gebhart/patrepeval huggingface dataset:
Abstract 2623: CHP-IL12 combined with surgery suppresses tumor metastasis and prolongs survival (2018)

Abstract Interleukin 12 (IL-12) is the most promising cytokine for treating tumors by itself or arming immunogenic cells but its toxicity and moderate response limit its clinical use. To avoid or minimize the toxicity issue and boost the anti-tumor immune response, our lab has discovered a comprehensive tumor-targeting carcinoma homing peptide (CHP). Fusion of this peptide encoding DNA sequence to IL12 encoding sequence in frame yields the proprietary product—CHP-IL12 (US patent 9,657,077 B2), or tumor-targeting IL12, which increased the accumulation of IL12 in tumor environment and decreased liver toxicity compared to wild-type IL12 (wt-IL12) gene therapy. Here, we report the therapeutic efficacy of this CHP-IL12 on metastasis and to comprehend the underlying mechanism description between CHP-IL12 and wildtype (wt)-IL12 for boosting anti-tumor response, two orthotopic and spontaneous tumor metastasis models (one adult and one pediatric tumor) were utilized. CHP-IL12 gene therapy showed greater efficacy in controlling growth of established tumors compared to wt-IL12. CHP-IL12 gene therapy, in combination with surgery, reduced number of metastatic nodules in lungs, livers and bones. CHP-IL12, compared to wt-IL12, conferred a potential immunostimulatory effect involving 1) reduction of T-reg cells, myeloid-derived suppressor cells (MDSC) and tumor associated macrophages (TAM); 2) recruitment of activated CD8+ T cells to the tumor. Moreover, CHP-IL12 increased IL12, IFNγ level in tumor environment and decreased IL12, IFNγ level in serum, which is the major cause of toxicity. Furthermore, in combination with surgery, CHP-IL12 gene therapy led to long-term survival and enhanced immunological memory development of tumor bearing mice compared to wt-IL12 gene therapy. These results collectively indicate that CHP-IL12 fusion gene therapy coupled with surgery has a powerful potency in inhibition of tumor metastasis and prolonging survival and a low potency in inducing toxicity. Therefore, CHP-IL12 fusion gene therapy in combination with surgery may translate into clinic as a promising anti-tumor strategy for both adult and pediatric tumors. Citation Format: Qingnan Zhao, Jiemiao Hu, Jeffry J. Cutrera, Abhisek Mitra, Xueqing Xia, Shulin Li. CHP-IL12 combined with surgery suppresses tumor metastasis and prolongs survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2623.
Limited feedback designs for two-way wireless relaying channels with physical network coding (2012)

In this paper, we propose a limited feedback system for two-way wireless relaying channels with physical network coding (PNC). The optimal system with full feedback has already been studied when a modulo operation is employed for the PNC. In this case, phase and power of channels of two end nodes are adjusted to maximize the minimum distance. Based on this full feedback system, we design new quantization methods for the phase and the power. From the observation of the minimum distance, we present a codebook design. Especially, for the quantization of power in the system with 16-QAM, a novel power quantization scheme is proposed to maximize the worst minimum distance. Finally, the simulation results confirm that our proposed scheme outperforms conventional limited systems with reduced complexity.
Efficient Well Placement Optimization with Gradient-based Algorithms and Adjoint Models (2008)

Abstract A key reservoir management decision taken throughout the life of a reservoir is the determination of optimal well locations that maximizes asset value (such as Net Present Value, NPV). Because this well placement optimization problem is a discrete-parameter problem (well locations are discrete parameters in the simulation model), gradients of the objective function (NPV) with respect to these parameters are not defined. Thus, gradient-based methods have not found much applicability to this problem, and most existing algorithms applied to this problem are stochastic in nature, such as genetic algorithms, simulated annealing, and stochastic perturbation methods. These methods are usually quite inefficient requiring hundreds of simulations and thus may have limited application to large-scale simulation models with many wells. We propose a novel, continuous approximation to the original discrete-parameter well placement problem such that gradients can be calculated on the approximate problem, and gradient-based algorithms can then be employed for efficiently determining the optimal well locations. The basic idea is to first replace the discrete parameters (i, j well location indices) with their continuous counterparts in the spatial domain (x, y well locations) and then obtain a continuous functional relationship between the objective function and these continuous parameters. Such a functional relationship is obtained by replacing the discontinuous Dirac-delta functions (defining wells as point sources) in the underlying governing PDE with continuous functions (which in the limit tends to the Dirac-delta function, such as the bivariate Gaussian function). Numerical discretization of the modified PDE leads to well terms in the mass balance equations that are continuous functions of the continuous well location variables. As a result of this continuous functional relationship, adjoints and gradient-based optimizations algorithms can now be applied to obtain the optimal well locations. The efficiency and practical applicability of the approach is demonstrated on a few synthetic waterflood optimization problems.
Synchronously pumped mode-locked CdS platelet laser (1981)

We report pulses as short as 8 ps obtained from a mode-locked cw optically-pumped semiconductor laser. The sample was a CdS platelet at a temperature of 95 K longitudinally pumped by a mode-locked Ar+ laser. The output power was 3.2 mW with 8-ps pulses, and powers greater than 10 mW have been observed with 10-ps pulses. Laser performance is quite independent of cavity length as compared to synchronously pumped dye lasers, indicating that passive pulse shaping may be taking place.
The sounds of silence: towards automated evaluation of student learning in a reading tutor that listens (1997)

We propose a paradigm for ecologically valid, authentic, unobtrusive, automatic, data-rich, fast, robust, and sensitive evaluation of computer-assisted student performance. We instantiate this paradigm in the context of a Reading Tutor that listens to children read aloud, and helps them. We introduce interword latency as a simple prosodic measure of assisted reading performance. Finally, to validate the measure and analyze performance improvement, we report initial experimental results from the first extended in-school deployment of the Reading Tutor.
Sound reproducing device for playing a record disc having a plurality of recorded grooves (1990)

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Superconducting properties of rapidly heated and quenched Nb/sub 3/Ga wires (2003)

Stoichiometric Nb/sub 3/Ga with good long range ordering shows a high T/sub c/ above 20 K and a high H/sub c2/(4.2 K) above 30 T. However, high J/sub c/ had not yet been reported for any Nb/sub 3/Ga fabricated through various methods, which was preventing the development of practical Nb/sub 3/Ga conductors in the last 30 years. Recently we could overcome the problem through a promising combination of RHQ (rapid heating and quenching) treatment and microcomposite precursor wire of Nb and NbGa/sub 3/. Nb/sub 3/Ga layers were formed directly through the RHQ treatment. Post annealing at 600-800/spl deg/C was very effective in improving the superconducting properties of the Nb/sub 3/Ga wire. The best values of T/sub c/ and B/sub c2/(4.2 K) of 19.7 K and 32 T were obtained, respectively. In addition the J/sub c/(4.2 K) values of Nb/sub 3/Ga layer at 20 T, 23 T, and 25 T were 370 A/mm/sup 2/, 250 A/mm/sup 2/ and 160 A/mm/sup 2/, respectively. These critical values are much higher than those of the commercialized (Nb,Ti)/sub 3/ Sn wire made through a bronze route.
MPEG-7: a content description standard beyond compression (2003)

The proliferation of multimedia content requires standard methods for content description to facilitate exchange and reuse of content among different applications along the media value chain. ISO is in the process of developing a content description standard called MPEG-7, which unlike the previous MPEG standards goes beyond compression. Formally called "Multimedia Content Description Interface", IMPEG-7 will provide a standardized description of various types of multimedia information by 2001. In this paper we outline the objectives, required technologies and some potential applications that can benefit from MPEG-7. We present several technologies that we have developed at Philips Research and proposed to the international standardization organization. These include visual descriptors for both still images and video. Examples include descriptors that enable visual search by similarity using color and edges and important visual entities such as faces and text.
Analogues of (3<i>R</i>)-7-Hydroxy-<i>N</i>-[(1<i>S</i>)-1-{[(3<i>R</i>,4<i>R</i>)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl}-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide (JDTic). Synthesis and in Vitro and in Vivo Opioid Receptor Antagonist Activity (2010)

The synthesis of compounds 6, 7a,b, 8a,b, 9a,b, and 10a,b where the amino -NH- group of JDTic (3) was replaced with an aromatic horizontal lineCH-, CH(2), O, S, or SO group was accomplished and used to further characterize the SAR of the compound 3 class of kappa opioid receptor antagonists. All of the compounds showed subnanomolar to low nanomolar K(e) values at the kappa opioid receptor. The most potent compound was 7a, where the amino -NH- group of 3 was replaced by a methylene (-CH(2)-) group. This compound had a K(e) = 0.18 nM and was 37- and 248-fold selective for the kappa relative to the mu and delta opioid receptors, respectively. Similar to compound 3, compound 7a antagonized selective kappa agonist U50,488-induced diuresis after sc administration in rats. In contrast to 3, where kappa antagonist activity lasted for three weeks, compound 7a did not show any kappa antagonist activity after one week.
Operation and Noise Transmission of an Axial Turbine Driven by a Pulse Detonation Combustor (2005)

Pulse Detonation Combustors (PDC’s), as part of a hybrid PDC-turbine engine, have potential thermodynamic benefits over existing Brayton-cycle gas turbines. The form of combustion is a cyclic, controlled series of detonations. These systems apply a near or quasi-constant volume combustion process that provides both heat addition and pressure. In a hybrid PDC-turbine engine, the goal of incorporating a pulsed detonation chamber upstream of a turbine is to extract more mechanical energy in a turbine that receives the products of a repeating, pressure-rise detonation process versus the constant pressure, steady-flows available in conventional gas turbines. A rig was built to investigate PDC-turbine interactions and was operated to gather data on performance, operability, and noise levels. The rig consists of a single pulsed detonation combustor firing into a partial-admission, two-stage axial turbine. This paper reports findings of critical risk areas including turbine response to PDC operation, mechanical robustness, noise and system control. At a PDC operating frequency of 5 Hz, the acoustic level near the rig was approximately 3 dB higher than from the turbine operating at the same speed with steady flow input. The noise level is 28 dB lower than a PDC with no turbine downstream operating at the same frequency and discharging directly into the room. Insights into the mechanism for noise reduction were gained via imaging experiments and CFD simulation. High speed video imaging in a 2D PDC-turbine cascade configuration showed significant shock reflection from the cascade. An unsteady, reacting flow computational study showed similar shock reflection as well as a shock system that forms downstream of the cascade. Together, these results show that shock waves are both transmitted and reflected by the turbine stages in proportions that are dependent upon turbine stage design.
Polyketide Chain Skipping Mechanism in the Biosynthesis of the Hybrid Nonribosomal Peptide−Polyketide Antitumor Antibiotic Leinamycin in <i>Streptomyces </i><i>a</i><i>troolivaceus</i> S-140 (2006)

A fundamental feature of modular polyketide synthases (PKSs) is the highly predictable relationship between the domain order and the chemical functional groups of resultant polyketide products. Sequence analysis and biochemical characterization of the leinamycin (LNM) biosynthetic gene cluster from Streptomyces atroolivaceus S-140 has revealed a gene, lnmJ, that encodes five PKS modules but with six acyl carrier protein (ACP) domains. The LnmJ PKS module 6 contains two ACP domains, ACP(6-1) and ACP(6-2), separated by a C-methyltransferase domain. Site-directed mutagenesis experiments were carried out with each of these ACPs to test alternative mechanisms proposed for their role in polyketide chain elongation. The in vivo results revealed a new type of polyketide chain "skipping" mechanism, in which either ACP is sufficient for LNM biosynthesis. Biochemical characterization in vitro showed that both ACPs can be loaded with a malonate extender unit by the LnmG acyl transferase; however, ACP(6-2) appears to be preferred because the loading efficiency is about 5-fold that of ACP(6-1). The results are consistent with ACP(6-2) being used for the initial chain elongation step wth ACP(6-1) being involved in the ensuing C-methylation process. These findings provide new insights into the polyketide chain skipping mechanism for modular PKSs.
Innovative Differential Protection of Power Transformers Using Low-Energy Current Sensors (2013)

Traditional differential protection systems are applied on large power transformers using current transformers (CTs). However, because of high secondary currents (often exceeding 100 kARMS), differential protection systems for electric arc furnace transformers have not been applied in the past due to the lack of commercially available CTs. This paper will present differential protection systems that have been in use for many years using Rogowski coil current sensors. These protection systems use high-precision printed circuit board Rogowski coil current sensors. This paper reviews the characteristics, designs, and application of these Rogowski coil sensors for advanced protection, control, and metering systems with new multifunction relays. This paper compares performance characteristics of new solutions based on Rogowski coil sensors with the conventional differential protection systems based on CTs, demonstrating that the new systems do not have the limitations of conventional technology. Operating experience from several site applications is included.
Carbon-nanotube-based resonant-circuit sensor for ammonia (2002)

We present the design and development of highly sensitive and fast-responsive microwave resonant sensors for monitoring the presence of ammonia gas. The sensor consists of a circular disk electromagnetic resonant circuit coated with either single- or multiwalled carbon nanotubes that are highly sensitive to adsorbed gas molecules. Upon exposure to ammonia, the electrical resonant frequency of the sensor exhibits a dramatic downshift of 4.375 MHz. The recovery and response times of these sensors are nominally 10 min. This technology is suitable for designing remote sensor systems to monitor gases inside sealed opaque packages and environmental conditions that do not allow physical wire connections.
Engineering Human Induced Pluripotent Stem Cells with Novel Chimeric Antigen Receptors to Generate Natural Killer (NK) Cell Cancer Immunotherapies with Targeted Anti-Tumor Activity (2017)

Chimeric antigen receptors (CARs) provide a powerful strategy to direct and enhance anti-tumor activity of immune effector cells. While most studies have evaluated CAR-expression in T cells, here we evaluate and optimize CAR constructs that are specifically designed with natural killer (NK) cell transmembrane and signaling domains. Since NK cell-mediated cytotoxicity does not require self-HLA expression, derivation of NK cells from human induced pluripotent stem cells (iPSCs), combined with the use of NK cell-specific CARs, enables production of a standardized, targeted allogeneic effector cell population. After screening 10 combinations of CARs using an anti-mesothelin (meso) scFv to target ovarian cancer cells, we identified a CAR construct containing the transmembrane domain of NKG2D, the 2B4 co-stimulatory domain, and the CD3ζ signaling domain that mediates a strong increase in intracellular NK cell signaling. iPSC-derived NK cells that express this novel CAR (NKCAR-iPSC-NK cells) have a surface phenotype similar to NK cells isolated from peripheral blood (PB-NK) and unmodified iPSC-derived NK cells. Interestingly, the NKCAR-iPSC-NK cells mediate improved killing of target-expressing targets more than iPSC-derived NK cells expressing a 3 rd generation CAR with CD28, CD137, and ζ signaling elements optimized for T cell-mediated activity (TCAR-iPSC-NK cells). We examined intracellular signaling pathways stimulated by our NKG2D-2B4-ζ CAR construct. In NKCAR-iPSC-NK cells, antigen (meso)-expressing targets promoted phosphorylation of Syk and Erk. Site-directed mutagenesis studies demonstrate the requirement for the NKG2D and 2B4 domains to mediate release of cytotoxic granules (CD107a), cytokine (IFN-γ) release and robust tumor cell lysis. Using an ovarian cancer xenograft model, a single dose of NKCAR-iPSC-NK cells markedly inhibited tumor growth, and mediated significantly enhanced survival (84 days) compared to NK cells isolated from peripheral blood (PB-NK cells) (70 day survival), non-CAR-expressing iPSC-NK cells (57 days), and TCAR-iPSC-NK cells (63 days) (p Disclosures Hermanson: Poseida Therapeutics: Employment. Bjordahl: Fate Therapeutics: Employment, Equity Ownership. Mahmood: Fate Therapeutics: Employment. Valamehr: Fate Therapeutics: Employment, Equity Ownership. Kaufman: Fate Therapeutics: Consultancy, Research Funding.
Nuclear factor‐κB and IκB kinase are constitutively active in human pancreatic cells, and their down‐regulation by curcumin (diferuloylmethane) is associated with the suppression of proliferation and the induction of apoptosis (2004)

Curcumin down-regulated NF-kappaB and growth control molecules induced by NF-kappaB in human pancreatic cells. These effects were accompanied by marked growth inhibition and apoptosis. Through these findings, the authors provided a biologic rationale for the treatment of patients with pancreatic carcinoma using this nontoxic phytochemical.
Wide Area Real Time Kinematics with Galileo and GPS Signals (2004)

The main factor limiting the range extension of the Real Time Kinematics technique beyond few tens of kilometers is the differential ionospheric correction between the roving and the nearest reference GNSS station. Such ionospheric correction impedes the real-time ambiguity fixing, and the corresponding accurate navigation at the sub-decimeter level. In this paper, the authors present the recent developments in the application of accurate real-time ionospheric corrections in the context of the future three-frequency systems, such as Galileo and Modernized GPS, regarding previous studies (Hernandez-Pajares et al. 2003b). Indeed, from new datasets gathered in the new three-frequency signal simulator placed at ESTEC/ESA, the feasibility of the Wide Area Real Time Kinematics is confirmed, mostly in single epoch mode (instantaneously): the navigation can be typically performed with few centimeters of error at distances of hundreds of kilometers from the nearest Galileo or Modernized GPS reference station. The new improved strategy adopted (WARTK3.2) includes a no-differenced approach, the ionospheric corrections integrity monitoring, and the capability of the roving user orientation determination with one single antenna at the level of few degrees of error. Moreover, the results obtained with the corresponding strategy adapted to the dual-frequency GPS data confirm both the previous results and the new capabilities of the technique. Particularly, several datasets have been analyzed. Firstly real GPS data have been studied corresponding to an experiment of urban navigation (UNBAR01), performed at Barcelona, Spain, in 2001, with Solar Maximum conditions and local ionospheric perturbations. On the other hand, several three-frequency datasets, simulated in radio-frequency, have been analyzed as well with WARTK-3.2, including a car and an aircraft, moving around the NE of Spain, at distances around 200 km away from the nearest reference site. The results show the
Oversampling sigma-delta modulator stabilized by local nonlinear feedback loop technique (2000)

The proposed scheme relates to a technique called "local nonlinear feedback loop (LNFL)" for stabilization of oversampling sigma-delta modulators (SDMs). SDM stabilized by the LNFL technique avoids the instability limitation without overall signal-to-noise ratio (SNR) degradation, because the LNFL technique keeps the input dynamic range within proper bounds (-/spl Delta//2, /spl Delta//2) absolutely to prevent integrators from overload, whether the critical integrator in SDM enters the unstable region or not. Unlike conventional methods, the nonlinear compensative operation in the proposed technique does not increase the quantization noise proportionally to cause the overall SNR degradation in the meanwhile. Besides, the proposed algorithm can be applied to various configurations of oversampling SDMs, such as single-loop and multiple-loop structures, for high stability and low-power very large scale integration applications.
Structural characterization of a novel human adeno-associated virus capsid with neurotropic properties (2020)

Recombinant adeno-associated viruses (rAAVs) are currently considered the safest and most reliable gene delivery vehicles for human gene therapy. Three serotype capsids, AAV1, AAV2, and AAV9, have been approved for commercial use in patients, but they may not be suitable for all therapeutic contexts. Here, we describe a novel capsid identified in a human clinical sample by high-throughput, long-read sequencing. The capsid, which we have named AAVv66, shares high sequence similarity with AAV2. We demonstrate that compared to AAV2, AAVv66 exhibits enhanced production yields, virion stability, and CNS transduction. Unique structural properties of AAVv66 visualized by cryo-EM at 2.5-Å resolution, suggest that critical residues at the three-fold protrusion and at the interface of the five-fold axis of symmetry likely contribute to the beneficial characteristics of AAVv66. Our findings underscore the potential of AAVv66 as a gene therapy vector.
Surface plasmon resonance probing of dynamic biomembrane processes (1995)

When the hypotenuse of a dielectric prism coated with the correct thickness of a suitable metal is illuminated with p-polarized light at the appropriate angle of incidence beyond critical the light couples into a bound surface wave on the outer surface of the metal. The coupling is marked by a sudden sharp and deep dip in the internal p-reflectance of the prism. This phenomenon is known as Surface Plasmon Resonance and this particular form of coupling is known as the Kretschmann [ 1 ] configuration. The resonance is a very sensitive function of the surface conditions and changes in its angular position and shape can be used as a probe of surface conditions. In particular it may be, and has been [ 2 ], used to track changes in a thin film deposited over the metal surface. The better the optical performance of the metal, the narrower is the resonance. The work reported here uses silver. Silver has very high optical performance and gives excellent resonance curves but suffers from long term durability problems.