Orientation-Constrained Rectangular Layouts

We construct partitions of rectangles into smaller rectangles from an input consisting of a planar dual graph of the layout together with restrictions on the orientations of edges and junctions of the layout. Such an orientation-constrained layout, if it exists, may be constructed in polynomial time, and all orientation-constrained layouts may be listed in polynomial time per layout.Comment: To appear at Algorithms and Data Structures Symposium, Banff, Canada, August 2009. 12 pages, 5 figure

THE VALUE TO THE SURGEON OF PARATHYROID HORMONE ASSAYS IN PRIMARY HYPERPARATHYROIDISM

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72424/1/j.1445-2197.1988.tb01084.x.pd

Improved Approximation Algorithms for Box Contact Representations ⋆

Abstract. We study the following geometric representation problem: Given a graph whose vertices correspond to axis-aligned rectangles with fixed dimensions, arrange the rectangles without overlaps in the plane such that two rectangles touch if the graph contains an edge between them. This problem is called CONTACT REPRESENTATION OF WORD NETWORKS (CROWN) since it formalizes the geometric problem behind drawing word clouds in which semantically related words are close to each other. CROWN is known to be NP-hard, and there are approximation algorithms for certain graph classes for the optimization version, MAX-CROWN, in which realizing each desired adjacency yields a certain profit. We present the first O(1)-approximation algorithm for the general case, when the input is a complete weighted graph, and for the bipartite case. Since the subgraph of realized adjacencies is necessarily planar, we also consider several planar graph classes (namely stars, trees, outerplanar, and planar graphs), improving upon the known results. For some graph classes, we also describe improvements in the unweighted case, where each adjacency yields the same profit. Finally, we show that the problem is APX-hard on bipartite graphs of bounded maximum degree.

Small Molecule Inhibited Parathyroid Hormone Mediated cAMP Response by N–Terminal Peptide Binding

Ligand binding to certain classes of G protein coupled receptors (GPCRs) stimulates the rapid synthesis of cAMP through G protein. Human parathyroid hormone (PTH), a member of class B GPCRs, binds to its receptor via its N–terminal domain, thereby activating the pathway to this secondary messenger inside cells. Presently, GPCRs are the target of many pharmaceuticals however, these drugs target only a small fraction of structurally known GPCRs (about 10%). Coordination complexes are gaining interest due to their wide applications in the medicinal field. In the present studies we explored the potential of a coordination complex of Zn(II) and anthracenyl–terpyridine as a modulator of the parathyroid hormone response. Preferential interactions at the N–terminal domain of the peptide hormone were manifested by suppressed cAMP generation inside the cells. These observations contribute a regulatory component to the current GPCR–cAMP paradigm, where not the receptor itself, but the activating hormone is a target. To our knowledge, this is the first report about a coordination complex modulating GPCR activity at the level of deactivating its agonist. Developing such molecules might help in the control of pathogenic PTH function such as hyperparathyroidism, where control of excess hormonal activity is essentially required

Hyponatremia-Induced Osteoporosis

There is a high prevalence of chronic hyponatremia in the elderly, frequently owing to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Recent reports have shown that even mild hyponatremia is associated with impaired gait stability and increased falls. An increased risk of falls among elderly hyponatremic patients represents a risk factor for fractures, which would be further amplified if hyponatremia also contributed metabolically to bone loss. To evaluate this possibility, we studied a rat model of SIADH and analyzed data from the Third National Health and Nutrition Examination Survey (NHANES III). In rats, dual-energy X-ray absorptiometry (DXA) analysis of excised femurs established that hyponatremia for 3 months significantly reduced bone mineral density by approximately 30% compared with normonatremic control rats. Moreover, micro-computed tomography (µCT) and histomorphometric analyses indicated that hyponatremia markedly reduced both trabecular and cortical bone via increased bone resorption and decreased bone formation. Analysis of data from adults in NHANES III by linear regression models showed that mild hyponatremia is associated with increased odds of osteoporosis (T-score –2.5 or less) at the hip [odds ratio (OR) = 2.85; 95% confidence interval (CI) 1.03–7.86; p < .01]; all models were adjusted for age, sex, race, body mass index (BMI), physical activity, history of diuretic use, history of smoking, and serum 25-hydroxyvitamin D [25(OH)D] levels. Our results represent the first demonstration that chronic hyponatremia causes a substantial reduction of bone mass. Cross-sectional human data showing that hyponatremia is associated with significantly increased odds of osteoporosis are consistent with the experimental data in rodents. Our combined results suggest that bone quality should be assessed in all patients with chronic hyponatremia. © 2010 American Society for Bone and Mineral Research

No significant effect on bone mineral density by high doses of vitamin D3 given to overweight subjects for one year

<p>Abstract</p> <p>Background</p> <p>In meta-analyses supplementation with vitamin D appears to reduce incidence of fractures, and in cross-sectional studies there is a positive association between serum 25-hydroxyvitamin D (25(OH)D) levels and bone mineral density (BMD). However, the effect of supplementation with high doses of vitamin D on BMD is more uncertain and could in theory have both positive and negative effects.</p> <p>Methods</p> <p>The study was a one year, double blind placebo-controlled intervention trial performed at the University Hospital of North Norway. 421 subjects, 21 - 70 years old, were included and 312 completed the study. The subjects were randomized to vitamin D₃40.000 IU per week (DD group), vitamin D₃20.000 IU per week (DP group), or placebo (PP group). All subjects were given 500 mg calcium daily. Serum 25(OH)D, osteoprotegrin (OPG), receptoractivator of nuclear factor-kappaB ligand (RANKL), and BMD at the lumbar spine and the hip were measured before and at the end of the study.</p> <p>Results</p> <p>At baseline the mean serum 25(OH)D levels were 58 nmol/L (all subjects) and increased to 141 and 100 nmol/L in the DD and DP groups, respectively. After one year, no significant differences were found between the three groups regarding change in BMD, serum OPG or RANKL.</p> <p>Conclusions</p> <p>Supplementation with high doses of vitamin D for one year does not appear to have a negative effect on BMD in healthy subjects. In order to disclose a positive effect, subjects with low BMD and/or low serum 25(OH)D levels need to be studied.</p> <p>Trial registration</p> <p>The trial was registered at ClinicalTrials.gov (NCT00243256).</p

PLCL1 rs7595412 variation is not associated with hip bone size variation in postmenopausal Danish women

<p>Abstract</p> <p>Background</p> <p>Bone size (BS) variation is under strong genetic control and plays an important role in determining bone strength and fracture risk. Recently, a genome-wide association study identified polymorphisms associated with hip BS variation in the <it>PLCL1 </it>(phospholipase c-like 1) locus. Carriers of the major A allele of the most significant polymorphism, rs7595412, have around 17% larger hip BS than non-carriers. We therefore hypothesized that this polymorphism may also influence postmenopausal complications.</p> <p>Methods</p> <p>The effects of rs7595412 on hip BS, bone mineral density (BMD), vertebral fractures, serum Crosslaps and osteocalcin levels were analyzed in 1,191 postmenopausal Danish women.</p> <p>Results</p> <p>This polymorphism had no influence on hip and spine BS as well as on femur and spine BMD. Women carrying at least one copy of the A allele had lower levels of serum osteocalcin as compared with those homozygous for the G allele (p = 0.03) whereas no effect on serum Crosslaps was detected. Furthermore, women homozygous for the A allele were more affected by vertebral fractures than those carrying at least one copy of the G allele (p = 0.04).</p> <p>Conclusions</p> <p>In postmenopausal women, our results suggest that the <it>PLCL1 </it>rs7595412 polymorphism has no obvious effect on hip BS or BMD but may be nominally associated with increased proportion of vertebral fracture and increased levels of osteocalcin.</p

Extragonadal Effects of Follicle-Stimulating Hormone on Osteoporosis and Cardiovascular Disease in Women during Menopausal Transition

The risk of osteoporosis and cardiovascular disease increases significantly in postmenopausal women. Until recently, the underlying mechanisms have been primarily attributed to estrogen decline following menopause. However, follicle-stimulating hormone (FSH) levels rise sharply during menopausal transition and are maintained at elevated levels for many years. FSH receptor has been detected in various extragonadal sites, including osteoclasts and endothelial cells. Recent advances suggest FSH may contribute to postmenopausal osteoporosis and cardiovascular disease. Here, we review the key actions through which FSH contributes to the risk of osteoporosis and cardiovascular disease in women as they transition through menopause. Advancing our understanding of the precise mechanisms through which FSH promotes osteoporosis and cardiovascular disease may provide new opportunities for improving health-span for postmenopausal women