gebhart/patrepeval huggingface dataset:
The proteolytic fragments generated by vertebrate proteasomes: structural relationships to major histocompatibility complex class I binding peptides. (1996)

Proteasomes are involved in the proteolytic generation of major histocompatibility complex (MHC) class I epitopes but their exact role has not been elucidated. We used highly purified murine 20S proteasomes for digestion of synthetic 22-mer and 41/44-mer ovalbumin partial sequences encompassing either an immunodominant or a marginally immunogenic epitope. At various times, digests were analyzed by pool sequencing and by semiquantitative electrospray ionization mass spectrometry. Most dual cleavage fragments derived from 22-mer peptides were 7-10 amino acids long, with octa- and nonamers predominating. Digestion of 41/44-mer peptides initially revealed major cleavage sites spaced by two size ranges, 8 or 9 amino acids and 14 or 15 amino acids, followed by further degradation of the latter as well as of larger single cleavage fragments. The final size distribution was slightly broader than that of fragments derived from 22-mer peptides. The majority of peptide bonds were cleaved, albeit with vastly different efficiencies. This resulted in multiple overlapping proteolytic fragments including a limited number of abundant peptides. The immunodominant epitope was generated abundantly whereas only small amounts of the marginally immunogenic epitope were detected. The frequency distributions of amino acids flanking proteasomal cleavage sites are correlated to that reported for corresponding positions of MHC class I binding peptides. The results suggest that proteasomal degradation products may include fragments with structural properties similar to MHC class I binding peptides. Proteasomes may thus be involved in the final stages of proteolytic epitope generation, often without the need for downstream proteolytic events.
Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma (2011)

Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are the two most common non-Hodgkin lymphomas (NHLs). Here we sequenced tumour and matched normal DNA from 13 DLBCL cases and one FL case to identify genes with mutations in B-cell NHL. We analysed RNA-seq data from these and another 113 NHLs to identify genes with candidate mutations, and then re-sequenced tumour and matched normal DNA from these cases to confirm 109 genes with multiple somatic mutations. Genes with roles in histone modification were frequent targets of somatic mutation. For example, 32% of DLBCL and 89% of FL cases had somatic mutations in MLL2, which encodes a histone methyltransferase, and 11.4% and 13.4% of DLBCL and FL cases, respectively, had mutations in MEF2B, a calcium-regulated gene that cooperates with CREBBP and EP300 in acetylating histones. Our analysis suggests a previously unappreciated disruption of chromatin biology in lymphomagenesis.
Polyclonality and Multispecificity of the CTL Response to a Single Viral Epitope (1998)

The molecular anatomy of an immunodominant, Ld restricted CTL epitope located between residues 28-39 in hepatitis B surface Ag was defined to explore the immunologic constraints on mutational escape from the CTL response during a viral infection. Using a panel of hepatitis B surface Ag residue 28-39-specific CTL clones, the response to this epitope was found to be extremely diverse at the level of TCR fine specificity and beta-chain usage. Although each clone recognized shared as well as unique residues within the epitope as TCR contact sites, even the shared residues were recognized differently by different TCRs. Despite these differences, all clones were comparably cytolytic following Ag stimulation and produced similar amounts of antiviral cytokines previously shown to inhibit HBV replication. These results demonstrate that the CTL response to individual viral epitopes can be markedly polyclonal and multispecific, such that mutational inactivation of a single TCR contact site will not usually lead to viral escape from all CTL clones of the same epitope specificity. Given these constraints and the fact that the CTL response is usually directed against several different epitopes during most viral infections, mutational inactivation of a single epitope is not likely to be sufficient to cause viral persistence.
Signature Detection and Matching for Document Image Retrieval (2008)

As one of the most pervasive methods of individual identification and document authentication, signatures present convincing evidence and provide an important form of indexing for effective document image processing and retrieval in a broad range of applications. However, detection and segmentation of free-form objects such as signatures from clustered background is currently an open document analysis problem. In this paper, we focus on two fundamental problems in signature-based document image retrieval. First, we propose a novel multiscale approach to jointly detecting and segmenting signatures from document images. Rather than focusing on local features that typically have large variations, our approach captures the structural saliency using a signature production model and computes the dynamic curvature of 2D contour fragments over multiple scales. This detection framework is general and computationally tractable. Second, we treat the problem of signature retrieval in the unconstrained setting of translation, scale, and rotation invariant nonrigid shape matching. We propose two novel measures of shape dissimilarity based on anisotropic scaling and registration residual error and present a supervised learning framework for combining complementary shape information from different dissimilarity metrics using LDA. We quantitatively study state-of-the-art shape representations, shape matching algorithms, measures of dissimilarity, and the use of multiple instances as query in document image retrieval. We further demonstrate our matching techniques in offline signature verification. Extensive experiments using large real-world collections of English and Arabic machine-printed and handwritten documents demonstrate the excellent performance of our approaches.
Folding and oxidation of recombinant human granulocyte colony stimulating factor produced in Escherichia coli. Characterization of the disulfide-reduced intermediates and cysteine—-serine analogs. (1992)

The folding and oxidation of recombinant human granulocyte colony-stimulating factor solubilized from Escherichia coli inclusion bodies was investigated. During the folding process, two intermediates, I1 and I2, were detected by kinetic studies using high performance liquid chromatography. I1 exists transiently and disappears quickly with the concomitant formation of I2. In contrast, I2 requires a longer time to fold into the final oxidized form, N. CuSO4 catalysis increases the folding rate of I2 from I1, while CuSO4 and elevated temperature (37 degrees C) have a dramatic effect on the folding rate of N from I2. These observations suggest the following sequential oxidative folding pathway. [sequence: see text] Peptide map analysis of the iodoacetate-labeled intermediates revealed that I1 represents the fully reduced granulocyte colony-stimulating factor containing 5 free cysteines; I2 is the partially oxidized species containing a single Cys36-Cys42 disulfide bond; and N, the final folded form, has two disulfide bonds. The physicochemical properties and biological activities of I1, I2, N, and several Cys----Ser analogs made by site-directed mutagenesis were further investigated. In guanidine hydrochloride-induced denaturation studies, the disulfide-reduced intermediates and the analogs missing either of the disulfide bonds are conformationally less stable than those of the wild type molecule or the analog with the free Cys at position 17 changed to Ser. Recombinant human granulocyte colony stimulating factor lacking either disulfide bond or both has overall secondary and tertiary structures different from those of the wild type molecule and exhibits lower biological activity. These studies show that disulfide bond formation is crucial for maintaining the molecule in a properly folded and biologically active form.
Topological and Functional Characterization of an Insect Gustatory Receptor (2011)

Insect gustatory receptors are predicted to have a seven-transmembrane structure and are distantly related to insect olfactory receptors, which have an inverted topology compared with G-protein coupled receptors, including mammalian olfactory receptors. In contrast, the topology of insect gustatory receptors remains unknown. Except for a few examples from Drosophila, the specificity of individual insect gustatory receptors is also unknown. In this study, the total number of identified gustatory receptors in Bombyx mori was expanded from 65 to 69. BmGr8, a silkmoth gustatory receptor from the sugar receptor subfamily, was expressed in insect cells. Membrane topology studies on BmGr8 indicate that, like insect olfactory receptors, it has an inverted topology relative to G protein-coupled receptors. An orphan GR from the bitter receptor family, BmGr53, yielded similar results. We infer, from the finding that two distantly related BmGrs have an intracellular N-terminus and an odd number of transmembrane spans, that this is likely to be a general topology for all insect gustatory receptors. We also show that BmGr8 functions independently in Sf9 cells and responds in a concentration-dependent manner to the polyalcohols myo-inositol and epi-inositol but not to a range of mono- and di-saccharides. BmGr8 is the first chemoreceptor shown to respond specifically to inositol, an important or essential nutrient for some Lepidoptera. The selectivity of BmGr8 responses is consistent with the known responses of one of the gustatory receptor neurons in the lateral styloconic sensilla of B. mori, which responds to myo-inositol and epi-inositol but not to allo-inositol.
Promissing new fabrication process developed for stacked LSI's (1984)

A stacked CMOS LSI fabrication process has been developed for the purpose of realizing a short fabrication turn-around time, high fabrication yield and high integration density. This process consists of, in addition to the conventional LSI process, fabrication of vertical interconnections, surface planarization and thermal compression to obtain electrical interconnections between 2 layers. A 2-layer, bulk/CMOS ring oscillator consisting of p-channel MOSFETs on the upper layer and n-channel MOSFETs on the lower layer has been made using this new fabrication process. It has 31 bulk/CMOS inverter stages, each of which contains a single Au vertical interconnection with area of 10 × 10 µm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . A typical propagation delay time per stage for this device is measured to be 1.86 nsec at a supply voltage of 5 V.
Reverse time migration in 3D heterogeneous TTI media (2008)

In this abstract, we discuss the implementation of a TTI reverse time migration. Also we address several practical issues regarding numerical accuracy, stability and artifact removal related to the numerical implementation. The impulse responses from modeling and migration, in both synthetic and real models and for both strong anisotropy and strong variations of symmetry axis, validate the proposed formulation and algorithm.
论摩尔根的《美洲土著的房屋及宅居生活》及其他 (1982)

象路易斯·亨利·摩尔根那样能对二十世纪有着巨大影响的十九世纪社会思想家,为数无几。所有知名的社会学者都至少通过两种途径对他们的社会发生影响:一种是直接的,是从他们对社会科学或哲学作出的贡献而产生的;另一种是隐蔽的,它相机改换整个文化对世界和社会的观点。可将这两种影响看作是科学战线和第五纵队。要分清一位学者是真正的科学家还是第五纵队的队员,首先要在摩尔根身上分清这一点,并和其他学者进行比较,是最为重要的。
Preliminary Studies of a Simultaneous PET/MRI Scanner Based on the RatCAP Small Animal Tomograph (2006)

We are developing a scanner that will allow the simultaneous acquisition of high resolution anatomical data using Magnetic Resonance Imaging (MRI) and quantitative physiological data using Positron Emission Tomography (PET). The approach is based on the technology used for the RatCAP conscious small animal PET tomograph which utilizes block detectors consisting of pixelated arrays of LSO crystals read out with matching arrays of avalanche photodiodes (APDs) and a custom-designed ASIC. A version of the detector is being developed that will be constructed out of all non-magnetic materials that can be operated inside the MRI field. We have demonstrated that the PET detector works inside the MRI field using 511 keV gamma rays, and have obtained MRI images with various detector components that show minimal distortion in the MRI image. We plan to improve on the image quality in the future using completely non-magnetic components and by tuning the MRI pulse sequences. The combined result will be a highly compact, low mass PET scanner that can operate inside an MRI magnet without distorting the MRI image, and can be retrofitted into existing MRI instruments.
Prospect of Targeting the CD40 Pathway for Cancer Therapy (2007)

The cell surface molecule CD40 is a member of the tumor necrosis factor receptor superfamily and is broadly expressed by immune, hematopoietic, vascular, epithelial, and other cells, including a wide range of tumor cells. CD40 itself lacks intrinsic kinase or other signal transduction activity but rather mediates its diverse effects via an intricate series of downstream adapter molecules that differentially alter gene expression depending on cell type and microenvironment. As a potential target for novel cancer therapy, CD40 may mediate tumor regression through both an indirect effect of immune activation and a direct cytotoxic effect on the tumor, resulting in a "two-for-one" mechanism of action of CD40 agonists. Several drug formulations that target the CD40 pathway have undergone phase 1 clinical evaluation in advanced-stage cancer patients, and initial findings show objective clinical responses and immune modulation in the absence of major toxicity.
Lee-metric BCH codes and their application to constrained and partial-response channels (1994)

Shows that each code in a certain class of BCH codes over GF(p), specified by a code length n/spl les/p/sup m/-1 and a runlength r/spl les/(p-1)/2 of consecutive roots in GF(p/sup m/), has minimum Lee distance /spl ges/2r. For the very high-rate range these codes approach the sphere-packing bound on the minimum Lee distance. Furthermore, for a given r, the length range of these codes is twice as large as that attainable by Berlekamp's (1984) extended negacyclic codes. The authors present an efficient decoding procedure, based on Euclid's algorithm, for correcting up to r-1 errors and detecting r errors, that is, up to the number of Lee errors guaranteed by the designed minimum Lee distance 2r. Bounds on the minimum Lee distance for r/spl ges/(p+1)/2 are provided for the Reed-Solomon case, i.e., when the BCH code roots are in GF(p). The authors present two applications. First, Lee-metric BCH codes can be used for protecting against bitshift errors and synchronization errors caused by insertion and/or deletion of zeros in (d, k)-constrained channels. Second, the code construction with its decoding algorithm can be formulated over the integer ring, providing an algebraic approach to correcting errors in partial-response channels where matched spectral-null codes are used.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Thioredoxin and Related Proteins as Multifunctional Fusion Tags for Soluble Expression in E. coli (2003)

Escherichia coli has traditionally been a popular host for the production of heterologous proteins because of its ease of genetic manipulation and growth. Recombinant proteins produced in E. coli have been useful for a variety of purposes, including the study of protein tertiary structure, structure-function experiments, enzymology, and as bio-pharmaceuticals. Despite an impressive body of literature describing the production of numerous non-native proteins in E. coli, successful results are in no way assured. The use of E. coli as a robust expression system has been hampered by several integral pitfalls. Low or undetectable expression levels can often be caused by inefficient translation initiation of eukaryotic mRNAs on bacterial ribosomes (1). Recombinant proteins produced in E. coli sometimes retain the N-terminal initiator methionine residue, as they may be a poor substrate for the host methionine aminopeptidase (2). In addition, individual purification schemes must be devised for each native recombinant protein produced in E. coli. But perhaps most importantly, it is very common for recombinant proteins expressed in E. coli to form insoluble, misfolded cytoplasmic complexes known as “inclusion bodies” (3). The likelihood of inclusion body formation is unpredictable but appears to increase in proportion to the size and complexity of the protein.
Optical Fiber Systems: Technology, Design, and Applications (1982)

Optical fiber systems: technology, design, and applications , Optical fiber systems: technology, design, and applications , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی
Commitment to meiosis in Saccharomyces cerevisiae: involvement of the SPO14 gene. (1992)

This paper describes the identification, cloning and phenotypic analysis of SPO14, a new gene required for meiosis and spore formation. Studies of strains carrying a temperature-sensitive mutation or a disruption/duplication allele indicate that spo14 mutants have the unusual property of being able to return to mitotic division, even from the late stages of meiotic development. Early meiotic events, such as DNA replication and intragenic and intergenic recombination, occur normally. In contrast, later meiotic processes are defective in spo14 mutants: the meiosis I division appears to be executed at slightly depressed levels, the meiosis II division is reduced more severely, and no spores are formed. Epistasis tests using mutants defective in recombination or reductional division support these findings. Based on these data, we suggest that the SPO14 gene product is involved in the coordinate induction of late meiotic events and that this induction is responsible for the phenomenon of commitment.
Technology evaluation: nimotuzumab, the Center of Molecular Immunology/YM BioSciences/Oncoscience. (2005)

A joint venture between YM BioSciences (formerly York Medical) and The Center of Molecular Immunology is collaborating with Oncoscience in Europe for the development of a humanized monoclonal antibody, nimotuzumab, for the potential treatment (TheraCIM and RadioTheraCIM) and diagnosis (DiaCIM) of cancers of epithelial origin, such as breast, lung, head and neck, and pancreatic cancer. The antibody is currently undergoing phase II clinical trials.
Allelic exchange in <i>Escherichia coli</i> using the <i>Bacillus subtilis sacB</i> gene and a temperature‐sensitive pSC101 replicon (1991)

To facilitate efficient allelic exchange of genetic information into a wild-type strain background, we improved upon and merged approaches using a temperature-sensitive plasmid and a counter-selectable marker in the chromosome. We first constructed intermediate strains of Escherichia coli K12 in which we replaced wild-type chromosomal sequences, at either the fimB-A or lacZ-A loci, with a newly constituted DNA cassette. The cassette consists of the sacB gene from Bacillus subtilis and the neomycin (kanamycin) resistance gene of Tn5, but, unlike another similar cassette, it lacks IS1 sequences. We found that sucrose sensitivity was highly dependent on incubation temperature and sodium chloride concentration. The DNA to be exchanged into the chromosome was first cloned into derivatives of plasmid pMAK705, a temperature-sensitive pSC101 replicon. The exchanges were carried out in two steps, first selecting for plasmid integration by standard techniques. In the second step, we grew the plasmid integrates under non-selective conditions at 42 degrees C, and then in the presence of sucrose at 30 degrees C, allowing positive selection for both plasmid excision and curing. Despite marked locus-specific strain differences in sucrose sensitivity and in the growth retardation due to the integrated plasmids, the protocol permitted highly efficient exchange of cloned DNA into either the fim or lac chromosomal loci. This procedure should allow the exchange of any DNA segment, in addition to the original or mutant allelic DNA, into any non-essential parts of the E. coli chromosome.
Tumor-infiltrating lymphocytes are dynamically desensitized to antigen but are maintained by homeostatic cytokine (2016)

T cells that enter tumors are largely tolerized, but how that process is choreographed and how the ensuing "dysfunctional" tumor-infiltrating lymphocytes (TILs) are maintained are poorly understood and are difficult to assess in spontaneous disease. We exploited an autochthonous model of breast cancer for high-resolution imaging of the early and later stages of tumor residence to understand the relationships between cellular behaviors and cellular phenotypes. "Dysfunctional" differentiation began within the first days of tumor residence with an initial phase in which T cells arrest, largely on tumor-associated macrophages. Within 10 days, cellular motility increased and resembled a random walk, suggesting a relative absence of TCR signaling. We then studied the concurrent and apparently contradictory phenomenon that many of these cells express molecular markers of activation and were visualized undergoing active cell division. We found that whereas proliferation did not require ongoing TCR/ZAP70 signaling, instead this is driven in part by intratumoral IL-15 cytokine. Thus, TILs undergo sequential reprogramming by the tumor microenvironment and are actively retained, even while being antigen insensitive. We conclude that this program effectively fills the niche with ineffective yet cytokine-dependent TILs, and we propose that these might compete with new clones, when they arise.
Trends in Medical Use and Abuse of Opioid Analgesics (2000)

The trend of increasing medical use of opioid analgesics to treat pain does not appear to contribute to increases in the health consequences of opioid analgesic abuse.
The Coronary Angiogenetic Effect of Heparin: Experimental Basis and Clinical Evidence (1997)

Heparin is a highly sulfated polysaccharide consisting of a repeating disaccharide structure as found in other glycosaminoglycanes. The intravenous and subcutaneous formulation of the drug is routinely used for its well-known, time-honored antithrombotic effect. However, available evidences linking heparin to angiogenesis raise the possibility of a therapeutically relevant antiischemic effect of the drug. Molecular biology data show that in a hypoxic milieu heparin could facilitate angiogenesis through interactions with a family of polypeptide growth factor mitogens that stimulate endothelial cell proliferation. Experimental data suggest that heparin can augment collateral circulation when combined with other potentially angiogenetic factors, such as repeated ischemia, coronary occlusion, or physical exercise. Clinical data, although very initial, encompassing a total of only 41 heparin-treated patients with coronary artery disease, suggest that heparin facilitates collateral development stimulated by exercise-induced myocardial ischemia in humans. According to the heparin-collateral hypothesis, the mechanism of action of heparin as an antiischemic medication would be independent of its anticoagulant action. The molecular targets of heparin are Factor Xa and IIa for antithrombotic action, heparin-binding growth factors (including fibroblast growth factor and vascular endothelial growth factor) for angiogenesis. The antithrombotic effect is not linked to a cellular target, whereas the angiogenetic effect directly stimulates endothelial cells. The molecular cofactor required for effect is antithrombin III for antithrombosis, and possibly endogenous adenosine for angiogenesis. The therapeutic effect is achieved within minutes or hours for antithrombosis, and within weeks or months for angiogenesis.