Mapping of serotype-specific, immunodominant epitopes in the NS-4 region of hepatitis C virus (HCV):use of type-specific peptides to serologically differentiate infections with HCV types 1, 2, and 3

The effect of sequence variability between different types of hepatitis C virus (HCV) on the antigenicity of the NS-4 protein was investigated by epitope mapping and by enzyme-linked immunosorbent assay with branched oligopeptides. Epitope mapping of the region between amino acid residues 1679 and 1768 in the HCV polyprotein revealed two major antigenic regions (1961 to 1708 and 1710 to 1728) that were recognized by antibody elicited upon natural infection of HCV. The antigenic regions were highly variable between variants of HCV, with only 50 to 60% amino acid sequence similarity between types 1, 2, and 3. Although limited serological cross-reactivity between HCV types was detected between peptides, particularly in the first antigenic region of NS-4, type-specific reactivity formed the principal component of the natural humoral immune response to NS-4. Type-specific antibody to particular HCV types was detected in 89% of the samples from anti-HCV-positive blood donors and correlated almost exactly with genotypic analysis of HCV sequences amplified from the samples by polymerase chain reaction. Whereas almost all blood donors appeared to be infected with a single virus type (97%), a higher proportion of samples (40%) from hemophiliacs infected from transfusion of non-heat-inactivated clotting factor contained antibody to two or even all three HCV types, providing evidence that long-term exposure may lead to multiple infection with different variants of HCV

Thrombocytosis and abnormal liver enzymes:A trigger for investigation of underlying malignancy

BackgroundThrombocytosis is often an incidental finding in primary care with a range of causes. Despite evidence of a strong association between thrombocytosis and malignancy, guidelines for investigating thrombocytosis in the absence of red flag symptoms remain unclear. A novel automated system of laboratory analysis, intelligent Liver Function Testing (iLFT), launched in Tayside in 2018 and has identified a patient group with thrombocytosis and abnormal liver test (LFT) results. This study analysed the outcome of these patients and investigated the use of thrombocytosis combined with LFTs in predicting risk of cancer.Methods and findingsBetween August 2018 and August 2020, 6792 patients underwent iLFT, with 246 found to have both thrombocytosis and at least one abnormal LFT. A random case-matched control group of 492 iLFT patients with normal platelet count and at least one abnormal LFT was created. 7.7% (95% CI 4.7-11.8%) of patients with thrombocytosis had cancer compared to 2.0% (1.0-3.7%) of controls. Patients ConclusionsThese findings suggest a substantial increased risk of cancer in patients with thrombocytosis and raised ALP. This could be developed as an adjunct to current investigation algorithms, highlighting high-risk patients and prompting further investigation (such as computed tomography scans) where indicated

Theory of High-Tc Superconductivity: Accurate Predictions of Tc

The superconducting transition temperatures of high-Tc compounds based on copper, iron, ruthenium and certain organic molecules are discovered to be dependent on bond lengths, ionic valences, and Coulomb coupling between electronic bands in adjacent, spatially separated layers [1]. Optimal transition temperature, denoted as T_c0, is given by the universal expression $k_BT_c0 = e^2 \Lambda / \ell\zeta$; $\ell$ is the spacing between interacting charges within the layers, \zeta is the distance between interacting layers and \Lambda is a universal constant, equal to about twice the reduced electron Compton wavelength (suggesting that Compton scattering plays a role in pairing). Non-optimum compounds in which sample degradation is evident typically exhibit Tc < T_c0. For the 31+ optimum compounds tested, the theoretical and experimental T_c0 agree statistically to within +/- 1.4 K. The elemental high Tc building block comprises two adjacent and spatially separated charge layers; the factor e^2/\zeta arises from Coulomb forces between them. The theoretical charge structure representing a room-temperature superconductor is also presented.Comment: 7 pages 5 references, 6 figures 1 tabl

Excitons in type-II quantum dots: Finite offsets

Quantum size effects for an exciton attached to a spherical quantum dot are calculated by a variational approach. The band line-ups are assumed to be type-II with finite offsets. The dependence of the exciton binding energy upon the dot radius and the offsets is studied for different sets of electron and hole effective masses

Effects of Cyclin Dependent Kinase 9 inhibition on zebrafish larvae

CDK9 is a known regulator of cellular transcription, growth and proliferation. Small molecule inhibitors are currently being developed and assessed in clinical trials as anti-cancer drugs. The zebrafish embryo provides an ideal model to explore the effects of CDK9 inhibition in-vivo. This has not been adequately explored previously at the level of a whole organism. We have compared and contrasted the effects of pharmacological and molecular inhibition of CDK9 on somatic growth, apoptosis and cellular proliferation in zebrafish larvae between 0 to 120 hours post fertilisation (hpf) using flavopiridol, a selective CDK9 antagonist, and CDK9-targeting morpholino. We demonstrate that the inhibition of CDK9 diminishes cellular proliferation and increases apoptosis. Subsequently, it affects somatic growth and development of a number of key embryonic structures including the brain, heart, eye and blood vessels. For the first time, we have localized CDK9 at a subcellular level in whole-mounted larvae. This works shows, at a high-throughput level, that CDK9 clearly plays a fundamental role in early cellular growth and proliferation

Narrow genetic base in forest restoration with holm oak (Quercus ilex L.) in Sicily

In order to empirically assess the effect of actual seed sampling strategy on genetic diversity of holm oak (Quercus ilex) forestations in Sicily, we have analysed the genetic composition of two seedling lots (nursery stock and plantation) and their known natural seed origin stand by means of six nuclear microsatellite loci. Significant reduction in genetic diversity and significant difference in genetic composition of the seedling lots compared to the seed origin stand were detected. The female and the total effective number of parents were quantified by means of maternity assignment of seedlings and temporal changes in allele frequencies. Extremely low effective maternity numbers were estimated (Nfe $\approx$ 2-4) and estimates accounting for both seed and pollen donors gave also low values (Ne $\approx$ 35-50). These values can be explained by an inappropriate forestry seed harvest strategy limited to a small number of spatially close trees

Global wave loads on a damaged ship

A computational tool was applied based on a two dimensional linear method to predict the hydrodynamic loads for damaged ships. Experimental tests on a ship model have also been carried out to predict the hydrodynamic loads in various design conditions. The results of the theoretical method and experimental tests are compared to validate the theoretical method. The extreme wave induced loads have been calculated by short term prediction. For the loads in intact condition, the prediction with duration of 20 years at sea state 5 is used, while for loads in damaged conditions the prediction in 96 hours exposure time at sea 3 is used. The maximum values of the most probable extreme amplitudes of dynamic wave induced loads in damaged conditions are much less than those in intact condition because of the reduced time. An opening could change the distribution of not only stillwater bending moment but also wave-induced bending moment. It is observed that although some cross sections are not structurally damaged, the total loads acting on these cross sections after damage may be increased dramatically compared to the original design load in intact condition

High temperature optical absorption investigation into the electronic transitions in sol–gel derived C12A7 thin films

Optical absorption into 6 mm thick sol–gel derived films, annealed at 1300 °C of 12CaO·7Al2O3 calcium aluminate binary compound on MgO〈100〉 single crystal substrates was studied at temperatures ranging from room temperature to 300 °C. Experimental data were analysed in both Tauc and Urbach regions. The optical band gap decreased from 4.088 eV at 25 °C to 4.051 eV at 300 °C, while Urbach energy increased from 0.191 eV at 25 °C to 0.257 eV at 300 °C. The relationship between the optical band gap and the Urbach energy at different temperatures showed an almost linear relationship from which the theoretical values of 4.156 and 0.065 eV were evaluated for the band gap energy and Urbach energy of a 12CaO·7Al2O3 crystal with zero structural disorder at 0 K

Combinatorics of Open Covers VI: Selectors for Sequences of Dense Sets

We consider the following two selection principles for topological spaces: [Principle 1:] { For each sequence of dense subsets, there is a sequence of points from the space, the n-th point coming from the n-th dense set, such that this set of points is dense in the space; [Principle 2:]{ For each sequence of dense subsets, there is a sequence of finite sets, the n-th a subset of the n-th dense set, such that the union of these finite sets is dense in the space. We show that for separable metric space X one of these principles holds for the space C_p(X) of realvalued continuous functions equipped with the pointwise convergence topology if, and only if, a corresponding principle holds for a special family of open covers of X. An example is given to show that these equivalences do not hold in general for Tychonoff spaces. It is further shown that these two principles give characterizations for two popular cardinal numbers, and that these two principles are intimately related to an infinite game that was studied by Berner and Juhasz