Optical Magnetometry

Some of the most sensitive methods of measuring magnetic fields utilize interactions of resonant light with atomic vapor. Recent developments in this vibrant field are improving magnetometers in many traditional areas such as measurement of geomagnetic anomalies and magnetic fields in space, and are opening the door to new ones, including, dynamical measurements of bio-magnetic fields, detection of nuclear magnetic resonance (NMR), magnetic-resonance imaging (MRI), inertial-rotation sensing, magnetic microscopy with cold atoms, and tests of fundamental symmetries of Nature.Comment: 11 pages; 4 figures; submitted to Nature Physic

Binding Modes of Peptidomimetics Designed to Inhibit STAT3

STAT3 is a transcription factor that has been found to be constitutively activated in a number of human cancers. Dimerization of STAT3 via its SH2 domain and the subsequent translocation of the dimer to the nucleus leads to transcription of anti-apoptotic genes. Prevention of the dimerization is thus an attractive strategy for inhibiting the activity of STAT3. Phosphotyrosine-based peptidomimetic inhibitors, which mimic pTyr-Xaa-Yaa-Gln motif and have strong to weak binding affinities, have been previously investigated. It is well-known that structures of protein-inhibitor complexes are important for understanding the binding interactions and designing stronger inhibitors. Experimental structures of inhibitors bound to the SH2 domain of STAT3 are, however, unavailable. In this paper we describe a computational study that combined molecular docking and molecular dynamics to model structures of 12 peptidomimetic inhibitors bound to the SH2 domain of STAT3. A detailed analysis of the modeled structures was performed to evaluate the characteristics of the binding interactions. We also estimated the binding affinities of the inhibitors by combining MMPB/GBSA-based energies and entropic cost of binding. The estimated affinities correlate strongly with the experimentally obtained affinities. Modeling results show binding modes that are consistent with limited previous modeling studies on binding interactions involving the SH2 domain and phosphotyrosine(pTyr)-based inhibitors. We also discovered a stable novel binding mode that involves deformation of two loops of the SH2 domain that subsequently bury the C-terminal end of one of the stronger inhibitors. The novel binding mode could prove useful for developing more potent inhibitors aimed at preventing dimerization of cancer target protein STAT3

The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review.

BACKGROUND: The management of articular cartilage defects presents many clinical challenges due to its avascular, aneural and alymphatic nature. Bone marrow stimulation techniques, such as microfracture, are the most frequently used method in clinical practice however the resulting mixed fibrocartilage tissue which is inferior to native hyaline cartilage. Other methods have shown promise but are far from perfect. There is an unmet need and growing interest in regenerative medicine and tissue engineering to improve the outcome for patients requiring cartilage repair. Many published reviews on cartilage repair only list human clinical trials, underestimating the wealth of basic sciences and animal studies that are precursors to future research. We therefore set out to perform a systematic review of the literature to assess the translation of stem cell therapy to explore what research had been carried out at each of the stages of translation from bench-top (in vitro), animal (pre-clinical) and human studies (clinical) and assemble an evidence-based cascade for the responsible introduction of stem cell therapy for cartilage defects. This review was conducted in accordance to PRISMA guidelines using CINHAL, MEDLINE, EMBASE, Scopus and Web of Knowledge databases from 1st January 1900 to 30th June 2015. In total, there were 2880 studies identified of which 252 studies were included for analysis (100 articles for in vitro studies, 111 studies for animal studies; and 31 studies for human studies). There was a huge variance in cell source in pre-clinical studies both of terms of animal used, location of harvest (fat, marrow, blood or synovium) and allogeneicity. The use of scaffolds, growth factors, number of cell passages and number of cells used was hugely heterogeneous. SHORT CONCLUSIONS: This review offers a comprehensive assessment of the evidence behind the translation of basic science to the clinical practice of cartilage repair. It has revealed a lack of connectivity between the in vitro, pre-clinical and human data and a patchwork quilt of synergistic evidence. Drivers for progress in this space are largely driven by patient demand, surgeon inquisition and a regulatory framework that is learning at the same pace as new developments take place

The Physics of the B Factories

This work is on the Physics of the B Factories. Part A of this book contains a brief description of the SLAC and KEK B Factories as well as their detectors, BaBar and Belle, and data taking related issues. Part B discusses tools and methods used by the experiments in order to obtain results. The results themselves can be found in Part C

Comparison of inpatient vs. outpatient anterior cervical discectomy and fusion: a retrospective case series

<p>Abstract</p> <p>Background</p> <p>Spinal surgery is increasingly being done in the outpatient setting. We reviewed our experience with inpatient and outpatient single-level anterior cervical discectomy and fusion with plating (ACDF+P).</p> <p>Methods</p> <p>All patients undergoing single-level anterior cervical discectomy and fusion with plating between August 2005 and May 2007 by two surgeons (RPB or JAF) were retrospectively reviewed. All patients underwent anterior cervical microdiscectomy, arthrodesis using structural allograft, and titanium plating. A planned change from doing ACDF+P on an inpatient basis to doing ACDF+P on an outpatient basis was instituted at the midpoint of the study. There were no other changes in technique, patient selection, instrumentation, facility, or other factors. All procedures were done in full-service hospitals accommodating outpatient and inpatient care.</p> <p>Results</p> <p>64 patients underwent ACDF+P as inpatients, while 45 underwent ACDF+P as outpatients. When outpatient surgery was planned, 17 patients were treated as inpatients due to medical comorbidities (14), older age (1), and patient preference (2). At a mean follow-up of 62.4 days, 90 patients had an excellent outcome, 19 patients had a good outcome, and no patients had a fair or poor outcome. There was no significant difference in outcome between inpatients and outpatients. There were 4 complications, all occurring in inpatients: a hematoma one week post-operatively requiring drainage, a cerebrospinal fluid leak treated with lumbar drainage, syncope of unknown etiology, and moderate dysphagia.</p> <p>Conclusion</p> <p>In this series, outpatient ACDF+P was safe and was not associated with a significant difference in outcome compared with inpatient ACDF+P.</p

Anti-erbB2 treatment induces cardiotoxicity by interfering with cell survival pathways

INTRODUCTION: Cardiac dysfunction is among the serious side effects of therapy with recombinant humanized anti-erbB2 monoclonal antibody. The antibody blocks ErbB-2, a receptor tyrosine kinase and co-receptor for other members of the ErbB and epidermal growth factor families, which is over-expressed on the surface of many malignant cells. ErbB-2 and its ligands neuregulin and ErbB-3/ErbB-4 are involved in survival and growth of cardiomyocytes in both postnatal and adult hearts, and therefore the drug may interrupt the correct functioning of the ErbB-2 pathway. METHODS: The effect of the rat-anti-erbB2 monoclonal antibody B-10 was studied in spontaneously beating primary myocyte cultures from rat neonatal hearts. Gene expression was determined by RT-PCR (reverse transcription polymerase chain reaction) and by rat stress-specific microarray analysis, protein levels by Western blot, cell contractility by video motion analysis, calcium transients by the FURA fluorescent method, and apoptosis using the TUNEL (terminal uridine nick-end labelling) assay. RESULTS: B-10 treatment induces significant changes in expression of 24 out of 207 stress genes analyzed using the microarray technique. Protein levels of ErbB-2, ErbB-3, ErbB-4 and neuregulin decreased after 1 day. However, both transcription and protein levels of ErbB-4 and gp130 increased several fold. Calreticulin and calsequestrin were overexpressed after three days, inducing a decrease in calcium transients, thereby influencing cell contractility. Apoptosis was induced in 20% cells after 24 hours. CONCLUSION: Blocking ErbB-2 in cultured rat cardiomyocytes leads to changes that may influence the cell cycle and affects genes involved in heart functions. B-10 inhibits pro-survival pathways and reduces cellular contractility. Thus, it is conceivable that this process may impair the stress response of the heart

Advances in Microbial Biofilm Prevention on Indwelling Medical Devices with Emphasis on Usage of Acoustic Energy

Microbial biofilms are a major impediment to the use of indwelling medical devices, generating device-related infections with high morbidity and mortality. Major efforts directed towards preventing and eradicating the biofilm problem face difficulties because biofilms protect themselves very effectively by producing a polysaccharide coating, reducing biofilm sensitivity to antimicrobial agents. Techniques applied to combating biofilms have been primarily chemical. These have met with partial and limited success rates, leading to current trends of eradicating biofilms through physico-mechanical strategies. Here we review the different approaches that have been developed to control biofilm formation and removal, focusing on the utilization of acoustic energy to achieve these objectives

Autoadjusting-CPAP effect on serum Leptin concentrations in Obstructive Sleep Apnoea patients

© 2008 Drummond et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens