gebhart/patrepeval huggingface dataset:
Vaccination with autologous non‐irradiated dendritic cells in patients with bcr/abl+ chronic myeloid leukaemia (2007)

In chronic myeloid leukaemia (CML), dendritic cells (DC) and leukaemic cells share a common progeny, leading to constitutive expression of putative tumour antigens, such as bcr/abl, in DC. In this phase-I/II study, autologous DC were used as a vaccine in patients with chronic phase bcr/abl+ CML, who had not achieved an adequate cytogenetic response after treatment with alpha-interferon or imatinib. Ten patients were enrolled, DC were generated from peripheral blood monocytes and vaccination consisted of four subcutaneous injections of increasing numbers of DC (1-50 x 10(6) cells per injection) on days 1, 2, 8 and 21. Vaccination was feasible and safe. Improvement of the cytogenetic/molecular response, as detected by fluorescence in situ hybridization of peripheral blood mononuclear cells (PBMC), was possibly related to vaccination in four of 10 patients. In three of these patients, T cells recognizing leukaemia-associated antigens became detectable. The proliferative capacity of PBMC in response to autologous DC increased after vaccination in all evaluable patients. We conclude that vaccination with autologous, non-irradiated 'leukaemic' DC is feasible, safe and induces anti-leukaemic T-cell responses in some CML patients. DC vaccination might be useful in CML as postremission therapy, i.e. after treatment with tyrosine kinase inhibitors.
Altered pharmacokinetic and tumour localization properties of Fab' fragments of a murine monoclonal anti-CEA antibody by covalent modification with low molecular weight dextran (1995)

This paper describes the modification of Fab' fragments of ZCE025, a murine monoclonal antibody recognizing carcinoembryonic antigen (CEA), with oxidized dextran of low molecular weight. This modification altered the in vitro and in vivo characteristics of the Fab'. The dextran conjugated fragments exhibited markedly reduced renal uptake and excretion and the prolonged residence time of the Fab' in the vascular compartment. The result was enhanced tumour localization of the derivative compounds compared with underivatized Fab', even though the process of chemical coordination reduced the immunoreactivity of the molecule. The isoelectric point of the molecule was much lower than the unaltered Fab' and previous research has shown this to reduce markedly its potential for inducing a human anti-mouse antibody (HAMA) response. Thus, the conjugation of Fab' fragments with low molecular weight oxidized dextrans can increase the bioavailability of these fragments for tumour localization, while simultaneously reducing their immunogenic potential and renal accumulation problems.
Prodrugs of 9-.beta.-D-arabinofuranosyladenine. 1. Synthesis and evaluation of some 5'-(O-acyl) derivatives (1978)

A number of 5'-(O-acyl) derivatives of 9-beta-D-arabinofuranosyladenine (ara-A, VIRA-A) (2a-k) were prepared by direct acylation of the parent nucleoside 1 in pyridine-N,N-dimethyliformamide. These compounds, designed as prodrugs for 1, offer a range of solubilities and lipophilicities indicating for several examples improved solubility and the potential for improved membrane transport over 1. All are resistant to deactivation by adenosine deaminase. Of special interest is the 5'-(O-valeryl) derivative 2d that shows a marked increase in antiviral activity over 1.
Listeriolysin O (2002)

Cholesterol-dependent cytolysins (CDCs)* are produced by a large number of pathogenic gram-positive bacteria. A member of this family, listeriolysin O (LLO), is produced by the intracellular pathogen Listeria monocytogenes. A unique feature of LLO is its low optimal pH activity (approximately 6) which permits escape of the bacterium from the phagosome into the host cell cytosol without damaging the plasma membrane of the infected cell. In a recent study (Glomski et al., 2002, this issue), Portnoy's group has addressed the molecular mechanism underlying the pH sensitivity of LLO. Unexpectedly, a single amino acid substitution in LLO L461T results in a molecule more active at neutral pH and promoting premature permeabilization of the infected cells, leading to attenuated virulence. This finding highlights how subtle changes in proteins can be exploited by bacterial pathogens to establish and maintain the integrity of their specific niches.
Fibers of tau fragments, but not full length tau, exhibit a cross β‐structure: Implications for the formation of paired helical filaments (2000)

Abstract We have used X‐ray fiber diffraction to probe the structure of fibers of tau and tau fragments. Fibers of fragments from the microtubule binding domain had a cross β‐structure that closely resembles that reported both for neurofibrillary tangles found in Alzheimer's disease brain and for fibrous lesions from other protein folding diseases. In contrast, fibers of full‐length tau had a different, more complex structure. Despite major differences at the molecular level, all fiber types exhibited very similar morphology by electron microscopy. These results have a number of implications for understanding the etiology of Alzheimer's and other tauopathic diseases. The morphology of the peptide fibers suggests that the region in tau corresponding to the peptides plays a critical role in the nucleation of fiber assembly. The dramatically different structure of the full length tau fibers suggests that some region in tau has enough inherent structure to interfere with the formation of cross β‐fibers. Additionally, the similar appearance by electron microscopy of fibrils with varying molecular structure suggests that different molecular arrangements may exist in other samples of fibers formed from tau.
Recent Advances in Self-Assembled Fluorescent DNA Structures and Probes (2015)

The combined efforts of chemistry, nanotechnology, and spectroscopy led to the development of self-assembled fluorescent DNA nanostructures, an inexhaustible source of refined and bizarre tools and powerful techniques for research and diagnostic applications. This multidisciplinary area has tremendous prospects for science and technology.
A design of SD-WAN-oriented wide area network access (2020)

This article proposes a converged SD-WAN architecture for the lack of flexibility of the existing SD-WAN architecture. The architecture takes the SDN controller as the core of the entire SD-WAN and deploys it in the corporate headquarters. Different from other SDN-WAN solutions, the forwarding layer of the integrated SD-WAN architecture uses Customer Premise Equipment (CPE)and OpenFlow switches as the main equipment to complete data forwarding and receiving functions.
Characteristics of Poly( p-pyridyl vinylene)/Poly(3-alkylthiophene) Heterojunction Photocell (1997)

Photoirradiation effects of a poly( p -pyridyl vinylene) (PPyV)/poly(3-hexylthiophene) (PAT6) heterojunction photocell have been investigated. The photovoltaic characteristics of the heterojunction photocell are considerably improved from those in a single-PAT6-layer photocell. Quenching of photoluminescence both in the PAT6 layer and in the PPyV layer has also been observed in the PPyV/PAT6 double layer. The observed photoirradiation effects of the heterojunction have been discussed in terms of interfacial photoinduced charge transfer between PAT6 and PPyV.
Moxonidine treatment of hypertensive patients with advanced renal failure (2003)

Add-on treatment with 0.3 mg/day moxonidine in hypertensive patients with renal failure is well tolerated and not inferior to 20 mg/day nitrendipine with respect to the incidence of specific adverse events. The idea of a sympatholytic drug to be renoprotective is appealing but needs further evaluation.
Sustained signaling through the B-cell receptor induces Mcl-1 and promotes survival of chronic lymphocytic leukemia B cells (2005)

The clinical course of chronic lymphocytic leukemia (CLL) differs significantly between patients with mutated (M-CLL) and unmutated (U-CLL) immunoglobulin (Ig) variable heavy-chain (V(H)) genes, implying a role for B-cell receptor (BCR) signaling in the pathogenesis of this disease. We have now investigated activation of downstream BCR signaling pathways in U-CLL and M-CLL B cells using soluble anti-IgM (sol-IgM) and immobilized anti-IgM (imm-IgM) antibodies as models for antigenic stimulation. Ligation of the BCR with sol-IgM induced incomplete responses in both CLL subsets, resembling the pattern described for tolerant B cells. This response was characterized by transient phosphorylation of extracellular signal-related kinase (ERK) and Akt (protein kinase B [PKB]), lack of activation of c-JUN NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), and variable activation of phospholipase Cgamma2 (PLCgamma2) and nuclear factor-kappaB (NF-kappaB). Stimulation with imm-IgM elicited a more complete BCR signal and significantly prolonged phosphorylation of ERK and Akt, indicating persistent or repetitive BCR signaling. Moreover, this type of stimulation increased the levels of the antiapoptotic protein myeloid cell leukemia-1 (Mcl-1) and protected from chemotherapy-induced apoptosis, whereas induction of apoptosis and down-regulation of Mcl-1 was observed following stimulation with sol-IgM. These data demonstrate that only sustained BCR signaling can promote survival of CLL B cells and indicate that the main difference between CLL with mutated and unmutated V(H) genes may reside in the availability of such stimulation.
Clinically approved PEGylated nanoparticles are covered by a protein corona that boosts the uptake by cancer cells (2017)

Today, liposomes are an advanced technology of drug carriers with a dozen drugs in clinical practice and many more in clinical trials. A bottleneck associated with the clinical translation of liposomes has long been 'opsonization', i.e. the adsorption of plasma proteins at the liposome surface resulting in their rapid clearance from circulation. For decades, the most popular way to avoid opsonization has been grafting polyethylene glycol (PEG) onto the liposome surface. Recent studies have clarified that grafting PEG onto the liposome surface reduces, but does not completely prevent protein binding. In this work, we employed dynamic light scattering, zeta-potential analysis, one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (1D-SDS-PAGE), semi-quantitative densitometry and cell imaging to explore the bio-nano-interactions between human plasma (HP) and Onivyde, a PEGylated liposomal drug that has recently been approved by the Food and Drug Administration (FDA) for the treatment of metastatic pancreatic ductal adenocarcinoma (PDAC). To properly evaluate the role of PEGylation, an unPEGylated variant of Onivyde was used as a reference. Collectively, our findings suggest that: (i) although PEGylated, Onivyde is not "stealth" in HP; (ii) surface chemistry is more important than PEGylation in controlling the bio-nano-interactions between Onivyde and plasma components. Of note is that the PC was found to boost the cellular uptake of Onivyde in the pancreas ductal adenocarcinoma cell line (PANC-1) thus suggesting its prominent role in its indication for PDAC treatment. Relevant implications for drug delivery and drug design are discussed.
Structure and stereochemistry of simmondsin (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructure and stereochemistry of simmondsinCarl A. Elliger, A. C. Waiss, and R. E. LundinCite this: J. Org. Chem. 1974, 39, 19, 2930–2931Publication Date (Print):September 1, 1974Publication History Published online1 May 2002Published inissue 1 September 1974https://pubs.acs.org/doi/10.1021/jo00933a026https://doi.org/10.1021/jo00933a026research-articleACS PublicationsRequest reuse permissionsArticle Views76Altmetric-Citations28LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Influence of recombinant hematopoietins and of fetal bovine serum on the globin synthetic pattern of human BFUe (1990)

We have studied the effects of recombinant hematopoietic growth factors, granulocyte-macrophage colony-stimulating factor (GM-CSF) and/or interleukin-3 (IL-3) on the globin program of adult human erythroid progenitors (BFUe) stimulated to terminal differentiation by erythropoietin under fetal bovine serum (FBS)-supplemented or FBS- deprived culture conditions. Fetal globin production by BFUe-derived erythroblasts was assessed at the protein and mRNA level and its cellular distribution was evaluated by immunofluorescence. Although hemoglobinization and maturation of BFUe-derived erythroblasts was by and large comparable in FBS-replete versus FBS-deprived cultures, the latter had significantly less (up to 20-fold) gamma-globin and gamma- globin mRNA levels. Reduced gamma-globin in serum-deprived cultures was also reflected by a smaller proportion of erythroblasts with detectable gamma-globin by immunofluorescence. Erythroid bursts induced by either GM-CSF or IL-3 produced similar levels of gamma-globin both in FBS- supplemented and in FBS-deprived cultures. These results, obtained even in cultures of highly enriched BFUe, suggest that GM-CSF and IL-3, although they significantly increase the number and size of erythroid bursts, do not by themselves exert a direct influence on the level of fetal globin synthesis. By contrast, factor(s) present in FBS appear to exert a dominant influence on fetal globin synthesis in vitro. Although FBS-deprived conditions appear to largely abrogate the in vitro activation of fetal hemoglobin (Hb F) in normal samples, they do support increased Hb F production in samples from patients with hereditary persistence of fetal hemoglobin or from cord blood.
Homogeneous Metathesis Polymerization by Well-Defined Group VI and Group VIII Transition-Metal Alkylidenes:  Fundamentals and Applications in the Preparation of Advanced Materials (2000)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHomogeneous Metathesis Polymerization by Well-Defined Group VI and Group VIII Transition-Metal Alkylidenes: Fundamentals and Applications in the Preparation of Advanced MaterialsMichael R. BuchmeiserView Author Information Institute of Analytical Chemistry and Radiochemistry, University of Innsbruck, Innrain 52 a, A-6020 Innsbruck, Austria Cite this: Chem. Rev. 2000, 100, 4, 1565–1604Publication Date (Web):March 16, 2000Publication History Received31 August 1999Published online16 March 2000Published inissue 1 April 2000https://doi.org/10.1021/cr990248aCopyright © 2000 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views4389Altmetric-Citations669LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (2 MB) Get e-AlertsSUBJECTS:Catalysts,Hydrocarbons,Monomers,Polymerization,Polymers Get e-Alerts
DNA triplex formation of oligonucleotide analogs consisting of linker groups and octamer segments that have opposite sugar-phosphate backbone polarities (1991)

The DNA oligomer analogues 3'd(CTTTCTTT)5'-P4-5'd(TTCTTCTT)3' (IV), 5'd-(TTTCTTTC)3'-P2-3'd(CTTTCTTT)5' (V), and 5'd(TTTCTTTC)3'-P2-3'd(CTTTCTTT)5'-P4-5'd-(TTCTTCTT)3' (VI) (P2 = P*P and P4 = P*P*P*P, where P = phosphate and * = 1,3-propanediol) have been synthesized. These oligomers consist of a linker group or groups and homopyrimidine oligonucleotides which have opposite sugar-phosphate backbone polarities. These oligomer analogues are designed to form triplexes with a duplex, 5'd(AAAGAAAGCCCTTTCTTTAAGAAGAA)3'.5'd(TTCTTCTTAAA- GAAAGGGCTTTCTTT)3' (I), which contains small homopurine clusters alternately located in both strands. The length of the linker groups, P2 and P4, was based upon a computer modeling analysis. Triplex formation by the unlinked octamers 5'd(TTCTTCTT)3' (II) and 5'd(TTTCTTTC)3' (III) and the linked oligomer analogues IV-VI with the target duplex was studied by thermal denaturation at pH 5.2. The order of stabilities of triplex formation by these oligomers was I-V much much greater than I-IV greater than I-(II, III). The mixture of I and VI showed two transitions corresponding to the dissociation of the third strand. The higher transition corresponded to the dissociation of 3'-3'-linked octamer segments, and the lower one corresponded to the dissociation of 5'-5'-linked octamer segments. The Tm of the latter transition was higher than that of the I-IV triplex; thus the triplex formed by the 5'-5'-linked octamer segment was stabilized by the triplex formed by the 3'-3'-linked octamer segments in the I-VI triplex. Triplex formation of this system was also studied in the presence of ethidium bromide.(ABSTRACT TRUNCATED AT 250 WORDS)
(R)-3,N-Dimethyl-N-[1-methyl-3-(4-methylpiperidin-1-yl)propyl]benzenesulfonamide:  The First Selective 5-HT7Receptor Antagonist (1998)

ADVERTISEMENT RETURN TO ISSUELetterNEXT(R)-3,N-Dimethyl-N-[1-methyl-3-(4-methylpiperidin-1-yl)propyl]benzenesulfonamide: The First Selective 5-HT7 Receptor AntagonistIan T. Forbes, Steven Dabbs, D. Malcolm Duckworth, Andrew J. Jennings, Frank D. King, Peter J. Lovell, Anthony M. Brown, Lissa Collin, Jim J. Hagan, Derek N. Middlemiss, Graham J. Riley, David R. Thomas, and Neil UptonView Author Information SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Third Avenue, Harlow, Essex, England, CM19 5AW Cite this: J. Med. Chem. 1998, 41, 5, 655–657Publication Date (Web):February 6, 1998Publication History Received4 August 1997Published online6 February 1998Published inissue 1 February 1998https://doi.org/10.1021/jm970519eCopyright © 1998 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views575Altmetric-Citations89LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (67 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Agonists,Antagonists,Central nervous system,Receptors,Rodent models Get e-Alerts
Molecular Targets of Gene Transfer Therapy for HIV Infection (1993)

THE ACQUIRED immunodeficiency syndrome (AIDS), caused by human immunodeficiency virus (HIV), is a chronic disease primarily characterized by a decrease in CD4-positive T lymphocytes. Subsequent immune system suppression and failure lead to frequent infection by opportunistic pathogens and, oftentimes along with neoplasms or other HIV-related pathology, death of the patient. During the last 10 years, considerable progress has been made in the development of treatments for various opportunistic infections. In addition, the use of nucleoside analogs (zidovudine, dideoxyinosine, dideoxycytodine), which interfere with reverse transcription and seem to slow viral spread, has become commonplace. Although these treatments can delay disease progression,<sup>1</sup>side effects associated with their use, and possibly the development of viral resistance to these drugs,<sup>2</sup>may inevitably lead to treatment failure. For these reasons, alternate therapies for HIV infection are needed. Included among the list of potential treatments is gene transfer therapy. Recent progress in ongoing clinical
Antibody therapeutics, antibody engineering, and the merits of protein stability. (2008)

Antibodies are highly soluble, multidomain proteins that are well suited for biopharmaceutical development; however, engineering antibodies to perform novel activities or to have enhanced clinical utility can have a detrimental effect on their biophysical properties. Various innovative designs, such as single-chain variable fragments (scFvs) and domain antibodies (dAbs), have been utilized to obtain the antigen-binding properties of natural antibodies, while using a minimal amount of the polypeptide sequence of an antibody. These designs can be used for generating diverse antibody libraries to support discovery and optimization and also serve as excellent building blocks for constructing more complex protein therapeutics, such as bispecific antibodies. However, engineered antibody-like proteins, including scFvs, are often unstable and prone to aggregation, compromising both protein production and quality. Research over the past few years has enhanced our understanding of how interdomain interactions within antibodies contribute to protein stability. This knowledge and sustained research to develop methods for modifying antibody fragments to improve stability have begun to have a positive impact on the quality of antibody libraries for discovery purposes and the viability of highly engineered proteins, such as bispecific antibodies, as therapeutics.
Primary and Secondary Hyperalgesia in a Rat Model for Human Postoperative Pain (1999)

Robust primary hyperalgesia to punctate and blunt mechanical stimuli was present. Hyperalgesia distant to the wound, or secondary hyperalgesia, occurred in response to punctate mechanical stimuli, was short-lived, and required greater forces. These results suggest that the most persistent pain behaviors in this model are largely primary hyperalgesia.