Exclusive development of T cell neoplasms in mice transplanted with bone marrow expressing activated Notch alleles

Notch is a highly conserved transmembrane protein that is involved in cell fate decisions and is found in organisms ranging from Drosophila to humans. A human homologue of Notch, TAN1, was initially identified at the chromosomal breakpoint of a subset of T-cell lymphoblastic leukemias/lymphomas containing a t(7;9) chromosomal translocation; however, its role in oncogenesis has been unclear. Using a bone marrow reconstitution assay with cells containing retrovirally transduced TAN1 alleles, we analyzed the oncogenic potential of both nuclear and extranuclear forms of truncated TAN1 in hematopoietic cells. Although the Moloney leukemia virus long terminal repeat drives expression in most hematopoietic cell types, retroviruses encoding either form of the TAN1 protein induced clonal leukemias of exclusively immature T cell phenotypes in approximately 50% of transplanted animals. All tumors overexpressed truncated TAN1 of the size and subcellular localization predicted from the structure of the gene. These results show that TAN1 is an oncoprotein and suggest that truncation and overexpression are important determinants of transforming activity. Moreover, the murine tumors caused by TAN1 in the bone marrow transplant model are very similar to the TAN1-associated human tumors and suggest that TAN1 may be specifically oncotropic for T cells

Individual, Neighborhood, and Situational Factors Associated with Violent Victimization and Offending

The criminological literature presents substantial evidence that victims and offenders in violent crimes share demographic characteristics, engage in similar lifestyles and activities, and reside in socially disorganized neighborhoods. However, research has examined these relationships separately using either victimization or offending data, and prior studies have not examined these relationships by comparing victims and offenders within the same incidents. This limits the effect of examining whether these factors are associated with victimization and offending in similar or distinct ways. Using a law enforcement database of victims (n = 1,248) and offenders (n = 1,735) involved within the same aggravated battery incidents (n = 1,015) in Bernalillo County, New Mexico, this research explores whether victims and offenders involved in non-lethal violence share certain individual, neighborhood and situational characteristics. Results suggest that victims and offenders live in socially disorganized neighborhoods and engage in risky lifestyles and violent offending behaviors in similar proportions. These findings highlight the overlapping factors associated with victimization and offending in non-lethal violent personal crimes. The implications of these findings are discussed

Previous Emergency Department Use Among Homicide Victims and Offenders: A Case-Control Study

We differentiate risk factors for future homicide victimization and offending, and we measure emergency department (ED) use among homicide victims, offenders, and controls. The design was a matched case-control study conducted in Bernalillo County, NM, and its university-affiliated health sciences center and hospital. All Bernalillo County homicide victims (N=124) and offenders (N=138) identified between January 1996 and December 2001 who were linked to university physician billing records and who had health care use during the 3 years before the homicide incident were included as cases. Randomly selected age-matched (±1 year) and sex-matched subjects with health care use within 3 years of their matched pair’s homicide were included as controls. Main outcome measures were the number and type of ED visits by cases and controls. Patients with ED visits for assault, firearm injuries, and substance abuse are at increased risk for homicide and often have an escalating number of visits leading up to the homicide event. ED-based identification and referral programs similar to those used for intimate partner violenc

Exploring Demographic, Structural, and Behavioral Overlap Among Homicide Offenders and Victims

Criminologists tend to focus their attention on the dynamics of offending, paying limited theoretical and empirical attention to the well-established relation between offending and victimization. However, a number of criminological theories predict similarities in the correlates and etiology of victimization and offending, suggesting substantial overlap across offender and victim populations. Empirical research confirms this overlap across offender and victim populations, at least among those involved in nonlethal incidents. This research explores whether similarities between offender and victim populations extends to homicide, using criminal justice, health care, and U.S. Census data linked to homicide offenders and victims in Bernalillo County, New Mexico, between 1996 and 2001. Findings indicate substantial overlap in the social contexts and risk behaviors of homicide offenders and victims. However, results also side with more recent suggestions that although many victims overlap with offender populations, there is also a group of victims that appears to be distinguishable from offender groups. These findings have important implications for both theory and intervention

Important Historical Efforts at Emergency Department Categorization in the United States and Implications for Regionalization

This article is drawn from a report created for the American College of Emergency Physicians (ACEP) Emergency Department (ED) Categorization Task Force and also reflects the proceedings of a breakout session, “Beyond ED Categorization—Matching Networks to Patient Needs,” at the 2010 Academic Emergency Medicine consensus conference, “Beyond Regionalization: Integrated Networks of Emergency Care.” The authors describe a brief history of the significant national and state efforts at categorization and suggest reasons why many of these efforts failed to persevere or gain wider implementation. The history of efforts to categorize hospital (and ED) emergency services demonstrates recognition of the potential benefits of categorization, but reflects repeated failures to implement full categorization systems or limited excursions into categorization through licensing of EDs or designation of receiving and referral facilities. An understanding of the history of hospital and ED categorization could better inform current efforts to develop categorization schemes and processes.ACADEMIC EMERGENCY MEDICINE 2010; 17:e154–e160 © 2010 by the Society for Academic Emergency MedicinePeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79214/1/j.1553-2712.2010.00931.x.pd

Categorization, Designation, and Regionalization of Emergency Care: Definitions, a Conceptual Framework, and Future Challenges

This article reflects the proceedings of a breakout session, “Beyond ED Categorization—Matching Networks to Patient Needs,” at the 2010 Academic Emergency Medicine consensus conference, “Beyond Regionalization: Integrated Networks of Emergency Care.” It is based on concepts and areas of priority identified and developed by the authors and participants at the conference. The paper first describes definitions fundamental to understanding the categorization, designation, and regionalization of emergency care and then considers a conceptual framework for this process. It also provides a justification for a categorization system being integrated into a regionalized emergency care system. Finally, it discusses potential challenges and barriers to the adoption of a categorization and designation system for emergency care and the opportunities for researchers to study the many issues associated with the implementation of such a system.ACADEMIC EMERGENCY MEDICINE 2010; 17:1306–1311 © 2010 by the Society for Academic Emergency MedicinePeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79324/1/j.1553-2712.2010.00932.x.pd

Concurrent codes:a holographic-type encoding robust against noise and loss

Concurrent coding is an encoding scheme with 'holographic' type properties that are shown here to be robust against a significant amount of noise and signal loss. This single encoding scheme is able to correct for random errors and burst errors simultaneously, but does not rely on cyclic codes. A simple and practical scheme has been tested that displays perfect decoding when the signal to noise ratio is of order -18dB. The same scheme also displays perfect reconstruction when a contiguous block of 40% of the transmission is missing. In addition this scheme is 50% more efficient in terms of transmitted power requirements than equivalent cyclic codes. A simple model is presented that describes the process of decoding and can determine the computational load that would be expected, as well as describing the critical levels of noise and missing data at which false messages begin to be generated

Ernst Freund as Precursor of the Rational Study of Corporate Law

Gindis, David, Ernst Freund as Precursor of the Rational Study of Corporate Law (October 27, 2017). Journal of Institutional Economics, Forthcoming. Available at SSRN: https://ssrn.com/abstract=2905547, doi: https://dx.doi.org/10.2139/ssrn.2905547The rise of large business corporations in the late 19th century compelled many American observers to admit that the nature of the corporation had yet to be understood. Published in this context, Ernst Freund's little-known The Legal Nature of Corporations (1897) was an original attempt to come to terms with a new legal and economic reality. But it can also be described, to paraphrase Oliver Wendell Holmes, as the earliest example of the rational study of corporate law. The paper shows that Freund had the intuitions of an institutional economist, and engaged in what today would be called comparative institutional analysis. Remarkably, his argument that the corporate form secures property against insider defection and against outsiders anticipated recent work on entity shielding and capital lock-in, and can be read as an early contribution to what today would be called the theory of the firm.Peer reviewe

Effect of 28 days of creatine ingestion on muscle metabolism and performance of a simulated cycling road race

<p>Abstract</p> <p>Purpose</p> <p>The effects of creatine supplementation on muscle metabolism and exercise performance during a simulated endurance road race was investigated.</p> <p>Methods</p> <p>Twelve adult male (27.3 ± 1.0 yr, 178.6 ± 1.4 cm, 78.0 ± 2.5 kg, 8.9 ± 1.1 %fat) endurance-trained (53.3 ± 2.0 ml* kg^-1* min^-1, cycling ~160 km/wk) cyclists completed a simulated road race on a cycle ergometer (Lode), consisting of a two-hour cycling bout at 60% of peak aerobic capacity (VO_2peak) with three 10-second sprints performed at 110% VO_{2 peak}every 15 minutes. Cyclists completed the 2-hr cycling bout before and after dietary creatine monohydrate or placebo supplementation (3 g/day for 28 days). Muscle biopsies were taken at rest and five minutes before the end of the two-hour ride.</p> <p>Results</p> <p>There was a 24.5 ± 10.0% increase in resting muscle total creatine and 38.4 ± 23.9% increase in muscle creatine phosphate in the creatine group (<it>P </it>< 0.05). Plasma glucose, blood lactate, and respiratory exchange ratio during the 2-hour ride, as well as VO_{2 peak}, were not affected by creatine supplementation. Submaximal oxygen consumption near the end of the two-hour ride was decreased by approximately 10% by creatine supplementation (P < 0.05). Changes in plasma volume from pre- to post-supplementation were significantly greater in the creatine group (⁺14.0 ± 6.3%) than the placebo group (^-10.4 ± 4.4%; <it>P </it>< 0.05) at 90 minutes of exercise. The time of the final sprint to exhaustion at the end of the 2-hour cycling bout was not affected by creatine supplementation (creatine pre, 64.4 ± 13.5s; creatine post, 88.8 ± 24.6s; placebo pre, 69.0 ± 24.8s; placebo post 92.8 ± 31.2s: creatine vs. placebo not significant). Power output for the final sprint was increased by ~33% in both groups (creatine vs. placebo not significant).</p> <p>Conclusions</p> <p>It can be concluded that although creatine supplementation may increase resting muscle total creatine, muscle creatine phosphate, and plasma volume, and may lead to a reduction in oxygen consumption during submaximal exercise, creatine supplementation does not improve sprint performance at the end of endurance cycling exercise.</p

Ionizing Radiation-Induced Oxidative Stress Alters miRNA Expression

). treatment, and 45 after etoposide treatment. Substantial overlap between the miRNA expression changes between agents was observed suggesting a signature miRNA response to cell stress. Changes in the expression of selected miRNA species varied in response to radiation dose and time. Finally, production of reactive oxygen species (ROS) increased with increasing doses of radiation and pre-treatment with the thiol antioxidant cysteine decreased both ROS production and the miRNA response to radiation., and etoposide. Additionally, pre-treatment with cysteine prevented radiation-induced alterations in miRNA expression which suggests that miRNAs are responsive to oxidative stress. Taken together, these results imply that miRNAs play a role in cellular defense against exogenous stress and are involved in the generalized cellular response to genotoxic oxidative stress