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Background: Gallbladder cancer (GBC) is an aggressive, uncommon malignancy, with variation in operative approaches adopted across centres and few large-scale studies to guide practice. We aimed to identify the extent of heterogeneity in GBC internationally to better inform the need for future multicentre studies. Methods: A 34-question online survey was disseminated to members of the European-African Hepatopancreatobiliary Association (EAHPBA), American Hepatopancreatobiliary Association (AHPBA) and Asia–Pacific Hepatopancreatobiliary Association (A-PHPBA) regarding practices around diagnostic workup, operative approach, utilization of neoadjuvant and adjuvant therapies and surveillance strategies. Results: Two hundred and three surgeons responded from 51 countries. High liver resection volume units (>50 resections/year) organised HPB multidisciplinary team discussion of GBCs more commonly than those with low volumes (p < 0.0001). Management practices exhibited areas of heterogeneity, particularly around operative extent. Contrary to consensus guidelines, anatomical liver resections were favoured over non-anatomical resections for T3 tumours and above, lymphadenectomy extent was lower than recommended, and a minority of respondents still routinely excised the common bile duct or port sites. Conclusion: Our findings suggest some similarities in the management of GBC internationally, but also specific areas of practice which differed from published guidelines. Transcontinental collaborative studies on GBC are necessary to establish evidence-based practice to minimise variation and optimise outcomes.

Background Synaptic degeneration and accumulation of amyloid β-peptides (Aβ) are hallmarks of the Alzheimer diseased brain. Aβ is synaptotoxic and produced by sequential cleavage of the amyloid precursor protein (APP) by the β-secretase BACE1 and by γ-secretase. If APP is instead cleaved by the α-secretase ADAM10, Aβ will not be generated. Although BACE1 is considered to be a presynaptic protein and ADAM10 has been reported to mainly localize to the postsynaptic density, we have previously shown that both ADAM10 and BACE1 are highly enriched in synaptic vesicles of rat brain and mouse primary hippocampal neurons. Results Here, using brightfield proximity ligation assay, we expanded our previous result in primary neurons and investigated the in situ synaptic localization of ADAM10 and BACE1 in rat and human adult brain using both pre- and postsynaptic markers. We found that ADAM10 and BACE1 were in close proximity with both the presynaptic marker synaptophysin and the postsynaptic marker PSD-95. The substrate APP was also detected both pre- and postsynaptically. Subcellular fractionation confirmed that ADAM10 and BACE1 are enriched to a similar degree in synaptic vesicles and as well as in the postsynaptic density. Conclusions We show that the α-secretase ADAM10 and the β-secretase BACE1 are located in both the pre- and postsynaptic compartments in intact brain sections. These findings increase our understanding of the regulation of APP processing, thereby facilitating development of more specific treatment strategies.

The use of human post-mortem brain material is of great value when investigating which pathological mechanisms occur in human brain, and to avoid translational problems which have for example been evident when translating animal research into Alzheimer disease (AD) clinical trials. The amyloid β (Aβ)-peptide, its amyloid precursor protein (APP) and the intermediate APP-c-terminal fragments (APP-CTFs) are all important players in AD pathogenesis. In order to elucidate which APP CTF that are the most common in brain tissue of different species and developmental stages, and whether there are any differences in these fragments between AD and control brain, we investigated the occurrence of these fragments using different APP c-terminal antibodies. We noticed that whereas the conventional APP-CTFα and CTFβ fragments were most prominent in rat and mouse brain tissue, the major western blotting band detected in human, macaque and guinea pig was of approximately 20 kDa in size, possibly corresponding to the newly discovered APP-CTFη. However, this band was also intensely stained with a total protein stain, as well as by several other antibodies. The staining intensity of the 20 kDa band by the APP antibodies varied considerably between samples and correlated with the staining intensity of this band by the total protein stain. This could potentially be due to non-specific binding of the antibodies to another protein of this size. In-gel digestion and mass spectrometry confirmed that small amounts of APP were present in this band, but many other proteins were identified as well. The major hit of the mass spectrometry analysis was myelin basic protein (MBP) and a myelin removal protocol removed proportionally more of the 20 kDa APP band than the full-length APP and APP-CTFα/β bands. However, the signal could not be immunodepleted with an MBP antibody. In summary, we report on a potentially non-specific western blotting band of approximately 20 kDa and call for precaution when analyzing proteins of this size in human brain tissue.

The toxic amyloid β-peptide (Aβ) is a key player in Alzheimer Disease (AD) pathogenesis and selective inhibition of the production of this peptide is sought for. Aβ is produced by the sequential cleavage of the Aβ precursor protein (APP) by β-secretase (to yield APP-C-terminal fragment β (APP-CTFβ) and soluble APPβ (sAPPβ)) and γ-secretase (to yield Aβ). We reasoned that proteins that associate with γ-secretase are likely to regulate Aβ production and to be targets of pharmaceutical interventions and therefore performed a pull-down assay to screen for such proteins in rat brain. Interestingly, one of the purified proteins was potassium/sodium hyperpolarization-activated cyclic nucleotide-gated ion channel 2 (HCN2), which has been shown to be involved in epilepsy. We found that silencing of HCN2 resulted in decreased secreted Aβ levels. To further investigate the mechanism behind this reduction, we also determined the levels of full-length APP, sAPP and APP-CTF species after silencing of HCN2. A marked reduction in sAPP and APP-CTF, as well as glycosylated APP levels was detected. Decreased Aβ, sAPP and APP-CTF levels were also detected after treatment with the HCN2 inhibitor ZD7288. These results indicate that the effect on Aβ levels after HCN2 silencing or inhibition is due to altered APP maturation or processing by β-secretase rather than a direct effect on γ-secretase. However, HCN2 and γ-secretase were found to be in close proximity, as evident by proximity ligation assay and immunoprecipitation. In summary, our results indicate that silencing or inhibition of HCN2 affects APP processing and thereby could serve as a potential treatment strategy.

Many attempts have been made to identify laboratory tests that are predictive of sperm fertility, both to improve the quality of stallion semen doses for artificial insemination (AI) and to identify potential breeding sires if no fertility data are available. Sperm quality at the stud is mostly evaluated by assessing subjective motility, although this parameter can be poorly indicative of fertility. Sperm morphology and chromatin integrity in Swedish stallions are correlated to pregnancy rate after AI. Because single layer centrifugation (SLC) selects for spermatozoa with normal morphology and good chromatin, retrospective analysis was carried out to investigate whether sperm yield after SLC is linked to potential fertility. Commercial semen doses for AI from 24 stallions (five stallions with four ejaculates each, 19 stallions with three ejaculates each; n = 77) obtained during the breeding season were cooled, and sent overnight to the Swedish University of Agricultural Sciences in an insulated box for evaluation, with other doses being sent to studs for commercial AI. On arrival at Swedish University of Agricultural Sciences, the semen was used for SLC and also for evaluation of sperm motility, membrane integrity, chromatin integrity, and morphology. The seasonal pregnancy rates for each stallion were available. The yield of progressively motile spermatozoa after SLC (calculated as a proportion of the initial load) was found to be highly correlated with pregnancy rate (r = 0.75; P0.001). Chromatin damage was highly negatively correlated with pregnancy rate (r = -0.69; P0.001). Pregnancy rate was also correlated with membrane integrity (r = 0.58; P0.01), progressive motility (r = 0.63; P0.01), and normal morphology (r = 0.45; P0.05). In conclusion, these preliminary results show that sperm yield after SLC is related to the potential fertility of the original ejaculate, and could be an alternative indicator of stallion fertility if breeding data are not available. Single layer centrifugation is fast (30 minutes) and does not require expensive equipment, whereas other assays require a flow cytometer and/or specialist skills. An additional option could be to transport semen doses to a laboratory for SLC if the stud personnel do not want to perform the procedure themselves.

Climate change vulnerability is disproportionately distributed between different population segments in society. This study qualitatively explores how key stakeholders in municipalities (i.e. planning and operational staff in municipalities and the vulnerable themselves) construct social vulnerability in relation to climate change with a specific focus on thermal stress (i.e. heat waves) and which adaptive responses they identify at different levels. The empirical material consists of five focus groups with actors in a large Swedish municipality where the “Vulnerability Factor Card Game” was used as stimulus material to create 10 fictional individuals. The results show that there is a substantial amount of local knowledge about vulnerability drivers and inter-relations between social factors and vulnerability. Local decision-makers also defined a wide range of possible adaptation measures at different municipal levels. Our study clearly indicates that contextualised knowledge, which could complement the q...

The stochastic effects in the lung of inhaled, insoluble particles of alpha- and beta-emitting particles and low-linear energy transfer (LET) thoracic irradiation were compared in rats using data from previously conducted studies. Male and female F344 rats were exposed briefly by nasal inhalation to relatively insoluble aerosols of CeO(2) or PuO(2) to achieve a range of four lung burdens. The mean lifetime beta doses to the lung were 3.6 + or - 1.3 Gy, 6.8 + or - 1.7 Gy, 12 + or - 4.5 Gy, and 37 + or - 5.9 Gy. The mean lifetime alpha doses to the lung were 0.06 + or - 0.03 Gy, 0.95 + or - 0.46 Gy, 3.7 + or - 1.6 Gy, and 12 + or - 2.4 Gy. Additional rats were exposed to fractionated thoracic doses of x rays given on 10 successive working days. The lifetime doses to the lung were 3.3 Gy, 5.7 Gy, 11 Gy, and 38 Gy. Appropriate sham controls were included in each group and all groups were observed for their life spans. Lung neoplasms were found after all exposures, with the incidence increasing with radiation dose. Rats exposed to PuO(2) had the highest incidence, 94% in the group with a dose of 12 Gy. The incidence in the groups exposed to inhaled CeO(2) or fractionated thoracic x-irradiation was not significantly different. The incidence of lung tumors in the PuO(2) groups was 21 times higher than that of the groups exposed to the lower LET radiations. These results support a radiation-weighting factor of 20, as recommended by ICRP 60.

Chromatographic separation patterns of emitted substances are proposed to be used as fingerprints of the defence chemistry in plants. The goal is to recognize the patterns of resistance agents in the chromatograms and to use these patterns for guidance in resistance breeding. This can be done by comparing a reference set of resistant plants with a reference set of nonresistant plants. One problem is the great number of data. A capillary gas chromatogram from a wounded leaf, e.g., may contain more than a hundred component peaks. Such multidimensional comparisons can only be made by a computer. The literature has been searched for computer programs suited for this purpose. The Statistical Isolinear Multiple Component Analysis method (SIMCA) is found to be best suited. It is theoretically estimated that the processing of chromatographic data by the SIMCA-method can enable the resistance breeder to classify unknown plants as resistant or nonresistant; to discern nonrelevant peaks in the chromatograms; to grade the importance of the resistance variables; and to predict the optimal levels for the different resistance agents. The results indicate that capillary gas chromatography and high pressure liquid chromatography can be adapted to handle the great number of samples needed in a breeding program. These methods together cover the molecular range of importance for resistance.

In our model for the evolutionary behaviour of resistance, the prerequisite for the evolution of a parasite-host relationship is a haphazard tolerance developed by the parasite to a sufficiently big sector of the non-host resistance of the plant. The main defence of plants is horizontal resistance evolved from remaining nonhost resistance. Genes of vertical resistance and vertical parasitic ability are microevolutionary gene-for-gene adaptations within the tolerated sector. The importance of supplementary vertical resistance increases with discontinuity of the host plant in time and space. A holistic approach to the biochemistry of resistance mimics the approach of the parasite, because a successful parasite must be able to cope with the whole chemophenotype of the plant. Chromatographic separation patterns can bring to view the invisible pattern of the chemical total defence and open possibilities to predict the durability of resistance. The patterns can be used to recognize and optimize comprehensive horizontal resistance, and to control that horizontal resistance is not lost at low parasite densities or when it is masked by vertical resistance. Other applications are recognition of strong vertical genes, control of the health consequenses of resistance breeding, and screening of germ plasm collections.

Synaptic degeneration and accumulation of the neurotoxic amyloid β-peptide (Aβ) in the brain are hallmarks of Alzheimer disease. Aβ is produced by sequential cleavage of its precursor protein, APP, by the β-secretase BACE1 and γ-secretase. However, Aβ generation is precluded if APP is cleaved by the α-secretase ADAM10 instead of BACE1. We have previously shown that Aβ can be produced locally at the synapse. To study the synaptic localization of the APP processing enzymes we used western blotting to demonstrate that, compared to total brain homogenate, ADAM10 and BACE1 were greatly enriched in synaptic vesicles isolated from rat brain using controlled-pore glass chromatography, whereas Presenilin1 was the only enriched component of the γ-secretase complex. Moreover, we detected ADAM10 activity in synaptic vesicles and enrichment of the intermediate APP-C-terminal fractions (APP-CTFs). We confirmed the western blotting findings using in situ proximity ligation assay to demonstrate close proximity of ADAM10 and BACE1 with the synaptic vesicle marker synaptophysin in intact mouse primary hippocampal neurons. In contrast, only sparse co-localization of active γ-secretase and synaptophysin was detected. These results indicate that the first step of APP processing occurs in synaptic vesicles whereas the final step is more likely to take place elsewhere. This article is protected by copyright. All rights reserved. (Less)

Fermat's principle and variational analysis is used to analyze the trajectories of light propagating in a radially inhomogeneous medium with a singularity in the center. It is found that the light trajectories are similar to those around a black hole, in the sense that there exists a critical radius within which the light cannot escape, but spirals into the singularity., Comment: 5 pages from tex file + 3 figures (eps files)

The decrease in foaling rates after artificial insemination with cooled semen warrants the search for new predictors of fertility. The objectives were to investigate levels of naturally occurring reactive oxygen species (ROS) in cooled, stored stallion semen doses for artificial insemination (AI), and their relationship with parameters of semen quality and with pregnancy rate. Semen was collected from warmblood stallions (n=15) and used to prepare commercial semen doses for AI. Sperm quality was evaluated after cooled transport to the laboratory overnight. The results were correlated with observed foaling and pregnancy rates. Hydroethidine and dichlorodihydrofluorescein diacetate were used as indicators for the ROS superoxide and hydrogen peroxide, respectively. Sperm morphology, motility, plasma membrane integrity and chromatin integrity were also evaluated. These variables were correlated with each other and with pregnancy rates. We found a high inter-individual variation in the ROS levels between stallions. The proportion of live, hydrogen peroxide-negative spermatozoa was correlated with progressive motility, whereas live hydrogen peroxide-negative spermatozoa and chromatin damage were negatively correlated, indicating that low levels of hydrogen peroxide were correlated with good chromatin integrity. The percentage of dead hydrogen peroxide-positive sperm was negatively related to the foaling rate. The negative relationships were stronger when combining results from both assays for ROS. These results for stored semen samples indicate that high individual variation exists for superoxide and hydrogen peroxide measurements, and that ROS status can influence sperm quality. Thus, ROS may be some of the factors influencing fertility. Moreover, combinations of ROS variables improved the correlation with fertility, indicating the usefulness of including these variables in a future model for prediction of the fertility of a semen sample.

OBJECTIVES—Deposits of carbonate rock like limestone and dolomite may contain tremolite asbestos. This study assessed the exposure to tremolite asbestos and the respiratory health of Swedish dolomite workers. METHODS—95% of 137 eligible workers at two dolomite producing companies completed a self administered questionnaire that included questions on respiratory symptoms and were examined with spirometry as well as chest radiography. Total exposure to dust was gravimetrically measured and the tremolite asbestos content of the dust was assessed with polarisation and phase contrast microscopy. RESULTS—Dolomite dust concentrations were moderate (median 2.8 mg/m3) and tremolite asbestos concentrations were generally below the limit of detection (

Little is known about physical activity level and knee function including jump capacity and fear of movement/reinjury more than 20 years after injury of the anterior cruciate ligament (ACL). Seventy persons with unilateral ACL injury participated (23 ± 2 years post-injury): 33 treated with physiotherapy in combination with surgical reconstruction (ACLR ), and 37 treated with physiotherapy alone (ACLPT ). These were compared with 33 age- and gender-matched controls. Assessment included knee-specific and general physical activity level [Tegner activity scale, International Physical Activity Questionnaire (IPAQ)], knee function [Lysholm score, Knee injury and Osteoarthritis Outcome Score (KOOS)], jump capacity (one-leg hop, vertical jump, side hops), and fear of movement/reinjury [Tampa Scale for Kinesiophobia (TSK)]. Outcomes were related to degree of osteoarthritis (OA). ACL-injured had lower Lysholm, KOOS, and Tegner scores than controls (P 0.001), while IPAQ score was similar. ACL-injured demonstrated inferior jump capacity in injured compared with noninjured leg (6-25%, P 0.001-P = 0.010 in the different jumps), while noninjured leg had equal jump capacity as controls. ACL groups scored 33 ± 7 and 32 ± 7 of 68 on TSK. Lower scores on Lysholm and KOOS symptom were seen for persons with moderate-to-high OA than for no-or-low OA, while there were no differences for physical activity and jump capacity. Regardless of treatment, there are still negative knee-related effects of ACL injury more than 20 years later.

Blood concentrations of doxo- and epirubicin were studied in mice after i.v. or i.p. administration under normal and hypothermic conditions. The animals either were pretreated i.p. with chlorpromazine at 15 mg/kg and allowed to cool to a rectal temperature of 28 degrees C or were given saline i.p. with their rectal temperature remaining at 37 degrees C. The anthracyclines were 14-14C-labeled and were given at a dose of 0.85 mg/kg. Blood samples were taken at 5, 15, and 25 min and 2, 6, 24, and 48 hours after injection and were analyzed by liquid scintillation counting. The blood concentration related to time was similar for the two anthracyclines. The peak concentration was highest for i.v. administration and was higher for the hypothermic groups. The peak concentration and the area under the curve were highest under hypothermic conditions. The terminal half-life was longer after i.p. administration. The ratio calculated for the blood concentration under hypothermic/normothermic conditions over time was substantially increased after i.p. administration, the increase being most pronounced for epirubicin. The pharmacokinetic characteristics found might be related to the anthracycline toxicity encountered in tumor-inoculated mice treated at different body temperatures.

Synaptic degeneration is one of the earliest hallmarks of Alzheimer disease. The molecular mechanism underlying this degeneration is not fully elucidated but one key player appears to be the synaptotoxic amyloid β-peptide (Aβ). The exact localization of the production of Aβ and the mechanisms whereby Aβ is released remain elusive. We have earlier shown that Aβ can be produced in crude synaptic vesicle fractions and it has been reported that increased synaptic activity results in increased secreted but decreased intracellular Aβ levels. Therefore, we considered whether Aβ could be produced in synaptic vesicles and/or released through the same mechanisms as neurotransmitters in synaptic vesicle exocytosis. Small amounts of Aβ were found to be produced in pure synaptic vesicle preparations. We also studied the release of glutamate and Aβ from rat cortical nerve terminals (synaptosomes). We found that large amounts of Aβ were secreted from non-stimulated synaptosomes, from which glutamate was not released. On the contrary, we could not detect any differences in Aβ release between non-stimulated synaptosomes and synaptosomes stimulated with KCl or 4-aminopyridine, whereas glutamate release was readily inducible in this system. To conclude, our results indicate that the major release mechanism of Aβ from isolated nerve terminals differs from the synaptic release of glutamate and that the activity-dependent increase of secreted Aβ, reported by several groups using intact cells, is likely dependent on post-synaptic events, trafficking and/or protein synthesis mechanisms.

A theoretical and experimental investigation is made of the leakage power in microwave transmit–receive switches. The peak leakage power is shown to be independent of incident peak power but to depend on the rise time of the incident pulse. The plateau leakage power through the switch is also estimated and shown to be independent of incident peak power. The theoretical predictions for peak leakage power and plateau leakage power are compared and found to be in good agreement with experimental results.

A new benthic sled is described.Favourable features of the sled include: simple operation, broad runners, balanced towing position, simple height adjustment of the sediment cutting edge and quick exchange of the collecting bag. Metallic parts are aluminium, making the sled light (15 kg). This sled has functioned well in coastal research for more than a decade.

The inflammatory cell composition and the expression of major histocompatibility complex (MHC) antigens in the central nervous system (CNS) of 13 cats with a spontaneous, Borna disease-like meningoencephalomyelitis (staggering disease) was investigated by immunohistochemistry with a panel of monoclonal and polyclonal antibodies. T lymphocytes were the predominating inflammatory cells within the adventitial space. CD4+ T cells were more abundant than CD8+ T cells. Scattered IgG-, IgA- and IgM-containing cells were found in the adventitial space and surrounding neuropil, often adjacent to neurons. There was a markedly increased MHC class II expression in cells morphologically resembling microglia. In several cats, Borna disease virus specific antigen was detected, but only in a few cells, mainly of macrophage character. Our findings indicate a long-standing inflammatory reaction in the CNS of cats with staggering disease, possibly triggered and sustained by a persistent viral infection.

We report methods used to synthesize and prepare Li12Si7 and Li22Si5 for nanoindentation testing. The alloys were made by heating lithium granules with silicon powder. X-ray diffraction, inductively coupled plasma-mass spectrometry, and optical microscopy confirmed that the alloys were single phase. Optical microscopy showed that the alloys were fully dense.

The emergence of automated image analysis algorithms has aided the enumeration, quantification, and immunohistochemical analyses of tumor cells in both whole section and tissue microarray samples. To date, the focus of such algorithms in the breast cancer setting has been on traditional markers in the common invasive ductal carcinoma subtype. Here, we aimed to optimize and validate an automated analysis of the cell cycle regulator cyclin D1 in a large collection of invasive lobular carcinoma and relate its expression to clinicopathologic data. The image analysis algorithm was trained to optimally match manual scoring of cyclin D1 protein expression in a subset of invasive lobular carcinoma tissue microarray cores. The algorithm was capable of distinguishing cyclin D1-positive cells and illustrated high correlation with traditional manual scoring (κ=0.63). It was then applied to our entire cohort of 483 patients, with subsequent statistical comparisons to clinical data. We found no correlation between cyclin D1 expression and tumor size, grade, and lymph node status. However, overexpression of the protein was associated with reduced recurrence-free survival (P=.029), as was positive nodal status (P.001) in patients with invasive lobular carcinoma. Finally, high cyclin D1 expression was associated with increased hazard ratio in multivariate analysis (hazard ratio, 1.75; 95% confidence interval, 1.05-2.89). In conclusion, we describe an image analysis algorithm capable of reliably analyzing cyclin D1 staining in invasive lobular carcinoma and have linked overexpression of the protein to increased recurrence risk. Our findings support the use of cyclin D1 as a clinically informative biomarker for invasive lobular breast cancer.

Background Cyclin D1 is a well-characterised cell cycle regulator with established oncogenic capabilities. Despite these properties, studies report contrasting links to tumour aggressiveness. It has previously been shown that silencing cyclin D1 increases the migratory capacity of MDA-MB-231 breast cancer cells with concomitant increase in 'inhibitor of differentiation 1' (ID1) gene expression. Id1 is known to be associated with more invasive features of cancer and with the epithelial-mesenchymal transition (EMT). Here, we sought to determine if the increase in cell motility following cyclin D1 silencing was mediated by Id1 and enhanced EMT-features. To further substantiate these findings we aimed to delineate the link between CCND1, ID1 and EMT, as well as clinical properties in primary breast cancer. Methods Protein and gene expression of ID1, CCND1 and EMT markers were determined in MDA-MB-231 and ZR75 cells by western blot and qPCR. Cell migration and promoter occupancy were monitored by transwell and ChIP assays, respectively. Gene expression was analysed from publicly available datasets. Results The increase in cell migration following cyclin D1 silencing in MDA-MB-231 cells was abolished by Id1 siRNA treatment and we observed cyclin D1 occupancy of the Id1 promoter region. Moreover, ID1 and SNAI2 gene expression was increased following cyclin D1 knock-down, an effect reversed with Id1 siRNA treatment. Similar migratory and SNAI2 increases were noted for the ER-positive ZR75-1 cell line, but in an Id1-independent manner. In a meta-analysis of 1107 breast cancer samples, CCND1 low/ID1 high tumours displayed increased expression of EMT markers and were associated with reduced recurrence free survival. Finally, a greater percentage of CCND1 low/ID1 high tumours were found in the EMT-like 'claudin-low' subtype of breast cancer than in other subtypes. Conclusions These results indicate that increased migration of MDA-MB-231 cells following cyclin D1 silencing can be mediated by Id1 and is linked to an increase in EMT markers. Moreover, we have confirmed a relationship between cyclin D1, Id1 and EMT in primary breast cancer, supporting our in vitro findings that low cyclin D1 expression can be linked to aggressive features in subgroups of breast cancer.

Experimental results of the conductivity noise in the superconducting transition region of YBCO thin films prepared by co-evaporation are presented. In the case of ex situ fabricated samples, Cooper-pair number fluctuations (induced by electron trapping) have been identified in the high-temperature part of the transition. Classical percolation noise was found in the low-temperature part of the transition. In the case of samples made by the in situ method, the noise is smaller by several orders of magnitude in the upper part of the transition. This indicates a much more ordered microstructure in these samples. Electron mobility fluctuations, shunted by the conductance of Cooper-pairs, were identified in this temperature range. In the low-temperature part of the transition, a new type of fluctuation has been discovered; the fluctuation of the volume fraction of the superconducting phase. This implies new scaling exponents very different from the exponents of classical percolation models. This effect is a consequence of intergrain critical current fluctuations and can be caused by, for instance, magnetic flux motion, defect motion or trapping of electrons in the barriers between grains. Moreover, in the in situ fabricated samples, a dimensional crossover, 3D→2D, of the percolating network has been observed. From this effect, the length scale of the microscopic disorder can be estimated.

Summary In 24 cats (Uppsala, Sweden) with neurological signs of “staggering disease” and typical neuropathology, 44% had Borna disease virus (BDV)-specific antibodies. In 173 cat sera (Berlin, Germany) of animals with unknown record, 7% were BDV positive. Out of 24 cats with undefined neurological disorders, 13% were BDV positive. Similarities in staggering disease of cats and Borna disease of horses and sheep suggest related etiological agents.

The lung neoplasms induced in rats by inhaled, internally deposited 144CeO2 were described and classified using histologic criteria. F344 rats were exposed once or repeatedly by inhalation to 144CeO2 and observed for their life span. There was significant life shortening only in those rats with the highest radiation doses. In these rats, there was a high percentage of squamous cell carcinomas of the lung, as well as much lower percentages of adenocarcinomas of the lung, hemangiosarcomas of the lung, and pleural mesotheliomas. At lower doses, adenocarcinomas were the most predominant tumor. These adenocarcinomas were subdivided based on their histologic pattern: alveolar, papillary, tubular, or undifferentiated. Neither the mode of exposure (single or repeated) nor the sex of the rat influenced the lung tumor incidence or tumor type. The lung neoplasms induced by this beta-emitting radionuclide are similar in nature to those induced by alpha-emitting radionuclides deposited in the lung in rats. However, the radiation-induced squamous cell carcinomas of the lung differ from those induced by heavy particle loads of nonradioactive compounds. The radiation-induced squamous cell carcinomas occur in higher incidence and have a more malignant behavior than those induced by heavy particle loads.

Thin films of YBa 2 Cu 3 O 7 (YBCO) were deposited on single crystalline LaAlO 3 substrates using d.c. magnetron sputtering. The quality of the films has been assessed by X-ray diffraction; YBa 2 Cu 3 O 7 grows epitaxially with the c -axis parallel to the substrate normal. For some choices of the deposition parameters in the sputtering process, it was found that secondary phases were precipitated in the films. By a deliberate at choice of deposition parameters, semi-coherently grown Y 2 O 3 (yttria) inclusions could be obtained. They had square platelet or cubical shapes with sizes from 5–20 nm and thickness ∼ 10 nm. The superconducting properties of the YBa 2 Cu 3 O 7 films were investigated using SQUID magnetometry. Magnetization measurements on films with different densities of semi-coherent Y 2 O 3 inclusions indicate an enhanced flux ppinning capability with increasing inclusion density.

The longitudinal component of the magnetization of a single crystal of Bi2.2Sr1.7CaCu2O8 has been investigated by SQUID-magnetometry when the magnetic field is applied at different angles 0-degrees ...

A simple analytical modeling is made of the main breakdown properties of high‐power microwave pulses propagating in air. Particular emphasis is given to breakdown levels, breakdown times, pulse erosion, and optimal pulse energy transfer. Comparison with recent experimental results shows good agreement.

Time-dependent susceptibility measurements have been performed on multilayered two-dimensional (2D) 40-\AA{}-wide ${\mathrm{Cu}}_{0.865}$${\mathrm{Mn}}_{0.135}$ spin-glass films, separated by Cu interlayers of width 10${\mathit{w}}_{\mathrm{il}}$1200 \AA{}. It is found that samples with ${\mathit{w}}_{\mathrm{il}}$30 \AA{} display 3D dynamic behavior. For 30${\mathit{w}}_{\mathrm{il}}$600 \AA{} a gradual decoupling of the spin-glass layers occurs, and for ${\mathit{w}}_{\mathrm{il}}$\ensuremath{\ge}600 \AA{} typical 2D behavior is observed. The effect of a finite interlayer coupling on the dynamic susceptibility is a distinct crossover from 2D dynamic behavior at short observation times to 3D dynamic behavior at long times. A clear influence on the spin-glass dynamics is still observable for interlayer thicknesses of order 500 \AA{}; i.e., multilayered spin-glass films are extremely sensitive probes of the effective range of Ruderman-Kittel-Kasuya-Yosida interaction mediated via metallic interlayers. The results also yield information on the relation between time scale and length scale in relaxation experiments, a fundamental concept of domain theories of the spin-glass phase.

Spontaneous conductivity fluctuations in high-Tc superconducting films on sapphire and SrTiO3 substrates have been measured through the superconducting transition. It is found that the normalized spectrum for the sapphire film is two orders of magnitude larger than for the SrTiO3 film, due to a stronger disorder. At sufficiently low temperatures, the normalized spectrum scales with the conductivity, which proves the existence of a percolation superconducting network.

High precision magnetic relaxation measurements have been performed on BiSrCaCuO single crystals with the field H applied parallel to the c-axis. At temperatures T/Tc > 0.5, the data exhibit two different field regimes. One for H H∗ where the relaxation follows a [ln(t/t0] -α dependence. This relaxation law is predicted in the collective flux creep theory for J ⪡ Jc as well as in the vortex-glass model. In the temperature range 0.25 < T/Tc < 0.4, there is a change in character of the measured decay of the magnetization. This change in character is interpreted to arise from thermal fluctuations of the flux-line lattice giving rise to a considerable reduction in the pinning strength above the depinning temperature.

On the basis of recent results from measurements of spontaneous conductivity fluctuations in YBa 2 Cu 3 O 7 thin films, it is proposed that a number of properties of high- T c superconductors can be understood by means of percolation theory. Using percolation theory, a quantitative analysis of the effects of disorder in these materials is obtained. Using this analysis, suggestions are made on how to achieve higher critical temperatures and stronger critical current densities.

The nonlinear ac susceptibility ${\mathrm{\ensuremath{\chi}}}_{\mathrm{nl}}^{\ensuremath{'}}$ of the short-range Ising spin glass ${\mathrm{Fe}}_{0.5}$${\mathrm{Mn}}_{0.5}$${\mathrm{TiO}}_{3}$ has been measured using a superconducting-quantum-interference-device magnetometer. The spin-glass temperature, ${\mathrm{T}}_{\mathrm{g}}$, and the critical exponent \ensuremath{\gamma} were estimated from the temperature dependence of the quadratic field term of ${\mathrm{\ensuremath{\chi}}}_{\mathrm{nl}}^{\ensuremath{'}}$, yielding ${\mathrm{T}}_{\mathrm{g}}$=20.70 and \ensuremath{\gamma}=4.0. Static-scaling analyses, using different scaling equations, gave similar results. Using \ensuremath{\gamma} and results from previous dynamic-scaling analyses, a number of critical exponents have been obtained through different scaling relations, e.g., \ensuremath{\delta}=8.4 and \ensuremath{\nu}=1.7. The results support the existence of a finite-temperature phase transition in a three-dimensional Ising spin glass.

The zero-field dynamics of a Cu(10 at% Mn) spin glass system has been investigated by means of zero-field-cooled magnetization measurements. By subjecting the sample to specific temperature variations just before the field application, new information about the nature of the spin glass phase is obtained. The results are in accord with some predictions from domain theories on the behaviour of the magnetic relaxation in spin glasses. Specifically, the experimental results support the prediction that the spin glass dynamics is governed by an interplay between a growing domain size and the overlap length.

Spontaneous conductivity fluctuations in high- T c superconducting films on sapphire and SrTiO 3 substrates have been measured through the superconducting transition. It is found that the normalized spectrum for the sapphire substrate film is two orders of magnitude larger than for the SrTiO 3 substrate film, due to a stronger disorder. At sufficiently low temperatures, in the superconducting transition region, the normalized spectrum scales with the conductivity. This is experimental evidence of a temperature controlled percolating superconducting network in high- T c superconductors.

The acute lethality of various cytotoxic drugs (doxorubicin, vinblastine and nitrogen mustard) and long-term survival in a syngenic mouse-tumour system were studied at normal body temperature and at 28 degrees C induced by chlorpromazine. Chlorpromazine-induced hypothermia itself neither caused acute toxicity nor influenced long-term survival. Doxorubicin (15 mg/kg) and nitrogen mustard (6 mg/kg) lethality was reduced at decreased temperature. The median survival time increased significantly from 35 days in normothermic to 52 days in hypothermic doxorubicin-treated mice. With nitrogen mustard, no increase in long-term survival was seen in the hypothermic group. The acute lethality of vinblastine was enhanced by hypothermia and the long-term tumour survival was unaffected. Hypothermia or possibly chlorpromazine considerably modulates drug toxicity and possibly anti-tumoural activity.

Monolithically integrated 4/spl times/4 semiconductor laser amplifier gate switch arrays comprising twenty-four integrated laser amplifiers have been designed, fabricated, and evaluated. Low fiber-to-fiber loss, low polarization dependence, high extinction ratio, and low crosstalk are reported. >

This paper describes the mask layout of a tree-structured strictly nonblocking 4/spl times/4 gate switch array. 16 amplifier gates are used in the interconnection region to control the switch state and four booster amplifiers are included just after the inputs and just before the outputs. The switches are fabricated in the InGaAsP/InP material system, and the fabrication process is based on metal-organic vapour-phase epitaxy (MOVPE) and reactive ion etching (RIE) to form the waveguide mesa; selective wet chemical etching is used to define the active sections in the direction of light propagation. Regrowth is performed in two steps by MOVPE: firstly, iron doped semi-insulating and n doped current blocking layers are selectively grown, and secondly, the contact layers are grown. To laterally isolate the active sections from each other, the contact layers outside the contacts are removed by RIE. Antireflective coatings are applied to the cleaved chips to reduce the optical feedback and for improved coupling efficiency. >

A spontaneous neurological disease in cats characterized by behavioural and motor disturbances was reported in Sweden by Kronevi et al (1974). Generally, the animals showed no gross pathological lesions. Detailed neuro-pathological investigation revealed mononuclear perivascular cuffing and gliosis throughout the brain and spinal cord consistent with a non-suppurative meningoencephalomyelitis. After this first report, the disease has become recognized in different parts of Sweden, preferably Uppland and the area around Lake Mälaren, and is referred to as “staggering disease” of cats. The clinical manifestation of the disease includes hindleg ataxia and paresis (Fig. 1), inability to retract the claws (Fig. 2), mental changes, anorexia, increased salivation, hypersensitivity to sound and light, hyperesthesia, impaired vision and seizures (Kronevi et al 1974, Ström et al 1992). Despite treatment with antimicrobial drugs and corticosteroids most cats deteriorate and die or have to be euthanised after 1-4 weeks of illness.

The time dependence of the low field susceptibility of a Bi2.2Sr1.7CaCu2O8 single crystal has been investigated in the field range 0.1-300 gauss and at temperatures 0.25

The dynamic properties of Cu (13.5 at. % Mn) spin‐glass films of various thicknesses have been investigated in a superconducting quantum‐interference device (SQUID) magnetometer. The films are produced in a dc‐sputtering system and fabricated in the form of multilayer samples. Utilizing zero‐field‐cooled magnetization and ac‐susceptibility measurements, the time‐dependent susceptibility has been probed over eight decades in time (10−4–104 s). Drastic changes of the dynamics are found upon varying the film thickness from 104 to 20 A. The most significant feature is a crossover from a behavior typical for bulk spin glasses for the 104‐A film, with a finite critical temperature and a critical slowing down that can be accurately described by a conventional power‐law divergence, to a slowing down for the very thin films that obeys a generalized Arrhenius law with a zero‐temperature critical point. Thus, these measurements indicate a crossover from three‐ to two‐dimensional spin‐glass dynamics when one spatial dimension is gradually diminished to a finite size.