Observation of Broadband Entanglement in Microwave Radiation from a Single Time-Varying Boundary Condition.

Entangled pairs of microwave photons are commonly produced in the narrow frequency band of a resonator, which represents a modified vacuum density of states. We generate and investigate the entanglement of a stream of photon pairs, generated in a semi-infinite broadband transmission line, terminated by a superconducting quantum interference device (SQUID). A weak pump signal modulates the SQUID inductance, resulting in a single time-varying boundary condition, and we detect all four quadratures of the microwave radiation emitted at two different frequencies separated by 0.7 GHz. Power calibration is done in situ, and we find positive logarithmic negativity and two-mode squeezing below the vacuum in the observed radiation, indicating entanglement.

Forces applied at the footrest during ergometer kayaking among female athletes at different competing levels - a pilot study.

BACKGROUND: Power output and force development during exercise are thought to be important indices of performance in elite athletes. The aim of this preliminary study was to determine the forces applied at the footrest during ergometric kayaking in individual kayakers at different competitive levels. METHODS: Three elite female kayakers participated voluntarily in the study. Oxygen consumption (VO2) and mean power were measured during paddling at three different work levels (15 W below onset of blood lactate accumulation (OBLA), at OBLA, 15 W above OBLA and all-out paddling) on a modified kayak ergometer. External force sensors were attached to the wires on right and left side connecting the paddle to the flywheel of the kayak ergometer. Individual footrests were built to enable measurements of pushing and pulling forces and to distinguish between the left and right foot. RESULT: The relative differences between the three athletes were similar for power, VO2peak and forces at the paddle. There were, however, differences in the forces applied at the footrest, where the most accomplished paddler generated forces 3 to 26 times as high as the least accomplished paddler. CONCLUSION: The relative differences between the three athletes were similar for power, VO2 and forces at the paddle. There were, however, dramatic differences in the forces applied at the footrest.

Effects of HI 6, diazepam and atropine on soman-induced IL-1 beta protein in rat brain.

The current treatment for soman-intoxication is the oxime HI 6 together with the anticholinergic drug atropine. This antidote combination is known to have effects on seizures, respiratory system, blood pressure and animal survival in experiments. However, the inflammatory responses following soman-intoxication leading to neuronal damage have not been fully evaluated. In this paper we focus on the cytokine IL-1beta induction in the rat brain after soman-intoxication (1.0 x LD50 and 1.1 x LD50) and during antidote treatment. We analyzed the IL-1beta levels in rat brain to determine the effects of time of antidote HI 6 and atropine; the effects of different combinations of HI 6 and atropine; and also the effects of antidotes diazepam and atropine following soman-intoxication. We observed that the initiation of the antidote combination of HI 6 and atropine following soman-intoxication was crucial for successful treatment. The study also demonstrated that atropine alone was more effective against IL-1beta up-regulation after soman-intoxication within the 2-h time frame, than the combination of the HI 6 and atropine, the therapy of choice in many countries. Furthermore, treatment with a combination of diazepam and atropine maintained IL-1beta levels at normal when administered at the onset of the seizures following soman exposure. Soman-intoxicated groups without seizures did not have an elevated cytokine level. This corroborates our earlier studies where soman-intoxicated animals with seizures had high levels of IL-1beta, while animals without seizures had normal values. Our results show that both time and the antidote regime are crucial to the success of treatment.

Sphingosine-induced apoptosis is dependent on lysosomal proteases.

We propose a new mechanism for sphingosine-induced apoptosis, involving relocation of lysosomal hydrolases to the cytosol. Owing to its lysosomotropic properties, sphingosine, which is also a detergent, especially when protonated, accumulates by proton trapping within the acidic vacuolar apparatus, where most of its action as a detergent would be exerted. When sphingosine was added in low-to-moderate concentrations to Jurkat and J774 cells, partial lysosomal rupture occurred dose-dependently, starting within a few minutes. This phenomenon preceded caspase activation, as well as changes of mitochondrial membrane potential. High sphingosine doses rapidly caused extensive lysosomal rupture and ensuing necrosis, without antecedent apoptosis or caspase activation. The sphingosine effect was prevented by pre-treatment with another, non-toxic, lysosomotropic base, ammonium chloride, at 10 mM. The lysosomal protease inhibitors, pepstatin A and epoxysuccinyl-L-leucylamido-3-methyl-butane ethyl ester ('E-64d'), inhibited markedly sphingosine-induced caspase activity to almost the same degree as the general caspase inhibitor benzyloxycarbonyl-Val-Ala-DL-Asp-fluoromethylketone ('Z-VAD-FMK'), although they did not by themselves inhibit caspases. We conclude that cathepsin D and one or more cysteine proteases, such as cathepsins B or L, are important mediators of sphingosine-induced apoptosis, working upstream of the caspase cascade and mitochondrial membrane-potential changes.

Soman-induced interleukin-1 beta mRNA and protein in rat brain.

Exposure to high doses of the toxic organophosphate compound soman, also known as a chemical warfare agent, causes a progression of toxic symptoms including hyper-secretions, convulsions, respiratory depression, and finally death. In previous studies, we have demonstrated pronounced effects following soman intoxication in dopaminergic, GABAergic, and cholinergic systems in rat brain. The aim of this study was to investigate the effects on the pro-inflammatory cytokine interleukin-1beta (IL-1beta), indicated as mRNA and protein production, at different time intervals following soman intoxication. The peak levels of mRNA was observed 30 min following soman exposure, while a significant increase in the protein was observed at 6 h. Immunohistochemistry analysis revealed the presence of IL-1beta protein in astrocytes and endothelial cells. In addition to the previously observed effects of soman, there is an induction of IL-1beta in the brain. This effect, which is highly correlated to convulsions, implicates IL-1beta as a possible mediator for long-term brain damage observed after soman intoxication.

Influence of expectations and actual pain experiences on satisfaction with postoperative pain management.

Experience of moderate or even severe postoperative pain has remained a clinical problem despite major progress in pain assessment and management. The aim of the present study was to assess any association between different pre- as well as postoperative factors, actual pain experiences in the postoperative period, and the overall patient satisfaction with the pain management. A random sample of surgical patients (n =191) responded to pre- and postoperative questionnaires detailing presence of preoperative baseline pain, expected and actually experienced postoperative pain levels and perceived adequacy of the pain relief provided. Patient satisfaction was assessed and factors of importance for satisfaction/dissatisfaction were analysed. It was found that 88% of the patients had previously undergone surgical procedures and that 53% of these patients claimed to have experienced moderate or severe pain at that time. Current pain prior to the present surgical procedure was reported by 61% of the patients. Most patients (91%) expected pain of moderate to severe intensity and 76% reported to have experienced such pain levels. In spite of this 81% of the patients claimed to be satisfied with the pain management while only 8% were dissatisfied. Sex, age, pre-operative expectation and actual experience of pain relief, and the overall pain experience were found to be factors associated with the probability of being satisfied/dissatisfied. Main characteristics of the dissatisfied patient were a younger age and female sex. It is concluded that patients commonly expect moderate to severe pain in the postoperative period and that the actual pain experience is mainly in accordance with the pre-operative expectations. Therefore, the validity of patient satisfaction as an optimal outcome variable in quality assurance processes of postoperative pain management may be questioned.

The prevalence of reading and spelling difficulties among inmates of institutions for compulsory care of juvenile delinquents.

Recent studies have focused on reading and writing disabilities among inmates in prisons and at juvenile institutions. Some studies in Sweden have demonstrated that more than half of the delinquents have serious reading difficulties, and for immigrants the situation is even worse. However, these studies have focused on small groups. Furthermore, little attention has been paid to different types of reading and writing difficulties. The main purpose of this investigation was to estimate the prevalence of reading and writing disabilities in juvenile institutions. The study analyses gender differences and differences between immigrants and Swedish pupils. The study included 163 pupils from 22 institutions and used three tests of literacy skills: word identification, spelling and reading comprehension. More than 70% showed some problems in reading and spelling. However, only 11% had serious difficulties. Moreover, the results showed that comprehension ability among immigrant boys was lower than among Swedish boys, despite the same level of word reading skill. The high prevalence of reading and writing disabilities seems primarily to be related to social and cultural factors, home backgrounds, limited school attendance and poor self-esteem rather than to constitutional problems of a dyslexic nature. The implication of this conclusion may be important for the intervention process.

Assessment of pain experiences after elective surgery.

Pain in the postoperative period has remained a clinical problem in spite of major progress in pain assessment and management. The aim of the present study was to describe in detail the time course of pain experiences of surgical patients (n=200) following elective surgical procedures. Visual analogue scale (VAS, 0-100 mm) was used for pain intensity ratings at 4, 24, 48, and 72 hours after surgery. Interviews were carried out to assess the occurrence of intermittent worst pain episodes during each 24-hour period and to relate such experiences to clinical events. At 4, 24, 48, and 72 hours postoperatively, 39%, 43%, 27%, and 16% of the patients, respectively, experienced moderate or even severe pain (VAS > or =40 mm) at rest. During the first 24 hours after surgery, 88% of the patients had experienced moderate or severe pain at some time (VAS > or =40 mm). Corresponding figures for the following 24 hour periods were 81% and 72%, respectively. Spontaneous pain breakthrough and movement/mobilization were identified as reasons for the worst pain episodes during the first 72-hour period after surgery. The probability of pain intensity of VAS >40 mm was calculated from individual regression functions. The probability was found to be much higher for patients receiving parenteral analgesics than for patients receiving prolonged epidural analgesia. Despite major improvements in pain assessment and management, postoperative patients often experience moderate to severe pain, and worst pain episodes occur even in the late postoperative phase. The present study emphasizes that in the clinical routine management of pain, further quality assurance efforts are necessary.

Hydrolytic and transphosphatidylation activities of phospholipase D from Savoy cabbage towards lysophosphatidylcholine.

The hydrolysis and transphosphatidylation of lysophosphatidylcholine (LPC), with a partially purified preparation of phospholipase D (PL D) from Savoy cabbage, was investigated. These reactions were about 20 times slower than the hydrolysis of phosphatidylcholine (PC) in a micellar system. For the transfer reaction, 2 M glycerol was included in the media, which suppressed the hydrolytic reaction. Both reactions presented similar V(max) values, suggesting that the formation of the phosphatidyl-enzyme intermediate is the rate-limiting step. The enzyme had an absolute requirement for Ca(2+), and the optimum concentration was approximately 40 mM CaCl(2). K(Ca)(app) was calculated to be 8.6+/-0.74 mM for the hydrolytic and 10+/-0.97 mM for the transphosphatidylation reaction. Both activities reached a maximum at pH 5.5, independent of Ca(2+) concentration. Kinetic studies showed that the Km(app) for the glycerol in the transphosphatidylation reaction is 388+/-37 mM. Km(app) for the lysophosphatidylcholine depended on Ca(2+) concentration and fell between 1 and 3 mM at CaCl(2) concentrations from 4 to 40 mM. SDS, TX-100, and CTAB did not activate the enzyme as reported for phosphatidylcholine hydrolysis; on the contrary, reaction rates decreased at detergent concentrations at or above that of lysophosphatidylcholine.

Enzymatic fatty acid exchange in digalactosyldiacylglycerol.

Six different lipases were screened for their ability of acidolysis between digalactosyldiacylglycerol (DGDG) and heptadecanoic acid in toluene. Lipases from Geotrichum candidum, Alcaligenes sp. and Penicillium camembertii did not catalyse the acidolysis reaction. Rhizopus arrhizus and Rhizomucor miehei (Lipozyme) catalysed the acidolysis but produced a mixture of DGMG, DGDG, acyl-DGMG and acyl-DGDG. The extra acyl group is bound to the primary hydroxyl of the digalactosyl moiety. Candida antarctica also catalysed the acidolysis but the TLC analysis showed bands with higher Rf values than acyl-DGDG, these probably being different tetra and higher esters. R. arrhizus lipase was the most promising enzyme under the conditions used, with no tetra esters being formed and giving the highest reaction rate of the enzymes investigated. Low water activity (0.06 or 0.11) and high fatty acid concentration (400 mM) increased the formation of acyl-DGDG whilst higher water activities (0.33 and 0.54) increased the amount of DGMG when R. arrhizus lipase was used as catalyst. At a water activity of 0.11 and a fatty acid concentration of 400 mM a yield of 24% modified DGDG was obtained. In this product the fatty acid originally present in the sn-1 position had been exchanged by heptadecanoic acid.

Heat-induced apoptosis in human prostatic stromal cells.

OBJECTIVE: To determine whether heat, used in transurethral microwave thermotherapy (TUMT) for benign prostatic hyperplasia and which causes necrotic lesions within the adenoma, induces apoptosis in benign human prostatic stromal cells. Materials and methods Prostatic stromal cells were cultured from benign human prostatic tissue. The origin of the cells was identified by immunohistochemical staining and transmission electron microscopy. Cell cultures were exposed to moderate hyperthermia (47 degrees C) for 1 h and any apoptosis detected by light microscopy, transmission electron microscopy and the measurement of induced caspase-3-like activity. RESULTS: The cultures contained a mixed population of smooth muscle cells and myofibroblasts. Twenty-four hours after heat exposure, 76% of the cells were apoptotic and the caspase activity had increased, whereas only 14% of the cells were necrotic. CONCLUSION: Moderate hyperthermia induces apoptosis in cultured human prostatic stromal cells.

alpha-tocopheryl succinate-induced apoptosis in Jurkat T cells involves caspase-3 activation, and both lysosomal and mitochondrial destabilisation.

Alpha-Tocopheryl succinate (alpha-TOS), but not a-tocopherol, triggered apoptosis in Jurkat T cells. Apoptosis was induced by alpha-TOS in a time- and concentration-dependent mode, and signs of apoptosis were visible at concentrations of alpha-TOS as low as 30 microM, and within 3-5 h after addition of the ester. Employing a specific fluorogenic substrate, caspase-3 was found to be activated rapidly in response to alpha-TOS at 50 microM. We also found that Jurkat T cells challenged with alpha-TOS, when exposed to the lysosomotropic weak base acridine orange, showed decreased lysosomal uptake of the dye. This is suggestive of the involvement of lysosomal destabilisation in apoptosis of the cells. Apoptosis of Jurkat T cells induced with alpha-TOS also involved a drop in the mitochondrial membrane potential, although this phenomenon occurred after the initiation of lysosomal rupture. All apoptotic features observed with alpha-TOS were very similar to those found when cross-linking of the Fas receptor triggered apoptosis. These findings are consistent with the recent idea that vitamin E can contribute to elimination of malignant cells by the induction of apoptosis, and can be of (patho)physiological significance.

Oxidative stress, growth factor starvation and Fas activation may all cause apoptosis through lysosomal leak.

Oxidative stress, growth factor starvation, and activation of the Fas/APO-1/CD95 receptor all induce apoptosis in a variety of cell-types, including the established human Jurkat T-cell line. Oxidative stress, in the form of exposure of the cells to a bolus dose of hydrogen peroxide, results in intralysosomal, iron-catalyzed oxidative reactions. This is accompanied by a time- and dose-dependent lysosomal destabilization--as evaluated by a decreased lysosomal uptake of the metachromatic fluorochrome, and weak base, acridine orange--in combination with leakage to the cytosol of lysosomal contents, including hydrolytic enzymes. Moderate lysosomal rupture is followed by apoptosis within initially intact plasma membranes, while necrosis and cell lysis are associated with a more complete lysosomal breach. Prior endocytosis of the potent iron-chelator desferrioxamine, resulting in binding of intralysosomal low molecular weight iron in a non-redox active form, largely prevents not only oxidative stress-induced lysosomal labilization, but apoptosis as well. When apoptosis is induced by the use of a monoclonal IgM anti-human Fas/APO-1/CD95 receptor antibody, the apoptotic process is again found to be accompanied by lysosomal leak. It is, however, not prevented by a preceding endocytosis of desferrioxamine and, consequently, could not be a function of intralysosomal iron-catalyzed oxidative reactions, but must be due to other mechanisms. Growth factor starvation of Jurkat cultures for a few days results in a high proportion of apoptotic cells, which contain lysosomes many of which have lost their proton gradient and appear to have released their contents. Overall, our results indicate that lysosomal leakage/rupture precedes apoptosis in Jurkat cells regardless of the initiating agent, but that such rupture may occur through multiple mechanisms. Lysosomal enzymes, leaking out of their normal vacuolar compartment, may then induce apoptosis, perhaps by proteolytic activation of the caspase-family of enzymes. Regardless of the precise mechanism, these observations suggest that partial rupture of the acidic vacuolar compartment may be one of the final pathways in apoptosis.

Toxicity in vitro of some silicon carbides and silicon nitrides: whiskers and powders.

The objectives of this work were to investigate the toxicity of silicon carbide whiskers and powders and silicon nitride whiskers and powders and to compare their toxicity with the toxicity of crocidolite. The effects studied were inhibition of the cloning efficiency of V79 cells, formation of DNA strand breaks by means of a nick translation assay, formation of oxygen radicals in three different assays, and the ability to stimulate neutrophils to produce hydroxyl radicals. All materials showed concentration-dependent inhibition of the cloning efficiency of V79 cells. The inhibition by the most toxic whiskers was in the same order of magnitude as that of crocidolite. Milled whiskers and powders were less toxic than the whiskers. There was a high DNA breaking potential for crocidolite and four of the silicon carbide whiskers and a rather low one for the other materials. Formation of hydroxyl radicals was found for crocidolite and one of the silicon carbide whiskers. In the neutrophil activation test, there was a great variation in the different materials' abilities to activate neutrophils. There was also a good correlation between chemiluminescence and H2O2 formation. The highest activation was found in neutrophils exposed to two of the silicon carbide whiskers and one milled whisker. The conclusion of the investigation is that some of the ceramic materials studied had damaging biological effects comparable to or greater than those of crocidolite. The results from the investigation clearly imply that caution is needed in the introduction of new ceramic fiber materials, so that the correct precautions and protective devices are used in order to avoid harm to the personnel handling the material.

Oxidant-induced apoptosis: a consequence of lethal lysosomal leak?

When macrophage-like J-774 cells are subjected to limited oxidative stress, such as exposure to hydrogen peroxide in a moderate bolus dose, some of their lysosomes rupture-as here assayed by the acridine orange relocalization test-secondary to intralysosomal, iron-catalysed, oxidative reactions. The resultant leakage into the cytosol of hydrolytic enzymes, such as cathepsin-D (as shown here), may initiate a slow degradation/fragmentation process of an apoptotic type within cells still having intact plasma membranes. In contrast, severe oxidative stress also results in extensive lysosomal rupture but leads to necrosis. The chelation of (normally occurring) intralysosomal low-molecular weight iron, by endocytotic uptake of desferrioxamine, largely prevents oxidative stress-induced apoptosis whereas lysosomal iron-loading, by endocytotic uptake of complexed ferric iron, considerably enhances the process. We conclude that oxidant-mediated and iron-catalysed lysosomal rupture leads to decompartmentalization of lysosomal enzymes which in turn may initiate and promote the apoptotic process.

Effects of water activity on reaction rates and equilibrium positions in enzymatic esterifications.

A technique of continuous water activity control was used to examine the effects of water activity on enzyme catalysis in organic media. Esterification catalyzed by Rhizopus arrhizus lipase was preferably carried out at a water activity of 0.33, which resulted in both maximal initial reaction rate and a high yield. When Pseudomonas lipase was used as catalyst it was beneficial to start the reaction at high water activity (giving the optimal reaction rate with this enzyme) and then shift to a lower water activity toward the end of the reaction to obtain a high yield. The apparent equilibrium constant of the reaction was influenced by the water activity of the organic solvent.

Green banana protection of gastric mucosa against experimentally induced injuries in rats. A multicomponent mechanism?

The protective capacities of fresh green (unripe) sweet bananas and of phosphatidylcholine and pectin (banana ingredients) against acute (ethanol- or indomethacin-induced) and chronic (indomethacin-induced) gastric mucosal lesions were evaluated in rats. Banana pulp was mixed with saline and given by gavage, as a pretreatment in a single dose. The identical protocol was used for pectin and phosphatidylcholine solution, and the dosages were adjusted to equal the amount of ingredients in the banana mixture, but higher concentrations were also given. The banana suspension reduced acute lesions, as did pectin and phosphatidylcholine in higher concentrations, but in concentrations as in fresh fruit no protective effects were observed except by pectin against indomethacin injury. In the model of chronic ulcers the banana suspension provided an incomplete and temporary protective effect. We conclude that the protective capacity of fresh green sweet bananas cannot be confined to only one active component. Pectin and phosphatidylcholine may protect gastric mucosa by strengthening the mucous-phospholipid layer, but the mechanism of protection afforded by bananas has to be further elucidated.

The rat gastric phospholipids: increased in ulcerated mucosa and decreased after healing.

The composition and content of the gastric phospholipids were followed during development and healing of indomethacin-induced chronic, antral ulcers in rats. The individual phospholipids were identified by thin-layer chromatography and quantitatively estimated by spectrophotometric analysis of phosphate. No changes were found in phospholipid composition and content after a 24-hour fast or during the first 24 h after indomethacin was given. The total phospholipid content and the content of lysophosphatidylcholine and phosphatidylcholine were increased on the 5th day, when chronic ulcers were established. After 4 weeks, when the ulcers were healed, the total phospholipid content, and content of phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol, respectively, were decreased, while the content of lysophosphatidylcholine was increased. In conclusion, the composition and content of gastric phospholipids were altered in rats with ulcers as well as in rats with healed ulcers.

Effect of reactive oxygen species on lysosomal membrane integrity. A study on a lysosomal fraction.

Using a lysosome-enriched "light mitochondrial" fraction of a rat liver homogenate, the effects of the reactive oxygen species hydrogen peroxide, superoxide- and hydroxyl radicals were determined. Alterations in the intralysosomal pH and the release of a lysosomal marker enzyme, N-acetyl-glucosaminidase, were used as indicators of changes in the lysosomal membrane integrity. Lipid peroxidation of the fraction was assayed by TBARS measurement. Neither superoxide radicals, generated by hypoxanthine/xanthine oxidase, nor a bolus dose of hydrogen peroxide (0.5-1.5 mM) induced any lysosomal damage. If, however, Fe(III)ADP was included in the superoxide radical-generating system, lysosomal membrane damage was detected, both as an increase in lysosomal pH and as a release of N-acetyl-glucosaminidase, but only after a lag phase of about 7 min. Lipid peroxidation, on the other hand, proceeded gradually. Lysosomes treated with hydrogen peroxide displayed similar dose-dependent alterations, albeit only if both Fe(III)ADP and the reducing amino acid cysteine were added. In the latter system, however, alterations of the lysosomal membrane stability occurred more rapidly, showing a lag phase of only 2 min. Lipid peroxidation, which proceeded faster and displayed no lag phase, levelled out within 10 min. The results indicate that neither superoxide radicals nor hydrogen peroxide are by themselves damaging to lysosomes. Available catalytically active iron in Fe(II) form, however, allows reactions yielding powerful oxidative species--probably hydroxyl radicals formed via Fenton reactions--to take place inducing peroxidation of the lysosomal membranes resulting in dissipation of the proton-gradient and leakage of their enzyme contents.