Impacts of Trogocytosis-Mediated Intracellular Signaling on CD4+ T cell Effector Cytokine Production and Differentiation

Trogocytosis is the direct intercellular transfer of membrane and membrane associated molecules. Unlike other passive-membrane transfer events, trogocytosed molecules may remain fully functional and become re-expressed on the surface of the trogocytosis-positive (trog+) recipient. This phenomenon commonly occurs between various cell types, including those of the immune system. CD4+ T cell trogocytosis occurs during their activation by antigen presenting cells (APC). Consequently, the acquired molecules include ligands for signaling receptors on the T cell. The impacts of CD4+ trogocytosis on the immune response are largely unknown. While it has been demonstrated that trog+ cells can present trogocytosed peptide:MHC (pMHC), and costimulatory molecules to activate other T cells, the consequences of trogocytosis on the individual trog+ CD4+ T cell have not been studied in-depth. We previously reported that trog+ cells perform cell-autonomous signaling by trogocytosed ligands engaging surface receptors, referred here to as trogocytosis-mediated signaling. This signaling led to the enhanced survival of trog+ cells in vitro compared to trog– cells after APC removal. Because the duration of T cell signaling influences the activation, lineage determination, and effector functionality of CD4+ T cells; trogocytosis-mediated signaling has the potential to uniquely modulate the effector-cytokine production and differentiation of trog+ CD4+ T cell after separation from APC. Examining this possibility is the foundation for this dissertation. Here, I will report my findings that: 1. Between 0-72 hrs post-separation from APC, trogocytosis-mediated signaling drives IL-4 and GATA-3 expression, consistent with T helper type-2 (TH2) differentiation; 3. Extended trogocytosis-mediated signaling (\u3e72 hrs) leads to the expression of Bcl-6, PD-1, CXCR5, and IL-21, consistent with T follicular helper (TFH) differentiation; 4. In absence of exogenous antigen (Ag), trogocytosis-mediated signaling is critical for the survival of the activated CD4+ T cells with high memory-potential. Despite the critical role for CD4+ T cells in generating protective immunity in the host, much remains unknown about the differentiation of CD4+ T cell effector subsets. The findings here present a novel mechanism for CD4+ T cell activation and differentiation via trogocytosis-mediated signaling, demonstrating the broad implications for such signaling in matters of public health

Iridium-Coated Rhenium Radiation-Cooled Rockets

Radiation-cooled rockets are used for a range of low-thrust propulsion functions, including apogee insertion, attitude control, and repositioning of satellites, reaction control of launch vehicles, and primary propulsion for planetary space- craft. The key to high performance and long lifetimes for radiation-cooled rockets is the chamber temperature capability. The material system that is currently used for radiation-cooled rockets, a niobium alloy (C103) with a fused silica coating, has a maximum operating temperature of 1370 C. Temperature limitations of C103 rockets force the use of fuel film cooling, which degrades rocket performance and, in some cases, imposes a plume contamination issue from unburned fuel. A material system composed of a rhenium (Re) substrate and an iridium (Ir) coating has demonstrated operation at high temperatures (2200 C) and for long lifetimes (hours). The added thermal margin afforded by iridium-coated rhenium (Ir/Re) allows reduction or elimination of fuel film cooling. This, in turn, leads to higher performance and cleaner spacecraft environments. There are ongoing government- and industry-sponsored efforts to develop flight Ir/ Re engines, with the primary focus on 440-N, apogee insertion engines. Complementing these Ir/Re engine development efforts is a program to address specific concerns and fundamental characterization of the Ir/Re material system, including (1) development of Ir/Re rocket fabrication methods, (2) establishment of critical Re mechanical properly data, (3) development of reliable joining methods, and (4) characterization of Ir/Re life-limiting mechanisms

Micromanipulation of InP lasers with optoelectronic tweezers for integration on a photonic platform

The integration of light sources on a photonic platform is a key aspect of the fabrication of self-contained photonic circuits with a small footprint that does not have a definitive solution yet. Several approaches are being actively researched for this purpose. In this work we propose optoelectronic tweezers for the manipulation and integration of light sources on a photonic platform and report the positional and angular accuracy of the micromanipulation of standard Fabry-Pérot InP semiconductor laser die. These lasers are over three orders of magnitude bigger in volume than any previously assembled with optofluidic techniques and the fact that they are industry standard lasers makes them significantly more useful than previously assembled microdisk lasers. We measure the accuracy to be 2.5 ± 1.4 µm and 1.4 ± 0.4° and conclude that optoelectronic tweezers are a promising technique for the micromanipulation and integration of optoelectronic components in general and semiconductor lasers in particular

Guidelines for data quality assurance

The UDRIVE project aims to colle ct on the region of 100,000 hours of naturalistic driving data in order to support the analysis related to o Crash causation, crash risk and normal driving o Distraction and inattention o Vulnerable road users o Driving styles related to eco-driving This document contains information relevant to data quality assurance for the UDRIVE project. Good quality data is a fundamental requirement for good quality analysis and data quality should be considered at all stages of the data processing chain: o Data Acquisition System Installation o During data collection o Database management • Data preprocessing • Data post-processing In order to deliver high quality data as an outcome from the UDRIVE project actions have been undertaken at each stage of the chain, following generic guidelines for data quality

Caspofungin Increases Fungal Chitin and Eosinophil and γδ T Cell-Dependent Pathology in Invasive Aspergillosis

The polysaccharide-rich fungal cell wall provides pathogen-specific targets for antifungal therapy and distinct molecular patterns that stimulate protective or detrimental host immunity. The echinocandin antifungal caspofungin inhibits synthesis of cell wall β-1,3-glucan and is used for prophylactic therapy in immune-suppressed individuals. However, breakthrough infections with fungal pathogen Aspergillus fumigatus are associated with caspofungin prophylaxis. In this study, we report in vitro and in vivo increases in fungal surface chitin in A. fumigatus induced by caspofungin that was associated with airway eosinophil recruitment in neutropenic mice with invasive pulmonary aspergillosis (IA). More importantly, caspofungin treatment of mice with IA resulted in a pattern of increased fungal burden and severity of disease that was reversed in eosinophil-deficient mice. Additionally, the eosinophil granule proteins major basic protein and eosinophil peroxidase were more frequently detected in the bronchoalveolar lavage fluid of lung transplant patients diagnosed with IA that received caspofungin therapy when compared with azole-treated patients. Eosinophil recruitment and inhibition of fungal clearance in caspofungin-treated mice with IA required RAG1 expression and γδ T cells. These results identify an eosinophil-mediated mechanism for paradoxical caspofungin activity and support the future investigation of the potential of eosinophil or fungal chitin-targeted inhibition in the treatment of IA

A Low Cost Technique for Adding Microlasers to a Silicon Photonic Platform

In this paper we report the physical micromanipulation of standard InP telecommunications laser die in a liquid medium by means of optoelectronic tweezers. Optoelectronic tweezers have been shown to use much less optical power than optical tweezers, they do not require a coherent light source to function and the creation of multiple traps is straightforward. These properties make the technique a very good candidate for the massive parallel micromanipulation of optoelectronic components for assembly on a photonic platform. We discuss the positional and orientation accuracy of the optoelectronic tweezers in relation to the alignment requirements for low-loss coupling between the light sources and the other components in a photonic platform. Our experiments indicate that the accuracy is better than 2 µm and 2◦ for translations and rotations, respectively

A Dual TLR Agonist Adjuvant Enhances the Immunogenicity and Protective Efficacy of the Tuberculosis Vaccine Antigen ID93

With over eight million cases of tuberculosis each year there is a pressing need for the development of new vaccines against Mycobacterium tuberculosis. Subunit vaccines consisting of recombinant proteins are an attractive vaccine approach due to their inherent safety compared to attenuated live vaccines and the uniformity of manufacture. Addition of properly formulated TLR agonist-containing adjuvants to recombinant protein vaccines enhances the antigen-specific CD4+ T cell response characterized by IFN-γ and TNF, both of which are critical for the control of TB. We have developed a clinical stage vaccine candidate consisting of a recombinant fusion protein ID93 adjuvanted with the TLR4 agonist GLA-SE. Here we examine whether ID93+GLA-SE can be improved by the addition of a second TLR agonist. Addition of CpG containing DNA to ID93+GLA-SE enhanced the magnitude of the multi-functional TH1 response against ID93 characterized by co-production of IFN-γ, TNF, and IL-2. Addition of CpG also improved the protective efficacy of ID93+GLA-SE. Finally we demonstrate that this adjuvant synergy between GLA and CpG is independent of TRIF signaling, whereas TRIF is necessary for the adjuvant activity of GLA-SE in the absence of CpG

A Pilot Search for Gravitational Self-Lensing Binaries with the Zwicky Transient Facility

Binary systems containing a compact object may exhibit periodic brightening episodes due to gravitational lensing as the compact object transits the companion star. Such "self-lensing" signatures have been detected before for white dwarf binaries. We attempt to use these signatures to identify detached stellar-mass neutron star and black hole binaries using data from the Zwicky Transient Facility (ZTF). We present a systematic search for self-lensing signals in Galactic binaries from a subset of high-cadence ZTF data taken in 2018. We identify 19 plausible candidates from the search, although because each candidate is observed to only brighten once, other origins such as stellar flares are more likely. We discuss prospects for more comprehensive future searches of the ZTF data.Comment: 12 pages. Submitted to the Open Journal of Astrophysic

Radar absorption, basal reflection, thickness and polarization measurements from the Ross Ice Shelf, Antarctica

Radio-glaciological parameters from the Moore’s Bay region of the Ross Ice Shelf, Antarctica, have been measured. The thickness of the ice shelf in Moore’s Bay was measured from reflection times of radio-frequency pulses propagating vertically through the shelf and reflecting from the ocean, and is found to be 576 ± 8 m. Introducing a baseline of 543 ± 7m between radio transmitter and receiver allowed the computation of the basal reflection coefficient, R, separately from englacial loss. The depth-averaged attenuation length of the ice column, 〈L〉 is shown to depend linearly on frequency. The best fit (95% confidence level) is 〈L(ν)〉= (460±20) − (180±40)ν m (20 dB km−1), for the frequencies ν = [0.100–0.850] GHz, assuming no reflection loss. The mean electric-field reflection coefficient is (1.7 dB reflection loss) across [0.100–0.850] GHz, and is used to correct the attenuation length. Finally, the reflected power rotated into the orthogonal antenna polarization i

Over what area did the oil and gas spread during the 2010 Deepwater Horizon oil spill?

Author Posting. © The Oceanography Society, 2016. This article is posted here by permission of The Oceanography Society for personal use, not for redistribution. The definitive version was published in Oceanography 29, no. 3 (2016): 96–107, doi:10.5670/oceanog.2016.74.The 2010 Deepwater Horizon (DWH) oil spill in the Gulf of Mexico resulted in the collection of a vast amount of situ and remotely sensed data that can be used to determine the spatiotemporal extent of the oil spill and test advances in oil spill models, verifying their utility for future operational use. This article summarizes observations of hydrocarbon dispersion collected at the surface and at depth and our current understanding of the factors that affect the dispersion, as well as our improved ability to model and predict oil and gas transport. As a direct result of studying the area where oil and gas spread during the DWH oil spill, our forecasting capabilities have been greatly enhanced. State-of-the-art oil spill models now include the ability to simulate the rise of a buoyant plume of oil from sources at the seabed to the surface. A number of efforts have focused on improving our understanding of the influences of the near-surface oceanic layer and the atmospheric boundary layer on oil spill dispersion, including the effects of waves. In the future, oil spill modeling routines will likely be included in Earth system modeling environments, which will link physical models (hydrodynamic, surface wave, and atmospheric) with marine sediment and biogeochemical components.This research was made possible by a grant from BP/The Gulf of Mexico Research Initiative to the CARTHE and Deep-C Consortia, and by contract M12PC00003 from the Bureau of Ocean Energy Management (BOEM)