Two polymorphic structures of Cp*GeCl were determined by single-crystal X-ray diffraction analysis: (I) a dimer in the form of a parallelogram in solid state (yellow crystals, P21/n) and (II) an ...infinite ladder of alternating parallelograms (colorless crystals, C2/c). Melting experiments in X-ray capillary tubes revealed that the C2/c polymorph converts to the P21/n polymorphic structure. Variable-temperature and concentration-dependent 1H NMR spectroscopy suggest an equilibrium between a monomer and either a dimer or higher oligomer species. Variable-temperature 1H NMR (from 25 to −80 °C) of Cp*GeCl (P21/n) dissolved in toluene-d 8 indicates that lower temperature favors the dimers and/or oligomers. Increasing concentration (from 0.05 to 0.65 M) also favors the dimer or oligomer structure. The addition of chloride ions (from 0.1 to 1.0 equiv) via the addition of tetrabutylammonium chloride to solutions prepared from Cp*GeCl resulted in the formation of Cp*2Ge. Addition of increasing amounts (from 5 to 42 mg) of Cp*GeCl to a sample of Cp*2Ge gave no evidence of exchange by 1H NMR spectroscopy. Similarly, the addition of one equivalent of methyl mesylate to various concentrations of Cp*GeCl (0.06, 0.09, and 1.8 M) did not result in the formation of methyl chloride, indicating that an equilibrium involving chloride ions is not operative.
The aim of this study was to investigate the systemic bioavailability and plasma profiles of 17β-estradiol (E
2) after the application of three matrix patches for the transdermal delivery of E
2: ...Menorest™, Tradelia™, and Estraderm MX™ claiming to deliver a dosage of 50 μg E
2/day. All three patches were each worn randomly by 21 postmenopausal women volunteers over a 4-day period (i.e. 96 h). Each of the three treatment periods were separated by an at least 7 day wash out period according to a randomized, 3-way crossover design. Blood samples were taken from the antecubital vein before and 3, 6, 9, 12, 24, 28, 33, 48, 57, 72, 81, and 96 h after application. E
2 plasma values were determined by a specific direct radioimmunoassay method. The following pharmacokinetic parameters were evaluated: AUC
0–96h,
C
max,
T
max,
C
min,
C
average. The time to reach the maximal E
2 value of 32 h was the only pharmacokinetic parameter which was identical for all three patches. Menorest™ produced the highest E
2 bioavailability judged by the AUC
0→96h=3967.8±1651.8 pg/ml,
C
average=41.3±21.3 pg/ml,
C
min=36.8±8.6 pg/ml. Tradelia™ showed statistically not significantly smaller
C
average=38.9±17.0 pg/ml, AUC
0→96h=3737.9±1637.6 pg/ml·per h, and
C
min=33.8±26.7 than Menorest™. Estraderm MX™ showed lowest E
2 plasma profiles
C
max=38.9±25.1 pg/ml,
C
average=33.2±17.1 pg/ml, AUC
0→96h=3192.1±1646.0 pg/ml per·h. Menorest™ showed the smallest fluctuation over the entire test period, similar to Estraderm MX™, while Tradelia™ showed the highest E
2-fluctuation (
P<0.01): Tradelia™ exhibited the highest
C
max=48.0±20.3 pg/ml. When E
2 baseline levels, prior to patch application are subtracted individually from the produced E
2 plasma level, Estraderm MX™ is not bioequivalent to Menorest™ (
P<0.05). A circadian curve pattern of the E
2 plasma level was observed for all patches: in the evening higher E
2 plasma level were always detected compared with the morning, however, less pronounced with Estraderm MX™. Individual comparison of AUC
0→96h of each patch exhibited a large interindividual variability of 2000–8000 pg/ml per h for all three patches but relatively small individual variability: women with high E
2 bioavailability (high responders) maintained high bioavailability in all applied patches, women identified as low and medium responders remained the same regardless of the applied patch. Menorest™ produced in 2/3 of all postmenopausal women with the highest E
2 bioavailability (AUC
0→96h), Tradelia™ was found in less than 1/3 (28.6%), and Estraderm™ MX in only one postmenopausal woman. Menorest™only produced the highest reduction in postmenopausal symptoms together with Tradelia™. Estraderm MX™ produced a smaller reduction in postmenopausal symptoms compared to Menorest™ and Tradelia™. The observed side-effects were approximately equal in all three patches, with a maximum value after 72 h. It can be concluded that the three patches for the transdermal delivery of E
2 claiming to deliver 50 μg E
2/day differed from each other in their pharmacokinetic performance, although statistically not significant: Menorest™ exhibited the highest
C
average, AUC and
C
min, and the lowest fluctuation, followed by Tradelia™ and Estraderm MX™.
The aim of our study was to clarify the kinetic performance of a membrane controlled reservoir system (MCRS) for beta-estradiol (E2) under in vitro conditions by determination of the role of membrane ...and adhesive layer on E2 flux control.
E2 and ethanol fluxes across EVA membrane or membrane coated with adhesive from saturated solutions in defined ethanol/PBS mixtures were measured in the symmetric and asymmetric configuration. Physicochemical parameters of the EVA membrane were determined.
The E2 flux across the 9% EVA membrane steadily increased with increasing ethanol concentrations in both configurations, due to enhanced uptake of E2 by the polymer and increasing membrane diffusivity. Permeation across the EVA membrane coated with an adhesive layer in symmetric and asymmetric configuration increased up to maximum values of 0.80+/-0.14 micrograms X cm-2 X h-1 and 0.37+/-0.02 micrograms X cm-2 X h-1, respectively, at 62.5% (v/v) ethanol. The fluxes then decreased with further increase in the volume fraction of ethanol due to a dramatically reduced permeability of the adhesive layer. For the asymmetric case, a linear dependence of E2 on the ethanol fluxes was observed.
The E2 flux from MCRS is strictly dependent on reservoir ethanol concentrations, whereas the adhesive layer represents the rate controlling barrier at high ethanol levels (> 70% v/v).
Cardiac pathologies leading to the development of organ fibrosis typically are associated with the appearance of interstitial myofibroblasts. This cell type plays a central role in excessive ...extracellular matrix deposition, thereby contributing to arrhythmogenic slow and discontinuous conduction by causing disorganization of the three-dimensional network of electrically coupled cardiomyocytes. Besides this involvement in structural remodeling, myofibroblasts recently have been discovered in-vitro to promote arrhythmogenesis by direct modification of cardiomyocyte electrophysiology following establishment of heterocellular electrical coupling. In particular, myofibroblasts were found to rescue impulse conduction between disjoined cardiac tissues by acting as passive electrical conduits for excitatory current flow. Although, in principle, such recovery of blocked conduction might be beneficial, propagation across myofibroblast conduits is substantially delayed, thereby promoting arrhythmogenic slow and discontinuous conduction. Second, moderately polarized myofibroblasts were found to induce cell density-dependent depolarization of cardiomyocytes, which causes arrhythmogenic slow conduction due to the reduction of fast inward currents. Finally, critical depolarization of cardiomyocytes by myofibroblasts was discovered to lead to the appearance of ectopic activity in a model of the infarct border zone. These findings obtained in vitro suggest that electrotonic interactions following gap junctional coupling between myofibroblasts and cardiomyocytes in structurally remodeled fibrotic hearts might directly initiate the main mechanisms underlying arrhythmogenesis, that is, abnormal automaticity and abnormal impulse conduction. If, in the future, similar arrhythmogenic mechanisms can be shown to be operational in intact hearts, myofibroblasts might emerge as a novel noncardiomyocyte target for antiarrhythmic therapy.
In cancer patients, appetite and immune status are significantly weakened. Two experimental fermented formulations without (group A, named as FSWW08) and with (group B, FSWW08) an extract from yam ...root were investigated against a placebo formulation with casein (group C) in a clinical study conducted in six cancer hospitals where cancer patients underwent radio or chemotherapy (patients undergoing radiation therapy n=78, patients undergoing chemotherapy n=184, total 262). IgG and IgA were increased by formulation A in patients despite receiving radio- or chemotherapy. Group A experienced statistically significant increases in lymphocyte transformation rates, whereas group B and group C did not. Formulations A and B either inhibited or lessened statistically significant decreases in white blood counts, whereas the placebo group experienced substantial decreases. Hemoglobin and platelet decreases were inhibited in group A, although not statistically significantly. Patients in group A received no blood transfusions, whereas many patients from the placebo group received blood transfusions. Appetite loss was reduced in group A from 57.9% to 13.3% and in group B from 70% to 35.8%. In the placebo group, an increase in appetite loss was detected under chemo and radiation therapy from 41.8% to 70.9%.
High Performance Linpack can maximize requirements throughout a computer system. An efficient multi-GPU double-precision general matrix multiply (DGEMM), together with adjustments to the HPL, is ...required to utilize a heterogeneous computer to its full extent. The authors present the resulting energy-efficiency measurements and suggest a cluster design that can utilize multiple GPUs.
ALICE HLT High Speed Tracking on GPU Gorbunov, S.; Rohr, D.; Aamodt, K. ...
IEEE transactions on nuclear science,
08/2011, Letnik:
58, Številka:
4
Journal Article
Recenzirano
The on-line event reconstruction in ALICE is performed by the High Level Trigger, which should process up to 2000 events per second in proton-proton collisions and up to 300 central events per second ...in heavy-ion collisions, corresponding to an input data stream of 30 GB/s. In order to fulfill the time requirements, a fast on-line tracker has been developed. The algorithm combines a Cellular Automaton method being used for a fast pattern recognition and the Kalman Filter method for fitting of found trajectories and for the final track selection. The tracker was adapted to run on Graphics Processing Units (GPU) using the NVIDIA Compute Unified Device Architecture (CUDA) framework. The implementation of the algorithm had to be adjusted at many points to allow for an efficient usage of the graphics cards. In particular, achieving a good overall workload for many processor cores, efficient transfer to and from the GPU, as well as optimized utilization of the different memories the GPU offers turned out to be critical. To cope with these problems a dynamic scheduler was introduced, which redistributes the workload among the processor cores. Additionally a pipeline was implemented so that the tracking on the GPU, the initialization and the output processed by the CPU, as well as the DMA transfer can overlap. The GPU tracking algorithm significantly outperforms the CPU version for large events while it entirely maintains its efficiency.
Many cancer patients do not die due to impaired organ functions, but as a result of reduced general conditions, such as cachexia, sarcopenia, depression, infections, or stress. Reduced general health ...may be caused by immune modifying cytokines released from the tumor into the body. Improvement of immunity would not only reduce cancer side effects through inhibiting cytokine release from the tumor into the blood, but also, according to a new hypothesis, modify the cancer stem cells (CSC) in the tumor, which are believed to drive cancer growth and metastasis. We reported previously several investigations with a dietary fermented soy formulation (FSWW08) in cancer patients, where we saw a) strong reduction of cancer symptoms, b) broken resistance to chemotherapy, and c) a strong reduction of chemotherapy’s toxic side effects, when taken in combination. This publication reports two new findings from a pilot study with postsurgical, treatment resistant patients conducted over four years. First, neither treatment resistance nor side effects were observed. Second, more patients have survived than expected. The improved health and immunity is detected together with increased CSC differentiation, suggesting lower aggressiveness, which was corroborated by increased gene expressions, particularly of steroidal hormones, MAPkinase, NF-κB, and tumor suppressor factor p53, a typical marker of “stemness” or cell differentiation. Although limited by its small, homogenous sample size, the results of this pilot study illustrate the relationship between CSCs differentiation, and the clinical symptoms of immunity, which influence survival outcomes and raise the clinical potential of measuring CSCs in ovarian, prostate, and breast cancers. The improved survival rates are also seen in larger cohort studies, which show similar gene expression profiles, which were induced by FSWW08 in the treatment resistant cancer patients in this study.
PDF