Proliferation tracing with single-cell mass cytometry optimizes generation of stem cell memory-like T cells.

Selective differentiation of naive T cells into multipotent T cells is of great interest clinically for the generation of cell-based cancer immunotherapies. Cellular differentiation depends crucially on division state and time. Here we adapt a dye dilution assay for tracking cell proliferative history through mass cytometry and uncouple division, time and regulatory protein expression in single naive human T cells during their activation and expansion in a complex ex vivo milieu. Using 23 markers, we defined groups of proteins controlled predominantly by division state or time and found that undivided cells account for the majority of phenotypic diversity. We next built a map of cell state changes during naive T-cell expansion. By examining cell signaling on this map, we rationally selected ibrutinib, a BTK and ITK inhibitor, and administered it before T cell activation to direct differentiation toward a T stem cell memory (TSCM)-like phenotype. This method for tracing cell fate across division states and time can be broadly applied for directing cellular differentiation

AN ASSAY OF GRAFT-HOST INTERACTIONS ACROSS STRONG AND WEAK HISTOCOMPATIBILITY BARRIERS IN MICE

1. A new assay of graft-host interactions has been presented. It consists of the early finding of liver infiltrates in responsive and unresponsive homologous recipients 1 to 3 days after the intravenous injection of competent lymphoid tissue in the mouse. 2. Evidence is presented that infiltrates are of donor origin, and are influenced by a homologous antigenic environment. They can be quantitatively increased by preimmunization of donor to recipient and decreased by preimmunization of recipient to donor. Furthermore, they are present in lethally x-irradiated or neonatally thymectomized unresponsive recipients after intravenous injection of competent homologous spleen cells. 3. Splenomegaly, which also occurs in this early period, is a product of both donor and host-specific immune reactivity together with a small non-specific component of host reactivity. 4. A comparison, of the responsiveness of lymphoid tissue from different strains to the same transplantation antigens is presented, together with the observation of differences in the reactivity of reciprocal donor-recipient injection combinations to each other. 5. Graft-host interactions with this model can be demonstrated in donor-host strain combinations isogenic at the H-2 locus without preimmunization of the donor. Differences in reactivity of reciprocal donor-recipient combinations of lymphoid tissue injections to each other can be detected in this group as well as in the groups differing at the strong H-2 locus

Interpretation, translation and intercultural communication in refugee status determination procedures in the UK and France

This article explores the interplay between language and intercultural communication within refugee status determination procedures in the UK and France, using material taken from ethnographic research that involved a combination of participant observation, semi-structured interviews and documentary analysis in both countries over a two-year period (2007–2009). It is concerned, in particular, to examine the role played by interpreters in facilitating intercultural communication between asylum applicants and the different administrative and legal actors responsible for assessing or defending their claims. The first section provides an overview of refugee status determination procedures in the UK and France, introducing the main administrative and legal contexts of the asylum process within which interpreters operate in the two countries. The second section compares the organisation of interpreting services, codes of conduct for interpreters and institutional expectations about the nature of interpreters’ activity on the part of the relevant UK and French authorities. The third section then explores some of the practical dilemmas for interpreters and barriers to communication that exist in refugee status determination procedures in the two countries. The article concludes by emphasising the complex and active nature of the interpreter's role in UK and French refugee status determination procedures

Conditioning with spatio-temporal patterns: Constraining the contribution of the hippocampus to configural learning

The conditions under which the hippocampus contributes to learning about spatio-temporal configural patterns are not fully established. The aim of Experiments 1–4 was to investigate the impact of hippocampal lesions on learning about where or when a reinforcer would be delivered. In each experiment, the rats received exposure to an identical set of patterns (i.e., spotted + morning, checked + morning, spotted + afternoon and checked + afternoon); and the contexts (Experiment 1), times of day (Experiment 2), or their configuration (Experiments 3 and 4) signalled whether or not a reinforcer would be delivered. The fact that hippocampal damage did not disrupt the formation of simple or configural associations involving spatio-temporal patterns is surprising, and suggests that the contribution of the hippocampus is restricted to mediated learning (or updating) involving spatio-temporal configurations

On Writ of Certiorari to the United States Court of Appeals for the Ninth Circuit, Brief of Product Liability Advisory Council, Inc., National Association of Manufacturers, Business Roundtable, and Chemical Manufacturers Association as Amici Curiae in Support of Respondent, William Daubert and Joyce Daubert, Individually and as Guardians Ad Litem for Jason Daubert, and Anita De Young, Individually and as Gaurdian Ad Litem for Eric Schuller v. Merrell Dow Pharmaceuticals, Inc.

The Federal Rules of Evidence exclude expert scientific testimony when it has been developed without regard for accepted scientific methods. This case focuses on expert scientific evidence. Such evidence plays a vital and often dispositive role in modern litigation. For scientific evidence to be helpful to the factfinder it must meet some minimal threshold of reliability. To hold otherwise would be to allow a system of adjudication based more on chance than on reason

Empowerment and the Transition to Housing for Homeless Mentally Ill People: An Anthropological Perspective

Often lacking in scholarly and policy-oriented discussions of homelessness are contextualized understandings of the problems faced, and the values held, by homeless mentally ill people. This article, using an anthropological perspective, examines issues that arise for homeless mentally ill individuals in making the transition from shelter living to permanent residences. The transition occurs as part of a housing initiative driven by the philosophy of consumer empowerment. Project participants are placed in independent apartments or evolving consumer households (ECH) — shared, staffed residences designed to transform themselves into consumer-directed living situations over time. The effects of an empowerment paradigm on the organization of space, the nature of social relations, and the management of economic resources in the ECHs are discussed to show that consumers and staff sometimes have contrasting views of what empowerment entails. It is suggested that anthropological research can help to illuminate the issues at stake in determining policy for homeless people with major mental illness