Law Enforcement Academy Performance Report, FY 2004

Agency Performance Report

The role of the T-cell receptor (TCR) in alpha beta/gamma delta lineage commitment: clues from intracellular TCR staining.

T cells belong to two mutually exclusive lineages expressing either alpha beta or gamma delta T-cell receptors (TCR). Although alpha beta and gamma delta cells are known to share a common precursor the role of TCR rearrangement and specificity in the lineage commitment process is controversial. Instructive lineage commitment models endow the alpha beta or gamma delta TCR with a deterministic role in lineage choice, whereas separate lineage models invoke TCR-independent lineage commitment followed by TCR-dependent selection and maturation of alpha beta and gamma delta cells. Here we review the published data pertaining to the role of the TCR in alpha beta/gamma delta lineage commitment and provide some additional information obtained from recent intracellular TCR staining studies. We conclude that a variant of the separate lineage model is best able to accommodate all of the available experimental results.

A limited role for beta-selection during gamma delta T cell development.

T cells belong to two distinct lineages expressing either alpha beta or gamma delta TCR. During alpha beta T cell development, it is clearly established that productive rearrangement at the TCR beta locus in immature precursor cells leads to the expression of a pre-TCR complex. Signaling through the pre-TCR results in the selective proliferation and maturation of TCR beta+ cells, a process that is known as beta-selection. However, the potential role of beta-selection during gamma delta T cell development is controversial. Whereas PCR-RFLP and sequencing techniques have provided evidence for a bias toward in-frame VDJ beta rearrangements in gamma delta cells (consistent with beta-selection), gamma delta cells apparently develop normally in mice that are unable to assemble a pre-TCR complex due to a deficiency in TCR beta or pT alpha genes. In this report, we have directly addressed the physiologic significance of beta-selection during gamma delta cell development in normal mice by quantitating intracellular TCR beta protein in gamma delta cells and correlating its presence with cell cycle status. Our results indicate that beta-selection plays a significant (although limited) role in gamma delta cell development by selectively amplifying a minor subset of gamma delta precursor cells with productively rearranged TCR beta genes.

The short arm of the law: judicial institutions and local governance in Brazil

This paper estimates the effect of judicial institutions on governance at the local level in Brazil. Our estimation strategy exploits a unique institutional feature of state judiciary branches which assigns prosecutors and judges to the most populous among contiguous counties forming a judiciary district. As a result of this assignment mechanism there are counties with nearly identical populations, some with and some without local judicial presence, which we exploit to impute counterfactual outcomes. Conditional on observable county characteristics, offenses per civil servant are about 35% lower in counties that have a local seat of the state judiciary. The lower incidence of infractions stems mostly from fewer violations of financial management regulations by local administrators, fewer instances of problems in project execution and project managment, fewer cases of non-existent or ineffective civil society oversight and fewer cases of improper handling of remittances to local residents.

A novel interferon-gamma regulated human melanoma-associated antigen, gp33-38, defined by monoclonal antibody Me14-D12. II. Molecular cloning of a genomic probe.

The human Me14-D12 antigen is a cell surface glycoprotein regulated by interferon-gamma (IFN-gamma) on tumor cell lines of neuroectodermal origin. It consists of two non-convalently linked subunits with apparent mol. wt sizes of 33,000 and 38,000. Here we describe the molecular cloning of a genomic probe for the Me14-D12 gene using the gene transfer approach. Mouse Ltk- cells were stably cotransfected with human genomic DNA and the Herpes Simplex virus thymidine kinase (TK) gene. Primary and secondary transfectants expressing the Me14-D12 antigen were isolated after selection in HAT medium by repeated sorting on a fluorescence activated cell sorter (FACS). A recombinant phage harboring a 14.3 kb insert of human DNA was isolated from a genomic library made from a positive secondary transfectant cell line. A specific probe derived from the phage DNA insert allowed the identification of two mRNAs of 3.5 kb and 2.2 kb in primary and secondary L cell transfectants, as well as in human melanoma cell lines expressing the Me14-D12 antigen. The regulation of Me14-D12 antigen by INF-gamma was retained in the L cell transfectants and could be detected both at the level of protein and mRNA expression.

The Law of Impersonal Transactions: Meaning and Difficulties

Most economic interactions happen in a context of sequential exchange in which innocent third parties suffer information asymmetry with respect to previous "originative" contracts. The law reduces transaction costs by protecting these third parties but preserves some element of consent by property right holders to avoid damaging property enforcement-e.g., it is they as principals who authorize agents in originative contracts. Judicial verifiability of these originative contracts is obtained either as an automatic byproduct of transactions or, when these would have remained private, by requiring them to be made public. Protecting third parties produces a sort of legal commodity which is easy to trade impersonally, improving the allocation and specialization of resources. Historical delay in generalizing this legal commoditization paradigm is attributed to path dependency-the law first developed for personal trade-and an unbalance in vested interests, as luddite legal professionals face weak public bureaucracies.

[Archives de la Parole]. , Son-in-law-at-home : a fable in Parja from Bastar (C.P) [i.e. Central Provinces] / [Sir George Grierson], éd. ; Linguistic survey of India ; [Bhima Parjā], voix

[Traditions. Asie. Inde. Madhya Pradesh. Chhattisgarh]

Report of Recommendations to the Iowa Law Enforcement Academy, June 30, 2005

State Audit Reports

Long-term, multilineage hematopoiesis occurs in the combined absence of beta-catenin and gamma-catenin

The canonical Wnt signaling pathway plays key roles in stem-cell maintenance, progenitor cell expansion, and lineage decisions. Transcriptional responses induced by Wnt depend on the association of either beta-catenin or gamma-catenin with lymphoid enhancer factor/T cell factor transcription factors. Here we show that hematopoiesis, including thymopoiesis, is normal in the combined absence of beta- and gamma-catenin. Double-deficient hematopoietic stem cells maintain long-term repopulation capacity and multilineage differentiation potential. Unexpectedly, 2 independent ex vivo reporter gene assays show that Wnt signal transmission is maintained in double-deficient hematopoietic stem cells, thymocytes, or peripheral T cells. In contrast, Wnt signaling is strongly reduced in thymocytes lacking TCF-1 or in nonhematopoietic cells devoid of beta-catenin. These data provide the first evidence that hematopoietic cells can transduce canonical Wnt signals in the combined absence of beta- and gamma-catenin

Gamma Knife radiosurgery in benign skull base tumors after planned subtotal resection: preliminary results in combined approaches

Aim: The management of large lesions of the skull base, such as vestibular schwanommas (VS), meningiomas (MEN) or pituitary adenomas (PA), is challenging, with microsurgery remaining the main treatment option. Planned subtotal resection is now being increasingly considered to reduce the risk of neurological deficits following complete resection. The residual part of the tumor can then be treated with Gamma Knife Radiosurgery (GKR) to achieve long-term growth control. Methods: This case series documents early results with planned subtotal resection followed by GKR in Lausanne University Hospital, between July 2010 and March 2012. There were 24 patients who underwent surgery, with 22 having already undergone GKR and 2 waiting for GKR. We analyzed clinical symptoms for all patients, as well as audiograms, ophthalmological and endocrinological tests, when indicated. Results: Nine patients had VS surgery (mean diameter 35 mm; range 30-44.5) through a retrosigmoid approach. There were no post-operative facial nerve deficits. Of the 3 patients whom had useful hearing pre-operatively, this improved in 2 and remained stable in 1. Four patients with clinoid MEN (mean diameter 26.5 mm; range 17-42) underwent subtotal resection of the tumor, and the component in the cavernous sinus was later treated with GKR. The visual status remained stable in 3 patients and one had complete visual recovery. 4 patients underwent subtotal resection of petro-clival MEN (mean diameter 36 mm; range 32-42): 3 had House-Brackmann (HB) grade 2 facial function that recovered completely; one continues to have HB grade 4 facial deficit following surgery. Of the 7 patients with PA (mean diameter 34.5 mm; range 20-54.5), 2 had acromegaly, the others were non functional PA. Six patients underwent trans-sphenoidal surgery, while one patient had a transcavernous sinus resection of the tumor (with prior staged trans-sphenoidal surgery). Visual status improved in 3 patients while the others remained stable. Two patients had transient diabetes insipidus following surgery. Up to now, no additional deficit or worsening has been reported after GKR. Conclusions: Our data suggest that planned subtotal resection has an excellent clinical outcome with respect to preservation of cranial nerves, and other neurological functions, and a good possibility of recovery of many of the pre-operative cranial nerve dysfunctions. The results in terms of tumor control following GKR need further long-term evaluation.

Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice.

This study demonstrates that endogenously produced interferon gamma (IFN-gamma) forms the basis of a tumor surveillance system that controls development of both chemically induced and spontaneously arising tumors in mice. Compared with wild-type mice, mice lacking sensitivity to either IFN-gamma (i.e., IFN-gamma receptor-deficient mice) or all IFN family members (i.e., Stat1-deficient mice) developed tumors more rapidly and with greater frequency when challenged with different doses of the chemical carcinogen methylcholanthrene. In addition, IFN-gamma-insensitive mice developed tumors more rapidly than wild-type mice when bred onto a background deficient in the p53 tumor-suppressor gene. IFN-gamma-insensitive p53(-/-) mice also developed a broader spectrum of tumors compared with mice lacking p53 alone. Using tumor cells derived from methylcholanthrene-treated IFN-gamma-insensitive mice, we found IFN-gamma's actions to be mediated at least partly through its direct effects on the tumor cell leading to enhanced tumor cell immunogenicity. The importance and generality of this system is evidenced by the finding that certain types of human tumors become selectively unresponsive to IFN-gamma. Thus, IFN-gamma forms the basis of an extrinsic tumor-suppressor mechanism in immunocompetent hosts.