Synthesis and biological activities of phenyl piperazine-based peptidomimetic growth hormone secretagogues

A new class of potent, orally active phenyl piperazine-based GH secretagogues have been discovered from attempts to mimic the arrangement of the phenyl substituent in the spiroindanyl piperidine and spiroindoline sulfonamide privileged structures of 4 and 1, respectively. The best of these compounds, 18 (EC50 = 2.8 nM) is nearly as potent as MK-0677 for releasing GH from rat pituitary cells.     

Dentine hypersensitivity: a clinical trial to compare 2 strontium densensitizing toothpastes with a conventional fluoride toothpaste

Sixty-nine patients, aged 63-98 years and admitted at the Geneva Geriatric Hospital, were included in the present retrospective study. They received clomipramine orally, 50 or 75 mg/day. Blood concentrations of clomipramine were measured as part of a routine drug monitoring program. Comparison with a reference population of patients aged < or = 65 years indicated that elderly patients with concomitant somatic diseases reach higher dose-normalized concentrations of clomipramine and increased parent drug to demethylated metabolite ratios, as a consequence of impaired demethylation (approximately 50%) and hydroxylation (approximately 25%). Sixty-five percent of patients showed clinical improvement, with a maximum rate of satisfactory response observed in major depression. Severe side effects, such as symptomatic hypotension or confusion, were seen in 20% of patients. Because of 10- and 15-fold interindividual variations in the concentrations of clomipramine and its metabolite, respectively, therapeutic drug monitoring can provide valuable assistance to clinical judgment in individual dose adjustment for patients whose old age, associated somatic diseases, and comedication necessitate additional precautions.     

The influence of processing and refrigeration on the bacterial numbers on beef and sheep offals

An investigation was carried out in a commercial abattoir on the influence of processing and refrigeration on a variety of beef and sheep offals. The influences of the different processes and the operations, to the bacterial load before refrigeration of the product, were determined. In general all the operations in the plant had an effect on the final bacterial load. The effect of inadequate refrigeration was noteworthy in all cases and this factor alone made the most significant contribution to the products having a poor shelf-life.     

The quantifier structure of sentences that characterize nondeterministic time complexity

For every nondeterministic Turing machineM of time complexityT(n), there is a second-order sentence of a very restricted form, whose set of finite models encodes the set of strings recognized byM. Specifically, has a relational symbol which is interpreted as addition restricted to finite segments of the natural numbers, and a prefix consisting of existentially quantified unary second-order variables followed by a universal-existential first-order part. Here, every input stringx is encoded by a model of sizeT(|x|). Using a closely related encoding of strings as models where the size of the model is the length of the string, a consequence is that ifT(n)=n ^d, then there is a sentence with a similar prefix but whose second-order variables ared-ary and whose finite models encode the strings accepted byM. Potential applications to low-level complexity are discussed.     

The role of the automation development group in analytical research and development at Dupont Merck

Laboratory robotics has been firmly established in many non-QC laboratories as a valuable tool for automating pharmaceutical dosage form analysis. Often a single project or product line is used to justify an initial robot purchase thus introducing robotics to the laboratory for the first time. However, to gain widespread acceptance within the laboratory and to justify further investment in robotics, existing robots must be used to develop analyses for existing manual methods as well as new projects beyond the scope off the original purchase justification. The Automation Development Group in Analytical Research and Development is a team of analysts primarily devoted to developing new methods and adapting existing methods for the robot. This team approach developed the expertise and synergy necessary to significantly expand the contribution of robotics to automation in the authors'' laboratory.     

Note: flowing ion population from a resonance cavity source

The experimental low energy plasma for hemispherical analyzers nominal testing thermal plasma facility of Dartmouth College uses a microwave plasma source which generates an ionosphere-like plasma through a two-step process. The plasma is initially generated inside a cylindrical, insulated, resonance cavity. This initial plasma must pass through a sheath in order to enter the main experimental region. This process imparts a significant flow velocity to the ions which has been neglected in previous analysis of this plasma source. We predict the flow energy of the ions to be between 12-15 eV depending on conservation laws and show agreement with experimental results.     

Friction-Induced Lines of Attraction and Repulsion for Parts Sliding on an Oscillated Plate

We show that the frictional forces arising from simultaneous small amplitude periodic translation and rotation of a rigid plate cause parts on the plate to converge to or diverge from a line coinciding with the rotation axis. The relative phase between the translation and rotation determines whether the parts are attracted to or repelled from the rotation axis. Assuming that both the translational and rotational accelerations of the plate are ldquobang-bangrdquo and have identical frequencies, we derive the resultant velocity fields for point parts on the plate. For many choices of phase the speed of the part is approximately proportional to its distance from the rotation axis. The strength of the velocity field can be controlled by modulating the amplitude of the translational acceleration, or modulating the relative phase between the translational and rotational acceleration profiles. We also determine the phases that maximize part speed towards and away from the rotation axis. These optimal phases not only maximize part speed but also generate velocity fields that are nearly independent of the coefficient of friction.     

Correlation between lymphocyte-induced donor-specific tolerance and donor cell recirculation. Role of class I and class II major histocompatibility complex

Intravenous infusion of mice with viable allogeneic lymphocytes can produce donor-specific enhancement of skin graft survival, but only if the injected lymphocytes can persist in the host's recirculating lymphocyte pool for at least 3 days. We have investigated the relative roles of class I and class II MHC for C57BL/6 mice infused with lymphoid cells from co-isogenic strains mutated at class I MHC (bm1) or class II MHC (bm12), and for A.TH lymphoid cells infused into C3H (class I different, class II identical) or A.TH (class II different, class I identical). Injected cells differing from the host at class I MHC, but not at class II MHC, can be rapidly removed by host natural immune mechanisms (probably NK cells). Persistence is favored if the injected cells also carry host class I MHC, i.e., tolerance is more readily induced by injecting F1 (A x B) into A rather than B into A, consistent with the "missing self" hypothesis of NK recognition, with class I MHC being the relevant self-marker. Injected cells differing from the host at class II MHC but not at class I MHC always persist for at least 3 days, even when class I-different cells are being actively removed.