gebhart/patrepeval huggingface dataset:
Apoptosis induction in prostate cancer cells and xenografts by combined treatment with Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand and CPT-11. (2003)

Because apoptosis is deregulated in most cancers, apoptosis-modulating approaches offer an attractive opportunity for clinical therapy of many tumors, including that of the prostate. LNCaP-derived C4-2 human prostate cancer cells are quite resistant to treatment with Apo2 ligand (Apo2L) or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), when using a nontagged, Zn-bound recombinant trimeric version that is devoid of any exogeneous sequences and therefore least likely to be immunogenic in human patients and that has been optimized for maximum efficacy and minimum toxicity. When combined with the topoisomerase I inhibitor CPT-11 (irinotecan), Apo2L/TRAIL exhibits enhanced apoptotic activity in C4-2 cells cultured in vitro as well as xenografted as tumors in vivo. Apoptosis both in vitro and in vivo was characterized by two major molecular events. First, apoptosis induction was accompanied by changes in expression levels of the Bcl-2 family genes and their products. However, whereas combination treatment applied to in vitro cell culture was characterized by a significant up-regulation and activation of Bax and down-regulation of Bcl-xL, the treatment applied to tumors induced Bak and Bcl-xS, whereas Bcl-omega and Bcl-xL were down-regulated. Because there are multiple members of the Bcl-2 family (24 members to date), these data indicate that, under different biological conditions, different proteins may be responsible for activating apoptosis and provide evidence for a differential regulation of the multidomain Bcl-2 protein-encoding genes, bax and bak. Increased Bax expression led to its activation, translocation to the mitochondria, and release of cytochrome c. In addition, this combination treatment induced apoptosis through potent activation of caspase-8 and the proapoptotic protein Bid, resulting in activation of effector caspase-3 and cleavage of its cellular target protein, poly(ADP-ribose) polymerase (PARP), events blocked by the pan-caspase inhibitor N-tert-butoxy-carbonyl-Val-Ala-Asp-fluoro methylketone (zVAD-fmk). Activation of multiple caspases and PARP cleavage were also observed in the C4-2 tumors treated with doses resulting in effective tumor control at 42 days after Apo2L/TRAIL plus CPT-11 treatment. Down-regulation of Bax by small interference (RNA) (siRNA) in C4-2 cells significantly prevented PARP cleavage and apoptosis. Strikingly, similar experiments in cells stably expressing a dominant-negative death receptor DR5 led to complete ablation of PARP cleavage and apoptosis, indicating the essential role of both mitochondrial and receptor-mediated apoptotic pathways. Our data indicate that the combined treatment of Apo2L/TRAIL and CPT-11 achieves tumor control in prostate cancer tumors through regulation of Bcl-2 family proteins and potent activation of caspases.
Chip-based frequency combs with sub-100 GHz repetition rates (2012)

By fabricating high-Q silicon-nitride spiral resonators, we demonstrate frequency combs spanning over 200 nm with free spectral ranges (FSRs) of 80, 40, and 20 GHz using cascaded four-wave mixing. We characterize the RF beat note for the 20 GHz FSR comb, and the measured linewidth of 3.6 MHz is consistent with thermal fluctuations in the resonator due to amplitude noise of the pump source. These combs represent an important advance towards developing a complementary metal-oxide-semiconductor (CMOS)-based system capable of linking the optical and electronic regimes.
A Novel Murine Model of Severe Pulmonary Arterial Hypertension (2011)

These data describe a novel murine model of PAH, which displays many of the hallmarks of the human disease, thus opening new avenues of investigation to better understand PAH pathophysiology.
Knockdown of STAT3 Expression by RNA Interference Inhibits the Induction of Breast Tumors in Immunocompetent Mice (2005)

Constitutively activated STAT3 is involved in the formation of multiple types of tumors including breast cancer. We examined the effects of Stat3 protein knockdown by RNA interference using a dicistronic lentivirus small hairpin (shRNA) delivery system on the growth of mammary tumors in BALB/c mice induced by the 4T1 cell line. A single exposure of 4T1 cells to shRNA/STAT3 lentivirus transduced 75% of the cells with green fluorescent protein (GFP) within 96 hours. In cells selected for GFP expression, neither Stat3 protein nor phosphotyrosine Stat3 was detected. Tumor formation induced by injecting 4T1 cells into the mammary fat pad was blocked by expression of the shRNA for STAT3 whereas all mice injected with 4T1 cells expressing only GFP efficiently formed tumors. c-Myc expression was reduced 75% in cells expressing greatly reduced levels of Stat3 compared with the GFP control. Of interest, the level of activated Src, which is known to activate Stat3, was virtually eliminated but the level of the Src protein itself remained the same. Importantly, expression of Twist protein, a metastatic regulator, was eliminated in STAT3 knockdown cells. Invasion activity of STAT3 knockdown cells was strongly inhibited. However, the proliferation rate of cells in Stat3 knockdown cells was similar to that of the GFP control; the cell cycle was also not affected. We conclude from these studies that activated Stat3 protein plays a critical role in the induction of breast tumors induced by 4T1 cells by enhancing the expression of several important genes including c-Myc and the metastatic regulator Twist. These studies suggest that stable expression of small interfering RNA for STAT3 has potential as a therapeutic strategy for breast cancer.
An efficient method for generating proteins with altered enzymatic properties: application to beta-lactamase. (1989)

Random-sequence or highly degenerate oligonucleotides have been useful for defining functionally important sequences both in proteins and in nucleic acids. In this approach, such oligonucleotides are used to replace a segment of DNA required for a desired function, and functional sequences are identified by an appropriate genetic or biochemical selection. Here, a collection of 500,000 [corrected] altered beta-lactamase proteins was generated by cloning a mixed-base oligonucleotide in place of the sequences coding for a 17-amino acid portion of the enzyme's active site. Approximately 2000 enzymes from this collection were able to confer ampicillin resistance on Escherichia coli. Fifty-eight of these were chosen for further study after characterization with various beta-lactam substrates. beta-Lactamases having altered specificity against different antibiotics, resistance to the suicide inhibitors clavulanic acid and sulbactam, and temperature-dependent activities were obtained. The amino acid residues responsible for these altered properties as well as for basic enzyme activity are defined. This approach should prove to be an effective and general tool for creating proteins with novel properties, especially in situations in which a high-resolution structure of the protein is not known.
Pyruvate carboxylase from Corynebacterium glutamicum: characterization, expression and inactivation of the pyc gene (1998)

In addition to phosphoenolpyruvate carboxylase (PEPCx), pyruvate carboxylase (PCx) has recently been found as an anaplerotic enzyme in the amino-acid-producing bacterium Corynebacterium glutamicum. Using oligonucleotides designed according to conserved regions of PCx amino acid sequences from other organisms, a 200 bp fragment central to the C. glutamicum PCx gene (pyc) was amplified from genomic DNA by PCR. This fragment was then used to identify and to subclone the entire C. glutamicum pyc gene. The cloned pyc gene was expressed in C. glutamicum, as cells harbouring the gene on plasmid showed four- to fivefold higher specific PCx activities when compared to the wild-type (WT). Moreover, increased PCx protein levels in the pyc-plasmid-carrying strain were readily detected after SDS-PAGE of cell-free extracts. DNA sequence analysis of the pyc gene, including its 5' and 3' flanking regions, and N-terminal sequencing of the pyc gene product predicts a PCx polypeptide of 1140 amino acids with an M(r) of 123070. The amino acid sequence of this polypeptide shows between 62% and 45% identity when compared to PCx enzymes from other organisms. Transcriptional analyses revealed that the pyc gene from C. glutamicum is monocistronic (3.5 kb mRNA) and that its transcription is initiated at an A residue 55 bp upstream of the translational start. Inactivation of the chromosomal pyc gene in C. glutamicum WT led to the absence of PCx activity and to negligible growth on lactate, indicating that PCx is essential for growth on this carbon source. Inactivation of both the PCx gene and the PEPCx gene in C. glutamicum led additionally to the inability to grow on glucose, indicating that no further anaplerotic enzymes for growth on carbohydrates exist in this organism.
The Trojan exosome hypothesis (2003)

We propose that retroviruses exploit a cell-encoded pathway of intercellular vesicle traffic, exosome exchange, for both the biogenesis of retroviral particles and a low-efficiency but mechanistically important mode of infection. This Trojan exosome hypothesis reconciles current paradigms of retrovirus-directed transmission with the unique lipid composition of retroviral particles, the host cell proteins present in retroviral particles, the complex cell biology of retroviral release, and the ability of retroviruses to infect cells independently of Envelope protein-receptor interactions. An exosomal origin also predicts that retroviruses pose an unsolvable paradox for adaptive immune responses, that retroviral antigen vaccines are unlikely to provide prophylactic protection, and that alloimmunity is a central component of antiretroviral immunity. Finally, the Trojan exosome hypothesis has important implications for the fight against HIV and AIDS, including how to develop new antiretroviral therapies, assess the risk of retroviral infection, and generate effective antiretroviral vaccines.
Isolation and Partial Sequence Analysis of Rat Basic Somatomedin* (1982)

Rat basic somatomedin (Sm) was prepared with an improved purification scheme from the pooled sera of Wistar Furth rats previously inoculated with cells from the pituitary tumor MStT/W15. Amicon hollow fiber diafiltration facilitated the processing of large batches of serum, eliminating the necessity of running smaller portions of material on gel filtration columns to achieve the same qualitative separation. The yield from this technique was excellent. Basic rat Sm was separated from a C3ades Arg component of complement by a narrow pH range isoelectric focusing step. Subsequent chromatography on carboxymethyl-cellulose and Sephadex resins was very efficient, providing a 100-fold purification, with a recovery of Sm activity of approximately 65%. The final product was judged to be pure by a variety of criteria. Structural analysis of this material has demonstrated that the amino-terminal sequences of rat basic Sm and human insulin-like growth factor I are strikingly similar, confirming the homology proposed earlier on the basis of receptor cross-reactivity.
Physically Based Deformable Models in Computer Graphics (2006)

Abstract Physically based deformable models have been widely embraced by the Computer Graphics community. Many problems outlined in a previous survey by Gibson and Mirtich have been addressed, thereby making these models interesting and useful for both offline and real‐time applications, such as motion pictures and video games. In this paper, we present the most significant contributions of the past decade, which produce such impressive and perceivably realistic animations and simulations: finite element/difference/volume methods, mass‐spring systems, mesh‐free methods, coupled particle systems and reduced deformable models‐based on modal analysis. For completeness, we also make a connection to the simulation of other continua, such as fluids, gases and melting objects. Since time integration is inherent to all simulated phenomena, the general notion of time discretization is treated separately, while specifics are left to the respective models. Finally, we discuss areas of application, such as elastoplastic deformation and fracture, cloth and hair animation, virtual surgery simulation, interactive entertainment and fluid/smoke animation, and also suggest areas for future research.
A general synthesis of 5-arylnicotinates (1984)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA general synthesis of 5-arylnicotinatesWayne J. Thompson and John GaudinoCite this: J. Org. Chem. 1984, 49, 26, 5237–5243Publication Date (Print):December 1, 1984Publication History Published online1 May 2002Published inissue 1 December 1984https://pubs.acs.org/doi/10.1021/jo00200a045https://doi.org/10.1021/jo00200a045research-articleACS PublicationsRequest reuse permissionsArticle Views3464Altmetric-Citations205LEARN 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
ATTENUATION OF ENDOTHELIUM-DEPENDENT RELAXATION OF PIG PULMONARY MICROVESSELS FOLLOWING CARDIOPULMONARY BYPASS IS MEDIATED BY C5a (1998)

Introduction: Cardiopulmonary bypass (CPB) is known to be associated with attenuation of endothelium-dependent [1] dilation of pulmonary arteries. We examined whether complement activation may be responsible for the attenuated responses. Methods: In compliance with institutional animal care committee standards, pigs, 20-25 kg, were placed on 1 hr of normothermic CPB with or without antibody(AB) to complement C5a (1.6 mg/kg IV) and then reperfused for 2 hr. Control pigs were not instrumented. Lungs were removed and pulmonary arteries of diameter [similar]100 [micro sign]m were dissected. Following preconstriction with the thromboxane analogue U46619 1 [micro sign]M, % relaxation to the endothelium-dependent agents adenosine diphosphate (AD) 10-9 [similar]10-4 M and substance P(SP) 10-12 [similar]10 (-6) M, the endothelium-independent dilator sodium nitroprusside (NP) 10-9 [similar]10-4 M, and the beta-adrenergic agonist isoproterenol(IS) 10-10 [similar]10-4 M were measured in vitro using video detection system. Neutrophil activation in the lung tissue was measured by myoelperoxidase activity (MPA). Data are presented as mean +/- SD of 6-8 vessels. Results: Following CPB without AB, relaxation of pig pulmonary arteries to AD, and SP, but not to NP or IS, was attenuated compared to control. This attenuation was not seen following CPB with AB. (Table 1)Table 1MPA was increased on CPB (27 +/- 16 u/g tissue), compared to control (4 +/- 3 u/g tissue) (P < 0.01). Following CPB with AB, the increase in MPA tended to be less (16 +/- 12 u/g tissue) (P = 0.55 vs. control, 0.18 vs. CPB). Discussion: In pigs, there is attenuation of endothelium-dependent relaxation of pulmonary arteries following CPB and reperfusion. This attenuation may be mediated by C5a and possibly related to netrophil activation and adherence
Abstract 3361: CD73 expression on tumor-infiltrating breast cancer leukocytes (2015)

Abstract Recent studies have shown that CD73 could be a new promising target in breast cancer (BC). CD73 is a cell surface ecto-nucleotidase, expressed by both tumor cells and immune cells, that catalyses the hydrolysis of AMP into adenosine in the tumor microenvironment. Adenosine has immunosuppressive and tumor-promoting effects and is therefore implicated in the mechanism of tumor immune escape. High CD73 gene expression has recently been associated with a poor prognosis in triple negative BC. While tumor expression of CD73 is well documented, expression of CD73 on tumor-infiltrating immune cells remains poorly characterized. We evaluated the expression of CD73 on immune cells present in fresh tissue homogenates (GentleMACS with no enzymatic digestion) from untreated primary breast tumors and compared to its expression to peripheral blood mononuclear cells (PBMC) from patients with breast cancer. In the peripheral blood, CD73 was found mostly expressed on CD4+ (mean percentage: 13.24±12.88%) and CD8+T cells (mean percentage: 40.78±19.42%) and a major subset of B cells (mean percentage: 51.93±21.83%). Analysis of fresh tumor tissues revealed that less than 25% of CD45+ tumor immune infiltrates express CD73 (mean percentage: 17.63± 5,1%) and was relatively similar to its expression on PBMC (mean percentage: 14.87± 9.5%). In the tumor immune infiltrates, B cells were the immune subset with the higher proportion of CD73+ cells (mean percentage: 53.27±14.63%) while the proportion of CD73+ was lower on tumor-infiltrating CD8+ T cells compared to CD8+ PBMC (p value: 0.022). Notably, we observed that CD73 expression was significantly higher on tumor-infiltrating NK cells and CD14+ myeloid cells compared to peripheral cells (p = 0.005 for NK cells, and p = 0.015 for CD14+ cells). Immunofluorescence analysis confirmed that CD73 is expressed by both tumor cells, CD45+ immune cells and stromal cells in breast cancer. These results suggest that CD73 is differentially expressed on tumor-infiltrating leukocytes compared to PBMCs. Modulation of CD73 activity on tumor-infiltrating leukocytes may therefore contribute to the mechanism-of-action of anti-CD73 therapies. Citation Format: Laurence Buisseret, Soizic Garaud, Bertrand Allard, Isabelle Cousineau, Guillaume Chouinard, Christos Sotiriou, Karen Willard-Gallo, John Stagg. CD73 expression on tumor-infiltrating breast cancer leukocytes. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3361. doi:10.1158/1538-7445.AM2015-3361
The pathophysiology and clinical relevance of platelet heterogeneity (1988)

Recent studies on platelet heterogeneity support the hypothesis that platelet production is regulated to maintain a constant functional platelet mass. In concept this form of regulation is analogous to the manner by which RBC production is controlled to maintain the oxygen-carrying capacity of blood. The platelet mass appears to correlate more closely with platelet function than the platelet count alone, since several factors in addition to the platelet count have been shown to influence the platelets' hemostatic function. These factors include platelet size, density, age, and previous hemostatic interactions. Application of these concepts to clinical problems has provided important insights into platelet physiology and reactivity. Failure to account for differences in platelet heterogeneity among individuals may introduce significant errors in the interpretation of data from laboratory and clinical investigations. However, despite advances, a number of practical issues remain to be resolved before measurements of platelet heterogeneity become accepted as routine clinical tests and are used in the diagnosis of pathologic states.
Inadequate white cell reduction by bedside filtration of red cell concentrates (1994)

Bedside filtration for white cell reduction at slow flow is inefficient for 1-day-old, buffy coat-reduced red cell concentrates.
Polyampholytes as Cryoprotective Agents for Mammalian Cell Cryopreservation (2010)

Cryoprotective agents (CPAs) such as dimethyl sulfoxide (DMSO), glycerol, ethylene glycol, and propylene glycol have been used for the cryopreservation of cells and tissues. DMSO is the most effective CPA but shows high cytotoxicity and can effect differentiation. ɛ-poly-L-lysine (PLL) derivatives show higher cryopreservation efficiency than the conventional CPAs. Culture medium solutions with 7.5 w/w% of PLL whose amino groups of more than 50 mol% were converted to carboxyl groups by succinic anhydride showed higher postthaw survival efficiency of L929 cells than those of current CPAs without the addition of any proteins. In addition, rat mesenchymal stem cells were cryopreserved more effectively than with DMSO and fully retained the potential for proliferation and differentiation. Furthermore, many kinds of cells could be cryopreserved with PLL having the appropriate ratio of COOH groups, regardless of the cell types, including adhesive and floating cells, human- and mouse-derived cells, primary cells, and established cell lines. The properties might be associated with the antifreeze protein properties. These results indicate that these polymeric extracellular CPAs may replace current CPAs and the high viability after thawing and nonnecessity of serum ensure that these CPAs may be used in various preservation fields.
Inhibition of forskolin-induced neurite outgrowth and protein phosphorylation by a newly synthesized selective inhibitor of cyclic AMP-dependent protein kinase, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), of PC12D pheochromocytoma cells. (1990)

A newly synthesized isoquinolinesulfonamide, H-89 (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline-sulfonamide), was shown to have a potent and selective inhibitory action against cyclic AMP-dependent protein kinase (protein kinase A), with an inhibition constant of 0.048 +/- 0.008 microM. H-89 exhibited weak inhibitory action against other kinases and Ki values of the compound for these kinases, including cGMP-dependent protein kinase (protein kinase G), Ca2+/phospholipid-dependent protein kinase (protein kinase C), casein kinase I and II, myosin light chain kinase, and Ca2+/calmodulin-dependent protein kinase II were 0.48 +/- 0.13, 31.7 +/- 15.9, 38.3 +/- 6.0, 136.7 +/- 17.0, 28.3 +/- 17.5, and 29.7 +/- 8.1 microM, respectively. Kinetic analysis indicated that H-89 inhibits protein kinase A, in competitive fashion against ATP. To examine the role of protein kinase A in neurite outgrowth of PC12 cells, H-89 was applied along with nerve growth factor (NGF), forskolin, or dibutyryl cAMP. Pretreatment with H-89 led to a dose-dependent inhibition of the forskolin-induced protein phosphorylation, with no decrease in intracellular cyclic AMP levels in PC12D cells, and the NGF-induced protein phosphorylation was not not inhibited. H-89 also significantly inhibited the forskolin-induced neurite outgrowth from PC12D cells. This inhibition also occurred when H-89 was added before the addition of dibutyryl cAMP. Pretreatment of PC12D cells with H-89 (30 microM) inhibited significantly cAMP-dependent histone IIb phosphorylation activity in cell lysates but did not affect other protein phosphorylation activity such as cGMP-dependent histone IIb phosphorylation activity, Ca2+/phospholipid-dependent histone IIIs phosphorylation activity, Ca2+/calmodulin-dependent myosin light chain phosphorylation activity, and alpha-casein phosphorylation activity. However, this protein kinase A inhibitor did not inhibit the NGF-induced neurite outgrowth from PC12D cells. Thus, the forskolin- and dibutyryl cAMP-induced neurite outgrowth is apparently mediated by protein kinase A while the NGF-induced neurite outgrowth is mediated by a protein kinase A-independent pathway.