Development, Implementation, and Pilot Evaluation of a Model-Driven Envelope Protection System to Mitigate the Hazard of In-Flight Ice Contamination on a Twin-Engine Commuter Aircraft

Fatal loss-of-control accidents have been directly related to in-flight airframe icing. The prototype system presented in this report directly addresses the need for real-time onboard envelope protection in icing conditions. The combination of prior information and real-time aerodynamic parameter estimations are shown to provide sufficient information for determining safe limits of the flight envelope during inflight icing encounters. The Icing Contamination Envelope Protection (ICEPro) system was designed and implemented to identify degradations in airplane performance and flying qualities resulting from ice contamination and provide safe flight-envelope cues to the pilot. The utility of the ICEPro system for mitigating a potentially hazardous icing condition was evaluated by 29 pilots using the NASA Ice Contamination Effects Flight Training Device. Results showed that real time assessment cues were effective in reducing the number of potentially hazardous upset events and in lessening exposure to loss of control following an incipient upset condition. Pilot workload with the added ICEPro displays was not measurably affected, but pilot opinion surveys showed that real time cueing greatly improved their awareness of a hazardous aircraft state. The performance of ICEPro system was further evaluated by various levels of sensor noise and atmospheric turbulence

The Harvest of Beluga Whales in Canada's Western Arctic: Hunter-based Monitoring of the Size and Composition of the Catch

Hunter-based beluga monitoring programs, in place in the Mackenzie Delta since 1973 and in the Paulatuk, Northwest Territories, area since 1989, have resulted in collection of data on the number of whales harvested and on the efficiency of the hunts. Since 1980, data on the standard length, fluke width, sex, and age of the landed whales have also been collected. The number of belugas landed each year averaged 131.8 (SD 26.5, n = 1337) between 1970 and 1979, 124.0 (SD 23.3, n = 1240) between 1980 and 1989, and 111.0 (SD 19.0, n = 1110) between 1990 and 1999. The human population increased during this same period. Removal of belugas from the Beaufort Sea stock, including landed whales taken in the Alaskan harvests, is estimated at 189 per year. The sex ratio of landed belugas from the Mackenzie Estuary was 2.3 males:1 female. Median ages were 23.5 yr (47 growth layer groups [GLG]) for females (n = 80) and 24 yr (48 GLG) for males (n = 286). More than 92% of an aged sample (n = 368) from the harvest consisted of whales 10 or more years old (20 GLG). The rate of removal is small in relation to the expected maximum net productivity rate of this stock. The continued availability of large, old individuals after centuries of harvesting and the apparent lack of change in the size and age structure of the catch in recent years also support a conclusion that the present level of harvest is sustainable.Des programmes de surveillance du bélouga gérés par les chasseurs et mis en oeuvre dans le delta du Mackenzie depuis 1973 et dans la région de Paulatuk (Territoires du Nord-Ouest) depuis 1989, ont abouti à la collecte de données sur le nombre de baleines blanches prélevées et sur l'efficacité des expéditions de chasse. Depuis 1980, on a également collecté des données sur la longueur standard, la largeur de la nageoire caudale, le sexe et l'âge des bélougas ramenés à terre. Le nombre moyen de bélougas ramenés à terre chaque année était de 131,8 (écart-type 26,5, n = 1337) entre 1970 et 1979, de 124,0 (écart-type 23,3, n = 1240) entre 1980 et 1989, et de 111,0 (écart-type 19,0, n = 1110) entre 1990 et 1999. La population humaine s'est accrue durant cette même période. On estime à 189 le nombre annuel de bélougas prélevés sur le stock de la mer de Beaufort, y compris ceux ramenés à terre qui font partie des récoltes de l'Alaska. Le rapport des sexes des bélougas ramenés à terre depuis l'estuaire du Mackenzie était de 2,3 mâles pour 1 femelle. La moyenne d'âge était de 23,5 (47 groupes de couches de croissance [GCC]) pour les femelles (n = 80) et 24 (48 GCC) pour les mâles (n = 286). Plus de 92 p. cent d'un échantillonnage (n = 368) prélevé sur la récolte et dont l'âge avait été déterminé, consistait en des baleines blanches de 10 ans ou plus (20 GCC). Le taux de retrait est faible par rapport à la productivité maximale nette à laquelle on peut s'attendre de ce stock particulier. La présence continue d'individus âgés et de grande taille après des siècles de prélèvements, et le manque apparent de changements dans le nombre des prises et leur distribution d'âge au cours des dernières années permettent de conclure que le niveau actuel des prélèvements est durable

Piloted Simulation to Evaluate the Utility of a Real Time Envelope Protection System for Mitigating In-Flight Icing Hazards

The utility of the Icing Contamination Envelope Protection (ICEPro) system for mitigating a potentially hazardous icing condition was evaluated by 29 pilots using the NASA Ice Contamination Effects Flight Training Device (ICEFTD). ICEPro provides real time envelope protection cues and alerting messages on pilot displays. The pilots participating in this test were divided into two groups; a control group using baseline displays without ICEPro, and an experimental group using ICEPro driven display cueing. Each group flew identical precision approach and missed approach procedures with a simulated failure case icing condition. Pilot performance, workload, and survey questionnaires were collected for both groups of pilots. Results showed that real time assessment cues were effective in reducing the number of potentially hazardous upset events and in lessening exposure to loss of control following an incipient upset condition. Pilot workload with the added ICEPro displays was not measurably affected, but pilot opinion surveys showed that real time cueing greatly improved their situation awareness of a hazardous aircraft state

My melancholy baby

Gift of Dr. Mary Jane Esplen.new song success by the writers of "sing me a song of the south", "let me really live tonight, sweetheart", "that's gratitude", "tomorrow" etc. etc. ; as sung by Billy Beard "the party from the south" ; and many popular ballad readers [note]Piano vocal [instrumentation]Come sweetheart mine, don't sit and pine [first line]Come to me, my melancholy baby [first line of chorus]E flat [key]Moderato [tempo]Popular song [form/genre]Flowers ; Billy Beard (photograph) [illustration]Publisher's advertisement on back cover [note]Music score for chorus in march time on inside back cover [note

Membrane Permeating Macrocycles: Design Guidelines from Machine Learning

The ability to predict cell-permeable candidate molecules has great potential to assist drug discovery projects. Large molecules that lie beyond the Rule of Five (bRo5) are increasingly important as drug candidates and tool molecules for chemical biology. However, such large molecules usually do not cross cell membranes and cannot access intracellular targets or be developed as orally bioavailable drugs. Here, we describe a random forest (RF) machine learning model for the prediction of passive membrane permeation rates developed using a set of over 1000 bRo5 macrocyclic compounds. The model is based on easily calculated chemical features/descriptors as independent variables. Our random forest (RF) model substantially outperforms a multiple linear regression model based on the same features and achieves better performance metrics than previously reported models using the same underlying data. These features include: (1) polar surface area in water, (2) the octanol-water partitioning coefficient, (3) the number of hydrogen-bond donors, (4) the sum of the topological distances between nitrogen atoms, (5) the sum of the topological distances between nitrogen and oxygen atoms, and (6) the multiple molecular path count of order 2. The last three features represent molecular flexibility, the ability of the molecule to adopt different conformations in the aqueous and membrane interior phases, and the molecular “chameleonicity.” Guided by the model, we propose design guidelines for membrane-permeating macrocycles. It is anticipated that this model will be useful in guiding the design of large, bioactive molecules for medicinal chemistry and chemical biology applications

Membrane Permeating Macrocycles: Design Guidelines from Machine Learning

The ability to predict cell-permeable candidate molecules has great potential to assist drug discovery projects. Large molecules that lie beyond the Rule of Five (bRo5) are increasingly important as drug candidates and tool molecules for chemical biology. However, such large molecules usually do not cross cell membranes and cannot access intracellular targets or be developed as orally bioavailable drugs. Here, we describe a random forest (RF) machine learning model for the prediction of passive membrane permeation rates developed using a set of over 1000 bRo5 macrocyclic compounds. The model is based on easily calculated chemical features/descriptors as independent variables. Our random forest (RF) model substantially outperforms a multiple linear regression model based on the same features and achieves better performance metrics than previously reported models using the same underlying data. These features include: (1) polar surface area in water, (2) the octanol-water partitioning coefficient, (3) the number of hydrogen-bond donors, (4) the sum of the topological distances between nitrogen atoms, (5) the sum of the topological distances between nitrogen and oxygen atoms, and (6) the multiple molecular path count of order 2. The last three features represent molecular flexibility, the ability of the molecule to adopt different conformations in the aqueous and membrane interior phases, and the molecular “chameleonicity.” Guided by the model, we propose design guidelines for membrane-permeating macrocycles. It is anticipated that this model will be useful in guiding the design of large, bioactive molecules for medicinal chemistry and chemical biology applications

A cyclic peptide inhibitor of the iNOS–SPSB protein–protein interaction as a potential anti-infective agent

SPRY domain- and SOCS box-containing proteins SPSB1, SPSB2, and SPSB4 interact with inducible nitric oxide synthase (iNOS), causing the iNOS to be polyubiquitinated and targeted for degradation. Inhibition of this interaction increases iNOS levels, and consequently cellular nitric oxide (NO) concentrations, and has been proposed as a potential strategy for killing intracellular pathogens. We previously described two DINNN-containing cyclic peptides (CP1 and CP2) as potent inhibitors of the murine SPSB-iNOS interaction. In this study, we report the crystal structures of human SPSB4 bound to CP1 and CP2 and human SPSB2 bound to CP2. We then used these structures to design a new inhibitor in which an intramolecular hydrogen bond was replaced with a hydrocarbon linkage to form a smaller macrocycle while maintaining the bound geometry of CP2 observed in the crystal structures. This resulting pentapeptide SPSB-iNOS inhibitor (CP3) has a reduced macrocycle ring size, fewer nonbinding residues, and includes additional conformational constraints. CP3 has a greater affinity for SBSB2 ( KD = 7 nM as determined by surface plasmon resonance) and strongly inhibits the SPSB2-iNOS interaction in macrophage cell lysates. We have also determined the crystal structure of CP3 in complex with human SPSB2, which reveals the structural basis for the increased potency of CP3 and validates the original design