Characterisation of the mechanobiology of stents in vitro

This paper was presented at the 4th Micro and Nano Flows Conference (MNF2014), which was held at University College, London, UK. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute, ASME Press, LCN London Centre for Nanotechnology, UCL University College London, UCL Engineering, the International NanoScience Community, www.nanopaprika.eu.Long-term efficacy of percutaneous coronary intervention (PCI) to treat coronary heart disease is hampered by incidence of in-stent restenosis (ISR). The regrowth of a healthy endothelial layer post-treatment, a key factor in successful vascular repair, has been shown to be affected by the high sensitivity of endothelial cells (EC) to shear stress. Characterisation of stented artery haemodynamics is required to understand the response of EC to complex flow and shear stress patterns induced by stent structure. A device for the in vitro study of coronary stents has been developed and fabricated in polydimethylsiloxane (PDMS). Balloon-mounted cobalt-chromium stents have been successfully deployed, and particle tracking has been employed to obtain streamlines under low flow rate. High-resolution flow-patterns can be imaged, and complemented with in silico analysis from μCT data. The device allows for the seeding of EC, and sustained exposure to shear stress. EC response can be investigated by comparing real-time footage of cellular migration and proliferation to the haemodynamics of the specific region

Pre-analytical factors affecting whole blood and plasma glucose concentrations in loggerhead sea turtles (Caretta caretta)

Blood glucose is vital for many physiological pathways and can be quantified by clinical chemistry analyzers and in-house point-of-care (POC) devices. Pre-analytical and analytical factors can influence blood glucose measurements. This project aimed to investigate pre-analytical factors on whole blood and plasma glucose measurements in loggerhead sea turtles (Caretta caretta) by evaluating the effects of storage (refrigeration) up to 48h after sampling and of packed cell volume (PCV) on whole blood glucose analysis by POC glucometer (time series n = 13); and by evaluating the effects of storage (room temperature and refrigeration) on plasma glucose concentrations using a dry slide chemistry analyzer (DCA) at various conditions: immediate processing and delayed plasma separation from erythrocytes at 24h and 48h (time series n = 14). The POC glucometer had overall strong agreement with the DCA (CCC = 0.76, r = 0.84, Cb = 0.90), but consistently overestimated glucose concentrations (mean difference: +0.4 mmol/L). The POC glucometer results decreased significantly over time, resulting in a substantial decline within the first 2h (0.41±0.47 mmol/L; 8±9%) that could potentially alter clinical decisions, thereby highlighting the need for immediate analysis using this method. The effects of PCV on glucose could not be assessed, as the statistical significance was associated with one outlier. Storage method significantly affected plasma glucose measurements using DCA, with room temperature samples resulting in rapid decreases of 3.57±0.89 mmol/L (77±9%) over the first 48h, while refrigerated samples provided consistent plasma glucose results over the same time period (decrease of 0.26±0.23 mmol/L; 6±5%). The results from this study provide new insights into optimal blood sample handling and processing for glucose analysis in sea turtles, show the suitability of the POC glucometer as a rapid diagnostic test, and confirm the reliability of plasma glucose measurements using refrigeration. These findings emphasize the need to consider pre-/analytical factors when interpreting blood glucose results from loggerhead sea turtles

Metaphoric coherence: Distinguishing verbal metaphor from `anomaly\u27

Theories and computational models of metaphor comprehension generally circumvent the question of metaphor versus “anomaly” in favor of a treatment of metaphor versus literal language. Making the distinction between metaphoric and “anomalous” expressions is subject to wide variation in judgment, yet humans agree that some potentially metaphoric expressions are much more comprehensible than others. In the context of a program which interprets simple isolated sentences that are potential instances of cross‐modal and other verbal metaphor, I consider some possible coherence criteria which must be satisfied for an expression to be “conceivable” metaphorically. Metaphoric constraints on object nominals are represented as abstracted or extended along with the invariant structural components of the verb meaning in a metaphor. This approach distinguishes what is preserved in metaphoric extension from that which is “violated”, thus referring to both “similarity” and “dissimilarity” views of metaphor. The role and potential limits of represented abstracted properties and constraints is discussed as they relate to the recognition of incoherent semantic combinations and the rejection or adjustment of metaphoric interpretations

The Photoreceptor Cell-Specific Nuclear Receptor Gene (PNR ) Accounts for Retinitis Pigmentosa in the Crypto-Jews from Portugal (Marranos), Survivors from the Spanish Inquisition

The last Crypto-Jews (Marranos) are the survivors of Spanish Jews who were persecuted in the late fifteenth century, escaped to Portugal and were forced to convert to save their lives. Isolated groups still exist in mountainous areas such as Belmonte in the Beira-Baixa province of Portugal. We report here the genetic study of a highly consanguineous endogamic population of Crypto-Jews of Belmonte affected with autosomal recessive retinitis pigmentosa (RP). A genome-wide search for homozygosity allowed us to localize the disease gene to chromosome 15q22-q24 (Zmax=2.95 at θ=0 at the D15S131 locus). Interestingly, the photoreceptor cell-specific nuclear receptor (PNR) gene, the expression of which is restricted to the outer nuclear layer of retinal photoreceptor cells, was found to map to the YAC contig encompassing the disease locus. A search for mutations allowed us to ascribe the RP of Crypto-Jews of Belmonte to a homozygous missense mutation in the PNR gene. Preliminary haplotype studies support the view that this mutation is relatively ancient but probably occurred after the population settled in Belmonte

Non-thermal transport of energy driven by photoexcited carriers in switchable solid states of GeTe

Phase change alloys have seen widespread use from rewritable optical discs to the present day interest in their use in emerging neuromorphic computing architectures. In spite of this enormous commercial interest, the physics of carriers in these materials is still not fully understood. Here, we describe the time and space dependence of the coupling between photoexcited carriers and the lattice in both the amorphous and crystalline states of one phase change material, GeTe. We study this using a time-resolved optical technique called picosecond acoustic method to investigate the \textit{in situ} thermally assisted amorphous to crystalline phase transformation in GeTe. Our work reveals a clear evolution of the electron-phonon coupling during the phase transformation as the spectra of photoexcited acoustic phonons in the amorphous ($a$-GeTe) and crystalline ($\alpha$-GeTe) phases are different. In particular and surprisingly, our analysis of the photoinduced acoustic pulse duration in crystalline GeTe suggests that a part of the energy deposited during the photoexcitation process takes place over a distance that clearly exceeds that defined by the pump light skin depth. In the opposite, the lattice photoexcitation process remains localized within that skin depth in the amorphous state. We then demonstrate that this is due to supersonic diffusion of photoexcited electron-hole plasma in the crystalline state. Consequently these findings prove the existence of a non-thermal transport of energy which is much faster than lattice heat diffusion

Nanoethics, science communication, and a fourth model for public engagement

This paper develops a fourth model of public engagement with science, grounded in the principle of nurturing scientific agency through online participatory bioethics. It argues that social media is an effective device through which to enable such engagement, as it has the capacity to empower users and transforms audiences into co-producers of knowledge, rather than consumers of content, the value of which is recognised within the citizen science movement. Social media also fosters greater engagement with the political and legal implications of science, thus promoting the value of scientific citizenship through the acquisition of science capital. This argument is explored by considering the case of nanoscience and nanotechnology, as an exemplar for how emerging technologies may be handled by the scientific community and science policy makers, and as a technology that has defined a second era of science communication

Rocking Promotes Sleep in Mice through Rhythmic Stimulation of the Vestibular System.

Rocking has long been known to promote sleep in infants and, more recently, also in adults, increasing NREM sleep stage N2 and enhancing EEG slow waves and spindles. Nevertheless, whether rocking also promotes sleep in other species, and what the underlying mechanisms are, has yet to be explored. In the current study, C57BL/6J mice equipped with EEG and EMG electrodes were rocked laterally during their main sleep period, i.e., the 12-h light phase. We observed that rocking affected sleep in mice with a faster optimal rate than in humans (1.0 versus 0.25 Hz). Specifically, rocking mice at 1.0 Hz increased time spent in NREM sleep through the shortening of wake episodes and accelerated sleep onset. Although rocking did not increase EEG activity in the slow-wave and spindle-frequency ranges in mice, EEG theta activity (6-10 Hz) during active wakefulness shifted toward slower frequencies. To test the hypothesis that the rocking effects are mediated through the vestibular system, we used the otoconia-deficient tilted (tlt) mouse, which cannot encode linear acceleration. Mice homozygous for the tlt mutation were insensitive to rocking at 1.0 Hz, while the sleep and EEG response of their heterozygous and wild-type littermates resembled those of C57BL/6J mice. Our findings demonstrate that rocking also promotes sleep in the mouse and that this effect requires input from functional otolithic organs of the vestibule. Our observations also demonstrate that the maximum linear acceleration applied, and not the rocking rate per se, is key in mediating the effects of rocking on sleep

Cone rod dystrophies

Cone rod dystrophies (CRDs) (prevalence 1/40,000) are inherited retinal dystrophies that belong to the group of pigmentary retinopathies. CRDs are characterized by retinal pigment deposits visible on fundus examination, predominantly localized to the macular region. In contrast to typical retinitis pigmentosa (RP), also called the rod cone dystrophies (RCDs) resulting from the primary loss in rod photoreceptors and later followed by the secondary loss in cone photoreceptors, CRDs reflect the opposite sequence of events. CRD is characterized by primary cone involvement, or, sometimes, by concomitant loss of both cones and rods that explains the predominant symptoms of CRDs: decreased visual acuity, color vision defects, photoaversion and decreased sensitivity in the central visual field, later followed by progressive loss in peripheral vision and night blindness. The clinical course of CRDs is generally more severe and rapid than that of RCDs, leading to earlier legal blindness and disability. At end stage, however, CRDs do not differ from RCDs. CRDs are most frequently non syndromic, but they may also be part of several syndromes, such as Bardet Biedl syndrome and Spinocerebellar Ataxia Type 7 (SCA7). Non syndromic CRDs are genetically heterogeneous (ten cloned genes and three loci have been identified so far). The four major causative genes involved in the pathogenesis of CRDs are ABCA4 (which causes Stargardt disease and also 30 to 60% of autosomal recessive CRDs), CRX and GUCY2D (which are responsible for many reported cases of autosomal dominant CRDs), and RPGR (which causes about 2/3 of X-linked RP and also an undetermined percentage of X-linked CRDs). It is likely that highly deleterious mutations in genes that otherwise cause RP or macular dystrophy may also lead to CRDs. The diagnosis of CRDs is based on clinical history, fundus examination and electroretinogram. Molecular diagnosis can be made for some genes, genetic counseling is always advised. Currently, there is no therapy that stops the evolution of the disease or restores the vision, and the visual prognosis is poor. Management aims at slowing down the degenerative process, treating the complications and helping patients to cope with the social and psychological impact of blindness