Project Minerva: A low cost manned Mars mission based on indigenous propellant production

Project Minerva is a low-cost manned Mars mission designed to deliver a crew of four to the Martian surface using only two sets of two launches from the Kennedy Space Center. Key concepts which make this mission realizable are the use of near-term technologies and in-situ propellant production, following the scenario originally proposed by R. Zubrin. The first set of launches delivers two unmanned payloads into low Earth orbit (LEO): the first payload consists of an Earth Return Vehicle (ERV), a propellant production plant, and a set of robotic vehicles; the second payload consists of the trans-Mars injection (TMI) upper stage. In LEO, the two payloads are docked and the configuration is injected into a Mars transfer orbit. The landing on Mars is performed with the aid of multiple aerobraking maneuvers. On the Martian surface, the propellant production plant uses a Sabatier/electrolysis type process to combine nine tons of hydrogen with carbon dioxide from the Martian atmosphere to produce over a hundred tons of liquid oxygen and liquid methane, which are later used as the propellants for the rover expeditions and the manned return journey of the ERV. The systems necessary for the flights to and from Mars, as well as those needed for the stay on Mars, are discussed. These systems include the transfer vehicle design, life support, guidance and communications, rovers and telepresence, power generation, and propellant manufacturing. Also included are the orbital mechanics, the scientific goals, and the estimated mission costs

Demographics and Incident Location of Gunshot Wounds at a Single Level I Trauma Center

Introduction:  Little is known surrounding the demographic and geospatial factors of firearm-related traumas in the Midwest Region.  The purpose of this study was to describe the overall incidence of firearm-related traumas and examine any racial/ethnic disparities that may exist. Methods:  A retrospective review was conducted of all patients 14 years or older who were admitted with a gunshot wound (GSW) to a Level I trauma center between 2016 and 2017.  Results:  Forty-nine percent of patients were Caucasian, 26.5% African American, and 19.6% Hispanic/Latino.  Hispanic/Latino patients were the youngest (25.8 ± 8.8) and Caucasians were the oldest (34.3 ± 14.1, P = 0.002).  Compared to Caucasian patients, African American (42.0%) and Hispanic/Latino (54.1%) patients were more likely to be admitted to the intensive care unit (ICU) (P = 0.034) and experienced longer ICU lengths of stay (2.5 ± 6.3 and 2.4 ± 4.7, P = 0.031, respectively).  African American patients (96.0%) experienced more assaults while Caucasians were more likely to receive gunshot wounds accidentally (26.9%, P = 0.001).  More African American (86.0%) and Hispanic/Latino (89.2%) patients were injured with a handgun and Caucasians sustained the highest number of shotgun/rifle related injuries (16.1%, P = 0.012).  Most GSWs occurred in zip codes 67202, 67203, 67213, 67211, and 67214.  Geographical maps indicated that GSWs were concentrated in low-income areas and areas with high minority populations.                                                                                                                                                                                              Conclusions:  Racial differences were noted, however, unlike national trends, most of our patients were older Caucasian males

Cyclin E overexpression sensitizes triple negative breast cancer to Wee1 kinase Inhibition

Purpose: Poor prognosis in triple-negative breast cancer (TNBC) is due to an aggressive phenotype and lack of biomarker-driven targeted therapies. Overexpression of cyclin E and phosphorylated-CDK2 are correlated with poor survival in TNBC patients, and the absence of CDK2 desensitizes cells to inhibition of Wee1 kinase, a key cell cycle regulator. We hypothesize that cyclin E expression can predict response to therapies, which include the Wee1 kinase inhibitor, AZD1775. Experimental Design: Mono and combination therapies with AZD1775 were evaluated in TNBC cell lines and multiple patient derived xenograft (PDX) models with different cyclin E expression profiles. The mechanism(s) of cyclin E-mediated replicative stress were investigated following cyclin E induction or CRISPR/Cas9 knockout by a number of assays in multiple cells lines. Results: Cyclin E overexpression (1) is enriched in TNBCs with high recurrence rates, (2) sensitizes TNBC cell lines and PDX models to AZD1775, (3) leads to CDK2-dependent activation of DNA replication stress pathways and (4) increases Wee1 kinase activity. Moreover, treatment of cells with either CDK2 inhibitors or carboplatin leads to transient transcriptional induction of cyclin E (in cyclin E-low tumors) and result in DNA replicative stress. Such drug mediated cyclin E induction in TNBC cells and PDX models sensitizes them to AZD1775 in a sequential treatment combination strategy. Conclusions: Cyclin E is a potential biomarker of response (1) for AZD1775 as monotherapy in cyclin E high TNBC tumors and (2) for sequential combination therapy with CDK2 inhibitor or carboplatin followed by AZD1775 in cyclin E low TNBC tumors

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

City of El Campo Downtown Revitalization Plan

The Revitalization Plan for Downtown El Campo is a planning document that provides guidance for the development of Downtown El Campo. This planning document includes an overview and analysis of the existing conditions in the City of El Campo and the El Campo Downtown Revitalization Area, a design proposal with vision, goals, and objectives for enhancing Downtown El Campo and a detailed implementation chapter for successful execution of the plan.This planning document presents the revitalization plan for downtown El Campo, Texas. This document was developed by Texas Target Communities (TTC) in partnership with the City of El Campo. The City of El Campo collaborated with Texas Target Communities in fall 2016 through the summer of 2017 to create a plan for revitalization of downtown El Campo. The purpose of the collaboration was to assess current community conditions, develop goals, objectives, and implementation strategies related to future development & growth strategies, through a public participatory process, in order to help guide the future growth of the City

Analysis of the interaction with the hepatitis C virus mRNA reveals an alternative mode of RNA recognition by the human La protein

Human La protein is an essential factor in the biology of both coding and non-coding RNAs. In the nucleus, La binds primarily to 3′ oligoU containing RNAs, while in the cytoplasm La interacts with an array of different mRNAs lacking a 3′ UUUOH trailer. An example of the latter is the binding of La to the IRES domain IV of the hepatitis C virus (HCV) RNA, which is associated with viral translation stimulation. By systematic biophysical investigations, we have found that La binds to domain IV using an RNA recognition that is quite distinct from its mode of binding to RNAs with a 3′ UUUOH trailer: although the La motif and first RNA recognition motif (RRM1) are sufficient for high-affinity binding to 3′ oligoU, recognition of HCV domain IV requires the La motif and RRM1 to work in concert with the atypical RRM2 which has not previously been shown to have a significant role in RNA binding. This new mode of binding does not appear sequence specific, but recognizes structural features of the RNA, in particular a double-stranded stem flanked by single-stranded extensions. These findings pave the way for a better understanding of the role of La in viral translation initiation

City of El Campo Downtown Revitalization Plan

The Revitalization Plan for Downtown El Campo is a planning document that provides guidance for the development of Downtown El Campo. This planning document includes an overview and analysis of the existing conditions in the City of El Campo and the El Campo Downtown Revitalization Area, a design proposal with vision, goals, and objectives for enhancing Downtown El Campo and a detailed implementation chapter for successful execution of the plan.This planning document presents the revitalization plan for downtown El Campo, Texas. This document was developed by Texas Target Communities (TTC) in partnership with the City of El Campo. The City of El Campo collaborated with Texas Target Communities in fall 2016 through the summer of 2017 to create a plan for revitalization of downtown El Campo. The purpose of the collaboration was to assess current community conditions, develop goals, objectives, and implementation strategies related to future development & growth strategies, through a public participatory process, in order to help guide the future growth of the City