299 research outputs found
Education in the working-class home: modes of learning as revealed by nineteenth-century criminal records
The transmission of knowledge and skills within the working-class household greatly troubled social commentators and social policy experts during the first half of the nineteenth century. To prove theories which related criminality to failures in working-class up-bringing, experts and officials embarked upon an ambitious collection of data on incarcerated criminals at various penal institutions. One such institution was the County Gaol at Ipswich. The exceptionally detailed information that survives on families, literacy, education and apprenticeships of the men, women and children imprisoned there has the potential to transform our understanding of the nature of home schooling (broadly interpreted) amongst the working classes in nineteenth-century England. This article uses data sets from prison registers to chart both the incidence and ‘success’ of instruction in reading and writing within the domestic environment. In the process, it highlights the importance of schooling in working-class families, but also the potentially growing significance of the family in occupational training
Combined quantitative measures of ER, PR, HER2, and KI67 provide more prognostic information than categorical combinations in luminal breast cancer.
Although most women with luminal breast cancer do well on endocrine therapy alone, some will develop fatal recurrence thereby necessitating the need to prospectively determine those for whom additional cytotoxic therapy will be beneficial. Categorical combinations of immunohistochemical measures of ER, PR, HER2, and KI67 are traditionally used to classify patients into luminal A-like and B-like subtypes for chemotherapeutic reasons, but this may lead to the loss of prognostically relevant information. Here, we compared the prognostic value of quantitative measures of these markers, combined in the IHC4-score, to categorical combinations in subtypes. Using image analysis-based scores for all four markers, we computed the IHC4-score for 2498 patients with luminal breast cancer from two European study populations. We defined subtypes (A-like (ER + and PR + : and HER2- and low KI67) and B-like (ER + and/or PR + : and HER2 + or high KI67)) by combining binary categories of these markers. Hazard ratios and 95% confidence intervals for associations with 10-year breast cancer-specific survival were estimated in Cox proportional-hazard models. We accounted for clinical prognostic factors, including grade, tumor size, lymph-nodal involvement, and age, by using the PREDICT-score. Overall, Subtypes [hazard ratio (95% confidence interval) B-like vs. A-like = 1.64 (1.25-2.14); P-value < 0.001] and IHC4-score [hazard ratio (95% confidence interval)/1 standard deviation = 1.32 (1.20-1.44); P-value < 0.001] were prognostic in univariable models. However, IHC4-score [hazard ratio (95% confidence interval)/1 standard deviation = 1.24 (1.11-1.37); P-value < 0.001; likelihood ratio chi-square (LRχ2) = 12.5] provided more prognostic information than Subtype [hazard ratio (95% confidence interval) B-like vs. A-like = 1.38 (1.02-1.88); P-value = 0.04; LRχ2 = 4.3] in multivariable models. Further, higher values of the IHC4-score were associated with worse prognosis, regardless of subtype (P-heterogeneity = 0.97). These findings enhance the value of the IHC4-score as an adjunct to clinical prognostication tools for aiding chemotherapy decision-making in luminal breast cancer patients, irrespective of subtype
In-Situ Infrared Transmission Study of Rb- and K-Doped Fullerenes
We have measured the four IR active molecular vibrations in
as a function of doping . We observe
discontinuous changes in the vibrational spectra showing four distinct phases
(presumably , and 6). The and modes
show the largest changes shifting downward in frequency in four steps as the
doping increases. Several new very weak modes are visible in the phase
and are possibly Raman modes becoming weakly optically active. We present
quantitative fits of the data and calculate the electron-phonon coupling of the
IR mode.Comment: 3 pages, Figure 1 included, 3 more figures available by request.
REVTEX v3.0 IRC60DO
Electron--Vibron Interactions and Berry Phases in Charged Buckminsterfullerene: Part I
A simple model for electron-vibron interactions on charged
buckminsterfullerene C, , is solved both at weak and
strong couplings. We consider a single vibrational multiplet interacting
with electrons. At strong coupling the semiclassical dynamical
Jahn-Teller theory is valid. The Jahn-Teller distortions are unimodal for
=1,2,4,5 electrons, and bimodal for 3 electrons. The distortions are
quantized as rigid body pseudo--rotators which are subject to geometrical Berry
phases. These impose ground state degeneracies and dramatically change zero
point energies. Exact diagonalization shows that the semiclassical level
degeneracies and ordering survive well into the weak coupling regime. At weak
coupling, we discover an enhancement factor of for the pair binding
energies over their classical values. This has potentially important
implications for superconductivity in fullerides, and demonstrates the
shortcoming of Migdal--Eliashberg theory for molecular crystals.Comment: 29 pages (+7 figures, 3 available upon request), LATEX,
report-number: BM515
Raman Scattering Study of Ba-doped C60 with t1g States
Raman spectra are reported for Ba doped fullerides, BaxC60(x=3,4,and 6). The
lowest frequency Hg modes split into five components for Ba4C60 and Ba6C60 even
at room temperature, allowing us a quantitative analysis based on the
electron-phonon couping theory. For the superconducting Ba4C60, the density of
states at the Fermi energy was derived as 7 eV-1, while the total value of
electron-phonon coupling \lambda was found to be 1.0, which is comparable to
that of K3C60. The tangential Ag(2) mode, which is known as a sensitive probe
for the degree of charge transfer on C60 molecule, shows a remarkable shift
depending on the Ba concentration, being roughly consistent with the full
charge transfer from Ba to C60. An effect of hybridization between Ba and C60
\pi orbitals is also discussed.Comment: 15 pages, 6 figures submitted to Phys. Rev. B (December 1,1998
Renormalization Group Approach to the Coulomb Pseudopotential for C_{60}
A numerical renormalization group technique recently developed by one of us
is used to analyse the Coulomb pseudopotential () in
for a variety of bare potentials. We find a large reduction in due to
intraball screening alone, leading to an interesting non-monotonic dependence
of on the bare interaction strength.
We find that is positive for physically reasonable bare parameters,
but small enough to make the electron-phonon coupling a viable mechanism for
superconductivity in alkali-doped fullerides. We end with some open problems.Comment: 12 pages, latex, 7 figures available from [email protected]
Midinfrared Conductivity in Orientationally Disordered Doped Fullerides
The coupling between the intramolecular vibrational modes and the doped
conduction electrons in is studied by a calculation of the
electronic contributions to the phonon self energies. The calculations are
carried out for an orientationally ordered reference solid with symmetry and for a model with quenched orientational disorder on the
fullerene sites. In both cases, the dispersion and symmetry of the renormalized
modes is governed by the electronic contributions. The current current
correlation functions and frequency dependent conductivity through the
midinfrared are calculated for both models. In the disordered structures, the
renormalized modes derived from even parity intramolecular phonons are resonant
with the dipole excited single particle spectrum, and modulate the predicted
midinfrared conductivity. The spectra for this coupled system are calculated
for several recently proposed microscopic models for the electron phonon
coupling, and a comparison is made with recent experimental data which
demonstrate this effect.Comment: 32 pages + 9 postscript figures (on request), REVTeX 3.
Superconductivity in Fullerides
Experimental studies of superconductivity properties of fullerides are
briefly reviewed. Theoretical calculations of the electron-phonon coupling, in
particular for the intramolecular phonons, are discussed extensively. The
calculations are compared with coupling constants deduced from a number of
different experimental techniques. It is discussed why the A_3 C_60 are not
Mott-Hubbard insulators, in spite of the large Coulomb interaction. Estimates
of the Coulomb pseudopotential , describing the effect of the Coulomb
repulsion on the superconductivity, as well as possible electronic mechanisms
for the superconductivity are reviewed. The calculation of various properties
within the Migdal-Eliashberg theory and attempts to go beyond this theory are
described.Comment: 33 pages, latex2e, revtex using rmp style, 15 figures, submitted to
Review of Modern Physics, more information at
http://radix2.mpi-stuttgart.mpg.de/fullerene/fullerene.htm
Integrative analyses identify modulators of response to neoadjuvant aromatase inhibitors in patients with early breast cancer
Introduction
Aromatase inhibitors (AIs) are a vital component of estrogen receptor positive (ER+) breast cancer treatment. De novo and acquired resistance, however, is common. The aims of this study were to relate patterns of copy number aberrations to molecular and proliferative response to AIs, to study differences in the patterns of copy number aberrations between breast cancer samples pre- and post-AI neoadjuvant therapy, and to identify putative biomarkers for resistance to neoadjuvant AI therapy using an integrative analysis approach.
Methods
Samples from 84 patients derived from two neoadjuvant AI therapy trials were subjected to copy number profiling by microarray-based comparative genomic hybridisation (aCGH, n = 84), gene expression profiling (n = 47), matched pre- and post-AI aCGH (n = 19 pairs) and Ki67-based AI-response analysis (n = 39).
Results
Integrative analysis of these datasets identified a set of nine genes that, when amplified, were associated with a poor response to AIs, and were significantly overexpressed when amplified, including CHKA, LRP5 and SAPS3. Functional validation in vitro, using cell lines with and without amplification of these genes (SUM44, MDA-MB134-VI, T47D and MCF7) and a model of acquired AI-resistance (MCF7-LTED) identified CHKA as a gene that when amplified modulates estrogen receptor (ER)-driven proliferation, ER/estrogen response element (ERE) transactivation, expression of ER-regulated genes and phosphorylation of V-AKT murine thymoma viral oncogene homolog 1 (AKT1).
Conclusions
These data provide a rationale for investigation of the role of CHKA in further models of de novo and acquired resistance to AIs, and provide proof of concept that integrative genomic analyses can identify biologically relevant modulators of AI response
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