Human pharmacology of 5-epi-sisomicin (Sch 22591) following intramuscular administration

5-epi-sisomicin was given as a single intramuscular injection of 1 mg/kg to six healthy male adults. Serum peak concentrations averaged 3.07 mg/l, the mean elimination half life was 179 min and the mean 24 h urinary recovery was 85.3%. Local and systemic tolerance was goo

Human pharmacokinetics and CSF penetration of clavulanic acid

Clavulanic acid, a product of Streptomyces clavuligerus with β-lactam structure, is a potent inhibitor of several β-lactamases. To study its pharmacokinetic and CSF penetration in patients without meningeal inflammation, a single oral dose of 250 mg of clavulanic acid was given to 21 patients. One patient was studied in a multiple dose schedule. Fifteen of these 21 patients had a diagnostic lumbar puncture and 3 neurosurgical patients had a continuous CSF drainage. Serum and urine concentrations of clavulanic acid were available from 22 patients. The mean peak serum concentration was 4·3 mg/l and individual peak serum concentrations ranged from 0·1-9·5 mg/i between 40 and 60 mm after ingestion of clavulanic acid. Urinary recovery between 300 and 400 mm ranged from 0·8-54·3% of the administered dose. The mean absorption half life was 0·26 h and the mean elimination half life was 0·9 h. Considerable degradation of clavulanic acid occurred in vitro at 37°C. In pooled human serum, phosphate buffer pH 7 and 5, an hourly loss of activity of about 10, 7 and 10% respectively, was observe

Computer-controlled in-vitro simulation of multiple dosing regimens

The bactericidal effect of gentarrucin on Pseudomonas aeruginosa ATCC 27853 was investigated in a computer controlled dynamic in-vitro model, which allows the simultaneous simulation of three different dosing regimens for several days. The same total dose reduced cfu-counts of Pseudomonas aeruginosa most effectively, when administered with peak concentrations of 32 mg/l every 32 h, whereas the other dosing regimens with peak concentrations of 16 mg/l every 16 h and 8 mg/l every 8 h were distinctly less effective following the second and subsequent doses. It was shown that the use of a microcomputer facilitates the in-vitro investigation of multiple dosing regimens but counting of cfu cannot be substituted by automatic measurements of turbidity when rapid bactericidal effects occu

Large Quantum Superpositions and Interference of Massive Nanometer-Sized Objects

We propose a method to prepare and verify spatial quantum superpositions of a nanometer-sized object separated by distances of the order of its size. This method provides unprecedented bounds for objective collapse models of the wave function by merging techniques and insights from cavity quantum optomechanics and matter wave interferometry. An analysis and simulation of the experiment is performed taking into account standard sources of decoherence. We provide an operational parameter regime using present day and planned technology.Comment: 4 pages, 2 figures, to appear in PR

A high-reflectivity high-Q micromechanical Bragg-mirror

We report on the fabrication and characterization of a micromechanical oscillator consisting only of a free-standing dielectric Bragg mirror with high optical reflectivity and high mechanical quality. The fabrication technique is a hybrid approach involving laser ablation and dry etching. The mirror has a reflectivity of 99.6%, a mass of 400ng, and a mechanical quality factor Q of approximately 10^4. Using this micromirror in a Fabry Perot cavity, a finesse of 500 has been achieved. This is an important step towards designing tunable high-Q high-finesse cavities on chip.Comment: 3 pages, 2 figure

Catalysis at Ciba-Geigy

After an introduction describing the significance and a short history of catalysis at Ciba-Geigy, the present role of the Catalysis Section within the Central Research Services is outlined. Its main activities are preparative services for the synthetic chemists in the fields of hydrogenation and high-pressure reactions, the development of catalytic processes and a research program in the fields of enantioselective catalysis, the modification of heterogeneous catalytic systems, acid-base catalysis and catalytic C–C-bond forming reactions. Because catalysis is considered by Ciba-Geigy to be a key technology, the main goal of its R+D program in catalysis is to create and maintain a reliable scientific and technical foundation for the optimal application of catalytic reactions throughout the company. Some results are presented that illustrate the work described above and an outlook on the opportunities of catalytic technologies in the fine chemicals industry is given

Tipologija i tehnologija dva suprotna ili usporedna metodološka pristupa

The authors are analysing the advantages and disadvantages of typological and technological approaches to the analysis of stone and ceramic artefacts. The concepts of typological and technological analysis are coexisting since the beginnings of prehistoric archaeology. Detailed concepts of palaeolithic typologies appeared in the fifties and the sixties. Later on begins a dispute between the authors supporting the so called typological concept and those being mainly interested in the technological study of stone material. The latter are emphasising the process of making tools, analysing all the debitage products and considering the tools only as the final result of a complex chain consisting of different stages of the raw material modification. The typological approach is a static one with the main goal to place finds in a chronological and cultural sequence. The technological approach is dynamic and tends to explain the behaviour of the ancient man and the social relations of prehistoric populations and groups through the reconstruction of the production process. Technology sometimes helps the cultural definition of archaeological material and might also complete the typological definition by showing the emergence of a particular artefact type. There is a difference between the technological production process of stone and ceramic products that is, considering the final product, mostly visible in the change of weight of the raw material. Production of stone material implies a reduction of the raw material while it is quite opposite with ceramic products, i.e. the raw material is being accumulated during the production of a ceramic object (Baumler 1995). Despite the obvious differences typology and technology are not opposed methodological approaches but rather parallel ones. Both methods should be used in the analysis of archaeological material since each has different goals. Thus there can be achieved a more complete interpretation of activities on a particular site as well as a more accurate reconstruction of different processes of prehistoric populations everyday life.Autori analiziraju prednosti i nedostatke tipološkog i tehnološkog metodološkog pristupa analizi litičkih i keramičkih artefakata. Tipološki pristup je statički pristup čiji je osnovni cilj stavljanje nalaza u krono-kulturološku sekvencu. Tehnološki pristup je dinamičan, te preko rekonstrukcije procesa proizvodnje isčitava ponašanje davnašnjeg čovjeka i socijalne odnose prapovijesnih populacija ili skupina. Unatoč vidnim razlikama tipologija i tehnologija nisu suprotstavljeni metodološki pristupi. Oba pristupa valja koristiti pri analizi arheološkog materijala

Control of intestinal bacterial proliferation in regulation of lifespan in Caenorhabditis elegans

<p>Abstract</p> <p>Background</p> <p>A powerful approach to understanding complex processes such as aging is to use model organisms amenable to genetic manipulation, and to seek relevant phenotypes to measure. <it>Caenorhabditis elegans </it>is particularly suited to studies of aging, since numerous single-gene mutations have been identified that affect its lifespan; it possesses an innate immune system employing evolutionarily conserved signaling pathways affecting longevity. As worms age, bacteria accumulate in the intestinal tract. However, quantitative relationships between worm genotype, lifespan, and intestinal lumen bacterial load have not been examined. We hypothesized that gut immunity is less efficient in older animals, leading to enhanced bacterial accumulation, reducing longevity. To address this question, we evaluated the ability of worms to control bacterial accumulation as a functional marker of intestinal immunity.</p> <p>Results</p> <p>We show that as adult worms age, several <it>C. elegans </it>genotypes show diminished capacity to control intestinal bacterial accumulation. We provide evidence that intestinal bacterial load, regulated by gut immunity, is an important causative factor of lifespan determination; the effects are specified by bacterial strain, worm genotype, and biologic age, all acting in concert.</p> <p>Conclusions</p> <p>In total, these studies focus attention on the worm intestine as a locus that influences longevity in the presence of an accumulating bacterial population. Further studies defining the interplay between bacterial species and host immunity in <it>C. elegans </it>may provide insights into the general mechanisms of aging and age-related diseases.</p

Force-Velocity and Power Characteristics of Rat Soleus Muscle Fibers after Hindlimb Suspension

The effects of 1, 2, and 3 wk of Hindlimb Suspension (HS) on force-velocity and power characteristics of single rat soleus fibers were determined. After 1, 2, or 3 wk of HS, small fiber bundles were isolated, placed in skinning solution, and stored at -20 C until studied. Single fibers were isolated and placed between a motor arm and force transducer, functional properties were studied, and fiber protein content was subsequently analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Additional fibers were isolated from soleus of control and after 1 and 3 wk of HS, and fiber type distribution and myosin light chain stoichiometry were determined from SDS-PAGE analysis. After 1 wk of HS, percent type I fibers declined from 82 to 74%, whereas hybrid fibers increased from 10 to 18%. Percent fast type 11 fibers increased from 8% in control and 1 wk of HS to 26% by 3 wk of HS. Most fibers showed an increased unloaded maximal shortening velocity (V(sub 0)), but myosin heavy chain remained entirely slow type I. The mechanism for increased V(sub 0) is unknown. There was a progressive decrease in fiber diameter (14, 30, and 38%) and peak force (38, 56, and 63%) after 1, 2, and 3 wk of HS, respectively. One week of HS resulted in a shift of the force-velocity curve, and between 2 and 3 wk of HS the curve shifted further such that V(sub 0) was higher than control at all relative loads less than 45% peak isometric force. Peak absolute power output of soleus fibers progressively decreased through 2 wk of HS but showed no further change at 3 wk. The results suggest that between 2 and 3 wk the HS-induced alterations in the force-velocity relationship act to maintain the power output of single soleus fibers despite a continued reduction in fiber force

Self-cooling of a micro-mirror by radiation pressure

We demonstrate passive feedback cooling of a mechanical resonator based on radiation pressure forces and assisted by photothermal forces in a high-finesse optical cavity. The resonator is a free-standing high-reflectance micro-mirror (of mass m=400ng and mechanical quality factor Q=10^4) that is used as back-mirror in a detuned Fabry-Perot cavity of optical finesse F=500. We observe an increased damping in the dynamics of the mechanical oscillator by a factor of 30 and a corresponding cooling of the oscillator modes below 10 K starting from room temperature. This effect is an important ingredient for recently proposed schemes to prepare quantum entanglement of macroscopic mechanical oscillators.Comment: 11 pages, 9 figures, minor correction