gebhart/patrepeval huggingface dataset:
Plasminogen, the Serum Proenzyme Activated by Factors from Cells Transformed by Oncogenic Viruses (1974)

The serum factor that participates in the fibrinolytic activity associated with tumor and transformed cells has been purified by two independent methods. The chromatographic, electrophoretic, and biochemical properties of this molecule are consistent with the properties of the known fibrinolytic pre-cursor, plasminogen. Purified plasminogen was isolated by affinity chromatography from fetal bovine, chicken, dog, and human sera and its activation by factors released from a variety of transformed cell cultures, including human tumor cell lines, was examined. The specificity of activation is absolute in the avian system, i.e. chicken plasminogen is activated only by the factor from cultures of chick embryo fibroblasts transformed by the Rous sarcoma virus. The mammalian plasminogens are activated to varying extents by the activators from all transformed cells tested.
Control of cell division in Escherichia coli: regulation of transcription of ftsQA involves both rpoS and SdiA-mediated autoinduction. (1996)

The conditioning of culture medium by the production of growth-regulatory substances is a well-established phenomenon with eukaryotic cells. It has recently been shown that many prokaryotes are also capable of modulating growth, and in some cases sensing cell density, by production of extracellular signaling molecules, thereby allowing single celled prokaryotes to function in some respects as multicellular organisms. As Escherichia coli shifts from exponential growth to stationary growth, many changes occur, including cell division leading to formation of short minicells and expression of numerous genes not expressed in exponential phase. An understanding of the coordination between the morphological changes associated with cell division and the physiological and metabolic changes is of fundamental importance to understanding regulation of the prokaryotic cell cycle. The ftsQA genes, which encode functions required for cell division in E. coli, are regulated by promoters P1 and P2, located upstream of the ftsQ gene. The P1 promoter is rpoS-stimulated and the second, P2, is regulated by a member of the LuxR subfamily of transcriptional activators, SdiA, exhibiting features characteristic of an autoinduction (quorum sensing) mechanism. The activity of SdiA is potentiated by N-acyl-homoserine lactones, which are the autoinducers of luciferase synthesis in luminous marine bacteria as well as of pathogenesis functions in several pathogenic bacteria. A compound(s) produced by E. coli itself during growth in Luria Broth stimulates transcription from P2 in an SdiA-dependent process. Another substance(s) enhances transcription of rpoS and (perhaps indirectly) of ftsQA via promoter P1. It appears that this bimodal control mechanism may comprise a fail-safe system, such that transcription of the ftsQA genes may be properly regulated under a variety of different environmental and physiological conditions.
Daily Hassles Reported by Chronic Fatigue Syndrome and Fibromyalgia Patients in Tertiary Care: A Controlled Quantitative and Qualitative Study (2002)

Patients recently diagnosed as suffering from CFS and/or FM are highly preoccupied and distressed by daily hassles that have a severe impact on their self-image, as well as their personal, social and professional functioning. An optimal therapeutic approach of CFS and FM should take account of this heavy psychosocial burden, which might refer to core themes of these patients' illness experience.
Efficient amplification and direct sequencing of mouse variable regions from any immunoglobulin gene family (1999)

We have designed two original sets of oligonucleotide primers hybridizing the relatively conserved motifs within the immunoglobulin signal sequences of each of the 15 heavy chain and 18 kappa light chain gene families. Comparison of these 5' primers with the immunoglobulin signal sequences referenced in the Kabat database suggests that these oligonucleotide primers should hybridize with 89.4% of the 428 mouse heavy chain signal sequences and with 91.8% of the 320 kappa light chain signal sequences with no mismatch. Following PCR amplification using the designed primers and direct sequencing of the amplified products, we obtained full-length variable sequences belonging to major (V(H)1, V(H)2, V(H)3, Vkappa1 and Vkappa21) but also small-sized (V(H)9, V(H)14, Vkappa2, Vkappa9A/9B, Vkappa12/13, Vkappa23 and Vkappa33/34) gene families, from nine murine monoclonal antibodies. This strategy could be a powerful tool for antibody sequence assessment whatever the V gene family before humanization of mouse monoclonal antibody or identification of paratope-derived peptides.
Germ-free and Colonized Mice Generate the Same Products from Enteric Prodefensins (2000)

The use of germ-free mice offers the possibility to study antibacterial components in a gut uncolonized by bacteria. We have developed a method to extract and high pressure liquid chromatography-fractionate the antibacterial factors present in the small intestine of a single mouse. By mass spectrometry and sequence analyses of fractions exhibiting antimicrobial activity, we identified and characterized the defensin region in germ-free mice as well as in colonized mice. Defensins made up around 15% of the total antibacterial activity both in germ-free and colonized mice. The intestine of germ-free mice exhibited the same set of mature enteric defensins (defensins 1, 2, 3, 4, and 6) as mice colonized by a normal microflora. Mature defensins are generated through processing of larger precursors by enzymatic removal of a signal peptide and a propiece. We found that all prodefensins were cleaved at a Ser/Ala-Leu bond, giving 34-residue propiece peptides and only trace amounts of the predicted 39-residue peptide. This first step must be followed by the removal of a residual peptide to render the mature defensins, indicating that the processing is more complex than previously anticipated. The same propieces were found in both germ-free and colonized mice, suggesting that the same processing operates independent of bacterial presence in the intestine.
Cathodoluminescence Investigations of Interfaces in InGaN/GaN/Sapphire Structures (2001)

Scanning electron microscopy and cathodoluminescence (CL) in spot and depth-profiling modes were used to evaluate the in-plane and in-depth uniformity of light emission from InGaN/GaN quantum well (QW) structures. The structures were grown by MOCVD on sapphire with a low-temperature (LT) GaN buffer. Depth-profiling CL investigations were used to identify the observed CL emissions, which show a complicated in-depth evolution. The influence of a LT GaN buffer on the structural and optical properties of the GaN/sapphire interface is discussed.
Crystal structure of the macrocycle-forming thioesterase domain of the erythromycin polyketide synthase: Versatility from a unique substrate channel (2001)

As the first structural elucidation of a modular polyketide synthase (PKS) domain, the crystal structure of the macrocycle-forming thioesterase (TE) domain from the 6-deoxyerythronolide B synthase (DEBS) was solved by a combination of multiple isomorphous replacement and multiwavelength anomalous dispersion and refined to an R factor of 24.1% to 2.8-A resolution. Its overall tertiary architecture belongs to the alpha/beta-hydrolase family, with two unusual features unprecedented in this family: a hydrophobic leucine-rich dimer interface and a substrate channel that passes through the entire protein. The active site triad, comprised of Asp-169, His-259, and Ser-142, is located in the middle of the substrate channel, suggesting the passage of the substrate through the protein. Modeling indicates that the active site can accommodate and orient the 6-deoxyerythronolide B precursor uniquely, while at the same time shielding the active site from external water and catalyzing cyclization by macrolactone formation. The geometry and organization of functional groups explain the observed substrate specificity of this TE and offer strategies for engineering macrocycle biosynthesis. Docking of a homology model of the upstream acyl carrier protein (ACP6) against the TE suggests that the 2-fold axis of the TE dimer may also be the axis of symmetry that determines the arrangement of domains in the entire DEBS. Sequence conservation suggests that all TEs from modular polyketide synthases have a similar fold, dimer 2-fold axis, and substrate channel geometry.
Characterization of the Growth Factor Activity of Amniotic Fluid on Cells from Hematopoietic and Lymphoid Organs of Different Life Stages (1996)

We investigated the proliferation-promoting effects of murine amniotic fluid (MAF) on in vitro cultured cells originally obtained from murine hematopoietic and lymphoid organs at different life stages. MAF promoted proliferation of the fetal liver cells (FLC), newborn spleen cells and adult bone marrow cells. The proliferation-promoting activity of MAF was extended to liver cells and spleen cells from mice younger than 2 weeks old. MAF did not, however, promote the proliferation of newborn or adult thymocytes, or of spleen cells, liver cells or peritoneal cells, liver cells or peritoneal cells from 2-week-old or older mice. Rather, it partially inhibited the proliferation of spleen cells, thymocytes and peritoneal cells from 1-year-old mice. These results suggest that MAF contains growth factors for hematopoietic stem cells but not for either mature or immature T lymphocytes. Supporting this view, the MAF activity was partially neutralized by a polyclonal anti-mouse stem cell factor (SCF) antibody. Moreover, the immunoblotting of MAF against anti-mouse SCF antibody revealed a band at 30-32 kDa corresponding to the previously reported SCF. Interestingly, MAF was able to maintain FLC and adult bone marrow cells alive in culture for a relatively long time (2 weeks). The MAF activity was further shown to be partially and cell type-dependently antagonized by TNF-alpha and TGF-beta. These results provided evidence that MAF contains potentially multiple growth factors preferentially affecting the early stage of hematopoiesis, one of which is SCF.
Classification of Neisseria meningitidis Group B into Distinct Serotypes. III. Application of a New Bactericidal-Inhibition Technique to Distribution of Serotypes among Cases and Carriers (1973)

The development of sensitive serologic techniques in this laboratory has enabled the subdivision of group B meningococci into 11 distinct serotypes. The establishment of serologic types within group B has permitted these preliminary epidemiologic studies of disease due to group B Neisseria meningitidis. A sensitive technique for bactericidal inhibition is described. This technique and two other methods have been used to serotype a large number of group B strains. Strains with the type 2 antigen (i.e., type 2-associated serotypes) were the most prevalent. Almost 75% of the group B, type 2-associated strains examined were isolated from patients with meningococcal disease. In addition, 69% of these type 2-associated strains were resistant to sulfisoxazole at a concentration of 0.1 mg/ 100 mI, whereas only 17% of non-type 2 serotypes were resistant to this level of sulfisoxazole. When strains from carriers were examined, the non-type 2 serotypes represented 78% of these carrier strains.
Cannabinoid CB2Receptors and Fatty Acid Amide Hydrolase Are Selectively Overexpressed in Neuritic Plaque-Associated Glia in Alzheimer's Disease Brains (2003)

The endocannabinoid system is still poorly understood. Recently, the basic elements that constitute it, i.e., membrane receptors, endogenous ligands, and mechanisms for termination of the signaling process, have been partially characterized. There is a considerable lack of information, however, concerning the distribution, concentration, and function of those components in the human body, particularly during pathological events. We have studied the status of some of the components of the endocannabinoid system, fatty acid amide hydrolase and cannabinoid CB1 and CB2 receptors, in postmortem brains from patients with Alzheimer's disease. Using specific polyclonal antibodies, we have performed immunohistochemical analysis in hippocampus and entorhinal cortex sections from brains of Alzheimer's disease patients. Our results show that both fatty acid amide hydrolase and cannabinoid CB2 receptors are abundantly and selectively expressed in neuritic plaque-associated astrocytes and microglia, respectively, whereas the expression of CB1 receptors remains unchanged. In addition, the hydrolase activity seems to be elevated in the plaques and surrounding areas. Thus, some elements of the endocannabinoid system may be postulated as possible modulators of the inflammatory response associated with this neurodegenerative process and as possible targets for new therapeutic approaches.
Parameters associated with chronic renal transplant failure. (1997)

In CPTF immunological as well as non immunological factors are independently associated with the decline of excretory allograft function in the late postoperative period.
Comparison of on-axis three-mirror-anastigmat telescopes (2007)

We compare and contrast the Korsch (1972) full-field three-mirror anastigmat telescope (TMA) to the Korsch (1977) annular-field TMA. Both TMAs offer flat fields with comparably good aberration correction and comparably good telephoto advantage. Both offer good accessibility of the focal plane. The advantages of the FFTMA are its extremely uniform focal length over its field, its nearly telecentric final focus, and the fact that there is no hole in the center of its field. The advantages of the AFTMA are its complete accessible cold stop (essential if a warm telescope is to be used to image the sky at near-IR wavelengths) and its low sensitivity to mirror location error. Either alternative can deliver diffraction-limited visible-wavelength images over a one degree diameter field with a two meter aperture.
Site-directed mutagenesis of adeno-associated virus type 2 structural protein initiation codons: effects on regulation of synthesis and biological activity (1994)

It has been shown that two of the three adeno-associated virus type 2 capsid proteins, B and C, are synthesized from a single spliced transcript. Protein C arises from an AUG codon at nucleotide 2810, whereas protein B is initiated by a unique eucaryotic initiation codon (ACG) that lies 65 triplets upstream from the C origin. The third capsid component, protein A, is synthesized from a second spliced transcript which uses an alternative 3' acceptor site. In this study we used oligonucleotide-directed mutagenesis to confirm the positions of the B initiation codon and the 3' acceptor sites for the alternatively spliced B/C and A protein messages. We also located definitively the protein A initiation codon, an AUG triplet mapping to nucleotide 2203. Mutagenesis of the B initiator permitted a direct test of the effect of increased B initiator strength on the translational efficiencies of the B and C proteins. It was found that conversion of the relatively inefficient protein B initiator (ACG) to an AUG enhanced the level of B synthesis while abolishing the synthesis of C from its downstream AUG initiator. Protein C synthesis thus depends on the strength of the B initiator, i.e., the relatively higher levels of C (approximately 20-fold greater than B) must result from frequent readthrough of the weak B initiator. Finally, we examined the abilities of mutants deficient in the synthesis of A, B, or C to produce infectious virions. We found that at least two of the structural proteins, B and C, are required for the production of infectious virions and that sequestration of single-stranded adeno-associated virus genomes from the pool of replicating DNA molecules does not occur in the absence of either of these proteins.
Truncation of the class II beta-chain cytoplasmic domain influences the level of class II/invariant chain-derived peptide complexes. (1996)

Previous studies have established that antigen presenting cells (APC) expressing major histocompatibility complex class II beta chains with truncated cytoplasmic domains are impaired in their capacity to activate T cells. While it had been widely accepted that this impairment is due to a defect in class II cytoplasmic domain-dependent signal transduction, we recently generated transgenic mice expressing only truncated class II beta chains, and functional analyses of APC from these mice revealed signaling-independent defects in antigen presentation. Here, we demonstrate that T cells primed on such transgenic APC respond better to stimulation by APC expressing truncated beta chains than by wild-type APC. This finding suggests that APC expressing truncated class II beta chains are not inherently defective in their antigen presenting capacity but, rather, may differ from wild-type APC in the peptide antigens that they present. Indeed, analysis of the peptides bound to class II molecules isolated from normal and transgenic spleen cells revealed clear differences. Most notably, the level of class II-associated invariant chain-derived peptides (CLIP) is significantly reduced in cells expressing only truncated beta chains. Prior studies have established that CLIP and antigenic peptides compete for binding to class II molecules. Thus, our results suggest that the cytoplasmic domain of the class II beta chain affects antigen presentation by influencing the level of CLIP/class II complexes.
REVIEWS (1963)

Journal Article REVIEWS Get access Gibbon's Journey from Geneva to Rome. His Journal from 20 April to 2 October 1764. Edited by GEORGES A. BONNARD. Pp. xxvi+268. London: Nelson, 1961. 50s. net D. M. LOW D. M. LOW Search for other works by this author on: Oxford Academic Google Scholar The Review of English Studies, Volume XIV, Issue 53, 1963, Pages 90–92, https://doi.org/10.1093/res/XIV.53.90 Published: 01 January 1963
Discovery and mechanism of ustekinumab (2011)

Monoclonal antibody (mAb) therapy was first established upon the approval of a mouse antibody for treatment of human acute organ rejection. However, the high incidence of immune response against the mouse mAb restricted therapeutic utility. Development of chimeric, "humanized" and human mAbs broadened therapeutic application to immune-mediated diseases requiring long-term treatment. Indeed, mAb therapeutics targeting soluble cytokines are highly effective in numerous immune-mediated disorders. A recent example is ustekinumab, a first-in-class therapeutic human immunoglobulin G1 kappa mAb that binds to the interleukins (IL)-12 and IL-23, cytokines that modulate lymphocyte function, including T-helper (Th) 1 and Th17 cell subsets. Ustekinumab was generated via recombinant human IL-12 immunization of human immunoglobulin (hu-Ig) transgenic mice. Ustekinumab binds to the p40 subunit common to IL-12 and IL-23 and prevents their interaction with the IL-12 receptor β1 subunit of the IL-12 and IL-23 receptor complexes. Ustekinumab is approved for treatment of moderate-to-severe plaque psoriasis and has demonstrated efficacy in Crohn disease and psoriatic arthritis. The clinical characterization of ustekinumab continues to clarify our understanding of human immune pathologies and may offer a novel therapeutic option for certain immune-mediated diseases.
Genetic defect in T lymphocyte‐specific homing into peripheral lymph nodes (1997)

Lymphocytes circulating in the bloodstream home into lymph nodes (LN). T cells predominate in peripheral LN (PLN) and B cells in spleen or mucosal tissue, e.g. Peyer's patches (PP). DDD/1 mice are unique in marked paucity of LN cells, especially T cells. T cell frequency in PLN was 20-40% in this strain, compared to 60-80% in others. Immunohistochemistry confirmed the low density of T cells in the subcortical area but normal colonization of B cells in cortical area in PLN of DDD/1. In contrast, the T cell content of peripheral blood and spleen was higher in DDD/1 but that in PP was not significantly different compared to other strains. It was thus concluded that this abnormality in DDD/1 results from a homing defect of T cells into PLN but not from lymphopenia. Genetical analysis showed that the defect in T cell-specific homing was regulated by a single autosomal recessive gene, tentatively designated plt (paucity of lymph node T cells). Reciprocal bone marrow transplantation indicated that the plt phenotype may arise from some defect in PLN stroma but not in lymphocytes. An in vivo homing assay using fluorescence-labeled lymphocytes demonstrated that the homing defect was specific for T cells but not for B cells. A Stamper-Woodruff assay revealed that the binding between lymphocytes and PLN high endothelial venules was normal and that L-selectin and its ligand, peripheral node vascular addressin (PNAd), were expressed and functioned normally in DDD/1. These results taken together indicate that the T cell-specific homing into PLN is disturbed at a post-adhesion stage in DDD/1. The product of the plt locus may play a pivotal role at this stage.
Taxane-Platinum Combinations in Advanced Non-Small Cell Lung Cancer: A Review (2004)

Platinum-based chemotherapy is the treatment of choice for patients with non-small cell lung cancer (NSCLC). As a result of their single-agent activities and synergistic effects, taxane-platinum combinations are often used as first-line therapy for this disease. Four large, multicenter, randomized phase III clinical trials (the TAX 326 trial, the Southwest Oncology Group 9509 trial, the Italian Lung Cancer Project, and the Eastern Cooperative Oncology Group 1594 trial) have compared taxane-platinum combinations (docetaxel and paclitaxel) with other platinum combinations (vinorelbine and gemcitabine) in chemotherapy-naïve patients with good performance status scores and advanced disease. The end points for these large randomized clinical trials were survival, response rate, adverse events, and quality of life (QOL). Of the taxane-platinum combinations tested, docetaxel-cisplatin was the only platinum combination to yield survival and response rates superior to another platinum combination. In adverse event terms, the taxane-platinum combination of paclitaxel-carboplatin demonstrated less grade 3 or 4 neutropenia and lower rates of febrile neutropenia than other taxane-platinum combinations but higher rates of irreversible grade 3 or 4 peripheral neuropathy than any of the other taxane-platinum combinations. Additional differences emerged when QOL data were evaluated. The docetaxel-platinum combination demonstrated broad QOL benefits for patients receiving this combination, and this benefit was not observed with the other platinum or taxane-platinum combinations. As our use of these taxane-platinum combinations expands, these differences in survival, response rate, adverse events, and QOL will permit us to better balance our treatment goals for all patients with all stages of NSCLC.
Induction of antigen-specific regulatory T cells in wild-type mice: Visualization and targets of suppression (2008)

Antigen-specific transplantation tolerance in the absence of immunosuppressive drugs is a rarely achieved goal. Immune responses to Y chromosome-encoded transplantation antigens (HY) can have life-threatening consequences in the clinic. Here, we have adopted a procedure developed in T cell antigen receptor (TCR)-transgenic mice to convert naïve T cells into male-specific Foxp3(+) regulatory T cells (Tregs) in WT female mice. For this purpose, female mice were infused by osmotic minipumps with a single class II MHC-presented HY peptide and Tregs visualized by tetramer staining. As a result, animals developed Treg-mediated long-term tolerance to all HY transplantation antigens, irrespective of whether they were recognized by CD4 or CD8 T cells, on skin or hematopoietic grafts from male donors.