gebhart/patrepeval huggingface dataset:
SIRT1 Expression is Associated With Poor Prognosis of Diffuse Large B-Cell Lymphoma (2008)

Sirtuin1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase. Recently, it is suggested that SIRT1 may be involved in the development of malignant tumors including mouse lymphoma. Therefore, we investigated the prevalence and the prognostic impact of SIRT1 expression in diffuse large B-cell lymphoma (DLBCL). Immunohistochemical expression of SIRT1, p53, bcl2, CD10, bcl6, and multiple myeloma-1 (MUM1) were evaluated by using a 2 mm core from 104 DLBCL patients for tissue microarray. Positive expression of SIRT1 was seen in 74% (77/104) of patients. In total DLBCL patients, SIRT1 and p53 expression were significantly associated with shorter overall survival (OS) by univariate analysis (P=0.001 and P=0.011, respectively). SIRT1 was also an independent prognostic factor by multivariate analysis (P=0.01). According to the expression patterns of CD10, bcl6, and MUM1, germinal center B cell (GCB) types were represented in 38 cases (37%) and non-GCB types were represented in 66 cases (63%). In the GCB type, only p53 expression was associated with a significantly shorter OS (P=0.032). In the non-GCB type, expression of SIRT1 correlated with shorter OS by univariate analyses (P=0.005) and multivariate analyses (P=0.049). In conclusion, we showed that SIRT1 expression is a clinically significant prognostic indicator for DLBCL patients.
Optical damage thresholds at 294 μm in fluoride glass fibers (1992)

Optical damage thresholds at lambda = 2.94 microm have been investigated in one single-mode (11-microm core, 125-microm cladding) and five multimode fluoride glass fibers. (These five fibers consist of three conventional ones, 70-microm core, 140-microm cladding, 150-microm core, 200-microm cladding, and 200-microm core, 250-microm cladding, and two low-attenuation ones, 200-microm core, 250-microm cladding, and 350-microm core, 400-microm cladding.) The induced surface damage is discussed by means of electron microscopic analysis. Power limits for safe transmission are presented.
Dual Signaling Role of the Protein Tyrosine Phosphatase SHP-2 in Regulating Expression of Acute-Phase Plasma Proteins by Interleukin-6 Cytokine Receptors in Hepatic Cells (1999)

One of the major actions of interleukin-6 (IL-6) is the transcriptional activation of acute-phase plasma proteins (APP) genes in liver cells. Signaling by the IL-6 receptor is mediated through the signal transducing subunit gp130 and involves the activation of Janus-associated kinases (JAKs), signal transducer and activator of transcription 3 (STAT3), and mitogen-activated protein (MAP) kinase. Functional analysis of gp130 in rat hepatoma cells by using transduced chimeric G-CSFR-gp130 receptor constructs demonstrates that SHP-2, the Src homology 2 (SH2) domain-containing protein tyrosine phosphatase, acts as a negative regulator of the JAK/STAT signaling in part by downregulating JAK activity, thereby indirectly moderating the induction of STAT3-dependent APP genes. This study shows that in hepatoma cells, the recruitment and tyrosine phosphorylation of SHP-2, but not SHC, is the primary signaling event associated with the activation of MAP kinases (ERK1/2) by gp130. Overexpression of truncated SHP-2 that lacks Grb2-interacting sites, but not the full-length catalytically inactive SHP-2, reduces ERK activation by IL-6, confirming the signal-mediating role of SHP-2. Activation of ERK1/2 is correlated with induction of the immediate-early response genes. Stimulation of the c-fos, c-jun, and egr-1 genes is essentially absent in cells expressing gp130 with a Y759F mutation, which is unable to recruit SHP-2. Interestingly, both JAK/STAT and SHP-2 pathways regulate the induction of the junB gene. Moreover, disengagement of SHP-2 from gp130 signaling not only enhances APP gene induction but also further reduces cell proliferation, in part correlated with the attenuated expression of immediate-early response genes. These results suggest that IL-6 regulation of APP genes is affected by SHP-2 in two ways: SHP-2 acts as a phosphatase on the JAK/STAT pathway and serves as linker to the MAP kinase pathway, which in turn moderates APP production.
3B-1 Noninvasive Insulin Delivery in Large Pigs (> 100 lbs) Using the Lightweight Cymbal Array (2007)

Use of needles for multiple injections of drugs, such as insulin for diabetes, can be painful. As a result, prescribed drug noncompliance can results in severe medical complications. In previous studies, ultrasound mediated transdermal drug delivery has shown a promising potential as a method for noninvasive drug administration. Yet for prospective human application, a milestone to a practical clinical device of this research requires that the efficacy of the cymbal array be demonstrated on animals larger than rats and rabbits. Larger and possessing a blood volume similar to humans, pig is an appropriate animal model for further experimentation in evaluating the practicability of this ultrasound device. Six Yorkshire pigs (100-140 lbs) were divided into two groups. As the control (n = 3), the first group did not receive any ultrasound exposure with the insulin. The second group (n = 3) was treated with ultrasound and insulin at 20 kHz with an I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">sptp</sub> = 100 mW/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> at a 20% duty cycle for 60 minutes. With the pigs in lateral recumbency after anesthesia, the ultrasound transducer with insulin was placed on the axillary area of the pig. At the beginning and every 15 minutes up to 90 minutes, the blood glucose level was determined using a glucose monitoring system. To compare the results of individual animals, the change of blood glucose level was normalized to each animal's initial glucose value at the start of the experiment. Although each animal had a different initial glucose level, the mean and standard error for the six animals was 146plusmn13 mg/dl (Figure 1). For the control group, the blood glucose level increased to 31plusmn21 mg/dl compared to the initial baseline over the 90 minute experiment. However for the ultrasound with insulin treated group, the glucose level decreased to -72plusmn5 mg/dl at 60 minutes (p < 0.05) and continued to decreased to -91plusmn23 mg/dl in 90 minutes (p < 0.05). Results demonstrate a promising pre-clinical outcome for the low profile cymbal array to be used for ultrasound enhanced in vivo insulin transport using an animal with a similar size and weight to a human. The cymbal array has potential as a practical ultrasound system for noninvasive transdermal insulin delivery for diabetes management.
Neuropeptide-induced Transactivation of a Neuronal Epidermal Growth Factor Receptor Is Mediated by Metalloprotease-dependent Formation of Heparin-binding Epidermal Growth Factor (2003)

Numerous external stimuli, including G protein-coupled receptor agonists, cytokines, growth factors, and steroids activate mitogen-activated protein kinases (MAPKs) through phosphorylation of the epidermal growth factor receptor (EGF-R). In immortalized hypothalamic neurons (GT1-7 cells), agonist binding to the gonadotropin-releasing hormone receptor (GnRH-R) causes phosphorylation of MAPKs that is mediated by protein kinase C (PKC)-dependent transactivation of the EGF-R. An analysis of the mechanisms involved in this process showed that GnRH stimulation of GT1-7 cells causes release/shedding of the soluble ligand, heparin binding epidermal growth factor (HB-EGF), as a consequence of metalloprotease activation. GnRH-induced phosphorylation of the EGF-R and, subsequently, of Shc, ERK1/2, and its dependent protein, p90RSK-1 (p90 ribosomal S6 kinase 1 or RSK-1), was abolished by metalloprotease inhibition. Similarly, blockade of the effect of HB-EGF with the selective inhibitor CRM197 or a neutralizing antibody attenuated signals generated by GnRH and phorbol 12-myristate 13-acetate, but not those stimulated by EGF. In contrast, phosphorylation of the EGF-R, Shc, and ERK1/2 by EGF and HB-EGF was independent of PKC and metalloprotease activity. The signaling characteristics of HB-EGF closely resembled those of GnRH and EGF in terms of the phosphorylation of EGF-R, Shc, ERK1/2, and RSK-1 as well as the nuclear translocation of RSK-1. However, neither the selective Src kinase inhibitor PP2 nor the overexpression of negative regulatory Src kinase and dominant negative Pyk2 had any effect on HB-EGF-induced responses. In contrast to GT1-7 cells, human embryonic kidney 293 cells expressing the GnRH-R did not exhibit metalloprotease induction and EGF-R transactivation during GnRH stimulation. These data indicate that the GnRH-induced transactivation of the EGF-R and the subsequent ERK1/2 phosphorylation result from ectodomain shedding of HBEGF through PKC-dependent activation of metalloprotease(s) in neuronal GT1-7 cells.
Synthesis and spectral properties of a hydrophobic fluorescent probe: 6-propionyl-2-(dimethylamino)naphthalene (1979)

Environmentally sensitive fluorescent probes involve two groups, an electron donor and an electron acceptor, attached to an aromatic ring system, and maximal effects may be expected when these groups are as far apart as feasible. The syntheisis, characterization, and spectroscopic properties of 6-propionyl-2-(dimethylamino)naphthalene (PRODAN), a compound that fulfills these conditions, are described. The maximum of emission is at 401 nm in cyclohexane solution and at 531 nm in water solution, indicating an increase of dipole moment of approximately 20 D units on excitation to the lowest singlet state. The effect of temperature upon the spectral distribution and the bandwidth of fluorescence of PRODAN in 1:1 complexes with albumin shows the existence of a dynamic relaxation process of the protein surroundings within th 2-4 ns of the fluorescence lifetime.
Scanning Probe Lithography. 4. Characterization of Scanning Tunneling Microscope-Induced Patterns in n-Alkanethiol Self-Assembled Monolayers (1997)

Self-assembled monolayers (SAMs) of n-alkanethiol molecules adsorbed onto Au(111) substrates act as lithographic resists, which can be selectively patterned using scanning tunneling microscopy (STM). We previously provided evidence that patterning is the result of faradaic electrochemical processes. Here, we provide a more detailed model for the patterning mechanism that involves penetration of the tip into the SAM, concerted SAM disruption, and subsequent SAM removal arising from electrochemical processes. Experiments, and a detailed analysis of the patterned features, are consistent with this model. Other key results of this study include the following: (1) the electrochemical nature of the patterning process defines the resolution of STM patterning under the conditions used in this study; (2) lithographically defined patterns are dimensionally stable for several days; (3) the STM tip penetrates the monolayer and very slowly modifies it regardless of bias and tunneling current.
Tat-SF1 Protein Associates with RAP30 and Human SPT5 Proteins (1999)

The potent transactivator Tat recognizes the transactivation response RNA element (TAR) of human immunodeficiency virus type 1 and stimulates the processivity of elongation of RNA polymerase (Pol) II complexes. The cellular proteins Tat-SF1 and human SPT5 (hSPT5) are required for Tat activation as shown by immunodepletion with specific sera and complementation with recombinant proteins. In nuclear extracts, small fractions of both hSPT5 and Pol II are associated with Tat-SF1 protein. Surprisingly, the RAP30 protein of the heterodimeric transcription TFIIF factor is associated with Tat-SF1, while the RAP74 subunit of TFIIF is not coimmunoprecipitated with Tat-SF1. Overexpression of Tat-SF1 and hSPT5 specifically stimulates the transcriptional activity of Tat in vivo. These results suggest that Tat-SF1 and hSPT5 are indispensable cellular factors supporting Tat-specific transcription activation and that they may interact with RAP30 in controlling elongation.
Protein Kinase Activity and Identification of a Toxic Effector Domain of the Target of Rapamycin TOR Proteins in Yeast (1999)

In complex with FKBP12, the immunosuppressant rapamycin binds to and inhibits the yeast TOR1 and TOR2 proteins and the mammalian homologue mTOR/FRAP/RAFT1. The TOR proteins promote cell cycle progression in yeast and human cells by regulating translation and polarization of the actin cytoskeleton. A C-terminal domain of the TOR proteins shares identity with protein and lipid kinases, but only one substrate (PHAS-I), and no regulators of the TOR-signaling cascade have been identified. We report here that yeast TOR1 has an intrinsic protein kinase activity capable of phosphorylating PHAS-1, and this activity is abolished by an active site mutation and inhibited by FKBP12-rapamycin or wortmannin. We find that an intact TOR1 kinase domain is essential for TOR1 functions in yeast. Overexpression of a TOR1 kinase-inactive mutant, or of a central region of the TOR proteins distinct from the FRB and kinase domains, was toxic in yeast, and overexpression of wild-type TOR1 suppressed this toxic effect. Expression of the TOR-toxic domain leads to a G 1 cell cycle arrest, consistent with an inhibition of TOR function in translation. Overexpression of the PLC1gene, which encodes the yeast phospholipase C homologue, suppressed growth inhibition by the TOR-toxic domains. In conclusion, our findings identify a toxic effector domain of the TOR proteins that may interact with substrates or regulators of the TOR kinase cascade and that shares sequence identity with other PIK family members, including ATR, Rad3, Mei-41, and ATM.
The Contribution of Interleukin (IL)-4 and IL-13 to the Epithelial–Mesenchymal Trophic Unit in Asthma (2001)

Interleukin (IL)-4 and IL-13 are key proinflammatory cytokines in asthma. Studies in transgenic mice show that both cytokines cause inflammation, but only IL-13 causes subepithelial fibrosis, a characteristic feature of asthma. We compared the in vitro profibrogenic effects of IL-4 and IL-13 using bronchial fibroblasts from asthmatic subjects. In the presence of transforming growth factor (TGF)-beta the cells transformed into contractile myofibroblasts and expressed alpha-smooth muscle actin and procollagen I. IL-4 and IL-13 also stimulated proliferation, but were relatively ineffective in promoting myofibroblast transformation. TGF-beta was more potent than the cytokines in stimulating release of endothelin-1 and vascular endothelial growth factor, whereas IL-4 and IL-13 were more potent stimuli for eotaxin release. Although neither IL-4 nor IL-13 induced profibrotic responses, both cytokines caused a corticosteroid-insensitive stimulation of TGF-beta2 release from primary bronchial epithelial cells. These data indicate that epithelial activation by IL-13 or IL-4 plays a critical role in initiating remodeling through release of TGF-beta2. TGF-beta2 then activates the underlying myofibroblasts to secrete matrix proteins and smooth muscle and vascular mitogens to propagate remodeling changes into the submucosa. In contrast, direct activation of submucosal fibroblasts by IL-4 and IL-13 has a proinflammatory effect via eotaxin release and recruitment of eosinophils into the airways.
Syntheses of mesoporous zirconia with anionic surfactants (1998)

Synthesis of mesoporous zirconia has been performed by slowly hydrolyzing zirconium propoxide in the presence of anionic surfactants: dodecyl phosphate or sulfate (P12 and Sf12) and hexadecyl sulfonate (So16). t-Plot surface areas >400 m2 g–1 and diffraction lines corresponding to spacings near 45 Å were measured for solids outgassed at 140–150 °C. This treatment does not remove the surfactant. After calcination in air at 500 °C and combustion of the surfactant the spacing increases to ca. 70 Å and the mesoporous volume is reduced by a factor of about 2, whereas the pore wall material crystallizes in the tetragonal phase. A schematic model in which the surfactant is a scaffold component is suggested in order to explain these results. It is very different from the templating mechanisms reported for zirconia by others. The high resolution electron microscopic study reveals the presence of a disorganized network of polygonal pores in the solids obtained through the mediation of surfactant. It is suggested that the chemistry of the hydrolysis solution is instrumental in the organization of the pore structure and in determining the thickness of the walls. In agreement with others, the fixation of PO4 or SO4 in the walls may help to preserve the porous structure.
CD4+T cells eliminate MHC class II-negative cancer cellsin vivoby indirect effects of IFN-γ (1999)

CD4(+) T cells can eliminate tumor cells in vivo in the absence of CD8(+) T cells. We have CD4(+) T cells specific for a MHC class II-restricted, tumor-specific peptide derived from a mutant ribosomal protein expressed by the UV light-induced tumor 6132A-PRO. By using neutralizing mAb specific for murine IFN-gamma and adoptive transfer of CD4(+) T cells into severe combined immunodeficient mice, we show that anti-IFN-gamma treatment abolishes the CD4(+) T cell-mediated rejection of the tumor cells in vivo. The tumor cells were MHC class II negative, and IFN-gamma did not induce MHC class II expression in vitro. Therefore, the tumor-specific antigenic peptide must be presented by host cells and not the tumor cells. Tumor cells transduced to secrete IFN-gamma had a markedly reduced growth rate in severe combined immunodeficient mice, but IFN-gamma did not inhibit the growth of the tumor cells in vitro. Furthermore, tumor cells stably expressing a dominant-negative truncated form of the murine IFN-gamma receptor alpha chain, and therefore insensitive to IFN-gamma, nevertheless were rejected by the adoptively transferred CD4(+) T cells. Thus, host cells, and not tumor cells, seem to be the target of IFN-gamma. Together, these results show that CD4(+) T cells can eliminate IFN-gamma-insensitive, MHC class II-negative cancer cells by an indirect mechanism that depends on IFN-gamma.
An Alternate Splicing Variant of the Human Telomerase Catalytic Subunit Inhibits Telomerase Activity (2000)

Telomerase, a cellular reverse transcriptase, adds telomeric repeats to chromosome ends. In normal human somatic cells, telomerase is repressed and telomeres progressively shorten, leading to proliferative senescence. Introduction of the telomerase (hTERT) cDNA is sufficient to produce telomerase activity and immortalize normal human cells, suggesting that the repression of telomerase activity is transcriptional. The telomerase transcript has been shown to have at least six alternate splicing sites (four insertion sites and two deletion sites), and variants containing both or either of the deletion sites are present during development and in a panel of cancer cell lines we surveyed. One deletion (beta site) and all four insertions cause premature translation terminations, whereas the other deletion (alpha site) is 36 bp and lies within reverse transcriptase (RT) motif A, suggesting that this deletion variant may be a candidate as a dominant-negative inhibitor of telomerase. We have cloned three alternately spliced hTERT variants that contain the alpha, beta or both alpha and beta deletion sites. These alternate splicing variants along with empty vector and wild-type hTERT were introduced into normal human fibroblasts and several telomerase-positive immortal and tumor cell lines. Expression of the alpha site deletion variant (hTERT alpha-) construct was confirmed by Western blotting. We found that none of the three alternate splicing variants reconstitutes telomerase activity in fibroblasts. However, hTERT alpha- inhibits telomerase activities in telomerase-positive cells, causes telomere shortening and eventually cell death. This alternately spliced dominant-negative variant may be important in understanding telomerase regulation during development, differentiation and in cancer progression.
Miniature field-flow fractionation system for analysis of blood cells (1994)

Field-flow fractionation is an analytical tool that has been historically used to separate species, ranging from molecules to particles or cells several micrometers in size. This technology can effect separation by size, density, charge, or other physical properties, depending on the configuration of the field-flow system. We have developed a miniature field-flow system to analyze cell populations in a small, 125-microns-deep channel 19 cm long. Gravity is used as the primary field to effect separation, and cell analysis is performed in < 20 min. Erythrocytes elute as a single peak when diluted blood is fractionated in this system. Analysis of blood samples from several donors (normal controls and patients with sickle cell anemia) yields erythrocyte peaks with slightly different mobilities (elution times). Peak mobility does not directly correlate with mean cell volume or other standard erythrocyte parameters. Cell density appears to be a key factor in determining cell mobility with this system.
Effect of structure on radiative recombination processes in amorphous silicon suboxide prepared by rf sputtering (2002)

We studied the relationship between the structure and photoluminescence (PL) mechanism of amorphous silicon suboxide (a-SiOx) thin films prepared by the cosputtering method. The microscopic structure of the film was estimated by x-ray photoemission spectroscopy and infrared absorption spectroscopy. Electronic states were investigated by optical absorption and photothermal deflection spectroscopy. The results indicate that the film is separated into two types of regions: Si-rich cluster regions and amorphous SiO2-rich regions. The size of the Si-rich cluster is estimated, according to the quantum confinement model in which no other effects are assumed to exist, to be less than several nm, when the oxygen fraction x is larger than 1.0. The PL peak energy increased monotonically with the x value, whereas it showed different temperature dependences between the larger x value samples and the smaller ones. The PL characteristics observed can consistently be explained by assuming that there are two origins for PL in the present samples: recombination between the tail states in a-Si-rich clusters and luminescence from localized states around the boundaries between the a-Si cluster and the a-SiO2 matrix.
Echocardiographic Evaluation Of Mechanical Dyssynchrony (2007)

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