Thermal and pressure stability of myrosinase enzymes from black mustard (Brassica nigra L. W.D.J Koch. var. nigra), brown mustard (Brassica juncea L. Czern. var. juncea) and yellow mustard (Sinapsis alba L. Subsp Maire) seeds

This study investigates the effects of temperature and pressure on inactivation of myrosinase extracted from black, brown and yellow mustard seeds. Brown mustard had higher myrosinase activity (2.75 un/mL) than black (1.50 un/mL) and yellow mustard (0.63 un/mL). The extent of enzyme inactivation increased with pressure (600-800 MPa) and temperature (30-70 °C) for all the mustard seeds. However, at combinations of lower pressures (200-400 MPa) and high temperatures (60-80 °C), there was less inactivation. For example, application of 300 MPa and 70 °C for 10 minutes retained 20%, 80% and 65% activity in yellow, black and brown mustard, respectively, whereas the corresponding activity retentions when applying only heat (70 °C, 10min) were 0%, 59% and 35%. Thus, application of moderate pressures (200-400 MPa) can potentially be used to retain myrosinase activity needed for subsequent glucosinolate hydrolysis.

Ibrutinib inhibits platelet integrin αIIbβ3 outside-in signaling and thrombus stability but not adhesion to collagen

OBJECTIVE: Ibrutinib is an irreversible Bruton tyrosine kinase inhibitor approved for treatment of Waldenstrom macroglobulinemia, chronic lymphocytic leukemia, and mantle cell lymphoma that increases the risk of bleeding among patients. Platelets from ibrutinib-treated patients exhibit deficiencies in collagen-evoked signaling in suspension; however, the significance of this observation and how it relates to bleeding risk is unclear, as platelets encounter immobile collagen in vivo. We sought to clarify the effects of ibrutinib on platelet function to better understand the mechanism underlying bleeding risk. APPROACH AND RESULTS: By comparing signaling in suspension and during adhesion to immobilized ligands, we found that the collagen signaling deficiency caused by ibrutinib is milder during adhesion to immobilized collagen. We also found that platelets in whole blood treated with ibrutinib adhered to collagen under arterial shear but formed unstable thrombi, suggesting that the collagen signaling deficiency caused by ibrutinib may not be the predominant cause of bleeding in vivo. However, clot retraction and signaling evoked by platelet adhesion to immobilized fibrinogen were also inhibited by ibrutinib, indicating that integrin αIIbβ3 outside-in signaling is also effected in addition to GPVI signaling. When ibrutinib was combined with the P2Y12 inhibitor, cangrelor, thrombus formation under arterial shear was inhibited additively. CONCLUSIONS: These findings suggest that (1) ibrutinib causes GPVI and integrin αIIbβ3 platelet signaling deficiencies that result in formation of unstable thrombi and may contribute toward bleeding observed in vivo and (2) combining ibrutinib with P2Y12 antagonists, which also inhibit thrombus stability, may have a detrimental effect on hemostasis.

Stereochemistry and thermal stability of tartaric acid on the intrinsically chiral Cu{531} surface

Intrinsically chiral metal surfaces provide enantiospecific reaction environments without the need of coadsorbed modifiers. Amongst the intrinsically chiral copper surfaces, Cu{531} has the smallest unit cell and the highest density of chiral sites. XPS, NEXAFS and TPD were employed to investigate the adsorption and decomposition behaviour of the two chiral enantiomers of tartaric acid on this surface. The results obtained from XPS and NEXAFS show that at saturation coverage both enantiomers of tartaric acid adsorb in a μ4 configuration through the two carboxylic groups,which are rotatedwith respect to each other by 90°±≈15°within the surface plane. At intermediate coverage the R,R enantiomer adopts a similar configuration, but the S,S enantiomer is different and shows a high degree of dissociation. Growth of multilayers is observed at high exposures when the sample is kept at below 370 K. TPD experiments show that multilayers desorb between 390 K and 470 K and decomposition of the chemisorbed layer occurs between 470 K and 600 K. The desorption spectra support a two-step decomposition mechanism with a O_C_C_O or HO–HC_CH–OH intermediate that leads to production of CO2 and CO. Enantiomeric differences are observed in the desorption features related to the decomposition of the chemisorbed layer.

Enhanced long-range forecast skill in boreal winter following stratospheric strong vortex conditions

There has been a great deal of recent interest in producing weather forecasts on the 2–6 week sub-seasonal timescale, which bridges the gap between medium-range (0–10 day) and seasonal (3–6 month) forecasts. While much of this interest is focused on the potential applications of skilful forecasts on the sub-seasonal range, understanding the potential sources of sub-seasonal forecast skill is a challenging and interesting problem, particularly because of the likely state-dependence of this skill (Hudson et al 2011). One such potential source of state-dependent skill for the Northern Hemisphere in winter is the occurrence of stratospheric sudden warming (SSW) events (Sigmond et al 2013). Here we show, by analysing a set of sub-seasonal hindcasts, that there is enhanced predictability of surface circulation not only when the stratospheric vortex is anomalously weak following SSWs but also when the vortex is extremely strong. Sub-seasonal forecasts initialized during strong vortex events are able to successfully capture the associated surface temperature and circulation anomalies. This results in an enhancement of Northern annular mode forecast skill compared to forecasts initialized during the cases when the stratospheric state is close to climatology. We demonstrate that the enhancement of skill for forecasts initialized during periods of strong vortex conditions is comparable to that achieved for forecasts initialized during weak events. This result indicates that additional confidence can be placed in sub-seasonal forecasts when the stratospheric polar vortex is significantly disturbed from its normal state.

New insights into the compressibility and high-pressure stability of Ni(CN)2: a combined study of neutron diffraction, Raman spectroscopy, and inelastic neutron scattering

Nickel cyanide is a layered material showing markedly anisotropic behaviour. High-pressure neutron diffraction measurements show that at pressures up to 20.1 kbar, compressibility is much higher in the direction perpendicular to the layers, c, than in the plane of the strongly chemically bonded metal-cyanide sheets. Detailed examination of the behaviour of the tetragonal lattice parameters, a and c, as a function of pressure reveal regions in which large changes in slope occur, for example, in c(P) at 1 kbar. The experimental pressure dependence of the volume data is fitted to a bulk modulus, B0, of 1050 (20) kbar over the pressure range 0–1 kbar, and to 124 (2) kbar over the range 1–20.1 kbar. Raman spectroscopy measurements yield additional information on how the structure and bonding in the Ni(CN)2 layers change with pressure and show that a phase change occurs at about 1 kbar. The new high-pressure phase, (Phase PII), has ordered cyanide groups with sheets of D4h symmetry containing Ni(CN)4 and Ni(NC)4 groups. The Raman spectrum of phase PII closely resembles that of the related layered compound, Cu1/2Ni1/2(CN)2, which has previously been shown to contain ordered C≡N groups. The phase change, PI to PII, is also observed in inelastic neutron scattering studies which show significant changes occurring in the phonon spectra as the pressure is raised from 0.3 to 1.5 kbar. These changes reflect the large reduction in the interlayer spacing which occurs as Phase PI transforms to Phase PII and the consequent increase in difficulty for out-of-plane atomic motions. Unlike other cyanide materials e.g. Zn(CN)2 and Ag3Co(CN)6, which show an amorphization and/or a decomposition at much lower pressures (~100 kbar), Ni(CN)2 can be recovered after pressurising to 200 kbar, albeit in a more ordered form.

Scale interactions between the MJO and the western maritime continent

State-of-the-art regional climate model simulations that are able to resolve key mesoscale circulations are used, for the first time, to understand the interaction between the large-scale convective environment of the MJO and processes governing the strong diurnal cycle over the islands of the Maritime Continent (MC). Convection is sustained in the late afternoon just inland of the coasts due to sea breeze convergence. Previous work has shown that the variability in MC rainfall associated with the MJO is manifested in changes to this diurnal cycle; land-based rainfall peaks before the active convective envelope of the MJO reaches the MC, whereas oceanic rainfall rates peak whilst the active envelope resides over the region. The model simulations show that the main controls on oceanic MC rainfall in the early active MJO phases are the large-scale environment and atmospheric stability, followed by high oceanic latent heat flux forced by high near-surface winds in the later active MJO phases. Over land, rainfall peaks before the main convective envelope arrives (in agreement with observations), even though the large-scale convective environment is only moderately favourable for convection. The causes of this early rainfall peak are convective triggers from land-sea breeze circulations that are strong due to high surface insolation and surface heating. During the peak MJO phases cloud cover increases and surface insolation decreases, which weakens the strength of the mesoscale circulations and reduces land-based rainfall, even though the large-scale environment remains favourable for convection at this time. Hence, scale interactions are an essential part of the MJO transition across the MC.

Effective interaction between monolayers of block copolymer compatiblizer in a polymer blend

The stability of ternary blends of two immiscible homopolymers and a block copolymer compatiblizer depends crucially on the effective interaction between the copolymermonolayers that form between the unlike homopolymer domains. Here, the interaction is calculated for blends involving A and B homopolymers of equal size with ABABdiblock copolymers of symmetric composition using both self-consistent field theory (SCFT) and strong-segregation theory (SST). If the homopolymers are larger than the copolymer molecules, an attractive interaction is predicted which would destroy the blend. This conclusion coupled with considerations regarding the elastic properties of the monolayer suggests that the optimum size of the homopolymer molecules is about 80% that of the copolymer molecule. A detailed examination of the theory demonstrates that the attraction results from the configurational entropy loss of the homopolymer molecules trapped between the copolymermonolayers. We conclude by suggesting how the monolayers can be altered in order to suppress this attraction and thus improve compatiblization.

Peptide based hydrogels for cancer drug release: modulation of stiffness, drug release and proteolytic stability of hydrogels by incorporating D-amino acid residue(s)

Synthetic tripeptide based noncytotoxic hydrogelators have been discovered for releasing an anticancer drug at physiological pH and temparature. Interestingly, gel stiffness, drug release capacity and proteolytic stability of these hydrogels have been successfully modulated by incorporating D-amino acid residues, indicating their potential use for drug delivery in the future.