A systematic analysis of human transmembrane E3-RING proteins

The reversible covalent conjugation of the small highly conserved ubiquitin protein modifier to selective substrates plays central roles in countless proteolytic and non-proteolytic cellular functions. Substrate protein ubiquitination is co-ordinated by the sequential activity of three distinct classes of proteins: (i) E1-activating enzymes, (ii) E2-conjugating enzymes, and (iii) E3-protein ligases. Really Interesting New Gene (RING) proteins represent the largest family of E3-proteins comprising over half of predicted human E3-ligases. As such, E3-RING proteins play pivotal roles in controlling both specificity and functionality within the ubiquitin system. E3-RING proteins function as catalytically inactive molecular scaffolds that position Ub~E2 and substrate proteins in close proximity for ubiquitination to occur. Within the active ligase complex, E3-RING proteins and E2 conjugating enzymes are believed to select protein substrate(s) and the form of conjugated ubiquitin upon them, respectively. Whilst E3-RING/E2 partners have been investigated in recent HTP screen approaches, a key area of data paucity exists for integral membrane E3-RING (TM-E3-RING) proteins. As such, high throughput yeast-two-hybrid assays were performed for the entire complement of TM-E3-RING proteins and E2-conjugating enzymes. A broad subset of TM-E3-RING/E2 positive and negative Y2H interactions was re-tested in secondary luciferase protein complementation assays (PCAs), which increased confidence in Y2H-derived interactions and extended network coverage. Data from these studies was collated with previously published binary TM-E3-RING/E2 interaction data to provide a high-confidence TM-E3-RING/E2 network consisting of 312 unique binary interactions. In vitro auto-ubiquitination assays were employed to assign functional activity to TM-E3-RING/E2 protein pairs, revealing high verification rates for both positive and negative Y2H or PCA binary interaction data. Furthermore, novel trends in the generation of different forms of ubiquitin modifications were identified between selective TM-E3-RING/E2 pairs. Finally, Y2H screens were also performed to identify TM-E3-RING dimerization events, which represent an emerging theme in ubiquitin system regulation. In total 71 TM-E3-RING/TM-E3-RING interactions were reported demonstrating high incidence of these binding events. Novel data was combined with known interactions to generate a TM-E3-RING network containing >500 binary interactions, encompassing both components of the core ubiquitin cascade and non-ubiquitome proteins. This TM-E3-RINGcentric network provides a valuable tool for the investigation of specificity and regulation of TM-E3-RING proteins and specific ubiquitin cascades

Global state and potential scope of investments in watershed services for large cities

Investments in watershed services (IWS) programs, in which downstream water users pay upstream watershed service suppliers for actions that protect drinking water, are increasing in number and scope. IWS programs represent over $170 million of investment in over 4.3 million ha of watersheds, providing water to over 230 million people. It is not yet fully clear what factors contribute to the establishment and sustainability of IWS. We conducted a representative global analysis of 416 of the world’s largest cities, including 59 (14%) with IWS programs. Using random forest ensemble learning methods, we evaluated the relative importance of social and ecological factors as predictors of IWS presence. IWS programs are more likely present in source watersheds with more agricultural land and less protected area than otherwise similar watersheds. Our results suggest potential to expand IWS as a strategy for drinking water protection and also contribute to decisions regarding suitable program locations

Map My Murder: A Digital Forensic Study of Mobile Health and Fitness Applications

The ongoing popularity of health and fitness applications catalyzes the need for exploring forensic artifacts produced by them. Sensitive Personal Identifiable Information (PII) is requested by the applications during account creation. Augmenting that with ongoing user activities, such as the user’s walking paths, could potentially create exculpatory or inculpatory digital evidence. We conducted extensive manual analysis and explored forensic artifacts produced by (n = 13) popular Android mobile health and fitness applications. We also developed and implemented a tool that aided in the timely acquisition and identification of artifacts from the examined applications. Additionally, our work explored the type of data that may be collected from health and fitness web platforms, and Web Scraping mechanisms for data aggregation. The results clearly show that numerous artifacts may be recoverable, and that the tested web platforms pose serious privacy threats

Electromagnetic Wave Theory and Applications

Contains table of contents for Section 3, reports on three research projects and a list of publications.California Institute of Technology/Jet Propulsion Laboratory Contract 959548National Aeronautics and Space Administration Grant NAGW-1617National Aeronautics and Space Administration Grant Contract 958461U.S. Navy - Office of Naval Research Grant N00014-92-J-1616U.S. Navy - Office of Naval Research Grant N00014-92-J-4098Digital Equipment Corporation AGMT DTD 11/16/93Joint Services Electronics Program Contract DAAL03-92-C-0001Joint Services Electronics Program Grant DAAH04-95-1-0038MIT Lincoln Laboratory P.O. No. BX-5424U.S. Navy - Office of Naval Research Grant N00014-90-J-1002U.S. Navy - Office of Naval Research Grant N00014-89-J-1019DEMACO Agreement 11/15/93Federal Aviation Administration Grant 94-G-007U.S. Army Cold Regions Research and Engineering Laboratory Contract DACA89-93-K-000

Using the AR-V7 biomarker to determine treatment in metastatic castrate resistant prostate cancer, a feasibility randomised control trial, conclusions from the VARIANT trial [version 2; peer review: 2 approved]

Background: Prostate cancer is the most commonly diagnosed malignancy in the UK. Castrate resistant prostate cancer (CRPC) can be difficult to manage with response to next generation hormonal treatment variable. AR-V7 is a protein biomarker that can be used to predict response to treatment and potentially better inform management in these patients. Our aim was to establish the feasibility of conducting a definitive randomised controlled trial comparing the clinical utility of AR-V7 biomarker assay in personalising treatments for patients with metastatic CRPC within the United Kingdom (UK) National Health Service (NHS).  Due to a number of issues the trial was not completed successfully, we aim to discuss and share lessons learned herein. Methods: We conducted a randomised, open, feasibility trial, which aimed to recruit 70 adult men with metastatic CRPC within three secondary care NHS trusts in the UK to be run over an 18-month period. Participants were randomised to personalised treatment based on AR-V7 status (intervention) or standard care (control). The primary outcome was feasibility, which included: recruitment rate, retention and compliance. Additionally, a baseline prevalence of AR-V7 expression was to be estimated. Results: Fourteen participants were screened and 12 randomised with six into each arm over a nine-month period. Reliability issues with the AR-V7 assay meant prevalence was not estimated. Due to limited recruitment the study did not complete to target. Conclusions: Whilst the trial did not complete to target, we have ascertained that men with advanced cancer are willing to take part in trials utilising biomarker guided treatment. A number of issues were identified that serve as important learning points in future clinical trials

The 13th Southern Hemisphere Conference on the Teaching and Learning of Undergraduate Mathematics and Statistics

Ngā mihi aroha ki ngā tangata katoa and warm greetings to you all. Welcome to Herenga Delta 2021, the Thirteenth Southern Hemisphere Conference on the Teaching and Learning of Undergraduate Mathematics and Statistics. It has been ten years since the Volcanic Delta Conference in Rotorua, and we are excited to have the Delta community return to Aotearoa New Zealand, if not in person, then by virtual means. Although the limits imposed by the pandemic mean that most of this year’s 2021 participants are unable to set foot in Tāmaki Makaurau Auckland, this has certainly not stopped interest in this event. Participants have been invited to draw on the concept of herenga, in Te Reo Māori usually a mooring place where people from afar come to share their knowledge and experiences. Although many of the participants are still some distance away, the submissions that have been sent in will continue to stimulate discussion on mathematics and statistics undergraduate education in the Delta tradition. The conference invited papers, abstracts and posters, working within the initial themes of Values and Variables. The range of submissions is diverse, and will provide participants with many opportunities to engage, discuss, and network with colleagues across the Delta community. The publications for this thirteenth Delta Conference include publications in the International Journal of Mathematical Education in Science and Technology, iJMEST, (available at https://www.tandfonline.com/journals/tmes20/collections/Herenga-Delta-2021), the Conference Proceedings, and the Programme (which has created some interesting challenges around time-zones), by the Local Organizing Committee. Papers in the iJMEST issue and the Proceedings were peer reviewed by at least two reviewers per paper. Of the ten submissions to the Proceedings, three were accepted. We are pleased to now be at the business end of the conference and hope that this event will carry on the special atmosphere of the many Deltas which have preceded this one. We hope that you will enjoy this conference, the virtual and social experiences that accompany it, and take the opportunity to contribute to further enhancing mathematics and statistics undergraduate education. Ngā manaakitanga, Phil Kane (The University of Auckland | Waipapa Taumata Rau) on behalf of the Local Organising Committ

The Somatic Genomic Landscape of Glioblastoma

We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer

Wireless power transfer for a micro remotely piloted vehicle

ISCAS '98 Symposium Digest, Vol. 6, pp. 590-593A prototype rectifying antenna (rectanna) to provide wireless power transfer (WPT) to a micro-removely piloted vehicle (MRPV) is developed. Microwave radiation at 1.3 GHz is converted into DC to drive a small motor and spin a mockup helicopter rotor blade. The rectenna serves a dual purpose as the antenna and outer body of the proposed vehicle and allows efficient reception of power over 360 degrees around the vehicle. Wireless power transfer to the mockup MRPV has been demonstrated with less than 1 watt of transmitted power at near field ranges. Rectification efficiencies up to 30% were measured for two rectifier circuit configurations using 1.3 GHz continuous wave (CW) and pulse modulated transmitted signals

Digital Tracking Array Using Off-the-Shelf Hardware

IEEE Antennas and Propagation Magazine, Vol. 50, No. 1, February 2008, p. 108The article of record as published may be located at http://dx.doi.org/10.1109/MAP.2008.4494509The design, development, and testing of a digital tracking array is described. The array operates at 2.4 GHz for tracking video and data from UAVs and other mobile transmitters. A monopulse tracking technique is used to keep the beam scanned to the direction of the incoming signal. The array is built entirely of commercial off-the-shelf (COTS) components. Calibration, measurement of patterns, and verification of the tracking function are also discussed