gebhart/patrepeval huggingface dataset:
Abstract 1584: MHC-restricted phosphopeptides as broad-based immunotherapeutic targets for cancer (2012)

Abstract Identification of the antigens (Ags) recognized by CD8+ T cells specific for melanoma and other types of cancer cells has been motivated by the expectation that they will serve as the basis for a therapeutic vaccine or will be useful for the stimulation of more effective CD8+ CTL for adoptive immunotherapy. Few of the currently identified Ags are derived from source proteins directly associated with transformation or metastasis, and many are self-Ags which may be subject to tolerance mechanisms. We have defined a new array of phosphorylated peptides presented by HLA-A1, -A2, -A3, -B7, -B44 and HLA-B27 that are presented on melanomas from multiple patients at &amp;gt;1 copy per cell and derived from source proteins associated with tumorigenesis and metastasis. We evaluated the immunogenicity of several of the HLA-A2-restricted phosphopeptide Ags in an HLA-transgenic murine model system and in vitro human T cell cultures, evaluated the presence of the phosphorylated source protein or display of the phosphorylated epitope on cancers of different histological types, and investigated the ability of phosphopeptide-specific CD8+ T cells to prevent outgrowth of cancer cells in a xenogenic model. Evaluation of metastatic melanoma tissue microarrays and cancer cell lysates demonstrated that the phosphorylated source proteins for β-catenin (Ser33-phosphorylated), Breast cancer anti-estrogen resistance −3 (BCAR3; Thr130-phosphorylated), and Insulin receptor substrate-2 (IRS2; Ser1100-phosphorylated) were broadly expressed in melanomas and other cancers but not normal tissues. In addition, these epitopes can be utilized to elicit phosphopeptide-specific T cells in both murine HLA-A2 transgenic mice in vivo and human in vitro culture. The phospho-β-catenin, phospho-IRS2 and phospho-BCAR3-specific-T cells that were generated differentiate between the phosphorylated and non-modified forms of their respective peptides and recognize the endogenously processed and presented phosphopeptide on the surface of cancer cells. Finally, adoptive transfer of these phosphopeptide-specific T cells slowed outgrowth of melanoma tumors implanted in immunodeficient NOD.SCID.IL2Rα-/- mice. Thus, we have defined a new set of post-translationally modified epitopes derived from source proteins associated with tumorigenesis and metastasis that are immunogenic and capable of slowing tumor outgrowth in a xenograft model. Based on these results, we are currently planning a clinical trial utilizing these HLA-A2-restricted phosphopeptides in melanoma patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1584. doi:1538-7445.AM2012-1584
Discovery ofN-(4-(3-Amino-1H-indazol-4-yl)phenyl)-N‘-(2-fluoro-5-methylphenyl)urea (ABT-869), a 3-Aminoindazole-Based Orally Active Multitargeted Receptor Tyrosine Kinase Inhibitor (2007)

In our continued efforts to search for potent and novel receptor tyrosine kinase (RTK) inhibitors as potential anticancer agents, we discovered, through a structure-based design, that 3-aminoindazole could serve as an efficient hinge-binding template for kinase inhibitors. By incorporating an N,N'-diaryl urea moiety at the C4-position of 3-aminodazole, a series of RTK inhibitors were generated, which potently inhibited the tyrosine kinase activity of the vascular endothelial growth factor receptor and the platelet-derived growth factor receptor families. A number of compounds with potent oral activity were identified by utilizing an estradiol-induced mouse uterine edema model and an HT1080 human fibrosarcoma xenograft tumor model. In particular, compound 17p (ABT-869) was found to possess favorable pharmacokinetic profiles across different species and display significant tumor growth inhibition in multiple preclinical animal models.
ENgineering Coupled Defects for Photonic Crystal-Based Optical Delay Lines, All-Optical Switches and Waveguide Intersections (2002)

Coupling of defects in photonic crystals has been theoretically investigated. Optical delay lines, all-optical switches, and waveguide intersections can be constructed by properly engineering the coupling of defects. Optical delay lines were experimentally fabricated and tested.
Three-dimensional direct-write lithography into photopolymer (2007)

We demonstrate a three-dimensional direct-write lithography system capable of writing deeply buried, localized index structures into diffusion-mediated photopolymer. The system is similar to that used for femtosecond writing in glass, but has a number of advantages including greater flexibility in the writing media and the ability to use low power, inexpensive, continuous-wave lasers. This system writes index structures both parallel and perpendicular to the writing beam in different types of photopolymers, providing control over the feature size and shape. We demonstrate that this system can be used to create single-mode waveguides that are deeply embedded in the photopolymer medium.
Cloning of the human and mouse type X collagen genes and mapping of the mouse type X collagen gene to chromosome 10 (1992)

Type X collagen, a homotrimer of alpha 1 (X) polypeptide chains, is specifically expressed by hypertrophic chondrocytes in regions of cartilage undergoing endochondral ossification. We have previously described the isolation of a small fragment of the human type X collagen gene (COL10A1) and its localization to the q21-q22 region of human chromosome 6 [Apte, S., Mattei, M.-G. & Olsen, B. R. (1991) FEBS Lett. 282, 393-396]. Using this fragment as a probe to screen genomic libraries, we report here the isolation of human and mouse genomic clones which contain the major part of the human and mouse type X collagen genes. In both species, the 14-kb genomic clones which were isolated contain a long open reading frame (greater than 2000 bp in length) which codes for the entire C-terminal non-collagenous (NC1) domain, the entire collagenous (COL) domain and part of the N-terminal non-collagenous (NC2) domain of the alpha 1(X) collagen chain. The human genomic clone contains the major part of the COL10A1 gene, in addition to the region we have previously cloned, and is highly similar to the corresponding portions of the mouse genomic clone (84.5% similarity at the nucleotide level, and 86.1% at the level of the conceptual translation product). The identification of the mouse genomic clone as the alpha 1(X) collagen gene (Col10a1) was confirmed by in situ hybridization of a fragment of the mouse genomic clone to sections from newborn mice. Hybridization was restricted to the hypertrophic chondrocytes of developing chondroepiphyses, being absent in small chondrocytes and in other tissues. Using interspecific backcross analysis, the locus for the mouse alpha 1 (X) collagen gene was assigned to chromosome 10. The cloning and chromosomal mapping of the human and mouse alpha 1 (X) collagen genes now permit the investigation of the possible role of type X collagen gene defects in the genesis of chondrodysplasias in both species and provide data essential for the generation of transgenic mice deficient in type X collagen.
Recoveries of bacteria after drying and heating in glutamate foams (1970)

A method of drying bacteria is described, in which the bacterial suspension was made in 40% sodium glutamate, and 0.1 ml. volumes of this in 8 ml. ampoules were dried in vacuo while being held in a water bath at 25 degrees C. After 1 hr. with the pump still running, the ampoules were immersed in water at 100 degrees C. The partly dried suspension expanded rapidly into a homogeneous white foam. After 30 min. the ampoules were taken off the manifold; small tubes containing dry P(2)O(5) were inserted in the ampoules which were then sealed in air. Preliminary results with three organisms, Salmonella ndolo, Staphylococcus aureus and Serratia marcescens showed high survivals immediately after the ;foaming' period, and good stability after 1 or 2 days at 100 degrees C.
Guanosine-rich oligodeoxynucleotides induce proliferation of macrophage progenitors in cultures of murine bone marrow cells (1999)

Widely used to specifically inhibit gene expression, synthetic oligodeoxynucleotides (ODN) can exert a plethora of non-antisense effects. Immunostimulation by CpG-ODN has attracted particular attention. ODN rich in the nucleotide guanosine (G-rich ODN) constitute another type of sequences displaying non-antisense-mediated effects. We have examined the effects of CpG- and G-rich ODN on primary mouse bone marrow cells (BMC) in vitro. CpG-ODN induced rapid proliferation of B cells and production of IL-6 and IL-12p40. However, when tested in agar colony assays, CpG-ODN failed to promote the formation of colonies. In marked contrast, G-rich non-CpG-ODN led to sustained proliferation of macrophage-like cells without inducing cytokines or hemopoietic growth factors. Unlike CpG-ODN, G-rich ODN effectively induced the formation of macrophage colonies in agar assays, indicating a direct action on progenitor cells. Electrophoretic mobility shift assays revealed specific binding of G-rich ODN to a non-nuclear protein. The ability of a panel of ODN to compete for binding correlated with their potential to induce proliferation of macrophage-like cells from primary mouse BMC. As such, these data reveal a so far unrecognized potential of G-rich ODN to signal directly outgrowth of macrophage progenitors from BMC.
Poly(ethylene oxide) star molecules: Synthesis, characterization, and applications in medicine and biology (1994)

Abstract Festschrift remark-It was an honor to be invited to honor Allan Hoffman on the occasion of his 60th birthday. It seems like yesterday that Allan and I shared an office in old Building 12 on the M.I.T. campus. At that time Allan had lost a bout with a snow covered mountain while on skis, and consequently moved about awkwardly in our already small room on crutches with a heavy cast. Despite these impediments, he carried on his classroom activities with typical energy. It was even earlier that at M.I.T., under the supervision of Ed Gilliland and myself, he carried out his doctoral research on the radiation grafting of styrene to polyethylene. Both he and I have dabbled in radiation chemistry on and off since then-he far more than I. Neither of us at that epoch had much idea about biomaterials or medical applications of materials-at least I did not-perhaps Allan had it in the back of his mind. The University of Washington, Seattle, is recognized as one of the great centers of biomedical engineering in the world, both in scope and in depth, and Allan has played a stellar role in the evolution of Seattle's reputation. He has also developed a reputation for outstanding work in biomaterials and is one of the most visible and internationally recognized leaders in the field.
Periodate-mediated glycosaminoglycan stabilization in bioprosthetic heart valves (2001)

Bioprosthetic heart valves (BPHVs) derived from glutaraldehyde-crosslinked porcine aortic valves are frequently used in heart valve replacement surgeries. However, the majority of bioprostheses fail clinically because of calcification and degeneration. We have recently shown that glycosaminoglycan (GAG) loss may be in part responsible for degeneration of glutaraldehyde-crosslinked bioprostheses. In the present studies, we used a mild reaction of periodate-mediated crosslinking to stabilize glycosaminoglycans in the bioprosthetic tissue. We demonstrate the feasibility of periodate reaction by crosslinking major components of extracellular matrix of bioprosthetic heart valve tissue, namely type I collagen and hyaluronic acid (HA). Uronic acid assay of periodate-fixed HA-collagen matrices showed 48% of HA disaccharides were bound to collagen. Furthermore, we show that such reactions are also feasible to fix glycosaminoglycans present in the middle spongiosa layer of bioprosthetic heart valves. The periodate reactions were compatible with conventional glutaraldehyde crosslinking and showed adequate stabilization of extracellular matrix as demonstrated by thermal denaturation temperature and collagenase assays. Moreover, uronic acid assays of periodate-fixed BPHV cusps showed 36% reduction in the amount of unbound GAG disaccharides as compared with glutaraldehyde-crosslinked cusps. We also demonstrate that calcification of BPHV cusps was significantly reduced in the periodate-fixed group as compared with the glutaraldehyde-fixed group in 21-day rat subdermal calcification studies (periodate-fixed tissue Ca 72.01 +/- 5.97 microg/mg, glutaraldehyde-fixed tissue Ca 107.25 +/- 6.56 microg/mg). We conclude that periodate-mediated GAG fixation could reduce structural degeneration of BPHVs and may therefore increase the useful lifetime of these devices.
Localization of Amyloid β Protein Messenger RNA in Brains from Patients with Alzheimer's Disease (1987)

The distribution of cells containing messenger RNA that encodes amyloid beta protein was determined in hippocampi and in various cortical regions from cynomolgus monkeys, normal humans, and patients with Alzheimer's disease by in situ hybridization. Both 35S-labeled RNA antisense and sense probes to amyloid beta protein messenger RNA were used to ensure specific hybridization. Messenger RNA for amyloid beta protein was expressed in a subset of neurons in the prefrontal cortex from monkeys, normal humans, and patients with Alzheimer's disease. This messenger RNA was also present in the neurons of all the hippocampal fields from monkeys, normal humans and, although to a lesser extent in cornu ammonis 1, patients with Alzheimer's disease. The distribution of amyloid beta protein messenger RNA was similar to that of the neurofibrillary tangles of Alzheimer's disease in some regions, but the messenger RNA was also expressed in other neurons that are not usually involved in the pathology of Alzheimer's disease.
Dial 'M' for Metonym: Universal Exports, M's Office Space and Empire (2000)

For James Bond, Britishness is most often realised outside the British Isles, within the old Empire. Whenever physically located in Britain proper, he is most likely to be found in the offices of Universal Exports otherwise known as the British Secret Service. M's office is a metonym for England, a stable point of departure for Bond's adventures, and a site from which to theorise the relationship between M (England) and Bond (Britain); ideology, iconography and office fittings; changes and challenges to that 'office space'; cognitive mapping and the resonance of a British signifier on the margins of empire.
Characterization of complex chromosomal abnormalities in uveal melanoma by fluorescence in situ hybridization, spectral karyotyping, and comparative genomic hybridization (2001)

Several nonrandom recurrent chromosomal changes are observed in uveal melanoma. Some of these abnormalities, e.g., loss of chromosome 3, gain of the q arm of chromosome 8, and chromosome 6 abnormalities, are of prognostic value. Cytogenetic analysis and/or fluorescence in situ hybridization (FISH) are used to detect these changes. In some cases, however, detailed cytogenetic analysis is not possible due to the presence of complex abnormalities. To define more accurately these cytogenetic changes, we have applied comparative genomic hybridization (CGH) and/or spectral karyotyping (SKY) to two uveal melanoma cell lines and five primary uveal melanomas, with partially defined and/or complex abnormalities. SKY provided additional information on 34/39 partially defined aberrant chromosomes and revealed a new abnormality, a der(17)t(7;17)(?;q?), that had not been recognized by conventional cytogenetics. Additionally, using SKY, abnormalities involving chromosome 6 or 8 were found to be twice as common as observed with cytogenetic analysis. CGH was especially useful in assigning the abnormalities identified by SKY to specific chromosomal regions and, in addition, resulted in the detection of a small deletion of chromosome region 3q13 approximately 21. We conclude that SKY and CGH, as methods complementary to cytogenetic and FISH analysis, provide more complete information on the chromosomal abnormalities occurring in uveal melanoma.
Automatic room detection and reconstruction in cluttered indoor environments with complex room layouts (2014)

We present a robust approach for reconstructing the main architectural structure of complex indoor environments given a set of cluttered 3D input range scans. Our method uses an efficient occlusion-aware process to extract planar patches as candidate walls, separating them from clutter and coping with missing data, and automatically extracts the individual rooms that compose the environment by applying a diffusion process on the space partitioning induced by the candidate walls. This diffusion process, which has a natural interpretation in terms of heat propagation, makes our method robust to artifacts and other imperfections that occur in typical scanned data of interiors. For each room, our algorithm reconstructs an accurate polyhedral model by applying methods from robust statistics. We demonstrate the validity of our approach by evaluating it on both synthetic models and real-world 3D scans of indoor environments.
Antibodies specifically targeting a locally misfolded region of tumor associated EGFR (2009)

Epidermal Growth Factor Receptor (EGFR) is involved in stimulating the growth of many human tumors, but the success of therapeutic agents has been limited in part by interference from the EGFR on normal tissues. Previously, we reported an antibody (mab806) against a truncated form of EGFR found commonly in gliomas. Remarkably, it also recognizes full-length EGFR on tumor cells but not on normal cells. However, the mechanism for this activity was unclear. Crystallographic structures for Fab:EGFR(287-302) complexes of mAb806 (and a second, related antibody, mAb175) show that this peptide epitope adopts conformations similar to those found in the wtEGFR. However, in both conformations observed for wtEGFR, tethered and untethered, antibody binding would be prohibited by significant steric clashes with the CR1 domain. Thus, these antibodies must recognize a cryptic epitope in EGFR. Structurally, it appeared that breaking the disulfide bond preceding the epitope might allow the CR1 domain to open up sufficiently for antibody binding. The EGFR(C271A/C283A) mutant not only binds mAb806, but binds with 1:1 stoichiometry, which is significantly greater than wtEGFR binding. Although mAb806 and mAb175 decrease tumor growth in xenografts displaying mutant, overexpressed, or autocrine stimulated EGFR, neither antibody inhibits the in vitro growth of cells expressing wtEGFR. In contrast, mAb806 completely inhibits the ligand-associated stimulation of cells expressing EGFR(C271A/C283A). Clearly, the binding of mAb806 and mAb175 to the wtEGFR requires the epitope to be exposed either during receptor activation, mutation, or overexpression. This mechanism suggests the possibility of generating antibodies to target other wild-type receptors on tumor cells.
ProLuCID: An improved SEQUEST-like algorithm with enhanced sensitivity and specificity (2015)

ProLuCID, a new algorithm for peptide identification using tandem mass spectrometry and protein sequence databases has been developed. This algorithm uses a three tier scoring scheme. First, a binomial probability is used as a preliminary scoring scheme to select candidate peptides. The binomial probability scores generated by ProLuCID minimize molecular weight bias and are independent of database size. A modified cross-correlation score is calculated for each candidate peptide identified by the binomial probability. This cross-correlation scoring function models the isotopic distributions of fragment ions of candidate peptides which ultimately results in higher sensitivity and specificity than that obtained with the SEQUEST XCorr. Finally, ProLuCID uses the distribution of XCorr values for all of the selected candidate peptides to compute a Z score for the peptide hit with the highest XCorr. The ProLuCID Z score combines the discriminative power of XCorr and DeltaCN, the standard parameters for assessing the quality of the peptide identification using SEQUEST, and displays significant improvement in specificity over ProLuCID XCorr alone. ProLuCID is also able to take advantage of high resolution MS/MS spectra leading to further improvements in specificity when compared to low resolution tandem MS data. A comparison of filtered data searched with SEQUEST and ProLuCID using the same false discovery rate as estimated by a target-decoy database strategy, shows that ProLuCID was able to identify as many as 25% more proteins than SEQUEST. ProLuCID is implemented in Java and can be easily installed on a single computer or a computer cluster. This article is part of a Special Issue entitled: Computational Proteomics.
β2‐Agonist administration reverses muscle wasting and improves muscle function in aged rats (2003)

The beta2-adrenoceptor agonist (beta2-agonist) fenoterol has potent anabolic effects on rat skeletal muscle. We conducted an extensive dose-response study to determine the most efficacious dose of fenoterol for increasing skeletal muscle mass in adult rats and used this dose in testing the hypothesis that fenoterol may have therapeutic potential for ameliorating age-related muscle wasting and weakness. We used adult (16-month-old) rats that had completed their growth and development, and old (28-month-old) rats that exhibited characteristic muscle wasting and weakness, and treated them daily with either fenoterol (1.4 mg kg(-1), i.p), or saline vehicle, for 4 weeks. Following treatment, functional characteristics of fast-twitch extensor digitorum longus (EDL) and predominantly slow-twitch soleus muscles of the hindlimb were assessed in vitro. Untreated old rats exhibited a loss of skeletal muscle mass and a decrease in force-producing capacity, in both fast and slow muscles, compared with adult rats (P < 0.05). However, there was no age-associated decrease in skeletal muscle beta-adrenoceptor density, nor was the muscle response to chronic beta-agonist stimulation reduced with age. Thus, muscle mass and force-producing capacity of EDL and soleus muscles from old rats treated with fenoterol was equivalent to, or greater than, untreated adult rats. The increase in mass and strength was attributed to a non-selective increase in the cross-sectional area of all muscle fibre types, in both the EDL and soleus. Fenoterol treatment caused a small increase in fatiguability due to a decrease in oxidative metabolism in both EDL and soleus muscles, with some cardiac hypertrophy. Further studies are needed to fully separate the desirable effects on skeletal muscle and the undesirable effects on the heart. Nevertheless, our results demonstrate that fenoterol is a powerful anabolic agent that can restore muscle mass and strength in old rats, and provide preliminary evidence of therapeutic potential for age-related muscle wasting and weakness.