gebhart/patrepeval huggingface dataset:
Modern molecular genetic approaches to complex traits: implications for psychiatric disorders. (1996)

The majority of common psychiatric disorders pose problems for geneticists because of their complex and non-Mendelian modes of inheritance. Early attempts to map genes for mental illness have so far largely overlooked this and sought genes of major effect in multiplex families using the lod score method of linkage analysis. However it seems that major genes are likely to be at best rare causes of common mental disorders, and the majority of cases probably reflect the interaction of several and perhaps many genes of comparatively small effect. There are two complementary sets of strategies that allow such genes to be identified. The first is to perform linkage analysis based on allele sharing in pairs of affected relatives. The second is to carry out association studies on samples of unrelated individuals. These methods and their applicability to psychiatric disorders are described. Psychiatric genetics has traditionally focussed on categorical phenotypes, but if valid continuous measures can be developed, powerful quantitative trait loci (QTL) approaches may also become feasible. Another important area is likely to be the study of relevant models in animals such as rodents in which genetic studies have many advantages. Finally we should not overlook the possibility that there are molecular explanations for irregular patterns of transmission such as mitochondrial inheritance, genomic imprinting and dynamic mutations.
Technology evaluation: lumiliximab, Biogen Idec. (2004)

Biogen Idec (formerly IDEC Pharmaceuticals) is developing lumiliximab, a primatized anti-CD23 macaque/human chimeric antibody that inhibits the production of the IgE antibody, for the potential treatment of allergic conditions.
Purification and Properties of a Ribose-binding Protein from Escherichia coli (1974)

Abstract Escherichia coli W3092 has a specific permease for ribose with a Km of 0.3 µm. An osmotic shock releasable ribosebinding protein was purified to homogeneity. The ribosebinding protein has an apparent molecular weight of 29,500 as judged by gel titration and sodium dodecyl sulfate polyacrylamide gel electrophoresis and an isoelectric point of 6.6. The binding protein is specific for d-ribose and 1 molecule of ribose is bound per molecule of protein with a dissociation constant of 0.13 µm. The high specificity for binding and transport also correspond with the ribose chemotactic system in E. coli (Adler, J., Hazelbauer, G. L., and Dahl, M. M. (1974) J. Bacteriol. 115, 824). The ribose-binding protein of E. coli cross-reacts immunologically with serum prepared against the Salmonella typhimurium ribose-binding protein but does not cross-react with sera prepared against a number of other binding proteins including the E. coli galactose-glucose-binding protein.
The biological effect of continuous passive motion on the healing of full-thickness defects in articular cartilage. An experimental investigation in the rabbit. (1980)

A new concept, continuous passive motion of a synovial joint in vivo, was investigated to determine its biological effect on the healing of full-thickness articular cartilage defects that penetrate the subchondral bone of knee joints of adolescent and adult rabbits. The effect of continuous passive motion was compared with the effects of immobilization and of intermittent active motion. This investigation included assessment of 480 defects in the knees of 120 adolescent rabbits and assessment of 108 defects in the knees of twenty-seven adult rabbits. The continuous passive motion was well tolerated by these animals, whose general well-being was undisturbed. The healing of the defects at weekly intervals up to four weeks was assessed by gross examination and by an analysis of two indices of healing determined by light microscopy: (1) the nature of the reparative tissue, and (2) the degree of metachromasia of the matrix as demonstrated by toluidine-blue staining. At three weeks this assessment revealed that in the adolescent rabbits, healing of the defects by hyaline articular cartilage was present in 8 per cent of forty defects in ten animals whose knees were immobilized, in 9 per cent of forty defects in ten animals whose knees were permitted intermittent active motion, and in 52 per cent of forty defects in ten animals whose knees were managed immediately after operation by continuous passive motion. At three weeks, in the adult animals, healing of the defects by hyaline articular cartilage was present in 3 per cent of thirty-six defects in nine animals whose knees were immobilized, in 5 per cent of thirty-six defects in nine animals whose knees were permitted intermittent active motion, and in 44 per cent of thirty-six defects in nine animals whose knees were managed immediately after operation by continuous passive motion. Thus, the metaplasia of the healing tissue within the defects from undifferentiated mesenchymal tissue to hyaline articular cartilage was not only much more rapid but also much more complete with continuous passive motion than with either immobilization or intermittent active motion.
Epidermal growth factor receptor content in human renal cell carcinomas (1994)

The determination of EGFR content in RCC may become an important prognostic factor for the biologic behavior of RCC.
Host Access Protocol specification (1984)

This document specifies the Host Access Protocol (HAP). Although HAP
was originally designed as the network-access level protocol for the
DARPA/DCA sponsored Wideband Packet Satellite Network, it is intended
that it evolve into a standard interface SATNET and TACNET (aka
MATNET) as well as the Wideband Network. HAP is an experimental
protocol, and will undergo further revision as new capabilities are
added and/or different satellite networks are suported.
Implementations of HAP should be performed in coordination with
satellite network development and operations personnel.
Matrix Remodeling after Stroke: De Novo Expression of Matrix Proteins and Integrin Receptors (1999)

Following an ischemic insult to the central nervous system a reorganization of cells and tissue takes place as the surrounding cells attempt to limit the injury, repair the damage, and restore normal architecture of the brain. This tissue remodeling requires de novo synthesis of genes and proteins which enables cells to actively change their relationship with the existing extracellular matrix and with other cells to reorganize the damaged tissue. We have identified two key molecular components of the matrix remodeling process after focal ischemia: osteopontin (OPN) and its integrin receptor alpha v beta 3 (alpha v beta 3). OPN is initially expressed by activated macrophages and microglia in the periinfarct region (24-48 hr) and at later times (5-15 days) in the core infarct. After focal stroke the alpha v beta 3 was upregulated by astrocytes in the periinfarct region. Spatial and temporal analyses demonstrated that at 5 days after injury the alpha v beta 3-positive astrocytes were at a distance from the osteopontin-expressing macrophages; by 15 days the alpha v beta 3-expressing astrocytes were localized within an osteopontin-rich matrix. In vitro OPN was shown to induce migration of astrocytes in a Boyden chamber system. These data suggest that OPN derived from microglia at the infarct border zone (and possible macrophages in the infarct core) may serve as an "astrokine" (suggested term for astrocyte chemoattractant) to organize the astrocyte scar after focal stroke. Our data demonstrate profound changes in brain matrix remodeling after focal ischemic stroke, including the synthesis and release of matrix proteins alien to the normal brain, the expression of integrin receptors that ligate these proteins, and possibly a novel function for microglial-derived OPN in astrocyte migration after focal ischemia that may drive glial activation, organization, and repair functions.
Analysis of the pH Requirement for Membrane Fusion of Different Isolates of the Paramyxovirus Parainfluenza Virus 5 (2006)

Paramyxoviruses enter cells by fusing their envelopes with the plasma membrane, a process that occurs at neutral pH. Recently, it has been found that there is an exception to this dogma in that a porcine isolate of the paramyxovirus parainfluenza virus 5 (PIV5), known as SER, requires a low-pH step for fusion (S. Seth, A. Vincent, and R. W. Compans, J. Virol. 77: 6520-6527, 2003). As a low-pH activation mechanism for fusion would greatly facilitate biophysical studies of paramyxovirus-mediated membrane fusion, we have reexamined the triggering of the PIV5 SER fusion protein. Using multiple assays, we could not find a requirement for low-pH triggering of PIV5 SER fusion. The challenge of discovering how the paramyxovirus receptor binding protein (HN, H, or G) activates the metastable fusion protein to cause membrane fusion at neutral pH remains.
Novel Step-Growth Polymers from the Thermal [2π + 2π] Cyclopolymerization of Aryl Trifluorovinyl Ether Monomers (1996)

Thermoplastic and thermosetting polymers comprising alternating arylene ether and 1,2-hexafluorocyclobutane subunits are prepared from aromatic bis- and tris-trifluorovinyl ether monomers. Step growth, addition type polymerization proceeds by the thermally induced [2π + 2π] cyclodimerization of the trifluorovinyl functionality. Monomers are conveniently prepared in two steps from phenolic starting materials and 1,2-dibromotetrafluoroethane or from Grignard reagents containing the flourinated vinyl group. Preparation and performance of these novel polymers are described with references to sources of further information.
The Efficacy of a Resistive Heating Under-Patient Blanket Versus a Forced-Air Warming System: A Randomized Controlled Trial (2008)

We demonstrated that, using either a resistive heating-blanket or forced-air warming systems, patients ended surgery in mild hypothermia after elective total hip replacement, but without significant differences between these two warming devices.
A Heparin-Binding Form of Placenta Growth Factor (PlGF-2) is Expressed in Human Umbilical Vein Endothelial Cells and in Placenta (1993)

Placenta Growth Factor (PlGF) was recently discovered as a secreted growth factor for vascular endothelial cells and based on its homology to vascular endothelial growth factor (VEGF), can be classified as a new member of this growth factor family. We have carried out polymerase chain amplification (PCR) of RNA from human umbilical vein endothelial cells and placenta tissue and discovered a second species of PlGF, PlGF-2. PlGF-2 has a 21-amino acid insertion not present in PlGF-1 coding for a highly basic region near the C-terminus. This is similar to VEGF189. Northern analysis has shown, that the PlGF gene is expressed only in a limited number of cell types and tissues, e.g. human umbilical vein endothelial cells (HUVE) and placenta. Infection of Sf158 insect cells with recombinant baculoviruses specific for the two forms showed, that both, PlGF-1 and PlGF-2 are secreted efficiently into the supernatant and PlGF-2 can bind with high affinity to heparin. Both PlGF forms had a similar mitogenic potency for bovine aortic endothelial cells. Binding studies with 125I-VEGF165 demonstrate, that supernatant of PlGF expressing insect cells can compete for receptor binding. Similar to VEGF, PlGF can exist in different forms which are probably generated by differential splicing. The occurrence of two molecular forms of this endothelial specific growth factor suggests different physiological roles of the two forms during placental development and differentiation.
Short antisense-locked nucleic acids (all-LNAs) correct alternative splicing abnormalities in myotonic dystrophy (2015)

Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystemic disorder caused by expansion of CTG triplet repeats in 3′-untranslated region of DMPK gene. The pathomechanism of DM1 is driven by accumulation of toxic transcripts containing expanded CUG repeats (CUGexp) in nuclear foci which sequester several factors regulating RNA metabolism, such as Muscleblind-like proteins (MBNLs). In this work, we utilized very short chemically modified antisense oligonucleotides composed exclusively of locked nucleic acids (all-LNAs) complementary to CUG repeats, as potential therapeutic agents against DM1. Our in vitro data demonstrated that very short, 8- or 10-unit all-LNAs effectively bound the CUG repeat RNA and prevented the formation of CUGexp/MBNL complexes. In proliferating DM1 cells as well as in skeletal muscles of DM1 mouse model the all-LNAs induced the reduction of the number and size of CUGexp foci and corrected MBNL-sensitive alternative splicing defects with high efficacy and specificity. The all-LNAs had low impact on the cellular level of CUGexp-containing transcripts and did not affect the expression of other transcripts with short CUG repeats. Our data strongly indicate that short all-LNAs complementary to CUG repeats are a promising therapeutic tool against DM1.
Gefitinib Targets EGFR Dimerization and ERK1/2 Phosphorylation to Inhibit Pleural Mesothelioma Cell Proliferation (2010)

Altered EGFR activity is a causal factor for human tumor development, including malignant pleural mesotheliomas. The aim of the present study was the evaluation of the effects of Gefitinib on EGF-induced mesothelioma cell proliferation and the intracellular mechanisms involved. Cell proliferation, DNA synthesis and apoptosis were measured by MTT, thymidine incorporation and FACS analysis; EGFR, ERK1/2 and Akt expression and phosphorylation by Western blot, whereas receptor sites were analyzed by binding studies. Gefitinib inhibited EGF-induced proliferation in two mesothelioma cell lines, derived from pleural effusion (IST-Mes2) or tumor biopsy (ZL55). The treatment with Gefitinib induced cell cycle arrest in both cell lines, while apoptosis was observed only for high concentrations and prolonged drug exposure. EGF-dependent mesothelioma cell proliferation was mediated by EGFR and ERK1/2 phosphorylation, while Akt was not affected. Gefitinib inhibited both EGFR and ERK1/2 activation, being maximal at drug concentrations that induce cytostatic effects, suggesting that the proapoptotic activity of Gefitinib is independent from EGFR inhibition. Gefitinib treatment increased EGFR Bmax, possibly through membrane stabilization of inactive receptor dimers that we show to be induced by the drug also in the absence of EGF. EGFR activation of ERK1/2 represents a key pathway for pleural mesothelioma cell proliferation. Low concentrations of Gefitinib cause mesothelioma cell cycle arrest through the blockade of EGFR activity while high concentrations induce apoptosis. Finally, we propose that the formation of inactive EGFR dimers may contribute to the antitumoral activity of Gefitinib. Keywords: Human malignant pleural mesothelioma cells, EGFR targeting, Gefitinib, preclinical chemotherapy
Fluorescent Amplifying Recognition for DNA G-Quadruplex Folding with a Cationic Conjugated Polymer:  A Platform for Homogeneous Potassium Detection (2005)

Single-stranded DNA with G-rich sequences can fold into secondary structures, G-quadruplexes, via intramolecular hydrogen-bonding interactions. This conformational change can be detected by a homogeneous assay method based on fluorescence resonance energy transfer (FRET) from a water-soluble cationic conjugated polymer (CCP) to a fluorescein chromophore labeled at the terminus of the G-quadruplex DNA. The space charge density around the DNA controls the efficiency of FRET from the CCP to the fluorescein. The higher FRET efficiency for the CCP/G-quadruplex pair is correlated to the stronger electrostatic interactions between the more condensed G-quadruplex and the CCP in comparison to the CCP/ssDNA pair. Since the potassium ion can specifically bind to the G-quadruplex DNA, the G-quartet-DNA/CCPs assembly can also be used as a platform to sense the potassium ion in water with high selectivity and sensitivity.
Grating interferometer for flatness testing (1996)

Two diffraction gratings placed in front of a f lat surface generate an interference pattern representing the surface deformations. The interference pattern is achromatic and has an equivalent wavelength between 4 and 40 microm, depending on the grating frequencies and the viewing angle. Using phase-shifting techniques, the grating interferometer provides high-precision profile measurements of both smooth and rough surfaces.
Development of Th1-Inducing Capacity in Myeloid Dendritic Cells Requires Environmental Instruction (2000)

Dendritic cells (DC) are key initiators of primary immune responses. Myeloid DC can secrete IL-12, a potent Th1-driving factor, and are often viewed as Th1-promoting APC. Here we show that neither a Th1- nor a Th2-inducing function is an intrinsic attribute of human myeloid DC, but both depend on environmental instruction. Uncommitted immature DC require exposure to IFN-gamma, at the moment of induction of their maturation or shortly thereafter, to develop the capacity to produce high levels of IL-12p70 upon subsequent contact with naive Th cells. This effect is specific for IFN-gamma and is not shared by other IL-12-inducing factors. Type 1-polarized effector DC, matured in the presence of IFN-gamma, induce Th1 responses, in contrast to type 2-polarized DC matured in the presence of PGE2 that induce Th2 responses. Type 1-polarized effector DC are resistant to further modulation, which may facilitate their potential use in immunotherapy.
Transcriptomic analysis of dystrophin RNAi knockdown reveals a central role for dystrophin in muscle differentiation and contractile apparatus organization (2010)

Our results suggest that in striated muscles, dystrophin is involved in orchestrating proper development and organization of myofibers as contractile units, depicting a novel pathophysiology for DMD where the absence of dystrophin results in maldeveloped myofibers prone to physical stress and damage. Therefore, it becomes apparent that any gene therapy approaches for DMD should target early stages in muscle development to attain a maximum clinical benefit. With a clear and specific definition of the transcriptome of dystrophin deficiency, manipulation of identified dysregulated molecules downstream of dystrophin may lead to novel ameliorative approaches for DMD.
Incomplete restoration of colony-stimulating factor 1 (CSF-1) function in CSF-1–deficient Csf1op/Csf1op mice by transgenic expression of cell surface CSF-1 (2003)

The primary macrophage growth factor, colony-stimulating factor 1 (CSF-1), is expressed as a secreted glycoprotein or proteoglycan found in the circulation or as a biologically active cell surface glycoprotein (csCSF-1). To investigate the in vivo roles of csCSF-1, we created mice that exclusively express csCSF-1, in a normal tissue-specific and developmental manner, by transgenic expression of csCSF-1 in the CSF-1-deficient osteopetrotic (Csf1(op)/Csf1(op)) background. The gross defects of Csf1(op)/Csf1(op) mice, including growth retardation, failure of tooth eruption, and abnormal male and female reproductive functions were corrected. Macrophage densities in perinatal liver, bladder, sublinguinal salivary gland, kidney cortex, dermis, and synovial membrane were completely restored, whereas only partial or no restoration was achieved in adult liver, adrenal gland, kidney medulla, spleen, peritoneal cavity, and intestine. Residual osteopetrosis, significantly delayed trabecular bone resorption in the subepiphyseal region of the long bone, and incomplete correction of the hematologic abnormalities in the peripheral blood, bone marrow, and spleens of CSF-1-deficient mice were also found in mice exclusively expressing csCSF-1. These data suggest that although csCSF-1 alone is able to normalize several aspects of development in Csf1(op)/Csf1(op) mice, it cannot fully restore in vivo CSF-1 function, which requires the presence of the secreted glycoprotein and/or proteoglycan forms.
Differential Expression of NK T Cell Vα24JαQ Invariant TCR Chain in the Lesions of Multiple Sclerosis and Chronic Inflammatory Demyelinating Polyneuropathy (2000)

Human V alpha 24+ NK T cells are a unique subset of lymphocytes expressing the V alpha 24J alpha Q invariant TCR chain. Because they can rapidly produce large amounts of regulatory cytokines, a reduction of NK T cells may lead to the development of certain autoimmune diseases. Using a single-strand conformation polymorphism method, we demonstrate that a great reduction of V alpha 24J alpha Q NK T cells in the peripheral blood is an immunological hallmark of multiple sclerosis, whereas it is not appreciable in other autoimmune/inflammatory diseases such as chronic inflammatory demyelinating polyneuropathy. The chronic inflammatory demyelinating polyneuropathy lesions were often found to be infiltrated with V alpha 24J alpha Q NK T cells, but multiple sclerosis lesions only rarely expressed the V alpha 24J alpha Q TCR. It is therefore possible that the extent of NK T cell alteration may be a critical factor which would define the clinical and pathological features of autoimmune disease. Although the mechanism underlying the NK T cell deletion remains largely unclear, a remarkable contrast between the CNS and peripheral nervous system diseases allows us to speculate a role of tissue-specific elements such as the level of CD1d expression or differences in the CD1d-bound glycolipid.
Catecholamine innervation of LH-RH neurons: a developmental study (1986)

Catecholamine innervation of luteinizing hormone-releasing hormone (LH-RH) cell subtypes in rats was investigated over development using double label, light microscopic immunocytochemistry. Similar results were observed in both sexes. The number of catecholamine-apposed sLH-RH cells remained constant, while the number of catecholamine-apposed iLH-RH cells increased as a function of age. These results suggest that LH-RH cell subtypes are differentially innervated and support the hypothesis that the development of iLH-RH cells represent newly innervated surfaces which are related to changes in the processing of incoming information relevant to reproductive maturation.
Mutational analysis of the discs large tumour suppressor identifies domains responsible for human papillomavirus type 18 E6-mediated degradation (2002)

The discs large (Dlg) tumour suppressor protein is targeted for ubiquitin-mediated degradation by the high-risk human papillomavirus E6 proteins. To understand further the mechanisms behind this, a mutational analysis of Dlg was undertaken. This study demonstrates that an intact PDZ domain 2 (PDZ2) on Dlg is necessary for the ability of E6 to bind and degrade Dlg. However, additional residues within the amino-terminal portion of Dlg are also required for optimal E6 activity. Stable cell lines expressing different Dlg mutants were also established and these confirm that Dlg is regulated intrinsically by the proteasome in the absence of E6; however, in this case, the sequences responsible for regulating Dlg stability lie predominantly within PDZ2. These results suggest that there are at least two mechanisms for regulating Dlg protein stability and that the pathways used by E6 are not necessarily the same as those used in the cell in its absence.
Transmission of the nucleic acid-induced character, caudal fin, to the offspring in goldfish. (1975)

The carp's egg-mRNA and DNA induced, single-tail-finned goldfish were used for mating. The offspring developed double, single and modified single tail fin. The combined frequency of the single and modified single tail fin formation in the mRNA-and DNA-injected series were 39.6% and 38.3% respectively. The corresponding frequency of the control series was 3.8%. These results show that the exogenous mRNA and DNA have altered the tail fin formation not only in the goldfish developed from the injected eggs but also in their offspring.