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Conceptually, extending the premise of bioelectronic interfaces down to thescale of single molecules is a straightforward goal. In practice, thechallenges are purely technological. Single-molecule bioelectronic deviceswould have to involve features much smaller than state-of-the-artsemiconductor electronics, and successful design would have uniquerequirements for sensitivity and stability.
These imposing specifications are balanced by the potential of enormousrewards, because single-molecule bioelectronics would be a breakthroughtechnology for biochemical research and applications. By peering past theensemble behaviors of traditional characterization, single-moleculetechniques aim to directly observe the stochastic fluctuations,instantaneous dynamics, and non-equilibrium behaviors that make up amolecule’s full functionality. Moreover, single-molecule measurementscan uncover the unusual reaction trajectories of a genetically mutatedprotein or a receptor interacting with pharmacological inhibitors. Buildinga better understanding of the precise roles of proteins in complexbiological processes is a grand challenge for biology, biochemistry, andbiophysics in the twenty-first century.
These potential benefits have spurred the development of a variety ofsingle-molecule techniques. Single-molecule fluorescence, specificallyFörster resonance energy transfer (FRET), has become a standard tool forsingle-molecule biochemistry [1]. Meanwhile, single-molecule bioelectronicshas remained elusive, despite the wide-ranging capabilities of modern solidstate electronics.
Depressive and anxiety disorders (common mental disorders) are the most common psychiatric condition encountered in primary healthcare.
Aims
To test the effectiveness of an intervention led by lay health counsellors in primary care settings (the MANAS intervention) to improve the outcomes of people with common mental disorders.
Method
Twenty-four primary care facilities (12 public, 12 private) in Goa (India) were randomised to provide either collaborative stepped care or enhanced usual care to adults who screened positive for common mental disorders. Participants were assessed at 2, 6 and 12 months for presence of ICD-10 common mental disorders, the severity of symptoms of depression and anxiety, suicidal behaviour and disability levels. All analyses were intention to treat and carried out separately for private and public facilities and adjusted for the design. The trial has been registered with clinicaltrials.gov (NCT00446407).
Results
A total of 2796 participants were recruited. In public facilities, the intervention was consistently associated with strong beneficial effects over the 12 months on all outcomes. There was a 30% decrease in the prevalence of common mental disorders among those with baseline ICD-10 diagnoses (risk ratio (RR) = 0.70, 95% CI 0.53–0.92); and a similar effect among the subgroup of participants with depression (RR = 0.76, 95% CI 0.59–0.98). Suicide attempts/plans showed a 36% reduction over 12 months (RR = 0.64, 95% CI 0.42–0.98) among baseline ICD-10 cases. Strong effects were observed on days out of work and psychological morbidity, and modest effects on overall disability. In contrast, there was little evidence of impact of the intervention on any outcome among participants attending private facilities.
Conclusions
Trained lay counsellors working within a collaborative-care model can reduce prevalence of common mental disorders, suicidal behaviour, psychological morbidity and disability days among those attending public primary care facilities.
Wang tiles are unit-size squares with coloured edges. In this paper, we approach one aspect of the study of tiling computability: the quest for a universal tile set. Using a complex construction, based on Robinson's classical construction and its different modifications, we build a tile set (pronounced ayin) that almost always simulates any tile set. By way of Banach–Mazur games on tilings topological spaces, we prove that the set of -tilings that do not satisfy the universality condition is meagre in the set of -tilings.
While nanowires and nanotubes have been shown to be electrically sensitive to various chemicals, not enough is known about the underlying mechanisms to control or tailor this sensitivity. By limiting the chemically sensitive region of a nanostructure to a single binding site, single molecule precision can be obtained to study the chemoresistive response. We have developed techniques using single-walled- carbon-nanotube (SWCNT) circuits that enable single-site experimentation and illuminate the dynamics of chemical interactions. Discrete changes in the circuit conductance reveal chemical processes happening in real-time and allow SWCNT sidewalls to be deterministically broken, reformed, and conjugated to target species.
While nanowires and nanotubes have been shown to be electrically sensitive to various chemicals, not enough is known about the underlying mechanisms to control or tailor this sensitivity. By limiting the chemically sensitive region of a nanostructure to a single binding site, single molecule precision can be obtained in order to study the chemoresistive response. We have developed techniques using single-walled-carbon-nanotube (SWCNT) circuits that enable single-site experimentation and illuminate the dynamics of chemical interactions. Discrete changes in the circuit conductance reveal chemical processes happening in real-time and allow SWCNT sidewalls to be deterministically broken, reformed, and conjugated to target species.
We have reported variants of the M13 bacteriophage major coat protein (P8) that enable high copy display of monomeric and oligomeric proteins, such as human growth hormone and steptavidin, on the surface of phage particles (Sidhu SS, Weiss GA, Wells JA. 2000. High copy display of large proteins on phage for functional selections. J Mol Biol 296:487–495). Here, we explore how an optimized P8 variant (opti-P8) could evolve the ability to efficiently display a protein fused to its N-terminus. Reversion of individual opti-P8 residues back to the wild-type P8 residue identifies a limited set of hydrophobic residues responsible for the high copy protein display. These hydrophobic amino acids bracket a conserved hydrophobic face on the P8 alpha helix thought to be in contact with the phage coat. Mutations additively combine to promote high copy protein display, which was further enhanced by optimization of the linker between the phage coat and the fusion protein. These data are consistent with a model in which protein display-enhancing mutations allow for better packing of the fusion protein into the phage coat. The high tolerance for phage coat protein mutations observed here suggests that filamentous phage coat proteins could readily evolve new capabilities.
A block copolymer consisting of liquid crystalline polyester segments and methylated polyamide segments has been synthesized. Solution polycondensation of acid chloride end-capped poly(terephthaloyl phenylhydroquinone) (LCP portion) with an amine terminated poly(N,N'-dimethylethylene sebacamide) was utilized to prepare the block copolymer. Characterization by differential scanning calorimetry, infrared spectroscopy, thermogravimetric analysis, optical microscopy and elemental analysis has been performed to verify the existence of the block copolymer that may have potential as a molecular composite material or self-reinforcing thermoplastic.