Miracle-dz/UniFAR-FTUs huggingface dataset:
Growth characteristics, angiotensin II generation, and microarray-determined gene expression in vascular smooth muscle cells from young spontaneously hypertensive rats

Background We have demonstrated that vascular smooth muscle cells (VSMCs) derived from spontaneously hypertensive rats (SHR) show exaggerated growth and produce angiotensin (Ang) II and growth factors. These may reflect intrinsic abnormalities in SHR that are not caused by excessive blood pressure, and are associated with genetic abnormalities. Objective To evaluate whether these characteristics of VSMCs from SHR are associated with hypertension or genetic factors. Design and methods VSMCs were obtained by an explant method from aortas of 4-week-old male SHR/Izumo and Wistar–Kyoto (WKY)/Izumo rats. We evaluated growth characteristics by [3H]thymidine incorporation and cell number increases, immunofluorescence of α-smooth muscle (α-SM) actin, mRNA expressions of phenotype markers, Ang II-generating system components, and growth factors by reverse transcription and polymerase chain reaction analysis, and Ang II levels by radioimmunoassay in VSMCs. Expression of 850 genes in VSMCs was evaluated by microarray. Results VSMCs from young SHR showed increased basal DNA synthesis and higher responses of DNA synthesis and cell numbers in response to calf serum. Ang II was significantly increased in conditioned medium and cell extracts from SHR-derived VSMCs than in those from WKY rat-derived VSMCs. mRNA expression of Ang II-generating proteinases, such as cathepsin D and angiotensin-converting enzyme, was greater in VSMCs from SHRs than in cells from WKY rats. Expression of transforming growth factor-β1, platelet-derived growth factor A-chain and basic fibroblast growth factor mRNAs was greater in VSMCs from SHRs than in cells from WKY rats. Expression of mRNAs of phenotype markers, such as matrix gamma-carboxyglutamic acid (Gla) and osteopontin, was also greater in VSMCs from SHR than in cells from WYK rats. Microarray study showed that VSMCs derived from young SHR increasingly express genes for many enzymes, adhesion molecules and cytokines. Conclusion This study determined that VSMCs derived from young SHR show exaggerated growth, produce Ang II and increasingly express several enzymes, adhesion molecules and cytokines, which are independent of hypertension and possibly associated with genetic abnormalities.
Cerebral Microbleeds Predict Impending Intracranial Hemorrhage in Infective Endocarditis

Background: Cerebral microbleeds (CMBs) detected by T2*-weighted MRI are a potential indicator of hypertension, microvascular disease and hemorrhagic stroke. An association between infective endocarditis (IE) and CMBs has been reported recently, but the clinical significance remains unclear. We hypothesized that CMBs in patients with IE are associated with vascular vulnerabilities such as mycotic aneurysm or pyogenic vasculitis. Methods: We retrospectively reviewed 26 consecutive patients with definite IE who underwent T2*-weighted MRI and were admitted to 2 medical centers in Osaka, Japan, between January 2006 and June 2010. We examined the incidence of symptomatic intracranial hemorrhage (ICH) occurring after initial MRI examination and investigated the association between ICH, CMBs and other clinical characteristics. Results: CMBs were identified in 14 patients (54%), and 72% of CMBs were found in the lobar region. Symptomatic ICH was observed in 8 patients (31%) during the 3-month follow-up period after initial MRI examination. In multiple logistic regression analyses, the presence of preceding ICH [odds ratio (OR) 40.0, 95% confidence interval (CI) 2.5–2,870] and the presence of CMBs (OR 34.0, 95% CI 1.3–17,300) were independent predictors of the development of ICH. Using cutoff values for CMBs of ≧2 and ≧3, the adjusted ORs for ICH increased (OR 42.1, 95% CI 1.9–24,300, and OR 70.1, 95% CI 2.5–105,000, respectively). Conclusions: In addition to prior ICH, the presence of CMBs was a strong predictor of impending ICH in patients with IE. CMBs might represent vascular vulnerability related to IE.
DAMPNESS IN BUILDINGS AS A RISK FACTOR FOR HEALTH EFFECTS . EUROPEAN MULTIDISCIPLINARY REVIEW OF THE ENTIRE LITERATURE ( EUROEXPO )

The scientific literature on health effects associated with “dampness” in buildings including literature between 1998 and 2000 has been reviewed by an European group (EUROEXPO). The groups consisted of scientists with experience from medicine, epidemiology, toxicology and engineering. Of the 104 reviewed articles 52 were excluded as they were judged as background papers or “non-informative” or “inconclusive” or the study did not present data on exposure, health effect or analysis of the association between exposure and health. The review groups concluded that “dampness” in buildings is a risk factor for health effects such as cough, wheeze, asthma, general symptoms and airway infections among atopics and nonatopics, both in domestic and public environments. However, the literature is inconclusive in respect of causative agents in such buildings. Suggested causative agents are mites, microbiological agents and organic chemicals from degraded building materials.
Pregnancy reduces serotonin-induced contraction of guinea pig uterine and carotid arteries.

Because platelet activation and serotonin have been implicated in preeclamptic hypertension, we investigated the effect of pregnancy on the contractile response to this agent. Prior studies have shown that the vascular contractions to norepinephrine, angiotensin II, and thromboxane are reduced during normal pregnancy by the altered release of endothelium-derived vasoactive substances. We hypothesized that the contraction to serotonin would also be reduced during pregnancy by an endothelium-dependent mechanism. Isolated ring segments from uterine and carotid arteries of near-term pregnant and nonpregnant guinea pigs were studied after stimulating a small amount of active tone with prostaglandin F2 alpha. Serotonin (10(-8) to 10(-5) M) contractile responses of both arteries were reduced by pregnancy. Regardless of pregnancy status, the contractile responses of the uterine artery to serotonin were severalfold greater than that of the carotid artery whose maximum averaged only 10% of the 120 mM KCl contraction. Denudation of uterine artery abolished acetylcholine-stimulated relaxation in vessels from pregnant and nonpregnant animals. However, serotonin-induced contractions were enhanced by denudation only in ring segments obtained from pregnant animals. Nitric oxide synthase inhibition by either NG-monomethyl-L-arginine (L-NMMA) or N omega-nitro-L-arginine and cyclooxygenase inhibition by indomethacin had no effect on serotonin-induced contraction of intact uterine artery regardless of pregnancy. L-NMMA modestly enhanced the intact carotid arterial response to 10(-5) M serotonin independent of pregnancy. (ABSTRACT TRUNCATED AT 250 WORDS)
Decay of molecules at spherical surfaces: Nonlocal effects.

The decay rates for molecules in the vicinity of a metallic sphere are investigated in a phenomenological approach for very close molecule-surface distances d. The Fuchs-Claro model [Phys. Rev. B 35, 3722 (1987)] is adopted to describe the polarizability of the sphere with the nonlocal dielectric response being accounted for within the hydrodynamic description. The results show significant differences when compared with those obtained previously within a local description for d\ensuremath{\lesssim}50 \AA{}, with extra resonances observed in the high-frequency regime, a phenomenon similar to that noted previously by Ruppin in his calculation of the extinction cross section for such spheres.
The design and optimisation of the square and circular inductor using MEMS technology

This paper presents the design and optimization of high quality (Q) factor inductors using Micro Electro-Mechanical Systems (mEMs) technology for 10GHz to 20GHz frequency band. Two inductors have been designed with square and circular topologies. Inductors are designed on Silicon-on-Sapphire (SOS) because of its advantages including high resistivity and low parasitic capacitance. The effects of various parameters such as the width of metal traces (W), the thickness of the metal (T) and the air gap (AG) on the Q-factor are thoroughly investigated. Results indicate that the optimization of the geometrical parameters has minimized the resistive, capacitive and inductive losses of the inductor.
Valproic Acid Increases Susceptibility to Endotoxin Shock Through Enhanced Release of High-Mobility Group Box 1

High-mobility group box 1 (HMGB1) is a nuclear factor and a secreted protein. During inflammation, HMGB1 is secreted into the extracellular space where it can interact with the receptor for advanced glycation end products and trigger proinflammatory signals. Extracellular HMGB1 plays a critical role in several inflammatory diseases such as sepsis and rheumatoid arthritis. Valproic acid (VPA) is one of the most frequently prescribed antiepileptic drugs. The present study was undertaken to investigate the effect of VPA on secretion of HMGB1 in systemic inflammatory responses induced by lipopolysaccharide. Pretreatment with VPA increased the susceptibility of mice to lipopolysaccharide in endotoxemia. Valproic acid induced HMGB1 release and nuclear factor &kgr;B activation in RAW-blue cells. Valproic acid promoted the phosphorylation of ERK1/2 but not that of p38 or JNK. The MEK1/2 inhibitor PD98059 also suppressed HMGB1 release and activation of nuclear factor &kgr;B induced by VPA. Valproic acid induced expression of &ggr;-aminobutyric acid receptors in macrophages, and picrotoxin, a &ggr;-aminobutyric acid A receptor antagonist, inhibited the VPA-activated phosphorylation of ERK and VPA-induced HMGB1 release. These results suggest that VPA may exacerbate innate immune responses to endotoxin through enhanced release of HMGB1.
Use of dipole moment as a parameter in drug-receptor interaction and quantitative structure-activity relationship studies.

The theoretical basis for using dipole moment as a free-energy related parameter in studying drug-receptor interaction and quantitative structure-activity relationship (QSAR) is presented. Over 300 group dipole moments for aromatic substituents were compiled using the dipole moments of monosubstituted benzene derivatives. Examples in the literature of using dipole moment in QSAR studies are also presented.
The use of contrast-enhanced ultrasound for the evaluation of solid abdominal organ injury in patients with blunt abdominal trauma

BACKGROUND The evaluation and management of blunt abdominal trauma is primarily nonoperative. Previous attempts to identify parenchymal solid-organ injury with sonography have been unsatisfactory. The use of Perflutren Lipid Microsphere (Definity) contrast-enhanced ultrasound (DUS) may provide an additional modality for evaluation of solid-organ injury with decreased risk of radiation exposure and contrast-related complications. METHODS Injured patients admitted to a state-designated Level I trauma center (January 2008 to July 2009), who showed evidence of solid-organ injury after blunt abdominal trauma on initial computed tomography (CT) were eligible for entry into the study. Patients underwent DUS examinations within 12 hours of initial CT. Ultrasound images were then compared with findings of CT for organ location, size, and grade of injury. RESULTS Twenty patients with evidence of solid-organ injury on CT were evaluated with DUS. DUS correctly identified five of eight liver lesions, with a sensitivity of 62.5%. DUS correctly identified all nine splenic lesions demonstrating a sensitivity of 100%. DUS correctly identified one of two kidney injuries, demonstrating a sensitivity of 50%. Overall, the positive predictive value for all solid-organ injuries was 100%, with negative predictive value of 20%. The overall sensitivity for DUS was 79% (15 of 19 patients), and specificity was 100% (15 of 15 patients). CONCLUSION Contrast-enhanced sonography is a potential new modality for the evaluation of solid-organ injury for patients with blunt abdominal trauma. With further research, DUS may provide a safe and accurate alternative to CT. LEVEL OF EVIDENCE Diagnostic study, level IV.
Vector control for linear induction machine with minimization of the end effects

Due to of its geometry, the Linear Induction Motor (LIM) has an end effects phenomena causing weakening of the air gap flux and the thrust force. In this work, we described the end effects of the motor by introducing speed dependent scale factors to the magnetizing inductance and series resistance in the d-axis equivalent circuit. Thrust force and flux equations are therefore modified. Also, a field orientation control scheme is developed taking into account the end effects. Starting from this study, the problems of the primary current variations, due to the end effects, is evaluated by simulation. To minimize the end effects in a linear induction machine a new order is developed. This control consists in imposing a primary flux φdr in order to minimize losses.
Contextual equivalence for a probabilistic language with continuous random variables and recursion

We present a complete reasoning principle for contextual equivalence in an untyped probabilistic language. The language includes continuous (real-valued) random variables, conditionals, and scoring. It also includes recursion, since the standard call-by-value fixpoint combinator is expressible. We demonstrate the usability of our characterization by proving several equivalence schemas, including familiar facts from lambda calculus as well as results specific to probabilistic programming. In particular, we use it to prove that reordering the random draws in a probabilistic program preserves contextual equivalence. This allows us to show, for example, that (let x = e1 in let y = e2 in e0) =ctx (let y = e2 in let x = e1 in e0) (provided x does not occur free in e2 and y does not occur free in e1) despite the fact that e1 and e2 may have sampling and scoring effects.
Serum 25-Hydroxy Vitamin D and Survival in Advanced Colorectal Cancer: A Retrospective Analysis

Higher serum 25-hydroxy vitamin D [25(OH)D] levels are associated with decreased colorectal cancer (CRC) incidence. In this retrospective study of Stage IV CRC patients, we evaluate whether 25(OH)D levels at diagnosis correlate with survival. Stored sera from carcinoembryonic antigen (CEA) measurements obtained between February 2005 and March 2006 were screened. The first 250 patients with CEA ±30 days of Stage IV CRC diagnosis were included. Serum 25(OH)D levels were determined and categorized as adequate ≥30 ng/mL, or deficient <30 ng/mL. Multivariable Cox regression models controlling for albumin and Eastern Cooperative Oncology Group performance status were used to investigate whether higher 25(OH)D levels were associated with prolonged survival. A total of 207 patients (83%) were vitamin D-deficient (median = 21 ng/mL), with deficiencies significantly more likely among non-Hispanic black patients (P = 0.009). Higher levels were associated with prolonged survival in categorical variable analysis: adequate vs. deficient, hazard ratio = 0.61, 95% confidence interval = 0.38–0.98, P = 0.041. A majority of newly diagnosed Stage IV CRC patients are vitamin D-deficient. Our data suggest that higher 25(OH)D levels are associated with better overall survival. Clinical trials to determine whether aggressive vitamin D repletion would improve outcomes for vitamin D-deficient CRC patients are warranted.
Extension of Murine Life Span by Overexpression of Catalase Targeted to Mitochondria

To determine the role of reactive oxygen species in mammalian longevity, we generated transgenic mice that overexpress human catalase localized to the peroxisome, the nucleus, or mitochondria (MCAT). Median and maximum life spans were maximally increased (averages of 5 months and 5.5 months, respectively) in MCAT animals. Cardiac pathology and cataract development were delayed, oxidative damage was reduced, H2O2 production and H2O2-induced aconitase inactivation were attenuated, and the development of mitochondrial deletions was reduced. These results support the free radical theory of aging and reinforce the importance of mitochondria as a source of these radicals.
The Neuroendocrine System and Stress, Emotions, Thoughts and Feelings**

The philosophy of mind is intimately connected with the philosophy of action. Therefore, concepts like free will, motivation, emotions (especially positive emotions), and also the ethical issues related to these concepts are of abiding interest. However, the concepts of consciousness and free will are usually discussed solely in linguistic, ideational and cognitive (i.e. "left brain") terms. Admittedly, consciousness requires language and the left-brain, but the aphasic right brain is equally conscious; however, what it "hears" are more likely to be music and emotions. Joy can be as conscious as the conscious motivation produced by the left-brain reading a sign that says, "Danger mines! " However, look in the index of a Western textbook of psychology, psychiatry or philosophy for positive emotions located in the limbic system. Notice how discussion of positive spiritual/emotional issues in consciousness and motivation are scrupulously ignored. For example, the popular notions of "love" being either Eros (raw, amoral instinct) or agape (noble, non-specific valuing of all other people) miss the motivational forest for the trees. Neither Eros (hypothalamic) nor agape (cortical) has a fraction of the power to relieve stress as attachment (limbic love), yet until the 1950s attachment was neither appreciated nor discussed by academic minds. This paper will point out that the prosocial, "spiritual" positive emotions like hope, faith, forgiveness, joy, compassion and gratitude are extremely important in the relief of stress and in regulation of the neuroendocrine system, protecting us against stress. The experimental work reviewed by Antonio Damasio and Barbara Fredrickson, and the clinical example of Alcoholics Anonymous, will be used to illustrate these points.
Title A knowledge-based weighting framework to boost the power of genome-wide association studies

Background: We are moving to second-wave analysis of genome-wide association studies (GWAS), characterized by comprehensive bioinformatical and statistical evaluation of genetic associations. Existing biological knowledge is very valuable for GWAS, which may help improve their detection power particularly for disease susceptibility loci of moderate effect size. However, a challenging question is how to utilize available resources that are very heterogeneous to quantitatively evaluate the statistic significances. Methodology/Principal Findings: We present a novel knowledge-based weighting framework to boost power of the GWAS and insightfully strengthen their explorative performance for follow-up replication and deep sequencing. Built upon diverse integrated biological knowledge, this framework directly models both the prior functional information and the association significances emerging from GWAS to optimally highlight single nucleotide polymorphisms (SNPs) for subsequent replication. In the theoretical calculation and computer simulation, it shows great potential to achieve extra over 15% power to identify an association signal of moderate strength or to use hundreds of whole-genome subjects fewer to approach similar power. In a case study on late-onset Alzheimer disease (LOAD) for a proof of principle, it highlighted some genes, which showed positive association with LOAD in previous independent studies, and two important LOAD related pathways. These genes and pathways could be originally ignored due to involved SNPs only having moderate association significance. Conclusions/Significance: With user-friendly implementation in an open-source Java package, this powerful framework will provide an important complementary solution to identify more true susceptibility loci with modest or even small effect size in current GWAS for complex diseases. Citation: Li M-X, Sham PC, Cherny SS, Song Y-Q (2010) A Knowledge-Based Weighting Framework to Boost the Power of Genome-Wide Association Studies. PLoS ONE 5(12): e14480. doi:10.1371/journal.pone. 0014480 Editor: Thomas Mailund, Aarhus University, Denmark Received June 22, 2010; Accepted December 11, 2010; Published December 31, 2010 Copyright: 2010 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by the Research Grant Council of Hong Kong (HKU7688/05M and HKU7752/08M, YQS) and the Research Fund for the Control of Infectious Diseases (RFCID) (no. 08070652, YQS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: songy@hkucc.hku. hk
Cascade reactions in an all-enzyme nanoreactor.

Good things come in small packages! Giant amphiphiles, consisting of a polymeric hydrophobic tail and a horseradish peroxidase head, were simultaneously synthesized and self-assembled into vesicles. During the self-assembly process, glucose oxidase was encapsulated to create enzymatic cascade nanoreactors (see picture; ABTS= 2,2′-azido-bis(3-ethylbenzthiazoline-6-sulfonic acid)).
Recurrent thromboembolism and major bleeding during oral anticoagulant therapy in patients with solid cancer: findings from the RIETE registry

Following an episode of venous thromboembolism (VTE), the risk of recurrent VTE and major bleeding complications during oral anticoagulant therapy with vitamin K antagonists (VKA) in cancer patients exceeds that observed in patients free from malignancy. [1][1]–[3][2] According to the results of
Three-Dimensional Vascular Network Assembly From Diabetic Patient-Derived Induced Pluripotent Stem Cells

Objective—In diabetics, hyperglycemia results in deficient endothelial progenitors and cells, leading to cardiovascular complications. We aim to engineer 3-dimensional (3D) vascular networks in synthetic hydrogels from type 1 diabetes mellitus (T1D) patient–derived human-induced pluripotent stem cells (hiPSCs), to serve as a transformative autologous vascular therapy for diabetic patients. Approach and Results—We validated and optimized an adherent, feeder-free differentiation procedure to derive early vascular cells (EVCs) with high portions of vascular endothelial cadherin-positive cells from hiPSCs. We demonstrate similar differentiation efficiency from hiPSCs derived from healthy donor and patients with T1D. T1D-hiPSC–derived vascular endothelial cadherin-positive cells can mature to functional endothelial cells–expressing mature markers: von Willebrand factor and endothelial nitric oxide synthase are capable of lectin binding and acetylated low-density lipoprotein uptake, form cords in Matrigel and respond to tumor necrosis factor-&agr;. When embedded in engineered hyaluronic acid hydrogels, T1D-EVCs undergo morphogenesis and assemble into 3D networks. When encapsulated in a novel hypoxia-inducible hydrogel, T1D-EVCs respond to low oxygen and form 3D networks. As xenografts, T1D-EVCs incorporate into developing zebrafish vasculature. Conclusions—Using our robust protocol, we can direct efficient differentiation of T1D-hiPSC to EVCs. Early endothelial cells derived from T1D-hiPSC are functional when mature. T1D-EVCs self-assembled into 3D networks when embedded in hyaluronic acid and hypoxia-inducible hydrogels. The capability of T1D-EVCs to assemble into 3D networks in engineered matrices and to respond to a hypoxic microenvironment is a significant advancement for autologous vascular therapy in diabetic patients and has broad importance for tissue engineering.