gebhart/patrepeval huggingface dataset:
The uses and properties of PEG-linked proteins. (1992)

Poly(ethylene glycol) (PEG) is a water soluble polymer that when covalently linked to proteins, alters their properties in ways that extend their potential uses. PEG-modified conjugates are being exploited in many different fields. The improved pharmacological performance of PEG-proteins when compared with their unmodified counterparts prompted the development of this type of conjugate as a therapeutic agent. Enzyme deficiencies for which therapy with the native enzyme was inefficient (due to rapid clearance and/or immunological reactions) can now be treated with equivalent PEG-enzymes. PEG-adenosine deaminase has already obtained FDA approval. PEG-modified cytokines have been constructed and, interestingly, one of the conjugates, PEG-modified granulocyte-macrophage colony-stimulating factor, showed dissociation of two biological properties. This novel observation may open new horizons to the application of PEGylation technology. The biotechnology industry has also found PEG-proteins very useful because PEG-enzymes can act as catalysts in organic solvents, thereby opening the possibility of producing desired stereoisomers, as opposed to the racemic mixture usually obtained in classical organic synthesis. Covalent attachment of PEG to proteins requires activation of the hydroxyl terminal group of the polymer with a suitable leaving group that can be displaced by nucleophilic attack of the epsilon-amino terminal of lysine residues (other nucleophilic groups can also interact). Several chemical groups have been exploited to activate PEG, thereby giving rise to a variety of PEG-proteins. Some of these varieties retain part of the activating group as a coupling moiety between PEG and protein and others provide a direct linkage. For each particular application, different coupling methods provide distinct advantages.(ABSTRACT TRUNCATED AT 250 WORDS)
Oligosaccharides and Discordant Xenotransplantation (1994)

The initiating factor in the hyperacute rejection of pig organs by human or non-human primates is believed to be related to the presence of preformed "natural" antibodies in the host. In 1991, we demonstrated that human anti-pig antibodies were IgG, IgM and IgA and bound most strongly to oligosaccharides with an alpha galactose (alpha Gal) terminal residue. These included (i) alpha Gal-R (alpha galactose), (ii) alpha Gall-3 beta Gal-R (B disaccharide), (iii) alpha Gall-3 beta Gall-4 beta GlcNAc-R (linear B type 2 trisaccharide) and (iv) alpha Gall-3 beta Gall-4 beta Glc-R (linear B type 6 trisaccharide) where R is (CH2) 8COOCH3. In vitro studies using both the chromium release assay and a live/dead staining technique demonstrated that the cytotoxicity of human sera towards pig cells can be significantly reduced or abolished by immunoadsorption of the serum with immunoaffinity columns of an alpha Gal structure, particularly those with an alpha 1-3 linkage, and not by a large selection of other carbohydrates. Similarly, human anti-pig antibodies can be largely inhibited or "neutralized" by the addition of an alpha 1-3Gal di- or trisaccharide to the serum. Staining of pig vascular endothelium utilizing a panel of carbohydrate-specific lectins and immunoaffinity antibodies demonstrated the presence of three different carbohydrate epitopes, namely (i) alpha Gall-3 beta Gall-4 beta GlcNAc-R (linear B type 2 trisaccharide (ii) alpha NeuAc2-3 beta Gall-4 beta GlcNAc-R (sialyl-N-acetyllactosamine), and (iii) beta Gall-4 beta GlcNAc-R (N-acetyllactosamine). We have investigated organs from several breeds of pig and have concluded that the alpha Gal epitope is either monomorphic or at least has a high incidence in porcine species, since we have not found any pig negative for this antigen. Human vascular endothelial cells have at their surface the same lactosamine-ended precursor and sialylated chains as pigs, but instead of terminal alpha Gal they express the fucosylated polymorphic ABH histo-blood group epitopes. As we have found no evidence that human or baboon plasma contain antibodies directed against sialic acid or lactosamine, and as human tissues contain both of these carbohydrates, it seems unlikely that either of these epitopes plays a role in the vascular rejection that takes place when pig organs are transplanted into primates. Unfortunately, the alpha Gal disaccharide and trisaccharides were not available to us in the large quantities required for extracorporeal immunoadsorption or continuous intravenous infusion in adult baboons.(ABSTRACT TRUNCATED AT 400 WORDS)
Two glucose/xylose transporter genes from the yeast Candida intermedia: first molecular characterization of a yeast xylose–H+ symporter (2006)

Candida intermedia PYCC 4715 was previously shown to grow well on xylose and to transport this sugar by two different transport systems: high-capacity and low-affinity facilitated diffusion and a high-affinity xylose-proton symporter, both of which accept glucose as a substrate. Here we report the isolation of genes encoding both transporters, designated GXF1 (glucose/xylose facilitator 1) and GXS1 (glucose/xylose symporter 1) respectively. Although GXF1 was isolated by functional complementation of an HXT-null (where Hxt refers to hexose transporters) Saccharomyces cerevisiae strain, isolation of the GXS1 cDNA required partial purification and micro-sequencing of the transporter, identified by its relative abundance in cells grown on low xylose concentrations. Both genes were expressed in S. cerevisiae and the kinetic parameters of glucose and xylose transport were determined. Gxs1 is the first yeast xylose/glucose-H+ symporter to be characterized at the molecular level. Comparison of its amino acid sequence with available sequence data revealed the existence of a family of putative monosaccharide-H+ symporters encompassing proteins from several yeasts and filamentous fungi.
Identification of malignant cells in multiple myeloma bone marrow with immunoglobulin VH gene probes by fluorescent in situ hybridization and flow cytometry. (1995)

Because it has been difficult to identify and separate malignant cells in human lymphoid malignancies, we have developed a flow cytometry-based fluorescent in situ hybridization (FISH) technique using immunoglobulin (Ig) heavy chain variable region (VH) gene probes. After obtaining the specific VH gene sequence expressed by the multiple myeloma IM-9 cell line and the malignant cells in five multiple myeloma patients, sense and antisense biotinylated single-stranded RNA probes were prepared by transcription from the malignant clone's VH DNA sequences. The cells from the IM-9 cell line and from the mononuclear bone marrow cells of multiple myeloma patients were fixed, hybridized with the above biotinylated RNA probes, incubated with streptavidin-phycoerythrin, and analyzed by FACS analysis. The myeloma cells stained positive with their own specific antisense VH biotinylated RNa probes, whereas sense and irrelevant antisense biotinylated probes demonstrated only background staining. Dilutional concentrations of the IM-9 cell line with normal bone marrow cells were also accurately quantitated by this procedure. The application of this technique will allow a more accurate assessment of tumor burden in patients with multiple myeloma and should permit an accurate method of tumor cell purification for clinical as well as biological studies. Furthermore, this technological advance should be equally effective at identifying specific VH gene-expressing cells in other lymphoid malignancies, as well as in nonmalignant B cell disorders.
PD 098059 Is a Specific Inhibitor of the Activation of Mitogen-activated Protein Kinase Kinase in Vitro and in Vivo (1995)

PD 098059 has been shown previously to inhibit the dephosphorylated form of mitogen-activated protein kinase kinase-1 (MAPKK1) and a mutant MAPKK1(S217E,S221E), which has low levels of constitutive activity (Dudley, D. T., Pang, L., Decker, S. J., Bridges, A. J., and Saltiel, A. R. (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 7686-7689). Here we report that PD 098059 does not inhibit Raf-activated MAPKK1 but that it prevents the activation of MAPKK1 by Raf or MEK kinase in vitro at concentrations (IC50 = 2-7 microM) similar to those concentrations that inhibit dephosphorylated MAPKK1 or MAPKK1(S217E,S221E). PD 098059 inhibited the activation of MAPKK2 by Raf with a much higher IC50 value (50 microM) and did not inhibit the phosphorylation of other Raf or MEK kinase substrates, indicating that it exerts its effect by binding to the inactive form of MAPKK1. PD 098059 also acts as a specific inhibitor of the activation of MAPKK in Swiss 3T3 cells, suppressing by 80-90% its activation by a variety of agonists. The high degree of specificity of PD 098059 in vitro and in vivo is indicated by its failure to inhibit 18 protein Ser/Thr kinases (including two other MAPKK homologues) in vitro by its failure to inhibit the in vivo activation of MAPKK and MAP kinase homologues that participate in stress and interleukin-1-stimulated kinase cascades in KB and PC12 cells, and by lack of inhibition of the activation of p70 S6 kinase by insulin or epidermal growth factor in Swiss 3T3 cells. PD 098059 (50 microM) inhibited the activation of p42MAPK and isoforms of MAP kinase-activated protein kinase-1 in Swiss 3T3 cells, but the extent of inhibition depended on how potently c-Raf and MAPKK were activated by any particular agonist and demonstrated the enormous amplification potential of this kinase cascade. PD 098059 not only failed to inhibit the activation of Raf by platelet-derived growth factor, serum, insulin, and phorbol esters in Swiss 3T3 cells but actually enhanced Raf activity. The rate of activation of Raf by platelet-derived growth factor was increased 3-fold, and the subsequent inactivation that occurred after 10 min was prevented. These results indicate that the activation of Raf is suppressed and that its inactivation is accelerated by a downstream component(s) of the MAP kinase pathway.
The Viscosity of Sulfur1 (1943)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Viscosity of Sulfur1Raymond F. Bacon and Rocco FanelliCite this: J. Am. Chem. Soc. 1943, 65, 4, 639–648Publication Date (Print):April 1, 1943Publication History Published online1 May 2002Published inissue 1 April 1943https://pubs.acs.org/doi/10.1021/ja01244a043https://doi.org/10.1021/ja01244a043research-articleACS PublicationsRequest reuse permissionsArticle Views1619Altmetric-Citations195LEARN 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
Clustering of integral membrane proteins of the human erythrocyte membrane stimulates autologous IgG binding, complement deposition, and phagocytosis. (1991)

Damaged or old erythrocytes are cleared rapidly from circulation. Because several common biochemical lesions can induce the clustering of integral membrane proteins, we have proposed that formation of microscopic protein aggregates in the membrane might constitute a cell surface marker that promotes removal of the defective/senescent cells. We demonstrate here that treatments that cluster integral membrane proteins in erythrocytes (1 mM ZnCl2, 1 mM acridine orange, and 0.35 microM melittin) induce autologous IgG binding, complement fixation, and phagocytosis by human monocytes in vitro. Removal of the clustering agents prior to incubation in autologous serum or cross-linking of cell surface proteins before addition of clustering agents prohibited the above response, while cross-linking after treatment with the clustering agents preserved the response even if the clustering agents were later removed. Furthermore, subsequent reversal of the chemical cross-link maintaining the clustered distribution also reversed the induction of IgG binding, complement deposition, and phagocytosis. Finally, by deleting or inactivating different steps in the phagocytosis pathway, the chronology of steps was shown to be: (i) integral protein clustering, (ii) IgG binding, (iii) complement deposition, and (iv) phagocytosis.
Upregulation of p75 Tumor Necrosis Factor Alpha Receptor inMycobacterium avium-Infected Mice: Evidence for a Functional Role (1999)

The bacterial growth and the production of tumor necrosis factor alpha (TNF-alpha) and TNF receptors (TNF-Rs) in the spleen and blood of BALB/c mice challenged with Mycobacterium avium complex (MAC) were monitored. Infection developed in two phases: the first, up to day 21, was associated with rapid MAC multiplication in the spleen and a drop in the mycobacteremia, and the second was associated with control of the infection in both compartments. In the spleen, TNF-alpha and TNF-RII mRNA levels peaked on day 21 and then slowly decreased; however, no increase in the level of TNF-RI mRNA was observed throughout these experiments. The level of circulating soluble TNF-RII (sTNF-RII) was transiently increased after day 21. In a model in which overproduction of bioactive TNF-alpha was triggered in response to a second infection with MAC, an increased production of sTNF-RII by cultured splenocytes was also observed. Administration of an antagonist anti-TNF-RII monoclonal antibody (MAb 6G1) to infected mice inhibited the bacterial growth in the spleen, suggesting that the TNF-RII and/or sTNF-RII was functionally involved in the mechanisms that control the infection. Overall, these observations suggest that upregulation of TNF-RII or sTNF-RII contributes to modulation of the TNF-alpha antibacterial activity in MAC infections.
High-efficiency dielectric reflection gratings: design, fabrication, and analysis (1999)

We report on reflection gratings produced entirely of dielectric materials. This gives the opportunity to enhance the laser damage threshold over that occurring in conventional metal gratings used for chirped-pulse-amplification, high-power lasers. The design of the system combines a dielectric mirror and a well-defined corrugated top layer to obtain optimum results. The rules that have to be considered for the design optimization are described. We optimized the parameters of a dielectric grating with a binary structure and theoretically obtained 100% reflectivity for the -1 order in the Littrow mounting for a 45 degrees angle of incidence. Subsequently we fabricated gratings by structuring a low-refractive-index top layer of a multilayer stack with electron-beam lithography. The multilayer system was fabricated by conventional sputtering techniques onto a flat fused-silica substrate. The parameters of the device were measured and controlled by light scatterometer equipment. We measured 97% diffraction efficiency in the -1 order and damage thresholds of 4.4 and 0.18 J/cm(2) with 5-ns and 1-ps laser pulses, respectively, at a wavelength of 532 nm in working conditions.
Treatment of allergic rhinitis (1994)

Allergic rhinitis is a common chronic respiratory illness that affects quality of life, productivity, and other comorbid conditions, including asthma. Treatment should be based on the patient's age and severity of symptoms. Patients should be advised to avoid known allergens and be educated about their condition. Intranasal corticosteroids are the most effective treatment and should be first-line therapy for mild to moderate disease. Moderate to severe disease not responsive to intranasal corticosteroids should be treated with second-line therapies, including antihistamines, decongestants, cromolyn, leukotriene receptor antagonists, and nonpharmacologic therapies (e.g., nasal irrigation). With the exception of cetirizine, second-generation antihistamines are less likely to cause sedation and impair performance. Immunotherapy should be considered in patients with a less than adequate response to usual treatments. Evidence does not support the use of mite-proof impermeable covers, air filtration systems, or delayed exposure to solid foods in infancy.
Using Microfluidics to Observe the Effect of Mixing on Nucleation of Protein Crystals (2005)

This paper analyzes the effect of mixing on nucleation of protein crystals. The mixing of protein and precipitant was controlled by changing the flow rate in a plug-based microfluidic system. The nucleation rate inversely depended on the flow rate, and flow rate could be used to control nucleation. For example, at higher supersaturations, precipitation happened at low flow rates while large crystals grew at high flow rates. Mixing at low flow velocities in a winding channel induces nucleation more effectively than mixing in straight channels. A qualitative scaling argument that relies on a number of assumptions is presented to understand the experimental results. In addition to helping fundamental understanding, this result may be used to control nucleation, using rapid chaotic mixing to eliminate formation of precipitates at high supersaturation and using slow chaotic mixing to induce nucleation at lower supersaturation.
Potent and selective inhibition of human nitric oxide synthases. Inhibition by non-amino acid isothioureas. (1994)

S-Ethylisothiourea was a potent competitive inhibitor of human nitric oxide synthase (NOS), with Ki values of 17, 36, and 29 nM for the inducible (i), endothelial (e), and neuronal (n) isozymes, respectively. Unlike some potent inhibitors of NOS, no time dependence was observed. S-Ethylisothiourea was not a detectable substrate for eNOS. S-Ethylisothiourea was also a potent inhibitor of mouse iNOS (Ki value of 5.2 nM), and its binding perturbed the spectrum of iNOS consistent with its altering the environment of the bound heme. The optimum binding of S-ethyl- and S-isopropylisothiourea relative to 70 other analogs suggested that these alkyl substitutions fit into a small hydrophobic pocket. Most isothioureas were 2-6-fold selective for the human iNOS (Ki for iNOS versus Ki for eNOS), with one being 19-fold selective. The cyclized mimics of S-ethylisothiourea, 2-NH2-thiazoline, and 2-NH2-thiazole, were also competitive inhibitors of human NOS. A third structural class of inhibitors, bisisothioureas, were, in general, the most selective in their inhibition of human iNOS. S,S'-(1,3-Phenylenebis(1,2-ethanediyl))bisisothiourea was 190-fold selective (Ki value of 0.047 microM against iNOS versus 9.0 microM against eNOS). These results demonstrate that potent and selective inhibition of human NOS isozymes is achievable.
MR-guided parenchymal delivery of adeno-associated viral vector serotype 5 in non-human primate brain (2017)

The present study was designed to characterize transduction of non-human primate brain and spinal cord with AAV5 viral vector after parenchymal delivery. AAV5-CAG-GFP (1 × 10<sup>13</sup> vector genomes per milliliter (vg ml<sup>-1</sup>)) was bilaterally infused either into putamen, thalamus or with the combination left putamen and right thalamus. Robust expression of GFP was seen throughout infusion sites and also in other distal nuclei. Interestingly, thalamic infusion of AAV5 resulted in the transduction of the entire corticospinal axis, indicating transport of AAV5 over long distances. Regardless of site of injection, AAV5 transduced both neurons and astrocytes equally. Our data demonstrate that AAV5 is a very powerful vector for the central nervous system and has potential for treatment of a wide range of neurological pathologies with cortical, subcortical and/or spinal cord affection.
The Composition of Cometary Volatiles (2004)

The composition of cometary ices provides key information on the chemical and physical properties of the outer solar nebula where comets formed, 4.6 G.y. ago. This chapter summarizes our current knowledge of the volatile composition of cometary nuclei, based on spectroscopic observations and in situ measurements of parent molecules and noble gases in cometary comae. The processes that govern the excitation and emission of parent molecules in the radio, infrared (IR), and ultraviolet (UV) wavelength regions are reviewed. The techniques used to convert line or band fluxes into molecular production rates are described. More than two dozen parent molecules have been identified, and we describe how each is investigated. The spatial distribution of some of these molecules has been studied by in situ measurements, long-slit IR and UV spectroscopy, and millimeter wave mapping, including interferometry. The spatial distributions of CO, H2CO, and OCS differ from that expected during direct sublimation from the nucleus, which suggests that these species are produced, at least partly, from extended sources in the coma. Abundance determinations for parent molecules are reviewed, and the evidence for chemical diversity among comets is discussed.
Activation of granulocyte cytotoxic function by purified mouse colony-stimulating factors. (1983)

Highly purified mouse colony-stimulating factors (CSF) were tested for their effect on neutrophil cytotoxic function in a homologous antibody-dependent cell-mediated cytotoxicity (ADCC) assay in which TNP-coupled mouse thymoma cells coated with mouse anti-TNP antibodies were used as targets, and purified normal mouse bone marrow neutrophils or induced peritoneal neutrophils were used as effector cells. Biochemically pure granulocyte-macrophage (GM)- and granulocyte (G)-CSF enhanced the cytotoxic activity of neutrophils obtained from both sources, allowing them to kill target cells at low antibody concentrations. Furthermore, GM- and G-CSF showed an additive effect, suggesting either the presence of separate receptors for GM- and G-CSF or of separate subsets of neutrophils. Induced peritoneal neutrophils showed a higher level of basal cytotoxic activity than did bone marrow neutrophils, suggesting neutrophil activation in vivo, but both reached similar levels of cytotoxicity upon maximal stimulation with CSF. In addition, CSF was found to be cross-reactive between mouse and human species in their enhancement of neutrophil cytotoxicity. By testing purified mouse CSF on human neutrophils, it could be shown that G-CSF and GM-CSF are functionally distinct molecules, because only G-CSF enhanced ADCC by human neutrophils. These experiments show that the purified factors that control the production of neutrophils by progenitor cells in vitro also activate differentiated neutrophils to carry out their cytotoxic activity in a more effective manner.
Pulse Interval and Width Modulation for Video Transmission (1978)

This paper proposes new pulse analog modulation system; Pulse Interval and Width Modulation suitable for light emitting diodes. In this system pulses have information on both their width and interval between them. Pulse Interval and Width Modulation is characterized by the following compared with Pulse Interval Modulation. First: Pulse repetition frequency is reduced by one half. Second: Duty ratio is 50 % on the average. Third: More power is needed while carrier to noise ratio could be improved instead. The paper shows how it works and comparison with another pulse analog modulation such as Pulse Frequency Modulation or Pulse Interval Modulation. The paper also shows an experiment of twin channel transmission employing two light emitting diodes, two optical fiber transmission lines and two PIN photodiodes as an example of application of Pulse Interval and Width Modulation.