Identification and Characterization of Genetic Factors Involved in Candida-Bacterial Interactions

Throughout existence, fungi and bacteria have long shared ecological niches and thus engage in numerous interactions to mutually enhance survival or antagonistically gain competitive advantages. Of importance to human health are those interactions that involve bacteria with the opportunistic fungi, Candida albicans. An important virulence factor of C. albicans is the ability to control morphology, which allows the transition between yeast, pseudohyphal, and hyphal phenotypes. Morphological control in C. albicans is governed by quorum sensing and the secreted autoregulatory molecule farnesol. Quorum sensing allows individual cells to sense the environment and respond as a group. Bacteria also use quorum sensing to communicate and control virulence. Despite their abundance in nature, very little is known about the interactions of C. albicans with bacteria on a genetic and molecular level. The objective of our research is to identify the genetic elements involved in C. albicans-bacterial interactions and characterize the genes that may participate in these relationships. To accomplish this, we screened a C. albicans mutant library for the ability to filament in the presence of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, where 3 typically, these three bacterial species inhibit C. albicans filamentation. We identified 836 C. albicans mutants that displayed a filamentous phenotype in the presence of bacteria. Collectively, 295 of these mutants filamented in the presence of all 3 bacterial species. Candidates were subsequently sequenced to identify the location of the mutation and the affected genetic element. CDR4, a putative ABC transporter, and ALS6, a putative adhesion, were further characterized for their specific involvement in Candida-bacterial interactions. Using a filamentation assay, cdr4 and als6 deletion strains demonstrated a decreased response to the inhibitory effects of farnesol, as well as bacterial molecules known to inhibit the production of hyphal-filaments. Additionally, the ability of cdr4 and als6 deletion strains to attach and form biofilms was significantly enhanced even in the presence of farnesol and bacterial inhibitors. The results of this study contribute to the body of knowledge involving polymicrobial interactions and these findings may lead to new antifungal targets for therapeutic interventions

3-D Printed Ultem 9085 Testing and Analysis

The purpose of this document is to analyze the mechanical properties of 3-D printed Ultem 9085. This document will focus on the capabilities, limitations, and complexities of 3D printing in general, and explain the methods by which this material is tested. Because 3-D printing is a relatively new process that offers an innovative means to produce hardware, it is important that the aerospace community understands its current advantages and limitations, so that future endeavors involving 3-D printing may be completely safe. This document encompasses three main sections: a Slosh damage assessment, a destructive test of 3-D printed Ultem 9085 samples, and a test to verify simulation for the 3-D printed SDP (SPHERES Docking Port). Described below, 'Slosh' and 'SDP' refer to two experiments that are built using Ultem 9085 for use with the SPHERES (Synchronized Position Hold, Engage, Reorient, Experimental Satellites) program onboard the International Space Station (ISS) [16]. The SPHERES Facility is managed out of the National Aeronautics and Space Administration (NASA) Ames Research Center in California

Self-Contained Avionics Sensing and Flight Control System for Small Unmanned Aerial Vehicle

A self-contained avionics sensing and flight control system is provided for an unmanned aerial vehicle (UAV). The system includes sensors for sensing flight control parameters and surveillance parameters, and a Global Positioning System (GPS) receiver. Flight control parameters and location signals are processed to generate flight control signals. A Field Programmable Gate Array (FPGA) is configured to provide a look-up table storing sets of values with each set being associated with a servo mechanism mounted on the UAV and with each value in each set indicating a unique duty cycle for the servo mechanism associated therewith. Each value in each set is further indexed to a bit position indicative of a unique percentage of a maximum duty cycle for the servo mechanism associated therewith. The FPGA is further configured to provide a plurality of pulse width modulation (PWM) generators coupled to the look-up table. Each PWM generator is associated with and adapted to be coupled to one of the servo mechanisms

Palliative care for Parkinson's disease: Patient and carer's perspectives explored through qualitative interview

Background: Palliative care is recommended for non-malignant illnesses, including Parkinson’s disease. However, past research with healthcare workers highlights unmet palliative needs in this population and referral rates to Specialist Palliative Care are low. Some healthcare workers perceive a ‘fear’ in their patients about introducing palliative care. However, less is known about the views of people with Parkinson’s disease and their carers about palliative care. Aim: (1) To explore the palliative care and related issues most affecting people with Parkinson’s disease and their families and (2) to examine perceptions about/understanding of palliative care. Design: This was a qualitative study; semi-structured interviews were conducted, transcribed and analysed using thematic analysis. Setting/participants: A total of 31 people participated, both people with Parkinson’s disease (n = 19) and carers (n = 12), across three Movement Disorder Clinics in the Republic of Ireland. Results: People with Parkinson’s disease and their carers were unfamiliar with the term palliative care. When informed of the role of palliative care, most felt that they would benefit from this input. People with Parkinson’s disease and carers experienced a high illness burden and wanted extra support. Crises requiring Specialist Palliative Care involvement may occur at diagnosis and later, with advancing illness. Participants wanted more information about palliative care and especially further supports to address their psychosocial needs. Conclusion: A holistic palliative care approach could address the complex physical and psychosocial symptoms experienced by people with Parkinson’s disease and their carers, and people with Parkinson’s disease and their carers are open to palliative care. Further research needs to explore how palliative care can be introduced into the routine care for people with Parkinson’s disease

Robust mouse tracking in complex environments using neural networks.

The ability to track animals accurately is critical for behavioral experiments. For video-based assays, this is often accomplished by manipulating environmental conditions to increase contrast between the animal and the background in order to achieve proper foreground/background detection (segmentation). Modifying environmental conditions for experimental scalability opposes ethological relevance. The biobehavioral research community needs methods to monitor behaviors over long periods of time, under dynamic environmental conditions, and in animals that are genetically and behaviorally heterogeneous. To address this need, we applied a state-of-the-art neural network-based tracker for single mice. We compare three different neural network architectures across visually diverse mice and different environmental conditions. We find that an encoder-decoder segmentation neural network achieves high accuracy and speed with minimal training data. Furthermore, we provide a labeling interface, labeled training data, tuned hyperparameters, and a pretrained network for the behavior and neuroscience communities

Delayed evaluation of combat-related penetrating neck trauma

ObjectiveThe approach to penetrating trauma of the head and neck has undergone significant evolution and offers unique challenges during wartime. Military munitions produce complex injury patterns that challenge conventional diagnosis and management. Mass casualties may not allow for routine exploration of all stable cervical blast injuries. The objective of this study was to review the delayed evaluation of combat-related penetrating neck trauma in patients after evacuation to the United States.MethodFrom February 2003 through April 2005, a series of patients with military-associated penetrating cervical trauma were evacuated to a single institution, prospectively entered into a database, and retrospectively reviewed.ResultsSuspected vascular injury from penetrating neck trauma occurred in 63 patients. Injuries were to zone II in 33%, zone III in 33%, and zone I in 11%. The remaining injuries involved multiple zones, including the lower face or posterior neck. Explosive devices wounded 50 patients (79%), 13 (21%) had high-velocity gunshot wounds, and 19 (30%) had associated intracranial or cervical spine injury. Of the 39 patients (62%) who underwent emergent neck exploration in Iraq or Afghanistan, 21 had 24 injuries requiring ligation (18), vein interposition or primary repair (4), polytetrafluoroethylene (PTFE) graft interposition (1), or patch angioplasty (1). Injuries occurred to the carotid, vertebral, or innominate arteries, or the jugular vein. After evacuation to the United States, all patients underwent radiologic evaluation of the head and neck vasculature. Computed tomography angiography was performed in 45 patients (71%), including six zone II injuries without prior exploration. Forty (63%) underwent diagnostic arteriography that detected pseudoaneurysms (5) or occlusions (8) of the carotid and vertebral arteries. No occult venous injuries were noted. Delayed evaluation resulted in the detection of 12 additional occult injuries and one graft thrombosis in 11 patients. Management included observation (5), vein or PTFE graft repair (3), coil embolization (2), or ligation (1).ConclusionsPenetrating multiple fragment injury to the head and neck is common during wartime. Computed tomography angiography is useful in the delayed evaluation of stable patients, but retained fragments produce suboptimal imaging in the zone of injury. Arteriography remains the imaging study of choice to evaluate for cervical vascular trauma, and its use should be liberalized for combat injuries. Stable injuries may not require immediate neck exploration; however, the high prevalence of occult injuries discovered in this review underscores the need for a complete re-evaluation upon return to the United States

Phase II Trial of IL-12 Plasmid Transfection and PD-1 Blockade in Immunologically Quiescent Melanoma.

PurposeTumors with low frequencies of checkpoint positive tumor-infiltrating lymphocytes (cpTIL) have a low likelihood of response to PD-1 blockade. We conducted a prospective multicenter phase II trial of intratumoral plasmid IL-12 (tavokinogene telseplasmid; "tavo") electroporation combined with pembrolizumab in patients with advanced melanoma with low frequencies of checkpoint positive cytotoxic lymphocytes (cpCTL).Patients and methodsTavo was administered intratumorally days 1, 5, and 8 every 6 weeks while pembrolizumab (200 mg, i.v.) was administered every 3 weeks. The primary endpoint was objective response rate (ORR) by RECIST, secondary endpoints included duration of response, overall survival and progression-free survival. Toxicity was evaluated by the CTCAE v4. Extensive correlative analysis was done.ResultsThe combination of tavo and pembrolizumab was well tolerated with adverse events similar to those previously reported with pembrolizumab alone. Patients had a 41% ORR (n = 22, RECIST 1.1) with 36% complete responses. Correlative analysis showed that the combination enhanced immune infiltration and sustained the IL-12/IFNγ feed-forward cycle, driving intratumoral cross-presenting dendritic cell subsets with increased TILs, emerging T cell receptor clones and, ultimately, systemic cellular immune responses.ConclusionsThe combination of tavo and pembrolizumab was associated with a higher than expected response rate in this poorly immunogenic population. No new or unexpected toxicities were observed. Correlative analysis showed T cell infiltration with enhanced immunity paralleling the clinical activity in low cpCTL tumors

Predicting COVID-19 infection risk in people who are immunocompromised by antibody testing.

People with blood cancers have an increased risk of severe COVID-19 disease despite booster vaccine doses.1 This group, like other disease groups at increased risk of severe COVID-19, includes individuals with highly heterogeneous immune responses to vaccination.2 Although vaccine response studies and population studies identify similar diseases and treatments associated with increased risk of severe COVID-19, a direct correlation between antibody levels after vaccination and infection risk has been difficult to define. Identification of a laboratory correlate of infection risk would allow doctors and policy makers to target additional COVID-19 treatment or prophylactic efforts to people who are most in need

Shallow seafloor gas emissions near Heard and McDonald Islands on the Kerguelen Plateau, Southern Indian Ocean

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Spain, E. A., Johnson, S. C., Hutton, B., Whittaker, J. M., Lucieer, V., Watson, S. J., Fox, J. M., Lupton, J., Arculus, R., Bradney, A., & Coffin, M. F. Shallow seafloor gas emissions near Heard and McDonald Islands on the Kerguelen Plateau, Southern Indian Ocean. Earth and Space Science, 7(3), (2020): e2019EA000695, doi:10.1029/2019EA000695.Bubble emission mechanisms from submerged large igneous provinces remains enigmatic. The Kerguelen Plateau, a large igneous province in the southern Indian Ocean, has a long sustained history of active volcanism and glacial/interglacial cycles of sedimentation, both of which may cause seafloor bubble production. We present the results of hydroacoustic flare observations around the underexplored volcanically active Heard Island and McDonald Islands on the Central Kerguelen Plateau. Flares were observed with a split‐beam echosounder and characterized using multifrequency decibel differencing. Deep‐tow camera footage, water properties, water column δ3He, subbottom profile, and sediment δ13C and δ34S data were analyzed to consider flare mechanisms. Excess δ3He near McDonald Islands seeps, indicating mantle‐derived input, suggests proximal hydrothermal activity; McDonald Islands flares may thus indicate CO2, methane, and other minor gas bubbles associated with shallow diffuse hydrothermal venting. The Heard Island seep environment, with subbottom acoustic blanking in thick sediment, muted 3He signal, and δ13C and δ34S fractionation factors, suggest that Heard Island seeps may either be methane gas (possibly both shallow biogenic methane and deeper‐sourced thermogenic methane related to geothermal heat from onshore volcanism) or a combination of methane and CO2, such as seen in sediment‐hosted geothermal systems. These data provide the first evidence of submarine gas escape on the Central Kerguelen Plateau and expand our understanding of seafloor processes and carbon cycling in the data‐poor southern Indian Ocean. Extensive sedimentation of the Kerguelen Plateau and additional zones of submarine volcanic activity mean additional seeps or vents may lie outside the small survey area proximal to the islands.We thank the Australian Marine National Facility (MNF) for its support in the form of sea time on RV Investigator , support personnel, scientific equipment, and data management. We also thank the captain, crew, and fellow scientists of RV Investigator voyage IN2016_V01. We also thank specifically the following: T. Martin, F. Cooke, S. L. Sow, N. Bax, J. Ford, and F. Althaus, CSIRO (Commonwealth Scientific and Industrial Research Organisation); Echoview Software Pty. Ltd. (Hobart, Australia); C. Dietz and C. Cook, Central Science Laboratory, University of Tasmania; C. Wilkinson and T. Baumberger, National Oceanic and Atmospheric Administration; R. Carey, University of Tasmania; T. Holmes, Institute for Marine and Antarctic Studies, University of Tasmania; N. Polmear; and A. Post, Geoscience Australia. The overall science of the project is supported by Australian Antarctic Science Program (AASP) grant 4338. E.S.' PhD research is supported by the Australian Research Council's Special Research Initiative Antarctic Gateway Partnership (Project ID SR140300001) and by an Australian Government Research Training Program Scholarship. S.C.J. is supported by iCRAG under SFI, European Regional Development Fund, and industry partners, as well as ANZIC‐IODP. J.M.W. is supported by ARC grant DE140100376 and DP180102280. This is PMEL publication number 4910. All IN2016_V01 data and samples acquired on IN2016_V01 are made publicly available in accordance with MNF policy