Comprehensive characterization of molecular interactions based on nanomechanics

Molecular interaction is a key concept in our understanding of the biological mechanisms of life. Two physical properties change when one molecular partner binds to another. Firstly, the masses combine and secondly, the structure of at least one binding partner is altered, mechanically transducing the binding into subsequent biological reactions. Here we present a nanomechanical micro-array technique for bio-medical research, which not only monitors the binding of effector molecules to their target but also the subsequent effect on a biological system in vitro. This label-free and real-time method directly and simultaneously tracks mass and nanomechanical changes at the sensor interface using micro-cantilever technology. To prove the concept we measured lipid vesicle (approximately 748*10(6) Da) adsorption on the sensor interface followed by subsequent binding of the bee venom peptide melittin (2840 Da) to the vesicles. The results show the high dynamic range of the instrument and that measuring the mass and structural changes simultaneously allow a comprehensive discussion of molecular interactions

Photodissociation and the Morphology of HI in Galaxies

Young massive stars produce Far-UV photons which dissociate the molecular gas on the surfaces of their parent molecular clouds. Of the many dissociation products which result from this ``back-reaction'', atomic hydrogen \HI is one of the easiest to observe through its radio 21-cm hyperfine line emission. In this paper I first review the physics of this process and describe a simplified model which has been developed to permit an approximate computation of the column density of photodissociated \HI which appears on the surfaces of molecular clouds. I then review several features of the \HI morphology of galaxies on a variety of length scales and describe how photodissociation might account for some of these observations. Finally, I discuss several consequences which follow if this view of the origin of HI in galaxies continues to be successful.Comment: 18 pages, 7 figures in 8 files, invited review paper for the conference "Penetrating Bars Through Masks of Cosmic Dust: The Hubble Tuning Fork Strikes a New Note", South Africa, June 2004. Proceedings to be published by Kluwer, eds. D.L. Block, K.C. Freeman, I. Puerari, R. Groess, & E.K. Bloc

Observation of Bose-Einstein Condensation in a Strong Synthetic Magnetic Field

Extensions of Berry's phase and the quantum Hall effect have led to the discovery of new states of matter with topological properties. Traditionally, this has been achieved using gauge fields created by magnetic fields or spin orbit interactions which couple only to charged particles. For neutral ultracold atoms, synthetic magnetic fields have been created which are strong enough to realize the Harper-Hofstadter model. Despite many proposals and major experimental efforts, so far it has not been possible to prepare the ground state of this system. Here we report the observation of Bose-Einstein condensation for the Harper-Hofstadter Hamiltonian with one-half flux quantum per lattice unit cell. The diffraction pattern of the superfluid state directly shows the momentum distribution on the wavefuction, which is gauge-dependent. It reveals both the reduced symmetry of the vector potential and the twofold degeneracy of the ground state. We explore an adiabatic many-body state preparation protocol via the Mott insulating phase and observe the superfluid ground state in a three-dimensional lattice with strong interactions.Comment: 6 pages, 5 figures. Supplement: 6 pages, 4 figure

We are all one together : peer educators\u27 views about falls prevention education for community-dwelling older adults - a qualitative study

Background: Falls are common in older people. Despite strong evidence for effective falls prevention strategies, there appears to be limited translation of these strategies from research to clinical practice. Use of peers in delivering falls prevention education messages has been proposed to improve uptake of falls prevention strategies and facilitate translation to practice. Volunteer peer educators often deliver educational presentations on falls prevention to community-dwelling older adults. However, research evaluating the effectiveness of peer-led education approaches in falls prevention has been limited and no known study has evaluated such a program from the perspective of peer educators involved in delivering the message. The purpose of this study was to explore peer educators’ perspective about their role in delivering peer-led falls prevention education for community-dwelling older adults. Methods: A two-stage qualitative inductive constant comparative design was used.In stage one (core component) focus group interviews involving a total of eleven participants were conducted. During stage two (supplementary component) semi-structured interviews with two participants were conducted. Data were analysed thematically by two researchers independently. Key themes were identified and findings were displayed in a conceptual framework. Results: Peer educators were motivated to deliver educational presentations and importantly, to reach an optimal peer connection with their audience. Key themes identified included both personal and organisational factors that impact on educators’ capacity to facilitate their peers’ engagement with the message. Personal factors that facilitated message delivery and engagement included peer-to-peer connection and perceived credibility, while barriers included a reluctance to accept the message that they were at risk of falling by some members in the audience. Organisational factors, including ongoing training for peer educators and formative feedback following presentations, were perceived as essential because they affect successful message delivery. Conclusions: Peer educators have the potential to effectively deliver falls prevention education to older adults and influence acceptance of the message as they possess the peer-to-peer connection that facilitates optimal engagement. There is a need to consider incorporating learnings from this research into a formal large scale evaluation of the effectiveness of the peer education approach in reducing falls in older adults

Linkage mapping bovine EST-based SNP

BACKGROUND: Existing linkage maps of the bovine genome primarily contain anonymous microsatellite markers. These maps have proved valuable for mapping quantitative trait loci (QTL) to broad regions of the genome, but more closely spaced markers are needed to fine-map QTL, and markers associated with genes and annotated sequence are needed to identify genes and sequence variation that may explain QTL. RESULTS: Bovine expressed sequence tag (EST) and bacterial artificial chromosome (BAC)sequence data were used to develop 918 single nucleotide polymorphism (SNP) markers to map genes on the bovine linkage map. DNA of sires from the MARC reference population was used to detect SNPs, and progeny and mates of heterozygous sires were genotyped. Chromosome assignments for 861 SNPs were determined by twopoint analysis, and positions for 735 SNPs were established by multipoint analyses. Linkage maps of bovine autosomes with these SNPs represent 4585 markers in 2475 positions spanning 3058 cM . Markers include 3612 microsatellites, 913 SNPs and 60 other markers. Mean separation between marker positions is 1.2 cM. New SNP markers appear in 511 positions, with mean separation of 4.7 cM. Multi-allelic markers, mostly microsatellites, had a mean (maximum) of 216 (366) informative meioses, and a mean 3-lod confidence interval of 3.6 cM Bi-allelic markers, including SNP and other marker types, had a mean (maximum) of 55 (191) informative meioses, and were placed within a mean 8.5 cM 3-lod confidence interval. Homologous human sequences were identified for 1159 markers, including 582 newly developed and mapped SNP. CONCLUSION: Addition of these EST- and BAC-based SNPs to the bovine linkage map not only increases marker density, but provides connections to gene-rich physical maps, including annotated human sequence. The map provides a resource for fine-mapping quantitative trait loci and identification of positional candidate genes, and can be integrated with other data to guide and refine assembly of bovine genome sequence. Even after the bovine genome is completely sequenced, the map will continue to be a useful tool to link observable phenotypes and animal genotypes to underlying genes and molecular mechanisms influencing economically important beef and dairy traits

"An Impediment to Living Life": Why and How Should We Measure Stiffness in Polymyalgia Rheumatica?

Objectives: To explore patients’ concepts of stiffness in polymyalgia rheumatica (PMR), and how they think stiffness should be measured. Methods: Eight focus groups were held at three centres involving 50 patients with current/previous PMR. Each group had at least one facilitator and one rapporteur making field notes. An interview schedule was used to stimulate discussion. Interviews were recorded, transcribed and analysed using an inductive thematic approach. Results: Major themes identified were: symptoms: pain, stiffness and fatigue; functional impact; impact on daily schedule; and approaches to measurement. The common subtheme for the experience of stiffness was “difficulty in moving”, and usually considered as distinct from the experience of pain, albeit with a variable overlap. Some participants felt stiffness was the “overwhelming” symptom, in that it prevented them carrying out “fundamental activities” and “generally living life”. Diurnal variation in stiffness was generally described in relation to the daily schedule but was not the same as stiffness severity. Some participants suggested measuring stiffness using a numeric rating scale or a Likert scale, while others felt that it was more relevant and straightforward to measure difficulty in performing everyday activities rather than about stiffness itself. Conclusions: A conceptual model of stiffness in PMR is presented where stiffness is an important part of the patient experience and impacts on their ability to live their lives. Stiffness is closely related to function and often regarded as interchangeable with pain. From the patients’ perspective, visual analogue scales measuring pain and stiffness were not the most useful method for reporting stiffness; participants preferred numerical rating scales, or assessments of function to reflect how stiffness impacts on their daily lives. Assessing function may be a pragmatic solution to difficulties in quantifying stiffness

Enterovirus specific anti-peptide antibodies

Enterovirus 71 (EV-71) is the main causative agent of hand, foot, and mouth disease (HFMD) which is generally regarded as a mild childhood disease. In recent years, EV71 has emerged as a significant pathogen capable of causing high mortalities and severe neurological complications in large outbreaks in Asia. A formalin-inactivated EV71 whole virus vaccine has completed phase III trial in China but is currently unavailable clinically. The high cost of manufacturing and supply problems may limit practical implementations in developing countries. Synthetic peptides representing the native primary structure of the viral immunogen which is able to elicit neutralizing antibodies can be made readily and is cost effective. However, it is necessary to conjugate short synthetic peptides to carrier proteins to enhance their immunogenicity. This review describes the production of cross-neutralizing anti-peptide antibodies in response to immunization with synthetic peptides selected from in silico analysis, generation of B-cell epitopes of EV71 conjugated to a promiscuous T-cell epitope from Poliovirus, and evaluation of the neutralizing activities of the anti-peptide antibodies. Besides neutralizing EV71 in vitro, the neutralizing antibodies were cross-reactive against several Enteroviruses including CVA16, CVB4, CVB6, and ECHO13

Impact Factor: outdated artefact or stepping-stone to journal certification?

A review of Garfield's journal impact factor and its specific implementation as the Thomson Reuters Impact Factor reveals several weaknesses in this commonly-used indicator of journal standing. Key limitations include the mismatch between citing and cited documents, the deceptive display of three decimals that belies the real precision, and the absence of confidence intervals. These are minor issues that are easily amended and should be corrected, but more substantive improvements are needed. There are indications that the scientific community seeks and needs better certification of journal procedures to improve the quality of published science. Comprehensive certification of editorial and review procedures could help ensure adequate procedures to detect duplicate and fraudulent submissions.Comment: 25 pages, 12 figures, 6 table