gebhart/patrepeval huggingface dataset:
Fluorine-, pyrene-, and nitroxide-labeled sphingomyelin: semi-synthesis and thermotropic properties. (1985)

A rapid, high-yield method has been developed for the N-acylation of sphingosine-1-phosphocholine (SPC) to obtain a series of sphingomyelin (SM) derivatives bearing different reporter groups in the N-acyl chain. The procedure utilizes a fatty acid activated as the N-hydroxysuccinimide ester. A 1:1 molar mixture of the activated fatty acid and SPC is refluxed in 5% aqueous NaHCO3-ethanol 9:1 (v/v) for 2-3 hr. After acidification, the precipitated SM is purified by column chromatography over silica gel. This procedure offers significant advantages over those reported for the synthesis of well-defined SM: i) only the amino (not the hydroxyl) group is acylated; ii) only one equivalent of fatty acid is required; and iii) the time necessary for the reaction to go to completion is short. The transition temperature and enthalpy of each SM derivative has been measured by differential scanning calorimetry and compared to its unlabeled analog.
Partition-Variant Desferrithiocin Analogues:  Organ Targeting and Increased Iron Clearance (2005)

Altering the lipophilicity (log P(app)) of desferrithiocin analogues can change the organ distribution of the chelators and lead to enhanced iron clearance. For example, alkylation of (S)-2-(2,4-dihydroxyphenyl)-4,5-dihydro-4-methyl-4-thiazolecarboxylic acid [(S)-4'-(HO)-DADFT] and its analogues to more lipophilic compounds, such as (S)-4,5-dihydro-2-(2-hydroxy-4-methoxyphenyl)-4-methyl-4-thiazolecarboxylic acid [(S)-4'-(CH3O)-DADFT], provides ligands that achieved between a 3- and 8-fold increase in chelator concentrations in the heart, liver, and pancreas (the organs most at risk in iron-overload disease) of treated rodents. The 4'-O-methylated compounds are demethylated to their hydroxylated counterparts in rodents; furthermore, this O-demethylation takes place in both rodent and human liver microsomes. The relationship between chelator lipophilicity and iron-clearing efficacy in the iron-overloaded Cebus apella primate is further underscored by a comparison of the iron-clearing efficiency of (S)-2-(2,3-dihydroxyphenyl)-4,5-dihydro-4-methyl-4-thiazolecarboxylic acid [(S)-3'-(HO)-DADFT] and its 3'-(CH3O) counterpart. Finally, these DFT analogues are shown to be both inhibitors of the iron-mediated oxidation of ascorbate as well as effective radical scavengers.
Eosinophils: Biological Properties and Role in Health and Disease (2008)

Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of diverse inflammatory responses, as well as modulators of innate and adaptive immunity. In this review, the biology of eosinophils is summarized, focusing on transcriptional regulation of eosinophil differentiation, characterization of the growing properties of eosinophil granule proteins, surface proteins and pleiotropic mediators, and molecular mechanisms of eosinophil degranulation. New views on the role of eosinophils in homeostatic function are examined, including developmental biology and innate and adaptive immunity (as well as their interaction with mast cells and T cells) and their proposed role in disease processes including infections, asthma, and gastrointestinal disorders. Finally, strategies for targeted therapeutic intervention in eosinophil-mediated mucosal diseases are conceptualized.
Properties of the adenovirus DNA polymerase. (1984)

The 140,000-Da adenovirus-encoded DNA polymerase (Ad Pol) is required for viral DNA replication both in vitro and in vivo. The polymerase co-purifies in a complex with the 80,000-Da precursor (pTP) of the terminal protein (TP) found covalently attached to the 5' ends of adenovirus DNA. To better understand their function in DNA replication, we have examined the properties of the Ad Pol and the pTP X Ad Pol complex on natural and synthetic DNA templates. The pTP X Ad Pol complex utilizes a variety of homopolymer template-primer combinations including poly(dC) X oligo(dG), poly(dA) X oligo(dT), poly(dT) X oligo(dA), and poly(dT) X oligo(rA). With poly(dT) as template and oligo(rA) or oligo(dA) as primer, DNA synthesis by the pTP X Ad Pol complex is stimulated as much as 100-fold by the 59,000-Da adenovirus DNA-binding protein (Ad DBP). ATP (4 mM) can further increase the rate of DNA synthesis 3- to 10-fold. The Ad DBP does not stimulate the activity of host (HeLa cell) DNA polymerase alpha with poly(dT) X oligo(dA) (or oligo(rA)) as the template-primer, and Escherichia coli single-stranded DNA binding protein cannot substitute for the Ad DBP in the stimulation of the Ad Pol activity. Under optimal conditions, poly(dA) chains 30,000 nucleotides in length are formed indicating that the Ad Pol can be a highly processive enzyme. An exonuclease activity co-sediments with the pTP X Ad Pol complex during glycerol gradient centrifugation, and co-purifies with the 140,000-Da Ad Pol after dissociation of the pTP X Ad Pol complex with urea. The Ad Pol-associated nuclease hydrolyzes single-stranded DNA in a 3'----5' direction and is at least 10-fold more active on single-stranded DNA than on duplex DNA. The Ad Pol has no detectable endonuclease activity on single-stranded DNA or duplex circular DNA. Analysis of the products of the nuclease activity showed that 5'-deoxynucleoside monophosphates were released during the hydrolysis of single-stranded DNA. The Ad DBP inhibits the hydrolysis of DNA by the polymerase-associated nuclease activity.
Proliferative action of erythropoietin is associated with rapid protein tyrosine phosphorylation in responsive B6SUt.EP cells. (1991)

Erythropoietin is a prime regulator of the growth and terminal differentiation of erythroid blood cells. However, little is understood concerning its molecular mechanism of action. Presently it is shown in the responsive, factor-dependent murine cell line B6SUt.EP that erythropoietin induces the tyrosine phosphorylation of six plasma membrane-associated proteins in a time- and concentration-dependent fashion (i.e. phosphoproteins PY153, PY140, PY100, PY93, PY74, and PY54). Among these, PY153 was prominent. For all proteins, maximal levels of phosphorylation were induced within 3-7 min at low factor concentrations (100-500 pM). These findings establish tyrosine kinase activation as a novel candidate pathway of erythropoietin-induced proliferation. In addition, the tyrosine phosphorylation of six proteins with identical Mr, as well as a Mr 104,000 protein, was induced in B6SUt.EP cells by interleukin 3. In contrast, no induced tyrosine phosphorylation was detectable in the erythropoietin-responsive, leukemic erythroid cell line. Rauscher Red 1, yet proteins of Mr 153,000 and 54,000 were shown to be phosphorylated constitutively at relative levels greater than those observed in B6SUt.EP cells. A possible role for these phosphoproteins in hematopoietic cell transformation is considered.
The effect of the inhibitor diphenylene iodonium on the superoxide-generating system of neutrophils. Specific labelling of a component polypeptide of the oxidase (1986)

NADPH-dependent superoxide production by the solubilized oxidase of neutrophils was inhibited 36% by diphenylene iodonium at a 1:1 stoichiometry with the enzyme flavoprotein content. Addition of diphenylene iodonium strongly inhibited the NADPH-dependent reduction of both FAD and cytochrome b-245 in steady-state kinetic experiments. Incubation of solubilized enzyme with diphenylene [125I]iodonium resulted in the specific labelling of a polypeptide of Mr 45,000. In the presence of NADPH the amount of label incorporated into the polypeptide was reduced. There was no difference in labelling between enzyme prepared from stimulated or unstimulated cells.
Stimulus-active polymer actuators for next-generation microfluidic devices (2016)

Microfluidic devices have not yet evolved into commercial off-the-shelf products. Although highly integrated microfluidic structures, also known as lab-on-a-chip (LOC) and micrototal-analysis-system (µTAS) devices, have consistently been predicted to revolutionize biomedical assays and chemical synthesis, they have not entered the market as expected. Studies have identified a lack of standardization and integration as the main obstacles to commercial breakthrough. Soft microfluidics, the utilization of a broad spectrum of soft materials (i.e., polymers) for realization of microfluidic components, will make a significant contribution to the proclaimed growth of the LOC market. Recent advances in polymer science developing novel stimulus-active soft-matter materials may further increase the popularity and spreading of soft microfluidics. Stimulus-active polymers and composite materials change shape or exert mechanical force on surrounding fluids in response to electric, magnetic, light, thermal, or water/solvent stimuli. Specifically devised actuators based on these materials may have the potential to facilitate integration significantly and hence increase the operational advantage for the end-user while retaining cost-effectiveness and ease of fabrication. This review gives an overview of available actuation concepts that are based on functional polymers and points out promising concepts and trends that may have the potential to promote the commercial success of microfluidics.
Lipophilic Hexadentate Aluminum, Gallium, Indium, and Iron Complexes of a New Phenolate-Derivatized Cyclohexanetriamine Ligand (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTLipophilic Hexadentate Aluminum, Gallium, Indium, and Iron Complexes of a New Phenolate-Derivatized Cyclohexanetriamine LigandJames E. Bollinger, Joel T. Mague, and D. Max RoundhillCite this: Inorg. Chem. 1994, 33, 7, 1241–1242Publication Date (Print):March 1, 1994Publication History Published online1 May 2002Published inissue 1 March 1994https://pubs.acs.org/doi/10.1021/ic00085a001https://doi.org/10.1021/ic00085a001research-articleACS PublicationsRequest reuse permissionsArticle Views129Altmetric-Citations23LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Death Receptor-Ligand Systems in Cancer, Cell Death, and Inflammation (2013)

The discovery of tumor necrosis factor (TNF) marked the beginning of one of the most fascinating journeys in modern biomedical research. For the moment, this journey has culminated in the development of drugs that inhibit TNF. TNF blockers have revolutionized the treatment of many chronic inflammatory diseases. Yet, the journey seems far from over. TNF is the founding member of a family of cytokines with crucial functions in cell death, inflammation, and cancer. Some of these factors, most prominently TNF, CD95L, and TRAIL, can induce cell death. The receptors that mediate this signal are therefore referred to as death receptors, even though they also activate other signals. Here I will take you on a journey into the discovery and study of death receptor-ligand systems and how this inspired new concepts in cancer therapy and our current understanding of the interplay between cell death and inflammation.
Transcutaneous Immunization with Cross-Reacting Material CRM 197 of Diphtheria Toxin Boosts Functional Antibody Levels in Mice Primed Parenterally with Adsorbed Diphtheria Toxoid Vaccine (2008)

Transcutaneous immunization (TCI) capitalizes on the accessibility and immunocompetence of the skin, elicits protective immunity, simplifies vaccine delivery, and may be particularly advantageous when frequent boosting is required. In this study we examined the potential of TCI to boost preexisting immune responses to diphtheria in mice. The cross-reacting material (CRM(197)) of diphtheria toxin was used as the boosting antigen and was administered alone or together with either one of two commonly used mucosal adjuvants, cholera toxin (CT) and a partially detoxified mutant of heat-labile enterotoxin of Escherichia coli (LTR72). We report that TCI with CRM(197) significantly boosted preexisting immune responses elicited after parenteral priming with aluminum hydroxide-adsorbed diphtheria toxoid (DTxd) vaccine. In the presence of LTR72 as an adjuvant, toxin-neutralizing antibody titers were significantly higher than those elicited by CRM(197) alone and were comparable to the functional antibody levels induced after parenteral booster immunization with the adsorbed DTxd vaccine. Time course study showed that high levels of toxin-neutralizing antibodies persisted for at least 14 weeks after the transcutaneous boost. In addition, TCI resulted in a vigorous antigen-specific proliferative response in all groups of mice boosted with the CRM(197) protein. These findings highlight the promising prospect of using booster administrations of CRM(197) via the transcutaneous route to establish good herd immunity against diphtheria.
SGN-CD33A (Vadastuximab Talirine) followed by Allogeneic Hematopoietic Stem Cell Transplant (AlloHSCT) Results in Durable Complete Remissions (CRs) in Patients with Acute Myeloid Leukemia (AML) (2016)

SGN-CD33A is an antibody-drug conjugate composed of an anti-CD33 engineered-cysteine antibody conjugated to 2 molecules of a pyrrolobenzodiazepine (PBD) dimer, a highly potent DNA crosslinking agent. Initial investigations with SGN-CD33A elicited durable CRs in patients (pts) with relapsed/refractory AML or pts with AML who declined standard induction chemotherapy (Stein 2014). This report details the experience of a subset of pts treated with SGN-CD33A who subsequently received alloHSCT without intervening therapy (N=7). A phase 1 study (NCT01902329) evaluating the safety and activity of SGN-CD33A is ongoing. AML pts (ECOG 0-1) must have declined intensive therapy, or have relapsed disease after initial CR of >3 months. SGN-CD33A is given as monotherapy IV q3wk. At baseline, pt median age was 54 years (range 37-78); the majority were ECOG 0 (4 of 7 pts). Two pts had AML evolved from prior MDS, and 5 pts had AML in first relapse. Adverse-risk cytogenetics were present in 2 pts, both with del(7q); 2 pts were favorable-risk due to mutated NPM1. Best responses with SGN-CD33A treatment (within 1 or 2 cycles at 20-60 mcg/kg/cycle) were 1 CR, 4 CRs with incomplete hematologic recovery (CRi), and 2 morphologic leukemia-free state (mLFS). The most commonly reported Grade 3/4 adverse events were febrile neutropenia (n=5), thrombocytopenia (n=4), anemia (n=3), and bone marrow hypocellularity (n=2). Conditioning regimens were myeloablative in 3 pts and reduced-intensity in 4 pts. Donor stem cell source was peripheral blood in 5 pts (3 related, 2 unrelated) and cord blood in 2 pts. Median time to transplant from last dose of SGN-CD33A was 73 days (range 55-119). Median time to engraftment following transplant was 17 days for neutrophils (range 1-26) and 35 days for platelets (range 1-50). All evaluable pts achieved a post-transplant best response of CR (n=3) or CRi (n=2); 2 pts died prior to response evaluation (1 pt each of GVHD and seizures suspected to be secondary to GHVD prophylaxis). None of the pts experienced sinusoidal obstructive syndrome (SOS) or any unexpected cardiac, pulmonary, or renal events post-transplant. All surviving pts (n=5) remain in remission as of date of last contact. Follow-up from time of transplant currently ranges from 6-69 weeks. To date, the overall survival range is 21-79 weeks since the first dose of SGN-CD33A. As an update to previous case reports, we present this limited series of subsequently transplanted pts in whom treatment with SGN-CD33A resulted in adequate disease control in the absence of off-target adverse effects. AlloHSCT was tolerated without unexpected toxicities; no events of SOS were observed. Engraftment did not appear to be affected by prior SGN-CD33A treatment. These data support further investigation of SGN-CD33A to eradicate AML blasts prior to alloHSCT; a clinical trial to explore this approach is being planned.
Greasemonkey Hacks: Tips & Tools for Remixing the Web with Firefox (2005)

Greasemonkey Hacks is an invaluable compendium 100 ingenious hacks for power users who want to master Greasemonkey, the hot new Firefox extension that allows you to write scripts that alter the web pages you visit. With Greasemonkey, you can create scripts that make a web site more usable, fix rendering bugs that site owners can't be bothered to fix themselves, or add items to a web site's menu bar. You can alter pages so they work better with technologies that speak a web page out loud or convert it to Braille. Greasemonkey gurus can even import, combine, and alter data from different web sites to meet their own specific needs. Greasemonkey has achieved a cult-like following in its short lifespan, but its uses are just beginning to be explored. Let's say you're shopping on an e-commerce site. You can create a script that will automatically display competitive prices for that particular product from other web sites. The possibilities are limited only by your imagination and your Greasemonkey expertise. Greasemonkey Hacks can't help you with the imagination part, but it can provide the expert hacks-complete with the sample code-you need to turn your brainstorms into reality. More than just an essential collection of made-to-order Greasemonkey solutions, Greasemonkey Hacks is crammed with sample code, a Greasemonkey API reference, and a comprehensive list of resources, to ensure that every resource you need is available between its covers. Some people are content to receive information from websites passively; some people want to control it. If you are one of the latter, Greasemonkey Hacks provides all the clever customizations and cutting-edge tips and tools you need to take command of any web page you view.
N-cadherin switching occurs in high Gleason grade prostate cancer (2005)

We have demonstrated for the first time that N-cadherin switching occurs in higher grade PC and correlates significantly with increasing Gleason patterns. N-cadherin may be as a useful biomarker of aggressive PC.
Key features of heat shock regulatory elements. (1988)

The promoters of heat shock protein genes are among the best-studied inducible eucaryotic promoters. Regions responsible for heat regulation have been identified previously by deletion experiments with several different heat shock genes. In this paper the critical importance of two novel features of heat shock regulatory elements was investigated. First, the elements were modular and, as a consequence, displayed a characteristic 5-nucleotide periodicity produced by multiple GAA blocks that were arranged in alternating orientations and at 2-nucleotide intervals. Functional heat shock regulatory elements appeared to include three or more of these blocks. Second, the nucleotides at the two positions immediately upstream from GAA segments played an important role in defining the competence of regulatory elements.
Systematic analysis of somatic mutations driving cancer: uncovering functional protein regions in disease development (2016)

Recent advances in sequencing technologies enable the large-scale identification of genes that are affected by various genetic alterations in cancer. However, understanding tumor development requires insights into how these changes cause altered protein function and impaired network regulation in general and/or in specific cancer types. In this work we present a novel method called iSiMPRe that identifies regions that are significantly enriched in somatic mutations and short in-frame insertions or deletions (indels). Applying this unbiased method to the complete human proteome, by using data enriched through various cancer genome projects, we identified around 500 protein regions which could be linked to one or more of 27 distinct cancer types. These regions covered the majority of known cancer genes, surprisingly even tumor suppressors. Additionally, iSiMPRe also identified novel genes and regions that have not yet been associated with cancer. While local somatic mutations correspond to only a subset of genetic variations that can lead to cancer, our systematic analyses revealed that they represent an accompanying feature of most cancer driver genes regardless of the primary mechanism by which they are perturbed during tumorigenesis. These results indicate that the accumulation of local somatic mutations can be used to pinpoint genes responsible for cancer formation and can also help to understand the effect of cancer mutations at the level of functional modules in a broad range of cancer driver genes. This article was reviewed by Sándor Pongor, Michael Gromiha and Zoltán Gáspári.
Chymase cleavage of stem cell factor yields a bioactive, soluble product (1997)

Stem cell factor (SCF) is produced by stromal cells as a membrane-bound molecule, which may be proteolytically cleaved at a site close to the membrane to produce a soluble bioactive form. The proteases producing this cleavage are unknown. In this study, we demonstrate that human mast cell chymase, a chymotrypsin-like protease, cleaves SCF at a novel site. Cleavage is at the peptide bond between Phe-158 and Met-159, which are encoded by exon 6 of the SCF gene. This cleavage results in a soluble bioactive product that is 7 amino acids shorter at the C terminus than previously identified soluble SCF. This research shows the identification of a physiologically relevant enzyme that specifically cleaves SCF. Because mast cells express the KIT protein, the receptor for SCF, and respond to SCF by proliferation and degranulation, this observation identifies a possible feedback loop in which chymase released from mast cell secretory granules may solubilize SCF bound to the membrane of surrounding stromal cells. The liberated soluble SCF may in turn stimulate mast cell proliferation and differentiated functions; this loop could contribute to abnormal accumulations of mast cells in the skin and hyperpigmentation at sites of chronic cutaneous inflammation.