gebhart/patrepeval huggingface dataset:
Covalent Conjugation of Small-Molecule Adjuvants to Nanoparticles Induces Robust Cytotoxic T Cell Responses via DC Activation (2016)

Specific recognitions of pathogen associated molecular patterns by Toll-like receptors (TLRs) initiate dendritic cell (DC) activation, which is critical for coordinating innate and adaptive immune responses. Imidazoquinolines as small-molecule TLR7 agonists often suffer from prompt dissemination and short half-life in the bloodstream, preventing their localization to the corresponding receptors and effective DC activation. We postulated that covalent incorporation of imidazoquinoline moieties onto the surface of biocompatible nanoparticles (∼30 nm size) would enhance their chemical stability, cellular uptake efficiency, and adjuvanticity. The fully synthetic adjuvant-nanocomplexes led to successful DC activation at lower nanomolar doses compared with free small-molecule agonists. Once a model antigen such as ovalbumin was used for immunization, we found that the nanocomplexes promoted an unusually strong cytotoxic T lymphocyte response, revealing their unique immunostimulatory capacity benefiting from multivalency and efficient transport to endosomal TLR7.
Δ-4-Androstene-3,17-Dione Binds Androgen Receptor, Promotes Myogenesisin Vitro, and Increases Serum Testosterone Levels, Fat-Free Mass, and Muscle Strength in Hypogonadal Men (2005)

Previous studies of Delta 4-androstene-3,17-dione (4-androstenedione) administration in men have not demonstrated sustained increments in testosterone levels, fat-free mass (FFM), and muscle strength, and failure to demonstrate androstenedione's androgenic/anabolic effects has stifled efforts to regulate its sales. To determine whether 4-androstenedione has androgenic/anabolic properties, we evaluated its association with androgen receptor (AR) and its effects on myogenesis in vitro. Additionally, we studied the effects of a high dose of 4-androstenedione on testosterone levels, FFM, and muscle strength in hypogonadal men. We determined the dissociation constant (K(d)) for 4-androstenedione using fluorescence anisotropy measurement of competitive displacement of fluorescent androgen from AR ligand-binding domain. AR nuclear translocation and myogenic activity of androstenedione were evaluated in mesenchymal, pluripotent C3H10T1/2 cells, in which androgens stimulate myogenesis through an AR pathway. We determined effects of a high dose of androstenedione (500 mg thrice daily) given for 12 wk on FFM, muscle strength, and hormone levels in nine healthy, hypogonadal men. 4-Androstenedione competitively displaced fluorescent androgen from AR ligand-binding domain with a lower affinity than dihydrotestosterone (K(d), 648 +/- 21 and 10 +/- 0.4 nm, respectively). In C3H10T1/2 cells, 4-androstenedione caused nuclear translocation of AR and stimulated myogenesis, as indicated by a dose-dependent increase in myosin heavy chain II+ myotube area and up-regulation of MyoD protein. Stimulatory effects of 4-androstenedione on myosin heavy chain II+ myotubes and myogenic determination factor expression were attenuated by bicalutamide, an AR antagonist. Administration of 1500 mg 4-androstenedione daily to hypogonadal men significantly increased serum androstenedione, total and free testosterone, estradiol, and estrone levels and suppressed SHBG and high-density lipoprotein cholesterol levels. 4-androstenedione administration was associated with significant gains in FFM (+1.7 +/- 0.5 kg; P = 0.012) and muscle strength in bench press (+4.3 +/- 3.1 kg; P = 0.006) and leg press exercises (+18.8 +/- 17.3 kg; P = 0.045). 4-androstenedione is an androgen that binds AR, induces AR nuclear translocation, and promotes myogenesis in vitro, with substantially lower potency than dihydrotestosterone. 4-androstenedione administration in high doses to hypogonadal men increases testosterone levels, FFM, and muscle strength, although at the dose tested, the anabolic effects in hypogonadal men are likely because of its conversion to testosterone.
A mutation in the dystrophin gene selectively affecting dystrophin expression in the heart. (1995)

We have previously shown in a large X-linked pedigree that a deletion removing the dystrophin muscle promoter, the first muscle exon and part of intron 1 caused a severe dilated cardiomyopathy with no associated muscle weakness. Dystrophin expression was present in the muscle of affected males and transcription studies indicated that this dystrophin originated from the brain and Purkinje cell isoforms, upregulated in this skeletal muscle. We have now studied dystrophin transcription and expression in the heart of one member of this family. In contrast to the skeletal muscle, dystrophin transcription and expression were absent in the heart, with the exception of the distal Dp71 dystrophin isoform, normally present in the heart. The 43- and 50-kD dystrophin-associated proteins were severely reduced in the heart, despite the presence of Dp71, but not in skeletal muscle. The absence of dystrophin and the down-regulation of the dystrophin-associated proteins in the heart accounted for the severe cardiomyopathy in this family. The mutation present in these males selectively affects dystrophin expression in the heart; this could be secondary to the removal of cardiac-specific regulatory sequences. This family may represent the first example of a mutation specifically affecting the cardiac expression of a gene, present physiologically in both the skeletal and cardiac muscles.
Characterization of N-glycolylneuraminic acid-containing gangliosides as tumor-associated Hanganutziu-Deicher antigen in human colon cancer. (1985)

Hanganutziu-Deicher (HD) antigen-active N-glycolylneuraminic acid (NeuGc)-containing gangliosides were isolated and characterized from human colon cancer tissues. The antigenic gangliosides were detected by thin-layer chromatography by our newly developed method (H. Higashi, Y. Fukui, S. Ueda, S. Kato, Y. Hirabayashi, M. Matsumoto, and M. Naiki. J. Biochem., 95: 1517-1520, 1984) of enzyme immunostaining using affinity-purified chicken antibody against hematoside containing NeuGc (II3NeuGc-LacCer) and horseradish peroxidase-conjugated rabbit anti-chicken lgG. One to six species of the antigenic gangliosides were isolated from seven of 16 cases of colon cancer, whereas no antigenic compound was detected in all apparently normal colorectal tissues from 17 individuals without colorectal cancer. Tissues from different patients showed different patterns of molecular species of the antigenic gangliosides. Densitometric determination indicated that HD antigenic sialic acid, NeuGc, accounted for about 1% or less of the total lipid-bound sialic acids. Four species of antigenic gangliosides were identified as hematoside and hematoside-containing O-acyl ester (II3NeuGc-LacCer and II3 4- or 7-O-acyl-NeuGc-LacCer), GM2-containing NeuGc (II3NeuGc-GgOse3Cer), and sialylparagloboside (IV3NeuGc-nLcOse4Cer) by their behaviors on 2-dimensional thin-layer chromatography, and the effects of mild alkaline treatment, sialidase treatment, periodate oxidation, and endo-beta-galactosidase treatment.
IP multicast for mobile hosts (1997)

We present alternative designs for efficiently supporting multicast for mobile hosts on the Internet. Methods for separately supporting multicasting and mobility along with their possible interactions are briefly described, and then various solutions to the combined problem are explored. We examine three different multicast delivery mechanisms and compare them based on their efficiency and impact on host protocol software. We describe proposals for integrating multicasting and mobility in the Internet architecture. We first present IP extensions for host mobility and other extensions for multicasting. We then examine local multicasting mechanisms, focusing on a group membership protocol that is optimized for wireless point-to-point links. Next, we examine the problems of sending and receiving multicast datagrams in a wide area network. For multicast reception, we describe three alternative proposals and compare them by examining both their applicability and their performance, as well as possible tradeoffs among the two.
Characterization ofO-glycosylation sites in recombinant B-chain of platelet-derived growth factor expressed in yeast using liquid secondary ion mass spectrometry, tandem mass spectrometry and edman sequence analysis (1990)

High-performance tandem mass spectrometry has been employed to structurally characterize intact O-linked glycopeptides and establish the complexity and extent of glycosylation for recombinant human platelet-derived growth factor B chain (rhPDGF-B) expressed in yeast. In addition, liquid secondary ion mass spectrometry (LSIMS) and Edman degradation have been employed to verify the protein sequence. LSIMS of high-performance liquid chromatographically fractionated proteolytic digests confirmed the complete amino acid sequence predicted by the human PDGF-B gene structure. Potential glycopeptides (as indicated by a mass shift of 162 or 324 Da from the mass of a predicted cleavage product) were sequenced using tandem mass spectrometry and Edman degradation. Ultraviolet matrix laser desorption mass spectrometry of rhPDGF-B dimer was used to determine the molecular weight distribution for the intact recombinant glycoprotein. In addition to the presence of unmodified peptides, corresponding peptides bearing monomannosyl moieties were found on serine 26 and threonines 20, 63, 88, 90 and 101. Further, dimannosyl moieties were found on threonines 6 and 63. These data reveal the presence of O-linked glycosylation at sites which do not fortify the concept of a consensus sequence involving proline residues, but which strengthen the concept of secondary and tertiary structure requirements. The advantages of high-energy collisionally induced dissociation analysis of O-linked glycopeptides over conventional base elimination and borohydride reduction and other mass spectrometric techniques are presented for the first time.
Colloidal Particles as Immunodiagnostics: Preparation and FFF Characterization (1999)

The preparation and characterization of two types of particles with covalently attached proteins is described. The first type is a Pluronic F108 coated polystyrene latex (PS) where the surfactant has been end-group activated with pyridyl disulfide groups (PS-F108-PDS) for the subsequent protein attachment, while the second type is a synthesized poly(styrene/acrolein) latex (PSA), whose surface aldehyde groups allow a direct immobilization of protein via Schiff's base formation. Human immunoglobulin (IgG) was first covalently bound to the surface of these particles and in a second step a polyclonal antibody directed against this protein, namely a rabbit anti human IgG (α-IgG), was specifically adsorbed. Determinations of the surface concentrations of protein adsorbed in the two steps were accomplished by the sedimentation field-flow fractionation (SdFFF) technique, as well as by the more conventional bicinchoninic acid (μBCA) and amino acid analysis (AAA) methods, whereby a reasonable agreement was found between the three. It is shown that the mode of linking antigen (IgG) to surface has a significant influence on the efficiency of its antibody binding, with the tethered attachment providing greater access to the antibody. This study represents the first example of SdFFF characterization of a multi-layered composite where the different layers consisted of different chemical species.
Cetuximab and First-Line Taxane/Carboplatin Chemotherapy in Advanced Non–Small-Cell Lung Cancer: Results of the Randomized Multicenter Phase III Trial BMS099 (2010)

PURPOSE To evaluate the efficacy of cetuximab plus taxane/carboplatin (TC) as first-line treatment of advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS This multicenter, open-label, phase III study enrolled 676 chemotherapy-naïve patients with stage IIIB (pleural effusion) or IV NSCLC, without restrictions by histology or epidermal growth factor receptor expression. Patients were randomly assigned to cetuximab/TC or TC. TC consisted of paclitaxel (225 mg/m(2)) or docetaxel (75 mg/m(2)), at the investigator's discretion, and carboplatin (area under the curve = 6) on day 1 every 3 weeks for < or = six cycles; cetuximab (400 mg/m(2) on day 1, 250 mg/m(2) weekly) was administered until progression or unacceptable toxicity. The primary end point was progression-free survival assessed by independent radiologic review committee (PFS-IRRC); overall response rate (ORR), overall survival (OS), quality of life (QoL), and safety were key secondary end points. PFS and ORR assessed by investigators were also evaluated. Results Median PFS-IRRC was 4.40 months with cetuximab/TC versus 4.24 months with TC (hazard ratio [HR] = 0.902; 95% CI, 0.761 to 1.069; P = .236). Median OS was 9.69 months with cetuximab/TC versus 8.38 months with TC (HR = 0.890; 95% CI, 0.754 to 1.051; P = .169). ORR-IRRC was 25.7% with cetuximab/TC versus 17.2% with TC (P = .007). The safety profile of this combination was manageable and consistent with its individual components. CONCLUSION The addition of cetuximab to TC did not significantly improve the primary end point, PFS-IRRC. There was significant improvement in ORR by IRRC. The difference in OS favored cetuximab but did not reach statistical significance.
Recombinant CD40 ligand stimulation of murine B cell growth and differentiation: cooperative effects of cytokines (1993)

The ligand for the B cell surface antigen CD40 was recently cloned from a murine thymoma cDNA library and shown to be expressed on activated T cells. In this study, we investigate the biological effects of murine recombinant CD40 ligand. The recombinant CD40 ligand expressed on the CV-1/EBNA monkey fibroblast cell line directly activated resting B cell to express elevated levels of cell surface class II major histocompatibility complex and CD23 molecules. CD40 ligand also stimulated B cell proliferation, reaching maximal levels on day 2 of culture and declining thereafter. This effect was positively regulated by other cytokines, most notably interleukin (IL)-4 and IL-5. By itself, CD40 ligand had no effect upon immunoglobulin secretion by B cells. However, when B cells were treated with CD40 ligand plus cytokines, immunoglobulin secretion was stimulated in a cytokine-dependent and isotype-specific manner. IL-4 was a potent co-stimulator of IgE and IgG1 in the presence of CD40 ligand, and IL-5 acted synergistically with IL-4 in these responses as well as in IgM and IgG3 production. Taken together, the results indicate that CD40 ligand is a potent regulatory molecule for B cell growth and differentiation, and its activities are potentiated in a cytokine-specific manner.
Modeling, Fabrication, and Optimization of Niobium Cavities (2005)

All technologies for the transmutation of nuclear waste require a large source of neutrons. One of the principal methods of generating these neutrons is by using a particle accelerator to bombard a heavy metal target. One of the more promising designs for particle accelerators for transmutation systems is the Superconducting Radio Frequency (RF) high-current linear accelerator (linac). The power supplies for these systems have three major components: niobium cavities, power couplers, and cryomodules. This research project will develop models to predict the behavior and performance of the niobium cavities, which will then be used to design and optimize the superconducting structures.\nThe overall goal of this research project is to develop a stronger understanding of the multipacting phenomenon, and to use this understanding to optimize the design of niobium cavities to minimize or eliminate this parasitic phenomenon.\nTo achieve this goal, the research team established the following objectives for the first year of this program: To study the effect of multipacting on niobium cavities with single and multiple cells; To improve the uniformity of surface finish in chemical etching; to investigate the relationship between the shape and surface condition of the cell and its performance; And, to provide a systematic approach for improving the performance of the niobium cavities.
Principles of knowledge representation and reasoning: proceedings of the second International Conference (KR91) (1991)

The proceedings of the Second International Conference on [title] held in Cambridge, Massachusetts, April 1991, comprise 55 papers on topics including the logical specifications of reasoning behaviors and representation formalisms, comparative analysis of competing algorithms and formalisms, and ana
Requirements for the establishment of high-titered human monoclonal antibodies against tetanus toxoid using the Epstein-Barr virus technique. (1981)

Abstract Epstein-Barr Virus (EBV) has been used in other laboratories to “immortalize” human B cell populations producing antibodies against a variety of haptens and antigens. In the present study we investigated the conditions necessary to achieve 100-fold higher amounts of stable monoclonal anti-tetanus toxoid antibody production than previously achieved. Peripheral blood mononuclear cells were enriched for B cells (&amp;gt; 85 to 90% slg+) by depletion of E+ cells and adherent monocytes. B cells from a multiply immunized (4 times) donor taken 2 to 3 wk after the last injection of tetanus toxoid (TT) contained the highest frequency of TT-binding cells and produced the greatest amount of anti-TT antibody 8 days after transformation with EBV. Antigen-binding cells were detected by biotinylated TT followed by FITC-conjugated avidin, and antibody was measured in culture supernatants with an ELISA technique using an affinity-purified human anti-TT immunoglobulin as standard. The method of preselecting antigen-binding cells prior to EBV transformation was critical. Negative preselection by removal of cells not binding antigen was most successful. B cells were allowed to bind TT and cap for 6 hr, after which time they had shed most of their surface Ig receptors. The non-TT-binding, slg+ cells were removed by rosetting with SRBC coupled to the F(ab′)2 portion of rabbit anti-human Ig. This technique resulted in a 6-fold increase in TT binding B cells and a 3-fold increase in anti-TT antibody production. Positive selection of TT-binding cells by rosetting with TT-coupled SRBC or by sorting “bright” (strongly binding) cells on the FACS was unsuccessful. Only a minority (2%) of the EBV-infected cells secreted antibody, as detected in a PFC assay, and bulk cultures quickly declined to 0 levels of anti-TT antibody production by 10 wk. Cloning of early cultures by limiting dilution on irradiated PBL feeder layers (cloning efficiency 30%) was necessary to obtain 3 clones producing relatively high amounts (1000 ng/ml) of anti-TT antibody of the IgM-kappa class. The monoclonality of this antibody was confirmed by isoelectric focusing. These clones have been stable to the present time (&amp;gt;6 mo) and were sub-cloned. In summary, we have outlined the immunization, preselection, and cloning techniques necessary to optimize the establishment of stable, long-term B cell clones producing relatively high amounts of anti-TT antibody. These techniques should be applicable to other protein antigens.
Advancements in 3D interactive devices for virtual environments (2003)

New commercially available interactive 3D tracking devices and systems for use in virtual environments are discussed. InterSense originally introduced the IS-900 scalable-area hybrid tracking system for virtual environments in 1999. In response to customer requests, we have almost completely revamped the system over the past two years. The major changes include a drastic 3-fold reduction in the size and weight of the wearable sensor devices, introduction of wireless tracking capability, a standardized I2C interface to allow OEM system integrators to add additional custom controls, and evolution of the system software interfaces, the performance, and the price. This paper will briefly describe the underlying technology changes that have allowed these advances to occur, and will outline some of the configuration possibilities that are now supported. Specific examples of how these devices and systems are being used to improve productivity in oil & gas seismic analysis & well field planning; automotive design & test; and, industrial/military training applications will be used to illustrate. Customization standards and future developments are discussed.
IP Payload Compression Protocol (IPComp) (2001)

This document describes a protocol intended to provide lossless compression for Internet Protocol datagrams in an Internet environment.
Dementia and neuropathology in Lewy body disease. (1993)

In order to elucidate the pathological differences between demented and nondemented patients with Lewy body disease, brains from 35 patients were clinicopathologically examined. In diffuse Lewy body disease, cortical lesions, including numerous Lewy bodies and senile changes, were found to be responsible for the dementia. In some of the cases with the brain-stem type of Lewy body disease, the dementia was attributed to an Alzheimer pathology, while in many cases the various combinations of degeneration in the subcortical nuclei, mainly the nucleus basalis of Meynert and locus ceruleus, played a major role in the dementia. Forty-four Japanese cases with diffuse Lewy body disease were reviewed. Then diffuse Lewy body disease was divided into two forms: a common form (33 cases) and a pure form (11 cases). In the common form, all cases showed progressive cortical dementia in the presenile or senile period. Parkinson syndrome was usually marked in the terminal stage. However, about a fifth of the cases had no parkinsonism. Neuropathologically, the common form had many concomitant senile changes in the cerebral cortex. Most cases with the pure form showed juvenile Parkinson syndrome followed by progressive cortical dementia, while a few cases were of presenile or senile occurrence. Neuropathologically, the pure form had no or few senile changes. This suggests that numerous cortical Lewy bodies alone can cause cortical dementia.
Peritoneal endometriosis: validation of an in-vivo model (2001)

This in-vivo model is a promising tool to test the effect of compounds such as different hormone agonists/antagonists or anti-angiogenic factors to develop new therapeutic concepts in endometriosis.
Proximity Communication flip-chip package with micron chip-to-chip alignment tolerances (2009)

As performance gains from scaling silicon slow, improvements in system performance must come from tighter integration. Proximity communication (PxC) enables designers to aggregate multiple chips that perform as a single large piece of silicon. PxC enables the heterogeneous integration of an optimized mix of process technology and functionality, such as DRAM, flash memory, and CMOS processor chips. PxC enables silicon die placed face-to-face to communicate using close-field capacitive coupling. In a 90 nm standard CMOS technology, using the packaging techniques described in this paper, PxC provides chip-to-chip latency of 2.5 ns at 4 Gb/s per channel with less than 2.5 mW/Gb/s, an areal bandwidth density of over 2 Tb/smm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> , and a BER less than 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-18</sup> . In this paper, we describe one of our packaging prototypes that enables PxC and provides its system-level benefits.