Cart Loader

For this senior design project, the team partnered with a startup, Dishcraft Robotics, to design and create a device that would decrease the time it takes to unload and load their products in and out of a truck. The team’s design, Cart Loader, consists of an aluminum structure that is able to hold their products. Outfitted with a rail system on the truck and the liftgate, the Cart Loader can move onto the liftgate and roll inside the truck, where the products can then be rolled off the Cart Loader. There was extensive finite element analysis done to ensure that the structure could handle the loads of the products. The Cart Loader can withstand loads of up to 1500 lbs with a factor of safety of 1.82. Even without the physical truck, testing was done on the Cart Loader. The Cart Loader ended up reducing the loading time from 60 minutes to 27.1 minutes. In addition, the Cart Loader accomplished the customer’s goals of a device that secures their products, is easy to use, and carries a large portion of their products in one load

Injury Patterns, Imaging Usage, and Disparities Associated With Car Restraint Use in Children

Background Motor vehicle collision (MVC) is a leading cause of accidental death in children. Despite effective forms of child safety restraint (eg, car seat and booster seat), studies demonstrate poor compliance with guidelines. The goal of this study was to delineate injury patterns, imaging usage, and potential demographic disparities associated with child restraint use following MVC. Methods A retrospective review of the North Carolina Trauma Registry was performed to determine demographic factors and outcomes associated with improper restraint of children (0-8 years) involved in MVC from 2013 to 2018. Bivariate analysis was performed by the appropriateness of restraint. Multivariable Poisson regression identified demographic factors for the relative risk of inappropriate restraint. Results Inappropriately restrained patients were older (5.1 years v. 3.6 yrs, P < .001) and weighed more (44.1 lbs v. 35.3 lbs, P < .001). A higher proportion of African American (56.9% v. 39.3%, P < .001) and Medicaid (52.2% v. 39.0%, P < .001) patients were inappropriately restrained. Multivariable Poisson regression showed that African American patients (RR 1.43), Asian patients (RR 1.51), and Medicaid payor status (RR 1.25) were associated with a higher risk of inappropriate restraint. Inappropriately restrained patients had a longer length of stay, but injury severity score and mortality were no different. Discussion African American children, Asian children, and Medicaid insurance payor status patients had an increased risk of inappropriate restraint use in MVC. This study describes unequal restraint patterns in children, which suggests opportunity for targeted patient education and necessitates research to further delineate the underlying etiology of these differences

Intron-containing RNA from the HIV-1 provirus activates type I interferon and inflammatory cytokines

HIV-1-infected people who take drugs that suppress viremia to undetectable levels are protected from developing AIDS. Nonetheless, these individuals have chronic inflammation associated with heightened risk of cardiovascular pathology. HIV-1 establishes proviruses in long-lived CD4+ memory T cells, and perhaps other cell types, that preclude elimination of the virus even after years of continuous antiviral therapy. Though the majority of proviruses that persist during antiviral therapy are defective for production of infectious virions, many are expressed, raising the possibility that the HIV-1 provirus or its transcripts contribute to ongoing inflammation. Here we found that the HIV-1 provirus activated innate immune signaling in isolated dendritic cells, macrophages, and CD4+ T cells. Immune activation required transcription from the HIV-1 provirus and expression of CRM1-dependent, Rev-dependent, RRE-containing, unspliced HIV-1 RNA. If rev was provided in trans, all HIV-1 coding sequences were dispensable for activation except those cis-acting sequences required for replication or splicing. These results indicate that the complex, post-transcriptional regulation intrinsic to HIV-1 RNA is detected by the innate immune system as a danger signal, and that drugs which disrupt HIV-1 transcription or HIV-1 RNA metabolism would add qualitative benefit to current antiviral drug regimens

Geomagnetically Induced Currents in the Irish Power Network during Geomagnetic Storms

Geomagnetically induced currents (GICs) are a well-known terrestrial space weather hazard. They occur in power transmission networks and are known to have adverse effects in both high and mid-latitude countries. Here, we study GICs in the Irish power transmission network (geomagnetic latitude 54.7--58.5$^{\circ}$ N) during five geomagnetic storms (06-07 March 2016, 20-21 December 2015, 17-18 March 2015, 29-31 October 2003 and 13-14 March 1989). We simulate electric fields using a plane wave method together with two ground resistivity models, one of which is derived from magnetotelluric measurements (MT model). We then calculate GICs in the 220, 275 and 400~kV transmission network. During the largest of the storm periods studied, the peak electric field was calculated to be as large as 3.8~V~km\textsuperscript{-1}, with associated GICs of up to 23~A using our MT model. Using our homogenous resistivity model, those peak values were 1.46~V~km\textsuperscript{-1} and 25.8~A. We find that three 400 and 275~kV substations are the most likely locations for the Irish transformers to experience large GICs.Comment: 14 pages, 11 Figures, 4 Table

Geomagnetic conditions in Ireland During the St. Patrick's Day 2015 Storm

<p>Poster at UK National Astronomy Meeting in Llandudno, Wales on July 5-9, 2015 (www.nam2015.org)</p> <p>Abstract:</p> <p>Two coronal mass ejections were launched in quick succession from the Sun on March 15, 2015. They impacted the Earth's magnetosphere two days later on St. Patrick's Day (March 17), resulting in a geomagnetic storm with a planetary K-Index of 8.</p> <p>Magnetic variations were measured across a recently deployed magnetometer network in Ireland and geoelectric fields were measured at a site in Co. Leitrim (magnetic latitude 57.08°). A local K-index maximum of 7 was calculated at Birr, Co. Offaly (magnetic latitude 55.97), while the aurora</p> <p>borealis accompanying the geomagnetic storm was visible as far south as Co. Waterford (magnetic latitude 55.13°).</p> <p>The British Geological Survey thin-sheet surface electric field model was used together with our magnetometer measurements to calculate electric fields and geomagnetically induced currents (GICs) in the Irish power grid.</p> <p>Although it was one of the most magnetically disturbed days in a decade, with dB/dt reaching ~50 nT/min, the peak GIC level estimated in the Irish power grid was ~10 Amps. Note, no adverse effects were reported in the Irish power grid demonstrating its resilience to geomagnetic storms of this magnitude.</p

Primate immunodeficiency virus Vpx and Vpr counteract transcriptional repression of proviruses by the HUSH complex [preprint]

Drugs that inhibit HIV-1 replication and prevent progression to AIDS do not eliminate HIV-1 proviruses from the chromosomes of long-lived CD4+ memory T cells. To escape eradication by these antiviral drugs, or by the host immune system, HIV-1 exploits poorly defined host factors that silence provirus transcription. These same factors, though, must be overcome by all retroviruses, including HIV-1 and other primate immunodeficiency viruses, in order to activate provirus transcription and produce new virus. Here we show that Vpx and Vpr, proteins from a wide range of primate immunodeficiency viruses, activate provirus transcription in human CD4+ T cells. Provirus activation required the DCAF1 adaptor that links Vpx and Vpr to the CUL4A/B ubiquitin ligase complex, but did not require degradation of SAMHD1, a well-characterized target of Vpx and Vpr. A loss-of-function screen for transcription silencing factors that mimic the effect of Vpx on provirus silencing identified all components of the Human Silencing Hub (HUSH) complex, FAM208A (TASOR/RAP140), MPHOSPH8 (MPP8), PPHLN1 (PERIPHILIN), and MORC2. Vpx associated with the HUSH complex components and decreased steady-state levels of these proteins in a DCAF-dependent manner. Finally, vpx and FAM208A knockdown accelerated HIV-1 and SIVMAC replication kinetics in CD4+ T cells to a similar extent, and HIV-2 replication required either vpx or FAM208A disruption. These results demonstrate that the HUSH complex restricts transcription of primate immunodeficiency viruses and thereby contributes to provirus latency. To counteract this restriction and activate provirus expression, primate immunodeficiency viruses encode Vpx and Vpr proteins that degrade HUSH complex components

Lv4 Is a Capsid-Specific Antiviral Activity in Human Blood Cells That Restricts Viruses of the SIVMAC/SIVSM/HIV-2 Lineage Prior to Integration

HIV-2 and SIVMAC are AIDS-causing, zoonotic lentiviruses that jumped to humans and rhesus macaques, respectively, from SIVSM-bearing sooty mangabey monkeys. Cross-species transmission events such as these sometimes necessitate virus adaptation to species-specific, host restriction factors such as TRIM5. Here, a new human restriction activity is described that blocks viruses of the SIVSM/SIVMAC/HIV-2 lineage. Human T, B, and myeloid cell lines, peripheral blood mononuclear cells and dendritic cells were 4 to \u3e 100-fold less transducible by VSV G-pseudotyped SIVMAC, HIV-2, or SIVSM than by HIV-1. In contrast, transduction of six epithelial cell lines was equivalent to that by HIV-1. Substitution of HIV-1 CA with the SIVMAC or HIV-2 CA was sufficient to reduce HIV-1 transduction to the level of the respective vectors. Among such CA chimeras there was a general trend such that CAs from epidemic HIV-2 Group A and B isolates were the most infectious on human T cells, CA from a 1 degrees sooty mangabey isolate was the least infectious, and non-epidemic HIV-2 Group D, E, F, and G CAs were in the middle. The CA-specific decrease in infectivity was observed with either HIV-1, HIV-2, ecotropic MLV, or ALV Env pseudotypes, indicating that it was independent of the virus entry pathway. As2O3, a drug that suppresses TRIM5-mediated restriction, increased human blood cell transduction by SIVMAC but not by HIV-1. Nonetheless, elimination of TRIM5 restriction activity did not rescue SIVMAC transduction. Also, in contrast to TRIM5-mediated restriction, the SIVMAC CA-specific block occurred after completion of reverse transcription and the formation of 2-LTR circles, but before establishment of the provirus. Transduction efficiency in heterokaryons generated by fusing epithelial cells with T cells resembled that in the T cells, indicative of a dominant-acting SIVMAC restriction activity in the latter. These results suggest that the nucleus of human blood cells possesses a restriction factor specific for the CA of HIV-2/SIVMAC/SIVSM and that cross-species transmission of SIVSM to human T cells necessitated adaptation of HIV-2 to this putative restriction factor

Humanized Mice for the Generation of HIV-1 Human Monoclonal Antibodies

Background: Despite the length of time HIV has been wreaking havoc on its victims, improvements in the prevention and treatment of HIV are needed. Anti-retroviral therapy can be effective but is expensive and not entirely accessible for people infected in third world countries. Several promising broadly neutralizing antibodies have been isolated from infected individuals; we propose that generating antigen specific human monoclonal antibodies using humanized mice further represents a promising approach to engineer prophylactic antibodies to reduce spread and infection of HIV. Methods: Immunodeficient mice were engrafted with fetal liver and thymus (BLT) prior to infection with different HIV isolates. HIV infection of the mice was monitored by viral load and antibody response followed by ELISA using gp120, gp41 or gp120/CD4 complex as antigens. Approximately 8-12 weeks post infection, spleens were harvested and splenocytes fused with human fusion partner HMMA 2.5 to isolate antibody-expressing hybridomas. Lead clones were scaled and purified for testing in functional assays such as TZM-bl neutralization assays as well as ADCVI to determine neutralizing and cytotoxic ability of the antibodies. Antibody sequences were also determined for analysis. Results: A robust, specific antibody response, of both IgG and IgA isotypes, was generated in response to HIV infection. Over 60 hybridomas were created that were not only immunoreactive with env antigens, but also had neutralization activity. Moreover, variable family usage was not limited and somatic mutation was clearly evident. Conclusions: These findings suggest that humanized BLT mice are a novel source for well-characterized, stable human monoclonal antibodies to HIV