Intrinsic aerobic capacity sets a divide for aging and longevity

<p><b>Rationale:</b> Low aerobic exercise capacity is a powerful predictor of premature morbidity and mortality for healthy adults as well as those with cardiovascular disease. For aged populations, poor performance on treadmill or extended walking tests indicates closer proximity to future health declines. Together, these findings suggest a fundamental connection between aerobic capacity and longevity.</p> <p><b>Objectives:</b> Through artificial selective breeding, we developed an animal model system to prospectively test the association between aerobic exercise capacity and survivability (aerobic hypothesis).</p> <p><b>Methods and Results:</b> Laboratory rats of widely diverse genetic backgrounds (N:NIH stock) were selectively bred for low or high intrinsic (inborn) treadmill running capacity. Cohorts of male and female rats from generations 14, 15, and 17 of selection were followed for survivability and assessed for age-related declines in cardiovascular fitness including maximal oxygen uptake (VO<sub>2max</sub>), myocardial function, endurance performance, and change in body mass. Median lifespan for low exercise capacity rats was 28% to 45% shorter than high capacity rats (hazard ratio, 0.06; P<0.001). VO<sub>2max</sub>, measured across adulthood was a reliable predictor of lifespan (P<0.001). During progression from adult to old age, left ventricular myocardial and cardiomyocyte morphology, contractility, and intracellular Ca<sup>2+</sup> handling in both systole and diastole, as well as mean blood pressure, were more compromised in rats bred for low aerobic capacity. Physical activity levels, energy expenditure (Vo<sub>2</sub>), and lean body mass were all better sustained with age in rats bred for high aerobic capacity.</p> <p><b>Conclusions:</b> These data obtained from a contrasting heterogeneous model system provide strong evidence that genetic segregation for aerobic exercise capacity can be linked with longevity and are useful for deeper mechanistic exploration of aging.</p&gt

Two-level pipelined systolic array graphics engine

The authors report a VLSI design of an advanced systolic array graphics (SAG) engine built from pipelined functional units which can generate realistic images interactively for high-resolution displays. They introduce a structured frame store system as an environment for the advanced SAG engine and present the principles and architecture of the advanced SAG engine. They introduce pipelined functional units into this SAG engine to meet the performance requirements. This is done by a formal approach where the original systolic array is represented at bit level by a finite, vertex-weighted, edge-weighted, directed graph. Two architectures built from pipelined functional units are described. A prototype containing nine processing elements was fabricated in a 1.6-¿m CMOS technolog

Systolic and Hyper-Systolic Algorithms for the Gravitational N-Body Problem, with an Application to Brownian Motion

A systolic algorithm rhythmically computes and passes data through a network of processors. We investigate the performance of systolic algorithms for implementing the gravitational N-body problem on distributed-memory computers. Systolic algorithms minimize memory requirements by distributing the particles between processors. We show that the performance of systolic routines can be greatly enhanced by the use of non-blocking communication, which allows particle coordinates to be communicated at the same time that force calculations are being carried out. Hyper-systolic algorithms reduce the communication complexity at the expense of increased memory demands. As an example of an application requiring large N, we use the systolic algorithm to carry out direct-summation simulations using 10^6 particles of the Brownian motion of the supermassive black hole at the center of the Milky Way galaxy. We predict a 3D random velocity of 0.4 km/s for the black hole.Comment: 33 pages, 10 postscript figure

Genetic variants of Y chromosome are associated with a protective lipid profile in black men

Objective— Gender and ethnicity modulate the phenotypic expression of cardiovascular risk factors. In particular, men are at higher risk of developing cardiovascular diseases compared to women, whereas black populations of African origin display reduced mortality from coronary heart disease (CHD) as compared to both whites and South Asians. Because the male-specific region (MSY) of the human Y chromosome is an obvious candidate for gender-related differences in the development of cardiovascular diseases, we aimed to identify genetic variants of MSY influencing cardiovascular risk profile in different ethnic groups. Methods and Results— We genotyped 4 polymorphisms of MSY (HindIII±, rs768983 of TBL1Y, rs3212292 of USP9Y, and rs9341273 of UTY genes) in 579 men of different ethnic groups (blacks, South Asians, and whites) from UK and in 301 whites in Italy. We found that the TBL1YA USP9YA haplotype, present only in blacks in whom it represents the most frequent allelic combinations (AA: n=125; all other combinations: n=45), was associated with lower levels of triglycerides (P=0.025) and higher levels of HDL-cholesterol (P=0.005) as compared to the other haplotypes. Conclusion— The TBL1YA USP9YA haplotype of the Y chromosome, present only in black people of African origin, attributes a favorable lipoprotein pattern, likely to contribute to their reduced susceptibility to coronary heart disease. The study evaluated the association of genetic variants of the male-specific region of the Y chromosome with cardiovascular risk factors in different ethnic groups. The most frequently observed haplotype in black people was associated with a favorable lipoprotein pattern, thus contributing to the lower rate of cardiovascular diseases in blacks

Changes and classification in myocardial contractile function in the left ventricle following acute myocardial infarction

In this research, we hypothesized that novel biomechanical parameters are discriminative in patients following acute ST-segment elevation myocardial infarction (STEMI). To identify these biomechanical biomarkers and bring computational biomechanics ‘closer to the clinic’, we applied state-of-the-art multiphysics cardiac modelling combined with advanced machine learning and multivariate statistical inference to a clinical database of myocardial infarction. We obtained data from 11 STEMI patients (ClinicalTrials.gov NCT01717573) and 27 healthy volunteers, and developed personalized mathematical models for the left ventricle (LV) using an immersed boundary method. Subject-specific constitutive parameters were achieved by matching to clinical measurements. We have shown, for the first time, that compared with healthy controls, patients with STEMI exhibited increased LV wall active tension when normalized by systolic blood pressure, which suggests an increased demand on the contractile reserve of remote functional myocardium. The statistical analysis reveals that the required patient-specific contractility, normalized active tension and the systolic myofilament kinematics have the strongest explanatory power for identifying the myocardial function changes post-MI. We further observed a strong correlation between two biomarkers and the changes in LV ejection fraction at six months from baseline (the required contractility (r = − 0.79, p < 0.01) and the systolic myofilament kinematics (r = 0.70, p = 0.02)). The clinical and prognostic significance of these biomechanical parameters merits further scrutinization

Embedded FIR filter design for real-time refocusing using a standard plenoptic video camera

Copyright 2014 Society of Photo-Optical Instrumentation Engineers and IS&T—The Society for Imaging Science and Technology. One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper are prohibited.A novel and low-cost embedded hardware architecture for real-time refocusing based on a standard plenoptic camera is presented in this study. The proposed layout design synthesizes refocusing slices directly from micro images by omitting the process for the commonly used sub-aperture extraction. Therefore, intellectual property cores, containing switch controlled Finite Impulse Response (FIR) filters, are developed and applied to the Field Programmable Gate Array (FPGA) XC6SLX45 from Xilinx. Enabling the hardware design to work economically, the FIR filters are composed of stored product as well as upsampling and interpolation techniques in order to achieve an ideal relation between image resolution, delay time, power consumption and the demand of logic gates. The video output is transmitted via High-Definition Multimedia Interface (HDMI) with a resolution of 720p at a frame rate of 60 fps conforming to the HD ready standard. Examples of the synthesized refocusing slices are presented

Association of PET-measured myocardial flow reserve with echocardiography-estimated pulmonary artery systolic pressure in patients with hypertrophic cardiomyopathy

BackgroundPulmonary hypertension (PH) is a known complication of HCM and is a strong predictor of mortality. We aim to investigate the relationship between microvascular dysfunction measured by quantitative PET and PH in HCM patients.MethodsEighty-nine symptomatic HCM patients were included in the study. Each patient underwent two 20-min 13N-NH3 dynamic PET scans for rest and stress conditions, respectively. A 2-tissue irreversible compartmental model was used to fit the segments time activity curves for estimating segmental and global myocardial blood flow (MBF) and myocardial flow reserve (MFR). Echocardiographic derived PASP was utilized to estimate PH.ResultsPatients were categorized into two groups across PASP: PH (PASP > 36 mmHg) and no-PH (PASP ≤ 36 mmHg). patients with PH had larger left atrium, ratio of higher inflow early diastole (E) and atrial contraction (A) waves, E/A, and ratio of inflow and peak early diastolic waves, E/e', significantly reduced global stress MBF (1.85 ± 0.52 vs. 2.13 ± 0.56 ml/min/g; p = 0.024) and MFR (2.21 ± 0.57 vs. 2.62 ± 0.75; p = 0.005), while the MBFs at rest between the two groups were similar. There were significant negative correlations between global stress MBF/MFR and PASP (stress MBF: r = -0.23, p = 0.03; MFR: r = -0.32, p = 0.002); for regional MBF and MFR measurements, the highest linear correlation coefficients were observed in the septal wall (stress MBF: r = -0.27, p = 0.01; MFR: r = -0.31, p = 0.003). Global MFR was identified to be independent predictor for PH in multivariate regression analysis.ConclusionEchocardiography-derived PASP is negatively correlated with global MFR measured by 13N-NH3 dynamic PET. Global MFR is suggested to be an index of PH in HCM patients.</div

Two-dimensional DCT/IDCT architecture

A fully parallel architecture for the computation of a two-dimensional (2-D) discrete cosine transform (DCT), based on row-column decomposition is presented. It uses the same one dimensional (1-D) DCT unit for the row and column computations and (N2+N) registers to perform the transposition. It possesses features of regularity and modularity, and is thus well suited for VLSI implementation. It can be used for the computation of either the forward or the inverse 2-D DCT. Each 1-D DCT unit uses N fully parallel vector inner product (VIP) units. The design of the VIP units is based on a systematic design methodology using radix-2” arithmetic, which allows partitioning of the elements of each vector into small groups. Array multipliers without the final adder are used to produce the different partial product terms. This allows a more efficient use of 4:2 compressors for the accumulation of the products in the intermediate stages and reduces the number of accumulators from N to one. Using this procedure, the 2-D DCT architecture requires less than N2 multipliers (in terms of area occupied) and only 2N adders. It can compute a N x N-point DCT at a rate of one complete transform per N cycles after an appropriate initial delay

Differences in physical activity time-use composition associated with cardiometabolic risks

This study investigates the association between the overall physical activity composition of the day (sedentary behavior (SB), light intensity physical activity (LIPA) and moderate-to-vigorous physical activity (MVPA)) and cardiometabolic health, and examines whether improved health can be associated with replacing SB with LIPA. A cross-sectional analysis of the Health Survey for England 2008 on N = 1411 adults was undertaken using a compositional analysis approach to examine the relationship between cardiometabolic risk biomarkers and physical activity accounting for co-dependency between relative amounts of time spent in different behavior. Daily time spent in SB, LIPA and MVPA was determined from waist-mounted accelerometry data (Actigraph GT1M) and modelled against BMI, waist circumference, waist-to-hip ratio, blood pressure, total and HDL cholesterol, HbA1c, and VO2 maximum. The composition of time spent in SB, LIPA and MVPA was statistically significantly associated with BMI, waist circumference, waist-to-hips ratio, HDL cholesterol and VO2 maximum (p < 0.001), but not HbA1c, systolic and diastolic blood pressure, or total cholesterol. Increase of relative time spent in MVPA was beneficially associated with obesity markers, HDL cholesterol, and VO2 maximum, and SB with poorer outcomes. The association of changes in LIPA depended on whether it displaced MVPA or SB. Increasing the proportion of MVPA alone may have the strongest potential association with adiposity outcomes and HDL cholesterol but similar outcomes could also be associated with a lower quantity of MVPA provided a greater quantity of SB is replaced overall with LIPA (around 10.5 min of LIPA is equivalent to 1 min of MVPA). Keywords: MVPA, Sedentary behavior, Physical activity, Compositional data analysis, Cardiometabolic health, Adipoisit