gebhart/patrepeval huggingface dataset:
Activation of p56lck through mutation of a regulatory carboxy-terminal tyrosine residue requires intact sites of autophosphorylation and myristylation. (1990)

Mutation of the major site of in vivo tyrosine phosphorylation of p56lck (tyrosine 505) to a phenylalanine constitutively enhances the p56lck-associated tyrosine-specific protein kinase activity. The mutant polypeptide is extensively phosphorylated in vivo at the site of in vitro Lck autophosphorylation (tyrosine 394) and is capable of oncogenic transformation of rodent fibroblasts. These observations have suggested that phosphorylation at Tyr-505 down regulates the tyrosine protein kinase activity of p56lck. Herein we have attempted to examine whether other posttranslational modifications may be involved in regulation of the enzymatic function of p56lck. The results indicated that activation of p56lck by mutation of Tyr-505 was prevented by a tyrosine-to-phenylalanine substitution at position 394. Furthermore, activation of p56lck by mutation of the carboxy-terminal tyrosine residue was rendered less efficient by substituting an alanine residue for the amino-terminal glycine. This second mutation prevented p56lck myristylation and stable membrane association and was associated with decreased in vivo phosphorylation at Tyr-394. Taken together, these findings imply that lack of phosphorylation at Tyr-505 may be insufficient for enhancement of the p56lck-associated tyrosine protein kinase activity. Our data suggest that activation of p56lck may be dependent on phosphorylation at Tyr-394 and that this process may be facilitated by myristylation, membrane association, or both.
A cost-effectiveness study of the management of intractable urinary incontinence by urinary catheterisation or incontinence pads. (1992)

Use of catheters reduces nursing time but may increase weekly equipment costs depending on the cost of laundry. Despite the high dropout rate among patients randomised to catheters a minority of patients (12/35) expressed a clear preference for catheters and we believe that more patients with intractable incontinence should be given a trial of catheterisation to assess acceptability. Bacteriuria was prevalent in pads or catheter patients but no major episodes of invasive infection were noted in either group.
Extraction and Quantification of Carbon Nanotubes in Biological Matrices with Application to Rat Lung Tissue (2013)

Extraction of carbon nanotubes (CNTs) from biological matrices such as rat lung tissue is integral to developing a quantification method for evaluating the environmental and human health exposure and toxicity of CNTs. The ability of various chemical treatment methods, including Solvable (2.5% sodium hydroxide/surfactant mixture), ammonium hydroxide, nitric acid, sulfuric acid, hydrochloric acid, hydrofluoric acid, hydrogen peroxide, and proteinase K, to extract CNTs from rat lung tissue was evaluated. CNTs were quantified using programmed thermal analysis (PTA). Two CNTs were used to represent the lower (500 °C) and upper (800 °C) PTA limit of CNT thermal stability. The recovery efficiency of each of the eight chemical reagents evaluated was found to depend on the ability to (1) minimize oxidation of CNTs, (2) remove interfering background carbon from the rat lung tissue, and (3) separate the solid-phase CNTs from the liquid-phase dissolved tissue via centrifugation. A two-step extraction method using Solvable and proteinase K emerged as the optimal approach, enabling a recovery of 98 ± 15% of a 2.9 ± 0.19 μg CNT loading that was spiked into whole rat lungs. Due to its high yield and applicability to low organ burdens of nanomaterials, this extraction method is particularly well suited for in vivo studies to quantify clearance rates and retained CNTs in lungs and other organs.
The basal layer in human squamous tumors harbors more UVA than UVB fingerprint mutations: A role for UVA in human skin carcinogenesis (2004)

We hypothesized that a substantial portion of the mutagenic alterations produced in the basal layer of human skin by sunlight are induced by wavelengths in the UVA range. Using laser capture microdissection we examined separately basal and suprabasal keratinocytes from human skin squamous cell carcinomas and premalignant solar keratosis for both UVA- and UVB-induced adduct formation and signature mutations. We found that UVA fingerprint mutations were detectable in human skin squamous cell carcinomas and solar keratosis, mostly in the basal germinative layer, which contrasted with a predominantly suprabasal localization of UVB fingerprint mutations in these lesions. The epidermal layer bias was confirmed by immunohistochemical analyses with a superficial localization of cyclobutane thymine dimers contrasting with the localization of 8-hydroxy-2'-deoxyguanine adducts to the basal epithelial layers. If unrepaired, these adducts may lead to fixed genomic mutations. The basal location of UVA-rather than UVB-induced DNA damage suggests that longer-wavelength UVR is an important carcinogen in the stem cell compartment of the skin. Given the traditional emphasis on UVB, these results may have profound implications for future public health initiatives for skin cancer prevention.
Fibre gratings (1993)

Mirrors play a crucial role in any laster or optics system. But, until recently, mirrors made directly in optical fibre – and hence ideal for integration into fibre-based telecommunication, laser and sensor systems – have not been available, limiting progress in a whole range of optical fibre technologies.
Novel breast-tumor-associated MUC1-derived peptides: Characterization in Db−/− × β2 microglobulin (β2m) null mice transgenic for a chimeric HLA-A2.1/Db-β2 microglobulin single chain (2000)

The MUC1 protein was found to be up-regulated in a spectrum of malignant tumors. T-cell responses to the MUC1 extracellular tandem repeat array (TRA) were observed in murine models as well as in breast-carcinoma patients. In the present study, we evaluated the anti-tumor potential of HLA-A2.1-motif-selected peptides from non-TRA domains of the molecule. Peptide immunogenicity was examined in the Db-/- x beta2 microglobulin (beta2m) null mice transgenic for a modified HLA-A2.1/Db-beta2 microglobulin single chain (HHD mice). Our results show the existence of 3 novel HLA-A2.1-restricted MUC1-derived cytotoxic T-lymphocyte (CTL) epitopes. These peptides are processed and presented by the HHD-transfected breast-tumor cell line MDA-MB-157. Moreover, CTL induced by these 3 peptides show higher lysis of target cells pulsed with breast-carcinoma-derived peptides than of targets pulsed with normal breast-tissue-derived peptides. These data suggest an important role for non-TRA MUC1-derived peptides as inducers of a MHC-restricted CTL reaction to a breast-carcinoma cell line and patient-derived tumor extracts.
Vaccination against tumor cells expressing breast cancer epithelial tumor antigen. (1990)

Ninety-one percent of breast tumors aberrantly express an epithelial tumor antigen (ETA) identified by monoclonal antibody H23. Vaccinia virus recombinants expressing tumor antigens have considerable promise in the active immunotherapy of cancer, and we have evaluated the potential of vaccinia recombinants expressing the secreted (S) and cell-associated (transmembrane, T) forms of H23 ETA to elicit immunity to tumor cells expressing ETA. Tumorigenic ras-transformed Fischer rat fibroblast lines FR-S and FR-T, expressing the S or T form of H23 ETA, respectively, were constructed for use in challenge experiments. Expression of H23 ETA in these lines was confirmed by Western blotting and immunofluorescence. When challenged by subcutaneous seeding of tumor cells, 97% (FR-S) and 91% (FR-T) of syngeneic Fischer rats rapidly developed tumors that failed to regress. Vaccination with recombinant vaccinia virus expressing ETA-T prior to challenge prevented tumor development in 82% of animals seeded with FR-T cells but in only 61% of animals seeded with FR-S. The vaccinia recombinant expressing the S form was a less effective immunogen, and vaccination protected only 29-30% of animals from developing tumors upon challenge with either FR-S or -T cells. The increased immunogenicity of the recombinant expressing ETA-T was reflected in elevated levels of ETA-reactive antibody in vaccinated animals, confirming that secreted antigens expressed from vaccinia virus are less effective immunogens than their membrane-associated counterparts.
Results of a phase IIa study of VX-809, an investigational CFTR corrector compound, in subjects with cystic fibrosis homozygous for the F508del-CFTR mutation (2011)

NCT00865904.
Tannin 1‐α‐O‐galloylpunicalagin induces the calcium‐dependent activation of endothelial nitric‐oxide synthase via the phosphatidylinositol 3‐kinase/Akt pathway in endothelial cells (2008)

Many polyphenols have been found to increase endothelial nitric oxide (NO) production. In our present study, we investigated the effects of 1-alpha-O-galloylpunicalagin upon endothelial nitric oxide synthase (eNOS) activity in endothelial cells (ECs). Both 1-alpha-O-galloylpunicalagin and punicalagin induced NO production in a dose-dependent manner in ECs. Despite having similar chemical structures, punicalagin induced lower levels of NO production than 1-alpha-O-galloylpunicalagin. After 1-alpha-O-galloylpunicalagin addition, a rise in the intracellular Ca(2+) concentration preceded NO production. The Ca(2+) ionophore A23187 stimulated eNOS phosphorylation and augmented NO production. Pretreatment with Ca(2+) chelators inhibited 1-alpha-O-galloylpunicalagin-induced eNOS phosphorylation and NO production. Treatment with 1-alpha-O-galloylpunicalagin did not alter the eNOS protein levels but, unlike punicalagin, induced a sustained activation of eNOS Ser(1179) phosphorylation. 1-alpha-O-galloylpunicalagin was also found to activate ERK1/2, JNK and Akt in ECs. Moreover, simultaneous treatment of these cells with specific phosphatidylinositol-3-kinase inhibitors significantly inhibited the observed increases in eNOS activity and phosphorylation levels. In contrast, the inhibition of (ERK)1/2, JNK and p38 had no influence on eNOS Ser(1179) phosphorylation. Our present results thus indicate that the 1-alpha-O-galloylpunicalagin-induced calcium-dependent activation of eNOS is primarily mediated via a phosphatidylinositol 3-kinase/Akt-dependent increase in eNOS activity, and occurs independently of the eNOS protein content.
Intracellular expression of Fc gamma RIII (CD16) and its mobilization by chemoattractants in human eosinophils. (1998)

We characterized the existence, translocation, and reabsorption during cellular activation of a constitutively expressed intracellular CD16 in the human eosinophil. By two-color flow cytometry, we showed that 6.5+/-0.3% of nonpurified eosinophils expressed surface CD16. After digestion with phosphatidylinositol-specific phospholipase C, surface CD16 on both neutrophils and eosinophils decreased substantially, suggesting that eosinophil CD16 is a glycosyl-phosphatidylinositol-linked isoform. However, CD16 was substantially expressed intracellularly in human eosinophils. Epitope-specific binding to CLB-gran11 mAb from non-NA2/NA2 donors demonstrated that intracellular eosinophil CD16 also differed from the transmembrane isoform of CD16 expressed on NK cells or macrophages. Western blot analysis performed with 3G8 or DJ130c mAb showed a broad band at approximately 65 to 80 kDa, which was the same as neutrophil CD16 from the same NA2/NA2 donors. Upon stimulation by chemoattractants C5a, FMLP, or platelet-activating-factor, eosinophilic intracellular CD16 was rapidly translocated to the eosinophil surface, expressed maximally at 30 s, and then gradually disappeared from the cell surface during the next 10 min. Intracellular flow cytometry of stimulated eosinophils and sandwich ELISA of stimulated eosinophil supernatants demonstrated that the disappearance was due to its rapid release into medium and reabsorption by the cells. Our data identify a CD16B that is consistently expressed intracellularly but only rarely on the surface of nonactivated human eosinophils. This CD16 is transiently expressed during stimulation by chemoattractants.
Structural gene identification and mapping by DNA-mRNA hybrid-arrested cell-free translation. (1977)

We present a simple method for directly correlating structural gene sequences in DNA with their corresponding mRNAs. This is based upon the fact that mRNA hybridized with its complementary DNA will not direct the cell-free synthesis of a complete polypeptide. Full translational activity of the mRNA is recovered upon the heat melting of the hybrid. Utilizing the rabbit beta globin clone PbetaG1, we demonstrate the application of hybrid-arrested translation for the identification of structural gene sequences within recombinant DNA molecules. In addition, the method is used to locate and order precisely several adenovirus 2 polypeptides within the viral genome.
An improved analysis and design methodology for RF Class-E power amplifiers with finite DC-feed inductance and switch On-resistance (2012)

Previous analytical efforts to incorporate the impact of finite switch ON-resistance into the design procedure of Class-E power amplifiers (PAs) have imposed one or both of the so-called “Class-E switching conditions”, namely zero voltage switching (ZVS) and zero derivative of voltage at switching (ZDVS). These are essential for high efficiency operation only in the absence of losses. In this work, more general design equations have been derived without imposition of either ZVS or ZDVS. The optimal design is found to exhibit neither ZVS nor ZDVS, thereby validating the analysis. For the first time, an attempt has been made to incorporate the input power into the analysis, which facilitates optimization of power-added efficiency (PAE). The resulting designs exhibit better performance in terms of output power and PAE compared to existing design approaches. The analytical results have been verified through Spectre-RF simulations at 5GHz in 0.18µm and 65nm CMOS. Through this design procedure, we further demonstrate that Class-E PAs at 5GHz based on thick-oxide devices in 0.18µm CMOS, despite their lower speed, outperform those based on 65nm CMOS devices due to their higher voltage-handling capability.
Topography feedback mechanism for the scanning electrochemical microscope based on hydrodynamic forces between tip and sample (1995)

The distance between microelectrode and sample is a crucial parameter in scanning electrochemical microscopy. Here we report on a technique where the hydrodynamic coupling between tip and sample is employed to measure and control this distance. We built an apparatus, where a microelectrode is vibrated laterally and the damping of the amplitude upon approach to the surface is measured optically. We show that amplitudes of up to 5 μm are easily obtained in an aqueous environment and that amplitudes below 1 nm can be detected with phase sensitive amplifiers. We measured the different vibration modes of the electrodes and identified the ones best suited for distance measurements. On hard surfaces we found the characteristic decay length of the coupling to be less than 1 μm and, within our measured range, independent of frequency and amplitude of the vibration. Measurements on an elastic surface of known spring constant revealed that the vibrating electrode exerts a repulsive normal force on the sample which may displace the surface and result in an increased apparent decay length of several μm. Under typical conditions this frequency- and amplitude-dependent force is in the order of several 100 μN. In parallel electrochemistry experiments we found that the reduction current at the microelectrode was only slightly increased by the vibration of the electrode and was a linear function of the amplitude.
Resonance-enhanced two-laser infrared multiple photon dissociation of gaseous ions (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTResonance-enhanced two-laser infrared multiple photon dissociation of gaseous ionsClifford H. Watson, Jeffrey A. Zimmerman, James E. Bruce, and John R. EylerCite this: J. Phys. Chem. 1991, 95, 16, 6081–6086Publication Date (Print):August 1, 1991Publication History Published online1 May 2002Published inissue 1 August 1991https://pubs.acs.org/doi/10.1021/j100169a010https://doi.org/10.1021/j100169a010research-articleACS PublicationsRequest reuse permissionsArticle Views87Altmetric-Citations30LEARN 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 options Get e-Alerts
Cellular Events Linked to Cardiac Remodeling in Heart Failure: Targets for Pharmacologic Intervention (2000)

Over the past decade, there has been a paradigm shift in the understanding of heart failure pathophysiology. Heart failure is no longer conceptualized as a hemodynamic disorder resulting from changes in renal and hormonal function. Rather, the syndrome of heart failure is more complex and is characterized by abnormal myocyte growth, proliferation of cells in the extracellular matrix, and myocyte cell loss (apoptosis)--all of which culminate in significant structural remodeling of the heart and loss of ventricular function. The loss of ventricle function is preceded by an initiating event such as myocardial infarction, which leads to changes in cell function, activation of specific neurohormones and peptides, which in turn are linked to the remodeling of the ventricle, and progression of heart failure. This article discusses how changes in myocyte and nonmyocyte structure may contribute to the progression of heart failure. Insight into these mechanisms will provide a better understanding of newer pharmacologic approaches in the treatment of heart failure.
Iron Chelation in the Treatment of Cancer: A New Role for Deferasirox? (2013)

Iron plays a crucial role in a number of metabolic pathways including oxygen transport, DNA synthesis, and ATP generation. Although insufficient systemic iron can result in physical impairment, excess iron has also been implicated in a number of diseases including ischemic heart disease, diabetes, and cancer. Iron chelators are agents which bind iron and facilitate its excretion. Experimental iron chelators have demonstrated potent anti-neoplastic properties in a number of cancers in vitro. These agents have yet to be translated into clinical practice, however, largely due to the significant side effects encountered in pre-clinical models. A number of licensed chelators, however, are currently in clinical use for the treatment of iron overload associated with certain non-neoplastic diseases. Deferasirox is one such agent and the drug has shown significant anti-tumor effects in a number of in vitro and in vivo studies. Deferasirox is orally administered and has demonstrated a good side effect profile in clinical practice to date. It represents an attractive agent to take forward into clinical trials of iron chelators as anti-cancer agents.
Sintokamide A Is a Novel Antagonist of Androgen Receptor That Uniquely Binds Activation Function-1 in Its Amino-terminal Domain (2016)

Androgen receptor (AR) is a validated drug target for all stages of prostate cancer including metastatic castration-resistant prostate cancer (CRPC). All current hormone therapies for CRPC target the C-terminal ligand-binding domain of AR and ultimately all fail with resumed AR transcriptional activity. Within the AR N-terminal domain (NTD) is activation function-1 (AF-1) that is essential for AR transcriptional activity. Inhibitors of AR AF-1 would potentially block most AR mechanisms of resistance including constitutively active AR splice variants that lack the ligand-binding domain. Here we provide evidence that sintokamide A (SINT1) binds AR AF-1 region to specifically inhibit transactivation of AR NTD. Consistent with SINT1 targeting AR AF-1, it attenuated transcriptional activities of both full-length AR and constitutively active AR splice variants, which correlated with inhibition of growth of enzalutamide-resistant prostate cancer cells expressing AR splice variants. In vivo, SINT1 caused regression of CRPC xenografts and reduced expression of prostate-specific antigen, a gene transcriptionally regulated by AR. Inhibition of AR activity by SINT1 was additive to EPI-002, a known AR AF-1 inhibitor that is in clinical trials (NCT02606123). This implies that SINT1 binds to a site on AF-1 that is unique from EPI. Consistent with this suggestion, these two compounds showed differences in blocking AR interaction with STAT3. This work provides evidence that the intrinsically disordered NTD of AR is druggable and that SINT1 analogs may provide a novel scaffold for drug development for the treatment of prostate cancer or other diseases of the AR axis.
Treatment of murine pulmonary mucormycosis with SCH 42427, a broad-spectrum triazole antifungal drug (1994)

Journal Article Treatment of murine pulmonary mucormycosis with SCH 42427, a broad-spectrum triazole antifungal drug Get access LUCIANO Z. GOLDANI, LUCIANO Z. GOLDANI Evans Memorial Department of Clinical Research and the Department of Medicine, Boston University Medical Center HospitalBoston, Massachusetts Search for other works by this author on: Oxford Academic PubMed Google Scholar ALAN M. SUGAR ALAN M. SUGAR Evans Memorial Department of Clinical Research and the Department of Medicine, Boston University Medical Center HospitalBoston, Massachusetts Dr Alan M. Sugar, The University Hospital, E-336, 88 East Newton Street, Boston, assachusetts 02118, USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Antimicrobial Chemotherapy, Volume 33, Issue 2, February 1994, Pages 369–372, https://doi.org/10.1093/jac/33.2.369 Published: 01 February 1994
A simple test for acetylator phenotype using caffeine. (1984)

A method is presented for the use of caffeine, in the forms commonly ingested by a large proportion of the world's population, to test for the clinically important acetylation polymorphism. Each of 146 subjects provided a spot sample of urine between 2 and 6 h after coffee, tea or cola soft drink consumption, and the molar ratio of 5-acetylamino-6- formylamino -3-methyluracil ( AFMU ) to 1-methylxanthine (1X) was determined by a simple h.p.l.c. assay. The ratio afforded segregation of three apparent modes of acetylation capacity in this population, in concordance with a standard sulphamethazine phenotyping procedure and with other methods using controlled caffeine intake and urine collections. The day-to-day consistency of the method was established in eight selected subjects.