Dynamic response signatures of a scaled model platform for floating wind turbines in an ocean wave basin.

Understanding of dynamic behaviour of offshore wind floating substructures is extremely important in relation to design, operation, maintenance and management of floating wind farms. This paper presents assessment of nonlinear signatures of dynamic responses of a scaled tension-leg platform (TLP) in a wave tank exposed to different regular wave conditions and sea states characterized by the Bretschneider, the Pierson-Moskowitz and the JONSWAP spectra. Dynamic responses of the TLP were monitored at different locations using load cells, a camera-based motion recognition system and a laser Doppler vibrometer. The analysis of variability of the TLP responses and statistical quantification of their linearity or nonlinearity, as non-destructive means of structural monitoring from the output-only condition, remains a challenging problem. In this study, the delay vector variance (DVV) method is used to statistically study the degree of nonlinearity of measured response signals from a TLP. DVV is observed to create a marker estimating the degree to which a change in signal nonlinearity reflects real-time behaviour of the structure and also to establish the sensitivity of the instruments employed to these changes. The findings can be helpful in establishing monitoring strategies and control strategies for undesirable levels or types of dynamic response and can help to better estimate changes in system characteristics over the life cycle of the structure.

Polygodial: a contact active antifouling biocide.

Ongoing investigation of the candidate antifouling (AF) biocide polygodial (PG) has revealed that this compound may be contact active, whereby it can confer effect while remaining bound within a stable matrix. To test this hypothesis, the AF activity of PG-laced coatings was compared to that of seawater in which PG-laced coatings had been soaked. Four coating types spanning high to low affinity for PG were examined and AF activity was assessed based on inhibition of settlement and metamorphosis of larvae of three fouling organisms: Ciona savignyi Herdman, Mytilus galloprovincialis Lamarck and Spirobranchus caraniferus Gray. Direct exposure to the coatings had a significantly greater impact on larval metamorphosis than indirect exposure to seawater in which the coatings had been soaked. In particular, metamorphosis was almost completely inhibited by high-affinity coatings containing ≥ 200 ng of PG per replicate, while corresponding soaking waters had no detectable effect. These findings support the assertion that PG is contact active.

Solvent system effects on the physical and mechanical properties of electrospun Poly(ε-caprolactone) scaffolds for in vitro lung models.

Mechanical properties are among the key considerations for the design and fabrication of complex tissue models and implants. In addition to the choice of material and the processing technique, the solvent system can significantly influence the mechanical properties of scaffolds. Poly(ε-caprolactone) (PCL) has been abundantly used to develop constructs, fibrous in particular, for pharmaceutical and biomedical research due to the flexibility offered by PCL-based fibrous matrices. The effect of solvent type on the morphological features of electrospun fibres has been extensively studied. Nevertheless, comprehensive studies on the impact of the solvent system on the mechanical properties of electrospun PCL fibres are lacking. This study elucidates the relationship between topographical, physical and mechanical properties of electrospun PCL fibrous meshes upon using various solvent systems. The results of the mechanical investigation highlight the significance of inter-fibre bonds on the mechanical properties of the bulk membranes and that the option of altering the solvent system composition could be considered for tuning the mechanical properties of the PCL scaffolds to serve specific biomedical application requirements. The applicability of the developed membranes as artificial ECM (Extracellular matrix) in the lung will then be investigated and compared to the commercial Polycarbonate (PC) membranes that are often used for in vitro lung models.

Native extracellular matrix orientation determines multipotent vascular stem cell proliferation in response to cyclic uniaxial tensile strain and simulated stent indentation.

Cardiovascular disease is the leading cause of death worldwide, with multipotent vascular stem cells (MVSC) implicated in contributing to diseased vessels. MVSC are mechanosensitive cells which align perpendicular to cyclic uniaxial tensile strain. Within the blood vessel wall, collagen fibers constrain cells so that they are forced to align circumferentially, in the primary direction of tensile strain. In these experiments, MVSC were seeded onto the medial layer of decellularized porcine carotid arteries, then exposed to 10%, 1 Hz cyclic tensile strain for 10 days with the collagen fiber direction either parallel or perpendicular to the direction of strain. Cells aligned with the direction of the collagen fibers regardless of the orientation to strain. Cells aligned with the direction of strain showed an increased number of proliferative Ki67 positive cells, while those strained perpendicular to the direction of cell alignment showed no change in cell proliferation. A bioreactor system was designed to simulate the indentation of a single, wire stent strut. After 10 days of cyclic loading to 10% strain, MVSC showed regions of densely packed, highly proliferative cells. Therefore, MVSC may play a significant role in in-stent restenosis, and this proliferative response could potentially be controlled by controlling MVSC orientation relative to applied strain.

Penetration of the blood-brain barrier: enhancement of drug delivery and imaging by bacterial glycopeptides.

The blood-brain barrier restricts the passage of many pharmacological agents into the brain parenchyma. Bacterial glycopeptides induce enhanced blood-brain barrier permeability when they are present in the subarachnoid space during meningitis. By presenting such glycopeptides intravenously, blood-brain barrier permeability in rabbits was enhanced in a reversible time- and dose-dependent manner to agents < or = 20 kD in size. Therapeutic application of this bioactivity was evident as enhanced penetration of the antibiotic penicillin and the magnetic resonance imaging contrast agent gadolinium-diethylene-triamine-pentaacetic acid into the brain parenchyma.

The DNA sequence and comparative analysis of human chromosome 10.

The finished sequence of human chromosome 10 comprises a total of 131,666,441 base pairs. It represents 99.4% of the euchromatic DNA and includes one megabase of heterochromatic sequence within the pericentromeric region of the short and long arm of the chromosome. Sequence annotation revealed 1,357 genes, of which 816 are protein coding, and 430 are pseudogenes. We observed widespread occurrence of overlapping coding genes (either strand) and identified 67 antisense transcripts. Our analysis suggests that both inter- and intrachromosomal segmental duplications have impacted on the gene count on chromosome 10. Multispecies comparative analysis indicated that we can readily annotate the protein-coding genes with current resources. We estimate that over 95% of all coding exons were identified in this study. Assessment of single base changes between the human chromosome 10 and chimpanzee sequence revealed nonsense mutations in only 21 coding genes with respect to the human sequence.

C60H2: Synthesis of the Simplest C60 Hydrocarbon Derivative.

The reaction of C(60) with BH(3): tetrahydrofuran in toluene followed by hydrolysis yielded C(60)H(2). This product was separated by high-performance liquid chromatography and characterized as the addition product of H(2) to a 6,6-ring fusion (1alb isomer). The (1)H nuclear magnetic resonance (NMR) spectrum of the product remained a sharp singlet between -80 degrees and +100 degrees C, which suggests a static structure on the NMR time scale. Hydrolysis of the proposed borane addition product with acetic acid-d(1) or D(2)O yielded C(60)HD, and its (3)J(HD) coupling constant is consistent with vicinal addition. The observation of a single C(60)H(2) isomer is in complete agreement with earlier calculations that indicated that at most 2 of the 23 possible isomers of C(60) would be observable at equilibrium at room temperature. These results suggest that organoborane chemistry may be applied to further functionalization of fullerenes.

Synthesis, Isolation, and Equilibration of 1,9- and 7,8-C70H2.

Equilibration of 1,9- and 7,8-C(70)H(2) has allowed the relative free energy of these isomers to be measured. These "simplest hydrocarbon derivatives of C(70)" are formed by hydroboration of C(70) at room temperature. Analysis of the platinum-catalyzed equilibration of these isomers yielded a relative free energy at 295 kelvin of 1.4 +/- 0.2 kilocalories per mole, with the 1,9 isomer being more stable. This value is in excellent agreement with the ab initio HF/6-31 G(*) calculated energy difference of 1.3 kilocalories per mole, whereas semiempirical calculations gave poor agreement.

An analysis of the strain field in biaxial Flexcell membranes for different waveforms and frequencies.

Mechanical stimuli have been shown to affect cell behaviour in terms of proliferation, apoptosis, and protein expression. In terms of cardiovascular diseases, for example, endothelial and smooth muscle cells exposed to an abnormal strain environment have been associated with atherosclerosis and in-stent restenosis. The FX-4000 system (Flexercell Tension Plus System, Flexcell Corporation, McKeesport, Pennsylvania, USA) is an in-vitro system that is widely used to strain cells in order to evaluate their response to strain. The precision, accuracy, and repeatability of the strains controlled by the system are therefore crucial to analyse and interpret the results confidently. The aim of this study was to investigate the mechanical behaviour of the FX-4000 Flexercell six-well-plate silicon membranes for static and dynamic cyclic strains by measuring the maximum peak strain and analysing the change in the membrane deformation after cyclic strain for 0 h, 24 h, and 48 h at different strain amplitudes and frequencies. The results of the tests conducted demonstrate notable differences between the measured strains of the membranes in comparison with both the inputs and the outputs of the Flexcell software. The calibration method used by Flexcell International assumes that the strain values determined for a given vacuum pressure on the silicone membranes are reliable for different waveforms and frequencies. The data reported here clearly indicate that this is not the case. The results indicate that a unique calibration pressure-strain curve must be determined for each test given the viscoelastic nature of the Flexcell system. A new method to calibrate the machine in house was applied using new pressure-strain equations. This new calibration method has been presented and should enable researchers using the Flexcell machine to set up their cell experiments more accurately.

Altered adenylyl cyclase activities and G-protein abnormalities in portal hypertensive rabbits.

Portal hypertension (PHT) is characterized by splanchnic hyperemia due to a reduction in mesenteric vascular resistance. We hypothesized that alterations in the activity of a guanine-nucleotide regulatory protein (G-protein) might be partially responsible for the marked circulatory disturbances observed in PHT. We, therefore, determined alterations in adenylyl cyclase/cAMP system in prehepatic portal hypertensive rabbits and correlated these changes to the activity of a G-protein. Basal and G-protein-stimulated adenylyl cyclase activities were lower in the PHT superior mesenteric artery (22-26%) and thoracic aorta (31-46%) membranes, but higher (178-321%) in portal vein. The functional activity of Gi alpha proteins (pertussis toxin-catalyzed ADP-dependent ribosylation) increased in the PHT superior mesenteric artery and thoracic aorta, but decreased in portal vein. Immunodetection revealed an increase in the Gi alpha protein subunits (Gi alpha 1/Gi alpha 2 and Gi alpha 3/Go alpha) in PHT thoracic aorta, without any change in Gs alpha proteins; and a decrease in the amount of Gi alpha proteins in PHT portal vein. There was no change in the amount of Gs alpha/Gi alpha in the PHT superior mesenteric artery. We conclude the hemodynamic alterations of PHT are associated with intrinsic alterations in G-protein-enzyme effector systems. These alterations are vessels specific and suggest a possible unique global derangement underlying the vasculopathy of PHT.

Access of asylum seeker children to acute paediatric services.

To investigate the interface between primary care and paediatric services in the referral of asylum seekers. Over a 3 month period a questionnaire was administered, and clinical data gathered on every child attending the A&E department of UCHG whose parents were seeking asylum in this country. Control data was obtained for the next Irish child seen on-call. At the time of presentation to the paediatric service, an Irish child was 4 times more likely (32%) to have initially been seen and referred by a GP than an asylum seeker child (8%); 80% of asylum seeker families had registered with a GP, compared to 96% of controls. 24% of asylum seeker families had called and used an emergency response ambulance to get to hospital, compared to just 4% of Irish children. The rate of subsequent admission to the paediatric ward from A&E was nearly that in asylum seeker children (24%) compared to Irish controls (40%), get to hospital, compared to just 4% of Irish children. Asylum seeker children are less likely to have seen a GP prior to A&E presentation, more likely to go to hospital by ambulance and less likely to be subsequently admitted, suggesting an over-dependence on paediatric hospital services in this population.

Endothelial cells inhibit flow-induced smooth muscle cell migration: role of plasminogen activator inhibitor-1.

BACKGROUND: The endothelium may play a pivotal role in hemodynamic force-induced vascular remodeling. We investigated the role of endothelial cell (EC) plasminogen activator inhibitor-1 (PAI-1) in modulating flow-induced smooth muscle cell (SMC) migration. METHODS AND RESULTS: Human SMCs cocultured with or without human ECs were exposed to static (0 mL/min) or flow (26 mL/min; shear stress 23 dyne/cm(2)) conditions for 24 hours in a perfused capillary culture system. SMC migration was then assessed with a Transwell migration assay. In the absence but not in the presence of ECs, pulsatile flow significantly increased the migration of SMCs (264+/-26%) compared with SMCs under static conditions, concomitant with a 3- and 4-fold increase in PAI-1 mRNA and protein, respectively, in cocultured ECs. In the presence of PAI-1-/- ECs, flow increased wild-type SMC migration (226+/-25%), an effect that was reversed by exogenous PAI-1. To determine whether the antimigratory activity of PAI-1 was dependent primarily on inhibition of PAs or its association with vitronectin, experiments were conducted with PAI-1R (a mutant PAI-1 that binds to vitronectin but does not inhibit PA) and PAI-1K (a mutant that inhibits PA but has reduced affinity for vitronectin). PAI-1R inhibited both basal and flow-induced migration, whereas PAI-1K inhibited flow-induced migration in the absence of any effect on baseline migration. CONCLUSIONS: Flow-induced EC PAI-1 inhibits flow-induced SMC migration in vitro. EC PAI-1 expression may be one of the predominant mechanisms responsible for controlling the process of vascular remodeling.

Nonanticoagulant heparin prevents coronary endothelial dysfunction after brief ischemia-reperfusion injury in the dog.

BACKGROUND: Coronary endothelial dysfunction after brief ischemia-reperfusion (IR) remains a clinical problem. We investigated the role of heparin and N-acetylheparin, a nonanticoagulant heparin derivative, in modulating coronary endothelial function after IR injury, with an emphasis on defining the role of the nitric oxide (NO)-cGMP pathway in the heparin-mediated effect. METHODS AND RESULTS: Male mongrel dogs were surgically instrumented, and the effects of both bovine heparin and N-acetylheparin on coronary endothelial vasomotor function, expressed as percent change from baseline flow after acetylcholine challenge, were studied after 15 minutes of regional ischemia of the left anterior descending artery (LAD) followed by 120 minutes of reperfusion. In dogs treated with placebo (saline), coronary vasomotor function was significantly (P

Endothelial dysfunction in cirrhosis and portal hypertension.

Portal hypertension (PHT) is a common clinical syndrome associated with chronic liver diseases; it is characterized by a pathological increase in portal pressure. Pharmacotherapy for PHT is aimed at reducing both intrahepatic vascular tone and elevated splanchnic blood flow. Due to the altered hemodynamic profile in PHT, dramatic changes in mechanical forces, both pressure and flow, may play a pivotal role in controlling endothelial and vascular smooth muscle cell signaling, structure, and function in cirrhotics. Nitric oxide, prostacyclin, endothelial-derived contracting factors, and endothelial-derived hyperpolarizing factor are powerful vasoactive substances released from the endothelium in response to both humoral and mechanical stimuli that can profoundly affect both the function and structure of the underlying vascular smooth muscle. This review will examine the contributory role of hormonal- and mechanical force-induced changes in endothelial function and signaling and the consequence of these changes on the structural and functional response of the underlying vascular smooth muscle. It will focus on the pivotal role of hormonal and mechanical force-induced endothelial release of vasoactive substances in dictating the reactivity of the underlying vascular smooth muscle, i.e., whether hyporeactive or hyperreactive, and will examine the extent to which these substances may exert a protective and/or detrimental influence on the structure of the underlying vascular smooth muscle in both a normal hemodynamic environment and following hemodynamic perturbations typical of PHT and cirrhosis. Finally, it will discuss the intracellular processes that regulate the release/expression of these vasoactive substances and that control the transformation of this normally protective cell to one that may promote the development of vasculopathy in PHT.

Interaction of Escherichia coli ribosomal protein S8 with its binding sites in ribosomal RNA and messenger RNA.

The ability of ribosomal protein S8 from Escherichia coli to interact with 12 variants of its 16 S rRNA binding site, as well as with a regulatory sequence within spc operon mRNA, has been assessed. Single-site alterations were introduced into the appropriate segment of the E. coli 16 S rRNA gene by mutagenesis in vitro. Their effects on S8-rRNA interaction were measured via a filter-binding assay, utilizing S8 binding sites transcribed in vitro from the altered 16 S rRNA gene fragments. Of the 12 rRNA mutants, six were unable to bind S8. Significantly, five of these occur within a small, phylogenetically conserved internal loop, defined by nucleotides 596-597 and 641-643, suggesting that this structure plays a major role in S8-16 S rRNA recognition. The reduced affinity of S8 for its binding site in these cases was closely correlated with growth defects that resulted from expression of the same mutations in vivo. Alterations at other positions in the S8 binding site had little influence on complex formation or cell growth, as long as they did not disrupt rRNA secondary structure. The specific interaction of S8 with a segment of the spc operon mRNA containing a putative site of translational feedback regulation was demonstrated using appropriate in vitro transcripts in conjunction with the filter-binding assay. The apparent association constant for the S8-mRNA interaction was determined to be approximately 5 x 10(6) M-1, about five times lower than for the interaction of S8 with wild-type 16 S rRNA. The structure of the regulatory binding site, determined by sequence analysis of spc operon mRNA protected by S8 from RNase digestion, was found to contain all of the characteristic features of the 16 S rRNA binding site, demonstrating that the protein associates with structurally similar domains in both RNAs.

Effects of fish oil on arteriosclerosis in the Japanese quail.

The effects of fish oil on the development of arteriosclerosis were assessed using a special susceptible strain (SEA) of Japanese quail (Coturnix coturnix japonica). Sixty four quail were randomly divided into two groups and placed on isocaloric and approximately isocholesterolic (2% by weight) diets. Group A (control) was supplemented with 10% beef tallow oil, while group B received 10% Menhaden fish oil. The birds were sacrificed at 10 weeks (early) and 15-16 weeks (late). Based on semiquantitative histological grading of the arteriosclerotic lesions in the proximal aorta and brachiocephalic arteries, a score from 1 (no lesion) to 5 (severe, diffuse lesions) was assigned. A total of 57 quail were evaluated (seven died prior to scheduled sacrifice). At the early period, the mean arteriosclerosis scores for group A (n = 8) and group B (n = 8) were 3.3 (SD 1.0) and 1.9(1.0) respectively (p less than 0.017); 63% of the quail in group A and 13% of those in group B had a score greater than or equal to 3 (p less than 0.25, NS). At the late period, the scores for group A (n = 20) and group B (n = 21) were 3.8(0.6) and 2.6(0.9), respectively (p less than 0.001); 95% of the birds in group A and 43% of those in group B had a score greater than or equal to 3 (p less than 0.005). Histopathological examination of the arteriosclerotic lesions revealed disruption of the innermost elastic lamina, increased proteoglycan deposition in the medial interlamellar spaces, and the distinct involvement of macrophage like cells. Compared to human disease, arteriosclerosis in the quail is marked by distinct similarities, as well as differences. The SEA strain of Japanese quail appears to be a practical model for the study of arteriosclerosis; fish oil reduces the severity of disease in these birds when fed a high cholesterol diet.

Autologous bone graft harvesting: a review of grafts and surgical techniques.

Spinal fusion with or without instrumentation often requires the use of bone graft. Bone graft may be autogenous or exogenous. There are various forms of bone graft which may be acquired from numerous sites. Knowledge of fusion biology is imperative for understanding the benefits and limitations of these grafts. Equally as important is the knowledge of outcome measures, management of donor-site morbidity, and potential reconstruction. This review details the methods of obtaining bone graft and details the properties of each, as well as discusses observed outcomes, donor-site morbidities, and reconstruction techniques.

Effect of a psychiatric liaison program on consultation rates and on detection of minor psychiatric disorders in cancer patients.

Because only 2% of the 47% of cancer patients with psychiatric disorders receive psychiatric consultations, the authors investigated the impact of a psychiatric liaison program on improving consultation rates on a gynecologic oncology unit. Consultation rates for gynecologic cancer patients before and after introduction of the program were compared to rates from other cancer patients in the same hospital during the same 7-year period. Rates for the gynecologic patients were higher after the program (9%) than before (4%), as were rates for follow-up consultations, and the detection of minor DSM-III disorders improved. The authors conclude that liaison improves access to psychiatric treatments that often enhance the quality of life for seriously ill patients.

Atrial natriuretic factor recognizes two receptor subtypes in endothelial cells cultured from bovine pulmonary artery.

In this study specific high affinity binding sites for atrial natriuretic factor (rANF(99-126] have been identified on cultured endothelial cells of bovine pulmonary artery origin (BPAEC). A time-dependent rise in cellular cGMP levels stimulated by rANF(99-126) was followed by release of the nucleotide into the incubation medium. The use of truncated, ring-deleted and linear atrial peptide analogs in competitive displacement analysis and measurement of cGMP accumulation indicated that only a minor proportion (5-11%) of the available receptor pool was of the ANF-B receptor subtype, linked to guanylate cyclase, with the remaining major proportion possibly of the ANF-C (clearance) receptor subtype. The existence of two ANF receptor subtypes in this cell culture model would suggest a significant role for the circulating peptide in modulation of pulmonary endothelial cell function, which would influence or complement its direct actions on the underlying vasculature of the pulmonary circulation.