gebhart/patrepeval huggingface dataset:
Adoptive Transfer of Type 1 CTL Mediates Effective Anti–Central Nervous System Tumor Response: Critical Roles of IFN-Inducible Protein-10 (2006)

The development of effective immunotherapeutic strategies for central nervous system (CNS) tumors requires a firm understanding of factors regulating the trafficking of tumor antigen-specific CTLs into CNS tumor lesions. Using C57BL/6 mice bearing intracranial (i.c.) ovalbumin-transfected melanoma (M05), we evaluated the efficacy and tumor homing of i.v. transferred type 1 or 2 CTLs (Tc1 or Tc2, respectively) prepared from ovalbumin-specific T-cell receptor-transgenic OT-1 mice. We also tested our hypothesis that intratumoral (i.t.) delivery of dendritic cells that had been transduced with IFN-alpha cDNA (DC-IFN-alpha) would enhance the tumor-homing and antitumor effectiveness of adoptively transferred Tc1 via induction of an IFN-gamma-inducible protein 10 (IP-10). In vitro, DC-IFN-alpha induced IP-10 production by M05 and enhanced the cytolytic activity of Tc1. In vivo, i.v. transferred Tc1 trafficked efficiently into i.c. M05 and mediated antitumor responses more effectively than Tc2, and their effect was IP-10 dependent. I.t. injections of DC-IFN-alpha remarkably enhanced the tumor homing, therapeutic efficacy, and in situ IFN-gamma production of i.v. delivered Tc1, resulting in the long-term survival and persistence of systemic ovalbumin-specific immunity. These data suggest that Tc1-based adoptive transfer therapy may represent an effective modality for CNS tumors, particularly when combined with strategies that promote a type 1 polarized tumor microenvironment.
Compact capacitance and capacitive coupling-noise modeling of Through-Oxide Vias in FDSOI based ultra-high density 3-D ICs (2011)

Fully-Depleted SOI (FDSOI) technology boosts the opportunity to make 3-D ICs with ultra-high integration density, due to the short and tiny Through-Oxide Vias (TOVs), which are made after removing the entire silicon under the buried-oxide layer. This work, for the first time, develops compact physical models for the capacitance of the TOV and the coupling capacitance between TOV and active regions in presence of periodical power lines, from fundamental electrostatic considerations. Calculation results from the models show good agreement with the simulation results from a full-3D capacitance solver. The models are further used to analyze the threshold voltage (V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">th</sub> ) variation in the FDSOI MOSFETs. The TOV in FDSOI and the Through-Silicon Via (TSV) in bulk CMOS based 3-D ICs are finally compared in terms of the self impedance as well as their impact on MOSFET V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">th</sub> variation through capacitive-noise coupling. These results provide important insights to TOV/TSV design and optimization in emerging 3-D ICs.
Growth Factor Receptors in Breast Cancer: Potential for Therapeutic Intervention (2003)

Increased expression and activation of receptor tyrosine kinases occurs frequently in human breast carcinomas. Several therapies targeting these receptors are currently in clinical trials. Therapeutic strategies include blockade of individual receptors with monoclonal antibodies and inhibition of tyrosine kinase function. Trastuzumab is the first of these biologic therapies to be approved for patients with human epidermal growth factor receptor 2 (HER2)-overexpressing metastatic breast cancer. Novel trastuzumab-based combinations are being investigated in patients with advanced breast cancer. Large clinical trials have also been launched in the adjuvant setting. Small molecules that inhibit specific tyrosine kinases (e.g., epidermal growth factor receptor, HER2) are in phase I and phase II clinical trials. Other growth-factor-targeted drugs that have reached clinical development include STI571 and antibodies directed at the insulin-like growth factor pathway. Biologic therapies directed against these important receptors are promising. In this review we discuss challenges and opportunities for the development of growth-factor-targeted approaches for the treatment of breast cancer.
A transgenic mouse model for lung adenocarcinoma. (1995)

Lung cancer is a leading cause of tumor-related deaths in humans but its origin and development are poorly understood. To study the biology of these tumors, appropriate animal and cell culture models will be of eminent importance. Uteroglobin is a marker protein for the nonciliated epithelial Clara cells lining the respiratory and terminal bronchioli of the lung. We have used the promoter and 5'-flanking sequences of the rabbit uteroglobin gene to target expression of the SV40 T antigen to the lung of transgenic mice. All transgenic founders as well as the descendants from an established line, UT7.1, developed multifocal bronchioloalveolar adenocarcinomas originating from Clara cells. At least three different stages in tumor development with progressive loss of the differentiated phenotype can be distinguished by immunohistochemical data and in situ hybridization. Only in the initial stage did bronchiolar cells express both uteroglobin and SV40 T antigen, whereas at later stages, only SV40 T antigen was detected, and the most advanced tumors were negative for both proteins. Starting from the lungs of UT7.1 mice, a bronchiolar cell line was established that maintains the features of differentiated Clara cells. This system provides a useful model for further studying the development and progression of lung adenocarcinomas in vivo and in vitro.
Non-invasive detection of crizotinib resistance in ALK-rearranged lung adenocarcinoma directs treatment with next-generation ALK inhibitors. (2016)

e20643 Background: Somatic mutations (SNVs) in ALK are a common mechanism of resistance to crizotinib, and may respond to next-generation ALK inhibitors. Historically, identification of these ALK SNVs required repeat tissue biopsies because they are absent in pre-treated tissue samples. Circulating tumor DNA (ctDNA) next-generation sequencing (NGS) may provide a non-invasive way to identify these SNVs. Methods: Guardant360 is a ctDNA NGS test that sequences complete exons in the ALK gene and the intronic breakpoints needed to identify ALK fusions. It includes other guideline-recommended somatic genomic targets: SNVs in 70 genes, select fusions, indels and amplifications. Results: In the first 10,000 advanced-solid-cancer patients (pts) tested by Guardant360, ALK SNVs and fusions were detected in 6% of pts. EML4 was the most common ALK fusion partner (81%); STRN (9%), KIF5B (5%), VCL (2.5%), KCL (2.5%). Among 24 pts with ALK-fusion-driven lung adenocarcinoma (LUAD), mutant allele fraction (MAF) of ALK fusion ranged from 0.06% to 12.5%. We found several co-occurring SNVs, of which 10% were known resistance SNVs in ALK (detected in 4 pts): F1174C/V (3), G1202R (2), L1198F (1), I1171T (1), and L1196M (1). We also found co-occurring SNVs in other genes that are absent in treatment-naïve pts, suggesting possible novel crizotinib-resistance mechanisms. ALK L1198F, a rare alteration shown to re-sensitize to crizotinib, was detected in a patient who expired before re-treatment. In a case with serial draws, pre-treated ALK fusion MAF was 0.91%; at progression, ALK fusion MAF was 0.4% and F1174C was detected at 1.0%. Tissue results from both time points were concordant with ctDNA. The patient started alectinib in January 2016, and response scans are pending. Conclusions: We comprehensively cataloged mutations that likely arose at progression in ALK-fusion-positive LUAD pts treated with crizotinib, including five well-described crizotinib-resistance alterations. These results add to the growing body of literature demonstrating that comprehensive ctDNA assays provide a non-invasive means of detecting known and novel resistance mechanisms that inform treatment decisions.
The application of carbon nanotube - polymer composite as gas sensing materials (2006)

This is the first report on the evaluation on the performance of the gas sensing properties of carbon nanotube-polymer composite materials for volatile organic compounds (VOCs). Single wall carbon nanotube-polymer (ethyl cellulose) (SWNT-EC) composite suspensions were prepared in chloroform with the help of poly(p-phenylenevinylene-co-2,5-dioctoxy-m-phenylenevinylene) (PmPV). The composite films were formed onto electrode substrates by spraying the suspensions. The gas sensing performance of the composite films well supports that these materials are suitable for VOC sensors. The dispersion quality of SWNT in the sol suspension is understood to be closely related to the sensing properties of the films. Enhancement in SWNT dispersion in the polymer matrix is expected to improve the sensing properties of the composite sensors.
Liquid-phase combinatorial synthesis. (1995)

A concept termed liquid-phase combinatorial synthesis (LPCS) is described. The central feature of this methodology is that it combines the advantages that classic organic synthesis in solution offers with those that solid-phase synthesis can provide, through the application of a linear homogeneous polymer. To validate this concept two libraries were prepared, one of peptide and the second of nonpeptide origin. The peptide-based library was synthesized by a recursive deconvolution strategy [Erb, E., Janda, K. D. & Brenner, S. (1994) Proc. Natl. Acad. Sci. USA 91, 11422-11426] and several ligands were found within this library to bind a monoclonal antibody elicited against beta-endorphin. The non-peptide molecules synthesized were arylsulfonamides, a class of compounds of known clinical bactericidal efficacy. The results indicate that the reaction scope of LPCS should be general, and its value to multiple, high-throughput screening assays could be of particular merit, since multimilligram quantities of each library member can readily be attained.
Genetically Targeted T Cells Eradicate Systemic Acute Lymphoblastic Leukemia Xenografts (2007)

Both in vivo costimulation and repeated administration enhance eradication of systemic tumor by genetically targeted T cells. The finding that modifications in CAR design as well as T-cell dosing allowed for the complete eradication of systemic disease affects the design of clinical trials using this treatment strategy.
Interaction of the herbicide glyphosate with its target enzyme 5-enolpyruvylshikimate 3-phosphate synthase in atomic detail (2001)

Biosynthesis of aromatic amino acids in plants, many bacteria, and microbes relies on the enzyme 5-enolpyruvylshikimate 3-phosphate (EPSP) synthase, a prime target for drugs and herbicides. We have identified the interaction of EPSP synthase with one of its two substrates (shikimate 3-phosphate) and with the widely used herbicide glyphosate by x-ray crystallography. The two-domain enzyme closes on ligand binding, thereby forming the active site in the interdomain cleft. Glyphosate appears to occupy the binding site of the second substrate of EPSP synthase (phosphoenol pyruvate), mimicking an intermediate state of the ternary enzyme.substrates complex. The elucidation of the active site of EPSP synthase and especially of the binding pattern of glyphosate provides a valuable roadmap for engineering new herbicides and herbicide-resistant crops, as well as new antibiotic and antiparasitic drugs.
Ionic Liquid Droplet as e-Microreactor (2006)

A powerful approach combining a droplet-based, open digital microfluidic lab-on-a-chip using task-specific ionic liquids as soluble supports to perform solution-phase synthesis is reported as a new tool for chemical applications. The negligible volatility of ionic liquids enables their use as stable droplet reactors on a chip surface under air. The concept was validated with different ionic liquids and with a multicomponent reaction. Indeed, we showed that different ionic liquids can be moved by electrowetting on dielectric (EWOD), and their displacement was compared with aqueous solutions. Furthermore, we showed that mixing ionic liquids droplets, each containing a different reagent, in "open" systems is an efficient way of carrying supported organic synthesis. This was applied to Grieco's tetrahydroquinolines synthesis with different reagents. Analysis of the final product was performed off-line and on-line, and the results were compared with those obtained in a conventional reaction flask. This technology opens the way to easy synthesis of minute amounts of compounds ad libitum without the use of complex, expensive, and bulky robots and allows complete automation of the process for embedded chemistry in a portable device. It offers several advantages, including simplicity of use, flexibility, and scalability, and appears to be complementary to conventional microfluidic lab-on-a-chip devices usually based on continuous-flow in microchannels.
Glucose Metabolism and Energy Homeostasis in Mouse Hearts Overexpressing Dominant Negative α2 Subunit of AMP-activated Protein Kinase (2003)

AMP-activated protein kinase (AMPK) is an energy-sensing enzyme that plays a pivotal role in regulating cellular metabolism for sustaining energy homeostasis under stress conditions. Activation of AMPK has been observed in the heart during acute and chronic stresses, but its functional role has not been completely understood because of the lack of effective activators and inhibitors of this kinase in the heart. We generated transgenic mice (TG) with cardiac-specific overexpression of a dominant negative mutant of the AMPK alpha2 catalytic subunit to clarify the functional role of this kinase in myocardial ischemia. In isolated perfused hearts subjected to a 10-min ischemia, AMPK alpha2 activity in wild type (WT) increased substantially (by 4.5-fold), whereas AMPK alpha2 activity in TG was similar to the level of WT at base line. Basal AMPK alpha1 activity was unchanged in TG and increased normally during ischemia. Ischemia stimulated a 2.5-fold increase in 2-deoxyglucose uptake over base line in WT, whereas the inactivation of AMPK alpha2 in TG significantly blunted this response. Using 31P NMR spectroscopy, we found that ATP depletion was accelerated in TG hearts during no-flow ischemia, and these hearts developed left ventricular dysfunction manifested by an early and more rapid increase in left ventricular end-diastolic pressure. The exacerbated ATP depletion could not be attributed to impaired glycolytic ATP synthesis because TG hearts consumed slightly more glycogen during this period of no-flow ischemia. Thus, AMPK alpha2 is necessary for maintaining myocardial energy homeostasis during ischemia. It is likely that the functional role of AMPK in myocardial energy metabolism resides both in energy supply and utilization.
CD40 Ligand Gene Defects Responsible for X-Linked Hyper-IgM Syndrome (1993)

The ligand for CD40 (CD40L) is a membrane glycoprotein on activated T cells that induces B cell proliferation and immunoglobulin secretion. Abnormalities in the CD40L gene were associated with an X-linked immunodeficiency in humans [hyper-IgM (immunoglobulin M) syndrome]. This disease is characterized by elevated concentrations of serum IgM and decreased amounts of all other isotypes. CD40L complementary DNAs from three of four patients with this syndrome contained distinct point mutations. Recombinant expression of two of the mutant CD40L complementary DNAs resulted in proteins incapable of binding to CD40 and unable to induce proliferation or IgE secretion from normal B cells. Activated T cells from the four affected patients failed to express wild-type CD40L, although their B cells responded normally to wild-type CD40L. Thus, these CD40L defects lead to a T cell abnormality that results in the failure of patient B cells to undergo immunoglobulin class switching.
Production of eicosapentaenoic acid from marine bacteria (1996)

A marine bacterium, judged as a new species close to Shewanella putrefaciens, was isolated from the intestinal contents of the Pacific mackerel. The isolated strain SCRC-2378 produced eicosapentaenoic acid (EPA) as the sole polyunsaturated fatty acid, which amounted to 24-40% of the total fatty acid in the cell, which corresponded to 2% of dry cell weight. Under the optimal growth conditions (pH 7.0, 20 degrees C, and grown aerobically for 12-18 h), the yield of SCRC-2738 reached 15 g of dry cells/L or 2 x 10(10) viable cells/mL. EPA existed as phospholipid and was found in the sn-2 position of phosphatidylethanolamine and phosphatidylglycerol. The 38 kbp (1,000 base pairs) genome DNA fragment was cloned from SCRC-2738 and expressed in Escherichia coli, which resulted in the production of EPA. The nucleotide sequence of the 38 kbp DNA fragment was determined. The DNA fragment contains eight open reading frames, and three of them possess homology with enzymes involved in fatty acid synthesis. Thus, it may be possible that these EPA biosynthesis genes are applied for EPA production in yeasts or higher plants, and offer a new method for EPA synthesis as new foods containing EPA.
Internet resource discovery at the University of Colorado (1993)

The author discusses aspects of Internet's resource discovery problem: how users specify searches, the difference between discovering classes of resources and locating appropriate instances, system-management problems that can be cast as global state discovery searches, issues involved with characterizing resources and with the efficient distribution of characterizing information, and social issues, especially privacy. Results of efforts to address these problems as part of the Networked Resource Discovery project at the University of Colorado are presented. These efforts use a variety of experimental approaches, including prototype systems, network measurement studies, and simulation studies.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A Protein Epitope Signature Tag (PrEST) Library Allows SILAC-based Absolute Quantification and Multiplexed Determination of Protein Copy Numbers in Cell Lines (2011)

Mass spectrometry-based proteomics increasingly relies on relative or absolute quantification. In relative quantification, stable isotope based methods often allow mixing at early stages of sample preparation, whereas for absolute quantification this has generally required recombinant expression of full length, labeled protein standards. Here we make use of a very large library of Protein Epitope Signature Tags (PrESTs) that has been developed in the course of the Human Protein Atlas Project. These PrESTs are expressed recombinantly in E. coli and they consist of a short and unique region of the protein of interest as well as purification and solubility tags. We first quantify a highly purified, stable isotope labeling of amino acids in cell culture (SILAC)-labeled version of the solubility tag and use it determine the precise amount of each PrEST by its SILAC ratios. The PrESTs are then spiked into cell lysates and the SILAC ratios of PrEST peptides to peptides from endogenous target proteins yield their cellular quantities. The procedure can readily be multiplexed, as we demonstrate by simultaneously determining the copy number of 40 proteins in HeLa cells. Among the proteins analyzed, the cytoskeletal protein vimentin was found to be most abundant with 20 million copies per cell, while the transcription factor and oncogene FOS only had 6000 copies. Direct quantification of the absolute amount of single proteins is possible via a SILAC experiment in which labeled cell lysate is mixed both with the heavy labeled solubility tag and with the corresponding PrEST. The SILAC-PrEST combination allows accurate and streamlined quantification of the absolute or relative amount of proteins of interest in a wide variety of applications.
Intelligent wheelchair based on the integration of human and environment observations (2003)

We proposed an intelligent wheelchair which can be controlled by turning one's face in the direction one would like to go. Although it can be used easily, there is a problem that unintentional movements of one's face may interfere with wheelchair motion. This paper presents our new intelligent wheelchair improved by observing its interior and exterior, i.e., the user and the environment. It effectively integrates autonomous capabilities and the interface by face direction. It uses sensor information obtained for autonomous navigation to solve the problem of control using face direction. Also, if it can understand the user's intentions from observing the face, it chooses an appropriate autonomous navigation function to reduce the user's burden of operation. When the user is off the wheelchair, they becomes a part of the exterior. In this case, it detects the user by recognizing his/her face. Then it can move according to the user's commands indicated by hand gestures.
Improved 3D reconstruction algorithm for ultrasound B-scan image with freehand tracker (2010)

EM algorithm for the reconstruction of freehand B-Scan ultrasound image was developed by Joao M. Sanches et al. The reconstruction has a parameter <i>K</i> which can be adjusted so that the results can be smoother or sharper depending to the value of <i>K</i>. In order to make the image smoother inside the organs but sharper in their boundaries simultaneously, we introduced a improved EM algorithm: EM algorithm with a diffusion filer or is referred as EMD algorithm. There was a cubic average filter inside the loop of the iteration of the EM algorithm. This average filter is replaced by a diffusion filter in the EMD algorithm. The diffusion filter offers an additional parameter <i>K<sub>d</sub></i> which can be used to adjust the reconstructed image with better optimization in both smoothness insider the human organ and sharpness in its boundary. Two above mentioned reconstruction algorithms for the freehand B-scan ultrasound image are compared through the simulation and the phantom measurements. In the simulation, strong noises are added to the ultrasound frame data. The parameters of two algorithms are optimized to get smallest errors. The errors are compared between two algorithms with optimized parameters. For the measurement with phantom, the Eigen's tracker system is used to continuously measure the coordinates of the ultrasound probe. The ultrasound B-scan frame is synchronously recorded with the probe coordinates. Zonare ultrasound machine is used to acquire the 2D frame images. The segmentation of the reconstruction results is done. The segmentation volumes of the prostate phantoms are compared. The results shows that EMD algorithm is better at reducing the noises and keeping the image edge comparing to EM algorithm. Eigen's tracker is cacaple to acquire freehand ultrasound data for a 3D image reconstruction with high quality.
Focal adhesion kinase: the first ten years (2003)

The protein tyrosine kinase focal adhesion kinase (FAK) plays a prominent role in integrin signaling. FAK activation, demonstrated by an increase in phosphorylation of Tyr397 as well as other sites in the protein, is best understood in the context of the engagement of integrins at the cell surface. Activation of FAK results in recruitment of a number of SH2-domain- and SH3-domain-containing proteins, which mediate signaling to several downstream pathways. FAK-dependent activation of these pathways has been implicated in a diverse array of cellular processes, including cell migration, growth factor signaling, cell cycle progression and cell survival.