Clustering by means of a Boltzmann machine with partial constraint satisfaction

The clustering problem refers to the partitioning of target sightings into sets. Two sightings are in the same set if and only if they are generated by sensor detections of the same target and are in the same great circle arc (GARC) trajectory of that target. A Boltzmann machine is developed whose sparse architecture provides for only partial constraint satisfaction of the associated cost function. This together with a special graphics interface serve as an aid in determining GARCs. Our approach differs from others in that the neural net is built to operate in conjunction with a non-neural tracker. This further restricts the architectural complexity of the network and facilitates future experimentation regarding decomposition of the neural net across several Von Neumann processors. Also, the Boltzmann machine architecture eases the effort of finding optimal or near optimal solutions. Results are presented. The demonstrated feasibility of neural GARC determination encourages investigation into the extension of its role in the track formation process utilizing an environment that includes supercomputers, neurocomputers, or optical hardware. The network architecture is capable of identifying a host of geometric forms other than GARCs and can thus be used in several domains including space, land, and ocean

LCAT cholesterol esterification is associated with the increase of ApoE/ApoA-I ratio during atherosclerosis progression in rabbit

Apolipoprotein A-I and Apolipoprotein E promote different steps of reverse cholesterol transport, including lecithin-cholesterol acyltransferase stimulation. Our aim was to study the changes in the levels of Apolipoprotein A-I, Apolipoprotein E, and lecithin-cholesterol acyltransferase activity during atherosclerosis progression in rabbits. Quantitative echocardiographic parameters were analyzed in order to evaluate, for the first time, whether atherosclerosis progression in rabbit is associated to apolipoproteins changes and alteration of indices of cardiac function, such as systolic strain and strain rate of the left ventricle. Atherosclerosis was induced by feeding rabbits for 8 weeks with 2 % cholesterol diet. The HDL levels of cholesterol and cholesteryl esters were measured by HPLC. The lecithin-cholesterol acyltransferase activity was evaluated both ex vivo, as cholesteryl esters/cholesterol molar ratio, and in vitro. Apolipoproteins levels were analyzed by ELISA. The HDL levels of cholesterol and cholesteryl esters increased, during treatment, up to 3.7- and 2.5-fold, respectively, compared to control animals. The lecithin-cholesterol acyltransferase activity in vitro was halved after 4 weeks. During cholesterol treatment, Apolipoprotein A-I level significantly decreased, whereas Apolipoprotein E concentration markedly increased. The molar ratio Apolipoprotein E/Apolipoprotein A-I was negatively correlated with the enzyme activity, and positively correlated with both increases in the intima-media thickness of common carotid wall and cardiac dysfunction signs, such as systolic strain and strain rate of the left ventricle. © 2012 University of Navarra

LCAT cholesterol esterification is associated with the increase of ApoE/ApoA-I ratio during atherosclerosis progression in rabbit

Apolipoprotein A-I and Apolipoprotein E promote different steps of reverse cholesterol transport, including lecithin-cholesterol acyltransferase stimulation. Our aim was to study the changes in the levels of Apolipoprotein A-I, Apolipoprotein E, and lecithin-cholesterol acyltransferase activity during atherosclerosis progression in rabbits. Quantitative echocardiographic parameters were analyzed in order to evaluate, for the first time, whether atherosclerosis progression in rabbit is associated to apolipoproteins changes and alteration of indices of cardiac function, such as systolic strain and strain rate of the left ventricle. Atherosclerosis was induced by feeding rabbits for 8 weeks with 2 % cholesterol diet. The HDL levels of cholesterol and cholesteryl esters were measured by HPLC. The lecithin-cholesterol acyltransferase activity was evaluated both ex vivo, as cholesteryl esters/cholesterol molar ratio, and in vitro. Apolipoproteins levels were analyzed by ELISA. The HDL levels of cholesterol and cholesteryl esters increased, during treatment, up to 3.7- and 2.5-fold, respectively, compared to control animals. The lecithin-cholesterol acyltransferase activity in vitro was halved after 4 weeks. During cholesterol treatment, Apolipoprotein A-I level significantly decreased, whereas Apolipoprotein E concentration markedly increased. The molar ratio Apolipoprotein E/Apolipoprotein A-I was negatively correlated with the enzyme activity, and positively correlated with both increases in the intima-media thickness of common carotid wall and cardiac dysfunction signs, such as systolic strain and strain rate of the left ventricle. © 2012 University of Navarra

Spatial Ecology Methods and Applications to Large Carnivore Conservation in Kenya

Thesis (Ph.D.)--Michigan State University. Integrative Biology - Doctor of Philosophy, 2024In this dissertation, I develop and apply various spatially explicit methods to quantify ecological conditions and space use of large carnivores in multifunctional landscapes such as protected areas and rangelands. I investigate how the social behavior and space use of several large carnivore species vary across ecological gradients within Kenyan protected areas exposed to high levels of pastoralist activity, identify avenues for future research in spatial ecology and conservation behavior, and provide methodology by which to pursue these lines of research. In Chapter One, I develop a novel approach to land cover classification in heterogeneous savanna landscapes and apply it to the Maasai Mara National Reserve, Kenya. This Reserve is of great value for conservation, international research collaborations, and use by local pastoralists for livestock grazing. I achieve unparalleled success in distinguishing among different grass heights as well as other diverse land cover types, thus providing a valuable tool by which to extract land cover for use as a spatially explicit predictor of wildlife behavior (e.g., space use, conflict with humans) and to monitor the effect of livestock grazing intensity on grass height and cover in future studies. In Chapter Two, I use these land cover data as well as a historical database of other environmental variables, livestock abundance, and large carnivore sightings to assess how carnivores have shifted their spatial distributions and habitat selection over the years in response to the presence and abundance of livestock and herders inside the Reserve. In Chapter Three, I provide guidelines for individual identification of hyaenids using naturally occurring markings, review the substantial utility of this method in past and ongoing basic research, and identify important avenues by which to apply this method to the monitoring and conservation of wild hyaenids and the mitigation of human-hyaenid conflict in shared landscapes. In Chapter Four, I seek to better understand the social system of a poorly understood and globally declining large carnivore, the striped hyena. Specifically, I conducted the first empirical study of pasting in striped hyenas and described social behavior at den sites, including the first reported case of allonursing, to show that this population is highly social and even exhibits cooperative care of offspring. The diversity of social systems observed across striped hyena populations in recent studies suggests that this species is much more behaviorally plastic than previously recognized. Overall, this dissertation contributes to our understanding of the complex relationships between carnivores\u2019 behavior and the environments in which they live, as well as how human activity mediates these interactions. Overlooking the behavioral adaptations that humans induce in large carnivores could prevent us from predicting trophic cascades that result in the loss of biodiversity and ecosystem function. Alternatively, seeking to understand these behavioral responses could facilitate the innovation of novel techniques by which to promote the coexistence of humans and carnivores in multifunctional landscapes.Description based on online resource. Title from PDF t.p. (Michigan State University Fedora Repository, viewed ).Includes bibliographical references

High Fat Diet and Inflammation - Modulation of Haptoglobin Level in Rat Brain

Obesity and dietary fats are well known risk factors for neurodegenerative diseases. The analysis of specific markers, whose brain level can be affected by diet, might contribute to unveil the intersection between inflammation/obesity and neurodegeneration. Haptoglobin (Hpt) is an acute phase protein, which acts as antioxidant by binding free haemoglobin (Hb), thus neutralizing its pro-oxidative action. We previously demonstrated that Hpt plays critical functions in brain, modulating cholesterol trafficking in neurons, beta-amyloid (Aβ) uptake by astrocyte, and limiting Aβ toxicity on these cells. A major aim of this study was to evaluate whether a long term (12 or 24 weeks) high-fat diet (HFD) influences Hpt and Hb expression in rat hippocampus. We also assessed the development of obesity-induced inflammation by measuring hippocampal TNF-alpha, and the extent of protein oxidation by titrating nitro-tyrosine (N-Tyr). Hpt concentration was lower in hippocampus of HFD rats than in control animals, HFD was also associated in hippocampus with the increase of Hb level, inflammation and protein oxidative modification, as evidenced by the increase in the concentration of TNF-alpha and nitro-tyrosine. In fact, TNF-alpha concentration was higher in rats receiving HFD for 12 or 24 weeks compared to controls. N-Tyr concentration was more elevated in hippocampus of HFD than in control rats in both 12 weeks and 24 weeks groups. Finally, we found that the treatment of the human glial cells with cholesterol and fatty acids significantly impairs Hpt secretion in the extracellular compartment. We hypothesize that the HFD-dependent decrease of Hpt in hippocampus, as associated with Hb increase, might enhance the oxidative stress induced by free Hb. Altogether our data, identifying Hpt as a molecule modulated in the brain by dietary fats, may represent one of the first steps in the comprehension of the molecular mechanisms underlying the diet-related effects in the nervous system

Clustering by means of a Boltzmann machine with partial constraint satisfaction

The clustering problem refers to the partitioning of target sightings into sets. Two sightings are in the same set if and only if they are generated by sensor detections of the same target and are in the same great circle arc (GARC) trajectory of that target. A Boltzmann machine is developed whose sparse architecture provides for only partial constraint satisfaction of the associated cost function. This together with a special graphics interface serve as an aid in determining GARCs. Our approach differs from others in that the neural net is built to operate in conjunction with a non-neural tracker. This further restricts the architectural complexity of the network and facilitates future experimentation regarding decomposition of the neural net across several Von Neumann processors. Also, the Boltzmann machine architecture eases the effort of finding optimal or near optimal solutions. Results are presented. The demonstrated feasibility of neural GARC determination encourages investigation into the extension of its role in the track formation process utilizing an environment that includes supercomputers, neurocomputers, or optical hardware. The network architecture is capable of identifying a host of geometric forms other than GARCs and can thus be used in several domains including space, land, and ocean

PRESTIGIO RING: "A 59-year-old HIV-1 positive, highly treatment-experienced woman failing darunavir/ ritonavir plus raltegravir"

Management of heavily treatment experienced (HTE) people with HIV remains a challenge. Tailored antiretroviral therapy (ART) is needed in this fragile population who almost invariably harbor viral quasispecies with resistance-associated mutations (RAMs). The reference method for HIV genotypic resistance testing (GRT) has long been Sanger sequencing (SS), but next-generation sequencing (NGS), following recent progress in workflow and cost-effectiveness, is replacing SS because of higher sensitivity. From the PRESTIGIO Registry, we present a case of a 59-year-old HTE woman who failed darunavir/ritonavir plus raltegravir at low-viremia levels due mainly to high pill burden and poor adherence. NGS-GRT was performed on HIV-RNA at failure and the results were compared to all past SS-GRT data available (historical genotype). In this case, NGS-GRT did not detect any minority drug-resistant variants. After discussing several therapeutic options, the treatment was changed to dolutegravir 50 mg twice daily plus doravirine 100 mg once a day, based on clinical history, adherence issues, and pill burden, as well as the historical SS-GRT and the latest NGS-GRT results. At six months follow-up visit, the patient had HIV-RNA below 30 copies/ml and CD4+ T cell count increased from 673 cells/ mm3 to 688 cells/ mm3. Close follow-up of this patient is ongoing

Designing a broad-spectrum integrative approach for cancer prevention and treatment

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notablesuccesses in some cancers; however, significant problems remain with this approach. Many targetedtherapies are highly toxic, costs are extremely high, and most patients experience relapse after a fewdisease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistantimmortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are notreliant upon the same mechanisms as those which have been targeted). To address these limitations, aninternational task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspectsof relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a widerange of high-priority targets (74 in total) that could be modified to improve patient outcomes. For thesetargets, corresponding low-toxicity therapeutic approaches were then suggested, many of which werephytochemicals. Proposed actions on each target and all of the approaches were further reviewed forknown effects on other hallmark areas and the tumor microenvironment. Potential contrary or procar-cinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixedevidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of therelationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. Thisnovel approach has potential to be relatively inexpensive, it should help us address stages and types ofcancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for futureresearch is offered

Faecal calprotectin: factors affecting levels and its potential role as a surrogate marker for risk of development of Crohn's Disease.

BACKGROUND: Faecal calprotectin (FC) is one of the most widely used non-invasive tests for the diagnosis and assessment of Crohn's disease (CD) activity. Despite this, factors other than disease activity which affect levels have not been extensively reviewed. This is of importance when using FC in the diagnostic setting but also may be of utility in studying the aetiology of disease. OBJECTIVES: Our review outlines environmental risk factors that affect FC levels influencing diagnostic accuracy and how these may be associated with risk of developing CD. FC as a surrogate marker could be used to validate risk factors established in case control studies where prospective studies are not feasible. Proof of this concept is provided by our identification of obesity as being associated with elevated FC, our subsequent confirmation of obesity as risk factor for CD and the subsequent verification in prospective studies, as well as associations of lack of physical activity and dietary fibre intake with elevated FC levels and their subsequent confirmation as risk factors in prospective studies. CONCLUSION: We believe that FC is likely to prove a useful surrogate marker for risk of developing CD. This review has given a theoretical basis for considering the epidemiological determinants of CD which to date has been missing