The Marriage Mirage: The Personal and Social Indentity Implications of Same-Gendered Matrimony

This Article will examine why so much is at stake in the political, social, and legal debate over same-gender marriage. It will not address the constitutional questions of whether there is a fundamental right to marry, although persuasive arguments have been advanced from both sides of the debate. This Article will focus on a more introspective view of the potential effects of legalizing same-gender marriage on the identities of gay men and lesbians in committed relationships and on the interaction between same-gender couples and society. Marriage would provide the integration sought by gay men and lesbians, but at the expense of significant social quandary. In Part I, this paper will dissect the meaning of marriage into its relational, traditional, and Christian aspects. Part II will explore the legal and constitutive qualities of same-gender marriage. Part III will discuss the impact of the law of marriage in its present form on the identities of gay men and lesbians, as they see themselves and as society views them. Part IV will look at how legalization of same-gender marriages might change the self-perception of gay couples, what legal benefits it would confer, and how the heterosexual majority might respond. This Article will conclude that the legalization of same-gender marriage is too big of a step and will suggest, instead, enactment of smaller benefits packages to mitigate economic and legal discrimination against same-gender couples, while society prepares for same-gender marriage

Administrator Opinion on the Need for Small and Large School Divisions Within the North Central Association

No abstract provided by author

Effect of Combined PD-1 and STAT3 Pathway Blockade Treatment on K-ras Mutant Lung Cancer

https://openworks.mdanderson.org/sumexp21/1175/thumbnail.jp

Substance P Causes Seizures in Neurocysticercosis

Neurocysticercosis (NCC), a helminth infection of the brain, is a major cause of seizures. The mediators responsible for seizures in NCC are unknown, and their management remains controversial. Substance P (SP) is a neuropeptide produced by neurons, endothelial cells and immunocytes. The current studies examined the hypothesis that SP mediates seizures in NCC. We demonstrated by immunostaining that 5 of 5 brain biopsies from NCC patients contained substance P (SP)-positive (+) cells adjacent to but not distant from degenerating worms; no SP+ cells were detected in uninfected brains. In a rodent model of NCC, seizures were induced after intrahippocampal injection of SP alone or after injection of extracts of cysticercosis granuloma obtained from infected wild type (WT), but not from infected SP precursor-deficient mice. Seizure activity correlated with SP levels within WT granuloma extracts and was prevented by intrahippocampal pre-injection of SP receptor antagonist. Furthermore, extracts of granulomas from WT mice caused seizures when injected into the hippocampus of WT mice, but not when injected into SP receptor (NK1R) deficient mice. These findings indicate that SP causes seizures in NCC, and, suggests that seizures in NCC in humans may be prevented and/or treated with SP-receptor antagonists

Naval expeditionary logistics support group, training and evaluation unit: an analysis of current operations while searching for training efficiencies

MBA Professional ReportThis paper used simulation modeling and process analysis to identify efficiencies that can be gained to improve capacity and flexibility of the Naval Expeditionary Logistics Support Group Training and Evaluation Unit. The primary objectives were 1) capacity planning in the aggregate, and 2) increasing capacity by identifying instructor qualification process constraints. The researchers first used aggregate planning methodology and determined that demand exceeded capacity. Arena simulation software was subsequently utilized to simulate the instructor qualification process to determine average total time in the system and to extract the non-value added processes. The study found that newly assigned instructor candidates are subject to an inordinately long training period respective to their tour length to achieve qualification for cargo handling training and evaluation. Reasons for long training periods include a lack of feeder rates, inconsistent demand, and multiple qualification objectives for each instructor. The researchers determined that changing instructor qualification processes as well as adding civilian personnel to the training process, non-value added time can be drastically reduced, increasing the percentage of time that members are fully qualified for tasking during a prescribed assignment to TEU. These recommendations result in an effective increase in personnel for tasking without increasing personnel manning assignments.http://archive.org/details/navalexpeditiona1094510400Approved for public release; distribution is unlimited

Administrator Opinion on the Need for Small and Large School Divisions Within the North Central Association

No abstract provided by author

Genetic and Small-Molecule Modulation of Stat3 in a Mouse Model of Crohn’s Disease

Crohn’s disease (CD), is an inflammatory bowel disease that can affect any part of the gastro-intestinal tract (GI) and is associated with an increased risk of gastro-intestinal cancer. In the current study, we determined the role of genetic and small-molecule modulation of STAT3 in a mouse model of CD. STAT3 has 2 isoforms (α, β) which are expressed in most cells in a 4:1 ratio (α: β). STAT3α has pro-inflammatory and anti-apoptotic functions, while STAT3β has contrasting roles. We used an animal model of CD consisting of intrarectal administration of 2,4,6-trinitrobenzene sulfonic acid and examined the severity of CD in transgenic-mice that express only STAT3α (∆β/∆β), as well as in wild-type (WT) mice administered TTI-101 (formerly C188-9), a small molecule STAT3 inhibitor. We determined that clinical manifestations of CD, such as mortality, rectal-bleeding, colonic bleeding, diarrhea, and colon shortening, were exacerbated in ∆β/∆β transgenic versus cage-control WT mice, while they were markedly decreased by TTI-101 treatment of WT mice. TTI-101 treatment also increased apoptosis of pathogenic CD4+ T cells and reduced colon levels of IL-17-positive cells. Our results indicate that STAT3 contributes to CD and that targeting of STAT3 with TTI-101 may be a useful approach to treating CD

Monoclonal Antibodies Specific for STAT3β Reveal Its Contribution to Constitutive STAT3 Phosphorylation in Breast Cancer

Since its discovery in mice and humans 19 years ago, the contribution of alternatively spliced Stat3, Stat3β, to the overall functions of Stat3 has been controversial. Tyrosine-phosphorylated (p) Stat3β homodimers are more stable, bind DNA more avidly, are less susceptible to dephosphorylation, and exhibit distinct intracellular dynamics, most notably markedly prolonged nuclear retention, compared to pStat3α homodimers. Overexpression of one or the other isoform in cell lines demonstrated that Stat3β acted as a dominant-negative of Stat3α in transformation assays; however, studies with mouse strains deficient in one or the other isoform indicated distinct contributions of Stat3 isoforms to inflammation. Current immunological reagents cannot differentiate Stat3β proteins derived from alternative splicing vs. proteolytic cleavage of Stat3α. We developed monoclonal antibodies that recognize the 7 C-terminal amino acids unique to Stat3β (CT7) and do not cross-react with Stat3α. Immunoblotting studies revealed that levels of Stat3β protein, but not Stat3α, in breast cancer cell lines positively correlated with overall pStat3 levels, suggesting that Stat3β may contribute to constitutive Stat3 activation in this tumor system. The ability to unambiguously discriminate splice alternative Stat3β from proteolytic Stat3β and Stat3α will provide new insights into the contribution of Stat3β vs. Stat3α to oncogenesis, as well as other biological and pathological processes

Modulation of STAT3 folding and function by TRiC/CCT chaperonin.

Signal transducer and activator of transcription 3 (Stat3) transduces signals of many peptide hormones from the cell surface to the nucleus and functions as an oncoprotein in many types of cancers, yet little is known about how it achieves its native folded state within the cell. Here we show that Stat3 is a novel substrate of the ring-shaped hetero-oligomeric eukaryotic chaperonin, TRiC/CCT, which contributes to its biosynthesis and activity in vitro and in vivo. TRiC binding to Stat3 was mediated, at least in part, by TRiC subunit CCT3. Stat3 binding to TRiC mapped predominantly to the β-strand rich, DNA-binding domain of Stat3. Notably, enhancing Stat3 binding to TRiC by engineering an additional TRiC-binding domain from the von Hippel-Lindau protein (vTBD), at the N-terminus of Stat3, further increased its affinity for TRiC as well as its function, as determined by Stat3's ability to bind to its phosphotyrosyl-peptide ligand, an interaction critical for Stat3 activation. Thus, Stat3 levels and function are regulated by TRiC and can be modulated by manipulating its interaction with TRiC