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PubMed2001

Before the experts arrive.

This article addresses the rare event of the hostage situation in a forensic psychiatric nursing setting. It has a specific focus on the initial response and the accompanying issues for nurses at the clinical interface as the situation emerges. The intention of this article is to both offer guidance and raise the profile of this unique management issue because little attention is drawn to early-stage hostage situations at an organizational level. When a hostage situation occurs, inadequate preparation can mean the difference between life and death for the hostage, negotiator, or hostage taker. This article provides an overview of the relevant literature and offers guidance about the actions required when a nurse suddenly becomes responsible for managing the early stages of such a traumatic event. Responses, safety, and communication factors concerning the hostage taker are covered.

Crisis Intervention↗

PubMed1992

The art of mammographic positioning.

The discovery of clinically occult breast cancer creates an exciting opportunity to alter the natural history of one of the major killers of women in our society. The skills required for this endeavor depend on high-quality images that provide the mammographer with sufficient information to construct three-dimensional perceptions recognizable as departures from normal architecture. Altering the natural course of breast cancer depends on early detection. Early detection of breast cancer depends on high-quality imaging techniques. Paramount among the imaging techniques for breast cancer detection is mammographic positioning. Optimal mammographic positioning is achieved by understanding the capabilities of available dedicated mammographic equipment and applying this understanding to take full advantage of natural breast mobility in overcoming various anatomic limitations. Compression of breast tissue, essential for proper parenchymal imaging, is achieved by moving one surface of the breast toward the other. The concept of moving the mobile surface of the breast toward the more fixed and immobile surface has been stressed as an important principle in optimizing the amount of tissue that can be imaged on standard mammographic views. Visualizing the fine details of a lesion or the margins of an area of clinical or perceived radiographic concern may be crucial to determining the need for biopsy. Visualization of such details is best achieved by projecting the suspected lesion into interface with adjacent radiolucent fat through separation of overlapping parenchyma by using spot compression or by tangential imaging against subcutaneous fat. Unique problems require creative, tailored solutions. Such tailoring is made less difficult by understanding and using equipment capability with breast anatomy and mobility. The very small, very large, or very dense breast can be imaged properly with modified techniques. Likewise, the augmented breast, mastectomy site, or axilla can be imaged with specialized techniques. Artistic application of these mammographic positioning principles will be rewarded with high-quality images, fewer missed breast cancers, and more lives saved.

Breast Neoplasms↗

PubMed1995

A C4HC3 zinc finger motif.

Metal-binding cysteine and histidine residues are often used to stabilise a protein fold through coordination of zinc ions. These zinc fingers are either involved in nucleic acid binding (TFIIIA, GAL4, nuclear receptors, retroviral gag...) or in yet unidentified biochemical functions (LIM and RING domains). The latter characterized by a unique histidine residue in the zinc binding motif (C2HC5 and C3HC4 for the LIM and RING respectively) may constitute protein/protein interaction interfaces. We have identified a new C4HC3 motif in a variety of proteins including the Drosophila trithorax and its human homologue ALL-1 involved in oncogenic translocations in acute leukaemias. This domain, for which we propose the name TTC (for trithorax consensus) is found in many transcriptional regulators or DNA-binding proteins. Interestingly, TTC was found in several bromodomain containing transcriptional adaptors including the E1A-binding p300 and the CREB-binding CBP proteins. In CBP, this domain does not appear to be involved in DNA, CREB or TFIIB binding. In the chromosomal translocations that involve the 11q23 locus, the C-terminal end of ALL-1 (which contains 4 TTC fingers) is constantly lost. The absence of these motifs in the fusion genes may relate to their leukemogenic potential.

Amino Acid Sequence↗

PubMed2004

Phases, periphases, and interphases equilibrium by molecular modeling. I. Mass equilibrium by the semianalytical stochastic perturbations method and application to a solution between (120) gypsum faces.

The SASP (semianalytical stochastic perturbations) method is an original mixed macro-nano-approach dedicated to the mass equilibrium of multispecies phases, periphases, and interphases. This general method, applied here to the reflexive relation C(k)<=>mu(k) between the concentrations C(k) and the chemical potentials mu(k) of k species within a fluid in equilibrium, leads to the distribution of the particles at the atomic scale. The macroaspects of the method, based on analytical Taylor's developments of chemical potentials, are intimately mixed with the nanoaspects of molecular mechanics computations on stochastically perturbed states. This numerical approach, directly linked to definitions, is universal by comparison with current approaches, DLVO Derjaguin-Landau-Verwey-Overbeek, grand canonical Monte Carlo, etc., without any restriction on the number of species, concentrations, or boundary conditions. The determination of the relation C(k)<=>mu(k) implies in fact two problems: a direct problem C(k)=>mu(k) and an inverse problem mu(k)=>C(k). Validation of the method is demonstrated in case studies A and B which treat, respectively, a direct problem and an inverse problem within a free saturated gypsum solution. The flexibility of the method is illustrated in case study C dealing with an inverse problem within a solution interphase, confined between two (120) gypsum faces, remaining in connection with a reference solution. This last inverse problem leads to the mass equilibrium of ions and water molecules within a 3 A thick gypsum interface. The major unexpected observation is the repulsion of SO(4) (2-) ions towards the reference solution and the attraction of Ca(2+) ions from the reference solution, the concentration being 50 times higher within the interphase as compared to the free solution. The SASP method is today the unique approach able to tackle the simulation of the number and distribution of ions plus water molecules in such extreme confined conditions. This result is of prime importance for all coupled chemical-mechanical problems dealing with interfaces, and more generally for a wide variety of applications such as phase changes, osmotic equilibrium, surface energy, etc., in complex chemical-physics situations.

Journal Article↗

PubMed2000

The functional implications of the dimerization of the catalytic subunits of the mammalian brain platelet-activating factor acetylhydrolase (Ib).

The mammalian brain contains significant amounts of the cytosolic isoform Ib of the platelet-activating factor acetylhydrolase (PAF-AH), a unique type of PLA2. This oligomeric protein complex contains three types of subunits: two homologous (63% identity) 26 kDa catalytic subunits (alpha(1) and alpha(2)) which harbor all the PAF-AH activity, and the 45 kDa beta-subunit (LIS1), a product of the causal gene for Miller-Dieker lissencephaly. During fetal development, the preferentially expressed alpha(1)-subunit forms a homodimer, which binds to a homodimer of LIS1, whereas in adult organisms alpha(1)/alpha(2) and alpha(2)/alpha(2) dimers, also bound to dimeric LIS1, are the prevailing species. The consequences of this "switching" are not understood, but appear to be of physiological significance. The alpha(1)- and alpha(2)-subunits readily associate with very high affinity to form homodimers. The nature of the interface has been elucidated by the 1.7 A resolution crystal structure of the alpha(1)/alpha(1) homodimer (Ho et al., 1997). Here, we examined the functional consequences of the dimerization in both types of alpha-subunits. We obtained monomeric protein in the presence of high concentrations (>50 mM) of Ca2+ ions, and we show that it is catalytically inactive and less stable than the wild type. We further show that Arg29 and Arg22 in one monomer contribute to the catalytic competence of the active site across the dimer interface, and complement the catalytic triad of Ser47, Asp192 and His195, in the second monomer. These results indicate that the brain PAF-acetylhydrolase is a unique PLA2 in which dimerization is essential for both stability and catalytic activity.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed2004

Residual function in peripheral nerve stumps of amputees: implications for neural control of artificial limbs.

PURPOSE: It is not known whether motor and sensory pathways associated with a missing or denervated limb remain functionally intact over periods of many months or years after amputation or chronic peripheral nerve transection injury. We examined the extent to which activity on chronically severed motor nerve fibers could be controlled by human amputees and whether distally referred tactile and proprioceptive sensations could be induced by stimulation of sensory axons in the nerve stumps. METHODS: Amputees undergoing elective stump procedures were invited to participate in this study. Longitudinal intrafascicular electrodes were threaded percutaneously and implanted in severed nerves of human amputees. The electrodes were interfaced to an amplifier and stimulator system controlled by a laptop computer. Electrophysiologic tests were conducted for 2 consecutive days after recovery from the surgery. RESULTS: It was possible to record volitional motor nerve activity uniquely associated with missing limb movements. Electrical stimulation through the implanted electrodes elicited discrete, unitary, graded sensations of touch, joint movement, and position, referring to the missing limb. CONCLUSIONS: These findings indicate that both central and peripheral motor and somatosensory pathways retain significant residual connectivity and function for many years after limb amputation. This implies that peripheral nerve interfaces could be used to provide amputees with prosthetic limbs that have more natural feel and control than is possible with current myoelectric and body-powered control systems.

Action Potentials↗

PubMed2000

Crystal structure of cancer chemopreventive Bowman-Birk inhibitor in ternary complex with bovine trypsin at 2.3 A resolution. Structural basis of Janus-faced serine protease inhibitor specificity.

Understanding molecular recognition on a structural basis is an objective with broad academic and applied significance. In the complexes of serine proteases and their proteinaceous inhibitors, recognition is governed mainly by residue P1 in accord with primary serine protease specificity. The bifunctional soybean Bowman-Birk inhibitor (sBBI) should, therefore, interact at LysI16 (subdomain 1) with trypsin and at LeuI43 (subdomain 2) with chymotrypsin. In contrast with this prediction, a 2:1 assembly with trypsin was observed in solution and in the crystal structure of sBBI in complex with trypsin, determined at 2.3 A resolution by molecular replacement. Strikingly, P1LeuI43 of sBBI was fully embedded into the S(1) pocket of trypsin in contrast to primary specificity. The triple-stranded beta-hairpin unique to the BBI-family and the surface loops surrounding the active site of the enzyme formed a protein-protein-interface far extended beyond the primary contact region. Polar residues, hydrophilic bridges and weak hydrophobic contacts were predominant in subdomain 1, interacting specifically with trypsin. However, close hydrophobic contacts across the interface were characteristic of subdomain 2 reacting with both trypsin and chymotrypsin. A Met27Ile replacement shifted the ratio with trypsin to the predicted 1:1 ratio. Thus, the buried salt-bridge responsible for trypsin specificity was stabilised in a polar, and destabilized in a hydrophobic, environment. This may be used for adjusting the specificity of protease inhibitors for applications such as insecticides and cancer chemopreventive agents.

Amino Acid Sequence↗

PubMed2006

Kinking the coiled coil--negatively charged residues at the coiled-coil interface.

The coiled coil is one of the most common protein-structure motifs. It is believed to be adopted by 3-5% of all amino acids in proteins. It comprises two or more alpha-helical chains wrapped around one another. The sequences of most coiled coils are characterized by a seven-residue (heptad) repeat, denoted (abcdefg)(n). Residues at the a and d positions define the helical interface (core) and are usually hydrophobic, though about 20% are polar or charged. We show that parallel coiled-coils have a unique pattern of their negatively charged residues at the core positions: aspartic acid is excluded from these positions while glutamic acid is not. In contrast the antiparallel structures are more permissive in their amino acid usage. We show further, and for the first time, that incorporation of Asp but not Glu into the a positions of a parallel coiled coil creates a flexible hinge and that the maximal hinge angle is being directly related to the number of incorporated mutations. These new computational and experimental observations will be of use in improving protein-structure predictions, and as rules to guide rational design of novel coiled-coil motifs and coiled coil-based materials.

Aspartic Acid↗

PubMed2006

Development of structure and function in the infant brain: implications for cognition, language and social behaviour.

Recent advances in cognitive neuroscience have allowed us to begin investigating the development of both structure and function in the infant brain. However, despite the rapid evolution of technology, surprisingly few studies have examined the intersection between brain and behaviour over the first years of life. Even fewer have done so in the context of a particular research question. This paper aims to provide an overview of four domains that have been studied using techniques amenable to elucidating the brain/behaviour interface: language, face processing, object permanence, and joint attention, with particular emphasis on studies focusing on early development. The importance of the unique role of development and the interplay between structure and function is stressed throughout. It is hoped that this review will serve as a catalyst for further thinking about the substantial gaps in our understanding of the relationship between brain and behaviour across development. Further, our aim is to provide ideas about candidate brain areas that are likely to be implicated in particular behaviours or cognitive domains.

Animals↗

PubMed2002

The structure of tomato aspermy virus by X-ray crystallography.

The three-dimensional structure of tomato aspermy virus (TAV) has been solved by X-ray crystallography and refined to an R factor of 0.218 for 3.4-40 A data (effective resolution of 4A). Molecular replacement, using cucumber mosaic virus (Smith et al., 2000), provided phases for the initial maps used for model building. The coat protein of the 280 A diameter virion has the canonical "Swiss roll" beta-barrel topology with a distinctive amino-terminal alpha-helix directed into the interior of the virus where it interacts with encapsidated RNA. The N-terminal helices are joined to the beta-barrels of protein subunits by extended polypeptides of six amino acids, which serve as flexible hinges allowing movement of the helices in response to local RNA distribution. Segments of three nucleotides of partially disordered RNA interact with the capsid, primarily through arginine residues, at interfaces between A and B subunits. Side chains of cys64 and cys106 form the first disulfide observed in a cucumovirus, including a unique cysteine, 106, in a region otherwise conserved. A positive ion, putatively modeled as a Mg(+)ion, lies on the quasi-threefold axis surrounded by three quasi-symmetric glutamate 175 side chains.

Amino Acid Sequence↗

PubMed2006

Sum frequency generation vibrational spectroscopic studies on a silane adhesion-promoting mixture at a polymer interface.

Sum frequency generation (SFG) vibrational spectroscopy was used to probe the interface between poly(ethylene terephthalate) with deuterated ethylene glycol subunits (d4-PET) and a silane adhesion-promoting mixture (SAPM) comprised of (3-glycidoxypropyl)trimethoxysilane (gamma-GPS) and a methylvinylsiloxanol (MVS). Such a mixture has been found to improve the adhesion of an addition-curing silicone elastomer to a range of plastic and metal substrates. Our results demonstrated that at the interface between d4-PET and a SAPM with a gamma-GPS/MVS ratio of 1:1 (w/w), the silane molecules not only segregated to the interface but also the methoxy headgroups likely adopted a greater net orientational order along the surface normal than at the d4-PET/gamma-GPS interface. The effects of varying the silane/siloxane ratio and using different siloxane oligomers on interfacial structures were also examined. This study provides unique molecular-level insights into the prerequisite conditions for adhesion of curable silicone adhesives.

Journal Article↗

PubMed2005

Supramolecular ordering of tripod dyes at the air/water interface.

Monolayers of 2-(3,4,5-(trisdodecyloxyl)phenyl)[1,3,4]oxadiazole based "tripod" dye, P2G, has been studied at the air/water interface with in situ X-ray reflectivity. Compression of the disordered Langmuir-Blodgett monolayer film induces a transition to a unique ordered phase, representing a supramolecular assembly with a unique spatial distribution and orientation of the molecules. At low pressure, the molecules having face-on orientation are interdigitated by the three arms. After first transition in the pi-A isotherm, the molecular conformation is turned into an edge-on orientation, where the molecules are self-assembled into supramolecular structures.

Journal Article↗

PubMed2006

Three-dimensional nanoscale composition mapping of semiconductor nanowires.

We demonstrate the three-dimensional composition mapping of a semiconductor nanowire with single-atom sensitivity and subnanometer spatial resolution using atom probe tomography. A new class of atom probe, the local electrode atom probe (LEAP) microscope, was used to map the position of single Au atoms in an InAs nanowire and to image the interface between a Au catalyst and InAs in three dimensions with 0.3-nm resolution. These results establish atom probe tomography as a uniquely powerful tool for analyzing the chemical composition of semiconductor nanostructures.

Arsenicals↗

PubMed2003

Identification of the protein kinase A regulatory RIalpha-catalytic subunit interface by amide H/2H exchange and protein docking.

An important goal after structural genomics is to build up the structures of higher-order protein-protein complexes from structures of the individual subunits. Often structures of higher order complexes are difficult to obtain by crystallography. We have used an alternative approach in which the structures of the individual catalytic (C) subunit and RIalpha regulatory (R) subunit of PKA were first subjected to computational docking, and the top 100,000 solutions were subsequently filtered based on amide hydrogen/deuterium (H/2H) exchange interface protection data. The resulting set of filtered solutions forms an ensemble of structures in which, besides the inhibitor peptide binding site, a flat interface between the C-terminal lobe of the C-subunit and the A- and B-helices of RIalpha is uniquely identified. This holoenzyme structure satisfies all previous experimental data on the complex and allows prediction of new contacts between the two subunits.

Amino Acid Sequence↗

PubMed2005

Siroheme- and [Fe4-S4]-dependent NirA from Mycobacterium tuberculosis is a sulfite reductase with a covalent Cys-Tyr bond in the active site.

The nirA gene of Mycobacterium tuberculosis is up-regulated in the persistent state of the bacteria, suggesting that it is a potential target for the development of antituberculosis agents particularly active against the pathogen in its dormant phase. This gene encodes a ferredoxin-dependent sulfite reductase, and the structure of the enzyme has been determined using x-ray crystallography. The enzyme is a monomer comprising 555 amino acids and contains a [Fe4-S4] cluster and a siroheme cofactor. The molecule is built up of three domains with an alpha/beta fold. The first domain consists of two ferredoxin-like subdomains, related by a pseudo-2-fold symmetry axis passing through the whole molecule. The other two domains, which provide much of the binding interactions with the cofactors, have a common fold that is unique to the sulfite/nitrite reductase family. The domains form a trilobal structure, with the cofactors and the active site located at the interface of all three domains in the center of the molecule. NirA contains an unusual covalent bond between the side chains of Tyr69 and Cys161 in the active site, in close proximity to the siroheme cofactor. Removal of this covalent bond by site-directed mutagenesis impairs catalytic activity, suggesting that it is important for the enzymatic reaction. These residues are part of a sequence fingerprint, able to distinguish between ferredoxin-dependent sulfite and nitrite reductases. Comparison of NirA with the structure of the truncated NADPH-dependent sulfite reductase from Escherichia coli suggests a binding site for the external electron donor ferredoxin close to the [Fe4-S4] cluster.

Bacterial Proteins↗

PubMed2003

The development of a theoretical framework and design tool for process usability assessment.

The purpose of usability engineering is to facilitate the deployment of new products by decreasing development costs and improving the quality of systems. This paper will discuss the development and delivery of a unique, theoretically based software tool that provides engineers and designers with easy access to the most recent advances in human-machine interface design. This research combines several theoretical views of the interaction process into a hybrid model. Based on this model, a software tool was produced that allows engineers to model the human interaction process within their design. The system then provides feedback on the interaction process through items such as: the amount of mental effort required by a user, the degree to which the system conforms to human capabilities, the expected time to complete the interaction, where potential human error may occur, as well as potential misunderstandings or points of confusion to the users. The designer may then use this information to improve the design of the system. Validation of this technique indicates that the hybrid model produces accurate predictions of usability attributes and that the technique transfers from the laboratory to the real world.

Adult↗

PubMed1997

Regulation of anti-double-stranded DNA B cells in nonautoimmune mice: localization to the T-B interface of the splenic follicle.

Systemic lupus erythematosus (SLE) and the MRL-lpr/lpr murine model for SLE are characterized by the presence of serum anti-double-stranded (ds)DNA antibodies (Abs), whereas nonautoimmune individuals have negligible levels of these Abs. To increase the frequency of anti-DNA B cells and identify the mechanisms involved in their regulation in nonautoimmune mice, we have used Ig transgenes (tgs). In the present study, we used the VH3H9 heavy (H) chain tg which expresses an H chain that was repeatedly isolated from anti-dsDNA Abs from MRL-lpr/lpr mice. Because the VH3H9 H chain can pair with endogenous L chains to generate anti-single-stranded DNA, anti-dsDNA, and non-DNA B cells, this allowed us to study the regulation of anti-dsDNA B cells in the context of a diverse B cell repertoire. We have identified anti-dsDNA B cells that are located at the T-B interface in the splenic follicle where they have an increased in vivo turnover rate. These anti-dsDNA B cells exhibit a unique surface phenotype suggesting developmental arrest due to antigen exposure.

Animals↗

PubMed2005

ASRP: the Arabidopsis Small RNA Project Database.

Eukaryotes produce functionally diverse classes of small RNAs (20-25 nt). These include microRNAs (miRNAs), which act as regulatory factors during growth and development, and short-interfering RNAs (siRNAs), which function in several epigenetic and post-transcriptional silencing systems. The Arabidopsis Small RNA Project (ASRP) seeks to characterize and functionally analyze the major classes of endogenous small RNAs in plants. The ASRP database provides a repository for sequences of small RNAs cloned from various Arabidopsis genotypes and tissues. Version 3.0 of the database contains 1920 unique sequences, with tools to assist in miRNA and siRNA identification and analysis. The comprehensive database is publicly available through a web interface at http://asrp.cgrb.oregonstate.edu.

Arabidopsis↗