gebhart/patrepeval huggingface dataset:
Are Mast Cells MASTers in Cancer? (2017)

Prolonged low-grade inflammation or smoldering inflammation is a hallmark of cancer. Mast cells form a heterogeneous population of immune cells with differences in their ultra-structure, morphology, mediator content, and surface receptors. Mast cells are widely distributed throughout all tissues and are stromal components of the inflammatory microenvironment that modulates tumor initiation and development. Although canonically associated with allergic disorders, mast cells are a major source of pro-tumorigenic (e.g., angiogenic and lymphangiogenic factors) and antitumorigenic molecules (e.g., TNF-α and IL-9), depending on the milieu. In certain neoplasias (e.g., gastric, thyroid and Hodgkin's lymphoma) mast cells play a pro-tumorigenic role, in others (e.g., breast cancer) a protective role, whereas in yet others they are apparently innocent bystanders. These seemingly conflicting results suggest that the role of mast cells and their mediators could be cancer specific. The microlocalization (e.g., peritumoral vs intratumoral) of mast cells is another important aspect in the initiation/progression of solid and hematologic tumors. Increasing evidence in certain experimental models indicates that targeting mast cells and/or their mediators represent a potential therapeutic target in cancer. Thus, mast cells deserve focused consideration also as therapeutic targets in different types of tumors. There are many unanswered questions that should be addressed before we understand whether mast cells are an ally, adversary, or innocent bystanders in human cancers.
C-reactive protein binds to phosphorylated carbohydrates (2000)

C-reactive protein (CRP) is a major acute phase protein in man. In order to more fully understand the physiological role of this serum protein, we have demonstrated high avidity binding for a defined chemically synthesized carbo-hydrate ligand which represents the repeating disaccharide of lipophosphoglycan, the major surface glycoconjugate of the unicellular parasite Leishmania donovani. Increasing the number of phosphorylated disaccharides in a molecule from one up to seven did not increase the avidity for CRP, however increasing this to 10 potential CRP binding sites did. In order to define the important features of this complex and variable structure for CRP binding we competed CRP binding to whole Leishmania parasites with amino, sulfated, phosphorylated, and unsubstituted monosaccharides, of which only phosphorylated monosaccharides were able to inhibit. Both the carbohydrate and the position of phosphorylation influenced the avidity for CRP. Synthetic oligosaccharides and phospho-oligosaccharides of various lengths and conformations were used to define the structural requirements for CRP recognition. The optimum structure for recognition of a single phosphate group was between two monosaccharide pyranose rings, and within a linear rather than a cyclic molecule. This stresses the importance of the interaction of the CRP binding site with both the carbohydrate and the phosphate group. CRP function may be mediated via the recognition of large arrays of phosphorylated carbohydrates as are characteristic of the surface of microorganisms.
Design for a Room Temperature Superconductor (2006)

The vision of ``room temperature superconductivity'' has appeared intermittently but prominently in the literature since 1964, when W. A. Little and V. L. Ginzburg began working on the `problem of high temperature superconductivity' around the same time. Since that time the prospects for room temperature superconductivity have varied from gloom (around 1980) to glee (the years immediately after the discovery of HTS), to wait-and-see (the current feeling). Recent discoveries have clarified old issues, making it possible to construct the blueprint for a viable room temperature superconductor.
Materials Science of Carbon Nanotubes: Fabrication, Integration, and Properties of Macroscopic Structures of Carbon Nanotubes (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
Improved fibre optic respiratory monitoring using a figure-of-eight coil (2005)

The macro-bending loss effect in optical fibres has been used to redevelop a sensor for the measurement of thoracic and abdominal circumferences in non-invasive respiratory monitoring. The new sensor uses a novel figure-of-eight loop configuration, which results in increased linearity of response, less mechanical resistance and hysteresis, as well as other benefits. The performance of the new sensor as applied to respiratory monitoring is examined, and indicates a higher resolution and sensitivity than the old. This enhanced performance enables measurement of respiratory and cardiac function using the same transducing fibre.
Simulating human tasks using simple natural language instructions (2002)

The authors report a simple natural language interface to a human task simulation system that graphically displays the performance of goal-directed tasks by an agent in a workspace. The inputs to the system are simple natural language commands requiring achievement of spatial relationships among objects in the workspace. To animate the behaviors denoted by instructions, a semantics of action verbs and locative expressions is devised in terms of physically based components, in particular geometric or spatial relations among the relevant objects. To generate human body motions to achieve such geometric goals, motion strategies and a planner that used them are devised.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Mutations in an avian IgY-Fc fragment reveal the locations of monocyte Fc receptor binding sites (2009)

The avian IgY antibody isotype shares a common ancestor with both mammalian IgG and IgE and so provides a means to study the evolution of their structural and functional specialisations. Although both IgG and IgE bind to their leukocyte Fc receptors with 1:1 stoichiometry, IgY binds to CHIR-AB1, a receptor expressed in avian monocytes, with 2:1 stoichiometry. The mutagenesis data reported here explain the structural basis for this difference, mapping the CHIR-AB1 binding site to the Cupsilon3/Cupsilon4 interface and not the N-terminal region of Cupsilon3 where, at equivalent locations, the IgG and IgE leukocyte Fc receptor binding sites lie. This finding, together with the phylogenetic relationship of the antibodies and their receptors, indicates that a substantial shift in the nature of Fc receptor binding occurred during the evolution of mammalian IgG and IgE.
Biomedical applications of the information-efficient spectral imaging sensor (ISIS) (1999)

The ISIS approach to spectral imaging seeks to bridge the gap between tuned multispectral and fixed hyperspectral imaging sensor. By allowing the definition of completely general spectral filter functions, truly optimal measurement can be made for a given task. These optimal measurements significantly improve signal to noise ratio and speed, minimize data volume and data rate, while preserving classification accuracy. This paper investigates the application of the ISIS sensing approach in two sample biomedical applications: prostate and colon cancer screening. It is shown that is these applications, two to three optimal measurements are sufficient to capture the majority of classification information for critical samples constituents. In the prostate cancer example, the optimal measurements allow 8 percent relative improvement in classification accuracy of critical cell constituents over a red, green, blue (RGB) sensor. In the colon cancer example, use of optimal measurements boost the classification accuracy of critical cell constituents by 28 percent relative to the RGB sensor. In both cases, optimal measurements match the performance achieved by the entire hyperspectral data set. The paper concludes that an ISIS style spectral imager can acquire these optimal spectral images directly, allowing improved classification accuracy imager can acquire these optimal spectral images directly, allowing improved classification accuracy over an RGB sensor. Compared to a hyperspectral sensor, the ISIS approach can achieve similar classification accuracy using a significantly lower number of spectral samples, thus minimizing overall sample classification time and cost.
Progestin-rhenium complexes: metal-labeled steroids with high receptor binding affinity, potential receptor-directed agents for diagnostic imaging or therapy (1991)

In order to investigate the possibility of developing diagnostic imaging agents for steroid-positive tumors that are labeled with the readily available radionuclide technetium-99m, we prepared four conjugate systems in which a progestin is linked to a metal chelate system. Three of these are bis-amino bis-thiol (BAT or N2S2) systems and are linked through carbon-21 of progesterone or the 17 alpha- or 11 beta-position of a nortestosterone type progestin. The fourth, an amino-amido-thiol-alcohol chelate (N2OS) system, is linked at the 16 alpha,17 alpha-positions of a dihydroprogesterone. As a model for technetium-labeled complexes, all four chelate systems were converted to their oxo-rhenium complexes. Of the four possible diastereomers in the 16 alpha,17 alpha-system, only one was isolated, while of the four possible diastereomers in the other systems, a syn pair and an anti pair (linker methylene vs rhenium-oxo, relative to the N2S2 plane) were separated in the 17 alpha-substituted series, a syn pair was isolated in the 21-substituted series, and a syn pair and the two individual anti diastereomers were separated in the 11 beta-substituted series. In competitive radiometric receptor binding assays, the 21-, 17 alpha-, and 16 alpha,17 alpha-linked systems had low affinity for the progesterone receptor (less than 0.3% that of promegestone (R5020) or 2% that of progesterone). By contrast, the two anti diastereomers of the 11 beta-linked system had affinities that were 10% and 44% that of R5020 (or 64% and 283% that of progesterone) and the syn pair had an affinity 25% that of R5020 (or 161% that of progesterone). The latter finding indicates that it is possible to prepare metal-labeled steroids that retain high affinity for steroid receptors. These and related systems, when complexed with radioactive metals, may be useful in vivo as receptor-directed agents for diagnostic imaging or therapy of steroid receptor-positive tumors.
Capsaicin‐Induced Ion Fluxes Increase Cyclic GMP but Not Cyclic AMP Levels in Rat Sensory Neurones in Culture (1989)

Capsaicin, which induces fluxes of sodium, calcium, and potassium ions in a subset of both neonatal and adult rat dorsal root ganglion neurones, increased cyclic GMP (cGMP) levels by a factor of 20 (EC50 0.07 microM) to 10-20 pmol cGMP/mg protein in these cells. Cyclic AMP (cAMP) levels were unaffected. Nonneuronal cells derived from rat ganglia, and both neurones and nonneuronal cells from chick were unresponsive to capsaicin. Capsaicin-induced cGMP elevation in rat dorsal root ganglion (DRG) neurones was unaffected by pertussis toxin, lowered by compounds that block voltage-sensitive calcium channels, and was abolished by the removal of extracellular calcium. Calcium, guanidine, and rubidium fluxes were unaffected by treatment of DRG cells with sodium nitroprusside or dibutyryl cGMP. The cGMP response to capsaicin is thus a function of capsaicin-evoked calcium uptake through voltage-sensitive calcium channels. Elevated cGMP levels do not, however, contribute to capsaicin-evoked ion fluxes or to their desensitisation.
Collagenous bone matrix-induced endochondral ossification hemopoiesis. (1976)

Transplantation of collagenous matrix from the rat diaphyseal bone to subcutaneous sites resulted in new bone formation by an endochondral sequence. Functional bone marrow develops within the newly formed ossicle. On day 1, the implanted matrix was a discrete conglomerate with fibrin clot and polymorphonuclear leukocytes. By day 3, the leukocytes disappeared, and this event was followed by migration and close apposition of fibroblast cell surface to the collagenous matrix. This initial matrix-membrane interaction culminated in differentiation of fibroblasts to chondroblasts and osteoblasts. The calcification of the hypertrophied chondrocytes and new bone formation were correlated with increased alkaline phosphatase activity and 45Ca incorporation. The ingrowth of capillaries on day 9 resulted in chondrolysis and osteogenesis. Further remodelling of bony trabeculae by osteoclasts resulted in an ossicle of cancellous bone. This was followed by emergence of extravascular islands of hemocytoblasts and their differentiation into functional bone marrow with erythropoietic and granulopoietic elements and megakaryocytes in the ossicle. The onset and maintenance of erythropoiesis in the induced bone marrow were monitored by 59Fe incorporation into protein-bound heme. These findings imply a role for extracellular collagenous matrix in cell differentiation.
Advances in apoptosis research (1997)

Apoptosis, also called programmed cell death, has attracted great attention in recent years. After its discovery by Carl Vogt in 1842, apoptosis research was dormant for more than a century. Its rediscovery in the second half of this century, and the coining of the term apoptosis in 1972 by Kerr, Wyllie, and Currie, ignited an unparalleled interest in this field of science. The number of publications related to apoptosis has been growing exponentially every year ever since. This is mainly due to three major advances, two of which have been made recently and one that is currently seen. First, studies with the small nematode Caenorhabditis elegans have identified a number of apoptosis regulating genes--the first evidence that cell death is an active process under genetic control. Many of these genes have mammalian homologs that, like their worm counterparts, seem to regulate mammalian apoptosis. Second, elucidation of the signal transduction pathways of apoptosis has lead especially to the identification of specific death signaling molecules such as a new family of cysteine proteases, the caspases. Third, it has now become clear that many diseases are characterized by dysregulation of apoptotic programs. Many of these programs involve a family of receptors and their ligands, the death receptor/ligand family. The hope now is to interfere with apoptosis regulation in these systems and to develop new therapeutic concepts.
Dissemination ofListeria monocytogenesby Infected Phagocytes (1999)

In vitro data suggest that blood-borne Listeria monocytogenes organisms enter the central nervous system (CNS) by direct invasion of endothelial cells or by cell-to-cell spread from infected phagocytes to endothelial cells. However, a role for infected phagocytes in neuroinvasion and dissemination of L. monocytogenes in vivo has not been confirmed experimentally. Experiments described here tested whether L. monocytogenes-infected peripheral blood leukocytes (PBL) circulated in bacteremic mice and could establish organ infection in vivo. A mean of 30.5% of bacteria cultured from whole blood were PBL associated, and microscopy showed that 22.2% of monocytes and 1.6% of neutrophils were infected. PBL-associated bacteria spread to endothelial cells in vitro, indicating their potential for virulence in vivo. To test this possibility, mice were injected intravenously with infected PBL and CFU of bacteria in liver, spleen, and brain were quantified and compared with values for mice injected with broth-grown bacteria and in vitro-infected macrophage cell lines. An inoculum of infected macrophage cell lines led to greater numbers of bacteria in the liver than the numbers produced by a similar inoculum of broth-grown bacteria. In contrast, brain infection was best established by infected PBL. Results of intraperitoneal injection of infected peritoneal cells compared with results of injection with infected J774A.1 cells suggested that unrestricted intracellular bacterial replication within J774A.1 cells contributed to excessive liver infection in those mice. These data show dissemination of intracellular L. monocytogenes and indicate that phagocyte-facilitated invasion has a role in CNS infection in vivo. Heterogeneity with regard to bactericidal activity as well as to other phagocyte characteristics is a critical feature of this mechanism.
Specific Loss of Histone H3 Lysine 9 Trimethylation and HP1γ/Cohesin Binding at D4Z4 Repeats Is Associated with Facioscapulohumeral Dystrophy (FSHD) (2009)

Facioscapulohumeral dystrophy (FSHD) is an autosomal dominant muscular dystrophy in which no mutation of pathogenic gene(s) has been identified. Instead, the disease is, in most cases, genetically linked to a contraction in the number of 3.3 kb D4Z4 repeats on chromosome 4q. How contraction of the 4qter D4Z4 repeats causes muscular dystrophy is not understood. In addition, a smaller group of FSHD cases are not associated with D4Z4 repeat contraction (termed "phenotypic" FSHD), and their etiology remains undefined. We carried out chromatin immunoprecipitation analysis using D4Z4-specific PCR primers to examine the D4Z4 chromatin structure in normal and patient cells as well as in small interfering RNA (siRNA)-treated cells. We found that SUV39H1-mediated H3K9 trimethylation at D4Z4 seen in normal cells is lost in FSHD. Furthermore, the loss of this histone modification occurs not only at the contracted 4q D4Z4 allele, but also at the genetically intact D4Z4 alleles on both chromosomes 4q and 10q, providing the first evidence that the genetic change (contraction) of one 4qD4Z4 allele spreads its effect to other genomic regions. Importantly, this epigenetic change was also observed in the phenotypic FSHD cases with no D4Z4 contraction, but not in other types of muscular dystrophies tested. We found that HP1gamma and cohesin are co-recruited to D4Z4 in an H3K9me3-dependent and cell type-specific manner, which is disrupted in FSHD. The results indicate that cohesin plays an active role in HP1 recruitment and is involved in cell type-specific D4Z4 chromatin regulation. Taken together, we identified the loss of both histone H3K9 trimethylation and HP1gamma/cohesin binding at D4Z4 to be a faithful marker for the FSHD phenotype. Based on these results, we propose a new model in which the epigenetic change initiated at 4q D4Z4 spreads its effect to other genomic regions, which compromises muscle-specific gene regulation leading to FSHD pathogenesis.
Synthesis and biological evaluation of phosphonamidate peptide inhibitors of enkephalinase and angiotensin-converting enzyme (1985)

The effectiveness of phosphonamidate peptide analogues as inhibitors of rat kidney or human brain metalloendopeptidase (enkephalinase, E.C. 3.4.24.11) and angiotensin-converting enzyme (ACE, 3.4.14.1) has been explored with a series of enkephalin analogues in which the scissile Gly3-Phe4 amide bond has been replaced with a phosphonamidate moiety. These compounds exhibited good inhibitory potency against enkephalinase with several of the analogues having Ki values in the submicromolar range as contrasted to micromolar or higher toward ACE. Within a series of [(N-acylamino)methyl] phosphonamidates there was a dramatic decrease in inhibitory activity against enkephalinase as the N-acyl moiety was substituted with larger, more hydrophobic acyl groups. Likewise, the inhibitory activity of the [(N-acylamino)methyl] phosphonamidates against ACE was attenuated by larger phenylalkyl acyl functionalities, although not to the same degree as against enkephalinase. However, phosphonamidate pentapeptide analogues of (Leu)enkephalin and (D-Ala2,D-Leu5)enkephalin showed good inhibitory potency against both enzymes. Interestingly, these two (Leu)enkephalin phosphonamidate analogues were completely inactive in the electrically stimulated guinea pig ileum and mouse vas deferens preparations. Conformational factors that may be involved in this inactivity are discussed.
Preoperative Gabapentin Decreases Anxiety and Improves Early Functional Recovery from Knee Surgery (2005)

Gabapentin has antihyperalgesic and anxiolytic properties. We thus tested the hypothesis that premedication with gabapentin would decrease preoperative anxiety and improve postoperative analgesia and early postoperative knee mobilization in patients undergoing arthroscopic anterior cruciate ligament repair under general anesthesia. Forty patients were randomly assigned to receive 1200 mg oral gabapentin or placebo 1-2 h before surgery; anesthesia was standardized. Patients received morphine, 0.1 mg/kg, 30 min before the end of surgery and postoperatively via a patient-controlled pump. Pain scores and morphine consumption were recorded over 48 h. Degrees of active and passive knee flexion and extension were recorded during physiotherapy on days 1 and 2. Preoperative anxiety scores were less in the gabapentin than control group (visual analog scale scores of 28 +/- 16 mm versus 66 +/- 15 mm, respectively; P < 0.001). The gabapentin group required less morphine than the control group (29 +/- 22 mg versus 69 +/- 40 mg, respectively; P < 0.001). Visual analog scale pain scores at rest and after mobilization were significantly reduced in the gabapentin group. First and maximal passive and active knee flexions at 24 and 48 h were significantly more extensive in the gabapentin than in the control group. In conclusion, premedication with 1200 mg gabapentin improved preoperative anxiolysis, postoperative analgesia, and early knee mobilization after arthroscopic anterior cruciate ligament repair.
Amino acid derivatives : a practical approach (1999)

Preface 1. Introduction 2. Acylation and alkoxycarbonylation of the amino group 3. Thioacylatin of the amino group of amino acids 4. Mono- and Di-alkylatin of the amino group 5. Reactions at the carboxy group of an amino acid: Amino acid salts 6. Reactions at the carboxy group of an amino acid: Esterification of amino acids 7. Carboxy group modifications synthesis of a homochiral ketone derived from L-tryptophan 8. Synthons derived from Aspartic and glutamic acids 9. Benzophenone schiff bases of a-Amino acid esters as electrophiles. Addition of grignard reagents and alkly-lithiums to produce threo-amino alcohols and aminopolyols 10. Synthetic uses of serine, threonine and cysteine 11. Synthetic uses of methionine 12. Metal-mediated modification of the side-chains of a-amino acids 13. Diastereocontrolled functionalisation of enantiomerically pure 5-phenyl-1, 4-Oxazin-2-ones by azomethine ylid generation and trapping 14. Reductive modifications of the carboxy-group 15. Reactions at the a-Carbon Atom of a-Amino acid derivatives 16. Modifications of the Aryl substitutents of a- and beta-aryl a-amino acids 17. Isolation and chromatographic purification of reaction products from amino acids Index