On Non-Elitist Evolutionary Algorithms Optimizing Fitness Functions with a Plateau

We consider the expected runtime of non-elitist evolutionary algorithms (EAs), when they are applied to a family of fitness functions with a plateau of second-best fitness in a Hamming ball of radius r around a unique global optimum. On one hand, using the level-based theorems, we obtain polynomial upper bounds on the expected runtime for some modes of non-elitist EA based on unbiased mutation and the bitwise mutation in particular. On the other hand, we show that the EA with fitness proportionate selection is inefficient if the bitwise mutation is used with the standard settings of mutation probability.Comment: 14 pages, accepted for proceedings of Mathematical Optimization Theory and Operations Research (MOTOR 2020). arXiv admin note: text overlap with arXiv:1908.0868

Hemodynamic latency is associated with reduced intelligence across the lifespan: an fMRI DCM study of aging, cerebrovascular integrity, and cognitive ability

Changes in neurovascular coupling are associated with both Alzheimer’s disease and vascular dementia in later life, but this may be confounded by cerebrovascular risk. We hypothesized that hemodynamic latency would be associated with reduced cognitive functioning across the lifespan, holding constant demographic and cerebrovascular risk. In 387 adults aged 18–85 (mean = 48.82), dynamic causal modeling was used to estimate the hemodynamic response function in the left and right V1 and V3-ventral regions of the visual cortex in response to a simple checkerboard block design stimulus with minimal cognitive demands. The hemodynamic latency (transit time) in the visual cortex was used to predict general cognitive ability (Full-Scale IQ), controlling for demographic variables (age, race, education, socioeconomic status) and cerebrovascular risk factors (hypertension, alcohol use, smoking, high cholesterol, BMI, type 2 diabetes, cardiac disorders). Increased hemodynamic latency in the visual cortex predicted reduced cognitive function (p < 0.05), holding constant demographic and cerebrovascular risk. Increased alcohol use was associated with reduced overall cognitive function (Full Scale IQ 2.8 pts, p < 0.05), while cardiac disorders (Full Scale IQ 3.3 IQ pts; p < 0.05), high cholesterol (Full Scale IQ 3.9 pts; p < 0.05), and years of education (2 IQ pts/year; p < 0.001) were associated with higher general cognitive ability. Increased hemodynamic latency was associated with reduced executive functioning (p < 0.05) as well as reductions in verbal concept formation (p < 0.05) and the ability to synthesize and analyze abstract visual information (p < 0.01). Hemodynamic latency is associated with reduced cognitive ability across the lifespan, independently of other demographic and cerebrovascular risk factors. Vascular health may predict cognitive ability long before the onset of dementias

A novel PKC activating molecule promotes neuroblast differentiation and delivery of newborn neurons in brain injuries

Neural stem cells are activated within neurogenic niches in response to brain injuries. This results in the production of neuroblasts, which unsuccessfully attempt to migrate toward the damaged tissue. Injuries constitute a gliogenic/non-neurogenic niche generated by the presence of anti-neurogenic signals, which impair neuronal differentiation and migration. Kinases of the protein kinase C (PKC) family mediate the release of growth factors that participate in different steps of the neurogenic process, particularly, novel PKC isozymes facilitate the release of the neurogenic growth factor neuregulin. We have demonstrated herein that a plant derived diterpene, (EOF2; CAS number 2230806-06-9), with the capacity to activate PKC facilitates the release of neuregulin 1, and promotes neuroblasts differentiation and survival in cultures of subventricular zone (SVZ) isolated cells in a novel PKC dependent manner. Local infusion of this compound in mechanical cortical injuries induces neuroblast enrichment within the perilesional area, and noninvasive intranasal administration of EOF2 promotes migration of neuroblasts from the SVZ towards the injury, allowing their survival and differentiation into mature neurons, being some of them cholinergic and GABAergic. Our results elucidate the mechanism of EOF2 promoting neurogenesis in injuries and highlight the role of novel PKC isozymes as targets in brain injury regeneration

Runtime analysis of non-elitist populations: from classical optimisation to partial information

Although widely applied in optimisation, relatively little has been proven rigorously about the role and behaviour of populations in randomised search processes. This paper presents a new method to prove upper bounds on the expected optimisation time of population-based randomised search heuristics that use non-elitist selection mechanisms and unary variation operators. Our results follow from a detailed drift analysis of the population dynamics in these heuristics. This analysis shows that the optimisation time depends on the relationship between the strength of the selective pressure and the degree of variation introduced by the variation operator. Given limited variation, a surprisingly weak selective pressure suffices to optimise many functions in expected polynomial time. We derive upper bounds on the expected optimisation time of non-elitist Evolutionary Algorithms (EA) using various selection mechanisms, including fitness proportionate selection. We show that EAs using fitness proportionate selection can optimise standard benchmark functions in expected polynomial time given a sufficiently low mutation rate. As a second contribution, we consider an optimisation scenario with partial information, where fitness values of solutions are only partially available. We prove that non-elitist EAs under a set of specific conditions can optimise benchmark functions in expected polynomial time, even when vanishingly little information about the fitness values of individual solutions or populations is available. To our knowledge, this is the first runtime analysis of randomised search heuristics under partial information

Counter-current chromatography for the separation of terpenoids: A comprehensive review with respect to the solvent systems employed

Copyright @ 2014 The Authors.This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.Natural products extracts are commonly highly complex mixtures of active compounds and consequently their purification becomes a particularly challenging task. The development of a purification protocol to extract a single active component from the many hundreds that are often present in the mixture is something that can take months or even years to achieve, thus it is important for the natural product chemist to have, at their disposal, a broad range of diverse purification techniques. Counter-current chromatography (CCC) is one such separation technique utilising two immiscible phases, one as the stationary phase (retained in a spinning coil by centrifugal forces) and the second as the mobile phase. The method benefits from a number of advantages when compared with the more traditional liquid-solid separation methods, such as no irreversible adsorption, total recovery of the injected sample, minimal tailing of peaks, low risk of sample denaturation, the ability to accept particulates, and a low solvent consumption. The selection of an appropriate two-phase solvent system is critical to the running of CCC since this is both the mobile and the stationary phase of the system. However, this is also by far the most time consuming aspect of the technique and the one that most inhibits its general take-up. In recent years, numerous natural product purifications have been published using CCC from almost every country across the globe. Many of these papers are devoted to terpenoids-one of the most diverse groups. Naturally occurring terpenoids provide opportunities to discover new drugs but many of them are available at very low levels in nature and a huge number of them still remain unexplored. The collective knowledge on performing successful CCC separations of terpenoids has been gathered and reviewed by the authors, in order to create a comprehensive document that will be of great assistance in performing future purifications. © 2014 The Author(s)

Anterior interosseous nerve syndrome: retrospective analysis of 14 patients

Introduction: The anterior interosseous nerve (AIN) is a only motor nerve innervating the deep muscles of the forearm. Its compression is rare. We present a retrospective analysis of 14 patients with an AIN syndrome with a variety of clinical manifestations who underwent operative and conservative treatment. Patients and methods: Fourteen patients (six female, eight male, mean age 48 ± 9 years) were included. In six patients, the right limb was affected, and in eight patients the left limb. Conservative treatment was started for every patient. If no signs of recovery appeared within 3 months, operative exploration was performed. Final assessment was performed between 2 and 9 years after the onset of paralysis (mean duration of follow-up 46 ± 11 months). Patients were examined clinically for return of power, range of motion, pinch and grip strengths. Also the disability of the arm, shoulder, and hand (DASH) score was calculated. Results: Seven of our 14 patients had incomplete AIN palsy with isolated total loss of function of flexor pollicis longus (FPL), five of FPL and flexor digitorum profundus (FDP)1 simultaneously, and two of FDP1. Weakness of FDP2 could be seen in four patients. Pronator teres was paralysed in two patients. Pain in the forearm was present in nine patients. Four patients had predisposing factors. Eight patients treated conservatively exhibited spontaneous recovery from their paralysis during 3-12 months after the onset. In six patients, the AIN was explored 12 weeks after the initial symptoms and released from compressing structures. Thirteen patients showed good limb function. In one patient with poor result a tendon transfer was necessary. The DASH score of patients treated conservatively and operatively presented no significant difference. Conclusion: AIN syndrome can have different clinical manifestations. If no signs of spontaneous recovery appear within 12 weeks, operative treatment should be performed

Reproductive tract infections in women seeking abortion in Vietnam

<p>Abstract</p> <p>Background</p> <p>Women requesting abortion are at increased risk of developing RTI complications. However, RTI control in many resource-poor countries including Vietnam have been faced with logistical and methodological problems due to lack of standardized definitions of RTIs, lack of well-validated diagnostic criteria, lack of accurate laboratory tests, and lack of diagnostic equipment and skills. This article investigates the prevalence of RTIs among Vietnamese abortion-seeking women, to evaluate the available diagnostic techniques, and to assess antibiotic resistance among aetiological agents of RTI.</p> <p>Method</p> <p>The study was conducted in Phu-San hospital (PSH) from December 2003 through April 2004 among 748 abortion clients. A structured questionnaire was used to collect data on socio-economic and reproductive characteristics. Specimens were collected for laboratory analyses of chlamydia, gonorrhoea, trichomoniasis, vaginal candidiasis (VC), bacterial vaginosis (BV) and syphilis. To assess the validity of the obtained results, the study was repeated among 100 women and the duplicate samples were analysed at PSH and Copenhagen University Hospital (CUH).</p> <p>Results</p> <p>In all 54% of the women were diagnosed as having an RTI, including 3.3% with sexually transmitted infections. Endogenous infections were most prevalent (VC 34% and BV 12%) followed by chlamydia (1.3%) and trichomoniasis (0.7%). The sensitivity of culture for VC and BV was 30% and 88%, respectively, when tests in PSH were measured against tests in CUH. Antibiotic resistance was common among bacterial isolates.</p> <p>Conclusion</p> <p>RTIs are common among women seeking abortion. The presence of RTIs is associated with an increased risk of developing iatrogenic infections, routine administration of prophylactic antibiotic to all women undergoing abortion should be considered. However, the choice of routine prophylactic antibiotics should be based on relevant surveillance data of antibiotic resistance. Moreover, since the accuracy of diagnosis is doubtful and to address the problem of under-diagnosed and treated RTIs new investment in diagnostic facilities with simple performed microscopy or improved rapid tests should also be taken into consideration.</p

Modeling Core Metabolism in Cancer Cells: Surveying the Topology Underlying the Warburg Effect

BACKGROUND: Alterations on glucose consumption and biosynthetic activity of amino acids, lipids and nucleotides are metabolic changes for sustaining cell proliferation in cancer cells. Irrevocable evidence of this fact is the Warburg effect which establishes that cancer cells prefers glycolysis over oxidative phosphorylation to generate ATP. Regulatory action over metabolic enzymes has opened a new window for designing more effective anti-cancer treatments. This enterprise is not trivial and the development of computational models that contribute to identifying potential enzymes for breaking the robustness of cancer cells is a priority. METHODOLOGY/PRINCIPAL FINDINGS: This work presents a constraint-base modeling of the most experimentally studied metabolic pathways supporting cancer cells: glycolysis, TCA cycle, pentose phosphate, glutaminolysis and oxidative phosphorylation. To evaluate its predictive capacities, a growth kinetics study for Hela cell lines was accomplished and qualitatively compared with in silico predictions. Furthermore, based on pure computational criteria, we concluded that a set of enzymes (such as lactate dehydrogenase and pyruvate dehydrogenase) perform a pivotal role in cancer cell growth, findings supported by an experimental counterpart. CONCLUSIONS/SIGNIFICANCE: Alterations on metabolic activity are crucial to initiate and sustain cancer phenotype. In this work, we analyzed the phenotype capacities emerged from a constructed metabolic network conformed by the most experimentally studied pathways sustaining cancer cell growth. Remarkably, in silico model was able to resemble the physiological conditions in cancer cells and successfully identified some enzymes currently studied by its therapeutic effect. Overall, we supplied evidence that constraint-based modeling constitutes a promising computational platform to: 1) integrate high throughput technology and establish a crosstalk between experimental validation and in silico prediction in cancer cell phenotype; 2) explore the fundamental metabolic mechanism that confers robustness in cancer; and 3) suggest new metabolic targets for anticancer treatments. All these issues being central to explore cancer cell metabolism from a systems biology perspective

Simulation of dilated heart failure with continuous flow circulatory support

Lumped parameter models have been employed for decades to simulate important hemodynamic couplings between a left ventricular assist device (LVAD) and the native circulation. However, these studies seldom consider the pathological descending limb of the Frank-Starling response of the overloaded ventricle. This study introduces a dilated heart failure model featuring a unimodal end systolic pressure-volume relationship (ESPVR) to address this critical shortcoming. The resulting hemodynamic response to mechanical circulatory support are illustrated through numerical simulations of a rotodynamic, continuous flow ventricular assist device (cfVAD) coupled to systemic and pulmonary circulations with baroreflex control. The model further incorporated septal interaction to capture the influence of left ventricular (LV) unloading on right ventricular function. Four heart failure conditions were simulated (LV and bi-ventricular failure with/ without pulmonary hypertension) in addition to normal baseline. Several metrics of LV function, including cardiac output and stroke work, exhibited a unimodal response whereby initial unloading improved function, and further unloading depleted preload reserve thereby reducing ventricular output. The concept of extremal loading was introduced to reflect the loading condition in which the intrinsic LV stroke work is maximized. Simulation of bi-ventricular failure with pulmonary hypertension revealed inadequacy of LV support alone. These simulations motivate the implementation of an extremum tracking feedback controller to potentially optimize ventricular recovery. © 2014 Wang et al

Cardiac contractile dysfunction in insulin-resistant rats fed a high-fat diet is associated with elevated CD36-mediated fatty acid uptake and esterification

Changes in cardiac substrate utilisation leading to altered energy metabolism may underlie the development of diabetic cardiomyopathy. We studied cardiomyocyte substrate uptake and utilisation and the role of the fatty acid translocase CD36 in relation to in vivo cardiac function in rats fed a high-fat diet (HFD).Rats were exposed to an HFD or a low-fat diet (LFD). In vivo cardiac function was monitored by echocardiography. Substrate uptake and utilisation were determined in isolated cardiomyocytes.Feeding an HFD for 8 weeks induced left ventricular dilation in the systolic phase and decreased fractional shortening and the ejection fraction. Insulin-stimulated glucose uptake and proline-rich Akt substrate 40 phosphorylation were 41% (p <0.001) and 45% (p <0.05) lower, respectively, in cardiomyocytes from rats on the HFD. However, long-chain fatty acid (LCFA) uptake was 1.4-fold increased (p <0.001) and LCFA esterification into triacylglycerols and phospholipids was increased 1.4- and 1.5-fold, respectively (both p <0.05), in cardiomyocytes from HFD compared with LFD hearts. In the presence of the CD36 inhibitor sulfo-N-succinimidyloleate, LCFA uptake and esterification were similar in LFD and HFD cardiomyocytes. In HFD hearts CD36 was relocated to the sarcolemma, and basal phosphorylation of a mediator of CD36-trafficking, i.e. protein kinase B (PKB/Akt), was increased.Feeding rats an HFD induced cardiac contractile dysfunction, which was accompanied by the relocation of CD36 to the sarcolemma, and elevated basal levels of phosphorylated PKB/Akt. The permanent presence of CD36 at the sarcolemma resulted in enhanced rates of LCFA uptake and myocardial triacylglycerol accumulation, and may contribute to the development of insulin resistance and diabetic cardiomyopathy