Terahertz underdamped vibrational motion governs protein-ligand binding in solution

Low-frequency collective vibrational modes in proteins have been proposed as being responsible for efficiently directing biochemical reactions and biological energy transport. However, evidence of the existence of delocalized vibrational modes is scarce and proof of their involvement in biological function absent. Here we apply extremely sensitive femtosecond optical Kerr-effect spectroscopy to study the depolarized Raman spectra of lysozyme and its complex with the inhibitor triacetylchitotriose in solution. Underdamped delocalized vibrational modes in the terahertz frequency domain are identified and shown to blue-shift and strengthen upon inhibitor binding. This demonstrates that the ligand-binding coordinate in proteins is underdamped and not simply solvent-controlled as previously assumed. The presence of such underdamped delocalized modes in proteins may have significant implications for the understanding of the efficiency of ligand binding and protein–molecule interactions, and has wider implications for biochemical reactivity and biological function

Comments on black holes I: The possibility of complementarity

We comment on a recent paper of Almheiri, Marolf, Polchinski and Sully who argue against black hole complementarity based on the claim that an infalling observer 'burns' as he approaches the horizon. We show that in fact measurements made by an infalling observer outside the horizon are statistically identical for the cases of vacuum at the horizon and radiation emerging from a stretched horizon. This forces us to follow the dynamics all the way to the horizon, where we need to know the details of Planck scale physics. We note that in string theory the fuzzball structure of microstates does not give any place to 'continue through' this Planck regime. AMPS argue that interactions near the horizon preclude traditional complementarity. But the conjecture of 'fuzzball complementarity' works in the opposite way: the infalling quantum is absorbed by the fuzzball surface, and it is the resulting dynamics that is conjectured to admit a complementary description.Comment: 34 pages, 6 figures, v3: clarifications & references adde

Radiosynthesis of the anticancer nucleoside analogue Trifluridine using an automated 18F-trifluoromethylation procedure.

Trifluoromethyl groups are widespread in medicinal chemistry, yet there are limited 18F-radiochemistry techniques available for the production of the complementary PET agents. Herein, we report the first radiosynthesis of the anticancer nucleoside analogue trifluridine, using a fully automated, clinically-applicable 18F-trifluoromethylation procedure. [18F]Trifluridine was obtained after two synthetic steps in 99%, and a molar activity of 0.4 GBq μmol-1 ± 0.05. Biodistribution and PET-imaging data using HCT116 tumour-bearing mice showed a 2.5 %ID g-1 tumour uptake of [18F]trifluridine at 60 minutes post-injection, with bone uptake becoming a prominent feature thereafter. In vivo metabolite analysis of selected tissues revealed the presence of the original radiolabelled nucleoside analogue, together with deglycosylated and phosphorylated [18F]trifluridine as the main metabolites. Our findings suggest a potential role for [18F]trifluridine as a PET radiotracer for elucidation of drug mechanism of action

Application of Graphene within Optoelectronic Devices and Transistors

Scientists are always yearning for new and exciting ways to unlock graphene's true potential. However, recent reports suggest this two-dimensional material may harbor some unique properties, making it a viable candidate for use in optoelectronic and semiconducting devices. Whereas on one hand, graphene is highly transparent due to its atomic thickness, the material does exhibit a strong interaction with photons. This has clear advantages over existing materials used in photonic devices such as Indium-based compounds. Moreover, the material can be used to 'trap' light and alter the incident wavelength, forming the basis of the plasmonic devices. We also highlight upon graphene's nonlinear optical response to an applied electric field, and the phenomenon of saturable absorption. Within the context of logical devices, graphene has no discernible band-gap. Therefore, generating one will be of utmost importance. Amongst many others, some existing methods to open this band-gap include chemical doping, deformation of the honeycomb structure, or the use of carbon nanotubes (CNTs). We shall also discuss various designs of transistors, including those which incorporate CNTs, and others which exploit the idea of quantum tunneling. A key advantage of the CNT transistor is that ballistic transport occurs throughout the CNT channel, with short channel effects being minimized. We shall also discuss recent developments of the graphene tunneling transistor, with emphasis being placed upon its operational mechanism. Finally, we provide perspective for incorporating graphene within high frequency devices, which do not require a pre-defined band-gap.Comment: Due to be published in "Current Topics in Applied Spectroscopy and the Science of Nanomaterials" - Springer (Fall 2014). (17 pages, 19 figures

Cancer incidence among the south Asian and non-south Asian population under 30 years of age in Yorkshire, UK.

Few studies have examined epidemiological differences between ethnic groups for children and young adults with cancer

The Population Structure of Acinetobacter baumannii: Expanding Multiresistant Clones from an Ancestral Susceptible Genetic Pool

Outbreaks of hospital infections caused by multidrug resistant Acinetobacter baumannii strains are of increasing concern worldwide. Although it has been reported that particular outbreak strains are geographically widespread, little is known about the diversity and phylogenetic relatedness of A. baumannii clonal groups. Sequencing of internal portions of seven housekeeping genes (total 2,976 nt) was performed in 154 A. baumannii strains covering the breadth of known diversity and including representatives of previously recognized international clones, and in 19 representatives of other Acinetobacter species. Restricted amounts of diversity and a star-like phylogeny reveal that A. baumannii is a genetically compact species that suffered a severe bottleneck in the recent past, possibly linked to a restricted ecological niche. A. baumannii is neatly demarcated from its closest relative (genomic species 13TU) and other Acinetobacter species. Multilocus sequence typing analysis demonstrated that the previously recognized international clones I to III correspond to three clonal complexes, each made of a central, predominant genotype and few single locus variants, a hallmark of recent clonal expansion. Whereas antimicrobial resistance was almost universal among isolates of these and a novel international clone (ST15), isolates of the other genotypes were mostly susceptible. This dichotomy indicates that antimicrobial resistance is a major selective advantage that drives the ongoing rapid clonal expansion of these highly problematic agents of nosocomial infections

Barriers to identifying eating disorders in pregnancy and in the postnatal period: a qualitative approach.

BACKGROUND: Eating Disorders (ED) are mental health disorders that typically effect women of childbearing age and are associated with adverse maternal and infant outcomes. UK healthcare guidance recommends routine enquiry for current and past mental illness in antenatal and postnatal care for all women, and that pregnant women with a known ED are offered enhanced monitoring and support. Midwives and health visitors are ideally placed to identify and support women with ED as they are often the primary point of contact during the antenatal and postnatal periods. However, research on the barriers to identifying ED in the perinatal period is limited. This study aimed to understand the barriers to disclosure and identification of ED in pregnancy and postnatally as perceived by women with past or current ED, and midwives and health visitors working in the UK National Health Service. METHODS: Two studies were undertaken: mixed-measures survey of pregnant and postnatal women with current or past ED; focus groups with student and qualified midwives and health visitors. RESULTS: Five themes emerged on the barriers to disclosure in pregnancy as perceived by women: stigma, lack of opportunity, preference for self-management, current ED symptomatology and illness awareness. Four themes were identified on the barriers to identification of ED in pregnancy and in the postnatal period as perceived by health professionals: system constraints, recognition of role, personal attitudes, and stigma and taboo. CONCLUSIONS: Several barriers to the identification of ED during and after pregnancy were described, the main factors were stigma and poor professional training. Perinatal mental health is becoming increasingly prioritised within national policy initiatives; however, ED continue to be neglected and increased awareness is needed. Similarly, clinical guidance aimed at responding to the rising prevalence of obesity focus on changing nutrition but not on assessing for the presence of ED behaviours that might be affecting nutrition. Improving education and training for health professionals may contribute to reducing stigma and increase confidence in identifying ED. The barriers identified in this research need to be addressed if recognition and response to women with ED during the perinatal period is to improve