gebhart/patrepeval huggingface dataset:
Docetaxel (Taxotere) in hormone-refractory prostate cancer. (2000)

Considerations of both molecular biology and data from in vitro studies suggest a potential for the combination of docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) with estramustine in the treatment of patients with hormone-refractory prostate cancer. Based on data from two phase I studies, the docetaxel dose recommended for phase II study in combination with estramustine in minimally and extensively pretreated patients is 70 mg/m2 and 60 mg/m2, respectively. The dose-limiting toxicity was neutropenia. In one phase I study, 63% of the 34 patients treated showed at least a 50% decline in prostate-specific antigen. An objective response was seen in 28% of patients with measurable disease, and overall median survival (22.8 months) is highly encouraging. In the second study, 82% of 17 patients showed a greater than 50% decline in prostate-specific antigen and, at the 70 mg/m2 dose level, two of six patients showed prostate-specific antigen normalization. Phase II studies have demonstrated more than 50% declines in 59% to 88% of patients treated at 70 mg/m2. Although reduction of the dose of estramustine appears to result in a somewhat lower response rate, the contribution made by estramustine to the efficacy of the estramustine/docetaxel combination must be established by randomized trials. Dexamethasone, however, does not appear to significantly contribute to the response rate of estramustine and docetaxel. Phase III studies comparing docetaxel plus estramustine with mitoxantrone plus corticosteroids are currently being planned. If the promise of docetaxel hormone-refractory prostate cancer is realized, it may be appropriate to design clinical trials that evaluate docetaxel-based regimens as adjuvant therapy in patients who are at a high risk for relapse after definitive local therapy.
Safety Pharmacology and Genotoxicity Evaluation of AVI-4658 (2010)

Duchenne muscular dystrophy (DMD) is caused by dystrophin gene mutations. Restoration of dystrophin by exon skipping was demonstrated with the phosphorodiamidate morpholino oligomers (PMO) class of splice-switching oligomers, in both mouse and dog disease models. The authors report the results of Good Laboratory Practice-compliant safety pharmacology and genotoxicity evaluations of AVI-4658, a PMO under clinical evaluation for DMD. In cynomolgus monkeys, no test article-related effects were seen on cardiovascular, respiratory, global neurological, renal, or liver parameters at the maximum feasible dose (320 mg/kg). Genotoxicity battery showed that AVI-4658 has no genotoxic potential at up to 5000 microg/mL in an in vitro mammalian chromosome aberration test and a bacterial reverse mutation assay. In the mouse bone marrow erythrocyte micronucleus test, a single intravenous injection up to 2000 mg/kg was generally well tolerated and resulted in no mutagenic potential. These results allowed initiation of systemic clinical trials in DMD patients in the United Kingdom.
Limiting effects of four-wave-mixing in high-power pulsed-fiber amplifiers (2007)

We present an experimental and theoretical analysis of four-wave-mixing (FWM) in nanosecond pulsed fiber amplifiers FWM leads to a saturation of the in-band amplified pulse energy and to distortions of the spectral and temporal profiles, and it is the main limiting effect in the ~1 ns temporal regime. A simple model considering both Raman and FWM contributions provides a good description of the measured behaviours, allowing optimization and design tradeoffs to be explored for mitigating FWM.
Prohead RNA of bacteriophageπ29: size, stoichiometry and biological activity (1989)

We previously demonstrated (Guo et al., 1987. Nucl. Acids Res. 15, 7081-7090) that purified proheads of bacteriophage phi 29 contain an RNA of 120 bases which is essential for DNA packaging. Here we report that this RNA exists primarily as a polymer of ca. 174 residues in phage-infected cells and that ca. 54 bases are cleaved from its 3'-terminus by adventitious nucleases during the purification of proheads. The long and short forms of the RNA had similar activity in in vitro DNA packaging and phage assembly. We report the sequence of the long form of the RNA and show that similar long and short forms can be isolated from the proheads of the phi 29 relatives phi 21, phi 15 and SF5. The concentration dependence in the reconstitution of RNA-free proheads suggests that one copy of the RNA is sufficient to restore DNA packaging activity to RNA-free proheads. However, quantitative measurements indicate that 5 to 6 copies of the RNA are present on proheads isolated from phage-infected cells.
Phasic activation of lateral geniculate and perigeniculate thalamic neurons during sleep with ponto-geniculo-occipital waves (1989)

Ponto-geniculo-occipital (PGO) waves are spiky field potentials generated in cholinergic nuclei of the dorsolateral mesopontine tegmentum just prior to and during rapid-eye-movement (REM) sleep and transferred toward thalamic nuclei. These events are commonly regarded as physiological correlates of oneiric behavior. We have examined the PGO-related discharges of physiologically identified neurons located in the dorsal lateral geniculate (LG) nucleus and perigeniculate (PG) sector of the reticular thalamic complex in chronically implanted, naturally sleeping cats. PGO focal waves and associated unit discharges were simultaneously recorded by the same microelectrode. PGO waves herald the other signs of REM sleep (EEG desynchronization and muscular atonia), appearing 30-90 sec before REM sleep over the EEG-synchronized activity of slow-wave sleep (pre-REM epoch). (1) Most PG neurons discharged bursts of action potentials in relation to PGO waves during both pre-REM and REM sleep. (2) The PGO-related activity of LG neurons was quite different. During the pre-REM stage, PGO waves correlated with a short (7-15 msec), high-frequency (300-500 Hz) spike burst of LG neurons, followed by a long (0.2-0.4 sec) train of single spikes, whereas during REM sleep, the PGO-related activity lacked the initial burst and consisted of a spike train that only slightly exceeded the tonically increased background firing of LG cells. The stereotyped characteristics of the PGO-related spike bursts during the pre-REM epoch suggest that they are the extracellular reflection of a low-threshold spike deinactivated by the tonic membrane hyperpolarization of LG cells associated with the EEG-synchronized sleep state. Such bursts are inactivated during the tonic depolarization of LG cells that occurs in REM sleep. The synchronous spike bursts discharged by LG cells in relation with the PGO waves of the pre-REM epoch probably underlie the much larger amplitude of the PGO waves of the pre-REM epoch as compared with those of the REM-sleep state. Since LG neurons have relatively low spontaneous firing rates during the EEG-synchronized pre-REM epoch, the PGO-related activity of this transitional stage leads to a higher signal-to-noise ratio in the visual thalamocortical channel than during REM sleep. We suggest that the PGO-related activity during the pre-REM epoch is related to vivid imagery during this stage of sleep.
Potential Hazards of Long-Term Acid Suppression (1990)

Neuroendocrine cell (carcinoid) tumours have been reported in the acid-secreting part of the stomach of rodents after long-term administration of a range of potent chemically diverse antisecretory agents. Although evidence shows a link between the sequence of acid suppression, hypergastrinaemia, and neuroendocrine cell hyperplasia, other factors are also thought to be involved in neoplastic transformation. Prolonged hypochlorhydria or achlorhydria resulting in bacterial colonization of the stomach may allow the generation of carcinogenic substances. Other as yet unidentified trophic factors may be involved in tumour formation. In view of the potential risks associated with these agents, there must be concern about the possible consequences in man of marked suppression of acid. It seems wise to limit the use of these more potent agents to situations in which conventional therapy has failed and to short-term treatment.
Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients (2020)

BackgroundThe dynamic changes of lymphocyte subsets and cytokines profiles of patients with novel coronavirus disease (COVID-19) and their correlation with the disease severity remain unclear.MethodsPeripheral blood samples were longitudinally collected from 40 confirmed COVID-19 patients and examined for lymphocyte subsets by flow cytometry and cytokine profiles by specific immunoassays.FindingsOf the 40 COVID-19 patients enrolled, 13 severe cases showed significant and sustained decreases in lymphocyte counts [0·6 (0·6-0·8)] but increases in neutrophil counts [4·7 (3·6-5·8)] than 27 mild cases [1.1 (0·8-1·4); 2·0 (1·5-2·9)]. Further analysis demonstrated significant decreases in the counts of T cells, especially CD8+ T cells, as well as increases in IL-6, IL-10, IL-2 and IFN-γ levels in the peripheral blood in the severe cases compared to those in the mild cases. T cell counts and cytokine levels in severe COVID-19 patients who survived the disease gradually recovered at later time points to levels that were comparable to those of the mild cases. Moreover, the neutrophil-to-lymphocyte ratio (NLR) (AUC=0·93) and neutrophil-to-CD8+ T cell ratio (N8R) (AUC =0·94) were identified as powerful prognostic factors affecting the prognosis for severe COVID-19.InterpretationThe degree of lymphopenia and a proinflammatory cytokine storm is higher in severe COVID-19 patients than in mild cases, and is associated with the disease severity. N8R and NLR may serve as a useful prognostic factor for early identification of severe COVID-19 cases.FundingThe National Natural Science Foundation of China, the National Science and Technology Major Project, the Health Commission of Hubei Province, Huazhong University of Science and Technology, and the Medical Faculty of the University of Duisburg-Essen and Stiftung Universitaetsmedizin, Hospital Essen, Germany.
High Incidence of Non-Random Template Strand Segregation and Asymmetric Fate Determination In Dividing Stem Cells and their Progeny (2007)

Decades ago, the "immortal strand hypothesis" was proposed as a means by which stem cells might limit acquiring mutations that could give rise to cancer, while continuing to proliferate for the life of an organism. Originally based on observations in embryonic cells, and later studied in terms of stem cell self-renewal, this hypothesis has remained largely unaccepted because of few additional reports, the rarity of the cells displaying template strand segregation, and alternative interpretations of experiments involving single labels or different types of labels to follow template strands. Using sequential pulses of halogenated thymidine analogs (bromodeoxyuridine [BrdU], chlorodeoxyuridine [CldU], and iododeoxyuridine [IdU]), and analyzing stem cell progeny during induced regeneration in vivo, we observed extraordinarily high frequencies of segregation of older and younger template strands during a period of proliferative expansion of muscle stem cells. Furthermore, template strand co-segregation was strongly associated with asymmetric cell divisions yielding daughters with divergent fates. Daughter cells inheriting the older templates retained the more immature phenotype, whereas daughters inheriting the newer templates acquired a more differentiated phenotype. These data provide compelling evidence of template strand co-segregation based on template age and associated with cell fate determination, suggest that template strand age is monitored during stem cell lineage progression, and raise important caveats for the interpretation of label-retaining cells.
A Myristoylated Calcium-binding Protein that Preferentially Interacts with the Alzheimer's Disease Presenilin 2 Protein (1999)

It is well established that mutations in the presenilin 1 and 2 genes cause the majority of early onset Alzheimer's disease (AD). However, our understanding of the cellular functions of the proteins they encode remains rudimentary. Knowledge of proteins with which the presenilins interact should lead to a better understanding of presenilin function in normal and disease states. We report here the identification of a calcium-binding protein, calmyrin, that interacts preferentially with presenilin 2 (PS2). Calmyrin is myristoylated, membrane-associated, and colocalizes with PS2 when the two proteins are overexpressed in HeLa cells. Yeast two-hybrid liquid assays, affinity chromatography, and coimmunoprecipitation experiments confirm binding between PS2 and calmyrin. Functionally, calmyrin and PS2 increase cell death when cotransfected into HeLa cells. These results allude to several provocative possibilities for a dynamic role of calmyrin in signaling, cell death, and AD.
Notes- Simple Preparation of a Very Active Raney Nickel Catalyst. (1961)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNotes- Simple Preparation of a Very Active Raney Nickel Catalyst.Xorge Dominguez, Irma Lopez, and Raul FrancoCite this: J. Org. Chem. 1961, 26, 5, 1625Publication Date (Print):May 1, 1961Publication History Published online1 May 2002Published inissue 1 May 1961https://pubs.acs.org/doi/10.1021/jo01064a078https://doi.org/10.1021/jo01064a078research-articleACS PublicationsRequest reuse permissionsArticle Views788Altmetric-Citations93LEARN 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
Cerebrospinal Fluid Biopterin Is Decreased in Alzheimer's Disease (1986)

Tetrahydrobiopterin is the cofactor in the hydroxylation of phenylalanine, tyrosine, and tryptophan leading to the eventual synthesis of the monoaminergic neurotransmitters, dopamine, norepinephrine, and serotonin, respectively. Total biopterin (90% of which is in the tetrahydro form) was measured in cerebrospinal fluid (CSF) and plasma of 30 patients with Alzheimer's disease and of 19 healthy controls. Plasma and CSF biopterin concentrations were not significantly correlated, but the mean CSF biopterin concentration in patients with Alzheimer's disease was significantly less than in age-matched controls, 13.5 pmol/mL as compared with 18.9 pmol/mL. The CSF biopterin concentration was not correlated with ventricular volume, as estimated by quantitative computed tomography, nor with the severity of dementia, as measured by various cognitive tests. The results suggest that a central biopterin deficiency exists in Alzheimer's disease.
Influence of calcium ions on the structure and stability of recombinant human deoxyribonuclease I in the aqueous and lyophilized states (1999)

The effect of calcium ions on the structure and stability of recombinant human DNase I (rhDNase) in the aqueous and solid (lyophilized) states was investigated. Fourier transform infrared (FTIR) spectroscopy was used to examine the overall secondary structure, while chemical stability was monitored in terms of deamidation and soluble aggregate formation at 40 degrees C. The exogenous calcium was removed by EGTA. This process can remove all but approximately one calcium ion per protein molecule. Analysis of the FTIR spectra in the amide III region in either the aqueous or lyophilized state demonstrated that removal of exogenous Ca2+ by EGTA-treatment had little effect on the secondary structure (and lyophilization-induced rearrangement thereof). For the aqueous solution, circular dichroism was used as an independent technique and confirmed that there was no large overall change in the secondary or tertiary structure upon the removal of calcium. The primary degradation route for the aqueous protein was deamidation. For the EGTA-treated protein, there was also severe covalent aggregation, e.g., formation of intermolecular disulfides facilitated by the cleavage of Cys173-Cys209. The aggregates exhibited a markedly different secondary structure compared to the native protein. For instance, the beta-sheet band observed at ca. 1620 cm-1 wavenumber in the amide I second derivative spectra was increased. Enzymatic activity was completely lost upon aggregation, consistent with the cleavage of the aforementioned native disulfide. For the protein lyophilized in the presence of Ca2+, there was no increase in deamidated species during solid-state storage; however, some aggregation was observed. For the lyophilized EGTA-treated protein, aggregation was even more pronounced, and there was some loss in enzymatic activity upon reconstitution. Thus, the removal of calcium ions by EGTA-treatment decreased the stability of rhDNase in both the aqueous and solid states even though no large overall calcium-induced structural changes could be observed by the techniques used in this study.
Profibrotic TGFβ responses require the cooperative action of PDGF and ErbB receptor tyrosine kinases (2013)

Transforming growth factor β (TGFβ) has significant profibrotic activity both in vitro and in vivo. This reflects its capacity to stimulate fibrogenic mediators and induce the expression of other profibrotic cytokines such as platelet-derived growth factor (PDGF) and epidermal growth factor (EGF/ErbB) ligands. Here we address both the mechanisms by which TGFβ induced ErbB ligands and the physiological significance of inhibiting multiple TGFβ-regulated processes. The data document that ErbB ligand induction requires PDGF receptor (PDGFR) mediation and engages a positive autocrine/paracrine feedback loop via ErbB receptors. Whereas PDGFRs are essential for TGFβ-stimulated ErbB ligand up-regulation, TGFβ-specific signals are also required for ErbB receptor activation. Subsequent profibrotic responses are shown to involve the cooperative action of PDGF and ErbB signaling. Moreover, using a murine treatment model of bleomycin-induced pulmonary fibrosis we found that inhibition of TGFβ/PDGF and ErbB pathways with imatinib plus lapatinib, respectively, not only prevented myofibroblast gene expression to a greater extent than either drug alone, but also essentially stabilized gas exchange (oxygen saturation) as an overall measure of lung function. These observations provide important mechanistic insights into profibrotic TGFβ signaling and indicate that targeting multiple cytokines represents a possible strategy to ameliorate organ fibrosis dependent on TGFβ.
lux genes and the applications of bacterial bioluminescence (1992)

Microbiology Society journals contain high-quality research papers and topical review articles. We are a not-for-profit publisher and we support and invest in the microbiology community, to the benefit of everyone. This supports our principal goal to develop, expand and strengthen the networks available to our members so that they can generate new knowledge about microbes and ensure that it is shared with other communities.
Regulation of Autophagy and Its Associated Cell Death by “Sphingolipid Rheostat” (2012)

The role of "sphingolipid rheostat" by ceramide and sphingosine 1-phosphate (S1P) in the regulation of autophagy remains unclear. In human leukemia HL-60 cells, amino acid deprivation (AA(-)) caused autophagy with an increase in acid sphingomyleinase (SMase) activity and ceramide, which serves as an autophagy inducing lipid. Knockdown of acid SMase significantly suppressed the autophagy induction. S1P treatment counteracted autophagy induction by AA(-) or C(2)-ceramide. AA(-) treatment promoted mammalian target of rapamycin (mTOR) dephosphorylation/inactivation, inducing autophagy. S1P treatment suppressed mTOR inactivation and autophagy induction by AA(-). S1P exerts biological actions via cell surface receptors, and S1P(3) among five S1P receptors was predominantly expressed in HL-60 cells. We evaluated the involvement of S1P(3) in suppressing autophagy induction. S1P treatment of CHO cells had no effects on mTOR inactivation and autophagy induction by AA(-) or C(2)-ceramide. Whereas S1P treatment of S1P(3) overexpressing CHO cells resulted in activation of the mTOR pathway, preventing cells from undergoing autophagy induced by AA(-) or C(2)-ceramide. These results indicate that S1P-S1P(3) plays a role in counteracting ceramide signals that mediate mTOR-controlled autophagy. In addition, we evaluated the involvement of ceramide-activated protein phosphatases (CAPPs) in ceramide-dependent inactivation of the mTOR pathway. Inhibition of CAPP by okadaic acid in AA(-)- or C(2)-ceramide-treated cells suppressed dephosphorylation/inactivation of mTOR, autophagy induction, and autophagy-associated cell death, indicating a novel role of ceramide-CAPPs in autophagy induction. Moreover, S1P(3) engagement by S1P counteracted cell death. Taken together, these results indicated that sphingolipid rheostat in ceramide-CAPPs and S1P-S1P(3) signaling modulates autophagy and its associated cell death through regulation of the mTOR pathway.
Gene Cloning Using cDNA Libraries in a Differential Competition Hybridization Strategy: Application to Cloning XP-A Related Genes (1988)

A competition hybridization strategy using size-cut cDNA libraries as both probe and competitor was designed for the cloning of genes whose mRNAs are either regulated transcriptionally or vary in abundance as a function of cell line or cell cycle. We used this strategy to construct cDNA libraries from a particular size fraction of mRNA from three members of a xeroderma pigmentosum (XP), complementation group A family. Size-cut cDNA libraries derived from the father's, mother's, and child's fibroblast cell line were used in a competition scheme to screen two lambda gt11 human cDNA libraries. Of the 15 positive lambda gt11 clones which have been characterized, at least 14 clones represent the same gene which is present in greater abundance in both the mother and father XP obligate heterozygotes relative to the homozygous affected child.
An object-oriented representation for product and design processes (1998)

We report on the development of a knowledge representation model, which is based on the SHARED object model reported in Shared Workspaces for Computer-Aided Collaborative Engineering (Wong, A. and Sriram, D., Technical Report, IESL 93-06, Intelligent Engineering Systems Laboratory, Department of Civil Engineering, MIT, March, 1993) and Research in Engineering Design (Wong, A. and Sriram, D., SHARED: An Information Model for Cooperative Product Development, 1993, Fall, 21-39). Our current model is implemented as a layered scheme, that incorporates both an evolving artifact and its associated design process. To represent artifacts as they evolve, we define objects recursively without a pre-defined granularity on this recursive decomposition. This eliminates the need for translations between levels of abstraction in the design process. The SHARED model extends traditional OOP in three ways: by allowing explicit relationship classes with inheritance hierarchies; by permitting constraints to be associated with objects and relationships; and by comparing `similar' objects at three different levels (form, function and behavior).