gebhart/patrepeval huggingface dataset:
Interleukin‐12 and B7.1 co‐stimulation cooperate in the induction of effective antitumor immunity and therapy of established tumors (1996)

Interleukin-12 (IL-12) promotes specific and long-lasting anti-tumor immunity mediated by T cells in a variety of murine tumor models. IL-12 also synergizes with B7.1 (CD80) co-stimulation to induce proliferation and cytokine production by both human and murine T cells in vitro. We evaluated the combined anti-tumor efficacy of IL-12 and B7.1 gene delivery in two apparently poorly immunogenic tumor models (TS/A and MCA207). In both of these models, expression of B7.1 and production of IL-12 in the inoculum led to improved anti-tumor immunity, with up to 80% long-term tumor-free animals (vs 0-20% of mice remaining tumor free when inoculated with either B7.1- or IL-12-transfected tumors alone). Tumor-free mice were capable of rejecting a subsequent rechallenge with the wild-type tumor in 66% of the cases. Cooperativity was dependent upon the level of IL-12 secreted by engineered cells. IL-12 delivery required B7 expression of therapeutic effects to be observed in these models. Vaccines provided at a site distal to a control, non-transfected tumor slowed (TS/A) or abrogated (MCA207) the progression of wild-type tumors. The synergistic anti-tumor effects associated with combined application of B7.1- and IL-12-transfected tumors were partially negated by systemic administration of the CD28-B7.1/B7.2 antagonist CTLA4-Ig or by inoculation with neutralizing antibodies directed against murine interferon-gamma or tumor necrosis factor-alpha, two cytokines elicited in response to IL-12 stimulation. These data support the potential clinical utility of combined gene therapy using IL-12- and B7.1-engineered autologous cells (tumor or fibroblasts) as a vaccine to elicit specific anti-tumor immunity.
Homologous recombination at c-fyn locus of mouse embryonic stem cells with use of diphtheria toxin A-fragment gene in negative selection. (1990)

In attempting to produce a mutant mouse with embryonic stem cells, the critical step is the efficient isolation of homologous recombinants; the frequency of the homologous recombination is usually low and the potency of the cells to differentiate into germ cells is unstable in culture. Here, we report an efficacious method for such isolation in which the diphtheria toxin A-fragment gene is used to negatively select nonhomologous recombinants. In contrast to the use of the herpes simplex virus thymidine kinase gene, the selection can be made singly by the neomycin analog G418 without using a drug such as ganciclovir, a nucleoside analog. At the c-fyn locus, the diphtheria-toxin negative selection enriched the recombinants about 10-fold, and half of the cells integrating with the neomycin phosphotransferase gene were homologous recombinants.
Relationships Among Pathogenic and Nonpathogenic Isolates ofFusarium oxysporumBased on the Partial Sequence of the Intergenic Spacer Region of the Ribosomal DNA (1996)

Using PCR, we amplified and sequenced approximately 1,000 bp of the 5' end of the intergenic spacer (IGS) of the rDNA in 15 isolates of Fusarium oxysporum and one isolate of F. subglutinans. Isolates were selected to represent diversity in our collection based on differences in pathogenic race, vegetative compatibility group (VCG), mitochondrial DNA (mtDNA) haplotype, IGS haplotype, and DNA fingerprint. The objective of this research was to clarify the origin of virulence within F. oxysporum, the relationship between pathogenic and nonpathogenic strains, and the evolution of the different races of F. oxysporum f. sp. melonis. Bootstrapped parsimony analysis of the partial IGS sequence data identified a phylogenetic tree with highly significant branches. The two F. oxysporum f. sp. melonis VCGs, 0131 and 0134, were separated into distinct lineages. Race was not distinguished by significant IGS sequence differences within the pathogen VCGs. One exception was a race 1 isolate which was associated with VCG 0131 but, based on both mtDNA and IGS haplotype, had greater affinity with VCG 0134. Two IGS sequence types were found in this race 1 isolate, one suggesting an affiliation with VCG 0131 and the other similar to isolates in VCG 0134. This may have resulted from past somatic or sexual interactions between F. oxysporum f. sp. melonis, VCGs 0131 and 0134. Nonpathogens that were vegetatively compatible with the pathogen were not closely related to the pathogen based on IGS sequence data. Thus, nonpathogens and pathogens may share common alleles at vegetative compatibility loci by coincidence rather than because of recent clonal derivation from a common ancestor.
Assessment of Neuroprotective Effects of Glutamate Modulation on Glaucoma-Related Retinal Ganglion Cell Apoptosis In Vivo (2006)

This novel SSP model was validated as a useful tool for screening neuroprotective strategies in vivo. Group II mGluR modulation may be a useful treatment for RGC death. Combination therapy optimized to limit neurotoxic effects of MK801 may be an effective neuroprotective approach in retinal degenerative disease. Furthermore, treatments that minimize secondary RGC degeneration may be most useful in glaucoma.
Two independent mechanisms essential for tumor angiogenesis: inhibition of human melanoma xenograft growth by interfering with either the vascular endothelial growth factor receptor pathway or the Tie-2 pathway. (1999)

Protein ligands and receptor tyrosine kinases that specifically regulate endothelial cell function are mainly involved in physiological as well as in disease-related angiogenesis. These ligand/receptor systems include the vascular endothelial growth factor (VEGF) and the angiopoietin (Ang) families, and their receptors, the VEGF receptor family and the tyrosine kinase with immunoglobulin-like and epidermal growth factor homology domains (Tie) family. In the present study, the contribution of these endothelium-specific ligand/receptor systems to tumor angiogenesis was evaluated. A375v human melanoma cells, which express at least the angiogenic growth factors VEGF, VEGF-C, and Ang-1, were stably transfected to overexpress the extracellular ligand-binding domains of the endothelium-specific receptor tyrosine kinases fms-like tyrosine kinase-1 (Flt-1), Flt-4, Tie-1, and Tie-2, respectively. In vitro proliferation and colony formation assays confirmed that expression of the extracellular receptor domains inhibited neither tumor cell mitogenesis nor the ability to produce anchorage-independent growth. Nude mouse xenografts revealed that interference with either the VEGF receptor pathway or the Tie-2 pathway resulted in a significant inhibition of tumor growth and tumor angiogenesis. In contrast, interference with the Flt-4 pathway or the Tie-1 pathway was without significant effect. Our results show that both the VEGF receptor pathway and the Tie-2 pathway are essential for A375v melanoma xenograft growth. The inhibition of the VEGF receptor pathway cannot be compensated by the Tie-2 pathway, nor vice versa. These findings suggest that the VEGF receptor pathway and the Tie-2 pathway have to be considered as two independent mediators essential for the process of in vivo angiogenesis.
Dissociative inhibition of dimeric enzymes. Kinetic characterization of the inhibition of HIV-1 protease by its COOH-terminal tetrapeptide (1991)

Human immunodeficiency virus 1 (HIV-1) protease is an aspartyl protease composed of two identical protomers linked by a four-stranded antiparallel beta-sheet consisting of the NH2- and COOH-terminal segments (Weber, I.T. (1990) J. Biol. Chem. 265, 10492-10496). Kinetic analysis of the HIV-1 protease-catalyzed hydrolysis of a fluorogenic substrate demonstrates that the enzyme is an obligatory dimer. At pH = 5.0, 0.1 M sodium acetate, 1 M NaCl, 1 mM EDTA buffer, 37 degrees C, the equilibrium dissociation constant, Kd = 3.6 +/- 1.9 nM. We found that the tetrapeptide Ac-Thr-Leu-Asn-Phe-COOH, corresponding to the COOH-terminal segment of the enzyme, is an excellent inhibitor of the enzyme. Kinetic analysis shows that the inhibitor binds to the inactive protomers and prevents their association into the active dimer (dissociative inhibition). The dissociative nature of this inhibition is consistent with the results obtained from sedimentation equilibrium experiments in which the apparent molecular weight of the enzyme was observed to be 20,800 +/- 1,500 and 12,100 +/- 300, in the absence and presence of the COOH-terminal tetrapeptide, respectively. The dissociation constant of the protomer-inhibitor complex is Ki = 45.1 +/- 1.8 microM. This is the first kinetic analysis and direct experimental demonstration of noncovalent dissociative inhibition.
Oxygen-dependent laser inactivation of murine norovirus using visible light lasers (2018)

Results suggest formation of short-lived reactive oxygen species such as singlet oxygen by visible laser light as the cause of virus inactivation rather than via an ISRS mechanism which induces resonant vibrations.
Ionization of bromouracil and fluorouracil stimulates base mispairing frequencies with guanine (1993)

To test whether ionized base pairs influence polymerase-catalyzed misinsertion rates, we measured the efficiency of forming 5-bromouracil (B), 5-fluorouracil (F), and thymine base pairs with guanine and adenine as a function of pH using avian myeloblastosis reverse transcriptase. When B, F, and T were present as dNTP substrates, misincorporation efficiencies opposite G, normalized to incorporation of C opposite G, increased by about 20-, 13-, and 7-fold, respectively, as reaction pH increased from 7.0 to 9.5. Incorporation efficiencies to form the correct base pairs, B.A and F.A, normalized to T.A, decreased by 4- and 8-fold, respectively, with increasing pH. The effects of pH on misincorporation efficiencies were about 10-fold greater when B, F, and T were present as template bases. The relative misincorporation efficiencies of G opposite template B, F, and T, normalized to incorporation of A opposite B, F, and T, increased by about 430-, 370-, and 70-fold, respectively, as pH was increased from 6.5 to 9.5, while correct incorporation of A opposite template B and F decreased about 10-fold over the same pH range. Plots depicting incorrect and correct incorporation efficiencies versus pH were fit to a pH titration equation giving the fraction of ionized base as a function of pH. We conclude that avian myeloblastosis reverse transcriptase forms B.G and F.G mispairs in an ionized Watson-Crick conformation in preference to a neutral wobble structure containing favored keto tautomers of B or F. Although participation of disfavored enol tautomers in enzyme-catalyzed base mispair formation cannot be ruled out, the results are inconsistent with the "standard" disfavored tautomer model of mutagenesis. Instead, the data support a model in which ionization of halouracil bases is primarily responsible for B- and F-induced mutagenesis.
Inhibition of tumorigenesis driven by different Wnt proteins requires blockade of distinct ligand-binding regions by LRP6 antibodies (2010)

Disregulated Wnt/beta-catenin signaling has been linked to various human diseases, including cancers. Inhibitors of oncogenic Wnt signaling are likely to have a therapeutic effect in cancers. LRP5 and LRP6 are closely related membrane coreceptors for Wnt proteins. Using a phage-display library, we identified anti-LRP6 antibodies that either inhibit or enhance Wnt signaling. Two classes of LRP6 antagonistic antibodies were discovered: one class specifically inhibits Wnt proteins represented by Wnt1, whereas the second class specifically inhibits Wnt proteins represented by Wnt3a. Epitope-mapping experiments indicated that Wnt1 class-specific antibodies bind to the first propeller and Wnt3a class-specific antibodies bind to the third propeller of LRP6, suggesting that Wnt1- and Wnt3a-class proteins interact with distinct LRP6 propeller domains. This conclusion is further supported by the structural functional analysis of LRP5/6 and the finding that the Wnt antagonist Sclerostin interacts with the first propeller of LRP5/6 and preferentially inhibits the Wnt1-class proteins. We also show that Wnt1 or Wnt3a class-specific anti-LRP6 antibodies specifically block growth of MMTV-Wnt1 or MMTV-Wnt3 xenografts in vivo. Therapeutic application of these antibodies could be limited without knowing the type of Wnt proteins expressed in cancers. This is further complicated by our finding that bivalent LRP6 antibodies sensitize cells to the nonblocked class of Wnt proteins. The generation of a biparatopic LRP6 antibody blocks both Wnt1- and Wnt3a-mediated signaling without showing agonistic activity. Our studies provide insights into Wnt-induced LRP5/6 activation and show the potential utility of LRP6 antibodies in Wnt-driven cancer.
Omnidirectional camera calibration based on an approximate factorization method (2010)

A standard perspective image can be represented with part center area of an omnidirectional image from Micusik [12], can we generalize a few camera calibration methods from the perspective image to the omnidirectional image using part information in the center area of the omnidirectional image? In this paper, a novel omnidirectional camera calibration based on the approximate factorization method from multiple images is presented. This method first performs the approximate projective factorization algorithm using part of image points, which are less distorted than other feature points, in the center area of the omnidirectional image. Then, assuming zero skew and the principal point at the center of omnidirectional image, the initial value of camera intrinsic parameters can be computed. Last, the distortion intrinsic parameters are refined on minimizing the objective function. We demonstrate this method in experiment with synthetic data and real fisheye images.
Proteins as Initiators of Controlled Radical Polymerization: Grafting-from via ATRP and RAFT (2011)

Many recent developments in polymer chemistry have advanced the synthesis of materials in which synthetic polymers are immobilized to biological (macro)molecules to enhance the solubility, stability, activity, or therapeutic utility of the biological entity. In particular, the versatility and robust nature of controlled radical polymerization (CRP) has enabled access to a diverse family of new polymer bioconjugates. While nitroxide-mediated, atom transfer radical (ATRP), and reversible addition-fragmentation chain transfer (RAFT) polymerizations have all proven useful for the preparation of well-defined end-functional polymers capable of being efficiently conjugated to biological molecules, ATRP and RAFT have proven especially proficient for the synthesis of conjugates by direct polymerization of vinyl monomers from biological components functionalized to contain a group capable of initiating chain growth. This Viewpoint highlights several recent advances that have relied on grafting-from by CRP, with particular attention devoted to a recent report that seeks to facilitate the process of grafting-from proteins via ATRP under biologically relevant conditions.
Organization of choline acetyltransferase-containing structures in the forebrain of the rat (1986)

The cholinergic structures in the forebrain of the rat were studied immunohistochemically with a monoclonal antibody to choline acetyltransferase (ChAT) which has proven to be particularly suited to reveal the trajectory of ChAT-positive fibers and their terminations. The habenulo-interpeduncular tract contained the most distinctly ChAT-positive fibers. Here, ChAT-positivity was demonstrated in the perikarya, fibers and terminal field. From the basal forebrain, ChAT-positive fiber bundles could be followed rostrally to the olfactory bulb, dorsomedially to the neocortex and hippocampus, and dorsocaudally to the hippocampus. Terminations of ChAT-positive fibers in these regions were either boutons terminaux (in the interpeduncular nucleus), finely granular (in the hippocampus) or a network of varicose fibers (in the olfactory bulb and neocortex). Cholinergic terminal fields were also demonstrated in the following regions: the nucleus of the lateral olfactory tract, the olfactory tubercle, the pyriform cortex, the lateral nucleus and part of the basal nucleus of the amygdala, the caudate-putamen, the nucleus accumbens, some thalamic nuclei, and the suprachiasmatic nucleus of the hypothalamus. In most of these regions, ChAT-positivity appeared as either fine granules or a meshwork of varicose fibers.
Molecular epidemiology of human rotaviruses in Melbourne, Australia, from 1973 to 1979, as determined by electrophoresis of genome ribonucleic acid (1981)

Rotaviruses contain a double-stranded ribonucleic acid genome consisting of 11 segments. Gel electrophoresis separates genome segments and allows identification of strain differences. This electrophoretic typing technique was applied to rotavirus specimens from 116 children and 72 newborn babies. Between 1973 and 1979, 17 different electropherotypes of rotavirus were observed in children with acute gastroenteritis. These electropherotypes showed a sequential pattern of appearance, with a limited number of electropherotypes present at any given time. By contrast, only two electropherotypes were identified from isolates from newborn babies in seven hospitals during 1975 to 1979. These two electropherotypes were very similar and were never identified in children with acute gastroenteritis. One of the neonatal electropherotypes was found in the nurseries of five different hospitals and persisted in one hospital for 4 years. Electrophoretic typing techniques can be applied routinely and reproducibly to small samples of feces and could prove to be of value in epidemiological studies of rotavirus infection
Sensitivity to change of 3 Systemic Lupus Erythematosus Disease Activity Indices: international validation. (1994)

Our study confirms that the SLEDAI, SLAM and BILAG are comparable disease activity measures. SLEDAI appears to be sensitive to change in disease activity over time.
Mechanisms of normal and tumor-derived angiogenesis (2002)

Often those diseases most evasive to therapeutic intervention usurp the human body's own cellular machinery or deregulate normal physiological processes for propagation. Tumor-induced angiogenesis is a pathological condition that results from aberrant deployment of normal angiogenesis, an essential process in which the vascular tree is remodeled by the growth of new capillaries from preexisting vessels. Normal angiogenesis ensures that developing or healing tissues receive an adequate supply of nutrients. Within the confines of a tumor, the availability of nutrients is limited by competition among actively proliferating cells, and diffusion of metabolites is impeded by high interstitial pressure (Jain RK. Cancer Res 47: 3039-3051, 1987). As a result, tumor cells induce the formation of a new blood supply from the preexisting vasculature, and this affords tumor cells the ability to survive and propagate in a hostile environment. Because both normal and tumor-induced neovascularization fulfill the essential role of satisfying the metabolic demands of a tissue, the mechanisms by which cancer cells stimulate pathological neovascularization mimic those utilized by normal cells to foster physiological angiogenesis. This review investigates mechanisms of tumor-induced angiogenesis. The strategies used by cancer cells to develop their own blood supply are discussed in relation to those employed by normal cells during physiological angiogenesis. With an understanding of blood vessel growth in both normal and abnormal settings, we are better suited to design effective therapeutics for cancer.
Fas-disabling small exocyclic peptide mimetics limit apoptosis by an unexpected mechanism (2004)

Fas ligand- (FasL) mediated apoptosis is an important element of tissue-specific organ damage. We have developed biologically active small exocyclic peptide mimetics that disable apoptotic functions of Fas. The most effective mimetic binds to both its receptor and FasL with comparable affinity. In vitro, the most effective antagonist blocked FasL-induced cytotoxicity completely and specifically. In vivo, the antagonistic mimetic also prevented Concanavilin A (Con A) induced hepatitis, a CD4(+) T cell-mediated animal model of liver injury. Although current approaches prevent Fas receptor signaling by excluding FasL binding to Fas, the small molecule mimetics reported here disable Fas by promoting a defective Fas-FasL receptor complex. This event desensitizes FasL-mediated apoptosis by inhibiting extracellular signal regulated kinase activity and up-regulating NF-kappaB.
Exploiting the glioblastoma peptidome to discover novel tumour-associated antigens for immunotherapy (2012)

Peptides presented at the cell surface reflect the protein content of the cell; those on HLA class I molecules comprise the critical peptidome elements interacting with CD8 T lymphocytes. We hypothesize that peptidomes from ex vivo tumour samples encompass immunogenic tumour antigens. Here, we uncover >6000 HLA-bound peptides from HLA-A*02(+) glioblastoma, of which over 3000 were restricted by HLA-A*02. We prioritized in-depth investigation of 10 glioblastoma-associated antigens based on high expression in tumours, very low or absent expression in healthy tissues, implication in gliomagenesis and immunogenicity. Patients with glioblastoma showed no T cell tolerance to these peptides. Moreover, we demonstrated specific lysis of tumour cells by patients' CD8(+) T cells in vitro. In vivo, glioblastoma-specific CD8(+) T cells were present at the tumour site. Overall, our data show the physiological relevance of the peptidome approach and provide a critical advance for designing a rational glioblastoma immunotherapy. The peptides identified in our study are currently being tested as a multipeptide vaccine (IMA950) in patients with glioblastoma.
Nutritional Approach to Restore Impaired Intestinal Barrier Function and Growth After Neonatal Stress in Rats (2006)

Our results suggest that an adapted diet containing specific long-chain polyunsaturated fatty acids, prebiotics and probiotics can revert the negative imprinting of neonatal stress on both intestinal barrier function and growth.
Investigation of interference in multiple-input multiple-output wireless transmission at W band for an optical wireless integration system (2013)

We experimentally investigate the interference in multiple-input multiple-output (MIMO) wireless transmission by adjusting the relative locations of horn antennas (HAs) in a 100 GHz optical wireless integration system, which can deliver a 50 Gb/s polarization-division-multiplexing quadrature-phase-shift-keying signal over 80 km single-mode fiber-28 and a 2×2 MIMO wireless link. For the parallel 2×2 MIMO wireless link, each receiver HA can only get wireless power from the corresponding transmitter HA, while for the crossover ones, the receiver HA can get wireless power from two transmitter HAs. At the wireless receiver, polarization demultiplexing is realized by the constant modulus algorithm (CMA) in the digital-signal-processing part. Compared to the parallel case, wireless interference causes about 2 dB optical signal-to-noise ratio penalty at a bit-error ratio (BER) of 3.8×10(-3) for the crossover cases if similar CMA taps are employed. The increase in CMA tap length can reduce wireless interference and improve BER performance. Furthermore, more CMA taps should be adopted to overcome the severe wireless interference when two pairs of transmitter and receiver HAs have different wireless distances.
Experimental heart failure in rats: effects on cardiovascular circadian rhythms and on myocardial β-adrenergic signaling (2000)

Heart failure in rats leads to disturbed circadian patterns in blood pressure and heart rate, and to desensitization of cardiac beta(1)-adrenoceptors, indicating chronic sympathetic overactivity.