Agricultural Information Sources for Farmers in Lesotho, Southern Africa

The baseline survey of the Lesotho Farming Systems Research (FSR) prototype areas was a collaborative effort of the Lesotho Ministry of Agriculture (MOA) Research Division and Washington State University\u27s Farming Systems Research Project. The project\u27s thrust was adaptive on-the farm demonstrations to stimulate farmers\u27 interest and adoption

A principled approach to the measurement of situation awareness in commercial aviation

The issue of how to support situation awareness among crews of modern commercial aircraft is becoming especially important with the introduction of automation in the form of sophisticated flight management computers and expert systems designed to assist the crew. In this paper, cognitive theories are discussed that have relevance for the definition and measurement of situation awareness. These theories suggest that comprehension of the flow of events is an active process that is limited by the modularity of attention and memory constraints, but can be enhanced by expert knowledge and strategies. Three implications of this perspective for assessing and improving situation awareness are considered: (1) Scenario variations are proposed that tax awareness by placing demands on attention; (2) Experimental tasks and probes are described for assessing the cognitive processes that underlie situation awareness; and (3) The use of computer-based human performance models to augment the measures of situation awareness derived from performance data is explored. Finally, two potential example applications of the proposed assessment techniques are described, one concerning spatial awareness using wide field of view displays and the other emphasizing fault management in aircraft systems

Pilot opinions on high level flight deck automation issues: Toward the development of a design philosophy

There has been much concern in recent years about the rapid increase in automation on commercial flight decks. The survey was composed of three major sections. The first section asked pilots to rate different automation components that exist on the latest commercial aircraft regarding their obtrusiveness and the attention and effort required in using them. The second section addressed general 'automation philosophy' issues. The third section focused on issues related to levels and amount of automation. The results indicate that pilots of advanced aircraft like their automation, use it, and would welcome more automation. However, they also believe that automation has many disadvantages, especially fully autonomous automation. They want their automation to be simple and reliable and to produce predictable results. The biggest needs for higher levels of automation were in pre-flight, communication, systems management, and task management functions, planning as well as response tasks, and high workload situations. There is an irony and a challenge in the implications of these findings. On the one hand pilots would like new automation to be simple and reliable, but they need it to support the most complex part of the job--managing and planning tasks in high workload situations

Mechanistic Characterization and Molecular Modeling of Hepatitis B Virus Polymerase Resistance to Entecavir

BACKGROUND: Entecavir (ETV) is a deoxyguanosine analog competitive inhibitor of hepatitis B virus (HBV) polymerase that exhibits delayed chain termination of HBV DNA. A high barrier to entecavir-resistance (ETVr) is observed clinically, likely due to its potency and a requirement for multiple resistance changes to overcome suppression. Changes in the HBV polymerase reverse-transcriptase (RT) domain involve lamivudine-resistance (LVDr) substitutions in the conserved YMDD motif (M204V/I +/- L180M), plus an additional ETV-specific change at residues T184, S202 or M250. These substitutions surround the putative dNTP binding site or primer grip regions of the HBV RT. METHODS/PRINCIPAL FINDINGS: To determine the mechanistic basis for ETVr, wildtype, lamivudine-resistant (M204V, L180M) and ETVr HBVs were studied using in vitro RT enzyme and cell culture assays, as well as molecular modeling. Resistance substitutions significantly reduced ETV incorporation and chain termination in HBV DNA and increased the ETV-TP inhibition constant (K(i)) for HBV RT. Resistant HBVs exhibited impaired replication in culture and reduced enzyme activity (k(cat)) in vitro. Molecular modeling of the HBV RT suggested that ETVr residue T184 was adjacent to and stabilized S202 within the LVDr YMDD loop. ETVr arose through steric changes at T184 or S202 or by disruption of hydrogen-bonding between the two, both of which repositioned the loop and reduced the ETV-triphosphate (ETV-TP) binding pocket. In contrast to T184 and S202 changes, ETVr at primer grip residue M250 was observed during RNA-directed DNA synthesis only. Experimentally, M250 changes also impacted the dNTP-binding site. Modeling suggested a novel mechanism for M250 resistance, whereby repositioning of the primer-template component of the dNTP-binding site shifted the ETV-TP binding pocket. No structural data are available to confirm the HBV RT modeling, however, results were consistent with phenotypic analysis of comprehensive substitutions of each ETVr position. CONCLUSIONS: Altogether, ETVr occurred through exclusion of ETV-TP from the dNTP-binding site, through different, novel mechanisms that involved lamivudine-resistance, ETV-specific substitutions, and the primer-template

BMQ

BMQ: Boston Medical Quarterly was published from 1950-1966 by the Boston University School of Medicine and the Massachusetts Memorial Hospitals

Analysis of ETVr through strand-specific DNA synthesis in culture.

<p>Cell culture ETV EC₅₀ determinations were made for wildtype and various resistant HBVs. The levels of HBV DNA synthesized in the presence of ETV was determined by HBV-specific probe hybridization to HBV nucleocapsid DNA from the cultures. The probes used were the typical double-stranded DNA probe, or strand-specific riboprobes which hybridized to a single HBV DNA strand. Comparison of strand-specific EC₅₀ versus double stranded EC₅₀ for wildtype polymerase (WT) or LVDr M204V+L180M HBV, or the LVDr substitutions with ETVr substitutions (+T184, +S202, +M250) as indicated. Values at 4000 nM indicate that 50% inhibition was not observed at the highest ETV concentration tested.</p

The T184-S202-204 hydrogen bonding network stabilizes the YMDD loop.

<p>The YMDD loop is shown with residues M204V+L180M and the H-bonding between residues T184, S202 and M204V are shown as dotted white lines.</p

Molecular homology model of resistant HBV RTs.

<p>The ETV-TP binding pocket of HBV RT. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009195#pone.0009195-Langley1" target="_blank">[3]</a>. (A) HBV RT with LVDr substitutions, M204V+L180M, (B) HBV RT with LVDr + S202G. HBV RT, ETV-TP and primer-template DNAs are labeled. The residues lining the pocket are orange, changes from LVDr are red, from ETVr are blue, and the M250, S202, and T184 residue positions (panel B) are pink. Panel A was essential reproduced from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009195#pone.0009195-Langley1" target="_blank">[3]</a> with permission.</p

Kinetic Parameters for HBV Polymerases.

a<p>Values are the mean ± standard deviation from at least three independent experiments.</p>b<p>Fold change from wildtype value.</p