A New Approach to the Synthesis of Conjugated Polymer: Nanocrystal Composites for Heterojunction Optoelectronics

We report a simple one pot process for the preparation of lead sulphide (PbS) nanocrystals in the conjugated polymer MEH-PPV, and we demonstrate electronic coupling between the two components.Comment: 3 pages, 2 figures, accepted Chem. Comm

A novel method for comparing topological models of protein structures enhanced with ligand information

This article is available open access through the publisher’s website through the link below. Copyright @ 2008 The Authors.We introduce TOPS+ strings, a highly abstract string-based model of protein topology that permits efficient computation of structure comparison, and can optionally represent ligand information. In this model, we consider loops as secondary structure elements (SSEs) as well as helices and strands; in addition we represent ligands as first class objects. Interactions between SSEs and between SSEs and ligands are described by incoming/outgoing arcs and ligand arcs, respectively; and SSEs are annotated with arc interaction direction and type. We are able to abstract away from the ligands themselves, to give a model characterized by a regular grammar rather than the context sensitive grammar of the original TOPS model. Our TOPS+ strings model is sufficiently descriptive to obtain biologically meaningful results and has the advantage of permitting fast string-based structure matching and comparison as well as avoiding issues of Non-deterministic Polynomial time (NP)-completeness associated with graph problems. Our structure comparison method is computationally more efficient in identifying distantly related proteins than BLAST, CLUSTALW, SSAP and TOPS because of the compact and abstract string-based representation of protein structure which records both topological and biochemical information including the functionally important loop regions of the protein structures. The accuracy of our comparison method is comparable with that of TOPS. Also, we have demonstrated that our TOPS+ strings method out-performs the TOPS method for the ligand-dependent protein structures and provides biologically meaningful results. Availability: The TOPS+ strings comparison server is available from http://balabio.dcs.gla.ac.uk/mallika/WebTOPS/topsplus.html.University of Glasgo

Sensorimotor Behavioral Tests for Use in a Juvenile Rat Model of Traumatic Brain Injury: Assessment of Sex Differences

Modeling juvenile traumatic brain injury (TBI) in rodents presents several unique challenges compared to adult TBI, one of which is selecting appropriate sensorimotor behavioral tasks that enable the assessment of the extent of injury and recovery over time in developing animals. To address this challenge, we performed a comparison of common sensorimotor tests in Long-Evans rats of various sizes and developmental stages (postnatal days 16–45, 35–190 g). Tests were compared and selected for their developmental appropriateness, scalability for growth, pre-training requirements, and throughput capability. Sex differences in response to TBI were also assessed. Grid walk, automated gait analysis, rotarod, beam walk, spontaneous forelimb elevation test, and measurement of motor activity using the force-plate actometer were evaluated. Grid walk, gait analysis, and rotarod failed to meet one or more of the evaluation criteria. Beam walk, spontaneous forelimb elevation test, and measurement of motor activity using the force-plate actometer satisfied all criteria and were capable of detecting motor abnormalities in rats subjected to controlled cortical impact on postnatal day 17. No sex differences were detected in the acute effects of TBI or functional recovery during the 28 days after injury using these tests. This demonstrates the utility of these tests for the evaluation of sensorimotor function in studies using rat models of pediatric TBI, and suggest that pre-pubertal males and females respond similarly to TBI with respect to sensorimotor outcomes

Training Paradigms in Hepato-Pancreatico-Biliary Surgery: an Overview of the Different Fellowship Pathways

Hepato-pancreatico-biliary (HPB) surgery, and the training of HPB surgeons, has evolved significantly over the last several decades. The current state of training in HPB surgery in North America is defined through three main pathways: the Complex General Surgical Oncology (CGSO) ACGME fellowship, the American Society of Transplant Surgeons (ASTS) fellowship, and the Americas Hepatopancreaticobiliary Association (AHPBA) fellowship. These fellowships offer variable experiences in pancreas, liver, and biliary cases, and each pathway offers a unique perspective on HPB surgery. The CGSO ACGME, ASTS, and AHPBA fellowships represent decades of work by the three major surgical leadership stakeholders to improve and ensure quality training of future HPB surgeons. The best care is provided by the HPB surgeon who has been trained to understand the importance of all available treatment options within the context of a multidisciplinary setting. The three fellowship pathways are outlined in this paper with the nuances and variations characteristic of the different training programs highlighted

Perfect storm? COVID-19, area deprivation, and their association with pediatric trauma

Introduction: Social determinants of health (SDOH) affect pediatric injury patterns as vulnerable populations are likely to experience more frequent or severe injuries. This study evaluates the association of COVID-19 and area deprivation with pediatric traumatic injuries. Methods: We retrospectively evaluated institutional level I pediatric trauma encounters from 1/2018-8/2022. Patients were assessed relative to the U.S. pandemic declaration date (3/11/2020): pre-COVID (\u3c3/11/2020), early post-COVID (3/11/2020-3/11/2021), and late post-COVID (\u3e3/11/2021). The Area Deprivation Index (ADI) measured SDH-related risk at a census block tract group level. Associations between ADI and COVID-19 and injury mechanism and outcomes (intensive care unit [ICU]/ventilator duration, hospital length of stay, and mortality) were assessed using chi-square for categorical and Spearman’s rank correlation for continuous variables. Results: 4,055 patients were included in the study. There was variability in injury patterns relative to the level of deprivation and the timing of COVID-19. MVCs (12.7% pre vs. 14.3% early post vs. 18.6% late post, p\u3c0.0001) and GSWs (1.2% pre vs. 2.6% early post vs. 2.0% late post, p=0.018) were more common after COVID-19 and more frequently experienced by children with higher deprivation indices. Higher ADI was also associated with worse outcomes (ICU days, r=0.049, p=0.006; ventilator days, r=0.035, p=0.047). Discussion: Children with vulnerable SDOH status appear to have been disproportionately affected by pediatric traumatic injuries following COVID-19. National-level stressors (COVID-19) impact behaviors on a population level and shift exposure risk to different injury mechanisms. Multi-level public health initiatives are needed to address disparate injury patterns based on SDOH exposure

Learning effective amino acid interactions through iterative stochastic techniques

The prediction of the three-dimensional structures of the native state of proteins from the sequences of their amino acids is one of the most important challenges in molecular biology. An essential ingredient to solve this problem within coarse-grained models is the task of deducing effective interaction potentials between the amino acids. Over the years several techniques have been developed to extract potentials that are able to discriminate satisfactorily between the native and non-native folds of a pre-assigned protein sequence. In general, when these potentials are used in actual dynamical folding simulations, they lead to a drift of the native structure outside the quasi-native basin. In this study, we present and validate an approach to overcome this difficulty. By exploiting several numerical and analytical tools we set up a rigorous iterative scheme to extract potentials satisfying a pre-requisite of any viable potential: the stabilization of proteins within their native basin (less than 3-4 \AA$$ cRMS). The scheme is flexible and is demonstrated to be applicable to a variety of parametrizations of the energy function and provides, in each case, the optimal potentials.Comment: Revtex 17 pages, 10 eps figures. Proteins: Structure, Function and Genetics (in press

A deficit of spatial remapping in constructional apraxia after right-hemisphere stroke

This Article is provided by the Brunel Open Access Publising Fund - Copyright @ 2010 Oxford University PressConstructional apraxia refers to the inability of patients to copy accurately drawings or three-dimensional constructions. It is a common disorder after right parietal stroke, often persisting after initial problems such as visuospatial neglect have resolved. However, there has been very little experimental investigation regarding mechanisms that might contribute to the syndrome. Here, we examined whether a key deficit might be failure to integrate visual information correctly from one fixation to the next. Specifically, we tested whether this deficit might concern remapping of spatial locations across saccades. Right-hemisphere stroke patients with constructional apraxia were compared to patients without constructional problems and neurologically healthy controls. Participants judged whether a pattern shifted position (spatial task) or changed in pattern (non-spatial task) across two saccades, compared to a control condition with an equivalent delay but without intervening eye movements. Patients with constructional apraxia were found to be significantly impaired in position judgements with intervening saccades, particularly when the first saccade of the sequence was to the right. The importance of these remapping deficits in constructional apraxia was confirmed through a highly significant correlation between saccade task performance and constructional impairment on standard neuropsychological tasks. A second study revealed that even single saccades to the right can impair constructional apraxia patients’ perception of location shifts. These data are consistent with the view that rightward eye movements result in loss of remembered spatial information from previous fixations, presumably due to constructional apraxia patients’ damage to the right-hemisphere regions involved in remapping locations across saccades. These findings provide the first evidence for a deficit in remapping visual information across saccades underlying right-hemisphere constructional apraxia.European Commission Marie Curie Intra-European Fellowship (011457 to C.R.) and a Wellcome Trust Senior Fellowship (to M.H.)

PocketMatch: A new algorithm to compare binding sites in protein structures

Background: Recognizing similarities and deriving relationships among protein molecules is a fundamental
requirement in present-day biology. Similarities can be present at various levels which can be detected through comparison of protein sequences or their structural folds. In some cases similarities obscure at these levels could be present merely in the substructures at their binding sites. Inferring functional similarities between protein molecules by comparing their binding sites is still largely exploratory and not as yet a routine protocol. One of
the main reasons for this is the limitation in the choice of appropriate analytical tools that can compare binding sites with high sensitivity. To benefit from the enormous amount of structural data that is being rapidly accumulated, it is essential to have high throughput tools that enable large scale binding site comparison.

Results: Here we present a new algorithm PocketMatch for comparison of binding sites in a frame invariant
manner. Each binding site is represented by 90 lists of sorted distances capturing shape and chemical nature of the site. The sorted arrays are then aligned using an incremental alignment method and scored to obtain PMScores for pairs of sites. A comprehensive sensitivity analysis and an extensive validation of the algorithm have been carried out. Perturbation studies where the geometry of a given site was retained but the residue types were changed randomly, indicated that chance similarities were virtually non-existent. Our analysis also demonstrates that shape information alone is insufficient to discriminate between diverse binding sites, unless
combined with chemical nature of amino acids.

Conclusions: A new algorithm has been developed to compare binding sites in accurate, efficient and
high-throughput manner. Though the representation used is conceptually simplistic, we demonstrate that along
with the new alignment strategy used, it is sufficient to enable binding comparison with high sensitivity. Novel methodology has also been presented for validating the algorithm for accuracy and sensitivity with respect to geometry and chemical nature of the site. The method is also fast and takes about 1/250th second for one comparison on a single processor. A parallel version on BlueGene has also been implemented