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Additional file 1: Supplementary Table 1. Clinical Characteristics of Progressors. Supplementary Table 2. Comparison of Baseline Clinical Characteristics in UCTD progressors and non-progressors. Supplementary Table 3. The IFN5 score as a predictor of clinical progression in ANA+ subjects lacking a SARD diagnosis, alone or in combination with other cytokines. Supplementary Figure 1. Cytokine levels in the ANA+ participant subsets stratified by sex. Scatterplots showing the results for the IFN5 score and the cytokines, IFN-α measured by high sensitivity ELISA, IFN-α measured by Simoa, CXCL-10, Galectin-9, and IFN-γ (all shown using logarithmic scales). From left to right, are shown results for healthy controls (ANA-HC), asymptomatic ANA+ individuals (ANA+NS), undifferentiated connective tissue disease (UCTD) patients, and systemic autoimmune rheumatic disease (SARD) patients (F, female; M, male). Each circle represents a single subject, with the bars indicating the median for the subjects and error bars denoting the interquartile range. Significant differences between males and females are indicated with asterisks, * p < 0.05, ** p < 0.01, and *** p < 0.001. Supplementary Figure 2. Cytokine levels in the ANA+ participant subsets stratified by ethnicity. Scatterplots showing the results for the IFN5 score and the cytokines, IFN-α measured by high sensitivity ELISA, IFN-α measured by Simoa, CXCL-10, Galectin-9, and IFN-γ (all shown using logarithmic scales). From left to right, are shown results for healthy controls (ANA-HC), asymptomatic ANA+ individuals (ANA+NS), undifferentiated connective tissue disease (UCTD) patients, and systemic autoimmune rheumatic disease (SARD) patients (C, Caucasian; NC, non-Caucasian). Each circle represents a single subject, with the bars indicating the median for the subjects and error bars denoting the interquartile range. Significant differences between Caucasians and non-Caucasians are indicated with asterisks, * p < 0.05, ** p < 0.01, and **** p < 0.0001. Supplementary Figure 3. Receiver operating characteristic curves for prediction of clinical progression in subjects followed for ≥ 2 years using the various cytokine measures. The clinical and serologic characteristics of the clinical progressor (n=13) and non-progressor (n=42) subjects are shown in Table 1. Results are shown for the IFN5 score and the cytokines, IFN-α measured by high sensitivity ELISA, IFN-α measured by Simoa, CXCL-10, Galectin-9, and IFN-γ. Numbers in brackets following the cytokine labels and the black dot on the curve indicate the calculated value of Youden’s Index, comparing progressors and non-progressors. The area under the curve (AUC) is shown in the bottom right corner.

A review of the literature on drinking behaviour of university students reveals that most research focuses on binge drinking behaviour: a serious concern that has the attention of the World Health Organization. Binge drinking is of particular concern for university students as they are a high risk subset in an already high risk age group. This thesis explores the characteristics of university students who choose to drink moderately in this otherwise high risk environment. The purpose of this exploratory study is to better understand who the moderate drinkers are, what are their consumption habits and what are their perceptions of alcohol and the alcohol consumption of their peers? This study is informed by two theoretically frameworks: positive psychology as the overarching lens focusing on those students who drink responsibly and social norm theory which holds that students are influenced by what they perceive others to be doing and thereby alter their own behaviour and thoughts to meet this perception. The participants are composed of three hundred and forty-eight undergraduate students registered in their first year of study living in on-campus university residences. Data is collected using an on-line survey including both forced choice and open-ended response questions. According to participant’s self-reported data, over 40% of male participants and 50% of female participants self-identify as moderate drinkers. These moderate drinkers view their relationship with alcohol as either positive or neutral yet highly over-estimate the frequency and consumption levels of alcohol of their peers and do not perceive that any of their peers abstain from alcohol. The findings further reveal that moderate drinkers see themselves as unique from their peer group. Self-identified moderate drinkers rarely feel pressure to drink more, feel alcohol has little or no importance to them in social settings and do not consider drinking habits as a factor in selecting their choice of friends. Self-identified moderate drinkers were consistent with prior research findings in over-estimating the consumption of their peers but do not appear to allow this misperception to influence their own drinking habits.

L. monocytogenes is a gram-positive bacterium that is a cause of food borne disease in humans. Experimental infection of mice with this pathogen has been highly informative on the role of innate and adaptive immune cells and specific cytokines in host immunity against intracellular pathogens. Production of IFN-γ by innate cells during sublethal infection with L. monocytogenes is important for activating macrophages and early control of the pathogen1-3. In addition, IFN-γ production by adaptive memory lymphocytes is important for priming the activation of innate cells upon reinfection4. The L. monocytogenes infection model thus serves as a great tool for investigating whether new therapies that are designed to increase IFN-γ production have an impact on IFN-γ responses in vivo and have productive biological effects such as increasing bacterial clearance or improving mouse survival from infection. Described here is a basic protocol for how to conduct intraperitoneal infections of C57BL/6J mice with the EGD strain of L. monocytogenes and to measure IFN-γ production by NK cells, NKT cells, and adaptive lymphocytes by flow cytometry. In addition, procedures are described to: (1) grow and prepare the bacteria for inoculation, (2) measure bacterial load in the spleen and liver, and (3) measure animal survival to endpoints. Representative data are also provided to illustrate how this infection model can be used to test the effect of specific agents on IFN-γ responses to L. monocytogenes and survival of mice from this infection.

Peroxisome proliferator-activated receptor (PPAR)alpha is a nuclear receptor that mediates gender differences in lipid metabolism. PPARalpha also functions to control inflammatory responses by repressing the activity of nuclear factor kappaB (NF-kappaB) and c-jun in immune cells. Because PPARalpha is situated at the crossroads of gender and immune regulation, we hypothesized that this gene may mediate sex differences in the development of T cell-mediated autoimmune disease. We show that PPARalpha is more abundant in male as compared with female CD4(+) cells and that its expression is sensitive to androgen levels. Genetic ablation of this gene selectively removed the brake on NF-kappaB and c-jun activity in male T lymphocytes, resulting in higher production of interferon gamma and tumor necrosis factor (but not interleukin 17), and lower production of T helper (Th)2 cytokines. Upon induction of experimental autoimmune encephalomyelitis, male but not female PPARalpha(-/-) mice developed more severe clinical signs that were restricted to the acute phase of disease. These results suggest that males are less prone to develop Th1-mediated autoimmunity because they have higher T cell expression of PPARalpha.

Section 110 Survey and Evaluation of 193 Previously Recorded Archaeological Sites at Wallisville Reservoir, Chambers and Liberty Counties, Texas. Through archival research at TARL, we re-identified 192 archaeological sites within the project area, encompassing an area of 9,966 acres within the Wallisville Reservoir; this included 6,875 acres in Chambers County and 3,091 acres in Liberty County, Texas. Archaeologists were unable to reach 33 of these sites by pedestrian or boat aided access, and two sites (41CH006 and 41LB093) were not re-located and appear to be outside of Corps of Engineers property. All of the remaining 157 sites were revisited; at each, archaeologists conducted surface and subsurface (shovel testing) investigations, recorded site size, type and extent of disturbance, cultural components, artifact densities, vegetation, and potential threats to archaeological deposits. Sites were evaluated according to these criteria for eligibility for inclusion on the NRHP, according to the criteria set forth by 36 CFR Part 60.

Peroxisome proliferator-activated receptors (PPARs; PPAR-alpha, PPAR-delta, and PPAR-gamma) comprise a family of nuclear receptors that sense fatty acid levels and translate this information into altered gene transcription. Previously, it was reported that treatment of mice with a synthetic ligand activator of PPAR-delta, GW0742, ameliorates experimental autoimmune encephalomyelitis (EAE), indicating a possible role for this nuclear receptor in the control of central nervous system (CNS) autoimmune inflammation. We show that mice deficient in PPAR-delta (PPAR-delta(-/-)) develop a severe inflammatory response during EAE characterized by a striking accumulation of IFN-gamma(+)IL-17A(-) and IFN-gamma(+)IL-17A(+) CD4(+) cells in the spinal cord. The preferential expansion of these T helper subsets in the CNS of PPAR-delta(-/-) mice occurred as a result of a constellation of immune system aberrations that included higher CD4(+) cell proliferation, cytokine production, and T-bet expression and enhanced expression of IL-12 family cytokines by myeloid cells. We also show that the effect of PPAR-delta in inhibiting the production of IFN-gamma and IL-12 family cytokines is ligand dependent and is observed in both mouse and human immune cells. Collectively, these findings suggest that PPAR-delta serves as an important molecular brake for the control of autoimmune inflammation.

Exposure wavelength has been changing dramatically as semiconductor design rules shrink, and for 32nm-node fine processes and beyond, it is predicted that the drop in optical contrast when using 193nm immersion lithography exposure technology will make it difficult to ensure good resolution performance in fine and dense resist patterns. To address this problem, studies have begun on extreme ultraviolet (EUV) lithography technology and double patterning technology that uses 193nm immersion lithography as alternative technologies, but many problems have been reported at the present stage of development. Against the above background, we investigated various process flows with the aim of reducing production processes and cost in double patterning technology that uses 193nm immersion lithography. We consequently developed an advanced process technique for use after 1st resist pattern formation and established a litho-litho-etch (LLE) process. The application of this technology decreases the number of total processes used in ordinary double patterning technology. In this paper, we focus on double patterning technology in 193nm immersion lithography and report on the performance of our original advanced process technique and on our evaluation of double patterning technology.

Peroxisome proliferator-activated receptor (PPAR)alpha is a nuclear receptor that mediates gender differences in lipid metabolism. PPARalpha also functions to control inflammatory responses by repressing the activity of nuclear factor kappaB (NF-kappaB) and c-jun in immune cells. Because PPARalpha is situated at the crossroads of gender and immune regulation, we hypothesized that this gene may mediate sex differences in the development of T cell-mediated autoimmune disease. We show that PPARalpha is more abundant in male as compared with female CD4(+) cells and that its expression is sensitive to androgen levels. Genetic ablation of this gene selectively removed the brake on NF-kappaB and c-jun activity in male T lymphocytes, resulting in higher production of interferon gamma and tumor necrosis factor (but not interleukin 17), and lower production of T helper (Th)2 cytokines. Upon induction of experimental autoimmune encephalomyelitis, male but not female PPARalpha(-/-) mice developed more severe clinical signs that were restricted to the acute phase of disease. These results suggest that males are less prone to develop Th1-mediated autoimmunity because they have higher T cell expression of PPARalpha.

Robotically assisted cardiac surgery has been presented as less invasive than conventional surgery, with shortened hospital stays and faster return to daily activities. We evaluated our experience with the da Vinci robot to determine whether we could in fact demonstrate those findings. All mitral and tricuspid valve repairs were performed by the same surgeon. Cardiopulmonary bypass was performed with femoral cannulation, antegrade cardioplegia, and transthoracic aortic cross-clamping. Multiple valve repair techniques were used, including quadrant resection, cord replacement, Alfieri leaflet coaptation, and ring annuloplasty. Access was by 2 ports and a 5-cm right anterolateral thoracotomy. All annuloplasty rings were secured using surgical clips. From October 2003 through September 2004, 32 patients underwent robotically assisted mitral valve repair. The mean age of our population was 676 years (range, 43-82 years). Four patients also underwent the 1st tricuspid valve repair using the da Vinci robot in the United States. There were 3 conversions for irreparable valves, 1 stroke, and 2 deaths. The average procedure time, cardiopulmonary bypass time, and aortic cross-clamp time were all reduced, when the first 20 patients were compared with the last 12. Length-of-stay also improved. One patient required early mitral valve replacement for recurrent regurgitation. Two patients required late (3 month) mitral valve replacement for recurrent regurgitation. We have shown that a dedicated nonacademic institute can develop a robotic cardiac surgery program and perform mitral and tricuspid valve repairs successfully. There is a several-case learning curve, and patient selection is paramount.