gebhart/patrepeval huggingface dataset:
The Molecular Mechanism of Hepcidin-mediated Ferroportin Down-Regulation (2007)

Ferroportin (Fpn) is the only known iron exporter in vertebrates. Hepcidin, a peptide secreted by the liver in response to iron or inflammation, binds to Fpn, inducing its internalization and degradation. We show that after binding of hepcidin, Fpn is tyrosine phosphorylated at the plasma membrane. Mutants of human Fpn that do not get internalized or that are internalized slowly show either absent or impaired phosphorylation. We identify adjacent tyrosines as the phosphorylation sites and show that mutation of both tyrosines prevents hepcidin-mediated Fpn internalization. Once internalized, Fpn is dephosphorylated and subsequently ubiquitinated. An inability to ubiquitinate Fpn does not prevent hepcidin-induced internalization, but it inhibits the degradation of Fpn. Ubiquitinated Fpn is trafficked through the multivesicular body pathway en route to degradation in the late endosome/lysosome. Depletion of proteins involved in multivesicular body trafficking (Endosome Sorting Complex Required for Transport proteins), by small-interfering RNA, reduces the trafficking of Fpn-green fluorescent to the lysosome.
Stem cell transplantation: Past, present and future (1994)

Attempted human allogeneic marrow transplants in the 1950s and 60s were largely unsuccessful. In the past two decades the probability of success has improved steadily depending on the type and stage of disease. Cure rates range from about 90% for nonmalignant diseases transplanted early to 15% for patients with advanced leukemia. Most marrow transplants have involved an HLA matched sibling donor but, more recently, through the National Marrow Donor Program, a matched unrelated volunteer marrow donor can be found for many patients without a family donor. Current research involves new preparative regimens for elimination of malignant cells, better prevention of graft-versus-host disease, and the use of hematopoietic growth factors and cytokines. Autologous transplants, which use the patient's own marrow, are increasing. The hematopoietic stem cell, which is responsible for marrow regeneration after a transplant, has been isolated and characterized. Stem cells for transplantation can now be obtained from the peripheral blood after mobilization of these cells by chemotherapy or hematopoietic growth factors. A variety of technological advances makes it possible to perform transplants with less time in the hospital and a corresponding saving in cost.
81: Amniotic Fluid and Chorionic Villi Derived Human Stem Cells for the Engineering of Tissues in Vivo (2004)

You have accessJournal of UrologyDiscussed Poster, Saturday, May 8, 2004, 1:00 - 5:00 pm1 Apr 200481: Amniotic Fluid and Chorionic Villi Derived Human Stem Cells for the Engineering of Tissues in Vivo Paolo De Coppi, Chester Koh, Georg Bartsch, Minhaj Siddiqui, James J. Yoo, Laura Perin, Hans G. Pohl, Paola Dal Cin, Shay Soker, and Anthony Atala Paolo De CoppiPaolo De Coppi More articles by this author , Chester KohChester Koh More articles by this author , Georg BartschGeorg Bartsch More articles by this author , Minhaj SiddiquiMinhaj Siddiqui More articles by this author , James J. YooJames J. Yoo More articles by this author , Laura PerinLaura Perin More articles by this author , Hans G. PohlHans G. Pohl More articles by this author , Paola Dal CinPaola Dal Cin More articles by this author , Shay SokerShay Soker More articles by this author , and Anthony AtalaAnthony Atala More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)37343-9AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "81: Amniotic Fluid and Chorionic Villi Derived Human Stem Cells for the Engineering of Tissues in Vivo." The Journal of Urology, 171(4S), p. 21 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 171Issue 4SApril 2004Page: 21 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Paolo De Coppi More articles by this author Chester Koh More articles by this author Georg Bartsch More articles by this author Minhaj Siddiqui More articles by this author James J. Yoo More articles by this author Laura Perin More articles by this author Hans G. Pohl More articles by this author Paola Dal Cin More articles by this author Shay Soker More articles by this author Anthony Atala More articles by this author Expand All Advertisement PDF downloadLoading ...
Human Neural Stem Cells: Isolation, Expansion and Transplantation (1999)

Neural stem cells, with the capacity to self renew and produce the major cell types of the brain, exist in the developing and adult rodent central nervous system (CNS). Their exact function and distribution is currently being assessed, but they represent an interesting cell population, which may be used to study factors important for the differentiation of neurons, astrocytes and oligodendrocytes. Recent evidence suggests that neural stem cells may also exist in both the developing and adult human CNS. These cells can be grown in vitro for long periods of time while retaining the potential to differentiate into nervous tissue. Significantly, many neurons can be produced from a limited number of starting cells, raising the possibility of cell replacement therapy for a wide range of neurological disorders. This review summarises this fascinating and growing field of neurobiology, with a particular focus on human tissues.
Packet video and its integration into the network architecture (1989)

Packet video is investigated from a systems point of view. The most important issues relating to its transmission are identified and studied in the context of a layered network architecture model, leading to a better understanding of the interactions between network and signal handling. The functions at a particular layer can thereby be made less dependent on network implementation and signal format. In the layered network model, the higher layers provide format conversion, hierarchical source coding, error recovery, resynchronization, cost/quality arbitration, session setup and tear-down, packetization, and multiplexing. Provisions from the network layers pertain mainly to real-time transmission. Special consideration is given to hierarchical source coding, error recovery, statistical behavior, and timing aspects. Simulation results indicating practical solutions to some of the issues raised are presented for a hierarchical packet-video subband coding system.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
EM-an environment manager for building networked virtual environments (2002)

The Environment Manager (EM) is a high-level tool for constructing both single-user and multi-user virtual environments. A script file is used to initialize and run virtual worlds. Independent applications can share information and cooperate with each other across the Internet. EM reduces the effort required to produce a networked virtual world by providing high-level support for application replication, network configuration, communication management and concurrency control. This paper describes the architecture and implementation of EM.
Structural Integrity of the γ-Carboxyglutamic Acid Domain of Human Blood Coagulation Factor IXa Is Required for Its Binding to Cofactor VIIIa (1996)

This report describes the analysis of a novel mutant human factor IX protein from a patient with hemophilia B (factor IX activity <1%; factor IX antigen 45%). Enzymatic amplification of all eight exons of the factor IX gene followed by direct sequence analysis reveals a single nucleotide change (a guanine --> adenine transition) in exon 2 at nucleotide 6409 which results in a glycine --> arginine substitution at amino acid 12 in the gamma-carboxyglutamic acid rich (Gla) domain of the mature protein. Factor IX was isolated by immunoaffinity chromatography from plasma obtained from the proband. The purified protein is indistinguishable from normal factor IX by polyacrylamide gel electrophoresis. Characterization of the variant in purified component assays reveals that it is activated normally by its physiologic activator factor XIa, but its phospholipid-dependent activation by the factor VIIa-tissue factor complex is diminished. In the presence of phospholipid and 5 mM Ca2+, the activities of variant and normal plasma-derived factor IX are similar; however, in the presence of activated factor VIIIa (intrinsic tenase complex), the normal augmentation of the cleavage of the specific substrate of factor IX, factor X, is not observed. The determination of the association constants for normal and variant factor IXa with factor VIIIa shows that the affinity of the activated variant factor IX for the cofactor factor VIIIa is 172-fold lower than normal. Competition studies using active site-inactivated factor IXas in the intrinsic tenase complex confirm that the defect in the variant protein is in its binding to factor VIIIa. We conclude that the structural integrity of the Gla domain of human factor IX is critical for the normal binding of factor IXa to factor VIIIa in the intrinsic tenase complex. In addition, a glycine at amino acid 12 is necessary for normal activation of factor IX by the factor VIIa-tissue factor complex.
Fast Gas Chromatography of Explosive Compounds Using a Pulsed‐Discharge Electron Capture Detector* (2006)

The detection of a mixture of nine explosive compounds, including nitrate esters, nitroaromatics, and a nitramine in less than 140 sec is described. The new method employs a commercially available pulsed-discharge electron capture detector (PDECD) coupled with a microbore capillary gas chromatography (GC) column in a standard GC oven to achieve on-column detection limits between 5 and 72 fg for the nine explosives studied. The PDECD has the benefit that it uses a pulsed plasma to generate the standing electron current instead of a radioactive source. The fast separation time limits on-column degradation of the thermally labile compounds and decreases the peak widths, which results in larger peak intensities and a concomitant improvement in detection limits. The combination of short analysis time and low detection limits make this method a potential candidate for screening large numbers of samples that have been prepared using techniques such as liquid-liquid extraction or solid-phase microextraction.
Fertilization and embryo development Opinion (1996)

Eukaryotic cells express a diverse array of carbohydratesequences on their cell surfaces linked either to protein orlipid membrane constituents (Paulson, 1989; Dwek, 1995).Perhaps the most significant role postulated for glycoconjugatesis their participation in cellular communication in complexmammalian species (Varki, 1993). Their diversity of structureand their often restricted temporal, spatial and tissue specificexpression certainly suggest the possibility that glycoconju-gates play a role in cellular communication. Only recently,however, has compelling evidence been obtained supporting arole for oligosaccharide participation in such processes.Over the past decade, there has been a virtual explosionin the number of cell adhesion molecules that have beenunambiguously demonstrated to bind to oligosaccharide ligands(Varki, 1993). When temporally or spatially expressed in arestricted manner, such ligands could represent appropriate'signals' for adhesion. For example, the predominant operatinghypothesis for initial mammalian gamete binding is thatlectin-like proteins on the spermatozoa recognize and bindto oligosaccharide sequences presented on the specializedextracellular matrix of the egg known as the zona pellucida(ZP) (Wassarman, 1990; Miller and Ax, 1990). Therefore thespecific oligosaccharide ligand on the zona pellucida could bethought of as a restricted 'signal' for sperm binding. Oncebinding is engaged, induction of the acrosome reaction occursvia a G protein-mediated event (Ward and Kopf, 1993).With the exception of fertilization or fertilization-relatedprocesses, there have been relatively few studies defining thepotential roles of glycoconjugates in human or mammalianreproductive physiology. The major focus of these other studieshas been to determine the sequence and physiological relevanceof oligosaccharides associated with glycoprotein hormones(Thotakura and Blithe, 1995). However, there are severalsignificant recent findings related to mammalian sperm-zonapellucida binding, some supporting the role of carbohydraterecognition in this process and others suggesting protein-protein interaction. This area of research is an instructivemicrocosm of the challenges and controversies associatedwith defining glycobiological relationships in the mammalianreproductive system and will be the primary focus of thisdiscussion.
Deobfuscation: Reverse Engineering Obfuscated Code (2006)

In recent years, code obfuscation has attracted attention as a low cost approach to improving software security by making it difficult for attackers to understand the inner workings of proprietary software systems. This paper examines techniques for automatic deobfuscation of obfuscated programs, as a step towards reverse engineering such programs. Our results indicate that much of the effects of code obfuscation, designed to increase the difficulty of static analyses, can be defeated using simple combinations of straightforward static and dynamic analyses. Our results have applications to both software engineering and software security. In the context of software engineering, we show how dynamic analyses can be used to enhance reverse engineering, even for code that has been designed to be difficult to reverse engineer. For software security, our results serve as an attack model for code obfuscators, and can help with the development of obfuscation techniques that are more resilient to straightforward reverse engineering.
A Convenient Route to Functionalized Carbon Nanotubes (2004)

Reductive alkylation of single-walled carbon nanotubes (SWNTs) using lithium and alkyl halides in liquid ammonia yields sidewall functionalized nanotubes that are soluble in common organic solvents. Atomic force microscopy (AFM) and high-resolution tunneling electron microscopy (HRTEM) of dodecylated SWNTs prepared from raw HiPco nanotubes show that extensive debundling has occurred. GC-MS analysis of the byproduct hydrocarbons demonstrates that alkyl radicals are intermediates in the alkylation step.
<title>777 LCD backlight life</title> (1994)

To ensure reliability goals for the 777 display systems are met, Honeywell began a three and one-half year life test of the display backlight systems in July of 1992. To date, sixteen backlight assemblies have accumulated over 12,500 hours of test operation using a luminance profile that is representative of that expected for 777 flight operations. This paper describes design and operating characteristics, life test design, and life test results for the backlight systems of the 777 flight deck displays.
Fluid integration of rotation and translation (2005)

Previous research has shown that rotation and orientation of items plays three major roles during collaboration: comprehension, coordination and communication. Based on these roles of orientation and advice from kinesiology research, we have designed the Rotate'N Translate (RNT) interaction mechanism, which provides integrated control of rotation and translation using only a single touch-point for input. We present an empirical evaluation comparing RNT to a common rotation mechanism that separates control of rotation and translation. Results of this study indicate RNT is more efficient than the separate mechanism and better supports the comprehension, coordination and communication roles of orientation.
Establishment of two human prostate cancer cell lines derived from a single bone metastasis. (1997)

Human prostate cancer cell lines are particularly difficult to establish, and most existing cell lines do not exhibit features commonly seen in human prostate cancer. Most available models either grow only in vivo as xenografts or are androgen insensitive and fail to express prostate-specific antigen (PSA). The lack of functionally relevant model systems of advanced prostate cancer has limited prostate cancer research and therapy development. Of 30 processed samples derived from patients with prostate cancer, we established two cell lines (MDA PCa 2a and MDA PCa 2b) that express PSA and androgen receptor, grow in vitro, and are androgen sensitive. Cells from these lines produced tumors in nude mice when injected either s. c. or orthotopically (intraprostatic). Both cell lines were established from a bone metastasis of a patient whose cancer was exhibiting androgen-independent growth. Although both were derived from two samples of the same specimen, they have different genetic features (as assessed by karyotype analysis) and different phenotypes (e.g., morphology and growth rate). It is likely that they are distinct clones isolated by the use of different culture procedures and reflect the genetic heterogeneity of the tumor. These new cell lines are the first available derived from a bone metastasis of an androgen-independent prostatic adenocarcinoma that grow both in vivo and in vitro and have retained PSA expression and androgen sensitivity. They therefore constitute important model systems to address critical questions related to the androgen-independent growth of human prostate cancer and to the complex process of bone metastasis.
ERNE-BS5 (2012)

Cytosine methylation is a DNA modification that has great impact on the regulation of gene expression and important implications for the biology and health of several living beings, including humans. Bisulfite conversion followed by next generation sequencing (BS-seq) of DNA is the gold standard technique used to detect DNA methylation at single-base resolution on a genome scale through the identification of 5-methylcytosine (5-mC). However, by converting unmethylated cytosines into thymines, BS-seq poses computational challenges to read alignment and aggravates the issue of multiple hits due to the ambiguity raised by the reduced sequence complexity.
Vascular Endothelial Growth Factor–Induced Endothelial Cell Migration and Proliferation Depend on a Nitric Oxide–Mediated Decrease in Protein Kinase Cδ Activity (1999)

Vascular endothelial growth factor (VEGF) promotes angiogenesis and endothelial cell (EC) migration and proliferation by affecting intracellular mediators, only some of which are known, distal to its receptors. Protein kinase C (PKC) participates in the function of VEGF, but the role of individual PKC isoenzymes is unknown. In this study, we tested the importance of the activity of specific PKC isoenzymes in human EC migration and proliferation in response to VEGF. PKCdelta specific activity was depressed by the addition of VEGF (by 41+/-8% [P<0.05] at 24 hours) in human umbilical vein ECs (HUVECs) and in a HUVEC-derived EC line, ECV, without changing the total amount of either protein or mRNA encoding PKCdelta. Neither basic fibroblast growth factor (FGF-2) nor serum altered PKCdelta specific activity. The VEGF-induced decrease of PKCdelta activity, which began at 8 hours after stimulation, was strongly blocked by pretreatment with the nitric oxide (NO) synthase inhibitor N(G)-monomethyl-L-arginine in HUVECs; NO release peaked within 2 hours after stimulation. An exogenous NO donor, sodium nitroprusside, also decreased PKCdelta activity. The inhibition by N(G)-monomethyl-L-arginine of VEGF-induced HUVEC migration and proliferation, but not that induced by FGF-2 or serum, suggested that the decrease in PKCdelta via NO pathway is required for VEGF-induced EC migration and proliferation. Overexpression of PKCdelta in ECV cells specifically prevented EC response to VEGF but not to FGF-2 or serum. Thus, we conclude that suppression of PKCdelta activity via a NO synthase mechanism is required for VEGF-induced EC migration and proliferation, but not for that induced by FGF-2 or serum.
Cooperative DNA binding of heterologous proteins: evidence for contact between the cyclic AMP receptor protein and RNA polymerase. (1988)

Four cAMP-independent receptor protein mutants (designated CRP* mutants) isolated previously are able to activate in vivo gene transcription in the absence of cAMP and their activity can be enhanced by cAMP or cGMP. One of the four mutant proteins, CRP*598 (Arg-142 to His, Ala-144 to Thr), has been characterized with regard to its conformational properties and ability to bind to and support abortive initiation from the lac promoter. In the absence of cGMP, CRP*598 shows a more open conformation than CRP, as indicated by its sensitivity to proteolytic attack and 5,5'-dithiobis(2-nitrobenzoic acid)-mediated subunit crosslinking. Binding of wild-type CRP to its site on the lac promoter and activation of abortive initiation by RNA polymerase on this promoter are effected by cAMP but not by cGMP. CRP*598 can activate lacP+-directed abortive initiation in the presence of cAMP and less efficiently in the presence of cGMP or in the absence of cyclic nucleotide. DNase I protection ("foot-printing") indicates that cAMP-CRP* binds to its site on the lac promoter whereas unliganded CRP* and cGMP-CRP* form a stable complex with the [32P]lacP+ fragment only in the presence of RNA polymerase, showing cooperative binding of two heterologous proteins. This cooperative binding provides strong evidence for a contact between CRP and RNA polymerase for activation of transcription. Although cGMP binds to CRP, it cannot replace cAMP in effecting the requisite conformational transition necessary for site-specific promoter binding. In contrast, the weakly active unliganded CRP*598 can be shifted to a functional state not only by cAMP but also by cGMP and RNA polymerase.
Alternatively folded states of an immunoglobulin (1991)

Well-defined, non-native protein structures of low stability have been increasingly observed as intermediates in protein folding or as equilibrium structures populated under specific solvent conditions. These intermediate structures, frequently referred to as molten globule states, are characterized by the presence of secondary structure, a lack of significant tertiary contacts, increased hydrophobicity and partial specific volume as compared to native structures, and low cooperativity in thermal unfolding. The present study demonstrates that under acidic conditions (pH less than 3) the antibody MAK33 can assume a folded stable conformation. This A-state is characterized by a high degree of secondary structure, increased hydrophobicity, a native-like maximum wavelength of fluorescence emission, and a tendency toward slow aggregation. A prominent feature of this low-pH conformation is the stability against denaturant and thermal unfolding that is manifested in highly cooperative reversible phase transitions indicative of the existence of well-defined tertiary contacts. These thermodynamic results are corroborated by the kinetics of folding from the completely unfolded chain to the alternatively folded state at pH 2. The given data suggest that MAK33 at pH 2 adopts a cooperative structure that differs from the native immunoglobulin fold at pH 7. This alternatively folded state exhibits certain characteristics of the molten globule but differs distinctly from it by its extraordinary structural stability that is characteristic for native protein structures.
Downregulation of Fanconi Anemia Genes in Sporadic Head and Neck Squamous Cell Carcinoma (2007)

Our data suggest that downregulation of FA genes is common in sporadic HNSCC. The clinical implications of this finding merit further study. .