gebhart/patrepeval huggingface dataset:
Abstract 4623: Human anti-nucleolin antibodies with broad spectrum anticancer activity (2012)

Abstract Extensive preclinical studies have validated nucleolin as a new therapeutic target in oncology. Confocal microscopy, immunohistochemistry, and cell fractionation studies have shown that this protein is highly overexpressed in the plasma membrane and cytoplasm of a wide variety of human hematological and solid tumor cells, but is usually undetectable on the cell surface or in the cytoplasm of the corresponding normal cells. We have utilized our licensed platform technology to generate a first-in-class panel of eight fully human monoclonal IgG1 antibodies (HuMAbs). These antibodies bind specifically to nucleolin on the tumor cell surface, which in turn elicits potent cytotoxicity to a variety of human tumor cell lines. One such example is CP101, which killed MV4-11 (AML), MCF-7 (breast), DU145 (prostate), PANC-1 and MIA PaCa-2 (pancreas) tumor cell lines with IC50 values ranging from (0.5-2.0 µg/ml; 3-12 nM) following exposure to the HuMAb for 96 hrs. These in vitro assays were performed in the absence of human complement and immune effector cells required for complement-dependent cellular cytotoxicity (CDCC) and antibody-dependent cellular cytotoxicity (ADCC), respectively. These results are consistent with published observations that anti-nucleolin HuMAbs can exploit the known shuttling function of cell surface nucleolin to gain intracellular access and induce direct tumor cytotoxicity. In contrast to its cytocidal effects on tumor cells, CP101 had no effect on the viability of either MCF-10A normal human breast epithelial cells or normal human CD19+ B cells, neither of which expresses nucleolin on the cell surface. In summary, the results suggest that anti-nucleolin HuMAbs are unique in that they can exert broad spectrum antitumor activity independently of the immune mechanism of CDCC and ADCC, while having no detectable effects on the viability of the corresponding normal cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4623. doi:1538-7445.AM2012-4623
Contribution of Surface Salt Bridges to Protein Stability, (2000)

The role of surface salt bridges in protein stabilization has been a source of controversy. Here we present the NMR structure of a hyperthermophilic rubredoxin variant (PFRD-XC4) and the thermodynamic analysis of two surface salt bridges by double mutant cycles. This analysis shows that the surface side chain to side chain salt bridge between Lys 6 and Glu 49 does not stabilize PFRD-XC4. The main chain to side chain salt bridge between the N-terminus and Glu 14 was, however, found to stabilize PFRD-XC4 by 1. 5 kcal mol(-)(1). The entropic cost of making a surface salt bridge involving the protein's backbone is reduced, since the backbone has already been immobilized upon protein folding.
Blockade of CCL1 Inhibits T Regulatory Cell Suppressive Function Enhancing Tumor Immunity without Affecting T Effector Responses (2010)

Intratumoral accumulation of T regulatory cells (Tregs) creates an immunosuppressive environment that reduces the efficacy of antitumor immunotherapy. The immunosuppressive milieu within tumors is largely brought about by the presence of Tregs, which maintain self-tolerance by directly inhibiting T cells, NK cells, and dendritic cells. Depletion of Tregs enhances antitumor immune responses; however, current depletion therapies also affect the function of CD4 and CD8 T effector cells. Previous studies from our laboratory indicate that intratumoral delivery of CpG-ODN strongly reduces the levels of Tregs within the tumor, which is mainly mediated by IL-6. Because IL-6 promotes growth of some human cancers, alternate pathways to inactivate Tregs were sought through microarray analysis, resulting in gene candidates that can be exploited to modulate the function of Tregs. Analysis of these candidates indicates that neutralization of chemokine (C-C motif) ligand 1 (CCL1) prevented de novo conversion and suppressive function of Tregs without affecting the function of T effector cells. The combination of CpG-ODN and anti-CCL1 treatments induced complete rejection of tumors in BALB-neuT tolerant mice, and result in the generation of long-term protective memory responses. Tumor rejection correlated with changes in the lymphocyte composition within the tumor; we observed decreased Treg numbers and a concomitant accumulation of tumoricidal cells such as CD8+NKG2D+ and NK cells. These studies demonstrate that neutralization of CCL1 can be used as an adjuvant to antitumor immunotherapy, as a means of reversing the immunosuppressive function of Tregs without compromising T cell effector function.
Combination vaccines for the treatment of grass pollen allergy consisting of genetically engineered hybrid molecules with increased immunogenicity (2002)

Most of the 400 million grass pollen-allergic patients worldwide are co-sensitized to several unrelated grass pollen allergens. Based on frequent co-sensitization patterns determined in 200 grass pollen-allergic patients, three recombinant hybrid molecules were developed by polymerase chain reaction-based mending of cDNAs coding for the major timothy grass pollen allergens (Phl p 1, Phl p 2, Phl p 5, Phl p 6) for vaccination against grass pollen allergy. The hybrids rP2-P6, rP6-P2, and rP5-P1 contained most of the epitopes of natural grass pollen extract and induced stronger lymphoproliferative responses in cultured mononuclear cells of grass pollen-allergic patients than did equimolar mixtures of the individual allergens. Immunization of mice with the hybrids yielded higher antibody titers than did immunization with the individual allergen components or grass pollen extract, which suggests that the individual components of the hybrids can serve as molecular scaffolds for each other to enhance their immunogenicity. Antibodies induced with the hybrids in mice inhibited the binding of grass pollen-allergic patients' immunoglobulin E to each of the individual allergens and grass pollen extract and may thus represent protective antibodies. The principle of increasing the immunogenicity of antigens by engineering hybrids thereof may be applied not only for the treatment of polysensitized allergic patients but also for general vaccine development.
Non‐viral gene transfer: Applications in developmental biology and gene therapy (1995)

The main limitation of non-viral gene transfer methods is their relatively low efficiency in vivo. However, a number of approaches can be taken to improve their performances, whether the aim is studying gene function during development or employing these techniques for gene therapy. Three non-viral delivery systems that we have been particularly involved in in developing are described: the cationic lipid, dioctadecylamidoglycylspermine (DOGS), the cationic polymer polyethylenimine (PEI) and free DNA. The application of each of these methods to different in vivo situations is presented: the use of DOGS for transfecting embryos and the developing mammalian nervous system; the recent application of PEI to the nervous system; and how naked DNA can be employed for transfecting different muscles and brain. The relative efficiencies are compared on the basis of luciferase reporter gene expression assessed in each tissue with the most appropriate vector system. Finally, the perspectives for constructing composite vectors combining safety and efficiency are considered briefly.
Redundant publication in hepatology (1996)

in Alcoholism: Clinical and Experimental Research. 4 The 80 patients with biopsy-proven alcoholic liver disease were not We are writing in response to your letter pointing out the always diagnosed as alcohol dependent by psychiatrists.existence of overlaps in content in our articles published in However, 62 of 80 patients and 60 healthy controls were used HEPATOLOGY 1 and the Journal of Hepatology. 2 The letter for analysis in the Alcoholism: Clinical and Experimental showed that we submitted the data to two different journals Research paper.The reference 4 had to be added in the two using the same materials while assuring each journal that journals.the material was not under consideration elsewhere.IndeedWe intend, in our individual ways, to ensure that an incithere are areas of duplication in the papers.We have to apolodent like this will not occur a second time.gize for this lapse of professional ethics.We read your previous editorial thoroughly. 3 We did not understand well enough the limits of the materials we could analyze.Although this MASAYOSHI YAMAUCHI, M.D.
Cdc6 and Cyclin E2 Are PTEN-Regulated Genes Associated with Human Prostate Cancer Metastasis (2009)

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is frequently inactivated in metastatic prostate cancer, yet the molecular consequences of this and their association with the metastatic phenotype are incompletely understood. We performed transcriptomic analysis and identified genes altered by conditional PTEN reexpression in C4-2, a human metastatic prostate cancer cell line with inactive PTEN. PTEN-regulated genes were disproportionately represented among genes altered in human prostate cancer progression and metastasis but not among those associated with tumorigenesis. From the former set, we identified two novel putative PTEN targets, cdc6 and cyclin E2, which were overexpressed in metastatic human prostate cancer and up-regulated as a function of PTEN depletion in poorly metastatic DU145 human prostate cancer cells harboring a wild type PTEN. Inhibition of cdc6 and cyclin E2 levels as a consequence of PTEN expression was associated with cell cycle G(1) arrest, whereas use of PTEN activity mutants revealed that regulation of these genes was dependent on PTEN lipid phosphatase activity. Computational and promoter-reporter evaluations implicated the E2F transcription factor in PTEN regulation of cdc6 and cyclin E2 expression. Our results suggest a hypothetical model whereby PTEN loss upregulates cell cycle genes such as cdc6 and cyclin E2 that in turn promote metastatic colonization at distant sites.
Immunohistochemical study of thyroid peroxidase in normal, hyperplastic, and neoplastic human thyroid tissues (1991)

An immunohistochemical study using two monoclonal antibodies (MoAb 30 and MoAb 47) against thyroid peroxidase (TPO) was performed on surgical specimens of human thyroid carcinoma (n = 65), adenoma (n = 70) and Graves' disease (n = 10). Normal adjacent thyroid tissue was used as positive control. Monoclonal antibody 30 reacted significantly with all adenoma and most carcinoma, whereas MoAb 47 reacted with 66 adenoma but only two carcinoma. Of the four adenomas that did not react with MoAb 47, three were of the fetal type. Both carcinoma reacting with MoAb 47 were of the well-differentiated follicular type. These findings further confirm the hypothesis that thyroid carcinoma is associated with changes in the quantity and antigenic properties of TPO. Although the alterations in antigenic behavior revealed by MoAb 47 are not 100% specific, they may allow more accurate diagnosis of malignancy in thyroid tumors.
Fatty Acid Composition of the Oil of Developing Seeds of Different Varieties of Safflower1 (1968)

The seed weight of safflower (Carthamus tinctorius L.) increased most rapidly during the first 15 days after flowering, and reached maximum dry weight in about 28 days. On a weight basis, oil content increased 5‐ to 10‐fold in the period 10 to 15 days after flowering. Expression of control by the genes governing differences in fatty acid composition began about l0 days after flowering.
Studies and Syntheses of Siderophores, Microbial Iron Chelators, and Analogs as Potential Drug Delivery Agents (2000)

Siderophores (microbial iron chelators) play an extremely important role in microbial pathogenicity. Microbial uptake of siderophore-iron complexes through active transport systems allow microbes to survive and proliferate even under iron deficient environments during invasion of a host. Due to their structural complexity, unique iron (III) chelation, acquisition properties, and their therapeutic potential, siderophores have attracted much attention in a broad range of disciplines. Tremendous progress has been made in siderophore syntheses, in determination of the structures and functions of outer membrane receptors (e.g. FhuA and FepA), and in the mechanistic insight into siderophore-iron-mediated active transport processes. One of the important practical applications of this active transport system is development of species-selective active drug transport (the Trojan Horse approach) to potentially treat infections due to drug resistant strains of microbes. Siderophore-drug conjugates have shown great potential in active drug delivery to target pathogenic microbes.
Intramolecular Dimers:  A New Strategy to Fluorescence Quenching in Dual-Labeled Oligonucleotide Probes (2002)

Many genomics assays use profluorescent oligonucleotide probes that are covalently labeled at the 5' end with a fluorophore and at the 3' end with a quencher. It is generally accepted that quenching in such probes without a stem structure occurs through Förster resonance energy transfer (FRET or FET) and that the fluorophore and quencher should be chosen to maximize their spectral overlap. We have studied two dual-labeled probes with two different fluorophores, the same sequence and quencher, and with no stem structure: 5'Cy3.5-beta-actin-3'BHQ1 and 5'FAM-beta-actin-3'BHQ1. Analysis of their absorption spectra, relative fluorescence quantum yields, and fluorescence lifetimes shows that static quenching occurs in both of these dual-labeled probes and that it is the dominant quenching mechanism in the Cy3.5-BHQ1 probe. Absorption spectra are consistent with the formation of an excitonic dimer, an intramolecular heterodimer between the Cy3.5 fluorophore and the BHQ1 quencher.
Threshold Voltage Control of Amorphous Gallium Indium Zinc Oxide TFTs by Suppressing Back-Channel Current (2008)

Effects of plasma treatments on the back-channel of amorphous (GIZO) thin film transistors (TFTs) are compared for and plasma. Acceptor-like states originating from the oxygen adsorbed on the back-channel of the GIZO TFTs suppress the back-channel current by capturing the electrons in the GIZO active layer and thus shift the threshold voltage to the positive direction. It is also shown that the oxygen in a silicon oxide passivation layer reduces the back-channel current. An enhancement-mode GIZO TFT has been successfully fabricated by combining the plasma treatment and the silicon oxide passivation layer.
Monoclonal antibody OKM5 inhibits the in vitro binding of Plasmodium falciparum-infected erythrocytes to monocytes, endothelial, and C32 melanoma cells. (1985)

Plasmodium falciparum-infected erythrocytes bind in vitro to human endothelial cells, monocytes, and a certain melanoma cell line. Evidence suggests that this interaction is mediated by similar mechanisms which lead to the sequestration of parasitized erythrocytes in vivo through their attachment to endothelial cells of small blood vessels. We show here that monoclonal antibody OKM5, previously shown to react with the membranes of endothelial cells, monocytes, and platelets, also reacts with the C32 melanoma cell line which also binds P. falciparum-infected erythrocytes. At relatively low concentrations, OKM5 inhibits and reverses the in vitro adherence of infected erythrocytes to target cells. As with monocytes, OKM5 antibody recognizes an 125I-labeled protein of approximately 88 Kd on the surface of C32 melanoma cells. It seems likely, therefore, that the 88 Kd polypeptide plays a role in cytoadherence, possibly as the receptor or part of a receptor for a ligand on the surface of infected erythrocytes.
Genome-level expression profiles in pediatric septic shock indicate a role for altered zinc homeostasis in poor outcome (2007)

Human septic shock involves multiple genome-level perturbations. We have conducted microarray analyses in children with septic shock within 24 h of intensive care unit admission, using whole blood-derived RNA. Based on sequential statistical and expression filters, there were 2,482 differentially regulated gene probes (1,081 upregulated and 1,401 downregulated) between patients with septic shock (n = 42) and controls (n = 15). Both gene lists encompassed several biologically relevant gene ontologies and canonical pathways. Notably, many of the genes downregulated in the patients with septic shock, relative to the controls, participate in gene ontologies related to metal or zinc homeostasis. Comparison of septic shock survivors (n = 33) and nonsurvivors (n = 9) demonstrated differential regulation of 63 gene probes. Among the 63 gene probes differentially regulated between septic shock survivors and nonsurvivors, two isoforms of metallothionein (MT) demonstrated increased expression in the nonsurvivors. Consistent with the ability of MT to sequester zinc in the intracellular compartment, nonsurvivors had lower serum zinc levels compared with survivors. In a corroborating study of murine sepsis, MT-null mice demonstrated a survival advantage compared with wild-type mice. These data represent the largest reported cohort of pediatric patients with septic shock that has undergone genome-level expression profiling based on microarray. The data are biologically plausible and demonstrate that genome-level alterations of zinc homeostasis may be prevalent in clinical pediatric septic shock.
New Techniques for Enhanced Quality of Computer Accompaniment (1988)

A computer accompaniment system has been extended with several techniques to solve problems associated with reliably recognizing and following a real-time performance. One technique is the use of an additional matcher to consider alternatives when the performance could be interpreted in two ways. Another is to delay corrective action when data from the matcher is suspect. Methods for handling grace notes, trills, and glissandi are also presented. The implementation of these and other techniques to produce an enhanced computer accompaniment system is discussed. 1. Introduction The basic technology for real-time computer accompaniment 1 of live musicians was first presented in 1984 [1, 2], however the first systems left a lot of room for improvement. We have been developing new computer accompaniment systems for two years in an effort to obtain higher reliability in the accompanist and also to deal with a more complete musical vocabulary. Like the first systems, the task is to accept a...
Combination of UWB and GPS for indoor-outdoor vehicle localization (2007)

GPS receivers are satellite-based devices widely used for vehicle localization that, given their limitations, are not suitable for performing within indoor or dense urban environments. On the other hand, Ultra-Wide Band (UWB), a technology used for efficient wireless communication, has recently being used for vehicle localization in indoor environments with promising results. This paper focuses on the combination of both technologies for accurate positioning of vehicles in a mixed scenario (both indoor and outdoor situations), which is typical in some industrial applications. Our approach is based on combining sensor information in a Monte Carlo Localization algorithm (also known as Particle Filter), which has revealed its suitability for probabilistically coping with a variety of sensory data. The performance of our approach has been satisfactorily tested on a real robot, endowed with a UWB master antenna and a GPS receiver, within an indoor-outdoor scenario where three UWB slave antennas were placed in the indoor area.
Emerging Tools for Single‐Cell Analysis (2000)

Color Plates F i g .7.15.Intensity and lifetime imaging of cellular chloride concentration.The cell is loaded with dih-MEQ* and imaged under conditions with 80 MHz and below 4mW laser power at 747 nm using 40x/1.3NAF-Fluar Zeiss objective.The lifetime images are from the modulation measurements.The scale bar is 20 micron.F i g .7.17.Lifetime image of cellular chloride concentration from the phase measurement.The above image displays τ phase value of the same measurement shown in Fig. 7.16B′.Very low lifetime features are indicated by white arrows.The lifetime value for these spots is between 2.0-2.5 ns, which is likely due to NADH (NAD + ) autofluorescence in the mitochondria.The fact that τ phase measures the low lifetime components is illustrated in Fig. 7.6B, where the phase lifetime stays low at high modulation even with less than 30% of total intensity for the component with lower lifetime value.
Characterization of p16(INK4A) expression in multiple myeloma and plasma cell leukemia. (1997)

Loss of p16(INK4A) (p16) expression is frequently associated with the development of epithelial and lymphoid malignancies. However, the frequency and significance of p16 abnormalities in multiple myeloma (MM) and the more aggressive phase of plasma cell leukemia (PCL) have not been well defined. Accordingly, the goal of this study was to define the expression and function of p16 in fresh samples of MM and PCL. We found that p16 protein was highly expressed in primary MM cells, although it was undetectable in fresh samples of PCL. Additionally, p16 protein was also absent in four of four MM-derived cell lines. To determine the mechanism for p16 underexpression in PCL and MM-derived cell lines, we performed PCR analysis to evaluate both gene deletion and the presence of methylation. Interestingly, the p16 gene was present and methylated in all patient PCL cells and MM cell lines, whereas it was unmethylated in patient MM cells and normal B cells. Furthermore, treatment with the demethylating agent 5-deoxyazacytidine or p16 retrofection restored p16 protein expression and induced G1 growth arrest in patient PCL cells and MM cell lines. These results suggest that inactivation of the p16 gene by methylation may be associated with decreased growth control and the development of PCL in a subset of patients with MM.
Purification of Clostridium thermocellum xylanase Z expressed in Escherichia coli and identification of the corresponding product in the culture medium of C. thermocellum (1988)

An endoxylanase encoded by the xynZ gene of Clostridium thermocellum was purified from Escherichia coli harbouring a fragment of the gene cloned in pUC8. The purified enzyme showed two active bands of Mr 41,000 and 39,000, the latter one presumably derived from the former through proteolysis. The enzyme was highly active on xylan and para-nitrophenyl-beta-D-xylobioside. The major end product of xylan hydrolysis was xylobiose. With an antiserum raised against the enzyme purified from E. coli, an immunoreactive polypeptide of Mr 90,000, corresponding to the entire xynZ gene product, was detected in a culture supernatant from C. thermocellum grown on cellulose. By immunological detection, xylanase Z was shown to be associated with a cellulose-binding, high-molecular-weight fraction whose properties coincided with those described previously for the cellulose-degrading complex of C. thermocellum known as the cellulosome.
Development of a Fear-of-Change Scale for the Psychological Inventory of Criminal Thinking Styles (PICTS) (2001)

Abstract A Fear-of-Change (FOC) scale for the Psychological Inventory of Criminal Thinking Styles (PICTS) was derived from a set of 24 candidate items. Responses supplied by 100 male medium security federal prisoners and 100 female minimum security federal prison camp inmates were used to construct and initially evaluate an 8-item FOC scale. The scale displayed a moderate degree of internal consistency and moderately high test-retest stability after 2 and 12 weeks, and correlated significantly with a previously administered measure of existential fear. It is concluded that while the FOC is an internally consistent and reasonably stable measure with some evidence of preliminary validity, more research is needed to determine whether it actually assesses fear of change.