gebhart/patrepeval huggingface dataset:
Noonan syndrome-causing SHP2 mutants inhibit insulin-like growth factor 1 release via growth hormone-induced ERK hyperactivation, which contributes to short stature (2012)

Noonan syndrome (NS), a genetic disease caused in half of cases by activating mutations of the tyrosine phosphatase SHP2 (PTPN11), is characterized by congenital cardiopathies, facial dysmorphic features, and short stature. How mutated SHP2 induces growth retardation remains poorly understood. We report here that early postnatal growth delay is associated with low levels of insulin-like growth factor 1 (IGF-1) in a mouse model of NS expressing the D61G mutant of SHP2. Conversely, inhibition of SHP2 expression in growth hormone (GH)-responsive cell lines results in increased IGF-1 release upon GH stimulation. SHP2-deficient cells display decreased ERK1/2 phosphorylation and rat sarcoma (RAS) activation in response to GH, whereas expression of NS-associated SHP2 mutants results in ERK1/2 hyperactivation in vitro and in vivo. RAS/ERK1/2 inhibition in SHP2-deficient cells correlates with impaired dephosphorylation of the adaptor Grb2-associated binder-1 (GAB1) on its RAS GTPase-activating protein (RASGAP) binding sites and is rescued by interfering with RASGAP recruitment or function. We demonstrate that inhibition of ERK1/2 activation results in an increase of IGF-1 levels in vitro and in vivo, which is associated with significant growth improvement in NS mice. In conclusion, NS-causing SHP2 mutants inhibit GH-induced IGF-1 release through RAS/ERK1/2 hyperactivation, a mechanism that could contribute to growth retardation. This finding suggests that, in addition to its previously shown beneficial effect on NS-linked cardiac and craniofacial defects, RAS/ERK1/2 modulation could also alleviate the short stature phenotype in NS caused by PTPN11 mutations.
The Mesentery, Systemic Inflammation, and Crohn’s Disease (2018)

10.1093/ibd/izy201_video1izy201.video15794169491001.
Antibodies to Polymerized Albumin in Woodchuck Hepatitis Virus Infection (1993)

Polymerized human serum albumin may play a role in the entry of hepatitis B virus into hepatocytes, and antibodies to polyalbumin that frequently appear during acute hepatitis may aid the process of viral clearance. We developed an enzyme-linked immunosorbent assay for antibodies to polymerized woodchuck albumin to enable us to evaluate further the role of these antibodies in an animal model system. Sera from 17 uninfected adult woodchucks and 8 newborns showed no binding to control plates coated with woodchuck transferrin, woodchuck albumin, or polymerized human serum albumin. One of 8 newborn animals demonstrated a significant antibody titer to polymerized woodchuck albumin, and 16 of 17 adults without evidence of prior woodchuck hepatitis virus infection had measurable serum antibody titers. Antibodies to polymerized woodchuck albumin could be adsorbed by prior incubation with the antigen. In 2 animals subjected to experimental infection, significant rises in polyalbumin antibody were seen. When 4 adult woodchucks were immunized with woodchuck polyalbumin, significant increases in antibody titer were observed in 2 of the 4 animals. Of the 4 immunized and 4 controls subsequently challenged with woodchuck hepatitis virus, 7 became viremic and all 8 developed antibody to woodchuck hepatitis virus core antigen. We conclude that naturally occurring antibodies to polymerized woodchuck albumin are observed in most adult woodchucks in the absence of woodchuck hepatitis virus infection and do not seem to confer immunity against infection with this virus.
Moderate Dose Escalation for Advanced Stage Hodgkin’s Disease Using the Bleomycin, Etoposide, Adriamycin, Cyclophosphamide, Vincristine, Procarbazine, and Prednisone Scheme and Adjuvant Radiotherapy: A Study of the German Hodgkin’s Lymphoma Study Group (1998)

The BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) regimen, a rearranged and accelerated version of the standard COPP/adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy, has been shown to be effective and safe in a previous pilot study for advanced stage Hodgkin's disease (HD). The present study aimed to determine a maximum practicable dose of three drugs, ie, etoposide, adriamycin, and cyclophosphamide, for which acute toxicities were acceptable and to assess the feasibility of the escalated scheme. Sixty untreated patients with advanced stage HD were enrolled in this study. Radiotherapy was given in 44 patients (73%) after chemotherapy to initial bulk lesions and residual disease. Granulocyte-colony stimulating factor (G-CSF) was given from day 8 to prevent prolonged neutrocytopenia and severe infections. The intended doses of adriamycin, etoposide, and cyclophosphamide in the BEACOPP schedule could be substantially escalated: adriamycin from 25 to 35, cyclophosphamide from 650 to 1,200, and etoposide from 100 to 200 mg/m2. The major toxicities were leukocytopenia and thrombocytopenia with considerable heterogeneity between individual patients. Of 60 patients, 56 (93%) achieved a complete remission (CR). At a median observation of 32 months, the rates of survival and freedom from treatment failure (FFTF) were estimated to be 91% (95% confidence interval 83% to 99%) and 90% (82% to 98%). These results show that a moderate dose escalation of adriamycin, cyclophosphamide, and etoposide of the baseline BEACOPP regimen is feasible. The escalated BEACOPP regimen shows very encouraging results in advanced stage HD and is now being compared in a randomized phase III study with BEACOPP at baseline dose level.
Probing the Limits of Electron and Ion Transport over Multiple Length Scales (2016)

As the demand for large scale batteries has grown, considerations such as earth abundance, cost, and toxicity have assumed a greater significance. Metal oxides such as magnetite (Fe 3 O 4 ) are worthy of evaluation as active materials for electrochemical energy storage due to its earth abundance, low cost, environmentally benign iron metal centers and high theoretical capacity, 926 mAh/g. Implementation in the future will require understanding of the fundamental electrochemical reduction-oxidation mechanisms of the electroactive materials is required, coupled with characterization at the mesoscale to understand the underlying contributors to localized resistance which must be addressed in order to achieve significant improvements to current capability and reversibility. An emerging paradigm for the implementation of close-packed materials in higher current applications is the tuning of the materials crystallite dimensions, where the reduction of crystallite size should minimize the path length for ion transport upon discharge, resulting in a reduction of both internal cell resistance and the resultant structural strain associated with lithium insertion. The electrochemical impact of controlled crystallite size of magnetite will be described. In addition to the crystallite size of the electroactive material, a complete study of an electroactive nanomaterial in the complex mesoscale environment of a composite battery electrode should also consider the level of electroactive particle agglomeration, and agglomerate distribution within the battery electrode. Nanocrystalline magnetite (Fe 3 O 4 ) powders and composite electrodes with different crystallite sizes were prepared, characterized, and electrochemically evaluated. Transmission electron microscopy (TEM) examination of cross-sectioned electrodes was used to quantify the aggregate size of the Fe 3 O 4 active material. Notably, although the crystallite sizes of two magnetite samples Fe 3 O 4 are different (28 and 9 nm), the observed sizes of the aggregates and aggregate distribution within the electrodes were similar, see TEM images of sectioned electrodes fabricated with the 28 nm (A,B) and 9 nm (C,D) sized Fe 3 O 4 in the Figure. Transmission x-ray microscopy (TXM) combined with x-ray absorption near edge spectroscopy (XANES) at the National Synchrotron Light Source (NSLS) were used to determine the distribution of the iron oxidation states within the electrodes before and after electrochemical testing. The impact of both crystallite size and agglomeration on electrochemical performance were assessed. Figure 1
Structural studies on human L' and L pyruvate kinase subunits (1981)

Conference Abstract| April 01 1981 Structural studies on human L' and L pyruvate kinase subunits M. P. SIMON; M. P. SIMON 1Institut de Pathologie Moléculaire, 75674 PARIS CEDEX 14 - FRANCE - Search for other works by this author on: This Site PubMed Google Scholar J. MARIE; J. MARIE 1Institut de Pathologie Moléculaire, 75674 PARIS CEDEX 14 - FRANCE - Search for other works by this author on: This Site PubMed Google Scholar A. KAHN A. KAHN 1Institut de Pathologie Moléculaire, 75674 PARIS CEDEX 14 - FRANCE - Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1981) 9 (2): 354P. https://doi.org/10.1042/bst009354pe Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation M. P. SIMON, J. MARIE, A. KAHN; Structural studies on human L' and L pyruvate kinase subunits. Biochem Soc Trans 1 April 1981; 9 (2): 354P. doi: https://doi.org/10.1042/bst009354pe Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 1981 Biochemical Society1981 Article PDF first page preview Close Modal You do not currently have access to this content.
Acquired Tracheomegaly in Very Preterm Neonates (1986)

Proximal airways are compliant structures at early gestational ages and may be susceptible to pressure-induced deformation following prolonged ventilatory support. Sixteen neonates (mean +/- SD gestational age, 27.0 +/- 0.6 weeks; mean +/- SD birth weight, 847 +/- 68 g) were studied to assess tracheal volume deformation. The neonates received ventilatory support for a mean +/- SD duration of 25.4 +/- 4.9 days. During this period the maximum peak inspiratory pressures ranged from 15 to 25 cm H2O, and respirations ranged from 20/min to 60/min. These neonates were studied at seven days postextubation and were individually matched for body weight with 16 nonventilated neonates. The width of the tracheal air column was measured at the lower border of the first thoracic (T-1) and third thoracic (T-3) vertebrae. The average tracheal width (average of T-1 and T-3) was significantly (38%) wider in the ventilated group, and the mean +/- SD tracheal width values were 3.79 +/- 0.29 mm, as compared with the control values of 2.74 +/- 0.31 mm. Based on these data it was estimated that the tracheal volume was 91% greater in the ventilated group. These observations demonstrate tracheal volume deformation and acquired tracheomegaly in neonates who have received mechanical ventilatory support. In addition to increased dead space ventilation, these findings also indicate underlying mechanical deformation of the tracheal wall.
ssDNA Pairing Accuracy Increases When Abasic Sites Divide Nucleotides into Small Groups (2015)

Accurate sequence dependent pairing of single-stranded DNA (ssDNA) molecules plays an important role in gene chips, DNA origami, and polymerase chain reactions. In many assays accurate pairing depends on mismatched sequences melting at lower temperatures than matched sequences; however, for sequences longer than ~10 nucleotides, single mismatches and correct matches have melting temperature differences of less than 3°C. We demonstrate that appropriately grouping of 35 bases in ssDNA using abasic sites increases the difference between the melting temperature of correct bases and the melting temperature of mismatched base pairings. Importantly, in the presence of appropriately spaced abasic sites mismatches near one end of a long dsDNA destabilize the annealing at the other end much more effectively than in systems without the abasic sites, suggesting that the dsDNA melts more uniformly in the presence of appropriately spaced abasic sites. In sum, the presence of appropriately spaced abasic sites allows temperature to more accurately discriminate correct base pairings from incorrect ones.
Integrins and Control of Interstitial Fluid Pressure (1997)

The present review summarizes recent information on the physiology of connective tissues, in particular, control of interstitial fluid pressure (Pif) and, thereby, interstitial volume. A combination of classic physiological techniques and techniques from cellular and molecular biology have provided new insights into control of Pif by connective tissue cells and the adhesion receptors anchoring them to structural connective tissue components.
Hepatitis B Virus Capsid Assembly Is Enhanced by Naturally Occurring Mutation F97L (2004)

In chronic hepatitis B virus (HBV) infections, one of the most common mutations to the virus occurs at amino acid 97 of the core protein, where leucine replaces either phenylalanine or isoleucine, depending on strain. This mutation correlates with changes in viral nucleic acid metabolism and/or secretion. We hypothesize that this phenotype is due in part to altered core assembly, a process required for DNA synthesis. We examined in vitro assembly of empty HBV capsids from wild-type and F97L core protein assembly domains. The mutation enhanced both the rate and extent of assembly relative to those for the wild-type protein. The difference between the two proteins was most obvious in the temperature dependence of assembly, which was dramatically stronger for the mutant protein, indicating a much more positive enthalpy. Since the structures of the mutant and wild-type capsids are essentially the same and the mutation is not involved in the contact between dimers, we suggest that the F97L mutation affects the dynamic behavior of dimer and capsid.
Analgesic Properties of Lidocaine in Mice (1979)

The analgesic properties of lidocaine and morphine were compared in mice using a hot plate stimulus. An analgesic response was defined as an increase in the time required for an animal to attempt to escape by jumping. When compared to saline-treated controls, lidocaine produced a statistically significant dose-related delay in response to heat. Dose-response curves for morphine and lidocaine indicated that morphine has greater potency and efficacy. Naloxone (1.0 mg/kg) reversed the analgesic response due to morphine (10 mg/kg) but had no effect on the analgesia produced by lidocaine (50 mg/kg).
Heat transfer and cure in pultrusion: Model and experimental verification (1993)

Abstract Though pultrusion has existed for nearly 40 years, factors affecting temperature and resin reactivity are not completely understood. A model is tested to help explain the effects of die temperature, line speed and initiator concentration on curing inside a pultrusion die. The model includes radio frequency preheating, heat conduction, heat of cure, changing thermal properties with temperature and degree of cure, and hindered heat transfer due to shrinkage of the profile away from the die. The analysis is compared to experimental temperature measurements for a 1‐in. (25‐mm) round die, where die temperature, line speed, and initiator concentration were varied. Temperature predictions by the model are in good agreement with the data for many of the conditions tested. Considerable disagreement still persists, however, under processing conditions with faster line speeds and lower die temperatures.
Canonical and cross-reactive binding of NK cell inhibitory receptors to HLA-C allotypes is dictated by peptides bound to HLA-C (2017)

Abstract Human NK cell activity is regulated by killer-cell Ig-like receptors (KIR) that bind HLA class I. Combinations of KIR and HLA genotypes are associated with disease, including susceptibility to viral infection and disorders of pregnancy. KIR2DL1 binds group C2 HLA-C (Lys80), while KIR2DL2/3 bind group C1 HLA-C (Asn80). The goal of this study was to determine how the endogenous HLA-C peptide repertoire influences specific binding of inhibitory KIR to HLA-C allotypes. HLA-C*05:01 (C2) and HLA-C*08:02 (C1) have identical sequences apart from the key KIR specificity determining residues at 77 and 80. Endogenous peptides were eluted from HLA-C*05:01 and used to test KIR2DL1 and KIR2DL2/3 binding to HLA-C*05:01 and HLA-C*08:02 and subsequent impact on NK cell function. Canonical binding of KIR2DL1 to C2 occurred with the majority of peptides tested, while KIR2DL2/3 binding to C1 occurred with a subset of peptides. Cross-reactive binding of KIR2DL2/3 with C2 was restricted to even fewer peptides. Unexpectedly, two peptides promoted binding of the C2 specific KIR2DL1 to the C1 allotype. KIR2DL2/3 binding to C1 is more peptide selective than KIR2DL1 binding to C2, providing an explanation for why KIR2DL3–C1 interactions appear weaker than KIR2DL1–C2. Cross-reactive KIR binding is characterized by even higher peptide selectivity. These differences in peptide selectivity may aid the interpretation of human disease associations with KIR and HLA, while peptide sequence-driven KIR binding provides a potential mechanism for pathogen or self-peptide to modulate KIR binding and NK cell activation.
Programming the DADO Machine: An Introduction to PPL/M (1982)

DADO (Stolfo and Shaw, 1982) is a highly parallel, tree-structured machine designed to provide significant performance improvements in the execution of Artificial Intelligence software. The DADO prototype, currently being constructed at Columbia University, comprises 1023 processing elements (PE's) each consisting of an Intel 8751 microcomputer chip and an Intel 2186 8K by 8 RAM chip. The PE's are interconnected in a complete binary tree. A full version of DADO would comprise on the order of a hundred thousand PE's each consisting ot a much smaller amount ot local memory, roughly 2K bytes of RAM. (The 8K RAM employed in the DADO prototype was chosen to allow a modest amount of flexibility in designing and implementing the software base for the full version of DADO.) In addition, a specialized combinatorial I/O switch is incorporated in the full DADO design to perform the most basic communication primitives at much higher speeds than is possible with sequential logic, as it is implemented on the prototype machine.
Time Domain Transforms (2012)

This chapter gives the exact mathematical details of the time domain transform used in many modern vector network analyzer (VNA). The VNA time domain transform is developed from the definition of the Fourier transform, by applying the various limits and compensations that are necessary when used in the VNA. The chapter provides some important details of Fourier analysis as applied to device measurements using VNAs. Since the data is measured in the frequency domain, the transformation we are most interested in is the inverse Fourier transform (IFT), generating the time domain response from the frequency domain data. The time domain transform of VNA measurements was first introduced in 1974, and has been widely used since its real-time commercial introduction with the HP 8510A, which allowed increased accuracy and real-time gating. VNA offer alternative assumptions, which yield two different modes of transformation: low-pass mode and band-pass mode. Controlled Vocabulary Terms discrete Fourier transforms; fast Fourier transforms; network analysers
Molecular Size of Collagen Peptide Reverses the Permeability of Caco-2 Cells (2010)

Intestinal permeability to size-classified fish collagen peptides (FCPs) was examined using Caco-2 monolayers. Minimum-sized FCPs were most efficiently transported across the Caco-2 monolayers. Permeability depended on peptide size. It was independent of the H(+)-coupled peptide transport system but was associated with tight junction permeability, suggesting that the paracellular pathway is responsible for transepithelial transport of collagen peptides.
Alternating copolymerization of cyclohexene oxide and sulfur dioxide (1980)

Abstract Copolymerization of cyclohexene oxide (CHO) and sulfur dioxide (SO 2 ) was conducted at 80°C by using a variety of catalysts both in the presence and absence of solvent. Aromatic tertiary amines such as pyridine gave an alternating copolymer of CHO and SO 2 in the presence of solvents such as 1,2‐dimethoxyethane. The alternating copolymer obtained was a white thermoplastic which could readily be thermoformed. It was soluble in acetone and chloroform but insoluble in water and hexane. From the reaction of the equimolar mixture of CHO, SO 2 and pyridine at 20°C, an 1 : 1 : 1 adduct of CHO, SO 2 and pyridine (see formula 2 ) could be isolated. This adduct was confirmed to be the active species for the present copolymerization.
Societal implications of nanoscience and nanotechnology in developing countries (2006)

The historically unprecedented developments of nanoscience and nanotechnology, in view of their phenomenal expansion and growth, in conjunction with their convergence with information science and molecular biology, confront our society and natural environment with new challenges. Technological revolutions have shown that discoveries at the frontiers of science have the potential to pave the way for radically innovative and integrated approaches, providing new solutions for some of the most pressing problems. In order to enable decision-makers to respond to what is best for people at large, the societal implications of the newly emerging fields need to be known and understood. Nanotechnology, unlike any other technology, can find applications in virtually all areas of human life. In spite of being an infant at its evolution, some of the known issues related to nanotechnology suggest a wide spectrum of potential societal impacts. The current public nano-discourse provides sociology with a unique opportunity to switch from a merely passive, observational role to an active participating one, especially where the key players involved meet to find joint and concerted solutions for development.
ErbB1 and ErbB4 generate opposing signals regulating mesenchymal cell proliferation during valvulogenesis (2017)

Heparin-binding EGF-like growth factor (HB-EGF) plays an indispensable role in suppression of cell proliferation during mouse valvulogenesis.However, ligands of the EGF receptor (EGFR/ErbB1), including HB-EGF, are generally considered as growth-promoting factors, as shown in cancers.HB-EGF binds to and activates ErbB1 and ErbB4.We investigated the role of ErbB receptors in valvulogenesis in vivo using ErbB1-and ErbB4-deficient mice, and an ex vivo model of endocardial cushion explants.We show that HB-EGF suppresses valve mesenchymal cell proliferation through a heterodimer of ErbB1 and ErbB4, and an ErbB1 ligand (or ligands) promotes cell proliferation through a homodimer of ErbB1.Moreover, a rescue experiment with cleavable or uncleavable isoforms of ErbB4 in ERBB4-null cells indicates that the cleavable JM-A, but not the uncleavable JM-B, splice variant of ErbB4 rescues the defect of the null cells.These data suggest that the cytoplasmic intracellular domain of ErbB4, rather than the membrane-anchored tyrosine kinase, achieves this suppression.Our study demonstrates that opposing signals generated by different ErbB dimer combinations function in the same cardiac cushion mesenchymal cells for proper cardiac valve formation.