A Mechanism for Ultra-Slow Oscillations in the Cortical Default Network

When the brain is in its noncognitive “idling” state, functional MRI measurements reveal the activation of default cortical networks whose activity is suppressed during cognitive processing. This default or background mode is characterized by ultra-slow BOLD oscillations (∼0.05 Hz), signaling extremely slow cycling in cortical metabolic demand across distinct cortical regions. Here we describe a model of the cortex which predicts that slow cycling of cortical activity can arise naturally as a result of nonlinear interactions between temporal (Hopf) and spatial (Turing) instabilities. The Hopf instability is triggered by delays in the inhibitory postsynaptic response, while the Turing instability is precipitated by increases in the strength of the gap-junction coupling between interneurons. We comment on possible implications for slow dendritic computation and information processing.     

A comparison of the prognostic value of BNP versus NT-proBNP after hospitalisation for heart failure

Aims

Concentrations of circulating B?type natriuretic peptides provide important prognostic information in heart failure (HF) patients. We directly compared the prognostic performance of brain natriuretic peptide (BNP) versus N?terminal-proBNP (NT-proBNP) measurements in a large population of HF patients at hospital discharge after an admission for decompensated HF.

Methods and results

BNP and NT-proBNP were measured in 563 stable HF patients before discharge. All patients were followed for a fixed period of 18 months. The primary endpoint was time to first major event (HF hospitalisation or death).Patients were in NYHA class II (47%) or III/IV (53%) at discharge and the mean age of the patients was 71?±?11 years, 217 (39%) females, mean left ventricular ejection fraction was 0.32?±?0.14 and 234 (42%) had an ischaemic aetiology of HF. During the study, 236 patients (42%) reached the primary endpoint. Multivariate odds ratios of the primary endpoint for doubling of baseline levels of BNP and NT-proBNP were 1.46 (95% CI 1.19–1.80, p?<?0.001) and 1.45 (95% CI 1.18–1.78, p?<?0.001), respectively. The multivariable adjusted areas under the receiver-operating characteristic curve for prediction of the primary endpoint for doubling of BNP and NT-proBNP were 0.69 and 0.68, respectively. Direct comparison of the prognostic value of BNP and NT-proBNP did not reveal significant differences.

Conclusions

BNP and NT-proBNP at discharge for hospitalisation for HF are powerful, and equally strong and independent predictors of all-cause death and HF rehospitalisation.

     

Safety and efficacy of a device to narrow the coronary sinus for the treatment of refractory angina: A single-centre real-world experience

Objective

The coronary sinus Reducer is a recently introduced device to treat patients with severe angina symptoms refractory to optimal medical therapy and not amenable for conventional revascularisation. We aimed to assess the safety and efficacy of the Reducer in a real-world cohort of patients with refractory angina.

Methods

This is a single-centre retrospective registry. Patients with severe angina symptoms, objective evidence of myocardial ischaemia using any adequate non-invasive modality and without options for conventional revascularisation were regarded eligible for Reducer implantation.

Results

Twenty-three patients (74?% male, mean age 70?±?8 years, 91.3?% previous bypass surgery, 82.6?% previous percutaneous intervention, 47.8?% previous myocardial infarction, 52.2?% diabetes mellitus) underwent Reducer implantation. The safety endpoint (successful implantation of the first device without device-related adverse events) was met in all patients. After a median follow-up of 9 (8–14) months the efficacy (any reduction in Canadian Cardiovascular Society (CCS) class and revascularisation-free survival) was reached in 17 patients (74?%): 8 patients (34.8?%) improved by 1 CCS class, 7 (30.4?%) by 2 CCS classes and 2 (8.7?%) by 3 CCS classes. One patient died 4 months after implantation because of progressive heart failure (not associated with Reducer implantation).

Conclusion

In this single-centre real-world experience, Reducer implantation was safe and demonstrated excellent clinical efficacy in the treatment of refractory angina at mid-term follow-up.

     

High Algebraic Order Methods for the Numerical Solution of the Schrödinger Equation

Abstract

A family of new hybrid four-step tenth algebraic order methods with phase-lag of order 16(2)22 is developed for the numerical solution of the Schrödinger equation. Based on the new methods a variable-step procedure is introduced. Numerical illustrations obtained for the approximation of the phase shift problem for the well known case of the Lenard-Jones potential and for the numerical solution of the coupled equations arising from the Schrödinger equation show that these new methods are better than other finite difference methods.     

Universal Algorithm for Identification of Fractional Brownian Motion. A?Case of Telomere Subdiffusion

We present a systematic statistical analysis of the recently measured individual trajectories of fluorescently labeled telomeres in the nucleus of living human cells. The experiments were performed in the U2OS cancer cell line. We propose an algorithm for identification of the telomere motion. By expanding the previously published data set, we are able to explore the dynamics in six time orders, a task not possible earlier. As a result, we establish a rigorous mathematical characterization of the stochastic process and identify the basic mathematical mechanisms behind the telomere motion. We find that the increments of the motion are stationary, Gaussian, ergodic, and even more chaotic—mixing. Moreover, the obtained memory parameter estimates, as well as the ensemble average mean square displacement reveal subdiffusive behavior at all time spans. All these findings statistically prove a fractional Brownian motion for the telomere trajectories, which is confirmed by a generalized p-variation test. Taking into account the biophysical nature of telomeres as monomers in the chromatin chain, we suggest polymer dynamics as a sufficient framework for their motion with no influence of other models. In addition, these results shed light on other studies of telomere motion and the alternative telomere lengthening mechanism. We hope that identification of these mechanisms will allow the development of a proper physical and biological model for telomere subdynamics. This array of tests can be easily implemented to other data sets to enable quick and accurate analysis of their statistical characteristics.     

The use of microsatellite markers for the detection of genetic similarity among winter bread wheat lines for chromosome 3A

Previous studies with chromosome substitution and recombinant inbred chromosome lines identified that chromosome 3A of wheat cv. Wichita contains alleles that influence grain yield, yield components and agronomic performance traits relative to alleles on chromosome 3A of Cheyenne, a cultivar believed to be the founder parent of many Nebraska developed cultivars. This study was carried out to examine the genetic similarity among wheat cultivars based on the variation in chromosome 3A. Forty-eight cultivars, two promising lines and four substitution lines (in duplicate) were included in the study. Thirty-six chromosome 3A-specific and 12 group-3 barley simple sequence repeat (SSR) primer pairs were used. A total of 106 polymorphic bands were scored. Transferability of barley microsatellite markers to wheat was 73%. The coefficient of genetic distance (D) among the genotypes ranged from 0.40 to 0.91 and averaged D=0.66. Cluster analysis by the unweighted pair-group method with arithmetic averages showed one large and one small cluster with eight minor clusters in the large cluster. Several known pedigree relationships largely corresponded with the results of SSR clusters and principal coordinate analysis. Cluster analysis was also carried out by using 22 alleles that separate Wichita 3A from Cheyenne 3A, and three clusters were identified (a small cluster related to Cheyenne of mainly western Nebraska wheat cultivars; a larger, intermediate cluster with many modern Nebraska wheat cultivars; a large cluster related to Wichita with many modern high-yielding or Kansas wheat cultivars). Using three SSR markers that identify known agronomically important quantitative trait loci (QTL) regions, we again separated the cultivars into three main clusters that were related to Cheyenne or Wichita, or had a different 3A lineage. These results suggest that SSR markers linked to agronomically important QTLs are a valuable asset for estimating both genetic similarity for chromosome 3A and how the chromosome has been used in cultivar improvement.     

A genome-wide analysis of the expansin genes in Malus × Domestica

Expansins were first identified as cell wall-loosening proteins; they are involved in regulating cell expansion, fruits softening and many other physiological processes. However, our knowledge about the expansin family members and their evolutionary relationships in fruit trees, such as apple, is limited. In this study, we identified 41 members of the expansin gene family in the genome of apple (Malus × Domestica L. Borkh). Phylogenetic analysis revealed that expansin genes in apple could be divided into four subfamilies according to their gene structures and protein motifs. By phylogenetic analysis of the expansins in five plants (Arabidopsis, rice, poplar, grape and apple), the expansins were divided into 17 subgroups. Our gene duplication analysis revealed that whole-genome and chromosomal-segment duplications contributed to the expansion of Mdexpansins. The microarray and expressed sequence tag (EST) data showed that 34 Mdexpansin genes could be divided into five groups by the EST analysis; they may also play different roles during fruit development. An expression model for MdEXPA16 and MdEXPA20 showed their potential role in developing fruit. Overall, our study provides useful data and novel insights into the functions and regulatory mechanisms of the expansin genes in apple, as well as their evolution and divergence. As the first step towards genome-wide analysis of the expansin genes in apple, our results have established a solid foundation for future studies on the function of the expansin genes in fruit development.     

Increasing the efficiency of digitization workflows for herbarium specimens

The New York Botanical Garden Herbarium has been databasing and imaging its estimated 7.3 million plant specimens for the past 17 years. Due to the size of the collection, we have been selectively digitizing fundable subsets of specimens, making successive passes through the herbarium with each new grant. With this strategy, the average rate for databasing complete records has been 10 specimens per hour. With 1.3 million specimens databased, this effort has taken about 130,000 hours of staff time. At this rate, to complete the herbarium and digitize the remaining 6 million specimens, another 600,000 hours would be needed. Given the current biodiversity and economic crises, there is neither the time nor money to complete the collection at this rate.Through a combination of grants over the last few years, The New York Botanical Garden has been testing new protocols and tactics for increasing the rate of digitization through combinations of data collaboration, field book digitization, partial data entry and imaging, and optical character recognition (OCR) of specimen images. With the launch of the National Science Foundation's new Advancing Digitization of Biological Collections program, we hope to move forward with larger, more efficient digitization projects, capturing data from larger portions of the herbarium at a fraction of the cost and time.     

A regression-based analytic model for capacity planning of multi-tier applications

The multi-tier implementation has become the industry standard for developing scalable client-server enterprise applications. Since these applications are performance sensitive, effective models for dynamic resource provisioning and for delivering quality of service to these applications become critical. Workloads in such environments are characterized by client sessions of interdependent requests with changing transaction mix and load over time, making model adaptivity to the observed workload changes a critical requirement for model effectiveness. In this work, we apply a regression-based approximation of the CPU demand of client transactions on a given hardware. Then, we use this approximation in an analytic model of a simple network of queues, each queue representing a tier, and show the approximation’s effectiveness for modeling diverse workloads with a changing transaction mix over time. Using two case studies, we investigate factors that impact the efficiency and accuracy of the proposed performance prediction models. Experimental results show that this regression-based approach provides a simple and powerful solution for efficient capacity planning and resource provisioning of multi-tier applications under changing workload conditions.

Age and Sex Structured Model for Assessing the Demographic Impact of Mother-to-Child Transmission of HIV/AIDS

Age and sex structured HIV/AIDS model with explicit incubation period is proposed as a system of delay differential equations. The model consists of two age groups that are children (0–14 years) and adults (15–49 years). Thus, the model considers both mother-to-child transmission (MTCT) and heterosexual transmission of HIV in a community. MTCT can occur prenatally, at labour and delivery or postnatally through breastfeeding. In the model, we consider the children age group as a one-sex formulation and divide the adult age group into a two-sex structure consisting of females and males. The important mathematical features of the model are analysed. The disease-free and endemic equilibria are found and their stabilities investigated. We use the Lyapunov functional approach to show the local stability of the endemic equilibrium. Qualitative analysis of the model including positivity and boundedness of solutions, and persistence are also presented. The basic reproductive number (ℛ₀) for the model shows that the adult population is responsible for the spread HIV/AIDS epidemic, thus up-to-date developed HIV/AIDS models to assess intervention strategies have focused much on heterosexual transmission by the adult population and the children population has received little attention. We numerically analyse the HIV/AIDS model to assess the community benefits of using antiretroviral drugs in reducing MTCT and the effects of breastfeeding in settings with high HIV/AIDS prevalence ratio using demographic and epidemiological parameters for Zimbabwe.     

Impacts of Incubation Delay on the Dynamics of an Eco-Epidemiological System—A Theoretical Study

Parasite and predator play significant role in trophic interaction, productivity and stability of an ecosystem. In this paper, we have studied a host-parasite-predator interaction that incorporates incubation delay. How the qualitative and quantitative behaviors of the system alter with the incubation delay have been discussed both from mathematical and biological point of views. It is observed that for a lower infection rate, the system is stable for all delays; but for a higher infection rate, there exists a threshold value of the delay above which the system is unstable and below which the system is stable leading to the persistence of all the species. Also, the instability arising from the incubation delay may be controlled if somehow the growth rate of predator population is increased. Numerical studies have also been performed to illustrate different analytical findings. Research is supported by UGC, India; F No. 32-173/2006(SR).     

A Dynamical Study of a Cellular Automata Model of the Spread of HIV in a Lymph Node

We conduct a mathematical study of a cellular automata model of the spread of the HIV virus in a lymph node. The model was proposed by Zorzenon dos Santos and Coutinho and captures the unique time scale of the viral spread. We give some rigorous mathematical results about the time scales and other dynamical aspects of the model as well as discuss parameter and model changes and their consequences.     

A multi-strategy collaborative prediction model for the runtime of online tasks in computing cluster/grid

An efficient function of a complicated or dynamic high performance computing environment requires the scheduler to dispatch the submitted tasks according to the identification of the idling resources. A derivative problem is to provide accurate forecasts of the tasks runtimes. This is usually needed to assist scheduling policies and fine tune scheduling decisions, and also used for future planning of resource allocation when conducting advance reservation. However, the characteristics of the existing prediction strategies determine that the sole strategy is not appropriate for all kinds of heterogeneous tasks. Aiming at this problem, a multi-strategy collaborative prediction model (MSCPM) for the runtime of online tasks is proposed, and a novel concept named Prediction Accuracy Assurance (PAA) as a criterion is introduced to quantitatively evaluate the precision of the prediction runtime provided by a specific prediction strategy.     

In Search for the Genetic Basis of Quality of Life in Healthy Swedish Women—A GWAS Study Using the iCOGS Custom Genotyping Array

Background

Quality of life (QoL) is increasingly measured in both research and clinical practice. QoL-assessments are built on a long, empirically-based, and stringent approach. There is ample evidence that QoL is, in part, heritable. We therefore performed a GWAS relating genetic variation to QoL in healthy females.

Methods

In 5,142 healthy females, background characteristics (e.g. demographic, clinical, lifestyle and psychological factors) and QoL by means of the EORTC QLQ-C30 were measured. Moreover, women were genotyped using a custom array including ~210,000 single nucleotide polymorphisms (SNPs). Initially, SNPs were related to each QoL-domain, by means of partially adjusted (controlling for age and population stratification) and fully adjusted (controlling for age, population stratification, and background characteristics) regression analyses. Additionally, gene-based analyses were performed relating the combined effect of SNPs within each gene to QoL using the statistical software package VEGAS.

Results

None of the associations between QoL and genetic variation (i.e. individual SNPs and genes) reached the bonferroni corrected significance level.

Conclusion

Reasons for a lack of association between genetic markers and QoL could be low variation in QoL-scores; selecting genetic markers not tagging QoL; or that the genetic effect that impacts one’s QoL is mediated through biological pathways rather than the effect of single SNPs or genes. Therefore, we opt for a pathway-based or system biology approach as a complementary and powerful approach to analyze the combined effect of genes and their biological implications in future studies focusing on QoL-issues.     

On the Number of Binary Characters Needed to Recover a Phylogeny Using Maximum Parsimony

We give an explicit construction to solve a conjecture of Mike Steel and David Penny that any phylogeny involving N taxa can be recovered unambiguously using on the order of log N binary characters and the method of maximum parsimony. Biologically, this means that homoplasy need not be a deterrent to parsimony methods. Some patterns of homoplasy are phylogenetically informative and can exponentially reduce the amount of data needed to resolve a phylogeny.     

RBE of 25 kV X-rays for the survival and induction of micronuclei in the human mammary epithelial cell line MCF-12A

The broad application of low energy X-rays below about 50 keV in radiation therapy and diagnostics and especially in mammography substantiates the precise determination of their relative biological effectiveness (RBE). A quality factor of 1 is stated for photons of all energies in the International Commission on Radiological Protection Recommendations. However, the RBE of low-energy X-rays compared to high-energy photons was found to be dependent on photon energy, cell line and endpoints studied, hence varying from less than one up to about four. In the present study, the human mammary epithelial cell line MCF-12A has been chosen due to the implementation of the results in the estimation of risk from mammography procedures. The RBE of 25 kV X-rays (W anode, 0.3 mm Al filter) relative to 200 kV X-rays (W anode, 0.5 mm Cu filter) was determined for clonogenic survival in the dose range 1–10 Gy and micronuclei (MN) induction in the range 0.5–3.5 Gy. The RBE for clonogenic survival was found to be significantly higher than 1 for surviving fractions in the range 0.005 < S < 0.2. The RBE decreased with increasing survival, with an RBE_0.1 at 10% survival of 1.13 ± 0.03. The effectiveness of soft X-rays for MN induction was found to be 1.40 ± 0.07 for the fraction of binuclear cells (BNC) with MN and 1.44 ± 0.17 for the number of MN per BNC. In contrast, the RBE determined from the number of MN per MN-bearing BNC was found to be 1.08 ± 0.32. This indicates that the effectiveness of 25 kV X-rays results from an increase in the number of damaged cells, which, however, do not have higher number of MN per cell.     

An Empirical Exploration of the (δμ)2 Genetic Distance for 213 Human Microsatellite Markers

Microsatellites are now used ubiquitously as genetic markers. One important application is to the assessment of population subdivision and phylogenetic relatedness. Such applications require a method of estimation of genetic distance. Here we examine the most widely used measure of microsatellite genetic distance, Goldstein et al.'s delta-mu squared ([delta mu]2), with respect to a large data set of 213 markers typed across samples from four diverse human populations. We find that (delta mu)2 yields plausible interpopulation distances. For the first time, we report significant interpopulation differences in mean microsatellite length, although the effect of these differences on (delta mu)2 is negligible. However, we also show that the method is extremely sensitive to one or two loci that contribute extreme values, even when a sample size of >200 loci is used. Some of these extreme loci can be removed on the grounds that some alleles carry large indels, but for others there is no clear justification for exclusion a priori. Our data suggest a rather recent African/non-African split, with an upper limit of some 70,000-80,000 years ago.