Sandwich - The 'Completest Medieval Town in England'

To the casual visitor of today, Sandwich appears as simply a small inland market town on the bank of a modest river. But locals and historians have long known that in the Middle Ages it was a strategic and commercial seaport of great significance, trading with northern Europe and the Mediterranean and growing prosperous on this business. The medieval fabric of the town has been preserved to a remarkable extent, but historians and archaeologists have never agreed on quite where the first settlement was located. Nor has there been close study of what the surviving medieval buildings can tell us about Sandwich's development. As well as providing a great amount of detail on the houses, churches and defences of medieval Sandwich, the authors apply the material evidence in order to draw out important social, economic and cultural facets in the evolution of the town. Maps, plans and photographs, all in full colour, supplement the text and graphically underline many of the conclusions

Sandwich - The 'Completest Medieval Town in England'

To the casual visitor of today, Sandwich appears as simply a small inland market town on the bank of a modest river. But locals and historians have long known that in the Middle Ages it was a strategic and commercial seaport of great significance, trading with northern Europe and the Mediterranean and growing prosperous on this business. The medieval fabric of the town has been preserved to a remarkable extent, but historians and archaeologists have never agreed on quite where the first settlement was located. Nor has there been close study of what the surviving medieval buildings can tell us about Sandwich's development. As well as providing a great amount of detail on the houses, churches and defences of medieval Sandwich, the authors apply the material evidence in order to draw out important social, economic and cultural facets in the evolution of the town. Maps, plans and photographs, all in full colour, supplement the text and graphically underline many of the conclusions

Birch bark tar in early Medieval England:continuity of tradition or technological revival?

International audienc

Long-term treatment with lanthanum carbonate reduces mineral and bone abnormalities in rats with chronic renal failure

Background. Lanthanum carbonate (FOSRENOL®, Shire Pharmaceuticals) is an effective non-calcium, non-resin phosphate binder for the treatment of hyperphosphataemia in patients with chronic kidney disease (CKD). In this study, we used a rat model of chronic renal failure (CRF) to examine the long-term effects of controlling serum phosphorus with lanthanum carbonate treatment on the biochemical and bone abnormalities associated with CKD–mineral and bone disorder (CKD–MBD)

The effects of habitat degradation on metacommunity structure of wood-inhabiting fungi in European beech forests

Intensive forest management creates habitat degradation by reducing the variation of forest stands in general, and by removing old trees and dead wood in particular. Non-intervention forest reserves are commonly believed to be the most efficient tool to counteract the negative effects on biodiversity, but actual knowledge of the conservation efficiency is limited, especially for recent reserves. The structure of ecological communities is often described with measures of nestedness, beta diversity and similarity between communities. We studied whether these measures differ among forest reserves with different management histories. For this purpose, we used a large data set of wood-inhabiting fungi collected from dead beech trees in European beech-dominated forest reserves. The structure of fungal assemblages showed high beta diversity, while nestedness and similarity was low. During the decomposition process of trees beta diversity between the communities occupying different trees increased in natural, but not in previously managed sites. Effects of management and decay process on nestedness were complex. We argue that the detected differences most likely reflect historical effects which have extirpated specialized species from the local species pools in managed sites, and resulted in more homogeneous communities in managed sites. It is alarming that community structure is affected the most in the latest decay stages where the decay process turns the dead wood into litter, and which is thus the interface between the wood decay and the litter-decaying ecosystem. The effects of simplified communities in late decay stages on soil biodiversity should be studied

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

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

How Linear Tension Converts to Curvature: Geometric Control of Bone Tissue Growth

This study investigated how substrate geometry influences in-vitro tissue formation at length scales much larger than a single cell. Two-millimetre thick hydroxyapatite plates containing circular pores and semi-circular channels of 0.5 mm radius, mimicking osteons and hemi-osteons respectively, were incubated with MC3T3-E1 cells for 4 weeks. The amount and shape of the tissue formed in the pores, as measured using phase contrast microscopy, depended on the substrate geometry. It was further demonstrated, using a simple geometric model, that the observed curvature-controlled growth can be derived from the assembly of tensile elements on a curved substrate. These tensile elements are cells anchored on distant points of the curved surface, thus creating an actin “chord” by generating tension between the adhesion sites. Such a chord model was used to link the shape of the substrate to cell organisation and tissue patterning. In a pore with a circular cross-section, tissue growth increases the average curvature of the surface, whereas a semi-circular channel tends to be flattened out. Thereby, a single mechanism could describe new tissue growth in both cortical and trabecular bone after resorption due to remodelling. These similarities between in-vitro and in-vivo patterns suggest geometry as an important signal for bone remodelling