Predicting clinical response to anticancer drugs using an ex vivo platform that captures tumour heterogeneity

Predicting clinical response to anticancer drugs remains a major challenge in cancer treatment. Emerging reports indicate that the tumour microenvironment and heterogeneity can limit the predictive power of current biomarker-guided strategies for chemotherapy. Here we report the engineering of personalized tumour ecosystems that contextually conserve the tumour heterogeneity, and phenocopy the tumour microenvironment using tumour explants maintained in defined tumour grade-matched matrix support and autologous patient serum. The functional response of tumour ecosystems, engineered from 109 patients, to anticancer drugs, together with the corresponding clinical outcomes, is used to train a machine learning algorithm; the learned model is then applied to predict the clinical response in an independent validation group of 55 patients, where we achieve 100% sensitivity in predictions while keeping specificity in a desired high range. The tumour ecosystem and algorithm, together termed the CANScript technology, can emerge as a powerful platform for enabling personalized medicine.

Characterization of type I interferon pathway during hepatic differentiation of human pluripotent stem cells and hepatitis C virus infection

Pluripotent stem cells are being actively studied as a cell source for regenerating damaged liver. For long-term survival of engrafting cells in the body, not only do the cells have to execute liver-specific function but also withstand the physical strains and invading pathogens. The cellular innate immune system orchestrated by the interferon (IFN) pathway provides the first line of defense against pathogens. The objective of this study is to assess the innate immune function as well as to systematically profile the IFN-induced genes during hepatic differentiation of pluripotent stem cells. To address this objective, we derived endodermal cells (day 5 post-differentiation), hepatoblast (day 15) and hepatocyte-like cells (day 21) from human embryonic stem cells (hESCs). Day 5, 15 and 21 cells were stimulated with IFN-alpha and subjected to IFN pathway analysis. Transcriptome analysis was carried out by RNA sequencing. The results showed that the IFN-alpha treatment activated STAT-JAK pathway in differentiating cells. Transcriptome analysis indicated stage specific expression of classical and non-classical IFN-stimulated genes (ISGs). Subsequent validation confirmed the expression of novel ISGs including RASGRP3, CLMP and TRANK1 by differentiated hepatic cells upon IFN treatment. Hepatitis C virus replication in hESC-derived hepatic cells induced the expression of ISGs - LAMP3, ETV7, RASGRP3, and TRANK1. The hESC-derived hepatic cells contain intact innate system and can recognize invading pathogens. Besides assessing the tissue-specific functions for cell therapy applications, it may also be important to test the innate immune function of engrafting cells to ensure adequate defense against infections and improve graft survival. (C) 2015 The Authors. Published by Elsevier B.V.

Evaluation of manufacturing techniques for a minifluidics demonstrator system

A multi-disciplinary team based at Heriot-Watt University and other Universities has been set up to tackle the design and manufacturing of lab-on-a-chip for industries as one of the demonstrators of the EPSRC Grand Challenge project "3D-Mintegration". The team focuses on the analysis of foetal genetic material extracted from maternal blood as a smart alternative to invasive prenatal testing such as amniocentesis. The first module of the microsystem envisaged achieves a separation of blood cells from plasma. This system permits the testing of different manufacturing techniques.

Das paradies in der politik ein kapitel negativer kosmologie

Abstract: The idea of a “paradise in politics” is an answer to the cosmogonic- anthropogonic problem that, through their bodies, the life of human beings has been shaped politically from the very beginning: all creation is a creation of bodies and bodies are power. All creation, furthermore, means separation, it emerges through a multiplicity of things and beings only. The conventional solution for the problem, in the realm of human beings, consists in forming societies out of a multiplicity of indivuals that remains as such. The solution of a “paradise in politics”, however, envisions a “healing” of creation through a bodily transmutation by which a world of bodies emerges that is freed from the problem of bodies: separation, power. The article discusses the negative cosmology with which all tales on a paradise in politics start. It shows the essential role of phantasy in the constitution of these tales, and elucidates the principal structural elements through which visions of a paradise in politics are built. A special attention is given to the parallelism between these visions and known religious thought, as in the case of the concepts of apokatastasis or perichoresis, for instance. Methodically, the article achieves a demonstration of its subject by an extensive presentation and analysis of two case studies: Rousseau’s vision of a “terrestrial paradise” and the attempt at “bodily redemption” put on the stage in 1968-69 by the “Living Theatre” Group with its performance “Paradise Now”.

Potential use of remote sensing to assess effects of wave action on plant re-establishment

Evaluation of the potential for remote sensing to detect a relationship between wave action factors and plant re-establishment after a habitat enhancement at Lake Kissimmee, Florida. Using Geographic Information Systems (GIS) and remote sensing, wave action factors were found to be inversely related to the probability of plant re-establishment. However, correlation of wave action factors with areal coverage of aquatic plants based on field measurements, were unable to detect a significant relationship. Other factors aside from wave action, including littoral slope and the presence of offshore vegetation, may have influenced plant re-establishment in these sites. Remote sensing techniques may be useful to detect large changes in plants communities, however small changes in plant coverages may not be detectable using this technique.

Preliminary guide to the indentification of the early life history stages of Callionymid fishes of the Western Central Atlantic

Callionymidae, along with the Draconettidae and Gobiesocidae, previously were placed in the order Gobiesociformes (Allen, 1984). Recently, Nelson (1994) placed the Callionymidae and Draconettidae in the percifonn suborder Callionymoidei. The family is represented by three species in the western central North Atlantic Ocean, Diplogrammus pauciradiatus, Paradiplogrammus bairdi and Foetorepus agassizi (Davis, 1966; Robins and Ray, 1986). A detailed review ofthe family including early life history infonnation is given by Houde (1984) and Watson (1996). (PDF contains 11 pages)

Partnerships for progress

A synthesis of the Jisc BCE open innovation and access to resources initiative

A taxonomic guide to the mysids of the South Atlantic Bight.

Following the examination of extensive collections from the National Museum of Natural History (NMNH), the Southeastern Regional Taxonomic Center (SERTC), and other regional institutions, 18 species of the family Mysidae are recognized and described from the South Atlantic Bight (Cape Lookout, North Carolina to Cape Canaveral, Florida). This report includes synonymies of previous records, as well as new species distribution records. Previous regional accounts of Metamysidopsis munda and Metamysidopsis mexicana are attributed to Metamysidopsis swifti. New regional records are established for Amathimysis brattegardi, Heteromysis beetoni, and Siriella thompsonii. Two other species tentatively identified as Amathimysis sp. (nr. serrata) and Mysidopsis sp. (cf. mortenseni) may represent new taxa. Neobathymysis renoculata is included and discussed as a potential regional species. An illustrated key to the species currently known from the South Atlantic Bight is presented. Relevant taxonomic, distributional, and ecological information is also included for each species. (PDF file contains 45 pages.)

Maintaining the "public good" nature of improved fish strains: dissemination of knowledge and materials

Many sources of information that discuss currents problems of food security point to the importance of farmed fish as an ideal food source that can be grown by poor farmers, (Asian Development Bank 2004). Furthermore, the development of improved strains of fish suitable for low-input aquaculture such as Tilapia, has demonstrated the feasibility of an approach that combines “cutting edge science” with accessible technology, as a means for improving the nutrition and livelihoods of both the urban poor and poor farmers in developing countries (Mair et al. 2002). However, the use of improved strains of fish as a means of reducing hunger and improving livelihoods has proved to be difficult to sustain, especially as a public good, when external (development) funding sources devoted to this area are minimal1. In addition, the more complicated problem of delivery of an aquaculture system, not just improved fish strains and the technology, can present difficulties and may go explicitly unrecognized (from Sissel Rogne, as cited by Silje Rem 2002). Thus, the involvement of private partners has featured prominently in the strategy for transferring to the public technology related to improved Tilapia strains. Partnering with the private sector in delivery schemes to the poor should take into account both the public goods aspect and the requirement that the traits selected for breeding “improved” strains meet the actual needs of the resource poor farmer. Other dissemination approaches involving the public sector may require a large investment in capacity building. However, the use of public sector institutions as delivery agents encourages the maintaining of the “public good” nature of the products.

Estimation of year class abundance and mortality of yellowfin tuna in the Eastern Tropical Pacific

ENGLISH: Age composition of catch, and growth rate, of yellowfin tuna have been estimated by Hennemuth (1961a) and Davidoff (1963). The relative abundance and instantaneous total mortality rate of yellowfin tuna during 1954-1959 have been estimated by Hennenmuth (1961b). It is now possible to extend this work, because more data are available; these include data for 1951-1954, which were previously not available, and data for 1960-1962, which were collected subsequent to Hennemuth's (1961b) publication. In that publication, Hennemuth estimated the total instantaneous mortality rate (Z) during the entire time period a year class is present in the fishery following full recruitment. However, this method may lead to biased estimates of abundance, and hence mortality rates, because of both seasonal migrations into or out of specific fishing areas and possible seasonal differences in availability or vulnerability of the fish to the fishing gear. Schaefer, Chatwin and Broadhead (1961) and Joseph etl al. (1964) have indicated that seasonal migrations of yellowfin occur. A method of estimating mortality rates which is not biased by seasonal movements would be of value in computations of population dynamics. The method of analysis outlined and used in the present paper may obviate this bias by comparing the abundance of an individual yellowfin year class, following its period of maximum abundance, in an individual area during a specific quarter of the year with its abundance in the same area one year later. The method was suggested by Gulland (1955) and used by Chapman, Holt and Allen (1963) in assessing Antarctic whale stocks. This method, and the results of its use with data for yellowfin caught in the eastern tropical Pacific from 1951-1962 are described in this paper. SPANISH: La composición de edad de la captura, y la tasa de crecimiento del atún aleta amarilla, han sido estimadas por Hennemuth (1961a) y Davidoff (1963). Hennemuth (1961b), estimó la abundancia relativa y la tasa de mortalidad total instantánea del atún aleta amarilla durante 1954-1959. Se puede ampliar ahora, este trabajo, porque se dispone de más datos; éstos incluyen datos de 1951 1954, de los cuales no se disponía antes, y datos de 1960-1962 que fueron recolectados después de la publicación de Hennemuth (1961b). En esa obra, Hennemuth estimó la tasa de mortalidad total instantánea (Z) durante todo el período de tiempo en el cual una clase anual está presente en la pesquería, consecutiva al reclutamiento total. Sin embargo, este método puede conducir a estimaciones con bias (inclinación viciada) de abundancia, y de aquí las tasas de mortalidad, debidas tanto a migraciones estacionales dentro o fuera de las áreas determinadas de pesca, como a posibles diferencias estacionales en la disponibilidad y vulnerabilidad de los peces al equipo de pesca. Schaefer, Chatwin y Broadhead (1961) y Joseph et al. (1964) han indicado que ocurren migraciones estacionales de atún aleta amarilla. Un método para estimar las tasas de mortalidad el cual no tuviera bias debido a los movimientos estacionales, sería de valor en los cómputos de la dinámica de las poblaciones. El método de análisis delineado y usado en el presente estudio puede evitar este bias al comparar la abundancia de una clase anual individual de atún aleta amarilla, subsecuente a su período de abundancia máxima en un área individual, durante un trimestre específico del año, con su abundancia en la misma área un año más tarde. Este método fue sugerido por Gulland (1955) y empleado por Chapman, Holt y Allen (1963) en la declaración de los stocks de la ballena antártica. Este método y los resultados de su uso, en combinación con los datos del atún aleta amarilla capturado en el Pacífico oriental tropical desde 1951-1962, son descritos en este estudio.

The Invertebrate Assemblage Associated with Macrocystis pyrifera and its Utilization as a Food Resource by Kelp Forest Fishes

The present study was designed to examine the following: (1) the taxonomic. spatial, and temporal patterns of availability of all invertebrate species associated with Macrocystis (excluding protozoans and nematodes); (2) the utilization of this invertebrate assemblage as food by kelp forest fishes within the Macrocystis "foliage- searching" feeding guild, as well as proximal mechanisms leading to observed patterns of resource partitioning; and (3) the dynamic relationship between availability and utilization of this food resource. The approach was largely descriptive. with observations collected during a 19-month period from June 1975 to December 1976. Chapter I is an investigation of the resource utilization patterns of four species of kelp forest fishes with respect to food-related resource dimensions. and tests aspects of current theory involving inter- and intraspecific competition. Chapter II is a detailed examination of the invertebrate assemblage associated with Macrocystis and presents life histories of the fishes examined during this study. (PDFs contains 387 pages, chapter 1 is 203 pages, chapter 2 is 184 pages)

Cephalopods from the stomachs of sperm whales taken off California

Cephalopod remains (beaks, bodies, and parts of bodies) were collected from the stomachs of 157 sperm whales (Physeter macrocephalus) taken off central California (lat. 37°-39°N). At least 24 species representing 14 families were identified. Frequencies of occurrence of the six most numerous taxa were Moroteuthis robusta 72.0%, Gonatopsis borealis 66.2%, Histioteuthis dofleini 36.9%, Galiteuthis spp. (including G. phyllura and G. pacifica) 36.3%, Octopoteuthis deletron 35.0%, and Vampyroteuthis infernalis 27.4%. One find of two Mesonychoteuthis hamiltoni beaks strongly suggests transequatorial migration by one large male sperm whale. (PDF file contains 18 pages.)