Sipuleucel-T for therapy of asymptomatic or minimally symptomatic, castrate-refractory prostate cancer: an update and perspective among other treatments

Sipuleucel-T is an autologous cell immunotherapy for castrate-refractory prostate cancer, with US Food and Drug Administration (FDA) approval in asymptomatic or minimally symptomatic prostate cancer. In this review we address the background of prostate cancer incidence and other available therapy onto which sipuleucel-T treatment has been added, with discussion of hormone-therapy, chemotherapy, and other investigational immunotherapies. The sipuleucel-T manufacturing process, toxicity and clinical benefit are reviewed, along with an examination of the issue of clinical benefit to survival, independent of apparent changes of prostate-specific antigen (PSA) levels. Sipuleucel-T therapy is appraised from clinician, patient and immunotherapeutic perspectives, with reference to the clinical data from the pivotal trial, the mechanism of action, and the treatment process

CubeSat Laser Infrared CrosslinK

The CubeSat Laser Infrared CrosslinK (CLICK) mission will demonstrate technology to advance the state of the art in communications between small spacecraft as well as the capability to gauge their relative distance and location. CLICK is comprised of two sequential missions. The first mission, CLICK A, is a risk reduction mission that will test out elements of the optical (laser) communications with a single 3-unit (3U) spacecraft. The key objective of this risk reduction testing is to demonstrate the fine steering mirror control system's high precision pointing performance which enables the use of a lower power laser in CLICK B/C. The goal of CLICK B/C, the second mission, is to demonstrate full-duplex (send and receive) optical communication crosslink between two 3U small spacecraft, in low-Earth-orbit, at distances between 15 and 360 miles (25 - 580 kilometres) apart at data rates greater than 20 Mbps

Investigating prostate cancer tumour-stroma interactions - clinical and biological insights from an evolutionary game

BACKGROUND: Tumours are made up of a mixed population of different types of cells that include normal structures as well as ones associated with the malignancy, and there are multiple interactions between the malignant cells and the local microenvironment. These intercellular interactions, modulated by the microenvironment, effect tumour progression and represent a largely under appreciated therapeutic target. We use observations of primary tumor biology from prostate cancer to extrapolate a mathematical model: specifically; it has been observed that in prostate cancer three disparate cellular outcomes predominate: (i) the tumour remains well differentiated and clinically indolent - in this case the local stromal cells may act to restrain the growth of the cancer; (ii) early in its genesis the tumour acquires a highly malignant phenotype, growing rapidly and displacing the original stromal population (often referred to as small cell prostate cancer) - these less common aggressive tumours are relatively independent of the local microenvironment; and, (iii) the tumour co-opts the local stroma - taking on a classic stromagenic phenotype where interactions with the local microenvironment are critical to the cancer growth. METHODS: We present an evolutionary game theoretical construct that models the influence of tumour-stroma interactions in driving these outcomes. We consider three characteristic and distinct cellular populations: stromal cells, tumour cells that are self-reliant in terms of microenvironmental factors and tumour cells that depend on the environment for resources but can also co-opt stroma. 
RESULTS: Using evolutionary game theory we explore a number of different scenarios that elucidate the impact of tumour-stromal interactions on the dynamics of prostate cancer growth and progression and how different treatments in the metastatic setting can affect different types of tumors.
CONCLUSIONS: The tumour microenvironment plays a crucial role selecting the traits of the tumour cells that will determine prostate cancer progression. Equally important, treatments like hormone therapy affect the selection of these cancer phenotypes making it very important to understand how they impact prostate cancer’s somatic evolution

Small Spacecraft Systems Virtual Institute’s Federated Databases and State of the Art of Small Spacecraft Report

NASA’s Small Spacecraft Systems Virtual Institute (S3VI) is collaborating with the Air Force Research Laboratory and Space Dynamics Laboratory on the development of a small spacecraft parts database called SmallSat Parts On Orbit Now (SPOON). The SPOON database contains small spacecraft parts and technologies categorized by major satellite subsystems developed by industry, academia and government. The State of the Art of Small Spacecraft Technology report reflects small spacecraft parts submitted to the SPOON database and technologies compiled from other sources that were assessed as the current state of the art in each of the major subsystems. The report, first commissioned by NASA’s Small Spacecraft Technology (SST) program in mid-2013, is developed in response to the continuing growth in interest in using small spacecraft for many types of missions in Earth orbit and beyond. Due to the high market penetration of CubeSats, particular emphasis is placed on the state of the art of CubeSat-related technology. The 2018 report is planned for release in late summer. A review of SPOON database functionality, federation of additional NASA-internal and external databases along with a common search capability, as well as an overview of the State of the Art of Small Spacecraft Technology report will be presented

Genetic steps to organ laterality in zebrafish.

All internal organs are asymmetric along the left-right axis. Here we report a genetic screen to discover mutations which perturb organ laterality. Our particular focus is upon whether, and how, organs are linked to each other as they achieve their laterally asymmetric positions. We generated mutations by ENU mutagenesis and examined F3 progeny using a cocktail of probes that reveal early primordia of heart, gut, liver and pancreas. From the 750 genomes examined, we isolated seven recessive mutations which affect the earliest left-right positioning of one or all of the organs. None of these mutations caused discernable defects elsewhere in the embryo at the stages examined. This is in contrast to those mutations we reported previously (Chen et al., 1997) which, along with left-right abnormalities, cause marked perturbation in gastrulation, body form or midline structures. We find that the mutations can be classified on the basis of whether they perturb relationships among organ laterality. In Class 1 mutations, none of the organs manifest any left-right asymmetry. The heart does not jog to the left and normally leftpredominant BMP4 in the early heart tube remains symmetric. The gut tends to remain midline. There frequently is a remarkable bilateral duplication of liver and pancreas. Embryos with Class 2 mutations have organotypic asymmetry but, in any given embryo, organ positions can be normal, reversed or randomized. Class 3 reveals a hitherto unsuspected gene that selectively affects laterality of heart. We find that visceral organ positions are predicted by the direction of the preceding cardiac jog. We interpret this as suggesting that normally there is linkage between cardiac and visceral organ laterality. Class 1 mutations, we suggest, effectively remove the global laterality signals, with the consequence that organ positions are effectively symmetrical. Embryos with Class 2 mutations do manifest linkage among organs, but it may be reversed, suggesting that the global signals may be present but incorrectly orientated in some of the embryos. That laterality decisions of organs may be independently perturbed, as in the Class 3 mutation, indicates that there are distinctive pathways for reception and organotypic interpretation of the global signals

Weak quenched disorder and criticality: resummation of asymptotic(?) series

In these lectures, we discuss the influence of weak quenched disorder on the critical behavior in condensed matter and give a brief review of available experimental and theoretical results as well as results of MC simulations of these phenomena. We concentrate on three cases: (i) uncorrelated random-site disorder, (ii) long-range-correlated random-site disorder, and (iii) random anisotropy. Today, the standard analytical description of critical behavior is given by renormalization group results refined by resummation of the perturbation theory series. The convergence properties of the series are unknown for most disordered models. The main object of these lectures is to discuss the peculiarities of the application of resummation techniques to perturbation theory series of disordered models.Comment: Lectures given at the Second International Pamporovo Workshop on Cooperative Phenomena in Condensed Matter (28th July - 7th August 2001, Pamporovo, Bulgaria). 51 pages, 12 figures, 1 style files include

Patients with ClearCode34-identified molecular subtypes of clear cell renal cell carcinoma represent unique populations with distinct comorbidities

The 34-gene classifier, ClearCode34, identifies prognostically distinct molecular subtypes of clear cell renal cell carcinoma (ccRCC) termed ccA and ccB. The primary objective of this study was to describe clinical characteristics and comorbidities of relevance in patients stratified by ClearCode34

A systematic review of the evidence on decoupling of GDP, resource use and GHG emissions, part II: synthesizing the insights

Strategies toward ambitious climate targets usually rely on the concept of "decoupling"; that is, they aim at promoting economic growth while reducing the use of natural resources and GHG emissions. GDP growth coinciding with absolute reductions in emissions or resource use is denoted as "absolute decoupling", as opposed to "relative decoupling", where resource use or emissions increase less so than does GDP. Based on the bibliometric mapping in part I (Wiedenhofer et al., this issue), we synthesize the evidence emerging from the selected 835 peer-reviewed articles. We evaluate empirical studies of decoupling related to final/useful energy, exergy, use of material resources, as well as CO2 and total GHG emissions. We find that relative decoupling is frequent for material use as well as GHG and CO2 emissions but not for useful exergy, a quality-based measure of energy use. Primary energy can be decoupled from GDP largely to the extent to which the conversion of primary energy to useful exergy is improved. Examples of absolute long-term decoupling are rare, but recently some industrialized countries have decoupled GDP from both production- and, weaklier, consumption-based CO2 emissions. We analyze policies or strategies in the decoupling literature by classifying them into three groups: (1) Green growth, if sufficient reductions of resource use or emissions were deemed possible without altering the growth trajectory. (2) Degrowth, if reductions of resource use or emissions were given priority over GDP growth. (3) Others, e.g. if the role of energy for GDP growth was analyzed without reference to climate change mitigation. We conclude that large rapid absolute reductions of resource use and GHG emissions cannot be achieved through observed decoupling rates, hence decoupling needs to be complemented by sufficiency-oriented strategies and strict enforcement of absolute reduction targets. More research is needed on interdependencies between wellbeing, resources and emissions

A systematic review of the evidence on decoupling of GDP, resource use and GHG emissions, part I: bibliometric and conceptual mapping

As long as economic growth is a major political goal, decoupling growth from resource use and emissions is a prerequisite for a sustainable net-zero emissions future. However, empirical evidence for absolute decoupling, i.e., decreasing resource use and emissions at the required scale despite continued economic growth, is scarce and scattered across different research streams. In this two-part systematic review, we assess how and to what extent decoupling has been observed and what can be learnt for addressing the sustainability and climate crisis. Based on a transparent approach, we systematically identify and screen more than 11,500 scientific papers, eventually analyzing full texts of 835 empirical studies on the relationship between economic growth (GDP), resource use (materials and energy) and greenhouse gas emissions. Part I of the review examines how decoupling has been investigated across three research streams: energy, materials and energy, and emissions. Part II synthesizes the empirical evidence and policy implications (Haberl et al. part II, in review). In part I, we examine the topical, temporal and geographical scopes, methods of analysis, institutional networks and prevalent conceptual angles. We find that in this rapidly growing literature, the vast majority of studies – decomposition, 'causality' and Environmental Kuznets Curve analysis – approach the topic from a statistical-econometric point of view, while hardly acknowledging thermodynamic principles on the role of energy and materials for socio-economic activities. A potentially fundamental incompatibility between economic growth and systemic societal changes to address the climate crisis is rarely considered. We conclude that the existing wealth of empirical evidence merits braver conceptual advances than we have seen thus far. Future work should focus on comprehensive multi-indicator long-term analyses, conceptually grounded on the fundamental biophysical basis of socio-economic activities, incorporating the role of global supply chains as well as the wider societal role and preconditions of economic growth

Small Spacecraft Systems Virtual Institute's Federated Databases and State of the Art of Small Spacecraft Technology Report

NASA's Small Spacecraft Systems Virtual Institute (S3VI) is collaborating with the Air Force Research Laboratory and Space Dynamics Laboratory on the development of a small spacecraft parts database called SmallSat Parts On Orbit Now (SPOON). The SPOON database contains small spacecraft parts and technologies categorized by major satellite subsystems developed by industry, academia and government. The State of the Art of Small Spacecraft Technology report reflects small spacecraft parts submitted to the SPOON database and technologies compiled from other sources that were assessed as the current state of the art in each of the major subsystems. The report, first commissioned by NASA's Small Spacecraft Technology Program in mid-2013, is developed in response to the continuing growth in interest in using small spacecraft for many types of missions in Earth orbit and beyond. Due to the high market penetration of CubeSats, particular emphasis is placed on the state of the art of CubeSat-related technology. The 2018 report is planned for release in late summer. A review of SPOON database functionality, federation of additional NASA-internal and external databases along with a common search capability, as well as an overview of the State of the Art of Small Spacecraft Technology report will be presented. The S3VI is jointly sponsored by NASA's Space Technology Mission Directorate and Science Mission Directorate