CIN2+ detection of the HPV DNA Array genotyping assay in comparison with the Cobas 4800 HPV test and cytology

BACKGROUND: HPV DNA Array is an E1-targeting PCR genotyping test, with capability of distinguishing 18 high-risk (16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82) and 11 low-risk HPV types (6, 11, 40, 42, 44, 54, 67, 69, 70, 85, 97). HPV DNA Array uses multiplex PCR for E1-gene sequence amplification. The amplicons are detected and genotyped by reverse hybridization to immobilized DNA probes spotted as triplets in single 96 well-plate wells and read by AID ELISPOT reader. METHODS: Aim of the study was to evaluate the clinical performance of the assay against internationally accepted and FDA approved Cobas 4800 HPV test (Roche Diagnostics). Study population comprised of 500 cervical samples. RESULTS: HPV DNA Array demonstrated a very high sensitivity of 100% for CIN2+ and 100% for CIN3+ detection, same as Cobas 4800. HPV DNA Array showed greater sensitivity for CIN2+ detection than cytology (100% vs. 13.6%). The agreement to Cobas 4800 for HPV detection, irrespective of type, was 81.4% with κ = 0.613. The agreement for HPV 16 was 92.8% (κ = 0.929), and for HPV 18 54.2% (κ = 0.681). CONCLUSION: HPV DNA Array demonstrated good clinical performance for detection of high-grade lesions, and may be considered for usage in a screening setting

Clinical performance of the HPV DNA Array genotyping assay in detection of CIN2+ lesions with BS GP5+/6+ MPG Luminex tested cervical samples

Human papillomavirus (HPV) detection is used for screening of cervical cancer and genotype-specific persistence has shown to be mandatory for dysplasia development. Aim of this study was to evaluate the clinical performance of HPV DNA Array for cervical intraepithelial neoplasia 2+ (CIN2+) lesion detection. HPV DNA Array is a polymerase chain reaction-based assay that targets E1 sequences of 29 HPV types (6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 44, 45, 51, 52, 53, 54, 56, 58, 59, 66, 67, 68, 69, 70, 73, 82, 85, and 97). The clinical evaluation was performed against the reference assay, BS-GP5+/6+ multiplex genotyping (MPG)-Luminex, with 600 cervical smear samples of a referral population. HPV DNA Array detected CIN2+ lesions with a sensitivity of 90.2%, identical to that of MPG-Luminex. Detection of CIN3+ lesions was with a sensitivity of 90.3%, as compared with 88.7% of MPG-Luminex. It demonstrated very good agreement for HPV detection, irrespective of type, of 91.5% (kappa = 0.832). HPV DNA Array is a simple and robust assay, with a short protocol of 4 hours hands-on time and automated readout by ELISpot AiDot software. It permits testing of up to 96 samples in one run and may be considered for use in organized screening programs and low resource settings

Unifying the Phase Diagrams of the Magnetic and Transport Properties of La_(2-x)Sr_xCuO_4, 0 < x < 0.05

An extensive experimental and theoretical effort has led to a largely complete mapping of the magnetic phase diagram of La_(2-x)Sr_xCuO_4, and a microscopic model of the spin textures produced in the x < 0.05 regime has been shown to be in agreement with this phase diagram. Here we use this same model to derive a theory of the impurity-dominated, low temperature transport. Then, we present an analysis of previously published data for two samples: x = 0.002 data from Chen et. al., and x = 0.04 data from Keimer et. al. We show that the transport mechanisms in the two systems are the same, even though they are on opposite sides of the observed insulator-to-metal transition. Our model of impurity effects on the impurity band conduction, variable-range hopping conduction, and coulomb gap conduction, is similar to that used to describe doped semiconductors. However, for La_(2-x)Sr_xCuO_4 we find that in addition to impurity-generated disorder effects, strong correlations are important and must be treated on a equal level with disorder. On the basis of this work we propose a phase diagram that is consistent with available magnetic and transport experiments, and which connects the undoped parent compound with the lowest x value for which La_(2-x)Sr_xCuO_4 is found to be superconducting, x about 0.06.Comment: 7 pages revtex with one .ps figur

Sr impurity effects on the magnetic correlations of LaSrCuO

We examine the low-temperature magnetic properties of moderately doped LaSrCuO paying particular attention to the spin-glass (SG) phase and the C-IC transition as they are affected by Sr impurity disorder. New measurements of the low-temperature susceptibility in the SG phase show an increase of an anomalously small Curie constant with doping. This behaviour is explained in terms of our theoretical work that finds small clusters of AFM correlated regions separated by disordered domain walls. The domain walls lead to a percolating sequence of paths connecting the impurities. We predict that for this spin morphology the Curie constant should scale as $1/(2 \xi(x,T=0)^2)$, a result that is quantitatively in agreement with experiment. Also, we find that the magnetic correlations in the ground states in the SG phase are commensurate, and that this behaviour should persist at higher temperatures where the holes should move along the domain walls. However, our results show that incommensurate correlations develop continuously around 5 % doping, consistent with recent measurements by Yamada.Comment: 30 pages, revtex, 8 .ps format figures (2 meant to be in colour), to be published in Physical Review B

Spin Gaps and Bilayer Coupling in YBa2_2Cu3_3O7−δ_{7-\delta} and YBa2_2Cu4_4O8_8

We investigate the relevance to the physics of underdoped YBa$_2$Cu$_3$O$_{\rm 6+x}$ and YBa$_2$Cu$_4$O$_8$ of the quantum critical point which occurs in a model of two antiferromagnetically coupled planes of antiferromagnetically correlated spins. We use a Schwinger boson mean field theory and a scaling analysis to obtain the phase diagram of the model and the temperature and frequency dependence of various susceptibilities and relaxation rates. We distinguish between a low $\omega ,T$ coupled-planes regime in which the optic spin excitations are frozen out and a high $\omega ,T$ decoupled-planes regime in which the two planes fluctuate independently. In the coupled-planes regime the yttrium nuclear relaxation rate at low temperatures is larger relative to the copper and oxygen rates than would be naively expected in a model of uncorrelated planes. Available data suggest that in YBa$_2$Cu$_4$O$_8$ the crossover from the coupled to the decoupled planes regime occurs at $T 700K$ or $T \sim 200K$. The predicted correlation length is of order 6 lattice constants at $T=200K$. Experimental data related to the antiferromagnetic susceptibility of YBa$_2$Cu$_4$O$_8$ may be made consistent with the theory, but available data for the uniform susceptibility are inconsistent with the theory.Comment: RevTex 3.

Dynamic clamp with StdpC software

Dynamic clamp is a powerful method that allows the introduction of artificial electrical components into target cells to simulate ionic conductances and synaptic inputs. This method is based on a fast cycle of measuring the membrane potential of a cell, calculating the current of a desired simulated component using an appropriate model and injecting this current into the cell. Here we present a dynamic clamp protocol using free, fully integrated, open-source software (StdpC, for spike timing-dependent plasticity clamp). Use of this protocol does not require specialist hardware, costly commercial software, experience in real-time operating systems or a strong programming background. The software enables the configuration and operation of a wide range of complex and fully automated dynamic clamp experiments through an intuitive and powerful interface with a minimal initial lead time of a few hours. After initial configuration, experimental results can be generated within minutes of establishing cell recording

Interplay between Kinase Domain Autophosphorylation and F-Actin Binding Domain in Regulating Imatinib Sensitivity and Nuclear Import of BCR-ABL

BACKGROUND: The constitutively activated BCR-ABL tyrosine kinase of chronic myeloid leukemia (CML) is localized exclusively to the cytoplasm despite the three nuclear localization signals (NLS) in the ABL portion of this fusion protein. The NLS function of BCR-ABL is re-activated by a kinase inhibitor, imatinib, and in a kinase-defective BCR-ABL mutant. The mechanism of this kinase-dependent inhibition of the NLS function is not understood. METHODOLOGY/PRINCIPAL FINDINGS: By examining the subcellular localization of mutant BCR-ABL proteins under conditions of imatinib and/or leptomycin B treatment to inhibit nuclear export, we have found that mutations of three specific tyrosines (Y232, Y253, Y257, according to ABL-1a numbering) in the kinase domain can inhibit the NLS function of kinase-proficient and kinase-defective BCR-ABL. Interestingly, binding of imatinib to the kinase-defective tyrosine-mutant restored the NLS function, suggesting that the kinase domain conformation induced by imatinib-binding is critical to the re-activation of the NLS function. The C-terminal region of ABL contains an F-actin binding domain (FABD). We examined the subcellular localization of several FABD-mutants and found that this domain is also required for the activated kinase to inhibit the NLS function; however, the binding to F-actin per se is not important. Furthermore, we found that some of the C-terminal deletions reduced the kinase sensitivity to imatinib. CONCLUSIONS/SIGNIFICANCE: Results from this study suggest that an autophosphorylation-dependent kinase conformation together with the C-terminal region including the FABD imposes a blockade of the BCR-ABL NLS function. Conversely, conformation of the C-terminal region including the FABD can influence the binding affinity of imatinib for the kinase domain. Elucidating the structural interactions among the kinase domain, the NLS region and the FABD may therefore provide insights on the design of next generation BCR-ABL inhibitors for the treatment of CML

Unity through truth

Renewed worries about the unity of the proposition have been taken as a crucial stumbling block for any traditional conception of propositions. These worries are often framed in terms of how entities independent of mind and language can have truth conditions: why is the proposition that Desdemona loves Cassio true if and only if she loves him? I argue that the best understanding of these worries shows that they should be solved by our theory of truth and not our theory of content. Specifically, I propose a version of the redundancy theory according to which ‘it is true that Desdemona loves Cassio’ expresses the same proposition as ‘Desdemona loves Cassio’. Surprisingly, this variant of the redundancy theory treats ‘is true’ as an ordinary predicate of the language, thereby defusing many standard criticisms of the redundancy theory

Neural Basis of Self and Other Representation in Autism: An fMRI Study of Self-Face Recognition

Autism is a developmental disorder characterized by decreased interest and engagement in social interactions and by enhanced self-focus. While previous theoretical approaches to understanding autism have emphasized social impairments and altered interpersonal interactions, there is a recent shift towards understanding the nature of the representation of the self in individuals with autism spectrum disorders (ASD). Still, the neural mechanisms subserving self-representations in ASD are relatively unexplored.We used event-related fMRI to investigate brain responsiveness to images of the subjects' own face and to faces of others. Children with ASD and typically developing (TD) children viewed randomly presented digital morphs between their own face and a gender-matched other face, and made "self/other" judgments. Both groups of children activated a right premotor/prefrontal system when identifying images containing a greater percentage of the self face. However, while TD children showed activation of this system during both self- and other-processing, children with ASD only recruited this system while viewing images containing mostly their own face.This functional dissociation between the representation of self versus others points to a potential neural substrate for the characteristic self-focus and decreased social understanding exhibited by these individuals, and suggests that individuals with ASD lack the shared neural representations for self and others that TD children and adults possess and may use to understand others