gebhart/patrepeval huggingface dataset:
Rapid Assembly of Synthetic Genes Encoding Protein Polymers (1999)

A general method is described for the rapid assembly of synthetic genes encoding protein polymers based on the Seamless cloning technique. Genes encoding repeats of the elastin-mimetic polypeptides [(Val-Pro-Gly-Val-Gly)4(Val-Pro-Gly-Xaa-Gly)] (Xaa = Lys 1; Ile, 2) were constructed using this technique. The use of this method eliminates the dependence of the concatamerization on a limited pool of nonpalindromic restriction endonucleases and reduces the number of subcloning steps. A synthetic gene of approximately 3000 base pairs in length was isolated that encoded a protein polymer based on repeat sequence 1. An inducible expression of this gene in bacterial cultures of recombinant E. coli afforded a 90 kDa protein polymer of 1 in high yield (64 mg/L of bacterial culture). The protein was purified to homogeneity using immobilized metal affinity chromatography. The sequence of the protein polymer was confirmed by N-terminal amino acid sequence analysis and MALDI-TOF mass spectrometry of site-specific proteolytic cleavage fragments.
Calvarial Regeneration in Primates With Autolyzed Antigen-Extracted Allogeneic Bone (1992)

The limited regenerative capacity of calvarial membranous bone provides an ideal system for investigation in the comparative physiology of bone regeneration. Cranial defects, 25 mm in diameter, were created in 24 adult male baboons (Papio ursinus). In each animal, defects were implanted with chemosterilized antigen-extracted, autolyzed allogeneic (AAA) bone, grafted with iliac corticocancellous grafts, or left ungrafted to monitor the spontaneous regeneration potential of the adult baboon calvaria. Antigen-extracted, autolyzed allogeneic bone implants were prepared from donor sub-adult baboon calvariae and processed so as to retain bone morphogenetic protein (BMP) in the bone matrix. Histomorphometric analysis of undecalcified sections (7-microns thick) prepared from specimens harvested at three, six, and nine months after surgery showed superior osteogenesis in AAA bone matrix implants, compared with autografts and untreated defects. The morphogenetic response was characterized by vascular invasion and mesenchymal cell aggregation after partial resorption and dissolution of the implanted matrix, followed by bone deposition at the calvarial interfaces, the pericranial and endocranial surfaces of the implants, and within the open diploic spaces of the implanted original AAA bone matrix. The superior osteogenesis in AAA bone implants appeared consistent with extensive osteoconductive invasion from the open diploic and endosteal spaces of the recipient calvariae. In addition, the finding of a delicate, trabecularlike bone, appositional to the central areas of the implanted matrix, suggests that AAA bone implants might also have acted as inductive substratum for bone differentiation.
The CD14+ CD16+ blood monocytes: their role in infection and inflammation (2006)

Blood monocyte subpopulations have been defined in man initially, and the two major types of monocytes are the CD14++ CD16- and the CD14+ CD16+ monocytes. These cells have been shown to exhibit distinct phenotype and function, and the CD14+ CD16+ were labeled proinflammatory based on higher expression of proinflammatory cytokines and higher potency in antigen presentation. The current review describes these properties, including the relationship to dendritic cells, and summarizes the host of publications about CD14+ CD16+ monocytes in inflammation and infectious disease in man, all of which suggest a crucial role of these cells in the disease processes. The review also covers the more recent description of homologues of these cells in other model species, which is expected to better define the role of monocyte subsets in disease.
Quality and Reliability — Relevance and Assessment for Electronic Assemblies (1989)

The physical and mathematical definitions, as well as the practical significance, of quality and reliability are explained, with particular regard to surface mount electronic components and assemblies. The validity of accelerated assessments of long‐term service performance is also discussed.
Reduction in oral immunogenicity of cholera toxin B subunit by N-terminal peptide addition (1993)

The mucosal adjuvanticity of cholera toxin and the potential of the B subunit of cholera toxin (CtxB) to serve as an oral vaccine carrier have prompted interest in the coupling of immunogenic peptides to this protein. The purpose of this study was to determine how such fusions affect the function of CtxB. Oligonucleotides were genetically fused to the 5' terminus of the ctxB gene to encode additional amino acids of 8, 12, and 24 residues in length. None of these additions affected the ability of CtxB to oligomerize, as determined by nondenaturing sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Circular dichroism revealed no difference in conformation between the modified B subunits, regardless of the length of the addition. However, when compared with native CtxB, additions to the N terminus induced a consistent change in the net conformation of the protein. By using a competitive enzyme immunoassay, the affinity of the modified B subunits for GM1 ganglioside was shown to gradually decrease with increasing length of the N-terminal addition. A similar pattern was observed for the ability of the chimeras to inhibit proliferation of concanavalin A-stimulated spleen cells in vitro, which is a previously described functional property of CtxB that is dependent on its binding to cells. Lastly, the oral immunogenicity of these chimeras was found to be less than that of native CtxB. These results indicate that large fusions to the N terminus of CtxB can significantly affect its biological properties and could reduce its value as a mechanism for effective mucosal immunization.
Successful definition of nanowire and porous Si regions of different porosity levels by regular positive photoresist using metal-assisted chemical etching (2011)

A simple and efficient method for selective formation of porous Si areas using regular photoresist as a masking layer is presented. Such a simple masking layer is sufficient to create a wide range of porosity levels through metal-assisted chemical etching (MaCE) using platinum, palladium and silver nanoparticles. Reproducible porous areas with a minimum feature size of 5 ?m were produced on Si wafers. The pore size and height are the functions of the etching time and type of nanoparticles. Using Ag nanopaticles we have been able to obtain Si nanowires of about 30 ?m height. Based on these results, a combination of positive photoresist and MaCE seems to be a reliable way for micron and submicron patterning of nanowire and porous areas on Si wafers, which is simple, inexpensive and compatible with integrated circuit fabrication techniques.
Cellular Regulation of Cytosolic Group IV Phospholipase A2 by Phosphatidylinositol Bisphosphate Levels (2000)

Cytosolic group IV phospholipase A2 (cPLA2) is a ubiquitously expressed enzyme with key roles in intracellular signaling. The current paradigm for activation of cPLA2 by stimuli proposes that both an increase in intracellular calcium and mitogen-activated protein kinase-mediated phosphorylation occur together to fully activate the enzyme. Calcium is currently thought to be needed for translocation of the cPLA2 to the membrane via a C2 domain, whereas the role of cPLA2 phosphorylation is less clearly defined. Herein, we report that brief exposure of P388D1 macrophages to UV radiation results in a rapid, cPLA2-mediated arachidonic acid mobilization, without increases in intracellular calcium. Thus, increased Ca2+ availability is a dispensable signal for cPLA2 activation, which suggests the existence of alternative mechanisms for the enzyme to efficiently interact with membranes. Our previous in vitro data suggested the importance of phosphatidylinositol 4,5-bisphosphate (PtdInsP2) in the association of cPLA2 to model membranes and hence in the regulation of cPLA2 activity. Experiments described herein show that PtdInsP2 also serves a similar role in vivo. Moreover, inhibition of PtdInsP2 formation during activation conditions leads to inhibition of the cPLA2-mediated arachidonic acid mobilization. These results suggest that cellular PtdInsP2 levels are involved in the regulation of group IV cPLA2 activation.
Requirement for Foxd3 in maintaining pluripotent cells of the early mouse embryo (2002)

Critical to our understanding of the developmental potential of stem cells and subsequent control of their differentiation in vitro and in vivo is a thorough understanding of the genes that control stem cell fate. Here, we report that Foxd3, a member of the forkhead family of transcriptional regulators, is required for maintenance of embryonic cells of the early mouse embryo. Foxd3-/- embryos die after implantation at approximately 6.5 days postcoitum with a loss of epiblast cells, expansion of proximal extraembryonic tissues, and a distal, mislocalized anterior organizing center. Moreover, it has not been possible to establish Foxd3-/- ES cell lines or to generate Foxd3-/- teratocarcinomas. Chimera analysis reveals that Foxd3 function is required in the epiblast and that Foxd3-/- embryos can be rescued by a small number of wild-type cells. Foxd3-/- mutant blastocysts appear morphologically normal and express Oct4, Sox2, and Fgf4, but when placed in vitro the inner cell mass initially proliferates and then fails to expand even when Fgf4 is added. These results establish Foxd3 as a factor required for the maintenance of progenitor cells in the mammalian embryo.
Overexpression of the Saccharomyces cerevisiae Mannosylphosphodolichol Synthase-Encoding Gene in Trichoderma reesei Results in an Increased Level of Protein Secretion and Abnormal Cell Ultrastructure (1999)

Production of extracellular proteins plays an important role in the physiology of Trichoderma reesei and has potential industrial application. To improve the efficiency of protein secretion, we overexpressed in T. reesei the DPM1 gene of Saccharomyces cerevisiae, encoding mannosylphosphodolichol (MPD) synthase, under homologous, constitutively acting expression signals. Four stable transformants, each with different copy numbers of tandemly integrated DPM1, exhibited roughly double the activity of MPD synthase in the respective endoplasmic reticulum membrane fraction. On a dry-weight basis, they secreted up to sevenfold-higher concentrations of extracellular proteins during growth on lactose, a carbon source promoting formation of cellulases. Northern blot analysis showed that the relative level of the transcript of cbh1, which encodes the major cellulase (cellobiohydrolase I [CBH I]), did not increase in the transformants. On the other hand, the amount of secreted CBH I and, in all but one of the transformants, intracellular CBH I was elevated. Our results suggest that posttranscriptional processes are responsible for the increase in CBH I production. The carbohydrate contents of the extracellular proteins were comparable in the wild type and in the transformants, and no hyperglycosylation was detected. Electron microscopy of the DPM1-amplified strains revealed amorphous structure of the cell wall and over three times as many mitochondria as in the control. Our data indicate that molecular manipulation of glycan biosynthesis in Trichoderma can result in improved protein secretion.
DNA Barcoding Reveals Habitual Clonal Dominance of Myeloma Plasma Cells in the Bone Marrow Microenvironment (2017)

Multiple myeloma (MM) is a hematological malignancy resulting from the uncontrolled proliferation of antibody-producing plasma cells in the bone marrow. At diagnosis, independent plasma cell tumors are found throughout the skeleton. The recirculation of mutant plasma cells from the initial lesion and their recolonization of distant marrow sites are thought to occur by a process similar to solid tumor metastasis. However, the efficiency of this bone marrow homing process and the proportion of disseminated cells that actively divide and contribute to new tumor growth in MM are both unknown. We used the C57BL/KaLwRij mouse model of myeloma, lentiviral-mediated DNA barcoding of 5TGM1 myeloma cells, and next-generation sequencing to investigate the relative efficiency of plasma cell migration to, and growth within, the bone marrow. This approach revealed three major findings: firstly, establishment of metastasis within the bone marrow was extremely inefficient, with approximately 0.01% of circulating myeloma cells becoming resident long term in the bone marrow of each long bone; secondly, the individual cells of each metastasis exhibited marked differences in their proliferative fates, with the majority of final tumor burden within a bone being attributable to the progeny of between 1 and 8 cells; and, thirdly, the proliferative fate of individual clonal plasma cells differed at each bone marrow site in which the cells "landed." These findings suggest that individual myeloma plasma cells are subjected to vastly different selection pressures within the bone marrow microenvironment, highlighting the importance of niche-driven factors, which determine the disease course and outcome.
Stimulation of rat liver glycogen synthesis by the adenosine kinase inhibitor 5-iodotubercidin (1993)

The adenosine kinase inhibitor 5-iodotubercidin (Itu) was found to have the following effects on glycogen metabolism in hepatocytes of fasted rats. (1) Itu strongly stimulated glycogen synthesis from different substrates (glucose, lactate plus pyruvate, dihydroxyacetone, glycerol and fructose). In cells incubated with these substrates, the well-known stimulating effect of amino acids and that of Itu was more than additive. (2) In parallel with the increase in glycogen deposition, there was an increase in synthase a and a decrease in phosphorylase a concentrations after administration of Itu. Synthase a was increased by Itu and amino acids in an additive manner, whereas the observed activation of phosphorylase after addition of amino acids was antagonized by Itu. (3) In contrast with amino acids, Itu increased neither the cell volume nor the aspartate and glutamate concentrations. (4) Itu enhanced the levels of cyclic AMP. The stimulation of glycogen deposition in the presence of Itu persisted when the cyclic AMP concentration was further increased by adenosine or 2-chloroadenosine. (5) Itu decreased the concentration of ATP, but its effects on glycogen synthesis, synthase a and phosphorylase a concentrations persisted when the ATP catabolism was prevented by adenosine. (6) The effect of Itu on glycogen synthesis was not the result of inhibition of adenosine kinase, since 5'-amino-5'-deoxyadenosine, another inhibitor of this enzyme, had no effect on glycogen deposition.
Billion-Scale Similarity Search with GPUs (2019)

Similarity search finds application in database systems handling complex data such as images or videos, which are typically represented by high-dimensional features and require specific indexing structures. This paper tackles the problem of better utilizing GPUs for this task. While GPUs excel at data parallel tasks such as distance computation, prior approaches in this domain are bottlenecked by algorithms that expose less parallelism, such as <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">k</i> -min selection, or make poor use of the memory hierarchy. We propose a novel design for <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">k</i> -selection. We apply it in different similarity search scenarios, by optimizing brute-force, approximate and compressed-domain search based on product quantization. In all these setups, we outperform the state of the art by large margins. Our implementation operates at up to 55 percent of theoretical peak performance, enabling a nearest neighbor implementation that is 8.5 × faster than prior GPU state of the art. It enables the construction of a high accuracy <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">k</i> -NN graph on 95 million images from the Yfcc100M dataset in 35 minutes, and of a graph connecting 1 billion vectors in less than 12 hours on 4 Maxwell Titan X GPUs. We have open-sourced our approach for the sake of comparison and reproducibility.
Peptide-MHC Class I Tetrameric Complexes Display Exquisite Ligand Specificity (2000)

The production of synthetic MHC-peptide tetramers has revolutionized cellular immunology by revealing enormous CD8(+) T cell expansions specific for peptides from various pathogens. A feature of these reagents, essential for their staining function, is that they bind T cells with relatively high avidity. This could, theoretically, promote cross-reactivity with irrelevant T cells leading to overestimates of epitope-specific T cell numbers. Therefore, we have investigated the fine specificity of CTL staining with these reagents for comparison with functional data. Using a panel of CTL clones with distinct fine specificity patterns for analogs of an HLA-B8-binding EBV epitope, together with B8 tetramers incorporating these peptides, we show a very good correlation between tetramer staining and peptide activity in cytotoxicity assays. Significant staining only occurred with tetramers that incorporate strong stimulatory agonist peptides and not weak agonists that are unlikely to induce full T cell activation at physiological levels of presentation. In almost every case where a peptide analog had >10-fold less activity than the optimal EBV peptide in cytotoxicity assays, the corresponding tetramer stained with >10-fold less intensity than the EBV epitope tetramer. Furthermore, by examining an EBV-specific clonotypic T cell expansion in EBV-exposed individuals, we show similar fine specificity in tetramer staining of fresh peripheral T cells. Collectively, our data demonstrate the exquisite specificity of class I MHC-peptide tetramers, underlining their accuracy in quantifying only those T cells capable of recognizing the low levels of cell surface peptide presented after endogenous Ag processing.
Carbanion-Mediated Photocages:  Rapid and Efficient Photorelease with Aqueous Compatibility (2005)

A new photocage is proposed, based on ketoprofen-derived compounds and mediated by carbanions. The new photocage has significant advantages over the widely used o-nitrobenzyl derivatives, including aqueous compatibility, faster photorelease, higher quantum yield, and innocuous byproducts. The photorelease of ibuprofen illustrates the properties of the new photocage.
Fas Ligand-Induced Apoptosis as a Mechanism of Immune Privilege (1995)

The eye is a privileged site that cannot tolerate destructive inflammatory responses. Inflammatory cells entering the anterior chamber of the eye in response to viral infection underwent apoptosis that was dependent on Fas (CD95)-Fas ligand (FasL) and produced no tissue damage. In contrast, viral infection in gld mice, which lack functional FasL, resulted in an inflammation and invasion of ocular tissue without apoptosis. Fas-positive but not Fas-negative tumor cells were killed by apoptosis when placed within isolated anterior segments of the eyes of normal but not FasL-negative mice. FasL messenger RNA and protein were detectable in the eye. Thus, Fas-FasL interactions appear to be an important mechanism for the maintenance of immune privilege.
TTHE ESTROGEN-PROGESTERONE INDUCTION OF SEXUAL RECEPTIVITY IN THE SPAYED FEMALE MOUSE1 (1944)

ESTROGEN followed after a suitable interval by a small amount of progesterone is more effective than estrogen alone in inducing mating responses in the spayed female guinea pig (Dempsey, Hertz and Young, 1936) and in the spayed female rat (Boling and Blandau, 1939). Heat could be induced consistently in the spayed females of these species only when the two hormones were injected in proper sequence. The estrous behavior following estrogen-progesterone administration more closely resembled normal estrus in character and duration than did that following the injection of estrogen alone. These investigators therefore concluded that in the normal female guinea pig and rat sexual receptivity is the result of a conditioning action of follicular estrogen followed by the action of progesterone secreted by the preovulatory follicle. The literature supporting this view has been extensively reviewed by Young (1941).
Isolation of cloned cDNA encoding mammalian ornithine decarboxylase. (1984)

During the growth of mammalian cells the level of ornithine decarboxylase ( OrnDCase ; L-ornithine carboxy-lyase, EC 4.1.1.17), the first enzyme in polyamine biosynthesis, undergoes rapid changes. As an initial step in the study of possible genetic mechanisms involved in these changes, we have isolated cDNA clones encoding OrnDCase . To obtain RNA enriched for OrnDCase messenger, mouse myeloma cells that overproduce OrnDCase were selected in the presence of the OrnDCase inhibitor, difluoromethylornithine. A pBR322 cDNA library was prepared from poly(A)+ RNA isolated from difluoromethylornithine-resistant cells, and the library was probed with [32P]cDNA representing mRNA sequences from resistant or parental (sensitive) cells. All clones hybridizing preferentially to the resistant cell probe shared nucleotide sequences. A representative clone containing 1.1 kilobases of cDNA was shown to encode OrnDCase sequences by in vitro translation of hybrid-selected mRNA followed by precipitation of the translation products with anti- OrnDCase antiserum. Using this cDNA clone as a probe, we found that mouse DNA yielded several restriction fragments that react with the OrnDCase cDNA. In the difluoromethylornithine-resistant myeloma cells, one of these DNA segments is amplified and the level of OrnDCase mRNA is greatly increased compared with that in parental plasmacytoma cells. The level of OrnDCase mRNA is also increased in cultured 3T3 cells stimulated with serum and in mouse kidneys after administration of androgen, indicating that OrnDCase gene transcription and/or mRNA stability are regulated during cell growth.
Biosynthesis of chiral 3-hydroxyvalerate from single propionate-unrelated carbon sources in metabolically engineered E. coli (2010)

Our work represents the first report of direct microbial production of enantiomerically pure 3HV from a single carbon source. Continued engineering of host strains and pathway enzymes will ultimately lead to more economical production of chiral 3HV.