A biomimetic pancreatic cancer on-chip reveals endothelial ablation via ALK7 signaling

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, lethal malignancy that invades adjacent vasculatures and spreads to distant sites before clinical detection. Although invasion into the peripancreatic vasculature is one of the hallmarks of PDAC, paradoxically, PDAC tumors also exhibit hypovascularity. How PDAC tumors become hypovascular is poorly understood. We describe an organotypic PDAC-on-a-chip culture model that emulates vascular invasion and tumor-blood vessel interactions to better understand PDAC-vascular interactions. The model features a 3D matrix containing juxtaposed PDAC and perfusable endothelial lumens. PDAC cells invaded through intervening matrix, into vessel lumen, and ablated the endothelial cells, leaving behind tumor-filled luminal structures. Endothelial ablation was also observed in in vivo PDAC models. We also identified the activin-ALK7 pathway as a mediator of endothelial ablation by PDAC. This tumor-on-a-chip model provides an important in vitro platform for investigating the process of PDAC-driven endothelial ablation and may provide a mechanism for tumor hypovascularity.R01 EB000262 - NIBIB NIH HHS; TL1 TR001410 - NCATS NIH HHS; UC4 DK104196 - NIDDK NIH HHS; UH3 EB017103 - NIBIB NIH HHSPublished versio

Prediction of hypertension by different anthropometric indices in adults: the change in estimate approach

To examine the relative contribution for the prediction of hypertension by waist circumference (WC), waist-to-stature ratio (WSR), or waist-to-hip ratio (WHR) to that by body mass index (BMI) to ascertain if WC, WSR, or WHR enhances the prediction of hypertension by BMI

Introduction of flat ribbon cable (FRC) sensor for density measurement of road materials using time domain reflectometry (TDR)

Moisture content and density of unbound granular pavement materials are important properties for compaction control providing a great influence on pavement performance. Time domain reflectometry (TDR) usually uses rod probe sensors, which can provide pointwise readings of density. However, pointwise readings might not be representative enough for a complete road section. This paper introduces the application of flat ribbon cable (FRC) sensor, which can be extended up to 6 meter to measure moisture and density of road materials. Soil specific calibration is done in the laboratory considering the variation of moisture and density of materials where sensors of three different lengths are considered to enable the development of length normalized calibration. The electric parameter used to derive soil density is the voltage drop, which occurs after the passage of an electromagnetic wave along the sensor embedded in the soil. Soil moisture is related to the permittivity of the soil sample, which is obtained from the travel time of the TDR signal. Laboratory results indicate that calibration functions are independent of moisture and density. These soil specific calibration functions are useful in measuring long term pavement performance and managing rutting of roads

Primary Biliary Lymphoma Mimicking Cholangiocarcinoma: A Characteristic Feature of Discrepant CT and Direct Cholangiography Findings

Primary non-Hodgkin's lymphoma arising from the bile duct is extremely rare and the reported imaging features do not differ from those of cholangiocarcinoma of the bile duct. We report a case of a patient with extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue (MALT), who presented with obstructive jaundice and describe the distinctive radiologic features that may suggest the correct preoperative diagnosis of primary lymphoma of the bile duct. Primary MALT lymphoma of the extrahepatic bile duct should be considered in the differential diagnosis when there is a mismatch in imaging findings on computed tomography or magnetic resonance imaging and cholangiography

The Therapeutic Effects of Bevacizumab in Patients with Polypoidal Choroidal Vasculopathy

A proper description of the biosynthesis of fungal β-lactam antibiotics requires detailed knowledge of the cell biology of the producing organisms. This involves a delineation of the compartmentalization of the biosynthetic pathways, and of the consequential transport steps across the cell-boundary plasma membrane and across organellar membranes. Of the enzymes of the penicillin biosynthetic pathway in Penicillium chrysogenum and Aspergillus nidulans, δ-(L-α-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS) and isopenicillin N synthase (IPNS) probably have a cytosolic location. Acyl-coenzyme A:isopenicillin N acyltransferase (IAT) is located in microbodies. Of the two enzymes that may be involved in activation of the side chain, acetyl-coenzyme A synthetase (ACS) is located in the cytosol, and phenylacetyl-coenzyme A ligase (PCL) is probably located in the microbody. All enzymes of the cephalosporin biosynthesis pathway in Cephalosporium acremonium probably have a cytosolic location. The vacuole may play an ancillary role in the supply of precursor amino acids, and in the storage of intermediates. The distribution of precursors, intermediates, end- and side-products, the transport of nutrients, precursors, intermediates and products across the plasma membrane, and the transport of small solutes across organellar membranes, is discussed. The relevance of compartmentalization is considered against the background of recent biotechnological innovations of fungal β-lactam biosynthesis pathways.

Estimating Demand for Infrastructure in Energy, Transport, Telecommunications, Water, and Sanitation in Asia and the Pacific: 2010-2020

Infrastructure plays a key role in promoting and sustaining rapid economic growth. Properly designed infrastructure can also make growth more inclusive by sharing its benefits with poorer groups and communities, especially by connecting remote areas and small and landlocked countries to major business centers. Even if the Asia-Pacific region has witnessed progress in infrastructure development, the growth of infrastructure lags behind its economic growth, and also behind international standards of infrastructure quantity and quality. Inadequate infrastructure can hamper the potential economic growth of Asian countries, weaken their international competitiveness, and adversely affect their poverty reduction efforts. The circumstances and effects of the recent economic and financial crisis provide a number of reasons to further develop national and regional infrastructure in Asia. Among these reasons is that regional infrastructure enhances competitiveness and productivity, which could help in economic recovery and in sustaining growth in the medium to long-term. Regional infrastructure also helps increase standard of living and reduce poverty by connecting isolated places and people with major economic centers and markets, narrowing the development gap among Asian economies. This paper estimates the need for infrastructure investment, including energy, transport, telecommunications, water, and sanitation during 2010-2020, in order to meet growing demands for services and facilitate further rapid growth in the region. By using top-down and bottom-up approaches, this paper provides a comprehensive estimate of Asia's need for infrastructure services. The estimates show that developing countries in Asia require financing of US$776 billion per year for national (US$747 billion) and regional (US$29 billion) infrastructure during 2010-2020 to meet growing demand

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment