Carbon/graphite fiber risk analysis and assessment study: An assessment of the risk to Douglas commercial transport aircraft

The potential hazard to electrical and electronic devices should there be a release of free carbon fibers due to an aircraft crash and fire was assessed. Exposure and equipment sensitivity data were compiled for a risk analysis. Results are presented in the following areas: DC-9/DC-10 electrical/electronic component characterization; DC-9 and DC-10 fiber transfer functions; potential for transport aircraft equipment exposure to carbon fibers; and equipment vulnerability assessment. Results reflect only a negligible increase in risk for the DC-9 and DC-10 fleets either now or projected to 1993

Why non-technical skills matter in surgery. New paradigms for surgical leaders

The surgical literature is paying more and more attention to the topic of soft or non-technical skills (NTS), defined as those cognitive and social skills that characterize high-performing individuals and teams. NTS are essential in supporting surgeons in dealing with unexpected situations. During the COVID-19 pandemic, NTS have been considered crucial in defining situation awareness, enhancing decision making, communicating among groups and teams, and fostering leadership. With a “looking back and planning forward” approach, the current perspective aims at deepening the contribution of NTS for surgeons to deal with the unexpected challenges posed by the COVID crisis, surgical emergencies, the introduction of new technologies in clinical practice, to understand how such skills may help shape the surgical leaders of the future

Identification and recovery of minor HIV-1 variants using the heteroduplex tracking assay and biotinylated probes

We describe a method to identify and recover minor human immunodeficiency virus type 1 (HIV-1) sequence variants from a complex population. The original heteroduplex tracking assay (HTA) was modified by incorporating a biotin tag into the probe to allow for direct sequence determination of the query strand. We used this approach to recover sequences from minor HIV-1 variants in the V3 region of the env gene, and to identify minor drug-resistant variants in pro. The biotin-HTA targeting of the V3 region of env allowed us to detect minor V3 variants, of which 45% were classified as CXCR4-using viruses. In addition, the biotin-protease HTA was able to detect mixtures of wild-type sequence and drug-resistance mutations in four subjects that were not detected by bulk sequence analysis. The biotin-HTA is a robust assay that first separates genetic variants then allows direct sequence analysis of major and minor variants

Upstaging nodal status in colorectal cancer using ex vivo fluorescence sentinel lymph node mapping: preliminary results

Background: Sentinel lymph node (SLN) mapping using near-infrared fluorescence (NIRF) imaging is a recent technique to improve nodal staging in several tumors. The presence of colorectal cancer (CRC) micro-metastases has recently been defined as N1 disease and no longer as N1mi, determining the need for adjuvant chemotherapy. In CRC, the reported rate of SLN micro-metastases detected by ultrastaging techniques is as high as 30%. The aim of this prospective study is to report the preliminary results of the sensitivity analysis of NIRF imaging for ex vivo SLN mapping and the research of micro-metastases in CRC, in patients with node-negative disease (NND). Material and methods: On the specimen of 22 CRC patients, 1 mL of ICG (5 mg/mL) was injected submucosally around the tumor to identify SLNs. NND SLNs were further investigated with ultrastaging techniques. Results: Three-hundred and sixty-three lymph nodes were retrieved (59 SLNs; mean per case: 2.7). The detection, sensitivity and false-negative rate were 100%, 100% and 0% respectively. Ultrastaging investigations showed no micro-metastases in the NND SLNs. Conclusions: The ex vivo SLN fluorescence-based detection in CRC was confirmed to be easy to perform and reliable. In this preliminary results report of an ongoing study, the SLN assay was congruent with the nodal status, as confirmed by histological investigations

Electromechanical Ski Release Binding With Mechanical Backup

FREQUENCY (Hz) Fig. 9 / axis responses for locations 2 and 3 for 1g input in X axis door assembly, so an estimated damping ratio of 0.02 was used. Conclusions The door assembly was designed and modelled within the given low mass budget. It survived the vibration tests which simulate the launch environment. These tests qualified the design for the flight structure. The door opening test which followed the vibration was satisfactory in that all the components of the door mechanism operated successfully

Evolution of the HIV-1 env Gene in the Rag2-/- C-/- Humanized Mouse Model

Rag2−/− γC−/− mice transplanted with human hematopoietic stem cells (DKO-hu-HSC mice) mimic aspects of human infection with human immunodeficiency virus type 1 (HIV-1), including sustained viral replication and CD4+ T-cell decline. However, the extent of HIV-1 evolution during long-term infection in these humanized mice, a key feature of the natural infection, has not been assessed fully. In this study, we examined the types of genotypic and phenotypic changes in the viral env gene that occur in the viral populations of DKO-hu-HSC mice infected with the CCR5-tropic isolate HIV-1JRCSF for up to 44 weeks. The mean rate of divergence of viral populations in mice was similar to that observed in a cohort of humans during a similar period of infection. Many amino acid substitutions were common across mice, including losses of N-linked glycosylation sites and substitutions in the CD4 binding site and in CD4-induced epitopes, indicating common selective pressures between mice. In addition, env variants evolved sensitivity to antibodies directed at V3, suggesting a more open conformation for Env. This phenotypic change was associated with increased CD4 binding efficiency and was attributed to specific amino acid substitutions. In one mouse, env variants emerged that exhibited a CXCR4-tropic phenotype. These sequences were compartmentalized in the mesenteric lymph node. In summary, viral populations in these mice exhibited dynamic behavior that included sequence evolution, compartmentalization, and the appearance of distinct phenotypic changes. Thus, humanized mice offer a useful model for studying evolutionary processes of HIV-1 in a complex host environment

Characterization of Blockade Antibody Responses in GII.2.1976 Snow Mountain Virus-Infected Subjects

Snow Mountain virus (GII.2.1976) is the prototype strain of GII.2 noroviruses (NoVs), which cause an estimated 8% of norovirus outbreaks, yet little is known about the immunobiology of these viruses. To define the human immune response induced by SMV infection and the antigenic relationship between different GII.2 strains that have circulated between 1976 and 2010, we developed a panel of four GII.2 variant virus-like particles (VLPs) and compared their antigenicities by enzyme immunoassay (EIA) and surrogate antibody neutralization (blockade) assays. Volunteers infected with GII.2.1976 developed a mean 167-fold increase in blockade response against the homotypic VLP by day 8 postchallenge. Blockade extended cross-genotype activity in some individuals but not cross-genogroup activity. Polyclonal sera from GII.2.1976-infected volunteers blocked GII.2.1976 significantly better than they blocked GII.2.2002, GII.2.2008, and GII.2.2010, suggesting that blockade epitopes within the GII.2 strains have evolved in the past decade. To potentially map these epitope changes, we developed mouse monoclonal antibodies (MAbs) against GII.2.1976 VLPs and compared their reactivities to a panel of norovirus VLPs. One MAb had broad cross-genogroup EIA reactivity to a nonblockade, linear, conserved epitope. Six MAbs recognized conformational epitopes exclusive to the GII.2 strains. Two MAbs recognized GII.2 blockade epitopes, and both blocked the entire panel of GII.2 variants. These data indicate that the GII.2 strains, unlike the predominant GII.4 strains, have undergone only a limited amount of evolution in blockade epitopes between 1976 and 2010 and indicate that the GII.2-protective component of a multivalent norovirus vaccine may not require frequent reformulation

Compensatory Evolution in RNA Secondary Structures Increases Substitution Rate Variation among Sites

There is growing evidence that interactions between biological molecules (e.g., RNA–RNA, protein–protein, RNA–protein) place limits on the rate and trajectory of molecular evolution. Here, by extending Kimura's model of compensatory evolution at interacting sites, we show that the ratio of transition to transversion substitutions (κ) at interacting sites should be equal to the square of the ratio at independent sites. Because transition mutations generally occur at a higher rate than transversions, the model predicts that κ should be higher at interacting sites than at independent sites. We tested this prediction in 10 RNA secondary structures by comparing phylogenetically derived estimates of κ in paired sites within stems (κp) and unpaired sites within loops (κu). Eight of the 10 structures showed an excellent match to the quantitative predictions of the model, and 9 of the 10 structures matched the qualitative prediction κp > κu. Only the Rev response element from the human immunovirus (HIV) genome showed the reverse pattern, with κp < κu. Although a variety of evolutionary forces could produce quantitative deviations from the model predictions, the reversal in magnitude of κp and κu could be achieved only by violating the model assumption that the underlying transition (or transversion) mutation rates were identical in paired and unpaired regions of the molecule. We explore the ability of the APOBEC3 enzymes, host defense mechanisms against retroviruses, which induce transition mutations preferentially in single-stranded regions of the HIV genome, to explain this exception to the rule. Taken as a whole, our findings suggest that κ may have utility as a simple diagnostic to evaluate proposed secondary structures

Retrovirus-mediated gene transfer to cystic fibrosis airway epithelial cells: effect of selectable marker sequences on long-term expression

Retrovirus-mediated gene transfer offers the potential for stable long-term expression of transduced genes in host cells subsequent to integration of vector DNA into the host genome. Using a murine amphotropic retrovirus vector containing an interleukin-2 receptor (IL-2R) gene as a reporter and a neomycin phosphotransferase