Characterizing Search Behavior in Productivity Software

Complex software applications expose hundreds of commands to users through intricate menu hierarchies. One of the most popular productivity software suites, Microsoft Office, has recently developed functionality that allows users to issue free-form text queries to a search system to quickly find commands they want to execute, retrieve help documentation or access web results in a unified interface. In this paper, we analyze millions of search sessions originating from within Microsoft Office applications, collected over one month of activity, in an effort to characterize search behavior in productivity software. Our research brings together previous efforts in analyzing command usage in large-scale applications and efforts in understanding search behavior in environments other than the web. Our findings show that users engage primarily in command search, and that re-accessing commands through search is a frequent behavior. Our work represents the first large-scale analysis of search over command spaces and is an important first step in understanding how search systems integrated with productivity software can be successfully developed

Determinants of Functionality in the Ubiquitin Conjugating Enzyme Family

AbstractThe E2 enzymes are key enzymes in the ubiquitin and ubiquitin-like protein ligation pathways. To understand the functionality of the different E2 enzymes, we analyzed 190 protein sequences and 211 structures and electrostatic potentials. Key findings include: The ScUbc1 orthologs are defined by a C-terminal UBA domain. An N-terminal sequence motif that is highly conserved in all E2s except for Cdc34 orthologs is important for the stabilization of the L7 loop and is likely to be involved in E1 binding. ScUbc11p has a different electrostatic potential from E2-Cp and other proteins with which it has high sequence similarity but different functionality. All the E2s known to ubiquitinate histones have a negative potential. The members of the NCUBE family have a positive electrostatic potential, although its form is different from that of the SUMO conjugating E2s. The specificities of only the ScUbc4/Ubc5 and ScUbc1p orthologs are reflected in their L4 and L7 loops

Инфекционно-токсический шок в акушерстве и гинекологии

ШОК ТОКСИЧЕСКИЙ /ДИАГН /ПАТОФИЗИОЛ /ТЕРСЕПТИЦЕМИЯИНФЕКЦИЯ /ОСЛЖЕНСКИЕ БОЛЕЗНИ /ОСЛ /СМЕРТНАБОРТ КРИМИНАЛЬНЫЙБАКТЕРИАЛЬНЫЕ ИНФЕКЦИИ /ОСЛГИСТЕРЭКТОМИЯГИНЕКОЛОГИЧЕСКИЕ ХИРУРГИЧЕСКИЕ ОПЕРАЦИ

Fractional 13C enrichment of isolated carbons using [1-13C]- or [2-13C]-glucose facilitates the accurate measurement of dynamics at backbone Ca and side-chain methyl positions in protein

A simple labeling approach is presented based on protein expression in [1-C-13]- or [2-C-13]-glucose containing media that produces molecules enriched at methyl carbon positions or backbone C-alpha sites, respectively. All of the methyl groups, with the exception of Thr and Ile(delta 1) are produced with isolated C-13 spins (i.e., no C-13-C-13 one bond couplings), facilitating studies of dynamics through the use of spin-spin relaxation experiments without artifacts introduced by evolution due to large homonuclear scalar couplings. Carbon-alpha sites are labeled without concomitant labeling at C-beta positions for 17 of the common 20 amino acids and there are no cases for which C-13(alpha)-(CO)-C-13 spin pairs are observed. A large number of probes are thus available for the study of protein dynamics with the results obtained complimenting those from more traditional backbone N-15 studies. The utility of the labeling is established by recording C-13 R-1 rho and CPMG-based experiments on a number of different protein systems

Deconvoluting Protein (Un)folding Structural Ensembles Using X-Ray Scattering, Nuclear Magnetic Resonance Spectroscopy and Molecular Dynamics Simulation

The folding and unfolding of protein domains is an apparently cooperative process, but transient intermediates have been detected in some cases. Such (un) folding intermediates are challenging to investigate structurally as they are typically not long-lived and their role in the (un) folding reaction has often been questioned. One of the most well studied (un) folding pathways is that of Drosophila melanogaster Engrailed homeodomain (EnHD): this 61-residue protein forms a three helix bundle in the native state and folds via a helical intermediate. Here we used molecular dynamics simulations to derive sample conformations of EnHD in the native, intermediate, and unfolded states and selected the relevant structural clusters by comparing to small/wide angle X-ray scattering data at four different temperatures. The results are corroborated using residual dipolar couplings determined by NMR spectroscopy. Our results agree well with the previously proposed (un) folding pathway. However, they also suggest that the fully unfolded state is present at a low fraction throughout the investigated temperature interval, and that the (un) folding intermediate is highly populated at the thermal midpoint in line with the view that this intermediate can be regarded to be the denatured state under physiological conditions. Further, the combination of ensemble structural techniques with MD allows for determination of structures and populations of multiple interconverting structures in solution

The number of violated restraints according to Fletcher et al. [45] The total number of NOE restraints is 735.

<p>The RMSD have been averaged over all structures in the S/WAXS refined ensemble.</p

Conformational sampling of EnHD at 8 different temperatures based on MD simulations.

<p>The plot also shows the correlation between radius of gyration and root mean square deviation from the NMR structure. The RMSD have been calculated for the mainchain and C_<i>β</i> atoms of all 61 residues.</p

Agreement of H^<i>N</i>-N RDCs to EnHD crystal structure at increasing temperatures.

<p>The Cornilescu Q factors were calculated using a sliding window from ‘Window start’ to ‘Window end’ to estimate the agreement of the given residue range. Q = 0.25 was used as the cut-off for the agreement [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0125662#pone.0125662.ref024" target="_blank">24</a>]. At 20°C (a) and 30°C (b) EnHD is fully folded, and any chosen residue window displays perfect agreement with the crystal structure. At 40°C (c) the agreement for the 10–55 fragment is not present, but the HTH motif remains structured. This indicates that H1 must be undocked from H2/H3. C. At 55°C (d) around the thermal midpoint of denaturation, some H^<i>N</i>-N RDCs for H2/H3 remain in agreement with the crystal structure.</p