Recent advances in the application of stable isotope ratio analysis in forensic chemistry

This review paper updates the previous literature in relation to the continued and developing use of stable isotope ratio analysis in samples which are relevant to forensic science. Recent advances in the analysis of drug samples, explosive materials, and samples derived from human and animal samples are discussed. The paper also aims to put the use of isotope ratio mass spectrometry into a forensic context and discuss its evidential potential

Optical lithography

Optical lithography is a photon-based technique comprised of projecting an image into a photosensitive emulsion (photoresist) coated onto a substrate such as a silicon wafer. It is the most widely used lithography process in the high volume manufacturing of nano-electronics by the semiconductor industry. Optical lithography’s ubiquitous use is a direct result of its highly parallel nature allowing vast amounts of information to be transferred very rapidly. For example, a modern leading edge lithography tool produces 150-300-mm patterned wafers per hour with 40-nm two-dimensional pattern resolution, yielding a pixel throughput of approximately 1.8T pixels/s. Continual advances in optical lithography capabilities have enabled the computing revolution over the past 50 years

The optical counterpart to gamma-ray burst GRB970228 observed using the Hubble Space Telescope

Although more than 2,000 astronomical gamma-ray bursts (GRBs) have been detected, and numerous models proposed to explain their occurrence, they have remained enigmatic owing to the lack of an obvious counterpart at other wavelengths. The recent ground-based detection of a transient source in the vicinity of GRB 970228 may therefore have provided a breakthrough. The optical counterpart appears to be embedded in an extended source which, if a galaxy as has been suggested, would lend weight to those models that place GRBs at cosmological distances. Here we report the observations using the Hubble Space Telescope of the transient counterpart and extended source 26 and 39 days after the initial gamma-ray outburst. We find that the counterpart has faded since the initial detection (and continues to fade), but the extended source exhibits no significant change in brightness between the two dates of observations reported here. The size and apparent constancy between the two epochs of HST observations imply that it is extragalactic, but its faintness makes a definitive statement about its nature difficult. Nevertheless, the decay profile of the transient source is consistent with a popular impulsive-fireball model, which assumes a merger between two neutron stars in a distant galaxy.Comment: 11 pages + 2 figures. To appear in Nature (29 May 1997 issue

Knot Theory: from Fox 3-colorings of links to Yang-Baxter homology and Khovanov homology

This paper is an extended account of my "Introductory Plenary talk at Knots in Hellas 2016" conference We start from the short introduction to Knot Theory from the historical perspective, starting from Heraclas text (the first century AD), mentioning R.Llull (1232-1315), A.Kircher (1602-1680), Leibniz idea of Geometria Situs (1679), and J.B.Listing (student of Gauss) work of 1847. We spend some space on Ralph H. Fox (1913-1973) elementary introduction to diagram colorings (1956). In the second section we describe how Fox work was generalized to distributive colorings (racks and quandles) and eventually in the work of Jones and Turaev to link invariants via Yang-Baxter operators, here the importance of statistical mechanics to topology will be mentioned. Finally we describe recent developments which started with Mikhail Khovanov work on categorification of the Jones polynomial. By analogy to Khovanov homology we build homology of distributive structures (including homology of Fox colorings) and generalize it to homology of Yang-Baxter operators. We speculate, with supporting evidence, on co-cycle invariants of knots coming from Yang-Baxter homology. Here the work of Fenn-Rourke-Sanderson (geometric realization of pre-cubic sets of link diagrams) and Carter-Kamada-Saito (co-cycle invariants of links) will be discussed and expanded. Dedicated to Lou Kauffman for his 70th birthday.Comment: 35 pages, 31 figures, for Knots in Hellas II Proceedings, Springer, part of the series Proceedings in Mathematics & Statistics (PROMS

Beyond Volume: The Impact of Complex Healthcare Data on the Machine Learning Pipeline

From medical charts to national census, healthcare has traditionally operated under a paper-based paradigm. However, the past decade has marked a long and arduous transformation bringing healthcare into the digital age. Ranging from electronic health records, to digitized imaging and laboratory reports, to public health datasets, today, healthcare now generates an incredible amount of digital information. Such a wealth of data presents an exciting opportunity for integrated machine learning solutions to address problems across multiple facets of healthcare practice and administration. Unfortunately, the ability to derive accurate and informative insights requires more than the ability to execute machine learning models. Rather, a deeper understanding of the data on which the models are run is imperative for their success. While a significant effort has been undertaken to develop models able to process the volume of data obtained during the analysis of millions of digitalized patient records, it is important to remember that volume represents only one aspect of the data. In fact, drawing on data from an increasingly diverse set of sources, healthcare data presents an incredibly complex set of attributes that must be accounted for throughout the machine learning pipeline. This chapter focuses on highlighting such challenges, and is broken down into three distinct components, each representing a phase of the pipeline. We begin with attributes of the data accounted for during preprocessing, then move to considerations during model building, and end with challenges to the interpretation of model output. For each component, we present a discussion around data as it relates to the healthcare domain and offer insight into the challenges each may impose on the efficiency of machine learning techniques.Comment: Healthcare Informatics, Machine Learning, Knowledge Discovery: 20 Pages, 1 Figur

Effect of Mouth Rinsing and Ingestion of Carbohydrate Solutions on Mood and Perceptual Responses During Exercise

Background: The aim of this study was to investigate whether mouth rinsing or ingesting carbohydrate (CHO) solutions impact on perceptual responses during exercise. Methods: Nine moderately trained male cyclists underwent a 90-min glycogen-reducing exercise, and consumed a low CHO meal, prior to completing an overnight fast. A 1-h cycle time trial was performed the following morning. Four trials, each separated by 7days, were conducted in a randomized, counterbalanced study design: 15% CHO mouth rinse (CHOR), 7.5% CHO ingestion (CHOI), placebo mouth rinse (PLAR) and placebo ingestion (PLAI). Solution volumes (1.5ml·g-1 ingestion trials and 0.33ml·kg-1 rinsing trials) were provided after every 12.5% of completed exercise. Perceptual scales were used to assess affective valence (feeling scale, FS), arousal (felt arousal scale, FAS), exertion (ratings of perceived exertion, RPE) and mood (profile of mood states, POMS) before, during and immediately after exercise. Results: There was no difference in RPE (CHOI, 14.0±9; CHOR, 14.2±.7; PLAI, 14.6±1.8; PLAR, 14.6±2.0; P=0.35), FS (CHOI, 0.0±1.7; CHOR, -0.2±1.5; PLAI, -0.8±1.4; PLAR, -0.8±1.6; P0.15), or FAS (CHOI, 3.6±1.1; CHOR, 3.5±1.0; PLAI, 3.4±1.4; PLAR, 3.3±1.3; P=725) scores between trials. While overall POMS score did not appear to differ between trials, the 'vigour' subscale indicated that CHOI may facilitate the maintenance of 'vigour' scores over time, in comparison to the steady decline witnessed in other trials (P=0.04). There was no difference in time trial performance between trials (CHOI, 65.3±4.8min; CHOR, 68.4±3.9min; PLAI, 68.7±5.3min; PLAR, 68.3±5.2min; P=0.21) but power output was higher in CHOI (231.0±33.2 W) relative to other trials (221-223.6 W; Plt0.01). Conclusions: In a CHO-reduced state, mouth rinsing with a CHO solution did not impact on perceptual responses during high-intensity exercise in trained cyclists and triathletes. On the other hand CHO ingestion improved perceived ratings of vigour and increased power output during exercise

The nuclear receptors of Biomphalaria glabrata and Lottia gigantea: Implications for developing new model organisms

© 2015 Kaur et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedNuclear receptors (NRs) are transcription regulators involved in an array of diverse physiological functions including key roles in endocrine and metabolic function. The aim of this study was to identify nuclear receptors in the fully sequenced genome of the gastropod snail, Biomphalaria glabrata, intermediate host for Schistosoma mansoni and compare these to known vertebrate NRs, with a view to assessing the snail's potential as a invertebrate model organism for endocrine function, both as a prospective new test organism and to elucidate the fundamental genetic and mechanistic causes of disease. For comparative purposes, the genome of a second gastropod, the owl limpet, Lottia gigantea was also investigated for nuclear receptors. Thirty-nine and thirty-three putative NRs were identified from the B. glabrata and L. gigantea genomes respectively, based on the presence of a conserved DNA-binding domain and/or ligand-binding domain. Nuclear receptor transcript expression was confirmed and sequences were subjected to a comparative phylogenetic analysis, which demonstrated that these molluscs have representatives of all the major NR subfamilies (1-6). Many of the identified NRs are conserved between vertebrates and invertebrates, however differences exist, most notably, the absence of receptors of Group 3C, which includes some of the vertebrate endocrine hormone targets. The mollusc genomes also contain NR homologues that are present in insects and nematodes but not in vertebrates, such as Group 1J (HR48/DAF12/HR96). The identification of many shared receptors between humans and molluscs indicates the potential for molluscs as model organisms; however the absence of several steroid hormone receptors indicates snail endocrine systems are fundamentally different.The National Centre for the Replacement, Refinement and Reduction of Animals in Research, Grant Ref:G0900802 to CSJ, LRN, SJ & EJR [www.nc3rs.org.uk]

Aptamer-based multiplexed proteomic technology for biomarker discovery

Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine

Non-identical smoothing operators for estimating time-frequency interdependence in electrophysiological recordings

Synchronization of neural activity from distant parts of the brain is crucial for the coordination of cognitive activities. Because neural synchronization varies both in time and frequency, time–frequency (T-F) coherence is commonly employed to assess interdependences in electrophysiological recordings. T-F coherence entails smoothing the cross and power spectra to ensure statistical consistency of the estimate, which reduces its T-F resolution. This trade-off has been described in detail when the cross and power spectra are smoothed using identical smoothing operators, which may yield spurious coherent frequencies. In this article, we examine the use of non-identical smoothing operators for the estimation of T-F interdependence, i.e., phase synchronization is characterized by phase locking between signals captured by the cross spectrum and we may hence improve the trade-off by selectively smoothing the auto spectra. We first show that the frequency marginal density of the present estimate is bound within [0,1] when using non-identical smoothing operators. An analytic calculation of the bias and variance of present estimators is performed and compared with the bias and variance of standard T-F coherence using Monte Carlo simulations. We then test the use of non-identical smoothing operators on simulated data, whose T-F properties are known through construction. Finally, we analyze empirical data from eyes-closed surface electroencephalography recorded in human subjects to investigate alpha-band synchronization. These analyses show that selectively smoothing the auto spectra reduces the bias of the estimator and may improve the detection of T-F interdependence in electrophysiological data at high temporal resolution

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition