gebhart/patrepeval huggingface dataset:
Random Substitution of Large Parts of the Propeptide of Yeast Proteinase A (1995)

The yeast aspartic protease, proteinase A, has a 54 amino-acid propeptide, which is removed during activation of the zymogen in the vacuole. Apart from being involved inhibition/activation, the propeptide has been shown to be essential for formation of a stable active enzyme (van den Hazel, H. B., Kielland-Brandt, M. C., and Winther, J. R. (1993) J. Biol. Chem. 268, 18002-18007). We have investigated the sequence requirements for function of the propeptide. The N-terminal half and the C-terminal half of the propeptide were replaced by random sequences at the genetic level, and collections of the mutants were subjected to a colony screen for ones exhibiting activity. A high frequency (around 1%) of active constructs was found, which indicates a very high tolerance for mutations in the propeptide. Thirty-nine functional mutant forms containing random sequence at either the N- or C-terminal half of the propeptide were characterized. Comparison of the propeptides of the active constructs suggests that a particular lysine residue is important for efficient biosynthesis of proteinase A.
Scaffold/Matrix-Attached Regions Act upon Transcription in a Context-Dependent Manner, (1996)

Scaffold/matrix-attached regions (S/MARs) are cis-acting elements with a function outside transcribed regions and in introns. Although they usually augment transcriptional rates, their action is highly context-dependent. We cloned an 800 bp S/MAR element from the upstream border of the human interferon-beta domain at various positions within a transcribed region of 4.3 kb. By use of retroviral gene transfer, the vector could be integrated into target cells as a single copy enabling a rigorous definition of the distance between the S/MAR and the transcriptional start site. At a distance of about 4 kb, the S/MAR supported transcriptional initiation, whereas at distances below 2.5 kb, transcription was essentially shut off. Controls proved the functionally of all constructs in the transient expression phase and ruled out any influence of S/MAR position on transcript stability. Moreover, no pausing or premature termination was observed within these elements. We suggest that the protein binding partners of S/MARs change according to the topological status, explaining these divergent S/MAR effects.
Control of discrete event systems modeled as hierarchical state machines (2002)

The authors examine a class of discrete event systems (DESs) modeled as asynchronous hierarchical state machines (AHSMs). For this class of DESs, they provide an efficient method for testing reachability, which is an essential step in many control synthesis procedures. This method utilizes the asynchronous nature and hierarchical structure of AHSMs, thereby illustrating the advantage of the AHSM representation as compared with its equivalent (flat) state machine representation. An application of the method is presented where an online minimally restrictive solution is proposed for the problem of maintaining a controlled AHSM within prescribed legal bounds.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
RIPK4 is Downregulated in Poorly Differentiated Tongue Cancer and is Associated with Migration/Invasion and Cisplatin-Induced Apoptosis (2014)

In the present work we found a correlation between RIPK4 expression and TSCC degree of differentiation, age, and gender. The better understanding of the molecular mechanism of RIPK4 in TSCC may provide a promising biomarker for tongue cancer prognosis and treatment.
Fabrication of thin films of multi-cation oxides (YBa2Cu3O7−δ) starting from nanoparticles of mixed ions (2006)

A new route, starting from nanoparticles of mixed ions, has been used to synthesize high-quality thin films of a complex perovskite (YBa2Cu3O7-delta, YBCO). Currently, the most promising approach for making YBCO films uses metal trifluoroacetates. In comparison, the present method using a colloidal dispersion of nanoparticles is seen to produce crystalline, well textured films at much faster heating rates and having much lower porosity. Whereas there is scope for further optimization, this effort has rapidly yielded superconducting films with transition temperature of 89.5 K and self-field critical current density up to 2.4 MA cm(-2) at 77 K.
Heavy-Oil Recovery from Thin Pay Zones by Electromagnetic Heating (1999)

There are many heavy oil reservoirs with thin pay zones (less than 10 m). Conventional thermal recovery methods such as steam injection are not cost-effective for these thin reservoirs, due to excessive heat loss through the overburden. In order to minimize heat losses, it is necessary to be able to carry out controlled heating of the pay zone. One such way to introduce heat to the reservoir in a controlled manner is electromagnetic heating. This article describes laboratory studies on electromagnetic heating of a scaled model of a heavy oil reservoir with a thin pay zone. The combination of electromagnetic heating and gas injection with horizontal wells was studied. Higher electromagnetic frequencies provide faster heating rates and can over come problems associated with discontinuity of the media through which electro magnetic waves must propagate in the reservoir. Heat loss can also be minimized with the use of higher frequencies. For less viscous oils (less than 1000 mPs.s), it is not necessary to heat the entire pay zone. Heating of the wellbore vicinity is sufficient. Oil recoveries as high as 45 % of OIIP (Original Oil in Place) were achieved using electromagnetic heating and gas injection compared to estimated primary recovery rates of less than 5 %. The results obtained in this work clearly show that electromagnetic heating provides an effective means of recovering heavy oil from reservoirs with thin pay zones.
Automatic position calibration of multiple microphones (2004)

We describe a method to determine automatically the relative three dimensional positions of multiple microphones using at least five loudspeakers in unknown positions. The only assumption we make is that there is a microphone which is very close to a loudspeaker. In our experimental setup, we attach one microphone to each loudspeaker. We derive the maximum likelihood estimator and the solution turns out to be a non-linear least squares problem. A closed form solution which can be used as the initial guess for the minimization routine is derived. We also derive an approximate expression for the covariance of the estimator using the implicit function theorem. Using this, we analyze the performance of the estimator with respect to the positions of the loudspeakers. The algorithm is validated using both Monte-Carlo simulations and a real-time experimental setup.
Effects of induced electric fields on finite neuronal structures: a simulation study (1993)

In this paper we present an analysis of magnetic stimulation of finite length neuronal structures using computer simulations. Models of finite neuronal structures in the presence of extrinsically applied electric fields indicate that excitation can be characterized by two driving functions: one due to field gradients and the other due to fields at the boundaries of neuronal structures. It is found that boundary field driving functions play an important role in governing excitation characteristics during magnetic stimulation. Simulations indicate that axons whose lengths are short compared to the spatial extent of the induced field are easier to excite than longer axons of the same diameter. Simulations also indicate that independent cellular dendritic processes are probably not excited during magnetic stimulation. Analysis of the temporal distribution of induced fields indicates that the temporal shape of the stimulus waveform modulates excitation thresholds and propagation of action potentials.
Bifidobacteria: their significance in human intestinal health (1997)

Bifidobacterium was first isolated in 1899 from a healthy breast-fed infant by Tissier of the Pasteur Institute in France. It is an anaerobic, Gram-positive, non-sporeforming, pleomorphic rod, and was originally named Bacillus bifidus communis. The name signifies the branching morphology of the bacteria; bifidus in Latin meaning cleft in two parts. Later, the bacterium was once placed within the genus Lactobacillus as L. bifidus. In 1960s, it was accepted as an independent genus and classified as Bifidobacterium. Apart from the properties mentioned above, the main phenotypic characteristics of Bifidobacterium is producing lactic acid and acetic acid as the main products of glucose utilization. Bifidobacterium species and classification There are currently about 30 known Bifidobacterium species. The Bifidobacterium species that inhabit the human intestinal tract are rather distinct from those that inhabit the intestines of animals (Mitsuoka, 1984). The representative species of human origin include B. longum, B. breve, B. infantis, B. bifidum, B. adoltescentis and B. pseudocatenulatum. Representatives of animal-derived species include B. pseudolongum, B. thermophilus and B. animalis. Species of animal origin are never isolated from the human intestinal tract and human origin species are almost never found in animal intestines. The reason for this host-specificity is unknown, but is suspected to be due to differences among species in the ability to colonize the host intestinal tracts. Among the Bifidobacterium species used in various yogurts, B. animalis is often identified (Yaeshima et al, 1996). The reason for using this species is that animal-derived species are more acid-resistant and therefore preserve better in the yogurt. Recently, the B. animalis strains isolated from these yogurts have been found to have some genetic differences compared to the type strain of B. animalis, and these strains have been named B. lactis (Meile et al, 1997). This species is also not an inhabitant of the human intestinal tract. The use of human-origin species as food supplement seems to be the reasonable and correct choice. Ecology in the human intestinal tract Before birth, the human foetus is germ-free and intestinal bacteria do not exist. From the time of birth, bacteria begin to colonize the intestinal tract forming the intestinal microflora. At birth, many bacterial species gain access into the intestinal tract, but bifidobacteria gradually become established as the main bacteria, and predominate in the intestinal microflora during the neonatal period. This tendency is especially marked in breast-fed infants. According to a study,
Thermodynamics and Statistical Mechanics at Negative Absolute Temperatures (1956)

The circumstances under which negative absolute temperatures can occur are discussed, and principles of thermodynamics and statistical mechanics at negative temperatures are developed. If the entropy of a thermodynamic system is not a monotonically increasing function of its internal energy, it possesses a negative temperature whenever ${(\frac{\ensuremath{\partial}S}{\ensuremath{\partial}U})}_{X}$ is negative. Negative temperatures are hotter than positive temperatures. When account is taken of the possibility of negative temperatures, various modifications of conventional thermodynamics statements are required. For example, heat can be extracted from a negative-temperature reservoir with no other effect than the performance of an equivalent amount of work. One of the standard formulations of the second law of thermodynamics must be altered to the following: It is impossible to construct an engine that will operate in a closed cycle and provide no effect other than (1) the extraction of heat from a positive-temperature reservoir with the performance of an equivalent amount of work or (2) the rejection of heat into a negative-temperature reservoir with the corresponding work being done on the engine. A thermodynamic system that is in internal thermodynamic equilibrium, that is otherwise essentially isolated, and that has an energetic upper limit to its allowed states can possess a negative temperature. The statistical mechanics of such a system are discussed and the results are applied to nuclear spin systems.
Context modeling using RNN for keyword detection (1993)

The authors present some experiments that show the capabilities of using recurrent neural networks (RNNs) in conjunction with hidden Markov models (HMMs) in the context of keyword spotting (KWS): the automatic recognition of a small set of keywords as they occur in unconstrained speech and/or noise. KWS is usually considered as a word recognition problem on continuous natural speech with no syntax model. However, in this work, simple finite-state grammars are introduced to generate keywords in unconstrained speech. In the proposed scheme a RNN performs both the decoding search of a null-grammar HMM network and the secondary process to determine true keywords or false alarms.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Difluorobenzocyclooctyne: Synthesis, Reactivity, and Stabilization by β-Cyclodextrin (2010)

Highly reactive cyclooctynes have been sought as substrates for Cu-free cycloaddition reactions with azides in biological systems. To elevate the reactivities of cyclooctynes, two strategies, LUMO lowering through propargylic fluorination and strain enhancement through fused aryl rings, have been explored. Here we report the facile synthesis of a difluorobenzocyclooctyne (DIFBO) that combines these modifications. DIFBO was so reactive that it spontaneously trimerized to form two asymmetric products that we characterized by X-ray crystallography. However, we were able to trap DIFBO by forming a stable inclusion complex with beta-cyclodextrin in aqueous media. This complex could be stored as a lyophilized powder and then dissociated in organic solvents to produce free DIFBO for in situ kinetic and spectroscopic analysis. Using this procedure, we found that the rate constant for the cycloaddition reaction of DIFBO with an azide exceeds those for difluorinated cyclooctyne (DIFO) and dibenzocyclooctyne (DIBO). Cyclodextrin complexation is therefore a promising approach for stabilizing compounds that possess the high intrinsic reactivities desired for Cu-free click chemistry.
Emerging drug profile: cyclin-dependent kinase inhibitors (2013)

Abstract As the rational application of targeted therapies in cancer supplants traditional cytotoxic chemotherapy, there is an ever-greater need for a thorough understanding of the complex machinery of the cell and an application of this knowledge to the development of novel therapeutics and combinations of agents. Here, we review the current state of knowledge of the class of targeted agents known as cyclin-dependent kinase (CDK) inhibitors, with a focus on chronic lymphocytic leukemia (CLL). Flavopiridol (alvocidib) is the best studied of the CDK inhibitors, producing a dramatic cytotoxic effect in vitro and in vivo, with the principal limiting factor of acute tumor lysis. Unfortunately, flavopiridol has a narrow therapeutic window and is relatively non-selective with several off-target (i.e. non-CDK) effects, which prompted development of the second-generation CDK inhibitor dinaciclib. Dinaciclib appears to be both more potent and selective than flavopiridol, with at least an order of magnitude greater therapeutic index, and is currently in phase III clinical trials. In additional to flavopiridol and dinaciclib, we also review the current status of other members of this class, and provide commentary as to the future direction of combination therapy including CDK inhibitors.
Spherical Image Processing for Immersive Visualisation and View Generation (2011)

This research presents the study of processing panoramic spherical images for immersive visualisation of real environments and generation of in-between views based on two views acquired. For visualisation based on one spherical image, the surrounding environment is modelled by a unit sphere mapped with the spherical image and the user is then allowed to navigate within the modelled scene. For visualisation based on two spherical images, a view generation algorithm is developed for modelling an indoor manmade environment and new views can be generated at an arbitrary position with respect to the existing two. This allows the scene to be modelled using multiple spherical images and the user to move smoothly from one sphere mapped image to another one by going through in-between sphere mapped images generated.
Measurements of diffusion coefficients in 1-D micro- and nanochannels using shear-driven flows (2005)

The present paper describes a method for measuring the molecular diffusion coefficient of fluorescent molecules in microfluidic systems. The proposed static shear-driven flow method allows one to perform diffusion measurements in a fast and accurate manner. The method also allows one to work in very thin (i.e. submicron) channels, hence allowing the investigation of diffusion in highly confined spaces. In the deepest investigated channels, the obtained results were comparable to the existing literature values, but when the channel size dropped below the micrometer range, a significant decrease (more than 30%) in molecular diffusivity was observed. The reduction of the diffusivity was most significant for the largest considered molecules (ssDNA oligomers with a size ranging between 25 to 100 bases), but the decrease was also observed for smaller tracer molecules (FITC). This decrease can be attributed to the interactions of the analyte molecules with the channel walls, which can no longer be neglected when the depth of the channel reaches a critical value. The change in diffusivity seems to become more explicit as the molecular weight of the analytes increases.
Platelet‐activating factor in stroke and brain injury (1991)

Platelet-activating factor, an endogenous phospholipid of proinflammatory, hemostatic, and vasoactive properties, is synthesized by neurons and in injured brain. Platelet-activating factor is released together with eicosanoids such as thromboxane A2, prostacyclin, and leukotrienes. Its effects in neurons are mediated through a specific receptor coupled to phospholipase C and phosphoinositol metabolism. The cerebrovascular effects of platelet-activating factor include disruption of the blood-brain barrier, edema formation, and vasospasm. It has also been described to possess direct toxicity to neuronal cells in culture. Discovery and development of several highly potent and selective antagonists to platelet-activating factor receptors facilitated experimental studies underscoring the role of this factor as an endogenous mediator in cerebral disorders, particularly cerebral ischemia and trauma. Significant biochemical, microvascular, functional, and behavioral recovery has been demonstrated using these antagonists in an array of experimental models of focal and global ischemia in the central nervous system (CNS). Clearly, studies of platelet-activating factor in experimental models of CNS ischemia and reperfusion injury open a new perspective on phospholipid metabolism in stroke and offer an exceptionally promising therapeutic prospect. Data supporting this factor as a mediator of specific pathological sequelae in stroke and neuroinjury are surveyed in this review. We discuss the mechanisms and significance of platelet-activating factor-mediated effects and propose directions for future studies.
Intracellular Cl regulates Na-K-Cl cotransport activity in human trabecular meshwork cells (1999)

The trabecular meshwork (TM) of the eye plays a central role in modulating intraocular pressure by regulating aqueous humor outflow, although the mechanisms are largely unknown. We and others have shown previously that aqueous humor outflow facility is modulated by conditions that alter TM cell volume. We have also shown that the Na-K-Cl cotransport system is a primary regulator of TM cell volume and that its activity appears to be coordinated with net efflux pathways to maintain steady-state volume. However, the cellular mechanisms that regulate cotransport activity and cell volume in TM cells have yet to be elucidated. The present study was conducted to investigate the hypothesis that intracellular Cl concentration ([Cl]i) acts to regulate TM cell Na-K-Cl cotransport activity, as has been shown previously for some other cell types. We demonstrate here that the human TM cell Na-K-Cl cotransporter is highly sensitive to changes in [Cl]i. Our findings reveal a marked stimulation of Na-K-Cl cotransport activity, assessed as ouabain-insensitive, bumetanide-sensitive K influx, in TM cells following preincubation of cells with Cl-free medium as a means of reducing [Cl]i. In contrast, preincubation of cells with media containing elevated K concentrations as a means of increasing [Cl]i results in inhibition of Na-K-Cl cotransport activity. The effects of reducing [Cl]i, as well as elevating [Cl]i, on Na-K-Cl cotransport activity are concentration dependent. Furthermore, the stimulatory effect of reduced [Cl]i is additive with cell-shrinkage-induced stimulation of the cotransporter. Our studies also show that TM cell Na-K-Cl cotransport activity is altered by a variety of Cl channel modulators, presumably through changes in [Cl]i. These findings support the hypothesis that regulation of Na-K-Cl cotransport activity, and thus cell volume, by [Cl]i may participate in modulating outflow facility across the TM.
Discrete Frequency Infrared Microspectroscopy and Imaging with a Tunable Quantum Cascade Laser (2012)

Fourier-transform infrared (FT-IR) imaging is a well-established modality but requires the acquisition of a spectrum over a large bandwidth, even in cases where only a few spectral features may be of interest. Discrete frequency infrared (DF-IR) methods are now emerging in which a small number of measurements may provide all the analytical information needed. The DF-IR approach is enabled by the development of new sources integrating frequency selection, in particular of tunable, narrow-bandwidth sources with enough power at each wavelength to successfully make absorption measurements. Here, we describe a DF-IR imaging microscope that uses an external cavity quantum cascade laser (QCL) as a source. We present two configurations, one with an uncooled bolometer as a detector and another with a liquid nitrogen cooled mercury cadmium telluride (MCT) detector and compare their performance to a commercial FT-IR imaging instrument. We examine the consequences of the coherent properties of the beam with respect to imaging and compare these observations to simulations. Additionally, we demonstrate that the use of a tunable laser source represents a distinct advantage over broadband sources when using a small aperture (narrower than the wavelength of light) to perform high-quality point mapping. The two advances highlight the potential application areas for these emerging sources in IR microscopy and imaging.