gebhart/patrepeval huggingface dataset:
Generation of tumoricidal cytotoxic T lymphocytes from healthy donors afterin vitro stimulation with a replication-incompetent vaccinia virus encoding MART-1/Melan-A 27-35 epitope (1997)

Active specific immunotherapy targeting tumor-associated antigens (TAA) requires reagents of high immunogenicity and safety. To address this issue, we constructed a recombinant vaccinia virus carrying a minigene insert encoding the HLA-A2.1-restricted MART-1/Melan-A27-35 melanoma TAA (rVV-M). To facilitate the entry of the antigenic epitope into the endoplasmic reticulum, a sequence coding for adenovirus E3/19K leader peptide was added. This rVV-M was made replication-incompetent by treatment with psoralen and UV light. Infection with rVV-M rendered HLA-A2.1 EBV-transformed lymphoblastoid cells sensitive to the cytotoxic effects of HLA-class-1-restricted, MART-1/Melan-A27-35-specific cytotoxic T lymphocytes (CTL). The capacity of rVV-M to generate HLA-A2.1-restricted MART-1/Melan A-specific CTL was demonstrated from tumor-infiltrating-lymphocyte (TIL) cultures and from healthy donors' peripheral-blood mononuclear cells (PBMC). MART-1/Melan-A27-35-specific CTL were generated from TIL after 2 weekly stimulation courses. Infection with rVV-M elicited a higher CTL response than addition of exogenous peptide, whereas, when a similar protocol was used to stimulate PBMC of healthy donors, significant and specific cytotoxic activity could be observed only upon rVV-M infection but not upon exogenous peptide addition. All CTL generated upon rVV-M stimulation were also able to efficiently kill melanoma cell lines expressing both MART-1/Melan-A and HLA-A2.1. In addition, TNF-alpha production could be induced in rVV-M-stimulated CTL upon co-culture with COS-7 cells transiently transfected with MART-1/Melan-A and HLA-A2.1 genes. This safe and highly immunogenic reagent could be of use in TAA-targeted clinical immunotherapy.
Plagiarism in natural and programming languages: an overview of current tools and technologies (2000)

This report discusses in detail methods of plagiarism and its detection in both natural and programming&#13;\nlanguages. The increase of material now available in electronic form and improved access to this via the&#13;\nInternet is allowing, with greater ease than ever before, plagiarism that is either intentional or unintentional.&#13;\nDue to increased availability of On-line material, people checking for plagiarism are finding the task&#13;\nincreasingly harder. Techniques for detecting both plagiarism in natural and programming languages are&#13;\ndiscussed in this report to provide the reader with a comprehensive introduction to this area. Also provided&#13;\nare examples of common techniques used in natural language plagiarism.
Enhancing antisense efficacy with multimers and multi-targeting oligonucleotides (MTOs) using cleavable linkers (2015)

The in vivo potency of antisense oligonucleotides (ASO) has been significantly increased by reducing their length to 8-15 nucleotides and by the incorporation of high affinity RNA binders such as 2', 4'-bridged nucleic acids (also known as locked nucleic acid or LNA, and 2',4'-constrained ethyl [cET]). We now report the development of a novel ASO design in which such short ASO monomers to one or more targets are co-synthesized as homo- or heterodimers or multimers via phosphodiester linkers that are stable in plasma, but cleaved inside cells, releasing the active ASO monomers. Compared to current ASOs, these multimers and multi-targeting oligonucleotides (MTOs) provide increased plasma protein binding and biodistribution to liver, and increased in vivo efficacy against single or multiple targets with a single construct. In vivo, MTOs synthesized in both RNase H-activating and steric-blocking oligonucleotide designs provide ≈4-5-fold increased potency and ≈2-fold increased efficacy, suggesting broad therapeutic applications.
Coadministration of a Tumor-Penetrating Peptide Enhances the Efficacy of Cancer Drugs (2010)

Poor penetration of anticancer drugs into tumors can be an important factor limiting their efficacy. We studied mouse tumor models to show that a previously characterized tumor-penetrating peptide, iRGD, increased vascular and tissue permeability in a tumor-specific and neuropilin-1-dependent manner, allowing coadministered drugs to penetrate into extravascular tumor tissue. Importantly, this effect did not require the drugs to be chemically conjugated to the peptide. Systemic injection with iRGD improved the therapeutic index of drugs of various compositions, including a small molecule (doxorubicin), nanoparticles (nab-paclitaxel and doxorubicin liposomes), and a monoclonal antibody (trastuzumab). Thus, coadministration of iRGD may be a valuable way to enhance the efficacy of anticancer drugs while reducing their side effects, a primary goal of cancer therapy research.
Sequence- and strand-specific cleavage in oligodeoxyribonucleotides and DNA containing 3'-thiothymidine (1992)

Oligonucleotides containing a 3'-thiothymidine residue (T3's) at the cleavage site for the EcoRV restriction endonuclease (between the central T and A residues of the sequence GATATC) have been prepared on an automated DNA synthesizer using 5'-O-monomethoxytritylthymidine 3'-S-(2-cyanoethyl N,N-di-isopropylphosphorothioamidite). The self-complementary sequence GACGAT3'sATCGTC was completely resistant to cleavage by EcoRV, while the heteroduplex composed of 5'-TCTGAT3'sATCCTC and 5'-GAGGATATCAGA (duplex 4) was cleaved only in the unmodified strand (5'-GAGGATATCAGA). In contrast, strands containing a 3'-S-phosphorothiolate linkage could be chemically cleaved specifically at this site with Ag+. A T3's residue has also been incorporated in the (-) strand of double-stranded closed circular (RF IV) M13mp18 DNA at the cleavage site of a unique EcoRV recognition sequence by using 5'-pCGAGCTCGAT3'sATCGTAAT as a primer for polymerization on the template (+) strand of M13mp18 DNA. On treatment of this substrate with EcoRV, only one strand was cleaved to produce the RF II or nicked DNA. Taken in conjunction with the cleavage studies on the oligonucleotides, this result demonstrates that the 3'-S-phosphorothiolate linkage is resistant to scission by EcoRV. Additionally, the phosphorothiolate-containing strand of the M13mp18 DNA could be cleaved specifically at the point of modification using iodine in aqueous pyridine. The combination of enzymatic and chemical techniques provides, for the first time, a demonstrated method for the sequence-specific cleavage of either the (+) or (-) strand.
A NEW MODEL OF HETEROTOPIC RAT HEART TRANSPLANTATION WITH APPLICATION FOR IN VIVO 31P NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY (1985)

The Department of Surgery, The Joseph Stokes, Jr. Research Institute, The Children's Hospital of Philadelphia, The Division of Plastic Surgery, The Harrison Department of Surgical Research, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
Spatial Data Management System (1978)

Abstract : The Architecture Machine Group has been developing an experimental information system which exploits the user's sense of spatiality to organize and access data. Conceptual roots lie in the observation that one can readily locate and retrieve some book from one's bookshelf, or the appointment calendar from one's desktop, on the basis of where it is, or where one put it, in a well- learned, familiar space. A prototype system has been developed that uses wall- sized, full color digital television with synchronized stereo sound to create a virtual spatial world, 'Dataland,' over which the user helicopters via joystick control. Items of interest seen through a graphics 'window' can be zoomed in upon and interactively perused. Data types include: maps, text, book-like items, letters, photographs, slides, movies, sound and television. Results thus far suggest that the user quickly learns (on the order of minutes) to navigate about such a space, and readily adopts a spatial way of regarding and discussing data. The approach of managing data spatially is offfered not as an alternative in competition with managing data on a symbolic or name basis, but as a complement thereto. This manner of dealing with data should have special appeal for that class of user for whom directness and immediacy are essential qualities for interaction.
2.4-Å Crystal Structure of the Asymmetric Platinum Complex {Pt(ammine)(cyclohexylamine)}2+ Bound to a Dodecamer DNA Duplex (2002)

cis-trans-cis-Ammine(cyclohexylamine)diacetatodichloroplatinum(IV) is an oral analog of the platinum anti-cancer drug cisplatin that is currently in phase III clinical trials. Its active form, [Pt(ammine)(cyclohexylamine)]2+, binds to DNA similarly to cisplatin, forming intra- and interstrand cross-links between adjacent purine bases. Since [Pt(ammine)(cyclohexylamine)]2+ contains two different ligands, it can form two isomeric 1,2-d(GpG) intrastrand cross-links. Here we report the 2.4-A resolution x-ray crystal structure of the major adduct between [Pt(ammine)(cyclohexylamine)]2+ and a DNA dodecamer, using the same sequence as previously reported for crystal structures of cisplatin-DNA (Takahara, P. M., Rosenzweig, A. C., Frederick, C. A., and Lippard, S. J. (1995) Nature 377, 649-652) and oxaliplatin-DNA (Spingler, B., Whittington, D. A., and Lippard, S. J. (2001) Inorg. Chem. 40, 5596-5602). Both duplexes in the asymmetric unit contain 1,2-intrastrand cross-links in which the cyclohexylamine ligand is directed toward the 3'-end of the platinated strand. The chair conformation of the cyclohexyl group is clearly resolved. Platination distorts the duplex, resulting in a global bend angle of about 38(o) and a dihedral angle between platinated guanine bases of approximately 31(o). Both end-to-end and end-to-groove packing interactions occur in the crystal lattice, the latter positioned in the minor groove across from the site of the platinum cross-link. A high degree of homology observed between this structure and the previously reported platinum-DNA structures suggests that these platinum complexes distort the DNA duplex in a very similar manner. These results suggest that differences in activity between these drugs are unlikely to result from gross conformational distortions in DNA structure following platinum intrastrand cross-link formation.
A survey of named entity recognition and classification (2007)

This survey covers fifteen years of research in the Named Entity Recognition and Classification (NERC) field, from 1991 to 2006. We report observations about languages, named entity types, domains and textual genres studied in the literature. From the start, NERC systems have been developed using hand-made rules, but now machine learning techniques are widely used. These techniques are surveyed along with other critical aspects of NERC such as features and evaluation methods. Features are word-level, dictionary-level and corpus-level representations of words in a document. Evaluation techniques, ranging from intuitive exact match to very complex matching techniques with adjustable cost of errors, are an indisputable key to progress.
Comparative Study of Two Chitin-Active and Two Cellulose-Active AA10-Type Lytic Polysaccharide Monooxygenases (2014)

Lytic polysaccharide monooxygenases (LPMOs), found in family 9 (previously GH61), family 10 (previously CBM33), and the newly discovered family 11 of auxiliary activities (AA) in the carbohydrate-active enzyme classification system, are copper-dependent enzymes that oxidize sp(3)-carbons in recalcitrant polysaccharides such as chitin and cellulose in the presence of an external electron donor. In this study, we describe the activity of two AA10-type LPMOs whose activities have not been described before and we compare in total four different AA10-type LPMOs with the aim of finding possible correlations between their substrate specificities, sequences, and EPR signals. EPR spectra indicate that the electronic environment of the copper varies within the AA10 family even though amino acids directly interacting with the copper atom are identical in all four enzymes. This variation seems to be correlated to substrate specificity and is likely caused by sequence variation in areas that affect substrate binding geometry and/or by variation in a cluster of conserved aromatic residues likely involved in electron transfer. Interestingly, EPR signals for cellulose-active AA10 enzymes were similar to those previously observed for cellulose-active AA9 enzymes. Mutation of the conserved phenylalanine positioned in close proximity to the copper center in AA10-type LPMOs to Tyr (the corresponding residue in most AA9-type LPMOs) or Ala, led to complete or partial inactivation, respectively, while in both cases the ability to bind copper was maintained. Moreover, substrate binding affinity and degradation ability seemed hardly correlated, further emphasizing the crucial role of the active site configuration in determining LPMO functionality.
A novel metabotropic glutamate receptor expressed in the retina and olfactory bulb (1995)

A novel metabotropic glutamate receptor, mGluR8, was identified by screening a mouse retina cDNA library. This receptor is most related to mGluR4, mGluR7, and mGluR6 (74%, 74%, and 70% identical amino acid residues, respectively). Similar to these receptors, stimulation by L-glutamate or L-2-amino-4-phosphonobutyrate (L-APB) of Chinese hamster ovary (CHO) cells stably transfected with mGluR8 result in the inhibition of forskolin-stimulated adenylyl cyclase. In situ hybridization studies revealed a strong expression of the mGluR8 gene in the olfactory bulb, accessory olfactory bulb, and mammillary body. A weaker expression was found in the retina, and in scattered cells in the cortex and hindbrain. During development, the distribution of mGluR8 expression was more widespread. These results extend the diversity of metabotropic glutamate receptors in the CNS. Because at least two APB receptors are expressed in the retina, the use of this drug to block selectively the ON pathway needs to be reconsidered. The pharmacology and expression of mGluR8 in mitral/tufted cells suggest it could be a presynaptic receptor modulating glutamate release by these cells at their axon terminals in the entorhinal cortex.
Prospective Identification of Tumorigenic Prostate Cancer Stem Cells (2005)

Existing therapies for prostate cancer eradicates the bulk of cells within a tumor. However, most patients go on to develop androgen-independent disease that remains incurable by current treatment strategies. There is now increasing evidence in some malignancies that the tumor cells are organized as a hierarchy originating from rare stem cells that are responsible for maintaining the tumor. We report here the identification and characterization of a cancer stem cell population from human prostate tumors, which possess a significant capacity for self-renewal. These cells are also able to regenerate the phenotypically mixed populations of nonclonogenic cells, which express differentiated cell products, such as androgen receptor and prostatic acid phosphatase. The cancer stem cells have a CD44+/alpha2beta1hi/CD133+ phenotype, and we have exploited these markers to isolate cells from a series of prostate tumors with differing Gleason grade and metastatic states. Approximately 0.1% of cells in any tumor expressed this phenotype, and there was no correlation between the number of CD44+/alpha2beta1hi/CD133+ cells and tumor grade. The identification of a prostate cancer stem cell provides a powerful tool to investigate the tumorigenic process and to develop therapies targeted to the stem cell.
The emerging importance of group II PAKs (2010)

The Rho-family GTPases Rho Rac and Cdc42 regulate many intracellular processes through their interaction with downstream effector proteins. The PAKs (p21-activated kinases) are a family of effector proteins for Rac and Cdc42. PAKs are important regulators of actin cytoskeletal dynamics, neurite outgrowth, cell survival, hormone signalling and gene transcription. There are six mammalian PAKs that can be divided into two groups: group I PAKs (PAK1-3) and group II PAKs (PAK4-6). Although the two PAK groups are architecturally similar, there are differences in their mode of regulation, suggesting that their cellular functions are likely to be different. Whereas much is known about group I PAKs, less is known about the more recently discovered PAK4, PAK5 and PAK6. This review will focus on the latest structural and functional results relating to the group II PAKs and discuss the emerging importance of group II PAKs in disease progression.
Adipose tissue engineering with cells in engineered matrices (2008)

Tissue engineering has shown promise for the development of constructs to facilitate large volume soft tissue augmentation in reconstructive and cosmetic plastic surgery. This article reviews the key progress to date in the field of adipose tissue engineering. In order to effectively design a soft tissue substitute, it is critical to understand the native tissue environment and function. As such, the basic physiology of adipose tissue is described and the process of adipogenesis is discussed. In this article, we have focused on tissue engineering using a cell-seeded scaffold approach, where engineered extracellular matrix substitutes are seeded with exogenous cells that may contribute to the regenerative response. The strengths and limitations of each of the possible cell sources for adipose tissue engineering, including adipose-derived stem cells, are detailed. We briefly highlight some of the results from the major studies to date, involving a range of synthetic and naturally derived scaffolds. While these studies have shown that adipose tissue regeneration is possible, more research is required to develop optimized constructs that will facilitate safe, predictable and long-term augmentation in clinical applications.
Anti-Cripto Mab inhibit tumour growth and overcome MDR in a human leukaemia MDR cell line by inhibition of Akt and activation of JNK/SAPK and bad death pathways (2007)

Doxorubicin (DOX) selection of CCRF-CEM leukaemia cell line resulted in multidrug resistance (MDR) CEM/A7R cell line, which overexpresses MDR, 1 coded P-glycoprotein (Pgp). Here, we report for the first time that oncoprotein Cripto, a founding member of epidermal growth factor-Cripto-FRL, 1-Criptic family is overexpressed in the CEM/A7R cells, and anti-Cripto monoclonal antibodies (Mab) inhibited CEM/A7R cell growth both in vitro and in an established xenograft tumour in severe combined immunodeficiency mice. Cripto Mab synergistically enhanced sensitivity of the MDR cells to Pgp substrates epirubicin (EPI), daunorubicin (DAU) and non-Pgp substrates nucleoside analogue cytosine arabinoside (AraC). In particular, the combination of anti-Cripto Mab at less than 50% of inhibition concentrations with noncytotoxic concentrations of EPI or DAU inhibited more than 90% of CEM/A7R cell growth. Cripto Mab slightly inhibited Pgp expression, and had little effect on Pgp function, indicating that a mechanism independent of Pgp was involved in overcoming MDR. We demonstrated that anti-Cripto Mab-induced CEM/A7R cell apoptosis, which was associated with an enhanced activity of the c-Jun N-terminal kinase/stress-activated protein kinase and inhibition of Akt phosphorylation, resulting in an activation of mitochondrial apoptosis pathway as evidenced by dephosphorylation of Bad at Ser136, Bcl-2 at Ser70 and a cleaved caspase-9.
From Hollow Nanosphere to Hollow Microsphere: Mild Buffer Provides Easy Access to Tunable Silica Structure (2008)

A facile synthesis method for producing silica hollow spheres from nano- to microsize level is realized by adjusting the hydrolysis and condensation kinetics of silane precursors in a mild buffer solution (NaH2PO4−Na2HPO4, pH ≈ 7.0) in the presence of F127 (EO106PO70EO106) surfactant. Characterization using transmission electron microscopy, field-emission scanning electron microscopy, and nitrogen sorption techniques reveals that the silica hollow nanospheres with outer diameter of about 12 nm can be obtained with tetramethoxysilane as silane precursor. Silica hollow nanospheres (∼20 nm) can also be prepared using tetraethoxysilane (TEOS) as silane precursor with the addition of hydrolysis and condensation catalyst NH4F. Using TEOS as the silane precursor without F−, the formation of silica hollow microspheres (0.5∼8 μm) was observed. Time-resolved in situ UV-Raman results show that TEOS does not hydrolyze at room temperature, and the hydrolysis of TEOS occurs immediately at room temperature when NH4F was added to the buffer solution. The fast hydrolysis and condensation rates of silane precursor favor the formation of hollow nanospheres through the condensation of silicate around a single micelle of F127 in NaH2PO4−Na2HPO4 buffer solution. The construction of hollow microspheres is attributed to the formation of O/W emulsion by the hydrophobic TEOS with the aid of F127 surfactant due to the existence of unhydrolyzed TEOS at room temperature under current synthetic conditions.
Wi-Fi (802.11b) and Bluetooth: enabling coexistence (2001)

This article provides an introduction to issues of coexistence between Bluetooth and Wi-Fi/sup TM/ (IEEE 802.11b), with particular attention to scenarios requiring simultaneous operation, or Sim-OP/sup TM/, of both systems in very close proximity. The article explains basic interference mechanisms and quantifies their impact through both actual measurements and simulation. We have developed a detailed simulator that fully models behavior of the physical layer (PHY) and media access control (MAC) of both Bluetooth and 802.11b; it is used to expand the analysis and project the mutual impact of collocated Bluetooth and 802.11b systems across a number of geometries, system parameter settings, and design choices, complementing efforts within the IEEE 802.15.2 Task Group, which are also discussed. The article concludes with a discussion of techniques with the potential to greatly improve the performance of collocated Bluetooth and Wi-Fi systems. A key result of this investigation is that while performance of both systems can degrade when they are collocated, a number of techniques can be employed to virtually eliminate the problems.
Nonvolatile memory technologies with emphasis on Flash a comprehensive guide to understanding and using Flash memory devices (2008)

Presented here is an all-inclusive treatment of Flash technology, including Flash memory chips, Flash embedded in logic, binary cell Flash, and multilevel cell Flash. The book begins with a tutorial of elementary concepts to orient readers who are less familiar with the subject. Next, it covers all aspects and variations of Flash technology at a mature engineering level: basic device structures, principles of operation, related process technologies, circuit design, overall design tradeoffs, device testing, reliability, and applications.