2,077 research outputs found
Mining whole sample mass spectrometry proteomics data for biomarkers: an overview
In this paper we aim to provide a concise overview of designing and conducting an MS proteomics experiment in such a way as to allow statistical analysis that may lead to the discovery of novel biomarkers. We provide a summary of the various stages that make up such an experiment, highlighting the need for experimental goals to be decided upon in advance. We discuss issues in experimental design at the sample collection stage, and good practise for standardising protocols within the proteomics laboratory. We then describe approaches to the data mining stage of the experiment, including the processing steps that transform a raw mass spectrum into a useable form. We propose a permutation-based procedure for determining the significance of reported error rates. Finally, because of its general advantages in speed and cost, we suggest that MS proteomics may be a good candidate for an early primary screening approach to disease diagnosis, identifying areas of risk and making referrals for more specific tests without necessarily making a diagnosis in its own right. Our discussion is illustrated with examples drawn from experiments on bovine blood serum conducted in the Centre for Proteomic Research (CPR) at Southampton University
Anisotropy Reversal of the Upper Critical Field at Low Temperatures and Spin-Locked Superconductivity in K2Cr3As3
We report the first measurements of the anisotropic upper critical field
for KCrAs single crystals up to 60 T and K. Our results show that the upper critical field parallel to the Cr
chains, , exhibits a paramagnetically-limited behavior,
whereas the shape of the curve (perpendicular to the Cr
chains) has no evidence of paramagnetic effects. As a result, the curves
and cross at K, so that
the anisotropy parameter
increases from near to at 0.6 K. This behavior of is inconsistent with triplet
superconductivity but suggests a form of singlet superconductivity with the
electron spins locked onto the direction of Cr chains
Recent Developments in Targeting Carbonic Anhydrase IX for Cancer Therapeutics
Carbonic anhydrase IX (CAIX) is a hypoxia-inducible enzyme that is overexpressed by cancer cells from many tumor types, and is a component of the pH regulatory system invoked by these cells to combat the deleterious effects of a high rate of glycolytic metabolism. CAIX functions to help produce and maintain an intracellular pH (pHi) favorable for tumor cell growth and survival, while at the same time participating in the generation of an increasingly acidic extracellular space, facilitating tumor cell invasiveness. Pharmacologic interference of CAIX catalytic activity using monoclonal antibodies or CAIX-specific small molecule inhibitors, consequently disrupting pH regulation by cancer cells, has been shown recently to impair primary tumor growth and metastasis. Many of these agents are in preclinical or clinical development and constitute a novel, targeted strategy for cancer therapy
On the metallicity dependence of crystalline silicates in oxygen-rich asymptotic giant branch stars and red supergiants
We investigate the occurrence of crystalline silicates in oxygen-rich evolved
stars across a range of metallicities and mass-loss rates. It has been
suggested that the crystalline silicate feature strength increases with
increasing mass-loss rate, implying a correlation between lattice structure and
wind density. To test this, we analyse Spitzer IRS and Infrared Space
Observatory SWS spectra of 217 oxygen-rich asymptotic giant branch stars and 98
red supergiants in the Milky Way, the Large and Small Magellanic Clouds and
Galactic globular clusters. These encompass a range of spectral morphologies
from the spectrally-rich which exhibit a wealth of crystalline and amorphous
silicate features to 'naked' (dust-free) stars. We combine spectroscopic and
photometric observations with the GRAMS grid of radiative transfer models to
derive (dust) mass-loss rates and temperature. We then measure the strength of
the crystalline silicate bands at 23, 28 and 33 microns. We detect crystalline
silicates in stars with dust mass-loss rates which span over 3 dex, down to
rates of ~10^-9 solar masses/year. Detections of crystalline silicates are more
prevalent in higher mass-loss rate objects, though the highest mass-loss rate
objects do not show the 23-micron feature, possibly due to the low temperature
of the forsterite grains or it may indicate that the 23-micron band is going
into absorption due to high column density. Furthermore, we detect a change in
the crystalline silicate mineralogy with metallicity, with enstatite seen
increasingly at low metallicity.Comment: Accepted for publication in MNRAS, 24 pages, 16 figure
Quantifying Proton Fields for Midline Brain Tumors: A Benefit/Cost Analysis of Planning Objectives
Purpose:
We sought to quantify the optimum number of beams by using a midline sagittal arrangement for midline brain tumors when considering the competing demands of a high degree of target conformation and maximizing reduction of nontarget brain dose. The volume of nontarget brain tissue receiving between 5 and 20 Gy (V5-V20) was selected to measure "low-dose bath" to normal brain.
Materials and Methods:
An exploratory model was developed with 6 midline brain targets created by using spheres of 1-, 3-, and 5-cm diameters located in superficial and deep locations. For each, five 3-dimensional proton treatment plans with uniform beam scanning were generated by using 1 to 5 fields. Dose-volume histograms were analyzed to calculate conformation number and V5-V20. A benefit/cost analysis was performed to determine the marginal gain in conformation number and the marginal cost of V5-V20 for the addition of each field and hypothesize the optimum number of treatment fields. We tested our hypothesis by re-planning 10 actual patient tumors with the same technique to compare the averages of these 50 plans to our model.
Results:
Our model and validation cohort demonstrated the largest marginal benefit in target conformation and the lowest marginal cost in normal brain V5-V20 with the addition of a second proton field. The addition of a third field resulted in a relative marginal benefit in target conformation of just 3.9% but a relative marginal cost in V5-V20 of 78.7%. Normal brain absolute V5-V20 increased in a nearly linear fashion with each additional field.
Conclusions:
When treating midline brain lesions with 3-dimensional proton therapy in an array of midline sagittal beams, our model suggests the most appropriate number of fields is 2. There was little marginal benefit in target conformation and increasing cost of normal brain dose when increasing the number of fields beyond this
A Bright Solitonic Matter-Wave Interferometer
We present the first realisation of a solitonic atom interferometer. A
Bose-Einstein condensate of atoms of rubidium-85 is loaded into a
horizontal optical waveguide. Through the use of a Feshbach resonance, the
-wave scattering length of the Rb atoms is tuned to a small negative
value. This attractive atomic interaction then balances the inherent
matter-wave dispersion, creating a bright solitonic matter wave. A Mach-Zehnder
interferometer is constructed by driving Bragg transitions with the use of an
optical lattice co-linear with the waveguide. Matter wave propagation and
interferometric fringe visibility are compared across a range of -wave
scattering values including repulsive, attractive and non-interacting values.
The solitonic matter wave is found to significantly increase fringe visibility
even compared with a non-interacting cloud.Comment: 6 pages, 4 figure
Integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization
Integrin-linked kinase (ILK) is a serine-threonine kinase and scaffold protein with well defined roles in focal adhesions in integrin-mediated cell adhesion, spreading, migration, and signaling. Using mass spectrometry–based proteomic approaches, we identify centrosomal and mitotic spindle proteins as interactors of ILK. α- and β-tubulin, ch-TOG (XMAP215), and RUVBL1 associate with ILK and colocalize with it to mitotic centrosomes. Inhibition of ILK activity or expression induces profound apoptosis-independent defects in the organization of the mitotic spindle and DNA segregation. ILK fails to localize to the centrosomes of abnormal spindles in RUVBL1-depleted cells. Additionally, depletion of ILK expression or inhibition of its activity inhibits Aurora A–TACC3/ch-TOG interactions, which are essential for spindle pole organization and mitosis. These data demonstrate a critical and unexpected function for ILK in the organization of centrosomal protein complexes during mitotic spindle assembly and DNA segregation
Magnetic quantum oscillations in YBaCuO and YBaCuO in fields of up to 85 T; patching the hole in the roof of the superconducting dome
We measure magnetic quantum oscillations in the underdoped cuprates
YBaCuO with , 0.69, using fields of up to 85 T. The
quantum-oscillation frequencies and effective masses obtained suggest that the
Fermi energy in the cuprates has a maximum at . On either
side, the effective mass may diverge, possibly due to phase transitions
associated with the T=0 limit of the metal-insulator crossover (low- side),
and the postulated topological transition from small to large Fermi surface
close to optimal doping (high side)
A quantum sensor: simultaneous precision gravimetry and magnetic gradiometry with a Bose-Einstein condensate
A Bose-Einstein condensate is used as an atomic source for a high precision
sensor. A atom F=1 spinor condensate of Rb is released
into free fall for up to ms and probed with a Mach-Zehnder atom
interferometer based on Bragg transitions. The Bragg interferometer
simultaneously addresses the three magnetic states, , facilitating a simultaneous measurement of the acceleration due
to gravity with an asymptotic precision of g/g and
the magnetic field gradient to a precision pT/m
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