Erratum to: A Mechanism to Explain Ototoxicity in Neonates Exposed to Bumetanide: Lessons to Help Improve Future Product Development in Neonates

http://ift.tt/2d1FXQ4

Palivizumab Exposure and the Risk of Autoimmune Disease: A Cross-National Cohort Study

Abstract

Background

Treatment with biologic pharmaceuticals may be associated with an increased risk of immune-mediated disease. Palivizumab is a humanized monoclonal antibody designed to provide passive immunity against respiratory syncytial virus infection. Palivizumab is primarily used in preterm children known to be immunologically immature. The long-term effect of palivizumab in terms of autoimmune diseases has not yet been investigated.

Aim

Our objective was to investigate whether exposure to palivizumab was associated with the development of autoimmune diseases in children.

Methods

This was a population-based cohort study including data from 769,523 Danish children born between 1 January 1999 and 31 December 2010 and data from 581,742 Swedish children born between 1 July 2005 and 31 December 2010.

Results

Of the 1,351,265 children included, 1192 (0.09 %) were exposed to palivizumab. Nine cases of autoimmune disease were diagnosed among palivizumab-exposed children during the period of observation. Among the children exposed to palivizumab, one child in Denmark developed inflammatory bowel disease; in Sweden, children developed juvenile arthritis (one child), diabetes mellitus (two children), celiac disease (four children), and inflammatory bowel disease (one child). The risk of autoimmune disease was not significantly increased after palivizumab exposure (hazard ratio adjusted for age and country: 1.54; 95 % confidence interval 0.80–2.95).

Conclusion

The risk of autoimmune disease was not increased after palivizumab exposure. Given the small number of incident cases of autoimmune disease observed, this finding should be interpreted with caution.

http://ift.tt/2drQRfZ

Characterization and Low-Resolution Structure of an Extremely Thermostable Esterase of Potential Biotechnological Interest from Pyrococcus furiosus

Abstract

Enzymes isolated from extremophiles often exhibit superior performance and potential industrial applications. There are several advantages performing biocatalysis at elevated temperatures, including enhanced reaction rates, increased substrate solubility and decreased risks of contamination. Furthermore, thermophilic enzymes usually exhibit high resistance against many organic solvents and detergents, and are also more resistant to proteolytic attack. In this study, we subcloned and characterized an esterase from the hyperthermophilic archaeon Pyrococcus furiosus (Pf_Est) that exhibits optimal activity around 80 °C using naphthol-derived substrates and p-nitrophenyl palmitate (pNPP). According to the circular dichroism spectra, the secondary structure of P. furiosus esterase, which is predominantly formed by a β-sheet structure, is very stable, even after incubation at 120°C. We performed SAXS to determine the low-resolution structure of Pf_Est, which is monomeric in solution at 80 °C and has a molecular weight of 28 kDa. The Km and V _max values for this esterase acting on pNPP were 0.53 mmol/L and 6.5 × 10⁻³ U, respectively. Pf_Est was most active in the immiscible solvents and retained more than 50 % in miscible solvents. Moreover, Pf_Est possesses transesterification capacity, presenting better results when isobutanol was used as an acyl acceptor (2.69 ± 0.14 × 10⁻² μmol/min mg) and the highest hydrolytic activity toward olive oil among different types of oils testes in this study. Collectively, these biophysical and catalytic properties are of interest for several biotechnological applications that require harsh conditions, including high temperature and the presence of organic solvents.

http://ift.tt/2cDz2M2

Distinct Immunoregulatory Mechanisms in Mesenchymal Stem Cells: Role of the Cytokine Environment

Abstract

Mesenchymal stem cells (MSCs) represent a population of cells which have the ability to regulate reactivity of T and B lymphocytes by multiple mechanisms. The immunoregulatory activities of MSCs are strictly influenced by the cytokine environment. Here we show that two functionally distinct cytokines, interleukin-4 (IL-4) and interferon-γ (IFN-γ), significantly potentiate the ability of MSCs to inhibit IL-10 production by activated regulatory B cells (Bregs). However, MSCs in the presence of IL-4 or IFN-γ inhibit the IL-10 production by different mechanisms. Preincubation of MSCs with IFN-γ led to the suppression, but pretreatment with IL-4 of neither MSCs nor B cells resulted in the suppression of IL-10 production. The search for candidate regulatory molecules expressed in cytokine-treated MSCs revealed different patterns of the gene expression. Pretreatment of MSCs with IFN-γ, but not with IL-4, induced expression of indoleamine-2,3-dioxygenase, cyclooxygenase-2 and programmed cell death-ligand 1. To identify the molecule(s) responsible for the suppression of IL-10 production, we used specific inhibitors of the putative regulatory molecules. We found that indomethacine, an inhibitor of cyclooxygenase-2 (Cox-2) activity, completely abrogated the inhibition of IL-10 production in cultures containing MSCs and IFN-γ, but had no effect on the suppression in cell cultures containing MSCs and IL-4. The results show that MSCs can inhibit the response of B cells to one stimulus by different mechanisms in dependence on the cytokine environment and thus support the idea of the complexity of immunoregulatory action of MSCs.

http://ift.tt/2cDiILz

Hyaluronic Acid (HA) Scaffolds and Multipotent Stromal Cells (MSCs) in Regenerative Medicine

Abstract

Traditional methods for tissue regeneration commonly used synthetic scaffolds to regenerate human tissues. However, they had several limitations, such as foreign body reactions and short time duration. In order to overcome these problems, scaffolds made of natural polymers are preferred. One of the most suitable and widely used materials to fabricate these scaffolds is hyaluronic acid. Hyaluronic acid is the primary component of the extracellular matrix of the human connective tissue. It is an ideal material for scaffolds used in tissue regeneration, thanks to its properties of biocompatibility, ease of chemical functionalization and degradability. In the last few years, especially from 2010, scientists have seen that the cell-based engineering of these natural scaffolds allows obtaining even better results in terms of tissue regeneration and the research started to grow in this direction. Multipotent stromal cells, also known as mesenchymal stem cells, plastic-adherent cells isolated from bone marrow and other mesenchymal tissues, with self-renew and multi-potency properties are ideal candidates for this aim. Normally, they are pre-seeded onto these scaffolds before their implantation in vivo. This review discusses the use of hyaluronic acid-based scaffolds together with multipotent stromal cells, as a very promising tool in regenerative medicine.

http://ift.tt/2dajD3c

Genomic and transcriptome analysis of triclosan response of a multidrug-resistant Acinetobacter baumannii strain, MDR-ZJ06

Abstract

During the last decade, an increasing amount of attention has focused on the potential threat of triclosan to both the human body and environmental ecology. However, the role of triclosan in the development of drug resistance and cross resistance is still in dispute ascribed to largely unknown of triclosan resistance mechanism. In this work, Acinetobacter baumannii MDR-ZJ06, a multidrug-resistant strain, was induced by triclosan, and the genomic variation and transcriptional levels were investigated, respectively. The comparative transcriptomic analysis found that several general protective mechanisms were enhanced under the triclosan condition, including responses to reactive oxygen species and cell membrane damage. Meanwhile, all of the detected fifteen single nucleotide polymorphisms were not directly associated triclosan tolerance. In summary, this work revealed the crucial role of the general stress response in A. baumannii under a triclosan stress condition, which informs a more comprehensive understanding of the role of triclosan in the spread of drug-resistant bacteria.

http://ift.tt/2dknS1A

Roseovarius lacus sp. nov., isolated from Yuncheng Saline Lake, China

Abstract

Strain GSS12^T, a Gram-negative, aerobic, non-flagellated, ovoid- to rod-shaped (0.5–0.7 × 0.9–3.0 µm) bacterium, was isolated from Yuncheng Saline Lake, China. Growth occurred with 0.5–16.0 % (w/v) NaCl (optimum 4.5 %), at pH 5.0–10.0 (optimum pH 6.0–6.5) and at 10–50 °C (optimum 37 °C). The major fatty acids (>5.0 %) found in GSS12^T were summed feature 8 (72.2 %), C_16:0 (9.0 %) and C_18:1ω7c 11-methyl (6.4 %). The DNA G+C content was 62.7 mol%. Analysis of the 16S rRNA gene sequences showed that strain GSS12^T forms a stable clade with species of the genus Roseovarius, being related to R. pacificus 81-2^T and R. litoreus GSW-M15^T with 97.9 and 96.7 % of sequence similarity, respectively. The DNA–DNA relatedness values between strain GSS12^T and R. pacificus 81-2^T and R. halotolerans HJ50^T were low (36 and 29 %, respectively). The phenotypic, physiological, biochemical and genetic characteristics support the assignment of strain GSS12^T to the genus Roseovarius and represent a novel species. The name Roseovarius lacus sp. nov. is proposed, with strain GSS12^T (=KCTC 52185^T =MCCC 1K02302^T) as the type strain.

http://ift.tt/2cUdoDk

Intracellular calcium oscillations in strongly metastatic human breast and prostate cancer cells: control by voltage-gated sodium channel activity

Abstract

The possible association of intracellular Ca²⁺ with metastasis in human cancer cells is poorly understood. We have studied Ca²⁺ signaling in human prostate and breast cancer cell lines of strongly versus weakly metastatic potential in a comparative approach. Intracellular free Ca²⁺ was measured using a membrane-permeant fluorescent Ca²⁺-indicator dye (Fluo-4 AM) and confocal microscopy. Spontaneous Ca²⁺ oscillations were observed in a proportion of strongly metastatic human prostate and breast cancer cells (PC-3M and MDA-MB-231, respectively). In contrast, no such oscillations were observed in weakly/non metastatic LNCaP and MCF-7 cells, although a rise in the resting Ca²⁺ level could be induced by applying a high-K⁺ solution. Various parameters of the oscillations depended on extracellular Ca²⁺ and voltage-gated Na⁺ channel activity. Treatment with either tetrodotoxin (a general blocker of voltage-gated Na⁺ channels) or ranolazine (a blocker of the persistent component of the channel current) suppressed the Ca²⁺ oscillations. It is concluded that the functional voltage-gated Na⁺ channel expression in strongly metastatic cancer cells makes a significant contribution to generation of oscillatory intracellular Ca²⁺ activity. Possible mechanisms and consequences of the Ca²⁺ oscillations are discussed.

http://ift.tt/2du66rv

A noninvasive swallowing measurement system using a combination of respiratory flow, swallowing sound, and laryngeal motion

Abstract

The assessment of swallowing function is important for the prevention of aspiration pneumonia. We developed a new swallowing monitoring system that uses respiratory flow, swallowing sound, and laryngeal motion. We applied this device to 11 healthy volunteers and 10 patients with dysphagia. Videofluoroscopy (VF) was conducted simultaneously with swallowing monitoring using our device. We measured laryngeal rising time (LRT), the time required for the larynx to elevate to the highest position, and laryngeal activation duration (LAD), the duration between the onset of rapid laryngeal elevation and the time when the larynx returned to the lowest position. In addition, we evaluated the coordination between swallowing and breathing. We found that LAD was correlated with a VF-derived parameter, pharyngeal response duration (PRD) in healthy subjects (LAD: 959 ± 259 ms vs. PRD: 1062 ± 149 ms, r = 0.60); however, this correlation was not found in the dysphagia patients. LRT was significantly prolonged in patients (healthy subjects: 320 ± 175 ms vs. patients: 465 ± 295 ms, P < 0.001, t test). Furthermore, frequency of swallowing immediately after inspiration was significantly increased in patients. Therefore, the new device may facilitate the assessment of some aspects of swallowing dysfunction.

http://ift.tt/2d9g1Rd

Cost-Effectiveness Analysis of Tyrosine Kinase Inhibitors for Patients with Advanced Gastrointestinal Stromal Tumors

Abstract

Introduction

The management of advanced gastrointestinal stromal tumors (GISTs) has been modified considerably by the availability of costly tyrosine kinase inhibitors (TKIs); however, the best therapeutic sequence in terms of cost and effectiveness remains unknown.

Objective

The aim of this study was to compare four potential strategies (reflecting the potential daily practice), each including imatinib 400 mg/day, as first-line treatment: S1 (imatinib₄₀₀/best supportive care [BSC]); S2 (imatinib₄₀₀/imatinib₈₀₀/BSC); S3 (imatinib₄₀₀/sunitinib/BSC); and S4 (imatinib₄₀₀/imatinib₈₀₀/sunitinib/BSC).

Methods

A Markov model was developed with a hypothetical cohort of patients and a lifetime horizon. Transition probabilities were estimated from the results of clinical trials. The analysis was performed from the French payer perspective, and only direct medical costs were included. Clinical and economic parameters were discounted, and the robustness of results was assessed.

Results

The least costly and effective strategy was S1, at a cost of €65,744 for 32.9 life months (reference). S3 was the most cost-effective strategy, with an incremental cost-effectiveness ratio (ICER) of €48,277/life-year saved (LYS). S2 was dominated, and S4 yielded an ICER of €363,320/LYS compared with S3. Sensitivity analyses confirmed the robustness of these results; however, when taking into account a price reduction of 80 % for imatinib, S2 and S4 become the most cost-effective strategies.

Conclusion

Our approach is innovative to the extent that our analysis takes into account the sequential application of TKIs. The results suggest that the S1 strategy is the best cost-effective strategy, but a price reduction of imatinib impacts on the results. This approach must continue, including new drugs and their impact on the quality of life of patients with advanced GISTs.

http://ift.tt/2cwriNy

Regulation of the NLRP3 inflammasome in Porphyromonas gingivalis -accelerated periodontal disease

Abstract

Objective

Porphyromonas gingivalis is involved in the pathogenesis of chronic inflammatory periodontal disease. Recent studies have suggested that the NLRP3 inflammasome plays an important role in the development of chronic inflammation. We investigated a possible association between the inflammasome in gingival inflammation and bone loss induced by P. gingivalis infection using NLRP3-deficient mice.

Methods

Wild-type and NLRP3-deficient mice were injected orally with P. gingivalis. We assessed alveolar bone loss, expression of pro-interleukin (IL)-1β, pro-IL-18, receptor activator of nuclear factor kappa-B ligand (RANKL), and osteoprotegerin (OPG) in gingival tissue, as well as IL-1β, IL-18, and IL-6 production and caspase-1 activity in peritoneal macrophages.

Results

Porphyromonas gingivalis challenge significantly increased alveolar bone loss; gingival gene expression of pro-IL-1β, pro-IL-18, and RANKL; production of IL-1β, IL-18, and IL-6; and caspase-1 activity in peritoneal macrophages of wild-type mice, but did not affect NLRP3-deficient mice. Meanwhile, OPG mRNA expression in gingival tissue and peritoneal IL-6 production were significantly higher in NLRP3-knockout mice.

Conclusions

Porphyromonas gingivalis activated innate immune cells via the NLRP3 inflammasome. These results suggest that the NLRP3 inflammasome, followed by a response from the IL-1 family, is critical in periodontal disease induced by wild-type P. gingivalis challenge via sustained inflammation.

http://ift.tt/2dkcO4y

Clinical Pharmacokinetics and Pharmacodynamics of Safinamide

Abstract

The symptoms of Parkinson's disease (PD) reflect disruptions of a number of brain neurotransmitter systems of varying type and degree. Pharmacological agents with multiple neurochemical mechanisms of action are therefore promising candidates for countering these problems and providing comprehensive symptomatic relief for patients. The pharmacological profile of safinamide includes reversible monoamine oxidase B inhibition, blockage of voltage-dependent Na⁺ channels, modulation of Ca²⁺ channels, and inhibition of glutamate release. Safinamide is administered once daily at oral doses of 50–100 mg; it is well-tolerated and safe. Clinical trials have found that it ameliorates motor symptoms when added to established levodopa or single dopamine receptor agonist therapy. The future role of safinamide in PD may be that it enables a reduction in the dosage of dopamine replacement therapies, thereby reducing the adverse effects associated with these treatments. The clinical convenience (once-daily administration), safety, and tolerability of safinamide are better than those of dopamine receptor agonists. The introduction of safinamide reflects a change of approach to drug development for anti-parkinsonian agents in that its broad spectrum of action corresponds to the multiple heterogeneous alterations of brain neurochemistry in PD, rather than being targeted at a single receptor type or neurochemical process. Safinamide is a promising new instrument for the effective symptomatic therapy of PD.

http://ift.tt/2d1mSNR

Evaluation of Concomitant Antiretrovirals and CYP2C9/CYP2C19 Polymorphisms on the Pharmacokinetics of Etravirine

Abstract

Background

Etravirine is a non-nucleoside reverse transcriptase inhibitor indicated in combination with other antiretrovirals for treatment-experienced HIV patients ≥6 years of age. Etravirine is primarily metabolized by cytochrome P450 (CYP) 2C9, CYP2C19, and CYP3A. This analysis determined the impact of concomitant antiretrovirals and CYP2C9/CYP2C19 phenotype on the pharmacokinetics of etravirine.

Methods

We used 4728 plasma concentrations from 817 adult subjects collected from four clinical studies to develop the population pharmacokinetic model. The presence of atazanavir/ritonavir, lopinavir/ritonavir, darunavir/ritonavir, tenofovir disoproxil fumarate, or enfuvirtide together with the CYP2C9 and CYP2C19 phenotype and other demographics were evaluated.

Results

A one-compartment model with first-order input and a lag-time best described the data. Estimates of apparent total clearance (CL/F), apparent central volume of distribution (V _c/F), first-order absorption rate constant (k _a), and absorption lag-time were 41.7 L/h, 972 L, 1.16 h, and 1.32 h, respectively. Estimates of between-subject variability on CL/F, V _c/F, and relative bioavailability (F) were 39.4 %CV (percentage coefficient of variation), 35.9 %CV and 35.5 %CV, respectively. Between-occasion variability on F was estimated to be 30.0 %CV. CL/F increased non-linearly with body weight and creatinine clearance (CL_CR), and also varied based on CYP2C9/CYP2C19 phenotype.

Conclusions

In this analysis, body weight, CL_CR, and CYP2C9/CYP2C19 phenotype were found to describe some of the variability in CL/F. It was not possible to show an impact of concomitant antiretrovirals on the pharmacokinetics of etravirine for adults predominantly taking coadministered boosted protease inhibitors as a background antiretroviral regimen.

http://ift.tt/2drxV0Z

Symbolization of dynamic data-driven systems for signal representation

Abstract

The underlying theory of symbolic time series analysis (STSA) has led to the development of signal representation tools in the paradigm of dynamic data-driven application systems (DDDAS), where time series of sensor signals are partitioned to obtain symbol strings that, in turn, lead to the construction of probabilistic finite state automata (PFSA). Although various methods for construction of PFSA from symbol strings have been reported in literature, similar efforts have not been expended on identification of an appropriate alphabet size for partitioning of time series, so that the symbol strings can be optimally or suboptimally generated in a specified sense. The paper addresses this critical issue and proposes an information-theoretic procedure for partitioning of time series to extract low-dimensional features, where the key idea is suboptimal identification of boundary locations of the partitioning segments via maximization of the mutual information between the state probability vector of PFSA and the members of the pattern classes. Robustness of the symbolization process has also been addressed. The proposed alphabet size selection and time series partitioning algorithm have been validated by two examples. The first example addresses parameter identification in a simulated Duffing system with sinusoidal input excitation. The second example is built upon an ensemble of time series of chemiluminescence data to predict lean blowout (LBO) phenomena in a laboratory-scale swirl-stabilized combustor apparatus.

http://ift.tt/2cDiaFp

Random bounce algorithm: real-time image processing for the detection of bats and birds

Abstract

Wind energy plants generate an impact on wildlife with significant fatality rates for various bat and bird species, e.g. due to a collision with the rotor blades. Monitoring approaches, such as vision-based systems, are needed to reduce their mortality by means of an optimized turbine control strategy as soon as flying animals are detected. Since manual analysis of the video data is ineffective, automatic video processing with real-time capabilities is required. In this paper, we propose the random bounce algorithm (RBA) as a novel real-time image processing method for vision-based detection of bats and birds. The RBA is combined with object tracking in order to extract flight trajectories. Its performance is compared with connected components object detection. Results from a laboratory flight tunnel as well as from a field study at a 2 MW wind energy plant in Southern Germany will be presented and discussed. We have successfully detected and tracked objects both in laboratory experiments with many animals and in field experiments with individual animals at a frame rate of 10 fps.

http://ift.tt/2dahWTI

Supervised bilateral two-dimensional locality preserving projection algorithm based on Gabor wavelet

Abstract

Bilateral two-dimensional locality preserving projection (B2DLPP) is an effective method for unsupervised linear dimensionality reduction, which directly extracts face features from image matrices based on locality criterion. Motivated by B2DLPP, this paper proposes a supervised bilateral two-dimensional locality preserving projection (SB2DLPP). Different from B2DLPP, the proposed method takes into account the class information when constructing the similarity matrix. It increases inter-class distance in the projection space so that better right and left-projection matrices are obtained. Furthermore, a Gabor-based supervised bilateral two-dimensional locality preserving projection method is proposed for face recognition. Gabor wavelet representations are adopted for face images to make the proposed method robust to illumination variations and facial expression changes. Then, SB2DLPP is applied to reduce feature dimension. The performance of the proposed method is evaluated and compared with other traditional face recognition schemes on the FERET, Yale and JAFFE databases. The experiment results demonstrate the effectiveness and superiority of the proposed approach.

http://ift.tt/2cDhMXx

No-reference image quality assessment in complex-shearlet domain

Abstract

The field of image quality measure (IQM) is growing rapidly in recent years. In particular, there was a significant progress in no-reference (NR) IQM methods. Natural scenes have certain statistical properties which vary in the presence of distortion. The statistical changes represent the loss of naturalness and can be efficiently quantified using shearlet transformation of images. In this paper, a general-purpose NR IQM approach is proposed based on the statistical characteristics of natural images in shearlet domain. The method utilizes a set of distortion-sensitive features extracted from statistical properties of shearlet coefficients. Phase and amplitude of an image contain important perceptual information; therefore, a complex version of the shearlet transform is employed to take advantage of phase and amplitude features in quality estimation. In quality prediction step, the features are used to train image classification and quality prediction models using a support vector machine. The experimental results show that the proposed NR IQM is highly correlated with subjective assessment and outperforms several full-reference and state-of-art NR IQMs.

http://ift.tt/2dahvZD

Efficiency of texture image filtering and its prediction

Abstract

Textures are typical elements of natural scene images widely used in pattern recognition and image classification. Noise, often being present in acquired images, deteriorates texture features (characteristics), and it is desirable both to suppress it and to preserve a texture. This task is quite difficult even for the most advanced filters, and the resulting denoising efficiency can be quite low. Due to this, it is desirable to predict a denoising efficiency before filtering to decide whether it is worth filtering a given image or not. In this paper, we analyze several quantitative criteria (metrics) that can characterize filtering efficiency. Prediction strategy is described and its accuracy is studied. Several modern filtering techniques are analyzed and compared. Based on this, practical recommendations are given.

http://ift.tt/2cDiyUq

A quality-on-demand electrocardiogram signal compression using modified set partitioning in hierarchical tree

Abstract

Biomedical signals enfold much crucial clinical information. Cardiac imperfection includes information on the morphology of its electrical signals. These signals are classically recorded over a considerable period, so the size of data file becomes bulky and hence compression is essential. This paper focuses on the implementation of electrocardiogram signal compression using wavelet-based progressive coding such as set partitioning in hierarchical tree and its modified version to achieve improvement in the speed at low bit rate. We obtained compression ratio up to 22:1 for MIT-BIH arrhythmia database record number 117 with a percent mean square difference of 0.9 and 0.73 % using orthogonal and biorthogonal wavelets, respectively. The coders accomplish bit rate control and produce a bit stream that is progressive in quality. It facilitates the user to trim the bit stream at desired point and make required quality restoration for the reduced file size with user-defined compression ratio or bit rate.

http://ift.tt/2daiPvf

Two-channel perfect reconstruction (PR) quadrature mirror filter (QMF) bank design using logarithmic window function and spline function

Abstract

In this work, two-channel perfect reconstruction quadrature mirror filter (QMF) bank has been proposed based on the prototype filter using windowing method. A novel window function based on logarithmic function along with the spline function is utilized for the design of prototype filter. The proposed window has a variable parameter ' \(\alpha \) ', which varies the peak side lobe level and rate of fall-off side lobe level which in turn affects the peak reconstruction error (PRE) and amplitude distortion ( \(e_{am}\) ) of the QMF bank . The transition width of the prototype is controlled by the spline function using the parameter ' \(\mu \) '. The perfect reconstruction condition is satisfied by setting the cutoff frequency ( \(\omega _{c}\) ) of the prototype low-pass filter at ' \(\pi /2\) '. The performance of the proposed design method has been evaluated in terms of mean square error in the pass band, mean square error in the stop band, first side lobe attenuation ( \(A_{1}\) ), peak reconstruction error (PRE) and amplitude error ( \(e_{am}\) ) for different values of ' \(\alpha \) ' and ' \(\mu \) '. The results are provided and compared with the existing methods.

http://ift.tt/2cDi5l2

Multi-frame real image restoration based on double loops with alternative maximum likelihood estimation

Abstract

A multi-frame blind restoration algorithm based on alternative maximum likelihood estimation using double loops is proposed to restore object images. An anisotropic regularization term is incorporated into the integral likelihood function to avoid over-smoothing of details of the restored images and improve the stability of image restoration. In order to make full use of the data relationship in the observed multi-frame images which contain the same objects with different point spread functions (PSF) in a short sequence, an iterative strategy based on double loops is employed in estimating the unknown different PSFs of the observed images. Experiments on synthetic and real turbulence-degraded images illustrate that the proposed algorithm is effective in restoring real turbulence-degraded images by using very few frames.

http://ift.tt/2dai7y8

Single-image super-resolution using kernel recursive least squares

Abstract

Online single-image super-resolution of an image has been obtained here. The high-resolution image is constructed from a dictionary of features that approximately spans the subspace of regression. This paper classifies the low-resolution image using the kernel k-means clustering algorithm and makes an extensive study using the approximate linear dependence kernel recursive least square and sliding window kernel recursive least squares for super-resolving the image from the existing low- and high-resolution images. The super-resolution using kernel recursive least square significantly provides an improvement up on the support vector regression solution, both in terms of speed, dictionary samples and also gives a better PSNR value.

http://ift.tt/2cDhUpO

Frame-level bit allocation for hierarchical coding of H.265/HEVC considering dependent rate-distortion characteristics

Abstract

Rate control plays an important role in video coding for rectifying the coded bit stream to meet the transmission bandwidth, which is related to two parts of bit allocation and quantization parameter acquirement. Considering that the bit allocation is a critical step due to its effect on the subsequent coding operation and rate-distortion performance, therefore in this paper an accurate H.265/HEVC frame-level bit allocation algorithm is proposed for higher coding efficiency. Concretely the feature regarding the inter-frame dependency is firstly analyzed based on the theoretical derivation. Then the hierarchically dependent characteristics are extracted and utilized to establish the bit allocation model. Experimental results show that the proposed method can guarantee a good consistency between the target bits and coded bits, where a PSNR improvement of about 0. 131 dB can be observed compared with the original H.265/HEVC bit allocation while keeping the same bit rate.

http://ift.tt/2dain05

Nonlinear smoothing of N -dimensional data using successive over-relaxation method

Abstract

Local smoothing of N-dimensional data can be performed in many ways. This paper is oriented to local penalization and its minimization which generates a system of nonlinear equations. This approach enables to realize trade-off between denoising, edge, and structure preserving. This is mainly useful in the case of discontinuous signals and images. Various penalization strategies can be used for this task, but only constrained penalizations (Tukey, Welsch, Andrews) are successful. Novel nonlinear method is inspired by successive over-relaxation scheme for linear systems of equations, but it is applied to nonlinear root-finding problem. The method is designed to be stable for several smoother types. Root bracketing inside inner loop is included in the procedure and extends the stability range in many applications. Numerical experiments are performed on 1D signal and 2D image. Optimum relaxation factors are found experimentally for maximum rate of convergence. The main results of experimental part are: preference of Tukey method in the case of discontinuous signal, similarity of proposed methods in the case of continuous signal, and efficiency of Tukey method followed by watershed transform in the case of image segmentation. Selected smoothers are recommended mainly for signals and images with discontinuities and can be useful in signal and image enhancement, analysis, segmentation, and classification.

http://ift.tt/2cDiTWX

Uncertainty principles for discrete signals associated with the fractional Fourier and linear canonical transforms

Abstract

The fractional Fourier transform (FRFT), which generalizes the classical Fourier transform, has gained much popularity in recent years because of its applications in many areas, including optics, radar, and signal processing. There are relations between duration in time and bandwidth in fractional frequency for analog signals, which are called the uncertainty principles of the FRFT. However, these relations are only suitable for analog signals and have not been investigated in discrete signals. In practice, an analog signal is usually represented by its discrete samples. The purpose of this paper is to propose an equivalent uncertainty principle for the FRFT in discrete signals. First, we define the time spread and the fractional frequency spread for discrete signals. Then, we derive an uncertainty relation between these two spreads. The derived results are also extended to the linear canonical transform, which is a generalized form of the FRFT.

http://ift.tt/2daiPf5

Homotopy deform method for reproducing kernel space for nonlinear boundary value problems

Abstract

In this paper, the combination of homotopy deform method (HDM) and simplified reproducing kernel method (SRKM) is introduced for solving the boundary value problems (BVPs) of nonlinear differential equations. The solution methodology is based on Adomian decomposition and reproducing kernel method (RKM). By the HDM, the nonlinear equations can be converted into a series of linear BVPs. After that, the simplified reproducing kernel method, which not only facilitates the reproducing kernel but also avoids the time-consuming Schmidt orthogonalization process, is proposed to solve linear equations. Some numerical test problems including ordinary differential equations and partial differential equations are analysed to illustrate the procedure and confirm the performance of the proposed method. The results faithfully reveal that our algorithm is considerably accurate and effective as expected.

http://ift.tt/2dhOWhx

Reduced Port Laparoscopic Cholecystectomy: Single and a Half Incision Lap Chole

Abstract

Laparoscopic cholecystectomy has almost replaced the age-old procedure of open cholecystectomy for gall stone disease. Further attempts are made to reduce the number of ports to give maximum benefits of minimally invasive surgery. The author has developed a technique where 10-mm port in supraumbilical area and 5-mm port in epigastric area are used and hence the nomenclature of single and a half incision laparoscopic cholecystectomy. It is different from two-port laparoscopic cholecystectomy where the second port is 10 mm. In total, 69 cases are performed without any complication. Conclusion: In our technique of single and a half incision laparoscopic cholecystectomy patients' safety is as much as in a conventional four-port surgery. Surgeon is comfortable to perform this operation. Cosmetically, it is better than four-port laparoscopic cholecystectomy without increase in cost. So, in our opinion, our technique should be acceptable to all surgeons and can give benefits of minimal access surgery to masses of people.

http://ift.tt/2cws4Kk

Long-Term Safety and Efficacy of Subcutaneously Administered Tocilizumab for Adult Rheumatoid Arthritis: A Multicenter Phase 3b Long-term Extension Study

Abstract

Introduction

To assess the long-term safety and efficacy of subcutaneous tocilizumab (TCZ-SC) in US patients with rheumatoid arthritis (RA) who rolled over from the two global phase 3 studies, SUMMACTA (NCT01194414) and BREVACTA (NCT1232569), into this open-label, single-arm, phase 3b study.

Methods

Patients continued to receive TCZ-SC 162 mg weekly or every other week or switched from intravenous TCZ to TCZ-SC 162 mg qw for up to 84 weeks. The primary endpoint was the proportion of patients with serious adverse events (SAEs). Secondary endpoints included clinical efficacy, laboratory abnormalities, and immunogenicity.

Results

Of the 217 patients treated, 76.5% were female, and the mean age was 58.4 years. A total of 23 patients (10.6%) had ≥1 SAE. The most common SAEs were infections (3.7%). Alanine aminotransferase elevations (38.2%) were not associated with hepatic injury. Grade 3/4 neutropenia (3%) was transient and not associated with serious infections. Immunogenicity was low (<1%) and not associated with SAEs. No anaphylaxis or deaths occurred. Thirteen patients (6.0%) withdrew due to safety reasons. Mean Clinical Disease Activity Index and Disease Activity Score in 28 joints remained stable throughout the trial.

Conclusions

The long-term safety of TCZ-SC during the long-term extension period was consistent with the safety profiles from SUMMACTA and BREVACTA, with no new safety signals. Efficacy improvements observed from baseline remained stable over time. These results demonstrated the durability of the safety and efficacy responses, and low immunogenicity, with long-term exposure to TCZ-SC in patients with RA.

Funding: F. Hoffmann-La Roche, Ltd.

Trial registration number: ClinicalTrials.gov identifier, NCT01662063.

http://ift.tt/2dbqgpL

Protozoa graze on the 2,6-dichlorobenzamide (BAM)-degrading bacterium Aminobacter sp. MSH1 introduced into waterworks sand filters

Abstract

Groundwater contamination by pesticide residues often leads to the closure of drinking water wells, making the development of new techniques to remediate drinking water resources of considerable interest. Pesticide-degrading bacteria were recently added to a waterworks sand filter in an attempt to remediate pesticide-polluted drinking water. The density of the introduced bacteria, however, decreased rapidly, which was partly attributed to predation by protozoa in the sand filter. This study investigated the effects of indigenous sand filter protozoa on the population density and degradation efficiency of degrader bacteria introduced into sand from a waterworks sand filter. The 2,6-dichlorobenzamide (BAM)-degrading bacterium Aminobacter sp. MSH1 was used as a model organism. The introduction of MSH1 at high cell densities was followed by a >1000-fold increase in the protozoan population size and at the same time a 29 % reduction in Aminobacter cell numbers. The protozoan population in the systems that had MSH1 added at a lower density only increased 50-fold, and a decrease in Aminobacter numbers was not detectable. Furthermore, a reduction in the number of Aminobacter and in BAM degradation efficiency was seen in flow-through sand filter columns inoculated with MSH1 and fed BAM-contaminated water, when comparing sand columns containing the indigenous microbial filter community, i.e. containing protozoa, to columns with sterilised sand. These results suggest that degrader bacteria introduced into waterworks sand filters are adversely affected by grazing from the indigenous protozoa, reducing the size of the degrader population and the sand filter degradation efficiency.

http://ift.tt/2cNxHjn

A new extracellular von Willebrand A domain-containing protein is involved in silver uptake in Microcystis aeruginosa exposed to silver nanoparticles

Abstract

Silver nanoparticles (AgNPs) can be toxic for cyanobacteria when present at low nanomolar concentrations, but the molecular mechanisms whereby AgNPs (or free Ag⁺ released from AgNPs) interact with these prokaryotic algal cells remain elusive. Here, we studied Ag uptake mechanisms in the prokaryotic cyanobacterium Microcystis aeruginosa exposed to AgNPs by measuring growth inhibition in the absence or presence of high-affinity Ag-binding ligands and by genetic transformation of E. coli with a protein predicted to be involved in Ag uptake. We discovered a new von Willebrand A (vWA) domain-containing protein in M. aeruginosa that mediates Ag uptake from AgNPs when expressed in E. coli. This new Ag transport protein, which is absent in eukaryotic algae, is a potential candidate explaining the higher AgNPs toxicity in cyanobacteria such as M. aeruginosa than that in eukaryotic algae. The present study provides new insights on Ag uptake mechanisms in the prokaryotic algae M. aeruginosa.

http://ift.tt/2dbqY6j

At-line determining spore germination of Penicillium chrysogenum bioprocesses in complex media

Abstract

Spore inoculum quality in filamentous bioprocesses is a critical parameter associated with viable spore concentration (1) and spore germination (2). It influences pellet morphology and, consequently, process performance. The state-of-the-art method to measure viable spore concentration is tedious, associated with significant inherent bias, and not applicable in real-time. Therefore, it is not usable as process analytical technology (PAT). Spore germination has so far been monitored using image analysis, which is hampered by complex medium background often observed in filamentous bioprocesses. The method presented here is based on the combination of viability staining and large-particle flow cytometry which enables measurements in real-time and hence aims to be applicable as a PAT tool. It is compatible with the complex media background and allows the quantification of metabolically active spores and the monitoring of spore germination. A distinction of germinated spores and not germinated spores was based on logistic regression, using multiparameteric data from flow cytometry. In a first step, a significant correlation between colony-forming unit (CFU) counts and viable spore concentration (1) in an industrially relevant model bioprocess was found. Spore germination (2) was followed over the initial process phase with close temporal resolution. The validation of the method showed an error below 5 %. Differences in spore germination for various spore inocula ages and spore inoculum concentrations were monitored. The real-time applicability of the method suggests the implementation as a PAT tool in filamentous bioprocesses.

http://ift.tt/2cNy0uD

Enzyme-free amplification and detection of bovine viral diarrhea virus RNA using hybridization chain reaction and gold nanoparticles

Abstract

A novel bovine viral diarrheal virus (BVDV)-RNA detection method was developed using a combination of the amplification capability of hybridization chain reaction (HCR) with the sensitivity of an unmodified-gold nanoparticle (AuNP) colorimetric detection assay. Two auxiliary probes were designed to target a conserved RNA sequence among the BVDV isolates. The complementary target BVDV-RNA was used as the initiator to trigger a cascade of hybridization events to yield nicked double-helix DNA analogous to the alternating copolymers. DNA in the form of a nicked double helix did not prevent salt-induced aggregation of AuNPs. In contrast, in the absence of the complementary target BVDV-RNA, free hairpins with single-stranded sticky ends adsorbed onto the AuNPs, stabilize them, and prevent salt-induced aggregation of the AuNP. The limit of detection (LOD) for the BVDV-RNA was estimated to be 0.008 tissue culture infective dose (TCID₅₀)/reaction. The method developed was highly selective and specific to detect BVDV isolates in clinical samples. This protocol offers a rapid, simple, and cost-effective assay for detecting BVDV.

http://ift.tt/2dbr666

Characterization of T-DNA insertion mutants with decreased virulence in the entomopathogenic fungus Beauveria bassiana JEF-007

Abstract

The bean bug, Riptortus pedestris, is a major agricultural pest that reduces crop quality and value. Chemical pesticides have contributed to pest management, but resistance to these chemicals has significantly limited their use. Alternative strategies with different modes of action, such as entomopathogenic fungi, are therefore of great interest. Herein, we explored how entomopathogenic fungi can potentially be used to control the bean bug and focused on identifying virulence-related genes. Beauveria bassiana (JEF isolates) were assayed against bean bugs under laboratory conditions. One isolate, JEF-007, showed >80 % virulence by both spray and contact exposure methods. Agrobacterium tumefaciens-mediated transformation (AtMT) of JEF-007 generated 249 random transformants, two of which (B1-06 and C1-49) showed significantly reduced virulence against Tenebrio molitor and R. pedestris immatures. Both species were used for rapid screening of virulence-reduced mutants. The two transformants had different morphologies, conidial production, and thermotolerance than the wild type. To determine the localization of the randomly inserted T-DNA, thermal asymmetric interlaced (TAIL) PCR was conducted and analysis of the two clones found multiple T-DNA insertions (two in B1-06 and three in C1-49). Genes encoding complex I intermediate-associated protein 30 (CIA30) and the autophagy protein (Atg22) were possibly disrupted by the T-DNA insertion and might be involved in the virulence. This work provides a strong platform for future functional genetic studies of bean bug-pathogenic B. bassiana. The genes putatively involved in fungal virulence should be experimentally validated by knockdown in future studies.

http://ift.tt/2cNxMnd

Genetic engineering of probiotic Escherichia coli Nissle 1917 for clinical application

Abstract

Escherichia coli strain Nissle 1917 (EcN) has been used as a probiotic. Genetic engineering has enhanced the utility of EcN in several vaccine and pharmaceutical preparations. We discuss in this mini review the genetics and physical properties of EcN. We also discuss the numerous genetic engineering strategies employed for EcN-based vaccine development, including recombinant plasmid transfer, genetic engineering of cryptic plasmids or the EcN chromosome, EcN bacterial ghosts and its outer membrane vesicles. We also provide a current update on the progress and the challenges regarding the use of EcN in vaccine development.

http://ift.tt/2dbpDMY

Biotransformation of chemical constituents of durian wine with simultaneous alcoholic fermentation by Torulaspora delbrueckii and malolactic fermentation by Oenococcus oeni

Abstract

This work represents the first study on the biotransformation of chemical constituents of durian wine via simultaneous alcoholic fermentation (AF) and malolactic fermentation (MLF) with non-Saccharomyces yeast and lactic acid bacteria (LAB), namely, Torulaspora delbrueckii Biodiva and Oenococcus oeni PN4. The presence of PN4 improved the utilization of sugars but did not affect ethanol production. MLF resulted in the significant degradation of malic acid with corresponding increases in pH and lactic acid. The final concentrations of acetic acid (1.29 g/L) and succinic acid (3.70 g/L) in simultaneous AF and MLF were significantly higher than that in AF (1.05 and 1.31 g/L) only. Compared with AF, simultaneous AF and MLF significantly elevated the levels of aroma compounds with higher levels of higher alcohols (isoamyl alcohol, active amyl alcohol, isobutyl alcohol, and 2-phenylethyl alcohol), acetate esters (ethyl acetate, isoamyl acetate), and ethyl esters (ethyl octanoate, ethyl dodecanoate). All the endogenous volatile sulfur compounds decreased to trace or undetectable levels at the end of fermentation. MLF accentuated the reduction of acetaldehyde and sulfides. The initially absent dipropyl disulfide was formed, then catabolized, especially in simultaneous AF and MLF. This study suggested that the simultaneous AF and MLF of non-Saccharomyces and LAB could modify the volatile compositions and potentially modulate the organoleptic properties of durian wine.

http://ift.tt/2cNxQU9

Exploring the transferase activity of Ffase from Schwanniomyces occidentalis , a β-fructofuranosidase showing high fructosyl-acceptor promiscuity

Abstract

The β-fructofuranosidase from the yeast Schwanniomyces occidentalis (Ffase) produces the prebiotic sugars 6-kestose and 1-kestose by transfructosylation of sucrose, which makes it of biotechnological interest. In this study, the hydrolase and transferase activity of this enzyme was kinetically characterized and its potential to synthesize new fructosylated products explored. A total of 40 hydroxylated compounds were used as potential fructosyl-acceptor alternatives to sucrose. Only 17 of them, including some monosaccharides, disaccharides, and oligosaccharides as well as alditols and glycosides were fructosylated. The best alternative acceptors were the alditols. The major transfer product of the reaction including mannitol was purified and characterized as 1-O-β-d-fructofuranosyl-d-mannitol, whose maximum concentration reached 44 g/L, representing about 7.3 % of total compounds in the mixture and 89 % of all products generated by transfructosylation. The reactions including erythritol produced 35 g/L of an isomer mixture comprising 1- and 4-O-β-d-fructofuranosyl-d-erythritol. In addition, Ffase produced 24 g/L of the disaccharide blastose by direct fructosylation of glucose, which makes it the first enzyme characterized from yeast showing this ability. Thus, novel fructosylated compounds with potential applications in food and pharmaceutical industries can be obtained due to the Ffase fructosyl-acceptor promiscuity.

http://ift.tt/2dbr1iO

Anaerobic digestion of chemically enhanced primary treatment (CEPT) sludge and the microbial community structure

Abstract

The effectiveness and treatment conditions of FeCl₃- and AlCl₃-coagulated municipal sewage sludge from chemically enhanced primary treatment (CEPT) using anaerobic digestion (AD) and the structure of microbial community were investigated. The results based on 297 measurements under different operational conditions demonstrate good average AD performance of CEPT sludge, that is, percent volatile solid reduction of 58 %, specific biogas production (or biogas yield) of 0.92 m³/kg volatile solids (VS) destroyed, and methane content of 65.4 %. FeCl₃ dosing, organic loading rate, temperature, and hydraulic retention time all significantly affected AD performance. FeCl₃ dosing greatly improved specific methane production (methane yield) by 38–54 % and significantly reduced hydrogen sulfide (H₂S) content in biogas (from up to 13,250 to <200 ppm), contributing to higher methane recovery and simplified biogas cleaning for power generation. Metagenomic analysis suggested that anaerobic digesters of both CEPT sludge and combined primary and secondary sludge were dominated by Bacteroidetes, Proteobacteria, Firmicutes, Actinobacteria, Thermotogae, and Chloroflexi. However, Methanomicrobia methanogens were better enriched in the anaerobic digesters of CEPT sludge than in the combined sludge. Further, different sources of CEPT sludge with various chemical properties nurtured shared and unique microbial community composition. Combined, this study supports AD as an efficient technology for CEPT sludge treatment and poses first insights into the microbial community structure.

http://ift.tt/2cNxInC

Conversion of lignin into value-added materials and chemicals via laccase-assisted copolymerization

Abstract

With today's environmental concerns and the diminishing supply of the world's petroleum-based chemicals and materials, much focus has been directed toward alternative sources. Woody biomass presents a promising option due to its sheer abundance, renewability, and biodegradability. Lignin, a highly irregular polyphenolic compound, is one of the major chemical constituents of woody biomass and is the second most abundant biopolymer on Earth, surpassed only by cellulose. The pulp and paper and cellulosic ethanol industries produce lignin on the scale of millions of tons each year as a by-product. Traditionally, lignin has been viewed as a waste material and burned as an inefficient fuel. However, in recent decades, research has focused on more economical ways to convert lignin into value-added commodities, such as biofuels, biomaterials, and biochemicals, thus developing and strengthening the concept of fully integrated biorefineries. Owing to the phenolic structure of lignin, it is possible to enzymatically graft molecules onto its surface using laccases (benzenediol:oxygen oxidoreductases, EC 1.10.3.2) to create exciting novel biomaterials. These environmentally friendly enzymes use oxygen as their only co-substrate and produce water as their sole by-product, and have thus found great industrial application. This mini-review highlights recent advances in the field of laccase-facilitated functionalization of lignin as well as promising future directions for lignin-based polymers.

http://ift.tt/2dbpKIv

Belowground communication: impacts of volatile organic compounds (VOCs) from soil fungi on other soil-inhabiting organisms

Abstract

We reviewed the impact of fungal volatile organic compounds (VOCs) on soil-inhabiting organisms and their physiological and molecular consequences for their targets. Because fungi can only move by growth to distinct directions, a main mechanism to protect themselves from enemies or to manipulate their surroundings is the secretion of exudates or VOCs. The importance of VOCs in this regard has been significantly underestimated. VOCs not only can be means of communication, but also signals that are able to specifically manipulate the recipient. VOCs can reprogram root architecture of symbiotic partner plants or increase plant growth leading to enlarged colonization surfaces. VOCs are also able to enhance plant resistance against pathogens by activating phytohormone-dependent signaling pathways. In some cases, they were phytotoxic. Because the response was specific to distinct species, fungal VOCs may contribute to regulate the competition of plant communities. Additionally, VOCs are used by the producing fungus to attack rivaling fungi or bacteria, thereby protecting the emitter or its nutrient sources. In addition, animals, like springtails, nematodes, and earthworms, which are important components of the soil food web, respond to fungal VOCs. Some VOCs are effective repellents for nematodes and, therefore, have applications as biocontrol agents. In conclusion, this review shows that fungal VOCs have a huge impact on soil fauna and flora, but the underlying mechanisms, how VOCs are perceived by the recipients, how they manipulate their targets and the resulting ecological consequences of VOCs in inter-kingdom signaling is only partly understood. These knowledge gaps are left to be filled by future studies.

http://ift.tt/2cNwskg

Medication adherence in patients with rheumatoid arthritis: why do patients not take what we prescribe?

Abstract

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease which results in extensive articular and extra-articular morbidity and increased mortality from cardiovascular disease. Despite an increasing range of non-biological and biological disease-modifying agents, poor patient adherence with medication is a significant barrier to effective control of the inflammation associated with RA. This review seeks to identify factors that affect patient adherence with medication, examine the effectiveness of interventions to address this issue and offer practical suggestions to improve medication adherence. The impact of health literacy on medication adherence and the novel role of musculoskeletal ultrasound as an educational intervention will also be discussed.

http://ift.tt/2dhNg7O