gebhart/patrepeval huggingface dataset:
Characterization of Sialyloligosaccharide Binding by Recombinant Soluble and Native Cell-associated CD22 (1995)

CD22, a B cell-specific receptor of the immunoglobulin superfamily, has been demonstrated to bind to oligosaccharides containing alpha 2-6-linked sialic acid (Sia) residues. Previously, we demonstrated that the minimal structure recognized by this lectin is the trisaccharide Sia alpha 2-6Gal beta 1-4GlcNAc, as found on N-linked, O-linked, or glycolipid structures (Powell, L., and Varki, A. (1994) J. Biol. Chem. 269, 10628-10636). Here we utilize a soluble immunoglobulin fusion construct (CD22Rg) to determine directly by equilibrium dialysis the stoichiometry (2:1) and dissociation constant (32 microM) for Neu5Ac alpha 2-6Gal beta 1-4Glc binding. Inhibition assays performed with over 30 different natural and synthetic sialylated and/or sulfated compounds are utilized to define in greater detail specific structural features involved in oligosaccharide-protein binding. Specifically, the critical features required for binding include the exocyclic hydroxylated side chain of the Sia residue and the alpha 2-6 linkage position to the underlying Gal unit. Surprisingly, alterations of the 2-, 3-, and 4-positions of the latter residue have limited effect on the binding. The nature of the residue to which the Gal is attached may affect binding. Bi(alpha 2-6)-sialylated biantennary oligosaccharides are capable of simultaneously interacting with both lectin sites present on the dimeric CD22Rg fusion construct, giving a marked improvement in binding over monosialylated compounds. Furthermore, data are presented indicating that full-length native CD22, expressed on the surface of Chinese hamster ovary cells, is structurally and functionally a multimeric protein, demonstrating a higher apparent affinity for multiply sialylated compounds over monosialylated compounds. These observations provide a mechanism for strong CD22-dependent cell adhesion despite the relatively low Kd for protein-sugar binding.
Use of a vaccine strain of measles virus genetically engineered to produce carcinoembryonic antigen as a novel therapeutic agent against glioblastoma multiforme. (2003)

Despite the most aggressive medical and surgical treatments, glioblastoma multiforme remains incurable with a median survival of <1 year. We investigated the antitumor potential of a novel viral agent, an attenuated strain of measles virus (MV), derived from the Edmonston vaccine lineage, genetically engineered to produce carcinoembryonic antigen (CEA). CEA production as the virus replicates can serve as a marker of viral gene expression. Infection of a variety of glioblastoma cell lines including U87, U118, and U251 at MOIs 0.1, 1, and 10 resulted in significant cytopathic effect consisting of excessive syncycial formation and massive cell death at 72-96 h from infection. terminal deoxynucleotidyltransferase-mediated nick end labeling assays demonstrated the mechanism of cell death to be predominantly apoptotic. The efficacy of this approach in vivo was examined in BALB/c nude mice by using both s.c. and intracranial orthotopic U87 tumor models. In the s.c. U87 model, mice with established xenografts were treated with a total dose of 8 x 10(7) plaque forming units of MV-CEA, administered i.v. Mice treated with UV light inactivated MV, and untreated mice with established U87 tumors were used as controls. There was statistically significant regression of s.c. tumors (P < 0.001) and prolongation of survival (P = 0.007) in MV-CEA treated animals compared with the two control groups. In the intracranial orthotopic U87 model, there was significant regression of intracranial U87 tumors treated with intratumoral administration of MV-CEA at a total dose of 1.8 x 10(6) plaque forming units as assessed by magnetic resonance image (P = 0.002), and statistically significant prolongation of survival as compared with mice that received UV-inactivated virus and untreated mice (P = 0.02). Histological examination of brains of MV-CEA-treated animals revealed complete regression of the tumor with the presence of a residual glial scar and reactive changes, mainly presence of hemosiderin-laden macrophages. In addition, CEA levels in the peripheral blood in both the s.c. and orthotopic models increased before tumor regression, indicating viral gene expression, and returned to normal when the tumors regressed. Ifnar(ko) CD46 Ge transgenic mice, susceptible to MV infection, were used to assess central nervous system toxicity of MV-CEA. Intracranial administration of MV-CEA into the caudate nucleus of Ifnar(ko) CD46 Ge did not result in clinical neurotoxicity. Pathologic examination demonstrated limited microglial infiltration surrounding the injection site. In summary, MV-CEA has potent antitumor activity against gliomas in vitro, as well as in both s.c. and orthotopic U87 animal models. Monitoring CEA levels in the serum can serve as a low-risk method of detecting viral gene expression during treatment, and could allow dose optimization and individualization of treatment.
Establishment and characterization of a novel Waldenström macroglobulinemia cell line, MWCL-1 (2011)

Waldenström macroglobulinemia (WM) is a rare, lymphoplasmacytic lymphoma characterized by hypersecretion of immunoglobulin M (IgM) protein and tumor infiltration into the bone marrow and lymphatic tissue. Our understanding of the mechanisms driving the development and progression of WM is currently by the shortage of representative cell models available for study. We describe here the establishment of a new WM cell line, MWCL-1. Comprehensive genetic analyses have unequivocally confirmed a clonal relationship between this novel cell line and the founding tumor. MWCL-1 cells exhibit an immunophenotype consistent with a diverse, tumor clone composed of both small B lymphocytes and larger lymphoplasmacytic cells and plasma cells: CD3⁻, CD19⁺, CD20⁺, CD27⁺, CD38⁺, CD49D⁺, CD138⁺, cIgM⁺, and κ⁺. Cytogenetic studies identified a monoallelic deletion of 17p13 (TP53) in both the cell line and the primary tumor. Direct DNA resequencing of the remaining copy of TP53 revealed a missense mutation at exon 5 (V143A, GTG>GCG). In accordance with primary WM tumors, MWCL-1 cells retain the ability to secrete high amounts of IgM protein in the absence of an external stimulus. The genetic, immunophenotypic, and biologic data presented here confirm the validity of the MWCL-1 cell line as a representative model of WM.
Recycling Chlorine from Hydrogen Chloride: A New and Economical Electrolytic Process (1998)

In the chemical industry, chlorine is one of the most widely used chemicals. The chlorine molecule is often used as a modifier or as an aid to manufacture other chemicals. Oftentimes, some or all of the chlorine used is reduced to hydrogen chloride, a waste byproduct.
GaAs/AlGaAs waveguide pin photodiodeswith non-absorbing inputfacets fabricated by quantum well intermixing (2000)

Waveguide photodiodes with non-absorbing input windows have been fabricated using a sputtered silica quantum well intermixing technique. Thermal modelling of the GaAs/AlGaAs photodiodes indicates that facet temperatures can be significantly reduced with window lengths of greater than 10 /spl mu/m. Device testing shows that optical damage occurs at double the power of conventional photodiodes with absorbing facets.
Investigational antibody drug conjugates for solid tumors (2011)

Key challenges the ADC field is facing, including potency and safety, can be addressed effectively by introducing novel research concepts with transformational potential for ADC development.
Semaphorins in cancer (2005)

The semaphorins are the products of a large family of genes currently containing more than 30 members. These genes are divided into eight classes of which classes 1, 2 and 8 contain invertebrate and viral semaphorins, while classes 3-7 contain the vertebrate semaphorins. The semaphorins have been implicated in diverse developmental processes such as axon guidance during nervous system development and regulation of cell migration. Plexin receptors function as binding and signal transducing receptors for all semaphorins except for the class-3 semaphorins which bind to neuropilins which subsequently activate signaling through associated plexins. The class-3 semaphorins semaphorin-3B (s3b) and semaphorin-3F (s3f) function additionally as potent inhibitors of tumor development in small cell lung carcinoma. Recent evidence indicates that these semaphorins modulate the adhesive and migratory properties of responsive malignant cells. S3f as well as semaphorin-3A (s3a) were also found to function as inhibitors of angiogenesis, and it was shown that the anti-angiogenic properties of s3f contribute significantly to its anti-tumorigenic properties. In contrast with these inhibitory semaphorins, there is some evidence indicating that semaphorins such as semaphorin-3C (s3c), semaphorin-3E (s3e), semaphorin-4D (s4d), semaphorin-5C (s5c) semaphorin-6A (s6a) and semaphorin-6b (s6b) may contribute to tumorigenesis or to tumor progression. In this review we discuss the semaphorins, their receptors and their signal transduction mechanisms, and evidence linking semaphorins to the control of tumorigenesis and tumor progression.
Chains of recurrences---a method to expedite the evaluation of closed-form functions (1994)

Chains of Recurrences (CR's) are introduced as an effective method to evaluate functions at regular intervals. Algebraic properties of CR's are examined and an algorithm that constructs a CR for a given function is explained. Finally, an implementation of the method in MAXIMA/Common Lisp is discussed.
Linkage of kdr-Type resistance and the para-Homologous sodium channel gene in German cockroaches (Blattella germanica) (1994)

Pyrethroids are an important class of insecticides for controlling insect pests, including the German cockroach. Unfortunately, many insects have developed resistance to pyrethroids. One of the most important mechanisms of resistance is kdr (knockdown resistance) which is characterized by neural insensitivity to pyrethroids and DDT. To investigate whether the voltage-dependent sodium channel is involved in kdr-type resistance in the German cockroach, we isolated a 120 bp DNA fragment of the para-homologous sodium channel gene from German cockroaches. Using this fragment as a probe, we identified a restriction fragment length polymorphism (RFLP) of the para-homologous sodium channel gene between susceptible and kdr-type resistant German cockroaches. RFLP analysis of F2 and backcross cockroach populations (total of 331 individuals) showed that all homozygous resistant individuals had a 3.7 kb EcoRI fragment, all homozygous susceptible individuals had a 3.0 kb EcoRI fragment, and all heterozygous individuals had both 3.7 and 3.0 kb fragments. No recombination was detected between the kdr-type resistance locus and the para-homologous sodium channel gene. This suggests that the kdr-type resistance locus and para-homologous sodium channel gene are identical or tightly linked (< 0.2 cM) in German cockroaches. Our results provide strong evidence that modification of para-homologous sodium channels is associated with kdr-type resistance.
A Porphyrin C-Nucleoside Incorporated into DNA (2002)

[reaction: see text] A free porphyrin coupled on 2-deoxy-D-ribose was synthesized and incorporated into DNA via phosphoramidite chemistry. Substitution at the ends of a 5'-modified self-complementary duplex was found to be thermally and thermodynamically stabilizing. The porphyrin moiety strongly intercalates in the duplex when located near the center, and retains its fluorescence properties in DNA.
RTM artifact removal via a fast algorithm for wavefield decomposition (2016)

In order to improve the quality and attenuate the artifacts of the reverse time migration (RTM) images, the wavefield decomposition via different wave propagation characteristics was proposed to cope with the backscattering RTM noise. The traditional wavefield decomposition algorithm, which is implemented in the frequency-wavenumber (f-k) domain, is computationally intensive compared with the numerical cost of RTM. In fact, the f-k domain method significantly depends on the optimization of the fast Fourier transform (FFT). To improve the numerical efficiency, we propose an algorithm to perform wavefield decomposition in the time-space domain via the Hilbert transform (HT). It can provide comparable accuracy as the f-k domain method. Furthermore, we propose an optimization scheme to speed up the HT for 3D wavefield decomposition based on current single instruction multiple data (SIMD) architecture and multi-core processors. The numerical examples demonstrate that the proposed approach can significantly reduce the computational cost while preserving the quality of wavefield decomposition. We apply the efficient approach to both the RTM images and angle domain common-image gathers from the 3D SEAM TTI model to validate the effectiveness and robustness. Presentation Date: Tuesday, October 18, 2016 Start Time: 1:00:00 PM Location: 140 Presentation Type: ORAL
Interactive Additive Diffraction Synthesis (2016)

Lens flare, comprising diffraction patterns of direct lights and ghosts of an aperture, is one of artistic artifacts in optical systems. The generation of far-field diffraction patterns has commonly used Fourier transform of the iris apertures. While such outcomes are physically faithful, more flexible and intuitive editing of diffraction patterns has not been explored so far. In this poster, we present a novel scheme of diffraction synthesis, which additively integrates diffraction elements. We decompose the apertures into curved edges and circular core so that they abstract non-symmetric streaks and circular core highlights, respectively. We then apply Fourier transform for each, rotate them, and finally composite them into a single output image. In this way, we can easily generate diffraction patterns similarly to that of the source aperture and more exaggerated ones, as well.
111 kW (0.5 mJ) pulse amplification at 1.5 μm using a gated cascade of three erbium-doped fiber amplifiers (1993)

The generation of high peak power pulses by amplification of the output from a distributed feedback diode laser is demonstrated using a cascade of three erbium-doped fiber amplifiers (EDFAs) separated by an acousto-optic gate. The optimized amplifier chain consisted of two high efficiency single-mode EDFAs pumped with 40 mW at 980 nm, followed by a multimode EDFA pumped with 1.5 W at 978 nm. At low repetition rates, peak output powers of 111 kW and energies of 0.5 mJ at 1.534 μm were obtained.
Spontaneous Peripheral T-cell Responses toward the Tumor-Associated Antigen Cyclin D1 in Patients with Clear Cell Renal Cell Carcinoma (2013)

Renal cell carcinoma (RCC) is a heterogeneous group of kidney cancers with clear cell RCC (ccRCC) as the major subgroup. To expand the number of clinically relevant tumor-associated antigens (TAA) that can be targeted by immunotherapy, we analyzed samples from 23 patients with primary ccRCC for the expression and immunogenicity of various TAAs. We found high-frequency expression of MAGE-A9 and NY-ESO-1 in 36% and 55% of samples, respectively, and overexpression of PRAME, RAGE-1, CA-IX, Cyclin D1, ADFP, C-MET, and RGS-5 in many of the tumor samples. We analyzed the blood of patients with HLA-A2(+) ccRCC for the presence of CD8(+) T cells specific for TAA-derived HLA-A2-restricted peptides and found spontaneous responses to cyclin D1 in 5 of 6 patients with Cyclin D1-positive tumors. Cyclin D1-specific CD8(+) T cells secreted TNF-α, IFN-γ, and interleukin-2 (IL-2), and degranulated, indicating the presence of polyfunctional tumor-specific CD8(+) T cells in the blood of these patients with ccRCC. The high frequency (43%) of Cyclin D1 overexpression and the presence of functional cyclin D1-specific T cells in 83% of these patients with ccRCC suggest that cyclin D1 may be a target for immunotherapeutic strategies.
Cationic PAMAM Dendrimers Aggressively Initiate Blood Clot Formation (2012)

Poly(amidoamine) (PAMAM) dendrimers are increasingly studied as model nanoparticles for a variety of biomedical applications, notably in systemic administrations. However, with respect to blood-contacting applications, amine-terminated dendrimers have recently been shown to activate platelets and cause a fatal, disseminated intravascular coagulation (DIC)-like condition in mice and rats. We here demonstrate that, upon addition to blood, cationic G7 PAMAM dendrimers induce fibrinogen aggregation, which may contribute to the in vivo DIC-like phenomenon. We demonstrate that amine-terminated dendrimers act directly on fibrinogen in a thrombin-independent manner to generate dense, high-molecular-weight fibrinogen aggregates with minimal fibrin fibril formation. In addition, we hypothesize this clot-like behavior is likely mediated by electrostatic interactions between the densely charged cationic dendrimer surface and negatively charged fibrinogen domains. Interestingly, cationic dendrimers also induced aggregation of albumin, suggesting that many negatively charged blood proteins may be affected by cationic dendrimers. To investigate this further, zebrafish embryos were employed to more specifically determine the speed of this phenomenon and the pathway- and dose-dependency of the resulting vascular occlusion phenotype. These novel findings show that G7 PAMAM dendrimers significantly and adversely impact many blood components to produce rapid coagulation and strongly suggest that these effects are independent of classic coagulation mechanisms. These results also strongly suggest the need to fully characterize amine-terminated PAMAM dendrimers in regard to their adverse effects on both coagulation and platelets, which may contribute to blood toxicity.
Evaluation of activity of putative superoxide dismutase mimics. Direct analysis by stopped-flow kinetics. (1993)

By stopped-flow kinetic analysis, we have directly evaluated the superoxide dismutase (SOD) activity of a number of organic nitroxides and iron- and manganese-based complexes that have been attributed with having SOD activity based upon competition experiments with cytochrome c. In 60 mM HEPES buffer, pH 8.1, or 50 mM potassium phosphate buffer, pH 7.8, Mn(II) and manganese complexes of desferal had no detectable SOD activity by stopped-flow analysis (catalytic rate constant (kcat) < 10(5.5) M-1 s-1), whereas Mn(II) and manganese complexes of desferal inhibited the reduction of cytochrome c by superoxide generated by the xanthine/xanthine oxidase system. Fe(II)-N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (FeTPEN) was eight times more active than Fe(III)-tris[N-(2-pyridylmethyl)-2-aminoethyl]amine(Fe-TPAA) in the cytochrome c assay, but only FeTPAA catalyzed the first-order decay of superoxide (kcat = 2.15 x 10(6) M-1 s-1) by stopped-flow. Fe(III)-tetrakis(4-N-methylpyridyl)porphine (FeTMPP) was active at low micromolar concentrations in both the cytochrome c and stopped-flow assays. At high micromolar concentrations, the organic nitroxides 2,2,6,6-tetramethylpiperidin-1-yloxy (TEMPO) and 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-yloxy (TEMPOL) were inhibitory in the cytochrome c assay, but showed no detectable SOD activity by stopped-flow. None of the tested compounds inhibited xanthine oxidase activity as shown by the measurement of urate production. Under the conditions of the cytochrome c assay, FeTPEN, TEMPO, and TEMPOL oxidized reduced cytochrome c which rationalizes the false positives for these compounds in this assay. The inhibitory activities of Mn(II) and the manganese desferal complexes in the cytochrome c assay appear to be due to a stoichiometric, not catalytic, reaction with superoxide as catalytic amounts of these agents do not induce a first-order decay of superoxide as shown by stopped-flow.
Identification of ciliary neurotrophic factor (CNTF) residues essential for leukemia inhibitory factor receptor binding and generation of CNTF receptor antagonists. (1996)

Ciliary neurotrophic factor (CNTF) drives the sequential assembly of a receptor complex containing the ligand-specific alpha-receptor subunit (CNTFR alpha) and the signal transducers gp130 and leukemia inhibitory factor receptor-beta (LIFR). The D1 structural motif, located at the beginning of the D-helix of human CNTF, contains two amino acid residues, F152 and K155, which are conserved among all cytokines that signal through LIFR. The functional importance of these residues was assessed by alanine mutagenesis. Substitution of either F152 or K155 with alanine was found to specifically inhibit cytokine interaction with LIFR without affecting binding to CNTFR alpha or gp130. The resulting variants behaved as partial agonists with varying degrees of residual bioactivity in different cell-based assays. Simultaneous alanine substitution of both F152 and K155 totally abolished biological activity. Combining these mutations with amino acid substitutions in the D-helix, which enhance binding affinity for the CNTFR alpha, gave rise to a potent competitive CNTF receptor antagonist. This protein constitutes a new tool for studies of CNTF function in normal physiology and disease.
In vivo tissue disposition of 3'-azido-3'-deoxythymidine and its anabolites in control and retrovirus-infected mice. (1997)

At present, 3'-azido-3'-deoxythymidine (AZT; zidovudine) remains the drug of choice for initiating AIDS therapy. This drug in itself is inactive; it needs to be converted intracellularly by a series of cellular kinases to AZT 5'-triphosphate (AZT-TP) to exert antiviral activity. The purpose of this study was to examine the in vivo disposition of the phosphorylated AZT anabolites in different target tissues and to investigate the effects of chronic retrovirus infection on the tissue disposition of AZT anabolites. Female C57BL/6 mice at 20 weeks after inoculation with LP-BM5 murine leukemia virus, as well as age-matched control animals, were dosed subcutaneously with 25 mg/kg of AZT. The dosing solution contained [3H]AZT with a specific activity of 87 mCi/mmol. The levels of AZT and its phosphorylated anabolites were determined in tissues collected at different times after AZT administration using an analytical method coupling an ion-pair HPLC separation procedure with radioactivity detection after the separation. The tissue-to-plasma AZT ratios in control mice could be ranked in the following order: kidneys > muscle approximately equal to spleen approximately equal to liver approximately equal to heart approximately equal to lung > thymus > lymph nodes > brain. Similar rank order was observed in infected animals, with the exception that significantly higher AZT levels were found in the lymph nodes, where the tissue-to-plasma AZT ratios in lymph nodes were higher than those in thymus tissues. Tissue AZT 5'-monophosphate profiles tended to parallel the AZT profiles in most tissues examined. Delays in the appearance of AZT 5'-diphosphate and AZT-TP were observed in all tissues tested. AZT-TP content was not detectable in any of the brain samples analyzed. The conversion of AZT to AZT anabolites was found to be highest in the spleen and bone marrow samples from both control and infected animals. Lymph nodes of the control animals showed poor ability to phosphorylate AZT to its active triphosphate moiety. This ability was significantly enhanced in infected animals. We concluded that the in vivo disposition of AZT anabolites after a single dose administration of AZT is tissue-specific in mice and that experimentally induced chronic retrovirus infection resulted in the most significant changes in the distribution of AZT into the lymph nodes and in the phosphorylation of AZT in this important target tissue. Further studies are needed to relate the tissue-specific disposition of AZT anabolites to the therapeutic problems encountered with AZT treatment.