Integrated Microfluidic Platform for Oral Diagnostics

While many point-of-care (POC) diagnostic methods have been developed for blood-borne analytes, development of saliva-based POC diagnostics is in its infancy. We have developed a portable microfluidic device for detection of potential biomarkers of periodontal disease in saliva. The device performs rapid microfluidic chip-based immunoassays (<3–10 min) with low sample volume requirements (10 ΜL) and appreciable sensitivity (nM–pM). Our microfluidic method facilitates hands-free saliva analysis by integrating sample pretreatment (filtering, enrichment, mixing) with electrophoretic immunoassays to quickly measure analyte concentrations in minimally pretreated saliva samples. The microfluidic chip has been integrated with miniaturized electronics, optical elements, such as diode lasers, fluid-handling components, and data acquisition software to develop a portable, self-contained device. The device and methods are being tested by detecting potential biomarkers in saliva samples from patients diagnosed with periodontal disease. Our microchip-based analysis can readily be extended to detection of biomarkers of other diseases, both oral and systemic, in saliva and other oral fluids.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73594/1/annals.1384.004.pd

Implications of unitarity and analyticity for the D\pi form factors

We consider the vector and scalar form factors of the charm-changing current responsible for the semileptonic decay D\rightarrow \pi l \nu. Using as input dispersion relations and unitarity for the moments of suitable heavy-light correlators evaluated with Operator Product Expansions, including O(\alpha_s^2) terms in perturbative QCD, we constrain the shape parameters of the form factors and find exclusion regions for zeros on the real axis and in the complex plane. For the scalar form factor, a low energy theorem and phase information on the unitarity cut are also implemented to further constrain the shape parameters. We finally propose new analytic expressions for the $D\pi$ form factors, derive constraints on the relevant coefficients from unitarity and analyticity, and briefly discuss the usefulness of the new parametrizations for describing semileptonic data.Comment: 10 pages, 7 figures, uses EPJ style files: expanded version of v1 with extended discussion, additional analysis, explanation, figure and references; corresponds to EPJA versio

The spiritual revolution and suicidal ideation: an empirical enquiry among 13- to 15-year-old adolescents in England and Wales

The association between conventional religiosity and suicide inhibition has been well explored and documented since the pioneering work of Durkheim. Commentators like Heelas and Woodhead point to ways in which conventional religiosity is giving way in England and Wales to a range of alternative spiritualities, including renewed interest in paranormal phenomena. Taking a sample of 3095 13- to 15-year-old adolescents, the present study examines the association between suicidal ideation and both conventional religiosity and paranormal beliefs, after controlling for individual differences in sex, age and personality (extraversion, neuroticism and psychoticism). The data demonstrate that, while conventional religiosity is slightly associated with lower levels of suicidal ideation, paranormal beliefs are strongly associated with higher levels of suicidal ideation

CTCF genetic alterations in endometrial carcinoma are pro-tumorigenic

CTCF is a haploinsufficient tumour suppressor gene with diverse normal functions in genome structure and gene regulation. However the mechanism by which CTCF haploinsufficiency contributes to cancer development is not well understood. CTCF is frequently mutated in endometrial cancer. Here we show that most CTCF mutations effectively result in CTCF haploinsufficiency through nonsense-mediated decay of mutant transcripts, or loss-of-function missense mutation. Conversely, we identified a recurrent CTCF mutation K365T, which alters a DNA binding residue, and acts as a gain-of-function mutation enhancing cell survival. CTCF genetic deletion occurs predominantly in poor prognosis serous subtype tumours, and this genetic deletion is associated with poor overall survival. In addition, we have shown that CTCF haploinsufficiency also occurs in poor prognosis endometrial clear cell carcinomas and has some association with endometrial cancer relapse and metastasis. Using shRNA targeting CTCF to recapitulate CTCF haploinsufficiency, we have identified a novel role for CTCF in the regulation of cellular polarity of endometrial glandular epithelium. Overall, we have identified two novel pro-tumorigenic roles (promoting cell survival and altering cell polarity) for genetic alterations of CTCF in endometrial cance

Spin-gravity coupling and gravity-induced quantum phases

External gravitational fields induce phase factors in the wave functions of particles. The phases are exact to first order in the background gravitational field, are manifestly covariant and gauge invariant and provide a useful tool for the study of spin-gravity coupling and of the optics of particles in gravitational or inertial fields. We discuss the role that spin-gravity coupling plays in particular problems.Comment: 18 pages, 1 figur

Observation of hard scattering in photoproduction events with a large rapidity gap at HERA

Events with a large rapidity gap and total transverse energy greater than 5 GeV have been observed in quasi-real photoproduction at HERA with the ZEUS detector. The distribution of these events as a function of the $\gamma p$ centre of mass energy is consistent with diffractive scattering. For total transverse energies above 12 GeV, the hadronic final states show predominantly a two-jet structure with each jet having a transverse energy greater than 4 GeV. For the two-jet events, little energy flow is found outside the jets. This observation is consistent with the hard scattering of a quasi-real photon with a colourless object in the proton.Comment: 19 pages, latex, 4 figures appended as uuencoded fil

Widespread aberrant alternative splicing despite molecular remission in chronic myeloid leukaemia patients

Vast transcriptomics and epigenomics changes are characteristic of human cancers, including leukaemia. At remission, we assume that these changes normalise so that omics-profiles resemble those of healthy individuals. However, an in-depth transcriptomic and epigenomic analysis of cancer remission has not been undertaken. A striking exemplar of targeted remission induction occurs in chronic myeloid leukaemia (CML) following tyrosine kinase inhibitor (TKI) therapy. Using RNA sequencing and whole-genome bisulfite sequencing, we profiled samples from chronic-phase CML patients at diagnosis and remission and compared these to healthy donors. Remarkably, our analyses revealed that abnormal splicing distinguishes remission samples from normal controls. This phenomenon is independent of the TKI drug used and in striking contrast to the normalisation of gene expression and DNA methylation patterns. Most remarkable are the high intron retention (IR) levels that even exceed those observed in the diagnosis samples. Increased IR affects cell cycle regulators at diagnosis and splicing regulators at remission. We show that aberrant splicing in CML is associated with reduced expression of specific splicing factors, histone modifications and reduced DNA methylation. Our results provide novel insights into the changing transcriptomic and epigenomic landscapes of CML patients during remission. The conceptually unanticipated observation of widespread aberrant alternative splicing after remission induction warrants further exploration. These results have broad implications for studying CML relapse and treating minimal residual disease.Ulf Schmitz, Jaynish S. Shah, Bijay P. Dhungel, Geoffray Monteuuis, Phuc-Loi Luu, Veronika Petrova, Cynthia Metierre, Shalima S. Nair, Charles G. Bailey, Verity A. Saunders, Ali G. Turhan, Deborah L. White, Susan Branford, Susan J. Clark, Timothy P. Hughes, Justin J.-L. Wong, and John E.J. Rask

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results