gebhart/patrepeval huggingface dataset:
FcγRII expression on follicular dendritic cells and immunoreceptor tyrosine‐based inhibition motif signaling in B cells (2003)

Immune complexes (IC) initiate immunoreceptor tyrosine-based inhibition motif (ITIM) signaling and inhibit B cell activation by coligating B cell receptor for antigen (BCR) and FcgammaRII. Nevertheless, IC on follicular dendritic cells (FDC) stimulate rapid germinal center (GC) B cell proliferation suggesting that interactions between IC and FDC render IC capable of B cell activation. To understand this, we studied the kinetics of FDC FcgammaRII and complement receptors 1 and 2 (CR1&2) expressions during the GC reaction and determined whether FDC FcgammaRII could bind Fc in IC and block ITIM signaling. Mice were immunized with sheep red blood cells (SRBC), and CR1&2 and FcgammaRII levels in FDC reticula were monitored. The role of FDC FcgammaRII was studied using anti-BCR-stimulated A20 cells. Levels of FDC FcgammaRII in spleens of SRBC-injected mice increased within 24 h and were dramatically increased (approximately 50-fold) on days 3 and 5. In contrast, CR1&2 levels increased less than twofold. Addition of normal FDC, but not FDC lacking FcgammaRII, reduced and reversed anti-BCR-induced SH2 domain-containing inositol phosphatase (SHIP)-1 phosphorylation in A20 cells. FDC were able to induce normal recall responses even after overnight incubation of the lymphocytes with IC to stimulate ITIM signaling. Engagement of Ig Fc with numerous FcgammaRII on FDC appears to minimize IC-induced ITIM signaling. Thus, rapid up-regulation of FDC FcgammaRII may explain why poorly immunogenic IC are rendered highly immunogenic when presented by FDC in GC.
Drilling Hard and Abrasive Rock Efficiently, or Generating Quality Cuttings? You No Longer Have to Choose… (2008)

Abstract The drilling of hard formations usually requires specific drilling systems to achieve an efficient rate of penetration. Due to the limited depth of cut, the solution often involves the use of high RPM drive systems such as turbines or high speed motors and a fixed cutter product is usually the drill bit of choice. With increasing well depth the roller cone option is normally avoided due to the low penetration rates and limited rotating hours obtainable with these drill bits. Roller cone use invariably leads to multiple trips and a significant increase in the time and cost of the drilling operation, especially for deeply buried reservoirs where hard rocks are generally encountered and bit diameter is reduced at TD. Unavoidably, in some applications roller cone bits continue to be used in order to obtain the quality cuttings necessary for the geologist to correctly assess the formation. This is typically the case when the reservoir interval is encountered and exact formation knowledge is critical. A new drilling solution has been developed to address this situation and is presented in this paper. The idea consists of a fixed cutter bit which leaves the center of the hole uncut. The lack of bit center leads to the creation of a core. This core is broken by the bit itself and ejected at the side through a specifically designed junk slot. The core is then carried to the surface along with the other cuttings. This process leads to very high quality cuttings for surface examination. The improvement is especially important where normal cuttings quality is poor due to the use of turbines or high speed motors together with impregnated diamond bits. Importantly, as the center part of the bit is uncut this new technology also provides a significant increase in the rate of penetration. In a fixed cutter bit the center is one of the most inefficient cutting areas as the rotational speed of the cutter is low to null. By removing the center, an increased ROP efficiency in the range of 15 to 25 percent can be obtained depending upon the bit diameter. The field tests that are presented in the paper show quantifiable improvements in terms of geological sample quality, cutting efficiency and drilling cost reduction.
Complete Amino Acid Sequence of Human Ornithine Decarboxylase Deduced from Complementary DNA (1987)

A complementary DNA (cDNA) encoding ornithine decarboxylase was isolated from a human liver cDNA library, and the nucleotide sequence coding for the entire enzyme was determined. The 1825-nucleotide-long cDNA contained an open reading frame of 1383 nucleotides, 87 nucleotides 5' from the first methionine codon, 346 nucleotides in the 3'-noncoding region, and a poly(A) tail of nine bases. Primer extension studies indicated that the 5'-noncoding region of the human ornithine decarboxylase mRNA was 335 nucleotides long. The amino acid sequence deduced from the open reading frame for a 461-residue polypeptide predicts a molecular weight of 51.156 for the human enzyme and has about 90% homology with the amino acid sequence of the murine ornithine decarboxylase (44 differences among the 461 amino acids). The nucleotide sequences of the human and murine ornithine decarboxylase mRNAs share an 85% homology, even in their 3'-noncoding regions. In contrast to rodent tissues with two ornithine decarboxylase mRNAs, normal human tissues appear to express only a single mRNA species with a molecular size of 2.25 kb. Southern blotting of human leukocyte DNA from 20 individuals indicated that the ornithine decarboxylase gene belongs to a multigene family in man and showed restriction fragment length polymorphism when cleaved with Pst I, but not when cleaved with Pvu II, Msp I, Hinc II, or Bam HI.
Superoxide dismutase plus catalase improve contractile function in the canine model of the "stunned myocardium". (1986)

Fifteen minutes of coronary occlusion followed by reperfusion does not result in myocardial necrosis; however, the contractile function and high energy phosphate content of the previously ischemic myocardium remains depressed or "stunned" for several hours to days after reperfusion. Oxygen-derived free radicals have been implicated in ischemia and reperfusion-induced injury in a variety of tissues. We wished to determine whether administration of free radical scavengers superoxide dismutase plus catalase before and during occlusion, and throughout reperfusion, could attenuate the "stunning" produced by 15 minutes of left anterior descending coronary artery occlusion in anesthetized, open-chest dogs. Segment shortening in the previously ischemic zone recovered to within only +/- 10% of preinfusion values in the control group during 3 hours of reperfusion, while, in the treated dogs, segment shortening returned to a maximum of 56 +/- 16% of preinfusion at 1 1/2 hours post-reperfusion (P less than 0.0003 compared to controls). Similarly, superoxide dismutase + catalase-treated dogs exhibited improved wall thickening during reperfusion (+30% to +70% of preinfusion values), compared to controls (0% to +10%). However, this improvement in contractile function in the treated group was not accompanied by increased adenosine triphosphate stores in the previously ischemic zone (31.8 +/- 0.8 vs. 28.2 +/- 2.2 nmol/mg protein for control vs. treated groups). Infusion of superoxide dismutase + catalase did not influence blood flow during occlusion or reperfusion. However, the treated group did exhibit a significant decrease in blood pressure during reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Identification of the membrane-type matrix metalloproteinase MT1-MMP in osteoclasts (1997)

The osteoclasts are the cells responsible for bone resorption. Matrix metalloproteinases (MMPs) appear crucial for this process. To identify possible MMP expression in osteoclasts, we amplified osteoclast cDNA fragments having homology with MMP genes, and used them as a probe to screen a rabbit osteoclast cDNA library. We obtained a cDNA of 1,972 bp encoding a polypeptide of 582 amino acids that showed more than 92% identity to human, mouse, and rat membrane-type 1 MMP (MT1-MMP), a cell surface proteinase believed to trigger cancer cell invasion. By northern blotting, MT1-MMP was found to be highly expressed in purified osteoclasts when compared with alveolar macrophages and bone stromal cells, as well as with various tissues. In situ hybridization on bone sections showed that MT1-MMP is expressed also in osteoclasts in vivo. Antibodies recognizing MT1-MMP reacted with specific plasma membrane areas corresponding to lamellipodia and podosomes involved, respectively, in migratory and attachment activities of the osteoclasts. These observations highlight how cells might bring MT1-MMP into contact with focal points of the extracellular matrix, and are compatible with a role of MT1-MMP in migratory and attachment activities of the osteoclast.
Affinity probes for the avermectin binding proteins (1992)

The design and synthesis of a series of avermectin affinity probes used in the identification and purification of the avermectin binding proteins is described. These modified avermectins fall into two design classes: ligands to covalently modify specific avermectin binding proteins [an 125I-labeled aryl azide photoprobe (15) and a tritiated aziridine analog (6)] and ligands for affinity chromatography applications [three biotinylated compounds (10, 12, and 13) and one resin-bound derivative (9)]. The binding affinities of these compounds for the Caenorhabditis elegans avermectin binding protein is presented as well as their biological activities against C. elegans and Artemia salina.
Directed biosynthesis of new saframycin derivatives with resting cells of Streptomyces lavendulae (1985)

Saframycin A is an antitumor antibiotic produced by Streptomyces lavendulae 314 which falls into the category of the N-heterocyclic quinone group. Biosynthetically the quinone ring is derived from two tyrosine molecules which condense to generate the basic ring system of saframycin A. The side chain also has been found to derive from two amino acids, i.e., glycine and alanine. Supplementation by various amino acid analogs of the side chain produced three new saframycin derivatives with a replaced side chain. These three saframycins, designated Yd-1, Yd-2, and Y3, contained 2-amino-n-butyric acid, glycine, and alanine residues, respectively. in place of the normal N-terminal pyruvic acid in the side chain of saframycin A. Feeding experiments with 13C-labeled dipeptide indicated that the amino acids are probably incorporated in the side chain as a dipeptide unit. It was also found that saframycin A is produced from saframycin Y3 by an enzymatic deamination reaction. Based on these results, saframycin biosynthesis in S. lavendulae is discussed.
Antibody–drug conjugates—A new wave of cancer drugs (2014)

Antibody-drug conjugates (ADCs) consist of cytotoxic drugs covalently linked to monoclonal antibodies directed to antigens differentially overexpressed in tumor cells. These loaded antibodies are expected to selectively deliver lethal cargoes to tumor cells and provide sustained clinical benefit to pre-selected cancer patients while, at the same time, minimizing systemic toxicity. Although on-target adverse events are not completely avoided and the true efficacy of these innovative agents still requires further clarification, proof-of-concept has already been achieved in clinical settings with immunoconjugates containing calicheamicin, auristatin or maytansine-based cytotoxic payloads. In this present article we review the characteristics of the preceding cytotoxic platforms and their chemical conjugation approaches.
Learning State Space Trajectories in Recurrent Neural Networks (1989)

Many neural network learning procedures compute gradients of the errors on the output layer of units after they have settled to their final values. We describe a procedure for finding ∂E/∂w ij , where E is an error functional of the temporal trajectory of the states of a continuous recurrent network and w ij are the weights of that network. Computing these quantities allows one to perform gradient descent in the weights to minimize E. Simulations in which networks are taught to move through limit cycles are shown. This type of recurrent network seems particularly suited for temporally continuous domains, such as signal processing, control, and speech.
Analysis of Cockcroft-Walton Voltage Multipliers with an Arbitrary Number of Stages (1969)

Expressions for the direct and alternating output voltages of Cockcroft-Walton voltage multipliers with an arbitrary number of stages are determined for the joint effects of charge dissipation in the load resistance and charge storage in the diode shunt capacitances.
Phytochrome A and Phytochrome B Have Overlapping but Distinct Functions in Arabidopsis Development (1994)

Plant responses to red and far-red light are mediated by a family of photoreceptors called phytochromes. In Arabidopsis thaliana, there are genes encoding at least five phytochromes, and it is of interest to learn if the different phytochromes have overlapping or distinct functions. To address this question for two of the phytochromes in Arabidopsis, we have compared light responses of the wild type with those of a phyA null mutant, a phyB null mutant, and a phyA phyB double mutant. We have found that both phyA and phyB mutants have a deficiency in germination, the phyA mutant in far-red light and the phyB mutant in the dark. Furthermore, the germination defect caused by the phyA mutation in far- red light could be suppressed by a phyB mutation, suggesting that phytochrome B (PHYB) can have an inhibitory as well as a stimulatory effect on germination. In red light, the phyA phyB double mutant, but neither single mutant, had poorly developed cotyledons, as well as reduced red-light induction of CAB gene expression and potentiation of chlorophyll induction. The phyA mutant was deficient in sensing a flowering response inductive photoperiod, suggesting that PHYA participates in sensing daylength. In contrast, the phyB mutant flowered earlier than the wild type (and the phyA mutant) under all photoperiods tested, but responded to an inductive photoperiod. Thus, PHYA and PHYB appear to have complementary functions in controlling germination, seedling development, and flowering. We discuss the implications of these results for possible mechanisms of PHYA and PHYB signal transduction.
Programmed Death Ligand-1 Immunohistochemistry: Friend or Foe? (2016)

The approval of anti-programmed death receptor (PD)-1 therapies for non-small cell lung cancer has directed the spotlight on programmed death ligand-1 (PD-L1) immunohistochemistry as the latest predictive biomarker potentially required in this disease. Several other drugs in this class will likely be approved in the future and each has been developed with a unique anti-PD-L1 immunohistochemistry test. The prospect of 5 drugs competing in the same treatment area, each possibly requiring PD-L1 immunohistochemistry testing, presents a challenge for pathologists unlike any previously faced. The key issue is whether laboratories will attempt to deliver the trial-validated assays for one or more of these treatments, or introduce instead one or more laboratory developed tests, or attempt to provide a single PD-L1 immunohistochemistry assay for all possible anti-PD-1 and anti-PD-L1 treatments that may be used. This paper discusses some of the issues, challenges, hazards, and possible solutions that have recently emerged in this most complex interface between cancer therapeutics and laboratory biomarker testing.
A protein kinase that phosphorylates the C-terminal repeat domain of the largest subunit of RNA polymerase II. (1989)

The unique C-terminal repeat domain (CTD) of the largest subunit (IIa) of eukaryotic RNA polymerase II consists of multiple repeats of the heptapeptide consensus sequence Tyr-Ser-Pro-Thr-Ser-Pro-Ser. The number of repeats ranges from 26 in yeast to 42 in Drosophila to 52 in mouse. The CTD is essential in vivo, but its structure and function are not yet understood. The CTD can be phosphorylated at multiple serine and threonine residues, generating a form of the largest subunit (II0) with markedly reduced mobility in NaDodSO4/polyacrylamide gels. To investigate this extensive phosphorylation, which presumably modulates functional properties of RNA polymerase II, we began efforts to purify a specific CTD kinase. Using CTD-containing fusion proteins as substrates, we have purified a CTD kinase from the yeast Saccharomyces cerevisiae. The enzyme extensively phosphorylates the CTD portion of both the fusion proteins and intact subunit IIa, producing products with reduced electrophoretic mobilities. The properties of the CTD kinase suggest that it is distinct from previously described protein kinases. Analogous activities were also detected in Drosophila and HeLa cell extracts.
Pharmacodynamics (PD) and genomic profiling of pts treated with cabiralizumab (cabira) + nivolumab (NIVO) provide evidence of on-target tumor immune modulations and support future clinical applications. (2018)

3020 Background: Colony stimulating factor 1 receptor (CSF-1R) signaling supports recruitment, development, and maintenance of immune suppressive macrophages within the tumor. Combining anti–CSF-1R with anti‒PD-1 showed enhanced efficacy in preclinical models. Cabira, a humanized IgG4 monoclonal antibody, disrupts CSF-1R binding to ligands CSF-1 and IL-34, thus blocking receptor activation. We report immunohistochemistry (IHC) and transcriptomic evidence of on-target PD effects of cabira + NIVO in treated pts, as well as the first insight into genotypic characteristics of pancreatic tumors exhibiting durable PRs with cabira + NIVO (Wainberg et al. J Immunother Cancer 2017;5(suppl 2) [abst O42]). Methods: PD activity of cabira + NIVO in pts with advanced tumors treated in a ph 1a/b trial (NCT02526017) was evaluated using peripheral and tumor biomarkers. Results: Cabira + NIVO induced increases in serum CSF-1 and decreases in peripheral nonclassical monocytes sustained during the 2-week dose interval. IHC analysis of pre- and on-treatment biopsies across tumor types showed increases in CD8 T-cell infiltrates and decreases in macrophage markers CSF-1R and CD163. Transcriptomes of paired biopsies showed increased CD8 and cytolytic gene signatures with concurrent increased expression of M1 macrophage-associated genes, supporting blockade of CSF-1R–driven M2 responses. Genomic analyses demonstrated 91 of 94 pts with low tumor mutation burden (TMB) below 10 mutations/megabase with only 1 microsatellite instability tumor identified. Responses were observed across tumor types. Of note, in the 4 PRs observed in pts with pancreatic cancer, all were microsatellite stable (MSS) and low TMB. Conclusions: Orthogonal IHC and transcriptome-wide analyses demonstrated cabira-mediated CSF-1R blockade in the periphery and tumor microenvironment in pts with advanced cancer. Ongoing analyses include identification of transcriptomic signatures associated with response. These data support further clinical development of cabira + NIVO in multiple indications, including MSS pancreatic cancer (NCT03336216). Clinical trial information: NCT02526017.
Unrolled Polar Decoders, Part I: Hardware Architectures. (2015)

This is the first in a two-part series of papers on unrolled polar decoders. In this paper (Part I), we present a family of architectures for hardware polar decoders using a reduced-complexity successive-cancellation decoding algorithm. The resulting fully-unrolled architectures are capable of achieving a coded throughput in excess of 400 Gbps on an FPGA, two orders of magnitude greater than current state-of-the-art polar decoders. Moreover, the proposed architectures are flexible in a way that makes it possible to explore the trade-off between resource usage and throughput.
Identification of Distinct Classes and Functional Domains of Wnts through Expression of Wild-Type and Chimeric Proteins in Xenopus Embryos (1995)

Wnts are secreted signaling factors which influence cell fate and cell behavior in developing embryos. Overexpression in Xenopus laevis embryos of a Xenopus Wnt, Xwnt-8, leads to a duplication of the embryonic axis. In embryos ventralized by UV irradiation, Xwnt-8 restores expression of the putative transcription factor goosecoid, and rescues normal axis formation. In contrast, overexpression of Xwnt-5A in normal embryos generates defects in dorsoanterior structures, without inducing goosecoid or a secondary axis. To determine whether Xwnt-4 and Xwnt-11 fall into one of these two previously described classes of activity, synthetic mRNAs were introduced into animal caps, normal embryos, and UV-treated embryos. The results indicate that Xwnt-4, Xwnt-5A, and Xwnt-11 are members of a single functional class with activities that are indistinguishable in these assays. To investigate whether distinct regions of Xwnt-8 and Xwnt-5A were sufficient for eliciting the observed effects of overexpression, we generated a series of chimeric Xwnts. RNAs encoding the chimeras were injected into normal and UV-irradiated Xenopus embryos. Analysis of the embryonic phenotypes and goosecoid levels reveals that chimeras composed of carboxy-terminal regions of Xwnt-8 and amino-terminal regions of Xwnt-5A are indistinguishable from the activities of native Xwnt-8 and that are the reciprocal chimeras elicit effects indistinguishable from overexpression of native Xwnt-5A. We conclude that the carboxy-terminal halves of these Xwnts are candidate domains for specifying responses to Xwnt signals.
EVOLUTION OF ANIMAL MITOCHONDRIAL DNA: RELEVANCE FOR POPULATION BIOLOGY AND SYSTEMATICS (1987)

In the past decade, mitochondrial DNA (mtDNA) analysis has become established as a powerful tool for evolutionary studies of animals. These studies, recently reviewed by Avise (8) and Wilson et al (149), have used mtDNA analyses to provide insights into population structure and gene flow, hybridization, biogeography, and phylogenetic relationships. Major advances have been made in our understanding of the molecular biology of animal mtDNA (reviewed in 7, 28). A powerful synergism exists between the two fields of research: Evolutionary studies provide comparative data on mtDNA organization and function, and molecular investigations can, and should, improve the level of sophistication of evolutionary studies that use mtDNA. Here we focus on molecular aspects of animal mtDNA that are especially relevant to its use in evolutionary studies. Thus, we consider the form and frequency of three types of change in mtDNA: base substitution, length variation, and sequence rearrangement. Attention is also given to the nature and possible consequences of interactions between nuclear and mitochondrial (mt) genes. In the concluding sections, we discuss the way in which the knowledge of molecular processes allows informed use of mtDNA variation in evolutionary studies. Only animal mtDNAs are considered. The molecular biology and evolution of chloroplast DNA and nonmetazoan mtDNAs have been reviewed elsewhere (41, 66, 111, 121, 123).
Optimized digital counting colonies of clonogenic assays using ImageJ software and customized macros: Comparison with manual counting (2011)

The colony counting using ImageJ and customized macros with optimized parameters was a reliable method for quantifying the number of colonies.
Mode of Action of Plant Defensins Suggests Therapeutic Potential (2003)

Higher vertebrates can rely both on an innate as well as an adaptive immune system for defense against invading pathogens. In contrast, plants can only employ an innate immune system that largely depends on the production of antimicrobial compounds such as plant defensins and other pathogenesis-related proteins. Plant defensins are ubiquitous, cationic, cysteine-rich plant peptides and have a folding pattern that shares high similarity to defense peptides of mammals and insects, suggesting an ancient and conserved origin. A large number of plant defensins appear to display antifungal activity. Some of these defensins have been found to interact with fungal-specific components in the plasmamembrane, resulting in membrane permeabilization. This makes them an attractive source of potential therapeutics to treat fungal infections.