gebhart/patrepeval huggingface dataset:
Demonstration of Coiled-Coil Interactions within the Kinesin Neck Region Using Synthetic Peptides (1997)

Kinesin is a dimeric motor protein that can move for several micrometers along a microtubule without dissociating. The two kinesin motor domains are thought to move processively by operating in a hand-over-hand manner, although the mechanism of such cooperativity is unknown. Recently, a approximately 50-amino acid region adjacent to the globular motor domain (termed the neck) has been shown to be sufficient for conferring dimerization and processive movement. Based upon its amino acid sequence, the neck is proposed to dimerize through a coiled-coil interaction. To determine the accuracy of this prediction and to investigate the possible function of the neck region in motor activity, we have prepared a series of synthetic peptides corresponding to different regions of the human kinesin neck (residues 316-383) and analyzed each peptide for its respective secondary structure content and stability. Results of our study show that a peptide containing residues 330-369 displays all of the characteristics of a stable, two-stranded alpha-helical coiled-coil. On the other hand, the NH2-terminal segment of the neck (residues approximately 316-330) has the capacity to adopt a beta-sheet secondary structure. The COOH-terminal residues of the neck region (residues 370-383) are not alpha-helical, nor do they contribute significantly to the overall stability of the coiled-coil, suggesting that these residues mark the beginning of a hinge located between the neck and the extended alpha-helical coiled coil stalk domain. Interestingly, the two central heptads of the coiled-coil segment in the neck contain conserved, "non-ideal" residues located within the hydrophobic core, which we show destabilize the coiled-coil interaction. These residues may enable a portion of the coiled-coil to unwind during the mechanochemical cycle, and we present a model in which such a phenomenon plays an important role in kinesin motility.
Neutrophil and B Cell Expansion in Mice That Lack the Murine IL-8 Receptor Homolog (1994)

Interleukin-8 (IL-8) is a proinflammatory cytokine that specifically attracts and activates human neutrophils. A murine gene with a high degree of homology to the two known human IL-8 receptors was cloned and then deleted from the mouse genome by homologous recombination in embryonic stem (ES) cells. These mice, although outwardly healthy, had lymphadenopathy, resulting from an increase in B cells, and splenomegaly, resulting from an increase in metamyelocytes, band, and mature neutrophils. Thus, this receptor may participate in the expansion and development of neutrophils and B cells. This receptor was the major mediator of neutrophil migration to sites of inflammation and may provide a potential therapeutic target in inflammatory disease.
Intracerebral tumor-associated hemorrhage caused by overexpression of the vascular endothelial growth factor isoforms VEGF 121 and VEGF 165 but not VEGF 189 (1997)

The vascular endothelial growth factor (VEGF) has been shown to be a significant mediator of angiogenesis during a variety of normal and pathological processes, including tumor development. Human U87MG glioblastoma cells express the three VEGF isoforms: VEGF121, VEGF165, and VEGF189. Here, we have investigated whether these three isoforms have distinct roles in glioblastoma angiogenesis. Clones that overexpressed each isoform were derived and inoculated into mouse brains. Mice that received VEGF121- and VEGF165-overexpressing cells developed intracerebral hemorrhages after 60-90 hr. In contrast, mice implanted with VEGF189-overexpressing cells had only slightly larger tumors than those caused by parental cells and little evidence of hemorrhage at these early times after implantation, whereas, after longer periods of growth, enhanced angiogenicity and tumorigenicity were apparent. There was rapid blood vessel growth and breakdown around the tumors caused by cells overexpressing VEGF121 and VEGF165, whereas there was similar vascularization but no eruption in the vicinity of those tumors caused by cells overexpressing VEGF189, and none on the border of the tumors caused by the parental cells. Thus, by introducing VEGF-overexpressing glioblastoma cells into the brain, we have established a reproducible and predictable in vivo model of tumor-associated intracerebral hemorrhage caused by the enhanced expression of single molecular species. Such a model should be useful for uncovering the role of VEGF isoforms in the mechanisms of angiogenesis and for investigating intracerebral hemorrhage due to ischemic stroke or congenital malformations.
Rapid characterization of sugar-binding specificity by in-solution proximity binding with photosensitizers (2011)

Cell-surface carbohydrates are known to participate in many important physiological and pathological activities by interacting with their corresponding proteins or receptors. Although several methods have been developed for studying carbohydrate-protein interactions, one major problem originates from the weak bindings of carbohydrates/proteins that are often lost during repeating wash steps. Herein, we established a homogeneous solution carbohydrate array in which polyacrylamide-based glycans are used for offering a multivalent environment. The method requires no wash step and can be carried out in a high-throughput manner. We characterized the carbohydrate-binding specificities of 11 lectins and 7 antibodies, the majority of which displayed the binding patterns in consistence with previous reports. These results demonstrate that our developed solution carbohydrate array provides a useful alternative that is better than or comparable with the current available methods.
Development of an Artificial Placenta: Survival of Isolated Goat Fetuses for Three Weeks with Umbilical Arteriovenous Extracorporeal Membrane Oxygenation (1993)

The purpose of our study was to examine the feasibility of long-term extrauterine incubation of an isolated premature fetus in artificial amniotic fluid with arteriovenous extracorporeal circulation. Two premature goat fetuses (age 120 and 128 days) were incubated in an isothermal artificial amniotic fluid incubator with arteriovenous extracorporeal membrane oxygenation via the umbilical vessels. We administered pancuronium bromide to suppress fetal movement and swallowing because movement and swallowing have been implicated in fetal deterioration during extrauterine fetal incubation. The fetuses maintained stable circulatory and respiratory parameters. The total incubation time was 494 and 543 h. The animals were then removed from the incubator and stimulated to initiate lung respiration. With ventilator support, both animals maintained stable blood-gas exchange and survived for more than 1 week. These results clearly indicate that umbilical arteriovenous extracorporeal membrane can effectively support extended extrauterine incubation of an isolated premature fetus.
Identification of an H2-Kb or H2-Db restricted and glypican-3-derived cytotoxic T-lymphocyte epitope peptide (2013)

Glypican-3 (GPC3) is overexpressed in human hepatocellular carcinoma (HCC) but not expressed in normal tissues except for placenta and fetal liver and therefore is an ideal target for cancer immunotherapy. In this study, we identified an H2-Kb or H2-Db restricted and murine GPC3 (mGPC3)-derived cytotoxic T-lymphocyte (CTL) epitope peptide in C57BL/6 (B6) mice, which can be used in the design of preclinical studies of various therapies with GPC3-target immunotherapy in vivo. First, 11 types of 9- to 10-mer peptides predicted to bind with H2-Kb or H2-Db were selected from the mGPC3 amino acid sequence based on the binding score as calculated by the BIMAS software. We evaluated the peptide-binding affinity and confirmed that all peptides were able to bind to H2-Kb or H2-Db by in vitro cellular binding assay. Subsequently, a mixed peptide vaccine and single peptide vaccine were given to B6 mice to evaluate immunogenic potential of the 11 selected peptides. Using the splenocytes from peptide-vaccinated mice, interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assays showed that mGPC3-1127-136 (AMFKNNYPSL) peptide was the most efficient for inducing CTLs among the 11 peptides. Next, we demonstrated that the mGPC3-1 peptide-specific CTL line could recognize mGPC3-expressing cancer cells, suggesting that mGPC3-1 peptide was an endogenously presented peptide. In conclusion, we identified mGPC3-1 as an H2-Kb or H2-Db restricted, mGPC3-derived CTL epitope peptide.
Sodium and T1ρ MRI for molecular and diagnostic imaging of articular cartilage (2006)

In this article, both sodium magnetic resonance (MR) and T1rho relaxation mapping aimed at measuring molecular changes in cartilage for the diagnostic imaging of osteoarthritis are reviewed. First, an introduction to structure of cartilage, its degeneration in osteoarthritis (OA) and an outline of diagnostic imaging methods in quantifying molecular changes and early diagnostic aspects of cartilage degeneration are described. The sodium MRI section begins with a brief overview of the theory of sodium NMR of biological tissues and is followed by a section on multiple quantum filters that can be used to quantify both bi-exponential relaxation and residual quadrupolar interaction. Specifically, (i) the rationale behind the use of sodium MRI in quantifying proteoglycan (PG) changes, (ii) validation studies using biochemical assays, (iii) studies on human OA specimens, (iv) results on animal models and (v) clinical imaging protocols are reviewed. Results demonstrating the feasibility of quantifying PG in OA patients and comparison with that in healthy subjects are also presented. The section concludes with the discussion of advantages and potential issues with sodium MRI and the impact of new technological advancements (e.g. ultra-high field scanners and parallel imaging methods). In the theory section on T1rho, a brief description of (i) principles of measuring T1rho relaxation, (ii) pulse sequences for computing T1rho relaxation maps, (iii) issues regarding radio frequency power deposition, (iv) mechanisms that contribute to T1rho in biological tissues and (v) effects of exchange and dipolar interaction on T1rho dispersion are discussed. Correlation of T1rho relaxation rate with macromolecular content and biomechanical properties in cartilage specimens subjected to trypsin and cytokine-induced glycosaminoglycan depletion and validation against biochemical assay and histopathology are presented. Experimental T1rho data from osteoarthritic specimens, animal models, healthy human subjects and as well from osteoarthritic patients are provided. The current status of T1rho relaxation mapping of cartilage and future directions is also discussed.
Injection-locked 1.55  µ m VCSELs with enhanced spur-free dynamic range (2002)

Injection locking is demonstrated to improve the analogue performance of long wavelength VCSELs. The third-harmonic spur-free dynamic range was improved by 9 dB/Hz2/3 to be 93 dB/Hz2/3, and the modulation bandwidth was increased twofold.
Monoclonal Antibodies: Methods And Protocols (2007)

Monoclonal Antibodies: Methods and Protocols examines a collection of state-of-the-art methods that employ monoclonal antibodies in a clinical setting with opening chapters focusing on the gold standard method for generating mouse monoclonal antibodies through hybridoma technology, future methods for engineering recombinant and humanized antibodies, methods for engineering soluble Fc fusion protein, and the use of antibodies and flow cytometry in the quantification of cell signaling proteins. Specific chapters describe how antibodies are used for the diagnosis and classification of hematologic diseases. Subsequent chapters examine the advantages and most recent advances of using bead-based immunoassays, including the ability of bead-based technology to multiplex and analyze several analytes simultaneously, and the use of beads in detecting fusion proteins resulting from chromosomal translocations. Concluding chapters provide additional examples of methodologies that employ monoclonal antibodies. Monoclonal Antibodies: Methods and Protocols provides descriptions of methods that cover a wide spectrum of applications in the field of monoclonal antibodies. This field will continue to expand and provide new and innovative techniques, not only in the laboratory, but also as a basis that complements targeted therapy
BluepRINT for Moderate-to-Low Penetrance Cancer Susceptibility Genes Needed: Breast Cancer and Beyond (2014)

RINT1 is a novel moderately penetrant cancer susceptibility gene seen in breast cancer as well as possibly in Lynch syndrome-related cancers.
Bioinspired Self‐Healing Superhydrophobic Coatings (2010)

Heal thyself! Self-healing superhydrophobic coatings are fabricated by preserving healing agents of reacted fluoroalkylsilane in layered polymeric coatings that are porous and rigidly flexible. When the top layer of fluoroalkyl chains decomposes or the coatings are scratched, the healing agents migrate to the surface to restore the superhydrophobicity of the coatings (see picture). Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Estrogen Replacement Therapy and Fractures in Older Women (1995)

Current use of estrogen appears to decrease the risk for fracture in older women. These results suggest that for protection against fractures, estrogen should be initiated soon after menopause and continued indefinitely.
Herpesvirus-induced cell fusion that is dependent on cell surface heparan sulfate or soluble heparin (1994)

The entry of enveloped viruses into animal cells and the cell-to-cell spread of infection via cell fusion require the membrane-fusing activity of viral glycoproteins. This activity can be dependent on variable cell factors or triggered by environmental factors. Here we show that cell fusion induced by herpes simplex virus glycoproteins is dependent on the presence of cell surface glycosaminoglycans, principally heparan sulfate, or on the addition of heparin to the medium. The role of the glycosaminoglycan is probably to alter the conformation of a viral heparin-binding glycoprotein required for the fusion.
Formation of Silicon-Gold Eutectic Bond Using Localized Heating Method (1998)

A new bonding technique is proposed by using localized heating to supply the bonding energy. Heating is achieved by applying a dc current through micromachined heaters made of gold which serves as both the heating and bonding material. At the interface of silicon and gold, the formation of eutectic bond takes place in about 5 minutes. Assembly of two substrates in microfabrication processes can be achieved by using this method. In this paper the following important results are obtained: 1) Gold diffuses into silicon to form a strong eutectic bond by means of localized heating. 2) The bonding strength reaches the fracture toughness of the bulk silicon. 3) This bonding technique greatly simplifies device fabrication and assembly processes.
Treatment of intractable rheumatoid arthritis with combined cyclophosphamide, azathioprine, and hydroxychloroquine. A follow-up study (1986)

Cyclophosphamide, azathioprine, and hydroxychloroquine sulfate were prescribed for 31 patients (26 women and five men) with rheumatoid arthritis refractory to conventional therapy. Maintenance drug dosages (mean ±SD) were as follows: cyclophosphamide, 30±24 mg/day; azathioprine, 74±44 mg/day; and hydroxychloroquine sulfate, 210±92 mg/day. Disease suppression began in 30 patients within three to 24 months (mean, nine months). Results after 43 months (range, 12 to 102 months) were as follows: 16, complete remission; seven, near remission; seven, partial disease suppression; one, no response. None remained in prolonged remission without some form of therapy. Treatment was discontinued in three patients because of pulmonary infection (two) or thrombocytopenia (one). Four patients had five malignant neoplasms (surgical cures) before therapy (two breast, one colon, one melanoma, one endometrial); four patients developed a malignant neoplasm during combined drug therapy (one colon, one endometrial, one lung, one erythroleukemia); and three died. The absolute risk of malignancy from combined drug therapy is still unclear. We concluded that (1) combined use of remittive agents may have promise in treatment of severe rheumatoid arthritis; (2) cyclophosphamide should be replaced with a nonalkylating agent; and (3) the place of combined drug therapy remains uncertain in the absence of controlled trials. (<i>JAMA</i>1986;255:2315-2319)
Structural Study of Lipomannan and Lipoarabinomannan fromMycobacterium chelonae (2002)

Lipomannan (LM) and lipoarabinomannan (LAM) are major glycolipids present in the mycobacterial cell wall that are able to modulate the host immune response. In this study, we have undertaken the structural determination of these important modulins in Mycobacterium chelonae, a fast growing pathogenic mycobacterial species. One-dimensional and two-dimensional NMR spectra were used to demonstrate that LM and LAM from M. chelonae, designated CheLM and CheLAM, respectively, possess structures that differ from the ones reported earlier in other mycobacterial species. Analysis by gas chromatography/mass spectrometry of the phosphatidyl-myo-inositol anchor, which is thought to play a role in the biological functions of these lipoglycans, pointed to a high degree of heterogeneity based on numerous combinations of acyl groups on the C-1 and C-2 positions of the glycerol moiety. Characterization of the mannan core of CheLM and CheLAM revealed the presence of novel alpha1,3-mannopyranosyl side chains. This motif, which reacted specifically with the lectin from Galanthus nivalis, was found to be unique among a panel of nine mycobacterial species. Then, CheLM and CheLAM were found to be devoid of both the mannooligosaccharide cap present in Mycobacterium tuberculosis and the inositol phosphate cap present in Mycobacterium smegmatis and other fast growing species. Tumor necrosis factor-alpha and interleukin-8 production were assessed from human macrophages with LAM preparations from different species. Our results suggest that the inositol phosphate capping may represent the major cytokine-inducing component of LAMs. This work not only underlines the diversity of LAM structures among various mycobacterial species but also provides new structures that could be useful to dissect the structure-function relationships of these complex molecules.
Clinical trial of continuous infusion verapamil, bolus vinblastine, and continuous infusion VP-16 in drug-resistant pediatric tumors. (1989)

We optimized the modulation of drug resistance by the irreversible augmentation of cytotoxicity of coincubating vinblastine (VNB) with VP-16 and the reversible increase in cytotoxicity of coincubation of verapamil (VPL) with VNB and VP-16. VPL was administered as a loading dose (i.v.) (0.15 mg/kg) and then administered as a constant infusion (0.005 mg/kg) over 6 days. 24 h after verapamil, VNB 2 mg/m2 IVP was administered and followed 1 h later by a 5-day simultaneous continuous infusion of VP-16 (200 mg/m2/day) to seven pediatric patients (11 courses) with refractory malignancies. The mean age at treatment was 7.5 +/- 5.3 years, mean prior anthracycline dose (303 +/- 210 mg/m2) with a range of 0-606 mg/m2. Toxicity was limited to cardiac and hematological. The median nadir of the WBC was 900 at 14.5 +/- 0.5 days and platelet count 32,000 at 15.5 +/- 0.8 days. There were two episodes of bacterial sepsis both of which responded to i.v. antibiotics. Five of 11 courses resulted in first-degree block and one course in second-degree block. At Hour 120 of the VPL infusion the PR interval was 0.18 +/- 0.01 versus 0.13 +/- 0.01 at Hour 0 (P less than 0.0004). The ejection fraction by two-dimensional echocardiogram was not significantly different at Hour 0, 24, or 120 of the infusion (60.6 +/- 2.7 versus 52.7 +/- 5.1 versus 51.8 +/- 5.0%). The cardiac index was also not significantly different at Hour 0, 24, or 120 (4.39 +/- 0.2 versus 4.21 +/- 0.6 versus 3.91 +/- 0.5 liters/min/m2). The 15-min VPL level was 1954.5 +/- 391/ng/ml and steady state levels at Hour 24 and 120 of the infusion were 468.1 +/- 59 and 422.8 +/- 52 ng/ml, respectively. Two of 11 treatment courses resulted in hypotension secondary to inordinately high 24-h levels of VPL (1233 and 1263 ng/ml). These two episodes required inotropic support but did not require the discontinuation of VPL. There were 8 of 11 partial responses, the majority of which consisted of peripheral cytoreduction of leukemic blasts and one M-2A response in AML. The levels of VPL achieved in this study have been shown to augment the in vitro cytotoxicity of vinblastine and VP-16 to resistant cell lines. Further clinical studies are needed to determined the maximal-tolerated dose of VPL in a Phase I study and to examine its efficacy in selected relapsed pediatric patients.
Introduction to parametric amplification of quantum signals with Josephson circuits (2016)

This short and opinionated review starts with the concept of quantum signals at microwave frequencies and focuses on the principle of linear parametric amplification. This process emerges from the dispersive nonlinearity of Josephson junctions driven with appropriate tones. We discuss two defining characteristics of the corresponding amplifying devices: i) the number of modes excited by the signal, idler and pump waves and ii) the number of independent ports through which these waves enter into the circuit.
Light intensity, temperature, and thickness dependence of the open-circuit voltage in solid-state dye-sensitized solar cells (2006)

We present an analytical and experimental investigation into the origin of the open-circuit voltage in the solid-state dye-sensitized solar cell. Through Kelvin probe microscopy, we demonstrate that a macroscopically uniform electric field exists throughout the nanocomposite between the electrodes. Considering a balance between drift and diffusion currents, and between charge generation and recombination, we develop an analytical expression for the open-circuit voltage which accurately follows experimental data. We find the open-circuit voltage increases with light intensity as $1.7\phantom{\rule{0.2em}{0ex}}kT∕q$, where $T$ is absolute temperature, however it decreases with increasing temperature and device thickness. The intensity dependence arises from the charge generation rate increasing more strongly with intensity than the recombination rate constant, resulting in increased chemical potential within the device. We find that the temperature dependence arises from a reduction in the charge lifetime and not from increased charge diffusion and mobility. The thickness dependence is found to derive from two factors; first, charge recombination sites are distributed throughout the film, enabling more charges to recombine in thicker films before influencing the potential at the electrodes, and second, the average optical power density within the film reduces with increasing film thickness.
Role of RGM coreceptors in bone morphogenetic protein signaling (2007)

Our results demonstrate that the RGMs play a significant role in BMP signaling and reveal that these molecules cannot functionally compensate for one another.