gebhart/patrepeval huggingface dataset:
New Product Development in the EEC 1986‐1995 (1990)

Details a study in five European countries on the market for nutritionally modified foods, particularly new balanced products. These are defined, and the major themes of reduction, substitutes, additions and “free from” are considered. The impact of trends on consumers, by country and region, and by typology are discussed. Practical consequences for production structures, marketing and distribution channels, and commercial and institutional catering are examined. Some marketing requirements and laws are suggested.
Ultrasound quantitation of respiratory organ motion in the upper abdomen (1994)

Organ motion can cause artefacts in abdominal imaging particularly with magnetic resonance imaging (MRI), and may often limit the diagnostic quality of an image. If spatial resolution and image quality are to improve in MRI and other imaging techniques, a more detailed understanding of organ motion is required. Despite the importance of organ motion little quantitative information is available to date. This study was the continuation of work instigated to investigate and quantify respiratory movements of upper abdominal organs for a group of healthy volunteers in order to provide the design criteria for a motion test object for use in MRI. A previous phase of the project allowed construction of a test object but refinements were needed to represent respiratory motion more closely as a consequence of the data presented in this paper. Improvements in the scanning technique and the recording procedure have revealed that, contrary to our initial findings, motion of the diaphragm and liver is predominantly in the superior-inferior (SI) direction with an average displacement (+/- SD) (quiet respiration) of 12 +/- 7 mm (range 7-28 mm) and 10 +/- 8 mm (range 5-17 mm), respectively. For some volunteers, motion of the kidneys can be complex, especially during deep inspiration. New data have been provided by this phase of the motion study on the displacement, velocity and acceleration of abdominal organs as a function of time. These data show that MRI motion artefact reduction techniques which assume that either organ displacement, velocity or acceleration are constant are only applicable during certain phases of the respiratory cycle.
Multimodal Protein Constructs for Herbivore Insect Control (2012)

Transgenic plants expressing combinations of microbial or plant pesticidal proteins represent a promising tool for the efficient, durable control of herbivorous insects. In this review we describe current strategies devised for the heterologous co-expression of pesticidal proteins in planta, some of which have already shown usefulness in plant protection. Emphasis is placed on protein engineering strategies involving the insertion of single DNA constructs within the host plant genome. Multimodal fusion proteins integrating complementary pesticidal functions along a unique polypeptide are first considered, taking into account the structural constraints associated with protein or protein domain grafting to biologically active proteins. Strategies that allow for the co- or post-translational release of two or more pesticidal proteins are then considered, including polyprotein precursors releasing free proteins upon proteolytic cleavage, and multicistronic transcripts for the parallel translation of single protein-encoding mRNA sequences.
Correlates of protection to influenza virus, where do we go from here? (2013)

Influenza vaccination is the cornerstone of prophylaxis. The regulatory authorities currently annually license vaccines based on serum antibodies directed toward the major surface glycoprotein haemagglutinin (HA). The most commonly used serological test, the haemagglutination inhibition (HI) assay utilizes red blood cells, which show considerable biological variation. There is a need for validated, standardized assays to reduce laboratory variation steps that are currently being taken by the regulatory agencies. Here we examine the historical evidence for defining the HI titer ≥ 40 as a surrogate correlate of protection and examine alternative assays. Moreover, the immune response to influenza is multifacated and there are probably multiple correlates of protection. We conclude there is a need for detailed immunological analysis including kinetic studies and head to head comparison of vaccines by a range of immunological assays to further define correlates of protection.
CD4+ T cell–independent vaccination against Pneumocystis carinii in mice (2001)

Host defenses are profoundly compromised in HIV-infected hosts due to progressive depletion of CD4+ T lymphocytes. Moreover, deficient CD4+ T lymphocytes impair vaccination approaches to prevent opportunistic infection. Therefore, we investigated a CD4+ T cell-independent vaccine approach to a prototypic AIDS-defining infection, Pneumocystis carinii (PC) pneumonia. Here, we demonstrate that bone marrow-derived dendritic cells (DCs) expressing the murine CD40 ligand, when pulsed ex vivo by PC antigen, elicited significant titers of anti-PC IgG in CD4-deficient mice. Vaccinated animals demonstrated significant protection from PC infection, and this protection was the result of an effective humoral response, since adoptive transfer of CD4-depleted splenocytes or serum conferred this protection to CD4-deficient mice. Western blot analysis of PC antigen revealed that DC-vaccinated, CD4-deficient mice predominantly reacted to a 55-kDa PC antigen. These studies show promise for advances in CD4-independent vaccination against HIV-related pathogens.
Pharmacokinetics of Monoclonal Antibodies (2006)

This chapter contains sections titled: Introduction The Human Immune System The Cellular Immune Response The Humoral Immune Response Physiological Antibodies Classes of Antibodies Immunoglobulin G Immunoglobulins A, D, M, and E Chemical Structure of Antibodies Therapeutic Antibodies Therapeutic Polyclonal Antibodies Therapeutic mAbs Murine mAbs Chimeric mAbs Humanized mAbs Human mAbs Further Species of mAbs Effector Functions and Modes of Action of Antibodies Biological Effector Functions of mAbs Modes of Action of mAbs Antibody-Dependent Cellular Cytotoxicity (ADCC) Complement-Dependent Cytotoxicity Blockage of Interaction between (Patho)Physiological Substance and Antigen Conjugated Unlabeled mAbs Radioactively Labeled mAbs Prerequisites for mAb Therapy The Patient The Antibody The Target Cell The Antigen Issues in the Bioanalysis of Antibodies Catabolism of Antibodies Proteolytic Degradation Neonatal Fc Receptor (Fc-Rn) Pharmacokinetic Characteristics of mAbs Absorption Distribution Transport Volume of Distribution Types of Binding Elimination Clearance Proteolysis Binding to Antigen Binding to Anti-Idiotype Antibodies Drug Interaction Studies Comparison of Pharmacokinetics of mAbs and Traditional Small-Molecule Drugs Pharmacokinetic Modeling of mAbs Noncompartmental Pharmacokinetic Analysis Individual Compartmental Pharmacokinetic Analysis Population Pharmacokinetic Analysis Structural Submodel Statistical Submodel Covariate Submodel Pharmacodynamics of mAbs Conclusions References
EGF Induced RET Inhibitor Resistance inCCDC6-RETLung Cancer Cells (2016)

EGF could trigger resistance to RET inhibition in CCDC6-RET lung cancer cells, and endothelial cells may confer resistance to RET inhibitors by EGF. E7080 and other RET inhibitors may provide therapeutic benefits in the treatment of RET-positive lung cancer patients.
Identification of a NewArabidopsisDisease Resistance Locus,RPS4,and Cloning of the Corresponding Avirulence Gene,avrRps4,fromPseudomonas syringaepv.pisi (1996)

A molecular genetic approach was used to study the interaction between Arabidopsis and an avirulence gene from Pseudomonas syringae pv. pisi. P. syringae pv. pisi strain 151 induces a hypersensitive response (HR) when inoculated on the Arabidopsis accession Po-1. A genomic cosmid library was constructed from DNA from P. syringae pv. pisi strain 151 and a cosmid was identified that causes the normally virulent P. syringae pv. tomato strain DC3000 to induce an HR on Po-1. The cosmid was subcloned and a 1.2-kb DNA fragment conferring avirulence activity was sequenced. The single significant open reading frame within the 1.2-kb fragment was designated avrRps4. An avrRps4-specific probe hybridizes to DNA from all P. syringae pv. pisi strains tested. P. syringae strains carrying avrRps4 induces an HR on specific accessions of both Arabidopsis and soybean. Arabidopsis accession Ws-0 is resistant to DC3000(avrRps4), whereas accession RLD is susceptible. Resistance segregates as a single dominant locus in a genetic cross between Ws-0 and RLD. This disease resistance locus, RPS4, was mapped to chromosome 5 between the molecular markers sAT2105 and KG-8.
Relationship between MALDI IMS Intensity and Measured Quantity of Selected Phospholipids in Rat Brain Sections (2010)

MALDI IMS positive ion images of rat brain show a regional distribution of phosphocholine species that is striking in the apparent distinctiveness and reproducibility of such depictions. The interpretation of these images, specifically the relationship between MALDI IMS ion intensity and the amount of the phosphocholine (PC) species in the tissue is complicated by numerous factors, such as ion suppression, ion molecule chemistry, and effects of tissue structure. This study was designed to test the hypothesis that the intensity of PC molecular species does relate to the quantity of molecules in a tissue sample. A set of comparison studies for a limited but representative selection of cell-derived PC molecular species was carried out using LC/MS/MS to measure the amounts of these species in brain tissue extracts. There was good correlation between the MALDI IMS ion abundance of PC molecular species and the relative abundance of corresponding PC molecular species in microdissected regions analyzed by LC/MS/MS.
Abstract 2590: Preclinical evaluation of ASG-5ME, a novel antibody-drug conjugate for pancreatic cancer (2010)

Abstract Antibody-drug conjugates (ADCs) have demonstrated promising activity and tolerability profiles in oncology clinical trials, including for Hodgkin lymphoma (brentuzumab vedotin) and breast cancer (trastuzumab-DM1), motivating the development of new ADCs targeting antigens in other prevalent cancers. An immunohistochemical survey of expression of the novel tumor antigen AGS-5 revealed strong staining in 90% of pancreatic cancer specimens tested. Importantly, this staining was largely uniform, with essentially all transformed cells demonstrating membranous staining. This observation along with the observation of equally abundant expression of AGS-5 in prostate and other cancers motivated the development of ASG-5ME, an ADC targeting AGS-5. The ADC is comprised of a fully human IgG2 monoclonal antibody conjugated to the potent tubulin-binding drug monomethylauristatin E, conjugated with an average of 3.7 drug molecules per antibody. Conjugation and analysis of this IgG2 ADC will be discussed. The resulting conjugate demonstrated antigen-dependent internalization and in vitro cytotoxicity at sub-saturating ADC concentrations, as well as potent in vivo antitumor activity in patient-derived xenograft models of pancreatic cancer. ASG-5ME has a long (12 day) T1/2 in mice. Taken together, these results support the clinical evaluation of ASG-5ME for treatment of pancreatic cancer Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2590.
Selective Detection of Hg(II) Ions from Cu(II) and Pb(II) Using AlGaN∕GaN High Electron Mobility Transistors (2007)

Bare Au-gated and thioglycolic acid functionalized Au-gated high electron mobility transistors were used to detect mercury(II) and copper(II) ions. Fast detection of was achieved for thioglycolic acid functionalized sensors. The thioglycolic acid functionalization increased the sensitivity for detection of mercury by 2.5 times over the bare Au-gated surface. Both surfaces had a selectivity of approximately 100-fold over other contaminating ions of sodium, magnesium, and lead and can be easily recycled. Our results show that portable, selective, and fast and sensors can be realized by combining bare Au-gated and thioglycolic acid-functionalized surface in one sensor.
Pressure-induced near infrared spectra response as a valuable source of information for soft tissue classification (2013)

Acquiring near infrared spectra in vivo usually requires a fiber-optic probe to be pressed against the tissue. The applied pressure can significantly affect the optical properties of the underlying tissue, and thereby the acquired spectra. The existing studies consider these effects to be distortions. In contrast, we hypothesize that the pressure-induced spectral response is site- and tissue-specific, providing additional information for the tissue classification. For the purpose of this study, a custom system was designed for dynamic pressure control and rapid acquisition of spectra. The pressure-induced spectral response was studied at three proximate skin sites of the human hand. The diffuse reflectance and scattering were found to decrease with the applied contact pressure. In contrast, the concentrations of chromophores, and consequently the absorption, increased with the applied contact pressure. The pressure-induced changes in the tissue optical properties were found to be site-specific and were modeled as a polynomial function of the applied contact pressure. A quadratic discriminant analysis classification of the tissue spectra acquired at the three proximate skin sites, based on the proposed pressure-induced spectral response model, resulted in a high (90%) average classification sensitivity and specificity, clearly supporting the working hypothesis.
MHC I–associated peptides preferentially derive from transcripts bearing miRNA response elements (2012)

MHC I-associated peptides (MIPs) play an essential role in normal homeostasis and diverse pathologic conditions. MIPs derive mainly from defective ribosomal products (DRiPs), a subset of nascent proteins that fail to achieve a proper conformation and the physical nature of which remains elusive. In the present study, we used high-throughput proteomic and transcriptomic methods to unravel the structure and biogenesis of MIPs presented by HLA-A and HLA-B molecules on human EBV-infected B lymphocytes from 4 patients. We found that although HLA-different subjects present distinctive MIPs derived from different proteins, these MIPs originate from proteins that are functionally interconnected and implicated in similar biologic pathways. Secondly, the MIP repertoire of human B cells showed no bias toward conserved versus polymorphic genomic sequences, were derived preferentially from abundant transcripts, and conveyed to the cell surface a cell-type-specific signature. Finally, we discovered that MIPs derive preferentially from transcripts bearing miRNA response elements. Furthermore, whereas MIPs of HLA-disparate subjects are coded by different sets of transcripts, these transcripts are regulated by mostly similar miRNAs. Our data support an emerging model in which the generation of MIPs by a transcript depends on its abundance and DRiP rate, which is regulated to a large extent by miRNAs.
Degradation of Aromatics and Chloroaromatics byPseudomonassp. Strain B13: Purification and Characterization of 3-Oxoadipate:Succinyl-Coenzyme A (CoA) Transferase and 3-Oxoadipyl-CoA Thiolase (2002)

The degradation of 3-oxoadipate in Pseudomonas sp. strain B13 was investigated and was shown to proceed through 3-oxoadipyl-coenzyme A (CoA) to give acetyl-CoA and succinyl-CoA. 3-Oxoadipate:succinyl-CoA transferase of strain B13 was purified by heat treatment and chromatography on phenyl-Sepharose, Mono-Q, and Superose 6 gels. Estimation of the native molecular mass gave a value of 115,000 +/- 5,000 Da with a Superose 12 column. Polyacrylamide gel electrophoresis under denaturing conditions resulted in two distinct bands of equal intensities. The subunit A and B values were 32,900 and 27,000 Da. Therefore it can be assumed that the enzyme is a heterotetramer of the type A2B2 with a molecular mass of 120,000 Da. The N-terminal amino acid sequences of both subunits are as follows: subunit A, AELLTLREAVERFVNDGTVALEGFTHLIPT; subunit B, SAYSTNEMMTVAAARRLKNGAVVFV. The pH optimum was 8.4. Km values were 0.4 and 0.2 mM for 3-oxoadipate and succinyl-CoA, respectively. Reversibility of the reaction with succinate was shown. The transferase of strain B13 failed to convert 2-chloro- and 2-methyl-3-oxoadipate. Some activity was observed with 4-methyl-3-oxoadipate. Even 2-oxoadipate and 3-oxoglutarate were shown to function as poor substrates of the transferase. 3-oxoadipyl-CoA thiolase was purified by chromatography on DEAE-Sepharose, blue 3GA, and reactive brown-agarose. Estimation of the native molecular mass gave 162,000 +/- 5,000 Da with a Superose 6 column. The molecular mass of the subunit of the denatured protein, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was 42 kDa. On the basis of these results, 3-oxoadipyl-CoA thiolase should be a tetramer of the type A4. The N-terminal amino acid sequence of 3-oxoadipyl-CoA thiolase was determined to be SREVYI-DAVRTPIGRFG. The pH optimum was 7.8. Km values were 0.15 and 0.01 mM for 3-oxoadipyl-CoA and CoA, respectively. Sequence analysis of the thiolase terminus revealed high percentages of identity (70 to 85%) with thiolases of different functions. The N termini of the transferase subunits showed about 30 to 35% identical amino acids with the glutaconate-CoA transferase of an anaerobic bacterium but only an identity of 25% with the respective transferases of aromatic compound-degrading organisms was found.
Adhesion Molecules in Multiple Sclerosis (2000)

Up-regulated adhesion molecules in blood and CSF indicate sustained potential for inflammation in the CNS throughout the clinical spectrum of MS. Therapies interfering with cell adhesion may be of key importance in suppressing MS.
14C-labeling of a novel atypical β-adrenoceptor agonist, SM-11044 (1996)

(2S,3R)-2-[3-(4-Fluorophenyl)]propylamino-3-(3,4-dihydroxyphenyl)-3-hydroxypropionic acid pyrrolidine amide hydrobromide (SM-11044) was labeled with carbon-14 for use in mammalian metabolic studies. The synthesis was achieved according to the scheme shown in Fig. 5. Grignard reaction of 3,4-methylenedioxy-phenylmagnesium bromide with [14C]carbon dioxide liberated from barium [14C]carbonate ((UNDERLINE)6(/UNDERLINE)) gave the acid ((UNDERLINE)5(/UNDERLINE)). Reduction of (UNDERLINE)5(/UNDERLINE) with lithium aluminum hydride followed by oxidation of the resulting benzyl alcohol ((UNDERLINE)11(/UNDERLINE)) with chromium oxide-pyridine complex afforded the aldehyde ((UNDERLINE)3(/UNDERLINE)). Condensation of (UNDERLINE)3(/UNDERLINE) with the optically active (R)-oxazolidinone ((UNDERLINE)10(/UNDERLINE)) yielded the alcohol ((UNDERLINE)12(/UNDERLINE)). Catalytic hydrogenation of (UNDERLINE)12(/UNDERLINE) and subsequent hydrolysis produced the optically active β-hydroxy-α-amino acid ((UNDERLINE)2(/UNDERLINE)), which was treated with N-carbomethoxyphthalimide to give the hydroxy acid ((UNDERLINE)13(/UNDERLINE)). Reaction of (UNDERLINE)13(/UNDERLINE) with pivaloyl chloride gave the corresponding mixed anhydride, which was allowed to react with pyrrolidine to provide the amide ((UNDERLINE)14(/UNDERLINE)). Deprotection of (UNDERLINE)14(/UNDERLINE) with hydrazine hydrate afforded the hydroxyamide (15). Condensation of (UNDERLINE)15(/UNDERLINE) with the aldehyde ((UNDERLINE)16(/UNDERLINE)) and subsequent reduction of the resulting imine with sodium cyanoborohydride produced the fluoride ((UNDERLINE)17(/UNDERLINE)). Cleavage of the methylenedioxy group of (UNDERLINE)17(/UNDERLINE) gave the free base of (UNDERLINE)1(/UNDERLINE), which was treated with hydrobromic acid to afford (UNDERLINE)1(/UNDERLINE). The overall yield was 11.1% from (UNDERLINE)6(/UNDERLINE).
Myc’s broad reach (2008)

The role of the myc gene family in the biology of normal and cancer cells has been intensively studied since the early 1980s. myc genes, responding to diverse external and internal signals, express transcription factors (c-, N-, and L-Myc) that heterodimerize with Max, bind DNA, and modulate expression of a specific set of target genes. Over the last few years, expression profiling, genomic binding studies, and genetic analyses in mammals and Drosophila have led to an expanded view of Myc function. This review is focused on two major aspects of Myc: the nature of the genes and pathways that are targeted by Myc, and the role of Myc in stem cell and cancer biology.
Intraocular injection of an aptamer that binds PDGF‐B: A potential treatment for proliferative retinopathies (2006)

Platelet-derived growth factor-B (PDGF-B) has been implicated in the pathogenesis of proliferative retinopathies and other scarring disorders in the eye. In this study, we sought to test the therapeutic potential of an aptamer that selectively binds PDGF-B, ARC126, and its PEGylated derivative, ARC127. Both ARC126 and ARC127 blocked PDGF-B-induced proliferation of cultured fibroblasts with an IC50 of 4 nM. Pharmacokinetic studies in rabbits showed similar peak vitreous concentrations of approximately 110 microM after intravitreous injection of 1 mg of either ARC126 or ARC127, but the terminal half-life was longer for ARC127 (98 versus 43 h). Efficacy was tested in rho/PDGF-B transgenic mice that express PDGF-B in photoreceptors and develop severe proliferative retinopathy resulting in retinal detachment. Compared to eyes injected with 20 microg of scrambled aptamer in which five of six developed detachments (three total and two partial), eyes injected with ARC126 (no detachment in five of six and one partial detachment), or ARC127 (no detachment in six of six) had significantly fewer retinal detachments. They also showed a significant reduction in epiretinal membrane formation. These data demonstrate that a single intravitreous injection of an aptamer that specifically binds PDGF-B is able to significantly reduce epiretinal membrane formation and retinal detachment in rho/PDGF-B mice. These striking effects in an aggressive model of proliferative retinopathy suggest that ARC126 and ARC127 should be considered for treatment of diseases in which PDGF-B has been implicated, including ischemic retinopathies such as proliferative diabetic retinopathy, proliferative vitreoretinopathy (PVR), and choroidal neovascularization.