bluuebunny/crossref_metadata_2025 huggingface dataset:
The Signer DNA-Symposium in Bern
Authors: Lienhard Schmitz M.
Published: June 2006

As the year 2003 was not only the 50th anniversary of the discovery of the DNA structure but also the 100th birthday of Rudolf Signer, the Department of Chemistry and Biochemistry at the University of Bern organized a Symposium on November 28th, in order to honour the pioneering work
of its former faculty colleague Rudolf Signer. The invited symposium speakers covered a number of aspects related to the person and work of Rudolf Signer as well as ongoing research on the structure, function and use of DNA and nucleic acids.
Fire Safety in Chemical Laboratories
Authors: Parent Remi
Published: June 2006

Fire safety in chemical laboratories is often the stepchild in industrial safety concepts. This is due to the small quantities of chemicals handled and underestimation of loss of research results and infrastructure. Managing fire safety in chemical laboratories depends more on prevention
than the work of fire fighters. In this article the safety policy of Givaudan is described in detail.
Tools and Procedures of the Science Officer in the Management of Hazardous-Material Incidents
Authors: Rönninger Stephan , Glarner Thomas
Published: June 2006

A chemical science officer ensures with his know-how, his experience based on continuous improvement and with the help of databases, optimal advice to the operational crew. In the event of incidents with hazardous materials, great attention must be given to self-protection of the operational
crew, to the shelter of residents, to the environment and to the prevention of destruction of assets. While minimizing the hazard, the chemical science officer works closely with the officer-in-charge, environmental authorities, police and chemical analysis groups.
Projet Ra&D à l'Ecole d'Ingénieurs et d'Architectes de Fribourg Développement d'un Nouvel Agent Anti-SIDA: NU 1320
Authors: Poffet Martine , Bourgeois Jean-Marc
Published: June 2006

The division of chemistry at the School of Engineering and Architecture of Fribourg is involved with the School of Engineering of Geneva in the development of a new drug for the treatment of AIDS. This recently discovered molecule, called NU 1320, has already shown a powerful antiviral
activity. NU 1320 is a nonnucleoside inhibitor, which stops the formation of the retrotranscription complexe of the HIV-virus. The concentration of NU 1320 to inhibit 50% of viral replication is 10–6 nM: such a low concentration and the non-toxicity will prevent the occurrence
of side effects for the patient. As a future potential HIV drug, the University of Applied Sciences of Western Switzerland (HES-SO) has invested in this research with the start of a project for the scale-up of this new antiviral molecule with the intention to perform in vivo tests.
Organization and Concept of Intervention of the Chemical Defence Bases in Switzerland
Authors: Ludescher Urs
Published: June 2006

In contrast to radiological risks, which are the responsibility of the federal authorities, the cantons have to deal with chemical risks. In agreement with the chemical defence concept of the Swiss Fire Fighters Association (SFFA) each canton should have a network of chemical defence
bases enabling efficient intervention on site within thirty minutes of a chemical accident. Due to the drafting of the 'Ordinance of 27 February 1991 on Protection against Major Accidents' after the disastrous chemical fire in Schweizerhalle on 1 November 1986, it has been possible to reduce
the chemical risks in Switzerland considerably. This could be achieved primarily by reduction of the amounts of hazardous materials in the facilities subject to the ordinance, but also by structural measures, the establishment of powerful intervention forces, and intervention planning. The
responsibility for the training of chemical defence specialists is divided between the SFFA and the cantons. The SFFA organizes training courses for officers-in-charge for chemical accidents and for instructors for chemical defence; the cantons and the chemical industry in turn are responsible
for the basic training of specialists and officers for chemical defence.
Training Hazardous-Materials Response Teams and Chemistry Students through Practical Experimentation
Authors: Hungerbühler Ernst , Gisler Markus
Published: June 2006

Large quantities of hazardous substances are required to meet the needs of today's industrial society. During the manufacture, transport, and use of these substances – whether they serve as raw materials, intermediate products or energy carriers – accidents and damage cannot
be totally excluded despite all the efforts and technical knowledge that may go into their prevention. Incidents involving hazardous chemicals always represent a substantial risk for accident response teams, the general population, and the environment. In order to keep damage to a minimum,
special attention must be given to training the specialists involved. It is possible to demonstrate the risks resulting from hazardous materials and the most suitable methods of effectively combating such risks by the use of thought-provoking practical experiments. This is shown with a number
of examples.
Biphasic Chemistry Utilising Ionic Liquids
Authors: Dyson Paul J.
Published: June 2006

Biphasic and multiphasic processes have emerged as effective methods to reduce the amount of volatile organic solvents used in the manufacture of chemicals. In this article some of the research conducted in my laboratory in this domain utilizing ionic liquids is described. Other dimensions
to our research interests in ionic liquids are also discussed including their conversion to porous nanomaterials.
Review of the Licensing Basis for RIA and LOCA Transients in Light of New Evidence on High Burnup Fuel Behavior
Authors: Zimmermann Martin A. , Bart Gerhard
Published: June 2006

The fuel of power reactors can be damaged by both rapid reactivity insertion accidents (RIA) and by Loss of Coolant Accidents (LOCA) due to the break of a coolant pipe. The consequences of such postulated accidents with a very low probability can be mitigated by dedicated safety systems.
Yet, the possible consequences need to be assessed as part of the safety evaluation in the framework of the reactor licensing process as these transients form part of the so-called design basis. Most importantly, coolability of the reactor core must be demonstrated. The current paper reviews
the important fuel related phenomena that may occur during such transients and their relation to the current licensing basis. Finally, possible changes in light of new experimental evidence from high burnup fuel behavior tests are discussed.
The Role of Water Chemistry for Environmentally Assisted Cracking in Low-Alloy Reactor Pressure Vessel and Piping Steels under Boiling Water Reactor Conditions
Authors: Seifert Hans-Peter , Ritter Stefan
Published: June 2006

The environmentally assisted initiation and propagation of cracks in structural materials is one of the most important degradation and ageing mechanisms in light water reactors (LWR) and may seriously affect plant availability and economics. In the first part of this paper a short general
introduction on environmentally assisted cracking (EAC) and its significance for LWR is given. Then the important role of water chemistry control in reducing the EAC risk in LWR is illustrated by current research results about the effect of chloride transients and hydrogen water chemistry
on the EAC crack growth behaviour of low-alloy reactor pressure vessel and piping steels under boiling water reactor conditions.
Nuclear Reactors: Physics and Materials
Authors: Yadigaroglu George
Published: June 2006

In the form of a tutorial addressed to non-specialists, the article provides an introduction to nuclear reactor technology and more specifically to Light Water Reactors (LWR); it also shows where materials and chemistry problems are encountered in reactor technology. The basics of reactor
physics are reviewed, as well as the various strategies in reactor design and the corresponding choices of materials (fuel, coolant, structural materials, etc.). A brief description of the various types of commercial power reactors follows. The design of LWRs is discussed in greater
detail; the properties of light water as coolant and moderator are put in perspective. The physicochemical and metallurgical properties of the materials impose thermal limits that determine the performance and the maximum power a reactor can deliver.
Water Chemistry in Pressurized Water Reactors – A Gösgen-Specific Overview
Authors: Lips Marcel
Published: June 2006

The three main water circuits of the Gösgen pressurized water reactor and their chemistries are described. In the primary water circuit the cooling water and its contents undergo chemical as well as radiochemical reactions. Chemical agents – such as boric acid – are
used for long-term reactivity control. The boron concentration therefore is dictated by reactor physics and may not be optimal from a chemical viewpoint. Under the given circumstances the chemistry of the primary water circuit cannot be adjusted to a sole optimum covering all the tasks. Nevertheless
it is possible to operate the power plant using a chemical regime that avoids excessive corrosion within the expected plant live time of 60 years. The water-steam cycle with its two phases must be conditioned chemically in a way to protect the water and steam side components from corrosion.
This is done by adding hydrazine to remove oxygen and to form ammonia, which is the main contributor to water alkalinisation. The cooling water system is open to the atmosphere and supplied by river water with continually changing contents. To avoid deposits on the system surfaces an upstream
water treatment plant is used to remove suspended matter and to precipitate calcium and magnesium. Thousands of tons of chemicals are needed to treat the required 20 billions of litres of water each year. Radioactive waste treatment plays an important role in the nuclear industry. Operational
waste is divided into three waste streams. Only one of these waste streams (waste water) is really influenced by water chemistry.
Materials for the Very High Temperature Reactor (VHTR): A Versatile Nuclear Power Station for Combined Cycle Electricity and Heat Production
Authors: Hoffelner Wolfgang
Published: June 2006

The International Generation IV Initiative provides a research platform for the development of advanced nuclear plants which are able to produce electricity and heat in a combined cycle. Very high-temperature gas-cooled reactors are considered as near-term deployable plants meeting
these requirements. They build on high-temperature gas-cooled reactors which are already in operation. The main parts of such an advanced plant are: reactor pressure vessel, core and close-to-core components, gas turbine, intermediate heat exchanger, and hydrogen production unit. The paper
discusses the VHTR concept, materials, fuel and hydrogen production based on discussions on research and development projects addressed within the generation IV community. It is shown that material limitations might restrict the outlet temperature of near-term deployable VHTRs to about 950
°C. The impact of the high temperatures on fuel development is also discussed. Current status of combined cycle hydrogen production is elaborated on.
Safety of Nuclear Waste Repositories
Authors: Hummel Wolfgang , Schneider Jürg W.
Published: June 2006

A short overview is given of different nuclear waste repository concepts, followed by a more detailed discussion of Swiss radioactive waste management planning. Waste types and characteristics and the concept for their disposal are summarised. The safety concept involving a multi-barrier
system is illustrated with the example of vitrified high-level waste. Important geochemical parameters and processes for repository safety are listed, and some selected aspects concerning porewater chemistry, solubility limits and sorption of radionuclides are discussed in detail with specific
examples.
Iodine Behaviour During a Severe Accident in a Nuclear Power Plant
Authors: Guentay Salih , Cripps Robin C. , Jäckel Bernd , Bruchertseifer Horst
Published: June 2006

Iodine is a main fission product of the fuel generated during power operation in nuclear power plants (NPPs). A severe NPP accident can cause fuel, containing fission products (FPs), control rod assemblies and core structures to melt and then release into the containment. The key signatures
of iodine behaviour during a NPP severe accident are reviewed, i.e. its release from the molten core in the reactor pressure vessel and transfer via the primary coolant system into the containment. Containment or filter failure would disperse radioactive iodine into the environment.
The iodine radioisotopes, 131I (T1/2 ca. 8 d) in particular, in sufficient concentrations can pose a health hazard. The overview focuses on the current state of knowledge on iodine behaviour in containment. The formation of volatile iodine species (molecular iodine
and organic iodides) by FP-radiation and recent efforts at PSI to suppress their release by reduction to non-volatile iodide for engineered systems are described. Despite extensively available data, further experimental studies are needed to reduce the significant uncertainties in model development.
In particular, additional studies on organic iodide formation are required, since these species form the major volatile fraction under certain conditions. Gas phase reactions and the potential effects of many other sump constituents are also important.
Fuel Production for LWRs – MOX Fuel Aspects
Authors: Deramaix Paul
Published: June 2006

Plutonium recycling in Light Water Reactors is today an industrial reality. It is recycled in the form of (U, Pu)O2 fuel pellets (MOX), fabricated to a large extent according to UO2 technology and pellet design. The similarity of physical, chemical, and neutron
properties of both fuels also allows MOX fuel to be burnt in nuclear plants originally designed to burn UO2. The industrial processes presently in use or planned are all based on a mechanical blending of UO2 and PuO2 powders. To obtain finely dispersed plutonium
and to prevent high local concentration of plutonium, the feed materials are micronised. In the BNFL process, the whole (UO2, PuO2) blend is micronised by attrition milling. According to the MIMAS process, developed by BELGONUCLEAIRE, a primary blend made of UO2
containing about 30% PuO2 is micronised in a ball mill, afterwards this primary blend is mechanically diluted in UO2 to obtain the specified Pu content. After mixing, the (U, Pu)O2 powder is pressed and the pellets are sintered. The sintering cover gas contains
moisture and 5 v/o H2. Moisture increases the sintering process and the U-Pu interdiffusion. After sintering and grinding, the pellets are submitted to severe controls to verify conformity with customer specifications (fissile content, Pu distribution, surface condition, chemical
purity, density, microstructure).
Encoded Self-Assembling Chemical Libraries
Authors: Melkko Samu , Sobek Jens , Guarda Greta , Scheuermann Jörg , Dumelin Christoph E. , Neri Dario
Published: June 2006

The display of chemical moieties at the extremity of synthetic oligonucleotides allows the self-assembly of large chemical libraries in which every chemical moiety is associated to a unique DNA sequence, serving as an 'identification bar code'. In this article, we describe the principles,
the potential, and the challenges of this novel technology, which promises to facilitate the isolation of high-affinity binders to protein targets of biological and pharmaceutical interest.
Application of RNAi in Biomedical Research
Authors: Hall Jonathan
Published: June 2006

Antisense techniques are powerful tools for the inhibition of gene expression in the target discovery and validation phases of pharmaceutical research. In particular, RNA interference has become a method of choice to investigate the roles of putative target genes in models of disease
states. This technique is technically demanding, particularly when it is applied in complex experiments such as high-throughput genome analysis or in animal models of disease. We describe here two areas of current research in our group, dedicated to advancing these techniques: the use of neural
networks to predict the biological activity of short interfering RNAs, and the application of siRNAs in animal models of disease.
In vitro Transcription and Purification of RNAs of Different Size
Authors: Gallo Sofia , Furler Maya , Sigel Roland K.O.
Published: June 2006

In vitro run-off transcription from a double-stranded DNA template by T7 RNA polymerase is an elegant way to obtain highly pure and uniform RNA oligonucleotides of lengths ranging from about 15 to several thousand nucleotides. Here we describe the different strategies applied
and optimized in our laboratory to enzymatically synthesize RNAs as necessary when working at the interface of bioinorganic chemistry, coordination chemistry, RNA biochemistry and structural biology.
Interaction of Mono- and Dinuclear Metal Complexes with Mono- and Oligonucleotides for Analytical, Radio- and Chemotoxic Purposes
Authors: Spingler Bernhard , Zobi Fabio , Antoni Philipp M. , Medina-Molner Alfredo , Alberto Roger
Published: June 2006

In this article we briefly describe our recent results concerning the interaction of mononuclear [M(CO)3]+ (M = Re, 99Tc and 99mTc) based complexes with guanine and plasmid DNA for chemo- and/or radiotherapeutic purposes. Furthermore, studies
with mono- and dinuclear, coordinatively unsaturated Ni(II) and Cu(II) complexes inducing B- to Z-DNA transitions are outlined. The strong interaction of [M(CO)3]+ with one guanine allows the direct introduction of this core into oligodeoxynucleotides (ODN), without their
previous derivatization, for further elucidation of their biological behavior. Vectors labeled in this way can later be used in radioimaging or -therapy studies. The [M(CO)3]+ core can also mediate the introduction of further biologically active or, for analytical purposes,
fluorescent molecules. Alternatively, ODNs can be derivatized with amino acid based chelators such as histidine. We describe the induction of structural changes in plasmid DNA observed after reaction with the [M(CO)3]+ moiety. This indicates a cisplatin-like behavior
useful for future chemotherapy. Finally, studies of the interaction of mono- and dinuclear complexes with ODN inducing B- to Z-DNA transitions are described and compared to the effect of common electrolytes alone. A clear correlation between salt type and salt concentration was found. These
complexes have a strong potential to be used for analytical or biological purposes as well.
Preparation of Modified RNA Sequences for Biological Research
Authors: Pitsch Stefan , Wenter Philipp , Stutz Alfred , Reymond Luc , Porcher Sébastien , Peer Andreas , Muller Evelyne , Meyyappan Muthulaniappan , Meylan Frédéric , Denarie Cyrille , Ackermann Damian , Wu Xiaolin
Published: June 2006

Our group is working on the development of reliable access to biologically relevant, long, and modified RNA sequences. Here, we briefly present the chemical synthesis of such sequences with 2?-O-triisopropylsilyloxymethyl (= 2?-O-tom) protected ribonucleoside phosphoramidites,
their template-directed enzymatic ligation, and some examples of modified nucleotides, designed to promote structural and biological studies.
Influence of Humic Acids on the Growth of the Microorganisms Utilizing Toxic Compounds (Comparison between Yeast and Bacteria)
Authors: Feifičová Dagmar , Šnajdr Jaroslav , Siglová Martina , Čejková Alena , Masák Jan , Jirků Vladimír
Published: June 2006

Humic acids, a heterogenic group of natural organic macromolecules with a complex polymeric structure, form a significant part of the soil and water environment. They have a high surface activity, thus they are able to interact with other components in the environment (mineral and microbial
cell surfaces, organic and inorganic compounds). This work is focused on humic acid effects on the growth of microorganisms utilizing phenolic compounds as the sole carbon and energy source. For this purpose a bacterial population Rhodococcus erythropolis and a yeast strain Candida
maltosa were used. Both microorganisms had been adapted to the degradation of phenol and phenolic compounds for many years. However, a toxic effect of these compounds still occurs. The addition of humic acids into the cultivation medium extended toleration of the bacteria to higher concentrations
of phenolic compounds and increased the growth of this microbial population as well. In the case of the yeast, humic acids inhibited the growth. Humic acids easily form an additive layer on the surface of the investigated microorganisms. The generated humic acid layer can probably serve as
a transport barrier and thus influence the growth of microbial populations.
Development, Production, and Application of Recombinant Yeast Biocatalysts in Organic Synthesis
Authors: Wohlgemuth Roland
Published: June 2006

The use of biocatalysts from yeast strains in organic synthesis is well established and covers a broad range of reaction classes. A particularly interesting reaction class is the regio- and stereospecific attachment of sugar moieties (i.e. glycosylation) to a variety of natural
products, from small molecules up to oligosaccharides and proteins. Since the bioactivity of many therapeutics depends on the proper glycosylation, the improvement of glycosylation methodology by chemical synthesis, biocatalysis or in vivo approaches is of major interest. We have developed
glycosyltransferase-toolkits for the straight-forward and quantitative transfer of a specific monosaccharide moiety to an acceptor substrate. The stable expression of the ?(1?4)-galactosyltransferase I in Saccharomyces cerevisiae and ?(1?3)-fucosyltransferase VI
in Pichia pastoris has enabled these biocatalysts to be prepared in large-scale for use in organic synthesis. The application of galactosyltransferase using UDP-galactose and fucosyltransferase using GDP-fucose as NDP-sugar donor in the regio- and stereospecific galactosylation and
fucosylation of small molecules is shown with a simplified reaction system. Optimisation of the reaction conditions allows for quantitative glycosylation reactions. The use of recombinant yeasts has been the key to performing this highly efficient glycosylation methodology and represents a
building block of biocatalytic glycomics for the future.
Hundertdreizehn Jahre Burgdorfer Chemie neigen sich zu Ende – Rückblick auf das grosse Klassentreffen vom 11. Juni 2005 Hundertdreizehn Jahre Burgdorfer Chemie neigen sich zu Ende – Rückblick auf das grosse Klassentreffen vom 11. Juni 2005
Authors: Baumberger Franz
Published: June 2006

On June 11th 2005, almost 400 alumni met in Burgdorf to visit their Chemistry Department. Some impressions about the activities of the day are summarized.
Application of Flow Cytometry to Saccharomyces cerevisiae Population Analysis
Authors: Sekavová Barbora , Melzoch Karel , Paulová Leona , Rychtera Mojmír
Published: June 2006

This study was focused on the development and the application of a rapid and reliable staining method for the characterisation of Saccharomyces cerevisiae cells. The experiments were carried out during the shaken flask batch cultivation of yeasts on YEPD medium under aerobic
conditions at 27 °C. Stained samples were analysed with an epifluorescence microscope or by employing a flow cytometer. Three different fluorescent probes such as propidium iodide (PI), fluorescein diacetate (FDA), and fluorescein isothiocyanate (FITC) were used for staining. PI was used
to determine cell viability in a native sample and DNA content in a sample fixed by ethanol. To assess protein distribution in the yeast population the FITC amine-reactive probe was used. Instantaneous cell enzyme activity was measured as the amount of fluorescein liberated from FDA by intracellular
esterase activity.
ETH Zürich und die Basler Chemie – eine grosse Tradition ETH Zürich und die Basler Chemie – eine grosse Tradition
Authors: Seebach Dieter
Published: June 2006

A historic account of the traditional relationship between the Chemistry Department of ETH Zürich and the Chemical Industry in Basel is presented. The development of ETH Zürich from a Swiss polytechnical school to one of the leading research institutions in the world and the
growth of the Swiss companies in the 'Dreiländereck' from dye-stuff producers to global top-players in the pharma- and agro businesses are shown to be closely connected. The strong personality of chemists such as Ruzicka, Reichstein, Karrer, Stoll, and Prelog is correlated with these
unique parallel evolutions. Recent changes, both in chemical research and in chemical industry, have led to a new situation in which the ETH Zürich chemistry department competes globally for the best students and researchers, and in which the companies do not only business, but also research,
development, production, and thus hiring, on a global scale. As chemistry moves into the bio-, medical-, and material sciences we have to safeguard a strong emphasis in teaching the basics of our science (inorganic, organic, physical chemistry, analysis and synthesis – the core of chemistry),
and at the same time make sure that our students and researchers learn the language(s) of the 'neighboring' sciences to be optimally prepared for jobs in industry. In addition, ETH Zürich and industry in Basel must continue to provide, at least to some extent, unrestricted funding and
support of the research groups in Zürich to ensure continuing success in the international competition. This will contribute substantially to the survival of a great tradition.
Computational Chemistry at Novartis
Authors: Lewis Richard , Ertl Peter , Jacoby Edgar , Tintelnot-Blomley Marina , Gedeck Peter , Wolf Romain M. , Peitsch Manuel C.
Published: June 2006

Computational approaches have become an integral part of modern drug discovery and medicinal chemistry. These approaches can be roughly classified into data/information mining (or filtering) and modelling/simulation methods. Taken together, they represent an ever growing source of hypotheses
used to guide experimental approaches and hence drug discovery decisions. Therefore, it is not only important to optimally understand and apply existing methods, but also invest in the development of new algorithms to further improve our selection of drug candidate. The present contribution
will describe a few approaches which have become routine at Novartis.
Polymeric Nanoparticles for Drug Delivery to the Posterior Segment of the Eye
Authors: Bejjani Riad Antoine , Behar-Cohen Francine , Benezra David , Gurny Robert , Delie Florence
Published: June 2006

Diseases of the posterior segment of the eye account for most cases of irreversible blindness worldwide. Drug delivery to this closed compartment remains a challenge because of the internal and external blood retinal barriers that selectively control drug penetration into the retina.
Direct intraocular (intravitreal) delivery is currently used to achieve high drug concentration in the vitreous and the retina but is usually associated with several side effects. Alternatively topical, periocular, and systemic routes of administration can be used but are associated with low
bioavailability and specific side effects. Therefore, intraocular sustained drug delivery systems are being designed to overcome these limitations. Polymeric nanoparticles loaded with therapeutic compounds are under investigation to provide new tools of administration to the eye. The first
part of this paper will briefly review the barriers to ocular delivery of drugs and the advantages of using polymeric nanoparticle carriers as drug delivery systems. In the second part, the results in terms of preparation and characterization of polymeric nanoparticles loaded with nucleic
acids, the study of the transretinal pathway of intravitreally injected nanoparticles and the assessment of their ability to efficiently deliver plasmids and oligonucleotides will be discussed.
Strategy in the Search for New Lead Compounds and Drugs from Plants
Authors: Hostettmann Kurt , Marston Andrew , Wolfender Jean-Luc
Published: June 2006

Plants represent an extraordinary reservoir of novel molecules and there is currently a resurgence of interest in the vegetable kingdom as a provider of new lead compounds for introduction into therapeutic screening programs. Plant constituents of interest are usually isolated following
a bioactivity-guided fractionation procedure. In order to render this approach more rapid and efficient, the dereplication of crude plant extracts with LC-hyphenated techniques (LC/UV-DAD, LC/MS and LC/NMR) represents a strategic element to avoid finding known constituents and to target the
isolation of new bioactive compounds. The development of simple and rapid bioassays is also crucial for an efficient localisation of active principles. In this respect, the use of bioautographic methods, which enable a direct screening of bioactive constituents on TLC is of great interest.
The combination of chemical and biological screening has proved to be very efficient for the survey of an important number of extracts and for the discovery of new lead compounds and several examples of this approach will be discussed in this paper.
Processing of Polymeric Dosage Forms for Advanced Drug Delivery: From Melt-Extrudates to Nanoparticles
Authors: Doelker Eric , Bilati Ugo , Nguyen Cun AN , Galindo-Rodriguez Sergio , Sarraf Abraham G.
Published: June 2006

Pharmaceutical technology has been directed towards solving the challenges brought by changes in drug discovery characterized by the advent, on the one hand, of sparingly water-soluble drugs exhibiting low oral bioavailability and, on the other, by the so-called biopharmaceuticals,
namely peptide and protein drugs as well as nucleic acid materials. The article reviews some of the results obtained in the laboratory in connection with oral and parenteral drug delivery. Hot-melt extrudates for oral administration appear to be very efficient for the sustained release of
highly water-soluble drugs, whereas pH-sensitive nanoparticles have proved very beneficial for increasing the bioavailability of protease inhibitors. Special attention is also paid to the scaling up aspect of the nanoparticle preparation methods. As for the parenteral route, biodegradable
implants and nanoparticles are examined for their potential to extend drug action. The important issue of premature degradation of peptide or protein drugs during manufacturing of particles is also addressed using tetracosactide and insulin as model drugs. In this respect, emphasis is put
on the use of MALDI-TOF MS for the direct assessment of the primary structure of proteins such as insulin in nanoparticles and simultaneous quantification. Finally, various means for preventing rapid clearance of colloidal carriers from the bloodstream by the reticuloendothelial system are
described, in particular the utilization of pegylated biodegradable polymers. The reduction of nanoparticle phagocytosis opens perspectives for improved drug targeting of organs.
Synthesis and Properties of Novel Poly(Hexyl-Substituted Lactides) for Pharmaceutical Applications
Authors: Trimaille Thomas , Gurny Robert , Möller Michael
Published: June 2006

Monohexyl-substituted lactide (mHLA) was synthesized by reaction of 2-hydroxyoctanoic acid with 2-bromopropionyl bromide, and polymerized with tin(II) 2-ethylhexanoate (Sn(Oct)2) or 4-dimethylaminopyridine (DMAP) in the presence of benzyl alcohol by ring-opening polymerization
(ROP). Poly(monohexyl-substituted lactide) (PmHLA) of predictable molecular weights and narrow polydispersities were obtained in convenient bulk conditions at 100 °C within short polymerization times. The polymerizations were well controlled, showing a 'living' character for targeted degrees
of polymerization up to DP = 60 as evidenced by molecular weight versus conversion studies and 1H NMR end group analysis. The hexyl groups have a strong impact on the glass transition temperature (Tg), which is low for PmHLA compared to standard poly(D,L-lactide) (PLA).
Tg and zero shear viscosities at 25 °C can be controlled by the polymer molecular weight, ranging from ?22 °C for Mn = 2800 g/mol to ?10 °C for Mn = 9100 g/mol and 140 to 4850 Pa.s, respectively. These data are in correspondence with
the Fox and Flory equations. The degradation mechanism of the PmHLA polymer in phosphate buffer pH 7.4 at 37 °C was shown to be similar to that of the standard PLA ('bulk erosion' type), with a slightly higher degradation rate, leading to the non-toxic degradation products lactic acid
and 2-hydroxyoctanoic acid. PmHLA has the great potential as an alternative to conventional PLA/PLGA for drug delivery systems. By the hexyl-substitution the biodegradable PLA-ester backbone is conserved but the hydrophobicity is increased in comparison to standard PLA, while a viscous polymer
is obtained. This leads to advantageous injectable solvent-free drug delivery systems, in which drugs can easily be incorporated by simple mixing.
Investigation of Medicinal Plants for the Treatment of Neglected Diseases
Authors: Queiroz Emerson F. , Ahua Kouassi Maximin , Hostettmann Kurt
Published: June 2006

Higher plants represent a rich source of new molecules with pharmacological properties, which could become lead compounds for the development of new drug products. During the last decades, the renewed interest in investigating natural substances has led to the introduction of several
important drugs, such as the anticancer substances vinblastine, vincristine, taxol and camptothecine derivatives, or the antimalarial agent artemisinin. Despite recent scientific and technological advances, parasitic diseases continue to affect millions of people in both tropical and subtropical
zones of the world. On the other hand the drugs used for the treatment of most parasitic diseases are extremely limited. In this field, natural products constitute a reservoir of new molecules with potential therapeutic interest. An outline is presented here of some important results obtained
by the Laboratory of Pharmacognosy and Phytochemistry of the University of Geneva on plants used to treat some of the neglected diseases. The strategy employed for the study of these plants is outlined, covering all aspects from the selection of plant material to the isolation of the active
substances. Different bioactivities have been investigated such as the search for new molluscicidal and larvicidal agents. Results are also included for antileishimanial and antimalarial compounds.
Information Technologies for the Prevention of Medication Errors
Authors: Bonnabry Pascal
Published: June 2006

Significant efforts are currently under way to improve the safety of the medication process in hospitals. Among other solutions, new developments involving information technologies (IT) have attracted growing attention, as they have the potential to attenuate a leading cause of error:
human failure. IT interventions focus on the three major steps of drug use: prescription (computerized physician order entry, CPOE), dispensing (automated dispensing systems, ADS) and administration (scanning barcodes or RFID tags). Although these technologies are used more and more in hospitals,
only few robust data are actually available to measure their real impact on patient safety. CPOE is the best studied, followed by ADS and scanning technologies. More data are necessary to demonstrate their usefulness or to generalize results obtained in selected environments. An increased
use of IT in future years seems to be unavoidable, but its implementation will be a real challenge, since cultural, human, technical, and ergonomic aspects will have to be taken into consideration to avoid failure. Moreover, these technologies can also potentially induce new risks, e.g.
data entry errors, that need a careful consideration during implementation. In conclusion, IT has a huge potential to help reduce the occurrence of medication errors in hospitals, but the real positive impact and the induced risks need to be systematically and scientifically evaluated in various
environments. In the Geneva university hospitals, some developments are under way to implement IT on pilot processes, with a concomitant evaluation by a systematic risk analysis method (FMECA).
Development of Rapid Analytical Methods in the Laboratory of Pharmaceutical Analytical Chemistry (LCAP)
Authors: Rudaz Serge , Geiser Laurent , Guillarme Davy , Veuthey Jean-Luc
Published: June 2006

The use of rapid and ultra-rapid analytical methods in the pharmaceutical domain is mandatory in the drug discovery, drug development, and quality control steps. Liquid chromatography (LC) and capillary electrophoresis (CE) are therefore particularly studied in the Laboratory of Pharmaceutical
Analytical Chemistry (LCAP) to perform fast and ultra-fast analyses of drugs present in different matrices. Due to its sensitivity and selectivity, mass spectrometry (MS) is considered today as the gold standard in pharmaceutical analysis and has been generally used as the detector of choice
for performing rapid analyses. This article gives a survey of the applied strategies achieved in the LCAP for the last five years such as: use of new chromatographic supports and small columns in LC; development of column switching techniques with extraction supports compatible with the direct
injection of biological matrices; use of immobilized enzyme reactors for rapid protein digestion; enhancement of electrophoretic mobility and development of different injection procedures in CE.
Application of Mass Spectrometry for Quantitative and Qualitative Analysis in Life Sciences
Authors: Hopfgartner Gérard , Varesio Emmanuel
Published: June 2006

Due to its ability to analyze macromolecules, as well as polar and thermally labile low molecular weight compounds, mass spectrometry has become a very important tool in bioanalysis in recent years. The Life Sciences Mass Spectrometry Laboratory (LSMS) at the School of Pharmaceutical
Sciences, University of Geneva, opened on April 1st, 2002. Its work is focused on the development and application of mass spectrometry for the qualitative and quantitative analysis of low molecular compounds and macromolecules present in biological fluids, tissues, organisms or cells. The
instruments used for the research include: single quadrupole, triple quadrupole and hybrid MS instruments such as triple quadrupole linear ion traps; equipped with electrospray, nanoelectrospray, atmospheric pressure chemical ionization and matrix-assisted laser desorption.
Statistical and Chemometric Tools Applied to Pharmaceutical Analysis
Authors: Veuthey Jean-Luc , Rudaz Serge
Published: June 2006

The Laboratory of Pharmaceutical Analytical Chemistry (LCAP) is involved in numerous projects and therefore has to use different analytical instrumentations. Separation techniques, such as chromatography or electrophoresis, remain the techniques of choice but need to be adapted in each
specific challenge. To better develop, optimize and validate analytical methodologies, the use of the multivariate approach is of utmost interest. Statistical experimental design is a powerful tool to quantify the effect of one or more variables on a set of measured responses. It provides
a methodological framework for changing operating parameters simultaneously by the help of experimental designs. These approaches involve the smallest possible number of useful experiments and provide maximum information. The relevant results obtained in pharmaceutical analysis compared to
a univariate approach come from their ability to detect and quantify variable interactions and therefore considerably increase the system knowledge. On the other hand, with the increase of modern computerized analytical techniques, the information could be present as hidden structures in the
huge amount of data. As a result, chemometric methods have been applied to extract information. For this purpose, principal component analysis (PCA) combined with other statistical techniques are now necessary to efficiently reduce and interpret complex data structure.
Chemical Biology and Synthesis: The Spring Meeting of the Swiss Chemical Society, March 10th, 2005, Department of Chemistry and Biochemistry, University of Bern
Authors: Archambaud Sylvie
Published: June 2006

The 2005 Spring Meeting of the Swiss Chemical Society was held at the University of Bern on March 10th, 2005. The one-day symposium was dedicated to recent advances in chemical biology and synthesis. The four speakers, Dennis P. Curran, Johann Mulzer, Scott Miller, and Samuel Danishefsky
covered a wide range of modern organic chemistry emphasizing "the formidable power of chemical synthesis" (Danishefsky) to investigate biologically relevant problems.
Optical Sensing and Switching with Designed Molecules
Authors: De Silva A. Prasanna , Magri David C.
Published: June 2006

Some of the recent research in optical sensor and switch molecules at Queen's University of Belfast is out-lined. The ion-induced absorption spectral changes of molecules with ICT (Internal Charge Transfer) excited states are used to demonstrate superposed logic where multiple logic
configurations are simultaneously observable. Similar spectral effects in multi-receptor structures give rise to XOR logic. The ion-induced luminescent spectral changes of molecules with ICT excited states can be combined with the phenomenon of Photoinduced Electron Transfer (PET) to exemplify
tristable systems. Insights can also be gained into the luminescence effects initiated in designed molecules by transition metal ions in non-aqueous media. The ion-induced luminescent spectral changes of PET systems with one or two receptors display YES and AND logic respectively. The latter
yield coincidence sensors for the direct detection of ion pairs. Overall, interesting optical sensors and switches can be produced from rather small molecules when the latter are fitted with ion-receptors.
Origin of the Kinetic Heterogeneity of Ultrafast Light-Induced Electron Transfer from Ru(II)-Complex Dyes to Nanocrystalline Semiconducting Particles
Authors: Wenger Bernard , Grätzel Michael , Moser Jacques-E.
Published: June 2006

Interfacial electron transfer from a molecular dye to a semiconductor is a keystone process in the conversion of light into electricity in dye-sensitized solar cells. The most successful devices developed so far are based on the sensitization of nanocrystalline titanium dioxide by ruthenium
polypyridyl complexes. The ultrafast electron injection from the widely used RuII(dcbpy)2(NCS)2 dye in particular has been intensely studied. Several research groups, including ours, have found that this reaction apparently proceeds with a fast sub-100 fs phase,
followed by a slower kinetic component with a time constant of 0.7–100 ps and accounting for 16–65% of the total yield. No convincing explanation has been provided for a clear understanding of the origin of this non-exponential kinetic behavior. In this contribution we show that
aggregation of dye molecules at the interface is actually responsible for the slow kinetic component of the interfacial electron transfer. A thorough control of the dissolution of the dye and of its adsorption onto nanocrystalline oxide films allowed the reduction of the portion of dye excited
states that react within the slow compartment and even made the latter completely disappear. In the absence of dye aggregates, femtosecond pump-probe studies of the sensitizer's oxidized state appearance yielded a rate constant for charge injection >5×1013 s?1,
corresponding to an electron transfer time of less than 20 fs.
Alkylation of Ethyl Pyruvate via Reductive Coupling of Alkenes and Ethyl 2-(Benzenesulfonylamino)acrylate
Authors: Darmency Vincent , Renaud Philippe
Published: June 2006

Radical coupling of B-alkylcatecholboranes, in situ generated from the corresponding alkenes, with ethyl 2-(benzenesulfonylamino)acrylate is reported. This reaction represents an extension of the radical allylation of Balkylcatecholboranes by allylsulfones. This unique process
allows the preparation of various ?-ketoesters (alkylated pyruvates) in a straightforward manner. It also demonstrates the generality of the radical mediated C–C bond formation starting from organoboranes and allylic benzenesulfonyl derivatives.
Transient Grating Investigations at Liquid–Liquid Interfaces
Authors: Punzi Angela , Brodard Pierre , Vauthey Eric
Published: June 2006

A new four-wave-mixing technique with evanescent optical fields generated by total internal reflection at a liquid–liquid interface is described. Several applications of this method to measure thermoacoustic and dynamic properties near liquid–liquid interfaces are presented.
Long-Range Electron Tunneling in Aqueous and Organic Glasses
Authors: Wenger Oliver S. , Gray Harry B. , Winkler Jay R.
Published: June 2006

Photoinduced electron transfer (ET) reactions have been investigated in glassy media at 77 K. Distance decay parameters for electron tunneling through water, 2-methyltetrahydrofuran, and toluene have been determined through measurements of donor luminescence quenching by randomly dispersed
electron acceptors. Remarkably different long-range ET efficiencies in the three solvents are in accord with the predictions of a super exchange model of distant electronic couplings. We conclude that tunneling energy effects play an important role in long-range ET reactions, and further that
the coupling drops off very rapidly across van der Waals gaps betwee nmolecules in glasses.
Alkali Metal Phenylphosphandiides, [M2PnPhn] (M = Li, Na)
Authors: Stein Daniel , Geier Jens , Schönberg Hartmut , Grützmacher Hansjörg
Published: June 2006

The reaction of phenyldichlorophosphane, PhPCl2, a commercially important precursor for organophosphorus compounds, with lithium and sodium as reducing metals was re-investigated with the aim to well-characterize the resulting oligophosphandiides, [M2(PnPhn)(solv)x]
(M = Li, Na). Experimental conditions for the optimal formation of these compounds were found for both series with M = Li and M = Na and several of these were crystallized and characterized by X-ray diffraction studies. As a result, we find that sodium strongly prefers ion triple structures
[M2(PnPhn)(solv)x] over solvent-separated ion pairs, [M(solv)m]+[MPnPhn(solv)n]?, which have a higher tendency to form with M = Li. Also, while [Na2(P4Ph4)(solv)x]
retains its structure in thf solution, [Li2(P4Ph4)(solv)x] partially dissociates into the radical anion (Ph2P2).? which is detected by EPR spectroscopy. The knowledge about the structures and the behavior of
the alkali metal diphosphandiides allows us to propose a reaction mechanism for their formation.
Copper Staining/Labeling and Scanning Electrochemical Microscopy Readout of Proteins on Poly(vinylidene difluoride) Membranes
Authors: Carano Maurizio , Lion Niels , Girault Hubert H.
Published: June 2006

Scanning Electrochemical Microscopy (SECM) is used in combination with copper labeling to visualize roteins on surfaces. Proteins are adsorbed on a poly(vinylidene difluoride) (PVDF) membrane and stained using a standard protocol involving copper salts. The latter are then reduced to
copper metal and further detected by SECM with ferrocene methanol as a redox mediator in aqueous solution. During the SECM scan, the potential is held at a value at which the oxidation of the redox mediator occurs and a positive feedback current is detected when scanning over copper clusters.
A negative feedback is observed elsewhere.
Bachem, a Swiss Speciality cGMP-Manufacturer: History and Future Prospects
Authors: Vorherr Thomas , Dick Fritz , Sax Beat
Published: June 2006

This article summarizes the development of the Bachem Group and the ongoing commitment regarding its production facilities in Switzerland. Bachem's core business, the manufacture of peptides from lab scale to market quantities, is explained using showcases to detail the high level of
know-how needed to successfully prepare very large biomolecules. Based on these examples, the complexity regarding production processes and allocation of manufacturing sites are elucidated.