Conceptual mechanization studies for a horizon definition spacecraft attitude control subsystem, phase A, part II, 10 October 1966 - 29 May 1967

Attitude control subsystem for spin stabilized spacecraft for mapping earths infrared horizon radiance profiles in 15 micron carbon dioxide absorption ban

Mapping Water Availability, Cost and Projected Consumptive Use in the Eastern United States with Comparisons to the West

The availability of freshwater supplies to meet future demand is a growing concern. Water availability metrics are needed to inform future water development decisions. Furthermore, with the help of water managers, water availability was mapped for over 1300 watersheds throughout the 31-contiguous states in the eastern U.S. complimenting a prior study of the west. The compiled set of water availability data is unique in that it considers multiple sources of water (fresh surface and groundwater, wastewater and brackish groundwater); accommodates institutional controls placed on water use; is accompanied by cost estimates to access, treat and convey each unique source of water, and; is compared to projected future growth in consumptive water use to 2030. Although few administrative limits have been set on water availability in the east, water managers have identified 315 fresh surface water and 398 fresh groundwater basins (with 151 overlapping basins) as Areas of Concern (AOCs) where water supply challenges exist due to drought related concerns, environmental flows, groundwater overdraft, or salt water intrusion. This highlights a difference in management where AOCs are identified in the east which simply require additional permitting, while in the west strict administrative limits are established. Although the east is generally considered water rich roughly a quarter of the basins were identified as AOCs; however, this is still in strong contrast to the west where 78% of the surface water basins are operating at or near their administrative limit. There was little effort noted on the part of eastern or western water managers to quantify non-fresh water resource

3 W of single-frequency output at 532 nm by intracavity frequency doubling of a diode-bar-pumped Nd:YAG ring laser 3 W of single-frequency output at 532 nm by intracavity frequency doubling of a diode-bar-pumped Nd:YAG ring laser

A beam-shaped 20W diode-bar has longitudinally pumped a Nd:YAG laser in a ring configuration. Unidirectional single-frequency operation is enforced by a Faraday rotator. Intracavity frequency doubling, using a KTP crystal has produced 3W of stable, single-frequency TEMoo output at 532nm

Pharmacology of DB844, an orally active aza analogue of pafuramidine, in a monkey model of second stage human African trypanosomiasis

Novel drugs to treat human African trypanosomiasis (HAT) are still urgently needed despite the recent addition of nifurtimox-eflornithine combination therapy (NECT) to WHO Model Lists of Essential Medicines against second stage HAT, where parasites have invaded the central nervous system (CNS). The pharmacology of a potential orally available lead compound, N-methoxy-6-{5-[4-(N-methoxyamidino) phenyl]-furan-2-yl}-nicotinamidine (DB844), was evaluated in a vervet monkey model of second stage HAT, following promising results in mice. DB844 was administered orally to vervet monkeys, beginning 28 days post infection (DPI) with Trypanosoma brucei rhodesiense KETRI 2537. DB844 was absorbed and converted to the active metabolite 6-[5-(4-phenylamidinophenyl)-furanyl-2-yl]-nicotinamide (DB820), exhibiting plasma C(max) values of 430 and 190 nM for DB844 and DB820, respectively, after the 14th dose at 6 mg/kg qd. A 100-fold reduction in blood trypanosome counts was observed within 24 h of the third dose and, at the end of treatment evaluation performed four days post the last drug dose, trypanosomes were not detected in the blood or cerebrospinal fluid of any monkey. However, some animals relapsed during the 300 days of post treatment monitoring, resulting in a cure rate of 3/8 (37.5%) and 3/7 (42.9%) for the 5 mg/kg×10 days and the 6 mg/kg×14 days dose regimens respectively. These DB844 efficacy data were an improvement compared with pentamidine and pafuramidine both of which were previously shown to be non-curative in this model of CNS stage HAT. These data show that synthesis of novel diamidines with improved activity against CNS-stage HAT was possible

Inspædia: [Almost] Everything About Simplicity, Playfulness and Inspiration

The aim of this paper is to disclose the new research developments and the results from the systematization of experience and user interaction with the Inspædia (a new web knowledge “Agora”), to inspire a dynamic, collaborative, and interactive intelligence among the inspædiers. We will explain in detail and describe the design process and discuss the ultimate design interaction concept & development regarding (almost everything about) simplicity and playfulness of the inspædiers’ experience to transform relevant information (related > meanfull > useful) in productive knowledge (inspiration > insight > foresight) in a very easy and quick way (usability: learnability; understandability; operability; attractiveness...), with a smile in the face (satisfaction) and a wow in the mind (or in the soul).Inspædia is the natural consequence and development of the prototype resulting from the research in Design PhD thesis Innovation, design et cetera (FA/UTL, 2012). Therefore, it is being developed with the Science Without Borders Program (2013-2016) with a Special Visiting Researcher fellowship grant of CAPES (Brazil), and under the post-doctoral in Design at the Faculty of Architecture, University of Lisbon (FA/UL); CIAUD – Reseach Centre of Architecture, Urbanism and Design (FA/UL); Faculty of Sciences and Technology, Nova University of Lisbon (FCT/UNL); NOVA-LINCS (FCT/UNL) and CITAD - Research Centre for Territory, Architecture and Design (FAA/ULL). The Inspædia research project was ranked in first place in Design scientific area and obtained a post-doctoral fellowship by FCT – Foundation for Science and Technology (Portugal). The project has been internationally disseminated at international Design conferences with indexed publications. It was presented and published both at AHFE 2014 (Krakow) and AHFE 2015 (Las Vegas). It was part of the biennial Experimentadesign tangential events in 2013 (EXD'13), 2015 (EXD'15) and was presented, by invitation, at the International Congress DESIGN I-CON (2015). During the last year we prototyped and tested (usability testing) with some inspædiers different approaches to achieve users’ needs > desires > expectations) in a challenging way, in order to provide the most powerful and memorable user experience

Efficacy, safety, and dose of Pafuramidine, a new oral drug for treatment of first stage sleeping sickness, in a phase 2a clinical study and phase 2b randomized clinical studies

Sleeping sickness (human African trypanosomiasis [HAT]) is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT.; The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID) for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC]) between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2), where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a) or 3 months (Phase 2b) after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent.; Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). These results support continuation of the development program for pafuramidine into Phase 3

Dynamic compaction of salt: Initial demonstration and performance testing

Reconsolidated crushed salt is proposed as the sole long-term shaft seal between the Waste Isolation Pilot Plant (WIPP) and the biosphere. The concept for a long-term shaft seal for the WIPP repository is to place crushed salt in the four shafts and to develop an effective seal as the surrounding salt creeps into the shafts, reconsolidating the salt. Permeability of the salt components is calculated to achieve performance objectives at some acceptable time in the future, an expectation which is a key to performance assessment calculations for the WIPP. Such a seal has never been constructed, and until now no performance measurements have been made on an appropriately large scale. A full understanding of construction methods, achievable initial density and permeability and time-wise performance of reconsolidating salt is required. This paper discusses nearly full-scale dynamic compaction of mine-run WIPP salt, preliminary measurements of density and permeability, and their variability within a relatively large volume of compacted materia

Carbenic nitrile imines: Properties and reactivity

Structures and properties of nitrile imines were investigated computationally at B3LYP and CCSD(T) levels. Whereas NBO analysis at the B3LYP DFT level invariably predicts a propargylic electronic structure, CCSD(T) calculations permit a clear distinction between propargylic, allenic, and carbenic structures. Nitrile imines with strong IR absorptions above ca. 2150 cm-1 have propargylic structures with a CN triple bond (RCNNSiMe 3 and R2BCNNBR2), and those with IR absorptions below ca. 2150 cm-1 are allenic (HCNNH, PhCNNH, and HCNNPh). Nitrile imines lacking significant cumulenic IR absorptions at 1900-2200 cm -1 are carbenic (R-(C:)-N=N-R′). Electronegative but lone pair-donating groups NR2, OR, and F stabilize the carbenic form of nitrile imines in the same way they stabilize "normal" singlet carbenes, including N-heterocyclic carbenes. NBO analyses at the CCSD(T) level confirm the classification into propargylic, allenic, and carbenic reactivity types. Carbenic nitrile imines are predicted to form azoketenes 21 with CO, to form [2+2] and [2+4] cycloadducts and borane adducts, and to cyclize to 1H-diazirenes of the type 24 in mildly exothermic reactions with activation energies in the range 29-38 kcal/mol. Such reactions will be readily accessible photochemically and thermally, e.g., under the conditions of matrix photolysis and flash vacuum thermolysis

Structure-activity relationships of analogs of pentamidine against Plasmodium falciparum and Leishmania mexicana amazonensis.

The antiprotozoal compound 1,5-di(4-amidinophenoxy)pentane (pentamidine) and 36 of its analogs were screened for in vitro activity against Leishmania mexicana amazonensis clone 669 C4S (MHOM/BR/73/M2269) and Plasmodium falciparum clones W2 (Indochina III/CDC) and D6 (Sierra Leone I/CDC). Pentamidine and each of the analogs tested exhibited activity in vitro against L. m. amazonensis and P. falciparum. The pentamidine analogs were more effective against the P. falciparum clones than against L. m. amazonensis. P. falciparum was extremely susceptible to these compounds, with 50% inhibitory concentrations as low as 0.03 microM. While none of the analogs exhibited marked improvement in antileishmanial activity compared with pentamidine, 12 of the pentamidine analogs showed activity approximately equal to or greater than that of the parent compound. From the promising activity exhibited by the pentamidine analogs in this in vitro study and their potential for reduced toxicity relative to the parent drug, pentamidine-related compounds hold promise as new agents for the treatment of protozoal infections

A High-Throughput, High-Resolution Strategy for the Study of Site-Selective DNA Binding Agents: Analysis of a “Highly Twisted” Benzimidazole-Diamidine

A general strategy for the rapid structural analysis of DNA binding ligands is described as it was applied to the study of RT29, a new benzimidazole-diamidine compound containing a highly twisted diphenyl ether linkage. By combining the existing high-throughput fluorescent intercalator displacement (HT-FID) assay developed by Boger et al. and a high-resolution (HR) host-guest crystallographic technique, a system was produced that was capable of determining detailed structural information pertaining to RT29-DNA interactions within ~ 3 days. Our application of the HT-HR strategy immediately revealed that RT29 has a preference for four-base pair, A/T-rich sites (AATT) and a similar tolerance and affinity for three A·T-base pair sites (such as ATTC) containing a G·C base pair. Based on these selectivities, oligonucleotides were designed and the host-guest crystallographic method was used to generate diffraction quality crystals. Analysis of the resulting crystal structures revealed that the diphenyl ether moiety of RT29 undergoes conformational changes that allow it to adopt a crescent shape that now complements the minor groove structure. The presence of a G·C base pair in the RT29 binding site of ATTC did not overly perturb its interaction with DNA - the compound adjusted to the nucleobases that were available through water-mediated interactions. Our analyses suggest that the HT-HR strategy may be used to expedite the screening of novel minor groove binding compounds leading to a direct, HR structural determination