Temperature dependence of micelle shape transitions in copolymer solutions: the role of inter-block incompatibility.

The nature of the transition between worm-like and spherical micelles in block copolymer dispersions varies between systems. In some formulations, heating drives a transition from worms to spheres, while in other systems the same transition is induced by cooling. In addition, a sphere-worm interconversion can be accompanied either by an increase or a decrease in the core solvation, even if the direction of the temperature dependence is the same. Here, self-consistent field theory is used to provide a potential explanation of this range of behaviour. Specifically, we show that, within this model, the dependence of the transition on the incompatibility χBS of the solvophobic block B and the solvent S (the parameter most closely related to the temperature) is strongly influenced by the incompatibility χAB between B and the solvophilic block A. When χAB is small (χAB < 0.1), it is found that increasing χBS produces a transition from worm-like micelles to spheres (or, more generally, from less curved to more curved structures). When χAB is above 0.1, increasing χBS drives the system from spheres to worm-like micelles. Whether a transition is observed within a realistic range of χBS is also found to depend on the fraction of solvophilic material in the copolymer. The relevance of our calculations to experiments is discussed, and we suggest that the direction of the temperature dependence may be controlled not only by the solution behaviour of the solvophobic block (upper critical solution temperature-like versus lower critical solution temperature-like) but also by χAB.

Heterotelechelic homopolymers mimicking high χ - ultralow N block copolymers with sub-2 nm domain size.

Three fluorinated, hydrophobic initiators have been utilised for the synthesis of low molecular mass fluoro-poly(acrylic acid) heterotelechelic homopolymers to mimic high chi (χ)-low N diblock copolymers with ultrafine domains of sub-2 nm length scale. Polymers were obtained by a simple photoinduced copper(ii)-mediated reversible-deactivation radical polymerisation (Cu-RDRP) affording low molecular mass (<3 kDa) and low dispersity (D = 1.04-1.21) homopolymers. Heating/cooling ramps were performed on bulk samples (ca. 250 µm thick) to obtain thermodynamically stable nanomorpologies of lamellar (LAM) or hexagonally packed cylinders (HEX), as deduced by small-angle X-ray scattering (SAXS). Construction of the experimental phase diagram alongside a detailed theoretical model demonstrated typical rod-coil block copolymer phase behaviour for these fluoro-poly(acrylic acid) homopolymers, where the fluorinated initiator-derived segment acts as a rod and the poly(acrylic acid) as a coil. This work reveals that these telechelic homopolymers mimic high χ-ultralow N diblock copolymers and enables reproducible targeting of nanomorphologies with incredibly small, tunable domain size.

Micelle shape transitions in block copolymer/homopolymer blends: comparison of self-consistent field theory with experiment.

Diblock copolymers blended with homopolymer may self-assemble into spherical, cylindrical, or lamellar aggregates. Transitions between these structures may be driven by varying the homopolymer diblock molecular weight or composition. Using self-consistent field theory (SCFT), we reproduce these effects. Our results are compared to x-ray scattering and transmission electron microscopy measurements by Kinning et al. and good agreement is found, although the tendency to form cylindrical and lamellar structures is sometimes overestimated due to our neglect of edge effects due to the finite size of these aggregates. Our results demonstrate that SCFT can provide detailed information on the self-assembly of isolated block copolymer aggregates.

Crossover behavior and multistep relaxation in a schematic model of the cut-off glass transition.

We study a schematic mode-coupling model in which the ideal glass transition is cut off by a decay of the quadratic coupling constant in the memory function. (Such a decay, on a time scale tau I , has been suggested as the likely consequence of activated processes.) If this decay is complete, so that only a linear coupling remains at late times, then the alpha relaxation shows a temporal crossover from a relaxation typical of the unmodified schematic model to a final strongly slower-than-exponential relaxation. This crossover, which differs somewhat in form from previous schematic models of the cutoff glass transition, resembles light-scattering experiments on colloidal systems, and can exhibit a "slower-than- alpha " relaxation feature hinted at there. We also consider what happens when a similar but incomplete decay occurs, so that a significant level of quadratic coupling remains for t>>tau I . In this case the correlator acquires a third, weaker relaxation mode at intermediate times. This empirically resembles the beta process seen in many molecular glass formers. It disappears when the initial as well as the final quadratic coupling lies on the liquid side of the glass transition, but remains present even when the final coupling is only just inside the liquid (so that the alpha relaxation time is finite, but too long to measure). Our results are suggestive of how, in a cutoff glass, the underlying "ideal" glass transition predicted by mode-coupling theory can remain detectable through qualitative features in dynamics.

Glass transition in fullerenes: mode-coupling theory predictions.

We report idealized mode-coupling theory results for the glass transition of ensembles of model fullerenes interacting via phenomenological two-body potentials. Transition lines are found for C60, C70, and C96 in the temperature-density plane. We argue that the observed glass transition behavior is indicative of kinetic arrest that is strongly driven by the interparticle attraction in addition to excluded-volume repulsion. In this respect, these systems differ from most standard glass-forming liquids. They feature arrest that occurs at lower densities and that is stronger than would be expected for repulsion-dominated hard-sphere-like or Lennard-Jones-type systems. The influence of attraction increases with increasing the number of carbon atoms per molecule. However, unrealistically large fullerenes would be needed to yield behavior reminiscent of recently investigated model colloids with strong short-ranged attraction (glass-glass transitions and logarithmic decay of time-correlation functions).

Sensitivity of arrest in mode-coupling glasses to low-q structure.

We quantify, within mode coupling theory, how changes in the liquid structure affect that of the glass. Apart from the known sensitivity to the structure factor S(q) at wave vectors around the first sharp diffraction peak q0, we find a strong (and inverted) response to structure at wave vectors below this peak: an increase in S(q0/2) lowers the degree of arrest over a wide q-range. This strong sensitivity to "caged cage" packing effects, on length scales of order 2d, is much weaker in attractive glasses where short-range bonding dominates the steric caging effect.

Langer's axillary arch: anatomy, embryological features and surgical implications.

Langer's arch is identified in up to 7% of axillary explorations; in a three-month period we identified three individuals among forty-six patients undergoing axillary surgery with this abnormality. Langer's arch is a muscular-tendinous structure that usually extends from latissimus dorsi to pectoralis major muscle. The purpose of this article is to describe the embryological derivation of this muscular variant from the panniculus carnosus and to define its anatomical features. The clinical implications both symptomatically and as an unexpected finding during axillary dissection, are also discussed.

Interfacial structure at a two-dimensional wedge filling transition: Exact results and a renormalization group study.

Interfacial structure and correlation functions near a two-dimensional wedge filling transition are studied using effective interfacial Hamiltonian models. An exact solution for short range binding potentials and results for Kratzer binding potentials show that sufficiently close to the filling transition a new length scale emerges and controls the decay of the interfacial profile relative to the substrate and the correlations between interfacial positions above different positions. This new length scale is much larger than the intrinsic interfacial correlation length, and it is related geometrically to the average value of the interfacial position above the wedge midpoint. The interfacial behavior is consistent with a breather mode fluctuation picture, which is shown to emerge from an exact decimation functional renormalization group scheme that keeps the geometry invariant.

Fluid adsorption near an apex: covariance between complete and critical wetting.

Critical wetting is an elusive phenomenon for solid-fluid interfaces. Using interfacial models we show that the diverging length scales, which characterize complete wetting at an apex, precisely mimic critical wetting with the apex angle behaving as the contact angle. Transfer matrix, renormalization group, and mean-field analysis show that this covariance is obeyed in 2D and 3D and for long- and short-ranged forces. This connection should be experimentally accessible and provides a means of checking theoretical predictions for critical wetting.

A mammographic dilemma: calcification or haemosiderin as a cause of opacities? Validation of a new digital diagnostic tool.

Core biopsies of an area of microcalcification demonstrated large collections of macrophages containing haemosiderin, with evidence of minimal microcalcification on H&E staining. Algorithms were developed that were capable of differentiating with high accuracy those signs due to calcification, using quantitative measurements such as the apparent volume composition of calcium. Using the linear attenuation coefficients of calcification and assuming an ellipsoid model for the 3-dimensional shape of calcification, we computed the relative calcification volume for each region of interest. The difference in the linear attenuation coefficients of iron and calcification allowed the two to be differentiated on a mammogram based on this measure of relative calcification volume.

Upregulation of basic fibroblast growth factor in breast carcinoma and its relationship to vascular density, oestrogen receptor, epidermal growth factor receptor and survival.

BACKGROUND: Angiogenesis, the process whereby endothelial cells divide and migrate to form new blood capillaries, has been assessed in tumours by measuring microvessel density. High microvessel density is a significant adverse prognostic factor in breast cancer. The angiogenic factor, basic fibroblast growth factor (bFGF), has been associated with tumourigenesis and metastasis in several human cancers. There are few quantitative studies of bFGF expression in normal tissues compared to cancer. PATIENTS AND METHODS: We have measured bFGF levels in 149 human primary breast carcinomas and assessed the findings in relation to microvessel density, oestrogen receptor (ER) and epidermal growth factor receptor (EGFR). Basic FGF levels were measured by ELISA. Western blotting and immunohistochemistry were carried out to confirm the presence of bFGF. RESULTS: Levels of bFGF were more than 10-fold higher in tumour cytosols compared to reduction mammoplasty tissue and 3-fold compared to non neoplastic cytosols from the same breast as the tumour (P < 0.0001). Immunohistochemistry showed bFGF protein was localised exclusively in the stroma whereas no bFGF staining was observed in the epithelial cells. High bFGF levels were significantly related to high ER (P = 0.01). Similarly, high bFGF levels were significantly related to low grade (P = 0.046) and to small tumour size (P = 0.04). No significant relationship was observed between bFGF and microvessel count, EGFR or age. In univariate analysis and in a Cox proportional hazard model bFGF did not reach significance for overall or relapse free survival. CONCLUSIONS: Our results show that although bFGF is elevated in breast carcinomas compared to normal breast tissue it is not related to microvessel density and it is not an independent predictor of survival in breast cancer patients. Basic FGF may be one of multiple factors that synergise with other growth factors such as VEGF to enhance angiogenesis.

The activity of HMG-CoA reductase and acetyl-CoA carboxylase in human apocrine sweat glands, sebaceous glands, and hair follicles is regulated by phosphorylation and by exogenous cholesterol.

Human apocrine and sebaceous glands function to secrete lipids, predominantly triglycerides, fatty acids, cholesterol and its esters, and, in the sebaceous gland, squalene. The enzymes that catalyze the important regulatory steps in cholesterol and fatty acid biosyntheses, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and acetyl-CoA carboxylase, respectively, were therefore studied in isolated human skin appendages, and their relevant kinetic parameters determined. The enzyme activities that were observed can account for previously described rates of incorporation of radiolabeled substrates into the appropriate lipids by glands in vitro. Reduced enzyme activities following homogenization in the presence of fluoride indicated that both of these enzymes in skin appendages are inactivated by phosphorylation. The activity of the enzyme known to catalyze this phosphorylation, the AMP-activated protein kinase, was also measured. Compactin was shown to inhibit HMG-CoA reductase in homogenates of these appendages. Conversely, incubation of whole sebaceous glands with compactin resulted in the stimulation of enzyme activity, which suggests that these appendages can respond to diminishing cholesterol levels. The effect of exogenous low density lipoprotein and 25-hydroxycholesterol on HMG-CoA reductase activity from skin appendages was investigated. HMG-CoA reductase activity in both apocrine and sebaceous glands was reduced following incubation with either low density lipoprotein or 25-hydroxycholesterol. Low density lipoprotein receptor and lipoprotein lipase mRNA expression was also detected in skin appendages. These results indicate that apocrine and sebaceous glands have the capacity to sequester dietary cholesterol and fatty acids that may have important implications for the understanding of both acne and axillary odor.

Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma.

Angiogenesis is a key process in tumor growth and metastasis and is a major independent prognostic factor in breast cancer. A range of cytokines stimulate the tumor neovasculature, and tumor-associated macrophages have been shown recently to produce several important angiogenic factors. We have quantified macrophage infiltration using Chalkley count morphometry in a series of invasive breast carcinomas to investigate the relationship between tumor-associated macrophage infiltration and tumor angiogenesis, and prognosis. There was a significant positive correlation between high vascular grade and increased macrophage index (P = 0.03), and a strong relationship was observed between increased macrophage counts and reduced relapse-free survival (P = 0.006) and reduced overall survival (P = 0.004) as an independent prognostic variable. These data indicate a role for macrophages in angiogenesis and prognosis in breast cancer and that this cell type may represent an important target for immunoinhibitory therapy in breast cancer.

The epidermal growth factor receptor as a prognostic marker: results of 370 patients and review of 3009 patients.

Epidermal growth factor receptor (EGFR) and estrogen receptor (ER) were assayed by ligand binding in tumors from 370 patients with primary breast carcinoma with a median follow up of 18 months. Forty seven percent (175/370) and 57% (210/370) of tumors had > 20 fmol/mg and > 10 fmol/mg of EGFR and ER respectively. There was a highly significant inverse relationship between EGFR and ER (p = 0.0032). There was also a significant association between EGFR and patient age (p = 0.0006) but not correlation between EGFR and lymph node status, tumor grade, or tumor size (p = 0.104, p = 0.198, and p = 0.085 respectively). In a univariate analysis of all patients, EGFR expression was not associated with a significant reduction in overall survival (OS). However, there was a significant decrease in relapse-free survival (RFS) and OS in node negative EGFR positive patients (p = 0.03 and p = 0.05 respectively). In a multivariate analysis (Cox proportional hazard model) of all patients, lymph node status was an independent prognostic indicator for OS and RFS (p < 0.00005) and p = 0.00005 respectively), ER status for RFS (p = 0.0006), and EGFR (in the node negative model) for RFS (p = 0.03). When all patients were stratified for EGFR and ER, there was a significant difference in RFS and OS such that EGFR positive and ER negative had the worst prognosis (p = 0.0034 and p = 0.005 respectively).

Current controversies in the surgical management of breast cancer.

BACKGROUND: Great advances have occurred in the surgical management of breast cancer during the past 2 decades, though areas of controversy still remain. The surgical treatment of breast cancer relates to management of the breast and of the axillary nodes. Areas of controversy relate to methods of breast conservation after preoperative chemotherapy for locally advanced disease. The ideals of such treatment are described and the various methods by which such results may be obtained are discussed. The importance of conservation of the nipple-areolar complex is stressed, and the various methods of reconstruction by which this can be achieved are discussed. The role of surgery to the axilla is also discussed, with particular reference to axillary sampling. Data relating to the control of axillary disease treated by irradiation and that obtained after surgery are compared. Current controversies: Breast conservation, partial and subcutaneous mastectomy, reconstruction (using implants, prostheses and myocutaneous flaps), the management of axillary disease and the role of adjuvant therapy are discussed.

Tumor angiogenesis in node-negative breast carcinomas--relationship with epidermal growth factor receptor, estrogen receptor, and survival.

Angiogenesis is essential for tumor growth and metastases. Studies in breast carcinomas suggest that microvessel quantitation as a measure of angiogenesis might be one of the most powerful prognostic tools available. Node negative breast cancer is a particular group for which better prognostic markers would be helpful. We therefore measured microvessel density in a series of well characterised node negative breast carcinomas to evaluate angiogenesis as a prognostic marker and assess its relationship to epidermal growth factor receptor (EGFR) and estrogen receptor (ER), which have previously been reported to be of value. 109 patients with a mean age of 55 years and a median follow-up of 25 months were examined. Vessels were immunohistochemically highlighted using an antibody to platelet endothelial cell adhesion molecule CD31, and microvessel density was quantified using a Chalkley point eyepiece graticule. No significant correlation was observed with patient age, tumor size, grade, ER, or EGFR expression. In a univariate analysis of survival, whereas ER expression was not a significant indicator of either relapse-free (RFS) or overall survival (OS), vascular count (VC) predicted both early RFS and OS (p = 0.01) and p = 0.028 respectively). Furthermore, in patients with ER positive tumors, a subgroup usually considered to have a good prognosis, there was a significant reduction in RFS and OS if tumors had high VCs (p = 0.05 and p = 0.002 respectively). A further statistically significant reduction in RFS (p = 0.05) was observed for EGFR positive highly vascular tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Cancer in pregnancy.

OBJECTIVE: To estimate the incidence of cancer arising in pregnancy and to report its recurrence in those women with a past history of the disease. DESIGN: Retrospective study over 11 years. SETTING: John Radcliffe Maternity Hospital. PATIENTS: 25,568 Oxford District Health Authority residents who delivered at the John Radcliffe Maternity Hospital, and 6775 residents who had a termination of pregnancy, between 1 January 1981 and 31 December 1985. INTERVENTIONS: Retrospective analysis of case records to identify pregnancies complicated by cancer and follow-up through patients' general practitioners. MAIN OUTCOME MEASURES: Maternal mortality and disease recurrence. RESULTS: The study identified 32 pregnancies complicated by cancer in 28 women and four terminations of pregnancy performed for cancer as the main or secondary indication. By the end of 1991, three women had died, one woman had been treated for disease recurrence, 17 women were in good health and seven women had been lost to follow-up. There were six cases of cancer arising de novo in pregnancy, i.e. an incidence of 2.35 per 10,000 deliveries (95% confidence interval 0.47 to 4.22). Only one pregnancy was complicated by disease recurrence. CONCLUSION: The incidence of cancer arising de novo in pregnancy is lower than the most quoted figure of 9.92 per 10,000 pregnancies.

Amphiregulin, epidermal growth factor receptor, and estrogen receptor expression in human primary breast cancer.

Amphiregulin is a recently described member of the epidermal growth factor family. Primary breast cancers were assessed for expression of amphiregulin by immunochemistry (111 cases), Northern, and/or dot blots (68 cases). Epidermal growth factor and estrogen receptors were measured in all cases. p53 and erbB-2 expression was assessed by immunohistochemistry for most cases. There was no association of these factors with amphiregulin expression, which was detected by immunochemistry in 40 of 111 cases. A significant association of amphiregulin expression assessed by Northern dot blots versus immunochemical staining was seen (P = 0.0016). Expression was not detected in adjacent nontumor tissue by immunochemistry. Amphiregulin was expressed in tumor epithelium, but not stromal or inflammatory cells. Expression was more common in lymph node positive cases (23 of 49; 47%) than lymph node negative cases (11 of 42; 26%; P = 0.04). The coexpression of epidermal growth factor receptor and amphiregulin in 35% of epidermal growth factor receptor positive cases raises the possibility of an autocrine loop in this subset of patients. Amphiregulin stimulates fibroblast growth and is up-regulated in breast cancer. A possible effect on tumor stroma may relate to the association with metastases.