The cytoplasmic domain of CD4 promotes the development of CD4 lineage T cells.

Thymocytes must bind major histocompatibility complex (MHC) proteins on thymic epithelial cells in order to mature into either CD8+ cytotoxic T cells or CD4+ helper T cells. Thymic precursors express both CD8 and CD4, and it has been suggested that the intracellular signals generated by CD8 or CD4 binding to class I or II MHC, respectively, might influence the fate of uncommitted cells. Here we test the notion that intracellular signaling by CD4 directs the development of thymocytes to a CD4 lineage. A hybrid protein consisting of the CD8 extracellular and transmembrane domains and the cytoplasmic domain of CD4 (CD884) should bind class I MHC but deliver a CD4 intracellular signal. We find that expression of a hybrid CD884 protein in thymocytes of transgenic mice leads to the development of large numbers of class I MHC-specific, CD4 lineage T cells. We discuss these results in terms of current models for CD4 and CD8 lineage commitment

Releasing Authority Chairs: A Comparative Snapshot Across Three Decades

This report provides a comparative analysis of releasing authority chairs' views of the issues and challenges confronting them at two points in time: 1988 and 2015. Drawing from two surveys, one conducted during the tenure of an ACA Parole Task Force that functioned from 1986-1988, and the other a survey published in 2016 by the Robina Institute called The Continuing Leverage of Releasing Authorities: Findings from a National Survey, this new publication highlights both change and constancy relative to a wide range of comparative markers including, but not limited to, structured decision tools, prison crowding and risk aversion, and the myriad factors considered in granting or denying parole

The Continuing Leverage of Releasing Authorities: Findings from a National Survey

The Robina Institute of Criminal Law and Criminal Justice launched a national survey of releasing authorities in March 2015 to each state, and the U.S. Parole Commission. The importance of the survey was underscored by an endorsement from the Association of Paroling Authorities International (APAI). We are pleased to present the results from this important survey here. This is the first comprehensive survey of parole boards completed in nearly 10 years. Its findings provide a rich database for better understanding the policy and practice of paroling authorities. The last survey to be conducted of paroling authorities was in 2007/2008.The current report offers an expansion and update of previous surveys. The results summarized throughout the report offer a timely resource for paroling authorities, correctional policy-makers and practitioners, legislators, and those with a public policy interest in sentencing and criminal justice operations. It is our hope that the document and its findings provide key justice system and other stakeholders with an incisive snapshot of the work of paroling authorities across the country in a manner that contributes to a larger conversation about sound and effective parole release and revocation practices.The completion of this comprehensive survey and the reporting of its findings offers a timely and invaluable resource for releasing authorities. It provides them and other key justice system stakeholders with a comparative understanding of their colleagues' work across the nation, and contributes to a larger conversation pertaining to effective parole release and revocation practices

Probation Revocation and Its Causes: Profiles of State and Local Jurisdictions, Hennepin County, Minnesota

This profile describes the structure and operations of probation violations in Hennepin County. Hennepin County Probation is a large department with over 900 probation staff, 65 judges and many more public defenders, city and county attorneys. Interviews were only conducted with a small sample of professionals and probationers involved in probation violations and revocations. The county attorneys are also not represented in this profile as they declined participation in the interviews

From Dichotomy to Ambidexterity: Transcending Traditions in Software Management

Despite documented best practices and specialized tools, managers continue to face major challenges in software development. While managers are traditionally advised to choose between plan-driven and agile principles, software organizations increasingly face situations in which they need to take advantage of both. There is, however, limited actionable advice on how managers can shape the organizational context to develop such capability. We therefore combine theory on ambidexterity and contextualist inquiry to report from a two-year action research study at TelSoft. As a result, we propose a model for how software organizations can become ambidextrous through the processes of diagnosing, visioning, intervening, and practicing and discuss the implications for research and practice into software management

Bone Marrow Stromal Cells: Characterization and Clinical Application

The bone marrow stroma consists of a heterogeneous population of cells that provide the structural and physiological support for hematopoietic cells. Additionally, the bone marrow stroma contains cells with a stem-cell-like character that allows them to differentiate into bone, cartilage, adipocytes, and hematopoietic supporting tissues. Several experimental approaches have been used to characterize the development and functional nature of these cells in vivo and their differentiating potential in vitro. In vivo, presumptive osteogenic precursors have been identified by morphologic and immunohistochemical methods. In culture, the stromal cells can be separated from hematopoietic cells by their differential adhesion to tissue culture plastic and their prolonged proliferative potential. In cultures generated from single-cell suspensions of marrow, bone marrow stromal cells grow in colonies, each derived from a single precursor cell termed the colony-forming unit-fibroblast. Culture methods have been developed to expand marrow stromal cells derived from human, mouse, and other species. Under appropriate conditions, these cells are capable of forming new bone after in vivo transplantation. Various methods of cultivation and transplantation conditions have been studied and found to have substantial influence on the transplantation outcome The finding that bone marrow stromal cells can be manipulated in vitro and subsequently form bone in vivo provides a powerful new model system for studying the basic biology of bone and for generating models for therapeutic strategies aimed at regenerating skeletal elements.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68070/2/10.1177_10454411990100020401.pd

An Acoustic Technique for the Noninvasive in-Situ Measurement of Crystal Size and Solution Concentration

We demonstrated the use of acoustic measurements for tracking potassium dihydrogen phosphate (KDP) crystal growth. Both KDP solution concentration and KDP crystal size can be found by using information derived from acoustic wave propagation in the solution. Acoustic measurements show good correlation to conductivity measurements for KDP solution concentration

Exploring Supervision Fees in Four Probation Jurisdictions in Texas

In 2014, the University of Minnesota's Robina Institute of Criminal Law and Criminal Justice began a multi-state study that was tasked with exploring nationwide variations in the practices and policies of probation violations and revocations. A distinctive finding that grew out of the Robina Institute's work in two Texas counties was that probation supervision fees play a major role throughout the state. Probationers are required as one of 25 standard conditions to pay supervision fees, and—depending on the case— they may have to pay additional program fees, fines, and restitution. Texas probation departments depend on supervision fees for a large share of their operating budgets, and they are responsible for collecting those fees. Because payment of fees is a formal condition of probation, probationers may be sanctioned if they fall delinquent. Additionally, their probation terms may be extended to allow more time to pay, or early termination may be denied. In interviews, some probationers believed they could be revoked to jail or prison for failure to pay supervision fees. However, we heard from probation officers that probationers were not revoked solely for fees. The officers told us that nonpayment may be one reason probationers are revoked, but only when combined with other violations.The Robina Institute was encouraged by other probation chiefs in Texas to add additional counties to our study. To understand the interaction between probation and criminal justice fees in greater depth, the Robina Institute conducted a mixed methods study with 4 probation jurisdictions in Texas. Quantitative data was analyzed to examine the average amount of fees ordered, the breakdown of the fees ordered, and the percent of probationers who were current and delinquent on their fees. The quantitative analysis also examined the outcomes for those who were delinquent on their fees. Qualitative interviews were conducted with probationers to understand how fees impacted them and their experience of probation, as well as how they handled paying their fees. Probation officers were also interviewed to examine how fees were utilized and how officers collected fees.This report highlights some of the findings from qualitative interviews with over 50 probation officers and 46 probationers in 4 probation jurisdictions. A separate report highlights our quantitative findings; future Robina Institute publications will explore the quantitative and qualitative data in greater depth, as well as legal issues associated with the imposition and collection of supervision fees.The first section of this report presents findings from the focus groups with the probation officers. The second section focuses on findings from the probationer focus groups

Predicting the safety and efficacy of butter therapy to raise tumour pHe: an integrative modelling study

Background: Clinical positron emission tomography imaging has demonstrated the vast majority of human cancers exhibit significantly increased glucose metabolism when compared with adjacent normal tissue, resulting in an acidic tumour microenvironment. Recent studies demonstrated reducing this acidity through systemic buffers significantly inhibits development and growth of metastases in mouse xenografts.\ud \ud Methods: We apply and extend a previously developed mathematical model of blood and tumour buffering to examine the impact of oral administration of bicarbonate buffer in mice, and the potential impact in humans. We recapitulate the experimentally observed tumour pHe effect of buffer therapy, testing a model prediction in vivo in mice. We parameterise the model to humans to determine the translational safety and efficacy, and predict patient subgroups who could have enhanced treatment response, and the most promising combination or alternative buffer therapies.\ud \ud Results: The model predicts a previously unseen potentially dangerous elevation in blood pHe resulting from bicarbonate therapy in mice, which is confirmed by our in vivo experiments. Simulations predict limited efficacy of bicarbonate, especially in humans with more aggressive cancers. We predict buffer therapy would be most effectual: in elderly patients or individuals with renal impairments; in combination with proton production inhibitors (such as dichloroacetate), renal glomular filtration rate inhibitors (such as non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors), or with an alternative buffer reagent possessing an optimal pK of 7.1–7.2.\ud \ud Conclusion: Our mathematical model confirms bicarbonate acts as an effective agent to raise tumour pHe, but potentially induces metabolic alkalosis at the high doses necessary for tumour pHe normalisation. We predict use in elderly patients or in combination with proton production inhibitors or buffers with a pK of 7.1–7.2 is most promising