Monoclonal antibody against cadherin-17 as a potential treatment for liver cancer

This journal suppl. entitled: Abstracts of The International Liver Congress™ 2012 – 47th annual meeting of the European Association for the Study of the Liver / Poster AbstractsBACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is a major type of liver cancer associated with high mortality. Prognosis is poor in HCC patients largely because of late diagnosis and limitations in treatment options. Therefore, this study aims to identify alternative target for HCC in hope to offer new treatments to patients. Cadherin-17 (CDH17) has been identified as an oncofetal molecule of HCC and that a suppression of its expression by RNA interference (RNAi) leads to anti-tumorigenesis. To supplement the drawbacks associated with the use of RNAi approach in biotherapy, we developed specific antibody against CDH17 for achieving similar purpose. METHODS: Hybridoma cell clones capable of secreting antibodies ...postprin

Quantitative analysis of the stratigraphic architecture of incised-valley fills: a global comparison of Quaternary systems

Facies models of the internal fills of incised valleys developed in shelf and coastal settings during cycles of relative sea-level change are largely conceptual, descriptive and qualitative in form; moreover, they are commonly bespoke to individual examples. Here, a database-driven quantitative statistical analysis of 87 late-Quaternary incised-valley fills (IVFs) has been undertaken to assess the general validity and predictive value of classical facies models for IVFs, and to investigate the relative importance of possible controls on their stratigraphic organization. Based on datasets from the published literature stored in a sedimentological database, the geometry and proportion of systems tracts, and of architectural elements of different hierarchies within IVFs are quantified. These variables were analysed to assess how they vary in relation to parameters that represent potential controlling factors: relative sea-level stage, continental-margin type, drainage-basin area, valley geometry, basin physiography and shoreline hydrodynamics. The stratigraphic organization of the studied coastal-plain IVFs is generally consistent with that represented in facies models, the primary control being the rate and magnitude of relative sea-level change. However, results from this study demonstrate significant variability in the stratigraphic architectures of IVFs, which is not accounted for by existing models. Variations in the facies architecture of coastal-plain and cross-shelf valley fills can be attributed to controls other than sea level, and expressed in relationships with continental-margin type, basin physiography, catchment area, river-system size and shoreline hydrodynamics. The following primary findings arise from this research. (i) Compared to their counterparts on passive margins, coastal-plain IVFs hosted on active margins contain, on average, a higher proportion of fluvial deposits and a lower proportion of central-basin estuarine deposits; estuarine deposits tend however to be thicker. This suggests a control on IVF stratigraphic architecture exerted by distinct characteristics of the tectonic setting of the host continental margins, notably basin physiography, rates and mode of sediment supply, and nature of sediment load. (ii) The thickness and proportion of lowstand systems tract are positively correlated with coastal-plain IVF dimensions, likely reflecting the role of drainage-basin area in dictating the scale of the fluvial systems that carved and infilled the valleys. (iii) Positive correlations are observed between the thickness of fluvial deposits, bayhead-delta deposits and central-basin estuarine deposits, versus coastal-plain IVF dimensions and valley catchment area. This suggests a control exerted by the river-system scale on sediment-supply rates and on the accommodation determined by valley size. (iv) Positive correlations between the thickness and proportion of barrier-complex deposits within cross-shelf IVFs versus mean shelf gradient indicate that the geometry of the shelf might control the establishment and preservation of barrier-island environments in incised valleys located on the shelf. (v) Correlations between the width of coastal-plain IVFs and present-day mean tidal range at the shoreline indicate that tidal dynamics may contribute to the widening of the incised valleys. Positive correlation is observed between the proportion of tide-dominated elements in highstand IVF deposits and IVF width, suggesting possible effects of interplays between hydrodynamic conditions and the geometry of incised valleys on their infills. This study highlights the complexity of the internal fills of incised valleys, which must be considered when attempting the application of facies models of IVFs to rock-record interpretations or as predictive tools in subsurface studies

Neogene-Quaternary post-rift tectonic reactivation of the Bohai Bay Basin, eastern China

Bohai Bay Basin, located in eastern China, is considered a Cenozoic rifted basin. The basin is atypical in terms of its Neogene–Quaternary postrift subsidence history in that it experienced intensive tectonic reactivation, rather than the relative tectonic quiescence experienced during this stage by most rift basins. This Neogene–Quaternary tectonic reactivation arose principally in response to two tectonic events: (1) activity on a dense array of shallow faults and (2) accelerated tectonic subsidence that occurred during the postrift stage. These two events were neither strictly temporally nor spatially equivalent. The dense array of shallow faults form a northwest–southeast-trending belt in the central part of the basin, with displacement induced by the reactivation of older northeast- and northwest-trending basement faults and an associated substantial component of strike-slip displacement occurring after 5.3 Ma. The intensive reactivation of these faults contributed to the atypically accelerated rate of postrift tectonic subsidence of the basin that commenced ca. . However, this was not the sole cause of this accelerated tectonic subsidence: A combination of geological activity deep within the crust led to the buildup of intraplate stresses, and this, combined with ongoing thermal subsidence, acted as an additional contributory factor that drove unusually high rates of subsidence for this basin. This episode of accelerated postrift tectonic reactivation resulted in conditions favorable for hydrocarbon accumulation

Comparative single dose pharmacokinetics and metabolism of racemic primaquine and its enantiomers in human volunteers

Primaquine (PQ) is a racemic drug used in treatment of malaria for six decades. Recent studies suggest that the two enantiomers of PQ are differentially metabolized in animals, and this results in different pharmacological and toxicological profiles. The current study characterizes the pharmacokinetic (PK) properties, metabolism and tolerability of the individual enantiomers of PQ in healthy human volunteers with normal glucose-6-phosphate dehydrogenase (G6PD) activity. Two cohorts (at two dose levels), each with 18 subjects, participated in three study arms in a crossover fashion: a single dose of the (−)-R enantiomer (RPQ), a single dose of the (+)-S enantiomer (SPQ), and a single dose of racemic PQ (RSPQ). PQ and its key metabolites carboxyprimaquine (cPQ) and PQ-N-carbamoyl glucuronide (PQ-N-CG) were analyzed. Clear differences were observed in PK and metabolism of the two enantiomers. Relative PQ exposure was higher with SPQ as compared to RPQ. PQ maximum plasma concentration (Cmax) and area under the plasma concentration-time curve were higher for SPQ, while the apparent volume of distribution and total body clearance were higher for RPQ. Metabolism of the two enantiomers showed dramatic differences: plasma PQ-N-CG was derived solely from SPQ, while RPQ was much more efficiently converted to cPQ than was SPQ. Cmax of cPQ and PQ-N-CG were 10 and 2 times higher, respectively, than the parent drugs. The study demonstrates that the PK properties of PQ enantiomers show clear differences, and metabolism is highly enantioselective. Such differences in metabolism suggest potentially distinct toxicity profiles in multi-dose regimens, especially in G6PD-deficient subjects

Cell sorting in a Petri dish controlled by computer vision.

Fluorescence-activated cell sorting (FACS) applying flow cytometry to separate cells on a molecular basis is a widespread method. We demonstrate that both fluorescent and unlabeled live cells in a Petri dish observed with a microscope can be automatically recognized by computer vision and picked up by a computer-controlled micropipette. This method can be routinely applied as a FACS down to the single cell level with a very high selectivity. Sorting resolution, i.e., the minimum distance between two cells from which one could be selectively removed was 50-70 micrometers. Survival rate with a low number of 3T3 mouse fibroblasts and NE-4C neuroectodermal mouse stem cells was 66 +/- 12% and 88 +/- 16%, respectively. Purity of sorted cultures and rate of survival using NE-4C/NE-GFP-4C co-cultures were 95 +/- 2% and 62 +/- 7%, respectively. Hydrodynamic simulations confirmed the experimental sorting efficiency and a cell damage risk similar to that of normal FACS

A fast two-phase non-isothermal reduced-order model for accelerating PEM fuel cell design development

A reduced-order model (ROM) is developed for proton exchange membrane fuel cells (PEMFCs) considering the non-isothermal two-phase effects, with the goal of enhancing computational efficiency and thus accelerating fuel cell design development. Using analytical order reduction and approximation methods, the fluxes and source terms in conventional 1D conservation equations are reduced to six computing nodes at the interfaces between each cell component. The errors associated with order reduction are minimized by introducing new approximation methods for the potential distribution, the transport properties, and the membrane hydration status. The trade-off between model accuracy and computational efficiency is studied by comparing the simulation results and computational times of the new model with a full 1D model. The new model is nearly two orders of magnitude faster without sacrificing too much accuracy (<4% difference) compared to the 1D model. The new model is then used to analyze the influence of the membrane electrode assembly (MEA) design on cell performance and internal state distributions, offering insights into MEA structural optimization. The model can be readily extended to account for more detailed physico-chemical processes, such as Knudsen diffusion or the influence of micro-porous layers, and it can be an effective tool for understanding and designing PEMFCs

Changing indications and socio-demographic determinants of (adeno)tonsillectomy among children in England--are they linked? A retrospective analysis of hospital data.

OBJECTIVE: To assess whether increased awareness and diagnosis of obstructive sleep apnoea syndrome (OSAS) and national guidance on tonsillectomy for recurrent tonsillitis have influenced the socio-demographic profile of children who underwent tonsillectomy over the last decade. METHOD: Retrospective time-trends study of Hospital Episodes Statistics data. We examined the age, sex and deprivation level, alongside OSAS diagnoses, among children aged <16 years who underwent (adeno)tonsillectomy in England between 2001/2 and 2011/12. RESULTS: Among children aged <16 years, there were 29,697 and 27,732 (adeno)tonsillectomies performed in 2001/2 and 2011/12, respectively. The median age at (adeno)tonsillectomy decreased from 7 (IQR: 5-11) to 5 (IQR: 4-9) years over the decade. (Adeno)tonsillectomy rates among children aged 4-15 years decreased by 14% from 350 (95%CI: 346-354) in 2001/2 to 300 (95%CI: 296-303) per 100,000 children in 2011/12. However, (adeno)tonsillectomy rates among children aged <4 years increased by 58% from 135 (95%CI: 131-140) to 213 (95%CI 208-219) per 100,000 children in 2001/2 and 2011/2, respectively. OSAS diagnoses among children aged <4 years who underwent surgery increased from 18% to 39% between these study years and the proportion of children aged <4 years with OSAS from the most deprived areas increased from 5% to 12%, respectively. CONCLUSIONS: (Adeno)tonsillectomy rates declined among children aged 4-15 years, which reflects national guidelines recommending the restriction of the operation to children with more severe recurrent throat infections. However, (adeno)tonsillectomy rates among pre-school children substantially increased over the past decade and one in five children undergoing the operation was aged <4 years in 2011/12.The increase in surgery rates in younger children is likely to have been driven by increased awareness and detection of OSAS, particularly among children from the most deprived areas

Some Field Theoretic Issues Regarding the Chiral Magnetic Effect

In this paper, we shall address some field theoretic issues regarding the chiral magnetic effect. The general structure of the magnetic current consistent with the electromagnetic gauge invariance is obtained and the impact of the infrared divergence is examined. Some subtleties on the relation between the chiral magnetic effect and the axial anomaly are clarified through a careful examination of the infrared limit of the relevant thermal diagrams.Comment: 19 pages, 4 figures in Latex. Typos fixed, version accepted to be published in JHE

ABCD Neurocognitive Prediction Challenge 2019: Predicting individual residual fluid intelligence scores from cortical grey matter morphology

We predicted residual fluid intelligence scores from T1-weighted MRI data available as part of the ABCD NP Challenge 2019, using morphological similarity of grey-matter regions across the cortex. Individual structural covariance networks (SCN) were abstracted into graph-theory metrics averaged over nodes across the brain and in data-driven communities/modules. Metrics included degree, path length, clustering coefficient, centrality, rich club coefficient, and small-worldness. These features derived from the training set were used to build various regression models for predicting residual fluid intelligence scores, with performance evaluated both using cross-validation within the training set and using the held-out validation set. Our predictions on the test set were generated with a support vector regression model trained on the training set. We found minimal improvement over predicting a zero residual fluid intelligence score across the sample population, implying that structural covariance networks calculated from T1-weighted MR imaging data provide little information about residual fluid intelligence.Comment: 8 pages plus references, 3 figures, 2 tables. Submission to the ABCD Neurocognitive Prediction Challenge at MICCAI 201