A history of the mills along the Neponset

Thesis (Ed.M.)--Boston University, 1951. This item was digitized by the Internet Archive

Functional and Transcriptional Characterization of Human Embryonic Stem Cell-Derived Endothelial Cells for Treatment of Myocardial Infarction

BACKGROUND: Differentiation of human embryonic stem cells into endothelial cells (hESC-ECs) has the potential to provide an unlimited source of cells for novel transplantation therapies of ischemic diseases by supporting angiogenesis and vasculogenesis. However, the endothelial differentiation efficiency of the conventional embryoid body (EB) method is low while the 2-dimensional method of co-culturing with mouse embryonic fibroblasts (MEFs) require animal product, both of which can limit the future clinical application of hESC-ECs. Moreover, to fully understand the beneficial effects of stem cell therapy, investigators must be able to track the functional biology and physiology of transplanted cells in living subjects over time. METHODOLOGY: In this study, we developed an extracellular matrix (ECM) culture system for increasing endothelial differentiation and free from contaminating animal cells. We investigated the transcriptional changes that occur during endothelial differentiation of hESCs using whole genome microarray, and compared to human umbilical vein endothelial cells (HUVECs). We also showed functional vascular formation by hESC-ECs in a mouse dorsal window model. Moreover, our study is the first so far to transplant hESC-ECs in a myocardial infarction model and monitor cell fate using molecular imaging methods. CONCLUSION: Taken together, we report a more efficient method for derivation of hESC-ECs that express appropriate patterns of endothelial genes, form functional vessels in vivo, and improve cardiac function. These studies suggest that hESC-ECs may provide a novel therapy for ischemic heart disease in the future

Measurement in Economics and Social Science

The paper discusses measurement, primarily in economics, from both analytical and historical perspectives. The historical section traces the commitment to ordinalism on the part of economic theorists from the doctrinal disputes between classical economics and marginalism, through the struggle of orthodox economics against socialism down to the cold-war alliance between mathematical social science and anti-communist ideology. In economics the commitment to ordinalism led to the separation of theory from the quantitative measures that are computed in practice: price and quantity indexes, consumer surplus and real national product. The commitment to ordinality entered political science, via Arrow’s ‘impossibility theorem’, effectively merging it with economics, and ensuring its sterility. How can a field that has as its central result the impossibility of democracy contribute to the design of democratic institutions? The analytical part of the paper deals with the quantitative measures mentioned above. I begin with the conceptual clarification that what these measures try to achieve is a restoration of the money metric that is lost when prices are variable. I conclude that there is only one measure that can be embedded in a satisfactory economic theory, free from unreasonable restrictions. It is the Törnqvist index as an approximation to its theoretical counterpart the Divisia index. The statistical agencies have at various times produced different measures for real national product and its components, as well as related concepts. I argue that all of these are flawed and that a single deflator should be used for the aggregate and the components. Ideally this should be a chained Törnqvist price index defined on aggregate consumption. The social sciences are split. The economic approach is abstract, focused on the assumption of rational and informed behavior, and tends to the political right. The sociological approach is empirical, stresses the non-rational aspects of human behavior and tends to the political left. I argue that the split is due to the fact that the empirical and theoretical traditions were never joined in the social sciences as they were in the natural sciences. I also argue that measurement can potentially help in healing this split

Machine learning for determining lateral flow device results for testing of SARS-CoV-2 infection in asymptomatic populations

Rapid antigen tests, in the form of lateral flow devices (LFD) allow testing of a large population for SARS-CoV-2. To reduce the variability seen in device interpretation, we show the design and testing of an AI algorithm based on machine learning. The machine learning (ML) algorithm is trained on a combination of artificially hybridised LFDs and LFD data linked to RT-qPCR result. Participants are recruited from assisted test sites (ATS) and health care workers undertaking self-testing and images analysed using the ML algorithm. A panel of trained clinicians are used to resolve discrepancies. In total, 115,316 images are returned. In the ATS sub study, sensitivity increased from 92.08% to 97.6% and specificity from 99.85% to 99.99%. In the self-read sub-study, sensitivity increased from 16.00% to 100%, and specificity from 99.15% to 99.40%. An ML-based classifier of LFD results outperforms human reads in asymptomatic testing sites and self-reading

Identifying Individual T Cell Receptors of Optimal Avidity for Tumor Antigens.

Cytotoxic T cells recognize, via their T cell receptors (TCRs), small antigenic peptides presented by the major histocompatibility complex (pMHC) on the surface of professional antigen-presenting cells and infected or malignant cells. The efficiency of T cell triggering critically depends on TCR binding to cognate pMHC, i.e., the TCR-pMHC structural avidity. The binding and kinetic attributes of this interaction are key parameters for protective T cell-mediated immunity, with stronger TCR-pMHC interactions conferring superior T cell activation and responsiveness than weaker ones. However, high-avidity TCRs are not always available, particularly among self/tumor antigen-specific T cells, most of which are eliminated by central and peripheral deletion mechanisms. Consequently, systematic assessment of T cell avidity can greatly help distinguishing protective from non-protective T cells. Here, we review novel strategies to assess TCR-pMHC interaction kinetics, enabling the identification of the functionally most-relevant T cells. We also discuss the significance of these technologies in determining which cells within a naturally occurring polyclonal tumor-specific T cell response would offer the best clinical benefit for use in adoptive therapies, with or without T cell engineering

Measuring effectiveness, efficiency and equity in a Payments for Ecosystem Services trial.

There is currently a considerable effort to evaluate the performance of payments for ecosystem services (PES) as an environmental management tool. The research presented here contributes to this work by using an experimental design to evaluate PES as a tool for supporting biodiversity conservation in the context of an African protected area. The trial employed a 'before and after' and 'with and without' design. We present the results of social and ecological surveys to investigate the impacts of the PES in terms of its effectiveness, efficiency and equity. We find the PES to be effective at bringing about additional conservation outcomes. However, we also found that increased monitoring is similarly effective in the short term, at lower cost. The major difference - and arguably the significant contribution of the PES - was that it changed the motives for protecting the park and improved local perceptions both of the park and its authority. We discuss the implications of these results for conservation efficiency, arguing that efficiency should not be defined in terms of short-term cost-effectiveness, but also in terms of the sustainability of behavioral motives. This insight helps us to resolve the apparent trade-off between goals of equity and efficiency in PES

Targeting the tumor vasculature to enhance T cell activity.

T cells play a critical role in tumor immune surveillance as evidenced by extensive mouse-tumor model studies as well as encouraging patient responses to adoptive T cell therapies and dendritic cell vaccines. It is well established that the interplay of tumor cells with their local cellular environment can trigger events that are immunoinhibitory to T cells. More recently it is emerging that the tumor vasculature itself constitutes an important barrier to T cells. Endothelial cells lining the vessels can suppress T cell activity, target them for destruction, and block them from gaining entry into the tumor in the first place through the deregulation of adhesion molecules. Here we review approaches to break this tumor endothelial barrier and enhance T cell activity

Topical capsaicin for pain management: therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch

Topical capsaicin formulations are used for pain management. Safety and modest efficacy of low-concentration capsaicin formulations, which require repeated daily self-administration, are supported by meta-analyses of numerous studies. A high-concentration capsaicin 8% patch (Qutenza™) was recently approved in the EU and USA. A single 60-min application in patients with neuropathic pain produced effective pain relief for up to 12 weeks. Advantages of the high-concentration capsaicin patch include longer duration of effect, patient compliance, and low risk for systemic effects or drug–drug interactions. The mechanism of action of topical capsaicin has been ascribed to depletion of substance P. However, experimental and clinical studies show that depletion of substance P from nociceptors is only a correlate of capsaicin treatment and has little, if any, causative role in pain relief. Rather, topical capsaicin acts in the skin to attenuate cutaneous hypersensitivity and reduce pain by a process best described as ‘defunctionalization’ of nociceptor fibres. Defunctionalization is due to a number of effects that include temporary loss of membrane potential, inability to transport neurotrophic factors leading to altered phenotype, and reversible retraction of epidermal and dermal nerve fibre terminals. Peripheral neuropathic hypersensitivity is mediated by diverse mechanisms, including altered expression of the capsaicin receptor TRPV1 or other key ion channels in affected or intact adjacent peripheral nociceptive nerve fibres, aberrant re-innervation, and collateral sprouting, all of which are defunctionalized by topical capsaicin. Evidence suggests that the utility of topical capsaicin may extend beyond painful peripheral neuropathies

The Victorian Newsletter (Spring 1967)

The Victorian Newsletter is edited for the English X Group of the Modern Language Association by William E. Buckler, New York University, New York, N.Y. 10003

CNS targets of adipokines

This is the author accepted manuscript. The final version is available from American Physiological Society via the DOI in this record.Our understanding of adipose tissue as an endocrine organ has been transformed over the last twenty years. During this time a number of adipocyte-derived factors or adipokines have been identified. This paper will review evidence for how adipokines acting via the central nervous system (CNS) regulate normal physiology and disease pathology. The reported CNS-mediated effects of adipokines are varied and include the regulation of energy homeostasis, autonomic nervous system activity, the reproductive axis, neurodevelopment, cardiovascular function, and cognition. Due to the wealth of information available and the diversity of their known functions, the archetypal adipokines leptin and adiponectin will be the focused on extensively. Other adipokines with established CNS actions will also be discussed. Due to the difficulties associated with studying CNS function on a molecular level in humans, the majority of our knowledge, and as such the studies described in this paper, comes from work in experimental animal models; however, where possible the relevant data from human studies are also highlighted