gebhart/patrepeval huggingface dataset:
Nucleosome: a major immunogen for pathogenic autoantibody-inducing T cells of lupus. (1993)

Only a fraction (12%) of 268 "autoreactive" T cell clones derived from lupus-prone mice can selectively induce the production of pathogenic anti-DNA autoantibodies in vitro and accelerate the development of lupus nephritis when transferred in vivo. The CDR3 loops of T cell receptor beta chains expressed by these pathogenic T helper (Th) clones contain a recurrent motif of anionic residues suggesting that they are selected by autoantigens with cationic residues. Herein, we found that approximately 50% of these pathogenic Th clones were specific for nucleosomal antigens, but none of them responded to cationic idiopeptides shared by variable regions of pathogenic anti-DNA autoantibodies. Nucleosomes did not stimulate the T cells as a nonspecific mitogen or superantigen. Only the pathogenic Th cells of lupus responded to nucleosomal antigens that were processed and presented via the major histocompatibility class II pathway. Although the presentation of purified mononucleosomes to the Th clones could be blocked by inhibitors of endosomal proteases, neither of the two components of the nucleosomes--free DNA or histones by themselves--could stimulate the Th clones. Thus critical peptide epitopes for the Th cells were probably protected during uptake and processing of the nucleosome particle as a whole. The nucleosome-specific Th clones preferentially augmented the production of IgG autoantibodies to histone-DNA complex in vitro. In vivo, nucleosome-specific, CD4+ T cells were not detectable in normal mice, but they were found in the spleens of lupus-prone mice as early as 1 mo of age, long before other autoimmune manifestations. Immunization of young, preautoimmune lupus mice with nucleosomes augmented the production of autoantibodies and markedly accelerated the development of severe glomerulonephritis. Previously, crude preparations containing nucleosomes were shown by others to have polyclonal mitogenic activity for B cells from normal as well as lupus mice. Identification here of pure mononucleosome as a lupus-specific immunogen for the Th cells that selectively help the pathogenic anti-DNA autoantibody producing B cells of lupus could lead to the design of specific therapy against this pathogenic autoimmune response.
Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell–mediated B-cell cytotoxicity (2010)

CD20 is an important target for the treatment of B-cell malignancies, including non-Hodgkin lymphoma as well as autoimmune disorders. B-cell depletion therapy using monoclonal antibodies against CD20, such as rituximab, has revolutionized the treatment of these disorders, greatly improving overall survival in patients. Here, we report the development of GA101 as the first Fc-engineered, type II humanized IgG1 antibody against CD20. Relative to rituximab, GA101 has increased direct and immune effector cell-mediated cytotoxicity and exhibits superior activity in cellular assays and whole blood B-cell depletion assays. In human lymphoma xenograft models, GA101 exhibits superior antitumor activity, resulting in the induction of complete tumor remission and increased overall survival. In nonhuman primates, GA101 demonstrates superior B cell-depleting activity in lymphoid tissue, including in lymph nodes and spleen. Taken together, these results provide compelling evidence for the development of GA101 as a promising new therapy for the treatment of B-cell disorders.
Compositional Analysis of Ni-Zr Powder during Amorphization by Mechanical Alloying (1987)

We prepared amorphous Ni-Zr powder by mechanical alloying. The solid-state amorphization reaction is monitored by X-ray diffraction, SEM and microprobe analysis. During the milling a layered structure of the crystalline elements develops. At the boundaries the amorphous alloy is formed by interdiffusion. The layers of the crystalline elements become thinner and the amorphous parts grow when the alloying period is increasing. The amorphous parts grow by cold welding of the smaller parts.
Juvocimenes: Potent Juvenile Hormone Mimics from Sweet Basil (1980)

Two compounds with highly potent juvenile hormone activity were isolated and identified from the oil of sweet basil, Ocimum basilicum L., Labiatae.
[Foveal electroretinogram: its application in the diagnosis of macular diseases. Preliminary report]. (1998)

Our preliminary clinical investigations manifest the value of the FCERGs in objective evaluations of macular diseases undetectable with conventional electroretinography.
Advances in the treatment of chronic hepatitis B virus infection (1998)

Recent advances in our understanding of the replicative mechanism of HBV, and the development of potent nucleoside analogues as clinically effective inhibitors of the HIV reverse transcriptase or herpesvirus polymerases has opened a new era in the treatment of chronic HBV infection. Single agent therapies, such as famciclovir, lamivudine or lobucavir, have had some success. There is now a logical basis for combination therapy, because of the clear need for prolonged treatment and the associated possibility that drug resistant strains will emerge with monotherapy, but the choice of agents to combine and the regimens in which they should be employed remain uncertain.Copyright 1998 John Wiley & Sons, Ltd.
MUC1 and MUC2 expression in pancreatic ductal carcinoma obtained by fine-needle aspiration (2003)

MUC1 is overexpressed in pancreatic ductal carcinoma with a predominantly membranous and variable cytoplasmic staining pattern. The results of the current study suggest that the phenotypic expression of MUC1 can be used as an ancillary marker for diagnosing pancreatic ductal carcinoma in cytologic preparations. Conversely, MUC2 does not appear to be a useful marker for recognizing pancreatic ductal carcinoma in FNA specimens.
Systemic administration of a TLR7 agonist attenuates regulatory T cells by dendritic cell modification and overcomes resistance to PD-L1 blockade therapy (2018)

Research on immune checkpoint blockade therapy has made great progress in cancer immunotherapy, but the number of patients who benefit from this therapy remains limited. In this study, we examined the effects of monotherapy with systemic low-dose resiquimod, a synthesized TLR7 agonist, and examined its combined effects with PD-L1 blockade in two PD-L1 blockade-resistant tumor models (SCCVII and Colon 26). Resiquimod monotherapy in SCCVII tumors, representing impaired CD8<sup>+</sup> T cell function and accelerated regulatory T cells (Tregs) within the tumors, efficiently reduced tumor growth with more recruitment of CD8<sup>+</sup> T cells and a reduction of Treg. The results of resiquimod monotherapy in Colon 26, representing impaired Treg recruitment, were inferior to that in SCCVII. Combined resiquimod treatment with PD-L1 blockade exerted clear additional effects, as it was associated with reduced tumor size, attenuation of Tregs, and an increased ratio of CD8<sup>+</sup> T cells/Tregs in both tumors. Systemic administration of low-dose resiquimod induced a transient and rapid activation of plasmacytoid and conventional dendritic cells, resulting in enhanced priming of T cells in regional lymph nodes. Experiments with more limited doses of resiquimod that did not yield beneficial effects after single treatment, showed additional effects to PD-L1 blockade and comparable antitumor effects when the frequency of anti-PD-L1 therapy was decreased. Our results suggest that systemic administration of low-dose resiquimod is useful as a companion drug to PD-1/PD-L1 blockade therapy.
Fundamental studies of interfacial rheology at multilayered model polymers for coextrusion process (2013)

International audience
Collective Photography (2009)

This paper offers the reader an insight into how photography and home video production could evolve in the near future through the evolution of geo-tagging (adding location and orientation parameters to an object). Technological advances in portable imaging and communications devices, e.g. digital cameras and smartphones, are bringing about a new era in media creation that could see us all automatically contributing to the documentation of society. We will demonstrate how enriched multimedia can be generated through the exploitation of socially generated spatiotemporal knowledge, extracted from the photos of others, or from any form of geo-referenced material. An overview of how geo-tags can be created is presented, ranging from integrated hardware to purely software solutions; we focus on a selection of promising cutting edge research projects in this field that aim to fully automate the geo-tagging process. Finally, we will propose ways to extract content and visualise geo-referenced material intelligently inside registered imagery using geographical reasoning.
Molecular Characterization of the Human Cα-formylglycine-generating Enzyme (2005)

Calpha-formylglycine (FGly) is the catalytic residue in the active site of sulfatases. In eukaryotes, it is generated in the endoplasmic reticulum by post-translational modification of a conserved cysteine residue. The FGly-generating enzyme (FGE), performing this modification, is an endoplasmic reticulum-resident enzyme that upon overexpression is secreted. Recombinant FGE was purified from cells and secretions to homogeneity. Intracellular FGE contains a high mannose type N-glycan, which is processed to the complex type in secreted FGE. Secreted FGE shows partial N-terminal trimming up to residue 73 without loosing catalytic activity. FGE is a calcium-binding protein containing an N-terminal (residues 86-168) and a C-terminal (residues 178-374) protease-resistant domain. The latter is stabilized by three disulfide bridges arranged in a clamp-like manner, which links the third to the eighth, the fourth to the seventh, and the fifth to the sixth cysteine residue. The innermost cysteine pair is partially reduced. The first two cysteine residues are located in the sequence preceding the N-terminal protease-resistant domain. They can form intramolecular or intermolecular disulfide bonds, the latter stabilizing homodimers. The C-terminal domain comprises the substrate binding site, as evidenced by yeast two-hybrid interaction assays and photocross-linking of a substrate peptide to proline 182. Peptides derived from all known human sulfatases served as substrates for purified FGE indicating that FGE is sufficient to modify all sulfatases of the same species.
Stimulation of GAL4 Derivative Binding to Nucleosomal DNA by the Yeast SWI/SNF Complex (1994)

The SWI/SNF protein complex is required for the enhancement of transcription by many transcriptional activators in yeast. Here it is shown that the purified SWI/SNF complex is composed of 10 subunits and includes the SWI1, SWI2/SNF2, SWI3, SNF5, and SNF6 gene products. The complex exhibited DNA-stimulated adenosine triphosphatase (ATPase) activity, but lacked helicase activity. The SWI/SNF complex caused a 10- to 30-fold stimulation in the binding of GAL4 derivatives to nucleosomal DNA in a reaction that required adenosine triphosphate (ATP) hydrolysis but was activation domain-independent. Stimulation of GAL4 binding by the complex was abolished by a mutant SWI2 subunit, and was increased by the presence of a histone-binding protein, nucleoplasmin. A direct ATP-dependent interaction between the SWI/SNF complex and nucleosomal DNA was detected. These observations suggest that a primary role of the SWI/SNF complex is to promote activator binding to nucleosomal DNA.
Long-term response in high-grade optic glioma treated with medically induced hypothyroidism and carboplatin (2013)

Glioblastoma multiforme (GBM) is the most malignant and frequent brain tumor, with an aggressive growth pattern and poor prognosis despite best treatment modalities. Long-term survival of patients with GBM is rare. Optic glioma represents 0.6-1.2% of all brain tumors. Unlike low-grade optic gliomas in children, optic gliomas in adults are highly aggressive and death usually occurs in less than a year. Prolonged progression-free survival and survival rates have been reported in association with induced hypothyroidism in two clinical trials for recurrent GBM. We present the clinical, radiological, and pathological findings in a patient with inoperable GBM of the optic chiasm. Following failure of initial, standard radiation and temozolomide therapy, chemical hypothyroidism was induced using the antithyroid thioamide, propylthiouracil, followed by carboplatin chemotherapy. Initial thyroid stimulating hormone, free T4, and free T3 analysis was carried out and then monthly. This patient responded rapidly to treatment (clinically and with tumor regression within 4 weeks) on two separate occasions with an extended remission period (2.5 years) and prolonged overall survival (4.5 years). We report the successful long-term tumor response to medically induced chemical hypothyroidism in conjunction with carboplatinum chemotherapy of an adult patient with grade IV GBM of the optic chiasm. These clinical observations find mechanistic support from the recent identification of potent mitogenic actions of the thyroid hormone, L-thyroxine, in malignant glioma through binding to a cognate thyroid hormone receptor on the αvβ3 integrin. Approaches to block its activity are now explored in preclinical studies.
Antigen-Antibody Complex as Therapeutic Vaccine for Viral Hepatitis B (1999)

In a previous study, hepatitis B surface antigen (HBsAg) complexed to human anti-HBs immunoglobulins (HBIG) in excess of HBsAg was used as therapeutic vaccine to treat chronic hepatitis B patients and promising results were obtained. To study the mechanisms of this approach, mice were immunized with HBsAg or IC (immunogenic complex, i.e. HBsAg complexed with mouse polyclonal anti-HBs). Studies indicate that IC induced enhanced immune responses by increasing uptake of HBsAg through Fc receptors on antigen presenting cells and modulated HBsAg processing and presentation. This modulation led to stimulation of T cell responses, and increased production of IL-2 and IFN-gamma. Assay for antibody subclasses showed that higher ratio of IgG 2a was observed in the IC immunized group, which correlated with the production of lymphokine pattern. When alum was used as the adjuvant, though antibody response was enhanced, production of cytokines decreased. When DNA from a recombinant plasmid was added to IC as an adjuvant, the titer of anti-HBs was significantly higher than those in mice immunized only with the DNA or the IC. Since DNA immunization can induce both cellular and humoral immune responses, combined immunization using IC and DNA might serve as another type of therapeutic vaccine for viral hepatitis B.
Prostate-specific antigen in milk of lactating women (1995)

Prostate-specific antigen (PSA) is believed to be a highly specific marker for normal and cancerous prostatic tissue. We recently found that 30-40% of breast tumors produce PSA. Other data from our group suggest that normal breast can also produce PSA under conditions of stimulation by steroid hormones. In addition, we detected PSA in amniotic fluid. Here we report the presence of PSA in breast milk of lactating women. PSA concentrations in breast milk were quite variable, ranging from < 0.01 microgram/L in 4 of 38 milks to 350 micrograms/L; the median was 0.47 microgram/L. PSA concentration in breast milk was not correlated with mother's age or the sex of the newborn. It did tend to decrease with increasing time postdelivery, but was still detectable 2 weeks postdelivery. PSA in milk was equally measurable by a highly sensitive PSA assay based on time-resolved fluorometry and by the IMx automated PSA method. As confirmed by Western blot analysis, PSA in milk was present predominantly in its 33-kDa form; the PSA-alpha 1-antichymotrypsin complex (100 kDa) was also present but its concentration was < 25% of total PSA. We conclude that the female breast can produce PSA and that PSA is secreted into the milk during lactation; however, the biological role of PSA in milk is unknown. These and other data presented by our group suggest that PSA, a serine protease, may play a role in control of growth in mammary and other tissues through regulation of growth factors, cytokines, and growth-factor-binding proteins.
Synchronized MIMD computing (1994)

Fast global synchronization provides simple, efficient solutions to many of the system problems of parallel computing. It achieves this by providing composition of both performance and correctness. If you understand the performance and meaning of parall
Cloning of the gene encoding peptide-binding protein 74 shows that it is a new member of the heat shock protein 70 family. (1993)

We have previously described peptide-binding proteins of 72 and 74 kDa (PBP72/74), which have been implicated as playing a role in antigen processing and are serologically related to the 70-kDa heat shock protein (hsp70) family. Here we report the cloning and sequencing of the cDNA encoding PBP74 in mice and in humans, accomplished by using amino acid sequence information obtained from the purified protein. We show that PBP74 is highly homologous to members of the hsp70 family but, significantly, is not identical to any known member of this family. Inspection of the cDNA nucleotide sequence indicates that it encodes a 46-residue N-terminal peptide which is not present in the mature protein. Transcription and translation in vitro of the PBP74 cDNA verified that it encodes a form of PBP74 which is larger than the mature protein. The presequence does not conform to known motifs for organelle-targeting sequences, and at present, its function is not known. By confocal microscopy, PBP74 was localized to cytoplasmic vesicles but not to the nucleus, mitochondria, or plasma membrane by using antibodies specific for the N-terminal 16 residues of PBP74. By RNA filter hybridization analysis, PBP74 mRNAs are detected in all cell types tested. Exposure of cells to heat shock does not result in an increase in the mRNA levels of PBP74, unlike the dramatic increase observed for the stress-inducible hsp70 mRNA. Thus, PBP74 appears to be a constitutive, new member of the hsp70 family.
Research feature - Comparison of three vertical search spiders (2003)

The Web's dynamic, unstructured nature makes locating resources difficult. Vertical search engines solve part of the problem by keeping indexes only in specific domains. They also offer more opportunity to apply domain knowledge in the spider applications that collect content for their databases. The authors used three approaches to investigate algorithms for improving the performance of vertical search engine spiders: a breadth-first graph-traversal algorithm with no heuristics to refine the search process, a best-first traversal algorithm that uses a hyperlink-analysis heuristic, and a spreading-activation algorithm based on modeling the Web as a neural network.
Synthesis and Electronic Structure of Cationic, Neutral, and Anionic Bis(imino)pyridine Iron Alkyl Complexes: Evaluation of Redox Activity in Single-Component Ethylene Polymerization Catalysts (2010)

A family of cationic, neutral, and anionic bis(imino)pyridine iron alkyl complexes has been prepared, and their electronic and molecular structures have been established by a combination of X-ray diffraction, Mössbauer spectroscopy, magnetochemistry, and open-shell density functional theory. For the cationic complexes, [((iPr)PDI)Fe-R][BPh(4)] ((iPr)PDI = 2,6-(2,6-(i)Pr(2)-C(6)H(3)N═CMe)(2)C(5)H(3)N; R = CH(2)SiMe(3), CH(2)CMe(3), or CH(3)), which are known single-component ethylene polymerization catalysts, the data establish high spin ferrous compounds (S(Fe) = 2) with neutral, redox-innocent bis(imino)pyridine chelates. One-electron reduction to the corresponding neutral alkyls, ((iPr)PDI)Fe(CH(2)SiMe(3)) or ((iPr)PDI)Fe(CH(2)CMe(3)), is chelate-based, resulting in a bis(imino)pyridine radical anion (S(PDI) = 1/2) antiferromagnetically coupled to a high spin ferrous ion (S(Fe) = 2). The neutral neopentyl derivative was reduced by an additional electron and furnished the corresponding anion, [Li(Et(2)O)(3)][((iPr)PDI)Fe(CH(2)CMe(3))N(2)], with concomitant coordination of dinitrogen. The experimental and computational data establish that this S = 0 compound is best described as a low spin ferrous compound (S(Fe) = 0) with a closed-shell singlet bis(imino)pyridine dianion (S(PDI) = 0), demonstrating that the reduction is ligand-based. The change in field strength of the bis(imino)pyridine coupled with the placement of the alkyl ligand into the apical position of the molecule induced a spin state change at the iron center from high to low spin. The relevance of the compounds and their electronic structures to olefin polymerization catalysis is also presented.
Refinement and Validation of an Alternative Bioassay for Potency Testing of Therapeutic Botulinum Type A Toxin (1996)

The type A neurotoxin produced by Clostridium botulinum is a potent neuromuscular blocking agent which causes paralysis by preventing the release of neurotransmitter from motor neurones. This property has led to the use of the toxin in the treatment of a number of neuromuscular diseases involving muscle spasms. At present, the only recognised assay with the specificity and sensitivity to estimate accurately the potency of botulinum toxin in clinical preparations is bioassay, in which lethality is used as the end point. Refinement of this assay, with respect to the end point, was explored on the basis of the development of flaccid paralysis of muscles following subcutaneous injection of the toxin at the inguinocrural region. Potency estimates, relative to in house reference preparations, for different therapeutic preparations obtained using flaccid paralysis as a scored response gave excellent agreement with estimates obtained in independent assay using the currently required control method. This study demonstrates that an alternative, more humane bioassay for potency testing of clostridia neurotoxins gives valid estimates equivalent to those currently in use.
Electrical switching in AgI based fast ion conducting glasses: Possibility for newer applications (1995)

A current controlled, high speed, near ideal electrical switching has been observed for the first time in microwave prepared AgI based fast ion conducting glasses. The switching is found to be memory type, which is not reverted to OFF state by the application of a resetting current pulse. The threshold fields exhibit a linear dependence on the sample thickness, with the fields decreasing with the increasing thickness. Also, the switching fields are almost independent of the temperature, clearly indicating that the memory switching in these samples is nonthermal in nature. The above results are satisfactorily explained on the basis of a chemical model.
Interleukin-2 (IL-2) gene therapy with allogeneic fibroblasts in the CT-26 model of murine colorectal carcinoma (1997)

We previously demonstrated the efficacy of a genetically engineered vaccine composed of syngeneic tumor cells mixed with syngeneic, IL-2 gene transduced fibroblasts in the CT-26 model of murine colorectal carcinoma. In this report, we describe a more practical approach to fibroblast mediated IL-2 gene therapy that employs syngeneic tumor cells mixed with allogeneic, IL-2 gene transduced fibroblasts. BALB/c mice were challenged with an injection of CT-26, 14 days following immunization with IL-2 modified syngeneic BALB/c 3T3 (H-2(d)) or allogeneic C3H 3T3 (H-2(k)) fibroblasts mixed with irradiated CT-26. Both syngeneic and allogeneic IL-2 modified fibroblasts provided significantly better protection compared to animals treated with control fibroblasts (syngeneic IL-2 fibroblasts 32/40-80% vs. control 15/45-33%, p<0.01; allogeneic IL-2 fibroblasts 25/37-68% vs. control 15/45-3345, p<0.01). There was no statistically significant difference between the groups immunized with syngeneic or allogeneic IL-2 modified fibroblasts. These findings support the evaluation of allogeneic IL-2 modified fibroblasts as a practical form of cytokine gene therapy for cancer.