gebhart/patrepeval huggingface dataset:
Slow Rate of Phosphodiester Bond Formation Accounts for the Strong Bias that Taq DNA Polymerase Shows against 2‘,3‘-Dideoxynucleotide Terminators (1996)

Taq and T7 DNA polymerases have become basic molecular biology "tools" for DNA sequence analysis. However, Taq, unlike T7 DNA polymerase, is strongly biased against the incorporation of 2',3'-dideoxynucleotide triphosphates (ddNTPs) indicating very different substrate selectivities. Equilibrium binding and rate constants were measured for 2',3'-ddNTPs as well as for several other 3'-substituted terminators and compared to 2'-deoxynucleotide substrates (dNTPs). In steady-state experiments, Taq Pol I was strongly biased in favor of dATP1 over ddATP incorporation by about 700 to 1, in contrast to T7 DNA polymerase which showed a preference of only about 4 to 1. Manganese reduced but did not eliminate selectivity against 2',3'-ddNTPs. Transient kinetic traces indicated different rate-limiting steps for substrate and terminator incorporation. Further mechanistic studies showed that the binding constants for substrates and terminators were equivalent. However, the rate constants for phosphodiester bond formation for 2',3'-ddNTPs were 200-3000-fold lower than for dNTPs. Alternative terminators showed only slight improvements. The data were consistent with a model in which both substrates and terminators undergo ground-state binding followed by formation of a tight-binding Enz.DNA.Nucleotide complex. Immediately after complex formation, substrates undergo a rapid nucleoside phosphoryl transfer reaction. However, the reaction rates for terminators were slower presumably due to misalignment of reactive groups in the active site. Thus, the strong bias that Taq DNA polymerase shows against terminators is due to a very slow "chemistry" step. Such a strong bias has several kinetic consequences for DNA sequence patterns. These consequences are discussed in the text.
Design and fabrication of a diffractive phase element for wavelength demultiplexing and spatial focusing simultaneously (1996)

The design of a diffractive phase element (DPE) that simultaneously implements wavelength demultiplexing and focusing is carried out on the basis of the general theory of amplitude-phase retrieval. The designed DPE is fabricated with optical contact lithography. Three masks are needed to produce the surface-relief structure of the DPE with eight quantized levels in depths. Experiments demonstrate that the designed DPE can successfully implement both the functions of demultiplexing three different-wavelength beams and focusing each component at a predesignated position simultaneously. Experimental measurements are in good agreement with the results of numerical simulations.
High density interconnect for polymer based ultrasound transducers (2005)

Electrical interconnect strategy is an essential part of ultrasound transducer array development. Methods available include soldering, conductive adhesive bonding, fine wire welding (wire bond), Z-axis conductive films and, presented for the first time in an ultrasonic transducer, anisotropic conductive adhesive (ACA) pastes and films (ACF). ACA pastes work by trapping a metal coated polymer sphere between conductors. The spheres are then held in place by the supporting heat cured epoxy matrix. Images of the component parts are presented, as is an image from a PVdF transducer array with ACA interconnects and a centre frequency of 25 MHz. This work is of particular use in high frequency ultrasound arrays where interconnect density is high and for 2D array where large element counts are prevalent.
Bi‐affinity α<sub>1</sub>‐adrenoceptor binding in normal rat brain in vivo (1991)

The specific binding in rat brain in vivo of [125I]HEAT ([125I]iodo-2-[beta-(4-hydroxyphenyl)ethylamino methyl), a selective alpha 1-adrenoceptor ligand, was analyzed by a method designed to distinguish sites with different affinities. The data indicate at least two sites with different affinities for the alpha 1-adrenoreceptor in normal rat brain in vivo: a high-affinity site with Kd (half-saturation constant) of 3.6 +/- 0.7 nM (AV +/- SD), and a low-affinity site with Kd of 668 +/- 552 nM. The density (Bmax) of the high-affinity site in nine brain regions--auditory, visual, sensorimotor (four layers) and frontal cortex and lateral thalamic and medial geniculate nuclei--varied from 2.2 +/- 0.8 to 14.6 +/- 0.6 pmole/g, while the low-affinity range was 149 +/- 44 to 577 +/- 30 pmole/g. The results also revealed a very dynamic relationship between the two sites regulated by the concentration of the ligand ranging from 80% preponderance of the high-affinity sites at low ligand concentrations to more than 95% preponderance of the low-affinity sites at high ligand concentrations.
CAR-T-Zellen: Update 2019 (2019)

Zusammenfassung Die chimäre Antigenrezeptortherapie (CAR-Therapie) entwickelte sich zu einem der vielversprechendsten immunonkologischen Therapieansätze für die Behandlung von Krebs. Aufgrund der klinischen Erfolge wurden bisher 2 CD19-spezifische CAR-T-Zell-Therapien in den USA und der EU zugelassen. Die bahnbrechenden Ergebnisse weckten sowohl in der Industrie als auch in der Forschung großes Interesse und sorgten für eine rasante Entwicklung in diesem Feld.
Direct introduction of aqueous eluents for on–line coupled liquid chromatography–capillary gas chromatography (1989)

Abstract The on‐line introduction of relatively large volumes of reversed‐phase (aqueous) eluents into a capillary GC column without severe distortion of components eluting at temperatures close to the solvent boiling point is described. The technique, which utilizes an uncoated inlet (retention gap), is based on complete evaporation of the solvent prior to reaching the stationary phase and introduction of components with a dispersion equivalent to that given by a micro‐LC system. Studies of the evaporation within the retention gap, accomplished by introduction of a nonvolatile dye and visual examination of the resulting band patterns, indicated minimum retention gap lengths necessary to prevent liquid solvent from reaching the capillary GC column when aqueous eluents are used. The determination of N‐Serve' (2‐chloro‐6‐[trichloro methyl]pyridine) in corn extract is described.
Scalar and vector imaging based on wave mode decoupling for elastic reverse time migration in isotropic and transversely isotropic media (2016)

ABSTRACT Recording P- and S-wave modes acquires more information related to rock properties of the earth’s interior. Elastic migration, as a part of multicomponent seismic data processing, potentially offers a great improvement over conventional acoustic migration to create a spatial image of some medium properties. In the framework of elastic reverse time migration, we have developed new scalar and vector imaging conditions assisted by efficient polarization-based mode decoupling to avoid crosstalk among the different wave modes for isotropic and transversely isotropic media. For the scalar imaging, we corrected polarity reversal of zero-lag PS images using the local angular attributes on the fly of angle-domain imaging. For the vector imaging, we naturally used the polarization information in the decoupled single-mode vector fields to automatically avoid the polarity reversal and to estimate the local angular attributes for angle-domain imaging. Examples of increasing complexity in 2D and 3D cases found that the proposed approaches can be used to obtain a physically interpretable image and angle-domain common-image gather at an acceptable computational cost. Decoupling and imaging the 3D S-waves involves some complexity, which has not been addressed in the literature. For this reason, we also attempted at illustrating the physical contents of the two separated S-wave modes and their contribution to seismic full-wave imaging.
Poly(aspartic‐acid) derivatives as polymeric micelle drug delivery systems (2006)

Abstract A novel amphiphilic biodegradable graft copolymer based on poly(aspartic acid) (PASP) was prepared by coupling monomethoxy poly(ethylene glycol) as the hydrophilic segment with PASP‐ g ‐octadecyl (PASP‐ g ‐OD) as the hydrophobic backbone. The critical micelle concentration of the copolymer was obtained by measuring the conductivity and fluorescence spectroscopy. Polymeric micelles were prepared with the solvent evaporation method, and the size distribution and morphology of the polymeric micelles were characterized by dynamic light scattering and transmission electron microscopy. The ability of the PASP derivatives to solubilize hydrophobic drugs was investigated using methotrexate (MTX), oleanolic acid, and podophyllotoxin (PODO) as models. The results demonstrated that drug solubility depends on the copolymer concentration, copolymer composition, as well as the physicochemical property of the drug. A stability study performed with PODO loaded by polymeric micelle solution demonstrated that the micelle carrier could protect the drug from being destroyed in a pH 7.4 buffer solution; however, the micelle did not protect it in a pH 9.5 buffer solution. Pharmacokinetic studies were carried out by intravenous administration of MTX loaded by polymeric micelle solution and MTX solution. The results demonstrated that the polymeric micelle prolonged the drug permanence in blood circulation with a mean residence time of about 2.37 times and increased the systemic bioavailability with the area under the drug concentration–time curve by about 2.34 times. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 2871–2878, 2006
Foreshock sequence of the 1992 Landers, California, earthquake and its implications for earthquake nucleation (1995)

The June 28, 1992, Landers, California, earthquake ( M w = 7.3) was preceded for about 7 hours by a foreshock sequence consisting of at least 28 events. In this study we examine the geometry and temporal development of the foreshocks using high‐precision locations based on cross correlation of waveforms recorded at nearby stations. By aligning waveforms, rather than trying to obtain travel time picks for each event independently, we are able to improve the timing accuracy greatly and to make very accurate travel time picks even for emergent arrivals. We perform a joint relocation using the improved travel times and reduce the relative location errors to less than 100 m horizontally and less than 200 m vertically. With the improved locations the geometry of the foreshock sequence becomes clear. The Landers foreshocks occurred at a right step of about 500 m in the mainshock fault plane. The nucleation zone as defined by the foreshock sequence is southeast trending to the south and nearly north trending to the north of the right step. This geometry is confirmed by the focal mechanisms of the foreshock sequence, which are right‐lateral and follow the trend as determined by the foreshock locations on the two straight segments of the fault, and are rotated clockwise for foreshocks that occur within the step. The extent of the foreshock sequence is approximately 1 km both vertically and horizontally. Modeling of the Coulomb stress changes due to all previous foreshocks indicates that the foreshocks probably did not trigger each other. This result is particularly clear for the M w = 4.4 immediate foreshock. Since stress transfer in the sequence appears not to have played a significant role in its development, we infer an underlying aseismic nucleation process, probably aseismic creep. Other studies have shown that earthquake nucleation may be controlled by fault zone irregularities. This appears to be true in the case of the Landers earthquake, although the size of the irregularity is so small that it is not detectable by standard location techniques.
Prevention by Chitosan of Myelotoxicity, Gastrointestinal Toxicity and Immunocompetent Organic Toxicity Induced by 5‐Fluorouracil without Loss of Antitumor Activity in Mice (1999)

We examined the antitumor activity and side effects (myelotoxicity, immunocompetent organic toxicity and gastrointestinal toxicity) of combined treatment with the cancer chemotherapy drug 5-fluorouracil (5-FU) and dietary fiber chitosan in sarcoma 180-bearing mice. 5-FU (12.5 mg/kg x 2/day) plus chitosan (150, 375 and 750 mg/kg x 2/day) inhibited the tumor growth as well as 5-FU alone. Chitosan (150 and 750 mg/kg x 2/day) blocked the reduction of blood leukocyte number caused by 5-FU administration, and it prevented the injury of the small intestinal mucosa membrane and delayed the onset of diarrhea induced by 5-FU. Furthermore, chitosan (750 mg/kg x 2/day) prevented the reduction of spleen weight induced by 5-FU in sarcoma 180-bearing mice, and the reduction of lymphocyte and CD8+ T cell numbers induced by 5-FU was also prevented by the oral administration of chitosan (750 mg/kg x 2/day) in C57BL/6 mice. Chitosan (150 and/or 750 mg/kg x 2/day) reduced the 5-FU incorporation into RNA fractions of small intestine and spleen without affecting the 5-FU incorporation into the tumor in sarcoma 180-bearing mice. These findings suggest that prevention of the 5-FU side effects by chitosan might be partly due to the selective inhibition of 5-FU uptake into the small intestine and spleen, resulting in the reduction of immune function toxicity, myelotoxicity and gastrointestinal toxicity of 5-FU. Therefore, it is concluded that the combination of chitosan and 5-FU might be useful for the prevention of side effects such as gastrointestinal toxicity, immunotoxicity and myelotoxicity caused by 5-FU.
Interaction of soy isolate with polysaccharide and its effect on film properties (1994)

Abstract When soy isolate was mixed with sodium alginate, the two polymers interacted to form electrostatic complexes. They also formed varying degrees of covalent bonding, depending on reaction time and the presence or absence of the reducing agent sodium cyanoborohydride. On the other hand, soy isolate and propyleneglycol alginate (PGA) formed mostly covalent complexes at alkaline pH. The interaction of soy protein with polysaccharide maintained or improved its solubility and emulsifying activity, particularly when covalent bonds were involved. The alkylated complexes also showed better film‐making properties. However, protein‐PGA films were more readily formed and had greater stability in water than the protein‐alginate films.
Effect of Discontinuous Microfractures on Ultratight Matrix Permeability of a Dual-Porosity Medium (2012)

Summary This paper examines the effects of matrix microfractures on the effective matrix permeability of a dual-porosity medium. An analytical model is presented, with composite matrix blocks consisting of a core in which unconnected microfractures do not contribute considerably to flow capacity and a surface layer where the microfractures connected to the matrix surface (resembling wormholes) cause a stimulation effect. The composite matrix flow is coupled with the flow in a network of macrofractures, as in the conventional dual-porosity idealizations of fractured media. This paper investigates the effect of matrix-surface stimulation and demonstrates improved fluid transfer from the matrix medium to the fracture network because of matrix microfractures. It is shown that matrix microfractures accelerate production by providing earlier and more-effective contribution of the matrix into flow rates. This contribution of the matrix because of microfractures cannot be simulated by enhanced matrix permeability because the microfractured surface layer of the matrix causes flow characteristics different from those of a homogeneous (unfractured) matrix. The effect of the microfractured surface layer of the matrix cannot be taken into account by a triple-porosity model used to incorporate two sets of connected natural fractures or connected fractures and vugs.
Immune Therapy in GI Malignancies: A Review (2015)

The balance between tumor-promoting and tumor-suppressing immune responses and the difference between them ultimately determine whether a cancer escapes immune recognition mechanisms. Defining the complex relationships between the tumor itself, the tumor environment, and the immune system has been critical in facilitating the development of successful immunotherapies. This review explores the role of oncogenes in inducing cancer-associated inflammation, the local and systemic factors that lead to immune suppression, and immunotherapy approaches to overcome immune privilege.
Critical impact of the kinetics of dendritic cells activation on the in vivo induction of tumor-specific T lymphocytes. (2003)

Dendritic cells (DCs) need activation for the priming of antigen-specific immune responses. Recently activated DCs were described to prime in vitro strong T helper cell type 1 (Th(1)) responses, whereas at later time points, the same cells preferentially prime Th(2) cells [Langenkemp, A. et al., Nat. Immunol. 1: 311-316, 2000]. Because the immune response against cancer strongly depends on CTLs of Th(1)-like phenotype (Tc(1)), we verified here whether the kinetics of DCs activation also impacted on in vivo priming of tumor-specific CTLs. After pulsing with the CTL epitope TRP-2(180-188), bone-marrow-derived DCs, exposed to lipopolysaccharide (LPS) for 8 h (8hDC), elicited a more powerful Tc(1) response in C57BL/6 mice than did untreated DCs, or DCs exposed to LPS for 48 h (48hDC). Indeed, 8hDCs were the most potent protective and therapeutic vaccine against B16 melanoma. Despite a higher expression of MHC and costimulatory molecules by 48hDCs, 8hDCs and 48hDCs showed comparable allostimulatory and migration potential, and susceptibility to CTL-mediated apoptosis. However, 8hDCs exhibited a significantly higher interleukin (IL)-12 production potential. Release of IL-12 was necessary to induce potent Tc(1) cells, because DCs from IL-12p40(-/-) mice, irrespective of their maturation level, generated low CTL responses, comparable with 48hDCs and 0hDCs from wild-type animals. Our data are relevant for the design of DC-based vaccines.
Cardiac contractile function and mitochondrial respiration in diabetes-related mouse models (2014)

We explored three animal models mimicking type 1 and 2 diabetes. While cardiac dysfunction was present in the three groups of mice, mitochondrial respiration impairment was only obvious in models reproducing features of type 2 diabetes.
Strict Control of Human Immunodeficiency Virus Type 1 Replication by a Genetic Switch: Tet for Tat (2001)

Live-attenuated human immunodeficiency virus type 1 (HIV-1) variants have shown great promise as AIDS vaccines, but continued replication can lead to the selection of faster-replicating variants that are pathogenic. We therefore designed HIV-1 genomes that replicate exclusively upon addition of the nontoxic effector doxycycline (dox). This was achieved by replacement of the viral TAR-Tat system for transcriptional activation by the Escherichia coli-derived Tet system for inducible gene expression. These designer "HIV-rtTA" viruses replicate in a strictly dox-dependent manner both in a T-cell line and in primary blood cells, and the rate of replication can be fine-tuned by simple variation of the dox concentration. These HIV-rtTA viruses provide a tool to perform genetics, e.g., selection and optimization experiments, with the E. coli-derived Tet reagents in a eukaryotic background. Furthermore, such viruses may represent improved vaccine candidates because their replication can be turned on and off at will.
FPGA Based Multiplex PWM Generator for Multilevel Converters Applied Wind Power Generator (2009)

With the direct-drive wind power system, full-power converter technology has been developed and applied. However, most of wind generators operate at rated voltage of 690 V in wind field at present while direct-drive power system needs the full-scale power converter. For the high-power output, power devices must support higher current. Before the breakthrough of the present level of the current rating, multi converters can meet the low-voltage, high-current condition under the parallel operation. In full-scale power converters of direct-drive wind power system, we combine carrier phase shifted technique and parallel converters successfully, and realize the normal operation in low frequency. More and more multilevel converter used in the larger wind power plant. With the development of multilevel converter , multi-pulse generator is needed. In this paper, a twelve-pair PWM generator based on FPGA is designed for three-phase voltage source 5-level inverters. Carrier phase shifted SPWM (CPS-SPWM) is applied as switch modulation strategy. CPS- SPWM can achieve a high equivalent switching frequency effect at rather low real device switching frequency, which is very suitable for high power equipments. A three-phase voltage source 5-level cascade inverters prototype is accomplished by this twelve-pair PWM generator. The experimental results verify the correctness of the design. Other modulation strategies, such as multilevel space vector modulation and sample time staggered space vector modulation, can also be accomplished by FPGA. This is of much significance to the further application of multi-modular converters and multilevel converters.
Smart Sensing Systems Using Wearable Optoelectronics (2020)

A wearable smart sensing system is capable of continuously monitoring biometric information such as respiration, pulse, and body temperature while attached to an arbitrary surface on the user's body to be utilized freely during activities. Research conducted on new materials, fabrication processes, structure of electrodes, and wireless communication technologies has made constant progress in the development of smart sensing systems that use entirely wearable forms of devices to go beyond conventional devices that are based on intrinsically rigid components, such as silicon. Among various platforms that can be used in the development of smart sensing systems, optoelectronics provides innovative sensing functions (e.g., human–machine interfaces and phototherapy) that can be transferred from traditional healthcare to smart healthcare, such as point of care. Optoelectronics are light‐mediated displays that allow a light source to be controlled and a large light spectrum to be detected. Recently, this platform that uses smart and wearable optoelectronic sensing systems has become increasingly advanced to better help human beings treat their diseases through self‐healthcare. Herein, recent advanced technologies in materials, structures, and wireless platforms for smart sensors using wearable optoelectronics are reviewed.
A mono surrogate for multiobjective optimization (2010)

Most surrogate approaches to multi-objective optimization build a surrogate model for each objective. These surrogates can be used inside a classical Evolutionary Multiobjective Optimization Algorithm (EMOA) in lieu of the actual objectives, without modifying the underlying EMOA; or to filter out points that the models predict to be uninteresting. In contrast, the proposed approach aims at building a global surrogate model defined on the decision space and tightly characterizing the current Pareto set and the dominated region, in order to speed up the evolution progress toward the true Pareto set. This surrogate model is specified by combining a One-class Support Vector Machine (SVMs) to characterize the dominated points, and a Regression SVM to clamp the Pareto front on a single value. The resulting surrogate model is then used within state-of-the-art EMOAs to pre-screen the individuals generated by application of standard variation operators. Empirical validation on classical MOO benchmark problems shows a significant reduction of the number of evaluations of the actual objective functions.