11 research outputs found
The Ability of Avian Radars to Track Near Miss Bird Strike Events: A Missing Informational Link
The management of problem wildlife within the airfield environment is a difficult job and today’s biologists require as much information as possible. Bird censuses and actual strike events provide a good picture, but there is a valuable data set out there that has been overlooked, until now. Recent advances in commercially available, digital avian tracking radars have for the first time enabled biologists to track and evaluate near-miss events to increase the safety margin for our pilots and crew. As a part of the Department of Defense, Environmental Securities Technology Certification Program (ESTCP) Project: Integration and Validation of Avian Radars, tens of thousands of hours of bird tracks have been recorded. During the evaluation of many of these tracks, it was discovered that the radar software is capable of tracking and reporting near- miss events between birds and aircraft. This capability has motivated a study to characterize near-miss events and their importance for BASH management. This presentation will discuss the importance of near-miss information and how it can be used to enhance aviation safety. The definition of a near-miss event will be discussed, along with how this type of information can be used as a part of a facility bird strike management program. A review of some archived data sets will illustrate the potential for deriving risk assessments from near-miss information
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Towards new antimalarial drug candidates from the endoperoxide class
Malaria, a disease caused by infection of protozoan parasites from genus Plasmodium, claims an estimated 600,000 lives annually, with the majority of these deaths in children. The utility of artemisinin and its derivates, which constitute the foundation of modern antimalarial care, is complicated by its suboptimal pharmacological parameters and by a concerning rise in genetically driven artemisinin partial resistance phenotypes in areas of high disease burden. Following limited clinical adoption of second generation synthetic trioxolane leads arterolane and artefenomel, small molecules which retain the endoperoxide-driven antiparasitic effect of artemisinin with improved properties and streamlined synthesis, there exists an urgent and undertargeted need for improved antimalarials in this class.Herein we report the design, synthesis, and in vitro and in vivo evaluation of a library of novel trans-3” substituted 1,2,4-trioxolanes. For carbamate substituted compounds in this class, we find promising antiparasitic efficacy, excellent metabolic stability, and a superior cure rate in a 2-day dosing regimen for lead compound 9d against the rodent P. berghei model of malaria, motivating future advancement of 9d into a humanized rodent malaria model (Chapter 2). We additionally report the synthesis and evaluation of trans-3”-aryl substituted congeners of artefenomel with a focus on carbamate-linked phenols bearing basic amine or other solubilizing functionality (Chapter 3). We find this class to broadly exhibit excellent antiparasitic efficacy and improved solubility and metabolic stability relevant to the 2nd generation trioxolanes. We advance the lead analog 17, which completely eliminates K13 C580Y parasites in vitro in the ring stage survival assay (RSA) and retains potent efficacy against high-RSA Ugandan clinical isolates. We furthermore report a stereoselective route to the (R,R)- and (S,S)- forms of 17, observing increased solubility of the separated enantiomeric forms versus the racemate. We extensively profile 17S as a clinical development candidate and found the compound to exhibit a protein binding and metabolic stability profile we predict should translate to extended drug exposures in human malaria patients.
We additionally explore the P. falciparum stress response as driven by PK4-mediated eIF2α phosphorylation (Chapter 4). We identify dozens of drug-like kinase inhibitors from the GSK PERK kinase set with potent antiparasitic effect. We find these inhibitors phenocopy the antiparasitic effect of bona fide PfPK4 inhibitor GSK-2606414 and plausibly retain the target profile of this comparator. We leverage our medium-throughput in vitro P. falciparum library screening pipeline to screen the SelleckChem antikinase library, reporting dozens of potent hits against the parasite and suggesting additional points of entry for targeting the P. falciparum kinome
Small-Molecule Inhibitors of Cathepsin L as Potential Anti-Metastatic Agents
The cathepsin family of cysteine proteases is overexpressed in a variety of cancer cell lines. Cathepsin L, one such protease, is secreted into the extracellular space and plays a critical role in degrading the extracellular matrix, and facilitating the metastasis of cancer cells from a primary tumor body to a secondary site. The Pinney and Trawick Research laboratories (Baylor University) have engaged in the design, synthesis, and biological evaluation of a variety of small-molecule inhibitors of cathepsin L for potential use as anti-metastatic agents. Two such compounds, KGP94 and KGP244, have shown significant potency as inhibitors of cathepsin L, and these results along with related biological studies have advanced these compounds as promising anti-metastatic
agents. A number of novel small-molecule analogues were synthesized that incorporate the benzophenone and benzoylbenzophenone backbones inherent to these two lead compounds in an ongoing effort to expand the library of compounds that could potentially interact with the cathepsin L active site
Role of near-miss bird strikes in assessing hazards
Management of problem wildlife within the airfield environment is a difficult job. Today’s Bird–Animal Aircraft Strike Hazard (BASH) program managers require as much information as possible to accomplish their tasks. Bird censuses and actual bird-strike events in and around the air operations area are used to make airfield management decisions and to assess the risk of bird hazards to aircraft. Both types of information are sampled rather sparsely. Avian radar is now being used as a new tool to provide continuous sampling of bird activity that significantly supplements visual censuses. The measure of risk used today is commonly expressed as the ratio of the number of bird strikes per 100,000 flying hours. While important, this measure of risk is relatively insensitive to improvements in safety measures that do not result in dramatically fewer bird strikes. Stated differently, a reduction in safety or an increase in risk (which reflects an increased likelihood of bird strikes occurring) is not anticipated, but, rather, it is calculated after the fact when increases in bird strikes have been experienced. As a result, BASH managers are at a disadvantage because they can respond only after bird strikes occur. To address this deficiency, we introduce a new method for assessing risk that is based on near-miss events that complements risk calculations based on reported bird strikes. Recent advances in commercially available, digital avian tracking radars enabled biologists to automatically monitor and assess near-miss events. Near-miss events occur much more frequently than bird strikes. A combined dataset of bird strikes and near-misses provides BASH managers with a more responsive metric to evaluate the success of their program over time than by using only the bird-strike dataset
Avian surveys near Camp Lemonnier and Day Forest, Djibouti, AfricaÂ
Two brief biodiversity surveys were conducted near Camp Lemonnier, Djibouti, in May 2014 and February 2016, and to the Day Forest (Forêt du Day) in February 2016. Our complete avian checklist of 143 species, with 96 species preserved as museum specimens is presented here. We document nesting for Spur-winged Lapwing Vanellus spinosus (Linnaeus, 1758), the occurrence of Crimson-rumped Waxbill Estrilda rhodopyga Sundevall, 1850, and confirm Little Tern Sternula albifrons (Pallas, 1764) in Djibouti. We comment on observations for the Critically Endangered Djibouti Spurfowl Pternistis ochropectus (Dorst & Jouanin 1952), and the Endangered Egyptian Vulture Neophron percnopterus (Linnaeus, 1758), and a previously noted Fringillidae (Crithagra sp.) Swainson, 1827 from the Day Forest. Hybridization between Somali Sparrow Passer castanopterus Blythi,1885 and House Sparrow Passer domesticus (Linnaeus, 1758) is documented with voucher specimens. Although these surveys and taxa lists represent brief inventories for the areas visited, they provide a foundation and reference for future work in this understudied region in the Horn of Africa
Avian surveys near Camp Lemonnier and Day Forest, Djibouti, AfricaÂ
Two brief biodiversity surveys were conducted near Camp Lemonnier, Djibouti, in May 2014 and February 2016, and to the Day Forest (Forêt du Day) in February 2016. Our complete avian checklist of 143 species, with 96 species preserved as museum specimens is presented here. We document nesting for Spur-winged Lapwing Vanellus spinosus (Linnaeus, 1758), the occurrence of Crimson-rumped Waxbill Estrilda rhodopyga Sundevall, 1850, and confirm Little Tern Sternula albifrons (Pallas, 1764) in Djibouti. We comment on observations for the Critically Endangered Djibouti Spurfowl Pternistis ochropectus (Dorst & Jouanin 1952), and the Endangered Egyptian Vulture Neophron percnopterus (Linnaeus, 1758), and a previously noted Fringillidae (Crithagra sp.) Swainson, 1827 from the Day Forest. Hybridization between Somali Sparrow Passer castanopterus Blythi,1885 and House Sparrow Passer domesticus (Linnaeus, 1758) is documented with voucher specimens. Although these surveys and taxa lists represent brief inventories for the areas visited, they provide a foundation and reference for future work in this understudied region in the Horn of Africa
Early adolescent Rai1 reactivation reverses transcriptional and social interaction deficits in a mouse model of Smith–Magenis syndrome
Conception, fetal growth, and calving seasonality of harbor porpoise (Phocoena phocoena) in the Salish Sea waters of Washington State, USA and southern British Columbia, Canada
We evaluated harbor porpoise (Phocoena phocoena L., 1758) strandings in the Salish Sea to determine calving seasonality (1980-2015). A total of 443 strandings were analyzed, of which 134 were calves and 53 neonates. Stranded calves were reported every month, but peaked in July, August, and September. Based on fetal size and an estimated fetal growth rate of 80 mm/month, mean conception date (and range) was back-calculated to 11 October ± 30 d (16 August - 31 December) and was later than in most other studies. Using mean length at birth (80 ± 5.8 cm), gestation was estimated to be approximately 10.8 months. Estimated birthing period was 16 July to 27 November, with a mean birth date of 10 September (± 30.7 d) and birth length of 80.0 cm. Estimated pregnancy rate (0.28 – 0.29) is lower than reported in other areas and is likely an underestimate due to missed early embryos, poor postmortem condition of a large proportion of the stranded adult females, and potential biases related to the animals that strand and are available. This study of harbor porpoise reproduction and calving in the Salish Sea is the first assessment of calving seasonality for this species in the northeast Pacific Ocean.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author