5,679 research outputs found
Phosphatidylinositol 3-kinase pathway genomic alterations in 60,991 diverse solid tumors informs targeted therapy opportunities.
BackgroundThe phosphatidylinositol 3-kinase (PI3K) pathway is frequently altered in cancer. This report describes the landscape of PI3K alterations in solid tumors as well as co-alterations serving as potential resistance/attenuation mechanisms.MethodsConsecutive samples were analyzed in a commercial Clinical Laboratory Improvement Amendment-certified laboratory using comprehensive genomic profiling performed by next-generation sequencing (315 genes). The co-alterations evaluated included the Erb-B2 receptor tyrosine kinase 2 (ERBB2), ERBB3, ERBB4, RAS, MET proto-oncogene tyrosine kinase (MET), and mitogen-activated protein kinase kinase (MAP2K) genes as well as tumor protein 53 (TP53), estrogen receptor 1 (ESR1), and androgen receptor (AR).ResultsAlterations in any of 18 PI3K-pathway associated genes were identified in 44% of 60,991 tumors. Although single base and insertions/deletions (indels) were the most frequent alterations, copy number changes and rearrangements were identified in 11% and 0.9% of patients, respectively. Overall, the most frequently altered genes were PIK3 catalytic subunit α (PIK3CA) (13%), phosphatase and tensin homolog (PTEN) (9%), and serine/threonine kinase 11 (STK11) (5%). Tumor types that frequently harbored at least 1 PI3K alteration were uterine (77%), cervical (62%), anal (59%), and breast (58%) cancers. Alterations also were discerned frequently in tumors with carcinosarcoma (89%) and squamous cell carcinoma (62%) histologies. Tumors with a greater likelihood of co-occurring PI3K pathway and MAPK pathway alterations included colorectal cancers (odds ratio [OR], 1.64; P < .001), mesotheliomas (OR, 2.67; P = .024), anal cancers (OR, 1.98; P = .03), and nonsquamous head and neck cancers (OR, 2.03; P = .019). The co-occurrence of ESR1 and/or AR alterations with PI3K alterations was statistically significant in bladder, colorectal, uterine, prostate, and unknown primary cancers.ConclusionsComprehensive genomic profiling reveals altered PI3K-related genes in 44% of solid malignancies, including rare disease and histology types. The frequency of alterations and the co-occurrence of resistance pathways vary by tumor type, directly affecting opportunities for targeted therapy
Strategic decision making in a management game : an experimental study of objective setting and consistency in complex decision making
The relation of internal communication and R&D project performance as a function of position in the R&D spectrum
"The research reported in this paper was supported by a grant (SIS75-11829) from the Division of Science Information, National Science Foundation.
Bulk high-Tc superconductors with drilled holes: how to arrange the holes to maximize the trapped magnetic flux ?
Drilling holes in a bulk high-Tc superconductor enhances the oxygen annealing
and the heat exchange with the cooling liquid. However, drilling holes also
reduces the amount of magnetic flux that can be trapped in the sample. In this
paper, we use the Bean model to study the magnetization and the current line
distribution in drilled samples, as a function of the hole positions. A single
hole perturbs the critical current flow over an extended region that is bounded
by a discontinuity line, where the direction of the current density changes
abruptly. We demonstrate that the trapped magnetic flux is maximized if the
center of each hole is positioned on one of the discontinuity lines produced by
the neighbouring holes. For a cylindrical sample, we construct a polar
triangular hole pattern that exploits this principle; in such a lattice, the
trapped field is ~20% higher than in a squared lattice, for which the holes do
not lie on discontinuity lines. This result indicates that one can
simultaneously enhance the oxygen annealing, the heat transfer, and maximize
the trapped field
Bloch-Nordsieck Violation in Spontaneously Broken Abelian Theories
We point out that, in a spontaneously broken U(1) gauge theory, inclusive
processes, whose primary particles are mass eigenstates that do not coincide
with the gauge eigenstates, are not free of infrared logarithms. The charge
mixing allowed by symmetry breaking and the ensuing Bloch-Nordsieck violation
are here analyzed in a few relevant cases and in particular for processes
initiated by longitudinal gauge bosons. Of particular interest is the example
of weak hypercharge in the Standard Model where, in addition, left-right mixing
effects arise in transversely polarized fermion beams.Comment: 4 pages, 1 figur
Simulations of electromagnetic effects in high frequency capacitively coupled discharges using the Darwin approximation
The Darwin approximation is investigated for its possible use in simulation
of electromagnetic effects in large size, high frequency capacitively coupled
discharges. The approximation is utilized within the framework of two different
fluid models which are applied to typical cases showing pronounced standing
wave and skin effects. With the first model it is demonstrated that Darwin
approximation is valid for treatment of such effects in the range of parameters
under consideration. The second approach, a reduced nonlinear Darwin
approximation-based model, shows that the electromagnetic phenomena persist in
a more realistic setting. The Darwin approximation offers a simple and
efficient way of carrying out electromagnetic simulations as it removes the
Courant condition plaguing explicit electromagnetic algorithms and can be
implemented as a straightforward modification of electrostatic algorithms. The
algorithm described here avoids iterative schemes needed for the divergence
cleaning and represents a fast and efficient solver, which can be used in fluid
and kinetic models for self-consistent description of technical plasmas
exhibiting certain electromagnetic activity
The ePetri dish, an on-chip cell imaging platform based on subpixel perspective sweeping microscopy (SPSM)
We report a chip-scale lensless wide-field-of-view microscopy imaging technique, subpixel perspective sweeping microscopy, which can render microscopy images of growing or confluent cell cultures autonomously. We demonstrate that this technology can be used to build smart Petri dish platforms, termed ePetri, for cell culture experiments. This technique leverages the recent broad and cheap availability of high performance image sensor chips to provide a low-cost and automated microscopy solution. Unlike the two major classes of lensless microscopy methods, optofluidic microscopy and digital in-line holography microscopy, this new approach is fully capable of working with cell cultures or any samples in which cells may be contiguously connected. With our prototype, we demonstrate the ability to image samples of area 6 mm × 4 mm at 660-nm resolution. As a further demonstration, we showed that the method can be applied to image color stained cell culture sample and to image and track cell culture growth directly within an incubator. Finally, we showed that this method can track embryonic stem cell differentiations over the entire sensor surface. Smart Petri dish based on this technology can significantly streamline and improve cell culture experiments by cutting down on human labor and contamination risks
Bloch-Nordsieck violating electroweak corrections to inclusive TeV scale hard processes
We point out that, since the colliders initial states (e+ e-,p p, p pbar, ...
) carry a definite nonabelian flavor, electroweak radiative corrections to
inclusive hard cross sections at the TeV scale are affected by peculiar
Bloch-Nordsieck violating double logs. We recall the setup of soft cancellation
theorems, and we analyze the magnitude of the noncancelling terms in the
example of electron - positron annihilation into hadrons.Comment: Minor typos corrected, references added. Final version to appear on
Phys. Rev. Let
Heat Capacity and Thermal Conductance Measurements of a Superconducting-Normal Mixed State by Detection of Single 3 eV Photons in a Magnetic Penetration Thermometer
We report on measurements of the detected signal pulses in a molybdenum-gold Magnetic Penetration Thermometer (MPT) in response to absorption of one or more 3 eV photons. We designed and used this MPT sensor for x-ray microcalorimetry. In this device, the diamagnetic response of a superconducting MoAu bilayer is used to sense temperature changes in response to absorbed photons, and responsivity is enhanced by a Meissner transition in which the magnetic flux penetrating the sensor changes rapidly to minimize free energy in a mixed superconducting normal state. We have previously reported on use of our MPT to study a thermal phonon energy loss to the substrate when absorbing x-rays. We now describe results of extracting heat capacity C and thermal conductance G values from pulse height and decay time of MPT pulses generated by 3 eV photons. The variation in C and G at temperatures near the Meissner transition temperature (set by an internal magnetic bias field) allow us to probe the behavior in superconducting normal mixed state of the condensation energy and the electron cooling power resulting from quasi-particle recombination and phonon emission. The information gained on electron cooling power is also relevant to the operation of other superconducting detectors, such as Microwave Kinetic Inductance Detectors
Interaction-induced Bose Metal in 2D
We show here that the regularization of the conductivity resulting from the
bosonic interactions on the `insulating' (quantum disordered) side of an
insulator-superconductor transition in 2D gives rise to a metal with a finite
conductivity, , as temperature tends to zero. The Bose
metal is stable to weak disorder and hence represents a concrete example of an
interaction-induced metallic phase. Phenomenological inclusion of dissipation
reinstates the anticipated insulating behaviour in the quantum-disordered
regime. Hence, we conclude that the traditionally-studied
insulator-superconductor transition, which is driven solely by quantum
fluctuations, corresponds to a superconductor-metal transition. The possible
relationship to experiments on superconducting thin films in which a
low-temperature metallic phase has been observed is discussed.Comment: A figure has been added and the physics has been clarified. To appear
in PR
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