AI solutions for human problems

Abstract Background Bronchiectasis is a chronic respiratory condition. Persistent bacterial colonisation in the stable state with increased and sometimes altered bacterial burden during exacerbations are accepted as key features in the pathophysiology. The extent to which respiratory viruses are present during stable periods and in exacerbations is less well understood. Methods This study aimed to determine the incidence of respiratory viruses within a cohort of bronchiectasis patients with acute exacerbations at a teaching hospital and, separately, in a group of patients with stable bronchiectasis. In the group of stable patients, a panel of respiratory viruses were assayed for using real time quantitative PCR in respiratory secretions and exhaled breath. The Impact of virus detection on exacerbation rates and development of symptomatic infection was evaluated. Results Routine hospital-based viral PCR testing was only requested in 28% of admissions for an exacerbation. In our cohort of stable bronchiectasis patients, viruses were detected in 92% of patients during the winter season, and 33% of patients during the summer season. In the 2-month follow up period, 2 of 27 patients presented with an exacerbation. Conclusions This pilot study demonstrated that respiratory viruses are commonly detected in patients with stable bronchiectasis. They are frequently detected during asymptomatic viral periods, and multiple viruses are often present concurrently

Protecting Ceria Nanocatalysts - The Role of Sacrificial Barriers

Forces acting on a functional nanomaterial during operation can cause plastic deformation and extinguish desirable catalytic activities. Here, we show that sacrificial materials, introduced into the catalytic composite device, can absorb some of the imposed stress, and protect the structural integrity and hence activity of the functional component. Specifcally, we use molecular dynamics (MD) to simulate uniaxial stress on a ceria (CeO2) nanocube, an important functional material with respect to oxidative catalysis, such as the conversion of CO to CO2. We predict that the nanocube, protected by a `soft' BaO or `hard' MgO sacrifcial barrier, is able to withstand 40.1 GPa or 26.5 GPa respectively before plastic deformation destroys the structure irreversibly; the sacrificial materials, BaO and MgO, capture 71% and 54% of the stress respectively. In comparison, the unprotected nanoceria catalyst deforms plastically at only 2.5 GPa. Furthermore, modelling reveals the deformation mechanisms and the importance of microstructural features, insights that are difficult to measure experimentally

Highly sensitive label-free antibody detection using a long period fibre grating sensor

An optical fibre long period grating (LPG) biosensor is appealing in the detection of biomolecules because of the high sensitivity, label-free and real-time measurement. The miniaturized size, ability of remote sensing and immunity to electromagnetic interference of the LPG biosensor provide various possibility of single-point sensing in situations such as point of care diagnostics and in vivo measurement. Two optical fibre LPG based biosensors are reported for detection of streptavidin (SV) and immunoglobulin M (IgM) respectively. The LPG is coated with a film containing three layers of Poly(allylamine hydrochloride)/gold coated silica nanoparticles via the layer-by-layer method. Biotin is covalently bonded to the surface of the gold shell by means of the formation of an amide bonds for detection of streptavidin. The concentration of SV in water for detection varied from 1.25 nM to 2.7 μM. The LPG sensor, operating close to the phase matching condition shows a high sensitivity of 3.88 (ng/mm2)−1 and a detection limit of 0.86 pg/mm2 for the detection of SV. The limit of detection is 22 times lower than previously demonstrated with this type of sensor. The developed IgM sensor has the same configuration of film but has anti-IgM embedded on the LPG instead of biotin, demonstrating versatility of the sensing platform. This was used for the detection of human IgM with concentrations from 15.6 μg/ml to 1 mg/ml. The LPG sensor exhibits a sensitivity of 11 nm (ng/mm2)−1 for the detection of IgM with a detection limit of 15 pg/mm2. The developed highly sensitive IgM sensor shows the potential application of clinical point of care for detection of lower concentration of IgM in vitro. The proposed biosensor exhibits high sensitivity and rapid detection of low concentrations biomolecules from the small size of SV to the large size of IgM

Association between maternal micronutrient status, oxidative stress and common genetic variants in antioxidant enzymes at 15 weeks’ gestation in nulliparous women who subsequently develop pre-eclampsia

Aims: Pre-eclampsia is a pregnancy-specific condition affecting 2-7% of women and a leading cause of perinatal and maternal morbidity and mortality. Deficiencies of specific micronutrient antioxidant activities associated with copper, selenium, zinc and manganese, have previously been linked to pre-eclampsia at time of disease. Our aims were to investigate whether maternal plasma micronutrient concentrations and related antioxidant enzyme activities are altered prior to pre-eclampsia onset and to examine the dependence on genetic variations in these antioxidant enzymes. Methods: Pre-disease plasma samples (15+1 weeks’ gestation) were obtained from women enrolled in the international SCreening fOr Pregnancy Endpoints (SCOPE) study who subsequently developed pre-eclampsia (n=244), and age- and BMI-matched normotensive controls (n=472). Micronutrient concentrations were measured by inductively coupled plasma mass spectrometry; associated antioxidant enzyme activities, selenoprotein-P, caeruloplasmin concentrations and activities, antioxidant capacity and markers of oxidative stress were measured by colorimetric assays. Sixty four tagSNPs within genes encoding the antioxidant enzymes and selenoprotein-P were genotyped using allele-specific competitive PCR. Results: Plasma copper and caeruloplasmin concentrations were modestly, but significantly elevated in women who subsequently developed pre-eclampsia (both P<0.001) compared to controls (median [IQR], copper: 1957.4 [1787, 2177.5] vs. 1850.0 [1663.5, 2051.5] µg/L; caeruloplasmin: 2.5[1.4, 3.2] vs. 2.2[1.2, 3.0] µg/ml). There were no differences in other micronutrients or enzymes between groups. No relationship was observed between genotype for single nucleotide polymorphisms (SNPs) and antioxidant enzyme activity. Conclusions: This analysis of a prospective cohort study reports maternal micronutrient concentrations in combination with associated antioxidant enzymes and SNPs in their encoding genes in women at 15 weeks’ gestation that subsequently developed pre-eclampsia. The modest elevation in copper may contribute to oxidative stress, later in pregnancy, in those women that go on to develop pre-eclampsia. The lack of evidence to support the hypothesis that functional SNPs influence antioxidant enzyme activity in pregnant women argues against a role for these genes in the aetiology of pre-eclampsia

Detection and molecular characterisation of Cryptosporidium parvum in British European hedgehogs (Erinaceus europaeus)

Surveillance was conducted for the occurrence of protozoan parasites of the genus Cryptosporidium in European hedgehogs (Erinaceus europaeus) in Great Britain. In total, 108 voided faecal samples were collected from hedgehogs newly admitted to eight wildlife casualty treatment and rehabilitation centres. Terminal large intestinal (LI) contents from three hedgehog carcasses were also analysed. Information on host and location variables, including faecal appearance, body weight, and apparent health status, was compiled. Polymerase Chain Reaction (PCR) targeting the 18S ribosomal RNA gene, confirmed by sequencing, revealed an 8% (9/111) occurrence of Cryptosporidium parvum in faeces or LI contents, with no significant association between the host or location variables and infection. Archived small intestinal (SI) tissue from a hedgehog with histological evidence of cryptosporidiosis was also positive for C. parvum by PCR and sequence analysis of the 18S rRNA gene. No other Cryptosporidium species were detected. PCR and sequencing of the glycoprotein 60 gene identified three known zoonotic C. parvum subtypes not previously found in hedgehogs: IIdA17G1 (n=4), IIdA19G1 (n=1) and IIdA24G1 (n=1). These subtypes are also known to infect livestock. Another faecal sample contained C. parvum IIcA5G3j which has been found previously in hedgehogs, and for which there is one published report in a human, but is not known to affect livestock. The presence of zoonotic subtypes of C. parvum in British hedgehogs highlights a potential public health concern. Further research is needed to better understand the epidemiology and potential impacts of Cryptosporidium infection in hedgehogs

STAT3 activation by E6 is essential for the differentiation-dependent HPV18 life cycle.

Human papillomaviruses (HPV) activate a number of host factors to control their differentiation-dependent life cycles. The transcription factor signal transducer and activator of transcription (STAT)-3 is important for cell cycle progression and cell survival in response to cytokines and growth factors. STAT3 requires phosphorylation on Ser727, in addition to phosphorylation on Tyr705 to be transcriptionally active. In this study, we show that STAT3 is essential for the HPV life cycle in undifferentiated and differentiated keratinocytes. Primary human keratinocytes containing high-risk HPV18 genomes display enhanced STAT3 phosphorylation compared to normal keratinocytes. Expression of the E6 oncoprotein is sufficient to induce the dual phosphorylation of STAT3 at Ser727 and Tyr705 by a mechanism requiring Janus kinases and members of the MAPK family. E6-mediated activation of STAT3 induces the transcription of STAT3 responsive genes including cyclin D1 and Bcl-xL. Silencing of STAT3 protein expression by siRNA or inhibition of STAT3 activation by small molecule inhibitors, or by expression of dominant negative STAT3 phosphorylation site mutants, results in blockade of cell cycle progression. Loss of active STAT3 impairs HPV gene expression and prevents episome maintenance in undifferentiated keratinocytes and upon differentiation, lack of active STAT3 abolishes virus genome amplification and late gene expression. Organotypic raft cultures of HPV18 containing keratinocytes expressing a phosphorylation site STAT3 mutant display a profound reduction in suprabasal hyperplasia, which correlates with a loss of cyclin B1 expression and increased differentiation. Finally, increased STAT3 expression and phosphorylation is observed in HPV positive cervical disease biopsies compared to control samples, highlighting a role for STAT3 activation in cervical carcinogenesis. In summary, our data provides evidence of a critical role for STAT3 in the HPV18 life cycle

Optical Observations of GRO J1655-40 in Quiescence I: A Precise Mass for the Black Hole Primary

We report photometric and spectroscopic observations of the black hole binary GRO J1655-40 in complete quiescence. In contrast to the 1995 photometry, the light curves from 1996 are almost completely dominated by ellipsoidal modulations from the secondary star. Model fits to the light curves, which take into account the temperature profile of the accretion disk and eclipse effects, yield an inclination of i=69.50 +/- 0.08 degrees and a mass ratio of Q=2.99 +/- 0.08. The precision of our determinations of i and Q allow us to determine the black hole mass to an accuracy of approximately 4% (7.02 +/- 0.22 solar masses). The secondary star's mass is 2.34 +/- 0.12 solar masses. The position of the secondary on the Hertzsprung-Russell diagram is consistent with that of a 2.3 solar mass star which has evolved off the main sequence and is halfway to the start of the giant branch. Using the new spectra we present an improved value of the spectroscopic period (2.62157 +/- 0.00015 days), radial velocity semiamplitude (228.2 +/- 2.2 km/sec), and mass function (3.24 +/- 0.09 solar masses). Evolutionary models suggest an average mass transfer rate for such a system of 3.4E-9 solar masses per year (2.16E+17 grams per second), which is much larger than the average mass transfer rates implied in the other six transient black hole systems, but still barely below the critical mass transfer rate required for stability.Comment: 30 pages, 12 figures, LaTeX (uses orosztwo.sty), to appear in ApJ, vol. 474 (March 10, 1997

Bovine tuberculosis epidemiology in Cameroon, Central Africa, based on the interferon gamma assay

Despite sub-Saharan Africa (SSA) accounting for ~20% of the global cattle population, prevalence estimates and related risk factors of bovine tuberculosis (bTB) are still poorly described. The increased sensitivity of the IFN-γ assay and its practical benefits suggest the test could be useful to investigate bTB epidemiology in SSA. This study used a population-based sample to estimate bTB prevalence, identify risk factors and estimate the effective reproductive rate in Cameroonian cattle populations. A cross-sectional study was conducted in the North West Region (NWR) and the Vina Division (VIN) of Cameroon in 2013. A regional stratified sampling frame of pastoral cattle herds produced a sample of 1,448 cattle from 100 herds. In addition, a smaller cross-sectional study sampled 60 dairy cattle from 46 small-holder co-operative dairy farmers in the NWR. Collected blood samples were stimulated with bovine and avian purified protein derivatives, with extracted plasma screened using the IFN-γ enzyme-linked immunosorbent assay (Prionics Bovigam®). Design-adjusted population prevalences were estimated, and multivariable mixed-effects logistic regression models using Bayesian inference techniques identified the risk factors for IFN-γ positivity. Using the IFN-γ assay, the prevalence of bTB in the dairy cattle was 21.7% (95% CI: 11.2–32.2). The design-adjusted prevalence of bTB in cattle kept by pastoralists was 11.4% (95% CI: 7.6–17.0) in the NWR and 8.0% (95% CI: 4.7–13.0) in the VIN. A within-herd prevalence estimate for pastoralist cattle also supported that the NWR had higher prevalence herds than the VIN. Additionally, the estimates of the effective reproductive rate Rt were 1.12 for the NWR and 1.06 for the VIN, suggesting different transmission rates within regional cattle populations in Cameroon. For pastoral cattle, an increased risk of IFN-γ assay positivity was associated with being male (OR = 1.89; 95% CI:1.15–3.09), increasing herd size (OR = 1.02; 95% CI:1.01–1.03), exposure to the bovine leucosis virus (OR = 2.45; 95% CI: 1.19–4.84) and paratuberculosis (OR = 9.01; 95% CI: 4.17–20.08). Decreased odds were associated with contacts at grazing, buffalo (OR = 0.20; 95% CI: 0.03–0.97) and increased contact with other herds [1–5 herds: OR = 0.16 (95% CI: 0.04–0.55); 6+ herds: OR = 0.18 (95% CI: 0.05–0.64)]. Few studies have used the IFN-γ assay to describe bTB epidemiology in SSA. This study highlights the endemic situation of bTB in Cameroon and potential public health risks from dairy herds. Further work is needed to understand the IFN-γ assay performance, particularly in the presence of co-infections, and how this information can be used to develop control strategies in the SSA contexts

Coherent Detector Arrays for Millimeter and Submillimeter Astronomy

Progress in many areas of astronomy requires large-area surveys and observations of extended objects. This includes the cosmic microwave background, nearby galaxies, the Milky Way, and regions of star-forming regions within our galaxy. The ability to carry out such studies is critically dependent on the development of affordable high-sensitivity focal plane arrays, for both spectral line and continuum observations. We discuss a program for the next decade to develop such technology for ground-based and spacebased millimeter and submillimeter astronomy. Appropriate technologies exist, but significant effort is required to make the transition from simply replicating individual pixels to approaching focal plane array design in an integrated fashion from feeds to spectrometers for spectral analysis. This advance is essential to realize the full potential of major new ground-based, suborbital, and future space facilities, and is relevant to the RMS and EOS panels. The recommended budget for this activity is $65M