Imaging biochemistry: applications to breast cancer.

The use of magnetic resonance spectroscopy (MRS) to investigate breast tumour biochemistry in vivo is reviewed. To this end, results obtained both from patients in vivo and from tumour extracts and model systems are discussed. An association has been observed between transformation and an increase in phosphomonoesters (PMEs) detected in the 31P MRS spectrum, as well as an increase in choline-containing metabolites detected in the 1H spectrum. A decrease in PME content after treatment is associated with response to treatment as assessed by tumour volume. Experiments in model systems aimed at understanding the underlying biochemical processes are presented, as well as data indicating the usefulness of MRS in monitoring the uptake and metabolism of some chemotherapeutic agents

New roles for nuclear receptors in prostate cancer

Prostate cancer has, for decades, been treated by inhibiting androgen signalling. This is effective in the majority of patients, but inevitably resistance develops and patients progress to life-threatening metastatic disease - hence the quest for new effective therapies for "castrate-resistant" prostate cancer (CRPC). Studies into what pathways can drive tumour recurrence under these conditions has identified several other nuclear receptor signalling pathways as potential drivers or modulators of CRPC. The nuclear receptors constitute a large (48 members) superfamily of transcription factors sharing a common modular functional structure. Many of them are activated by the binding of small lipophilic molecules, making them potentially druggable. Even those for which no ligand exists or has yet been identified may be tractable to activity modulation by small molecules. Moreover, genomic studies have shown that in models of CRPC other nuclear receptors can potentially drive similar transcriptional responses to the androgen receptor, while analysis of expression and sequencing databases shows disproportionately high mutation and copy number variation rates among the superfamily. Hence the nuclear receptor superfamily is of intense interest in the drive to understand how prostate cancer recurs and how we may best treat such recurrent disease. This reviews aims to provide a snapshot of current knowledge of the roles of different nuclear receptors in prostate cancer, a rapidly-evolving field of research

Airports at Risk: The Impact of Information Sources on Security Decisions

Security decisions in high risk organizations such as airports involve obtaining ongoing and frequent information about potential threats. Utilizing questionnaire survey data from a sample of airport employees in European Airports across the continent, we analyzed how both formal and informal sources of security information affect employee's decisions to comply with the security rules and directives. This led us to trace information network flows to assess its impact on the degree employees making security decisions comply or deviate with the prescribed security rules. The results of the multivariate analysis showed that security information obtained through formal and informal networks differentially determine if employee will comply or not with the rules. Information sources emanating from the informal network tends to encourage employees to be more flexible in their security decisions while formal sources lead to be more rigid with complying with rules and protocols. These results suggest that alongside the formal administrative structure of airports, there exists a diverse and pervasiveness set of informal communications networks that are a potent factor in determining airport security levels

Is early center-based child care associated with tantrums and unmanageable behavior over time up to school entry?

Background. Existing research suggests that there is a relationship between greater exposure to center-based child care and child behavioral problems though the mechanism for the impact is unclear. However the measure used to document child care has usually been average hours, which may be particularly unreliable in the early months when fewer children are in center care. In addition individual trajectories for behavior difficulties have not been studied. Objective. The purpose of the current study was to examine whether the extent of exposure to center-based child care before two years predicted the trajectory of children’s difficult behavior (i.e., tantrums and unmanageable behavior) from 30 to 51 months controlling for child and maternal characteristics. Method. Data were drawn from UK-based Families, Children and Child Care (FCCC) study (n=1201). Individual growth models were fitted to test the relation between early center-based child care experiences and subsequent difficult behavior. Results. Children with more exposure to center-based care before two had less difficult behavior at 30 months, but more increase over time. Initial levels were predicted by higher difficult temperament and lower verbal ability. Higher difficult temperament and lower family socio-economic status predicted its change over time. Conclusion. Findings suggest that early exposure to center-based care before two years old is a risk factor for subsequent behavior problems especially when children have a longer period of exposure. A possible explanatory process is that child coping strategies to manage frustration are less well developed in a group context, especially when they lag behind in expressive language

Pulmonary stretch receptor activity during partial liquid ventilation in cats with healthy lungs

Aim: To study whether pulmonary stretch receptor (PSR) activity in mechanically ventilated young cats with healthy lungs during partial liquid ventilation (PLV) is different from that during gas ventilation (GV). Methods: In 10 young cats (4.4 +/- 0.4 months, 2.3 +/- 0.3 kg; mean B SD), PSR instantaneous impulse frequency (PSR f(imp)) was recorded from single fibres in the vagal nerve during GV and PLV with perfluorocarbon (30 ml/kg) at increasing positive inspiratory pressures (PIP; 1.2, 1.8, 2.2 and 2.7 kPa), and at a positive end-expiratory pressure of 0.5 kPa. Results: All PSRs studied during GV maintained their phasic character with increased impulse frequency during inspiration during PLV. Peak PSR fimp was lower at PIP 1.2 kPa (p < 0.05) and at PIP 2.7 kPa (p = 0.10) during PLV than during GV, giving a lower number of PSR impulses at these two settings during PLV (p < 0.05). Conclusion: The phasic character of PSR activity is similar during GV and PLV. PSR activity is not higher during PLV than during GV in cats with healthy lungs, indicating no extensive stretching of the lung during PLV. Copyright (C) 2004 S. Karger AG, Basel

Hsp90 orchestrates transcriptional regulation by Hsf1 and cell wall remodelling by MAPK signalling during thermal adaptation in a pathogenic yeast

Acknowledgments We thank Rebecca Shapiro for creating CaLC1819, CaLC1855 and CaLC1875, Gillian Milne for help with EM, Aaron Mitchell for generously providing the transposon insertion mutant library, Jesus Pla for generously providing the hog1 hst7 mutant, and Cathy Collins for technical assistance.Peer reviewedPublisher PD

Inflation on the Brane with Vanishing Gravity

Many existing models of brane inflation suffer from a steep irreducible gravitational potential between the branes that causes inflation to end too early. Inspired by the fact that point masses in 2+1 D exert no gravitational force, we propose a novel unwarped and non-supersymmetric setup for inflation, consisting of 3-branes in two extra dimensions compactified on a sphere. The size of the sphere is stabilized by a combination of a bulk cosmological constant and a magnetic flux. Computing the 4D effective potential between probe branes in this background, we find a non-zero contribution only from exchange of level-1 KK modes of the graviton and radion. Identifying antipodal points on the 2-sphere projects out these modes, eliminating entirely the troublesome gravitational contribution to the inflationary potential.Comment: 19 pages, 11 figures, JHEP forma

Breast imaging technology: Imaging biochemistry - applications to breast cancer

The use of magnetic resonance spectroscopy (MRS) to investigate breast tumour biochemistry in vivo is reviewed. To this end, results obtained both from patients in vivo and from tumour extracts and model systems are discussed. An association has been observed between transformation and an increase in phosphomonoesters (PMEs) detected in the (31)P MRS spectrum, as well as an increase in choline-containing metabolites detected in the (1)H spectrum. A decrease in PME content after treatment is associated with response to treatment as assessed by tumour volume. Experiments in model systems aimed at understanding the underlying biochemical processes are presented, as well as data indicating the usefulness of MRS in monitoring the uptake and metabolism of some chemotherapeutic agents