137 research outputs found
Microscopic mechanisms of spin-dependent electric polarization in 3d oxides
We present a short critical overview of different microscopic models for
nonrelativistic and relativistic magnetoelectric coupling including the
so-called "spin current scenario", ab-initio calculations, and several recent
microscopic approaches to a spin-dependent electric polarization in 3d oxides.Comment: 8 pages, 3 figure
Temperature correction to the Casimir force in cryogenic range and anomalous skin effect
Temperature correction to the Casimir force is considered for real metals at
low temperatures. With the temperature decrease the mean free path for
electrons becomes larger than the field penetration depth. In this condition
description of metals with the impedance of anomalous skin effect is shown to
be more appropriate than with the permittivity. The effect is crucial for the
temperature correction. It is demonstrated that in the zero frequency limit the
reflection coefficients should coincide with those of ideal metal if we demand
the entropy to be zero at T=0. All the other prescriptions discussed in the
literature for the term in the Lifshitz formula give negative entropy. It
is shown that the temperature correction in the region of anomalous skin effect
is not suppressed as it happens in the plasma model. This correction will be
important in the future cryogenic measurements of the Casimir force.Comment: 12 pages, 2 figures, to be published in Phys. Rev.
Survival, pathologic response, and genomics in CALGB 40601 (Alliance), a neoadjuvant Phase III trial of paclitaxel-trastuzumab with or without lapatinib in HER2-positive breast cancer
PURPOSE CALGB 40601 assessed whether dual versus single human epidermal growth factor receptor 2 (HER2) -targeting drugs added to neoadjuvant chemotherapy increased pathologic complete response (pCR). Here, we report relapse-free survival (RFS), overall survival (OS), and gene expression signatures that predict pCR and survival. PATIENTS AND METHODS Three hundred five women with untreated stage II and III HER2-positive breast cancer were randomly assigned to receive weekly paclitaxel combined with trastuzumab plus lapatinib (THL), trastuzumab (TH), or lapatinib (TL). The primary end point was pCR, and secondary end points included RFS, OS, and gene expression analyses. mRNA sequencing was performed on 264 pretreatment samples. RESULTS One hundred eighteen patients were randomly allocated to THL, 120 to TH, and 67 to TL. At more than 7 years of follow-up, THL had significantly better RFS and OS than did TH (RFS hazard ratio, 0.32; 95% CI, 0.14 to 0.71; P 5.005; OS hazard ratio, 0.34; 95% CI, 0.12 to 0.94; P 5.037), with no difference between TH and TL. Of 688 previously described gene expression signatures, significant associations were found in 215 with pCR, 45 with RFS, and only 22 with both pCR and RFS (3.2%). Specifically, eight immune signatures were significantly correlated with a higher pCR rate and better RFS. Among patients with residual disease, the immunoglobulin G signature was an independent, good prognostic factor, whereas the HER2-enriched signature, which was associated with a higher pCR rate, showed a significantly shorter RFS. CONCLUSION In CALGB 40601, dual HER2-targeting resulted in significant RFS and OS benefits. Integration of intrinsic subtype and immune signatures allowed for the prediction of pCR and RFS, both overall and within the residual disease group. These approaches may provide means for rational escalation and de-escalation treatment strategies in HER2-positive breast cancer
Integrated analysis of RNA and DNA from the phase III trial CALGB 40601 identifies predictors of response to trastuzumab-based neoadjuvant chemotherapy in HER2-positive breast cancer
Purpose: Response to a complex trastuzumab-based regimen is affected by multiple features of the tumor and its microenvironment. Developing a predictive algorithm is key to optimizing HER2-targeting therapy. Experimental Design: We analyzed 137 pretreatment tumors with mRNA-seq and DNA exome sequencing from CALGB 40601, a neoadjuvant phase III trial of paclitaxel plus trastuzumab with or without lapatinib in stage II to III HER2-positive breast cancer. We adopted an Elastic Net regularized regression approach that controls for covarying features within high-dimensional data. First, we applied 517 known gene expression signatures to develop an Elastic Net model to predict pCR, which we validated on 143 samples from four independent trials. Next, we performed integrative analyses incorporating clinicopathologic information with somatic mutation status, DNA copy number alterations (CNA), and gene signatures. Results: The Elastic Net model using only gene signatures predicted pCR in the validation sets (AUC ¼ 0.76). Integrative analyses showed that models containing gene signatures, clinical features, and DNA information were better pCR predictors than models containing a single data type. Frequently selected variables from the multiplatform models included amplifications of chromosome 6p, TP53 mutation, HER2-enriched subtype, and immune signatures. Variables predicting resistance included Luminal/ERþ features. Conclusions: Models using RNA only, as well as integrated RNA and DNA models, can predict pCR with improved accuracy over clinical variables. Somatic DNA alterations (mutation, CNAs), tumor molecular subtype (HER2E, Luminal), and the microenvironment (immune cells) were independent predictors of response to trastuzumab and paclitaxel-based regimens. This highlights the complexity of predicting response in HER2-positive breast cancer
Surface-impedance approach solves problems with the thermal Casimir force between real metals
The surface impedance approach to the description of the thermal Casimir
effect in the case of real metals is elaborated starting from the free energy
of oscillators. The Lifshitz formula expressed in terms of the dielectric
permittivity depending only on frequency is shown to be inapplicable in the
frequency region where a real current may arise leading to Joule heating of the
metal. The standard concept of a fluctuating electromagnetic field on such
frequencies meets difficulties when used as a model for the zero-point
oscillations or thermal photons in the thermal equilibrium inside metals.
Instead, the surface impedance permits not to consider the electromagnetic
oscillations inside the metal but taking the realistic material properties into
account by means of the effective boundary condition. An independent derivation
of the Lifshitz-type formulas for the Casimir free energy and force between two
metal plates is presented within the impedance approach. It is shown that they
are free of the contradictions with thermodynamics which are specific to the
usual Lifshitz formula for dielectrics in combination with the Drude model. We
demonstrate that in the impedance approach the zero-frequency contribution is
uniquely fixed by the form of impedance function and does not need any of the
ad hoc prescriptions intensively discussed in the recent literature. As an
example, the computations of the Casimir free energy between two gold plates
are performed at different separations and temperatures. It is argued that the
surface impedance approach lays a reliable framework for the future
measurements of the thermal Casimir force.Comment: 21 pages, 3 figures, to appear in Phys. Rev.
Persistent Spin Currents in Helimagnets
We demonstrate that weak external magnetic fields generate dissipationless
spin currents in the ground state of systems with spiral magnetic order. Our
conclusions are based on phenomenological considerations and on microscopic
mean-field theory calculations for an illustrative toy model. We speculate on
possible applications of this effect in spintronic devices.Comment: 9 pages, 6 figures, updated version as published, Journal referenc
Thermal correction to the Casimir force, radiative heat transfer, and an experiment
The low-temperature asymptotic expressions for the Casimir interaction
between two real metals described by Leontovich surface impedance are obtained
in the framework of thermal quantum field theory. It is shown that the Casimir
entropy computed using the impedance of infrared optics vanishes in the limit
of zero temperature. By contrast, the Casimir entropy computed using the
impedance of the Drude model attains at zero temperature a positive value which
depends on the parameters of a system, i.e., the Nernst heat theorem is
violated. Thus, the impedance of infrared optics withstands the thermodynamic
test, whereas the impedance of the Drude model does not. We also perform a
phenomenological analysis of the thermal Casimir force and of the radiative
heat transfer through a vacuum gap between real metal plates. The
characterization of a metal by means of the Leontovich impedance of the Drude
model is shown to be inconsistent with experiment at separations of a few
hundred nanometers. A modification of the impedance of infrared optics is
suggested taking into account relaxation processes. The power of radiative heat
transfer predicted from this impedance is several times less than previous
predictions due to different contributions from the transverse electric
evanescent waves. The physical meaning of low frequencies in the Lifshitz
formula is discussed. It is concluded that new measurements of radiative heat
transfer are required to find out the adequate description of a metal in the
theory of electromagnetic fluctuations.Comment: 19 pages, 4 figures. svjour.cls is used, to appear in Eur. Phys. J.
Normal and Lateral Casimir Forces between Deformed Plates
The Casimir force between macroscopic bodies depends strongly on their shape
and orientation. To study this geometry dependence in the case of two deformed
metal plates, we use a path integral quantization of the electromagnetic field
which properly treats the many-body nature of the interaction, going beyond the
commonly used pairwise summation (PWS) of van der Waals forces. For arbitrary
deformations we provide an analytical result for the deformation induced change
in Casimir energy, which is exact to second order in the deformation amplitude.
For the specific case of sinusoidally corrugated plates, we calculate both the
normal and the lateral Casimir forces. The deformation induced change in the
Casimir interaction of a flat and a corrugated plate shows an interesting
crossover as a function of the ratio of the mean platedistance H to the
corrugation length \lambda: For \lambda \ll H we find a slower decay \sim
H^{-4}, compared to the H^{-5} behavior predicted by PWS which we show to be
valid only for \lambda \gg H. The amplitude of the lateral force between two
corrugated plates which are out of registry is shown to have a maximum at an
optimal wavelength of \lambda \approx 2.5 H. With increasing H/\lambda \gtrsim
0.3 the PWS approach becomes a progressively worse description of the lateral
force due to many-body effects. These results may be of relevance for the
design and operation of novel microelectromechanical systems (MEMS) and other
nanoscale devices.Comment: 20 pages, 5 figure
Macrophage polarisation affects their regulation of trophoblast behaviour
Introduction
During the first trimester of human pregnancy, fetally-derived extravillous trophoblast (EVT) cells invade into uterine decidua and remodel the uterine spiral arteries to ensure that sufficient blood reaches the maternal-fetal interface. Decidual macrophages have been implicated in the regulation of decidual remodelling and aberrant activation of these immune cells is associated with pre-eclampsia.
Methods
The monocytic cell line THP-1 was activated to induce an M1 or M2 phenotype and the conditioned media was used to treat the EVT cell line SGHPL-4 in order to determine the effect of macrophage polarisation on trophoblast behaviour in-vitro. SGHPL-4 cell functions were assessed using time-lapse microscopy, endothelial-like tube formation assays and western blot.
Results
The polarisation state of the THP-1 cells was found to differentially alter the behaviour of trophoblast cells in-vitro with pro-inflammatory M1 conditioned media significantly inhibiting trophoblast motility, impeding trophoblast tube formation, and inducing trophoblast expression of caspase 3, when compared to anti-inflammatory M2 conditioned media.
Discussion
Macrophages can regulate trophoblast functions that are critical during decidual remodelling in early pregnancy. Importantly, there is differential regulation of trophoblast function in response to the polarisation state of these cells. Our studies indicate that the balance between a pro- and anti-inflammatory environment is important in regulating the cellular interactions at the maternal-fetal interface and that disturbances in this balance likely contribute to pregnancy disorders associated with poor trophoblast invasion and vessel remodelling
Recommended from our members
Technology and Discourse: A Comparison of Face-to-face and Telephone Employment Interviews
Very little research has investigated the comparability of telephone and face-to-face employment interviews. This exploratory study investigated interviewers' questioning strategies and applicants' causal attributions produced during semi structured telephone and face-to-face graduate recruitment interviews (N=62). A total of 2044 causal attributions were extracted from verbatim transcripts of these 62 interviews. It was predicted that an absence of visual cues would lead applicants to produce, and interviewers to focus on, information that might reduce the comparative anonymity of telephone interviews. Results indicate that applicants produce more personal causal attributions in telephone interviews. Personal attributions are also associated with higher ratings in telephone, but not face-to-face interviews. In face-to-face interviews, applicants who attributed outcomes to more global causes received lower ratings. There was also a non-significant tendency for interviewers to ask more closed questions in telephone interviews. The implications of these findings for research and practice are discussed
- …