684 research outputs found
Slicing and Allocation of Transformable Resources for the Deployment of Multiple Virtualized Infrastructure Managers (VIMs)
In the context of 5G networks, the concept of network slicing allows network providers to flexibly share infrastructures with mobile service providers and verticals. While this concept has been widely investigated considering mostly the network issues, in this work we focus on a slice as a service model that takes into account the data center (DC) perspective. In particular, we propose an architecture where DC slices are created over transformable (compute and storage) resources, which can be virtualized or de-virtualized on-demand. Then, on top of each slice, an on-demand VIM is instantiated to control the allocated resources. As a realization of this architecture, we introduce the DC Slice Controller, a system able to deploy and delivery full operational VIMs based on generic templates. We evaluate the effectiveness of the proposed system deploying three VIMs (VLSP, Kubernetes, and OpenStack) over commodity hardware. Experimental results show that the DC Slice Controller can timely provide a slice even when dealing with sophisticated VIMs such as OpenStack. As an example, we were able to delivery a fully functional OpenStack in four nodes in less than 10 minutes
Orally active antischistosomal early leads identified from the open access malaria box.
BACKGROUND: Worldwide hundreds of millions of schistosomiasis patients rely on treatment with a single drug, praziquantel. Therapeutic limitations and the threat of praziquantel resistance underline the need to discover and develop next generation drugs. METHODOLOGY: We studied the antischistosomal properties of the Medicines for Malaria Venture (MMV) malaria box containing 200 diverse drug-like and 200 probe-like compounds with confirmed in vitro activity against Plasmodium falciparum. Compounds were tested against schistosomula and adult Schistosoma mansoni in vitro. Based on in vitro performance, available pharmacokinetic profiles and toxicity data, selected compounds were investigated in vivo. PRINCIPAL FINDINGS: Promising antischistosomal activity (IC50: 1.4-9.5 µM) was observed for 34 compounds against schistosomula. Three compounds presented IC50 values between 0.8 and 1.3 µM against adult S. mansoni. Two promising early leads were identified, namely a N,N'-diarylurea and a 2,3-dianilinoquinoxaline. Treatment of S. mansoni infected mice with a single oral 400 mg/kg dose of these drugs resulted in significant worm burden reductions of 52.5% and 40.8%, respectively. CONCLUSIONS/SIGNIFICANCE: The two candidates identified by investigating the MMV malaria box are characterized by good pharmacokinetic profiles, low cytotoxic potential and easy chemistry and therefore offer an excellent starting point for antischistosomal drug discovery and development
miR-132/212 knockout mice reveal roles for these miRNAs in regulating cortical synaptic transmission and plasticity
miR-132 and miR-212 are two closely related miRNAs encoded in the same intron of a small non-coding gene, which have been suggested to play roles in both immune and neuronal function. We describe here the generation and initial characterisation of a miR-132/212 double knockout mouse. These mice were viable and fertile with no overt adverse phenotype. Analysis of innate immune responses, including TLR-induced cytokine production and IFNβ induction in response to viral infection of primary fibroblasts did not reveal any phenotype in the knockouts. In contrast, the loss of miR-132 and miR-212, while not overtly affecting neuronal morphology, did affect synaptic function. In both hippocampal and neocortical slices miR-132/212 knockout reduced basal synaptic transmission, without affecting paired-pulse facilitation. Hippocampal long-term potentiation (LTP) induced by tetanic stimulation was not affected by miR-132/212 deletion, whilst theta burst LTP was enhanced. In contrast, neocortical theta burst-induced LTP was inhibited by loss of miR-132/212. Together these results indicate that miR-132 and/or miR-212 play a significant role in synaptic function, possibly by regulating the number of postsynaptic AMPA receptors under basal conditions and during activity-dependent synaptic plasticity
The role of the RACK1 ortholog Cpc2p in modulating pheromone-induced cell cycle arrest in fission yeast
The detection and amplification of extracellular signals requires the involvement of multiple protein components. In mammalian cells the receptor of activated C kinase (RACK1) is an important scaffolding protein for signal transduction networks. Further, it also performs a critical function in regulating the cell cycle by modulating the G1/S transition. Many eukaryotic cells express RACK1 orthologs, with one example being Cpc2p in the fission yeast Schizosaccharomyces pombe. In contrast to RACK1, Cpc2p has been described to positively regulate, at the ribosomal level, cells entry into M phase. In addition, Cpc2p controls the stress response pathways through an interaction with Msa2p, and sexual development by modulating Ran1p/Pat1p. Here we describe investigations into the role, which Cpc2p performs in controlling the G protein-mediated mating response pathway. Despite structural similarity to Gβ-like subunits, Cpc2p appears not to function at the G protein level. However, upon pheromone stimulation, cells overexpressing Cpc2p display substantial cell morphology defects, disorientation of septum formation and a significantly protracted G1 arrest. Cpc2p has the potential to function at multiple positions within the pheromone response pathway. We provide a mechanistic interpretation of this novel data by linking Cpc2p function, during the mating response, with its previous described interactions with Ran1p/Pat1p. We suggest that overexpressing Cpc2p prolongs the stimulated state of pheromone-induced cells by increasing ste11 gene expression. These data indicate that Cpc2p regulates the pheromone-induced cell cycle arrest in fission yeast by delaying cells entry into S phase
Clinical usefulness of microsatellite instability for the prediction of gastric adenoma or adenocarcinoma in patients with chronic gastritis
To assess a role of microsatellite instability (MSI) in the development of gastric adenocarcinoma or adenoma from chronic gastritis, we analysed mutations of five microsatellite loci in gastritis, adenoma and adenocarcinoma retrospectively. Gastric mucosa was biopsied from the same area in each patient at different periods and examined for MSI. Only one of 55 patients with chronic gastritis revealed MSI-H phenotype and the other 54 patients showed microsatellite stable (MSS) phenotypes. In six of 17 patients with gastric adenoma or well-differentiated adenocarcinoma, MSI-positive phenotypes were demonstrated. Interestingly, all of six patients showing MSI, including three high-level MSI (MSI-H) cases and three low-level (MSH-L) cases, had already revealed MSI at the stage of chronic gastritis. In two of three MSI-H cases, the identical MSI patterns had been observed at the stage of gastritis 1.5–7 years before the final diagnosis of adenocarcinoma. The adjacent gastritis mucosa within 10 mm from the carcinoma demonstrated MSI as well. MSI was not found in any of 35 patients with Helicobacter pylori infection, but found in one of 30 patients without infection. Moreover, two of three cases of gastric adenoma or well-differentiated adenocarcinoma with MSI-H at the stage of chronic gastritis showed no evidence of Helicobacter pylori infection throughout the observation periods. These results indicate that MSI in biopsy specimens at the stage of chronic gastritis may predict the risk of the progression to adenoma and well-differentiated adenocarcinoma, and that Helicobacter pylori infection itself may not induce MSI directly in the gastric mucosa. © 2000 Cancer Research Campaig
Surprisingly Simple Spectra
The large N limit of the anomalous dimensions of operators in
super Yang-Mills theory described by restricted Schur polynomials, are studied.
We focus on operators labeled by Young diagrams that have two columns (both
long) so that the classical dimension of these operators is O(N). At large N
these two column operators mix with each other but are decoupled from operators
with columns. The planar approximation does not capture the large N
dynamics. For operators built with 2, 3 or 4 impurities the dilatation operator
is explicitly evaluated. In all three cases, in a certain limit, the dilatation
operator is a lattice version of a second derivative, with the lattice emerging
from the Young diagram itself. The one loop dilatation operator is diagonalized
numerically. All eigenvalues are an integer multiple of and there
are interesting degeneracies in the spectrum. The spectrum we obtain for the
one loop anomalous dimension operator is reproduced by a collection of harmonic
oscillators. This equivalence to harmonic oscillators generalizes giant
graviton results known for the BPS sector and further implies that the
Hamiltonian defined by the one loop large dilatation operator is
integrable. This is an example of an integrable dilatation operator, obtained
by summing both planar and non-planar diagrams.Comment: 34 page
Variation in Symbiodinium ITS2 Sequence Assemblages among Coral Colonies
Endosymbiotic dinoflagellates in the genus Symbiodinium are
fundamentally important to the biology of scleractinian corals, as well as to a
variety of other marine organisms. The genus Symbiodinium is
genetically and functionally diverse and the taxonomic nature of the union
between Symbiodinium and corals is implicated as a key trait
determining the environmental tolerance of the symbiosis. Surprisingly, the
question of how Symbiodinium diversity partitions within a
species across spatial scales of meters to kilometers has received little
attention, but is important to understanding the intrinsic biological scope of a
given coral population and adaptations to the local environment. Here we address
this gap by describing the Symbiodinium ITS2 sequence
assemblages recovered from colonies of the reef building coral Montipora
capitata sampled across Kāne'ohe Bay, Hawai'i. A
total of 52 corals were sampled in a nested design of Coral Colony(Site(Region))
reflecting spatial scales of meters to kilometers. A diversity of
Symbiodinium ITS2 sequences was recovered with the majority
of variance partitioning at the level of the Coral Colony. To confirm this
result, the Symbiodinium ITS2 sequence diversity in six
M. capitata colonies were analyzed in much greater depth
with 35 to 55 clones per colony. The ITS2 sequences and quantitative composition
recovered from these colonies varied significantly, indicating that each coral
hosted a different assemblage of Symbiodinium. The diversity of
Symbiodinium ITS2 sequence assemblages retrieved from
individual colonies of M. capitata here highlights the problems
inherent in interpreting multi-copy and intra-genomically variable molecular
markers, and serves as a context for discussing the utility and biological
relevance of assigning species names based on Symbiodinium ITS2
genotyping
Effect of remote ischemic preconditioning in the expression of IL-6 and IL-10 in a rat model of liver ischemia-reperfusion injury
Microdeletion del(22)(q12.2) encompassing the facial development-associated gene, MN1 (meningioma 1) in a child with Pierre-Robin sequence (including cleft palate) and neurofibromatosis 2 (NF2): a case report and review of the literature
<p>Abstract</p> <p>Background</p> <p>Pierre-Robin sequence (PRS) is defined by micro- and/or retrognathia, glossoptosis and cleft soft palate, either caused by deformational defect or part of a malformation syndrome. Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome caused by mutations in the <it>NF2 </it>gene on chromosome 22q12.2. NF2 is characterized by bilateral vestibular schwannomas, spinal cord schwannomas, meningiomas and ependymomas, and juvenile cataracts. To date, NF2 and PRS have not been described together in the same patient.</p> <p>Case presentation</p> <p>We report a female with PRS (micrognathia, cleft palate), microcephaly, ocular hypertelorism, mental retardation and bilateral hearing loss, who at age 15 was also diagnosed with severe NF2 (bilateral cerebellopontine schwannomas and multiple extramedullary/intradural spine tumors). This is the first published report of an individual with both diagnosed PRS and NF2. High resolution karyotype revealed 46, XX, del(22)(q12.1q12.3), FISH confirmed a deletion encompassing <it>NF2</it>, and chromosomal microarray identified a 3,693 kb deletion encompassing multiple genes including <it>NF2 </it>and <it>MN1 </it>(meningioma 1).</p> <p>Five additional patients with craniofacial dysmorphism and deletion in chromosome 22-adjacent-to or containing <it>NF2 </it>were identified in PubMed and the DECIPHER clinical chromosomal database. Their shared chromosomal deletion encompassed <it>MN1</it>, <it>PITPNB </it>and <it>TTC28</it>. <it>MN1</it>, initially cloned from a patient with meningioma, is an oncogene in murine hematopoiesis and participates as a fusion gene (<it>TEL</it>/<it>MN1</it>) in human myeloid leukemias. Interestingly, <it>Mn1</it>-haploinsufficient mice have abnormal skull development and secondary cleft palate. Additionally, <it>Mn1 </it>regulates maturation and function of calvarial osteoblasts and is an upstream regulator of <it>Tbx22</it>, a gene associated with murine and human cleft palate. This suggests that deletion of <it>MN1 </it>in the six patients we describe may be causally linked to their cleft palates and/or craniofacial abnormalities.</p> <p>Conclusions</p> <p>Thus, our report describes a <it>NF2</it>-adjacent chromosome 22q12.2 deletion syndrome and is the first to report association of <it>MN1 </it>deletion with abnormal craniofacial development and/or cleft palate in humans.</p
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