Assembly Time Modeling Through Connective Complexity Metrics

This paper presents an approach for the development of surrogate models predicting the assembly time of a system based on complexity metrics of the physical system architecture when detailed geometric information is unavailable. A convention for modelling physical architecture is presented, followed by a sample of 10 analysed systems used for training and three systems used for validation. These systems are evaluated on complexity metrics developed from graph theoretic measures. An example model is developed based on a series of regressions of trends observed within the sample data. This is validated against the systems that are not used to develop the model. The model developed uses average path length, part count and path length density to approximate assembly time within the standard deviation of the subjective variation possible in Boothroyd and Dewhurst design for assembly (DFA) analysis. While the specific example model developed is generalisable only to systems similar to those in the sample set, the capability to develop mappings between physical architecture and assembly time in early-stage design is demonstrated

Viability of Hunting as a Means of Wild Hog Population Management on Federal Property

The Big South Fork National River and Recreation Area allows hunter to purchase permits and hunt wild hogs on property with the intention of curbing increases in wild hog populations. In order to assess outcomes of the wild hog hunting permit program, researchers collaborated with site managers to develop protocol and solicit information from permit holders regarding number of animals seen and harvested, sex of animals harvested, geographic areas hunted, length and number of hunts, and open qualitative feedback regarding the program. All permit holders agreeing to be contacted during permit registration were called with 37.57% (N=65) of permit holder completing the telephone survey. While more hogs were seen than harvested, the total harvested hogs was 52. Results indicate hunting is not a viable option for population management in and of itself, as the number if wild hogs harvested was minimal. A longitudinal study is necessary to overcome case study (single year) limitations, such as weather, hunter economics, herd movement, herd reproduction and so forth. Salient variables may warrant consideration, including marketing of permit program, number of hunters within acceptable driving distance to hunting location, and much more. Herd management initiatives beyond hunting may be considered when necessary to control wild hog populations

Transplantation of organs from deceased donors with meningitis and encephalitis: a UK registry analysis.

BACKGROUND: Deceased organ donors, where the cause of death is meningitis or encephalitis, are a potential concern because of the risks of transmission of a potentially fatal infection to recipients. METHODS: Using the UK Transplant Registry, a retrospective cohort analysis of deceased organ donors in the UK was undertaken to better understand the extent to which organs from deceased donors with meningitis and/or encephalitis (M/E) (of both known and unknown cause) have been used for transplantation, and to determine the associated recipient outcomes. RESULTS: Between 2003 and 2015, 258 deceased donors with M/E were identified and the causative agent was known in 188 (72.9%). These donors provided 899 solid organs for transplantation (455 kidneys and 444 other organs). The only recorded case of disease transmission was from a donor with encephalitis of unknown cause at time of transplantation who transmitted a fatal nematode infection to 2 kidney transplant recipients. A further 3 patients (2 liver and 1 heart recipient) died within 30 days of transplantation from a neurological cause (cerebrovascular accident) with no suggestion of disease transmission. Overall, patient and graft survival in recipients of organs from donors with M/E were similar to those for all other types of deceased organ donor. CONCLUSION: Donors dying with M/E represent a valuable source of organs for transplantation. The risk of disease transmission is low but, where the causative agent is unknown, caution is required.National Institute of Health Research, Blood and Transplant Research Unit (NIHR BTRU) on Organ Donation and Transplantation at the University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT), and the NIHR Cambridge Biomedical Research CentreThis is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1111/tid.1262

Deceased Organ Donors With a History of Increased Risk Behavior for the Transmission of Blood-Borne Viral Infection: The UK Experience.

BACKGROUND: Deceased organ donors are routinely screened for behaviors that increase the risk of transmissible blood-borne viral (BBV) infection, but the impact of this information on organ donation and transplant outcome is not well documented. Our aim was to establish the impact of such behavior on organ donation and utilization, as well transplant recipient outcomes. METHODS: We identified all UK deceased organ donors from 2003 to 2015 with a disclosed history of increased risk behavior (IRB) including intravenous drug use (IVDU), imprisonment and increased risk sexual behavior. RESULTS: Of 17 262 potential donors, 659 (3.8%) had IRB for BBV and 285 (1.7%) were seropositive for BBV, of whom half had a history of IRB (mostly IVDU [78.5%]). Of actual donors with IRB, 393 were seronegative for viral markers at time of donation. A history of recent IVDU was associated with fewer potential donors proceeding to become actual organ donors (64% vs 75%, P = 0.007). Donors with IRB provided 1091 organs for transplantation (624 kidneys and 467 other organs). Transplant outcome was similar in recipients of organs from donors with and without IRB. There were 3 cases of unexpected hepatitis C virus transmission, all from an active IVDU donor who was hepatitis C virus seronegative at time of donation, but was found to be viremic on retrospective testing. CONCLUSIONS: Donors with a history of IRB provide a valuable source of organs for transplantation with good transplant outcomes and there is scope for increasing the use of organs from such donors.The National Institute of Health Research, Blood and Transplant Research Unit (NIHR BTRU) on Organ Donation and Transplantation at the University of Cambridge in collaboration with Newcastle University and in partnership funded this research with NHS Blood and Transplant (NHSBT)

EPOCHS Paper II: The Ultraviolet Luminosity Function from 7.5<z<13.57.5<z<13.5 using 110 square arcminutes of deep, blank-field data from the PEARLS Survey and Public Science Programmes

We present an analysis of the ultraviolet luminosity function (UV LF) and star formation rate density of distant galaxies ($7.5 < z < 13.5$) in the `blank' fields of the Prime Extragalactic Areas for Reionization Science (PEARLS) survey combined with Early Release Science (ERS) data from the CEERS, GLASS and NGDEEP surveys/fields. We use a combination of SED fitting tools and quality cuts to obtain a reliable selection and characterisation of high-redshift ($z>6.5$) galaxies from a consistently processed set of deep, near-infrared imaging. Within an area of 110 arcmin$^{2}$, we identify 214 candidate galaxies at redshifts $z>6.5$ and we use this sample to study the ultraviolet luminosity function (UV LF) in four redshift bins between $7.5<z<13.5$. The measured number density of galaxies at $z=8$ and $z=9$ match those of past observations undertaken by the em Hubble Space Telescope (HST). However, towards higher redshifts we find that the evolution of the UV LF is mild, resulting in higher measured number densities of UV luminous galaxies at $z=10.5$ and $z=12.5$ compared to predictions from simulations and past HST observations. When examining the star formation rate density of galaxies at this time period, our observations are still consistent with a constant star formation efficiency, are slightly lower than previous early estimations using JWST and support galaxy driven reionization at $z\sim8$.Comment: 28 Pages, 4 Tables, 9 Figures, Submitted to Ap

TSP-1 Secreted by Bone Marrow Stromal Cells Contributes to Retinal Ganglion Cell Neurite Outgrowth and Survival

BACKGROUND: Bone marrow stromal cells (BMSCs) are pluripotent and thereby a potential candidate for cell replacement therapy for central nervous system degenerative disorders and traumatic injury. However, the mechanism of their differentiation and effect on neural tissues has not been fully elucidated. This study evaluates the effect of BMSCs on neural cell growth and survival in a retinal ganglion cell (RGCs) model by assessing the effect of changes in the expression of a BMSC-secreted protein, thrombospondin-1 (TSP-1), as a putative mechanistic agent acting on RGCs. METHODS AND FINDINGS: The effect of co-culturing BMSCs and RGCs in vitro was evaluated by measuring the following parameters: neurite outgrowth, RGC survival, BMSC neural-like differentiation, and the effect of TSP-1 on both cell lines under basal secretion conditions and when TSP-1 expression was inhibited. Our data show that BMSCs improved RGC survival and neurite outgrowth. Synaptophysin, MAP-2, and TGF-beta expression are up-regulated in RGCs co-cultured with BMSCs. Interestingly, the BMSCs progressively displayed neural-like morphology over the seven-day study period. Restriction display polymerase chain reaction (RD-PCR) was performed to screen for differentially expressed genes in BMSCs cultured alone or co-cultured with RGCs. TSP-1, a multifactorial extracellular matrix protein, is critically important in the formation of neural connections during development, so its function in our co-culture model was investigated by small interfering RNA (siRNA) transfection. When TSP-1 expression was decreased with siRNA silencing, BMSCs had no impact on RGC survival, but reduced neurite outgrowth and decreased expression of synaptophysin, MAP-2 and TGF-beta in RGCs. Furthermore, the number of BMSCs with neural-like characteristics was significantly decreased by more than two-fold using siRNA silencing. CONCLUSIONS: Our data suggest that the TSP-1 signaling pathway might have an important role in neural-like differentiation in BMSCs and neurite outgrowth in RGCs. This study provides new insights into the potential reparative mechanisms of neural cell repair

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity

The SARS-CoV-2 Omicron BA.1 variant emerged in 20211 and has multiple mutations in its spike protein2. Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However,&nbsp;in lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared with Delta. The differences in replication were mapped to the entry efficiency of the virus on the basis&nbsp;of spike-pseudotyped&nbsp;virus assays. The defect in entry of Omicron pseudotyped virus to specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2, and deletion of TMPRSS2 affected Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways3 demonstrated that the Omicron spike inefficiently uses the cellular protease TMPRSS2, which promotes cell entry through plasma membrane fusion, with greater dependency on cell entry through the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to use TMPRSS2, syncytium formation by the Omicron spike was substantially impaired compared with the Delta spike. The less efficient spike cleavage of Omicron at S1/S2 is associated with a shift in cellular tropism away from TMPRSS2-expressing cells, with implications for altered pathogenesis