Improving Usability And Scalability Of Big Data Workflows In The Cloud

Big data workflows have recently emerged as the next generation of data-centric workflow technologies to address the five “V” challenges of big data: volume, variety, velocity, veracity, and value. More formally, a big data workflow is the computerized modeling and automation of a process consisting of a set of computational tasks and their data interdependencies to process and analyze data of ever increasing in scale, complexity, and rate of acquisition. The convergence of big data and workflows creates new challenges in workflow community. First, the variety of big data results in a need for integrating large number of remote Web services and other heterogeneous task components that can consume and produce data in various formats and models into a uniform and interoperable workflow. Existing approaches fall short in addressing the so-called shimming problem only in an adhoc manner and unable to provide a generic solution. We automatically insert a piece of code called shims or adaptors in order to resolve the data type mismatches. Second, the volume of big data results in a large number of datasets that needs to be queried and analyzed in an effective and personalized manner. Further, there is also a strong need for sharing, reusing, and repurposing existing tasks and workflows across different users and institutes. To overcome such limitations, we propose a folksonomy- based social workflow recommendation system to improve workflow design productivity and efficient dataset querying and analyzing. Third, the volume of big data results in the need to process and analyze data of ever increasing in scale, complexity, and rate of acquisition. But a scalable distributed data model is still missing that abstracts and automates data distribution, parallelism, and scalable processing. We propose a NoSQL collectional data model that addresses this limitation. Finally, the volume of big data combined with the unbound resource leasing capability foreseen in the cloud, facilitates data scientists to wring actionable insights from the data in a time and cost efficient manner. We propose BARENTS scheduler that supports high-performance workflow scheduling in a heterogeneous cloud-computing environment with a single objective to minimize the workflow makespan under a user provided budget constraint

Government Influence and the Failure of Fannie Mae and Freddie Mac

In 2008 two government-sponsored enterprises, Fannie Mae and Freddie Mac, were placed into conservatorship due to insolvency. The financial bailout of the two publically traded corporations came at the expense of the American tax payer. This study investigates the relationship between direct and indirect government influence and the increasing risk taking of Fannie Mae and Freddie Mac from the late 1990’s through their conservatorship in 2008. As government-sponsored enterprises Fannie Mae and Freddie Mac have many special advantages that other publically traded companies did not possess. These advantages allowed Fannie Mae and Freddie Mac to increase their profitability. Theoretical literature regarding Congress and the bureaucracy suggests that the actions of bureaucrats can be linked to the preferences of Congressional members because bureaucrats are responsive to potential threats or perceived threats from the legislature. This theory is applicable to Fannie Mae and Freddie Mac, and is used to explain why the government was able to directly and indirectly influence the government-sponsored enterprises. Overall this investigation has determined that the United States government pursued a clear mission that determined to increase the availability of housing to all Americans, specifically to low-income and under-served individuals, through the use of the government-sponsored enterprises. Despite this link there is no conclusive data to show that the pursuit of this housing mission led Fannie Mae and Freddie Mac to operate in riskier business segments. This study has also found that motivation regarding profit-seeking and compensation structure provide a more plausible explanation for why the government-sponsored enterprises began to engage in riskier business practices that led to their insolvency

Regulation of Inflammatory Signalling by Caspases and M1-linked Ubiquitin Chains in Drosophila melanogaster

The NF-κB family of transcription factors are master regulators of innate immune responses and their dysregulation can lead to chronic inflammation and cause diseases like inflammatory bowel disease and cancer. To treat inflammatory diseases, a deeper understanding of regulation of the inflammatory NF-κB pathway at the molecular level is needed. As the signalling mechanisms regulating the NF-κB pathway are highly conserved, the fruit fly Drosophila melanogaster serves as an excellent model to understand the basic principles of the regulatory machinery. The NF-κB pathway activity is tightly regulated by ubiquitin signalling, as E3 ligases conjugate ubiquitin chains to important mediators of the pathway, regulating their function. In this thesis, I have studied how caspases and ubiquitin E3 ligases activate and restrain NF-κB signalling. We described a Drosophila interleukin 1β-converting enzyme (Drice)-mediated regulation of the Drosophila inhibitor of apoptosis 2 (Diap2), an E3 ligase that generates K63-linked ubiquitin chains, and a potent inducer of NF-κB. Drice functions by restraining Diap2 function under basal conditions in order to avoid unnecessary activation of NF-κB pathway induced by commensal bacteria. We also described the formation of M1-linked ubiquitin chains in flies upon infection, and identified Linear ubiquitin E3 ligase (LUBEL) as the enzyme responsible for formation of these chains. We found that M1-linked ubiquitin chains are important for activation of the NF-κB pathway in the intestinal epithelial tissue, showcasing the tissue specific regulation of NF-κB activation. We found previously unknown targets of M1-ubiquitination in the Drosophila Imd pathway, the Inhibitor of κB kinase γ (IKKγ) Kenny, and Death related ced-3/Nedd2-like caspase (Dredd). Similar to mammalian IKKγ, we also found that Kenny associated with M1-linked Ub chains, showing the conservation of function between mediators of mammalian and Drosophila NF-κB pathway. Finally, we found a novel mode of regulation of Kenny, where cleavage by Dredd protected Kenny from autophagosomal degradation, and this process was dependent on M1-ubiquitination. Our findings from this thesis have improved the understanding of the Drosophila NF-κB pathway by uncovering new mechanisms of regulation of NF-κB signalling by ubiquitination and caspases.NF-κB-transkriptionsfaktorfamiljen är nyckelreglerare av det medfödda immunförsvaret och okontrollerad reglering av NF-κB:s aktivitet kan leda till kronisk inflammation och förorsaka sjukdomar som inflammatorisk tarmsjukdom och cancer. För att behandla inflammatoriska sjukdomar krävs en djupare förståelse av de molekylära mekanismer som reglerar den inflammatoriska NF-κB-signaleringsräckan. Eftersom dessa signaleringsmekanismer är välbevarade, fungerar bananflugan, Drosophila melanogaster som en utmärkt modellorganism för att förstå de grundläggande principerna för NF-κB-reglering. Aktiveringen av NF-κB-signaleringsräckan regleras noggrant av en proteinmodifikation som kallas ubikvitinering, eftersom E3-ubikvitinligaser konjugerar ubikvitinkedjor till viktiga NF-κB-signalförmedlare, vilket därmed kontrollerar deras funktion. I denna avhandling har jag studerat hur kaspaser och E3- ubikvitinligaser aktiverar och hämmar NF-κB-signalering. Vi har beskrivit hur kaspaset Drosophila interleukin-1β-converting enzyme (Drice) kontrollerar Drosophila inhibitor of apoptosis 2 (Diap2), som är ett E3-ligas som genererar K63-kopplade ubikvitinkedjor och är en effektiv aktiverare av NF-κB. Drice fungerar genom att hämma Diap2-funktionen under basala förhållanden för att undvika att kommensala bakterier aktiverar NF-κB i onödan. Vi har också beskrivit att M1-kopplade ubikvitinkedjor syntetiseras vid bakteriell infektion i bananflugan, och har identifierat att Linear ubiquitin E3-ligase (LUBEL) är enzymet ansvarigt för bildandet av dessa kedjor. Vi har funnit att M1-kopplade ubikvitinkedjor är viktiga för aktiveringen av NF-κB-signaleringsräckan i tarmepitelvävnad, vilket påvisar en vävnadsspecifik reglering av NF-κB-aktiveringen. Vi har även funnit tidigare okända målproteiner för M1-ubikvitinering i bananflugans Imdsignaleringsräcka; kinaset Inhibitor of κB kinase γ (IKKγ) Kenny och kaspaset Death related ced-3/Nedd2-like caspase (Dredd). Vi har funnit att Kenny binder till M1-kopplade ubikvitinkedjor på samma sätt som IKKγ-proteinet i däggdjur, vilket antyder att NF-κB-signalförmedlare fungerar liknande i däggdjur och bananflugan. Slutligen har vi funnit en ny regleringsmekanism för Kenny, där Dredd skyddar Kenny från autofagosomal nedbrytning genom att klyva bort degraderingssignalsekvensen i Kenny. Dessutom har vi visat att denna process är beroende av M1-ubikvitinering. Sammanfattningsvis har resultaten från denna avhandling förbättrat förståelsen av de mekanismer som styr Drosophilas NF-κB-signalering och avslöjat nya regleringsmekanismer för NF-κB-signalering genom ubikvitinering och kaspaser

The effect of mitochondrial superoxide on drosophila lifespan

One of the aims of this research is to create a system with high mitochondrial oxidative stress. This was done by knocking down Superoxide dismutase 2 using RNA interference technology in Drosophila melanogaster. This knocking down would result in a decreased efficiency of the flies to dismutate superoxide and thus resulting in high superoxide levels. The consequences of such a system whose conditions are similar to that seen in late-life stages were studied. According to the Mitochondrial Free Radical Theory of Aging (MFRTA) the damage caused by ROS produced during normal metabolism is determinant of aging. The validity of MFRTA was checked in this system. Also from previous work, it is known that alternative enzymes NDI1 and AOX reduce ROS production and that NDI1 extends lifespan in flies. The mechanism by which NDI1 extends lifespan was not clear. We set out to investigate how NDI extends lifespan by coexpressing NDI1 and AOX in the flies expressing SOD2 RNAi using a binary system GAL4/UAS. NDI1 was previously found to decrease ROS production as well as increase complex I specific substrate oxidation. Here we try to find if NDI1 functions by a ROS dependent or independent method to extend lifespan. The alternative enzyme AOX was expressed in parallel to be used as a control due to its location in the electron transport chain (ETC) and its complementation of complex III as opposed to NDI1 which compliments complex I of the ETC

Autoimmune Parkinsonism: A Newer Manifestation of Contactin-Associated Protein-Like 2 Autoimmunity: A Case Report

Contactin-associated protein-like 2 (CASPR2) antibodies are part of an expanding spectrum of disorders. Although they were initially associated with Morvan’s syndrome and peripheral nerve hyperexcitability, their clinical manifestations are more varied than previously recognized. In this report, we present a rare case of a middle-aged woman who experienced gait disturbances, sleep disturbances, behavioral changes, and postural abnormalities over a period of five months. A thorough examination revealed a Parkinsonian phenotype. Considering the timeline and symptomatology, an autoimmune work-up was conducted, which detected CASPR2 antibodies in the patient’s serum. Treatment with high-dose intravenous Methylprednisolone followed by rituximab effectively reversed her clinical manifestations without residual neurological deficits

Barriers to Changing Dietary Behavior

Abstract Dietary change requires giving up long established patterns of eating behavior and acquiring new habits. ‘Noncompliance’ to diet advice may be a result of inability to provide diet self-management training and getting the right messages across to change eating behavior. Using a pre-tested questionnaire based interview, we carried out a study amongst 350 adults (> 20 years) with type 2 diabetes from two metro cities in South India, who had previously received diet advice with the objective to understand perceptions, attitudes and practices, as well as study factors that enhance or reduce compliance to diet advice. Ninety six patients (28%) followed diet for the full duration of diabetes (Group1), 131 (38%) followed diet for a partial duration varying between more than a quarter to three quarters of the total diabetes duration (Group 2) and 115 (34%) did not follow diet advice (Group 3) – followed for a duration less than a quarter of their diabetes duration. Study results show that many factors both patient and health care provider related influence outcomes of dietary advice. Factors that have a positive impact on compliance are – older age, shorter duration, nuclear family, good family support, less busy work life, higher health consciousness, advice given by dietician, more frequent visits to dietician, advice that includes elements to promote overall health not merely control of blood sugar, diet counseling that is easy to understand and use and includes healthy food options, cooking methods, practical guidance to deal with lifestyle issues. We conclude that patient barriers related to life circumstance are mostly non-modifiable, most modifiable barriers are related to behavioural aspect and the inability of the health care provider to provide individualized diet advice and self management training. Efforts must be made to improve counseling skills

Ursolic acid inhibits colistin efflux and curtails colistin resistant Enterobacteriaceae

Abstract Colistin resistance in Enterobacteriaceae especially Klebsiella pneumoniae and Escherichia coli is driving the evolution of pan drug resistant strains. Screening a library of 13 plant nutraceuticals led to the identification of acetyl shikonin and ursolic acid, which exhibited synergy with colistin against extremely drug resistant (XDR) clinical strains of E. coli (U3790) and K. pneumoniae (BC936). Ursolic acid caused a significant colistin MIC reversal of 16-fold in U3790 and 4-fold in BC936 strains. Ursolic acid also potentiated the bactericidal effect of colistin against both U3790 and BC936 by causing ~ 4 to 4.5 log fold decline in CFU of both clinical isolates in a time kill assay. At 2× minimum effective concentration, ursolic acid was non-toxic to zebrafish as evidenced by brain and liver enzyme profiles and by histopathology studies. In combination with colistin, ursolic acid reduced bacterial bioburden of U3790/BC936 by 1–1.58 log fold from the infected muscle tissue of zebrafish. Mechanistic explorations via studies on real time efflux, membrane potential and intracellular accumulation of dansyl chloride tagged colistin revealed that colistin efflux is inhibited by ursolic acid. In addition, ursolic acid also enhanced outer membrane permeability which probably facilitates colistin’s attack on outer and inner membranes. Our study shows that ursolic acid synergizes with colistin by inhibiting colistin efflux in Enterobacteriaceae that helps to curtail colistin resistant Enterobacteriaceae.https://deepblue.lib.umich.edu/bitstream/2027.42/148135/1/13568_2019_Article_750.pd

Bioconversion of waste cooking oil for the production of poly-3-hydroxybutyrate using Bacillus cereus MPTDC

557-562Used cooking oil is generated as a byproduct during frying process. It cannot be reused for cooking process due to health issues such as cancer and other digestive disorders. Alternative strategy is utilization of this waste cooking oil for production of poly-3-hydroxybutyrate (PHB) a biopolymer which can be used as a substitute for petroleum derived plastics or other value added products. In the present investigation, we used waste cooking oil as carbon source for PHB production by Bacillus cereus MPTDC. The optimum conditions of PHB production by Bacillus cereus MPTDC were waste cooking oil concentration of 2% (v/v), incubation time of 96 h, ammonium sulphate concentration of 7.5% and yeast extract concentration of 0.2%. Under optimized conditions the strain produced 3.777 g/L of PHB. The results indicate the potential of used cooking oil as carbon source for PHB production by Bacillus cereus MPTDC

Bioconversion of waste cooking oil for the production of poly-3-hydroxybutyrate using Bacillus cereus MPTDC

Used cooking oil is generated as a byproduct during frying process. It cannot be reused for cooking process due to health issues such as cancer and other digestive disorders. Alternative strategy is utilization of this waste cooking oil for production of poly-3-hydroxybutyrate (PHB) a biopolymer which can be used as a substitute for petroleum derived plastics [ABG1] or other value added products. In the present investigation, we used waste cooking oil as carbon source for PHB production by Bacillus cereus MPTDC. The optimum conditions of PHB production by Bacillus cereus MPTDC were waste cooking oil concentration of 2% (v/v), incubation time of 96 h, ammonium sulphate concentration of 7.5% and yeast extract concentration of 0.2%. Under optimized conditions the strain produced 3.777 g/L of PHB. The results indicate the potential of used cooking oil as carbon source for PHB production by Bacillus cereus MPTDC