bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ORF2 glycoprotein of hepatitis E virus inhibits cellular NF-κB activity by blocking ubiquitination mediated proteasomal degradation of IκBα in human hepatoma cells
Authors: Surjit Milan , Varshney Bhavna , Lal Sunil K 
Published: May 2012

AbstractBackgroundNuclear factor kappa B (NF-κB) is a key transcription factor that plays a crucial role in host survival during infection by pathogens. Therefore, it has been a priority of many pathogens to manipulate the cellular NF-κB activity in order to create a favorable environment for their survival inside the host.ResultsWe observed that heterologous expression of the open reading frame 2 (ORF2) protein in human hepatoma cells led to stabilization of the cellular I kappa B alpha (IκBα) pool, with a concomitant reduction in the nuclear localization of the p65 subunit of NF-κB and inhibition of NF-κB activity. Although basal or TPA induced phosphorylation of IκBα was not altered, its ubiquitination was markedly reduced in ORF2 expressing cells. Further analysis revealed that ORF2 protein could directly associate with the F-box protein, beta transducin repeat containing protein (βTRCP) and ORF2 over expression resulted in reduced association of IκBα with the SKP1 and CUL1 components of the SCFβTRCPcomplex. Chromatin immunoprecipitation (ChIP) assay of the proximal promoter regions of MHC-I heavy chain and IL-8 genes using p65 antibody and LPS stimulated ORF2 expressing cell extract revealed decreased association of p65 with the above regions, indicating that ORF2 inhibited p65 binding at endogenous promoters.ConclusionsIn this report we suggest a mechanism by which ORF2 protein of HEV may inhibit host cell NF-κB activity during the course of a viral infection.
Segmentation of corpus callosum using diffusion tensor imaging: validation in patients with glioblastoma
Authors: Nazem-Zadeh Mohammad-Reza , Saksena Sona , Babajani-Fermi Abbas , Jiang Quan , Soltanian-Zadeh Hamid , Rosenblum Mark , Mikkelsen Tom , Jain Rajan 
Published: May 2012

Abstract

Background
This paper presents a three-dimensional (3D) method for segmenting corpus callosum in normal subjects and brain cancer patients with glioblastoma.

Methods
Nineteen patients with histologically confirmed treatment naïve glioblastoma and eleven normal control subjects underwent DTI on a 3T scanner. Based on the information inherent in diffusion tensors, a similarity measure was proposed and used in the proposed algorithm. In this algorithm, diffusion pattern of corpus callosum was used as prior information. Subsequently, corpus callosum was automatically divided into Witelson subdivisions. We simulated the potential rotation of corpus callosum under tumor pressure and studied the reproducibility of the proposed segmentation method in such cases.

Results
Dice coefficients, estimated to compare automatic and manual segmentation results for Witelson subdivisions, ranged from 94% to 98% for control subjects and from 81% to 95% for tumor patients, illustrating closeness of automatic and manual segmentations. Studying the effect of corpus callosum rotation by different Euler angles showed that although segmentation results were more sensitive to azimuth and elevation than skew, rotations caused by brain tumors do not have major effects on the segmentation results.

Conclusions
The proposed method and similarity measure segment corpus callosum by propagating a hyper-surface inside the structure (resulting in high sensitivity), without penetrating into neighboring fiber bundles (resulting in high specificity).
FLJ10540 is associated with tumor progression in nasopharyngeal carcinomas and contributes to nasopharyngeal cell proliferation, and metastasis via osteopontin/CD44 pathway
Authors: Chen Chang-Han , Shiu Li-Yen , Su Li-Jen , Huang Chi-Ying F , Huang Shun-Chen , Huang Chao-Cheng , Yin Yu-Fang , Wang Wei-Sheng , Tsai Hsin-Ting , Fang Fu-Min , Chuang Wan-Chu , Kang Hong-Chang , Hwang Chung-Feng 
Published: May 2012

Abstract

Background
Nasopharyngeal carcinoma (NPC) is well-known for its highly metastatic characteristics, but little is known of its molecular mechanisms. New biomarkers that predict clinical outcome, in particular the ability of the primary tumor to develop metastatic tumors are urgently needed. The aim of this study is to investigate the role of FLJ10540 in human NPC development.

Methods
A bioinformatics approach was used to explore the potentially important regulatory genes involved in the growth/metastasis control of NPC. FLJ10540 was chosen for this study. Two co-expression strategies from NPC microarray were employed to identify the relationship between FLJ10540 and osteopontin. Quantitative-RT-PCR, immunoblotting, and immunohistochemistry analysis were used to investigate the mRNA and protein expression profiles of FLJ10540 and osteopontin in the normal and NPC tissues to confirm microarray results. TW01 and Hone1 NPC cells with overexpression FLJ10540 or siRNA to repress endogenous FLJ10540 were generated by stable transfection to further elucidate the molecular mechanisms of FLJ10540-elicited cell growth and metastasis under osteopontin stimulation.

Results
We found that osteopontin expression exhibited a positive correlation with FLJ10540 in NPC microarray. We also demonstrated comprehensively that FLJ10540 and osteopontin were not only overexpressed in NPC specimens, but also significantly correlated with advanced tumor and lymph node-metastasis stages, and had a poor 5-year survival rate, respectively. Stimulation of NPC parental cells with osteopontin results in an increase in FLJ10540 mRNA and protein expressions. Functionally, FLJ10540 transfectant alone, or stimulated with osteopontin, exhibited fast growth and increased metastasis as compared to vehicle control with or without osteopontin stimulation. Conversely, knockdown of FLJ10540 by siRNA results in the suppression of NPC cell growth and motility. Treatment with anti-CD44 antibodies in NPC parental cells not only resulted in a decrease of FLJ10540 protein, but also affected the abilities of FLJ10540-elicited cell growth and motility in osteopontin stimulated-NPC cells.

Conclusions
These findings suggest that FLJ10540 may be critical regulator of disease progression in NPC, and the underlying mechanism may involve in the osteopontin/CD44 pathway.
Cryopreservation of human vascular umbilical cord cells under good manufacturing practice conditions for future cell banks
Authors: Polchow Bianca , Kebbel Kati , Schmiedeknecht Gerno , Reichardt Anne , Henrich Wolfgang , Hetzer Roland , Lueders Cora 
Published: May 2012

Abstract

Background

In vitro fabricated tissue engineered vascular constructs could provide an alternative to conventional substitutes. A crucial factor for tissue engineering of vascular constructs is an appropriate cell source. Vascular cells from the human umbilical cord can be directly isolated and cryopreserved until needed. Currently no cell bank for human vascular cells is available. Therefore, the establishment of a future human vascular cell bank conforming to good manufacturing practice (GMP) conditions is desirable for therapeutic applications such as tissue engineered cardiovascular constructs.

Materials and methods
A fundamental step was the adaption of conventional research and development starting materials to GMP compliant starting materials. Human umbilical cord artery derived cells (HUCAC) and human umbilical vein endothelial cells (HUVEC) were isolated, cultivated, cryopreserved (short- and long-term) directly after primary culture and recultivated subsequently. Cell viability, expression of cellular markers and proliferation potential of fresh and cryopreserved cells were studied using trypan blue staining, flow cytometry analysis, immunofluorescence staining and proliferation assays. Statistical analyses were performed using Student’s t-test.

Results
Sufficient numbers of isolated cells with acceptable viabilities and homogenous expression of cellular markers confirmed that the isolation procedure was successful using GMP compliant starting materials. The influence of cryopreservation was marginal, because cryopreserved cells mostly maintain phenotypic and functional characteristics similar to those of fresh cells. Phenotypic studies revealed that fresh cultivated and cryopreserved HUCAC were positive for alpha smooth muscle actin, CD90, CD105, CD73, CD29, CD44, CD166 and negative for smoothelin. HUVEC expressed CD31, CD146, CD105 and CD144 but not alpha smooth muscle actin. Functional analysis demonstrated acceptable viability and sufficient proliferation properties of cryopreserved HUCAC and HUVEC.

Conclusion
Adaptation of cell isolation, cultivation and cryopreservation to GMP compliant starting materials was successful. Cryopreservation did not influence cell properties with lasting impact, confirming that the application of vascular cells from the human umbilical cord is feasible for cell banking. A specific cellular marker expression profile was established for HUCAC and HUVEC using flow cytometry analysis, applicable as a GMP compliant quality control. Use of these cells for the future fabrication of advanced therapy medicinal products GMP conditions are required by the regulatory authority.
A novel image de-noising method based on spherical coordinates system
Authors: Zhang Degan , Kang Xuejing , Wang Jinghui 
Published: May 2012

Abstract
In this article, a novel image de-noising method is proposed. This method is based on spherical coordinates system. First, spherical transform is re-defined in wavelet domain, and the properties of the spherical transform in wavelet domain are listed. Then, a new adaptive threshold in spherical coordinate system is presented. It has been proved based on Besov space norm theory. After that, a novel curve shrinkage function is proposed to overcome the limitation of the traditional shrinkage functions. The new function can reach and exceed the true value and enhance the edge of the image. Finally, the multi-scale product in wavelet domain is introduced to spherical coordinates system. This article names the multi-scale product in spherical coordinates system as Multi-Scale Norm Product. The experimental results compared the improved algorithm with other methods from the peak signal-to-noise ratio, mean square error, and running time. The results indicate that improved algorithm is simple and effective.
RASSF1C modulates the expression of a stem cell renewal gene, PIWIL1
Authors: Reeves Mark E , Baldwin Melissa L , Aragon Robert , Baldwin Scott , Chen Shin-Tai , Li Xinmin , Mohan Subburaman , Amaar Yousef G 
Published: May 2012

AbstractBackgroundRASSF1A and RASSF1C are two major isoforms encoded by the Ras association domain family 1 (RASSF1) gene through alternative promoter selection and mRNA splicing. RASSF1A is a well established tumor suppressor gene. Unlike RASSF1A, RASSF1C appears to have growth promoting actions in lung cancer. In this article, we report on the identification of novel RASSF1C target genes in non small cell lung cancer (NSCLC).MethodsOver-expression and siRNA techniques were used to alter RASSF1C expression in human lung cancer cells, and Affymetrix-microarray study was conducted using NCI-H1299 cells over-expressing RASSF1C to identify RASSF1C target genes.ResultsThe microarray study intriguingly shows that RASSF1C modulates the expression of a number of genes that are involved in cancer development, cell growth and proliferation, cell death, and cell cycle. We have validated the expression of some target genes using qRT-PCR. We demonstrate that RASSF1C over-expression increases, and silencing of RASSF1C decreases, the expression of PIWIL1 gene in NSCLC cells using qRT-PCR, immunostaining, and Western blot analysis. We also show that RASSF1C over-expression induces phosphorylation of ERK1/2 in lung cancer cells, and inhibition of the MEK-ERK1/2 pathway suppresses the expression of PIWIL1 gene expression, suggesting that RASSF1C may exert its activities on some target genes such as PIWIL1 through the activation of the MEK-ERK1/2 pathway. Also, PIWIL1 expression is elevated in lung cancer cell lines compared to normal lung epithelial cells.ConclusionsTaken together, our findings provide significant data to propose a model for investigating the role of RASSF1C/PIWIL1 proteins in initiation and progression of lung cancer.
Interspecies differences in membrane-associated protease activities of thyrocytes and their relevance for thyroid cancer studies
Authors: Fröhlich Eleonore , Maier Elke , Wahl Richard 
Published: May 2012

AbstractBackgroundTo understand the role of proteases involved in human thyroid cancer progression and tissue invasion, thyrocytes from other species could potentially be used provided their characteristics are similar. It is not known whether dipeptidyl peptidase IV and aminopeptidase N activities, which are overexpressed in human thyroid cancer, are, as in human, also absent in normal thyrocytes of other species, making them suitable models for studies on the regulation of these proteases.MethodsTo assess the role of these proteases, activity was measured in thyroid tissue of human, mouse, rat, porcine, bovine and ovine origin. The lysosomal protease, dipeptidyl peptidase II, was used for comparison.ResultsMurine, rat, ovine, bovine and human thyrocytes all lacked dipeptidyl peptidase IV and aminopeptidase N activity, but porcine thyrocytes were found to possess both. In contrast, lysosomal dipeptidyl peptidase II was strongly expressed in all species. These activity patterns were maintained in cultured cells. Cultured porcine thyrocytes formed follicles with typical morphology upon stimulation with TSH but differed from human thyrocytes in their response to thiamazole.ConclusionsThese species differences in the expression of dipeptidyl peptidase IV and aminopeptidase N, indicate that porcine thyrocytes cannot be considered appropriate for the study of proteases in human cancer development.
Using an expiratory resistor, arterial pulse pressure variations predict fluid responsiveness during spontaneous breathing: an experimental porcine study
Authors: Dahl Michael K , Vistisen Simon T , Koefoed-Nielsen Jacob , Larsson Anders 
Published: May 2012

Abstract
Introduction
Fluid responsiveness prediction is difficult in spontaneously breathing patients. Because the swings in intrathoracic pressure are minor during spontaneous breathing, dynamic parameters like pulse pressure variation (PPV) and systolic pressure variation (SPV) are usually small. We hypothesized that during spontaneous breathing, inspiratory and/or expiratory resistors could induce high arterial pressure variations at hypovolemia and low variations at normovolemia and hypervolemia. Furthermore, we hypothesized that SPV and PPV could predict fluid responsiveness under these conditions.

Methods
Eight prone, anesthetized and spontaneously breathing pigs (20 to 25 kg) were subjected to a sequence of 30% hypovolemia, normovolemia, and 20% and 40% hypervolemia. At each volemic level, the pigs breathed in a randomized order either through an inspiratory and/or an expiratory threshold resistor (7.5 cmH2O) or only through the tracheal tube without any resistor. Hemodynamic and respiratory variables were measured during the breathing modes. Fluid responsiveness was defined as a 15% increase in stroke volume (ΔSV) following fluid loading.

Results
Stroke volume was significantly lower at hypovolemia compared with normovolemia, but no differences were found between normovolemia and 20% or 40% hypervolemia. Compared with breathing through no resistor, SPV was magnified by all resistors at hypovolemia whereas there were no changes at normovolemia and hypervolemia. PPV was magnified by the inspiratory resistor and the combined inspiratory and expiratory resistor. Regression analysis of SPV or PPV versus ΔSV showed the highest R2 (0.83 for SPV and 0.52 for PPV) when the expiratory resistor was applied. The corresponding sensitivity and specificity for prediction of fluid responsiveness were 100% and 100%, respectively, for SPV and 100% and 81%, respectively, for PPV.

Conclusions
Inspiratory and/or expiratory threshold resistors magnified SPV and PPV in spontaneously breathing pigs during hypovolemia. Using the expiratory resistor SPV and PPV predicted fluid responsiveness with good sensitivity and specificity.
Rapid development of intestinal cell damage following severe trauma: a prospective observational cohort study
Authors: de Haan Jacco J , Lubbers Tim , Derikx Joep P , Relja Borna , Henrich Dirk , Greve Jan-Willem , Marzi Ingo , Buurman Wim A 
Published: May 2012

Abstract
Introduction
Loss of intestinal integrity has been implicated as an important contributor to the development of excessive inflammation following severe trauma. Thus far, clinical data concerning the occurrence and significance of intestinal damage after trauma remain scarce. This study investigates whether early intestinal epithelial cell damage occurs in trauma patients and, if present, whether such cell injury is related to shock, injury severity and the subsequent inflammatory response.

Methods
Prospective observational cohort study in 96 adult trauma patients. Upon arrival at the emergency room (ER) plasma levels of intestinal fatty acid binding protein (i-FABP), a specific marker for damage of differentiated enterocytes, were measured. Factors that potentially influence the development of intestinal cell damage after trauma were determined, including the presence of shock and the extent of abdominal trauma and general injury severity. Furthermore, early plasma levels of i-FABP were related to inflammatory markers interleukin-6 (IL-6), procalcitonin (PCT) and C-reactive protein (CRP).

Results
Upon arrival at the ER, plasma i-FABP levels were increased compared with healthy volunteers, especially in the presence of shock (P < 0.01). The elevation of i-FABP was related to the extent of abdominal trauma as well as general injury severity (P < 0.05). Circulatory i-FABP concentrations at ER correlated positively with IL-6 and PCT levels at the first day (r2 = 0.19; P < 0.01 and r2 = 0.36; P < 0.001 respectively) and CRP concentrations at the second day after trauma (r2 = 0.25; P < 0.01).

Conclusions
This study reveals early presence of intestinal epithelial cell damage in trauma patients. The extent of intestinal damage is associated with the presence of shock and injury severity. Early intestinal damage precedes and is related to the subsequent developing inflammatory response.
Belief Propagation for Min-Cost Network Flow: Convergence and Correctness
Authors: Gamarnik David , Shah Devavrat , Wei Yehua 
Published: May 2012

Distributed, iterative algorithms operating with minimal data structure while performing little computation per iteration are popularly known as message passing in the recent literature. Belief propagation (BP), a prototypical message-passing algorithm, has gained a lot of attention across disciplines, including communications, statistics, signal processing, and machine learning as an attractive, scalable, general-purpose heuristic for a wide class of optimization and statistical inference problems. Despite its empirical success, the theoretical understanding of BP is far from complete. With the goal of advancing the state of art of our understanding of BP, we study the performance of BP in the context of the capacitated minimum-cost network flow problem—a cornerstone in the development of the theory of polynomial-time algorithms for optimization problems and widely used in the practice of operations research. As the main result of this paper, we prove that BP converges to the optimal solution in pseudopolynomial time, provided that the optimal solution of the underlying network flow problem instance is unique and the problem parameters are integral. We further provide a simple modification of the BP to obtain a fully polynomial-time randomized approximation scheme (FPRAS) without requiring uniqueness of the optimal solution. This is the first instance where BP is proved to have fully polynomial running time. Our results thus provide a theoretical justification for the viability of BP as an attractive method to solve an important class of optimization problems.
Tocilizumab for the Treatment of Juvenile Idiopathic Arthritis
Authors: Decelle Kendra , Horton Evan R 
Published: May 2012

OBJECTIVE: To evaluate the pharmacology, clinical efficacy, safety, and role of tocilizumab for the treatment of juvenile idiopathic arthritis. DATA SOURCES: A literature search via MEDLINE through PubMed (1970-December 2011) and International Pharmaceutical Abstracts (1970-December 2011) was performed to identify clinical trials and review articles. The key search terms tocilizumab, anti-interleukin 6, and juvenile idiopathic arthritis were used, with several combinations of terms. Bibliographies of selected articles were examined to identify additional references, and ongoing trials were identified through a review of www.clinicaltrials.gov . STUDY SELECTION AND DATA EXTRACTION: Articles were limited to those published in English and studies in humans. Studies included in the review examined pediatric data in systemic and polyarticular juvenile idiopathic arthritis. Background information was obtained through reviews of literature on a wide variety of autoimmune disease states in both adult and pediatric populations. DATA SYNTHESIS: Tocilizumab is Food and Drug Administration–approved for use in patients aged 2 years and older with systemic juvenile idiopathic arthritis. Tocilizumab was superior to placebo in triggering a symptomatic response during Phase 2 and 3 clinical trials. Tocilizumab was determined to be safe, with only a small number of serious adverse drug events occurring within studies. CONCLUSIONS: Tocilizumab provides expansion of the available options for the treatment of systemic juvenile idiopathic arthritis, specifically in patients who have not responded to conventional therapies. Tocilizumab is relatively well tolerated and has proven efficacy for up to 52 weeks. Further studies are warranted to determine its utility as a first-line option for systemic juvenile idiopathic arthritis as well as its role within the treatment of polyarticular juvenile idiopathic arthritis.
Diffusion-limited aggregation in dry nanocrystal films
Authors: Saba Michele , Quochi Francesco , Orrù Marta , Mura Andrea , Bongiovanni Giovanni 
Published: May 2012

ABSTRACTWe demonstrate that drop cast films of colloidal nanocrystals containing excess surfactants develop aggregation over several weeks after solvent evaporation. Fingered structures, typical of diffusion-limited aggregation, are created because of the residual mobility that nanocrystals retain in the film. We are able to control the aggregation through the concentration of surfactant molecules and the drying temperature of the films.