On the Application of a Monolithic Array for Detecting Intensity-Correlated Photons Emitted by Different Source Types

It is not widely appreciated that many subtleties are involved in the accurate measurement of intensity-correlated photons; even for the original experiments of Hanbury Brown and Twiss (HBT). Using a monolithic 4x4 array of single-photon avalanche diodes (SPADs), together with an off-chip algorithm for processing streaming data, we investigate the difficulties of measuring second-order photon correlations g2 in a wide variety of light fields that exhibit dramatically different correlation statistics: a multimode He-Ne laser, an incoherent intensity-modulated lamp-light source and a thermal light source. Our off-chip algorithm treats multiple photon-arrivals at pixel-array pairs, in any observation interval, with photon fluxes limited by detector saturation, in such a way that a correctly normalized g2 function is guaranteed. The impact of detector background correlations between SPAD pixels and afterpulsing effects on second-order coherence measurements is discussed. These results demonstrate that our monolithic SPAD array enables access to effects that are otherwise impossible to measure with stand-alone detectors.Comment: 17 pages, 6 figure

Disaturated-phosphatidylcholine and Surfactant protein-B turnover in human acute lung injury and in control patients

<p>Abstract</p> <p>Background</p> <p>Patients with Adult Respiratory Distress Syndrome (ARDS) and Acute Lung Injury (ALI) have low concentrations of disaturated-phosphatidylcholine and surfactant protein-B in bronchoalveolar lavage fluid. No information is available on their turnover.</p> <p>Objectives</p> <p>To analyze disaturated-phosphatidylcholine and surfactant protein-B turnover in patients with ARDS/ALI and in human adults with normal lungs (controls).</p> <p>Methods</p> <p>²H₂O as precursor of disaturated-phosphatidylcholine-palmitate and 1¹³C-Leucine as precursor of surfactant protein-B were administered intravenously to 12 patients with ARDS/ALI and to 8 controls. Disaturated-phosphatidylcholine and surfactant protein-B were isolated from serial tracheal aspirates, and their fractional synthetic rate was derived from the ²H and ¹³C enrichment curves, obtained by gas chromatography mass spectrometry. Disaturated-phosphatidylcholine, surfactant protein-B, and protein concentrations in tracheal aspirates were also measured.</p> <p>Results</p> <p>1) Surfactant protein-B turned over at faster rate than disaturated-phosphatidylcholine both in ARDS/ALI patients and in controls. 2) In patients with ARDS/ALI the fractional synthesis rate of disaturated-phosphatidylcholine was 3.1 times higher than in controls (p < 0.01), while the fractional synthesis rate of surfactant protein-B was not different. 3) In ARDS/ALI patients the concentrations of disaturated-phosphatidylcholine and surfactant protein-B in tracheal aspirates were markedly and significantly reduced (17% and 40% of the control values respectively).</p> <p>Conclusions</p> <p>1) Disaturated-phosphatidylcholine and surfactant protein-B have a different turnover both in healthy and diseased lungs. 2) In ARDS/ALI the synthesis of these two surfactant components may be differently regulated.</p

Varus distal femoral osteotomy in young adults with valgus knee

<p>Abstract</p> <p>Background</p> <p>Musculoskeletal disorders specially knee osteoarthritis are the most common causes of morbidity in old patients. Disturbance of the mechanical axis of the lower extremity is one of the most important causes in progression of knee osteoarthritis. The purpose of the present study was to analyze the surgical results of distal femoral varus osteotomy in patients with genu valgum.</p> <p>Methods</p> <p>In this study, after recording history and physical examination, appropriate radiographs were taken. We did varus distal femoral osteotomy by standard medial subvastus approach and 90-angle blade plate fixation then followed the patients clinically and radiographically.</p> <p>Results</p> <p>This study was done on 23 knees (16 patients) age 23.3 years (range, 17 to 41 years). The mean duration of following up was 16.3 months (range, 8 to 25 months). Based on paired T test, there were statistically significant difference between pre- and postoperative tibiofemoral and congruence angles (p < 0.001, t = 21.3 and p < 0.001, t = 10.1 respectively). Pearson correlation between the amount of tibiofemoral and congruence angle correction was also statistically significant (p = 0.02 and r = 0.46).</p> <p>Conclusion</p> <p>Distal femoral varus osteotomy with blade plate fixation can be a reliable procedure for the treatment of valgus knee deformity. In this procedure, with more tibiofemoral angle correction, more congruence angle correction can be achieved. Therefore, along with genu valgum correction, the patella should be stabilized simultaneously.</p

Butyrate down-regulates CD44 transcription and liver colonisation in a highly metastatic human colon carcinoma cell line

Over-expression of the adhesion molecule CD44 and its splice variants, especially CD44v6, is associated with poor prognosis and metastasis. We aimed at regulating the expression of CD44 in the highly metastatic human colon cancer cell line HM7 and thereby affecting its metastatic ability. HM7 cells show constitutive expression of CD44 standard and variants isoforms, which were significantly down-regulated by treatment with butyrate. Butyrate significantly inhibited transcription of the CD44 gene and abolished epidermal growth factor-mediated up-regulation of the reporter gene luciferase subcloned upstream to the CD44 promoter (−1.1 kb) and transfected to HM7 cells. Nuclear proteins from butyrate-treated cells bound to an epidermal growth factor receptor element motif present in the CD44 promoter. Epidermal growth factor receptor element-site directed mutations eliminated the inducibility of the luciferase reporter gene and did not allowed binding of nuclear proteins harvested from butyrate-treated cells. Butyrate induced CD44 gene repression by specifically interacting with an epidermal growth factor receptor element nuclear transcriptional factor. This interaction affects CD44 transcriptional activity vis-à-vis in vivo metastatic ability of HM7 cells. These results provide additional insight into the anticarcinogenic properties of butyrate

Representation of target-bound drugs by computed conformers: implications for conformational libraries

BACKGROUND: The increasing number of known protein structures provides valuable information about pharmaceutical targets. Drug binding sites are identifiable and suitable lead compounds can be proposed. The flexibility of ligands is a critical point for the selection of potential drugs. Since computed 3D structures of millions of compounds are available, the knowledge of their binding conformations would be a great benefit for the development of efficient screening methods. RESULTS: Integration of two public databases allowed superposition of conformers for 193 approved drugs with 5507 crystallised target-bound counterparts. The generation of 9600 drug conformers using an atomic force field was carried out to obtain an optimal coverage of the conformational space. Bioactive conformations are best described by a conformational ensemble: half of all drugs exhibit multiple active states, distributed over the entire range of the reachable energy and conformational space. A number of up to 100 conformers per drug enabled us to reproduce the bound states within a similarity threshold of 1.0 Å in 70% of all cases. This fraction rises to about 90% for smaller or average sized drugs. CONCLUSION: Single drugs adopt multiple bioactive conformations if they interact with different target proteins. Due to the structural diversity of binding sites they adopt conformations that are distributed over a broad conformational space and wide energy range. Since the majority of drugs is well represented by a predefined low number of conformers (up to 100) this procedure is a valuable method to compare compounds by three-dimensional features or for fast similarity searches starting with pharmacophores. The underlying 9600 generated drug conformers are downloadable from the Super Drug Web site [1]. All superpositions are visualised at the same source. Additional conformers (110,000) of 2400 classified WHO-drugs are also available

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Search for squarks and gluinos with the ATLAS detector in final states with jets and missing transverse momentum using √s=8 TeV proton-proton collision data

A search for squarks and gluinos in final states containing high-p T jets, missing transverse momentum and no electrons or muons is presented. The data were recorded in 2012 by the ATLAS experiment in s√=8 TeV proton-proton collisions at the Large Hadron Collider, with a total integrated luminosity of 20.3 fb−1. Results are interpreted in a variety of simplified and specific supersymmetry-breaking models assuming that R-parity is conserved and that the lightest neutralino is the lightest supersymmetric particle. An exclusion limit at the 95% confidence level on the mass of the gluino is set at 1330 GeV for a simplified model incorporating only a gluino and the lightest neutralino. For a simplified model involving the strong production of first- and second-generation squarks, squark masses below 850 GeV (440 GeV) are excluded for a massless lightest neutralino, assuming mass degenerate (single light-flavour) squarks. In mSUGRA/CMSSM models with tan β = 30, A 0 = −2m 0 and μ > 0, squarks and gluinos of equal mass are excluded for masses below 1700 GeV. Additional limits are set for non-universal Higgs mass models with gaugino mediation and for simplified models involving the pair production of gluinos, each decaying to a top squark and a top quark, with the top squark decaying to a charm quark and a neutralino. These limits extend the region of supersymmetric parameter space excluded by previous searches with the ATLAS detector

Novel variants in the PRDX6 Gene and the risk of Acute Lung Injury following major trauma

<p>Abstract</p> <p>Background</p> <p>Peroxiredoxin 6 (<it>PRDX6</it>) is involved in redox regulation of the cell and is thought to be protective against oxidant injury. Little is known about genetic variation within the PRDX6 gene and its association with acute lung injury (ALI). In this study we sequenced the <it>PRDX6 </it>gene to uncover common variants, and tested association with ALI following major trauma.</p> <p>Methods</p> <p>To examine the extent of variation in the <it>PRDX6 </it>gene, we performed direct sequencing of the 5' UTR, exons, introns and the 3' UTR in 25 African American cases and controls and 23 European American cases and controls (selected from a cohort study of major trauma), which uncovered 80 SNPs. <it>In silico </it>modeling was performed using Patrocles and Transcriptional Element Search System (TESS). Thirty seven novel and tagging SNPs were tested for association with ALI compared with ICU at-risk controls who did not develop ALI in a cohort study of 259 African American and 254 European American subjects that had been admitted to the ICU with major trauma.</p> <p>Results</p> <p>Resequencing of critically ill subjects demonstrated 43 novel SNPs not previously reported. Coding regions demonstrated no detectable variation, indicating conservation of the protein. Block haplotype analyses reveal that recombination rates within the gene seem low in both Caucasians and African Americans. Several novel SNPs appeared to have the potential for functional consequence using <it>in silico </it>modeling. Chi²analysis of ALI incidence and genotype showed no significant association between the SNPs in this study and ALI. Haplotype analysis did not reveal any association beyond single SNP analyses.</p> <p>Conclusions</p> <p>This study revealed novel SNPs within the <it>PRDX6 </it>gene and its 5' and 3' flanking regions via direct sequencing. There was no association found between these SNPs and ALI, possibly due to a low sample size, which was limited to detection of relative risks of 1.93 and above. Future studies may focus on the role of <it>PRDX6 </it>genetic variation in other diseases, where oxidative stress is suspected.</p

Serum biomarkers in Acute Respiratory Distress Syndrome an ailing prognosticator

The use of biomarkers in medicine lies in their ability to detect disease and support diagnostic and therapeutic decisions. New research and novel understanding of the molecular basis of the disease reveals an abundance of exciting new biomarkers who present a promise for use in the everyday clinical practice. The past fifteen years have seen the emergence of numerous clinical applications of several new molecules as biologic markers in the research field relevant to acute respiratory distress syndrome (translational research). The scope of this review is to summarize the current state of knowledge about serum biomarkers in acute lung injury and acute respiratory distress syndrome and their potential value as prognostic tools and present some of the future perspectives and challenges