System-of-Systems Technology-Portfolio-Analysis Tool

Advanced Technology Life-cycle Analysis System (ATLAS) is a system-of-systems technology-portfolio-analysis software tool. ATLAS affords capabilities to (1) compare estimates of the mass and cost of an engineering system based on competing technological concepts; (2) estimate life-cycle costs of an outer-space-exploration architecture for a specified technology portfolio; (3) collect data on state-of-the-art and forecasted technology performance, and on operations and programs; and (4) calculate an index of the relative programmatic value of a technology portfolio. ATLAS facilitates analysis by providing a library of analytical spreadsheet models for a variety of systems. A single analyst can assemble a representation of a system of systems from the models and build a technology portfolio. Each system model estimates mass, and life-cycle costs are estimated by a common set of cost models. Other components of ATLAS include graphical-user-interface (GUI) software, algorithms for calculating the aforementioned index, a technology database, a report generator, and a form generator for creating the GUI for the system models. At the time of this reporting, ATLAS is a prototype, embodied in Microsoft Excel and several thousand lines of Visual Basic for Applications that run on both Windows and Macintosh computers

From Enchantment to Disillusion: A Narrative Exploration of Cannabis Use Disorder Among Young Israeli Combat Veterans

Introduction: Substance use is common among military personnel and war veterans, especially combat veterans. Despite substantially high prevalence of cannabis use and Cannabis Use Disorder (CUD) consistently reported among veterans, little is known about psychological factors which may underlie CUD among this population.Methods: In this study, we used narrative analysis in order to interpret retrospective in-depth interviews of combat veterans (N = 12) who were released from mandatory military duty during the past 5 years and currently qualified for a diagnosis of CUD. Participants were recruited from a larger quantitative study were eligible for participation if they screened positive for a diagnosis of CUD according to the Cannabis Use Disorder Identification Test- Revised (CUDIT-R) questionnaire. CUD diagnosis was validated in-person using the cannabis section of the Alcohol Use Disorder and Associated Disabilities Interview Schedule-5 (AUDADIS-5) interview protocol. All interviews were transcribed and coded using the content analysis procedure.Findings: Five main themes were extracted: (a) Traumatic events (b) Attitudes toward cannabis use (c) Combatant identity (d) The role of authority/father figures, and (e) Moral crisis. A meta-theme has been identified, “from enchantment to disillusion,” representing a gradual psychological shift from a hopeful, highly motivated stance into the current state of mental rupture and moral injury, which are unsuccessfully compensated by excessive use of cannabis.Conclusions: This study shed light on the etiology of CUD among young combat veterans, highlighting the role of supposed self-medication for trauma and sense of betrayal

Effects of Smoking and Genotype on the PSR Index of Periodontal Disease in Adults Aged 18–49

Studies have found both genetic and environmental influences on chronic periodontitis. The purpose of this study was to examine the relationships among previously identified genetic variants, smoking status, and two periodontal disease-related phenotypes (PSR1 and PSR2) in 625 Caucasian adults (aged 18–49 years). The PSR Index was used to classify participants as affected or unaffected under the PSR1 and PSR2 phenotype definitions. Using logistic regression, we found that the form of the relationship varied by single nucleotide polymorphism (SNP): For rs10457525 and rs12630931, the effects of smoking and genotype on risk were additive; whereas for rs10457526 and rs733048, smoking was not independently associated with affected status once genotype was taken into consideration. In contrast, smoking moderated the relationships of rs3870371 and rs733048 with affected status such that former and never smokers with select genotypes were at increased genetic risk. Thus, for several groups, knowledge of genotype may refine the risk prediction over that which can be determined by knowledge of smoking status alone. Future studies should replicate these findings. These findings provide the foundation for the exploration of novel pathways by which periodontitis may occur

The Effect of LXR Activators on AP-1 Proteins in Keratinocytes

Oxysterols, via activation of liver X receptor (LXR), regulate keratinocyte differentiation by stimulating transglutaminase cross-linking of several constituent proteins leading to the formation of the cornified envelope. We previously reported that oxysterols increase the expression of one of these cross-linked proteins, involucrin, and that this effect can be abolished by mutations of the distal activator protein (AP)-1 response element in the involucrin promoter. Furthermore, oxysterols increase AP-1 binding in an electrophoretic gel mobility shift assay and increase the expression of an AP-1 reporter. In this study, we describe the individual components of the AP-1 complex that are involved in the oxysterol-mediated AP-1 activation and stimulation of keratinocyte differentiation. We identified Fra-1 within the AP-1 DNA binding complex by supershift analysis of nuclear extracts from oxysterol-treated, cultured keratinocytes and confirmed that oxysterol treatment increased the levels of Fra-1 by western blot analysis. Additionally, on Western and Northern analysis, oxysterol treatment increased two other AP-1 proteins, Jun-D and c-Fos, whereas Fra-2, Jun-B, and c-Jun were not changed. Similar alterations in AP-1 proteins occurred when 25-OH-cholesterol or non-steroidal LXR agonists (GW3965, TO-901317) were used. These results indicate that oxysterols induce specific AP-1 proteins, thereby activating involucrin, one of the genes required for epidermal differentiation

Correlation between kinetic and kinematic measures, clinical tests and subjective self-evaluation questionnaires of the affected upper limb in people after stroke

IntroductionAssessment of stroke recovery should include multiple sources of information in order to obtain a complete understanding of the individual’s rehabilitation progress. Self-evaluation questionnaires’ scores do not always correspond to the scores of commonly used clinical evaluation tools. The purpose of this study was to assess the relationship between self-evaluation questionnaires, clinical tests, and kinematic and kinetic analyses of the affected upper limb after stroke, and to determine the correlation between these measures and self-reported general function 2–4 years after the stroke.MethodsTwenty-six subjects recovering from stroke were included in the study. Spearman’s correlation coefficient was used to measure the correlation between Stroke Impact Scale (SIS), Motor activity Log (MAL), Fugl-Meyer Assessment (FMA) and Action Reach Arm Test (ARAT) scores, and kinematic and kinetic analyses. A logistic regression was used to assess the extent to which these measures may predict the participants’ functional self-reported status 2–4 years post stroke.ResultsSections regarding hand function, hand force and general ADL of the self-evaluation questionnaires correlated with kinematic variables. However, only questionnaires that focus on hand function correlated with clinical tests. Mean and maximal hand velocity had the strongest correlations with self-evaluation questionnaires and with the clinical tests, more than other kinematic variables. Self-evaluation questionnaires and clinical tests were found to be correlated with hand kinetic metrics force-to-time ratio and number of force peaks. SIS hand force domain, mean velocity and maximal velocity predicted self-reported general function 2–4 years after the stroke.ConclusionSelf-evaluation questionnaires should be considered for wider use in the clinical evaluation of a patient’s stroke recovery, since they add important information on the individual’s functional status, which is not reflected in the clinical tests

Genome-Wide Association Study of Periodontal Health Measured by Probing Depth in Adults Ages 18−49 years

The etiology of chronic periodontitis clearly includes a heritable component. Our purpose was to perform a small exploratory genome-wide association study in adults ages 18–49 years to nominate genes associated with periodontal disease−related phenotypes for future consideration. Full-mouth periodontal pocket depth probing was performed on participants (N = 673), with affected status defined as two or more sextants with probing depths of 5.5 mm or greater. Two variations of this phenotype that differed in how missing teeth were treated were used in analysis. More than 1.2 million genetic markers across the genome were genotyped or imputed and tested for genetic association. We identified ten suggestive loci (p-value ≤ 1E-5), including genes/loci that have been previously implicated in chronic periodontitis: LAMA2, HAS2, CDH2, ESR1, and the genomic region on chromosome 14q21-22 between SOS2 and NIN. Moreover, we nominated novel loci not previously implicated in chronic periodontitis or related pathways, including the regions 3p22 near OSBPL10 (a lipid receptor implicated in hyperlipidemia), 4p15 near HSP90AB2P (a heat shock pseudogene), 11p15 near GVINP1 (a GTPase pseudogene), 14q31 near SEL1L (an intracellular transporter), and 18q12 in FHOD3 (an actin cytoskeleton regulator). Replication of these results in additional samples is needed. This is one of the first research efforts to identify genetic polymorphisms associated with chronic periodontitis-related phenotypes by the genome-wide association study approach. Though small, efforts such this are needed in order to nominate novel genes and generate new hypotheses for exploration and testing in future studies

Novel caries loci in children and adults implicated by genome-wide analysis of families

Background: Dental caries is a common chronic disease among children and adults alike, posing a substantial health burden. Caries is affected by multiple genetic and environmental factors, and prior studies have found that a substantial proportion of caries susceptibility is genetically inherited. Methods: To identify such genetic factors, we conducted a genome-wide linkage scan in 464 extended families with 2616 individuals from Iowa, Pennsylvania and West Virginia for three dental caries phenotypes: (1) PRIM: dichotomized as zero versus one or more affected primary teeth, (2) QTOT1: age-adjusted quantitative caries measure for both primary and permanent dentitions including pre-cavitated lesions, and (3) QTOT2: age-adjusted quantitative caries excluding pre-cavitated lesions. Genotyping was conducted for approximately 600,000 SNPs on an Illumina platform, pruned to 127,511 uncorrelated SNPs for the analyses reported here. Results: Multipoint non-parametric linkage analyses generated peak LOD scores exceeding 2.0 for eight genomic regions, but no LOD scores above 3.0 were observed. The maximum LOD score for each of the three traits was 2.90 at 1q25.3 for PRIM, 2.38 at 6q25.3 for QTOT1, and 2.76 at 5q23.3 for QTOT2. Some overlap in linkage regions was observed among the phenotypes. Genes with a potential role in dental caries in the eight chromosomal regions include CACNA1E, LAMC2, ALMS1, STAMBP, GXYLT2, SLC12A2, MEGF10, TMEM181, ARID1B, and, as well as genes in several immune gene families. Our results are also concordant with previous findings from association analyses on chromosomes 11 and 19. Conclusions: These multipoint linkage results provide evidence in favor of novel chromosomal regions, while also supporting earlier association findings for these data. Understanding the genetic etiology of dental caries will allow designing personalized treatment plans based on an individual’s genetic risk of disease

A Preliminary Genome-Wide Association Study of Pain-Related Fear: Implications for Orofacial Pain

Background. Acute and chronic orofacial pain can significantly impact overall health and functioning. Associations between fear of pain and the experience of orofacial pain are well-documented, and environmental, behavioral, and cognitive components of fear of pain have been elucidated. Little is known, however, regarding the specific genes contributing to fear of pain. Methods. A genome-wide association study (GWAS; ) was performed to identify plausible genes that may predispose individuals to various levels of fear of pain. The total score and three subscales (fear of minor, severe, and medical/dental pain) of the Fear of Pain Questionnaire-9 (FPQ-9) were modeled in a variance components modeling framework to test for genetic association with 8.5 M genetic variants across the genome, while adjusting for sex, age, education, and income. Results. Three genetic loci were significantly associated with fear of minor pain (8q24.13, 8p21.2, and 6q26; for all) near the genes TMEM65, NEFM, NEFL, AGPAT4, and PARK2. Other suggestive loci were found for the fear of pain total score and each of the FPQ-9 subscales. Conclusions. Multiple genes were identified as possible candidates contributing to fear of pain. The findings may have implications for understanding and treating chronic orofacial pain

Efficient CRISPR/Cas9 Genome Editing in Alfalfa Using a Public Germplasm

Because its ability to acquire large amounts of nitrogen by symbiosis, tetraploid alfalfa is the main source of vegetable proteins in meat and milk production systems in temperate regions. Alfalfa cultivation also adds fixed nitrogen to the soil, improving the production of non-legumes in crop rotation and reducing the use of nitrogen fertilizers derived from fossil fuel. Despite its economic and ecological relevance, alfalfa genetics remains poorly understood, limiting the development of public elite germplasm. In this brief article, we reported the high-efficiency of alfalfa mutagenesis by using the public clone C23 and the CRISPR/Cas9 system. Around half of the GUS overexpressing plants (35S-GUS under C23 genomic background) transformed with an editing plasmid containing two sgRNAs against the GUS gene and the Cas9 nuclease exhibited absence of GUS activity. Nucleotide analysis showed that the inactivation of GUS in CRISPR/Cas9-editing events were produced via different modifications in the GUS gene, including frameshift and non-sense mutations. Using the CRISPR/Cas9 system and two sgRNAs, we have also edited the alfalfa gene NOD26, generating plants with different doses of alleles at this locus, including complete gene knockout at high efficiency (11%). Finally, we discuss the potential applications of genome-editing technologies to polyploid research and to alfalfa improvement public programs.Fil: Bottero, Ana Emilia. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo | Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo; ArgentinaFil: Massa, Gabriela Alejandra. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Innovación Para la Producción Agropecuaria y El Desarrollo Sostenible. - Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Buenos Aires Sur. Estacion Experimental Agropecuaria Balcarce. Instituto de Innovación Para la Producción Agropecuaria y El Desarrollo Sostenible.; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; ArgentinaFil: Gonzalez, Matías Nicolás. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Innovación Para la Producción Agropecuaria y El Desarrollo Sostenible. - Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Buenos Aires Sur. Estacion Experimental Agropecuaria Balcarce. Instituto de Innovación Para la Producción Agropecuaria y El Desarrollo Sostenible.; ArgentinaFil: Stritzler, Margarita. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo | Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo; ArgentinaFil: Tajima, Hiromi. University of California; Estados UnidosFil: Gómez, Cristina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo | Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo; ArgentinaFil: Frare, Romina Alejandra. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo | Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo; ArgentinaFil: Feingold, Sergio. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Innovación Para la Producción Agropecuaria y El Desarrollo Sostenible. - Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Buenos Aires Sur. Estacion Experimental Agropecuaria Balcarce. Instituto de Innovación Para la Producción Agropecuaria y El Desarrollo Sostenible.; ArgentinaFil: Blumwald, Eduardo. University of California; Estados UnidosFil: Ayub, Nicolás Daniel. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo | Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo; ArgentinaFil: Soto, Gabriela Cynthia. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo | Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo; Argentin