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The emergence of SARS-CoV-2 variants complicates efforts to control the COVID-19 pandemic. Increasing genomic surveillance of SARS-CoV-2 is imperative for early detection of emerging variants, to trace the movement of variants, and to monitor effectiveness of countermeasures. Additionally, determining the amount of viable virus present in clinical samples is helpful to better understand the impact these variants have on viral shedding. In this study, we analyzed nasal swab samples collected between March 2020 and early November 2021 from a cohort of United States (U.S.) military personnel and healthcare system beneficiaries stationed worldwide as a part of the Defense Health Agency’s (DHA) Global Emerging Infections Surveillance (GEIS) program. SARS-CoV-2 quantitative real time reverse-transcription PCR (qRT-PCR) positive samples were characterized by next-generation sequencing and a subset was analyzed for isolation and quantification of viable virus. Not surprisingly, we found that the Delta variant is the predominant strain circulating among U.S. military personnel beginning in July 2021 and primarily represents cases of vaccine breakthrough infections (VBIs). Among VBIs, we found a 50-fold increase in viable virus in nasal swab samples from Delta variant cases when compared to cases involving other variants. Notably, we found a 40-fold increase in viable virus in nasal swab samples from VBIs involving Delta as compared to unvaccinated personnel infected with other variants prior to the availability of approved vaccines. This study provides important insight about the genomic and virological characterization of SARS-CoV-2 isolates from a unique study population with a global presence.ImpactThe COVID-19 pandemic is currently a leading cause of death globally and new SARS-CoV-2 variants continue to emerge. Genomic surveillance of variants is necessary to characterize mutations that could affect transmissibility and spread, antigenicity or virulence. Furthermore, wet lab studies are necessary to evaluate how genetic differences may affect viral fitness and transmissibility. The Delta variant is currently the predominant strain globally and determining factors that drive its ability to spread rapidly is important. In this study, we characterized SARS-CoV-2 positive samples from U.S. military personnel and their beneficiaries by next-generation sequencing and isolation of viable virus. Consistent with other studies, we found higher levels of infectious virus from Delta samples when compared to non-Delta infections. Strikingly, we found the difference in titer between Delta and other strains to be so profound as to be unaffected by vaccination status, suggesting that increased transmissibility of the Delta variant is in part due to higher amounts of virus shedding. This helps explain the rapid spread of the Delta variant and provides the impetus to increase control measures such as vaccination, boosters, masking and distancing requirements. It will be necessary to continue genomic and virological characterization of new variants, such as Omicron.

This paper focuses on the application of computer vision and convolutional neural network techniques in the automotive industry to reduce the amount of time required to locate a vacant parking spot and to reduce driving time. The main motivation for a vacant parking spot detector is such that today’s drivers are facing major difficulties in finding available spots in largely populated cities. This often time leads to increased congestion and frustration for the driver because they are forced to continue their search for a parking spot. Our approach is able to solve this issue and provide the driver with useful information through the use of transfer learning methodologies. The main contribution of this paper is to examine and improve on previously implemented transfer learning methods in order to better increase the detection accuracy. This paper differs from previous attempts such that it considers all environmental factors such as weather and time of day. Other models are not able to handle these conditions with a high accuracy and subsequently falter. When compared to previous attempts, our implementation focuses solely on the reliance of transfer learning. The results indicate that our model is capable of identifying vacant parking spaces under all conditions with competitive accuracies. The proposed model is able to surpass the accuracy of the latest attempt at solving this issue.

Modular and reconfigurable robots (MRRs) are unique and highly versatile for their self-innovation potential. Multiple working mode (MWM) on-line control adds potential by enabling each spring-assisted MRR (SA-MRR) joint module to switch independently between primary (motor-only) mode, and secondary, redundant actuation (spring-assisted) mode. In this work we proposed the spring-assisted mode as an on-board, physical innovation aid for uncertain, task-critical manipulation acts in uncontrolled environments. The spring-assisted mode is characterized by synergy of the spring and motor energy, and strengthens the SA-MRR by complementing the net actuation effort to help overcome task failure, to improve competency at ordinary tasks, and to enhance SA-MRR suitability as a tool for new tasks. Spring modules are fully reconfigurable offline through component swapping, and human–robot collaboration safety is considered. Task-specific, physical innovation with the SA-MRR was investigated by applying the spring-assisted mode directly to strenuous task segments in simulation case studies, demonstrating effectiveness of the proposed MWM approach.

Recently a novel spring-assisted modular and reconfigurable robot (SA-MRR) has been developed at our laboratory to reinforce its performance and to enable safe and dexterous operation in shared human-robot environments. Upon spring engagement at any joint position, the joint output torque becomes the sum of the actuator torque and spring torque, and the joint displacement range is mechanically limited. Restricting the manipulator's joint displacement limits individually allows the workspace to be confined selectively to a subspace of its entire or natural workspace, and creates an opportunity for a human to enter safely into the robot's natural workspace even while the robot continues to operate. Furthermore, the SA-MRR operating under spring-assistance offers functional benefits; the spring torque may counterbalance the manipulator and payload weight to avail the actuator torque fully for manipulation—an act which may simultaneously increase dexterity and decrease power consumption. The shared human-robot workspace notion as enabled by the SA-MRR is explored first in this work. Then, capabilities of a 3-DOF SA-MRR are investigated through simulations for dexterous operations and for payload handling within limited workspaces.

SummaryIndividuals with Hermansky-Pudlak Syndrome (HPS) lack platelet dense granules and have no ADP-autocrine response. Despite these platelet deficiencies, HPS patients exhibit a surprisingly mild bleeding phenotype. We hypothesize that activation of the PAR4 thrombin receptor compensates for the lack of an ADP-autocrine response by the P2Y12 ADP receptor in individuals with HPS. Here, we determine that PAR4 activation by thrombin occurs well after ADP release from dense granules in normal individuals. However, the signal from PAR4 stabilizes platelet-platelet aggregate formation in the absence of P2Y12 activation by ADP. Thus, the strong signal emanating from PAR4 during platelet aggregation would provide an explanation for the mild bleeding diathesis of HPS.

Transmembrane signaling through G protein-coupled receptors (GPCRs) controls a diverse array of cellular processes including metabolism, growth, motility, adhesion, neuronal signaling and blood coagulation. The numerous GPCRs and their key roles in both normal physiology and disease have made them the target for more than 50% of all prescribed drugs. GPCR agonists and antagonists act on the extracellular side of the receptors, whereas the intracellular surface has not yet been exploited for development of new therapeutic agents. Here, we demonstrate the utility of novel cell-penetrating peptides, termed 'pepducins', that act as intracellular inhibitors of signal transference from receptors to G proteins. Attachment of a palmitate lipid to peptides based on the third intracellular loop of protease-activated receptor 1 (PAR1) or PAR4 (refs. 3-5) yielded potent inhibitors of thrombin-mediated aggregation of human platelets. Infusion of the anti-PAR4 pepducin into mice extended bleeding time and protected against systemic platelet activation, consistent with the phenotype of PAR4-deficient mice. We show that pepducins might be used to ascertain the physiological roles of GPCRs and rapidly determine the potential therapeutic value of blockade of a particular signaling pathway.

Tuberculosis is a major cause of death in mankind and drug resistant tuberculosis has posed a problem for therapy. Immunotherapy is an option for better control of tuberculosis. We discovered two types of novel SMNH compounds which were active as adjuvants since they activated respectively NOD2 and TLR-7 receptors in macrophages. Since these cytosolic pattern recognition pathways lead to bactericidal mechanisms, we tested the efficacy of the SMNHs to activate macrophages to kill mycobacteria. Methods: Human THP1 macrophages were treated with either NOD-2 (SB44, SB44-1) or TLR-7 (SB9922) SMNH followed by infection with M. tuberculosis. Three days later macrophages were lysed and plated for bacterial counts. Cytokines from BMs were estimated using sandwich ELISA and autophagic markers were evaluated using monodansyl cadaverine and fluorescence microscopy. Results: Both NOD2 and TLR-7 activating SMNH compounds reduced the numbers of M. tuberculosis in human macrophages by 1-log10 over 3 days of culture. These SMNHs also reduced the numbers of M. tuberculosis within mouse BMs between 1-2log10 over 3 days. SMNHs activated autophagic processes in macrophages underscoring a new mechanism to kill intracellular M. tuberculosis. Since the main scaffold of SB44 has been used as an adjuvant in human trials, we anticipate that SB44 and SB9922 like compounds can be used as adjuncts to drugs for treating ongoing infections of M. tuberculosis in humans.