gebhart/patrepeval huggingface dataset:
Nuclear pore complex glycoproteins contain cytoplasmically disposed O-linked N-acetylglucosamine. (1987)

A novel form of protein-saccharide linkage consisting of single N-acetylglucosamine (GlcNAc) residues attached in O-linkages directly to the polypeptide backbone has been described (Holt, G. D., and G. W. Hart, 1986, J. Biol. Chem., 261:8049-8057). This modification was found on proteins distributed throughout the cell, although proteins bearing O-linked GlcNAc moieties were particularly abundant in the cytosolic and nuclear envelope fractions of rat liver. In the accompanying article (Snow, C. M., A. Senior, and L. Gerace, 1987, J. Cell. Biol., 104: 1143-1156), the authors describe monoclonal antibodies directed against eight proteins localized to the nuclear pore complex. These proteins occur on the cytoplasmic and nucleoplasmic (but not lumenal) sides of nuclear membranes. In this report, we demonstrate that all members of this group of pore complex proteins bear multiple O-linked GlcNAc residues. Further, we show that the O-linked GlcNAc moieties are linked via serine (and possibly threonine) side chains to these proteins. Perturbing the O-linked GlcNAc residues either by covalently attaching galactose to them or by releasing them with beta-N-acetylglucosaminidase strongly diminishes the immunoreactivity of the proteins with all of the monoclonal antibodies. However, the O-linked GlcNAc moieties are only part of the epitopes recognized, since O-GlcNAc-containing limit pronase fragments of nuclear pore complex proteins cannot be immunoprecipitated by these antibodies. These findings, taken together with those in the accompanying article, are a direct demonstration that proteins of the cytoplasm and nucleoplasm bear O-linked GlcNAc residues.
PEX11 promotes peroxisome division independently of peroxisome metabolism (2002)

The PEX11 peroxisomal membrane proteins are the only factors known to promote peroxisome division in multiple species. It has been proposed that PEX11 proteins have a direct role in peroxisomal fatty acid oxidation, and that they only affect peroxisome abundance indirectly. Here we show that PEX11 proteins are unique in their ability to promote peroxisome division, and that PEX11 overexpression promotes peroxisome division in the absence of peroxisomal metabolic activity. We also observed that mouse cells lacking PEX11beta display reduced peroxisome abundance, even in the absence of peroxisomal metabolic substrates, and that PEX11beta(-/-) mice are partially deficient in two distinct peroxisomal metabolic pathways, ether lipid synthesis and very long chain fatty acid oxidation. Based on these and other observations, we propose that PEX11 proteins act directly in peroxisome division, and that their loss has indirect effects on peroxisome metabolism.
Detection and partial sequence analysis of gastrin mRNA by using an oligodeoxynucleotide probe. (1979)

We have used a specific deoxyoligonucleotide probe to detect gastrin mRNA in poly(A)-enriched RNA preparations from hog antrum. The nucleotide sequence of the oligonucleotide, d(C-T-C-C-T-C-C-A-T-C-C-A), was deduced from the unique amino acid sequence Trp-Met-Glu-Glu of gastrin. When used with hog antral RNA, the dodecanucleotide is an effective primer for the synthesis of gastrin-specific cDNA as judged by nucleotide sequence analysis of cDNA isolated by polyacrylamide gel electrophoresis. We have determined an 81-nucleotide sequence corresponding to the region of the gastrin mRNA that codes for the known amino acid sequence of the G34 progastrin intermediate species, and we have demonstrated the presence of two consecutive basic residues preceding the G34 sequence in the prohormone. Hybridization of gastrin cDNA or synthetic dodecanucleotide to hog antral RNA separated by gel electrophoresis on agarose gels in the presence of methylmercuric hydroxide indicates that the mRNA coding for gastrin is about 620 nucleotides long. These results suggest that the gastrin precursor peptide contains 110-140 amino acids. This method should be of general application for detection and characterization of mRNAs corresponding to proteins of known amino acid sequence.
Amplified spontaneous Raman scattering in fiber Raman amplifiers (1986)

Amplified spontaneous Raman scattered light power in forward and backward Raman amplifiers is theoretically and experimentally studied under the assumption of the constant Raman gain coefficient in the bandwidth of an optical filter. On the basis of the results, the power ratio of the amplified signal to amplified spontaneous scattering is discussed. As a result, it is clarified that the effect of amplified spontaneous Raman scattering on the signal to noise ratio for backward Raman scattering is larger than for forward Raman scattering.
Scale‐Up Studies in Asymmetric Transfer Hydrogenation (2010)

This chapter contains sections titled: Background Reaction Components Case Studies Conclusions Acknowledgment References
Critical Role for IL-13 in the Development of Allergen-Induced Airway Hyperreactivity (2001)

Airway hyperresponsiveness to a variety of specific and nonspecific stimuli is a cardinal feature of asthma, which affects nearly 10% of the population in industrialized countries. Eosinophilic pulmonary inflammation, eosinophil-derived products, as well as Th2 cytokines IL-13, IL-4, and IL-5, have been associated with the development of airway hyperreactivity (AHR), but the specific immunological basis underlying the development of AHR remains controversial. Herein we show that mice with targeted deletion of IL-13 failed to develop allergen-induced AHR, despite the presence of vigorous Th2-biased, eosinophilic pulmonary inflammation. However, AHR was restored in IL-13(-/-) mice by the administration of recombinant IL-13. Moreover, adoptive transfer of OVA-specific Th2 cells generated from TCR-transgenic IL-13(-/-) mice failed to induce AHR in recipient SCID mice, although such IL-13(-/-) Th2 cells produced high levels of IL-4 and IL-5 and induced significant airway inflammation. These studies definitively demonstrate that IL-13 is necessary and sufficient for the induction of AHR and that eosinophilic airway inflammation in the absence of IL-13 is inadequate for the induction of AHR. Therefore, treatment of human asthma with antagonists of IL-13 may be very effective.
Multiple displacement amplification as a pre‐polymerase chain reaction (pre‐PCR) to process difficult to amplify samples and low copy number sequences from natural environments (2005)

Microbial assessment of natural biodiversity is usually achieved through polymerase chain reaction (PCR) amplification. Deoxyribonucleic acid (DNA) sequences from natural samples are often difficult to amplify because of the presence of PCR inhibitors or to the low number of copies of specific sequences. In this study, we propose a non-specific preamplification procedure to overcome the presence of inhibitors and to increase the number of copies prior to carrying out standard amplification by PCR. The pre-PCR step is carried out through a multiple displacement amplification (MDA) technique using random hexamers as priming oligonucleotides and phi 29 DNA polymerase in an isothermal, whole-genome amplification reaction. Polymerase chain reaction amplification using specific priming oligonucleotides allows the selection of the sequences of interest after a preamplification reaction from complex environmental samples. The procedure (MDA-PCR) has been tested on a natural microbial community from a hypogean environment and laboratory assemblages of known bacterial species, in both cases targeting the small subunit ribosomal RNA gene sequences. Results from the natural community showed successful amplifications using the two steps protocol proposed in this study while standard, direct PCR amplification resulted in no amplification product. Amplifications from a laboratory assemblage by the two-step proposed protocol were successful at bacterial concentrations >or= 10-fold lower than standard PCR. Amplifications carried out in the presence of different concentrations of fulvic acids (a soil humic fraction) by the MDA-PCR protocol generated PCR products at concentrations of fulvic acids over 10-fold higher than standard PCR amplifications. The proposed procedure (MDA-PCR) opens the possibility of detecting sequences represented at very low copy numbers, to work with minute samples, as well as to reduce the negative effects on PCR amplifications of some inhibitory substances commonly found in environmental samples.
Alzheimer's disease drug development pipeline: 2018 (2018)

The AD drug development pipeline is slightly larger in 2018 than in 2017. Trials increasingly include preclinical and prodromal populations. There is an increase in nonamyloid mechanisms of action for drugs in earlier phases of drug development. Biomarkers are increasingly used in AD drug development but are not used uniformly for AD diagnosis confirmation.
Telomere length measurement by fluorescence in situ hybridization and flow cytometry: Tips and pitfalls (2002)

The use of flow-FISH for telomere length measurements in nucleated blood cells requires tight adherence to an optimized protocol. The method described here can be used to determine rapidly the telomere length in subsets of nucleated blood cells.
Physically Based Real-Time Auralization of Interactive Virtual Environments (2011)

Over the last decades, Virtual Reality (VR) technology has emerged to be a powerful tool for a wide variety of applications covering conventional use, e.g., in science, design, medicine and engineering, as well as in more visionary applications such as the creation of virtual spaces that aim to act real. However, the high capabilities of today's VR-systems are mostly limited to first-class visual rendering. In order to boost the range of applications, state-of-the-art systems aim to reproduce virtual environments as realistically as possible for the purpose of maximizing the user's feeling of immersion, presence and acceptance. Such immersive systems deliver multiple sensory stimuli and provide an opportunity to act interactively, as reality is neither mono-modal nor static. Analogous to visualization, the auralization of virtual environments describes the simulation of sound propagation inside enclosures where methods of Geometrical Acoustics are mostly applied for a high-quality synthesis of aural stimuli that go along with a certain realistic behavior. Here, best results are achieved by combining deterministic methods for the computation of early specular sound reflections with stochastic approaches for the computation of the reverberant sound field. By adapting acceleration algorithms from Computer Graphics, current implementations can manage the computational load of moving sound sources around a moving receiver in real-time - even for complex but static architectural scenarios. In the course of this thesis, the design and implementation of the real-time room acoustics simulation software RAVEN will be described, which is a vital part of the implemented 3D sound-rendering system of RWTH Aachen University's immersive VR-system. RAVEN relies on present-day knowledge of room acoustical simulation techniques and enables a physically accurate auralization of sound propagation in complex environments including important wave effects such as sound scattering, airborne sound insulation between rooms and sound diffraction. Despite this realistic sound field rendering, not only spatially distributed and freely movable sound sources and receivers are supported at runtime but also modifications and manipulations of the environment itself. All major features are evaluated by investigating both the overall accuracy of the room acoustics simulation and the performance of implemented algorithms, and possibilities for further simulation optimizations are identified by assessing empirical studies of subjects operating in immersive environments.
Tyrosine kinase inhibitor (TKI)‐induced cardiotoxicity: approaches to narrow the gaps between preclinical safety evaluation and clinical outcome (2012)

Although therapies targeted to inhibit the activity of certain tyrosine kinases (TK) have helped advance cancer therapy in recent years, reports of cardiac toxicity following treatment with tyrosine kinase inhibitors (TKIs) were unexpected and not well predicted by preclinical studies. Such clinical findings exposed gaps in current preclinical drug testing for predicting the development of cardiac toxicities in humans. These gaps included a lack of a comprehensive TKI mechanism of action determination and appropriate cardiac functional evaluation. New preclinical approaches are suggested to address these issues. In addition to tyrosine kinase inhibition, other factors that may play a role in drug-induced cardiac effects should be assessed, such as unintended secondary targets of TKIs, toxic drug metabolites and drug accumulation in the heart. Both on-target and off-target toxic effects of TKIs on cultured cardiac myocytes have now been shown to be detectable, providing a rationale for using cardiomyocytes as a screening tool to study potential TKI-mediated cardiotoxicity. Incorporating isolated perfused heart methodology to chronic/subchronic rodent studies or including echocardiography in chronic large animal toxicity studies may improve the detection of changes in cardiac function over current methods, and they may eventually become a routine tool for screening drugs with suspected cardiotoxic potential. Further, assessing drug toxicity and efficacy together in an animal model of disease is highly informative for candidate drug selection, and should be encouraged to assess specific safety endpoints, such as cardiovascular function. Together, these approaches will help better close the gaps between preclinical testing and clinical outcomes.
10.1016/s0967-0653(98)85314-3 (2000)

Sequential heterotrophic/autotrophic cultivation method was investigated for production of high concentration of Chlorella biomass with high cellular protein and chlorophyll contents. By using autotrophic growth medium, which contains glucose as organic carbon source, for heterotrophic culture, the protein and chlorophyll contents of the cells could be increased by simply illuminating the culture broth and aerating with CO2-enriched air at the end of the heterotrophic culture. A system was then constructed for continuous sequential heterotrophic/autotrophic production of algal biomass. The system was composed of the conventional mini-jar fermentor for the heterotrophic phase and a tubular photobioreactor for the autotrophic phase. The exhaust gas from the heterotrophic phase was used for aeration of the autotrophic phase in order to reduce the CO2 emission into the atmosphere. With this system, it was possible to produce high Chlorella biomass concentration (14 g L-1) containing 60.1% protein and 3.6% chlorophyll continuously for more than 640 h. During the steady state, about 27% of the CO2 produced in the heterotrophic phase was re-utilized in the autotrophic phase. When the tubular photobioreactor was replaced with a 3.5-L internally illuminated photobioreactor, the productivity increased from 2 g L-1 d-1 to 4 g L-1 d-1. However, the chlorophyll content of the cells was lower due to the lower light supply coefficient of the photobioreactor.
The pathocenosis moment: Mirko Grmek, the Annales and the vagaries of the longue durée. (2005)

Grmek's important article on pathocenosis, which appeared in 1969 in the Annales, did not achieve the fame and significance which it seemed to merit. This needs to be explained not only in terms of Grmek's own history, but also in changes in intellectual fashion, including in the Annales themselves. The work was also eclipsed by W.H. McNeill's best-selling Plagues and Peoples. History's 'cultural turn' since the 1980s has also limited the article's perceived utility. Nevertheless, the value of the concept is underlined by the articles in this collection.
ORGANIC PHOSPHORUS COMPOUNDS 91.1SYNTHESIS AND PROPERTIES OF 1-AMINO-2-ARYLETHYLPHOSPHONIC AND-PHOSPHINIC ACIDS AS WELL AS -PHOSPHINE OXIDES (1990)

Abstract The preparation, physical and spectroscopic properties of l-amino-2-arylethylphosphonic, and -phosphinic acids as well as -phosphine oxides, the phosphorus analogues of phenylalanine are described, and the reactions of l-amino-2-(4-fluorophenyl) ethylphosphonates with acetals, isocyanides, esters, acid anhydrides, activated aromatic nitro- and halogen compounds, and with N-protected alanine are reported. It is shown that several of the 1-amino-2-arylethylphosphonic acids are strong inhibitors of PAL and anthocyanin synthesis and also are quite active botryticides. Among the active compounds were l-amino-2-(4-fluorophenyl)ethylphosphonic acid, 3f, and the methyl-substituted compounds 3k, 31, and 3m. The fluoroderivative 3f was also effective as a seed-dressing agent in barley showing a 100% protection against the fungus Fusarium nivale at 600 ppm.
PCR amplification of specific alleles (PASA) is a general method for rapidly detecting known single-base changes. (1992)

Previous data suggested that PCR amplification of specific alleles (also known as allele-specific amplification and amplification refractory mutation system) is not a general method for rapidly and accurately detecting known single-base changes. Herein we present our experience with the use of PCR amplification of specific alleles to detect 69 polymorphic or mutant alleles. Our results indicate that with proper optimization, all alleles were reliably distinguished.
The Nitrogen-Containing Bisphosphonate, Zoledronic Acid, Influences RANKL Expression in Human Osteoblast-Like Cells by Activating TNF-α Converting Enzyme (TACE) (2004)

Our studies indicate that ZOL, in addition to its direct effects on mature OCs, may inhibit the recruitment and differentiation of OCs by cleavage of transmembrane RANKL in OB-like cells by upregulating the sheddase, TACE.
Stiffness Control of Balance in Quiet Standing (1998)

Our goal was to provide some insights into how the CNS controls and maintains an upright standing posture, which is an integral part of activities of daily living. Although researchers have used simple performance measures of maintenance of this posture quite effectively in clinical decision making, the mechanisms and control principles involved have not been clear. We propose a relatively simple control scheme for regulation of upright posture that provides almost instantaneous corrective response and reduces the operating demands on the CNS. The analytic model is derived and experimentally validated. A stiffness model was developed for quiet standing. The model assumes that muscles act as springs to cause the center-of-pressure (COP) to move in phase with the center-of-mass (COM) as the body sways about some desired position. In the sagittal plane this stiffness control exists at the ankle plantarflexors, in the frontal plane by the hip abductors/adductors. On the basis of observations that the COP-COM error signal continuously oscillates, it is evident that the inverted pendulum model is severely underdamped, approaching the undamped condition. The spectrum of this error signal is seen to match that of a tuned mass, spring, damper system, and a curve fit of this "tuned circuit" yields omega n the undamped natural frequency of the system. The effective stiffness of the system, Ke, is then estimated from Ke = I omega n2, and the damping B is estimated from B = BW X I, where BW is the bandwidth of the tuned response (in rad/s), and I is the moment of inertia of the body about the ankle joint. Ten adult subjects were assessed while standing quietly at three stance widths: 50% hip-to-hip distance, 100 and 150%. Subjects stood for 2 min in each position with eyes open; the 100% stance width was repeated with eyes closed. In all trials and in both planes, the COP oscillated virtually in phase (within 6 ms) with COM, which was predicted by a simple 0th order spring model. Sway amplitude decreased as stance width increased, and Ke increased with stance width. A stiffness model would predict sway to vary as Ke-0.5. The experimental results were close to this prediction: sway was proportional to Ke(-0.55). Reactive control of balance was not evident for several reasons. The visual system does not appear to contribute because no significant difference between eyes open and eyes closed results was found at 100% stance width. Vestibular (otolith) and joint proprioceptive reactive control were discounted because the necessary head accelerations, joint displacements, and velocities were well below reported thresholds. Besides, any reactive control would predict that COP would considerably lag (150-250 ms) behind the COM. Because the average COP was only 4 ms delayed behind the COM, reactive control was not evident; this small delay was accounted for by the damping in the tuned mechanical system.
Studies on the nonmevalonate pathway to terpenes: The role of the GcpE (IspG) protein (2001)

Recombinant Escherichia coli cells engineered for the expression of the xylB gene in conjunction with genes of the nonmevalonate pathway were supplied with (13)C-labeled 1-deoxy-D-xylulose. Cell extracts were analyzed directly by NMR spectroscopy. (13)C-labeled 2C-methyl-D-erythritol 2,4-cyclodiphosphate was detected at high levels in cells expressing xylB, ispC, ispD, ispE, and ispF. The additional expression of the gcpE gene afforded 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate as an intermediate of the nonmevalonate pathway. Hypothetical mechanisms involving conserved cysteine residues are proposed for the enzymatic conversion of 2C-methyl-D-erythritol 2,4-cyclodiphosphate into 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate catalyzed by the GcpE protein.
Expression of High-affinity Binding of Human Immunoglobulin E by Transfected Cells (1989)

The receptor with high affinity for immunoglobulin E (IgE) on mast cells and basophils is critical in initiating allergic reactions. It is composed of an IgE-binding alpha subunit, a beta subunit, and two gamma subunits. The human alpha subunit was expressed on transfected cells in the presence of rat beta and gamma subunits or in the presence of the gamma subunit alone. The IgE binding properties of the expressed human alpha were characteristic of receptors on normal human cells. These results now permit a systematic analysis of human IgE binding and a search for therapeutically useful inhibitors of that binding.
A Gene-Expression Signature as a Predictor of Survival in Breast Cancer (2002)

The gene-expression profile we studied is a more powerful predictor of the outcome of disease in young patients with breast cancer than standard systems based on clinical and histologic criteria.
Effect of Deleting the R Domain on CFTR-Generated Chloride Channels (1991)

The cystic fibrosis transmembrane conductance regulator (CFTR), which forms adenosine 3',5'-monophosphate (cAMP)-regulated chloride channels, is defective in patients with cystic fibrosis. This protein contains two putative nucleotide binding domains (NBD1 and NBD2) and an R domain. CFTR in which the R domain was deleted (CFTR delta R) conducted chloride independently of the presence of cAMP. However, sites within CFTR other than those deleted also respond to cAMP, because the chloride current of CFTR delta R increased further in response to cAMP stimulation. In addition, deletion of the R domain suppressed the inactivating effect of a mutation in NBD2 (but not NBD1), a result which suggests that NBD2 interacts with the channel through the R domain.