170,077 research outputs found
Bringing Global Sourcing into The Classroom: Experiential Learning Via a Global Software Development Project
The growing trend in offshore software development has imposed new skills requirements on collaborating global partners. In the U.S. this has translated into skill sets that include communications, project management, business analysis, and team management. In a virtual setting, these skills take on a complex proportion. This paper describes an educational initiative in offshore software development between undergraduate students enrolled in a project management course at Marquette University, USA and graduate business students enrolled in an Information Systems Analysis and Design course at Management Development Institute, India. The course replicated an offshore client/vendor relationship in a virtual setting. For faculty considering such initiatives, this paper describes the setting and factors critical to success of this initiative and cautions against others that can be detrimental to such an effort
Separase prevents genomic instability by controlling replication fork speed
Proper chromosome segregation is crucial for preserving genomic integrity, and errors in this process cause chromosome mis-segregation, which may contribute to cancer development. Sister chromatid separation is triggered by Separase, an evolutionary conserved protease that cleaves the cohesin complex, allowing the dissolution of sister chromatid cohesion. Here we provide evidence that Separase participates in genomic stability maintenance by controlling replication fork speed. We found that Separase interacted with the replication licensing factors MCM2-7, and genome-wide data showed that Separase co-localized with MCM complex and cohesin. Unexpectedly, the depletion of Separase increased the fork velocity about 1.5-fold and caused a strong acetylation of cohesin's SMC3 subunit and altered checkpoint response. Notably, Separase silencing triggered genomic instability in both HeLa and human primary fibroblast cells. Our results show a novel mechanism for fork progression mediated by Separase and thus the basis for genomic instability associated with tumorigenesis
Separase prevents genomic instability by controlling replication fork speed
Proper chromosome segregation is crucial for preserving genomic integrity, and errors in this process cause chromosome mis-segregation, which may contribute to cancer development. Sister chromatid separation is triggered by Separase, an evolutionary conserved protease that cleaves the cohesin complex, allowing the dissolution of sister chromatid cohesion. Here we provide evidence that Separase participates in genomic stability maintenance by controlling replication fork speed. We found that Separase interacted with the replication licensing factors MCM2-7, and genome-wide data showed that Separase co-localized with MCM complex and cohesin. Unexpectedly, the depletion of Separase increased the fork velocity about 1.5-fold and caused a strong acetylation of cohesin's SMC3 subunit and altered checkpoint response. Notably, Separase silencing triggered genomic instability in both HeLa and human primary fibroblast cells. Our results show a novel mechanism for fork progression mediated by Separase and thus the basis for genomic instability associated with tumorigenesis
Experimental and Numerical Investigation of Unforced unsteadiness in a Vaneless Radial Diffuser
The paper reports combined experimental and numerical investigations of unforced un- steadiness in a vaneless radial diffuser. Experimental data were obtained within the diffuser using stereoscopic time resolved Particle Image Velocimetry (PIV) recording three velocity components in a plane (2D/3C), coupled with unsteady pressure transducers. To characterize the inception and the evolution of the unsteady phenomena, spectral analyses of the pressure signals were carried out both in frequency and time-frequency domains and the PIV results were post processed by an original averaging method. Two partial flow rates were investigated in detail in this paper. A single unforced unsteadiness was identified for the lowest flow rate, whereas, two competitive intermittent modes were recognized for the higher mass flow. Numerical analyses were carried out on the same pump by the commercial code CFX. All the computations were performed using the unsteady transient model and the turbulence was modelled by the Scale-Adaptive Simulation (SAS) model. Numerical pressure signals were compared with the experimental data to verify the development of the same pressure fluctua- tions
Investigating the role of histone deacetylase HDAC4 in long-term memory formation : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Genetics at Massey University, Manawatu, New Zealand
Listed in 2017 Dean's List of Exceptional ThesesEpigenetic mechanisms are emerging as master regulators of cognitive abilities such
as learning and memory. It has been previously shown that the histone deacetylase
HDAC4 plays a critical role in memory formation in both mammals and insects although
the specific mechanisms through which it acts have not yet been elucidated. HDAC4
undergoes nucleocytoplasmic shuttling and, in neurons, it is largely cytoplasmic implying
it may play both nuclear and non-nuclear functions. To identify upstream regulators and
downstream targets of HDAC4, a genetic interaction screen was performed in the fruit fly
Drosophila melanogaster, a powerful model system to study the genetic mechanisms of
neurological disease. Twenty-nine genes were found to interact with HDAC4 suggesting
they are part of the same molecular pathway. Functional network analysis revealed that
many of the genes could be grouped into three biological categories comprising
transcriptional factors, SUMOylation machinery enzymes and cytoskeletal
regulators/interactors. Within the latter, Ankyrin2 was selected for further analysis as it is
implicated in synaptic stability and in human intellectual disability. In addition HDAC4
harbours a conserved ankyrin binding domain. Immunohistochemical analyses showed
widespread distribution of Ankyrin2 throughout the adult brain and coincident
distribution with HDAC4 was observed in the axons of the mushroom body, a key
structure for memory formation in flies. Both HDAC4 and Ankyrin2 were also found to
regulate mushroom body development. RNAi-mediated depletion of Ankyrin2 in the adult
brain impaired long-term memory in the courtship suppression assay, a model of
associative memory and preliminary evidence of a physical association between HDAC4
and Ankyrin2 was also demonstrated. The genes identified in the screen provide new
avenues for investigation of the mechanisms through which HDAC4 regulates memory
formation and preliminary analyses suggest that interaction with the cytoskeletal adaptor
Ankyrin2 may involve remodelling of the actin/spectrin cytoskeleton, phenomenon that
underlies memory related processes like synaptic plasticity and neuronal excitability
The mRNA degradation factor Xrn1 regulates transcription elongation in parallel to Ccr4
Co-transcriptional imprinting of mRNA by Rpb4 and Rpb7 subunits of RNA polymerase II (RNAPII) and by the Ccr4–Not complex conditions its posttranscriptional fate. In turn, mRNA degradation factors like Xrn1 are able to influence RNAPII-dependent transcription, making a feedback loop that contributes to mRNA homeostasis. In this work, we have used repressible yeast GAL genes to perform accurate measurements of transcription and mRNA degradation in a set of mutants. This genetic analysis uncovered a link from mRNA decay to transcription elongation. We combined this experimental approach with computational multi-agent modelling and tested different possibilities of Xrn1 and Ccr4 action in gene transcription. This double strategy brought us to conclude that both Xrn1-decaysome and Ccr4–Not regulate RNAPII elongation, and that they do it in parallel. We validated this conclusion measuring TFIIS genome-wide recruitment to elongating RNAPII. We found that xrn1Δ and ccr4Δ exhibited very different patterns of TFIIS versus RNAPII occupancy, which confirmed their distinct role in controlling transcription elongation. We also found that the relative influence of Xrn1 and Ccr4 is different in the genes encoding ribosomal proteins as compared to the rest of the genome
High-Energy-Physics Event Generation with PYTHIA 6.1
PYTHIA version 6 represents a merger of the PYTHIA 5, JETSET 7 and SPYTHIA
programs, with many improvements. It can be used to generate
high-energy-physics `events', i.e. sets of outgoing particles produced in the
interactions between two incoming particles. The objective is to provide as
accurate as possible a representation of event properties in a wide range of
reactions. The underlying physics is not understood well enough to give an
exact description; the programs therefore contain a combination of analytical
results and various models. The emphasis in this article is on new aspects, but
a few words of general introduction are included. Further documentation is
available on the web.Comment: 1 + 27 pages, submitted to Computer Physics Communication
Insertion of proteins into the inner membrane of mitochondria: the role of the Oxa1 complex
The inner mitochondrial membrane harbors a large number of proteins that display a wide range of topological arrangements. The majority of these proteins are encoded in the cell\u27s nucleus, but a few polytopic proteins, all subunits of respiratory chain complexes are encoded by the mitochondrial genome. A number of distinct sorting mechanisms exist to direct these proteins into the mitochondrial inner membrane. One of these pathways involves the export of proteins from the matrix into the inner membrane and is used by both proteins synthesized within the mitochondria, as well as by a subset of nuclear encoded proteins. Prior to embarking on the export pathway, nuclear encoded proteins using this sorting route are initially imported into the mitochondrial matrix from the cytosol, their site of synthesis. Protein export from the matrix into the inner membrane bears similarities to Sec-independent protein export in bacteria and requires the function of the Oxa1 protein. Oxa1 is a component of a general protein insertion site in yeast mitochondrial inner membrane used by both nuclear and mitochondrial DNA encoded proteins. Oxa1 is a member of the conserved Oxa1/YidC/Alb3 protein family found throughout prokaryotes throughout eukaryotes (where it is found in mitochondria and chloroplasts). The evidence to demonstrate that the Oxa1/YidC/Alb3 protein family represents a novel evolutionarily conserved membrane insertion machinery is reviewed here
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