Figures of Merit Software: Description, User's Guide, Installation Notes, Versions Description, and License Agreement

Figures of Merit (FoMs) and the FoM software provide a method for quantitatively evaluating the quality of a regolith simulant by comparing the simulant to a reference material. FoMs may be used for comparing a simulant to actual regolith material, specification by stating the value a simulant s FoMs must attain to be suitable for a given application and comparing simulants from different vendors or production runs. FoMs may even be used to compare different simulants to each other. A single FoM is conceptually an algorithm that computes a single number for quantifying the similarity or difference of a single characteristic of a simulant material and a reference material and provides a clear measure of how well a simulant and reference material match or compare. FoMs have been constructed to lie between zero and 1, with zero indicating a poor or no match and 1 indicating a perfect match. FoMs are defined for modal composition, particle size distribution, particle shape distribution, (aspect ratio and angularity), and density. This TM covers the mathematics, use, installation, and licensing for the existing FoM code in detail

Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction - (TOPCARE-AMI)

Background - Experimental studies suggest that transplantation of blood-derived or bone marrow–derived progenitor cells beneficially affects postinfarction remodeling. The safety and feasibility of autologous progenitor cell transplantation in patients with ischemic heart disease is unknown

FLT3 mutations in Early T-Cell Precursor ALL characterize a stem cell like leukemia and imply the clinical use of tyrosine kinase inhibitors

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) has been identified as high-risk subgroup of acute T-lymphoblastic leukemia (T-ALL) with a high rate of FLT3-mutations in adults. To unravel the underlying pathomechanisms and the clinical course we assessed molecular alterations and clinical characteristics in a large cohort of ETP-ALL (n = 68) in comparison to non-ETP T-ALL adult patients. Interestingly, we found a high rate of FLT3-mutations in ETP-ALL samples (n = 24, 35%). Furthermore, FLT3 mutated ETP-ALL was characterized by a specific immunophenotype (CD2+/CD5-/CD13+/CD33-), a distinct gene expression pattern (aberrant expression of IGFBP7, WT1, GATA3) and mutational status (absence of NOTCH1 mutations and a low frequency, 21%, of clonal TCR rearrangements). The observed low GATA3 expression and high WT1 expression in combination with lack of NOTCH1 mutations and a low rate of TCR rearrangements point to a leukemic transformation at the pluripotent prothymocyte stage in FLT3 mutated ETP-ALL. The clinical outcome in ETP-ALL patients was poor, but encouraging in those patients with allogeneic stem cell transplantation (3-year OS: 74%). To further explore the efficacy of targeted therapies, we demonstrate that T-ALL cell lines transfected with FLT3 expression constructs were particularly sensitive to tyrosine kinase inhibitors. In conclusion, FLT3 mutated ETP-ALL defines a molecular distinct stem cell like leukemic subtype. These data warrant clinical studies with the implementation of FLT3 inhibitors in addition to early allogeneic stem cell transplantation for this high risk subgroup

Elevated levels of diesel range organic compounds in groundwater near Marcellus gas operations are derived from surface activities

Author Posting. © The Author(s), 2015. This is the author's version of the work. It is posted here by permission of National Academy of Sciences for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences of the United States of American 112 (2015): 13184-13189, doi: 10.1073/pnas.1511474112 .Hundreds of organic chemicals are utilized during natural gas extraction via high volume hydraulic fracturing (HVHF). However, it is unclear if these chemicals, injected into deep shale horizons, reach shallow groundwater aquifers and impact local water quality, either from deep underground injection sites or from the surface or shallow subsurface. Here, we report detectable levels of organic compounds in shallow groundwater samples from private residential wells overlying the Marcellus Shale in northeastern Pennsylvania. Analyses of purgeable and extractable organic compounds from 64 groundwater samples revealed trace levels of volatile organic compounds, well below the Environmental Protection Agency’s maximum contaminant levels, and low levels of both gasoline range (GRO; 0-8 ppb) and diesel range organic compounds (DRO; 0-157 ppb). A compound-specific analysis revealed the presence of bis(2-ethylhexyl)phthalate, which is a disclosed HVHF additive, that was notably absent in a representative geogenic water sample and field blanks. Pairing these analyses with 1) inorganic chemical fingerprinting of deep saline groundwater, 2) characteristic noble gas isotopes, and 3) spatial relationships between active shale gas extraction wells and wells with disclosed environmental health and safety (EHS) violations, we differentiate between a chemical signature associated with naturally occurring saline groundwater and a one associated with alternative anthropogenic routes from the surface (e.g., accidental spills or leaks). The data support a transport mechanism of DRO to groundwater via accidental release of fracturing fluid chemicals derived from the surface rather than subsurface flow of these fluids from the underlying shale formation.The authors thank Duke University’s Pratt School of Engineering and the National Science Foundation’s CBET Grant Number 1336702 and NSF EAGER (EAR-1249255) for financial support.2016-04-1

Blinatumomab vs historical standard therapy of adult relapsed/refractory acute lymphoblastic leukemia

We compared outcomes from a single-arm study of blinatumomab in adult patients with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia (R/R ALL) with a historical data set from Europe and the United States. Estimates of complete remission (CR) and overall survival (OS) were weighted by the frequency distribution of prognostic factors in the blinatumomab trial. Outcomes were also compared between the trial and historical data using propensity score methods. The historical cohort included 694 patients with CR data and 1112 patients with OS data compared with 189 patients with CR and survival data in the blinatumomab trial. The weighted analysis revealed a CR rate of 24% (95% CI: 20-27%) and a median OS of 3.3 months (95% CI: 2.8-3.6) in the historical cohort compared with a CR/CRh rate of 43% (95% CI: 36-50%) and a median OS of 6.1 months (95% CI: 4.2-7.5) in the blinatumomab trial. Propensity score analysis estimated increased odds of CR/CRh (OR=2.68, 95% CI: 1.67-4.31) and improved OS (HR=0.536, 95% CI: 0.394-0.730) with blinatumomab. The analysis demonstrates the application of different study designs and statistical methods to compare novel therapies for R/R ALL with historical data

Horizontal DNA transfer mechanisms of bacteria as weapons of intragenomic conflict

Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framework for understanding the evolutionary origins of HDT. To test this hypothesis, we developed a mathematical model of a clonally descended bacterial population undergoing HDT through transmission of mobile genetic elements (MGEs) and genetic transformation. Including the known bias of transformation toward the acquisition of shorter alleles into the model suggested it could be an effective means of counteracting the spread of MGEs. Both constitutive and transient competence for transformation were found to provide an effective defence against parasitic MGEs; transient competence could also be effective at permitting the selective spread of MGEs conferring a benefit on their host bacterium. The coordination of transient competence with cell-cell killing, observed in multiple species, was found to result in synergistic blocking of MGE transmission through releasing genomic DNA for homologous recombination while simultaneously reducing horizontal MGE spread by lowering the local cell density. To evaluate the feasibility of the functions suggested by the modelling analysis, we analysed genomic data from longitudinal sampling of individuals carrying Streptococcus pneumoniae. This revealed the frequent within-host coexistence of clonally descended cells that differed in their MGE infection status, a necessary condition for the proposed mechanism to operate. Additionally, we found multiple examples of MGEs inhibiting transformation through integrative disruption of genes encoding the competence machinery across many species, providing evidence of an ongoing "arms race." Reduced rates of transformation have also been observed in cells infected by MGEs that reduce the concentration of extracellular DNA through secretion of DNases. Simulations predicted that either mechanism of limiting transformation would benefit individual MGEs, but also that this tactic's effectiveness was limited by competition with other MGEs coinfecting the same cell. A further observed behaviour we hypothesised to reduce elimination by transformation was MGE activation when cells become competent. Our model predicted that this response was effective at counteracting transformation independently of competing MGEs. Therefore, this framework is able to explain both common properties of MGEs, and the seemingly paradoxical bacterial behaviours of transformation and cell-cell killing within clonally related populations, as the consequences of intragenomic conflict between self-replicating chromosomes and parasitic MGEs. The antagonistic nature of the different mechanisms of HDT over short timescales means their contribution to bacterial evolution is likely to be substantially greater than previously appreciated