Third post-Newtonian angular momentum flux and the secular evolution of orbital elements for inspiralling compact binaries in quasi-elliptical orbits

The angular-momentum flux from an inspiralling binary system of compact objects moving in quasi-elliptical orbits is computed at the third post-Newtonian (3PN) order using the multipolar post-Minkowskian wave generation formalism. The 3PN angular-momentum flux involves the instantaneous, tail, and tail-of-tails contributions as for the 3PN energy flux, and in addition a contribution due to nonlinear memory. We average the angular-momentum flux over the binary's orbit using the 3PN quasi-Keplerian representation of elliptical orbits. The averaged angular-momentum flux provides the final input needed for gravitational-wave phasing of binaries moving in quasi-elliptical orbits. We obtain the evolution of orbital elements under 3PN gravitational radiation reaction in the quasi-elliptic case. For small eccentricities, we give simpler limiting expressions relevant for phasing up to order e(2). This work is important for the construction of templates for quasi-eccentric binaries, and for the comparison of post-Newtonian results with the numerical relativity simulations of the plunge and merger of eccentric binaries.

Effect of pulse profile variations on measurement of eccentricity in orbits of Cen X-3 and SMC X-1

It has long been argued that better timing precision allowed by satellites like Rossi X-ray Timing Explorer (RXTE) will allow us to measure the orbital eccentricity and the angle of periastron of some of the bright persistent high-mass X-ray binaries (HMXBs) and hence a possible measurement of apsidal motion in these system. Measuring the rate of apsidal motion allows one to estimate the apsidal motion constant of the mass losing companion star and hence allows for the direct testing of the stellar structure models for these giant stars present in the HMXBs. In the present paper, we use the archival RXTE data of two bright persistent sources, namely Cen X-3 and SMC X-1, to measure the very small orbital eccentricity and the angle of periastron. We find that the small variations in the pulse profiles of these sources, rather than the intrinsic time resolution provided by RXTE, limit the accuracy with which we can measure arrival time of the pulses from these sources. This influences the accuracy with which one can measure the orbital parameters, especially the very small eccentricity and the angle of periastron in these sources. The observations of SMC X-1 in the year 2000 were taken during the high-flux state of the source and we could determine the orbital eccentricity and omega using this data set.

Prediction of individual genetic risk to prostate cancer using a polygenic score

BACKGROUND Polygenic risk scores comprising established susceptibility variants have shown to be informative classifiers for several complex diseases including prostate cancer. For prostate cancer it is unknown if inclusion of genetic markers that have so far not been associated with prostate cancer risk at a genome-wide significant level will improve disease prediction. METHODS We built polygenic risk scores in a large training set comprising over 25,000 individuals. Initially 65 established prostate cancer susceptibility variants were selected. After LD pruning additional variants were prioritized based on their association with prostate cancer. Six-fold cross validation was performed to assess genetic risk scores and optimize the number of additional variants to be included. The final model was evaluated in an independent study population including 1,370 cases and 1,239 controls. RESULTS The polygenic risk score with 65 established susceptibility variants provided an area under the curve (AUC) of 0.67. Adding an additional 68 novel variants significantly increased the AUC to 0.68 (P = 0.0012) and the net reclassification index with 0.21 (P = 8.5E-08). All novel variants were located in genomic regions established as associated with prostate cancer risk. CONCLUSIONS Inclusion of additional genetic variants from established prostate cancer susceptibility regions improves disease prediction. Prostate 75:1467–1474, 2015. © 2015 Wiley Periodicals, Inc.

Type II beta-turn conformation of pivaloyl-L-prolyl-a-aminoiso-butyryl-N-methylamide: Theoretical, spectroscopic and X-ray studies

Pivaloyl-L-Pro-Aib-N-methylamihdaes been shown to possess one intramolecular hydrogen bond in (CD&SO solution, by 'H-nmr methods, suggesting the existence of p-turns, with Pro-Aib as the corner residues. Theoretical conformational analysis suggests that Type II P-turn conformations are about 2 kcal mol-' more stable than Type 111 structures. A crystallographic study has established the Type I1 /%turn in the solid state. The molecule crystallizes in the space group P21 with a = 5.865 8, b = 11.421 A, c = 12.966 A, /3 = 97.55", and 2 = 2. The structure has been refined to a final R value of 0.061. The Type I1 p-turn conformation is stabilized by an intramolecular 4 - 1 hydrogen bond between the methylamide NH and the pivaloyl CO group. The conformational angles are @pro= -57.8", $pro = 139.3', @Aib = 61.4', and $Ajb = 25.1'. The Type 11 /%turn conformation for Pro-Aib in this peptide is compared with the Type I11 structures observed for the same segment in larger peptides.

High-pressure Raman and infrared spectroscopic studies of ZrP2O7

High-pressure Raman and mid-infrared spectroscopic studies were carried out on ZrP2O7 to 23.2 and 13 GPa respectively. In the pressure range 0.7-4.3 GPa the lattice mode at 248 cm(-1) disappears, new modes appear around 380 and 1111 cm(-1) and the strong symmetric stretching mode at 476 cm(-1) softens, possibly indicating a subtle phase transition. Above 8 GPa all the modes broaden, and all of the Raman modes disappear beyond 18 GPa. On decompression from the highest pressure, 23.2, to 0 GPa all of the modes reappear but with larger full width at half maximum. Lattice dynamics of the high temperature phase of ZrP2O7 were studied using first principles method and compared with experimental values. (C) 2009 Elsevier Ltd. All rights reserved.

Individual variation in in vitro efficacy of antiplatelet medication - aspirin and clopidogrel

Antiplatelet medication is known to decrease adverse effects in patients with atherothrombotic disease. However, despite ongoing antiplatelet medication considerable number of patients suffer from atherothrombotic events. The aims of the study were 1) to evaluate the individual variability in platelet functions and compare the usability of different methods in detecting it, 2) to assess variability in efficacy of antiplatelet medication with aspirin (acetylsalicylic acid) or the combination of aspirin and clopidogrel and 3) to investigate the main genetic and clinical variables as well as potential underlying mechanisms of variability in efficacy of antiplatelet medication. In comparisons of different platelet function tests in 19 healthy individuals PFA-100® correlated with traditional methods of measuring platelet function and was thus considered appropriate for testing individual variability in platelet activity. Efficacy of ongoing 100mg aspirin daily was studied in 101 patients with coronary artery disease (CAD). Aspirin response was measured with arachidonic acid (AA)-induced platelet aggregation, which reflects cyclo-oxygenase (COX)-1 dependent thromboxane (Tx) A2 formation, and PFA-100®, which evaluates platelet activation under high shear stress in the presence of collagen and epinephrine. Five percent of patients failed to show inhibition of AA-aggregation and 21% of patients had normal PFA-100® results despite aspirin and were thus considered non-responders to aspirin. Interestingly, the two methods of assessing aspirin efficacy, platelet aggregation and PFA-100®, detected different populations as being aspirin non-responders. It could be postulated that PFA-100® actually measures enhanced platelet function, which is not directly associated with TxA2 inhibition exerted by aspirin. Clopidogrel efficacy was assessed in 50 patients who received a 300mg loading dose of clopidogrel 2.5 h prior to percutaneous coronary intervention (PCI) and in 51 patients who were given a loading dose of 300mg combined with a five day treatment of 75mg clopidogrel daily mimicking ongoing treatment. Clopidogrel response was assessed with ADP-induced aggregations, due to its mechanism of action as an inhibitor of ADP-induced activation. When patients received only a loading dose of clopidogrel prior to PCI, 40% did not gain measurable inhibition of their ADP-induced platelet activity (inhibition of 10% or less). Prolongation of treatment so that all patients had reached a plateau of inhibition exerted by clopidogrel, decreased the incidence of non-responders to 20%. Polymorphisms of COX-1 and GP VI, as well as diabetes and female gender, were associated with decreased in vitro aspirin efficacy. Diabetes also impaired the in vitro efficacy of short-term clopidogrel. Decreased response to clopidogrel was associated with limited inhibition by ARMX, an antagonist of P2Y12-receptor, suggesting the reason for clopidogrel resistance to be receptor-dependent. Conclusions: Considerable numbers of CAD patients were non-responders either to aspirin, clopidogrel or both. In the future, platelet function tests may be helpful to individually select effective and safe antiplatelet medication for these patients.

Boundary-layer effects on internal flow choking in dual-thrust solid rocket motors

Theoretical studies have been carried out to examine internal flow choking in the inert simulators of a dual-thrust motor. Using a two-dimensional k-omega turbulence model, detailed parametric studies have been carried out to examine aerodynamic choking and the existence of a fluid throat at the transition region during the startup transient of dual-thrust motors. This code solves standard k-omega turbulence equations with shear flow corrections using a coupled second-order-implicit unsteady formulation. In the numerical study, a fully implicit finite volume scheme of the compressible, Reynolds-averaged, Navier-Stokes equations is employed. It was observed that, at the subsonic inflow conditions, there is a possibility of the occurrence of internal flow choking in dual-thrust motors due to the formation of a fluid throat at the beginning of the transition region induced by area blockage caused by boundary-layer-displacement thickness. It has been observed that a 55% increase in the upstream port area of the dual-thrust motor contributes to a 25% reduction in blockage factor at the transition region, which could negate the internal How choking and supplement with an early choking of the dual-thrust motor nozzle. If the height of the upstream port relative to the motor length is too small, the developing boundary layers from either side of the port can interact, leading to a choked,flow. On the other hand, if the developing boundary layers are far enough apart, then choking does not occur. The blockage factor is greater in magnitude for the choked case than for the unchoked case. More tangible explanations are presented in this paper for the boundary-layer blockage and the internal flow choking in dual-thrust motors, which hitherto has been unexplored.

Flow during individual and co-operative gameplay

This study aims to further research in the field of video games by examining flow during individual and co-operative gameplay. Using a puzzle game called Droppit, we examined differences in flow based on two modes of play: single player vs. co-operative gameplay. Co-operative gameplay was found to induce greater flow in participants than single player gameplay. Additionally, co-operative gameplay participants had increased feelings of Challenge-Skill Balance, Unambiguous Feedback, Transformation of Time and Autotelic Experience. Our findings suggest that co-operative gameplay, involving puzzle-based problems, may result in increased flow during video game play.

Dielectric anisotropy and relaxation studies of the homologous series of N-(4-n-alkyloxy-2-hydroxy-benzylidene)-4-carbethoxyaniline

Dielectric properties of the homologous series of newly synthesized nonchiral compounds N-(4-n-alkyloxy-2-hydroxy-benzylidene)-4-carbethoxyaniline, (n = 6, 8, 10, 12) having wide temperature range (∼60°C) smectic A (SmA) phase, have been studied by the impedance spectroscopy in the frequency range of 100 Hz to 1 MHz. Measurements have been carried out for two principal alignments (planar as well as homeotropic) of the SmA phase. Dielectric anisotropy (Δε' = ε'∥ - ε'⊥) for all the members of the series has been found to be negative for the whole temperature range of SmA phase. Magnitude of the dielectric anisotropy (|Δε'|) has been found to decrease with the number of alkyl chains. Relaxation frequencies corresponding to the rotation of the individual molecules about their short axes, lie below 1 MHz and obey the Arrhenius law by which activation energies have been determined. However, the relaxation frequencies corresponding to the rotation of the molecules about their short axes apparently lie above 10 MHz.

Thrombophilia and direct thrombin inhibitor lepirudin clinical and monitoring aspects

Thrombophilia (TF) predisposes both to venous and arterial thrombosis at a young age. TF may also impact the thrombosis or stenosis of hemodialysis (HD) vascular access in patients with end-stage renal disease (ESRD). When involved in severe thrombosis TF may associate with inappropriate response to anticoagulation. Lepirudin, a potent direct thrombin inhibitor (DTI), indicated for heparin-induced thrombocytopenia-related thrombosis, could offer a treatment alternative in TF. Monitoring of narrow-ranged lepirudin demands new insights also in laboratory. The above issues constitute the targets in this thesis. We evaluated the prevalence of TF in patients with ESRD and its impact upon thrombosis- or stenosis-free survival of the vascular access. Altogether 237 ESRD patients were prospectively screened for TF and thrombogenic risk factors prior to HD access surgery in 2002-2004 (mean follow-up of 3.6 years). TF was evident in 43 (18%) of the ESRD patients, more often in males (23 vs. 9%, p=0.009). Known gene mutations of FV Leiden and FII G20210A occurred in 4%. Vascular access sufficiently matured in 226 (95%). The 1-year thrombosis- and stenosis-free access survival was 72%. Female gender (hazards ratio, HR, 2.5; 95% CI 1.6-3.9) and TF (HR 1.9, 95% CI 1.1-3.3) were independent risk factors for the shortened thrombosis- and stenosis-free survival. Additionally, TF or thrombogenic background was found in relatively young patients having severe thrombosis either in hepatic veins (Budd-Chiari syndrome, BCS, one patient) or inoperable critical limb ischemia (CLI, six patients). Lepirudin was evaluated in an off-label setting in the severe thrombosis after inefficacious traditional anticoagulation without other treatment options except severe invasive procedures, such as lower extremity amputation. Lepirudin treatments were repeatedly monitored clinically and with laboratory assessments (e.g. activated partial thromboplastin time, APTT). Our preliminary studies with lepirudin in thrombotic calamities appeared safe, and no bleeds occurred. An effective DTI lepirudin calmed thrombosis as all patients gradually recovered. Only one limb amputation was performed 3 years later during the follow-up (mean 4 years). Furthermore, we aimed to overcome the limitations of APTT and confounding effects of warfarin (INR of 1.5-3.9) and lupus anticoagulant (LA). Lepirudin responses were assessed in vitro by five specific laboratory methods. Ecarin chromogenic assay (ECA) or anti-Factor IIa (anti-FIIa) correlated precisely (r=0.99) with each other and with spiked lepirudin in all plasma pools: normal, warfarin, and LA-containing plasma. In contrast, in the presence of warfarin and LA both APTT and prothrombinase-induced clotting time (PiCT®) were limited by non-linear and imprecise dose responses. As a global coagulation test APTT is useful in parallel to the precise chromogenic methods ECA or Anti-FIIa in challenging clinical situations. Lepirudin treatment requires multidisciplinary approach to ensure appropriate patient selection, interpretation of laboratory monitoring, and treatment safety. TF seemed to be associated with complicated thrombotic events, in venous (BCS), arterial (CLI), and vascular access systems. TF screening should be aimed to patients with repeated access complications or prior unprovoked thromboembolic events. Lepirudin inhibits free and clot-bound thrombin which heparin fails to inhibit. Lepirudin seems to offer a potent and safe option for treatment of severe thrombosis. Multi-centered randomized trials are necessary to assess the possible management of complicated thrombotic events with DTIs like lepirudin and seek prevention options against access complications.

Long-term results of operative treatment for Hirschsprung's disease and internal anal sphincter achalasia

The aim of the study was to evaluate long-term results of operative treatment for Hirschsprung's disease(HD) and internal anal sphincter achalasia. Fecal continence and quality of life were evaluated by a questionnaire in 100 adult patients who had undergone surgery for HD, during 1950-75. Fecal continence was evaluated using a numerical scoring described by Holschneider. Fifty-four of the 100 patients underwent clinical examination, rigid sigmoidoscopy and manometric evaluation. In anorectal manometry basal resting pressure(BRP)and maximal squeeze pressure(MSP) were measured and voluntary sphincter force(VSF) was calculated by subtracting the BRP from MSP. The results of operative treatment for adult HD were compared with the results of the patients operated in childhood. In adult HD the symptoms are such mild that the patients attain adolescence or even adulthood. The patients with HD and cartilage-hair-hypoplasia were specifically evaluated. The outcome of the patients with internal anal sphincter achalasia operated on by myectomy was evaluated by a questionnaire and continence was evaluated using a numerical scoring described by Holschneider. Of the 100 patients operated on for HD 38 patients had completely normal bowel habits. A normal or good continence score was found in 91 our of 100 patients. Nine patients had fair continence. One of the patients with fair continence had Down's syndrome and two were mentally retarded for other reasons. Only one patient suffered from constipation. In anorectal manometry the difference in BRP between patients with normal and good continence was statistically significant, whereas the difference between good and fair continence groups was not statistically significant. The differences on MSP and VSF between patient groups with different continence outcome were not statistically significant. The differences between patient groups and normal controls were statistically significant in BRP and MSP. In VSF there was not statistically significant difference between the patients and the normal controls. The VSF reflects the working power of the muscles including external sphincter, levator ani and gluteal muscles. The patients operated at adult age had as good continence as patients operated in childhood. The patients with HD and cartilage-hair-hypoplasia had much more morbidity and mortality than non-cartilage-hair-hypoplasia HD patients. The mortality was as high as 38%. In patients with internal anal sphincter achalasia the constipation was cured or alleviated by myectomy whereas a significant number suffered from soiling-related social problems.

Spectroscopic investigations and luminescence spectra of Nd3+ and Dy3+ doped different phosphate glasses

Spectral properties of Nd3+ and Dy3+ ions in different phosphate glasses were studied and several spectroscopic parameters were reported. Covalency of rare-earth-oxygen bond was studied in these phosphate glass matrices with the variation of modifier in host glass matrix Using Judd-Ofelt intensity parameters (Omega(2), Omega(4) and Omega(6)), radiative transition probabilities (A) and radiative lifetimes (tau(R)) of certain excited states of Nd3+ and Dy3+ ions are estimated in these glass matrices. From the magnitudes of branching ratios (beta(R)) and integrated absorption cross-sections (Sigma), certain transitions of both the ions are identified for laser excitation. From the emission spectra, peak stimulated emission cross-sections (sigma(P)) are evaluated for the emission transitions observed in all these phosphate glass matrices for both Nd3+ and Dy3+ ions. (C) 2009 Elsevier B.V. All rights reserved.

Quantitation and characterization of glutathionyl haemoglobin as an oxidative stress marker in chronic renal failure by mass spectrometry

Objectives: Glutathionyl haemoglobin (GS-Hb) belonging to the class of glutathionylated proteins has been investigated as a possible marker of oxidative stress in different chronic diseases. The purpose of this study was to examine whether glutathionyl haemoglobin can serve as an oxidative stress marker in non-diabetic chronic renal failure patients on different renal replacement therapies (RRT) through its quantitation, and characterization of the specific binding site of glutathione in haemoglobin molecule by mass spectrometric analysis. Design and methods: The study group consisted of non-diabetic chronic renal failure patients on renal replacement therapy (RRT): hemodialysis (HD), continuous ambulatory peritoneal dialysis (CAPD) and renal allograft transplant (Txp) patients. Haemoglobin samples of these subjects were analyzed by liquid chromatography electrospray ionization mass spectrometry for GS-Hb quantitation. Characterization of GS-Hb was done by tandem mass spectrometry. Levels of erythrocyte glutathione (GSH) and lipid peroxidation (as thiobarbituric acid reacting substances) were measured spectrophotometrically, while glycated baernoglobin (HbA1c) was measured by HPLC. Results: GS-Hb levels were markedly elevated in the dialysis group and marginally in the transplant group as compared to the controls. GS-Hb levels correlated positively with lipid peroxidation and negatively with the erythrocyte glutathione levels in RRT groups indicating enhanced oxidative stress. De novo sequencing of the chymotryptic fragment of GS-Hb established that glutathione is attached to Cys-93 of the beta globin chain. Mass spectrometric quantitation of total glycated haemoglobin showed good agreement with HbA1c estimation by conventional HPLC method. Conclusions: Glutathionyl haemoglobin can serve as a clinical marker of oxidative stress in chronic debilitating therapies like RRT. Mass spectrometry provides a reliable analytical tool for quantitation and residue level characterization of different post-translational modifications of haemoglobin. (c) 2007 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

On gravitational fields of stars in f(R) gravity theories

Einstein's general relativity is a classical theory of gravitation: it is a postulate on the coupling between the four-dimensional, continuos spacetime and the matter fields in the universe, and it yields their dynamical evolution. It is believed that general relativity must be replaced by a quantum theory of gravity at least at extremely high energies of the early universe and at regions of strong curvature of spacetime, cf. black holes. Various attempts to quantize gravity, including conceptually new models such as string theory, have suggested that modification to general relativity might show up even at lower energy scales. On the other hand, also the late time acceleration of the expansion of the universe, known as the dark energy problem, might originate from new gravitational physics. Thus, although there has been no direct experimental evidence contradicting general relativity so far - on the contrary, it has passed a variety of observational tests - it is a question worth asking, why should the effective theory of gravity be of the exact form of general relativity? If general relativity is modified, how do the predictions of the theory change? Furthermore, how far can we go with the changes before we are face with contradictions with the experiments? Along with the changes, could there be new phenomena, which we could measure to find hints of the form of the quantum theory of gravity? This thesis is on a class of modified gravity theories called f(R) models, and in particular on the effects of changing the theory of gravity on stellar solutions. It is discussed how experimental constraints from the measurements in the Solar System restrict the form of f(R) theories. Moreover, it is shown that models, which do not differ from general relativity at the weak field scale of the Solar System, can produce very different predictions for dense stars like neutron stars. Due to the nature of f(R) models, the role of independent connection of the spacetime is emphasized throughout the thesis.