The Role of Oxygen Tension in Penile Erection and Its Relationship to Erectile Dysfunction

The corpus cavernosum of the penis is one of the few vascular beds in which there is a change in oxygen tension with function (blood PO2 25-40mm Hg in the flaccid state, and 90-100mm Hg in the erect state). This change in oxygen tension exposes the components of the corpus cavernosum to a variety of cytokines, humoral, vasoactive, and growth factors which may affect the structure and function of the endothelial cells, smooth muscle cells, neurons and extracellular matrix. Among these cell types, endothelial cells are the first line of defense to blood-borne stress and can affect the underlying smooth muscle via paracrine mechanisms. Impotence is defined as the inability to obtain or sustain an erection sufficient for vaginal penetration and can result from a variety of pathological conditions, vascular disease, endocrine disease, neurological disease, and psychogenic disorders. The penis is a vascular organ and as such is susceptible to the effects of vascular diseases. This review will discuss the basic etiology of erection and vasculogenic erectile dysfunction and explore the role oxygen tension in regulating various cellular and humoral factors as well as trabecular structure and function

Exposure effects in person perception: Familiarity, similarity, and attraction

Two experiments explored the relationship between familiarity, similarity, and attraction. In the first experiment, subjects viewed photographs of faces at various exposure frequencies and then rated them for likeableness and similarity. Familiar people were regarded by the subjects as both more likeable and more similar to themselves. The effects of familiarity on perceived similarity were primarily mediated by changes in attraction, although some evidence of a direct link between familiarity and perceived similarity was also found. In the second experiment, subjects viewed the same stimuli at a single exposure frequency, and received bogus information regarding the similarity of the people shown therein. Subsequent ratings of likeableness and perceived familiarity revealed that people who seemed similar to the subjects were regarded as both more likeable and more familiar. The effects of similarity on perceived familiarity were almost entirely mediated by changes in attraction. Some of the theoretical implications of these findings are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23882/1/0000121.pd

A strong test of exposure effects

A strong test of exposure effects was made by eliminating confounding demand characteristics through the use of a between-subject design. Each subject viewed novel stimuli at a single frequency level, and then rated them on several affective scales. Frequency of stimulus exposure was systematically varied across subjects. Stimuli were rated more positively with increasing exposure, despite the fact that subjects were unaware of any differences in exposure frequencies, and clearly unable to identify the experimental hypothesis. An awareness of the relationship between repeated exposure and affect was thus shown to be an unnecessary condition for the occurrence of exposure effects.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/21817/1/0000217.pd

Lunar lander and return propulsion system trade study

This trade study was initiated at NASA/JSC in May 1992 to develop and evaluate main propulsion system alternatives to the reference First Lunar Outpost (FLO) lander and return-stage transportation system concept. Thirteen alternative configurations were developed to explore the impacts of various combinations of return stage propellants, using either pressure or pump-fed propulsion systems and various staging options. Besides two-stage vehicle concepts, the merits of single-stage and stage-and-a-half options were also assessed in combination with high-performance liquid oxygen and liquid hydrogen propellants. Configurations using an integrated modular cryogenic engine were developed to assess potential improvements in packaging efficiency, mass performance, and system reliability compared to non-modular cryogenic designs. The selection process to evaluate the various designs was the analytic hierarchy process. The trade study showed that a pressure-fed MMH/N2O4 return stage and RL10-based lander stage is the best option for a 1999 launch. While results of this study are tailored to FLO needs, the design date, criteria, and selection methodology are applicable to the design of other crewed lunar landing and return vehicles

Brief Of Law Professors Bruce P. Frohnen, Robert P. George, Alan J. Meese, Michael P. Moreland, Nathan B. Oman, Michael Stokes Paulsen, Rodney K. Smith, Steven D. Smith, And O. Carter Snead As Amici Curiae In Support Of Petitioners

Suppose a federal law required government officials to enter a Catholic church and use church property to distribute contraceptives and abortifacients over church’s objection. Such a law would surely burden the church’s religion, even if the government paid for the objectionable medications and compensated the church for the use of its resources. By commandeering church property, such a law would force the church to be complicit in activity to which it has serious religious objection

Association Between Pain Sensitization and Disease Activity in Patients With Rheumatoid Arthritis: A Cross‐Sectional Study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141868/1/acr23266.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141868/2/acr23266_am.pd

Genome-Wide Association Study and Gene Expression Analysis Identifies CD84 as a Predictor of Response to Etanercept Therapy in Rheumatoid Arthritis

Anti-tumor necrosis factor alpha (anti-TNF) biologic therapy is a widely used treatment for rheumatoid arthritis (RA). It is unknown why some RA patients fail to respond adequately to anti-TNF therapy, which limits the development of clinical biomarkers to predict response or new drugs to target refractory cases. To understand the biological basis of response to anti-TNF therapy, we conducted a genome-wide association study (GWAS) meta-analysis of more than 2 million common variants in 2,706 RA patients from 13 different collections. Patients were treated with one of three anti-TNF medications: etanercept (n = 733), infliximab (n = 894), or adalimumab (n = 1,071). We identified a SNP (rs6427528) at the 1q23 locus that was associated with change in disease activity score (ΔDAS) in the etanercept subset of patients (P = 8×10-8), but not in the infliximab or adalimumab subsets (P>0.05). The SNP is predicted to disrupt transcription factor binding site motifs in the 3′ UTR of an immune-related gene, CD84, and the allele associated with better response to etanercept was associated with higher CD84 gene expression in peripheral blood mononuclear cells (P = 1×10-11 in 228 non-RA patients and P = 0.004 in 132 RA patients). Consistent with the genetic findings, higher CD84 gene expression correlated with lower cross-sectional DAS (P = 0.02, n = 210) and showed a non-significant trend for better ΔDAS in a subset of RA patients with gene expression data (n = 31, etanercept-treated). A small, multi-ethnic replication showed a non-significant trend towards an association among etanercept-treated RA patients of Portuguese ancestry (n = 139, P = 0.4), but no association among patients of Japanese ancestry (n = 151, P = 0.8). Our study demonstrates that an allele associated with response to etanercept therapy is also associated with CD84 gene expression, and further that CD84 expression correlates with disease activity. These findings support a model in which CD84 genotypes and/or expression may serve as a useful biomarker for response to etanercept treatment in RA patients of European ancestry. © 2013 Cui et al

Most Common SNPs Associated with Rheumatoid Arthritis in Subjects of European Ancestry Confer Risk of Rheumatoid Arthritis in African-Americans

Large-scale genetic association studies have identified over 20 rheumatoid arthritis (RA) risk alleles among individuals of European ancestry. The influence of these risk alleles has not been comprehensively studied in African-Americans. We therefore sought to examine whether these validated RA risk alleles are associated with RA in an African-American population

Immunodetection of nmt55/p54(nrb) isoforms in human breast cancer

BACKGROUND: We previously identified and characterized a novel 55 kDa nuclear protein, termed nmt55/p54(nrb), whose expression was decreased in a subset of human breast tumors. The objective of this study was to determine if this reduced expression in human breast tumors was attributed to the regulation of mRNA transcription or the presence of altered forms of this protein. RESULTS: Northern blot analysis and ribonuclease protection assay indicated that nmt55/p54(nrb) mRNA is expressed at varying levels in estrogen receptor positive (ER+) and estrogen receptor negative (ER-) human breast tumors suggesting that reduced expression of nmt55/p54(nrb) protein in ER- tumors was not due to transcriptional regulation. To determine if multiple protein isoforms are expressed in breast cancer, we utilized Western blot and immunohistochemical analyses, which revealed the expression of an nmt55/p54(nrb) protein isoform in a subset of ER+ tumors. This subset of ER+ human breast tumors expressed an altered form of nmt55/p54(nrb) that was undetectable with an amino-terminal specific antibody suggesting that this isoform contains alterations or modifications within the amino terminal domain. CONCLUSIONS: Our study indicates that nmt55/p54(nrb) protein is post-transcriptionally regulated in human breast tumors leading to reduced expression in ER- tumors and the expression of an amino terminal altered isoform in a subset of ER+ tumors. The potential involvement of nmt55/p54(nrb) in RNA binding and pre-mRNA splicing may be important for normal cell growth and function; thus, loss or alteration of protein structure may contribute to tumor growth and progression

An African Ancestry-Specific Allele of CTLA4 Confers Protection against Rheumatoid Arthritis in African Americans

Cytotoxic T-lymphocyte associated protein 4 (CTLA4) is a negative regulator of T-cell proliferation. Polymorphisms in CTLA4 have been inconsistently associated with susceptibility to rheumatoid arthritis (RA) in populations of European ancestry but have not been examined in African Americans. The prevalence of RA in most populations of European and Asian ancestry is ∼1.0%; RA is purportedly less common in black Africans, with little known about its prevalence in African Americans. We sought to determine if CTLA4 polymorphisms are associated with RA in African Americans. We performed a 2-stage analysis of 12 haplotype tagging single nucleotide polymorphisms (SNPs) across CTLA4 in a total of 505 African American RA patients and 712 African American controls using Illumina and TaqMan platforms. The minor allele (G) of the rs231778 SNP was 0.054 in RA patients, compared to 0.209 in controls (4.462×10−26, Fisher's exact). The presence of the G allele was associated with a substantially reduced odds ratio (OR) of having RA (AG+GG genotypes vs. AA genotype, OR 0.19, 95% CI: 0.13–0.26, p = 2.4×10−28, Fisher's exact), suggesting a protective effect. This SNP is polymorphic in the African population (minor allele frequency [MAF] 0.09 in the Yoruba population), but is very rare in other groups (MAF = 0.002 in 530 Caucasians genotyped for this study). Markers associated with RA in populations of European ancestry (rs3087243 [+60C/T] and rs231775 [+49A/G]) were not replicated in African Americans. We found no confounding of association for rs231778 after stratifying for the HLA-DRB1 shared epitope, presence of anti-cyclic citrullinated peptide antibody, or degree of admixture from the European population. An African ancestry-specific genetic variant of CTLA4 appears to be associated with protection from RA in African Americans. This finding may explain, in part, the relatively low prevalence of RA in black African populations