155 research outputs found
Measuring the Effectiveness of the Communications Electronics Life Cycle Management Command (CE-LCMC) Internship Pilot Training Program
Joint Applied ProjectOver the next seven years, more than 50 percent of DoD’s acquisition workforce will be eligible for
retirement. To replace these highly skilled acquisition professionals, the Department of Defense (DoD) will need
to efficiently and effectively train employees who are entering the contracting profession. In 2003, the
Communications Electronics Life Cycle Management Command (CE-LCMC) established a pilot training program
that was intended to accelerate the training and development of contracting interns. The purpose of this study was
to examine the effectiveness of this program from the perspectives of the 91 participating interns, the Contracting
Officers who work with these interns, and the managers/supervisors in the Acquisition Center. Based on the
analysis of five surveys, recommendations are offered for the improvement of the CE-LCMC’s pilot intern
training program.http://archive.org/details/measuringeffecti109457604United States Army,United States Army,United States Arm
Comparative development and evolution of two lateral line phenotypes in Lake Malawi cichlids
A comparison of the pattern and timing of development of cranial lateral line canals and canal neuromasts in three species of Lake Malawi cichlids, Labeotropheus fuelleborni and Metriaclima zebra (narrow lateral line canals), and Aulonocara baenschi (widened lateral line canals) was used to test the hypothesis that the evolution of widened canals (thought to be an adaptive phenotype in the lateral line system) from narrow canals is the result of heterochrony. Using histological analysis and scanning electron microscopy, this study has provided the first detailed and quantitative description of the development of widened lateral line canals in a teleost, and has demonstrated that: 1) canal neuromast number and the pattern of canal morphogenesis are conserved among species with different adult canal phenotypes, 2) heterochrony (“dissociated heterochrony” in particular) can explain the evolution of widened canals and variation in morphology between canals within a species with respect to canal diameter and neuromast size, and 3) the morphology of the lateral line canals and the dermal bones in which they are found (e.g., the mandibular canal the dentary and anguloarticular bones of the mandible) can evolve independently of each other, thus requiring the addition of another level of complexity to discussions of modularity and integration in the skull of bony fishe
Targeting of 5-aza-2'-deoxycytidine residues by chromatin-associated DNMT1 induces proteasomal degradation of the free enzyme.
5-Aza-2'-deoxycytidine (5-aza-dC) is a nucleoside analogue with cytotoxic and DNA demethylating effects. Here we show that 5-aza-dC induces the proteasomal degradation of free (non-chromatin bound) DNMT1 through a mechanism which is dependent on DNA synthesis and the targeting of incorporated 5-aza-dC residues by DNMT1 itself. Thus, 5-aza-dC induces Dnmt1 degradation in wild-type mouse ES cells, but not in Dnmt [3a(-/-), 3b(-/-)] mouse ES cells which express Dnmt1 but lack DNA methylation (<0.7% of CpG methylated) and contain few hemi-methylated CpG sites, these being the preferred substrates for Dnmt1. We suggest that adducts formed between DNMT1 and 5-aza-dC molecules in DNA induce a ubiquitin-E3 ligase activity which preferentially targets free DNMT1 molecules for degradation by the proteasome. The proteasome inhibitor MG132 prevents DNMT1 degradation and reduces hypomethylation induced by 5-aza-dC
VEZF1 elements mediate protection from DNA methylation
There is growing consensus that genome organization and long-range gene regulation involves partitioning of the genome into domains of distinct epigenetic chromatin states. Chromatin insulator or barrier elements are key components of these processes as they can establish boundaries between chromatin states. The ability of elements such as the paradigm β-globin HS4 insulator to block the range of enhancers or the spread of repressive histone modifications is well established. Here we have addressed the hypothesis that a barrier element in vertebrates should be capable of defending a gene from silencing by DNA methylation. Using an established stable reporter gene system, we find that HS4 acts specifically to protect a gene promoter from de novo DNA methylation. Notably, protection from methylation can occur in the absence of histone acetylation or transcription. There is a division of labor at HS4; the sequences that mediate protection from methylation are separable from those that mediate CTCF-dependent enhancer blocking and USF-dependent histone modification recruitment. The zinc finger protein VEZF1 was purified as the factor that specifically interacts with the methylation protection elements. VEZF1 is a candidate CpG island protection factor as the G-rich sequences bound by VEZF1 are frequently found at CpG island promoters. Indeed, we show that VEZF1 elements are sufficient to mediate demethylation and protection of the APRT CpG island promoter from DNA methylation. We propose that many barrier elements in vertebrates will prevent DNA methylation in addition to blocking the propagation of repressive histone modifications, as either process is sufficient to direct the establishment of an epigenetically stable silent chromatin stat
A Model for Rigorously Applying the Exploration, Preparation, Implementation, Sustainment (EPIS) Framework in the Design and Measurement of a Large Scale Collaborative Multi-Site Study
Background This paper describes the means by which a United States National Institute on Drug Abuse (NIDA)-funded cooperative, Juvenile Justice-Translational Research on Interventions for Adolescents in the Legal System (JJ-TRIALS), utilized an established implementation science framework in conducting a multi-site, multi-research center implementation intervention initiative. The initiative aimed to bolster the ability of juvenile justice agencies to address unmet client needs related to substance use while enhancing inter-organizational relationships between juvenile justice and local behavioral health partners. Methods The EPIS (Exploration, Preparation, Implementation, Sustainment) framework was selected and utilized as the guiding model from inception through project completion; including the mapping of implementation strategies to EPIS stages, articulation of research questions, and selection, content, and timing of measurement protocols. Among other key developments, the project led to a reconceptualization of its governing implementation science framework into cyclical form as the EPIS Wheel. The EPIS Wheel is more consistent with rapid-cycle testing principles and permits researchers to track both progressive and recursive movement through EPIS. Moreover, because this randomized controlled trial was predicated on a bundled strategy method, JJ-TRIALS was designed to rigorously test progress through the EPIS stages as promoted by facilitation of data-driven decision making principles. The project extended EPIS by (1) elucidating the role and nature of recursive activity in promoting change (yielding the circular EPIS Wheel), (2) by expanding the applicability of the EPIS framework beyond a single evidence-based practice (EBP) to address varying process improvement efforts (representing varying EBPs), and (3) by disentangling outcome measures of progression through EPIS stages from the a priori established study timeline. Discussion The utilization of EPIS in JJ-TRIALS provides a model for practical and applied use of implementation frameworks in real-world settings that span outer service system and inner organizational contexts in improving care for vulnerable populations. Trial registration NCT02672150. Retrospectively registered on 22 January 2016
Introductory programming: a systematic literature review
As computing becomes a mainstream discipline embedded in the school curriculum and acts as an enabler for an increasing range of academic disciplines in higher education, the literature on introductory programming is growing. Although there have been several reviews that focus on specific aspects of introductory programming, there has been no broad overview of the literature exploring recent trends across the breadth of introductory programming.
This paper is the report of an ITiCSE working group that conducted a systematic review in order to gain an overview of the introductory programming literature. Partitioning the literature into papers addressing the student, teaching, the curriculum, and assessment, we explore trends, highlight advances in knowledge over the past 15 years, and indicate possible directions for future research
Contemporary Tendencies in Mediation
Editors: Humberto dalla Bernardina de Pinho, Juliana Loss de AndradePresentation / Humberto Dalla Bernardina de Pinho, Juliana Loss de Andrade. -- Mediation in England / Neil Andrews. -- Un Reto para la Mediación: el Diseño de su Código Deontológico / Nuria Belloso Martín. -- Alternative Dispute Resolution and Aboriginal-Crown Reconciliation in Canada / Roshan Danesh, Jessica Dickson. -- A False ‘Prince Charming’ Keeps ‘Sleeping Beauty’ in a Coma: On Voluntary Mediation Being the True Oxymoron of Dispute Resolution Policy / Giuseppe De Palo. -- Programa de Derivación Judicial en Puerto Rico Desde la Perspectiva de la Mediación / Jacqueline N. Font-Guzmán. -- Mediation in Switzerland / Isabelle Hering. -- Reconocimiento y eficacia de los acuerdos de mediación mercantil internacional / Juliana Loss de Andrade. -- The Uses of Mediation / Lela P. Love, Joseph B. Stulberg. -- Multi-Dimensional Mediation / Paul E. Mason. -- “Italy Is Doing It – Should We Be?” Civil and Commercial Mediation in Italy / Giovanni Matteucci. -- Limites dos Meios Alternativos de Conflito / José Marinho Paulo Junior. -- New Perspectives of Civil and Commercial Mediation in Brazil / Humberto Dalla Bernardina de Pinho. -- Practical Impacts of Theoretical Lenses / Elton Simoes, Andrea Maia. -- Development and Resistance in South Europe Justice Systems to Restorative Justice / Helena Soleto Muño
The structure–activity relationships of L3MBTL3 inhibitors: flexibility of the dimer interface
We recently reported the discovery of UNC1215, a potent and selective chemical probe for the L3MBTL3 methyllysine reader domain. In this article, we describe the development of structure-activity relationships (SAR) of a second series of potent L3MBTL3 antagonists which evolved from the structure of the chemical probe UNC1215. These compounds are selective for L3MBTL3 against a panel of methyllysine reader proteins, particularly the related MBT family proteins, L3MBTL1 and MBTD1. A co-crystal structure of L3MBTL3 and one of the most potent compounds suggests that the L3MBTL3 dimer rotates about the dimer interface to accommodate ligand binding
Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial
Background
Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy
Mapping development and health effects of cooking with solid fuels in low-income and middle-income countries, 2000–18: a geospatial modelling study
Background: More than 3 billion people do not have access to clean energy and primarily use solid fuels to cook. Use of solid fuels generates household air pollution, which was associated with more than 2 million deaths in 2019. Although local patterns in cooking vary systematically, subnational trends in use of solid fuels have yet to be comprehensively analysed. We estimated the prevalence of solid-fuel use with high spatial resolution to explore subnational inequalities, assess local progress, and assess the effects on health in low-income and middle-income countries (LMICs) without universal access to clean fuels. Methods: We did a geospatial modelling study to map the prevalence of solid-fuel use for cooking at a 5 km × 5 km resolution in 98 LMICs based on 2·1 million household observations of the primary cooking fuel used from 663 population-based household surveys over the years 2000 to 2018. We use observed temporal patterns to forecast household air pollution in 2030 and to assess the probability of attaining the Sustainable Development Goal (SDG) target indicator for clean cooking. We aligned our estimates of household air pollution to geospatial estimates of ambient air pollution to establish the risk transition occurring in LMICs. Finally, we quantified the effect of residual primary solid-fuel use for cooking on child health by doing a counterfactual risk assessment to estimate the proportion of deaths from lower respiratory tract infections in children younger than 5 years that could be associated with household air pollution. Findings: Although primary reliance on solid-fuel use for cooking has declined globally, it remains widespread. 593 million people live in districts where the prevalence of solid-fuel use for cooking exceeds 95%. 66% of people in LMICs live in districts that are not on track to meet the SDG target for universal access to clean energy by 2030. Household air pollution continues to be a major contributor to particulate exposure in LMICs, and rising ambient air pollution is undermining potential gains from reductions in the prevalence of solid-fuel use for cooking in many countries. We estimated that, in 2018, 205 000 (95% uncertainty interval 147 000–257 000) children younger than 5 years died from lower respiratory tract infections that could be attributed to household air pollution. Interpretation: Efforts to accelerate the adoption of clean cooking fuels need to be substantially increased and recalibrated to account for subnational inequalities, because there are substantial opportunities to improve air quality and avert child mortality associated with household air pollution. Funding: Bill & Melinda Gates Foundation
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