126 research outputs found
Temperatures achieved in human and canine neocortex during intraoperative passive or active focal cooling
Focal cortical cooling inhibits seizures and prevents acquired epileptogenesis in rodents. To investigate the potential clinical utility of this treatment modality, we examined the thermal characteristics of canine and human brain undergoing active and passive surface cooling in intraoperative settings. Four patients with intractable epilepsy were treated in a standard manner. Before the resection of a neocortical epileptogenic focus, multiple intraoperative studies of active (custom-made cooled irrigation-perfused grid) and passive (stainless steel probe) cooling were performed. We also actively cooled the neocortices of two dogs with perfused grids implanted for 2 hours. Focal surface cooling of the human brain causes predictable depth-dependent cooling of the underlying brain tissue. Cooling of 0.6–2°C was achieved both actively and passively to a depth of 10–15 mm from the cortical surface. The perfused grid permitted comparable and persistent cooling of canine neocortex when the craniotomy was closed. Thus, the human cortex can easily be cooled with the use of simple devices such as a cooling grid or a small passive probe. These techniques provide pilot data for the design of a permanently implantable device to control intractable epilepsy
The 100 most eminent psychologists of the 20th century.
A rank-ordered list was constructed that reports the first 99 of the 100 most eminent psychologists of the 20th century. Eminence was measured by scores on 3 quantitative variables and 3 qualitative variables. The quantitative variables were journal citation frequency, introductory psychology textbook citation frequency, and survey response frequency. The qualitative variables were National Academy of Sciences membership, election as American Psychological Association (APA) president or receipt of the APA Distinguished Scientific Contributions Award, and surname used as an eponym. The qualitative variables were quantified and combined with the other 3 quantitative variables to produce a composite score that was then used to construct a rank-ordered list of the most eminent psychologists of the 20th century. The discipline of psychology underwent a remarkable transformation during the 20th cen-tury, a transformation that included a shift away from the European-influenced philosophical psychology of the late 19th century to th
Progressive induction of left ventricular pressure overload in a large animal model elicits myocardial remodeling and a unique matrix signature
ObjectivePatients with severe left ventricular pressure overload secondary to aortic stenosis can present with signs and symptoms of heart failure despite normal left ventricular ejection fraction. This process occurs, at least in part, as a result of left ventricular pressure overload–induced extracellular matrix remodeling that promulgates increased left ventricular stiffness and impaired diastolic function. However, the determinants that drive extracellular matrix remodeling in this form of left ventricular pressure overload remain to be fully defined.MethodsLeft ventricular pressure overload was induced in mature pigs (n = 15) by progressive ascending aortic cuff inflation (once per week for 4 weeks), whereby left ventricular mass, left ventricular ejection fraction, and regional myocardial stiffness (rKm) were compared with referent controls (n = 12). Determinants of extracellular matrix remodeling were assessed by measuring levels of mRNA expression for fibrillar collagens, matrix metalloproteinases, and tissue inhibitors of matrix metalloproteinase 1 and 4.ResultsWith left ventricular pressure overload, left ventricular mass and rKm increased by 2- and 3-fold, respectively, compared with control, with no change in left ventricular ejection fraction. Left ventricular myocardial collagen increased approximately 2-fold, which was accompanied by reduced solubility (ie, increased cross-linking) with left ventricular pressure overload, but mRNA expression for fibrillar collagen and matrix metalloproteinases remained relatively unchanged. In contrast, a robust increase in mRNA expression for tissue inhibitors of matrix metalloproteinase-1 and 4 occurred with left ventricular pressure overload.ConclusionsIn a progressive model of left ventricular pressure overload, which recapitulates the phenotype of aortic stenosis, increased extracellular matrix accumulation and subsequently increased myocardial stiffness were not due to increased fibrillar collagen expression but rather to determinants of post-translational control that included increased collagen stability (thereby resistant to matrix metalloproteinase degradation) and increased endogenous matrix metalloproteinase inhibition. Targeting these extracellular matrix post-translational events with left ventricular pressure overload may hold both diagnostic and therapeutic relevance
Supercharged cellulases show superior thermal stability and enhanced activity towards pretreated biomass and cellulose
Non-productive binding of cellulolytic enzymes to various plant cell wall components, such as lignin and cellulose, necessitates high enzyme loadings to achieve efficient conversion of pretreated lignocellulosic biomass to fermentable sugars. Protein supercharging was previously employed as one of the strategies to reduce non-productive binding to biomass. However, various questions remain unanswered regarding the hydrolysis kinetics of supercharged enzymes towards pretreated biomass substrates and the role played by enzyme interactions with individual cell wall polymers such as cellulose and xylan. In this study, CBM2a (from Thermobifida fusca) fused with endocellulase Cel5A (from T. fusca) was used as the model wild-type enzyme and CBM2a was supercharged using Rosetta, to obtain eight variants with net charges spanning −14 to +6. These enzymes were recombinantly expressed in E. coli, purified from cell lysates, and their hydrolytic activities were tested against pretreated biomass substrates (AFEX and EA treated corn stover). Although the wild-type enzyme showed greater activity compared to both negatively and positively supercharged enzymes towards pretreated biomass, thermal denaturation assays identified two negatively supercharged constructs that perform better than the wild-type enzyme (∼3 to 4-fold difference in activity) upon thermal deactivation at higher temperatures. To better understand the causal factor of reduced supercharged enzyme activity towards AFEX corn stover, we performed hydrolysis assays on cellulose-I/xylan/pNPC, lignin inhibition assays, and thermal stability assays. Altogether, these assays showed that the negatively supercharged mutants were highly impacted by reduced activity towards xylan whereas the positively supercharged mutants showed dramatically reduced activity towards cellulose and xylan. It was identified that a combination of impaired cellulose binding and lower thermal stability was the cause of reduced hydrolytic activity of positively supercharged enzyme sub-group. Overall, this study demonstrated a systematic approach to investigate the behavior of supercharged enzymes and identified supercharged enzyme constructs that show superior activity at elevated temperatures. Future work will address the impact of parameters such as pH, salt concentration, and assay temperature on the hydrolytic activity and thermal stability of supercharged enzymes
Glycosylation Is Vital for Industrial Performance of Hyperactive Cellulases
In the terrestrial biosphere, biomass deconstruction is conducted by microbes employing a variety of complementary strategies, many of which remain to be discovered. Moreover, the biofuels industry seeks more efficient (and less costly) cellulase formulations upon which to launch the nascent sustainable bioenergy economy. The glycan decoration of fungal cellulases has been shown to protect these enzymes from protease action and to enhance binding to cellulose. We show here that thermal tolerant bacterial cellulases are glycosylated as well, although the types and extents of decoration differ from their Eukaryotic counterparts. Our major findings are that glycosylation of CelA is uniform across its three linker peptides and composed of mainly galactose disaccharides (which is unique) and that this glycosylation dramatically impacts the hydrolysis of insoluble substrates, proteolytic and thermal stability, and substrate binding and changes the dynamics of the enzyme. This study suggests that the glycosylation of CelA is crucial for its exceptionally high cellulolytic activity on biomass and provides the robustness needed for this enzyme to function in harsh environments including industrial settings
Design and construction of the MicroBooNE Cosmic Ray Tagger system
The MicroBooNE detector utilizes a liquid argon time projection chamber
(LArTPC) with an 85 t active mass to study neutrino interactions along the
Booster Neutrino Beam (BNB) at Fermilab. With a deployment location near ground
level, the detector records many cosmic muon tracks in each beam-related
detector trigger that can be misidentified as signals of interest. To reduce
these cosmogenic backgrounds, we have designed and constructed a TPC-external
Cosmic Ray Tagger (CRT). This sub-system was developed by the Laboratory for
High Energy Physics (LHEP), Albert Einstein center for fundamental physics,
University of Bern. The system utilizes plastic scintillation modules to
provide precise time and position information for TPC-traversing particles.
Successful matching of TPC tracks and CRT data will allow us to reduce
cosmogenic background and better characterize the light collection system and
LArTPC data using cosmic muons. In this paper we describe the design and
installation of the MicroBooNE CRT system and provide an overview of a series
of tests done to verify the proper operation of the system and its components
during installation, commissioning, and physics data-taking
Ionization Electron Signal Processing in Single Phase LArTPCs II. Data/Simulation Comparison and Performance in MicroBooNE
The single-phase liquid argon time projection chamber (LArTPC) provides a
large amount of detailed information in the form of fine-grained drifted
ionization charge from particle traces. To fully utilize this information, the
deposited charge must be accurately extracted from the raw digitized waveforms
via a robust signal processing chain. Enabled by the ultra-low noise levels
associated with cryogenic electronics in the MicroBooNE detector, the precise
extraction of ionization charge from the induction wire planes in a
single-phase LArTPC is qualitatively demonstrated on MicroBooNE data with event
display images, and quantitatively demonstrated via waveform-level and
track-level metrics. Improved performance of induction plane calorimetry is
demonstrated through the agreement of extracted ionization charge measurements
across different wire planes for various event topologies. In addition to the
comprehensive waveform-level comparison of data and simulation, a calibration
of the cryogenic electronics response is presented and solutions to various
MicroBooNE-specific TPC issues are discussed. This work presents an important
improvement in LArTPC signal processing, the foundation of reconstruction and
therefore physics analyses in MicroBooNE.Comment: 54 pages, 36 figures; the first part of this work can be found at
arXiv:1802.0870
A Deep Neural Network for Pixel-Level Electromagnetic Particle Identification in the MicroBooNE Liquid Argon Time Projection Chamber
We have developed a convolutional neural network (CNN) that can make a
pixel-level prediction of objects in image data recorded by a liquid argon time
projection chamber (LArTPC) for the first time. We describe the network design,
training techniques, and software tools developed to train this network. The
goal of this work is to develop a complete deep neural network based data
reconstruction chain for the MicroBooNE detector. We show the first
demonstration of a network's validity on real LArTPC data using MicroBooNE
collection plane images. The demonstration is performed for stopping muon and a
charged current neutral pion data samples
Ionization Electron Signal Processing in Single Phase LArTPCs I. Algorithm Description and Quantitative Evaluation with MicroBooNE Simulation
We describe the concept and procedure of drifted-charge extraction developed
in the MicroBooNE experiment, a single-phase liquid argon time projection
chamber (LArTPC). This technique converts the raw digitized TPC waveform to the
number of ionization electrons passing through a wire plane at a given time. A
robust recovery of the number of ionization electrons from both induction and
collection anode wire planes will augment the 3D reconstruction, and is
particularly important for tomographic reconstruction algorithms. A number of
building blocks of the overall procedure are described. The performance of the
signal processing is quantitatively evaluated by comparing extracted charge
with the true charge through a detailed TPC detector simulation taking into
account position-dependent induced current inside a single wire region and
across multiple wires. Some areas for further improvement of the performance of
the charge extraction procedure are also discussed.Comment: 60 pages, 36 figures. The second part of this work can be found at
arXiv:1804.0258
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