gebhart/patrepeval huggingface dataset:
Theory of Molecular Size Distribution and Gel Formation in Branched Polymers II. General Cross Linking (1944)

A statistical calculation of the gel point and of the molecular size distribution is made for cross-linked high polymers of arbitrary initial size distribution. The weight-average polymerization degree of the cross-linked polymer depends only on the weight-average polymerization degree of the initial polymer and the degree of cross linking. The results obtained also apply to certain vinyl-divinyl copolymers. Polymerization degrees can be estimated from observations of the gel point.
Ribosome‐inactivating proteins up to date (1986)

Ribosome-inactivating proteins (RIPs) from plants inactivate eukaryotic ribosomes, as far as studied by rendering their 60 S subunit unable to bind elongation factor 2. These proteins seem widely distributed and possibly ubiquitous in plants. They are either type 1, those consisting of a single polypeptide chain, or type 2 (ricin and related toxins), those consisting of two chains, one of which is a galactose-binding lectin. The literature on RIPs from 1982 has been reviewed with respect to the chemical and biological properties of RIPs, their use for the preparation of immunotoxins and new perspectives.
Some Thoughts on Electrospray Ionization Mechanisms (2011)

Electrospray ionization (ESI) mechanisms are highly complex, due to a series of physical and chemical phenomena taking place on a complex system, as a solution is. In fact, even if the solution of an analyte in a protic medium can be considered at first sight to be a two-component system, the presence of solvent dissociation equilibria and the possible interactions solvent-solvent dissociation products, solvent dissociation products-analyte make this system highly complex, also for the presence of possible ionic compounds (for example, Na(+), K(+)) which strongly affect the above equilibria. A high number of research articles have been published, mainly devoted to charged droplet production and to gas-phase ion generation. They all show the high complexity of the processes affecting electrospray measurements related to either the chemical equilibria present in the condensed phase and to electrolysis processes at the emitter tip or to the processes occurring in the sprayed droplets. As a result, the chemical composition inside the small droplets from which the analyte ions are generated can be significantly different from those in sprayed solution. In this review, after a short survey of the proposed ESI mechanisms, some experiments are described. They were performed to examine if ion mobility in solution, before the formation of the sprayed charged droplets, can affect the ESI results. The data, obtained by studying both inorganic and organic analytes, indicate that the ESI spectra are dependent on the analyte dimension and charge state which, as a consequence, affect their ion mobility in solution.
Anthropomorphic Soft Fingertip with Tactile Receptors in the Skin (2005)

The manipulation ability of robotic fingers is too less than the human's ability. One of the reasons is that the sensing ability of the robotic finger is too poor. Tactile sensing is useful for obtaining the information about the object and contact conditions. To improve the manipulation ability of robotic fingers, this paper proposes a design of an anthropomorphic soft fingertip with distributed tactile receptors. The fingertip consists of two silicon rubber layers of different hardness containing two kinds of receptors, strain gauges and PVDF (polyvinylidene fluoride) films. The structure of the fingertip is similar to that of a human's; it consists of a bone, an inner, an outer layer, and randomly distributed receptors inside. Experimental results demonstrate the sensing ability of the fingertip: it can discriminate five different materials by pushing and rubbing the objects.
Depth-selective data analysis for time-domain fNIRS: moments vs. time windows (2020)

Time-domain measurements facilitate the elimination of the influence of extracerebral, systemic effects, a key problem in functional near-infrared spectroscopy (fNIRS) of the adult human brain. The analysis of measured time-of-flight distributions of photons often relies on moments or time windows. However, a systematic and quantitative characterization of the performance of these measurands is still lacking. Based on perturbation simulations for small localized absorption changes, we compared spatial sensitivity profiles and depth selectivity for moments (integral, mean time of flight and variance), photon counts in time windows and their ratios for different time windows. The influence of the instrument response function (IRF) was investigated for all measurands and for various source-detector separations. Variance exhibits the highest depth selectivity among the moments. Ratios of photon counts in different late time windows can achieve even higher selectivity. An advantage of moments is their robustness against the shape of the IRF and instrumental drifts.
Requirement of Mature Dendritic Cells for Efficient Activation of Influenza A-Specific Memory CD8+ T Cells (2000)

It is critical to identify the developmental stage of dendritic cells (DCs) that is most efficient at inducing CD8+ T cell responses. Immature DCs can be generated from monocytes with GM-CSF and IL-4, while maturation is accomplished by the addition of stimuli such as monocyte-conditioned medium, CD40 ligand, and LPS. We evaluated the ability of human monocytes and immature and mature DCs to induce CD8+ effector responses to influenza virus Ags from resting memory cells. We studied replicating virus, nonreplicating virus, and the HLA-A*0201-restricted influenza matrix protein peptide. Sensitive and quantitative assays were used to measure influenza A-specific immune responses, including MHC class I tetramer binding assays, enzyme-linked immunospot assays for IFN-gamma production, and generation of cytotoxic T cells. Mature DCs were demonstrated to be superior to immature DC in eliciting IFN-gamma production from CD8+ effector cells. Furthermore, only mature DCs, not immature DCs, could expand and differentiate CTL precursors into cytotoxic effector cells over 7 days. An exception to this was immature DCs infected with live influenza virus, because of the virus's known maturation effect. Finally, mature DCs pulsed with matrix peptide induced CTLs from highly purified CD8+ T cells without requiring CD4+ T cell help. These differences between DC stages were independent of Ag concentrations or the number of immature DCs. In contrast to DCs, monocytes were markedly inferior or completely ineffective stimulators of T cell immunity. Our data with several qualitatively different assays of the memory CD8+ T cell response suggest that mature cells should be considered as immunotherapeutic adjuvants for Ag delivery.
Porcine ear skin: an in vitro model for human skin (2006)

The results obtained are similar to those of human skin, indicating the suitability of this porcine tissue as a model for human skin.
Suppression of nerve growth factor-directed neurite outgrowth in PC12 cells by sphingosine, an inhibitor of protein kinase C. (1988)

The formation of vertebrate neural circuitry is regulated in part by neurotrophic agents, such as nerve growth factor (NGF); however, the biochemical mechanisms involved in neurite outgrowth have yet to be completely resolved. Phorbol ester tumor promoters are known to influence the extension of neurites in a variety of neurodevelopmental systems, and protein kinase C, the major phorbol ester receptor, has been implicated in this process. In the present study, sphingosine, a specific pharmacological inhibitor of protein kinase C, was employed to investigate the role of this enzyme in the elaboration of neurites in PC12 pheochromocytoma cells. Normally, PC12 cells respond to NGF by morphologically differentiating into sympathetic neuron-like cells, exhibiting a marked hypertrophy, and extending slender neurites piloted by well defined growth cones. The elaboration of NGF-induced neurites was found to be reversibly inhibited by sphingosine in a dose-dependent manner (IC50 = 2.5-5 microM), while similar concentrations of several structural analogs were inactive. The suppression of neurite outgrowth by sphingosine was antagonized by the addition of 12-O-tetradecanoylphorbol 13-acetate (TPA), which binds to and directly activates protein kinase C. In the presence of NGF, TPA treatment increased the incidence of neurite outgrowth, and this increase, in turn, was antagonized by sphingosine. The binding of [3H]phorbol 12,13-dibutyrate to specific phorbol ester binding sites in PC12 cells was inhibited by sphingosine at concentrations similar to those which inhibited neurite outgrowth. The effects of sphingosine on TPA-directed protein phosphorylation were examined in situ, revealing inhibition of [32P]phosphate incorporation into cellular proteins. The specific TPA-directed phosphorylation of tyrosine hydroxylase was inhibited by sphingosine, as was the resulting increase in enzyme activity. The effects of sphingosine on the levels of alpha- and beta-tubulin mRNAs were also examined in an effort to delimit the locus of protein kinase C action. Concentrations of sphingosine which suppressed neurite outgrowth did not inhibit the NGF-directed elevation of tubulin transcript levels. Taken together, these results reveal the presence of a sphingosine-sensitive pathway in neurite outgrowth and indicate that protein kinase C plays a role in mediating the neuritogenic effects of NGF. Furthermore, the results suggest that protein kinase C acts at a distal segment of the neurite growth pathway.
HTLV-I-Induced T-Cell Activation (1996)

Infection by the human T-cell lymphotropic virus type I (HTLV-I) causes T-cell activation by at least two separate mechanisms. One mechanism involves activation of the T cells harboring the virus and is exemplified by in vivo infected nonimmortalized T-cell clones that display a prolonged state of activation. This HTLV-I-induced T-cell activation is inhibited by rapamycin, a drug that inhibits p70 S6-kinase and blocks cell cycle in G1, but is not inhibited by FK506 or cyclosporin A, both of which inhibit interleukin-2 (IL-2) production. The phenotype of this pathway is consistent with an hyperactive IL-2R pathway or CD28 pathway, indicating that HTLV-I may contribute a costimulatory signal to the infected T cell. As a separate mechanism, HTLV-I-infected T cells can induce activation of uninfected T cells via T-T-cell interaction mediated by the LFA-3-CD2 pathway. This may induce IL-2 production from the uninfected T cells, leading to a more generalized activation of the immune system that potentially could provide a basis for some of the diseases associated with HTLV-I. Moreover, this THTLV-I-T-cell interaction could explain the spontaneous proliferation observed in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis.
Oxidative-Stability Enhancement and Charge Transport Mechanism in Glyme–Lithium Salt Equimolar Complexes (2011)

The oxidative stability of glyme molecules is enhanced by the complex formation with alkali metal cations. Clear liquid can be obtained by simply mixing glyme (triglyme or tetraglyme) with lithium bis(trifluoromethylsulfonyl)amide (Li[TFSA]) in a molar ratio of 1:1. The equimolar complex [Li(triglyme or tetraglyme)(1)][TFSA] maintains a stable liquid state over a wide temperature range and can be regarded as a room-temperature ionic liquid consisting of a [Li(glyme)(1)](+) complex cation and a [TFSA](-) anion, exhibiting high self-dissociativity (ionicity) at room temperature. The electrochemical oxidation of [Li(glyme)(1)][TFSA] takes place at the electrode potential of ~5 V vs Li/Li(+), while the oxidation of solutions containing excess glyme molecules ([Li(glyme)(x)][TFSA], x > 1) occurs at around 4 V vs Li/Li(+). This enhancement of oxidative stability is due to the donation of lone pairs of ether oxygen atoms to the Li(+) cation, resulting in the highest occupied molecular orbital (HOMO) energy level lowering of a glyme molecule, which is confirmed by ab initio molecular orbital calculations. The solvation state of a Li(+) cation and ion conduction mechanism in the [Li(glyme)(x)][TFSA] solutions is elucidated by means of nuclear magnetic resonance (NMR) and electrochemical methods. The experimental results strongly suggest that Li(+) cation conduction in the equimolar complex takes place by the migration of [Li(glyme)(1)](+) cations, whereas the ligand exchange mechanism is overlapped when interfacial electrochemical reactions of [Li(glyme)(1)](+) cations occur. The ligand exchange conduction mode is typically seen in a lithium battery with a configuration of [Li anode|[Li(glyme)(1)][TFSA]|LiCoO(2) cathode] when the discharge reaction of a LiCoO(2) cathode, that is, desolvation of [Li(glyme)(1)](+) and insertion of the resultant Li(+) into the cathode, occurs at the electrode-electrolyte interface. The battery can be operated for more than 200 charge-discharge cycles in the cell voltage range of 3.0-4.2 V, regardless of the use of ether-based electrolyte, because the ligand exchange rate is much faster than the electrode reaction rate.
The impact of system bandwidth on a frequency hopped channel (1995)

Studies of code division multiple access (CDMA) have shown that frequency hopping (FH) possesses many of the advantages claimed by direct sequence (DS) spread spectrum techniques. The paper investigates the propagation issues associated with a FH system. To maximise the effectiveness of coding and interleaving in the system requires uncorrelated fading between adjacent hop periods. The criteria which the paper explores therefore include the effects of varying hop frequency bin separation as compared with the coherence bandwidth of the channel. The paper considers the propagation characterisation of a narrowband FH signal, with measurements taken in the City of Bristol. These measurements are used to determine how the overall performance of a FH system is affected by certain critical system parameters, namely hop bin separation and hop rate
Novel Glucocorticoid Antedrugs Possessing a 17β-(γ-Lactone) Ring (2001)

The chemical synthesis and structure-activity relationships of a novel series of 17beta-glucocorticoid butyrolactones possessing either a 16alpha,17alpha-isopropylidene or -butylidene group are described. The sulfur-linked gamma-lactone group was incorporated onto the 17beta-position of the androstane nucleus via Barton ester decarboxylation and trapping the generated 17-radical with butyrolactone disulfides. The glucocorticoid butyrolactones were hydrolyzed in human plasma by the enzyme paraoxonase to the respective hydroxy acids, which were very weak glucocorticoid agonists. The rate of hydrolysis in plasma was very rapid (t1/2 = 4-5 min) in the case of lactones possessing a sulfur atom in the alpha-position of the butyrolactone group, whereas carbon-linked lactones were stable in plasma. 16alpha,17alpha-Butylidenes were more potent glucocorticoid agonists than the corresponding isopropylidene derivatives. Similarly, 1,4-dien-3-ones were more potent than the corresponding 4-en-3-ones. The butyrolactones linked to the steroidal nucleus via the beta-position were more potent glucocorticoid agonists than those linked through the alpha-position of the lactone. The most potent compounds were also shown to be stable in human lung S9 fraction, showed much lower systemic effects than budesonide in the thymus involution test, and possessed topical antiinflammatory activity in the rat ear edema model.
Sui generis: gene therapy and delivery systems for the treatment of glioblastoma (2015)

Gene therapy offers a multidimensional set of approaches intended to treat and cure glioblastoma (GBM), in combination with the existing standard-of-care treatment (surgery and chemoradiotherapy), by capitalizing on the ability to deliver genes directly to the site of neoplasia to yield antitumoral effects. Four types of gene therapy are currently being investigated for their potential use in treating GBM: (i) suicide gene therapy, which induces the localized generation of cytotoxic compounds; (ii) immunomodulatory gene therapy, which induces or augments an enhanced antitumoral immune response; (iii) tumor-suppressor gene therapy, which induces apoptosis in cancer cells; and (iv) oncolytic virotherapy, which causes the lysis of tumor cells. The delivery of genes to the tumor site is made possible by means of viral and nonviral vectors for direct delivery of therapeutic gene(s), tumor-tropic cell carriers expressing therapeutic gene(s), and "intelligent" carriers designed to increase delivery, specificity, and tumoral toxicity against GBM. These vehicles are used to carry genetic material to the site of pathology, with the expectation that they can provide specific tropism to the desired site while limiting interaction with noncancerous tissue. Encouraging preclinical results using gene therapies for GBM have led to a series of human clinical trials. Although there is limited evidence of a therapeutic benefit to date, a number of clinical trials have convincingly established that different types of gene therapies delivered by various methods appear to be safe. Due to the flexibility of specialized carriers and genetic material, the technology for generating new and more effective therapies already exists.
Abstract 1774: Selection for the EGFR T790M gatekeeper resistance mutation may vary among different small molecule EGFR TKIs (2010)

Abstract Mutations within exons encoding the kinase domain of EGFR confer increased sensitivity of non-small cell lung carcinomas to the tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib. Unfortunately, all patients whose disease responds initially to these therapies eventually develop acquired resistance. In ∼50% of cases, resistance is associated with acquisition of a second-site ‘gatekeeper’ mutation within EGFR, T790M. More potent ‘2nd generation’ EGFR inhibitors theoretically able to overcome T790M-mediated resistance have displayed limited clinical success. In preclinical models of acquired resistance, many of these TKIs (HKI-272, BIBW2992, PF00299804) actually select for the emergence of EGFR T790M-harboring clones. To determine if EGFR TKIs in general lead to the emergence of T790M, we modeled acquired resistance in vitro with the reversible TKI, XL647 (Symphony Evolution, Inc., Rockville, MD), the irreversible EGFR TKI, BIBW2992 (synthesized at MSKCC), and erlotinib. EGFR mutant TKI-sensitive PC-9 cells (lung adenocarcinoma, del E746-A750) were grown with increasing concentrations of XL647 for ∼160 days. Polyclonal resistant (XL-R) cells were derived that proliferated in drug concentrations ∼50-fold higher than the initial IC50. No other secondary mutations within EGFR were detected by direct sequencing, and the T790M mutation was not found using more sensitive mutation detection methods (e.g. SNaPShot; limit of detection ∼5%). By contrast, both BIBW2992- and erlotinib-resistant PC-9 cells (PC-9 BI-R and PC-9 E-R) harbored T790M, as shown by direct sequencing. No resistant cells displayed MET amplification, another known resistance mechanism. Crystal structure data revealed that XL647 binds reversibly within the ATP binding pocket of EGFR T790M with a similar orientation to erlotinib. Therefore, structural differences alone do not readily explain the differential selective pressure for EGFR T790M with gefitinib/erlotinib vs. XL647. Interestingly, PC-9 XL-R cells remained intermediately sensitive to erlotinib. Consistent with the in vitro observations, early clinical trial data revealed that only 1 of 6 patients with EGFR mutant lung cancer harbored T790M after developing acquired resistance to XL647. Furthermore, at least 2 of these patients subsequently derived clinical benefit from single-agent erlotinib. Collectively, these data suggest that the propensity to develop T790M-mediated resistance varies among different TKIs. We are currently exploring why the selective pressure for resistance conferred by XL647 is different from that of other EGFR TKIs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1774.
Epitaxygens: mesomorphic properties of triptycene derivatives (1993)

Abstract The structure of mesophases derived from a triptycene subunit substituted with five paraffinic chains has been determined by X-ray diffraction at small angles. They all show a smectic ordering. This is the first example of a smectogen whose rigid core belongs to the D3h symmetry. A hexagonal order has been observed in the X-ray diffraction patterns; it has been associated with a p31m packing of the rigid cores within the layers. The intralamellar cell parameter is in agreement with the molecular dimensions determined from CPK models. The calculated molecular length is in accordance with the experimental interlamellar distance. The difference in mesomorphic behaviour between the five and six chain derivatives is discussed.
Bactericidal Monoclonal Antibodies Specific to the Lipopolysaccharide O Antigen from Multidrug-Resistant Escherichia coli Clone ST131-O25b:H4 Elicit Protection in Mice (2015)

The Escherichia coli sequence type 131 (ST131)-O25b:H4 clone has spread worldwide and become responsible for a significant proportion of multidrug-resistant extraintestinal infections. We generated humanized monoclonal antibodies (MAbs) that target the lipopolysaccharide O25b antigen conserved within this lineage. These MAbs bound to the surface of live bacterial cells irrespective of the capsular type expressed. In a serum bactericidal assay in vitro, MAbs induced >95% bacterial killing in the presence of human serum as the complement source. Protective efficacy at low antibody doses was observed in a murine model of bacteremia. The mode of action in vivo was investigated by using aglycosylated derivatives of the protective MAbs. The significant binding to live E. coli cells and the in vitro and in vivo efficacy were corroborated in assays using bacteria grown in human serum to mimic relevant clinical conditions. Given the dry pipeline of novel antibiotics against multidrug-resistant Gram-negative pathogens, passive immunization with bactericidal antibodies offers a therapeutic alternative to control infections caused by E. coli ST131-O25b:H4.
GenBank (2007)

GenBank (R) is a comprehensive database that contains publicly available nucleotide sequences for more than 260 000 named organisms, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects. Most submissions are made using the web-based BankIt or standalone Sequin programs and accession numbers are assigned by GenBank staff upon receipt. Daily data exchange with the European Molecular Biology Laboratory Nucleotide Sequence Database in Europe and the DNA Data Bank of Japan ensures worldwide coverage. GenBank is accessible through NCBI's retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, begin at the NCBI Homepage: www.ncbi.nlm.nih.gov.