Effective use of TNF antagonists

Tumor necrosis factor (TNF) antagonists are biologic response modifiers that have significantly improved functional outcomes in patients with rheumatoid arthritis (RA). RA is a progressive disease in which structural joint damage can continue to develop even in the face of symptomatic relief. Before the introduction of biologic agents, the management of RA involved the use of disease-modifying antirheumatic drugs (DMARDs) early in the course of disease. This focus on early treatment, combined with the availability of the anti-TNF agents, has contributed to a shift in treatment paradigms favoring the early and timely use of DMARDs with biologic therapies. Improvement in symptom control does not always equate to a reduction in disease progression or disability. With the emergence of structure-related outcome measures as the primary means for assessing the effectiveness of antirheumatic agents, the regular use of X-rays is recommended for the continued monitoring and evaluation of patients. In addition to the control of symptoms and improvement in physical function, a reduction in erosions and joint-space narrowing should be considered among the goals of therapy, leading to a better quality of life. Adherence to therapy is an important element in optimizing outcomes. Durability of therapy with anti-TNF agents as reported from clinical trials can also be achieved in the clinical setting. Concomitant methotrexate therapy might be important in maintaining TNF antagonist therapy in the long term. Overall, the TNF antagonists have led to improvements in clinical and radiographic outcomes in patients with RA, especially those who have failed to show a complete response to methotrexate

Arteriogenic Revascularization Does Not Induce Vascular Function Impairment

Functional hyperemia and arteriolar vasodilation are impaired with chronic ischemia. We sought to examine the impact of chronic ischemia on collateral artery function. For this we used two hindlimb ischemia models to dissect the impact of different repair processes on collateral function. Ligation of the femoral artery increases shear stress in the muscular branch and results in outward remodeling and arteriogenesis. In contrast, resection of the femoral artery proximal to the muscular branch induces blood flow divergence and neutral remodeling along with expectedly greater hypoxia and inflammation. On day 14 after each surgery the diameter of the muscular branch was measured using sidestream dark field (SDF) imaging before and after gracilis muscle stimulation. A slight, but not statistically significant, impairment in functional vasodilation was observed in ligated mice (69±10% average diameter increase compared to 74±7% average diameter increase). Resected mice exhibited slightly (not statistically significant) enhanced collateral artery functional vasodilation (104±16% average diameter increase) but were also refractory to the restoration of resting vascular tone following the cessation of stimulation. Outward remodeling did not significantly impair vascular function, whereas neutral remodeling and tissue hypoxia induced impaired vascular tone

Chapel Bar

Living and learning in a post Modernist era, different than Post-Modern, offers a unique view of Modernism only possible after-the-fact. The Form Follows Function principle is beaten into our brains to the point of nearly blind adherence, but perhaps there is a valuable perspective to be gained by manipulating form and imposing different variations to a single function

Cyanobacterial and chloroplast F1-ATPases: cross-reconstitution of photophosphorylation and subunit immunological relationships

The photosynthetic F1-ATPase from the cyanobacterium Spirulina platensis was recently purified in a five-subunit, reconstitutively active form (Hicks, D.B. and Yocum, C.F. (1986) Arch. Biochem. Biophys. 245, 220-229). Here we report on the similarities of the cyanobacterial F1 to the higher plant chloroplast F1 (CF1), as judged by two distinct methods. The ability of each coupling factor to reconstitute photophosphorylation in photosynthetic membranes depleted of F1 content by 2 M NaBr treatment was tested. Addition of either the homologous enzyme (e.g., Spirulina F1, Spirulina membranes) or the heterologous enzyme (e.g., spinach CF1 Spirulina membranes) to depleted membranes increased the rate of phenazine methosulfate-dependent cyclic photophosphorylation from nearly zero to up to 70 [mu]mol ATP/h per mg Chl. Antibodies against four subunits of CF1 ([alpha], [gamma], [delta] and [var epsilon]) and against [beta] of Escherichia coli F1 were reacted with the Spirulina enzyme by protein blotting. The [alpha], [beta] and [gamma] subunits of Spirulina F1 cross-reacted with antibodies against the corresponding subunits from spinach. The cross-reactivity of the [gamma] subunit correlated with previous observations that Spirulina membrane ATPase activity can be modulated by light and dithiothreitol, in a similar fashion to their effect on the enzyme from spinach chloroplasts. The ability of cyanobacterial and chloroplast enzymes to restore activity to heterologous membranes in the absence of immunological similarities between their respective [delta] and [var epsilon] subunits may suggest that structural features other than particular amino acid sequences of these subunits are paramount in their roles in binding F1 to the membrane and in sealing proton leaks.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26048/1/0000121.pd

Chronic hindlimb ischemia impairs functional vasodilation and vascular reactivity in mouse feed arteries

Vasodilation of lower leg arterioles is impaired in animal models of chronic peripheral ischemia. In addition to arterioles, feed arteries are a critical component of the vascular resistance network, accounting for as much as 50% of the pressure drop across the arterial circulation. Despite the critical importance of feed arteries in blood flow control, the impact of ischemia on feed artery vascular reactivity is unknown. At 14 days following unilateral resection of the femoral–saphenous artery–vein pair, functional vasodilation of the profunda femoris artery was severely impaired, 11 ± 9 versus 152 ± 22%. Although endothelial and smooth muscle-dependent vasodilation were both impaired in ischemic arteries compared to control arteries (Ach: 40 ± 14 versus 81 ± 11%, SNP: 43 ± 12 versus and 85 ± 11%), the responses to acetylcholine and sodium nitroprusside were similar, implicating impaired smooth muscle-dependent vasodilation. Conversely, vasoconstriction responses to norepinephrine were not different between ischemic and control arteries, −68 ± 3 versus −66 ± 3%, indicating that smooth muscle cells were functional following the ischemic insult. Finally, maximal dilation responses to acetylcholine, ex vivo, were significantly impaired in the ischemic artery compared to control, 71 ± 9 versus 97 ± 2%, despite a similar generation of myogenic tone to the same intravascular pressure (80 mmHg). These data indicate that ischemia impairs feed artery vasodilation by impairing the responsiveness of the vascular wall to vasodilating stimuli. Future studies to examine the mechanistic basis for the impact of ischemia on vascular reactivity or treatment strategies to improve vascular reactivity following ischemia could provide the foundation for an alternative therapeutic paradigm for peripheral arterial occlusive disease

Development of a photosynthesis model with an emphasis on ecological applications

Photosynthesis was measured in leaves of Phaseolus vulgaris and analyzed according to the set of equations outlined previously by Tenhunen et al. (1976).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47716/1/442_2004_Article_BF00582889.pd

Developing a Digital Framework for the Medieval Gaelic World: Project Report

In 2020, the Research Network entitled ‘Developing a Digital Framework for the Medieval Gaelic World’ was established.1 This project was funded by UKRI-AHRC and the Irish Research Council under the ‘UK-Ireland Collaboration in the Digital Humanities Networking Call’ (grant numbers AH/V00235X/1 and IRC/V00235X/1). The network aimed to bring together scholars working across various aspects of medieval Celtic Studies in order to assess where we stand in terms of the digitisation of resources relating to medieval Ireland and Scotland, and to work towards a consensus on the way forward

Developing a Digital Framework for the Medieval Gaelic World: Report (Draft)

The abstract is included in the text

Sloan Digital Sky Survey Imaging of Low Galactic Latitude Fields: Technical Summary and Data Release

The Sloan Digital Sky Survey (SDSS) mosaic camera and telescope have obtained five-band optical-wavelength imaging near the Galactic plane outside of the nominal survey boundaries. These additional data were obtained during commissioning and subsequent testing of the SDSS observing system, and they provide unique wide-area imaging data in regions of high obscuration and star formation, including numerous young stellar objects, Herbig-Haro objects and young star clusters. Because these data are outside the Survey regions in the Galactic caps, they are not part of the standard SDSS data releases. This paper presents imaging data for 832 square degrees of sky (including repeats), in the star-forming regions of Orion, Taurus, and Cygnus. About 470 square degrees are now released to the public, with the remainder to follow at the time of SDSS Data Release 4. The public data in Orion include the star-forming region NGC 2068/NGC 2071/HH24 and a large part of Barnard's loop.Comment: 31 pages, 9 figures (3 missing to save space), accepted by AJ, in press, see http://photo.astro.princeton.edu/oriondatarelease for data and paper with all figure