Insights into dietary flavonoids as molecular templates for the design of anti-platelet drugs

Flavonoids are low-molecular weight, aromatic compounds derived from fruits, vegetables, and other plant components. The consumption of these phytochemicals has been reported to be associated with reduced cardiovascular disease (CVD) risk, attributed to their anti-inflammatory, anti-proliferative, and anti-thrombotic actions. Flavonoids exert these effects by a number of mechanisms which include attenuation of kinase activity mediated at the cell-receptor level and/or within cells, and are characterized as broad-spectrum kinase inhibitors. Therefore, flavonoid therapy for CVD is potentially complex; the use of these compounds as molecular templates for the design of selective and potent small-molecule inhibitors may be a simpler approach to treat this condition. Flavonoids as templates for drug design are, however, poorly exploited despite the development of analogues based on the flavonol, isoflavonone, and isoflavanone subgroups. Further exploitation of this family of compounds is warranted due to a structural diversity that presents great scope for creating novel kinase inhibitors. The use of computational methodologies to define the flavonoid pharmacophore together with biological investigations of their effects on kinase activity, in appropriate cellular systems, is the current approach to characterize key structural features that will inform drug design. This focussed review highlights the potential of flavonoids to guide the design of clinically safer, more selective, and potent small-molecule inhibitors of cell signalling, applicable to anti-platelet therapy.

The national food safety control system of China: a systematic review

In recent years, there have been increasing concerns over the safety of the Chinese food supply. Although many of these have only raised concern internally within China, several major food safety issues have had international repercussions. In response, China has implemented new food safety laws and management systems to improve its national food safety control system and reduce public and international concerns. This paper has describes and discusses the components of the Chinese system using the five key elements of a national food control system identified by the World Health Organization (WHO) and the Food and Agriculture Organization (FAO) as essential for an effective system. The latest Chinese national food safety control has made significantly improvement on its regulation framework, however, more work need to be done on standards, law enforcement, and information exchange.

Fine-grained multi-phase array designs

Hybrid multiprocessor architectures which combine re-configurable computing and multiprocessors on a chip are being proposed to transcend the performance of standard multi-core parallel systems. Both fine-grained and coarse-grained parallel algorithm implementations are feasible in such hybrid frameworks. A compositional strategy for designing fine-grained multi-phase regular processor arrays to target hybrid architectures is presented in this paper. The method is based on deriving component designs using classical regular array techniques and composing the components into a unified global design. Effective designs with phase-changes and data routing at run-time are characteristics of these designs. In order to describe the data transfer between phases, the concept of communication domain is introduced so that the producer–consumer relationship arising from multi-phase computation can be treated in a unified way as a data routing phase. This technique is applied to derive new designs of multi-phase regular arrays with different dataflow between phases of computation.

Social approach in preschool children with Williams syndrome: the role of the face

Background Indiscriminate social approach behaviour is a salient aspect of the Williams syndrome (WS) behavioural phenotype. The present study examines approach behaviour in preschoolers with WS and evaluates the role of the face in WS social approach behaviour. Method Ten preschoolers with WS (aged 3-6 years) and two groups of typically developing children, matched to the WS group on chronological or mental age, participated in an observed play session. The play session incorporated social and non-social components including two components that assessed approach behaviour towards strangers, one in which the stranger’s face could be seen and one in which the stranger’s face was covered. Results In response to the non-social aspects of the play session, the WS group behaved similarly to both control groups. In contrast, the preschoolers with WS were significantly more willing than either control group to engage with a stranger, even when the stranger’s face could not be seen. Conclusion The findings challenge the hypothesis that an unusual attraction to the face directly motivates social approach behaviour in individuals with WS.

Crystal design approaches for the synthesis of paracetamol co-crystals

Crystal engineering principles were used to design three new co-crystals of paracetamol. A variety of potential cocrystal formers were initially identified from a search of the Cambridge Structural Database for molecules with complementary hydrogen-bond forming functionalities. Subsequent screening by powder X-ray diffraction of the products of the reaction of this library of molecules with paracetamol led to the discovery of new binary crystalline phases of paracetamol with trans-1,4- diaminocyclohexane (1); trans-1,4-di(4-pyridyl)ethylene (2); and 1,2-bis(4-pyridyl)ethane (3). The co-crystals were characterized by IR spectroscopy, differential scanning calorimetry, and 1H NMR spectroscopy. Single crystal X-ray structure analysis reveals that in all three co-crystals the co-crystal formers (CCF) are hydrogen bonded to the paracetamol molecules through O−H···N interactions. In co-crystals (1) and (2) the CCFs are interleaved between the chains of paracetamol molecules, while in co-crystal (3) there is an additional N−H···N hydrogen bond between the two components. A hierarchy of hydrogen bond formation is observed in which the best donor in the system, the phenolic O−H group of paracetamol, is preferentially hydrogen bonded to the best acceptor, the basic nitrogen atom of the co-crystal former. The geometric aspects of the hydrogen bonds in co-crystals 1−3 are discussed in terms of their electrostatic and charge-transfer components.

Periodic auroral events at the high-latitude convection reversal in the 16 MLT region

Combined optical and radar observations of two breakup-like auroral events near the polar cap boundary, within 74–76° MLAT and 1210 – 1240 UT (roughly 1540 – 1610 MLT) on 9 Jan. 1989 are reported. A two-component structure of the auroral phenomenon is indicated, with a local intensification of the pre-existing arc as well as a separate, tailward moving discrete auroral event on the poleward side of the background aurora, close to the reversal between well-defined zones of sunward and tailward ion flows. The all-sky TV observations do not indicate a connection between the two components, which also show different optical spectral composition. The 16 MLT background arc is located on sunward convecting field lines, as opposed to the 12–14 MLT auroral emission observed on this day. Although the magnetospheric plasma source (s) of the 16 MLT events are not easily identified from these ground-based data alone, it is suggested that the lower and higher latitude components, may map to the plasma sheet boundary layer and along open field lines to the magnetopause boundary, respectively. The events occur at the time of enhancements of westward ionospheric ion flow and corresponding eastward electrojet current south of 74° MLAT. Thus, they seem to be very significant events, involving periodic (10 min period), tailward moving filaments of field-aligned current/discrete auroral emission at the 16 MLT polar cap boundary.

The emergence of integrated private reporting

Purpose: Private social and environmental reporting (SER) has grown considerably in recent years, consistent with a rise in institutional investor engagement and dialogue with investee companies. We interpret the emergence of integrated private reporting through the lens of institutional logics. We frame the emergence of integrated private reporting as a merging of two hitherto separate and possibly rival institutional logics. Methodology/Approach: We interviewed 19 companies listed on the FTSE100 and 20 UK institutional investors. The interviews were semi-structured and analysed in an interpretive fashion. Findings and Implications: We provide evidence to suggest that private SER is beginning to merge with private financial reporting and that, as a result integrated private reporting is emerging. This trend is mirroring the international trend in public reporting toward an integrated approach. Specifically, we find that specialist social responsible investment managers are starting to attend private financial reporting meetings whilst mainstream fund managers are starting to attend private meetings on environmental, social and governance (ESG) issues. Further, senior company directors are becoming increasingly conversant with ESG issues. We interpret our findings as two possible scenarios: (i) there is a genuine hybridisation occurring in UK institutional investment such that integrated private reporting is emerging, or; (ii) the financial logic is absorbing and effectively neutralising the responsible investment logic. Originality: This is the first research investigating the evolution of private integrated reporting.

The effects of explicit versus parameterized convection on the MJO in a large-domain high-resolution tropical case study. Part II: Processes leading to differences in MJO development

High-resolution simulations over a large tropical domain (∼20◦S–20◦N and 42◦E–180◦E) using both explicit and parameterized convection are analyzed and compared during a 10-day case study of an active Madden-Julian Oscillation (MJO) event. In Part II, the moisture budgets and moist entropy budgets are analyzed. Vertical subgrid diabatic heating profiles and vertical velocity profiles are also compared; these are related to the horizontal and vertical advective components of the moist entropy budget which contribute to gross moist stability, GMS, and normalized GMS (NGMS). The 4-km model with explicit convection and good MJO performance has a vertical heating structure that increases with height in the lower troposphere in regions of strong convection (like observations), whereas the 12-km model with parameterized convection and a poor MJO does not show this relationship. The 4-km explicit convection model also has a more top-heavy heating profile for the troposphere as a whole near and to the west of the active MJO-related convection, unlike the 12-km parameterized convection model. The dependence of entropy advection components on moisture convergence is fairly weak in all models, and differences between models are not always related to MJO performance, making comparisons to previous work somewhat inconclusive. However, models with relatively good MJO strength and propagation have a slightly larger increase of the vertical advective component with increasing moisture convergence, and their NGMS vertical terms have more variability in time and longitude, with total NGMS that is comparatively larger to the west and smaller to the east.

Should healthy eating programmes incorporate interaction with foods in different sensory modalities? A review of the evidence

Commercial interventions seeking to promote fruit and vegetable consumption by encouraging preschool- and school-aged children to engage with foods with ‘all their senses’ are increasing in number. We review the efficacy of such sensory interaction programmes and consider the components of these that are likely to encourage food acceptance. Repeated exposure to a food's flavour has robust empirical support in terms of its potential to increase food intake. However, children are naturally reluctant to taste new or disliked foods, and parents often struggle to provide sufficient taste opportunities for these foods to be adopted into the child's diet. We therefore explore whether prior exposure to a new food's non-taste sensory properties, such as its smell, sound, appearance or texture, might facilitate the food's introduction into the child's diet, by providing the child with an opportunity to become partially familiar with the food without invoking the distress associated with tasting it. We review the literature pertaining to the benefits associated with exposure to foods through each of the five sensory modalities in turn. We conclude by calling for further research into the potential for familiarisation with the visual, olfactory, somaesthetic and auditory properties of foods to enhance children's willingness to consume a variety of fruits and vegetables.