DNA mismatch repair deficient mice in cancer research

Because the phenomena of managing and therapeutically responding to confused elderly hospitalized patients is complex and difficult, a group of advanced practice nurses, supported by a pharmacist, nursing administration, and a School of Nursing professor, was commissioned to explore the research-based literature and provide practice recommendations for these patients. This article identifies one process undertaken for synthesizing and grounding an immense body of literature related to confused elderly patients. The literature review served to begin clarifying the differences between the diagnosis and required interventions for managing either acute or chronic confusion. These interventions were articulated within a protocol format (Marker model) familiar to staff members at our institution. The development, implementation, and evaluation of the protocol is presented, as well as suggestions for further research.     

Analysis of malachite green and metabolites in fish using liquid chromatography atmospheric pressure chemical ionization mass spectrometry

Malachite green (MG), a traditional agent used in aquaculture, is structurally related to other carcinogenic triphenylmethane dyes. Although MG is not approved for use in aquaculture, its low cost and high efficacy make illicit use likely. We developed sensitive and specific methods for determination of MG and its principal metabolite, leucoMG (LMG), in edible fish tissues using isotope dilution liquid chromatography atmosphere pressure chemical ionization mass spectrometry. MG and LMG concentrations were measured in filets from catfish treated with MG under putative use conditions (ca. 250 and 1000 ppb, respectively) and from commercial trout samples (0-3 and 0-96 ppb, respectively). Concentrations of LMG in edible fish tissues always exceeded those of MG. A rapid cone voltage switching acquisition procedure was used to simultaneously produce molecular ions for quantification and diagnostic fragment ions for confirmation of MG and metabolites. The accurate and precise agreement between diagnostic ion intensity ratios produced by LMG in authentic standards and incurred fish samples was used to unambiguously confirm the presence of LMG in edible fish tissue. This suggested the validity of using LMG as a marker residue for regulatory determination of MG misuse. Additional metabolites derived from oxidative metabolism of MG or LMG (demethylation and N-oxygenation) were identified in catfish and trout filets, including a primary arylamine which is structurally related to known carcinogens. The ability to simultaneously quantify residues of MG and LMG, and to confirm the chemical structure of a marker residue by using LC/MS, suggests that this procedure may be useful in monitoring the food supply for the unauthorized use of MG in aquaculture.     

The application of complex quantized feedback in integrated wireless receivers

Integrated wireless receiver architectures, such as direct-conversion receivers, offer many advantages over the conventional heterodyne receivers including smaller size, lower cost, and reduced power consumption. However, the design of monolithic receivers, using direct-conversion, involves many challenges including dealing with low-frequency disturbances, namely, dc-offset and 1/f noise (especially in CMOS implementations), in-phase (I) and quadrature (Q) amplitude and phase mismatch, local oscillator (LO) leakage, and even-order distortions. A cost-effective method to minimize the low-frequency disturbances is to use ac-coupling in the baseband signal path. However, it results in baseline wander effects, especially in spectrally efficient modulation schemes such as quadrature amplitude modulation (QAM) where the baseband signal spectrum contains a significant amount of energy near dc. A system solution to mitigate the effects of low-frequency disturbance is presented in this paper. The quantized feedback (QFB) technique is used in conjunction with ac-coupling to minimize the baseline wander effects. A cross-coupled (CC) QFB extension to compensate for the receiver local oscillator phase error as well as the IQ mismatch is also described. Simulation results are presented to demonstrate the effectiveness of this complex QFB technique.     

Characterization of the binding sites for plasminogen and tissue-type plasminogen activator in cytokeratin 8 and cytokeratin 18

Cytokeratin 8 (CK8) is an intermediate filament protein that penetrates to the external surfaces of breast cancer cells and is released from cells in the form of soluble heteropolymers. CK8 binds plasminogen and tissue-type plasminogen activator (t-PA) and accelerates plasminogen activation on cancer cell surfaces. The plasminogen-binding site is located at the C-terminus of CK8. In this study, we prepared GST-fusion proteins which contained either 174 amino acids from the C-terminus of CK8 (CK8f) or 134 amino acids from the C-terminus of CK18 (CK18f). A third GST-CK fusion protein was identical to CK8fexcept that the C-terminal lysine was mutated to glutamine (CK8fK483Q). CK8f bound plasminogen; the K(D) was 0.5 microM. Binding was completely inhibited by epsilonACA. CK8fK483Q also bound plasminogen, albeit with decreased affinity (K(D) approximately 1.5 microM). CK18f did not bind plasminogen at all. All three fusion proteins bound t-PA equivalently, providing the first evidence that CK18 may function as a t-PA receptor, t-PA and plasminogen cross-competed for binding to CK8f. Thus, t-PA and plasminogen cannot bind to the same CK8f monomer simultaneously. Nevertheless, CK8f still promoted plasminogen activation, probably reflecting the fact that CK8f was purified in dimeric or tetrameric form. These studies demonstrate that CK8 may promote plasminogen activation by t-PA only when present in an oligomerized state. CK18 may participate in the oligomer, together with CK8, based on its ability to bind t-PA.     

Fracture mechanics analysis of cracking in plain and reinforced concrete using the boundary element method

Boundary element formulations for modelling the nonlinear behaviour of concrete are reviewed. The analysis based on the dual boundary element method (BEM) to represent the cracks in concrete is presented. The fictitious crack is adopted to represent the fracture process zone in concrete. The influence of reinforcements on the concrete is considered as a distribution of forces over the region of attachment. The yielding of reinforcement is considered when the total force at any section of the reinforcement is greater than the yielding force and is assumed to be broken when the strain reaches the maximum strain. In using the BEM to simulate cracks, the crack path need not be known in advance since it can be calculated during the iteration process and as such remeshing becomes obsolete. The numerical results obtained are compared to the FEM analysis.