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At least 199 records · Page 11

Piperidine CD4-Mimetic Compounds Expose Vulnerable Env Epitopes Sensitizing HIV-1-Infected Cells to ADCC

The ability of the HIV-1 accessory proteins Nef and Vpu to decrease CD4 levels contributes to the protection of infected cells from antibody-dependent cellular cytotoxicity (ADCC) by preventing the exposure of Env vulnerable epitopes. Small-molecule CD4 mimetics (CD4mc) based on the indane and piperidine scaffolds such as (+)-BNM-III-170 and (S)-MCG-IV-210 sensitize HIV-1-infected cells to ADCC by exposing CD4-induced (CD4i) epitopes recognized by non-neutralizing antibodies that are abundantly present in plasma from people living with HIV. Here, we characterize a new family of CD4mc, (S)-MCG-IV-210 derivatives, based on the piperidine scaffold which engages the gp120 within the Phe43 cavity by targeting the highly conserved Asp 368 Env residue. We utilized structure-based approaches and developed a series of piperidine analogs with improved activity to inhibit the infection of difficult-to-neutralize tier-2 viruses and sensitize infected cells to ADCC mediated by HIV+ plasma. Moreover, the new analogs formed an H-bond with the α-carboxylic acid group of Asp 368 , opening a new avenue to enlarge the breadth of this family of anti-Env small molecules. Overall, the new structural and biological attributes of these molecules make them good candidates for strategies aimed at the elimination of HIV-1-infected cells.

59 BASIC BIOLOGICAL SCIENCES↗

Cybersecurity Resiliency of Marine Renewable Energy Systems-Part 1: Identifying Cybersecurity Vulnerabilities and Determining Risk

Technology innovation, market demand, and the potential impacts of a changing climate are driving the marine renewable energy (MRE) industry to develop market-ready systems to provide low-carbon electricity for emerging, off-grid markets. The advanced operational and information technology devices used in MRE systems create a pathway for a cyber threat actor to gain unauthorized access to data or disrupt operation. To improve the resiliency of MRE systems as a predictable, affordable, and reliable source of energy from oceans and rivers, guidance was developed for an end users' organization that describes a framework for identifying and managing cybersecurity risk. The development of the cybersecurity guidance is based on standards described in the Risk Management Framework and Cybersecurity Framework developed by the National Institute of Standards and Technology (NIST). This paper is the first of a two-part series that describes an approach to determine the cybersecurity risk for MRE systems based on assessing potential cyber threats, identifying vulnerabilities (people, processes, and technology, including physical and operational environment), and evaluating the consequences a cyberattack would have on operation of the MRE system and impact on end users' mission and business objectives. MRE developers and stakeholders can use this approach to assess their current cybersecurity risk posture to incorporate appropriate cybersecurity controls to reduce the consequences and impacts from a cyberattack on MRE systems. This approach can be refined further as MRE systems are deployed and operational configurations are available.

97 MATHEMATICS AND COMPUTING↗

Climate-driven deoxygenation elevates fishing vulnerability for the ocean's widest ranging shark

Climate-driven expansions of ocean hypoxic zones are predicted to concentrate pelagic fish in oxygenated surface layers, but how expanding hypoxia and fisheries will interact to affect threatened pelagic sharks remains unknown. Here, analysis of satellite-tracked blue sharks and environmental modelling in the eastern tropical Atlantic oxygen minimum zone (OMZ) shows shark maximum dive depths decreased due to combined effects of decreasing dissolved oxygen (DO) at depth, high sea surface temperatures, and increased surface-layer net primary production. Multiple factors associated with climate-driven deoxygenation contributed to blue shark vertical habitat compression, potentially increasing their vulnerability to surface fisheries. Greater intensity of longline fishing effort occurred above the OMZ compared to adjacent waters. Higher shark catches were associated with strong DO gradients, suggesting potential aggregation along suitable DO gradients contributed to habitat compression and higher fishing-induced mortality. Fisheries controls to counteract deoxygenation effects on shark catches will be needed as oceans continue warming.

Vedor, Marisa↗

Gaps in global wildlife trade monitoring leave amphibians vulnerable

As the biodiversity crisis continues, we must redouble efforts to understand and curb pressures pushing species closer to extinction. One major driver is the unsustainable trade of wildlife. Trade in internationally regulated species gains the most research attention, but this only accounts for a minority of traded species and we risk failing to appreciate the scale and impacts of unregulated legal trade. Despite being legal, trade puts pressure on wild species via direct collection, introduced pathogens, and invasive species. Smaller species-rich vertebrates, such as reptiles, fish, and amphibians, may be particularly vulnerable to trading because of gaps in regulations, small distributions, and demand of novel species. Here, we combine data from five sources: online web searches in six languages, Convention on International Trade in Endangered Species (CITES) trade database, Law Enforcement Management Information System (LEMIS) trade inventory, IUCN assessments, and a recent literature review, to characterise the global trade in amphibians, and also map use by purpose including meat, pets, medicinal, and for research. We show that 1215 species are being traded (17% of amphibian species), almost three times previous recorded numbers, 345 are threatened, and 100 Data Deficient or unassessed. Traded species origin hotspots include South America, China, and Central Africa; sources indicate 42% of amphibians are taken from the wild. Newly described species can be rapidly traded (mean time lag of 6.5 years), including threatened and unassessed species. The scale and limited regulation of the amphibian trade, paired with the triptych of connected pressures (collection, pathogens, invasive species), warrants a re-examination of the wildlife trade status quo, application of the precautionary principle in regard to wildlife trade, and a renewed push to achieve global biodiversity goals.

Hughes, Alice C.↗

A modular approach for assessing the effect of radiation environments on man in operational systems. The radiobiological vulnerability of man during task performance

A modular approach for assessing the affects of radiation environments on man in operational systems has been developed. The feasibility of the model has been proved and the practicality has been assessed. It has been applied to one operational system to date and information obtained has been submitted to systems analysts and mission planners for the assessment of man's vulnerability and impact on systems survivability. In addition, the model has been developed so that the radiobiological data can be input to a sophisticated man-machine interface model to properly relate the radiobiological stress with other mission stresses including the effects of a degraded system.

Ewing, D. E.↗

The vulnerability of commercial aircraft avionics to carbon fibers

Avionics components commonly used in commercial aircraft were tested for vulnerability to failure when operated in an environment with a high density of graphite fibers. The components were subjected to a series of exposures to graphite fibers of different lengths. Lengths used for the tests were (in order) 1 mm, 3 mm, and 10 mm. The test procedure included subjecting the equipment to characteristic noise and shock environments. Most of the equipment was invulnerable or did not fail until extremely high average exposures were reached. The single exception was an air traffic control transponder produced in the early 1960's. It had the largest case open area through which fibers could enter and it had no coated boards.

Meyers, J. A.↗

As assessment of power system vulnerability to release of carbon fibers during commercial aviation accidents

The vulnerability of a power distribution system in Bedford and Lexington, Massachusetts to power outages as a result of exposure to carbon fibers released in a commercial aviation accident in 1993 was examined. Possible crash scenarios at Logan Airport based on current operational data and estimated carbon fiber usage levels were used to predict exposure levels and occurrence probabilities. The analysis predicts a mean time between carbon fiber induced power outages of 2300 years with an expected annual consequence of 0.7 persons losing power. In comparison to historical outage data for the system, this represents a 0.007% increase in outage rate and 0.07% increase in consequence.

Larocque, G. R.↗

Electronic equipment vulnerability to fire released carbon fibers

The vulnerability of electronic equipment to damage by carbon fibers released from burning aircraft type structural composite materials was investigated. Tests were conducted on commercially available stereo power amplifiers which showed that the equipment was damaged by fire released carbon fibers but not by the composite resin residue, soot and products of combustion of the fuel associated with burning the carbon fiber composites. Results indicate that the failure rates of the equipment exposed to the fire released fiber were consistent with predictions based on tests using virgin fibers.

Pride, R. A.↗

Fallible humans and vulnerable systems - Lessons learned from aviation

It is suggested that the problems being experienced in complex automatic systems are essentially due to the failure of information management and communication. The failure covers the entire spectrum: display devices and techniques, coding information so as to reduce human error, and information economy, i.e., resisting the temptation to bombard the operator with unlimited information simply because the system possesses the capability to do so. Since there has been great progress in hardware engineering, it is suggested that further attention is needed in the 'soft' side of systems. The approach should focus on (1) preventing human cognitive slips and (2) making the systems less vulnerable to such slips when they do occur. Most of the examples are taken from studies of cockpit automation.

Wiener, Earl L.↗

Vulnerability of manned spacecraft to crew loss from orbital debris penetration

Orbital debris growth threatens the survival of spacecraft systems from impact-induced failures. Whereas the probability of debris impact and spacecraft penetration may currently be calculated, another parameter of great interest to safety engineers is the probability that debris penetration will cause actual spacecraft or crew loss. Quantifying the likelihood of crew loss following a penetration allows spacecraft designers to identify those design features and crew operational protocols that offer the highest improvement in crew safety for available resources. Within this study, a manned spacecraft crew survivability (MSCSurv) computer model is developed that quantifies the conditional probability of losing one or more crew members, P(sub loss/pen), following the remote likelihood of an orbital debris penetration into an eight module space station. Contributions to P(sub loss/pen) are quantified from three significant penetration-induced hazards: pressure wall rupture (explosive decompression), fragment-induced injury, and 'slow' depressurization. Sensitivity analyses are performed using alternate assumptions for hazard-generating functions, crew vulnerability thresholds, and selected spacecraft design and crew operations parameters. These results are then used to recommend modifications to the spacecraft design and expected crew operations that quantitatively increase crew safety from orbital debris impacts.

Williamsen, J. E.↗

Managing a Vulnerability Testing Program

A good vulnerability testing program can help reduce system compromises, provide a way of assessing and measuring improvements in security, and motivate everyone to get involved.

Ray, John↗

Method and Apparatus for Reducing the Vulnerability of Latches to Single Event Upsets

A delay circuit includes a first network having an input and an output node, a second network having an input and an output, the input of the second network being coupled to the output node of the first network. The first network and the second network are configured such that: a glitch at the input to the first network having a length of approximately one-half of a standard glitch time or less does not cause the voltage at the output of the second network to cross a threshold, a glitch at the input to the first network having a length of between approximately one-half and two standard glitch times causes the voltage at the output of the second network to cross the threshold for less than the length of the glitch, and a glitch at the input to the first network having a length of greater than approximately two standard glitch times causes the voltage at the output of the second network to cross the threshold for approximately the time of the glitch. The method reduces the vulnerability of a latch to single event upsets. The latch includes a gate having an input and an output and a feedback path from the output to the input of the gate. The method includes inserting a delay into the feedback path and providing a delay in the gate.

Robert L Shuler, Jr.↗

Method and Apparatus for Reducing the Vulnerability of Latches to Single Event Upsets

A delay circuit includes a first network having an input and an output node, a second network having an input and an output, the input of the second network being coupled to the output node of the first network. The first network and the second network are configured such that: a glitch at the input to the first network having a length of approximately one-half of a standard glitch time or less does not cause tile voltage at the output of the second network to cross a threshold, a glitch at the input to the first network having a length of between approximately one-half and two standard glitch times causes the voltage at the output of the second network to cross the threshold for less than the length of the glitch, and a glitch at the input to the first network having a length of greater than approximately two standard glitch times causes the voltage at the output of the second network to cross the threshold for approximately the time of the glitch. A method reduces the vulnerability of a latch to single event upsets. The latch includes a gate having an input and an output and a feedback path from the output to the input of the gate. The method includes inserting a delay into the feedback path and providing a delay in the gate.

Robert L Shuler Jr.↗

Effects of Global Change on U.S. Urban Areas: Vulnerabilities, Impacts, and Adaptation

Human settlements, both large and small, are where the vast majority of people on the Earth live. Expansion of cities both in population and areal extent, is a relentless process that will accelerate in the 21st century. As a consequence of urban growth both in the United States and around the globe, it is important to develop an understanding of how urbanization will affect the local and regional environment. Of equal importance, however, is the assessment of how cities will be impacted by the looming prospects of global climate change and climate variability. The potential impacts of climate change and variability has recently been annunciated by the IPCC's "Climate Change 2007" report. Moreover, the U.S. Climate Change Science Program (CCSP) is preparing a series of "Synthesis and Assessment Products" (SAPs) reports to support informed discussion and decision making regarding climate change and variability by policy matters, resource managers, stakeholders, the media, and the general public. We are authors on a SAP describing the effects of global climate change on human settlements. This paper will present the elements of our SAP report that relate to what vulnerabilities and impacts will occur, what adaptation responses may take place, and what possible effects on settlement patterns and characteristics will potentially arise, on human settlements in the U.S. as a result of climate change and climate variability. We will also present some recommendations about what should be done to further research on how climate change and variability will impact human settlements in the U.S., as well as how to engage government officials, policy and decision makers, and the general public in understanding the implications of climate change and variability on the local and regional levels. Additionally, we wish to explore how technology such as remote sensing data coupled with modeling, can be employed as synthesis tools for deriving insight across a spectrum of impacts (e.g. public health, urban planning for mitigation strategies) on how cities can cope and adapt to climate change and variability. This latter point parallels the concepts and ideas presented in the U.S. National Academy of Sciences, Decadal Survey report on "Earth Science Applications from Space: National Imperatives for the Next Decade and Beyond" wherein the analysis of the impacts of climate change and variability, human health, and land use change are listed as key areas for development of future Earth observing remote sensing systems.

Quattrochi, Dale A.↗

Using Remotely Sensed Data to Map Urban Vulnerability to Heat

This slide presentation defines remote sensing, and presents examples of remote sensing and astronaut photography, which has been a part of many space missions. The presentation then reviews the project aimed at analyzing urban vulnerability to climate change, which is to test the hypotheses that Exposure to excessively warm weather threatens human health in all types of climate regimes; Heat kills and sickens multitudes of people around the globe every year -- directly and indirectly, and Climate change, coupled with urban development, will impact human health. Using Multiple Endmember Spectral Mixing Analysis (MESMA), and the Phoenix urban area as the example, the Normalized Difference Vegetation Index (NDVI) is calculated, a change detection analysis is shown, and surface temperature is shown.

Stefanov, William L.↗

Effects of Global Change on U.S. Urban Areas: Vulnerabilities, Impacts, and Adaptation

This slide presentation reviews some of the effects that global change has on urban areas in the United States and how the growth of urban areas will affect the environment. It presents the elements of our Synthesis and Assessment Report (SAP) report that relate to what vulnerabilities and impacts will occur, what adaptation responses may take place, and what possible effects on settlement patterns and characteristics will potentially arise, on human settlements in the U.S. as a result of climate change and climate variability. We will also present some recommendations about what should be done to further research on how climate change and variability will impact human settlements in the U.S., as well as how to engage government officials, policy and decision makers, and the general public in understanding the implications of climate change and variability on the local and regional levels. Additionally, we wish to explore how technology such as remote sensing data coupled with modeling, can be employed as synthesis tools for deriving insight across a spectrum of impacts (e.g. public health, urban planning for mitigation strategies) on how cities can cope and adapt to climate change and variability. This latter point parallels the concepts and ideas presented in the U.S. National Academy of Sciences, Decadal Survey report on "Earth Science Applications from Space: National Imperatives for the Next Decade and Beyond" wherein the analysis of the impacts of climate change and variability, human health, and land use change are listed as key areas for development of future Earth observing remote sensing systems.

Quattrochi, Dale A.↗

20,000 Years of Societal Vulnerability and Adaptation to Climate Change in Southwest Asia

The Fertile Crescent, its hilly flanks and surrounding drylands has been a critical region for studying how climate has influenced societal change, and this review focuses on the region over the last 20,000 years. The complex social, economic, and environmental landscapes in the region today are not new phenomena and understanding their interactions requires a nuanced, multidisciplinary understanding of the past. This review builds on a history of collaboration between the social and natural palaeoscience disciplines. We provide a multidisciplinary, multiscalar perspective on the relevance of past climate, environmental, and archaeological research in assessing present day vulnerabilities and risks for the populations of southwest Asia. We discuss the complexity of palaeoclimatic data interpretation, particularly in relation to hydrology, and provide an overview of key time periods of palaeoclimatic interest. We discuss the critical role that vegetation plays in the human–climate–environment nexus and discuss the implications of the available palaeoclimate and archaeological data, and their interpretation, for palaeonarratives of the region, both climatically and socially. We also provide an overview of how modelling can improve our understanding of past climate impacts and associated change in risk to societies. We conclude by looking to future work, and identify themes of “scale” and “seasonality” as still requiring further focus. We suggest that by appreciating a given locale's place in the regional hydroscape, be it an archaeological site or palaeoenvironmental archive, more robust links to climate can be made where appropriate and interpretations drawn will demand the resolution of factors acting across multiple scales.

Levant↗