Mechanical Systems with Symmetry, Variational Principles, and Integration Algorithms

This paper studies variational principles for mechanical systems with symmetry and their applications to integration algorithms. We recall some general features of how to reduce variational principles in the presence of a symmetry group along with general features of integration algorithms for mechanical systems. Then we describe some integration algorithms based directly on variational principles using a discretization technique of Veselov. The general idea for these variational integrators is to directly discretize Hamilton’s principle rather than the equations of motion in a way that preserves the original systems invariants, notably the symplectic form and, via a discrete version of Noether’s theorem, the momentum map. The resulting mechanical integrators are second-order accurate, implicit, symplectic-momentum algorithms. We apply these integrators to the rigid body and the double spherical pendulum to show that the techniques are competitive with existing integrators

H2-Fueled ATP Synthesis on an Electrode: Mimicking Cellular Respiration

ATP, the molecule used by living organisms to supply energy to many different metabolic processes, is synthesized mostly by the ATPase synthase using a proton or sodium gradient generated across a lipid membrane. We present evidence that a modified electrode surface integrating a NiFeSe hydrogenase and a F1F0 -ATPase in a lipid membrane can couple the electrochemical oxidation of H2 to the synthesis of ATP. This electrode-assisted conversion of H2 gas into ATP could serve to generate this biochemical fuel locally when required in biomedical devices or enzymatic synthesis of valuable product

Variational Integrators and the Newmark Algorithm for Conservative and Dissipative Mechanical Systems

The purpose of this work is twofold. First, we demonstrate analytically that the classical Newmark family as well as related integration algorithms are variational in the sense of the Veselov formulation of discrete mechanics. Such variational algorithms are well known to be symplectic and momentum preserving and to often have excellent global energy behavior. This analytical result is veried through numerical examples and is believed to be one of the primary reasons that this class of algorithms performs so well. Second, we develop algorithms for mechanical systems with forcing, and in particular, for dissipative systems. In this case, we develop integrators that are based on a discretization of the Lagrange d'Alembert principle as well as on a variational formulation of dissipation. It is demonstrated that these types of structured integrators have good numerical behavior in terms of obtaining the correct amounts by which the energy changes over the integration run

A Selective, Efficient and Environmentally Friendly Method for the Oxidative Cleavage of Glycols

A catalytic methodology for the oxidative cleavage of vicinal diols is described as an advantageous alternative in terms of the environmental impact on classical methods involving toxic oxidants. The novel strategy is based on the use of dioxomolybdenum(VI) complexes as catalysts and dimethyl sulfoxide (DMSO) as an oxidant and displays high selectivity and a broad scope for glycol cleavage. In addition, the developed system is also useful for the oxidation of acyloins to diketones.Ministerio de Economía y Competitividad (MINECO) and FEDER (CTQ2013-48937-C2-1-P) and Junta de Castilla y León (BU237U13

Hubble PanCET: An isothermal day-side atmosphere for the bloated gas-giant HAT-P-32Ab

This is the author accepted manuscript. The final version is available from OUP via the DOI in this recordWe present a thermal emission spectrum of the bloated hot Jupiter HAT-P-32Ab from a single eclipse observation made in spatial scan mode with the Wide Field Camera 3 (WFC3) aboard the Hubble Space Telescope (HST). The spectrum covers the wavelength regime from 1.123 to 1.644 microns which is binned into 14 eclipse depths measured to an averaged precision of 104 parts-per million. The spectrum is unaffected by a dilution from the close M-dwarf companion HAT-P-32B, which was fully resolved. We complemented our spectrum with literature results and performed a comparative forward and retrieval analysis with the 1D radiative-convective ATMO model. Assuming solar abundance of the planet atmosphere, we find that the measured spectrum can best be explained by the spectrum of a blackbody isothermal atmosphere with Tp = 1995 +/- 17K, but can equally-well be described by a spectrum with modest thermal inversion. The retrieved spectrum suggests emission from VO at the WFC3 wavelengths and no evidence of the 1.4 micron water feature. The emission models with temperature profiles decreasing with height are rejected at a high confidence. An isothermal or inverted spectrum can imply a clear atmosphere with an absorber, a dusty cloud deck or a combination of both. We find that the planet can have continuum of values for the albedo and recirculation, ranging from high albedo and poor recirculation to low albedo and efficient recirculation. Optical spectroscopy of the planet's day-side or thermal emission phase curves can potentially resolve the current albedo with recirculation degeneracy.NN, DKS and TME acknowledge funding from the European Research Council under the European Unions Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 336792. JG acknowledges support from a Leverhulme Trust Research Project Grant. G.W.H. and M.H.W. acknowledge long-term support from Tennessee State University and the State of Tennessee through its Centers of Excellence program and from the Space Telescope Science Institue under HST-GO-14767. This work has been carried out in the frame of the National Centre for Competence in Research PlanetS supported by the Swiss National Science Foundation (SNSF). DE and VB acknowledge the financial support of the SNSF. This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (project FOUR ACES; grant agreement No 724427)

An optical transmission spectrum for the ultra-hot Jupiter WASP-121b measured with the Hubble Space Telescope

This is the author accepted manuscript. The final version is available from American Astronomical Society / IOP Publishing via the DOI in this record.We present an atmospheric transmission spectrum for the ultra-hot Jupiter WASP-121b, measured using the Space Telescope Imaging Spectrograph (STIS) onboard the Hubble Space Telescope (HST). Across the 0.47-1 micron wavelength range, the data imply an atmospheric opacity comparable to - and in some spectroscopic channels exceeding - that previously measured at near-infrared wavelengths (1.15-1.65 micron). Wavelength-dependent variations in the opacity rule out a gray cloud deck at a confidence level of 3.8-sigma and may instead be explained by VO spectral bands. We find a cloud-free model assuming chemical equilibrium for a temperature of 1500K and metal enrichment of 10-30x solar matches these data well. Using a free-chemistry retrieval analysis, we estimate a VO abundance of -6.6(-0.3,+0.2) dex. We find no evidence for TiO and place a 3-sigma upper limit of -7.9 dex on its abundance, suggesting TiO may have condensed from the gas phase at the day-night limb. The opacity rises steeply at the shortest wavelengths, increasing by approximately five pressure scale heights from 0.47 to 0.3 micron in wavelength. If this feature is caused by Rayleigh scattering due to uniformly-distributed aerosols, it would imply an unphysically high temperature of 6810+/-1530K. One alternative explanation for the short-wavelength rise is absorption due to SH (mercapto radical), which has been predicted as an important product of non-equilibrium chemistry in hot Jupiter atmospheres. Irrespective of the identity of the NUV absorber, it likely captures a significant amount of incident stellar radiation at low pressures, thus playing a significant role in the overall energy budget, thermal structure, and circulation of the atmosphere.Support for program GO-14767 was provided by NASA through a grant from the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555. T.M.E., D.K.S., and N.N. acknowledge funding from the European Research Council under the European Unions Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 336792. G.W.H. and M.H.W. acknowledge support from Tennessee State University and the State of Tennessee through its Centers of Excellence program. J.S.F. acknowledges funding by the Spanish MINECO grant AYA2016-79425-C3-2-P. J.K.B. is supported by a Royal Astronomical Society Research Fellowship. This work has been carried out in the frame of the National Centre for Competence in Research PlanetS supported by the Swiss National Science Foundation (SNSF). V.B. and D.E. have received funding from the European Research Council (ERC) under the European Unions Horizon 2020 research and innovation programme (project Four Aces; grant agreement no. 724427)

Adjunctive Volasertib in Patients With Acute Myeloid Leukemia not Eligible for Standard Induction Therapy : A Randomized, Phase 3 Trial

In this phase 3 trial, older patients with acute myeloid leukemia ineligible for intensive chemotherapy were randomized 2:1 to receive the polo-like kinase inhibitor, volasertib (V; 350 mg intravenous on days 1 and 15 in 4-wk cycles), combined with low-dose cytarabine (LDAC; 20 mg subcutaneous, twice daily, days 1-10; n = 444), or LDAC plus placebo (P; n = 222). Primary endpoint was objective response rate (ORR); key secondary endpoint was overall survival (OS). Primary ORR analysis at recruitment completion included patients randomized >= 5 months beforehand; ORR was 25.2% for V+LDAC and 16.8% for P+LDAC (n = 371; odds ratio 1.66 [95% confidence interval (CI), 0.95-2.89]; P = 0.071). At final analysis (>= 574 OS events), median OS was 5.6 months for V+LDAC and 6.5 months for P+LDAC (n = 666; hazard ratio 0.97 [95% CI, 0.8-1.2]; P = 0.757). The most common adverse events (AEs) were infections/infestations (grouped term; V+LDAC, 81.3%; P+LDAC, 63.5%) and febrile neutropenia (V+LDAC, 60.4%; P+LDAC, 29.3%). Fatal AEs occurred in 31.2% with V+LDAC versus 18.0% with P+LDAC, most commonly infections/infestations (V+LDAC, 17.1%; P+LDAC, 6.3%). Lack of OS benefit with V+LDAC versus P+LDAC may reflect increased early mortality with V+LDAC from myelosuppression and infections.Peer reviewe

Novel dynamic outcome indicators and clinical endpoints in myelodysplastic syndrome; the European LeukemiaNet MDS Registry and MDS-RIGHT project perspective

Available evidence suggests that in most patients with LR-MDS the risk of death is not related to disease progression but is mainly attributable to non-leukemic death. 2,17 In addition, a proportion of these patients have prolonged survival that precludes the design of clinical trials adopting OS as a primary endpoint. These challenges have resulted in potentially biased assessment of the effectiveness and appropriate use of the available interventions in this patient population. The EUMDS Registry has identified novel meaningful outcome indicators and clinical endpoints, and reliable measures of response to HCI (Figure 4). The results of our analysis indicate that RBCT density is strongly associated with a decreased OS, even at relatively low dose densities. In addition, we observed that an early decrease in platelet count is an independent adverse prognostic indicator in LR-MDS, and combining relative platelet drop and transfusion dependency allows early identification of patients at risk of rapid progression, and may guide early therapeutic interventions, including allogeneic hematopoietic stem cell transplantation or experimental interventions. Taken together, these results indicate that regular RBCT requirement, early platelet count kinetics, and restriction in HRQoL are early independent and meaningful outcome indicators, and reliable measures of effectiveness of therapeutic interventions, evaluated in this set of studies. These findings support the integration of RBCT requirement and HRQoL in the general core outcome sets and in response criteria in patients with LR-MDS, and have important implications for clinical practice and the design of clinical endpoints. Our results strongly support the adoption of freedom from transfusion as a meaningful clinical endpoint in patients with LR-MDS. Anemia is the main determinant of therapeutic intervention in patients with LR-MDS, and ESA are recommended as first-line treatment for patients with symptomatic anemia. 10 The observational studies within the EUMDS Registry showed that the response rate, as well as the capacity of these agents to delay the onset of a regular RBCT need, is most pronounced in RBCT-naïve patients. These results identified early initiation of treatment with ESA as a major treatment response indicator, and indicate that ESA should be recommended in LR-MDS patients with symptomatic anemia before starting regular RBCT. After the onset of RBCT dependency, patients with LR-MDS are prone to long-term accumulation of iron. 1,43 The EUMDS Registry studies provided evidence that elevated LPI levels are associated with reduced survival in RBCT dependent patients, whereas iron chelation therapy normalizes LPI levels. These findings suggest that NTBI and LPI may serve as early indicators of iron toxicity and a means to measure the effectiveness of iron chelation therapy in patients with LR-MDS. However, qualified NTBI and LPI are only currently available in specialized laboratories. 44 Large observational cohorts with detailed clinical and laboratory data, like the EUMDS cohort, are the ideal framework in which to identify well defined MDS subtypes that may benefit from novel targeted treatments. An example of such a subtype is MDS with loss of parts of chromosome 5, namely del5q; these patients have a relatively favorable outcome on lenalidomide treatment. In order to identify homogeneous subsets of patients within MDS, preliminary evidence has suggested that recently identified mutations in splicing factors may recognize distinct disease entities within myeloid neoplasms. 45 Splicing modulators are now in pre-clinical testing, and are very likely to lead to the introduction of effective drugs for specific groups of MDS patients. Luspatercept, a specific inhibitor of growth and differentiation factor-11, a member of the transforming growth factor β superfamily, induced substantial improvement of anemia, especially in patients with ring sideroblasts. 46 Characterization of individual cases by new genetic markers (one of the main objectives of the MDS-RIGHT project) will allow refined classification of patients into biological subgroups that are expected to respond differently to therapeutic interventions to guide discontinuation of those interventions that are less effective or less cost-effective. The main question is whether RCT data and retrospective cohort data in selected tertiary care centers are representative of the 'real world' data of the older patients with LR-MDS in the general population. A careful comparison of the 'real world' data and the RCT data will be needed in order to provide a clear answer to these questions. Meanwhile, the current analyses of data collected over 10 years in the EUMDS Registry provides relevant and important information which could help assess prognosis and response to standard interventions in this older patient group

Activity coefficients at infinite dilution of volatile compounds in water: effect of temperature and salt concentration

Activity coefficients at infinite dilution in water have been determined for some aroma compounds detected in brown crab liquid effluent produced during boiling (1-octen-3-ol, 1-penten-3-ol, 3-methylbutanal, hexanal, benzaldehyde, 2,3-pentadione, and ethyl acetate) by using the headspace gas chromatography technique (HSGC). Experimental data have been obtained over the temperature range of (40 to 50) °C. In this work, activity coefficients at infinite dilution for different kinds of systems have been considered: one component solute + water and multicomponent solute + water. No significant differences were observed between activity coefficients obtained in these two kinds of systems. Additionally the effect of salt concentration at 40 °C has been studied by varying the salt concentration from (0 to 1.71) mol·kg−1. Experimental data were fitted as a function of salt concentration by using the Setschenow equation, obtaining the salting-out coefficient.MICINN through CTQ2008-04999-PP