Searching the World-Wide-Web using nucleotide and peptide sequences

*Background:* No approaches have yet been developed to allow instant searching of the World-Wide-Web by just entering a string of sequence data. Though general search engines can be tuned to accept ‘processed’ queries, the burden of preparing such ‘search strings’ simply defeats the purpose of quickly locating highly relevant information. Unlike ‘sequence similarity’ searches that employ dedicated algorithms (like BLAST) to compare an input sequence from defined databases, a direct ‘sequence based’ search simply locates quick and relevant information about a blunt piece of nucleotide or peptide sequence. This approach is particularly invaluable to all biomedical researchers who would often like to enter a sequence and quickly locate any pertinent information before proceeding to carry out detailed sequence alignment. 

*Results:* Here, we describe the theory and implementation of a web-based front-end for a search engine, like Google, which accepts sequence fragments and interactively retrieves a collection of highly relevant links and documents, in real-time. e.g. flat files like patent records, privately hosted sequence documents and regular databases. 

*Conclusions:* The importance of this simple yet highly relevant tool will be evident when with a little bit of tweaking, the tool can be engineered to carry out searches on all kinds of hosted documents in the World-Wide-Web.

*Availability:* Instaseq is free web based service that can be accessed by visiting the following hyperlink on the WWW
http://instaseq.georgetown.edu 
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Modulating Integrin αIIbβ3 Activity through Mutagenesis of Allosterically Regulated Intersubunit Contacts

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Biochemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.biochem.9b00430.Integrin αIIbβ3, a transmembrane heterodimer, mediates platelet aggregation when it switches from an inactive to an active ligand-binding conformation following platelet stimulation. Central to regulating αIIbβ3 activity is the interaction between the αIIb and β3 extracellular stalks, which form a tight heterodimer in the inactive state and dissociate in the active state. Here, we demonstrate that alanine replacements of sensitive positions in the heterodimer stalk interface destabilize the inactive conformation sufficiently to cause constitutive αIIbβ3 activation. To determine the structural basis for this effect, we performed a structural bioinformatics analysis and found that perturbing intersubunit contacts with favorable interaction geometry through substitutions to alanine quantitatively accounted for the degree of constitutive αIIbβ3 activation. This mutational study directly assesses the relationship between favorable interaction geometry at mutation-sensitive positions and the functional activity of those mutants, giving rise to a simple model that highlights the importance of interaction geometry in contributing to the stability between protein–protein interactions.NIH P01 HL40387NIH R35 GM122603National Science Foundation 1709506National Science Foundation 165011

Room-Temperature Quantum Bit Memory Exceeding One Second

Stable quantum bits, capable both of storing quantum information for macroscopic time scales and of integration inside small portable devices, are an essential building block for an array of potential applications. We demonstrate high-fidelity control of a solid-state qubit, which preserves its polarization for several minutes and features coherence lifetimes exceeding 1 second at room temperature. The qubit consists of a single $^{13}C$ nuclear spin in the vicinity of a nitrogen-vacancy color center within an isotopically purified diamond crystal. The long qubit memory time was achieved via a technique involving dissipative decoupling of the single nuclear spin from its local environment. The versatility, robustness, and potential scalability of this system may allow for new applications in quantum information science.Physic

Approximate Quantum Cloning with Nuclear Magnetic Resonance

Here we describe a Nuclear Magnetic Resonance (NMR) experiment that uses a three qubit NMR device to implement the one to two approximate quantum cloning network of Buzek et al.Comment: 4 pages RevTeX4 including 5 postscript figures. Submitted to PR

Bright spots: seeds of a good Anthropocene

The scale, rate, and intensity of humans’ environmental impact has engendered broad discussion about how to find plausible pathways of development that hold the most promise for fostering a better future in the Anthropocene. However, the dominance of dystopian visions of irreversible environmental degradation and societal collapse, along with overly optimistic utopias and business‐as‐usual scenarios that lack insight and innovation, frustrate progress. Here, we present a novel approach to thinking about the future that builds on experiences drawn from a diversity of practices, worldviews, values, and regions that could accelerate the adoption of pathways to transformative change (change that goes beyond incremental improvements). Using an analysis of 100 initiatives, or “seeds of a good Anthropocene”, we find that emphasizing hopeful elements of existing practice offers the opportunity to: (1) understand the values and features that constitute a good Anthropocene, (2) determine the processes that lead to the emergence and growth of initiatives that fundamentally change human–environmental relationships, and (3) generate creative, bottom‐up scenarios that feature well‐articulated pathways toward a more positive future

Liquid phase blending of metal-organic frameworks.

The liquid and glass states of metal-organic frameworks (MOFs) have recently become of interest due to the potential for liquid-phase separations and ion transport, alongside the fundamental nature of the latter as a new, fourth category of melt-quenched glass. Here we show that the MOF liquid state can be blended with another MOF component, resulting in a domain structured MOF glass with a single, tailorable glass transition. Intra-domain connectivity and short range order is confirmed by nuclear magnetic resonance spectroscopy and pair distribution function measurements. The interfacial binding between MOF domains in the glass state is evidenced by electron tomography, and the relationship between domain size and Tg investigated. Nanoindentation experiments are also performed to place this new class of MOF materials into context with organic blends and inorganic alloys

Optimised power harvesting by controlling the pressure applied to molecular junctions

A major potential advantage of creating thermoelectric devices using self-assembled molecular layers is their mechanical flexibility. Previous reports have discussed the advantage of this flexibility from the perspective of facile skin attachment and the ability to avoid mechanical deformation. In this work, we demonstrate that the thermoelectric properties of such molecular devices can be controlled by taking advantage of their mechanical flexibility. The thermoelectric properties of self-assembled monolayers (SAMs) fabricated from thiol terminated molecules were measured with a modified AFM system, and the conformation of the SAMs was controlled by regulating the loading force between the organic thin film and the probe, which changes the tilt angle at the metal-molecule interface. We tracked the thermopower shift vs. the tilt angle of the SAM and showed that changes in both the electrical conductivity and Seebeck coefficient combine to optimize the power factor at a specific angle. This optimization of thermoelectric performance via applied pressure is confirmed through the use of theoretical calculations and is expected to be a general method for optimising the power factor of SAMs

Oral steroids for the resolution of otitis media with effusion (OME) in children (OSTRICH): study protocol for a randomised controlled trial

Background Otitis media with effusion (OME) is an accumulation of fluid in the middle ear affecting about 80% of children by the age of 4 years. While OME usually resolves spontaneously, it can affect speech, behaviour and development. Children with persistent hearing loss associated with OME are usually offered hearing aids or insertion of ventilation tubes through the tympanic membrane. Oral steroids may be a safe and effective treatment for OME, which could be delivered in primary care. It has the potential to benefit large numbers of children and reduce the burden of care on them and on health services. However, previous trials have either been too small with too short a follow up period, or of too poor quality to give a definite answer. The aim of the OSTRICH trial is to determine if a short course of oral steroids improves the hearing of children with OME in the short and longer term. Methods/Design 380 participants (children aged 2-8 years) are recruited from Hospital Ear, Nose and Throat departments in Wales and England. A trained clinician seeks informed consent from parents of children with symptoms attributable to OME for at least 3 months and with confirmed bilateral hearing loss at study entry. Participants are randomised to a course of oral steroid or a matched placebo for one week. Outcomes include audiometry, tympanometry and otoscopy assessments, symptoms, adverse effects, functional health status, quality of life, resource use and cost effectiveness. Participants are followed up at 5 weeks, and at 6 and 12 months after the day of randomisation. The primary outcome is audiometry-confirmed satisfactory hearing at 5 weeks. Discussion There is an important evidence gap regarding clinical and cost effectiveness of short courses of oral steroid treatment for OME. Identifying an effective, safe, non-surgical intervention for OME in children for use in primary care would be of great benefit to children, their families and the NHS

Quantitative association tests of immune responses to antigens of Mycobacterium tuberculosis: a study of twins in West Africa.

There is now considerable evidence that host genetic factors are important in determining the outcome of infection with Mycobacterium tuberculosis (MTB). The aim of this study was to assess the role of several candidate genes in the variation observed in the immune responses to MTB antigens. In-vitro assays of T-cell proliferation, an in-vivo intradermal delayed hypersensitivity response; cytokine and antibody secretions to several mycobacterial peptide antigens were assessed in healthy, but exposed, West African twins. Candidate gene polymorphisms were typed in the NRAMP1, Vitamin D receptor, IL10, IL4, IL4 receptor and CTLA-4 genes. Variants of the loci IL10 (-1082 G/A), CTLA-4 (49 A/G) and the IL4 receptor (128 A/G) showed significant associations with immune responses to several antigens. T-cell proliferative responses and antibody responses were reduced, TNF-alpha responses were increased for subjects with the CTLA-4 G allele. The T-cell proliferative responses of subjects with IL10 GA and GG genotypes differed significantly. IL4 receptor AG and GG genotypes also showed significant differences in their T-cell proliferative responses to MTB antigens. These results yield a greater understanding of the genetic mechanisms that underlie the immune responses in tuberculosis and have implications for the design of therapeutic interventions