Assessment of breath volatile organic compounds in acute cardiorespiratory breathlessness: a protocol describing a prospective real-world observational study

Introduction Patients presenting with acute undifferentiated breathlessness are commonly encountered in admissions units across the UK. Existing blood biomarkers have clinical utility in distinguishing patients with single organ pathologies but have poor discriminatory power in multifactorial presentations. Evaluation of volatile organic compounds (VOCs) in exhaled breath offers the potential to develop biomarkers of disease states that underpin acute cardiorespiratory breathlessness, owing to their proximity to the cardiorespiratory system. To date, there has been no systematic evaluation of VOC in acute cardiorespiratory breathlessness. The proposed study will seek to use both offline and online VOC technologies to evaluate the predictive value of VOC in identifying common conditions that present with acute cardiorespiratory breathlessness. Methods and analysis A prospective real-world observational study carried out across three acute admissions units within Leicestershire. Participants with self-reported acute breathlessness, with a confirmed primary diagnosis of either acute heart failure, community-acquired pneumonia and acute exacerbation of asthma or chronic obstructive pulmonary disease will be recruited within 24 hours of admission. Additionally, school-age children admitted with severe asthma will be evaluated. All participants will undergo breath sampling on admission and on recovery following discharge. A range of online technologies including: proton transfer reaction mass spectrometry, gas chromatography ion mobility spectrometry, atmospheric pressure chemical ionisation-mass spectrometry and offline technologies including gas chromatography mass spectroscopy and comprehensive two-dimensional gas chromatography-mass spectrometry will be used for VOC discovery and replication. For offline technologies, a standardised CE-marked breath sampling device (ReCIVA) will be used. All recruited participants will be characterised using existing blood biomarkers including C reactive protein, brain-derived natriuretic peptide, troponin-I and blood eosinophil levels and further evaluated using a range of standardised questionnaires, lung function testing, sputum cell counts and other diagnostic tests pertinent to acute disease. Ethics and dissemination The National Research Ethics Service Committee East Midlands has approved the study protocol (REC number: 16/LO/1747). Integrated Research Approval System (IRAS) 198921. Findings will be presented at academic conferences and published in peer-reviewed scientific journals. Dissemination will be facilitated via a partnership with the East Midlands Academic Health Sciences Network and via interaction with all UK-funded Medical Research Council and Engineering and Physical Sciences Research Council molecular pathology nodes. Trial registration number NCT0367299

Two Methods of analyse DNA sequences: Predicting coding regions and Clustering homologous DNA

With the exponential growth of DNA sequences in the past twenty years, it has became ineffective to analyze DNA sequences only through the traditional biological experiments. Various mathematical methods and computer algorithms are applied to sequence analyses and related research areas, which help the biological study to be upgraded into automatic programming from manual operation. Especially, there are two important research areas to study DNA sequences in bioinformatics. One is to predict the coding regions on DNA sequences, another is to determine the evolutionary relationship based on DNA sequences. In this thesis, two mathematical methods are introduced to show our achievements in these two research areas respectively. In chapter two, we introduce a simple parameter called TICOR (Threshold to Identify Coding Region) to distinguish the coding regions from non-coding regions. The method only takes the linear computation time which is much better than those of Fourier Transform and other methods. Moreover, we are able to estimate the proportion of coding regions to the length of the whole DNA sequence simply basing on the parameter TICOR. Finally, we develop a novel method to predict the coding regions from DNA sequences, which we call TICORSCAN. We do the test on the ROSETTA dataset with our TICORSCAN method and other popular method, such as GENSCAN and TWINSCAN. The prediction accuracy shows that our TICORSCAN method is able to predict the coding regions more efficiently. Secondly, we report a novel mathematical method to transform the DNA sequences into the distribution vectors in chapter three. The distribution vectors correspond to points in the sixty dimensional Euclidean space. Each component of the distribution vectors represents the distribution of one kind of nucleotide in k segments of the DNA sequence. The statistical properties of the distribution vectors are demonstrated and examined with huge datasets of human DNA sequences and random sequences. The determined expectation and standard deviation can make the mapping stable and practicable. Moreover, we apply the distribution vectors to the clustering of the mitochondrial complete genomes from 80 placental mammals and the gene Haemagglutinin (HA) of 60 H1N1 viruses from Human, Swine and Avian. The 80 mammals and 60 H1N1 viruses are classified accurately and rapidly compared to the multiple sequence alignment methods. The results indicate that the distribution vectors can reveal the similarity and evolutionary relationship among homologous DNA sequences based on the distances between any two of these distribution vectors. The advantage of fast computation offers the distribution vectors the opportunity to deal with the huge amount of DNA sequences efficiently

Supplemental Material, Online_appendice_accepted - From Urban Core to Wealthy Towns: Nonschool Fiscal Disparities across Municipalities

<p>Supplemental Material, Online_appendice_accepted for From Urban Core to Wealthy Towns: Nonschool Fiscal Disparities across Municipalities by Bo Zhao in Public Finance Review</p

Supplemental Material, PFR_Online_Appendix_Tables_accepted - From Urban Core to Wealthy Towns: Nonschool Fiscal Disparities across Municipalities

<p>Supplemental Material, PFR_Online_Appendix_Tables_accepted for From Urban Core to Wealthy Towns: Nonschool Fiscal Disparities across Municipalities by Bo Zhao in Public Finance Review</p

Measuring Residual Dipolar Couplings in Excited Conformational States of Nucleic Acids by CEST NMR Spectroscopy

Nucleic acids undergo structural transitions to access sparsely populated and transiently lived conformational statesor excited conformational statesthat play important roles in diverse biological processes. Despite ever-increasing detection of these functionally essential states, 3D structure determination of excited states (ESs) of RNA remains elusive. This is largely due to challenges in obtaining high-resolution structural constraints in these ESs by conventional structural biology approaches. Here, we present nucleic-acid-optimized chemical exchange saturation transfer (CEST) NMR spectroscopy for measuring residual dipolar couplings (RDCs), which provide unique long-range angular constraints in ESs of nucleic acids. We demonstrate these approaches on a fluoride riboswitch, where one-bond ¹³C-¹H RDCs from both base and sugar moieties provide direct structural probes into an ES of the ligand-free riboswitch

Strong Plasmonic Coupling between Graphene Ribbon Array and Metal Gratings

The collective oscillation of the massless electrons in graphene ribbons can interact with photons to create graphene plasmon polaritons. The resonance-induced absorption is critical in signal detection and energy harvesting applications. However, because of their atomic thickness, high absorptance is difficult to achieve with graphene ribbons alone. In this work, a hybrid plasmonic system composed of an array of graphene ribbons over a periodic metal grating is theoretically investigated. It is shown that the localized resonances, that is, magnetic polaritons, in metal gratings can couple with the plasmonic resonance in graphene ribbons, resulting in significantly enhanced absorption in graphene. Moreover, the coupling phenomenon depends on the width of the ribbons and the relative positions of the ribbon and the grating. The coupling between the grating and a continuous graphene monolayer sheet is also investigated and the results are compared to those with graphene ribbons. The findings of this work may facilitate the design of optoelectronic devices and metamaterials structures based on hybrid nanostructures and graphene

A new denudatine type C₂₀-diterpenoid alkaloid from <i>Aconitum sinchiangense</i> W. T. Wang

<p>A new denudatine-type C₂₀-diterpenoid alkaloid, designated as sinchianine (<b>1</b>), together with eight known diterpenoid alkaloids, 12-acetyl-12-<i>epi</i>-napelline (<b>2</b>), 12-<i>epi</i>-napelline (<b>3</b>), neoline (<b>4</b>), talatisamine (<b>5</b>), 14-<i>O</i>-acetylsenbusine A (<b>6</b>) and benzoylaconine (<b>7</b>), songorine (<b>8</b>) and aconitine (<b>9</b>), were isolated from the whole herb of <i>Aconitum sinchiangense</i> W. T. Wang. Their structures were elucidated on the basis of extensive spectroscopic analyses (NMR and HR-ESI-MS) and comparison with data reported in the literature.</p

Characterizing Slow Chemical Exchange in Nucleic Acids by Carbon CEST and Low Spin-Lock Field <i>R</i>_1ρ NMR Spectroscopy

Quantitative characterization of dynamic exchange between various conformational states provides essential insights into the molecular basis of many regulatory RNA functions. Here, we present an application of nucleic-acid-optimized carbon chemical exchange saturation transfer (CEST) and low spin-lock field <i>R</i>_1ρ relaxation dispersion (RD) NMR experiments in characterizing slow chemical exchange in nucleic acids that is otherwise difficult if not impossible to be quantified by the ZZ-exchange NMR experiment. We demonstrated the application on a 47-nucleotide fluoride riboswitch in the ligand-free state, for which CEST and <i>R</i>_1ρ RD profiles of base and sugar carbons revealed slow exchange dynamics involving a sparsely populated (<i>p</i> ∼ 10%) and shortly lived (τ ∼ 10 ms) NMR “invisible” state. The utility of CEST and low spin-lock field <i>R</i>_1ρ RD experiments in studying slow exchange was further validated in characterizing an exchange as slow as ∼60 s^–1

Thermal dependence of heart rates of embryos and hatchlings in the turtles <i>Chrysemys picta</i> (a) and <i>Graptemys pseudogeographica kohnii</i> (b).

<p>Heart rates were measured by non-invasive methods, and are expressed as mean ± standard error. Heart rates did not change with the developmental stage of embryos or with the age of hatchlings, but were greater for embryos than for hatchlings when the animals were tested at high temperatures. Specifically, Turkey's test indicated that significant differences occurred at 30 and 33°C in <i>C. picta</i>, and 25, 30 and 33.5°C in <i>G. pseudogeographica kohnii</i>.</p

Q₁₀ values of heart rate in different life-history stages in two species of turtles, <i>Chrysemys picta</i> and <i>Graptemys pseudogeographica kohnii</i>.

<p>In most cases, Q₁₀ values of heart rate in embryos were higher than those of hatchlings.</p