In-gas-cell laser ionization spectroscopy in the vicinity of 100Sn: Magnetic moments and mean-square charge radii of N=50-54 Ag

In-gas-cell laser ionization spectroscopy studies on the neutron deficient 97-101Ag isotopes have been performed with the LISOL setup. Magnetic dipole moments and mean-square charge radii have been determined for the first time with the exception of 101Ag, which was found in good agreement with previous experimental values. The reported results allow tentatively assigning the spin of 97,99Ag to 9/2 and confirming the presence of an isomeric state in these two isotopes, whose collapsed hyperfine structure suggests a spin of 1/2 . The effect of the N=50 shell closure is not only manifested in the magnetic moments but also in the evolution of the mean-square charge radii of the isotopes investigated, in accordance with the spherical droplet model predictions

No excess of mitochondrial DNA deletions within muscle in progressive multiple sclerosis

BACKGROUND: Mitochondrial dysfunction is an established feature of multiple sclerosis (MS). We recently described high levels of mitochondrial DNA (mtDNA) deletions within respiratory enzyme-deficient (lacking mitochondrial respiratory chain complex IV with intact complex II) neurons and choroid plexus epithelial cells in progressive MS. OBJECTIVES: The objective of this paper is to determine whether respiratory enzyme deficiency and mtDNA deletions in MS were in excess of age-related changes within muscle, which, like neurons, are post-mitotic cells that frequently harbour mtDNA deletions with ageing and in disease. METHODS: In progressive MS cases (n=17), known to harbour an excess of mtDNA deletions in the central nervous system (CNS), and controls (n=15), we studied muscle (paraspinal) and explored mitochondria in single fibres. Histochemistry, immunohistochemistry, laser microdissection, real-time polymerase chain reaction (PCR), long-range PCR and sequencing were used to resolve the single muscle fibres. RESULTS: The percentage of respiratory enzyme-deficient muscle fibres, mtDNA deletion level and percentage of muscle fibres harbouring high levels of mtDNA deletions were not significantly different in MS compared with controls. CONCLUSION: Our findings do not provide support to the existence of a diffuse mitochondrial abnormality involving multiple systems in MS. Understanding the cause(s) of the CNS mitochondrial dysfunction in progressive MS remains a research priority

Sustained correction of B-cell development and function in a murine model of X-linked agammaglobulinemia (XLA) using retroviral-mediated gene transfer

X-linked agammaglobulinemia (XLA) is a human immunodeficiency caused by mutations in Bruton tyrosine kinase (Btk) and characterized by an arrest in early B-cell development, near absence of serum immunoglobulin, and recurrent bacteria infections. Using Btk- and Tec-deficient mice (BtkTec-/-) as a model for XLA, we determined if Btk gene therapy could correct this disorder. Bone marrow (BM) from 5-fluorouracil (5FU)-treated BtkTec-/- mice was transduced with a retroviral vector expressing human Btk and transplanted into BtkTec-/- recipients. Mice engrafted with transduced hematopoietic cells exhibited rescue of both primary and peripheral B-lineage development, revocery of peritoneal B1 B cells, and correction of serum immunoglobulin M (IgM) and IgG3 levels. Gene transfer also restored T-independent type II immune responses, and B-cell antigen receptor (BCR) proliferative responses. B-cell progenitors derived from Btk-transduced stem cells exhibited higher levels of Btk expression than non-B cells; and marking studies demonstrated a selective advantage for Btk-transduced B-lineage cells. BM derived from primary recipients also rescued Btk-dependent function in secondary hosts that had received a transplant. Together, these data demonstrate that gene transfer into hematopoietic stem cells can reconstitute Btk-dependent B-cell development and function in vivo, and strongly support the feasibility of pursuing Btk gene transfer for XLA

Comparison of two different models for pile thermal response test interpretation

Thermal response tests (TRTs) are regularly used to characterise the thermal resistance of borehole heat exchangers and to assess the thermal conductivity of the surrounding ground. It is becoming common to apply the same in situ testing technique to pile heat exchangers, despite international guidance suggesting that TRTs should be limited to hole diameters of 152 mm (6 in.). This size restriction arises from the increased thermal inertia of larger diameter heat exchangers, which invalidates the assumption of a steady state within the concrete needed to interpret the test data by traditional line source analysis techniques. However, new methods of analysis for pile heat exchangers have recently been developed that take account of the transient behaviour of the pile concrete. This paper applies these new methods to data from a multi-stage TRT conducted on a small diameter test pile. The thermal conductivity and thermal resistance determined using this method are then compared with those from traditional analytical approaches based on a line source analysis. Differences between the approaches are discussed, along with the observation that the thermal resistance may not be constant over the different test stages

Enhanced prediction of breast cancer prognosis by evaluating expression of p53 and prostate-specific antigen in combination

p53 gene mutation is the most common genetic alteration in neoplastic diseases, including breast cancer, for which p53 alteration may indicate poor prognosis. Recent clinical evidence suggests that prostate-specific antigen (PSA) expression may identify breast cancer patients with favourable outcome. Assessment of p53 and PSA in combination, potentially offering improved prediction, has not yet been performed. Extracts from 952 primary breast carcinomas were assayed for PSA and p53 by quantitative enzyme-linked immunosorbent assays (ELISAs) developed by the authors. Concentrations of each marker were classified as negative or positive on the basis of median and 30th percentile cut-off points for p53 and PSA respectively. Patients followed for a median of 6 years having different combinations of negative or positive status for PSA and p53 were compared with respect to the relative risks (RRs) for relapse and death by Cox proportional hazards regression analysis, in which an interaction term was also evaluated, and with respect to disease-free survival (DFS) and overall survival (OS) probabilities by Kaplan–Meier plots and log-rank tests. Multivariate models were adjusted for oestrogen and progesterone receptor status, nodal status, patient age, tumour size, DNA ploidy, S phase fraction and receipt of chemotherapy. Interactions were not found between the status of PSA and p53 in the Cox models, in which PSA-negativity (RR = 1.47, P = 0.020 for DFS, and RR = 1.49, P = 0.023 for OS) and p53-positivity (RR = 1.46, P = 0.017 for DFS, and RR = 1.41, P = 0.033 for OS) were individually associated with prognosis. Evaluation of a combined three-level variable revealed that PSA(–)/p53(+) patients had significantly higher risks for relapse (RR = 2.13, P < 0.001) and death (RR = 2.08, P = 0.001) than PSA(+)/p53(–) patients, and that patients positive or negative for both markers had intermediate risks for the outcome events in the same multivariate analysis (RR = 1.45 for both DFS and OS). The results of our study demonstrate that the assessment of combined PSA and p53 expression status by ELISAs, easily applicable to breast tumour extracts prepared for steroid hormone receptor analyses, may stratify breast cancer patients into groups differing by relapse and death risks of greater magnitude than offered by the assessment of either p53 or PSA alone. © 1999 Cancer Research Campaig

The involvement of replication in single stranded oligonucleotide-mediated gene repair

Targeted gene repair mediated by single-stranded oligonucleotides (SSOs) has great potential for use in functional genomic studies and gene therapy. Genetic changes have been created using this approach in a number of prokaryotic and eukaryotic systems, including mouse embryonic stem cells. However, the underlying mechanisms remain to be fully established. In one of the current models, the ‘annealing-integration’ model, the SSO anneals to its target locus at the replication fork, serving as a primer for subsequent DNA synthesis mediated by the host replication machinery. Using a λ-Red recombination-based system in the bacterium Escherichia coli, we systematically examined several fundamental premises that form the mechanistic basis of this model. Our results provide direct evidence strongly suggesting that SSO-mediated gene repair is mechanistically linked to the process of DNA replication, and most likely involves a replication intermediate. These findings will help guide future experiments involving SSO-mediated gene repair in mammalian and prokaryotic cells, and suggest several mechanisms by which the efficiencies may be reliably and substantially increased

Dissolution Control of Mg by Cellulose Acetate–Polyelectrolyte Membranes

Cellulose acetate (CA)-based membranes are used for Mg dissolution control: the permeability of the membrane is adjusted by additions of the polyelectrolyte, poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA). Spin-coated films were characterized with FT-IR, and once exposed to an aqueous solution the film distends and starts acting as a membrane which controls the flow of ions and H2 gas. Electrochemical measurements (linear sweep voltammograms, open-circuit potential, and polarization) show that by altering the CA:PDMAEMA ratio the dissolution rate of Mg can be controlled. Such a control over Mg dissolution is crucial if Mg is to be considered as a viable, temporary biomedical implant material. Furthermore, the accumulation of corrosion products between the membrane and the sample diminishes the undesirable effects of high local pH and H2 formation which takes place during the corrosion process.Peer reviewe