1,610 research outputs found
Synthesis of (S)- and (R)-5-oxo-piperazine-2-carboxylic acid and its application to peptidomimetics.
Monitoring and Optimization of Building Operations of a Low-Energy School Building
The ambitious design and energy concept of the new Gebhard-Müller-Schule (GMS) school building in Biberach/Riss, Germany proved itself during the first three school years of operation. The intended target value of 30 kWh/(m2a) overall heating energy consumption was almost met during the second year of operation in 2006 and finally achieved in 2007, due to well-working optimization measures, which were identified through monitoring of the building operation. Heating and cooling energy is mainly provided by a groundwater well plant, which serves as a heat source for two heat pumps as well as a direct cooling source for supplying the radiant heating and cooling system that is integrated in the concrete floor and ceiling slabs (thermally activated building component systems – TABS). Indoor air conditioning and server room cooling are also connected to the groundwater cooling system. The main component of the groundwater well plant is a submersible pump on the bottom of the well which is located underneath the building. The pump supplies the building reliably with geothermal energy, but also consumes a significant amount of electricity. Monitoring and optimization of the building’s operation, funded by the Federal Ministry of Economics and Technology in Germany, revealed fundamental findings about the operation of the system and the possibilities to improve the building’s performance. Since 2005, the measurements show a continuous increase in efficiency, particularly in the field of auxiliary energies. This significantly increased performance clearly shows the potential of the use of groundwater for heating and cooling purposes and of thermally activated building component systems. In addition the measurements reveal the sensitivity of the system efficiency in terms of operating parameters
Ibuprofen Ameliorates Fatigue- And Depressive-Like Behavior in Tumor-Bearing Mice
Aims: Cancer-related fatigue (CRF) is often accompanied by depressed mood, both of which reduce functional status and quality of life. Research suggests that increased expression of pro-inflammatory cytokines is associated with skeletal muscle wasting and depressive- and fatigue-like behaviors in rodents and cancer patients. We have previously shown that treatment with ibuprofen, a nonsteroidal anti-inflammatory drug, preserved muscle mass in tumor-bearing mice. Therefore, the purpose of the present study was to determine the behavioral effects of ibuprofen in a mouse model of CRF.
Main methods: Mice were injected with colon-26 adenocarcinoma cells and treated with ibuprofen (10 mg/kg) in the drinking water. Depressive-like behavior was determined using the forced swim test (FST). Fatigue-like behaviors were determined using voluntary wheel running activity (VWRA) and grip strength. The hippocampus, gastrocnemius muscle, and serum were collected for cytokine analysis.
Key findings: Tumor-bearing mice showed depressive-like behavior in the FST, which was not observed in mice treated with ibuprofen. VWRA and grip strength declined in tumor-bearing mice, and ibuprofen attenuated this decline. Tumor-bearing mice had decreased gastrocnemius muscle mass and increased expression of IL-6, MAFBx and MuRF mRNA, biomarkers of protein degradation, in the muscle. Expression of IL-1β and IL-6 was also increased in the hippocampus. Treatment with ibuprofen improved muscle mass and reduced cytokine expression in both the muscle and hippocampus of tumor-bearing mice.
Significance: Ibuprofen treatment reduced skeletal muscle wasting, inflammation in the brain, and fatigue- and depressive-like behavior in tumor-bearing mice. Therefore, ibuprofen warrants evaluation as an adjuvant treatment for CRF
Implementation and modeling of a femtosecond laser-activated streak camera
8 June 2017) A laser-activated streak camera was built to measure the duration of femtosecond electron pulses. The streak velocity of the device is 1.89 mrad/ps, which corresponds to a sensitivity of 34.9 fs/pixels. The streak camera also measures changes in the relative time of arrival between the laser and electron pulses with a resolution of 70 fs RMS. A full circuit analysis of the structure is presented to describe the streaking field and the general behavior of the device. We have developed a general mathematical model to analyze the streaked images. The model provides an accurate method to extract the pulse duration based on the changes of the electron beam profile when the streaking field is applied
Fluoxetine Prevents the Development of Depressive-like Behavior in a Mouse Model of Cancer Related Fatigue
Cancer patients frequently suffer from fatigue, a complex syndrome associated with tiredness and depressed mood. Cancer-related fatigue (CRF) can be present at the time of diagnosis, escalates during treatment, and can persist for years after treatment. CRF negatively influences quality of life, limits functional independence, and is associated with decreased survival in patients with incurable disease. We have previously shown that increased pro-inflammatory cytokine expression in the brain contributes to depressive- and fatigue-like behaviors in a mouse model of CRF. Inflammatory cytokines increase the activity of indoleamine 2,3-dioxygenase (IDO) and kynurenine 3-monooxygenase (KMO), which competitively reduce serotonin synthesis. Reduced serotonin availability in the brain and increased production of alternative neuroactive metabolites of tryptophan are thought to contribute to the development of depression and fatigue. The purpose of this study was to determine the effects of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), on brain cytokines and behavioral measures of fatigue and depression in tumor-bearing mice. Here we show that tumor growth increased brain expression of pro-inflammatory cytokines and KMO. Treatment with fluoxetine had no effect on tumor growth, muscle wasting, fatigue behavior, or cytokine expression in the brain. Fluoxetine, however, reduced depressive-like behaviors in tumor bearing mice. In conclusion, our data confirm that increased brain expression of pro-inflammatory cytokines is associated with tumor-induced fatigue- and depressive-like behaviors. However, it is possible to separate the effects of tumor growth on mood and fatigue-like behaviors using SSRIs such as fluoxetine
Tumor Growth Increases Neuroinflammation, Fatigue and Depressive-like Behavior Prior to Alterations in Muscle Function
Cancer patients frequently suffer from fatigue, a complex syndrome associated with loss of muscle mass, weakness, and depressed mood. Cancer-related fatigue (CRF) can be present at the time of diagnosis, during treatment, and persists for years after treatment. CRF negatively influences quality of life, limits functional independence, and is associated with decreased survival in patients with incurable disease. Currently there are no effective treatments to reduce CRF. The aim of this study was to use a mouse model of tumor growth and discriminate between two main components of fatigue: loss of muscle mass/function and altered mood/motivation. Here we show that tumor growth increased fatigue- and depressive-like behaviors, and reduced body and muscle mass. Decreased voluntary wheel running activity (VWRA) and increased depressive-like behavior in the forced swim and sucrose preference tests were evident in tumor-bearing mice within the first two weeks of tumor growth and preceded the loss of body and muscle mass. At three weeks, tumor-bearing mice had reduced grip strength but this was not associated with altered expression of myosin isoforms or impaired contractile properties of muscles. These increases in fatigue and depressive-like behaviors were paralleled by increased expression of IL-1β mRNA in the cortex and hippocampus. Minocycline administration reduced tumor-induced expression of IL-1β in the brain, reduced depressive-like behavior, and improved grip strength without altering muscle mass. Taken together, these results indicate that neuroinflammation and depressed mood, rather than muscle wasting, contribute to decreased voluntary activity and precede major changes in muscle contractile properties with tumor growth
Detection of blood aspiration in deadly head gunshots comparing postmortem computed tomography (PMCT) and autopsy
BACKGROUND: The aim of our study was to analyze the reliability of postmortem computed tomography (PMCT) versus autopsy in detecting signs of blood aspiration in a distinct group of patients following deadly head, mouth or floor of mouth gunshot injuries. METHODS: In this study, in 41 cases PMCT was compared to autopsy reports, the gold standard of postmortem exams, regarding detection of blood aspiration. PMCT was evaluated for the presence and level of typical signs of blood aspiration in the major airways and lung using a semi-quantitative scale ranging from level 0 (no aspiration) to 3 (significant aspiration) also taking density values of the described potential aspiratory changes into account. RESULTS: Overall, in 29 (70.7%) of 41 enrolled cases PMCT and autopsy revealed the same level of aspiration. A difference of one level between PMCT and autopsy resulted for 5 (12.2%) of the remaining 12 cases. More than one level difference between both methods resulted for 7 cases (17.2%). Autopsy described no signs of aspiration in 10 cases, compared to 31 cases with reported blood aspiration. In contrast, PMCT revealed no signs of blood aspiration in 15 cases whereas 26 cases were rated as positive for signs of aspiration in the major airways. In 18 of these 26 cases considered positive for blood aspiration by autopsy and PMCT, clear signs of aspiration signs were also described bilaterally by both methods. CONCLUSIONS: The presented study provides evidence for the assumption that PMCT seems to be helpful in the detection of blood aspiration in cases of deadly head gunshots. In conclusion, it seems reasonable to suggest performing PMCT additionally to traditional postmortem exams in cases of suspected aspiration to rule out false-negative cases and to possibly allow for a more detailed and rather evidence based examination reconnoitering the cause of death. However, the adequate use of PMCT in this context needs further evaluation and the definition of an objective scale for aspiration detection on PMCT needs to be established in future studies
Losartan Treatment Attenuates Tumor-induced Myocardial Dysfunction
Fatigue and muscle wasting are common symptoms experienced by cancer patients. Data from animal models demonstrate that angiotensin is involved in tumor-induced muscle wasting, and that tumor growth can independently affect myocardial function, which could contribute to fatigue in cancer patients. In clinical studies, inhibitors of angiotensin converting enzyme (ACE) can prevent the development of chemotherapy-induced cardiovascular dysfunction, suggesting a mechanistic role for the renin–angiotensin–aldosterone system (RAAS). In the present study, we investigated whether an angiotensin (AT) 1-receptor antagonist could prevent the development of tumor-associated myocardial dysfunction. Methods and results: Colon26 adenocarcinoma (c26) cells were implanted into female CD2F1 mice at 8 weeks of age. Simultaneously, mice were administered Losartan (10 mg/kg) daily via their drinking water. In vivo echocardiography, blood pressure, in vitro cardiomyocyte function, cell proliferation assays, and measures of systemic inflammation and myocardial protein degradation were performed 19 days following tumor cell injection. Losartan treatment prevented tumor-induced loss of muscle mass and in vitro c26 cell proliferation, decreased tumor weight, and attenuated myocardial expression of interleukin-6. Furthermore, Losartan treatment mitigated tumor-associated alterations in calcium signaling in cardiomyocytes, which was associated with improved myocyte contraction velocity, systolic function, and blood pressures in the hearts of tumor-bearing mice. Conclusions: These data suggest that Losartan may mitigate tumor-induced myocardial dysfunction and inflammation
Efficient computation of matched solutions of the Kapchinskij-Vladimirskij envelope equations for periodic focusing lattices
A new iterative method is developed to numerically calculate the periodic,
matched beam envelope solution of the coupled Kapchinskij-Vladimirskij (KV)
equations describing the transverse evolution of a beam in a periodic, linear
focusing lattice of arbitrary complexity. Implementation of the method is
straightforward. It is highly convergent and can be applied to all usual
parameterizations of the matched envelope solutions. The method is applicable
to all classes of linear focusing lattices without skew couplings, and also
applies to all physically achievable system parameters -- including where the
matched beam envelope is strongly unstable. Example applications are presented
for periodic solenoidal and quadrupole focusing lattices. Convergence
properties are summarized over a wide range of system parameters.Comment: 20 pages, 5 figures, Mathematica source code provide
Correlation of mRNA delivery timing and protein expression in lipid-based transfection
Non-viral gene delivery is constrained by the dwell time that most synthetic nucleic acid nanocarriers spend inside endosomal compartments. In order to overcome this endosomal-release bottleneck, methods are required that measure nanocarrier uptake kinetics and transfection efficiency simultaneously. Here, we employ live-cell imaging on single-cell arrays (LISCA) to study the delivery-time distribution of lipid-based mRNA complexes under varied serum conditions. By fitting a translation-maturation model to hundreds of individual eGFP reporter fluorescence time courses, the protein expression onset times and the expression rates after transfection are determined. Using this approach, we find that delivery timing and protein expression rates are not intrinsically correlated at the single-cell level, even though population-averaged values of both parameters conjointly change as a function of increasing external serum protein fraction. Lipofectamine-mediated delivery showed decreased transfection efficiency and longer delivery times with increasing serum protein concentration. This is in contrast to ionizable lipid nanoparticle (i-LNP)-mediated transfer, which showed increased efficiency and faster uptake in the presence of serum. In conclusion, the interdependences of single-cell expression rates and onset timing provide additional clues on uptake and release mechanisms, which are useful for improving nucleic acid delivery
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