Modification of turbulent dissipation rates by a deep Southern Ocean eddy

This is the final version. Available from AGU via the DOI in this recordAll data used in this study are available by communication with the author and will be archived at British Oceanographic Data CentreThe impact of a mesoscale eddy on the magnitude and spatial distribution of diapycnal ocean mixing is investigated using a set of hydrographic and microstructure measurements collected in the Southern Ocean. These data sampled a baroclinic, middepth eddy formed during the disintegration of a deep boundary current. Turbulent dissipation is suppressed within the eddy but is elevated by up to an order of magnitude along the upper and lower eddy boundaries. A ray tracing approximation is employed as a heuristic device to elucidate how the internal wave field evolves in the ambient velocity and stratification conditions accompanying the eddy. These calculations are consistent with the observations, suggesting reflection of internal wave energy from the eddy center and enhanced breaking through critical layer processes along the eddy boundaries. These results have important implications for understanding where and how internal wave energy is dissipated in the presence of energetic deep geostrophic flows.DIMES is supported by the Natural Environment Research Council (NERC) grants NE/E007058/1 and NE/E005667/1 and U.S. National Science Foundation grants OCE‐1231803, OCE‐0927583, and OCE‐1030309. K.L.S. and J.A.B. are supported by NERC

Adapted motivational interviewing to improve the uptake of treatment for glaucoma in Nigeria: study protocol for a randomized controlled trial.

BACKGROUND: Glaucoma is a chronic eye disease associated with irreversible visual loss. In Africa, glaucoma patients often present late, with very advanced disease. One-off procedures, such as laser or surgery, are recommended in Africa because of lack of or poor adherence to medical treatment. However, acceptance of surgery is usually extremely low. To prevent blindness, adherence to treatment needs to improve, using acceptable, replicable and cost-effective interventions. After reviewing the literature and interviewing patients in Bauchi (Nigeria) motivational interviewing (MI) was selected as the intervention for this trial, with adaptation for glaucoma (MIG). MI is designed to strengthen personal motivation for, and commitment to a specific goal by eliciting and exploring a person's reasons for change within an atmosphere of acceptance and compassion. The aim of this study is to assess whether MIG increases the uptake of laser or surgery amongst glaucoma patients where this is the recommended treatment. The hypothesis is that MIG increases the uptake of treatment. This will be the first trial of MI in Africa. METHODS: This is a hospital based, single centre, randomized controlled trial of MIG plus an information sheet on glaucoma and its treatment (the latter being "standard care") compared with standard care alone for glaucoma patients where the treatment recommended is surgery or laser.Those eligible for the trial are adults aged 17 years and above who live within 200 km of Bauchi with advanced glaucoma where the examining ophthalmologist recommends surgery or laser. After obtaining written informed consent, participants will be randomly allocated to MIG plus standard care, or standard care alone. Motivational interviewing will be delivered in Hausa or English by one of two MIG trained personnel. One hundred and fifty participants will be recruited to each arm. The primary outcome is the proportion of participants undergoing laser or surgery within two months of the date given to re attend for the procedure. MIG quality will be assessed using the validated MI treatment integrity scale. DISCUSSION: Motivational interviewing may be an important tool to increase the acceptance of treatment for glaucoma. The approach is potentially scalable and may be useful for other chronic conditions in Africa. TRIAL REGISTRATION: ISRCTN79330571 (Controlled-Trials.com)

Fr-TM-align: a new protein structural alignment method based on fragment alignments and the TM-score

©2008 Pandit and Skolnick; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This article is available from: http://www.biomedcentral.com/1471-2105/9/531doi:10.1186/1471-2105-9-531Background: Protein tertiary structure comparisons are employed in various fields of contemporary structural biology. Most structure comparison methods involve generation of an initial seed alignment, which is extended and/or refined to provide the best structural superposition between a pair of protein structures as assessed by a structure comparison metric. One such metric, the TM-score, was recently introduced to provide a combined structure quality measure of the coordinate root mean square deviation between a pair of structures and coverage. Using the TM-score, the TM-align structure alignment algorithm was developed that was often found to have better accuracy and coverage than the most commonly used structural alignment programs; however, there were a number of situations when this was not true. Results: To further improve structure alignment quality, the Fr-TM-align algorithm has been developed where aligned fragment pairs are used to generate the initial seed alignments that are then refined using dynamic programming to maximize the TM-score. For the assessment of the structural alignment quality from Fr-TM-align in comparison to other programs such as CE and TMalign, we examined various alignment quality assessment scores such as PSI and TM-score. The assessment showed that the structural alignment quality from Fr-TM-align is better in comparison to both CE and TM-align. On average, the structural alignments generated using Fr-TM-align have a higher TM-score (~9%) and coverage (~7%) in comparison to those generated by TM-align. Fr- TM-align uses an exhaustive procedure to generate initial seed alignments. Hence, the algorithm is computationally more expensive than TM-align. Conclusion: Fr-TM-align, a new algorithm that employs fragment alignment and assembly provides better structural alignments in comparison to TM-align. The source code and executables of Fr- TM-align are freely downloadable at: http://cssb.biology.gatech.edu/skolnick/files/FrTMalign/

Immunological Sex Differences in Socially Promiscuous African Ground Squirrels

Differences in how males and females respond to foreign antigens are common across taxa. Such sexual differences in the immune system are predicted to be greater in species with high promiscuity and sociality as these factors increase the likelihood of disease transmission. Intense sperm competition is thought to further this sexual dichotomy as increased investment in spermatogenesis likely incurs additional immunological costs. Xerus inauris, a ground squirrel found throughout southern Africa, is extremely social and promiscuous with one of the highest male reproductive investments among rodents. These life-history attributes suggest males and females should demonstrate a large dichotomy in immunity. Contrary to our prediction, we found no difference in spleen mass between the sexes. However, we did find significant biases in leukocyte types and red blood cell counts, possibly reflecting responses to parasite types. Among males, we predicted greater investments in spermatogenesis would result in reduced immunological investments. We found a negative association between testes and spleen size and a positive relationship between testes and number of lice suggesting trade-offs in reproductive investment possibly due to the costs associated with spermatogenesis and immunity. We suggest when measuring sexual differences in immunity it is important to consider the effects of reproductive pressures, parasite types, and life history costs

The holistic phase model of early adult crisis

The objective of the current study was to explore the structural, temporal and experiential manifestations of crisis episodes in early adulthood, using a holistic-systemic theoretical framework. Based on an analysis of 50 interviews with individuals about a crisis episode between the ages of 25 and 35, a holistic model was developed. The model comprises four phases: (1) Locked-in, (2) Separation/Time-out, (3) Exploration and (4) Rebuilding, which in turn have characteristic features at four levels—person-in-environment, identity, motivation and affect-cognition. A crisis starts out with a commitment at work or home that has been made but is no longer desired, and this is followed by an emotionally volatile period of change as that commitment is terminated. The positive trajectory of crisis involves movement through an exploratory period towards active rebuilding of a new commitment, but ‘fast-forward’ and ‘relapse’ loops can interrupt Phases 3 and 4 and make a positive resolution of the episode less likely. The model shows conceptual links with life stage theories of emerging adulthood and early adulthood, and it extends current understandings of the transitional developmental challenges that young adults encounter

Best Practices in Researching Service-Learning at Community Colleges

In recent years, an increasing number of community colleges have integrated some form of service-learning into their programs or courses with the idea that it will promote civic engagement, increase student satisfaction with their courses and college experience as a whole, and improve learning outcomes. There is a good amount of research published on service-learning programs and outcomes conducted at four-year institutions, though there is a dearth of studies available on service-learning at community colleges. Because community colleges serve a purpose unique from that of four-year colleges and universities, both in their mission and often in the students they serve, research on service-learning at community colleges should also be distinct from investigations at the four-year level

Financial considerations in the conduct of multi-centre randomised controlled trials: evidence from a qualitative study.

National Coordinating Centre for Research Methodology; Medical Research Council, UK Department of Health; Chief Scientist OfficeNot peer reviewedPublisher PD

Using Structure to Explore the Sequence Alignment Space of Remote Homologs

Protein structure modeling by homology requires an accurate sequence alignment between the query protein and its structural template. However, sequence alignment methods based on dynamic programming (DP) are typically unable to generate accurate alignments for remote sequence homologs, thus limiting the applicability of modeling methods. A central problem is that the alignment that is “optimal” in terms of the DP score does not necessarily correspond to the alignment that produces the most accurate structural model. That is, the correct alignment based on structural superposition will generally have a lower score than the optimal alignment obtained from sequence. Variations of the DP algorithm have been developed that generate alternative alignments that are “suboptimal” in terms of the DP score, but these still encounter difficulties in detecting the correct structural alignment. We present here a new alternative sequence alignment method that relies heavily on the structure of the template. By initially aligning the query sequence to individual fragments in secondary structure elements and combining high-scoring fragments that pass basic tests for “modelability”, we can generate accurate alignments within a small ensemble. Our results suggest that the set of sequences that can currently be modeled by homology can be greatly extended

Time-resolved crystallography using the Hadamard transform

YesWe describe a method for performing time-resolved X-ray crystallographic experiments based on the Hadamard transform, in which time resolution is defined by the underlying periodicity of the probe pulse sequence, and signal/noise is greatly improved over that for the fastest pump-probe experiments depending on a single pulse. This approach should be applicable on standard synchrotron beamlines and will enable high-resolution measurements of protein and small-molecule structural dynamics. It is also applicable to other time-resolved measurements where a probe can be encoded, such as pump-probe spectroscopy.Wellcome Trust 4-year PhD program “The Molecular Basis of Biological Mechanisms” 089312/Z/09/Z. This work was also supported by the EPSRC Award “Dynamic Structural Science at the Research Complex at Harwell” EP/I01974X/1 and by BBSRC Award BB/H001905/1

Paracrine effects of TLR4-polarised mesenchymal stromal cells are mediated by extracellular vesicles

Mesenchymal stromal cells (MSCs) are adult stem cells able to give rise to bone, cartilage and fat cells. In addition, they possess immunomodulatory and immunosuppressive properties that are mainly mediated through secretion of extracellular vesicles (EVs). In a previous issue of Journal of Translational Medicine, Ti and colleagues demonstrated that preconditioning of MSCs with bacterial lipopolysaccharides results in secretion of EVs that can polarise mac‑ rophages towards anti-inflammatory M2 phenotype. Moreover, the authors suggest that EVs of lipopolysaccharide (LPS)-treated MSCs are superior to EVs of untreated MSCs concerning their ability to support wound healing. Our commentary critically discusses parallel efforts of other laboratories to generate conditioned media from stem cells for therapeutic applications, and highlights impact and significance of the study of Ti et al. Finally, we summarise its limitations and spotlight areas that need to be addressed to better define the underlying molecular mechanisms