Implementation of Operational Framework in the Nlp (Based On Mof and Itil Standards)

An operational framework, as proposed by the Microsoft Operational Framework (MOF) and the Information Technology Infrastructure Library (ITIL) provides a process model for controlling and managing Information Technology (IT) operations. With a strict focus on IT operations, it provides the processes and terminology to coordinate and integrate the functional elements of an IT department. The Systems Engineering and Applications Development (SEAD) practicum is composed of four main groups; Data Access, Network, Integrated Services and Development. This professional project will propose the beginning framework for overall operation and integration of the SEAD Practicum with an emphasis on service support and documentation. The key deliverable of this project is the determination of a documentation standard and the creation of documentation of common processes that are performed routinely by the SEAD group. This will serve as a basis for transitioning between subsequent practicum and as a foundation upon which other MOF and ITIL processes and standards can be implemented

Support Networks of Primary Caregivers Receiving Family Preservation Services: An Exploratory Study

Copyright 1994 Families International, Inc.The authors describe network characteristics and support resources from a clinical sample of 40 families. Data were obtained by family workers during the first two weeks of intervention. Case vignettes illustrate the multiple uses to which this information was put. Implications for future research and practice are discussed

Training Competences in Industrial Risk Prevention with Lego (R) Serious Play (R): A Case Study

This paper proposes the use of the Lego (R) Serious Play (R) (LSP) methodology as a facilitating tool for the introduction of competences for Industrial Risk Prevention by engineering students from the industrial branch (electrical, electronic, mechanical and technological engineering), presenting the results obtained in the Universities of Cadiz and Seville in the academic years 2017-2019. Current Spanish legislation does not reserve any special legal attribution, nor does it require specific competence in occupational risk prevention for the regulated profession of a technical industrial engineer (Order CIN 351:2009), and only does so in a generic way for that of an industrial engineer (Order CIN 311:2009). However, these universities consider the training in occupational health and safety for these future graduates as an essential objective in order to develop them for their careers in the industry. The approach is based on a series of challenges proposed (risk assessments, safety inspections, accident investigations and fire protection measures, among others), thanks to the use of "gamification" dynamics with Lego (R) Serious Play (R). In order to carry the training out, a set of specific variables (industrial sector, legal and regulatory framework, business organization and production system), and transversal ones (leadership, teamwork, critical thinking and communication), are incorporated. Through group models, it is possible to identify dangerous situations, establish causes, share and discuss alternative proposals and analyze the economic, environmental and organizational impact of the technical solutions studied, as well as take the appropriate decisions, in a creative, stimulating, inclusive and innovative context. In this way, the theoretical knowledge which is acquired is applied to improve safety and health at work and foster the prevention of occupational risks, promoting the commitment, effort, motivation and proactive participation of the student teams

Alichur Dome, South Pamir, Western India-Asia Collisional Zone: Detailing the Neogene Shakhdara-Alichur Syn-collisional Gneiss-Dome Complex and Connection to Lithospheric Processes

Neogene, syn‐collisional extensional exhumation of Asian lower–middle crust produced the Shakhdara–Alichur gneiss‐dome complex in the South Pamir. The <1 km‐thick, mylonitic–brittle, top‐NNE, normal‐sense Alichur shear zone (ASZ) bounds the 125 × 25 km Alichur dome to the north. The Shakhdara dome is bounded by the <4 km‐thick, mylonitic–brittle, top‐SSE South Pamir normal‐sense shear zone (SPSZ) to the south, and the dextral Gunt wrench zone to its north. The Alichur dome comprises Cretaceous granitoids/gneisses cut by early Miocene leucogranites; its hanging wall contains non/weakly metamorphosed rocks. The 22–17 Ma Alichur‐dome‐injection‐complex leucogranites transition from foliation‐parallel, centimeter‐ to meter‐thick sheets within the ASZ into discordant intrusions that may comprise half the volume of the dome core. Secondary fluid inclusions in mylonites and mylonitization‐temperature constraints suggest Alichur‐dome exhumation from 10–15 km depth. Thermochronologic dates bracket footwall cooling between ~410–130 °C from ~16–4 Ma; tectonic cooling/exhumation rates (~42 °C/Myr, ~1.1 km/Myr) contrast with erosion‐dominated rates in the hanging wall (~2 °C/Myr, <0.1 km/Myr). Dome‐scale boudinage, oblique divergence of the ASZ and SPSZ hanging walls, and dextral wrenching reflect minor approximately E–W material flow out of the orogen. We attribute broadly southward younging extensional exhumation across the central South Pamir between ~20–4 Ma to: (i) Mostly northward, foreland‐directed flow of hot crust into a cold foreland during the growth of the Pamir orocline; and (ii) Contrasting effects of basal shear related to underthrusting Indian lithosphere, enhancing extension in the underthrust South Pamir and inhibiting extension in the non‐underthrust Central Pamir

Variation in pre-PCR processing of FFPE samples leads to discrepancies in BRAF and EGFR mutation detection: a diagnostic RING trial.

Aims Mutation detection accuracy has been described extensively; however, it is surprising that pre-PCR processing of formalin-fixed paraffin-embedded (FFPE) samples has not been systematically assessed in clinical context. We designed a RING trial to (i) investigate pre-PCR variability, (ii) correlate pre-PCR variation with EGFR/BRAF mutation testing accuracy and (iii) investigate causes for observed variation. Methods 13 molecular pathology laboratories were recruited. 104 blinded FFPE curls including engineered FFPE curls, cell-negative FFPE curls and control FFPE tissue samples were distributed to participants for pre-PCR processing and mutation detection. Follow-up analysis was performed to assess sample purity, DNA integrity and DNA quantitation. Results Rate of mutation detection failure was 11.9%. Of these failures, 80% were attributed to pre-PCR error. Significant differences in DNA yields across all samples were seen using analysis of variance (p<0.0001), and yield variation from engineered samples was not significant (p=0.3782). Two laboratories failed DNA extraction from samples that may be attributed to operator error. DNA extraction protocols themselves were not found to contribute significant variation. 10/13 labs reported yields averaging 235.8ng (95% CI 90.7 to 380.9) from cell-negative samples, which was attributed to issues with spectrophotometry. DNA measurements using Qubit Fluorometry demonstrated a median fivefold overestimation of DNA quantity by Nanodrop Spectrophotometry. DNA integrity and PCR inhibition were factors not found to contribute significant variation. Conclusions In this study, we provide evidence demonstrating that variation in pre-PCR steps is prevalent and may detrimentally affect the patient's ability to receive critical therapy. We provide recommendations for preanalytical workflow optimisation that may reduce errors in down-stream sequencing and for next-generation sequencing library generation

Effects of Thyroxine Exposure on Osteogenesis in Mouse Calvarial Pre-Osteoblasts

The incidence of craniosynostosis is one in every 1,800-2500 births. The gene-environment model proposes that if a genetic predisposition is coupled with environmental exposures, the effects can be multiplicative resulting in severely abnormal phenotypes. At present, very little is known about the role of gene-environment interactions in modulating craniosynostosis phenotypes, but prior evidence suggests a role for endocrine factors. Here we provide a report of the effects of thyroid hormone exposure on murine calvaria cells. Murine derived calvaria cells were exposed to critical doses of pharmaceutical thyroxine and analyzed after 3 and 7 days of treatment. Endpoint assays were designed to determine the effects of the hormone exposure on markers of osteogenesis and included, proliferation assay, quantitative ALP activity assay, targeted qPCR for mRNA expression of Runx2, Alp, Ocn, and Twist1, genechip array for 28,853 targets, and targeted osteogenic microarray with qPCR confirmations. Exposure to thyroxine stimulated the cells to express ALP in a dose dependent manner. There were no patterns of difference observed for proliferation. Targeted RNA expression data confirmed expression increases for Alp and Ocn at 7 days in culture. The genechip array suggests substantive expression differences for 46 gene targets and the targeted osteogenesis microarray indicated 23 targets with substantive differences. 11 gene targets were chosen for qPCR confirmation because of their known association with bone or craniosynostosis (Col2a1, Dmp1, Fgf1, 2, Igf1, Mmp9, Phex, Tnf, Htra1, Por, and Dcn). We confirmed substantive increases in mRNA for Phex, FGF1, 2, Tnf, Dmp1, Htra1, Por, Igf1 and Mmp9, and substantive decreases for Dcn. It appears thyroid hormone may exert its effects through increasing osteogenesis. Targets isolated suggest a possible interaction for those gene products associated with calvarial suture growth and homeostasis as well as craniosynostosis. © 2013 Cray et al

Immune Amplification of Murine CD8+ Suppressor T Cells Induced via An Immune-Privileged Site: Quantifying Suppressor T Cells Functionally

BACKGROUND: CD8(+) suppressor T cells exert antigen-specific suppression of the expression of hypersensitivity by activated T cells. Therefore, CD8(+) suppressor T cells serve a major regulatory role for the control of active immunity. Accordingly, the number and/or activity of CD8(+) suppressor T cells should be influenced by an immune response to the antigen. To test this hypothesis we used an adoptive transfer assay that measures the suppression of the expression of delayed-type hypersensitivity (DTH) by CD8(+) suppressor T cells to quantify the antigen-specific suppression of DTH by these suppressor T cells. METHODS: Suppressor T cells were induced in the spleens of mice by the injection of antigen into the anterior chamber of an eye. Following this injection, the mice were immunized by the same antigen injected into the anterior chamber. Spleen cells recovered from these mice (AC-SPL cells) were titrated in an adoptive transfer assay to determine the number of AC-SPL cells required to effect a 50% reduction of antigen-induced swelling (Sw50) in the footpad of immunized mice challenged by antigen. RESULTS: Suppression of the expression of DTH is proportional to the number of AC-SPL cells injected into the site challenged by antigen. The number of AC-SPL cells required for a 50% reduction in DTH-induced swelling is reduced by injecting a cell population enriched for CD8(+) AC-SPL cells. Immunizing the mice receiving intracameral antigen to the same antigen decreases the RSw50 of AC-SPL cells required to inhibit the expression of DTH. CONCLUSIONS: The results provide the first quantitative demonstration that the numbers of antigen-specific splenic CD8(+) suppressor T cells are specifically amplified by antigen during an immune response

Common Gamma Chain Cytokines Promote Rapid In Vitro Expansion of Allo-Specific Human CD8+ Suppressor T Cells

Human CD8+ regulatory T cells, particularly the CD8+CD28− T suppressor cells, have emerged as an important modulator of alloimmunity. Understanding the conditions under which these cells are induced and/or expanded would greatly facilitate their application in future clinical trials. In the current study, we develop a novel strategy that combines common gamma chain (γc) cytokines IL-2, IL-7 and IL-15 and donor antigen presenting cells (APCs) to stimulate full HLA-mismatched allogeneic human CD8+ T cells which results in significant expansions of donor-specific CD8+CD28− T suppressor cells in vitro. The expanded CD8+CD28− T cells exhibit increased expressions of CTLA-4, FoxP3, and CD25, while down-regulate expressions of CD56, CD57, CD127, and perforin. Furthermore, these cells suppress proliferation of CD4+ T cells in a contact-dependent and cytokine-independent manner. Interestingly, the specificity of suppression is restricted by the donor HLA class I antigens but promiscuous to HLA class II antigens, providing a potential mechanism for linked suppression. Taken together, our results demonstrate a novel role for common γc cytokines in combination with donor APCs in the expansion of donor-specific CD8+CD28− T suppressor cells, and represent a robust strategy for in vitro generation of such cells for adoptive cellular immunotherapy in transplantation

The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups.

The elucidation of breast cancer subgroups and their molecular drivers requires integrated views of the genome and transcriptome from representative numbers of patients. We present an integrated analysis of copy number and gene expression in a discovery and validation set of 997 and 995 primary breast tumours, respectively, with long-term clinical follow-up. Inherited variants (copy number variants and single nucleotide polymorphisms) and acquired somatic copy number aberrations (CNAs) were associated with expression in ~40% of genes, with the landscape dominated by cis- and trans-acting CNAs. By delineating expression outlier genes driven in cis by CNAs, we identified putative cancer genes, including deletions in PPP2R2A, MTAP and MAP2K4. Unsupervised analysis of paired DNA–RNA profiles revealed novel subgroups with distinct clinical outcomes, which reproduced in the validation cohort. These include a high-risk, oestrogen-receptor-positive 11q13/14 cis-acting subgroup and a favourable prognosis subgroup devoid of CNAs. Trans-acting aberration hotspots were found to modulate subgroup-specific gene networks, including a TCR deletion-mediated adaptive immune response in the ‘CNA-devoid’ subgroup and a basal-specific chromosome 5 deletion-associated mitotic network. Our results provide a novel molecular stratification of the breast cancer population, derived from the impact of somatic CNAs on the transcriptome