 2000 © 2000 Wiley‐Liss, Inc.
The mechanical behaviour of cemented granular materials at high pressures

The mechanical behaviour of cemented granular materials has been an important topic in geotechnical engineering since decades. Historically, most research on ce-mented granular materials has been performed at relatively low confining pressures. Problems relating to cemented granular materials at high-pressure are still not fully understood. However, understanding of the behaviour of cemented granular materials at high-pressure is highly important in deep foundations, particularly for offshore piling, deep mine shafts, high earth dams, and oil-bearing strata. To address the problem, artificially cemented sand specimens with varying degrees of cement contents and initial relative densities were prepared in the laboratory to simulate the natural cementation characteristics. A high-pressure triaxial compression apparatus was utilized to investigate the effect of initial relative density, cement content, and confining pressure on the mechanical behaviour of artificially cemented sand. High-pressure tests including isotropic compression, drained and undrained triaxial shearing and microscopic studies of the materials were carried out on the artificially cemented sand specimens in the Nottingham Centre for Geomechanics laboratory at the University of Nottingham. Complexities with artificial specimen preparation and with high-pressure testing were identified and tackled. The experimental results indicate that there is significant effect of cement contents and confining pressures on the mechanical behaviour of cemented materials. Particularly, these effects were notified on isotropic compression, peaks strength, strength parameters, shear banding, particle crushing, yielding, and stress-dilatancy relationships. For example, reduction in compressibility, reduction in particle crushing and shift in normal compression line by the increase in cement content of the material during isotropic compression were significant. Progressive suppression in the dilation of cemented sand by the gradual increase in confining pressure, increase in the peak strength, developing of curved failure envelope, increase in the yield strength and formation of conjugate shear banding during progressive failure during triaxial compression were worth noticeable. This concludes that the significance of high-pressure and cement content cannot be ignored in the design considerations. However, more research needs to be carried out at further high pressures in order to see the convergence of failure envelopes and the initiation of bond breakage and particle crushing to give a reasonable design framework for foundations.
Association of fasting insulin and C peptide with diabetic retinopathy in Latinos with type 2 diabetes

Objective Residual insulin secretion provides important protection against the development of diabetic retinopathy in type 1 diabetes. The data to support this in type 2 diabetes are unclear. We therefore tested in type 2 diabetes whether markers of residual beta-cell function are associated with the development of diabetic retinopathy, an important microvascular complication of diabetes. Design Prospective, cross-sectional, family-based study. Participants 585 Latino type 2 diabetic participants, ascertained in families via a proband either with known diabetes duration of greater than 10 years and/or with diabetic retinopathy. Outcome measures Circulating levels of fasting insulin and C peptide measured and correlated to degree of diabetic retinopathy, assessed by digital fundus photography and graded using the Modified Airlie House Classification and the Early Treatment Diabetic Retinopathy Study scale (range: levels 10–85). Results Fasting plasma insulin (β=−0.29; 95% CI −0.38 to −0.20; p<0.0001) and C peptide (β=−0.21; 95% CI −0.30 to −0.13; p<0.0001) concentrations in these diabetic participants were significantly correlated with retinopathy and its degree of severity. This relationship remained significant after adjusting for potential covariates including age, gender, glycosylated hemoglobin, duration of diabetes, blood pressure, and renal function. Conclusions These data suggest that residual endogenous insulin secretion is associated with the presence of diabetic retinopathy and its severity in Latinos with familial type 2 diabetes. It remains to be proven whether beta-cell targeted therapies, to maintain beta-cell mass and/or function in addition to glycemic control, will further the goal of preventing diabetic microvascular disease.
An Optimal Wheel Torque Distribution Controller for Automated Vehicle Trajectory Following

This paper proposes an automated vehicle trajectory following system that uses four constrained wheel torques to regulate a vehicle on a reference trajectory. The constrained wheel torques can be achieved using the two-wheel drive and differential brakes. The proposed control algorithm is developed using the following steps. First, the sliding-mode control is used to find stability constraints for trajectory following when the vehicle system is subjected to modeling errors. Second, these stability constraints, along with other actuator constraints, are particularly tuned for the proposed control distribution method. The proposed control distribution method determines four longitudinal tire forces and minimizes actuator control efforts. Finally, these tire forces are converted to traction/braking wheel torques. The proposed method has the following advantages: 1) It achieves both robust trajectory following and optimal control efforts, 2) the optimal control effort is obtained analytically instead of from a numerical search, and 3) the robust performance of this vehicle control system can be theoretically verified. The proposed method is evaluated using numerical simulations on two front-drive vehicle models: a full-state vehicle model and a sedan model from the Carsim commercial software. The simulation results indicate that, in both cases, the proposed method can regulate the vehicle to finish a “double-lane change” when the vehicle is moving at an initial speed of 90 km/h. The maximum lateral acceleration is 6.56 m/s2, and the regulated position error is less than 6.9 cm.
Non-alcoholic fatty liver disease–From the cardiologist perspective

Non-alcoholic fatty liver disease (NAFLD) includes a range of disorders characterized by excess accumulation of triglycerides within the liver. While simple steatosis may be clinically stable, non-alcoholic steatohepatitis (NASH) can be progressive. Inflammation is believed to be the driving force behind NASH and the progression to fibrosis and subsequent cirrhosis. NAFLD is globally considered a significant health concern not only because of its incidence but also because of its economic impact. The fact that NAFLD is associated with cardiovascular disease is widely recognized, as well as the fact that NAFLD patient mortality rises when such an association is present. In particular, NAFLD is associated with coronary and carotid atherosclerosis, endothelial dysfunction and arterial rigidity, ventricles function, valves morphology, congestive heart failure, and arrhythmias (especially atrial fibrillation). Additionally, the hypercoagulability status in NAFLD patient may be suggested by the presence of inflammatory and coagulation markers. In order to differentiate between milder forms and the more severe ones that necessitate aggressive therapy, individualized risk scores may be used. This narrative review will analyze and interpret the papers published in PubMed in the last 16 years, in an attempt to expand our understanding of the NASH as a possible cardiovascular risk factor.
Effectiveness and tissue compatibility of a 12‐week treatment of chronic venous leg ulcers with an octenidine based antiseptic – a randomized, double‐blind controlled study

The aim of this study was to evaluate the cytotoxic effect of octenidine dihydrochloride/phenoxyethanol (OHP) found in vitro by conducting a randomized, double‐blind controlled clinical study focusing on its safe and effective use in chronic venous leg ulcers. In total, 126 male and female patients were treated with either OHP (n = 60) or Ringer solution (n = 66). The treatment lasted over a period of maximum 12 weeks. For the assessment of the wound‐healing process, clinical outcome parameters were employed, that is, time span until 100% epithelization, wound status and the wound surface area were analysed. Side effects were recorded during the study period. The median time to complete ulcer healing was comparable between the OHP and Ringer solution groups (92 versus 87 days; P = 0·952), without being influenced by wound size or duration of the target ulcer (P‐values: 0·947/0·978). In patients treated with OHP, fewer adverse events (AEs) were observed compared with the Ringer group (17% versus 29% of patients reported 20 versus 38 AEs). OHP is well suitable for the treatment of chronic wounds without cytotoxic effects. Furthermore, OHP does not impair the wound healing in chronic venous ulcers.
Identification of Aminoimidazole and Aminothiazole Derivatives as Src Family Kinase Inhibitors

Src family kinases (SFKs) are a family of non‐receptor tyrosine kinases (TKs) implicated in the regulation of many cellular processes. The aberrant activity of these TKs has been associated with the growth and progression of cancer. In particular, c‐Src is overexpressed or hyperactivated in a variety of solid tumors and is most likely a strong promoting factor for the development of metastasis. Herein, the synthesis of new 4‐aminoimidazole and 2‐aminothiazole derivatives and their in vitro biological evaluation are described for their potential use as SFK inhibitors. Initially, 2‐aminothiazole analogues of dasatinib and 4‐aminoimidazole derivatives were synthesized and tested against the SFKs Src, Fyn, Lyn, and Yes. Five hits were identified as the most promising compounds, with Ki values in the range of 90–480 nm. A combination of molecular docking, homology modeling, and molecular dynamics were then used to investigate the possible binding mode of such compounds within the ATP binding site of the SFKs. Finally, the antiproliferative activities of the best candidates were evaluated against SH‐SY5Y and K562 cell lines. Compound 3 b [2‐(4‐{2‐methyl‐6‐[(5‐phenylthiazol‐2‐yl)amino]pyrimidin‐4‐yl}piperazin‐1‐yl)ethanol] was found to be the most active inhibitor.