gebhart/patrepeval huggingface dataset:
Mechanisms of HIV Receptor and Co-Receptor Down-Regulation by Prostratin: Role of Conventional and Novel PKC Isoforms (2004)

Prostratin is an unusual non-tumour promoting phorbol ester with potential as an inductive adjuvant therapy for highly active antiretroviral therapy (HAART) due to its ability to up-regulate viral expression from latent provirus. In addition, prostratin is also able to inhibit de novo HIV infection most probably because it induces down-regulation of HIV receptors from the surface of target cells. In this study, we investigate the mechanisms by which prostratin down-regulates HIV receptor and co-receptor surface expression in lymphocytic and monocytic cell lines. Our results indicate that prostratin induces down-regulation of surface expression of CD4 and CXCR4, but not CCR5, in various cell lines. Down-regulation of CD4 and CXCR4 by prostratin is achieved by internalization through receptor-mediated endocytosis and/or macropinocytosis, which is then followed by degradation of these molecules. Because prostratin is a protein kinase C (PKC) activator, we next examined the potential contribution of distinct PKC isoforms to down-regulate CD4 and CXCR4 in response to prostratin stimulation. Although exposure of cells to prostratin or phorbol-myristate-acetate (PMA) induces the translocation of several PKC isoforms to the plasma membrane, the use of specific PKC inhibitors revealed that novel PKCs are the main mediators of the prostratin-induced CD4 down-regulation, whereas both conventional and novel PKCs contribute to CXCR4 down-regulation. Altogether these results showed that prostratin, through the activation of conventional and/or novel PKC isoforms, rapidly reduces cell surface expression of CD4 and CXCR4, but not CCR5, by inducing their internalization and degradation.
Effect of NMDA Lesion of the Medial Preoptic Neurons on Sleep and Other Functions (1998)

This study was undertaken to determine the effects of the destruction of the medial preoptic area (mPOA) neurons by N-methyl D-aspartic acid (NMDA), on sleep-wakefulness (S-W), locomotor activity, body weight, rectal temperature, and food and water intake in rats. The NMDA lesion of the mPOA produced long-lasting insomnia with marked reduction in the deeper stages of sleep, including paradoxical sleep. The reduction in the duration of sleep episodes in the lesioned rats indicated their inability to maintain sleep. The insomnia resulting from a decreased sleep pressure did not alter the sleep-initiating ability. Though the day-night distribution of sleep remained largely unaffected, there was an increase in locomotor activity during the light period. There was no increase in food intake to compensate for the high energy expenditure resulting not only from hyperactivity but also from hyperthermia in the mPOA-lesioned rats. Thus, body weights of the rats were reduced even without any change in food and water intake. However, the changes in body temperature and locomotor activity after the mPOA neuronal loss may not have exerted a major influence on S-W, as the alterations in all these parameters had different time courses.
A Phase I Trial of Perifosine (NSC 639966) on a Loading Dose/Maintenance Dose Schedule in Patients with Advanced Cancer (2004)

Perifosine (NSC 639966) is a synthetic, substituted heterocyclic alkylphosphocholine that acts primarily at the cell membrane targeting signal transduction pathways. Early clinical trials were limited because of dose-limiting gastrointestinal toxicity, and parenteral dosing of this class of agents is not possible because of their hemolytic properties; therefore, related compounds with an improved therapeutic index were developed. Toxicity was minimized and efficacy improved by using a loading dose/maintenance dose schedule, and therefore, this schedule was carried into clinical trials. This phase I trial enrolled 42 patients with incurable solid malignancies. The starting doses were 100 mg p.o. x four doses (every 6 hours) load followed by a 50 mg p.o. once daily maintenance dose with escalation of either component in successive dose levels. No treatment related deaths occurred. The maximum-tolerated dose was determined to be 150 mg p.o. x four doses load and 100 mg p.o. once daily maintenance. Dose-limiting toxicities such as nausea, diarrhea, dehydration, and fatigue were seen early during the loading phase and were surmountable with the use of prophylactic 5-HT3 receptor antagonists, dexamethasone, and loperamide. Toxicities during the chronic phase were difficult to manage and, given that pharmacokinetic data showed biologically active serum concentrations (based on preclinical data), raised the question of less frequent maintenance dosing. Pharmacokinetic data confirmed the maintenance of stable drug levels with chronic dosing and the long half-life. One partial response was seen, as were multiple patients with stable disease beyond course 2. These results suggest perifosine activity in sarcoma and perhaps renal cell carcinoma (stable disease in two patients who continued for 6 and 14 courses), thus justifying additional investigation of this agent in a phase II sarcoma trial.
Role of superoxide in deoxyribonucleic acid strand scission (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRole of superoxide in deoxyribonucleic acid strand scissionStephen A. Lesko, Ronald J. Lorentzen, and Paul O. P. Ts'oCite this: Biochemistry 1980, 19, 13, 3023–3028Publication Date (Print):June 24, 1980Publication History Published online1 May 2002Published inissue 24 June 1980https://pubs.acs.org/doi/10.1021/bi00554a029https://doi.org/10.1021/bi00554a029research-articleACS PublicationsRequest reuse permissionsArticle Views220Altmetric-Citations218LEARN 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
Horizontal cosmic ray muon radiography for imaging nuclear threats (2014)

Muon tomography is a technique that uses information contained in the Coulomb scattering of cosmic ray muons to generate three dimension images of volumes between tracking detectors. Advantages of this technique are the muons ability to penetrate significant overburden and the absence of any additional dose beyond the natural cosmic ray flux. Disadvantages include the long exposure times and limited resolution because of the low flux. Here we compare the times needed to image objects using both vertically and horizontally mounted tracking detectors and we develop a predictive model for other geometries.
Several extracellular domains of the neural cell adhesion molecule L1 are involved in neurite outgrowth and cell body adhesion (1993)

The neural cell adhesion molecule L1 is a multidomain protein that plays important roles in cell adhesion, migration, and neurite outgrowth. To analyze structure-function relationships of L1 in neurite outgrowth and cell body adhesion, we have expressed and purified a set of different fragments of the extracellular part of this glycoprotein in CHO cells and in Escherichia coli. When neurite outgrowth from small cerebellar neurons was measured on substrate-coated L1 or L1 fragments, neurite outgrowth was promoted by the immunoglobulin-like domains I-II, III-IV, and V-VI, and by the fibronectin type III homologous repeats 1-2, while the fibronectin type III homologous repeats 3-5 were ineffective. In contrast, cell bodies of small cerebellar neurons adhered mostly to the immunoglobulin-like domains I-II and V-VI, and to the fibronectin type III homologous repeats 3-5, but less to the immunoglobulin-like domains III-IV and fibronectin type III homologous repeats 1-2. In both assays, the neuronal cell surface receptor for all active protein fragments was identified as L1. No significant differences in functional activities were found between fragments with and without carbohydrate structures. These findings indicate that L1 uses several domains for homophilic interactions overlapping for the two functions analyzed here, but also showing some regional specialization. Furthermore, we show that a homophilic molecule uses several domains in one function, with neurite outgrowth requiring more domains than adhesion for maximal activity.
Phosphoproteomic analysis of Her2/neu signaling and inhibition (2006)

Her2/neu (Her2) is a tyrosine kinase belonging to the EGF receptor (EGFR)/ErbB family and is overexpressed in 20-30% of human breast cancers. We sought to characterize Her2 signal transduction pathways further by using MS-based quantitative proteomics. Stably transfected cell lines overexpressing Her2 or empty vector were generated, and the effect of an EGFR and Her2 selective tyrosine kinase inhibitor, PD168393, on these cells was characterized. Quantitative measurements were obtained on 462 proteins by using the SILAC (stable isotope labeling with amino acids in cell culture) method to monitor three conditions simultaneously. Of these proteins, 198 showed a significant increase in tyrosine phosphorylation in Her2-overexpressing cells, and 81 showed a significant decrease in phosphorylation. Treatment of Her2-overexpressing cells with PD168393 showed rapid reversibility of the majority of the Her2-triggered phosphorylation events. Phosphoproteins that were identified included many known Her2 signaling molecules as well as known EGFR signaling proteins that had not been previously linked to Her2, such as Stat1, Dok1, and delta-catenin. Importantly, several previously uncharacterized Her2 signaling proteins were identified, including Axl tyrosine kinase, the adaptor protein Fyb, and the calcium-binding protein Pdcd-6/Alg-2. We also identified a phosphorylation site in Her2, Y877, which is located in the activation loop of the kinase domain, is distinct from the known C-terminal tail autophosphorylation sites, and may have important implications for regulation of Her2 signaling. Network modeling, which combined phosphoproteomic results with literature-curated protein-protein interaction data, was used to suggest roles for some of the previously unidentified Her2 signaling proteins.
High-throughput, high-performance ofdm via pseudo-orthogonal carrier interferometry spreading codes (2003)

The paper introduces to orthogonal frequency-division multiplexing (OFDM) systems a novel pseudo-orthogonal carrier interferometry spreading code which spreads each parallel data stream over all the OFDM carriers. Pseudo-orthogonal carrier interferometry (PO-CI) spreading codes are carefully selected to introduce the following benefits to OFDM: up to 2N parallel data streams can be coded onto N carriers, with little degradation in performance; when rate 1/2 channel coding is applied in addition to PO-CI spreading codes, the resulting binary phase-shift keying OFDM systems demonstrate the performance of coded OFDM and the throughput of uncoded OFDM; PO-CI codes are carefully selected to spread in a manner which eliminates the peak-to-average power ratio problems characteristic of traditional OFDM.
Human Werner Syndrome DNA Helicase Unwinds Tetrahelical Structures of the Fragile X Syndrome Repeat Sequence d(CGG) (1999)

Formation of hairpin and tetrahelical structures by a d(CGG) trinucleotide repeat sequence is thought to cause expansion of this sequence and to engender fragile X syndrome. Here we show that human Werner syndrome DNA helicase (WRN), a member of the RecQ family of helicases, efficiently unwinds G'2 bimolecular tetraplex structures of d(CGG)7. Unwinding of d(CGG)7 by WRN requires hydrolyzable ATP and Mg2+ and is proportional to the amount of added helicase and to the time of incubation. The efficiencies of unwinding of G'2 d(CGG)7 tetraplex with 7 nucleotide-long single-stranded tails at their 3' or 5' ends are, respectively, 3.5- and 2-fold greater than that of double-stranded DNA. By contrast, WRN is unable to unwind a blunt-ended d(CGG)7 tetraplex, bimolecular tetraplex structures of a telomeric sequence 5'-d(TAGACATG(TTAGGG)2TTA)-3', or tetramolecular quadruplex forms of an IgG switch region sequence 5'-d(TACAGGGGAGCTGGGGTAGA)-3'. The ability of WRN to selectively unwind specific tetrahelices may reflect a specific role of this helicase in DNA metabolism.
LONG CHAIN FATTY ACIDS IN HEALTH AND NUTRITION (1996)

ABSTRACT The typical western diet which is low in long chain omega‐3 fatty acids and high in long chain omega‐6 fatty acids may not supply the appropriate balance for optimal metabolism. The imbalance is believed to cause a variety of disease symptoms ranging from cardiovascular disease, hypertension, inflammatory and auto‐immune disorders, depression and disrupted neurological functions. In the area of cardiovascular disease new research on arrhythmias is exciting and shows that application of omega‐3 fatty acids can produce rapid results. In addition omega‐3 fatty acids are showing benefits in preventing restenosis following angioplasty in approximately half of the reported studies. Significant research in infant nutrition indicates that long chain polyunsaturated fatty acids are “conditionally essential” for growth and development. Adequate intake of docosahexaenoic acid (DHA) and arachidonic acid (AA) is critical during pregnancy, lactation and infancy for proper development of the fetus and infant. Premature babies are particularly at risk for inadequacies. Thus, many specialist groups are recommending that infant formulas include long chain fatty acids at levels matching breast milk. Recommendations by many academic and governmental bodies propose that daily intakes on long chain omega‐3 fatty acids be increased as a step in reducing certain chronic diseases.
Varying strategies and devices for endovascular repair of abdominal aortic aneurysms. (1997)

The endovascular repair of abdominal aortic aneurysms has been investigated in a clinical setting since 1991. Although initially the procedure was performed using surgeon-made devices, it did not take long for the medical industry to realize the potential of this procedure. There are six commercially made devices, which are unique, each with their own strengths and weaknesses. This article describes the principal endovascular graft types that are currently under investigation as well as the strategies for their use. In addition, the inclusion criteria for endovascular repair of abdominal aortic aneurysms are discussed.
Direct formation of alcohols by hydrocarbonylation of alkenes under mild conditions using rhodium trialkylphosphine catalysts (1996)

The complex[RhH(PEt3)3] catalysed the hydroformylation of hex-1-ene to heptanal and 2-methylhexanal in toluene, but heptanol and 2-methylhexanol were significant products in tetrahydrofuran especially over long reaction times(16h). In protic solvents only alcohols were produced even after short reaction times. The reactions are very rapid and also occur readily with alkenes such as hex-2-ene, propene, ethene, styrene and 3,3-dimethylbutene. The highest rates observed are for ethene (54 000 turnovers h–1) and the products in all cases are alcohols. Other phosphines containing primary alkyl groups also produced alcohols, but in contrast reactions in ethanol using rhodium complexes containing PPh3, PPh2Et, PPhEt2 or PPri3 produced significant amounts of aldehydes and/or acetals whilst Me2PCH2CH2PMe2 inhibited the reaction. The NMR studies showed that species present in equilibrium in ethanol solution are [RhH(CO)(PEt3)3], [RhH(CO)2(PEt3)2], [Rh2(CO)4(PEt3)4], [Rh2(CO)2(PEt3)6] and PEt3 but that [RhH(CO)(PEt3)3] predominates under the catalytic conditions. Reactions carried out under D2–CO in EtOH produced, 90% BuCHDCH2CD2OH/D and 10% BuCHDCH2CHDOH/D but hydrogenation of heptanal under the same conditions gave a mixture of C6H13CHDOH/D (39%) and C6H13CH2OH/D (61%). These results are interpreted to indicate that the alcohols produced from hex-1-ene are primary reaction products and not produced via intermediate aldehydes. A new mechanism for this direct hydrocarbonylation is proposed in which the key acyl intermediate becomes protonated by the alcoholic solvent because of the high electron density it bears as a result of the presence of the electron-donating trialkylphosphines. Oxidative addition of H2 followed by two H-atom transfers leads directly to the alcohol. High pressure NMR studies showed that [Rh{C(O ⋯ HOEt)Et}(CO)2(PEt3)2] is present during catalytic hydrocarbonylation of ethene in ethanol. Two different cycles are proposed to explain the products obtained from the catalytic reaction of heptanal with D2–CO. Again, protonation, this time of the metal, appears to be important.
Finite element modeling of electromagnetic signal propagation in a phantom arm (2001)

Improving the control of artificial arms remains a considerable challenge. It may be possible to graft remaining peripheral nerves in an amputated limb to spare muscles in or near the residual limb and use these nerve-muscle grafts as additional myoelectric control signals. This would allow simultaneous control of multiple, degrees of freedom (DOF) and could greatly improve the control of artificial limbs. For this technique to be successful, the electromyography (EMG) signals from the nerve-muscle grafts would need to be independent of each other with minimal crosstalk. To study EMG signal propagation and quantify crosstalk, finite element (FE) models were developed in a phantom-arm model. The models were validated with experimental data collected by applying sinusoidal excitations to a phantom-arm model and recording the surface electric potential distribution. There was a very high correlation (r > 0.99) between the FEM data and the experimental data, with the error in signal magnitude generally less than 5%. Simulations were then performed using muscle dielectric properties with static, complex, and full electromagnetic solvers. The results indicate that significant displacement currents can develop (> 50% of total current) and that the fall-off of surface signal power varies with how the signal source is modeled. Index Terms-Control, electromyography (EMG), finite element (FE), modeling, prosthesis.
Fc-mediated immune precipitation. III. Visualization by electron microscopy. (1983)

Fc-mediated interactions between immune complexes are of major importance for the precipitin reaction. In the present study these interactions were investigated by means of electron microscopy. Keyhole limpet haemocyanin (KLH) was adsorbed to a thin glow charged carbon supporting film and reacted with either rabbit anti-KLH IgG or anti-KLH F(ab')2 fragments. The Fc-Fc interactions were investigated by reacting these surface-adsorbed antibody-rich KLH immune complexes with soluble, antigen-rich ferritin-anti-ferritin complexes using either rabbit anti-ferritin IgG or the corresponding isomolar F(ab')2 fragments as antibody. Fc-Fc interactions were indicated by the formation of clusters or ring structures of ferritin molecules, which were only seen when using KLH anti-KLH IgG and ferritin-anti-ferritin IgG complexes. When F(ab')2 fragments were used as antibody, no reaction between KLH anti-KLH complexes and ferritin-anti-ferritin complexes could be demonstrated.
Characterization of paired tumor and non-tumor cell lines established from patients with breast cancer (1998)

The goal of our study was to develop a panel of tumor cell lines along with paired non-malignant cell lines or strains collected from breast cancers, predominantly primary tumors. From a total of 189 breast tumor samples consisting of 177 primary tumors and 12 metastatic tissues, we established 21 human breast tumor cell lines that included 18 cell lines derived from primary tumors and 3 derived from metastatic lesions. Cell lines included those from patients with germline BRCA1 and FHIT gene mutations and others with possible genetic predisposition. For 19 tumor cell lines, we also established one or more corresponding non-malignant cell strains or B lymphoblastoid (BL) lines, which included 16 BL lines and 7 breast epithelial (2) or stromal (5) cell strains. The present report describes clinical, pathological and molecular information regarding the normal and tumor tissue sources along with relevant personal information and familial medical history. Analysis of the breast tumor cell lines indicated that most of the cell lines had the following features: they were derived from large tumors with or without axillary node metastases; were aneuploid and exhibited a moderate to poorly differentiated phenotype; were estrogen receptor (ER)- and progesterone receptor (PR)-negative; and overexpressed p53 and HER2/neu proteins. Of 13 patients with primary breast cancers receiving curative intent mastectomies, 7 were dead after a mean period of 10 months. Our panel of paired tumor and non-malignant cell lines should provide important new reagents for breast cancer research.