gebhart/patrepeval huggingface dataset:
Single-Cytokine-Producing CD4 Memory Cells Predominate in Type 1 and Type 2 Immunity (2000)

The patterns of Ag-induced cytokine coexpression in normal, in vivo-primed CD4 memory T cells has remained controversial because the low frequency at which these cells occur has effectively prevented direct ex vivo measurements. We have overcome this limitation by using two-color cytokine enzyme-linked immunospot assays and computer-assisted image analysis. We found CD4 memory cells that simultaneously expressed IL-2, IL-3, IL-4, IL-5, and IFN-gamma to be rare (0-10%). This cytokine segregation was seen in adjuvant-induced type 1, type 2, and mixed immunity to OVA, in Leishmania infection regardless of the Ag dose used or how long after immunization the assay was performed. The data suggest that type 1 and type 2 immunity in vivo is not mediated by classic Th1 or Th2 cells but by single-cytokine-producing memory cells.
Translational Control of the Antiapoptotic Function of Ras (2000)

Activated Ras has been shown to provide powerful antiapoptotic signals to cells through well defined transcriptional and post- translational pathways, whereas translational control as a mechanism of Ras survival signaling remains unexplored. Here we show a direct relationship between assembly of the cap-dependent translation initiation apparatus and suppression of apoptosis by oncogenic Ras in vitro and in vivo. Decreasing protein synthesis with rapamycin, which is known to inhibit cap-dependent translation, increases the susceptibility of Ras-transformed fibroblasts to cytostatic drug-induced apoptosis. In contrast, suppressing global protein synthesis with equipotent concentrations of cycloheximide actually prevents apoptosis. Enforced expression of the cap-dependent translational repressor, the eukaryotic translation initiation factor (eIF) 4E-binding protein (4E-BPI), sensitizes fibroblasts to apoptosis in a manner strictly dependent on its ability to sequester eIF4E from a translationally active complex with eIF4GI and the co-expression of oncogenic Ras. Ectopic expression of 4E-BP1 also promotes apoptosis of Ras-transformed cells injected into immunodeficient mice and markedly diminishes their tumorigenicity. These results establish that eIF4E-dependent protein synthesis is essential for survival of fibroblasts bearing oncogenic Ras and support the concept that activation of cap-dependent translation by extracellular ligands or intrinsic survival signaling molecules suppresses apoptosis, whereas synthesis of proteins mediating apoptosis can occur independently of the cap.
<title>"Comparative Thermal Modeling Of Er:YAG, Ho:YAG And CO<formula><inf><roman>2</roman></inf></formula> Laser Pulses For Tissue Vaporization"</title> (1987)

We will present a thermal model for laser pulses with pulse widths small compared to the material&apos;s thermal time constant. This model will then be used to generate computer plots of the zones of vaporized tissue as well as the predicted tissue temperature rise. Using published values of absorption coefficients, we will predict the vaporization energy thresholds for Er:YAG (2.94&mu;m), Ho:YAG (2.1&mu;m) and CO<sub>2</sub> (10.6&mu;m) laser pulses. We will also examine the extent of the thermally denatured zone surrounding the zone of vaporization. Using typical energies available from these lasers we will then predict material removed per pulse, and per second.
Quick Access to Optically Pure 2-(1-Hydroxybenzyl)piperidine and Pyrrolidine (2006)

Optically pure 2-(1-hydroxybenzyl)piperidine and pyrrolidine were prepared by reaction of oxygenated 2-(p-tolylsulfinyl)benzyl carbanions with the appropriate chlorinated N-sulfinylimines followed by subsequent elimination of the sulfinyl groups. The main reaction is a tandem process involving nucleophilic addition of the sulfinylbenzyl carbanion to the C=N bond followed by intramolecular elimination of the chlorine by the resulting amide. The matched pair of the reagents (exhibiting the same configuration at their respective sulfinyl moieties) evolves with a complete control of the stereoselectivity at the two newly created chiral carbons.
The art of strain improvement of industrial lactic acid bacteria without the use of recombinant DNA technology (2014)

The food industry is constantly striving to develop new products to fulfil the ever changing demands of consumers and the strict requirements of regulatory agencies. For foods based on microbial fermentation, this pushes the boundaries of microbial performance and requires the constant development of new starter cultures with novel properties. Since the use of ingredients in the food industry is tightly regulated and under close scrutiny by consumers, the use of recombinant DNA technology to improve microbial performance is currently not an option. As a result, the focus for improving strains for microbial fermentation is on classical strain improvement methods. Here we review the use of these techniques to improve the functionality of lactic acid bacteria starter cultures for application in industrial-scale food production. Methods will be described for improving the bacteriophage resistance of specific strains, improving their texture forming ability, increasing their tolerance to stress and modulating both the amount and identity of acids produced during fermentation. In addition, approaches to eliminating undesirable properties will be described. Techniques include random mutagenesis, directed evolution and dominant selection schemes.
A Novel Alkaline α-Galactosidase from Melon Fruit with a Substrate Preference for Raffinose1 (1999)

The cucurbits translocate the galactosyl-sucrose oligosaccharides raffinose and stachyose, therefore, alpha-galactosidase (alpha-D-galactoside galactohydrolase, EC 3.2.1.22) is expected to function as the initial enzyme of photoassimilate catabolism. However, the previously described alkaline alpha-galactosidase is specific for the tetrasaccharide stachyose, leaving raffinose catabolism in these tissues as an enigma. In this paper we report the partial purification and characterization of three alpha-galactosidases, including a novel alkaline alpha-galactosidase (form I) from melon (Cucumis melo) fruit tissue. The form I enzyme showed preferred activity with raffinose and significant activity with stachyose. Other unique characteristics of this enzyme, such as weak product inhibition by galactose (in contrast to the other alpha-galactosidases, which show stronger product inhibition), also impart physiological significance. Using raffinose and stachyose as substrates in the assays, the activities of the three alpha-galactosidases (alkaline form I, alkaline form II, and the acid form) were measured at different stages of fruit development. The form I enzyme activity increased during the early stages of ovary development and fruit set, in contrast to the other alpha-galactosidase enzymes, both of which declined in activity during this period. In the mature, sucrose-accumulating mesocarp, the alkaline form I enzyme was the major alpha-galactosidase present. We also observed hydrolysis of raffinose at alkaline conditions in enzyme extracts from other cucurbit sink tissues, as well as from young Coleus blumei leaves. Our results suggest different physiological roles for the alpha-galactosidase forms in the developing cucurbit fruit, and show that the newly discovered enzyme plays a physiologically significant role in photoassimilate partitioning in cucurbit sink tissue.
Drug discovery technologies (1990)

Drug discovery technologies , Drug discovery technologies , کتابخانه مرکزی دانشگاه علوم پزشکی تهران
The meddling microbes midst our medicines (2013)

It is not surprising that the complex metabolic machinery of the gut microbiome has accidental, or directed, ability to alter our medicines and influence their efficacy. What is not known is the extent to which this has contributed to drug failures or contraindications, or to the derailment of clinical trials. Some studies are unraveling the mechanisms by which the microbiota alter specific drugs, such as digoxin, and contribute to variations in efficacies between patient populations. Microbiome profiling, therefore, may well become an inevitable arm of all clinical trials in the future.
Regulation of Adenylyl Cyclase-Coupled beta-Adrenergic Receptors (1988)

HETEROLOGOUS DESENSITIZATION.. .••••• ...•• 409 Receptor Alterations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . .... . . . . . . . . . . . . ....... . ... . . . . . . . .... . . . . . . . . . . . 409 Alterations in Guanine Nucleotide Regulatory Proteins.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ......... 410 Adenylyl Cyclase Alterations . . . . . . . . . . . . .. .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 412 HOMOLOGOUS DESENSITIZATION . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . .. . .. .. . . . . . . . . . . . . . . . ... . . . . . . . . ........ . . . . . ...... 413 Functional Uncoupling/Sequestration. . . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...... . . . . . . . . . . . 413 Down-Regulation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 414 Role of Receptor Phosphorylation i n Homologous Desensitization . . . . . . . . . . . . . . . , . . . . . . . . . . . . . 415 Involvement of a Receptor-Specific Kinase .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 415 Identification of the Phosphorylation Sites and Their Contribution to the Desensitization Process. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 418 Mechanism of Homologous Desensitization . . . . . . . . . ...... . . . . . . .. .. ... . . . . . . . . . . . .. . .... .... . . . . . . . . . ... 419
Transduced p16INK4a peptides inhibit hypophosphorylation of the retinoblastoma protein and cell cycle progression prior to activation of Cdk2 complexes in late G1. (1999)

Progression of cells through the G1 phase of the cell cycle requires cyclin D:Cdk4/6 and cyclin E:Cdk2 complexes; however, the duration and ordering of these complexes remain unclear. To address this, we synthesized a peptidyl mimetic of the Cdk4/6 inhibitor, p16INK4a that contained an NH2-terminal TAT protein transduction domain. Transduction of TAT-p16 wild-type peptides into cells resulted in the loss of active, hypophosphorylated pRb and elicited an early G1 cell cycle arrest, provided cyclin E:Cdk2 complexes were inactive. We conclude that cyclin D:Cdk4/6 activity is required for early G1 phase cell cycle progression up to, but not beyond, activation of cyclin E:Cdk2 complexes at the restriction point and is thus nonredundant with cyclin E:Cdk2 in late G1.
Congestion avoidance and control (1988)

In October of '86, the Internet had the first of what became a series of 'congestion collapses'. During this period, the data throughput from LBL to UC Berkeley (sites separated by 400 yards and three IMP hops) dropped from 32 Kbps to 40 bps. Mike Karels1 and I were fascinated by this sudden factor-of-thousand drop in bandwidth and embarked on an investigation of why things had gotten so bad. We wondered, in particular, if the 4.3BSD (Berkeley UNIX) TCP was mis-behaving or if it could be tuned to work better under abysmal network conditions. The answer to both of these questions was “yes”.
Definition of an Amino-terminal Domain of the Human T-cell Leukemia Virus Type 1 Envelope Surface Unit That Extends the Fusogenic Range of an Ecotropic Murine Leukemia Virus (2000)

International audience
Temporal lobe epilepsy caused by domoic acid intoxication: Evidence for glutamate receptor–mediated excitotoxicity in humans (1995)

We describe the development of temporal lobe epilepsy in an 84-year-old man who had suffered domoic acid intoxication. Following intoxication he had nausea, vomiting, confusion, and coma. Generalized convulsions and complex partial status epilepticus progressively developed. After 3 weeks he improved and was seizure free with severe residual memory deficit. Electroencephalograms initially showed periodic epileptiform discharges, later evolving to epileptic abnormalities over frontotemporal regions with diffuse slow waves. Eight months after the intoxication the electroencephalogram was normal. One year after the acute episode, complex partial seizures developed. Electroencephalograms showed epileptic discharges independently over both temporal lobes, with left-sided predominance. Magnetic resonance imaging revealed a hyperintense T2-weighted signal and atrophy of both hippocampi; a positron emission tomographic scan showed bitemporal decreased glucose metabolism. Pneumonia developed and the patient died 3 1/4 years after the intoxication. Autopsy disclosed severe bilateral hippocampal sclerosis. The seizures following acute domoic acid intoxication, the postmortem pathology, and the fact that temporal lobe epilepsy developed 1 year after intoxication indicate that the human hippocampus is also vulnerable to kainate receptor excitotoxicity, and provide strong evidence supporting the role of excitotoxic injury in epileptogenesis. This report provides a unique human parallel to, and validates the animal model of, kainate-induced epilepsy as an important tool for studying temporal lobe epilepsy.
Activity-dependent fluorescent staining and destaining of living vertebrate motor nerve terminals (1992)

Living motor nerve terminals from several species can be stained in an activity-dependent fashion by certain styryl dyes, such as RH414, RH795, and a new dye, FM1-43, which can be imaged independently of the others. The dyes evidently become trapped within recycled synaptic vesicles. In frog cutaneus pectoris muscle, bright fluorescent spots spaced regularly along the length of the nerve terminals appear after stimulation in the presence of the dye. The spots align well with postsynaptic ACh receptors and are persistent for many hours, unless further stimulation is given, in which case the spots disappear. Destaining, like staining, requires transmitter release and proceeds gradually over several minutes at high stimulus frequencies (e.g., 30 Hz), and fluorescent spots in the same terminal disappear at about the same rate. We suggest that each spot is a cluster of hundred of synaptic vesicles and that the mechanism of staining involves the ability of the dyes to partition reversibly into the outer leaflet of surface membranes, without being able to penetrate the entire membrane thickness. Then, during endocytosis following transmitter release, dye molecules become trapped in recycled synaptic vesicle membranes. The dyes therefore make it possible optically to study vesicle exocytosis and recycling in living nerve terminals in real time, and should be useful for marking terminals in a variety of preparations according to their level of activity.
Eph kinases and ephrins support thrombus growth and stability by regulating integrin outside-in signaling in platelets (2005)

The ability of activated platelets to adhere to each other at sites of vascular injury depends on the integrin alpha(IIb)beta(3). However, as aggregation continues, other signaling and adhesion molecules can contribute as well. We have previously shown that human platelets express on their surface the Eph receptor kinases EphA4 and EphB1 and the Eph kinase ligand ephrinB1. We now show that EphA4 is physically associated with alpha(IIb)beta(3) in resting platelets, increases its surface expression when platelets are activated, and colocalizes with alpha(IIb)beta(3) at sites of contact between platelets. We also show that Eph/ephrin interactions can support the stable accumulation of platelets on collagen under flow and contribute to postengagement "outside-in" signaling through alpha(IIb)beta(3) by stabilizing platelet aggregates and facilitating tyrosine phosphorylation of the beta(3) cytoplasmic domain. beta(3) phosphorylation allows myosin to bind to alpha(IIb)beta(3) and clot retraction to occur. The data support a model in which the onset of aggregation permits Eph/ephrin interactions to occur, after which signaling downstream from ephrinB1 and its receptors favors continued growth and stability of the thrombus by several mechanisms, including positive effects on outside-in signaling through alpha(IIb)beta(3).
Brown-midrib genes of maize: a review (1993)

&mdash; The efficiency of forage for ruminant animals primarily depends on cell-wall constituent content, mostly cellulose and hemicellulose, and on their digestibility, mostly reduced by lignin incrustration. Four brown-midrib genes (bm1, bm2, bm3 and bm4) have been described in maize. Brown-midrib plants were described as having a lower li- gnin content than normal genotypes; the ratios of hydroxycinnamic acids released after alkaline hydrolysis, and the ra- tios between monomeric units released after alkaline nitrobenzene oxidation or thioacidolysis also differed in normal and brown-midrib plants. The bm3 gene, allowing an important decrease of lignin content, and a better improvement in plant digestibility, was also the most studied. When cattle were fed bm3 plants, intake and digestibility were higher compared to normal isogenic ones, and the rate of digestion was also higher. However, the agronomical value of the brown-midrib genotypes was distinctively lower than that of their normal isogenic counterparts and this was particular- ly notable on the bm3 gene. This observation also appeared to be genotype-specific, suggesting the possibility of producing brown-midrib genotypes that are practically as good as the normal ones, but only when using well-adapted breeding methods, with normal lines of a very high agronomical value. maize / brown-midrib genes / feeding value / lignin / agronomic value Rsum &mdash; Les gnes brown-midrib chez le mas. Revue bibliographique. L'utilisation des fourrages par les rumi- nants dpend essentiellement de la teneur en constituants paritaux, principalement cellulose et hmicelluloses, et de leur digestibilit, rduite particulirement par la prsence de lignines dans ces parois. Quatre gnes brown-midrib (bm1, bm2, bm3, bm4) ont t mis en vidence chez le mas. Les plantes brown midrib diffrent des mas normaux, particulirement par une teneur rduite en lignines, par des rapports modifis, entre les acides hydroxycinnamiques li- brs aprs hydrolyse alcaline des lignines, et par des rapports galement modifs entre les units monomriques li- bres aprs oxydation alcaline au nitrobenzne ou thioacidolyse de cette lignine. Le gne bm3, qui conduit une forte rduction de teneur en lignines et surtout, rsultat obtenu ds les premires mesures de digestibilit in vitro, la plus importante augmentation de digestibilit, a fait l'objet du plus grand nombre d'tudes. Cela a permis de confirmer que les gnotyes bm3 taient mieux ingrs par les ruminants, avaient, in vivo, une meilleure digestibilit, avec une vitesse de digestion plus leve. En revanche, la valeur agronomique des mas brown-midrib est plus faible que celle des mas normaux, particulirement en ce qui concerne le gne bm3. Cependant la variabilit gntique mise en vi- dence pour des caractres agronomiques suggre qu'il doit tre possible d'obtenir des gnotypes bm3 pratiquement du niveau des gnotypes normaux, condition d'employer des mthodes de slection adaptes, et en n'introgressant que les lignes normales de trs bon niveau agronomique. mas / brown-midrib / valeur alimentaire / lignine /
Evaluation of robot automated drug dissolution measurements (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEvaluation of robot automated drug dissolution measurementsAndrew N. Papas, Maurice Y. Alpert, Salvatore M. Marchese, James W. Fitzgerald, and Michael F. DelaneyCite this: Anal. Chem. 1985, 57, 7, 1408–1411Publication Date (Print):June 1, 1985Publication History Published online1 May 2002Published inissue 1 June 1985https://pubs.acs.org/doi/10.1021/ac00284a051https://doi.org/10.1021/ac00284a051research-articleACS PublicationsRequest reuse permissionsArticle Views129Altmetric-Citations24LEARN 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
Platelet activating factor‐induced apoptosis is inhibited by ectopic expression of the platelet activating factor G‐protein coupled receptor (2002)

The pro-inflammatory lipid mediator platelet activating factor (PAF: 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) accumulates in ischemia, epilepsy, and human immunodeficiency virus-1-associated dementia and is implicated in neuronal loss. The present study was undertaken to establish a role for its G-protein coupled receptor in regulating neurotoxicity. PC12 cells do not express PAF receptor mRNA as demonstrated by northern analysis and RT-PCR. In the absence of the G-protein coupled receptor, PAF (0.1-1 micro m) triggered chromatin condensation, DNA strand breaks, oligonucleosomal fragmentation, and nuclear disintegration characteristic of apoptosis. Lyso-PAF (0.001-1 micro m), the immediate metabolite of PAF, did not elicit apoptotic death. Concentrations of PAF or lyso-PAF that exceeded critical micelle concentration had physicochemical effects on plasma membrane resulting in necrosis. Apoptosis but not necrosis was inhibited by the PAF antagonist BN52021 (1-100 micro m) but not CV3988 (0.2-20 micro m). Ectopic PAF receptor expression protected PC12 transfectants from ligand-induced apoptosis. PAF receptor-mediated protection was inhibited by CV3988 (1 micro m). These data provide empirical evidence that: (i) PAF can initiate apoptosis independently of its G-protein coupled receptor; (ii) PAF signaling initiated by its G-protein coupled receptor is cytoprotective to PC12 cells; (iii) the pro- and anti-apoptotic effects of PAF on PC12 cells can be pharmacologically distinguished using two different PAF antagonists.