gebhart/patrepeval huggingface dataset:
Gadolinium(iii) complexes as MRI contrast agents: ligand design and properties of the complexes (2008)

Magnetic resonance imaging is a commonly used diagnostic method in medicinal practice as well as in biological and preclinical research. Contrast agents (CAs), which are often applied are mostly based on Gd(III) complexes. In this paper, the ligand types and structures of their complexes on one side and a set of the physico-chemical parameters governing properties of the CAs on the other side are discussed. The solid-state structures of lanthanide(III) complexes of open-chain and macrocyclic ligands and their structural features are compared. Examples of tuning of ligand structures to alter the relaxometric properties of gadolinium(III) complexes as a number of coordinated water molecules, their residence time (exchange rate) or reorientation time of the complexes are given. Influence of the structural changes of the ligands on thermodynamic stability and kinetic inertness/lability of their lanthanide(III) complexes is discussed.
Convective Heat Transfer in a Gas-Fired Pulsating Combustor (1969)

The effect of longitudinal combustion-driven oscillations on convective heat transfer rates was studied using a tubular, propane-fired combustor which resonated as a quarter-wavelength organ pipe at a frequency of 100 cps. The combustor was provided with damping tubes of variable length which enabled the amplitude of the oscillations to be varied, to the extent of damping them out completely. Heat transfer coefficients were measured with and without the presence of combustion-driven oscillations. It was found that heat transfer coefficients were highest at a position of maximum velocity amplitude, where improvements of over 100 percent were obtained. Satisfactory prediction of the effects of the oscillations was obtained by using the quasisteady-state theory.
Thalidomide derivative CC-4047 inhibits osteoclast formation by down-regulation of PU.1 (2005)

CC-4047, an immunomodulatory analog of thalidomide, inhibits multiple myeloma with unknown effects on the human osteoclast lineage. Early osteoclast progenitors are of hematopoietic origin and differentiate into mature bone resorbing multinucleated osteoclasts. We investigated the effects of CC-4047 and thalidomide on human osteoclastogenesis, using in vitro receptor activator of NFkappa-B ligand/macrophage colony-stimulating factor-stimulated bone marrow cell cultures. Treating bone marrow cultures with CC-4047 for 3 weeks decreased osteoclast formation accompanied by complete inhibition of bone resorption. The inhibitory effect was similar when cultures were treated for 3 weeks or for only the first week (90% inhibition), indicating that CC-4047 inhibits early stages of osteoclast formation. Inhibition of osteoclastogenesis by CC-4047 was mediated by a shift of lineage commitment to granulocyte colony-forming units at the expense of granulocyte-macrophage colony-forming units. Further studies revealed that this shift in lineage commitment was mediated through down-regulation of PU.1. Treatment with thalidomide resulted in significantly less potent inhibition of osteoclast formation and bone resorption. These results provide evidence that CC-4047 blocks osteoclast differentiation during early phases of osteoclastogenesis. Therefore, CC-4047 might be a valuable drug for targeting both tumors and osteoclastic activity in patients with multiple myeloma and other diseases associated with osteolytic lesions.
A major chromatin regulator determines resistance of tumor cells to T cell–mediated killing (2018)

Many human cancers are resistant to immunotherapy, for reasons that are poorly understood. We used a genome-scale CRISPR-Cas9 screen to identify mechanisms of tumor cell resistance to killing by cytotoxic T cells, the central effectors of antitumor immunity. Inactivation of >100 genes-including <i>Pbrm1</i>, <i>Arid2</i>, and <i>Brd7</i>, which encode components of the PBAF form of the SWI/SNF chromatin remodeling complex-sensitized mouse B16F10 melanoma cells to killing by T cells. Loss of PBAF function increased tumor cell sensitivity to interferon-γ, resulting in enhanced secretion of chemokines that recruit effector T cells. Treatment-resistant tumors became responsive to immunotherapy when <i>Pbrm1</i> was inactivated. In many human cancers, expression of <i>PBRM1</i> and <i>ARID2</i> inversely correlated with expression of T cell cytotoxicity genes, and <i>Pbrm1</i>-deficient murine melanomas were more strongly infiltrated by cytotoxic T cells.
Antiangiogenic gene therapy of cancer utilizing a recombinant adenovirus to elevate systemic endostatin levels in mice. (2000)

Gene therapy represents a possible alternative to the chronic delivery of recombinant antiangiogenic proteins to cancer patients. Inducing normal host tissues to produce high circulating levels of these proteins may be more effective than targeting antiangiogenic genes to tumor tissue specifically. Previously reported gene therapy approaches in mice have achieved peak circulating endostatin levels of 8-33 ng/ml. Here we report plasma endostatin levels of 1770 ng/ml after administration of a recombinant adenovirus. Growth of MC38 adenocarcinoma, which is relatively resistant to adenoviral infection, was inhibited by 40%. These findings encourage gene delivery approaches that use the host as a "factory" to produce high circulating levels of antiangiogenic agents.
Nitroxides as potential contrast enhancing agents for MRI application: Influence of structure on the rate of reduction by rat hepatocytes, whole liver homogenate, subcellular fractions, and ascorbate (1987)

With an eye toward the development of nitroxides as potential contrast enhancing agents for MRI applications, we have compared the rates of reduction of 24 nitroxides of diverse structures by rat whole liver homogenate, hepatocytes, subcellular fractions, and ascorbate (10 eq excess). Our results indicate that five-membered ring nitroxides and alpha-carboxy alpha-aryl tert-butyl nitroxides are significantly more resistant toward bioreduction than six-membered ring and heterocyclic-substituted nitroxides in all systems. In the case of six-membered ring nitroxides the presence of either negatively charged or positively charged groups increases the susceptibility toward ascorbate reduction. The presence of carboxylate groups tends to enhance the resistance of all the nitroxides toward reduction by liver homogenate, hepatocytes, and subcellular fractions. trans-Azethoxyl nitroxides exhibited the best overall resistance toward bioreduction. The T1 relaxants of selected nitroxides were measured and found to be similar.
Three-dimensional hypoxic culture of human mesenchymal stem cells encapsulated in a photocurable, biodegradable polymer hydrogel: A potential injectable cellular product for nucleus pulposus regeneration (2014)

Nucleus pulposus (NP) tissue damage can induce detrimental mechanical stresses and strains on the intervertebral disc, leading to disc degeneration. This study demonstrates the potential of a novel, photo-curable, injectable, synthetic polymer hydrogel (pHEMA-co-APMA grafted with polyamidoamine (PAA)) to encapsulate and differentiate human mesenchymal stem cells (hMSC) towards a NP phenotype under hypoxic conditions which could be used to restore NP tissue function and mechanical properties. Encapsulated hMSC cultured in media (hMSC and chondrogenic) displayed good cell viability up to day 14. The genotoxicity effects of ultraviolet (UV) on hMSC activity confirmed the acceptability of 2.5min of UV light exposure to cells. Cytotoxicity investigations revealed that hMSC cultured in media containing p(HEMA-co-APMA) grafted with PAA degradation product (10% and 20%v/v concentration) for 14days significantly decreased the initial hMSC adhesion ability and proliferation rate from 24hrs to day 14. Successful differentiation of encapsulated hMSC within hydrogels towards chondrogenesis was observed with elevated expression levels of aggrecan and collagen II when cultured in chondrogenic media under hypoxic conditions, in comparison with culture in hMSC media for 14days. Characterization of the mechanical properties revealed a significant decrease in stiffness and modulus values of cellular hydrogels in comparison with acellular hydrogels at both day 7 and day 14. These results demonstrate the potential use of an in vivo photo-curable injectable, synthetic hydrogel with encapsulated hMSC for application in the repair and regeneration of NP tissue.
PYPAF1, a PYRIN-containing Apaf1-like Protein That Assembles with ASC and Regulates Activation of NF-κB (2002)

The PYRIN domain is a recently identified protein-protein interaction domain that is found at the N terminus of several proteins thought to function in apoptotic and inflammatory signaling pathways. We report here that PYPAF1 (PYRIN-containing Apaf1-like protein 1) is a novel PYRIN-containing signaling protein that belongs to the nucleotide-binding site/leucine-rich repeat (NBS/LRR) family of signaling proteins. The expression of PYPAF1 is highly restricted to immune cells, and its gene maps to chromosome 1q44, a locus that is associated with the rare inflammatory diseases Muckle-Wells syndrome and familial cold urticaria. To identify downstream signaling partners of PYPAF1, we performed a mammalian two-hybrid screen and identified ASC as a PYRIN-containing protein that interacts selectively with the PYRIN domain of PYPAF1. When expressed in cells, ASC recruits PYPAF1 to distinct cytoplasmic loci and induces the activation of NF-kappaB. Furthermore, coexpression of PYPAF1 with ASC results in a potent synergistic activation of NF-kappaB. These findings suggest that PYPAF1 and ASC function as upstream activators of NF-kappaB signaling.
A stereo display prototype with multiple focal distances (2004)

Typical stereo displays provide incorrect focus cues because the light comes from a single surface. We describe a prototype stereo display comprising two independent fixed-viewpoint volumetric displays. Like autostereoscopic volumetric displays, fixed-viewpoint volumetric displays generate near-correct focus cues without tracking eye position, because light comes from sources at the correct focal distances. (In our prototype, from three image planes at different physical distances.) Unlike autostereoscopic volumetric displays, however, fixed-viewpoint volumetric displays retain the qualities of modern projective graphics: view-dependent lighting effects such as occlusion, specularity, and reflection are correctly depicted; modern graphics processor and 2-D display technology can be utilized; and realistic fields of view and depths of field can be implemented. While not a practical solution for general-purpose viewing, our prototype display is a proof of concept and a platform for ongoing vision research. The design, implementation, and verification of this stereo display are described, including a novel technique of filtering along visual lines using 1-D texture mapping.
A bacteriocin gene cluster able to enhance plasmid maintenance in Lactococcus lactis (2014)

Inserting the Lcn972 cluster into segregational unstable plasmids prevents their lost by segregation and probable could be applied as an alternative to the use of antibiotics to support safer and more sustainable biotechnological applications of genetically engineered L. lactis.
Regulation by long‐chain fatty acids of the expression of cholesteryl ester transfer protein in HepG2 cells (2001)

Cholesteryl ester transfer protein (CETP) is an important determinant of lipoprotein function, especially high density lipoprotein (HDL) metabolism, and contributes to the regulation of plasma HDL levels. Since saturated and polyunsaturated fatty acids (FA) appear to influence the CETP activity differently, we decided to investigate the effects of FA on the expression of CETP mRNA in HepG2 cells using an RNA blot hybridization analysis. Long-chain FA (>18 carbons) at a 0.5 mM concentration were added to the medium and incubated with cells for 48 h at 37 degrees C under 5% CO2. After treatment with 0.5 mM arachidonic (AA), eicosapentaenoic (EPA), and docosahexaenoic acid (DHA), the levels of CETP mRNA were less than 50% of the control levels (AA, P = 0.0005; EPA, P < 0.01; DHA, P < 0.0001), with a corresponding significant decrease in the CETP mass. These results suggest that FA regulate the gene expression of CETP in HepG2 and this effect is dependent upon the degree of unsaturation of the acyl carbon chain in FA.
Examination of Influenza Specific T Cell Responses after Influenza Virus Challenge in Individuals Vaccinated with MVA-NP+M1 Vaccine (2013)

Current influenza vaccines stimulate neutralising antibody to the haemagglutinin antigen but as there is antigenic drift in HA it is difficult to prepare a vaccine in advance against an emergent strain. A potential strategy is to induce CD8(+) and CD4(+) T cells that recognize epitopes within internal proteins that are less subject to antigenic drift. Augmenting humoral responses to HA with T cell responses to more conserved antigens may result in a more broadly protective vaccine. In this study, we evaluate the quality of influenza specific T cell responses in a clinical trial using MVA-NP+M1 vaccination followed by influenza virus challenge. In vaccinated volunteers, the expression of Granzyme A, Perforin and CD57 on influenza HLA A*02 M158-66 antigen specific cells was higher than non-vaccinated volunteers before and after challenge despite a similar frequency of antigen specific cells. BCL2 expression was lower in vaccinated volunteers. These data indicate that antigen specific T cells are a useful additional measure for use in human vaccination or immunization studies.
Differential expression of the c‐kit proto‐oncogene in germ cell tumours (1995)

The c-kit proto-oncogene product and its ligand stem cell factor play an important role in haematopoiesis, spermatogenesis, and melanogenesis. Using an anti-c-kit antiserum raised against a synthetic peptide, we studied the immunohistochemical expression of the c-kit gene product in 60 germ cell tumours (GCTs) (53 testicular, 7 extragonadal), derived from primary GCTs in 45 cases and metastatic tumours in 15 cases. Twenty-eight out of 28 seminomas showed c-kit membranous staining in the majority of cells. A similar pattern of expression was seen in intratubular germ cell neoplasia. Nine out of 29 (32 per cent) non-seminomas displayed cytoplasmic, but not membranous, c-kit immunoreactivity in occasional cells. In three mixed GCTs, c-kit expression was limited to the seminoma component. In normal testis, c-kit expression was observed in some basal tubular cells, corresponding to undifferentiated spermatogonia. These results suggest a role for c-kit in the oncogenesis of GCT, where down-regulation of c-kit might be a critical step during progression from seminomas to non-seminomas. Immunohistochemical analysis of c-kit should be considered as a diagnostic aid for GCT and in particular may be helpful in the identification of certain extragonadal seminomas.
Selective Inhibition of CCR2 Expressing Lymphomyeloid Cells in Experimental Autoimmune Encephalomyelitis by a GM-CSF-MCP1 Fusokine (2009)

We describe the generation of a fusion cytokine consisting of GM-CSF in tandem with N-terminal-truncated MCP-1 (6-76), hereafter GMME1. Treatment of activated T cells with recombinant GMME1 protein leads to proinflammatory cytokine reduction and apoptosis via a CCR2-restricted pathway. Similarly, cell death is triggered in macrophages cultured with GMME1, while an inhibition of Ab production from plasma cells is observed. Treatment of CD4 T cells derived from experimental autoimmune encephalomyelitis mice with GMME1 leads to p38 hyperphosphorylation, inhibition of p44/42, AKT and STAT3 phosphorylation, and caspase-3 activation. GMME1 administration to experimental autoimmune encephalomyelitis mice suppresses symptomatic disease and correlates with decreased levels of inflammatory cytokines including IL-17, MOG-specific Ab titers, and blockade of CD4 and CD8 T cell infiltration in spinal cords. We propose that GMME1 defines a new class of agents for the treatment of autoimmune ailments by selectively targeting lymphomyeloid cells expressing CCR2.
A cancer-associated PCNA expressed in breast cancer has implications as a potential biomarker (2006)

Two isoforms of proliferating cell nuclear antigen (PCNA) have been observed in breast cancer cells. Commercially available antibodies to PCNA recognize both isoforms and, therefore, cannot differentiate between the PCNA isoforms in malignant and nonmalignant breast epithelial cells and tissues. We have developed a unique antibody that specifically detects a PCNA isoform (caPCNA) associated with breast cancer epithelial cells grown in culture and breast-tumor tissues. Immunostaining studies using this antibody suggest that the caPCNA isoform may be useful as a marker of breast cancer and that the caPCNA-specific antibody could potentially serve as a highly effective detector of malignancy. We also report here that the caPCNA isoform functions in breast cancer-cell DNA replication and interacts with DNA polymerase delta. Our studies indicate that the caPCNA isoform may be a previously uncharacterized detector of breast cancer.
Enhanced neutrophil response in chronic obstructive pulmonary disease (2001)

BACKGROUND Neutrophils are likely to play a major role in the inflammatory response seen in chronic obstructive pulmonary disease (COPD). This study sought to address the hypothesis that an enhanced neutrophil response to proinflammatory agents in COPD may contribute to their recruitment and activation in the lungs. METHODS Circulating neutrophils were obtained from 10 patients with COPD, eight long term smokers with normal lung function, and eight healthy never smoking controls. The in vitro production of reactive oxygen species (ROS) was measured by the NADPH oxidase method (respiratory burst) and the surface expression of several adhesion molecules (Mac-1, LFA-1 and l -selectin) was measured by flow cytometry. Measurements were obtained under basal conditions and after stimulation with phorbol myristate acetate (PMA) and tumour necrosis factor alpha (TNFα). mRNA levels of p22- phox (a subunit of NADPH oxidase) and Mac-1 (CD11b) were also determined by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS Patients with COPD showed enhanced respiratory burst compared with smokers with normal lung function, both under basal conditions (mean (SE) fluorescence intensity (MFI) 15.1 (0.5) v 11.6 (0.5); mean difference –3.4 (95% CI of the difference –5.1 to –1.8), p&lt;0.01) and after PMA stimulation (MFI 210 (7) v 133 (10); mean difference –77 (95% CI of the difference –102 to –52), p&lt;0.01). Mac-1 surface expression was also enhanced in patients with COPD, both under basal conditions (MFI 91 (5) v 45 (3); mean difference –46 (95% CI of the difference –61 to –31), p&lt;0.001) and after stimulation with TNFα (MFI 340 (15) v 263 (11); mean difference –77 (95% CI of the difference –119 to –34), p=0.001). These differences were also apparent when patients with COPD were compared with non-smokers (p&lt;0.05). The mRNA levels of p22- phox and Mac-1 (CD11b) were similar in patients with COPD and smokers with normal lung function, suggesting that the observed differences were due to post-transcriptional regulation. CONCLUSIONS These results demonstrate an enhanced neutrophil response to proinflammatory agents in patients with COPD which may contribute to their enhanced recruitment and activation in the lungs of these patients. These findings support those of other studies which have indicated that the neutrophil is likely to play a major role in the pathogenesis of this disease.
The B subunit of a rat heteromeric CCAAT-binding transcription factor shows a striking sequence identity with the yeast Hap2 transcription factor. (1990)

CBF is a heteromeric mammalian transcription factor that binds to CCAAT sequences in a number of promoters such as the two type I collagen promoters, the albumin promoter, the major histocompatibility complex class II promoter, and others. It is composed of two components, A and B, that are both needed for DNA binding. We have isolated a rat cDNA containing the complete 341-amino acid coding sequence of the B component of CBF. Expression of this cDNA in vitro generates a polypeptide that shows the same dependency on the A component as the native B component in the formation of a complex with a CCAAT-containing DNA. The C-terminal portion of the B component from residue 260 to residue 312 shows a 75% sequence identity with a portion of the Hap2 protein, a component of a heteromeric CCAAT-binding protein in yeast. In contrast, the rest of the protein shows little sequence homology with Hap2, although both proteins contain glutamine-rich domains. In the B component of CBF this domain spans the amino-terminal 60% of the protein, whereas in Hap2 this domain is much smaller. Hence, only a few changes in one domain of this protein were tolerated during evolution between yeast and mammals, whereas the rest of the protein diverged much more extensively.
Blocking of α4β7 Gut-Homing Integrin during Acute Infection Leads to Decreased Plasma and Gastrointestinal Tissue Viral Loads in Simian Immunodeficiency Virus-Infected Rhesus Macaques (2010)

Intravenous administration of a novel recombinant rhesus mAb against the α4β7 gut-homing integrin (mAb) into rhesus macaques just prior to and during acute SIV infection resulted in significant decrease in plasma and gastrointestinal (GI) tissue viral load and a marked reduction in GI tissue proviral DNA load as compared with control SIV-infected rhesus macaques. This mAb administration was associated with increases in peripheral blood naive and central memory CD4(+) T cells and maintenance of a high frequency of CCR5(+)CD4(+) T cells. Additionally, such mAb administration inhibited the mobilization of NK cells and plasmacytoid dendritic cells characteristically seen in the control animals during acute infection accompanied by the inhibition of the synthesis of MIP-3α by the gut tissues. These data in concert suggest that blocking of GI trafficking CD4(+) T cells and inhibiting the mobilization of cell lineages of the innate immune system may be a powerful new tool to protect GI tissues and modulate acute lentiviral infection.
Multicarrier communication systems with low sensibility to nonlinear amplification (2008)

Actualment estem entrant a una nova era de la informacio amb gran demanda de sistemes de comunicacio sense fils. Nous serveis com dades i video requereixen transmissions fiables d'alta velocitat, fins i tot en escenaris d'alta mobilitat. A mes a mes, la dificultat d'assignar el limitat espectre radioelectric juntament amb la necessitat d'incrementar el temps de vida de les bateries dels terminals mobils, requereix el diseny de transceptors que usin la potencia i l'ampla de banda disponibles de manera eficient. Les comunicacions multiportadora basades en OFDM son capaces de satisfer la majoria d'aquests requeriments. Pero, entre altres reptes, reduir la sensibilitat a la amplificacio no-lineal es un factor clau durant el diseny. En aquesta tesi doctoral s'analitza la sensibilitat dels sistemes multiportadora basats en OFDM a l'amplificacio no-lineal i es consideren formes eficients per superar aquest problema. La tesi s'enfoca principalment al problema de reduir les fluctuacions de l'envolupant del senyal transmes. En aquest sentit es presenta tambe un estudi de les metriques de l'envolupant del senyal, PAPR i CM. A mes a mes, basant-nos en l'analisis presentat es proposen noves tecniques per sistemes OFDM i MC-SS. Per MC-SS, tambe es tracta el diseny d'una tecnica de postprocessament en forma de detector multiusuari per canals no-lineals.
New, efficient electroluminescent materials based on organometallic Ir complexes (2001)

Reaction of IrCl3 with fluorinated 2-arylpyridines in the presence of AgO2CCF3 affords fac-tris-cyclometalated arylpyridine Ir complexes exhibiting excellent processing and electroluminescent properties which can be fine-tuned via systematic control of the nature and position of the substituents on the aromatic rings.