gebhart/patrepeval huggingface dataset:
Cytokine release syndrome induced by the 145-2C11 anti-CD3 monoclonal antibody in mice: prevention by high doses of methylprednisolone (1991)

The hamster mAb 145-2C11 specific for the CD3 complex of murine T lymphocytes shares many properties with OKT3, including the induction of T cell activation. In vivo, the injection of 145-2C11 entails a variety of pathologic changes in relation to the systemic release of cytokines. We tested the effects on this cytokine release syndrome of different doses of methylprednisolone (m-PDS) given at various intervals of time before the 145-2C11 mAb. The administration of high doses of m-PDS (50 mg/kg) 2 to 3 h before the mAb resulted in an almost complete inhibition of the systemic release of TNF-alpha, IL-2, and IL-6. As far as the pathologic changes are concerned, the hypothermia, the acute renal tubular necrosis, and the fatty infiltration of the liver were completely prevented whereas the hypoglycemia was only partially attenuated. The protective effect of m-PDS on the toxicity of 145-2C11 was confirmed by the reduction of the mortality rate among galactosamine-sensitized mice. The inhibition of the release of cytokines by m-PDS did not affect the immunosuppression triggered by 145-2C11 as assessed by the CTL activity against alloantigens measured 48 h after the injection of the mAb. We conclude that the administration of very high doses of glucocorticoids 2 to 3 h before 145-2C11 prevents the release of cytokines and attenuates the acute toxicity of the mAb. Similar protocols could allow mitigation of the cytokine-release syndrome induced by the OKT3 mAb in man.
Induction of IDO-1 by Immunostimulatory DNA Limits Severity of Experimental Colitis (2010)

The chronic inflammatory bowel diseases are characterized by aberrant innate and adaptive immune responses to commensal luminal bacteria. In both human inflammatory bowel disease and in experimental models of colitis, there is an increased expression of the enzyme IDO. IDO expression has the capacity to exert antimicrobial effects and dampen adaptive immune responses. In the murine trinitrobenzene sulfonic acid model of colitis, inhibition of this enzyme leads to worsened disease severity, suggesting that IDO acts as a natural break in limiting colitis. In this investigation, we show that induction of IDO-1 by a TLR-9 agonist, immunostimulatory (ISS) DNA, critically contributes to its colitis limiting capacities. ISS DNA induces intestinal expression of IDO-1 but not the recently described paralog enzyme IDO-2. This induction occurred in both epithelial cells and in subsets of CD11c(+) and CD11b(+) cells of the lamina propria, which also increase after ISS-oligodeoxynucleotide. Signaling required for intestinal IDO-1 induction involves IFN-dependent pathways, as IDO-1 was not induced in STAT-1 knockout mice. Using both the trinitrobenzene sulfonic acid and dextran sodium sulfate models of colitis, we show the importance of IDO-1s induction in limiting colitis severity. The clinical parameters and histological correlates of colitis in these models were improved by administration of the TLR-9 agonist; however, when the function of IDO is inhibited, the colitis limiting effects of ISS-oligodeoxynucleotide were abrogated. These findings support the possibility that targeted induction of IDO-1 is an approach deserving further investigation as a therapeutic strategy for diseases of intestinal inflammation.
Corn Breeding (1988)

Corn breeding for the development of inbred lines and hybrids in various parts of the world expanded rapidly after World War II. Pedigree selection is the most widely used breeding method to develop inbred lines for use as parents of hybrids. The scheme of the pedigree selection program depends on the skills of the individual breeder, primary breeding goals, the resources available for advancing the progenies, intensity of selection, and scope of testing. Though gamete selection is not used as extensively as pedigree and backcross methods, it does have some intrinsic features that interest breeders, and, consequently, gamete selection is included in some breeding programs. After the initial sampling of the landrace cultivars, breeding methods that emphasized inbred line modification have been widely used. Although B64 and B68 were derived from the same backcross generation, the differences in breeding methods used isolated lines with differences large enough to justify release.
A Novel Scheme for Low Bitrate Unified Speech and Audio Coding – MPEG RM0 (2009)

Coding of speech signals at low bitrates, such as 16 kbps, has to rely on an efficient speech reproduction model to achieve reasonable speech quality. However, for audio signals not fitting to the model this approach generally fails. On the other hand, generic audio codecs, designed to handle any kind of audio signal, tend to show unsatisfactory results for speech signals, especially at low bitrates. To overcome this, a process was initiated by ISO/MPEG, aiming to standardize a new codec with consistent high quality for speech, music and mixed content over a broad range of bitrates. After a formal listening test evaluating several proposals MPEG has selected the best performing codec as the reference model for the standardization process. This paper describes this codec in detail and shows that the new reference model reaches the goal of consistent high quality for all signal types.
A 3D stackable Carbon Nanotube-based nonvolatile memory (NRAM) (2010)

A 4 Mbit nonvolatile memory with a Carbon Nanotube (CNT) storage element has been manufactured in a 0.25 μm CMOS process at a production fab. The CNT storage element is integrated in BEOL, requires minimal additional processing steps, and only a single additional mask. The memory can be RESET in 50 nanoseconds and SET in 500 nanoseconds. Demonstrated read access time of the development vehicle is 50 nanoseconds. Write endurance is in excess of 10,000 cycles, and robust data retention has been demonstrated. The CNT storage element is scalable to <; 5 nm, and voltage and current consumption during write operations are low. As intrinsic NRAM SET & RESET times are <; 1 nanosecond, improvements in performance are anticipated.
Synthesis and antiallergic activity of a novel series of 5-lipoxygenase inhibitors (1986)

A series of novel substituted [[(phenoxymethyl)phenyl]amino]oxoalkanoic acid esters have been synthesized. These compounds were tested in vitro for their ability to inhibit the synthesis of 5-hydroxyeicosatetraenoic acid and leukotriene (LT) B4 from rat polymorphonuclear leukocytes (PMN) and in vivo as inhibitors ovalbumin- (OA) and LTD4-induced bronchospasm in the guinea pig. Compounds 5-12 and 25 had IC50's between 1 and 5.6 microM in the rat PMN 5-lipoxygenase assay. Compounds 1, 3, and 16 inhibited OA-induced bronchoconstriction (61%, 64%, and 57%, respectively), but only 1 showed activity against LTD4-induced bronchoconstriction. When tested against LTD4-induced contraction of isolated guinea pig tracheal spiral strips, 1 was a competitive inhibitor with a pKB of 4.94.
Relationships Between Angiotensin I Converting Enzyme Gene Polymorphism, Plasma Levels, and Diabetic Retinal and Renal Complications (1994)

Insulin-dependent diabetes mellitus (IDDM), cardiovascular morbidity, and vital prognosis are linked to diabetic nephropathy, which is probably determined by renal hemodynamic abnormalities and by a genetic predisposition. Angiotensin I converting enzyme (ACE) regulates systemic and renal circulations through angiotensin II formation and kinins metabolism. Plasma and cellular ACE levels are genetically determined; an insertion/deletion polymorphism of the ACE gene is strongly associated with ACE levels, subjects homozygote for insertion (genotype II) having the lowest plasma values. We studied the relationship between the ACE gene polymorphism or plasma levels and microcirculatory disorders of IDDM through two independent studies: one involved 57 subjects with or without diabetic retinopathy, and the other compared 62 IDDM subjects with diabetic nephropathy to 62 diabetic control subjects with the same characteristics (including retinopathy severity) but with normal kidney function. The ACE genotype distribution was not different in diabetic subjects with or without retinopathy and in a healthy population. Conversely, an imbalance of ACE genotype distribution, with a low proportion of II subjects, was observed in IDDM subjects with diabetic nephropathy compared with their control subjects (P = 0.006). Plasma ACE levels were mildly elevated in all diabetic groups, independently of retinopathy, but they were higher in subjects with nephropathy than in those without nephropathy (P = 0.0022). The II genotype of ACE gene is a marker for reduced risk for diabetic nephropathy.
mRNA‐Display‐Based Selections for Proteins with Desired Functions: A Protease‐Substrate Case Study (2008)

mRNA-display is an amplification-based, iterative rounds of in vitro protein selection technique that circumvents a number of difficulties associated with yeast two-hybrid and phage display. Because of the covalent linkage between the genotype and the phenotype, mRNA-display provides a powerful means for reading and amplifying a peptide or protein sequence after it has been selected from a library with a diversity in the range of 10(12)-10(13). In this paper, we briefly review the recent progress in using mRNA-display to identify affinity reagents, binding partners, and enzyme substrates from synthetic peptide or natural proteome libraries. To facilitate the use of mRNA-display in research laboratories without previous experience, we provide a detailed analysis of the critical steps of an mRNA-display-based selection in a case study for the identification of the natural substrates of caspases, including the generation of an mRNA-displayed proteome library, removal of abundant sequences, and selection of proteins with desired functions. The advantages and technical limitations of mRNA-display as a general peptide or protein selection tool are also addressed.
Lighting-Up the Dynamics of Telomerization and DNA Replication by CdSe−ZnS Quantum Dots (2003)

CdSe-ZnS core-shell quantum dots (QDs) act as photochemical centers for lighting-up the dynamics of telomerization or DNA replication.
Watershed segmentation of high resolution magnetic resonance images of articular cartilage of the knee (2002)

High-resolution in-vivo Magnetic Resonance Imaging (MRI) can be used effectively to determine variation in cartilage morphometry - a crucial parameter for assessment of osteoarthritis. Segmentation of cartilage from surrounding tissues is a necessary preliminary step to the quantitation process. In this in-vivo study we implement the immersion based watershed algorithm to develop a novel and reliable cartilage segmentation technique. The protocol has been successfully applied to determine morphometric differences among normal, mild and severe osteoarthritic patient populations.
Enantioselective Cyclopropanation with TADDOL‐Derived Phosphate Ligands (2006)

Abstract The synthesis of new chiral TADDOL‐derived phosphate ligands is described. The ligands were efficiently synthesized on a multi‐gram scale in three steps starting from the readily available corresponding TADDOL and were fully characterized. An X‐ray structure was obtained and compared to known BINOL‐phosphates. Their use in the asymmetric Simmons–Smith cyclopropanation of both functionalized and unfunctionalized olefins gave the desired cyclopropanes in good yields and good to moderate enantioselectivities.
Primary structural analysis of the polypeptide portion of human C5a anaphylatoxin. Polypeptide sequence determination and assignment of the oligosaccharide attachment site in C5a. (1978)

The C5a molecule is one of two spasmogenic fragments (i.e. C3a and C5a) released from serum components C3 and C5 during complement activation. These fragments are called anaphylatoxins because their ability to stimulate mast cell histamine release, smooth muscle contraction, and increased vascular permeability may lead to a fatal reaction resembling anaphylactic shock in experimental animals. In addition, the C5a molecule, which is a glycoprotein, is perhaps the most potent of all humoral chemoattractants for polymorphonuclear leukocytes. Most of the structural analyses in this study were performed on the desArg 74 form of human C5a (C5adesArg). C5adesArg represents a natural form of C5a that is recovered from activated serum when no inhibitors are added to block the action of serum carboxypeptidase. The complete primary structure of the human C5a polypeptide portion is reported here. A partial characterization of intact human C5a has been previously reported (Fernandez, H. N., and Hugli, T. E. (1976) J. Immunol. 117, 1688--1694). The polypeptide portion of C5a contains 74 amino acids, accounting for a molecular weight of 8,200 while the carbohydrate portion accounts for approximately 3,000. The carbohydrate portion of C5a exists as a single complex oligosaccharide unit attached to an asparagine at position 64. An unusual feature of the C5a molecule is its large content of half-cystine, which accounts for more than 9% of its total residues. Two repeating Cys sequences occur in the linear structure and 6 of the 7 half-cystines in C5a are located at nearly identical positions to those in the human C3a molecule. In fact, sequence similarities between C3a and C5a indicate their common genetic ancestry. The role of C5a and C5adesArg as chemotactic factors prompted comparisons of their structural features with those of the chemotactically active formyl-Met peptides (Schiffman E., Corcoran, B. A., and Wahl, S. M. (1975) Proc. Natl. Acad. Sci. U.S.A. 72, 1059--1062). Removal of the COOH-terminal arginyl residue from C5a reduces chemotactic activity; therefore, the terminal portion of this molecule appears to play an active role in stimulating leukocyte migration. Hence the COOH-terminal sequence of C5a was examined for structural similarities to that of the formyl-Met peptides. Since methionine assumes a special functional importance in the formyl-Met peptides, attention is focused on the single methionyl residue in C5a. This methionyl residue, located near the COOH terminus of the molecule, may play an active role in the functional expression of C5a as a chemotactic factor. Although human and pig C3a show a close structural and functional relationship to C5a they lack the ability to excite leukotaxis, and this difference may correlate with the absence of a methionyl residue near the COOH terminus of C3a.
Synthesis and characterization of biodegradable hydrophobic-hydrophilic hydrogel networks with a controlled swelling property (2000)

A biodegradable polymer network hydrogel system with both hydrophilic and hydrophobic components was synthesized and characterized. The hydrophilic and hydrophobic components were dextran and poly(D,L)lactic acid (PDLLA), respectively. These two polymers were chemically modified for incorporating unsaturated groups for subsequent UV crosslinking to generate a hydrogel with a three-dimensional network structure. The effects of the reaction conditions on the synthesis of a dextran derivative of allyl isocyanate (dex-AI) were studied. All newly synthesized materials were characterized by Fourier transform infrared and NMR. The swelling property of the hydrogels was studied in buffer solutions of different pHs. The results of this study showed that a wide-range swelling property was obtained by changes in the dex-AI/PDLLA composition ratio, the type and degree of unsaturated groups incorporated into dextran, and the UV photocrosslinking time. The solvent extraction effect on the swelling property of the hydrogels was also studied. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 2392–2404, 2000
Removal of inhibitor(s) of the polymerase chain reaction from formalin fixed, paraffin wax embedded tissues. (1991)

A problem associated with use of the polymerase chain reaction to amplify specific DNA fragments from formalin fixed, paraffin wax embedded tissues is the not infrequent failure of amplification. One possible reason for this could be the presence of inhibitor(s), which interfere with the activity of the reaction. It has been shown that such inhibitor(s) exist when amplifying the human beta globin gene (which exists in human genomic DNA as a single copy gene) from routine clinical samples. A variety of methods to remove such inhibitor(s) were investigated. The results indicate that inhibitor(s) are removed by proteinase K digestion, followed by purification with phenol/chloroform, and centrifugation through a Centricon-30 membrane (30,000 molecular weight cut off). Other factors, including the length and concentration of the DNA sequence to be amplified, can also affect amplification.
Giant Mitochondria in Human Muscle With Inclusions (1967)

RECENTLY, two reports have been published on myopathies characterized primarily by abnormalities of mitochondria. In the first, Luft et al<sup>1</sup>described a severely hypermetabolic patient with loosely coupled oxidative phosphorylation in mitochondria and, in the second, Shy et al<sup>2</sup>described pleoconial and megaconial conditions, both related to aberrent mitochondria. In Luft's patient as well as in the one with megaconial myopathy, the mitochondria in the muscle fibers were unusually large and contained striking paracrystalline inclusions. This paper reports on four patients with similar mitochondrial changes and discusses the significance of this lesion. <h3>Report of Cases</h3> In the four patients in our study, a diagnosis of either dermatomyositis, polymyositis, nephritis, or spinal muscular atrophy had been made. Each diagnosis was based on physical examination, electromyography, biopsy findings, and laboratory data. Brief summaries are given below. <h3>Case 1.—</h3> This 48-year-old man was found at 43 to have grossly elevated levels
Rational design of a chimeric endonuclease targeted to NotI recognition site (2007)

A cleavage-deficient variant of NotI restriction endonuclease (GCGGCCGC) was isolated by random mutagenesis of the notIR gene. The NotI variant D160N was shown to bind DNA and protect plasmid DNA from EagI (CGGCCG) and NotI digestions. The EDTA-resistant BmrI restriction endonuclease cleaves DNA sequence ACTGGG N5/N4. The N-terminal cleavage domain of BmrI (residues 1-198) with non-specific nuclease activity was fused to the NotI variant D160N with a short linker. The engineered chimeric endonuclease (CH-endonuclease) recognizes NotI sites specifically in the presence of high salt (100-150 mM NaCl) and divalent cations Mg++ or Ca++. In contrast to wild-type NotI, which cuts within its recognition sequence, BmrI198-NotI (D160N) cleaves DNA outside of NotI sites, resulting in deletion of the NotI site and the adjacent sequences. The fusion of the BmrI cleavage domain to cleavage-deficient variants of Type II restriction enzymes to generate novel cleavage sites will provide useful tools for DNA manipulation.
A Three-Dimensional Time-of-Flight CMOS Image Sensor With Pinned-Photodiode Pixel Structure (2010)

A pixel architecture for providing not only normal 2-D images but also depth information by using a conventional pinned photodiode is presented. This pixel architecture allows the sensor to generate a real-time 3-D image of an arbitrary object. The operation of the pixel is based on the time-of-flight principle detecting the time delay between the emitted and reflected infrared light pulses in a depth image mode. The pixel contains five transistors. Compared to the conventional 4-T CMOS image sensor, the new pixel includes an extra optimized transfer gate for high-speed charge transfer. A fill factor of more than 60% is achieved with a 12 × 12 μm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> size for increasing the sensitivity. A fabricated prototype sensor successfully captures 64 × 16 depth images between 1 and 4 m at a 5-MHz modulation frequency. The depth inaccuracy is measured under 2% at 1 m and 4% at 4 m and is verified by noise analysis.
Identification of Colonic Dysplasia and Neoplasia by Diffuse Reflectance Spectroscopy and Pattern Recognition Techniques (1998)

Diffuse reflectance spectroscopy of colonic tissue was employed to determine whether the spectra can be used to distinguish between neoplastic and non-neoplastic tissue in vivo. A total of 224 spectra were obtained in the wavelength range of 350–800 nm from 107 non-neoplastic tissue samples (84 normal mucosa, 23 hyperplastic polyps) and 53 neoplastic tissue samples (44 adenomatous polyps, 9 adenocarcinomas). Pattern recognition algorithms including multiple linear regression (MLR), linear discriminant analysis (LDA), and backpropagating neural network (BNN) were used to distinguish between the two tissue classes. The spectra were randomly separated into training and prediction sets for data analyses. The mean predictive accuracies of distinguishing neoplastic tissue from non-neoplastic tissue with MLR, LDA, and BNN were 85, 82, and 85%, respectively. In a similar fashion, the more clinically relevant problem of distinguishing adenomatous polyps from hyperplastic polyps was assessed. The mean predictive accuracies of distinguishing adenomatous polyps from hyperplastic polyps with MLR, LDA, and BNN were 85, 81, and 82%, respectively. The major spectral differences between tissues were attributed to changes in blood volume, oxygen saturation of hemoglobin, mean vessel depth within tissue, and tissue scattering.
Trace-based just-in-time type specialization for dynamic languages (2009)

Dynamic languages such as JavaScript are more difficult to compile than statically typed ones. Since no concrete type information is available, traditional compilers need to emit generic code that can handle all possible type combinations at runtime. We present an alternative compilation technique for dynamically-typed languages that identifies frequently executed loop traces at run-time and then generates machine code on the fly that is specialized for the actual dynamic types occurring on each path through the loop. Our method provides cheap inter-procedural type specialization, and an elegant and efficient way of incrementally compiling lazily discovered alternative paths through nested loops. We have implemented a dynamic compiler for JavaScript based on our technique and we have measured speedups of 10x and more for certain benchmark programs.
Optimized Chemical Proteomics Assay for Kinase Inhibitor Profiling (2015)

Solid supported probes have proven to be an efficient tool for chemical proteomics. The kinobeads technology features kinase inhibitors covalently attached to Sepharose for affinity enrichment of kinomes from cell or tissue lysates. This technology, combined with quantitative mass spectrometry, is of particular interest for the profiling of kinase inhibitors. It often leads to the identification of new targets for medicinal chemistry campaigns where it allows a two-in-one binding and selectivity assay. The assay can also uncover resistance mechanisms and molecular sources of toxicity. Here we report on the optimization of the kinobead assay resulting in the combination of five chemical probes and four cell lines to cover half the human kinome in a single assay (∼ 260 kinases). We show the utility and large-scale applicability of the new version of kinobeads by reprofiling the small molecule kinase inhibitors Alvocidib, Crizotinib, Dasatinib, Fasudil, Hydroxyfasudil, Nilotinib, Ibrutinib, Imatinib, and Sunitinib.