A protein-based set of reference markers for liver tissues and hepatocellular carcinoma

Background: During the last decade, investigations have focused on revealing genes or proteins that are involved in HCC carcinogenesis using either genetic or proteomic techniques. However, these studies are overshadowed by a lack of good internal reference standards. The need to identify "housekeeping" markers, whose expression is stable in various experimental and clinical conditions, is therefore of the utmost clinical relevance in quantitative studies. This is the first study employed 2-DE analysis to screen for potential reference markers and aims to correlate the abundance of these proteins with their level of transcript expression. Methods: A Chinese cohort of 224 liver tissues samples (105 cancerous, 103 non-tumourous cirrhotic, and 16 normal) was profiled using 2-DE analysis. Expression of the potential reference markers was confirmed by western blot, immunohistochemistry and real-time quantitative PCR. geNorm algorithm was employed for gene stability measure of the identified reference markers. Results: The expression levels of three protein markers beta-actin (ACTB), heat shock protein 60 (HSP60), and protein disulphide isomerase (PDI) were found to be stable using p-values (p > 0.99) as a ranking tool in all 224 human liver tissues examined by 2-DE analysis. Of high importance, ACTB and HSP 60 were successfully validated at both protein and mRNA levels in human hepatic tissues by western blot, immunohistochemistry and real-time quantitative PCR. In addition, no significant correlation of these markers with any clinicopathological features of HCC and cirrhosis was found. Gene stability measure of these two markers with other conventionally applied housekeeping genes was assessed by the geNorm algorithm, which ranked ACTB and HSP60 as the most stable genes among this cohort of clinical samples. Conclusion: Our findings identified 2 reference markers that exhibited stable expression across human liver tissues with different conditions thus should be regarded as reliable reference moieties for normalisation of gene and protein expression in clinical research employing human hepatic tissues. © 2009 Sun et al; licensee BioMed Central Ltd.published_or_final_versio

Evidence for Two Superconducting Gaps in MgB2MgB_2

We have measured the Raman spectra of polycrystalline MgB$_{2}$ from 25 {\cm} to 1200 {\cm}. When the temperature was decreased below the superconducting transition temperature $T_c$, we observed a superconductivity-induced redistribution in the electronic Raman continuum. Two pair-breaking peaks appear in the spectra, suggesting the presence of two superconducting gaps. Furthermore, we have analyzed the measured spectra using a quasi two-dimensional model in which two s-wave superconducting gaps open on two sheets of Fermi surface. For the gap values we have obtained $\Delta_1 = 22 cm^{-1}$ (2.7 meV) and $\Delta_2 = 50 cm^{-1}$ (6.2 meV). Our results suggest that a conventional phonon-mediated pairing mechanism occurs in the planar boron $\sigma$ bands and is responsible for the superconductivity of MgB$_{2}$.Comment: 3 figure

A glassy contribution to the heat capacity of hcp 4^4He solids

We model the low-temperature specific heat of solid $^4$He in the hexagonal closed packed structure by invoking two-level tunneling states in addition to the usual phonon contribution of a Debye crystal for temperatures far below the Debye temperature, $T < \Theta_D/50$. By introducing a cutoff energy in the two-level tunneling density of states, we can describe the excess specific heat observed in solid hcp $^4$He, as well as the low-temperature linear term in the specific heat. Agreement is found with recent measurements of the temperature behavior of both specific heat and pressure. These results suggest the presence of a very small fraction, at the parts-per-million (ppm) level, of two-level tunneling systems in solid $^4$He, irrespective of the existence of supersolidity.Comment: 11 pages, 4 figure

Functional emulation of high resolution tsunami modelling over Cascadia

he rarity of tsunamis impels the scientific community to rely on numerical simulation for planning and risk assessment purposes because of the low availability of actual data from historic events. Numerical models, also called simulators, typically produce time series of outputs. Due to the large computational cost of such simulators, statistical emulation is required to carry out uncertainty quantification tasks, as emulators efficiently approximate simulators. There is thus a need to create emulators that respect the nature of time series outputs. We introduce here a novel statistical emulation of the input-output dependence of these computer models. We employ the Outer Product Emulator with two enhancements. Functional registration and Functional Principal Components techniques improve the predictions of the emulator. Our phase registration method captures fine variations in amplitude. Smoothness in the time series of outputs is modelled, and we are thus able to select more representative, and more parsimonious, regression functions than a fixed basis method such as a Fourier basis. We apply this approach to the high resolution tsunami wave propagation and coastal inundation for the Cascadia region in the Pacific Northwest. The coseismic representation in this analysis is novel, and more realistic than in previous studies. With the help of the emulator, we can carry out sensitivity analysis of the maximum wave elevation with respect to the source characteristics, and we are able to propagate uncertainties from the source characteristics to wave heights in order to issue probabilistic statements about tsunami hazard for Cascadia

Glide and Superclimb of Dislocations in Solid 4^4He

Glide and climb of quantum dislocations under finite external stress, variation of chemical potential and bias (geometrical slanting) in Peierls potential are studied by Monte Carlo simulations of the effective string model. We treat on unified ground quantum effects at finite temperatures $T$. Climb at low $T$ is assisted by superflow along dislocation core -- {\it superclimb}. Above some critical stress avalanche-type creation of kinks is found. It is characterized by hysteretic behavior at low $T$. At finite biases gliding dislocation remains rough even at lowest $T$ -- the behavior opposite to non-slanted dislocations. In contrast to glide, superclimb is characterized by quantum smooth state at low temperatures even for finite bias. In some intermediate $T$-range giant values of the compressibility as well as non-Luttinger type behavior of the core superfluid are observed.Comment: Updated version submitted to JLTP as QFS2010 proceedings; 11 pages, 6 figure

NIKA: A millimeter-wave kinetic inductance camera

Current generation millimeter wavelength detectors suffer from scaling limits imposed by complex cryogenic readout electronics. To circumvent this it is imperative to investigate technologies that intrinsically incorporate strong multiplexing. One possible solution is the kinetic inductance detector (KID). In order to assess the potential of this nascent technology, a prototype instrument optimized for the 2 mm atmospheric window was constructed. Known as the N\'eel IRAM KIDs Array (NIKA), it was recently tested at the Institute for Millimetric Radio Astronomy (IRAM) 30-meter telescope at Pico Veleta, Spain. The measurement resulted in the imaging of a number of sources, including planets, quasars, and galaxies. The images for Mars, radio star MWC349, quasar 3C345, and galaxy M87 are presented. From these results, the optical NEP was calculated to be around $1 \times 10^{-15}$ W$/$Hz$^{1/2}$. A factor of 10 improvement is expected to be readily feasible by improvements in the detector materials and reduction of performance-degrading spurious radiation.Comment: Accepted for publication in Astronomy & Astrophysic

Quantum Monte Carlo calculations of the one-body density matrix and excitation energies of silicon

Quantum Monte Carlo (QMC) techniques are used to calculate the one-body density matrix and excitation energies for the valence electrons of bulk silicon. The one-body density matrix and energies are obtained from a Slater-Jastrow wave function with a determinant of local density approximation (LDA) orbitals. The QMC density matrix evaluated in a basis of LDA orbitals is strongly diagonally dominant. The natural orbitals obtained by diagonalizing the QMC density matrix resemble the LDA orbitals very closely. Replacing the determinant of LDA orbitals in the wave function by a determinant of natural orbitals makes no significant difference to the quality of the wave function's nodal surface, leaving the diffusion Monte Carlo energy unchanged. The Extended Koopmans' Theorem for correlated wave functions is used to calculate excitation energies for silicon, which are in reasonable agreement with the available experimental data. A diagonal approximation to the theorem, evaluated in the basis of LDA orbitals, works quite well for both the quasihole and quasielectron states. We have found that this approximation has an advantageous scaling with system size, allowing more efficient studies of larger systems.Comment: 13 pages, 4 figures. To appear in Phys. Rev.

Sensitive detection of colorectal cancer in peripheral blood by septin 9 DNA methylation assay

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer deaths despite the fact that detection of this cancer in early stages results in over 90% survival rate. Currently less than 45% of at-risk individuals in the US are screened regularly, exposing a need for better screening tests. We performed two case-control studies to validate a blood-based test that identifies methylated DNA in plasma from all stages of CRC. METHODOLOGY/PRINCIPAL FINDINGS: Using a PCR assay for analysis of Septin 9 (SEPT9) hypermethylation in DNA extracted from plasma, clinical performance was optimized on 354 samples (252 CRC, 102 controls) and validated in a blinded, independent study of 309 samples (126 CRC, 183 controls). 168 polyps and 411 additional disease controls were also evaluated. Based on the training study SEPT9-based classification detected 120/252 CRCs (48%) and 7/102 controls (7%). In the test study 73/126 CRCs (58%) and 18/183 control samples (10%) were positive for SEPT9 validating the training set results. Inclusion of an additional measurement replicate increased the sensitivity of the assay in the testing set to 72% (90/125 CRCs detected) while maintaining 90% specificity (19/183 for controls). Positive rates for plasmas from the other cancers (11/96) and non-cancerous conditions (41/315) were low. The rate of polyp detection (>1 cm) was approximately 20%. CONCLUSIONS/SIGNIFICANCE: Analysis of SEPT9 DNA methylation in plasma represents a straightforward, minimally invasive method to detect all stages of CRC with potential to satisfy unmet needs for increased compliance in the screening population. Further clinical testing is warranted

The Green Bank Northern Celestial Cap Pulsar Survey - I: Survey Description, Data Analysis, and Initial Results

We describe an ongoing search for pulsars and dispersed pulses of radio emission, such as those from rotating radio transients (RRATs) and fast radio bursts (FRBs), at 350 MHz using the Green Bank Telescope. With the Green Bank Ultimate Pulsar Processing Instrument, we record 100 MHz of bandwidth divided into 4,096 channels every 81.92 $\mu s$. This survey will cover the entire sky visible to the Green Bank Telescope ($\delta > -40^\circ$, or 82% of the sky) and outside of the Galactic Plane will be sensitive enough to detect slow pulsars and low dispersion measure ($<$30 $\mathrm{pc\,cm^{-3}}$) millisecond pulsars (MSPs) with a 0.08 duty cycle down to 1.1 mJy. For pulsars with a spectral index of $-$1.6, we will be 2.5 times more sensitive than previous and ongoing surveys over much of our survey region. Here we describe the survey, the data analysis pipeline, initial discovery parameters for 62 pulsars, and timing solutions for 5 new pulsars. PSR J0214$+$5222 is an MSP in a long-period (512 days) orbit and has an optical counterpart identified in archival data. PSR J0636$+$5129 is an MSP in a very short-period (96 minutes) orbit with a very low mass companion (8 $M_\mathrm{J}$). PSR J0645$+$5158 is an isolated MSP with a timing residual RMS of 500 ns and has been added to pulsar timing array experiments. PSR J1434$+$7257 is an isolated, intermediate-period pulsar that has been partially recycled. PSR J1816$+$4510 is an eclipsing MSP in a short-period orbit (8.7 hours) and may have recently completed its spin-up phase.Comment: 18 pages, 10 figures, 5 tables, accepted by Ap

Defects and glassy dynamics in solid He-4: Perspectives and current status

We review the anomalous behavior of solid He-4 at low temperatures with particular attention to the role of structural defects present in solid. The discussion centers around the possible role of two level systems and structural glassy components for inducing the observed anomalies. We propose that the origin of glassy behavior is due to the dynamics of defects like dislocations formed in He-4. Within the developed framework of glassy components in a solid, we give a summary of the results and predictions for the effects that cover the mechanical, thermodynamic, viscoelastic, and electro-elastic contributions of the glassy response of solid He-4. Our proposed glass model for solid He-4 has several implications: (1) The anomalous properties of He-4 can be accounted for by allowing defects to freeze out at lowest temperatures. The dynamics of solid He-4 is governed by glasslike (glassy) relaxation processes and the distribution of relaxation times varies significantly between different torsional oscillator, shear modulus, and dielectric function experiments. (2) Any defect freeze-out will be accompanied by thermodynamic signatures consistent with entropy contributions from defects. It follows that such entropy contribution is much smaller than the required superfluid fraction, yet it is sufficient to account for excess entropy at lowest temperatures. (3) We predict a Cole-Cole type relation between the real and imaginary part of the response functions for rotational and planar shear that is occurring due to the dynamics of defects. Similar results apply for other response functions. (4) Using the framework of glassy dynamics, we predict low-frequency yet to be measured electro-elastic features in defect rich He-4 crystals. These predictions allow one to directly test the ideas and very presence of glassy contributions in He-4.Comment: 33 pages, 13 figure