Riverine sustainment 2012

Student Integrated ProjectIncludes supplementary materialThis technical report analyzed the Navy's proposed Riverine Force (RF) structure and capabilities for 2012. The Riverine Sustainment 2012 Team (RST) examined the cost and performance of systems of systems which increased RF sustainment in logistically barren environments. RF sustainment was decomposed into its functional areas of supply, repair, and force protection. The functional and physical architectures were developed in parallel and were used to construct an operational architecture for the RF. The RST used mathematical, agent-based and queuing models to analyze various supply, repair and force protection system alternatives. Extraction of modeling data revealed several key insights. Waterborne heavy lift connectors such as the LCU-2000 are vital in the re-supply of the RF when it is operating up river in a non-permissive environment. Airborne heavy lift connectors such as the MV-22 were ineffective and dominated by the waterborne variants in the same environment. Increase in manpower and facilities did appreciable add to the operational availability of the RF. Mean supply response time was the biggest factor effecting operational availability and should be kept below 24 hours to maintain operational availability rates above 80%. Current mortar defenses proposed by the RF are insufficient.N

Extensive Promoter-Centered Chromatin Interactions Provide a Topological Basis for Transcription Regulation

Higher-order chromosomal organization for transcription regulation is poorly understood in eukaryotes. Using genome-wide Chromatin Interaction Analysis with Paired-End-Tag sequencing (ChIAPET), we mapped long-range chromatin interactions associated with RNA polymerase II in human cells and uncovered widespread promoter-centered intragenic, extragenic, and intergenic interactions. These interactions further aggregated into higher-order clusters, wherein proximal and distal genes were engaged through promoter-promoter interactions. Most genes with promoter-promoter interactions were active and transcribed cooperatively, and some interacting promoters could influence each other implying combinatorial complexity of transcriptional controls. Comparative analyses of different cell lines showed that cell-specific chromatin interactions could provide structural frameworks for cell-specific transcription, and suggested significant enrichment of enhancer-promoter interactions for cell-specific functions. Furthermore, genetically-identified disease-associated noncoding elements were found to be spatially engaged with corresponding genes through long-range interactions. Overall, our study provides insights into transcription regulation by three-dimensional chromatin interactions for both housekeeping and cell-specific genes in human cells

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Sequoyah foreign language translation system business case analysis

Sequoyah, which is the Department of Defense (DoD)'s Program of Record for automated foreign language translation, is to identify current and developing technologies to meet warfighter requirements for foreign language support. Sequoyah aspires to have MLT capability embedded in other systems, such as Soldier as a System (SaaS) and Future Combat System (FCS), so as to provide automated capability to meet the warfighters' foreign language translation needs when a human linguist is unavailable. The purpose of this thesis is to analyze the potential cost savings and benefits of utilizing MLT systems as a complement to the host nation linguists required to be hired to support military operations. This thesis will develop a Business case for the following purposes: Analyze the best circumstances in military operations that MLT systems can be used to complement human linguists or when human linguist is not available. Determine the comparative costs of MLT systems vs. host nation linguists using techniques from the field of cost estimation. Although the use of computers is very prevalent in today's society, they simply cannot replace human beings in performing some of the tasks that require thinking and understanding. Bar-Hillel, an early machine translation researcher, used a seemingly simple sentence "The box is in the pen" to point out that "to decide whether the sentence is talking about a writing instrument pen or a child's play pen, it would be necessary for a computer to know about the relative sizes of objects in the real world. The point is that accurate translation requires an understanding of the text, which includes an understanding of the situation and an enormous variety of facts about the world in which we live." Hence, this study does not advocate replacing human linguists with MLT systems but rather to explore the circumstances that MLT systems can be used to complement host nation linguists or when there is no linguist available.http://archive.org/details/sequoyahforeignl109453123Singapore Defense Science and Technology Agency author (civilian).Approved for public release; distribution is unlimited

PAF promotes stemness and radioresistance of glioma stem cells.

An integrated genomic and functional analysis to elucidate DNA damage signaling factors promoting self-renewal of glioma stem cells (GSCs) identified proliferating cell nuclear antigen (PCNA)-associated factor (PAF) up-regulation in glioblastoma. PAF is preferentially overexpressed in GSCs. Its depletion impairs maintenance of self-renewal without promoting differentiation and reduces tumor-initiating cell frequency. Combined transcriptomic and metabolomic analyses revealed that PAF supports GSC maintenance, in part, by influencing DNA replication and pyrimidine metabolism pathways. PAF interacts with PCNA and regulates PCNA-associated DNA translesion synthesis (TLS); consequently, PAF depletion in combination with radiation generated fewer tumorspheres compared with radiation alone. Correspondingly, pharmacological impairment of DNA replication and TLS phenocopied the effect of PAF depletion in compromising GSC self-renewal and radioresistance, providing preclinical proof of principle that combined TLS inhibition and radiation therapy may be a viable therapeutic option in the treatment of glioblastoma multiforme (GBM). Proc Natl Acad Sci U S A 2017 Oct 24; 114(43):E9086-E9095

Telomere Dysfunction Drives Aberrant Hematopoietic Differentiation and Myelodysplastic Syndrome

SummaryMyelodysplastic syndrome (MDS) risk correlates with advancing age, therapy-induced DNA damage, and/or shorter telomeres, but whether telomere erosion directly induces MDS is unknown. Here, we provide the genetic evidence that telomere dysfunction-induced DNA damage drives classical MDS phenotypes and alters common myeloid progenitor (CMP) differentiation by repressing the expression of mRNA splicing/processing genes, including SRSF2. RNA-seq analyses of telomere dysfunctional CMP identified aberrantly spliced transcripts linked to pathways relevant to MDS pathogenesis such as genome stability, DNA repair, chromatin remodeling, and histone modification, which are also enriched in mouse CMP haploinsufficient for SRSF2 and in CD34+ CMML patient cells harboring SRSF2 mutation. Together, our studies establish an intimate link across telomere biology, aberrant RNA splicing, and myeloid progenitor differentiation

Large-Scale Whole-Genome Sequencing of Three Diverse Asian Populations in Singapore

Because of Singapore's unique history of immigration, whole-genome sequence analysis of 4,810 Singaporeans provides a snapshot of the genetic diversity across East, Southeast, and South Asia.</p