Tracer kinetic modeling of the 5-HT1A receptor ligand [carbonyl-11C]WAY-100635 for PET

[Carbonyl-11C]WAY-100635 is a promising PET radioligand for the 5-HT1A receptor, having demonstrated more favorable characteristics for in vivo imaging than the previously available [O-methyl-11C]WAY-100635. The current study evaluates different tracer kinetic modelling strategies for the quantification of 5-HT1A receptor binding in human brain. Mathematical modelling of the carbonyl-labeled radiotracer is investigated using compartmental structures, including both plasma input and reference tissue approaches. Furthermore, the application of basis function methods allows for the investigation of parametric imaging, providing functional maps of both delivery and binding of the radioligand. Parameter estimates of binding from normal volunteers indicate a low intra- versus a high intersubject variability. It is concluded that a simplified reference tissue approach may be used to quantify 5-HT1A binding either in terms of ROI data or as parametric images.     

Inositol 1,4,5-trisphosphate receptor function in neonatal cardiomyocytes

We have previously reported that the metabolism of inositol(1,4,5)trisphosphate (Ins(1,4,5)P3) is altered when rat neonatal ventricular cardiomyocytes are isolated and cultured. In the current study we show that the mass content of Ins(1,4,5)P3 is lower in the isolated cells than in the intact tissue. However, the properties of the Ins(1,4,5)P3 receptors were not different in the two preparations and the isolated cells remained insensitive to Ins(1,4,5)P3 in terms of 45Ca2+ release. Thus, despite the altered pattern of metabolism of Ins(1,4,5)P3 in isolated neonatal cells, the properties of the receptors were similar to those reported in other myocardial preparations.     

Association analysis in an evolutionary context: cladistic analysis of the DRD2 locus to test for association with alcoholism

Recent clinical trials of adjuvant therapy for early stage breast cancer support two general observations. First, overall survival is not impacted by the extent of surgery. Low rates of axillary relapse in patients treated with total mastectomy alone combined with the availability of systemic therapy as a substitute for surgical control of the axilla mean that patients can often be spared the morbidity of axillary node dissection. In problematic cases, newer diagnostic approaches, such as sentinel node biopsy, can help in making appropriate treatment decisions. Second, systemic therapy can reduce the clinical manifestations of disease. The incorporation of more sophisticated approaches to predicting outcomes, to varying timing and dose of treatment, and to developing new modalities of treatment, including immunotherapy, will contribute to a general strategy aimed at reducing the tumor to a harmless parasite. These observations support a paradigm shift in our definition of 'adjuvant'. Rather than referring to the use of systemic therapy after the patient's known disease has been surgically removed, adjuvant therapy would be re-defined to refer to local therapy used to eradicate any residual tumor remaining after systemic therapy has been completed.     

Crystalline silicon on glass (CSG) thin-film solar cell modules

Crystalline silicon on glass (CSG) solar cell technology was developed to address the difficulty that silicon wafer-based technology has in reaching the very low costs required for large-scale photovoltaic applications as well as the perceived fundamental difficulties with other thin-film technologies. The aim was to combine the advantages of standard silicon wafer-based technology, namely ruggedness, durability, good electronic properties and environmental soundness with the advantages of thin-films, specifically low material use, large monolithic construction and a desirable glass superstrate configuration. The challenge has been to match the different preferred processing temperatures of silicon and glass and to obtain strong solar absorption in notoriously weakly-absorbing silicon of only 1.4 μm thickness, the thinnest active layer of the key thin-film contenders. A rugged, durable silicon thin-film technology has been developed arguably with the lowest likely manufacturing cost of these contenders and confirmed efficiency for small pilot line modules already in the 8–9% energy conversion efficiency range, on the path to 12–13%.     

Degradation chemistry of gemcitabine hydrochloride, a new antitumor agent

The anti-tumor agent gemcitabine hydrochloride, a beta-difluoronucleoside, is remarkably stable in the solid state. In 0.1 N HCI solution at 40 degrees C, deamination of gemcitabine occurs, yielding its uridine analogue. Approximately 86% of the initial gemcitabine remains after 4 weeks under these conditions. Cleavage of the N-glycosidic bond of gemcitabine or conversion to its alpha-anomer in 0.1 N HCI solution is not observed over a 4-week period. However, this work has shown that gemcitabine hydrochloride anomerizes in 0.1 N NaOH at 40 degrees C. Approximately 72% of the initial gemcitabine remains after 4 weeks under the basic conditions used. Uridine hydrolysis products are also formed under these conditions. The anormerization reaction, which is unusual under basic conditions, has been confirmed by characterization of the chromatographically isolated alpha-anomer by NMR and mass spectrometry. A mechanism involving an acyclic intermediate is proposed.