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Biomedical subjects

D Clark

Publications and source records attributed to D Clark.

At least 19 recordsLinked to original sources

RNA interference in parasitic helminths: current situation, potential pitfalls and future prospects.

RNA interference (RNAi) has become an invaluable tool for the functional analysis of genes in a wide variety of organisms including the free-living nematode Caenorhabditis elegans. Recently, attempts have been made to apply this technology to parasitic helminths of animals and plants with variable success. Gene knockdown has been reported for Schistosoma mansoni by soaking or electroporating different life-stages in dsRNA. Similar approaches have been tested on parasitic nematodes which clearly showed that, under certain conditions, it was possible to interfere with gene expression. However, despite these successes, the current utility of this technology in parasite research is questionable. First, problems have arisen with the specificity of RNAi. Treatment of the parasites with dsRNA resulted, in many cases, in non-specific effects. Second, the current RNAi methods have a limited efficiency and effects are sometimes difficult to reproduce. This was especially the case in strongylid parasites where only a small number of genes were susceptible to RNAi-mediated gene knockdown. The future application of RNAi in parasite functional genomics will greatly depend on how we can overcome these difficulties. Optimization of the dsRNA delivery methods and in vitro culture conditions will be the major challenges.

Animals↗

The potential for sodium hexametaphosphate (SHMP) found in common children drinks to limit acid production in the oral biofilm.

OBJECTIVE: Sodium hexametaphosphate (SHMP) is a widely used industrial preservative commonly found in children's drinks. In this paper we examined the effect of SHMP incorporated into children's drinks on acid production by the oral biofilm by monitoring salivary concentrations of lactic acid. MATERIALS AND METHOD: Twelve healthy adult subjects with an average age 36 years (range 26-54 years) consumed 10 ml from four children's beverages (Coca Cola and three types of Sunny Delight supplemented with SHMP) and a standard solution of sucrose. Saliva was collected at intervals following exposure of the oral biofilm to the drinks and the clearance of carbohydrates and the appearance of lactate was measured using standard enzymatic techniques. RESULTS: All the carbohydrates derived from the drinks were cleared from saliva within 15 min of consumption. Comparison of two drinks [Sunny D Normal and Sunny C] with the same carbohydrate, but different SHMP concentrations suggested that SHMP in these beverages had no significant effect on acid production. CONCLUSIONS: In this clinical study the role of SHMP, incorporated in common beverages, did not inhibit acid production from carbohydrates.

Acids↗

Identification of an excitatory amino acid-mediated component of the ventral tegmental area local field potential response to medial prefrontal cortex stimulation: effect of acute d-amphetamine.

The induction of sensitisation to the behavioural effects of d-amphetamine - a model of drug addiction - involves the potentiation of exctiatory amino acid (EAA)-ergic synapses on dopaminergic neurons in the ventral tegmental area (VTA). Such potentiation has been reported as early as 2 hr post-injection, however earlier time points have not been assessed. Consequently, we examined the effects of systemic d-amphetamine on an EAA-mediated component of the VTA local field potential response to stimulation of the medial prefrontal cortex, an EAAergic afferent critical for sensitisation, over the immediate 2 hr post-injection period. D-amphetamine and saline both depressed the amplitude of this component to a similar extent throughout the recording session. It is concluded that overt aspects of EAA-mediated potentiation appear to be delayed with respect to drug administration, which may have implications for sensitisation's putative role in linking drug-related environmental stimuli and the central effects of the drug.

Animals↗

Measurement of bottom-quark hadron masses in exclusive J/psi decays with the CDF detector.

We measure the masses of b hadrons in exclusively reconstructed final states containing a J/psi --> mu-mu+ decay using 220 pb(-1) of data collected by the CDF II experiment. We find: m(B+) = 5279.10 +/- 0.41(stat.) +/- 0.36(sys.) MeV/c2, m(B0) = 5279.63 +/- 0.53(stat.) +/- 0.33(sys.) MeV/c2, m(B(s)0) = 5366.01 +/- 0.73(stat.) +/- 0.33(sys.) MeV/c2, m(lambda(b)0) = 5619.7 +/- 1.2(stat.) +/- 1.2(sys.) MeV/c2. m(B+) - m(B0) = -0.53 +/- 0.67(stat.) +/- 0.14(sys.) MeV/c2, m(B(s)0) - m(B0) = 86.38 +/- 0.90(stat.) +/- 0.06(sys.) MeV/c2, m(lambda(b)0) - m(B0) = 339.2 +/- 1.4(stat.) +/- 0.1(sys.) MeV/c2. The measurements of the B(s)0, lambda(b)0 mass, m(B(s)0) - m(B0) and m(lambda(b)0) - m(B0) mass difference are of better precision than the current world averages.

Journal Article↗

A proteome analysis of the anterior cingulate cortex gray matter in schizophrenia.

The Anterior Cingulate Cortex (ACC, Brodmans Area 24) is implicated in the pathogenesis of schizophrenia due to its normal functions and connectivity together with reports of structural, morphological and neurotransmitter aberrations within this brain area in the disease state. Two-dimensional gel electrophoresis (2DE) was employed to scan and compare the ACC gray matter proteomes between schizophrenia (n = 10) and control (n = 10) post-mortem human tissue. This proteomic approach has detected 42 protein spots with altered levels in the schizophrenia cohort, which to our knowledge is the first proteomic analysis of the ACC in schizophrenia. Thirty nine of these proteins were subsequently identified using mass spectrometry and functionally classified into metabolism and oxidative stress, cytoskeletal, synaptic, signalling, trafficking and glial-specific groups. Some of the identified proteins have previously been implicated in the disease pathogenesis and some offer new insights into schizophrenia. Investigating these proteins, the genes encoding these proteins, their functions and interactions may shed light on the molecular mechanisms underlying the heterogeneous symptoms characteristic of schizophrenia.

Adult↗

Proviral load and immune markers associated with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Peru.

Human T-lymphotropic virus type 1 (HTLV-1) is the aetiological agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The objective of this study is to identify which ex vivo and in vivo markers are associated independently with HAM/TSP in a Peruvian population. Eighty-one subjects (33 men/48 women) were enrolled: 35 presented with HAM/TSP, 33 were asymptomatic HTLV-1 carriers (ACs) and 13 were HTLV-1-seronegative controls (SCs). Ex vivo markers included T cell proliferation and Th1 [interferon (IFN)-gamma], Th2 [interleukin (IL)-4, IL-5], proinflammatory [tumour necrosis factor (TNF)-alpha] and anti-inflammatory (IL-10) cytokine production in non-stimulated peripheral blood mononuclear cell (PBMC) cultures. In vivo CD4(+) T cell count, markers of Th1 [interferon-inducible protein (IP)-10] and Th2 (sCD30) activity in plasma and HTLV-1 proviral load in PBMCs were also evaluated. In univariate analysis, several markers, including T cell proliferation, IFN-gamma, IP-10, sCD30 and proviral load were associated with HAM/TSP, but in a multiple logistic regression analysis only the proviral load remained associated significantly with disease manifestation [adjusted OR 9.10 (1.24-66.91)]. Our findings suggest that HAM/TSP is associated primarily with proviral load, whereas the observed association with some immune markers seems secondary.

Adult↗

Making sense of dying: a review of narratives written since 1950 by people facing death from cancer and other diseases.

UNLABELLED: This article reviews a sample of narratives written since 1950 by people knowingly facing death as a result of cancer and other diseases, in order to compare experiences and show how these relate to wider changes in practice in end of life care. METHODS: A bibliographic search of libraries, archives, journals and internet sources located English spoken literature, including books, poems, newspapers, journal articles, diaries, and internet postings of writings by people facing terminal disease. Bibliometric and qualitative content analysis explored changing authorship, experiences, purpose in writing, and reported the impact on readers. RESULTS: The initial search located a wide range of published and unpublished narratives, to which inclusion/exclusion criteria were applied, yielding 148 narratives by different authors since 1950. A purposive sub-sample of 63 of these narratives was reviewed. DISCUSSION: Over the last half century there have been changes in both the volume of available literature and patterns of writing about end of life experience. Therapeutic benefits of writing are reported as a way of making sense of dying combined with a strong sense of purpose in sharing the story. There is a clear awareness of social needs when dying, along with issues of communication with medical staff, symptom control, realities of suffering, and spiritual aspects of dying. Differences are found in the nature and style of writing about cancer in comparison to other illnesses.

Attitude to Death↗

Search for new physics using high-mass tau pairs from 1.96 TeV pp collisions.

We present the results of a search for anomalous resonant production of tau lepton pairs with large invariant mass, the first such search using the CDF II Detector in Run II of the Tevatron pp collider. Such anomalous production could arise from various new physics processes. In a data sample corresponding to 195 pb(-1) of integrated luminosity we predict 2.8+/-0.5 events from standard model background processes and observe 4. We use this result to set limits on the production of heavy scalar and vector particles decaying to tau lepton pairs.

Journal Article↗

Measurement of B(t --> Wb)/B(t--> Wq) at the collider detector at fermilab.

We present a measurement of the ratio of top-quark branching fractions R = B(t --> Wb)/B(t --> Wq), where q can be a b, s, or a d quark, using lepton-plus-jets and dilepton data sets with an integrated luminosity of approximately 162 pb(-1) collected with the Collider Detector at Fermilab during Run II of the Tevatron. The measurement is derived from the relative numbers of tt events with different multiplicity of identified secondary vertices. We set a lower limit of R > 0.61 at 95% confidence level.

Journal Article↗

Search for long-lived doubly charged Higgs bosons in pp collisions at sqrt[s] = 1.96 TeV.

We present a search for long-lived doubly charged Higgs bosons (H(+/- +/-)), with signatures of high ionization energy loss and muonlike penetration. We use 292 pb(-1) of data collected in pp collisions at sqrt[s] = 1.96 TeV by the CDF II detector at the Fermilab Tevatron. Observing no evidence of long-lived doubly charged particle production, we exclude H(+/- +/-)(L) and H(+/- +/-)(R) bosons with masses below 133 GeV/c(2) and 109 GeV/c(2), respectively. In the degenerate case we exclude H(+/- +/-) mass below 146 GeV/c(2). All limits are quoted at the 95% confidence level.

Journal Article↗

Evidence for B0 s-->phiphi decay and measurements of branching ratio and A(CP) for B+ -->phiK+.

We present the first evidence of charmless decays of the B(0)(s) meson, the decay B(0)(s)--> phiphi, and a measurement of the branching ratio BR(B(0)(s)--> phiphi) using 180 pb(-1) of data collected by the CDF II experiment at the Fermilab Tevatron collider. In addition, the BR and direct CP asymmetry for the B+-->phiK+ decay are measured. We obtain BR(B(0)(s)--> phiphi)=[14(+6)(-5)(stat)+/-6(syst)] x 10(-6), BR(B+-->phiK+)=[7.6+/-1.3(stat)+/-0.6(syst)] x 10(-6), and A(CP)(B+-->phiK+)= -0.07+/-0.17(stat)+0.03 / -0.02(syst). Both decays are governed in the standard model by second order (penguin) b-->s(-)ss amplitudes.

Journal Article↗

Measurement of the cross section for prompt diphoton production in pp collisions at square root of s=1.96 TeV.

We report a measurement of the rate of prompt diphoton production in pp collisions at square root of s=1.96 TeV using a data sample of 207 pb(-1) collected with the upgraded Collider Detector at Fermilab. The background from nonprompt sources is determined using a statistical method based on differences in the electromagnetic showers. The cross section is measured as a function of the diphoton mass, the transverse momentum of the diphoton system, and the azimuthal angle between the two photons and is found to be consistent with perturbative QCD predictions.

Journal Article↗

Search for anomalous kinematics in tt dilepton events at CDF II.

We report on a search for anomalous kinematics of tt dilepton events in pp collisions at square root of s=1.96 TeV using 193 pb(-1) of data collected with the CDF II detector. We developed a new a priori technique designed to isolate the subset in a data sample revealing the largest deviation from standard model (SM) expectations and to quantify the significance of this departure. In the four-variable space considered, no particular subset shows a significant discrepancy, and we find that the probability of obtaining a data sample less consistent with the SM than what is observed is 1.0%-4.5%.

Journal Article↗

Measurement of the W(+)W(-) production cross section in pp collisions at square root[s]=1.96 TeV using dilepton events.

We present a measurement of the W(+)W(-) production cross section using 184 pb(-1) of p(p) collisions at a center-of-mass energy of 1.96 TeV collected with the Collider Detector at Fermilab. Using the dilepton decay channel W(+)W(-)-->l(+)nul(-), where the charged leptons can be either electrons or muons, we find 17 candidate events compared to an expected background of 5.0(+2.2)(-0.8) events. The resulting W(+)W(-) production cross-section measurement of sigma(pp-->W(+)W(-))=14.6(+5.8)(-5.1)(stat)(+1.8)(-3.0)(syst) +/- 0.9(lum) pb agrees well with the standard model expectation.

Journal Article↗

Measurement of partial widths and search for direct CP violation in D0 meson decays to K-K+ and pi-pi+.

We present a measurement of relative partial widths and decay rate CP asymmetries in K-K+ and pi(-)pi(+) decays of D0 mesons produced in pp collisions at sqrt[s]=1.96 TeV. We use a sample of 2x10(5) D(*+)-->D0pi(+) (and charge conjugate) decays with the D0 decaying to K-pi(+), K-K+, and pi(-)pi(+), corresponding to 123 pb(-1) of data collected by the Collider Detector at Fermilab II experiment at the Fermilab Tevatron collider. No significant direct CP violation is observed. We measure Gamma(D0-->K-K+)/Gamma(D0-->K-pi(+))=0.0992+/-0.0011+/-0.0012, Gamma(D0-->pi(-)pi(+))/Gamma(D0-->K-pi(+))=0.035 94+/-0.000 54+/-0.000 40, A(CP)(K-K+)=(2.0+/-1.2+/-0.6)%, and A(CP)(pi(-)pi(+))=(1.0+/-1.3+/-0.6)%, where, in all cases, the first uncertainty is statistical and the second is systematic.

Journal Article↗

Search for excited and exotic electrons in the egamma decay channel in pp collisions at sqrt[s] = 1.96 TeV.

We present a search for excited and exotic electrons (e(*)) decaying to an electron and a photon, both with high transverse momentum. We use 202 pb(-1) of data collected in pp collisions at sqrt[s] = 1.96 TeV with the Collider Detector at Fermilab II detector. No signal above standard model expectation is seen for associated ee(*) production. We discuss the e(*) sensitivity in the parameter space of the excited electron mass M(e(*)) and the compositeness energy scale Lambda. In the contact interaction model, we exclude 132 GeV/c(2)<M(e(*))<879 GeV/c(2) for Lambda = M(e(*)) at 95% confidence level (C.L.). In the gauge-mediated model, we exclude 126 GeV/c(2) < M(e(*)) < 430 GeV/c(2) at 95% C.L. for the phenomenological coupling f/Lambda approximately 10(-2) GeV-1.

Journal Article↗

Measurement of the lifetime difference between Bs mass eigenstates.

We present measurements of the lifetimes and polarization amplitudes for B(0)(s)-->J/psiphi and B(0)(d)-->J/psiK(*0) decays. Lifetimes of the heavy and light mass eigenstates in the B(0)(s) system are separately measured for the first time by determining the relative contributions of amplitudes with definite CP as a function of the decay time. Using 203+/-15 B(0)(s) decays we obtain tau(L) = (1.05(+0.16)(-0.13) +/- 0.02) ps and tau(H) = (2.07(+0.58)(-0.46) +/- 0.03) ps. Expressed in terms of the difference DeltaGamma(s) and average Gamma(s), of the decay rates of the two eigenstates, the results are DeltaGamma(s)/Gamma(s) = (65(+25)(-33) +/- 1)% and DeltaGamma(s) = (0.47(+0.19)(-0.24) +/- 0.01) ps(-1).

Journal Article↗

First measurements of inclusive W and Z cross sections from run II of the fermilab tevatron collider.

We report the first measurements of inclusive W and Z cross sections times leptonic branching ratios for pp collisions at square root[s]=1.96 TeV, based on their decays to electrons and muons. The data correspond to an integrated luminosity of 72 pb(-1) recorded with the CDF detector at the Fermilab Tevatron. We test e-mu universality in W decays, and we measure the ratio of leptonic W and Z rates from which the leptonic branching fraction B(W-->lnu) can be extracted as well as an indirect value for the total width of the W and the Cabibbo-Kobayashi-Maskawa matrix element, |V(cs)|.

Journal Article↗