Nonlinear modeling of cardiovascular response to exercise

This study experimentally investigates the relationships between central cardiovascular variables and oxygen uptake based on nonlinear analysis and modeling. Ten healthy subjects were studied using cycle-ergometry exercise tests with constant workloads ranging from 25 Watt to 125 Watt. Breath by breath gas exchange, heart rate, cardiac output, stroke volume and blood pressure were measured at each stage. The modeling results proved that the nonlinear modeling method (Support Vector Regression) outperforms traditional regression method (reducing Estimation Error between 59% and 80%, reducing Testing Error between 53% and 72%) and is the ideal approach in the modeling of physiological data, especially with small training data set

Suppression of diet-induced hypercholesterolemia by turtle jelly, a traditional Chinese functional food, in rats

Author name used in this publication: Jian-Hong WuAuthor name used in this publication: Daniel Kam-Wah Mok2012-2013 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Associations of apolipoprotein E exon 4 and lipoprotein lipase S447X polymorphisms with acute ischemic stroke and myocardial infarction

Background: Because apolipoprotein E (apoE) and lipopoprotein lipase (LPL) polymorphisms interact with each other and with other factors to affect lipid metabolism, we sought to determine their separate and combined effects in association with ischemic vascular disease. Methods: We performed a case-control study of 816 subjects: 246 acute ischemic stroke patients, 234 acute myocardial infarction patients, and 336 controls. APOE exon 4 and LPL S447X genotypes were determined. Results: APOE ε2 and ε4 homozygotes were increased in stroke (4.5% vs. 1.0%, p = 0.008), while in myocardial infarction the ε4 allele was increased (12.6% vs. 9.5%, p = 0.006) but ε2 was decreased (3.7% vs. 12.1%, p = 0.000006). For subjects with either APOE ε2 or ε4 alleles, LPL X alleles were increased in vascular disease (OR = 2.2, p = 0.01). LPL X alleles displayed opposite tendencies toward association with disease when subjects were divided by sex, smoking, or APOE genotype. Meta-analysis and regression analysis of previous studies supported the sex and smoking dichotomies. Conclusion: This is the first report of an association of vascular disease with an interaction of APOE exon 4 and LPL S447X genotypes. Therefore, APOE genotypes and LPL S447X interactions with apoE, sex, and smoking may affect the risk of myocardial infarction and ischemic stroke. © 2006 by Walter de Gruyter.published_or_final_versio

Role of miR-338-5p as a novel modulator of chemoresistannce in esophageal cancer

Conference Theme: Anticancer Drug Action and Drug Resistance: from Cancer Biology to the ClinicINTRODUCTION: Multimodal treatment incorporating surgical resection and the use of chemotherapeutic drugs is commonly used in the management of esophageal cancer. However, resistance to chemotherapy drugs may contribute to poor treatment outcome and cancer recurrence. Increasing evidence suggests that miRNAs regulate the sensitivity of cancer to chemotherapeutic drugs. 5-Fluorouracil (5-FU) is an antimetabolite agent ...postprin

Populating the swampland: the case of U(1)^496 and E_8 x U(1)^248

For d=10 N=1 SUGRA coupled to d=10 N=1 SYM, anomaly cancellation places severe constraints on the allowed gauge groups. Besides the ones known to appear in string theory, only U(1)^496 and E_8 x U(1)^248 are allowed. There are no known theories of quantum gravity that reduce in some limit to these two last supergravity theories, and in this note I present some evidence that those quantum theories might not exist. The first observation is that, upon compactification, requring that the quantum theory possesses a moduli space with finite volume typically implies the existence of singularities where the 4d gauge group is enhanced, but for these two theories that gauge enhancement is problematic from the 10d point of view. I also point out that while these four supergravity theories present repulson-type singularities, the known mechanism that repairs those singularities for the first two - the non-Abelian enhancon - is not available for the last two theories. In short, these two supergravity theories might be too Abelian for their own good.Comment: 12 page

A scalar field condensation instability of rotating anti-de Sitter black holes

Near-extreme Reissner-Nordstrom-anti-de Sitter black holes are unstable against the condensation of an uncharged scalar field with mass close to the Breitenlohner-Freedman bound. It is shown that a similar instability afflicts near-extreme large rotating AdS black holes, and near-extreme hyperbolic Schwarzschild-AdS black holes. The resulting nonlinear hairy black hole solutions are determined numerically. Some stability results for (possibly charged) scalar fields in black hole backgrounds are proved. For most of the extreme black holes we consider, these demonstrate stability if the ``effective mass" respects the near-horizon BF bound. Small spherical Reissner-Nordstrom-AdS black holes are an interesting exception to this result.Comment: 34 pages; 13 figure

SRA-Domain Proteins Required for DRM2-Mediated De Novo DNA Methylation

De novo DNA methylation and the maintenance of DNA methylation in asymmetrical sequence contexts is catalyzed by homologous proteins in plants (DRM2) and animals (DNMT3a/b). In plants, targeting of DRM2 depends on small interfering RNAs (siRNAs), although the molecular details are still unclear. Here, we show that two SRA-domain proteins (SUVH9 and SUVH2) are also essential for DRM2-mediated de novo and maintenance DNA methylation in Arabidopsis thaliana. At some loci, SUVH9 and SUVH2 act redundantly, while at other loci only SUVH2 is required, and this locus specificity correlates with the differing DNA-binding affinity of the SRA domains within SUVH9 and SUVH2. Specifically, SUVH9 preferentially binds methylated asymmetric sites, while SUVH2 preferentially binds methylated CG sites. The suvh9 and suvh2 mutations do not eliminate siRNAs, suggesting a role for SUVH9 and SUVH2 late in the RNA-directed DNA methylation pathway. With these new results, it is clear that SRA-domain proteins are involved in each of the three pathways leading to DNA methylation in Arabidopsis

Characterization of Full-Length Enterovirus 71 Strains from Severe and Mild Disease Patients in Northeastern China

Human enterovirus 71 (EV71)-associated hand, foot, and mouth disease (HFMD) has been a leading cause of childhood infection in China since 2008. Epidemic and molecular characteristics of HFMD have been examined in many areas of China, including the central and southern regions. However, clinical and genetic characterization of EV71 in the northeastern region of China is scarce. In this study, a series of analyses were performed on seven full-length EV71 sequences from HFMD patients who had either severe or mild disease. We have determined that these seven circulating EV71 viruses from Changchun, China are actually complex recombinant viruses involving multiple type A human enterovirus (HEV). Classified as EV71 subtype C4 (EV71 C4), these Changchun EV71 viruses contain genetic recombination events between the CA4, CA5, EV71B4 and EV71C1 strains. Most of the structural protein region (P1) of these viruses resembled that of the prototype EV71 C1 strains. The non-structural protein domains (P2 and P3) showed a high degree of similarity with CA4, CA5 and EV71 B4 in different regions. The 5′UTR had unclassified recombination,while partial 3D region of these viruses showed a high degree of similarity to CA16. Phylogenetic analysis of full-length or partial sequences of isolates from severe or mild disease patients in Changchun always formed a single cluster in various phylogenetic analyses of different genomic regions, suggesting that all seven strains originated from one single common ancestor. There was no correlation between viral genomic sequence and virulence. Thus, we found that circulating recombinant forms of EV71 are prevalent among HFMD patients in Northeastern China. The existence of a unique cluster of EV71 related viruses in Northeast China has important implications for vaccine development that would address the increasing prevalence of HFMD

Automated and unsupervised detection of malarial parasites in microscopic images

<p>Abstract</p> <p>Background</p> <p>Malaria is a serious infectious disease. According to the World Health Organization, it is responsible for nearly one million deaths each year. There are various techniques to diagnose malaria of which manual microscopy is considered to be the gold standard. However due to the number of steps required in manual assessment, this diagnostic method is time consuming (leading to late diagnosis) and prone to human error (leading to erroneous diagnosis), even in experienced hands. The focus of this study is to develop a robust, unsupervised and sensitive malaria screening technique with low material cost and one that has an advantage over other techniques in that it minimizes human reliance and is, therefore, more consistent in applying diagnostic criteria.</p> <p>Method</p> <p>A method based on digital image processing of Giemsa-stained thin smear image is developed to facilitate the diagnostic process. The diagnosis procedure is divided into two parts; enumeration and identification. The image-based method presented here is designed to automate the process of enumeration and identification; with the main advantage being its ability to carry out the diagnosis in an unsupervised manner and yet have high sensitivity and thus reducing cases of false negatives.</p> <p>Results</p> <p>The image based method is tested over more than 500 images from two independent laboratories. The aim is to distinguish between positive and negative cases of malaria using thin smear blood slide images. Due to the unsupervised nature of method it requires minimal human intervention thus speeding up the whole process of diagnosis. Overall sensitivity to capture cases of malaria is 100% and specificity ranges from 50-88% for all species of malaria parasites.</p> <p>Conclusion</p> <p>Image based screening method will speed up the whole process of diagnosis and is more advantageous over laboratory procedures that are prone to errors and where pathological expertise is minimal. Further this method provides a consistent and robust way of generating the parasite clearance curves.</p

Differential hypoglycaemic, anorectic, autonomic and emetic effects of the glucagon-like peptide receptor agonist, exendin-4, in the conscious telemetered ferret.

Background: Rodents are incapable of emesis and consequently the emetic potential of glucagon-like peptide-1 receptor (GLP-1R) agonists in studies designed to assess a potential blood glucose lowering action of the compound was missed. Therefore, we investigated if the ferret, a carnivore with demonstrated translation capability in emesis research, would identify the emetic potential of the GLP-1R agonist, exendin-4, and any associated effects on gastric motor function, appetite and cardiovascular homeostasis. Methods: The biological activity of the GLP-1R ligands was investigated in vivo using a glucose tolerance test in pentobarbitone-anesthetised ferrets and in vitro using organ bath studies. Radiotelemetry was used to investigate the effect of exendin-4 on gastric myoelectric activity (GMA) and cardiovascular function in conscious ferrets; behaviour was also simultaneously assessed. Western blot was used to characterize GLP-1R distribution in the gastrointestinal and brain tissues. Results: In anesthetised ferrets, exendin-4 (30 nmol/kg, s.c.) reduced experimentally elevated blood glucose levels by 36.3%, whereas the GLP-1R antagonist, exendin (9–39) (300 nmol/kg, s.c.) antagonised the effect and increased AUC0–120 by 31.0% when injected alone (P < 0.05). In animals with radiotelemetry devices, exendin-4 (100 nmol/kg, s.c.) induced emesis in 1/9 ferrets, but inhibited food intake and decreased heart rate variability (HRV) in all animals (P < 0.05). In the animals not exhibiting emesis, there was no effect on GMA, mean arterial blood pressure, heart rate, or core body temperature. In the ferret exhibiting emesis, there was a shift in the GMA towards bradygastria with a decrease in power, and a concomitant decrease in HRV. Western blot revealed GLP-1R throughout the gastrointestinal tract but exendin-4 (up to 300 nM) and exendin (9–39), failed to contract or relax isolated ferret gut tissues. GLP-1R were found in all major brain regions and the levels were comparable those in the vagus nerve. Conclusions: Peripherally administered exendin-4 reduced blood glucose and inhibited feeding with a low emetic potential similar to that in humans (11% vs 12.8%). A disrupted GMA only occurred in the animal exhibiting emesis raising the possibility that disruption of the GMA may influence the probability of emesis occurring in response to treatment with GLP-1R agonists