gebhart/patrepeval huggingface dataset:
Enhanced tumor uptake of macromolecules induced by a novel vasoactive interleukin 2 immunoconjugate. (1991)

Low uptake of monoclonal antibodies (MAbs) in cancer lesions is a significant problem in cancer therapy. Recent studies have shown that antibody uptake in tumor is controlled in large part by the tumor blood flow and the vascular permeability of the tumor endothelium. We have hypothesized that these physiological properties of tumor vessels may be altered by pretreatment with vasoactive drugs or peptides linked to tumor-specific MAbs. To test this hypothesis, two MAbs, Lym-1 directed against human malignant lymphomas and B72.3 reactive with the TAG-72 antigen expressed in solid tumors, were chemically conjugated with human recombinant interleukin 2 (IL-2). IL-2 has been used in humans to activate lymphokine-activated killer cells for the treatment of cancer but is also known to produce a generalized vascular permeability by an unknown mechanism when used systemically. Chemical conjugation of IL-2 to MAbs appears to destroy its cytokine function as shown by T-cell proliferation studies in vitro. Despite this finding, MAb/IL-2 immunoconjugates retain their ability to produce an enhanced vascular permeability when injected i.v. into nude mice bearing relevant tumor models only. Biodistribution studies using 125I-labeled tracer Lym-1 have demonstrated that the Lym-1/IL-2 immunoconjugate can increase antibody uptake in tumor by a factor of 4 in a time (2.5-h pretreatment)- and dose (30 micrograms/mouse)-dependent manner. In contrast, treatment of mice with free IL-2 and antibody showed this effect in all organs of the mouse including the tumor. Bidirectional crossover imaging studies in individual tumor-bearing nude mice showed improved uptake and decreased blood pool when the MAb/IL-2 immunoconjugates were used compared to controls. Finally, tumor blood flow and vascular permeability studies demonstrate that the physiological effect of the MAb/IL-2 is due to a reversible and specific vascular leakage at the tumor site. These studies indicate that pretreatment with this novel immunoconjugate may enhance the diagnostic and therapeutic potential of MAbs, drugs, and other macromolecules for the treatment of cancer.
Optimized silicon-rich oxide (SRO) deposition process for 5 V only flash EEPROM applications (1993)

A process for depositing in-situ very-thin (<10 nm) SiO/sub 2/ films on top of a silicon-rich oxide (SRO) layer in a standard low-pressure chemical vapor deposition (LPCVD) reactor has been optimized. Polysilicon-gate MOS capacitors using this stacked dielectric have shown high tunneling current at low voltages and an extraordinary endurance to electrical stress. Capacitors with 7 nm LPCVD SiO/sub 2/ on top of 10 nm SRO did not show any relevant shift on either the low or high portion of the I-V characteristic, after a fluence of more than 500 C/cm/sup 2/ at J=0.1 A/cm/sup 2/. The results add further support to the usefulness of implementing these stacked dielectric structures in a variety of nonvolatile memory devices.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Parameters controlling the rate of gene targeting frequency in the protozoan parasite Leishmania (1997)

In this study we investigated the role of several parameters governing the efficiency of gene targeting mediated by homologous recombination in the protozoan parasite Leishmania. We evaluated the relative targeting frequencies of different replacement vectors designed to target several sequences within the parasite genome. We found that a decrease in the length of homologous sequences <1 kb on one arm of the vector linearly influences the targeting frequency. No homologous recombination was detected, however, when the flanking homologous regions were <180 bp. A requirement for a very high degree of homology between donor and target sequences was found necessary for efficient gene targeting in Leishmania , as targeted recombination was strongly affected by base pair mismatches. Targeting frequency increased proportionally with copy number of the target only when the target was part of a linear amplicon, but remained unchanged when it was present on circles. Different chromosomal locations were found to be targeted with significantly variable levels of efficiency. Finally, different strains of the same species showed differences in gene targeting frequency. Overall, gene targeting mediated by homologous recombination in Leishmania shares similarities to both the yeast and the mammalian recombination systems.
The E-Selectin Ligand Basigin/CD147 Is Responsible for Neutrophil Recruitment in Renal Ischemia/Reperfusion (2009)

E-selectin and its ligands are essential for extravasation of leukocytes in inflammation. Here, we report that basigin (Bsg)/CD147 is a ligand for E-selectin that promotes renal inflammation in ischemia/reperfusion. Compared with wild-type mice, Bsg-deficient (Bsg(-/-)) mice demonstrated striking suppression of neutrophil infiltration in the kidney after renal ischemia/reperfusion. Although E-selectin expression increased similarly between the two genotypes, Bsg(-/-) mice exhibited less renal damage, suggesting that Bsg on neutrophils contribute to renal injury in this model. Neutrophils expressed Bsg with N-linked polylactosamine chains and Bsg(-)(/)(-) neutrophils showed reduced binding to E-selectin. Bsg isolated from HL-60 cells bound to E-selectin, and tunicamycin treatment to abolish N-linked glycans from Bsg abrogated this binding. Furthermore, Bsg(-)(/)(-) neutrophils exhibited reduced E-selectin-dependent adherence to human umbilical vein endothelial cells in vitro. Injection of labeled neutrophils into mice showed that Bsg(-)(/)(-) neutrophils were less readily recruited to the kidney after renal ischemia/reperfusion than Bsg(+/+) neutrophils, regardless of the recipient's genotype. Taken together, these results indicate that Bsg is a physiologic ligand for E-selectin that plays a critical role in the renal damage induced by ischemia/reperfusion.
Endocytosis-like protein uptake in the bacterium Gemmata obscuriglobus (2010)

Endocytosis is a process by which extracellular material such as macromolecules can be incorporated into cells via a membrane-trafficking system. Although universal among eukaryotes, endocytosis has not been identified in Bacteria or Archaea. However, intracellular membranes are known to compartmentalize cells of bacteria in the phylum Planctomycetes, suggesting the potential for endocytosis and membrane trafficking in members of this phylum. Here we show that cells of the planctomycete Gemmata obscuriglobus have the ability to uptake proteins present in the external milieu in an energy-dependent process analogous to eukaryotic endocytosis, and that internalized proteins are associated with vesicle membranes. Occurrence of such ability in a bacterium is consistent with autogenous evolution of endocytosis and the endomembrane system in an ancestral noneukaryote cell.
Efficient and Accurate Evolutionary Multi-Objective Optimization Paradigms for Satellite Constellation Design (2007)

Covers advancements in spacecraft and tactical and strategic missile systems, including subsystem design and application, mission design and analysis, materials and structures, developments in space sciences, space processing and manufacturing, space operations, and applications of space technologies to other fields.
Decline in the expression of the serine proteinase inhibitor maspin is associated with tumour progression in ductal carcinomas of the breast (2001)

Maspin is an inhibitor of serine proteinases with tumour suppressor activity. Its expression appears to be reduced in advanced stages of breast cancer. A large series of archival breast tissue specimens has been examined, including normal glands (n=7), fibrocystic change (n=22), ductal carcinoma in situ (DCIS, n=12), infiltrating carcinomas (n=128) and their lymph node metastases (n=65), using a specific monoclonal antibody. Myoepithelium invariably showed strong maspin expression. In epithelial cells, the strongest expression was found in normal breast and fibrocystic change. A significant stepwise decrease in maspin expression (p<0.0001) occurred in the sequence DCIS - invasive cancer - lymph node metastasis. However, a subset of infiltrating carcinomas showed strong maspin expression, significantly associated with a lower rate of lymph node metastasis at the time of diagnosis (p<0.01). This was independent of tumour size and grade. The in vivo observations presented here are in keeping with data obtained in prior in vitro experiments. Maspin emerges as an indicator of tumour progression and metastatic potential, and might be exploited to predict breast cancer prognosis. According to in vitro data, its tumour suppressor activity is likely to involve both the modulation of cell motility/invasiveness and the inhibition of angiogenesis.
Microbiome Profiling by Illumina Sequencing of Combinatorial Sequence-Tagged PCR Products (2010)

We developed a low-cost, high-throughput microbiome profiling method that uses combinatorial sequence tags attached to PCR primers that amplify the rRNA V6 region. Amplified PCR products are sequenced using an Illumina paired-end protocol to generate millions of overlapping reads. Combinatorial sequence tagging can be used to examine hundreds of samples with far fewer primers than is required when sequence tags are incorporated at only a single end. The number of reads generated permitted saturating or near-saturating analysis of samples of the vaginal microbiome. The large number of reads allowed an in-depth analysis of errors, and we found that PCR-induced errors composed the vast majority of non-organism derived species variants, an observation that has significant implications for sequence clustering of similar high-throughput data. We show that the short reads are sufficient to assign organisms to the genus or species level in most cases. We suggest that this method will be useful for the deep sequencing of any short nucleotide region that is taxonomically informative; these include the V3, V5 regions of the bacterial 16S rRNA genes and the eukaryotic V9 region that is gaining popularity for sampling protist diversity.
Intracellular Generation of Sphingosine 1-Phosphate in Human Lung Endothelial Cells (2007)

Sphingosine 1-phosphate (S1P) regulates diverse cellular functions through extracellular ligation to S1P receptors, and it also functions as an intracellular second messenger. Human pulmonary artery endothelial cells (HPAECs) effectively utilized exogenous S1P to generate intracellular S1P. We, therefore, examined the role of lipid phosphate phosphatase (LPP)-1 and sphingosine kinase1 (SphK1) in converting exogenous S1P to intracellular S1P. Exposure of (32)P-labeled HPAECs to S1P or sphingosine (Sph) increased the intracellular accumulation of [(32)P]S1P in a dose- and time-dependent manner. The S1P formed in the cells was not released into the medium. The exogenously added S1P did not stimulate the sphingomyelinase pathway; however, added [(3)H]S1P was hydrolyzed to [(3)H]Sph in HPAECs, and this was blocked by XY-14, an inhibitor of LPPs. HPAECs expressed LPP1-3, and overexpression of LPP-1 enhanced the hydrolysis of exogenous [(3)H]S1P to [(3)H]Sph and increased intracellular S1P production by 2-3-fold compared with vector control cells. Down-regulation of LPP-1 by siRNA decreased intracellular S1P production from extracellular S1P but had no effect on the phosphorylation of Sph to S1P. Knockdown of SphK1, but not SphK2, by siRNA attenuated the intracellular generation of S1P. Overexpression of wild type SphK1, but not SphK2 wild type, increased the accumulation of intracellular S1P after exposure to extracellular S1P. These studies provide the first direct evidence for a novel pathway of intracellular S1P generation. This involves the conversion of extracellular S1P to Sph by LPP-1, which facilitates Sph uptake, followed by the intracellular conversion of Sph to S1P by SphK1.
Switchable liquid crystalline photopolymer media for holography (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSwitchable liquid crystalline photopolymer media for holographyJian Zhang and Michael B. SponslerCite this: J. Am. Chem. Soc. 1992, 114, 4, 1506–1507Publication Date (Print):February 1, 1992Publication History Published online1 May 2002Published inissue 1 February 1992https://pubs.acs.org/doi/10.1021/ja00030a071https://doi.org/10.1021/ja00030a071research-articleACS PublicationsRequest reuse permissionsArticle Views195Altmetric-Citations24LEARN 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
C-type natriuretic peptide production by the human kidney is blunted in chronic heart failure (2009)

CNP (C-type natriuretic peptide) is a vasodilatory peptide produced by vascular endothelium and the human heart with a short half-life. CNP has been identified within the human kidney; however, few results are available on whether the human kidney is a systemic source of CNP. The aim of the present study was to establish whether CNP is secreted by the human kidney and if synthesis is blunted in CHF (chronic heart failure). A total of 20 male subjects (age, 57+/-2 years; mean+/-S.E.M.) undergoing CHF assessment (n=13) or investigation of paroxysmal supraventricular arrhythmia (normal left ventricular function in sinus rhythm during procedure) (n=7) were recruited. Renal CNP production was determined from concomitant plasma concentrations in the aorta and renal vein. When considering all subjects, a significant step-up in plasma CNP was found from the aorta to renal vein (3.0+/-0.3 compared with 8.3+/-2.4 pg/ml respectively; P=0.0045). The mean increase in CNP was 5.3+/-2.4 pg/ml (range, -0.9 to +45.3 pg/ml). In patients with CHF, the aortic concentration was 3.3+/-0.4 pg/ml compared with a renal vein concentration of 4.3+/-0.6 pg/ml (P=0.11). In those with normal left ventricular function, the respective values were 2.5+/-0.5 and 15.7+/-6.0 pg/ml (P=0.01). In conclusion, CNP is synthesized and secreted into the circulation by the normal human kidney, where it may have paracrine actions. Net renal secretion of CNP appears to be blunted in patients with CHF.
Localization algorithms for distributed platform among vehicles (2009)

There are theoretical and empirical RSS-based algorithms proposed and many studies have been made by comparing the performance of these algorithms. However, there is a lack of theoretical basis and understanding on the orientation of vehicles without GPS. This paper presents a model for an orientation-aware location tracking manner for the detections of vehicles using wireless sensors based on IEEE 802.15.4 standard protocol. For path loss model, our experiment shows a better prediction of RSS when attenuation factors for different orientations are considered in the model. On the other hand, orientation-aware fingerprint algorithm, which currently stands as one of the most accurate RSS-based localization algorithm, is also examined in our experiment to have a basis of comparison with an empirical algorithm.
Cell Concentration and Separation in the Field of a Standing Ultrasonic Wave for Medicine and Biotechnology (2013)

This work is carried out to determine the empirical boundary conditions of concentration/separation of yeast cells, red blood cells of rats and guinea pigs in standing ultrasonic wave, based on the performed theoretical calculations. The results indicated that increase flow rate of the medium above the theoretically calculated values of cell retention in a standing ultrasonic wave causes them to wash away from the camera separation ultrasound.
Restoration of hemoglobin A synthesis in erythroid cells from peripheral blood of thalassemic patients (2000)

Mononuclear cells from peripheral blood of thalassemic patients were treated with morpholino oligonucleotides antisense to aberrant splice sites in mutant beta-globin precursor mRNAs (pre-mRNAs). The oligonucleotides restored correct splicing and translation of beta-globin mRNA, increasing the hemoglobin (Hb) A synthesis in erythroid cells from patients with IVS2-654/beta(E), IVS2-745/IVS2-745, and IVS2-745/IVS2-1 genotypes. The maximal Hb A level for repaired IVS2-745 mutation was approximately 30% of normal; Hb A was still detectable 9 days after a single treatment with oligonucleotide. Thus, expression of defective beta-globin genes was repaired and significant level of Hb A was restored in a cell population that would be targeted in clinical applications of this approach.
Phytochemical Composition and Pigment Stability of Açai (Euterpe oleracea Mart.) (2004)

Anthocyanin and polyphenolic compounds present in açai (Euterpe oleracea Mart.) were determined and their respective contribution to the overall antioxidant capacity established. Color stability of açai anthocyanins against hydrogen peroxide (0 and 30 mmol/L) over a range of temperatures (10-30 degrees C) was also determined and compared to common anthocyanin sources. Additionally, stability in a model beverage system was evaluated in the presence of ascorbic acid and naturally occurring polyphenolic cofactors. Cyanidin 3-glucoside (1040 mg/L) was the predominant anthocyanin in açai and correlated to antioxidant content, while 16 other polyphenolics were detected from 4 to 212 mg/L. Red grape anthocyanins were most stable in the presence of hydrogen peroxide, while açai and pigments rich in acylated anthocyanins displayed lower color stability in a temperature-dependent manner. In the presence of ascorbic acid, acylated anthocyanin sources generally had increased color stability. Açai was recognized for its functional properties for use in food and nutraceutical products.
Quadrivalent Vaccine against Human Papillomavirus to Prevent High-Grade Cervical Lesions (2007)

In young women who had not been previously infected with HPV-16 or HPV-18, those in the vaccine group had a significantly lower occurrence of high-grade cervical intraepithelial neoplasia related to HPV-16 or HPV-18 than did those in the placebo group. (ClinicalTrials.gov number, NCT00092534 [ClinicalTrials.gov].).
A structured kinetic modeling framework for the dynamics of hybridoma growth and monoclonal antibody production in continuous suspension cultures (1989)

A structured kinetic model is developed to describe the dynamics of hybridoma growth and the production of monoclonal antibodies and metabolic waste products in suspension culture. The crucial details of known metabolic processes in hybridoma cells are incorporated by dividing the cell mass into four intracellular metabolic pools. The model framework and structure allow the dynamic calculation of the instantaneous specific growth rate of a hybridoma culture. The steady state and dynamic simulations of the model equations exhibit excellent agreement with experimentally observed trends in substrate utilization and product formation. The model represents the first to include any degree of metabolic detail and structure in describing a hybridoma culture. In so doing, it provides the basic modeling framework for incorporating further details of metabolism and can be a useful tool to study various strategies for enhancing hybridoma growth as well as viability and the production of monoclonal antibodies in suspension cultures.
Novel Quantitative Flow Cytometry-Based Signaling Assays Reveal a Potential Role for HSP90 Inhibitors in the Treatment of JAK2 Mutant-Positive Diseases. (2005)

Abstract The V617F mutation in the JAK2 tyrosine kinase, recently described in a majority of patients with myeloproliferative disorders (MPDs), confers growth factor independence in vitro and oncogenicity in mice. Therefore, targeted inhibition of mutant JAK2 kinase activity may be an effective strategy for treatment of MPD patients with this mutation. The ability to measure the activation status of JAK2 in patient samples will thus be of substantial value for monitoring therapeutic efficacy. We have developed quantitative flow cytometry-based assays for rapid and reproducible measurement of intracellular total and phosphorylated proteins of the canonical JAK/STAT pathway, as well as heat shock proteins (HSPs). In this study we examined the ability of these assays to detect altered levels of total and phosphorylated JAK/STAT signaling pathway components and HSP in a cell line (HEL) that is homozygous for the V617F JAK2 mutant. HEL cell cultures were incubated with 17AAG, a geldanamycin analog with clinical utility in a broad range of diseases. 17AAG exerts its inhibitory effect by binding to heat shock protein 90 (HSP90), preventing its chaperone association with client oncoproteins. AKT is among these client proteins and a component of the JAK/STAT pathway, representing a potential therapeutic target. 17AAG exposure reduced total AKT protein levels by 42%. 17AAG also inhibited mutant JAK2 activity by 66% and had a smaller effect (17%) on total JAK2 levels, suggesting that mutant JAK2 activation may rely on HSP90, either directly or through dependence on other client proteins. Exposure to 17AAG also reduced levels of P-STAT5 (50%) and, to a lesser extent, total STAT5 (27%). 17AAG-treated cells showed a 55% reduction in HSP90 levels and a 14% increase in HSP70 protein levels. JAK Inhibitor I (Calbiochem), a potent pan-JAK Inhibitor that blocks JAK1, JAK2, and JAK3 activity, caused reductions in P-JAK2 and P-STAT5 levels (29% and 26% decreases, respectively). However, the combining of JAK Inhibitor I with 17AAG did not result in an enhanced effect beyond what was observed with 17AAG treatment alone. Similar results were seen with AG490, a potent and selective JAK2 inhibitor. 17AAG caused a 40% decrease in viable cells after 18 hrs of treatment, compared with a 35% reduction for the pan-JAK inhibitor and a 20% decrease for AG490. Combining 17AAG with the pan-JAK inhibitor or AG490 caused only minor enhancement of these cytotoxic effects (46% and 41% reduction in cell viability, respectively). Our data support the potential utility of HSP90 inhibitors such as 17AAG in the development of small-molecule therapy for mutant JAK2 kinase-positive MPD. These results also show that flow cytometry-based assays for JAK/STAT signaling components and HSPs can be used to quantitatively monitor drug efficacy at the protein level in intact cells. These tests are likely to have broad clinical utility given the spectrum of diseases in which a pathogenic role for mutant JAK2 kinase is implicated.