No description available.

Indiana University-Purdue University Indianapolis (IUPUI) / Alzheimer’s disease (AD) is a neurodegenerative disease histopathologically characterized by the coexistence of amyloid plaques and neurofibrillary tangles, mainly consisting of amyloid β peptides hyperphosphorylated tau proteins, respectively. Multiple proteins and pathways are involved in the pathogenesis of AD, including Aβ precursor protein (APP), β-site APP-cleaving enzyme (BACE1), neprilysin, endothelin converting enzyme (ECE), repressor element-1 silencing transcription factor (REST), microtubule-associated protein tau, glycogen synthase kinase, and pro-inflammatory cytokines. However, how these proteins and pathways are dysregulated and converge in AD pathogenesis remains unclear. Genetic, epigenetic and environmental factors play important roles in disease progression. MicroRNAs (miRNAs), a group of small noncoding RNAs, are important epigenetic regulators that participate in AD development. We have identified three miRNAs capable of targeting several proteins in different AD-related pathways: miR-181-5p, miR-153-3p and miR-101-3p. We tested miR-181 activity with recombinant reporter gene- MME 3’-UTR constructs. All four miR-181-5p (miR-181a, miR-181b, miR-181c and miR-181d) sequences downregulated the reporter signal. Human differentiated neural cells were transfected with miR-181d-5p mimics. miR-181d-5p treatment significantly reduced MME mRNA levels, protein levels and enzyme activity. In addition, miR-181d-5p increased tau and phosphorylated tau levels proportionally. We further demonstrate that miR-153-3p reduced REST 3’-UTR activities, mRNA and protein levels in multiple human cell lines. Moreover, we show that miR-153-3p, by knocking down REST protein, induces apoptosis in HeLa cells but not differentiated neural cells. In addition, miR-153-3p regulates neuronal differentiation in neuronal stem cells, potentially via REST knockdown. We further found that miR-153 levels were correlated with a reduced likelihood of developing AD. Last, we demonstrated that miR-101-3p reduced ECE1 and GSK3β protein levels in multiple cell lines. miR-101-3p increased REST and pro-inflammatory cytokine secretion in microglia cells. In sum, we tested the hypothesis that miRNAs can serve as the master regulator of AD pathogenesis. / 2024-07-01

Today’s economy and infrastructure is dependent on raw natural resources, like crude oil and natural gases, that are optimally transported through a net- work of hundreds of thousands of miles of pipelines throughout America[28]. A damaged pipe can negatively a↵ect thousands of homes and businesses so it is vital that they are monitored and quickly repaired[1]. Ideally, pipeline operators are able to detect damages before they occur, but ensuring the in- tegrity of the vast amount of pipes is unrealistic and would take an impractical amount of time and manpower[1]. Natural disasters, like earthquakes, as well as construction are just two of the events that could potentially threaten the integrity of pipelines. Due to the diverse collection of data sources, the necessary geospatial data is scat- tered across di↵erent physical locations, stored in di↵erent formats, and owned by di↵erent organizations. Pipeline companies do not have the resources to manually gather all input factors to make a meaningful analysis of the land surrounding a pipe. Our solution to this problem involves creating a single, centralized system that can be queried to get all necessary geospatial data and related informa- tion in a standardized and desirable format. The service simplifies client-side computation time by allowing our system to find, ingest, parse, and store the data from potentially hundreds of repositories in varying formats. An online web service fulfills all of the requirements and allows for easy remote access to do critical analysis of the data through computer based decision support systems (DSS). Our system, REST API for Pipeline Integrity Data (RAPID), is a multi- tenant REST API that utilizes HTTP protocol to provide a online and intuitive set of functions for DSS. RAPID’s API allows DSS to access and manage data stored in a geospatial database with a supported Django web framework. Full documentation of the design and implementation of RAPID’s API are detailed in this thesis document, supplemented with some background and validation of the completed system.

Few biological systems are as ubiquitous as the circadian rhythm, a distributed yet inter-connected “system of systems” that coordinates the timing of physiological processes via a self-regulating, flexible network present at every level of biological organization, from cells to cities. Its functional role as the interface between time-dependent internal processes and external environmental cues exposes the circadian rhythm to disruption if these drift out of synchrony. This is especially common in industrialized human societies, where the abun-dance of resources – in combination with the fact that anthropogenic calendars have largely supplanted the sun as the primary determinant of our daily cycles of rest, activity, and sleep – disrupts the circadian rhythm’s ability to synchronize biological processes with each other and the geophysical solar day. Humans are now beholden to two increasingly disconnected clocks, and the ever-accelerating curve of human progress suggests our biological and so-cial times will only grow more disconnected. Longitudinal “out-of-clinic” monitoring is an ecologically valid alternative to well-controlled laboratory studies that can provide insight into how human circadian and behav-ioral rhythms exist in day-to-day life, and so has great potential to provide contextual data for translating chronobiological science into clinical intervention. However, methodological diversity, inconsistent terminology, insufficient reporting, and the sheer number of potential factors has slowed progress. Herein is presented scientific work focused on detecting and quantifying some of these factors, particularly “sociogenic” determinants such as the seven-day week. Through rhythmometric analysis of longitudinal in-home actigraphy, weekly be-havioral patterns were observed in both young adult males (n = 24, mean age = 23.46 years) and older adults with Parkinson’s disease (n = 13 [7 male], mean age = 60.62 years, mean Hoehn & Yahr Stage = 2.31) that evince a seven-day “circaseptan” rhythm of circadi-an and sleep disruption. This is hypothesized to be dependent upon the seven-day calendar week, particularly the regular and abrupt shifts in timing between work and rest days. These perturbations vary by chronotype in young adults, and by disease severity in Parkin-son’s disease. Collectively, these results contribute to the growing evidence that our daily rhythms are shaped by sociogenic factors in addition to well-documented environmental and biological mechanisms. Moreover, the study of these subtle infradian patterns presents serious – yet surmountable – methodological challenges that must be overcome in order to accurately monitor, quantify, analyze, report, and apply findings from observational studies of naturalistic human behavior to scientific and clinical problems.

Introduction: Space is an extreme environment exposing astronauts to microgravity and cosmic radiation resulting in immune dysfunction. To overcome the complex challenges of studying astronauts in space, bed rest studies represent an alternative model simulating microgravity exposure on Earth. We sought to characterize the steady state transcriptome changes in leukocytes isolated from two microgravity models: (1) participants to 60 days of bed rest and (2) astronauts to ~6 months of spaceflight. Methods: The bed rest study recruited twenty healthy men receiving a nutritional supplement or not; the spaceflight study had fourteen male and female astronauts participate. For both studies, ten blood samples were collected over three study phases, leukocytes were isolated, and transcriptomes were quantified using high throughput RNA-sequencing. My pipeline of data analysis applied differential expression (DE) methods and functional enrichment to identify gene expression changes and pathways responding to the altered gravity environments of both bed rest and spaceflight models. Results: Temporal differential expression identified transcriptome modulation reflecting multisystem shifts and immune dysregulation in response to the transitions to and from bed rest (2,415 DE genes) and spaceflight (247 DE genes). Interestingly, later bed rest and in-flight timepoints trended towards stable RNA levels with no differential expression. The bed rest study found the nutritional intervention had no mitigating effects on transcriptome changes (0 DE genes), and the spaceflight study revealed down-regulation in response to spaceflight followed by an opposite up-regulation upon return to Earth. Conclusion: The altered gravity environments of bed rest and spaceflight significantly modulated leukocyte transcriptome compositions revealing immune dysfunction at the molecular level. Future analyses utilizing the higher quality bed rest dataset is required to isolate the effect of microgravity from other space stressors and apply validation experiments to develop gene biomarkers indicative of immune deconditioning.

No description available.

The typical user base for computer applications has transformed, over time, from mostly technically-oriented individuals to include a vast range of the world's population - the majority of whom have little to no technical proficiency. As such, user interfaces have evolved from text-based shell input into multimedia interfaces which typically provide support for receiving input from a number of disparate devices that are operated in conjunction to manipulate a given program. A problem arises when applications add in support for explicit devices; which leads to strong coupling between the underlying code and the defined set of devices that they support. In a nutshell, support for new peripherals almost always requires that the original application be recompiled and /or its internal configuration modified to incorporate the given device(s). Portal, an interaction independence framework, seeks to add a layer of abstraction between arbitrary application code and the devices they support; allowing developers to deal in the realm of abstract program actions instead of crafting code to handle a variety of concrete device inputs. This should eliminate the need for custom device-tailored code for each user-wielded peripheral that an application must support and will enable application device support to be managed via configuration changes to the Portal middleware framework, rather than being hard-coded into an application. This thesis will define the conceptual design of the Portal framework while, at the same time, elaborating on the role that web services will play within it; investigate two pervasive service-oriented architecture paradigms, SOAP and REST, in order to gauge their potential effectiveness in meeting Portal's underlying back-end data transmission requirements; provide implementations for the Portal service-oriented architecture and data model; and, finally, critically evaluate both implementations with an emphasis on their performance with regard to both efficiency and scalability. / Master of Science

Increased resting energy expenditure has been postulated to be one of the contributory factors in the development of cancer cachexia. Body composition and resting energy expenditure were evaluated in six male and seven female normal controls in order to validate methodology. Identical methods were then applied to seven male sarcoma patients with localized disease. Only the age and sex-matched group of controls were compared to the sarcoma patient group. All patients had received no prior cancer treatment. Body composition assessment included measurement of body fat using four-site skinfold measures. measurement of total body potassium (40K) as an indicator of body cell mass. and calculation of body surface area. Resting energy expenditure was measured by indirect calorimetry in an enclosed plexiglass hood and compared to predicted resting energy expenditure as determined by the Harris and Benedict formulae. Measured resting energy expenditure per unit body surface area was significantly increased in the sarcoma group: 1610.7 +/- 369.2 (sarcoma) vs. 1290.3 +/- 74.3 kcal/m²/day (controls), p<.05. Percent body cell mass was significantly decreased in the sarcoma group: 32.6 +/- 3.8% (sarcoma) vs. 39.8 +/- 3.7% (controls), p<.05. Predicted resting energy expenditure underestimated measured values by 42.1 +/-13.0% in the sarcoma group and 29.7 +/- 5.4% in the control group. Results of this study suggest that in otherwise asymptomatic cancer patients with metabolically active tumors, such as sarcomas, increased resting energy expenditure contributes to the onset of cancer cachexia prior to any signs of overt host depletion. / M.S.

Suspension of the body in the head-down posture (90° below the horizontal) for traction and added resistance to exercise has generated considerable interest in recent years. However, recent investigators of inversion have cautioned individuals not to participate in such activities until further research could be performed on the effects of exercise in the head-down position. The purpose of this investigation was to examine the acute metabolic and hemodynamic responses of men at rest and during exercise in the inverted posture (90° head-down tilt) versus the supine and standing postures. The parameters investigated were oxygen consumption(V̇O₂), heart rate(HR), systolic blood pressure (SBP), and diastolic blood pressure(DBP). Eleven male recreational athletes underwent 6 sessions of postural change. The baseline posture was sitting and the critical positions were supine, standing, and inverted. The subjects were asked to remain in each of these postures for three minutes. In the first 2 sessions, oxygen consumption(V̇O₂), was measured at rest and during 45° hip-f1exion respectively, The V̇O₂ in the inverted posture at rest was found to be 1.7% greater than the V̇O₂ in the standing and the supine postures. V̇O₂ in the inverted posture during exercise was 7% and 36.5% greater than in the supine and standing postures, respective1y. A statistical significance in HR at rest in the standing posture versus the inverted and supine postures was observed. During 45° hip-flexion activity, the HR in the standing posture was found to be significantly faster than the supine posture. The HR in the inverted posture was significantly faster than the supine posture as well. At rest, there was no significant increase in SBP as re1ated to posture. During exercise, the SBP was significant1y greater; at rest in each of the postures. Both postural and exercise factors significantly affected the DBP. The post-hoc analyses showed supine resting DBP was significantly lower than in the other two resting postures. During exercise, the standing BP was significantly greater than the supine and inverted DBP. These data demonstrate: A) V̇O₂ in the supine and inverted postures is significantly greater than in the standing postures. B) a statistically significant increase in HR occurs in the standing posture as compared to the supine and inverted postures; however, it does not appear to be clinically significant, C) with the arms maintained in the anatomical position for all postural changes, the SBP was not significantly affected by the change of posture, but was significantly increased with exercise. D) and DBP in the standing posture was statistically greater than in the other two postures and DBP in the inverted posture was significantly elevated above that found in the supine posture. / Master of Science

Visualisering är en ofta förekommande metod som används vid utveckling av en ny produkt för att redan i ett tidigt stadium kunna visa den färdiga produkten i form av en prototyp eller annan digital ritning. Det är dock inte lika vanligt att visualisera själva utvecklingen av produkten eller vilken fas den befinner sig i, vilket kan leda till osäkerhet inom utvecklingsgruppen och ge det fortsatta arbetet av produkten en tvetydig bild. Projektgrupperna på företaget CGI Östersund jobbar enligt den agila systemutvecklingsmetoden Scrum där arbetet delas upp i olika delleveranser och ärenden, vilket gör det möjligt att visualisera utvecklingsprocessen. Den här undersökningen har studerat Scrum-metoden ytterligare och därefter tagit fram ett visualiseringsverktyg bestående av en REST-webbtjänst i Java och en webbklient som hämtar information från ett ärendehanteringssystem, JIRA, som företaget använder sig av. Informationen presenteras sedan i form av olika grafer beroende på vad som skall visualiseras. Verktygets funktion och konstruktion har sedan utvärderats med användbarhetstester och även jämförts med ett liknande verktyg som redan finns i den befintliga JIRA-plattformen. Användbarhetstesterna utfördes både innan och efter implementation där det första testet enbart bestod av mock-ups och det andra när verktyget hade fått ett fungerande resultat. Resultatet har visat att det fortfarande råder en del oklarhet i verktygets mer invecklade funktioner, men att helheten av de olika delsystemen är förståelig i dess användbarhet. Jämförelsen med visualiseringen i JIRA visar att liknelserna är stora och att det i nuläget finns både för- och nackdelar med att använda den här lösningen. Verktyget är i övrigt uppbyggd med moderna tekniker och står på en bra grund för vidare utveckling från företagets sida. / Visualization is a frequent method used in the development of a new product to see the finished product to an early stage in the form of a prototype or digital drawing. However, it is not as common to visualize the actual development of the product or what phase it is in, which can lead to confusion within the development team and provide further the work of the product an ambiguous picture. Project teams at the company CGI Östersund works according to the agile system development methodology Scrum where the work is divided into different partial deliveries and issues, making it possible to visualize the development process. This investigation has studied the Scrum method further and then developed a visualization tool consisting of a REST web service in Java and a web client that retrieves information from a issue tracking system, JIRA, which the company uses. The information is then presented in the form of various graphs depending on what is to be visualized. The tool's function and design has been evaluated with usability testing and also then compared with a similar tool that is already in the existing JIRA platform. Usability tests were conducted both before and after implementation, the first test consisted only of mock-ups and the second when the tool had a functioning results. The results have shown that there is still some ambiguity in the tool's more complex features, but to the whole of the various subsystems is understandable in its usability. The comparison with the visualization in JIRA shows that the parables are great and that at present there are both advantages and disadvantages of using this solution. The tool is otherwise constructed with modern techniques and stands on a good basis for further development from the company.