To determine whether the exposure to long term enriched environment (EE) would result in a continuous improvement of neurological recovery and ameliorate the loss of brain tissue after traumatic ...brain injury (TBI) vs. standard housing (SH). Male Sprague-Dawley rats (300-350 g, n=28) underwent lateral fluid percussion brain injury or SHAM operation. One TBI group was held under complex EE for 90 days, the other under SH. Neuromotor and sensorimotor dysfunction and recovery were assessed after injury and at days 7, 15, and 90 via Composite Neuroscore (NS), RotaRod test, and Barnes Circular Maze (BCM). Cortical tissue loss was assessed using serial brain sections. After day 7 EE animals showed similar latencies and errors as SHAM in the BCM. SH animals performed notably worse with differences still significant on day 90 (p<0.001). RotaRod test and NS revealed superior results for EE animals after day 7. The mean cortical volume was significantly higher in EE vs. SH animals (p=0.003). In summary, EE animals after lateral fluid percussion (LFP) brain injury performed significantly better than SH animals after 90 days of recovery. The window of opportunity may be wide and also lends further credibility to the importance of long term interventions in patients suffering from TBI.
Using a cross-linking approach, we have analyzed the function of Skp, a presumed molecular chaperone of the periplasmic space of Escherichia coli, during the biogenesis of an outer membrane protein ...(OmpA). Following its transmembrane translocation, OmpA interacts with Skp in close vicinity to the plasma membrane. In vitro, Skp was also found to bind strongly and specifically to pOmpA nascent chains after their release from the ribosome suggesting the ability of Skp to recognize early folding intermediates of outer membrane proteins. Pulse labeling of OmpA in spheroplasts prepared from an skp null mutant revealed a specific requirement of Skp for the release of newly translocated outer membrane proteins from the plasma membrane. Δskp mutant cells are viable and show only slight changes in the physiology of their outer membranes. In contrast, double mutants deficient both in Skp and the periplasmic protease DegP (HtrA) do not grow at 37 °C in rich medium. We show that in the absence of an active DegP, a lack of Skp leads to the accumulation of protein aggregates in the periplasm. Collectively, our data demonstrate that Skp is a molecular chaperone involved in generating and maintaining the solubility of early folding intermediates of outer membrane proteins in the periplasmic space of Gram-negative bacteria.
The Large Hadron Collider (LHC) in 2015 will collide proton beams with increased luminosity from 1034 up to 3 × 1034cm−2s−1. ATLAS is an LHC experiment designed to measure decay properties of high ...energetic particles produced in the protons collisions. The higher luminosity places stringent operational and physical requirements on the ATLAS Trigger in order to reduce the 40MHz collision rate to a manageable event storage rate of 1kHz while at the same time, selecting those events with valuable physics meaning. The Level-1 Trigger is the first rate-reducing step in the ATLAS Trigger, with an output rate of 100kHz and decision latency of less than 2.5µs. It is composed of the Calorimeter Trigger (L1Calo), the Muon Trigger (L1Muon) and the Central Trigger Processor (CTP). By 2015, there will be a new electronics element in the chain: the Topological Processor System (L1Topo system). The L1Topo system consist of a single AdvancedTCA shelf equipped with three L1Topo processor blades. It will make it possible to use detailed information from L1Calo and L1Muon processed in individual state-of-the-art FPGA processors. This allows the determination of angles between jets and or leptons and calculates kinematic variables based on lists of selected sorted objects. The system is designed to receive and process up to 6Tb s of real time data. The paper reports the relevant upgrades of the Level-1 trigger with focus on the topological processor design and commissioning.
A suitable representation of the regional gravity field is used to estimate relative offsets between national height system realizations in Europe. The method used is based on a gravimetric approach ...and benefits from the significant improvements in the determination of the global gravity field by the recent satellite gravity missions the Gravity Recovery and Climate Experiment (GRACE) and the Gravity field and steady-state Ocean Circulation Explorerr (GOCE). The potential of these missions for the unification of height reference frames is analyzed in terms of accuracy and spatial resolution. The results of the gravimetric approach are compared to the independent results of the geodetic leveling approach. Advantages and drawbacks of both methods are discussed.
This paper describes outcomes of the 2019 Cryo-EM Model Challenge. The goals were to (1) assess the quality of models that can be produced from cryogenic electron microscopy (cryo-EM) maps using ...current modeling software, (2) evaluate reproducibility of modeling results from different software developers and users and (3) compare performance of current metrics used for model evaluation, particularly Fit-to-Map metrics, with focus on near-atomic resolution. Our findings demonstrate the relatively high accuracy and reproducibility of cryo-EM models derived by 13 participating teams from four benchmark maps, including three forming a resolution series (1.8 to 3.1 Å). The results permit specific recommendations to be made about validating near-atomic cryo-EM structures both in the context of individual experiments and structure data archives such as the Protein Data Bank. We recommend the adoption of multiple scoring parameters to provide full and objective annotation and assessment of the model, reflective of the observed cryo-EM map density.
The influence of propylen glycol (PG), ethanol, and oleic acid (OA) on nortriptyline hydrochloride (NTH) penetration through human epidermis was studied in vitro at two different pH values (5.5 and ...7.4). The influence of lactic acid and polysorbate 80 was studied for a pH of 5.5. Permeation studies through Heat Separated Epidermis, as well as the enhancing effect of the different vehicles, showed a pH dependency. A pH value of 5.5 in the donor solution decreases significantly the permeability coefficient (
K
p) with respect to a pH value of 7.4 (0.011
±
0.004
×
10
−6 versus 0.36
±
0.04
×
10
−6
cm/s). The vehicles showed an increasing enhancement effect in the order: polysorbate 80
>
ethanol/PG/OA
>
PG
>
ethanol
>
ethanol/lactic acid
>
lactic acid at pH 5.5 while they reduced the permeation of NTH at pH 7.4. Considering the results obtained at pH 5.5, the maximum enhancement ratios were found for polysorbate 80 and the combination ethanol/PG/OA (10.72 and 3.90). Both vehicles were selected for designing a NTH transdermal delivery system (NTH-TDS) using (hydroxypropyl)methyl-cellulose as polymer. The NTH-TDS based on the combination of ethanol/PG/OA showed an enhancement ratio with respect to control of 2.09 and the addition of polysorbate 80 to the matrix, of 5.82.
Study on the use of complementary and alternative medicine (CAM) in lung cancer patients has been widely neglected. Therefore, we initiated a study on the use of CAM in lung cancer patients in ...addition to radiation treatment. Overall, 120 patients from 3 institutions were interviewed by a standardized questionnaire. Besides the tumor parameters and the use of CAM, the reason for the use, patient information of the medication, the information sources and the subjective condition of the patient. Altogether, 54% of the patients reported using CAM (66% of female patients, 52% of male patients). The most frequently used CAM measures were vitamin combinations (17%), mistletoe (15%), and selenium (12%). A total of 52% reported the wish to support the tumor treatment as a reason for using CAM and 27% had a 'better feeling' using CAM. 50% of CAM was bought by the patients themselves and 50% were prescribed by their family physicians. The use of CAM is frequent in lung cancer patients. Our results suggest that it is very important to obtain information on the CAM use of patients and, particularly in controlled clinical trials, to prospectively document it.
The generation of respirable aerosols of a functionalized colloidal carrier has been investigated in this study. Lectin-functionalized liposomes, which proved to show improved cell association (using ...A549 cell line and primary human alveolar cells) even in the presence of a commercial lung surfactant preparation, have been developed. The stability of non-functionalized liposomes during nebulization using a jet nebulizer (Pari II provocation nebulizer, operated using an air flow of 30 l/min) was firstly investigated, and the experimental and formulation conditions were optimized and applied for the preparation of lectin-functionalized liposomes. The incorporation of cholesterol enhanced the stability of the liposomes during nebulization (from 15–20% leakage of a hydrophilic marker to 8% upon cholesterol incorporation) and upon incubation with lung surfactant preparation. Nebulization of the functionalized liposomes did not significantly influence their physical stability. Their enhanced cell binding capability (compared to non-functionalized liposomes) was also maintained. A drop in cell association compared to fresh functionalized liposomes was detected after nebulization, nevertheless, the binding was still significantly higher than that of the non-functionalized liposomes. The deposition of the liposomal preparation in lung periphery, proved by the deposition of the liposomal preparation on the lower stages of an ASTRA type cascade impinger and a mean median aerodynamic diameter (MMAD) of 2.85 μm, makes it a potential candidate as a macromolecule-drug carrier for local and/or systemic administration.
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