Amplification of the androgen receptor may not explain the development of androgen-independent prostate cancer

Objective To examine the role of androgen receptor (AR) gene amplification and aneusomy of the X chromosome in the development of antiandrogen-resistant prostate cancer. Patients and methods Twenty patients with prostate cancer resistant to androgen-deprivation therapy were selected for study. The records of patients with tumours before and after antiandrogen therapy, and with a full clinical follow-up, were retrieved. AR gene amplification and X chromosome copy number were assessed by fluorescence in situ hybridization using a labelled probe at locus Xq11-13 for the AR gene and a labelled a-satellite probe for the X chromosome. At least 20 nuclei were scored over three tumour areas by two independent observers. Results Aneusomy of the X chromosome was reported respectively in seven (35%) and 11 (55%) tumours before and after hormone relapse, the AR gene copy number was increased in seven (35%) and 13 (65%), respectively, and AR gene amplification was detected in one (5%) and three (15%), respectively. Neither increased AR copy number nor AR amplification in primary tumours precluded a biological response to androgen-deprivation therapy. Conclusion The rate of AR gene amplification is too low to be solely responsible for the development of antiandrogen-resistant prostate cancer. Also, the presence of amplified AR and cells aneusomic for the X chromosome in primary tumours that respond to androgen-deprivation therapy suggests that an increase in AR gene copy number does not prevent a tumour from responding to this therapy. Therefore other mechanisms which could cause hormone-refractory prostate cancer must be investigated before it is understood why so many patients relapse with this disease

HOBt·DCHA-Mediated Synthesis of Sterically Hindered Peptides employing Fmoc-Amino Acid Chlorides in Both Solution-Phase and Solid Phase Methods

The synthesis of peptides employing Fmoc-amino acid chlorides in presence of HOBt·DCHA salt in solution as well as by the solid-phase methods is described. The coupling was found to be complete in 30 min and free from racemization. The synthesis of β-casomorphin by solid-phase protocol employing Fmoc-amino acid chloride/HOBt·DCHA in DMF–CH2Cl2 has also been outlined. The final peptide was obtained in 80% yield and was fully characterized

Kondo Effect of Quantum Dots in the Quantum Hall Regime

Quantum dots in the quantum Hall regime can have pairs of single Slater determinant states that are degenerate in energy. We argue that these pairs of many body states may give rise to a Kondo effect which can be mapped into an ordinary Kondo effect in a fictitious magnetic field. We report on several properties of this Kondo effect using scaling and numerical renormalization group analysis. We suggest an experiment to investigate this Kondo effect.Comment: To appear in Phys. Rev. B (5 pages, 4 figures); references added; several changes in tex

Me3Al-mediated domino nucleophilic addition/intramolecular cyclisation of 2-(2-oxo-2-phenylethyl)benzonitriles with amines; a convenient approach for the synthesis of substituted 1-aminoisoquinolines

A simple and efficient protocol for the construction of 1-aminoisoquinolines was achieved by treating 2-(2-oxo-2- phenylethyl)benzonitriles with amines in the presence of Me 3 Al. The reaction proceeds via a domino nucleophilic addition with subsequent intramolecular cyclisation. This method provides a wide variety of substituted 1-aminoisoquinolines with good func- tional group tolerance. Furthermore, the synthetic utility of this protocol was demonstrated in the successful synthesis of the anti- tumor agent CWJ-a-5 in gram scale

Nonequilibrium Transport through a Kondo Dot in a Magnetic Field: Perturbation Theory

Using nonequilibrium perturbation theory, we investigate the nonlinear transport through a quantum dot in the Kondo regime in the presence of a magnetic field. We calculate the leading logarithmic corrections to the local magnetization and the differential conductance, which are characteristic of the Kondo effect out of equilibrium. By solving a quantum Boltzmann equation, we determine the nonequilibrium magnetization on the dot and show that the application of both a finite bias voltage and a magnetic field induces a novel structure of logarithmic corrections not present in equilibrium. These corrections lead to more pronounced features in the conductance, and their form calls for a modification of the perturbative renormalization group.Comment: 16 pages, 7 figure

Hemospermia

The majority of patients can be treated with minimal investigations and simple reassurance. In older patients or those with persistent hemospermia or associated symptoms modern diagnostic techniques are of proven benefit

Synthesis of peptidyl ureas employing O-succinimidyl-(9H-fluoren-9- ylmethoxycarbonylamino)methylcarbamate derivatives as activated monomers

A convenient and efficient method for the synthesis of dipeptidyl ureas and urea acids employing O-succinimidyl-(9H-fluoren-9-ylmethoxycarbonyl amino)methylcarbamates has been described. All the compounds, obtained in good yields, have been fully characterized by mass and NMR spectra. © 2006 Bentham Science Publishers Ltd

Keratinizing squamous metaplasia of the bladder: a review

Currently there is not enough data to identify keratinizing squamous metaplasia of the bladder as a pre-malignant condition; this term being reserved for those with obvious histological dysplasia. However at present all patients should undergo regular follow-up

Insights into geographical window based SSIM for comparison of OD matrices

The rich structural information of travel patterns in terms of number of trips distributed to different destinations within a region is an essential element that cannot be ignored during any statistical assessments such as comparison of Origin-Destination (OD) matrices. While most of the traditional indicators fail to compare the structural differences between OD matrices, Structural Similarity (SSIM) index outperforms them by comparing the structure, mean and standard deviations within one single formulation. In the existing literature with respect to OD matrices comparison, the application of SSIM is still theoretical in nature and there is no clarity on the level of acceptability of SSIM values due to its sensitivity towards the local window size. Thus SSIM in the context of OD matrices has to be further refined especially by emphasising on the size and physical significance of local window and local SSIM values, so that it can be applied best in practice. In this light, the paper proposes a practical approach for computing SSIM based on geographical windows that has a physical significance in terms of size and shape of windows, geographical correlation and its potential to analyse local travel patterns due to different travel distributions in different sections of the network. Also, using real Bluetooth zonal OD matrices from Brisbane network, the study also demonstrates the potential of SSIM over traditional indicators.</p