A space-based radio frequency transient event classifier

The FORTE (Fast On-Orbit Recording of Transient Events) satellite will record RF transients in space. These transients will be classified onboard the spacecraft with an Event Classifier--specialized hardware that performs signal preprocessing and neural network classification. The authors describe the Event Classifier, future directions, and implications for telecommunications satellites. Telecommunication satellites are susceptible to damage from environmental factors such as deep dielectric charging and surface discharges. The event classifier technology the authors are developing is capable of sensing the surface discharges and could be useful for mitigating their effects. In addition, the techniques they are using for processing weak signals in noisy environments are relevant to telecommunications

Lead Optimization of 3,5-Disubstituted-7-Azaindoles for the Treatment of Human African Trypanosomiasis.

Neglected tropical diseases such as human African trypanosomiasis (HAT) are prevalent primarily in tropical climates and among populations living in poverty. Historically, the lack of economic incentive to develop new treatments for these diseases has meant that existing therapeutics have serious shortcomings in terms of safety, efficacy, and administration, and better therapeutics are needed. We now report a series of 3,5-disubstituted-7-azaindoles identified as growth inhibitors of Trypanosoma brucei, the parasite that causes HAT, through a high-throughput screen. We describe the hit-to-lead optimization of this series and the development and preclinical investigation of 29d, a potent antitrypanosomal compound with promising pharmacokinetic (PK) parameters. This compound was ultimately not progressed beyond in vivo PK studies due to its inability to penetrate the blood-brain barrier (BBB), critical for stage 2 HAT treatments.The authors acknowledge funding from the National Institute of Allergy and Infectious Diseases (M.P.P. and M.N., R01AI114685; M.P.P., 1R21AI127594, R01AI124046; C.R.C., R21AI126296; https://www.niaid.nih.gov/), the Spanish Ministerio de Economí a, Industria y Competitividad (M.N., SAF2015-71444-P; D.G.-P., SAF2016-79957-R; http://www.mineco.gob.es), Subdireccion General de Redes ́ y Centros de Investigacion Cooperativa (RICET, https://www.ricet.es/) (M.N., RD16/0027/0019; D.G.P., RD16/ 0027/0014), and RTI2018-097210-B-I00 (MINCIU-FEDER) to F.G. An ACS MEDI Predoctoral Fellowship for D.M.K. is gratefully acknowledged, as is support from the National Science Foundation for K.F. (CHE-1262734). We thank AstraZeneca, Charles River Laboratories, and GlaxoSmithKline for the provision of the in vitro ADME and physicochemical properties data. The use of JChem/ChemAxon software is acknowledged

Reconfigurable computer array: The bridge between high speed sensors and low speed computing

A universal limitation of RF and imaging front-end sensors is that they easily produce data at a higher rate than any general-purpose computer can continuously handle. Therefore, Los Alamos National Laboratory has developed a custom Reconfigurable Computing Array board to support a large variety of processing applications including wideband RF signals, LIDAR and multi-dimensional imaging. The boards design exploits three key features to achieve its performance. First, there are large banks of fast memory dedicated to each reconfigurable processor and also shared between pairs of processors. Second, there are dedicated data paths between processors, and from a processor to flexible I/O interfaces. Third, the design provides the ability to link multiple boards into a serial and/or parallel structure

A space-based radio frequency transient event classifier

The Department of Energy is currently investigating economical and reliable techniques for space-based nuclear weapon treaty verification. Nuclear weapon detonations produce RF transients that are signatures of illegal nuclear weapons tests. However, there are many other sources of RF signals, both natural and man-made. Direct digitization of RF signals requires rates of 300 MSamples per second and produces 10{sup 13} samples per day of data to analyze. it is impractical to store and downlink all digitized RF data from such a satellite without a prohibitively expensive increase in the number and capacities of ground stations. Reliable and robust data processing and information extraction must be performed onboard the spacecraft in order to reduce downlinked data to a reasonable volume. The FORTE (Fast On-Orbit Recording of Transient Events) satellite records RF transients in space. These transients will be classified onboard the spacecraft with an Event Classifier specialized hardware that performs signal preprocessing and neural network classification. The authors describe the Event Classifier requirements, scientific constraints, design and implementation

Accumulation of plutonium in mammalian wildlife tissues following dispersal by accidental-release tests

We examined the distribution of plutonium (Pu) in the tissues of mammalian wildlife inhabiting the relatively undisturbed, semi-arid former Taranaki weapons test site, Maralinga, Australia. The accumulation of absorbed Pu was highest in the skeleton (83% ± 6%), followed by muscle (10% ± 9%), liver (6% ± 6%), kidneys (0.6% ± 0.4%), and blood (0.2%). Pu activity concentrations in lung tissues were elevated relative to the body average. Foetal transfer was higher in the wildlife data than in previous laboratory studies. The amount of Pu in the gastrointestinal tract was highly elevated relative to that absorbed within the body, potentially increasing transfer of Pu to wildlife and human consumers that may ingest gastrointestinal tract organs. The Pu distribution in the Maralinga mammalian wildlife generally aligns with previous studies related to environmental exposure (e.g. Pu in humans from worldwide fallout), but contrasts with the partitioning models that have traditionally been used for human worker-protection purposes (approximately equal deposition in bone and liver) which appear to under-predict the skeletal accumulation in environmental exposure conditions

A Cysteine Protease Inhibitor Rescues Mice from a Lethal Cryptosporidium parvum Infection

Host-parasite interactio

Ensuring robust radiological risk assessment for wildlife: insights from the International Atomic Energy Agency EMRAS and MODARIA programmes

In response to changing international recommendations and national requirements, a number of assessment approaches, and associated tools and models, have been developed over the last circa 20 years to assess radiological risk to wildlife. In this paper, we summarise international intercomparison exercises and scenario applications of available radiological assessment models for wildlife to aid future model users and those such as regulators who interpret assessments. Through our studies, we have assessed the fitness for purpose of various models and tools, identified the major sources of uncertainty and made recommendations on how the models and tools can best be applied to suit the purposes of an assessment. We conclude that the commonly used tiered or graded assessment tools are generally fit for purpose for conducting screening-level assessments of radiological impacts to wildlife. Radiological protection of the environment (or wildlife) is still a relatively new development within the overall system of radiation protection and environmental assessment approaches are continuing to develop. Given that some new/developing approaches differ considerably from the more established models/tools and there is an increasing international interest in developing approaches that support the effective regulation of multiple stressors (including radiation), we recommend the continuation of coordinated international programmes for model development, intercomparison and scenario testing

Hiv-1 Gp41 And Gp160 Are Hyperthermostable Proteins In A Mesophilic Environment - Characterization Of Gp41 Mutants

HIV gp41(24-157) unfolds cooperatively over the pH range of 1.0-4.0 with T(m) values of > 100 degrees C. At pH 2.8, protein unfolding was 80% reversible and the DeltaH(vH)/DeltaH(cal) ratio of 3.7 is indicative of gp41 being trimeric. No evidence for a monomer-trimer equilibrium in the concentration range of 0.3-36 micro m was obtained by DSC and tryptophan fluorescence. Glycosylation of gp41 was found to have only a marginal impact on the thermal stability. Reduction of the disulfide bond or mutation of both cysteine residues had only a marginal impact on protein stability. There was no cooperative unfolding event in the DSC thermogram of gp160 in NaCl/P(i), pH 7.4, over a temperature range of 8-129 degrees C. When the pH was lowered to 5.5-3.4, a single unfolding event at around 120 degrees C was noted, and three unfolding events at 93.3, 106.4 and 111.8 degrees C were observed at pH 2.8. Differences between gp41 and gp160, and hyperthermostable proteins from thermophile organisms are discussed. A series of gp41 mutants containing single, double, triple or quadruple point mutations were analysed by DSC and CD. The impact of mutations on the protein structure, in the context of generating a gp41 based vaccine antigen that resembles a fusion intermediate state, is discussed. A gp41 mutant, in which three hydrophobic amino acids in the gp41 loop were replaced with charged residues, showed an increased solubility at neutral pH

Evaluation of a class of isatinoids identified from a high-throughput screen of human kinase inhibitors as anti-Sleeping Sickness agents

New treatments are needed for neglected tropical diseases (NTDs) such as Human African trypanosomiasis (HAT), Chagas disease, and schistosomiasis. Through a whole organism high-throughput screening campaign, we previously identified 797 human kinase inhibitors that grouped into 59 structural clusters and showed activity against T. brucei, the causative agent of HAT. We herein report the results of further investigation of one of these clusters consisting of substituted isatin derivatives, focusing on establishing structure-activity and -property relationship scope. We also describe their in vitro absorption, distribution, metabolism, and excretion (ADME) properties. For one isatin, NEU-4391, which offered the best activity-property profile, pharmacokinetic parameters were measured in mice.The authors wish to acknowledge funding from the National Institute of Allergy and Infectious Diseases (MPP & MN: R01AI114685; MPP R21AI126296, R21AI127594; CRC: R21AI126296, R21AI133393. https://www.niaid.nih.gov/), the Spanish Ministerio de Economía, Industria y Competitividad, (MN: SAF2015-71444-P; DG-P: SAF2016-79957-R. http://www.mineco.gob.es), Junta de Andalucía (FG: CTS-7282. https://www.juntadeandalucia.es) and Subdirección General de Redes y Centros de Investigación Cooperativa (RICET) (MN: RD16/0027/0019; DG-P: RD16/0027/0014. https://bit.ly/2OegOnX). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe