Search

BackgroundPre-clinical models demonstrate that platelet activation is involved in the spread of malignancy. Ongoing clinical trials are assessing whether aspirin, which inhibits platelet activation, can prevent or delay metastases.MethodsUrinary 11-dehydro-thromboxane B2 (U-TXM), a biomarker of in vivo platelet activation, was measured after radical cancer therapy and correlated with patient demographics, tumour type, recent treatment, and aspirin use (100 mg, 300 mg or placebo daily) using multivariable linear regression models with log-transformed values.ResultsIn total, 716 patients (breast 260, colorectal 192, gastro-oesophageal 53, prostate 211) median age 61 years, 50% male were studied. Baseline median U-TXM were breast 782; colorectal 1060; gastro-oesophageal 1675 and prostate 826 pg/mg creatinine; higher than healthy individuals (~500 pg/mg creatinine). Higher levels were associated with raised body mass index, inflammatory markers, and in the colorectal and gastro-oesophageal participants compared to breast participants (P ConclusionsPersistently increased thromboxane biosynthesis was detected after radical cancer therapy, particularly in colorectal and gastro-oesophageal patients. Thromboxane biosynthesis should be explored further as a biomarker of active malignancy and may identify patients likely to benefit from aspirin.

Purpose To measure right ventricular (RV) trabecular complexity by its fractal dimension (FD) in healthy subjects and patients with pulmonary hypertension (PH) and to assess its relationship with hemodynamic and functional parameters and future cardiovascular events. Materials and Methods This retrospective study used data acquired from May 2004 to October 2013 in 256 patients with newly diagnosed PH who underwent cardiac MRI, right-sided heart catheterization, and 6-minute walk distance testing, with median follow-up of 4.0 years. A total of 256 healthy control subjects underwent cardiac MRI only. Biventricular FD, volumes, and function were assessed on short-axis cine images. Reproducibility was assessed with the intraclass correlation coefficient, correlation between variables was assessed with the Pearson correlation test, and mortality prediction was compared by using uni- and multivariable Cox regression analyses. Results RV FD reproducibility had an intraclass correlation coefficient of 0.97 (95% confidence interval [CI]: 0.96, 0.98). RV FD was higher in patients with PH (median, 1.310; interquartile range [IQR], 1.281-1.341) than in healthy subjects (median, 1.264; IQR, 1.242-1.295; P.001), with the greatest difference near the apex. RV FD was associated with pulmonary vascular resistance (r = 0.30, P.001). At univariable Cox regression analysis, RV FD was a significant predictor of death (hazard ratio [HR], 1.256; 95% CI: 1.011, 1.560; P = .04); however, at multivariable analysis, RV FD did not enable prediction of survival independently of conventional parameters of RV remodeling (HR, 1.179; 95% CI: 0.871, 1.596; P = .29). Conclusion Fractal analysis of RV trabecular complexity is a highly reproducible measure of remodeling in patients with PH that is associated with afterload, although the gain in survival prediction over traditional markers is not significant. Published under a CC BY 4.0 license. Online supplemental material is available for this article.

Visual Abstract, Highlights • The effects of apelin on pulmonary hemodynamics in patients with PAH are unknown. • Systemic infusion caused a significant reduction in pulmonary vascular resistance and increase in cardiac output without a change in heart rate or systemic vascular resistance. • This effect was most prominent in the subgroup of patients receiving concomitant PDE5 inhibition. • Apelin agonism is a novel potential therapeutic target for PAH., Summary Apelin agonism causes systemic vasodilatation and increased cardiac contractility in humans, and improves pulmonary arterial hypertension (PAH) in animal models. Here, the authors examined the short-term pulmonary hemodynamic effects of systemic apelin infusion in patients with PAH. In a double-blind randomized crossover study, 19 patients with PAH received intravenous (Pyr1)apelin-13 and matched saline placebo during invasive right heart catheterization. (Pyr1)apelin-13 infusion caused a reduction in pulmonary vascular resistance and increased cardiac output. This effect was accentuated in the subgroup of patients receiving concomitant phosphodiesterase type 5 inhibition. Apelin agonism is a novel potential therapeutic target for PAH. (Effects of Apelin on the Lung Circulation in Pulmonary Hypertension; NCT01457170)

Direct Magnitude Estimations (DME) and Equal Appearing Interval (EAI) scaling techniques were used to compare listeners' perceptions of the extent of accent from recorded speech samples of international students enrolled in a United States university who spoke English as a second language. Twenty five international students served as speakers by reading the same brief passage for recording purposes. Twenty five American-born students with no formal training or experience with accents or accent reduction rated the extent of the accent on each of the spoken samples using both scaling techniques. Statistical analysis of the listener's perceptions indicated no significant differences between the DME or EAI scaling procedures and a scatterplot comparing the data sets for each technique produced a significant linear relationship between the data for the two techniques. Based on these findings it would appear that either technique could be employed to obtain a valid assessment of the extent of accent in international students. An EAI scaling technique would appear to be the technique of choice because of the ease of administration. However, future study is needed to refine the technique into a clinical procedure for routine use in assessing the extent of perceived accent and gauging the success of accent reduction intervention.Key Words: Accent Assessment, International Students, DME, EAI, IndiaInstitutions of higher education in the United States recognize the inherent value of recruiting the best and brightest students from around the world (Institute of International Education, 2011). The number of international students enrolled in American universities is increasing. A 2007 report on enrollment showed a record 623,805 international students were enrolled in U.S. colleges and universities (Association of International Educators, 2009). Recent data reported in the Chronicle of Higher Education (Fischer, 2009) indicated that for 2008-2009 there were 672,000 foreign students enrolled in American universities. In 2010/11, the number of international students enrolled in American universities had swelled to 723,000 (Marklein, 2011). These international students facilitate the preparation of American students for a globally connected marketplace by sharing their various cultures, perspectives, and ways of thinking. However, the continuing influx of international students into institutions of higher education in the United States poses verbal communication challenges for the institutions and the international students. English as a second language is often spoken by the majority of these international students and their accents can jeopardize effective communication. Even after gaining sufficient English language literacy skills to successfully matriculate in academic programs in U.S. colleges and universities, the intelligibility of conversational speech among international students may be significantly compromised in academic and social contexts by their accents. Accordingly, institutions of higher education should share some portion of the responsibility for assisting foreign students as they pursue opportunities to overcome accent-based communication barriers.The American Speech-Language-Hearing Association (2009) defined accent as "the unique way that speech is pronounced by a group of people speaking the same language." Despite the number of individuals presenting themselves for accent reduction, Shah (2007), in the development of a prototype accent assessment tool, reported that none of the 13 protocols reviewed for assessment of foreign accent were evidenced based, norm referenced, or standardized. Accent reduction, sometimes referred to as elocution or accent modification, should begin with a systematic, valid and objective assessment of the accent prior to formal intervention. In short, a suitable instrument is needed that can reliably quantify deviations in the individual's current accent from the target reference accent and from which progress in accent reduction can be gauged. …

Estrogen plays an important role in skeletal physiology by maintaining a remodeling balance between the activity of osteoblasts and osteoclasts. In an attempt to decipher the mechanism through which estrogen elicits its action on osteoblasts, experimentation necessitated the development of a culturing environment reduced in estrogenic compounds. The selected medium (OPTI-MEM) is enriched to sustain cultures under reduced fetal bovine serum (FBS) conditions and is devoid of the pH indicator phenol red, a suspected estrogenic agent. This protocol reduced the concentration of FBS supplementation to 0% through successive 24 h incubations with diminishing amounts of total FBS (1%, 0.1%, and 0%). The protocol does not appear to alter the viability, cell morphology, or osteoblast-like phenotype of 7F2 and UMR-106 cell lines when compared with control cells grown in various concentrations of FBS. Although the rate of mitotic divisions declined, the 7F2 and UMR-106 cultures continued to express osteoblast-specific markers and exhibited estrogen responsiveness. These experimental findings demonstrate that the culture protocol developed did not alter the osteoblast nature of the cell lines and provides a model system to study estrogen’s antiresorptive role on skeletal turnover.

The number of percutaneous coronary interventions (PCI) performed annually has increased rapidly over the last two decades. Coronary angioplasties are now commonly complemented with the insertion of coronary artery stents. Initially bare metal stents (BMS) were developed with drug-eluting stents (DES) subsequently being introduced. Drug-eluting stents reduce in-stent restenosis at the cost of prolonged anti-platelet therapy. While observational studies suggest that coronary artery bypass graft surgery protects against perioperative cardiac events in non-cardiac surgery, no such evidence exists for PCI. In order to prevent stent thrombosis, patients need to receive dual anti-platelet therapy (generally aspirin and clopidogrel) for four to six weeks with BMS, and at least one year with DES. Patients on dual anti-platelet therapy are at risk of severe bleeding during surgery. However, withdrawal of dual anti-platelet therapy is associated with the risk of stent thrombosis. The risk of cardiac complications seems to exceed the risk of bleeding, and maintenance of dual anti-platelet therapy is advocated whenever possible. Surgery in closed cavities (neurosurgery, intraocular surgery) necessitates the withdrawal of dual anti-platelet therapy. There is a significant risk of perioperative complications in patients who have DES, or recently inserted BMS, and consequently surgery should not be performed without a discussion involving the surgeon, cardiologist, anaesthetist, and the patient.

A carbon-rich black layer, dating to ≈12.9 ka, has been previously identified at ≈50 Clovis-age sites across North America and appears contemporaneous with the abrupt onset of Younger Dryas (YD) cooling. The in situ bones of extinct Pleistocene megafauna, along with Clovis tool assemblages, occur below this black layer but not within or above it. Causes for the extinctions, YD cooling, and termination of Clovis culture have long been controversial. In this paper, we provide evidence for an extraterrestrial (ET) impact event at ≅12.9 ka, which we hypothesize caused abrupt environmental changes that contributed to YD cooling, major ecological reorganization, broad-scale extinctions, and rapid human behavioral shifts at the end of the Clovis Period. Clovis-age sites in North American are overlain by a thin, discrete layer with varying peak abundances of ( i ) magnetic grains with iridium, ( ii ) magnetic microspherules, ( iii ) charcoal, ( iv ) soot, ( v ) carbon spherules, ( vi ) glass-like carbon containing nanodiamonds, and ( vii ) fullerenes with ET helium, all of which are evidence for an ET impact and associated biomass burning at ≈12.9 ka. This layer also extends throughout at least 15 Carolina Bays, which are unique, elliptical depressions, oriented to the northwest across the Atlantic Coastal Plain. We propose that one or more large, low-density ET objects exploded over northern North America, partially destabilizing the Laurentide Ice Sheet and triggering YD cooling. The shock wave, thermal pulse, and event-related environmental effects (e.g., extensive biomass burning and food limitations) contributed to end-Pleistocene megafaunal extinctions and adaptive shifts among PaleoAmericans in North America.

Details are given of a simple and easily constructed instrument, employing a thermistor detector, for work on gas chromatography. Some necessary precautions and conditions for use of a thermistor detector are outlined, changes in signal strength and direction with variation of detector position are discussed and the over-all sensitivity and response to differing materials is described.

The utility of interventional cardiology has developed significantly over the last two decades with the introduction of coronary angioplasty and stenting, with the associated antiplatelet medications. Acute coronary stent occlusion carries a high morbidity and mortality, and the adoption of therapeutic strategies for prophylaxis against stent thrombosis has major implications for surgeons and anaesthetists involved in the management of these patients in the perioperative period. Currently, there is limited published information to guide the clinician in the optimal care of patients who have had coronary stents inserted when they present for non-cardiac surgery. This review examines the available literature on the perioperative management of these patients. A number of key issues are identified: the role of surgery vs percutaneous coronary intervention for coronary revascularization in the preoperative period; the different types of coronary stents currently available; the emerging issues related to drug-eluting stents; the pathophysiology of coronary stent occlusion; and the recommended antiplatelet regimes that the patient with a coronary stent will be receiving. The role of preoperative platelet function testing is also discussed, and the various available tests are listed. Appropriate management by all the clinicians involved with patients with coronary stents undergoing a variety of non-cardiac surgical procedures is essential to avoid a high incidence of postoperative cardiac mortality and morbidity. The review examines the evidence available for the perioperative strategies aimed at reducing adverse outcomes in a number of different clinical scenarios.

A series of random and block copolymers of styrene and methylmethacrylate has been prepared and characterized and the adsorption behavior on silica found from several solvents, in particular, from benzene and trichloroethylene. Specific adsorption measure-ments have been supplemented by infrared determinations of bound fractions. Relatively few methacrylate groups are necessary to bind the copolymers to the silica surface. Little variation in specific adsorption is found over a wide range of copolymer composition and within this range the fraction of bound groups (of both structures) is approximately constant. Only rather small differences in adsorption behavior are shown by the random and block copolymer structures.

A copolymer of allyl alcohol and styrene has been crosslinked in solution by reaction with diacid chlorides. The reaction rate is first order in acid chloride but of complex order in hydroxyl. Measurements are reported of the extent of reaction at gelation and of gel time as a function of concentration and of the size of the crosslinker. The fraction of crosslinks formed intramolecularly is calculated: the value of this fraction depends strongly on dilution and, to a lesser extent, on the length of the crosslinker chain. The swelling and compressional modulus of gels prepared in solution (preswollen networks) depend on dilution and crosslinker size in the same general manner as does the fraction of intramolecular links.

Atherosclerosis is a common condition in both the developed and developing world and is now recognised to be an inflammatory condition leading to the development of ischaemic heart disease, cerebrovascular disease and peripheral vascular disease. Ischaemic heart disease is a major risk factor in the pathogenesis of perioperative adverse cardiovascular events which lead to significant morbidity and mortality within the high risk surgical patient population. Current methods of evaluating the likelihood of postoperative cardiovascular complications depend largely on risk scoring systems, and the preoperative assessment of the functional status of the cardiovascular system. However, the possible role of inflammation in the generation of atherosclerosis has led to the identification of several biochemical markers such as acute phase proteins, cellular adhesion molecules and cytokines. An alternative approach therefore is the measurement of preoperative levels of these biomarkers with the aim of assessing pre-existing disease activity. This review summarises the pathophysiology of atherosclerosis and perioperative myocardial infarction, and discusses the possible future role of biomarkers in the risk stratification of patients undergoing non-cardiac surgery.

Background: The Norfolk and Norwich University Hospital (NNUH) is situated in rural Norfolk, and ambulance journey times are often >30 min. Longer ambulance journeys could lead to a greater risk of hypercapnia, if inappropriately high concentrations of oxygen are given during an exacerbation of COPD. Aim: To investigate the effect of high concentration oxygen (HCO, FiO2 > 0.28) on COPD patients, and the outcome of instituting a simple protocol to reduce such exposure. Design: Retrospective audit. Method: An audit was conducted of all patients admitted with an exacerbation of COPD to the NNUH during the 2 months from 1 December 2001 to 31 January 2002 ( n = 108). Results were shared with paramedics, and guidelines agreed for the initial provision of lower concentrations of oxygen (LCO, FiO2 ⩽ 0.28). A second audit was conducted a year later between 1 December 2002 and 31 January 2003 ( n = 103). Results: HCO caused significant ( p < 0.01) acidosis and inappropriately high PaO2 and PaCO2, compared to initial LCO therapy. There was a significantly increased complication rate during admission ( p < 0.01) in those COPD patients receiving HCO compared to LCO, particularly when ambulance journeys exceeded 30 min. The second audit demonstrated a significant ( p < 0.001) reduction in the number of patients initially receiving HCO, but the complication rate was unaltered. Discussion: A simple intervention, such as providing paramedics with 28% Venturi masks, can reduce the number of COPD patients exposed to HCO. A randomized controlled trial is long overdue to establish whether HCO or LCO as initial management is associated with the most favourable prognosis in different hospital settings.

This study was designed to assess the relative contributions of genetic and environmental factors to the variation and covariation of quantitative ultrasound (QUS) measurements and their relationships to bone mineral density (BMD). Forty-nine monozygotic (MZ) and 44 dizygotic (DZ) female twins between 20 and 83 years of age (53 ± 13 years, mean ± SD) were studied. Digital (phalangeal) QUS (speed of sound [SOS]) and calcaneal QUS (broadband ultrasound attenuation [BUA] and velocity of sound [VOS]) were measured using a DBM Sonic 1200 ultrasound densitometer and a CUBA ultrasound densitometer, respectively. Femoral neck (FN), lumbar spine (LS), and total body (TB) BMD were measured using dual-energy X-ray absorptiometry. Familial resemblance and hence heritability (proportion of variance of a trait attributable to genetic factors) were assessed by analysis of variance, univariate, and multivariate model-fitting genetic analyses. In both QUS and BMD parameters, MZ twins were more alike than DZ pairs. Estimates of heritability for age- and weight-adjusted BUA, VOS, and SOS were 0.74, 0.55, and 0.82, respectively. Corresponding indices of heritability for LS, FN, and TB BMD were 0.79, 0.77, and 0.82, respectively. In cross-sectional analysis, both BUA and SOS, but not VOS, were independently associated with BMD measurements. However, analysis based on intrapair differences suggested that only BUA was related to BMD. Bivariate genetic analysis indicated that the genetic correlations between BUA and BMD ranged between 0.43 and 0.51 (p < 0.001), whereas the environmental correlations ranged between 0.20 and 0.28 (p < 0.01). While the genetic correlations within QUS and BMD measurements were significant, factor analysis indicates that common genes affect BMD at different sites. Also, individual QUS measurements appear to be influenced by some common sets of genes rather than by environmental factors. Significant environmental correlations were only found for BMD measurements and ranged between 0.50 and 0.65 (p < 0.001). These data suggest that QUS and BMD measurements are highly heritable traits. While it appears that there is a common set of genes influencing both QUS and BMD measurements, specific genes yet to be identified appear to have greater effects than that of shared genes in each trait.

Bone mineral density (BMD) and bone turnover are both heritable. Although bone turnover affects bone mass, it is not clear whether these parameters are under common genetic or environmental control. The relative contribution of genetic and environmental factors to the determination of an index of bone turnover, bone specific alkaline phosphatase (BSAP), and the extent of common genetic regulation with BMD, were examined in 97 female twin pairs, aged 50 +/- 15 years (mean +/- SD), consisting of 48 monozygotic (MZ) and 49 dizygotic (DZ) pairs. BSAP was analyzed by radioimmunometric assay. Bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN) was measured by dual-energy X-ray absorptiometry. Twin resemblance for variable traits was assessed by intraclass correlation coefficients. Estimates of genetic and environmental components of variance were based on univariate and multivariate genetic models. As expected, BSAP in premenopausal women (9.8 +/- 4.3 microg/L) was significantly lower than in postmenopausal women (13.3 +/- 6.6 microg/L, p < 0.001), but similar to the subgroup of postmenopausal women on hormone replacement therapy (10.8 +/- 2.6 microg/L, p = 0.15). Although BSAP and BMD were correlated in a cross-sectional analysis (r = -0.35, p < 0.001 for LS-BMD; r = -0.16, p = 0.03 for FN-BMD), the intrapair difference in BSAP was not significantly correlated with the intrapair difference in BMD for MZ twin pairs. After adjustment for menopausal status, the intraclass correlation for BSAP was significantly higher in MZ than DZ twins (0.60 +/- 0.09 vs. 0.27 +/- 0.13, p = 0.03). Univariate model-fitting analyses indicated a heritability of 63% for BSAP, and 77% and 72% for lumbar spine and femoral neck BMD, respectively. By multivariate analyses, genes specifically influencing BSAP accounted for 16% of the total genetic variance in LS-BMD and 4% of the total genetic variance in FN-BMD. There was no evidence for shared environmental factors affecting BSAP and BMD. These findings indicate that BSAP and BMD are heritable and negatively correlated. However, the genetic loci influencing BSAP and BMD appear to be largely independent as are any environmental factors.

The most important floating aquatic weeds (FAWs) are Eichhornia crassipes, Salvinia molesta and Pistia stratiotes. E. crassipes and P. stratiotes reproduce sexually. All three species reproduce asexually. E. crassipes and S. molesta have particularly high growth rates. All can form dense mats and growth rates are increased by high nutrient levels and temperatures. Spread between continents and watersheds is largely the result of human activities. Spread within watersheds is mostly via floating propagules. FAWs are known to affect water resource management, the continued existence of human riverine and wetland communities, and conservation of biodiversity. Waterways can be blocked, and the efficiency of irrigation and hydro generation impaired. People are affected by reduction of the fish catch, inability to travel by boat and consequent isolation from gardens, markets and health services, and also changes in populations of vectors of human and animal diseases. Biodiversity can be reduced and conservation value affected. It is proposed that rational application of physical, chemical and biological control of FAWs, and reduction of nutrient input should be part of every strategy for the sustainable management of wetlands.

Nine Lichtenstein's hartebeest ( Alcelaphus lichtensteini ) were sampled for nasal bots ( Oestrinae ) in a woodland area of central western Zambia. Larvae of the genera Gedoelstia , Oestrus and Kirkioestrus were found in mixed infestations in the nasal cavities and paranasal sinuses. A maximum count of 252 larvae was recorded from one head but no obvious pathogenicity was detectable in this or any other hartebeest. The significance of these findings is discussed in relation to the host specificity of the nasal bots and to gedoelstial myiasis of domestic livestock in the area where they interact with infected hartebeest.

Binary magnesium alloys containing chromium, manganese, or titanium were made using a physical vapour deposition technique. The corrosion resistance of the alloys was assessed in aqueous chloride solutions using total immersion tests in quiescent 600 mmol L−1 NaCI solutions. Alloying with manganese or titanium was found to lower the corrosion rate of magnesium over most of the compositional ranges of interest, whereas addition of chromium had a detrimental effect on the corrosion resistance of magnesium. The lowest corrosion rate was recorded for a Mg–Ti alloy where the value obtained was about 80 times lower than that found for vapour deposited pure magnesium. Open circuit corrosion potential measurements conducted in 600 mmol L−1 NaCl solution showed that additions of chromium, titanium, and manganese also produced deposits which were significantly more noble than pure magnesium, suggesting that these alloys would be less susceptible to galvanic corrosion.MST/3064

This paper reviews the evolution of heavy-duty power generation and industrial combustion turbines in the United States from a Westinghouse Electric Corporation perspective. Westinghouse combustion turbine genealogy began in March of 1943 when the first wholly American designed and manufactured jet engine went on test in Philadelphia, and continues today in Orlando, Florida, with the 230 MW, 501G combustion turbine. In this paper, advances in thermodynamics, materials, cooling, and unit size will be described. Many basic design features such as two-bearing rotor, cold-end drive, can-annular internal combustors, CURVIC clutched turbine disks, and tangential exhaust struts have endured successfully for over 40 years. Progress in turbine technology includes the clean coal technology and advanced turbine systems initiatives of the U.S. Department of Energy.

Could focused population screening detect osteoporosis earlier and improve the management of this major health care problem? Quantitative ultrasound of the calcaneus is currently being proposed as a suitable screening technique. Correlations between quantitative ultrasound of the calcaneus and dual energy x-ray absorptiometry of bone mineral density of the spine and proximal femur are not high enough to reliably predict bone mineral density at the lumbar spine or proximal femur from the ultrasound results. Some ongoing longitudinal studies suggest that quantitative ultrasound may none the less detect individuals at increased risk of fracture, but its use for mass screening for osteoporosis would be premature.

Common vitamin D receptor (VDR) gene alleles have recently been shown to contribute to the genetic variability in bone mass and bone turnover, however, the physiological mechanisms involved are unknown. To examine this, the response to 7 days of 2 micrograms oral 1,25-dihydroxyvitamin D[1,25-(OH)2D] (calcitriol) stimulation was assessed in 21 premenopausal women, homozygous for one or other of the common VDR alleles (bb, n = 11; BB, n = 10). Indices of bone turnover and calcium homeostasis were measured during 2 weeks. Baseline osteocalcin, 1,25-(OH)2D, type I collagen carboxyterminal telopeptide, and inorganic phosphate levels were significantly higher and spinal bone mineral density was significantly lower in the BB allelic group. After calcitriol administration, similar levels of 1,25-(OH)2D were attained throughout the study in both genotypic groups. The increase in serum osteocalcin levels in the BB group was significantly less than that in the bb group (11% vs. 32%, P = 0.01). The genotype-related baseline difference in osteocalcin levels was not apparent at the similar serum 1,25-(OH)2D levels. By contrast, the baseline differences in phosphate and type I collagen carboxyterminal telopeptide persisted throughout the study. Serum ionized calcium levels did not differ between genotypes, nor did it move out of normal range values. However, parathyroid hormone was less suppressed in the low bone density group (38% vs. 11%, P = 0.01). These data indicate that the VDR alleles are associated with differences in the vitamin D endocrine system and may have important implications in relation to the pathophysiology of osteoporosis.

Calcitonin gene-related peptide (CGRP) was examined for its effects on intracellular free Ca2+ concentration ([Ca2+]i) in UMR 106 osteoblast-like cells. Cells loaded with the Ca2+ dye FURA-2 dose-dependently responded to CGRP (1-100 nM) with transient two-fold increases in [Ca2+]i. An intracellular source for this Ca2+ transient was suggested by the failure of membrane depolarization with high extracellular K+ or acute depletion of extracellular Ca2+ ([Ca2+]e) with EGTA to attenuate this response. After cells were incubated for 45 min with 0.1 mM extracellular Ca2+ to deplete intracellular Ca2+ stores, CGRP produced a 25-30% decrease in [Ca2+]i rather than a transient increase. This calcium decrease was mimicked by membrane depolarization or by pinacidil, a specific activator of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels, and blocked by glybenclamide, a specific blocker of KATP channels. Our data suggest that CGRP has diverse Ca2+ regulatory effects in UMR 106 cells, mobilizing Ca2+ from intracellular stores via classical signaling while possibly promoting cellular Ca2+ efflux or inhibiting uptake through voltage-dependent Ca2+ channels via KATP-mediated hyperpolarization.

This paper presents a numerical investigation in the influence of loading on the trabecular architecture of a femoral head using structural optimization. Previous literature has shown that structural optimization can be used to simulate the response of bone to external loading conditions, in the cases of os-calcis and vertebrae of which the loading conditions may be considered relatively simple. The geometry of a typical femoral head is modeled in the two-dimensional finite element environment with 8-noded quadrilateral elements. Three load cases were considered: 1) the single leg stance phase of gait; 2) the extreme of abduction experienced on a daily basis; 3) the extreme of adduction experienced on a daily basis. These were chosen to give an insight into the influence of difference loading conditions on various architectural features of the femoral head. The results obtained from structural optimization applied to investigate the effects of frequency of load cases suggests that the frequency of load cases is not directly proportional to their influence on the trabecular architecture. The paper also presents some preliminary results, using the same technique, of the influence of a prosthetic femoral stem on the architecture of the surrounding trabecular bone.

To better understand the role of PueA and PueB from Pseudomonas chlororaphis in polyurethane degradation, the present study was conducted to create insertional mutants in their respective genes.Growth kinetic studies showed that the pueA knockout mutant had a greater effect than the pueB knockout mutant. The pueA mutant had an 80% decrease in cell density from that of the wild type, while the pueB mutant had an 18% decrease in cell density. Polyurethane utilization followed Michaelis-Menten kinetics. The pueA and pueB mutants exhibited a 17% and 10% decrease respectively in growth rate using polyurethane when compared with the wild type.In this present study, pueA and pueB, are shown to be part of an ABC transporter gene cluster that consists of seven open reading frames. Mutational analysis results suggest that PueA may play a more major role in polyurethane degradation than PueB based on cell density and growth rates.The results from this study provide a starting point for the eventual enhancement and bioremediation of polyurethane waste. Understanding the role of polyurethane-degrading enzymes is useful for the creation of strains for this purpose.

The human inflammatory caspases, including caspase-1, -4, -5 and -12, are considered as key regulators of innate immunity protecting from sepsis and numerous inflammatory diseases. Caspase-1 is activated by proximity-induced dimerization following recruitment to inflammasomes but the roles of the remaining inflammatory caspases in inflammasome assembly are unclear. Here, we use caspase bimolecular fluorescence complementation to visualize the assembly of inflammasomes and dimerization of inflammatory caspases in single cells. We observed caspase-1 dimerization induced by the coexpression of a range of inflammasome proteins and by lipospolysaccharide (LPS) treatment in primary macrophages. Caspase-4 and -5 were only dimerized by select inflammasome proteins, whereas caspase-12 dimerization was not detected by any investigated treatment. Strikingly, we determined that certain inflammasome proteins could induce heterodimerization of caspase-1 with caspase-4 or -5. Caspase-5 homodimerization and caspase-1/-5 heterodimerization was also detected in LPS-primed primary macrophages in response to cholera toxin subunit B. The subcellular localization and organization of the inflammasome complexes varied markedly depending on the upstream trigger and on which caspase or combination of caspases were recruited. Three-dimensional imaging of the ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain)/caspase-1 complexes revealed a large spherical complex of ASC with caspase-1 dimerized on the outer surface. In contrast, NALP1 (NACHT leucine-rich repeat protein 1)/caspase-1 complexes formed large filamentous structures. These results argue that caspase-1, -4 or -5 can be recruited to inflammasomes under specific circumstances, often leading to distinctly organized and localized complexes that may impact the functions of these proteases.

A plate assay to screen and detect bacterial polyurethanase in agar medium containing a colloidal polyester-polyurethane and rhodamine B is presented.Substrate hydrolysis causes the formation of orange fluorescent halos visible upon u.v. irradiation. The logarithm of polyurethanase activity from a purified polyurethanase protein is linearly correlated with the diameter of halos, thereby allowing quantification of polyurethanase activities ranging from 0.81 to 7.29 Units.The potential advantages of this system are in identification and recovery of viable polyurethanolytic bacteria and quantification of polyurethanase activity.These advantages are derived largely from the intense fluorescence observed due to the hydrolysis of substrate reacting with rhodamine B allowing for the use of low substrate concentrations and corresponding decrease in time required detecting low levels of enzyme activity.