Video enhancement using adaptive spatio-temporal connective filter and piecewise mapping

This paper presents a novel video enhancement system based on an adaptive spatio-temporal connective (ASTC) noise filter and an adaptive piecewise mapping function (APMF). For ill-exposed videos or those with much noise, we first introduce a novel local image statistic to identify impulse noise pixels, and then incorporate it into the classical bilateral filter to form ASTC, aiming to reduce the mixture of the most two common types of noises - Gaussian and impulse noises in spatial and temporal directions. After noise removal, we enhance the video contrast with APMF based on the statistical information of frame segmentation results. The experiment results demonstrate that, for diverse low-quality videos corrupted by mixed noise, underexposure, overexposure, or any mixture of the above, the proposed system can automatically produce satisfactory results

Extracellular Matrix Aggregates from Differentiating Embryoid Bodies as a Scaffold to Support ESC Proliferation and Differentiation

Embryonic stem cells (ESCs) have emerged as potential cell sources for tissue engineering and regeneration owing to its virtually unlimited replicative capacity and the potential to differentiate into a variety of cell types. Current differentiation strategies primarily involve various growth factor/inducer/repressor concoctions with less emphasis on the substrate. Developing biomaterials to promote stem cell proliferation and differentiation could aid in the realization of this goal. Extracellular matrix (ECM) components are important physiological regulators, and can provide cues to direct ESC expansion and differentiation. ECM undergoes constant remodeling with surrounding cells to accommodate specific developmental event. In this study, using ESC derived aggregates called embryoid bodies (EB) as a model, we characterized the biological nature of ECM in EB after exposure to different treatments: spontaneously differentiated and retinoic acid treated (denoted as SPT and RA, respectively). Next, we extracted this treatment-specific ECM by detergent decellularization methods (Triton X-100, DOC and SDS are compared). The resulting EB ECM scaffolds were seeded with undifferentiated ESCs using a novel cell seeding strategy, and the behavior of ESCs was studied. Our results showed that the optimized protocol efficiently removes cells while retaining crucial ECM and biochemical components. Decellularized ECM from SPT EB gave rise to a more favorable microenvironment for promoting ESC attachment, proliferation, and early differentiation, compared to native EB and decellularized ECM from RA EB. These findings suggest that various treatment conditions allow the formulation of unique ESC-ECM derived scaffolds to enhance ESC bioactivities, including proliferation and differentiation for tissue regeneration applications. © 2013 Goh et al

Effects of normalization on quantitative traits in association test

<p>Abstract</p> <p>Background</p> <p>Quantitative trait loci analysis assumes that the trait is normally distributed. In reality, this is often not observed and one strategy is to transform the trait. However, it is not clear how much normality is required and which transformation works best in association studies.</p> <p>Results</p> <p>We performed simulations on four types of common quantitative traits to evaluate the effects of normalization using the logarithm, Box-Cox, and rank-based transformations. The impact of sample size and genetic effects on normalization is also investigated. Our results show that rank-based transformation gives generally the best and consistent performance in identifying the causal polymorphism and ranking it highly in association tests, with a slight increase in false positive rate.</p> <p>Conclusion</p> <p>For small sample size or genetic effects, the improvement in sensitivity for rank transformation outweighs the slight increase in false positive rate. However, for large sample size and genetic effects, normalization may not be necessary since the increase in sensitivity is relatively modest.</p

Coxiella burnetii Phagocytosis Is Regulated by GTPases of the Rho Family and the RhoA Effectors mDia1 and ROCK

The GTPases belonging to the Rho family control the actin cytoskeleton rearrangements needed for particle internalization during phagocytosis. ROCK and mDia1 are downstream effectors of RhoA, a GTPase involved in that process. Coxiella burnetii, the etiologic agent of Q fever, is internalized by the host´s cells in an actin-dependent manner. Nevertheless, the molecular mechanism involved in this process has been poorly characterized. This work analyzes the role of different GTPases of the Rho family and some downstream effectors in the internalization of C. burnetii by phagocytic and non-phagocytic cells. The internalization of C. burnetii into HeLa and RAW cells was significantly inhibited when the cells were treated with Clostridium difficile Toxin B which irreversibly inactivates members of the Rho family. In addition, the internalization was reduced in HeLa cells that overexpressed the dominant negative mutants of RhoA, Rac1 or Cdc42 or that were knocked down for the Rho GTPases. The pharmacological inhibition or the knocking down of ROCK diminished bacterium internalization. Moreover, C. burnetii was less efficiently internalized in HeLa cells overexpressing mDia1-N1, a dominant negative mutant of mDia1, while the overexpression of the constitutively active mutant mDia1-ΔN3 increased bacteria uptake. Interestingly, when HeLa and RAW cells were infected, RhoA, Rac1 and mDia1 were recruited to membrane cell fractions. Our results suggest that the GTPases of the Rho family play an important role in C. burnetii phagocytosis in both HeLa and RAW cells. Additionally, we present evidence that ROCK and mDia1, which are downstream effectors of RhoA, are involved in that processFil: Salinas Ojeda, Romina Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Ortiz Flores, Rodolfo Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Distel, Jesús Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Aguilera, Milton Osmar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Colombo, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Beron, Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentin

Paroxysmal autonomic instability with dystonia in a patient with tuberculous meningitis: a case report

<p>Abstract</p> <p>Introduction</p> <p>This case report describes an extremely rare combination of paroxysmal autonomic instability with dystonia and tuberculous meningitis. Paroxysmal autonomic instability with dystonia is normally associated with severe traumatic brain injury.</p> <p>Case presentation</p> <p>A 69-year-old man of Indonesian descent was initially suspected of having a community-acquired pneumonia, which was seen on chest X-ray and computed tomography of the chest. However, a bronchoscopy showed no abnormalities. He was treated with amoxicillin-clavulanic acid in combination with ciprofloxacin. However, nine days after admission he was disorientated and complained of headache. Neurological examination revealed no further abnormalities. A lumbar puncture revealed no evidence of meningitis. He was then transferred to our hospital. At that time, initial cultures of bronchial fluid for <it>Mycobacterium tuberculosis </it>turned positive, as well as polymerase chain reaction for <it>Mycobacterium tuberculosis</it>. Later, during his stay in our intensive care unit, he developed periods with hypertension, sinus tachycardia, excessive transpiration, decreased oxygen saturation with tachypnea, pink foamy sputum, and high fever. This constellation of symptoms was accompanied by dystonia in the first days. These episodes lasted approximately 30 minutes and improved after administration of morphine, benzodiazepines or clonidine. Magnetic resonance imaging showed an abnormal signal in the region of the hippocampus, thalamus and the anterior parts of the lentiform nucleus and caudate nucleus.</p> <p>Conclusions</p> <p>In patients with (tuberculous) meningitis and episodes of extreme hypertension and fever, paroxysmal autonomic instability with dystonia should be considered.</p

Rucaparib for patients with platinum-sensitive, recurrent ovarian carcinoma (ARIEL3): post-progression outcomes and updated safety results from a randomised, placebo-controlled, phase 3 trial

BACKGROUND: In ARIEL3, rucaparib maintenance treatment significantly improved progression-free survival versus placebo. Here, we report prespecified, investigator-assessed, exploratory post-progression endpoints and updated safety data. METHODS: In this ongoing (enrolment complete) randomised, placebo-controlled, phase 3 trial, patients aged 18 years or older who had platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 who had received at least two previous platinum-based chemotherapy regimens and responded to their last platinum-based regimen were randomly assigned (2:1) to oral rucaparib (600 mg twice daily) or placebo in 28-day cycles using a computer-generated sequence (block size of six with stratification based on homologous recombination repair gene mutation status, progression-free interval following penultimate platinum-based regimen, and best response to most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary endpoint of investigator-assessed progression-free survival has been previously reported. Prespecified, exploratory outcomes of chemotherapy-free interval (CFI), time to start of first subsequent therapy (TFST), time to disease progression on subsequent therapy or death (PFS2), and time to start of second subsequent therapy (TSST) and updated safety were analysed (visit cutoff Dec 31, 2017). Efficacy analyses were done in all patients randomised to three nested cohorts: patients with BRCA mutations, patients with homologous recombination deficiencies, and the intention-to-treat population. Safety analyses included all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT01968213. FINDINGS: Between April 7, 2014, and July 19, 2016, 564 patients were enrolled and randomly assigned to rucaparib (n=375) or placebo (n=189). Median follow-up was 28·1 months (IQR 22·0-33·6). In the intention-to-treat population, median CFI was 14·3 months (95% CI 13·0-17·4) in the rucaparib group versus 8·8 months (8·0-10·3) in the placebo group (hazard ratio [HR] 0·43 [95% CI 0·35-0·53]; p<0·0001), median TFST was 12·4 months (11·1-15·2) versus 7·2 months (6·4-8·6; HR 0·43 [0·35-0·52]; p<0·0001), median PFS2 was 21·0 months (18·9-23·6) versus 16·5 months (15·2-18·4; HR 0·66 [0·53-0·82]; p=0·0002), and median TSST was 22·4 months (19·1-24·5) versus 17·3 months (14·9-19·4; HR 0·68 [0·54-0·85]; p=0·0007). CFI, TFST, PFS2, and TSST were also significantly longer with rucaparib than placebo in the BRCA-mutant and homologous recombination-deficient cohorts. The most frequent treatment-emergent adverse event of grade 3 or higher was anaemia or decreased haemoglobin (80 [22%] patients in the rucaparib group vs one [1%] patient in the placebo group). Serious treatment-emergent adverse events were reported in 83 (22%) patients in the rucaparib group and 20 (11%) patients in the placebo group. Two treatment-related deaths have been previously reported in this trial; there were no new treatment-related deaths. INTERPRETATION: In these exploratory analyses over a median follow-up of more than 2 years, rucaparib maintenance treatment led to a clinically meaningful delay in starting subsequent therapy and provided lasting clinical benefits versus placebo in all three analysis cohorts. Updated safety data were consistent with previous reports. FUNDING: Clovis Oncology

Web-based monitoring tools for Resistive Plate Chambers in the CMS experiment at CERN

The Resistive Plate Chambers (RPC) are used in the CMS experiment at the trigger level and also in the standard offline muon reconstruction. In order to guarantee the quality of the data collected and to monitor online the detector performance, a set of tools has been developed in CMS which is heavily used in the RPC system. The Web-based monitoring (WBM) is a set of java servlets that allows users to check the performance of the hardware during data taking, providing distributions and history plots of all the parameters. The functionalities of the RPC WBM monitoring tools are presented along with studies of the detector performance as a function of growing luminosity and environmental conditions that are tracked over time

Temperature influence on DXA measurements: bone mineral density acquisition in frozen and thawed human femora

<p>Abstract</p> <p>Background</p> <p>Determining bone mineral density (BMD) with dual-energy x-ray absorptiometry (DXA) is an established and widely used method that is also applied prior to biomechanical testing. However, DXA is affected by a number of factors. In order to delay decompositional processes, human specimens for biomechanical studies are usually stored at about -20°C; similarly, bone mineral density measurements are usually performed in the frozen state. The aim of our study was to investigate the influence of bone temperature on the measured bone mineral density.</p> <p>Methods</p> <p>Using DXA, bone mineral density measurements were taken in 19 fresh-frozen human femora, in the frozen and the thawed state. Water was used to mimic the missing soft tissue around the specimens. Measurements were taken with the specimens in standardized internal rotation. Total-BMD and single-BMD values of different regions of interest were used for evaluation.</p> <p>Results</p> <p>Fourteen of the 19 specimens showed a decrease in BMD after thawing. The measured total-BMD of the frozen specimens was significantly (1.4%) higher than the measured BMD of the thawed specimens.</p> <p>Conclusion</p> <p>Based on our findings we recommend that the measurement of bone density, for example prior to biomechanical testing, should be standardized to thawed or frozen specimens. Temperature should not be changed during measurements. When using score systems for data interpretation (e.g. T- or Z-score), BMD measurements should be performed only on thawed specimens.</p

Type 2 Diabetes Is Associated with Altered NF-κB DNA Binding Activity, JNK Phosphorylation, and AMPK Phosphorylation in Skeletal Muscle after LPS

Systemic inflammation is often associated with impaired glucose metabolism. We therefore studied the activation of inflammatory pathway intermediates that interfere with glucose uptake during systemic inflammation by applying a standardised inflammatory stimulus in vivo. After ethical approval, informed consent and a thorough physical examination, 10 patients with type 2 diabetes and 10 participants with normal glucose tolerance (NGT) were given an intravenous bolus of E. coli lipopolysaccharide (LPS) of 0.3 ng/kg. Skeletal muscle biopsies and plasma were obtained at baseline and two, four and six hours after LPS. Nuclear factor (NF)-κB p65 DNA binding activity measured by ELISA, tumor necrosis factor-α and interleukin-6 mRNA expression analysed by real time reverse transcription polymerase chain reaction, and abundance of inhibitor of NF-κB (IκB)α, phosphorylated c-Jun-N-terminal kinase (JNK), AMP-activated protein kinase (AMPK), and acetyl-CoA carboxylase measured by Western blotting were detected in muscle biopsy samples. Relative to subjects with NGT, patients with type 2 diabetes exhibited a more pronounced increase in NF-κB binding activity and JNK phosphorylation after LPS, whereas skeletal muscle cytokine mRNA expression did not differ significantly between groups. AMPK phosphorylation increased in volunteers with NGT, but not in those with diabetes. The present findings indicate that pathways regulating glucose uptake in skeletal muscle may be involved in the development of inflammation-associated hyperglycemia. Patients with type 2 diabetes exhibit changes in these pathways, which may ultimately render such patients more prone to develop dysregulated glucose disposal in the context of systemic inflammation