In vivo quantification of citrate concentration and water T2 relaxation time of the pathologic prostate gland using H MRS and MRI

We have previously reported a striking correlation between water T₂ relaxation time and citrate concentration in the normal prostate (Liney G.P.; Lowry M.; Turnbull L.W.; Manton D.J.; Knowles A.J.; Blackband S.J.; Horsman A. Proton MR T₂ maps correlate with the citrate concentration in the prostate. NMR Biomed. 9:59–64; 1996). In this study we present data from similar studies of the pathologic gland. The findings support the hypothesis that measurement of both citrate concentration and water T₂ relaxation time in vivo may aid the differentiation of prostatic carcinoma from benign disease and normal tissue.     

Differentiability of cone-monotone functions on separable Banach space

Motivated by applications to (directionally) Lipschitz functions, we provide a general result on the almost everywhere Gâteaux differentiability of real-valued functions on separable Banach spaces, when the function is monotone with respect to an ordering induced by a convex cone with non-empty interior. This seemingly arduous restriction is useful, since it covers the case of directionally Lipschitz functions, and necessary. We show by way of example that most results fail more generally.

     

Phase Modulation in Interferometry: Phase-Drift Suppression over a Wide Range of the Modulation Index

We propose a new technique for processing the heterodyne beat signals obtained in interferometry by sinusoidal modulation of the optical path difference. This technique achieves a high degree of signal stabilization with respect to phase drifts, while removing earlier restrictions imposed on the modulation index. Four Fourier harmonics of the interference signal allow the determination of the current modulation index, and then the coherent component of the intensity can be calculated. The method was tested both numerically and experimentally, and compared to a previous technique that uses the same input data. The effects of phase drifts are canceled on a wide range of the modulation index values, while the reference method achieves the same performance only for particular isolated values. A simplified version of the method is proposed for cases when the signal-to-noise ratio is low.On leave from the National Institute for Laser, Plasma, and Radiation Physics, PO Box MG-36, Bucharest, Romania.     

On the Nonembeddability and Crossing Numbers of Some Kleinical Polyhedral Maps on the Torus

We define a family of graph bundles over cycles which embed naturally on the Klein bottle and which are analogous to the celebrated toroidal grid graphs (cartesian product of a cycle with a cycle). We give a criterion for a polyhedral map on the Klein bottle to fail to embed on the torus, and use this to calculate toroidal crossing numbers of two one-parameter infinite families of our Kleinical graphs.Mathematics Subject Classification (1991): 05C10     

Epitope Structure of the Carbohydrate Recognition Domain of Asialoglycoprotein Receptor to a Monoclonal Antibody Revealed by High-Resolution Proteolytic Excision Mass Spectrometry

Recent studies suggest that the H1 subunit of the carbohydrate recognition domain (H1CRD) of the asialoglycoprotein receptor is used as an entry site into hepatocytes by hepatitis A and B viruses and Marburg virus. Thus, molecules binding specifically to the CRD might exert inhibition towards these diseases by blocking the virus entry site. We report here the identification of the epitope structure of H1CRD to a monoclonal antibody by proteolytic epitope excision of the immune complex and high-resolution MALDI-FTICR mass spectrometry. As a prerequisite of the epitope determination, the primary structure of the H1CRD antigen was characterised by ESI-FTICR-MS of the intact protein and by LC-MS/MS of tryptic digest mixtures. Molecular mass determination and proteolytic fragments provided the identification of two intramolecular disulfide bridges (seven Cys residues), and a Cys-mercaptoethanol adduct formed by treatment with β-mercaptoethanol during protein extraction. The H1CRD antigen binds to the monoclonal antibody in both native and Cys-alkylated form. For identification of the epitope, the antibody was immobilized on N-hydroxysuccinimide (NHS)-activated Sepharose. Epitope excision and epitope extraction with trypsin and FTICR-MS of affinity-bound peptides provided the identification of two specific epitope peptides (5–16) and (17–23) that showed high affinity to the antibody. Affinity studies of the synthetic epitope peptides revealed independent binding of each peptide to the antibody.     

Thymidine analogues for tracking DNA synthesis

Replicating cells undergo DNA synthesis in the highly regulated, S-phase of the cell cycle. Analogues of the pyrimidine deoxynucleoside thymidine may be inserted into replicating DNA, effectively tagging dividing cells allowing their characterisation. Tritiated thymidine, targeted using autoradiography was technically demanding and superseded by 5-bromo-2-deoxyuridine (BrdU) and related halogenated analogues, detected using antibodies. Their detection required the denaturation of DNA, often constraining the outcome of investigations. Despite these limitations BrdU alone has been used to target newly synthesised DNA in over 20,000 reviewed biomedical studies. A recent breakthrough in "tagging DNA synthesis" is the thymidine analogue 5-ethynyl-2'-deoxyuridine (EdU). The alkyne group in EdU is readily detected using a fluorescent azide probe and copper catalysis using 'Huisgen's reaction' (1,3-dipolar cycloaddition or 'click chemistry'). This rapid, two-step biolabelling approach allows the tagging and imaging of DNA within cells whilst preserving the structural and molecular integrity of the cells. The bio-orthogonal detection of EdU allows its application in more experimental assays than previously possible with other "unnatural bases". These include physiological, anatomical and molecular biological experimentation in multiple fields including, stem cell research, cancer biology, and parasitology. The full potential of EdU and related molecules in biomedical research remains to be explored.