Search

Gamma-hydroxybutyric acid (GHB) has become one of the most dangerous illicit drugs of abuse today. It is used as a recreational and date rape drug because of its depressant effect on the central nervous system, which may cause euphoria, amnesia, respiratory arrest, and coma. There is an urgent need for a simple, easy-to-use assay for GHB determination in urine and blood. In this article, a rapid enzymatic assay adapted to clinical chemistry analyzers for the detection of GHB is presented.

Exposure is considered to be an essential ingredient of cognitive-behavioral therapy treatment of social phobia and of most anxiety disorders. To assess the impact of the amount of exposure on outcome, 30 social phobic patients were randomly allocated to 1 of 2 group treatments of 8 weekly sessions: Self-Focused Exposure Therapy which is based essentially on prolonged exposure to public speaking combined with positive feedback or a more standard cognitive and behavioral method encompassing psychoeducation, cognitive work, working through exposure hierarchies of feared situations for exposure within and outside the group. The results show that the 2 methods led to significant and equivalent symptomatic improvements which were maintained at 1-year follow-up. There was a more rapid and initially more pronounced decrease in negative cognitions with the Self-Focused Exposure Therapy, which included no formal cognitive work, than with the more standard approach in which approximately a third of the content was cognitive. In contrast, decrease in social avoidance was more persistent with standard cognitive-behavior therapy which involved less exposure. The results indicate that positive cognitive change can be achieved more rapidly with non cognitive methods while avoidance decreases more reliably with a standard approach rather than an approach with an exclusive focus on exposure.

As a basic operation of mechanical process engineering, pressure filtration and its scale‐up has been described in detail in the literature. But, the pharmaceutical development of active substances, in particular, calls for a scale‐up of relatively small quantities to execute downstream processes in a lean and reliable manner. Therefore, development depends on conclusions from smaller filter equipment. In this study, results from laboratory nutsche filters with filter surface areas of 1.4 cm2and 9.6 cm2were compared with results from a 20 cm2nutsche. It has been shown that no reproducible and reliable data could be generated using the 1.4‐cm2nutsche. While this was possible using the 9.6 cm2nutsche, the permeability was greater than with the recommended 20 cm2nutsche so that a correction factor has to be introduced.

Scuticociliatosis is a disease of fish induced by ciliated parasites of the genus Scuticociliatida.It has been described in sea horses (Hippocampussp.), flounders (Paralichthys olivaceus), and turbots (Scophthalmus maximus). Here we present a case study of a population of sea dragons chronically infected with scuticociliates identified as Philasterides dicentrarchiby histopathology and PCR. Beginning in 2004, over a period of 19 months, 10 sea dragons (Phycodurus equesand Phyllopteryx taeniolatus) were found dead in an aquarium of the Zoological Garden Basle, Switzerland. Clinically, the animals showed only faint symptoms of disease over a short period of time. At necropsy, macroscopic lesions were confined to the skin with multiple, often hemorrhagic, ulcerations. Histologically, epidermal ulcers were associated with necrosis and inflammation of the underlying dermis and musculature. Numerous ciliates, with a morphology consistent with scuticociliates, were present in these lesions. In several animals these ciliates had invaded blood vessels and were detected in gills and internal organs including kidney, thyroid gland, and central nervous system (CNS). In these organs, mild degenerative lesions and inflammatory reactions were evident. The ciliates were identified as Philasterides dicentrarchibased on small-subunit ribosomal RNA (SSUrRNA) gene sequences obtained by polymerase chain reaction (PCR) on DNA extracted from paraffin-embedded tissue sections. Our report shows that scuticociliate infections of sea dragons can develop into a systemic infection and that both species of sea dragons can be affected.

Als Grundoperation der mechanischen Verfahrenstechnik ist die Druckfiltration und deren Scale up in der Literatur ausführlich beschrieben. Jedoch erfordert insbesondere die pharmazeutische Entwicklung von Wirkstoffen ein Scale up kleinerer Mengen und ist deshalb auf Angaben von kleinerem Filterequipment angewiesen. In dieser Arbeit wurden Resultate von Labornutschen mit Filterflächen von 1,4 cm2und 9,6 cm2mit denen einer den VDI-Richtlinien entsprechenden 20-cm2-Nutsche verglichen. Es hat sich gezeigt, dass mit der 1,4-cm2-Nutsche keine reproduzierbaren und verlässlichen Daten generiert werden konnten. Mit der 9,6-cm2-Nutsche ist dies zwar gelungen, die Permeablitäten waren jedoch größer als bei der empfohlenen 20-cm2-Nutsche, weshalb ein Korrekturfaktor einzuführen ist.

An improved global positioning system (GPS)–based animal tracking system is needed to meet quickly evolving demands of ecological research, range livestock production, and natural resource management. Commercially available tracking systems lack the data storage capacity needed to frequently collect animal location data (e.g., 15-minute intervals or less) over long-term deployment periods (e.g., 1 year or more). Some commercial systems have remote data–download capabilities, reducing the need to recapture tagged animals for data retrieval, but these systems download data via satellite (Argos), global system for mobile communications (GSM) cellular telephone, or telemetry radio frequencies. Satellite systems are excessively expensive, and GSM cellular coverage is extremely limited within the United States. Radio-based systems use narrow-band very-high– or ultra-high frequencies requiring the user to obtain frequency allocations. None of these existing systems were designed to provide continual, real-time data access. The Clark GPS Animal Tracking System (Clark ATS) was developed to meet the evolving demands of animal ethologists, ecologists, natural resource managers, and livestock producers. The Clark ATS uses memory-card technology for expandable data storage from 16 megabytes to 8 gigabytes. Remote data downloading and program uploading is accomplished using spread-spectrum radio transceivers, which do not require narrow-band radio frequency allocations. These radios also transmit, at a user-defined time interval, a real-time, GPS-location beacon to any Clark ATS base station within range (about 24km or 15 miles line of sight). Advances incorporated into the Clark ATS make it possible to evaluate animal behavior at very fine spatial- and temporal-resolution over long periods of time. The real-time monitoring provided by this system enables researchers to accurately examine animal distribution and activity responses to acute, short-term disturbances relative to longer-term behavioral patterns. The Clark ATS also provides a huge time- and cost-savings to researchers and natural resource managers attempting to relocate a tagged animal in the field for direct observation or other operations.

Impulsivity is an important and multifaceted psychological construct. Recently, Whiteside and Lynam (2001) have developed the UPPS Impulsive Behavior Scale that distinguishes four dimensions of impulsivity: Urgency, lack of Premeditation, lack of Perseverance, and Sensation seeking. In the present study, we investigated the psychometric properties of a French adaptation of the UPPS Impulsive Behavior Scale. Two hundred and thirty-four undergraduate students completed the UPPS Scale. Exploratory and confirmatory analyses revealed a four factors solution similar to that found in the original study. Also, the results indicated that there was good to very good internal reliability for the four subscales.

The main purpose of this study was to validate a French version of the Cognitive Emotion Regulation Questionnaire (CERQ). A sample of 224 young adults completed the French translation of the CERQ and the Beck Depression Inventory II. Exploratory and confirmatory factor analyses showed that a nine-factor model also explained the data collected with the French version. Internal reliability scores for each strategy ranged from .68 to .87. As in the original version, we found that the emotion regulation strategies could be grouped into adaptive and less adaptive cognitive regulation strategies. In addition, we observed that Self-blame and Rumination are key cognitive regulation strategies predicting whether high or low depressive symptoms are reported.

The purpose of the present study was to explore the links among the four facets of impulsivity (urgency, lack of premeditation, lack of perseverance, and sensation seeking) proposed by Whiteside and Lynam (2001)and decision-making processes. Thirty undergraduate students completed a self-report questionnaire evaluating impulsivity as well as a task measuring decision-making processes, the Iowa Gambling Task. Zero-order correlations and multilevel analysis revealed that only lack of premeditation was specifically linked to disadvantageous decisions on the Gambling Task. This suggests that premeditation is related to decision making influenced by somatic (or emotional) markers.

N400 event-related potential (ERP) components have been observed during semantic incongruity detection in language, face identity andor expression. However, it is still unclear whether semantic processing is functionally equivalent, since no study has directly investigated within the same participants the occurrence of the N400s for language and faces. We recorded ERPs while subjects performed incongruity detection on words, facial identities and facial expressions, with conditions matched to involve context integration. N400s were identified on central-parietal electrodes only for language and face identity processing. Scalp topographies of these N400s differed but a LORETA inverse solution identified a common functional generator in the left lateral frontal cortex, suggesting a general role of this brain region in selecting and contextually integrating semantic information.

PSI is still the only location in which proton therapy is applied using a dynamic beam scanning technique on a very compact gantry. Recently, this system is also being used for the application of intensity-modulated proton therapy (IMPT). This novel technical development and the success of the proton therapy project altogether have led PSI in Year 2000 to further expand the activities in this field by launching the project PROSCAN. The first step is the installation of a dedicated commercial superconducting cyclotron of a novel type. The second step is the development of a new gantry, Gantry 2. For Gantry 2 we have chosen an iso-centric compact gantry layout. The diameter of the gantry is limited to 7,5 m, less than in other gantry systems (∼10–12 m). The space in the treatment room is comfortably large, and the access on a fixed floor is possible any time around the patient table. Through the availability of a faster scanning system, it will be possible to treat the target volume repeatedly in the same session. For this purpose, the dynamic control of the beam intensity at the ion source and the dynamic variation of the beam energy will be used directly for the shaping of the dose.

A highly stable octacoordinated Y‐DOTA‐D‐Phe‐amide(see picture) allows the first use of the powerful β‐emitter 90Y, coupled to a bioactive peptide, in internal radiotherapy of cancer. The same peptide labelled with the γ‐emitter, 67Ga, shows improved biodistribution as a consequence of the hexacoordination of the GaIIIcomplex with a pendant, ionised, acetic acid group.

Abstract.: Recent advances in receptor-mediated tumour imaging have resulted in the development of a new somatostatin analogue, DOTA-dPhe1-Tyr3-octreotide. This new compound, named DOTATOC, has shown high affinity for somatostatin receptors, ease of labelling and stability with yttrium-90 and favourable biodistribution in animal models. The aim of this work was to evaluate the biodistribution and dosimetry of DOTATOC radiolabelled with indium-111, in anticipation of therapy trials with 90Y-DOTATOC in patients. Eighteen patients were injected with DOTATOC (10 µg), labelled with 150–185 MBq of 111In. Blood and urine samples were collected throughout the duration of the study (0–2 days). Planar and single-photon emission tomography images were acquired at 0.5, 3–4, 24 and 48 h and time-activity curves were obtained for organs and tumours. A compartmental model was used to determine the kinetic parameters for each organ. Dose calculations were performed according to the MIRD formalism. Specific activities of >37 GBq/ µmol were routinely achieved. Patients showed no acute or delayed adverse reactions. The residence time for 111In-DOTATOC in blood was 0.9±0.4 h. The injected activity excreted in the urine in the first 24 h was 73%±11%. The agent localized primarily in spleen, kidneys and liver. The residence times in source organs were: 2.2±1.8 h in spleen, 1.7±1.2 h in kidneys, 2.4±1.9 h in liver, 1.5±0.3 h in urinary bladder and 9.4±5.5 h in the remainder of the body; the mean residence time in tumour was 0.47 h (range: 0.03–6.50 h). Based on our findings, the predicted absorbed doses for 90Y-DOTATOC would be 7.6±6.3 (spleen), 3.3±2.2 (kidneys), 0.7±0.6 (liver), 2.2±0.3 (bladder), 0.03±0.01 (red marrow) and 10.1 (range: 1.4–31.0) (tumour) mGy/MBq. These results indicate that high activities of 90Y-DOTATOC can be administered with low risk of myelotoxicity, although with potentially high radiation doses to the spleen and kidneys. Tumour doses were high enough in most cases to make it likely that the disired therapeutic response desired would be obtained.

A new, analytically valid procedure is described to assess the exposure of human beings to the so-called microbial volatile organic compounds (MVOCs) in air. The method can be used routinely for large sample numbers and is especially valuable as a basis for further research on the correlation between single MVOCs and indoor mould growth. The procedure is based on the fact that fungi produce a variety of volatile organic compounds, such as 3-methylbutan-1-ol, 3-methylbutan-2-ol, fenchone, heptan-2-one, hexan-2-one, octan-3-one, octan-3-ol, pentan-2-ol, α-terpineol, and thujopsene, which they emit into the indoor environment. Using diffusive samplers, these MVOCs are adsorbed onto charcoal during a sampling interval of four weeks. The described method is thus superior to existing methods which use short-term active sampling. After desorption with carbon disulfide, the MVOCs were determined by dual-column gas chromatography with flame ionization detection using the large-volume injection technique for sample introduction. The detection limits ranged between 0.15 and 0.53 µg m–3, within-series precision was found to range between 6.5 and 19.0%, and recovery was between 77 and 118%. The procedure has been sucessfully applied in the context of a large field study to measure the indoor MVOC exposure in children's rooms of 132 dwellings. The objective of the study was to examine the relation between indoor mould growth, the indoor MVOC exposure and the prevalence of adverse health effects. Information about mould formation has been obtained by a questionnaire and by the determination of colony forming units of mould fungi in mattress dust. With the exception of 3-methylbutan-2-ol, fenchone, nonan-2-one, octan-2-one, and thujopsene, indoor air concentrations of all MVOCs under investigation were significantly higher inside damp and mouldy dwellings. From the primary MVOCs under investigation, 3-methylbutan-1-ol, hexan-2-one, heptan-2-one, and octan-3-ol were found to be most reliable indicators for mould formation. A correlation was also found between selected MVOCs and the occurance of mould species in mattress dust. Aspergillus sp. correlated with heptan-2-one, hexan-2-one, octan-3-ol, octan-3-one, and α-terpineol, while the occurrance of Eurotium sp. was correlated with higher indoor air concentrations of 3-methylbutan-1-ol, 3-methylbutan-2-ol, heptan-2-one, hexan-2-one, octan-3-ol, and thujopsene. Children living in dwellings with elevated MVOC levels had a higher prevalence of asthma, hay fever, wheezing, and irritations of the eyes. These positive associations persisted after controlling for confounding factors such as age, sex, body-mass index, number of siblings, social status, passive smoking, type of heating, and ventilation habits. However, they were not statistically significant. This lack of significance may be a result of the small number of investigated samples.

The concentrations of cadmium, copper, and zinc have been determined in tissue samples of kidney cortex collected from 399 deceased persons autopsied in Dusseldorf and Duisburg, West Germany. The mean concentrations (geometric means) were: Cd: 17.0 μg/g wet weight (range <0.4-94.3 μg/g); Cu: 1.6/ μg/g (range 0.5-8.7 μg/g); Zn: 29.1 μg/g (range 6.3-91.6 μg/g). Zinc was shown to accumulate with age in the kidney cortex in a way similar to cadmium with peak concentrations at ages between 30 and 50 years. In contrast to cadmium and zinc, the copper content did not increase with age. The calculation of the regression line between individual cadmium and zinc concentrations, expressed as μmol/g wet weight, gave a slope constant 0.723 (regression equation: ZnKc = 0.723 CdKc + 0.342; r=0.46, P <0.001), which corresponds to a somewhat less than equimolar increase of zinc. There was a significant increase of the Cd/Zn ratio in kidney cortex during the first decades of life followed by a decrease at ages over 70 years. The “basal zinc”; content in kidney cortex showed a slight decrease until age 70 years followed by an increase at higher ages.

Holograms may be recorded in photorefractive LiNbO3:Cu with pulsed infrared light (wavelength ?=1064 nm, Q-switched Nd:YAG laser), if the crystals are previously or simultaneously illuminated with a green (?=532 nm) light pulse. We study refractive index changes and time constants of as-grown and thermally treated crystals with different copper concentrations. A model explaining this effect is discussed.

The growth of LiNbO3 single crystals from a melt with the Li/Nb ratio of 0.946, to which 6 wt.% K2O has been added, leads to stoichiometric specimens, essentially free of potassium, with (50±0.15) mol% Li2O in the crystal. This is established by studying the composition dependence of the following properties: linewidths of the electron paramagnetic resonance (EPR) of Fe3+, energy of the fundamental absorption edge, Raman linewidths of phonon modes, and dispersion of the optical birefringence. Comparison of the results with relevant calibration scales leads to the above composition. In all cases the Li2O content was found to be closer to 50% than that of a LiNbO3 crystal vapor-phase equilibrated to 49.9mol% Li2O. The photorefractive effect at light intensities I≥107 W/m2 is suppressed in this stoichiometric material. The features of the ternary system K2O-Li2O-Nb2O5, which are possibly responsible for the unexpected growth of stoichiometric LiNbO3 from the indicated melts, are discussed.

Holographic gratings are recorded in LiNbO3: Fe using frequency-doubled pulses of aQ-switched Nd : YAG laser (light wavelength? = 532 nm, pulse durationtp = 20ns). We monitor diffraction efficiencies of the holograms during and several milliseconds after exposure. Variations of Fe2+ concentration, light intensity, and fringe spacing show that different types of gratings are involved: photochromic, thermooptic, pyroelectric, and space-charge gratings. The influence of the internal pyroelectric field on the light-induced charge transport is discussed in terms of a two-center model. Pyroelectric and bulk photovoltaic effect are shown to partially compensate each other. In LiNbO3: Fe, the photovoltaic effect is the dominant charge-driving force for our recording conditions.

In lithium niobate crystals the focused beam of an argon-ion laser induces birefringence changes. We investigate the intensity dependences of the saturation value of these birefringence changes, the photoconductivity, and the photorefractive sensitivity in nominally pure crystals with different lithium contents and in an iron-doped sample. All experimental results can be described assuming Fe^2+/3+centers—of low concentration in the nominally pure samples—and, in addition, intrinsic Nb_Li polarons as a second photoactive center.

Holographic recording experiments are performed in iron-doped photorefractivc LiNbO3 using twostep (light wavelengths λ = 1064 nm and λ = 532 nm) excitations. Variations of Fe2+ concentration and light intensity show that two-step excitations via an excited Fe2 state are responsible for the large holographic sensitivity. The experimental results indicate that the dominant charge driving force is the photovoltaic effect.

Abstract. In vitro octreotide receptor binding of [¹¹¹In-DOTA⁰,d-Phe¹,Tyr³]octreotide (¹¹¹In-DOTATOC) and the in vivo metabolism of ⁹⁰Y- or ¹¹¹In-labelled DOTATOC were investigated in rats in comparison with [¹¹¹In-DTPA⁰]octreotide [¹¹¹In-DTPAOC). ¹¹¹In-DOTATOC was found to have an affinity similar to octreotide itself for the octreotide receptor in rat cerebral cortex microsomes. Twenty-four hours after injection of ⁹⁰Y- or ¹¹¹In-labelled DOTATOC, uptake of radioactivity in the octreotide receptor-expressing tissues pancreas, pituitary, adrenals and tumour was a factor of 2-6 that after injection of ¹¹¹In-DTPAOC. Uptake of labelled DOTATOC in pituitary, pancreas, adrenals and tumour was almost completely blocked by pretreatment with 0.5 mg unlabelled octreotide, indicating specific binding to the octreotide receptors. These findings strongly indicate that ⁹⁰Y-DOTATOC is a promising radiopharmaceutical for radiotherapy and that ¹¹¹In-DOTATOC is of potential value for diagnosis of patients with octreotide receptor-positive lesions, such as most neuroendocrine tumours.

In LiNbO_3 at light intensities above 10^6 W/m^2 much stronger refractive index changes can be induced, as expected from measurements at low intensities. Most experimental data have been published on iron-doped LiNbO_3 crystals. We propose a two-center charge-transport model for LiNbO3:Fe that describes most results at low and high intensities quantitatively. It explains the intensity dependence of steady-state refractive index changes and enhanced holographic sensitivities at high light intensities as well as the presence of light-induced absorption changes.

Reduced LiNbO3 crystals change their optical absorption under illumination with blue or green pump light. We measure the dependence of this effect on pump intensity I at different probe wavelengths. Steady-state absorption changes and build-up velocities are found to be proportional to the square root of I. Rates of relaxation towards equilibrium in the dark increase exponentially with temperature. Our experimental results can be well described by light-induced dissociation of bipolarons into small polarons unstable at room temperature.

We report on a comparative study of the optical damage-resistant impurities Mg and Zn, as well as In and Sc in LiNbO3. In LiNbO3 doped with these ions a certain behavior of physical properties (e.g., the shape of OH stretch mode bands, phase-matching temperatures of optical frequency doubling, etc.) on the impurity concentration is observed. The corresponding ('threshold') concentrations are about 5-7 mol.% for the divalent cations Mg and Zn and only 1 mol.% for the trivalent In and Sc. The results are discussed assuming that these ions incorporate on Li-sites thus removing the intrinsic defect NbLi from the lattice.

Calretinin-22k (CR-22k) is a splice product of calretinin (CR) found specifically in cancer cells, and possesses four EF-hands and a differently processed C-terminal end. The Ca2+-binding properties of recombinant human calretinin CR-22k were investigated by flow dialysis and spectroscopic methods and compared with those of CR. CR possesses four Ca2+-binding sites with positive cooperativity (nH = 1.3) and a [Ca2+]0.5 of 1.5 microM, plus one low affinity site with an intrinsic dissociation constant (K'D) of 0.5 mM. CR-22k contains three Ca2+-binding sites with nH of 1.3 and [Ca2+]0.5 of 1.2 microM, plus a low affinity site with K'D of 1 mM. All the sites seem to be of the Ca2+-specific type. Limited proteolysis and thiol reactivity suggest that that the C terminus of full-length CR, but not of CR-22k, is in close proximity of site I leading to mutual shielding. Circular dichroism (CD) spectra predict that the content of alpha-helix in CR and CR-22k is similar and that Ca2+ binding leads to very small changes in the CD spectra of both proteins. The optical properties are very similar for CR-22k and CR, even though CR-22k possesses one additional Trp at the C-terminal end, and revealed that the Trp residues are organized into a hydrophobic core in the metal-free proteins and become even better shielded from the aqueous environment upon binding of Ca2+. The fluorescence of the hydrophobic probe 2-p-toluidinylnaphtalene-6-sulfonate is markedly enhanced by the two proteins already in the absence of Ca2+ and is further increased by binding of Ca2+. The trypsinolysis patterns of CR and CR-22k are markedly dependent on the presence or absence of Ca2+. Together, our data suggest the presence of an allosteric conformational unit encompassing sites I-III for CR-22k and I-IV for CR, with a very similar conformation and conformational changes for both proteins. In the allosteric unit of CR, site IV is fully active, whereas in CR-22k this site has a 80-fold decreased affinity, due to the decreased amphiphilic properties of the C-terminal helix of this site. Some very specific Ca2+-dependent conformational changes suggest that both CR and CR-22k belong to the "sensor"-type family of Ca2+-binding proteins.

We analyzed the biodistribution of the ¹¹¹In-labelled murine anti-tenascin-C MAb BC-2 after intralesional injection in 15 glioblastoma patients. The activated ligand DTPA was conjugated via the isothiocyanato-benzyl group onto BC-2. Conjugates were labelled with ¹¹¹In, displaying immunoreactivity greater than 90% and labelling efficiency of 99 ± 1%. In contrast to i.v. injections, excellent tumor uptake was obtained by direct intralesional injection of conjugates that showed only slow systemic release. In serum, conjugates were found to be intact; in urine, only low-molecular-weight decay products were detected. In 8 patients, outflow from the site of injection into systemic circulation was low; daily activity in the serum and urine was found to be below 2% of the total injected radioactivity; most of the injected activity was retained within the tumor, resulting in effective half-lives of 58 ± 5 hr. In contrast, higher outflow up to 10% of regionally injected ¹¹¹In-DTPA-BC-2 MAb into systemic circulation resulted in considerable shortening of the effective half-lives to 20 to 40 hr in 7 patients. This outflow was found to correlate with tumor size and blood/brain barrier disruption. In one patient, HPLC analysis of tumor cyst fluid 3 and 6 days after intralesional injection revealed conjugates to be intact and allowed the estimate of about 70% of the total injected ¹¹¹In-DTPA-BC-2 to be confined to tumor tissue. We conclude that different outflow patterns can be observed following locoregional injection of ¹¹¹In-DTPA-BC-2, leading to considerable variations in the effective half-lives of isotopes within the tumor, requiring adjustment of the radiation dose in therapeutic trials.Int. J. Cancer 71: 810-816, 1997. © 1997 Wiley-Liss Inc.

The effects of chronic low-level tetrachloroethene (TCE) exposure on functions of the central nervous system (CNS) were measured in subjects living in the neighborhood of dry cleaning shops with a mean residential time of 10.6 years. Neurobehavioral tests were performed using a German version of the NES battery. Additionally, pattern reversal visual-evoked potentials (VEPs) were recorded. The mean blood TCE concentration in the subjects was 17.8 μg/liter and the median indoor TCE air concentration measured in the residences was 1.36 mg/m3. The outcome of the NES subtests for vigilance, simple reaction time, as well as visual memory differed statistically significantly between the exposed subjects and the controls, whereas for VEP latencies the differences were statistically not significant. It is concluded that despite the low exposure levels, CNS functions might be affected by TCE in subjects living close to a dry cleaning facility if the exposure lasts for several years.

Bovine seminal ribonuclease (RNase) diverged from pancreatic RNase after a gene duplication ca. 35 million years ago. Members of the seminal RNase gene family evidently remained as unexpressed pseudogene for much of its evolutionary history. Between 5 and 10 million years ago, however, after the divergence of kudu but before the divergence of ox, evidence suggests that the pseudogene was repaired and expressed. Intriguingly, detailed analysis of the sequences suggests that the repair may have involved gene conversion, transfer of information from the pancreatic gene to the RNase pseudogene. Further, the ratio of non-silent to silent substitutions suggests that the pancreatic RNases are divergently evolving under functional constraints, the seminal RNase pseudogenes are diverging under no functional constraints, while the genes expressed in the seminal plasma are evolving extremely rapidly in their amino acid sequences, as if to fulfil a new physiological role.

The colloidal synthesis of ZnO−WO3 heteroaggregates composed of 3−5 nm particles is presented. These sols can be used to prepare nanocrystalline ZnWO4 xerogels, powders, and thin films with strong blue fluorescence (quantum yield between 25 and 50% at room temperature). The conversion of the precursor aggregates into nano- and microcrystalline monoclinic ZnWO4 Sanmartinite has been followed by XRD, DTA−TG−MS, SEM, FTIR, optical absorption, and fluorescence methods. The ZnWO4 crystallites start to develop at 350 °C, and their mean crystal size increases with temperature to 35 nm at 400 °C and 120 nm at 600 °C. At the same time, the fluorescence intensity increases by 3 orders of magnitude within the aforementioned temperature regime, no matter whether X-rays or UV photons are used to excite the samples. In complementary time-resolved X-ray fluorescence investigations, two recombination processes in the micro- and millisecond range were detected. In weakly fluorescing ZnO−WO3 aggregate samples at sizes between 10 and 30 nm, the slow millisecond process dominates the recombination of the charge carriers whereas in 50−275 nm crystals and above, the faster 2.5 μs process dominates the decay kinetics. Accordingly, the slow afterglow process is attributed to a recombination between electrons and holes deeply trapped at the surface of the heteroaggregates. The faster 2.5 μs recombination process takes place only in the perfectly developed Sanmartinite phase.

We report on a detailed investigation (EPR, SHG, optical absorption, luminescence and Raman scattering) on the new damage-resistant impurity indium in LiNbO3, where the increased photoconductivity strongly reduces the photorefractive effect. EPR and optical absorption measurements point to a complete disappearance of the Nb antisite in LiNbO3: In for all In concentrations. We believe that the very effective driving out of Nb antisites by In is due to the trivalent charge state of In and the possibility of charge self-compensation. Similarities in the properties of Mg-, Zn- or Indoped samples are discussed. Simultaneous doping with In and Zn leads to an addition of both contributions, in particular for optical frequency doubling and luminescence. Raman studies prove that In does not improve the stoichiometry of the crystals. Indium doping provides the possibility to control simultaneously phase-matching conditions and to reduce drastically photorefraction. Therefore, In co-doped LiNbO3 compositions are promising materials for applications after solving contemporary growth problems.

Light-induced refractive index changes in LiNbO3:Fe crystals are investigated at high light intensities (>109 Wm-2). Holographic gratings are recorded and erased with frequency-doubled pulses of a Q-switched Nd:YAG laser. We find new intensity dependent contributions to the holographic sensitivity, to the photoconductivity, and to the saturation value of refractive index change. Light-induced absorption changes are also detected. These results indicate that the Fe2+/Fe3+ charge transport model, well established for low intensities, has to be modified for high intensities by assuming additional centers which trap and supply electrons.

In LiNbO3:Fe,Me crystals (Me = K, Mg, Zn) elementary holograms are recorded and erased with frequency-doubled, ordinarily polarized pulses of a Q-switched Nd:YAG laser. At high light intensities (I > 109 Wm-2) holographic sensitivities and saturation values of refractive index changes grow with increasing intensity and a contribution to photo-conductivity appears increasing quadratically withI. The intensity-dependent parts of the holographic quantities are diminished by increasing the lithium content of the samples or by doping the crystals with magnesium or zinc. Experimental results can be described by a two-center charge transport model, which is the Fe2+/3+ model supplemented by shallow traps, namely niobium ions occupying lithium sites.

A static capillary gas chromatographic method using three different detectors [photoionization detector (PID), electron capture detector (ECD) and flame ionization detector (FID)] switched in series is presented for the determination of volatile organic compounds (VOCs) in sub µg l–1 levels. The method was applied for the analysis of selected environmentally and occupationally relevant non-halogenated and chlorinated aromatic hydrocarbons (e.g., benzene, toluene, xylenes, dichlorobenzenes) as well as chlorinated aliphatic hydrocarbons (e.g., trichloroethene, tetrachloroethene) in blood samples. Detailed investigations, in respect to the figures of merit were carried out. For most of the selected VOCs detection limits (calculated as the three-fold standard deviation of low level calibration standards) in the range from 26 (benzene) to 67 ng l–1 (m/p-xylene) were achieved which are comparable with those reported for dynamic headspace techniques in combination with mass spectrometric detection. For the individual VOCs the within-series precision varied from 4 to 19% and the day-to-day precision from 11 to 28%. Regarding PID as well as FID the calibration graphs for all substances were linear up to at least 10 µg l–1 while the ECD response was linear up to concentrations of about 0.6 µg l–1 for the halogenated compounds. Our method is applicable for the quantitative determination of VOCs in blood in the occupationally as well as in the physiologically relevant (normal) concentration range.

Photoanodic (water and methanol oxidation) and cathodic (oxygen reduction) processes occurring at illuminated (with near - UV light) bulk and particulate anatase and rutile TiO2films were analysed. (Photo) current-potential curves recorded for both anodic and cathodic processes point to large differences in activity between the two forms of TiO2. In particular, in the presence of various organic compounds, the photocurrent onset potential of anatase tends to shift negatively (sometimes as much as 0.3 V), thus increasing drastically the difference with respect to the potential of oxygen reduction. The situation is quite different for the rutile samples, the photocurrent onset potential of which appears practically unaffected by the addition of organic species to the solution and remains close to the onset potential of oxygen reduction. The reverse reaction with respect to the photoanodic process, involving species generated by the photo-oxidation of water and OH−ions, is shown to play often an essential role in determining the photocurrent onset potential (i.e. the operating mixed potential) of the photocatalyst. This is the prevailing situation for rutile but is much less frequent for anatase. In fact, a number of species, especially among organic compounds, appear able to compete efficiently for positive holes with OH groups adsorbed at the anatase surface, leading to a virtual suppression of the reverse reaction. In such a case, the reduction of oxygen present in the solution becomes the main cathodic process. This description is consistent with the fact that, in most cases of real photodegradation processes, the anatase form of TiO2exhibits much greater activity than the rutile form.

Hybrid Monte Carlo Techniques for the solution of elliptical and parabolic partial differential equa tions have been developed. This paper primarily con cerns the implementation of these techniques with a small, general-purpose digital conputer, a modest analog computer, and a minimal interface.

Tumor mutation burden (TMB) is evaluated as a biomarker of response to immunotherapy. We present the efforts of the Onconetwork Immuno-Oncology Consortium to validate a commercial targeted sequencing test for TMB calculation. A three-phase study was designed to validate the Oncomine Tumor Mutational Load (OTML) assay at nine European laboratories. Phase 1 evaluated reproducibility and accuracy on seven control samples. In phase 2, six formalin-fixed, paraffin-embedded samples tested with FoundationOne were reanalyzed with the OTML panel to evaluate concordance and reproducibility. Phase 3 involved analysis of 90 colorectal cancer samples with known microsatellite instability (MSI) status to evaluate TMB and MSI association. High reproducibility of TMB was demonstrated among the sites in the first and second phases. Strong correlation was also detected between mean and expected TMB in phase 1 (r2 = 0.998) and phase 2 (r2 = 0.96). Detection of actionable mutations was also confirmed. In colorectal cancer samples, the expected pattern of MSI-high/high-TMB and microsatellite stability/low-TMB was present, and gene signatures produced by the panel suggested the presence of a POLEmutation in two samples. The OTML panel demonstrated robustness and reproducibility for TMB evaluation. Results also suggest the possibility of using the panel for mutational signatures and variant detection. Collaborative efforts between academia and companies are crucial to accelerate the translation of new biomarkers into clinical research.