3,901 research outputs found
Reducing Systems Implementation Failure: A conceptual Framework for the Improvement of Financial Systems Implementations within the Financial Services Industries
The financial industry continues to change, become more global, complex and important to economies all around the work. The industry continues to be in flux and the world financial crisis has resulted in changes that have changed the industry for good. The need for agile, accurate and detailed financial systems has never been so important. This research discusses the issues associated with implementing financial systems within financial services companies, a conceptual framework has been built that will help reduce the risk of implementation failure in future financial systems implementations. Financial experts can use the framework to reduce system implementation risk; help deliver projects on time to budget whilst meet the functionality requirements of stakeholders
Plasmodium falciparum CRK4 directs continuous rounds of DNA replication during schizogony.
: Plasmodium parasites, the causative agents of malaria, have evolved a unique cell division cycle in the clinically relevant asexual blood stage of infection(1). DNA replication commences approximately halfway through the intracellular development following invasion and parasite growth. The schizont stage is associated with multiple rounds of DNA replication and nuclear division without cytokinesis, resulting in a multinucleated cell. Nuclei divide asynchronously through schizogony, with only the final round of DNA replication and segregation being synchronous and coordinated with daughter cell assembly(2,3). However, the control mechanisms for this divergent mode of replication are unknown. Here, we show that the Plasmodium-specific kinase PfCRK4 is a key cell-cycle regulator that orchestrates multiple rounds of DNA replication throughout schizogony in Plasmodium falciparum. PfCRK4 depletion led to a complete block in nuclear division and profoundly inhibited DNA replication. Quantitative phosphoproteomic profiling identified a set of PfCRK4-regulated phosphoproteins with greatest functional similarity to CDK2 substrates, particularly proteins involved in the origin of replication firing. PfCRK4 was required for initial and subsequent rounds of DNA replication during schizogony and, in addition, was essential for development in the mosquito vector. Our results identified an essential S-phase promoting factor of the unconventional P. falciparum cell cycle. PfCRK4 is required for both a prolonged period of the intraerythrocytic stage of Plasmodium infection, as well as for transmission, revealing a broad window for PfCRK4-targeted chemotherapeutics.<br/
Membranes, molecules and biophysics: enhancing monocyte derived dendritic cell (MDDC) immunogenicity for improved anti-cancer therapy
Despite great medical advancement in the treatment of cancer, cancer remains a disease of global significance. Chemotherapeutics can be very expensive and drain medical resources at a national level and in some cases the cost of treatment is so great that it prohibits their use by local health authorities. Drug resistance is also a major limiting factor to the successful treatment of cancer with many patients initially responding well but then becoming refractory to treatment with the same drug and in some case may become multi-drug resistant. The immune system is known to be important in the prevention of tumors by eliminating pre-cancerous or cancerous cells. This concept of immune surveillance has largely been super-ceded by the concept of immunoediting whereby the immune system imposes a selective pressure on tumor cells which may either control tumor growth or inadvertently select for tumor cells which have evolved to escape the immune response and which may induce tumor development. Stimulation of the immune system by vaccination offers many benefits in the treatment of cancer. It is highly cost effective and vaccines can be manipulated to include multi-antigens which in some cases may overcome equilibrium (and selective pressure) while also preventing the establishment of reactivated cancer cells, since cancer antigen-specific memory would be induced following the initial vaccination/booster phase. To date studies using vaccination as a treatment for cancer have been a little disappointing, probably due to insufficient level of immunogenicity. In this review we will discuss methods of manipulation of the immune system to increase the anti-cancer activity of dendritic cells in vivo and how monocyte derived dendritic cells may be manipulated ex vivo to provide more robust, patient-specific treatments
Molecular Valves for Controlling Gas Phase Transport Made from Discrete Angstrom-Sized Pores in Graphene
An ability to precisely regulate the quantity and location of molecular flux
is of value in applications such as nanoscale 3D printing, catalysis, and
sensor design. Barrier materials containing pores with molecular dimensions
have previously been used to manipulate molecular compositions in the gas
phase, but have so far been unable to offer controlled gas transport through
individual pores. Here, we show that gas flux through discrete angstrom-sized
pores in monolayer graphene can be detected and then controlled using
nanometer-sized gold clusters, which are formed on the surface of the graphene
and can migrate and partially block a pore. In samples without gold clusters,
we observe stochastic switching of the magnitude of the gas permeance, which we
attribute to molecular rearrangements of the pore. Our molecular valves could
be used, for example, to develop unique approaches to molecular synthesis that
are based on the controllable switching of a molecular gas flux, reminiscent of
ion channels in biological cell membranes and solid state nanopores.Comment: to appear in Nature Nanotechnolog
Giant Faraday rotation in single- and multilayer graphene
Optical Faraday rotation is one of the most direct and practically important
manifestations of magnetically broken time-reversal symmetry. The rotation
angle is proportional to the distance traveled by the light, and up to now
sizeable effects were observed only in macroscopically thick samples and in
two-dimensional electron gases with effective thicknesses of several
nanometers. Here we demonstrate that a single atomic layer of carbon - graphene
- turns the polarization by several degrees in modest magnetic fields. The
rotation is found to be strongly enhanced by resonances originating from the
cyclotron effect in the classical regime and the inter-Landau-level transitions
in the quantum regime. Combined with the possibility of ambipolar doping, this
opens pathways to use graphene in fast tunable ultrathin infrared
magneto-optical devices
Towards a large-scale quantum simulator on diamond surface at room temperature
Strongly-correlated quantum many-body systems exhibits a variety of exotic
phases with long-range quantum correlations, such as spin liquids and
supersolids. Despite the rapid increase in computational power of modern
computers, the numerical simulation of these complex systems becomes
intractable even for a few dozens of particles. Feynman's idea of quantum
simulators offers an innovative way to bypass this computational barrier.
However, the proposed realizations of such devices either require very low
temperatures (ultracold gases in optical lattices, trapped ions,
superconducting devices) and considerable technological effort, or are
extremely hard to scale in practice (NMR, linear optics). In this work, we
propose a new architecture for a scalable quantum simulator that can operate at
room temperature. It consists of strongly-interacting nuclear spins attached to
the diamond surface by its direct chemical treatment, or by means of a
functionalized graphene sheet. The initialization, control and read-out of this
quantum simulator can be accomplished with nitrogen-vacancy centers implanted
in diamond. The system can be engineered to simulate a wide variety of
interesting strongly-correlated models with long-range dipole-dipole
interactions. Due to the superior coherence time of nuclear spins and
nitrogen-vacancy centers in diamond, our proposal offers new opportunities
towards large-scale quantum simulation at room temperatures
Genome wide association mapping of grain arsenic, copper, molybdenum and zinc in rice (Oryza sativa L.) grown at four international field sites
Peer reviewedPublisher PD
Cadmium Exposure and Neurodevelopmental Outcomes in U.S. Children
Background: Low-level environmental cadmium exposure in children may be associated with adverse neurodevelopmental outcomes
JLab Measurements of the 3He Form Factors at Large Momentum Transfers
The charge and magnetic form factors, FC and FM, of 3He have been extracted
in the kinematic range 25 fm-2 < Q2 < 61 fm-2 from elastic electron scattering
by detecting 3He recoil nuclei and electrons in coincidence with the High
Resolution Spectrometers of the Hall A Facility at Jefferson Lab. The
measurements are indicative of a second diffraction minimum for the magnetic
form factor, which was predicted in the Q2 range of this experiment, and of a
continuing diffractive structure for the charge form factor. The data are in
qualitative agreement with theoretical calculations based on realistic
interactions and accurate methods to solve the three-body nuclear problem
Seasonal changes in patterns of gene expression in avian song control brain regions.
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Photoperiod and hormonal cues drive dramatic seasonal changes in structure and function of the avian song control system. Little is known, however, about the patterns of gene expression associated with seasonal changes. Here we address this issue by altering the hormonal and photoperiodic conditions in seasonally-breeding Gambel's white-crowned sparrows and extracting RNA from the telencephalic song control nuclei HVC and RA across multiple time points that capture different stages of growth and regression. We chose HVC and RA because while both nuclei change in volume across seasons, the cellular mechanisms underlying these changes differ. We thus hypothesized that different genes would be expressed between HVC and RA. We tested this by using the extracted RNA to perform a cDNA microarray hybridization developed by the SoNG initiative. We then validated these results using qRT-PCR. We found that 363 genes varied by more than 1.5 fold (>log(2) 0.585) in expression in HVC and/or RA. Supporting our hypothesis, only 59 of these 363 genes were found to vary in both nuclei, while 132 gene expression changes were HVC specific and 172 were RA specific. We then assigned many of these genes to functional categories relevant to the different mechanisms underlying seasonal change in HVC and RA, including neurogenesis, apoptosis, cell growth, dendrite arborization and axonal growth, angiogenesis, endocrinology, growth factors, and electrophysiology. This revealed categorical differences in the kinds of genes regulated in HVC and RA. These results show that different molecular programs underlie seasonal changes in HVC and RA, and that gene expression is time specific across different reproductive conditions. Our results provide insights into the complex molecular pathways that underlie adult neural plasticity
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