Polarization-sensitive optical projection tomography for muscle fiber imaging

Optical projection tomography (OPT) is a tool used for three-dimensional imaging of millimeter-scale biological samples, with the advantage of exhibiting isotropic resolution typically in the micron range. OPT can be divided into two types: transmission OPT (tOPT) and emission OPT (eOPT). Compared with eOPT, tOPT discriminates different tissues based on their absorption coefficient, either intrinsic or after specific staining. However, it fails to distinguish muscle fibers whose absorption coefficients are similar to surrounding tissues. To circumvent this problem, in this article we demonstrate a polarization sensitive OPT system which improves the detection and 3D imaging of muscle fibers by using polarized light. We also developed image acquisition and processing protocols that, together with the system, enable the clear visualization of muscles. Experimental results show that the muscle fibers of diaphragm and stomach, difficult to be distinguished in regular tOPT, were clearly displayed in our system, proving its potential use. Moreover, polarization sensitive OPT was fused with tOPT to investigate the stomach tissue comprehensively. Future applications of polarization sensitive OPT could be imaging other fiberlike structures such as myocardium or other tissues presenting high optical anisotropy.This work is supported by the National Basic Research Program of China (973 Program) under Grant 2011CB707700, the National Natural Science Foundation of China under Grant No. 81227901, 61231004, 81501616, 81301346, 81527805 the Chinese Academy of Sciences Fellowship for Young Foreign Scientists under Grant No. 2010Y2GA03, 2013Y1GA0004, the Chinese Academy of Sciences Visiting Professorship for Senior International Scientists under Grant No. 2012T1G0036, 2013T1G0013, the Instrument Developing Project of the Chinese Academy of Sciences under Grant No. YZ201502, YZ201457 and the Strategic Priority Research Program (B) of Chinese Academy of Sciences (XDB02060010). A. Arranz acknowledges support from the Marie Curie Intra-European Fellowship program IEF-2010-275137. J.R. acknowledges support from EC FP7 IMI project PREDICT-TB, the EC FP7 CIG grant HIGH-THROUGHPUT TOMO, and the Spanish MINECO project grant FIS2013-41802-R MESO-IMAGING

Lamivudine plus adefovir is a good option for chronic hepatitis B patients with viral relapse after cessation of lamivudine treatment

<p>Abstract</p> <p>Aim</p> <p>Currently, there is no consensus on the retreatment recommendation of chronic hepatitis B (CHB) patients with viral rebound after cessation of treatment. In the search of reasonable treatment, we compared the efficacy and safety of adefovir (ADV) plus lamivudine (LAM) and LAM alone for the retreatment of patients with viral relapse but without genotypic resistance after cessation of LAM.</p> <p>Methods</p> <p>This is a prospective controlled study, and a total of 53 hepatitis B e antigen (HBeAg)-positive patients with viral rebound but without resistance were received either LAM plus ADV or LAM alone treatment.</p> <p>Results</p> <p>After 1-year treatment, more patients who received LAM plus ADV than those who received LAM alone had ALT normalization (84% versus 53.6%, P = 0.018) or HBV DNA levels below 1000 copies/mL (80% versus 42.9%, P < 0.006). Seven patients receiving LAM plus ADV had HBeAg seroconversion, as compared with 0 in patients receiving ALM alone (28% versus 0%, P = 0.003). During 1-year retreatment, five patients receiving LAM alone had virological breakthrough and all of them had LAM resistance strains (rtM204V/I), while no LAM- or ADV- associated resistance strains were detected in patients receiving LAM plus ADV. All patients receiving LAM plus ADV were well tolerated, and no serious side effects were noted.</p> <p>Conclusions</p> <p>Patients treated with LAM plus ADV exhibited significantly greater virological, biochemical and serological responses compared with LAM alone. These data suggested that combination of LAM plus ADV would be a good option for the retreatment of CHB patients with viral relapse after cessation of LAM.</p

p53 functions as a negative regulator of osteoblastogenesis, osteoblast-dependent osteoclastogenesis, and bone remodeling

p53 is a well known tumor suppressor. We show that p53 also regulates osteoblast differentiation, bone formation, and osteoblast-dependent osteoclast differentiation. Indeed, p53−/− mice display a high bone mass phenotype, and p53−/− osteoblasts show accelerated differentiation, secondary to an increase in expression of the osteoblast differentiation factor osterix, as a result. Reporter assays indicate that p53 represses osterix transcription by the minimal promoter in a DNA-binding–independent manner. In addition, p53−/− osteoblasts have an enhanced ability to favor osteoclast differentiation, in association with an increase in expression of macrophage-colony stimulating factor, which is under the control of osterix. Furthermore, inactivating p53 is sufficient to rescue the osteoblast differentiation defects observed in mice lacking c-Abl, a p53-interacting protein. Thus, these results identify p53 as a novel regulator of osteoblast differentiation, osteoblast-dependent osteoclastogenesis, and bone remodeling

Sulfated tyrosines 27 and 29 in the N-terminus of human CXCR3 participate in binding native IP-10

Aim: Human CXCR3, a seven-transmembrane segment (7TMS), is predominantly expressed in Th1-mediated responses. Interferon-γ-inducible protein 10 (IP-10) is an important ligand for CXCR3. Their interaction is pivotal for leukocyte migration and activation. Tyrosine sulfation in 7TMS is a posttranslational modification that contributes substantially to ligand binding. We aimed to study the role of tyrosine sulfation of CXCR3 in the protein's binding to IP-10. Methods: Plasmids encoding CXCR3 and its mutants were prepared by PCR and site-directed mutagenesis. HEK 293T cells were transfected with plasmids encoding CXCR3 or its variants using calcium phosphate. Transfected cells were labeled with [35S]-cysteine and methionine or [35S]-Na2SO3 and then analyzed by immunoprecipitation to measure sulfation. Experiments with 125I-labeled IP-10 were carried out to evaluate the affinity of CXCR3 for its ligand. Calcium influx assays were used to measure intercellular signal transduction. Results: Our data show that sulfate moieties are added to tyrosines 27 and 29 of CXCR3. Mutation of these two tyrosines to phenylalanines substantially decreases binding of CXCR3 to IP-10 and appears to eliminate the associated signal transduction. Tyrosine sulfation of CXCR3 is enhanced by tyrosyl protein sulfotransferases (TPSTs), and it is weakened by shRNA constructs. The binding ability of CXCR3 to IP-10 is increased by TPSTs and decreased by shRNAs. Conclusions: This study identifies two sulfated tyrosines in the N-terminus of CXCR3 as part of the binding site for IP-10, and it underscores the fact that tyrosine sulfation in the N-termini of 7TMS receptors is functionally important for ligand interactions. Our study suggests a molecular target for inhibiting this ligand-receptor interaction

Phylogenetic and molecular characterization of coxsackievirus A24 variant isolates from a 2010 acute hemorrhagic conjunctivitis outbreak in Guangdong, China

<p>Abstract</p> <p>Background</p> <p>Acute hemorrhagic conjunctivitis is a common disease in China. As a notifiable disease, cases are registered by ophthalmologists on the AHC surveillance system. An AHC outbreak caused by CA24v was observed in Guangdong Province in 2007 by the National Disease Supervision Information Management System. Three years later, a larger outbreak occurred in Guangdong during the August-October period (2010). To characterize the outbreak and compare the genetic diversity of CA24v, which was determined to be the cause of the outbreak, the epidemiology and the molecular characterization of CA24v were analyzed in this study.</p> <p>Results</p> <p>A total of 69,635 cases were reported in the outbreak. 73.5% of index cases originated from students, children in kindergarten and factory workers, with the ≦ 9 age group at the highest risk. The male to female ratio was 1.84:1 among 0-19 years. 56 conjunctival swabs were collected to identify the causative agent from five cities with the AHC outbreak. 30 virus strains were isolated, and two of the genomes had the highest identity values (95.8%) with CA24v genomes. Four CA24v genotypes were identified by phylogenetic analysis for the VP1 and 3C regions. CA24v which caused the outbreak belonged to genotype IV. Furthermore, full nucleotide sequences for four representative isolates in 2010 and 2007 were determined and compared. 20 aa mutations, two nt insertions and one nt deletion were observed in the open reading frame, with 5'- and 3'- UTR respectively between them.</p> <p>Conclusions</p> <p>CA24v was determined to be the pathogen causing the outbreak and belongs to genotype IV. VP1 is more informative than 3C^Profor describing molecular epidemiology and we hypothesize that accumulative mutations may have promoted the outbreak.</p

Intelligent velocity picking considering an expert experience based on the Chan–Vese model and mean-shift clustering

The velocity of seismic data can initially be established by identifying energy clusters on velocity spectra at different moments, which is crucial to the migration imaging and the stacking of common midpoint (CMP) gathers in the seismic data processing. However, the identification of energy clusters currently relies on manual work, with low efficiency and different standards. With the increasing application of wide-frequency, wide-azimuth, and high-density seismic exploration technology, the amount of seismic data has increased significantly, greatly increasing the cost of manual labor and time. In this paper, an intelligent velocity picking method based on the Chan–Vese (CV) model and mean-shift clustering algorithm was proposed. It can be divided into three steps. First, a velocity trend band is set up on the velocity spectrum by experts to avoid multiples and other noises. Then, the velocity trend band is applied to the Chan–Vese model as the initial time condition to segment the velocity spectrum and obtain the velocity candidate region. Finally, mean-shift clustering is adopted to cluster the useful energy clusters retained in the candidate region derived from the Chan–Vese model. When implementing the mean-shift clustering algorithm, the Gaussian kernel function and the energy of the velocity spectrum are utilized to control the efficiency and accuracy of the cluster. The tests of the model and real data prove that the proposed method can dramatically improve the accuracy and efficiency of velocity picking compared with the K-means and manual picking method

Self-adaptive seismic data reconstruction and denoising using dictionary learning based on morphological component analysis

Data reconstruction and data denoising are two critical preliminary steps in seismic data processing. Compressed Sensing states that a signal can be recovered by a series of solving algorithms if it is sparse in a transform domain, and has been well applied in the field of reconstruction, when, sparse representation of seismic data is the key point. Considering the complexity and diversity of seismic data, a single mathematical transformation will lead to incomplete sparse expression and bad restoration effects. Morphological Component Analysis (MCA) decomposes a signal into several components with outstanding morphological features to approximate the complex internal data structure. However, the representation ability of combined dictionaries is constrained by the number of dictionaries, and cannot be self-adaptively matched with the data features. Dictionary learning overcomes the limitation of fixed base function by training dictionaries that are fully suitable for processed data, but requires huge amount of time and considerable hardware cost. To solve the above problems, a new dictionary library (K-Singluar Value Decomposition learning dictionary and Discrete Cosine Transform dictionary) is hereby proposed based on the efficiency of fixed base dictionary and the high precision of learning dictionary. The self-adaptive sparse representation is achieved under the Morphological Component Analysis framework and is successfully applied to the reconstruction and denoising of seismic data. Real data tests have proved that the proposed method performs better than single mathematical transformation and other combined dictionaries

The density of macrophages in the invasive front is inversely correlated to liver metastasis in colon cancer

<p>Abstract</p> <p>Background</p> <p>Although an abundance of evidence has indicated that tumor-associated macrophages (TAMs) are associated with a favorable prognosis in patients with colon cancer, it is still unknown how TAMs exert a protective effect. This study examined whether TAMs are involved in hepatic metastasis of colon cancer.</p> <p>Materials and methods</p> <p>One hundred and sixty cases of pathologically-confirmed specimens were obtained from colon carcinoma patients with TNM stage IIIB and IV between January 1997 and July 2004 at the Cancer Center of Sun Yat-Sen University. The density of macrophages in the invasive front (CD68TF_Hotspot) was scored with an immunohistochemical assay. The relationship between the CD68TF_Hotspotand the clinicopathologic parameters, the potential of hepatic metastasis, and the 5-year survival rate were analyzed.</p> <p>Results</p> <p>TAMs were associated with the incidence of hepatic metastasis and the 5-year survival rate in patients with colon cancers. Both univariate and multivariate analyses revealed that the CD68TF_Hotspotwas independently prognostic of survival. A higher 5-year survival rate among patients with stage IIIB after radical resection occurred in patients with a higher macrophage infiltration in the invasive front (81.0%) than in those with a lower macrophage infiltration (48.6%). Most importantly, the CD68TF_Hotspotwas associated with both the potential of hepatic metastasis and the interval between colon resection and the occurrence of hepatic metastasis.</p> <p>Conclusion</p> <p>This study showed evidence that TAMs infiltrated in the invasive front are associated with improvement in both hepatic metastasis and overall survival in colon cancer, implying that TAMs have protective potential in colon cancers and might serve as a novel therapeutic target.</p

SUSY-Induced Top Quark FCNC Processes at Linear Colliders

In the Minimal Supersymmetric Model (MSSM) the hitherto unconstrained flavor mixing between top-squark and charm-squark will induce the flavor-changing neutral-current (FCNC) interaction between top quark and charm quark, which then give rise to various processes at the next generation linear collider (NLC), i.e., the top-charm associated productions via $e^+ e^-$, $e^- \gamma$ and $\gamma \gamma$ collisions as well as the top quark rare decays $t \to c V$ ($V=g$, $\gamma$ or $Z$). All these processes involve the same part of the parameter space of the MSSM. Through a comparative analysis for all these processes at the NLC, we found the best channel to probe such SUSY-induced top quark FCNC is the top-charm associated production in $\gamma \gamma$ collision, which occurs at a much higher rate than $e^+ e^-$ or $e^- \gamma$ collision and may reach the detectable level for some part of the parameter space. Since the rates predicted by the Standard Model are far below the detectable level, the observation of such FCNC events would be a robust indirect evidence of SUSY.Comment: 12 pages, 8 figures (more refs added, discussions extended

A Y-shape connection device for pediatric patients with an indwelling catheter (Dia = 8Fr) during urodynamic studies, especially for filling phase measurements: a single-center prospective study for safety and effectiveness

IntroductionThis prospective study aimed to assess the effectiveness of a Y-shape connection device in reducing pain and bleeding in pediatric patients with indwelling catheters during urodynamic studies (UDS), while also obtaining effective results in the filling phase.MethodsA total of 45 pediatric patients with a mean age of 13 years were included, all of whom underwent both a UDS with the Y-shape connection device (Method A) and a standard UDS procedure (Method B).ResultsThe Y-shape connection device demonstrated similar overall urodynamic parameters compared to the standard procedure, while also resulting in significantly less bleeding (P = 0.006) and lower VAS scores during (1.12 ± 0.58 vs. 3.88 ± 1.01, P = 0.001) and after (0.12 ± 0.08 vs 2.91 ± 0.89, P = 0.001) the procedure. No adverse events were reported at the 1-month follow-up.DiscussionThese findings suggest that the Y-shape connection device can effectively reduce pain and bleeding during and after UDS in pediatric patients with indwelling catheters (Dia = 8Fr), while also obtaining effective results in the filling phase. Therefore, this Y-shape connection device has a more significant value for children who require urodynamic studies and place more emphasis on filling phase parameters.Clinical trial registrationChiCTR2300068280