TARGETING 5-ENOLPYRUVYLSHIKIMATE-3-PHOSPHATE SYNTHASE AND THE SHIKIMATE PATHWAY

Bacteria, plants, fungi, and apicomplexan parasites require the functionality of the shikimate pathway for biosynthesis of essential aromatic compounds. Animals lack the enzymes that constitute the shikimate pathway, making these attractive antimicrobial targets. Glyphosate (the active ingredient in Roundup herbicide) inhibits the shikimate pathway enzyme 5-enolpyruvyl-shikimate-3-phosphate synthase (EPSPS), but has limited antimicrobial activity. Several EPSPS point-substitutions can induce glyphosate tolerance, and some species possess EPSPS with intrinsic glyphosate insensitivity. To aid development of second-generation EPSPS inhibitors, I probed the inhibition of glyphosate-tolerant EPSPS. I examined the effects of mutations at Pro101 and Thr97 on the structure, function, and glyphosate sensitivity of E. coli EPSPS; I kinetically characterized the glyphosate-tolerant Staphylococcus aureus EPSPS and Agrobacterium sp. strain CP4 EPSPS and determined the three-dimensional structure of the CP4 enzyme; I studied the interaction of EPSPS with analogs of the substrate and the tetrahedral intermediate; and I conducted high throughput screening to identify novel EPSPS inhibitors

Food Limitation And The Adaptive Significance Of Clutch Size In American Coots (fulica Americana)

For many species of birds, egg formation costs are considered important constraints on timing of breeding, clutch size, and egg size. For American Coots (Fulica americana), body reserves and current food availability are both thought to affect these aspects of reproduction. In order to test the egg formation hypothesis, I conducted numerous observational and manipulative experiments on wild, free-ranging American Coots. Clutch size declined with laying date in five out of six years, contrary to seasonal patterns of food availability in prairie wetlands. Clutch size increased during two of three years in response to supplemental feeding. Laying date was only slightly affected by food supplements. Coots renested rapidly following clutch destruction, and some females produced phenomenal numbers of consecutive or near-consecutive eggs (to a maximum of 35 in 37 d). Because the average clutch was usually 8-11 eggs, these data provided a strong refutation of the egg formation hypothesis.;Egg size exhibited little change in response to most factors, and egg composition was only slightly more sensitive to such factors as annual variation and supplemental feeding. Egg size and quality (relative protein, lipid, and energy content) were positively correlated with clutch size, contrary to predictions based on life-history trade-offs. I suggest that among-individual variation in inherent quality overshadows these expected trade-offs.;Analysis of nutrient reserve dynamics of adult coots did not support earlier claims that coots rely on stored fat and protein for egg production. In general, coots exhibited little sign of nutritional stress during breeding, although supplemental feeding did result in increased fat and protein reserves. Among postlaying female coots, there were significant positive correlations between size of reserves and measures of previous reproductive performance. These observations lend further support to the idea that individual females are inherently superior or inferior breeders, but they do not give any indication why this might be so.;I conclude that coots are not food limited during egg laying or incubation. Further work is needed on the potential role of food limitation during brood-rearing, particularly with regards to variation in brood size and hatching asynchrony

Dynamic Pattern Formation in a Vesicle-Generating Microfluidic Device

Spatiotemporal pattern formation occurs in a variety of nonequilibrium physical and chemical systems. Here we show that a microfluidic device designed to produce reverse micelles can generate complex, ordered patterns as it is continuously operated far from thermodynamic equilibrium. Flow in a microfluidic system is usually simple—viscous effects dominate and the low Reynolds number leads to laminar flow. Self-assembly of the vesicles into patterns depends on channel geometry and relative fluid pressures, enabling the production of motifs ranging from monodisperse droplets to helices and ribbons

In Great Power Wars, Americans Could Again Become POWs

With the return of great power competition comes another renewed threat most of us probably have not thought about in a long time: American soldiers could become prisoners of war. To put it in perspective, the last conflict where America suffered hundreds of POWs was the Vietnam War. Today, after two decades of fighting non-state insurgents, Survival, Evasion, Resistance, and Escape, or SERE, training for U.S. service members has been tailored to match the counterinsurgency operational environment. But in a large-scale conflict between peer countries, aircrews bail out over enemy-controlled territory, wounded soldiers are captured by an advancing enemy, logistic convoys are ambushed, and the turmoil that comes with a moving battlefield creates risk for troops being captured by the enemy. If that is the more likely battlespace of the future, then there is a need to change once again how we prepare soldiers for being captured

Spatial and Temporal Habitat Use of an Asian Elephant in Sumatra

Increasingly, habitat fragmentation caused by agricultural and human development has forced Sumatran elephants into relatively small areas, but there is little information on how elephants use these areas and thus, how habitats can be managed to sustain elephants in the future. Using a Global Positioning System (GPS) collar and a land cover map developed from TM imagery, we identified the habitats used by a wild adult female elephant (Elephas maximus sumatranus) in the Seblat Elephant Conservation Center, Bengkulu Province, Sumatra during 2007–2008. The marked elephant (and presumably her 40–60 herd mates) used a home range that contained more than expected medium canopy and open canopy land cover. Further, within the home range, closed canopy forests were used more during the day than at night. When elephants were in closed canopy forests they were most often near the forest edge vs. in the forest interior. Effective elephant conservation strategies in Sumatra need to focus on forest restoration of cleared areas and providing a forest matrix that includes various canopy types

Government cyber breach shows need for convergence

The SolarWinds breach points out the importance of having both offensive and defensive cyber force experience. The breach is an ongoing investigation, and we will not comment on the investigation. Still, in general terms, we want to point out the exploitable weaknesses in creating two silos — OCO and DCO. The separation of OCO and DCO, through the specialization of formations and leadership, undermines broader understanding and value of threat intelligence. The growing demarcation between OCO and DCO also have operative and tactical implications. The Multi-Domain Operations (MDO) concept emphasizes the competitive advantages that the Army — and greater Department of Defense — can bring to bear by leveraging the unique and complementary capabilities of each service. It requires that leaders understand the capabilities their organization can bring to bear in order to achieve the maximum effect from the available resources. Cyber leaders must have exposure to a depth and the breadth of their chosen domain to contribute to MDO. Unfortunately, within the Army’s operational cyber forces, there is a tendency to designate officers as either offensive cyber operations (OCO) or defensive cyber operations (DCO) specialists. The shortsighted nature of this categorization is detrimental to the Army’s efforts in cyberspace and stymies the development of the cyber force, affecting all soldiers. The Army will suffer in its planning and ability to operationally contribute to MDO from a siloed officer corps unexposed to the domain’s inherent flexibility

Sharing Cyber Capabilities within the Alliance - Interoperability Through Structured Pre-Authorization Cyber

Sharing cyber weapon/cyber capabilities requires trust between the member states, becoming a high-end policy decision due to the concerns of proliferation and the investment in designing a cyber-weapon that has a limited ’shelf-life’. The digital nature of cyber weapons creates a challenge. A cyber weapon can spread quickly, either self-propagating such as worms or via disclosure (and subsequent reuse) by malware researchers or malicious actors, raising proliferation concerns. Additionally, a cyber-weapon can be copied by the adversary or reverse engineered. Once the weapon is released, the adversary will eventually address the vulnerability, and the opportunity is gone. These factors raise the threshold between member states to share cyber weapons and cyber capabilities. Alliances, like NATO, prepare for a unified multinational, multi-domain fight; meanwhile, the national cyber forces are still operating as solitaires with limited interoperability and sharing. There is a need in the collective defence posture to integrate the multinational cyber force to achieve interoperability

POWs in the Age of the Internet

A future great power conflict could potentially involve large numbers of prisoners of war (POWs)—US, Allied, and partner nations—imprisoned by regimes that could seek to utilize and exploit these captives for propaganda gain. Deepfakes and digital manipulation technology provide an advantageous opportunity for a captor aiming to mitigate international humanitarian law concerns regarding the rules for POW treatment. Such an adversary could use manipulated audio and images of POWs to forward their cause, undermine the Alliance cohesion, attack the mutual will to fight, and reduce POWs’ will to resist. The risk of becoming a POW has steadily disappeared from the minds of US military members after two decades of counterinsurgency and antiterrorism operations. The memories of the Cold War and the Soviet occupation of Eastern Europe—and the general understanding of what captivity means—are diminishing. This prospect, however, should not be forgotten as the potential for the capture of sizeable numbers of POWs in a large-scale conflict is a distinct possibility. The general strategic direction has recently changed from counterterrorism and antiterrorism operations toward great power competition and potentially protracted conflicts involving near-peer nation-states. Since the Cold War, air mobility, standoff weaponry, capabilities for deep strikes into enemy territory, and faster decision cycles have created a new battlefield. The modern battlefield is ever changing. High-paced engagements and mobility cross multiple war-fighting domains create the potential for a fragmented, fluid fight. In this unpredictable, widespread, rapidly changing, and violent environment, the potential for large numbers of POWs is high

Short-term variability in satellite-derived cloud cover and galactic cosmic rays: an update

Previous work by Todd and Kniveton (2001) (TK2001) has indicated a statistically significant association (at the daily timescale) between short-term reductions in galactic cosmic rays, specifically Forbush decrease (FD) events, and reduced cloud cover, mainly over Antarctica (as recorded in International Satellite Cloud Climatology Project (ISCCP) D1 data). This study presents an extension of the previous work using an extended dataset of FD events and ISCCP cloud data over the period 1983-2000, to establish how stable the observed cloud anomalies are. Composite analysis of ISCCP data based on a sample of 32 FD events (excluding those coincident with solar proton events) indicates cloud anomalies with a very similar space/time structure to that previously reported, although of smaller magnitude. Substantial reductions in high level cloud (up to 12% for zonal mean, compared to 18% reported by TK2001) are observed over the high geomagnetic latitudes, especially of the southern hemisphere immediately following FD event onset. Largest anomalies are centred on the Antarctic plateau region during austral winter. However, the largest cloud anomalies occur where the accuracy of the ISCCP cloud retrievals is likely to be lowest, such that the results must be treated with extreme caution. Moreover, significant positive composite mean surface and tropospheric temperature anomalies centred over the same region are also observed for the FD sample from the National Center for Environmental Prediction (NCEP) reanalysis data. Such increased temperatures are inconsistent with the radiative effect of a reduction in high-level cloud during local winter. Overall, the results do not provide strong evidence of a direct galactic cosmic ray/cloud association at short timescales. The results highlight (a) the potential problems of data quality in the high latitude regions (b) the problems inherent in inferring cause and effect relationships from observational data alone (c) the need for further research to test competing hypotheses