gebhart/patrepeval huggingface dataset:
Two inhibitors of pro‐inflammatory cytokine release, interleukin‐10 and interleukin‐4, have contrasting effects on release of soluble p75 tumor necrosis factor receptor by cultured monocytes (1994)

The biological activity of the pro-inflammatory cytokine, tumor necrosis factor (TNF)-alpha depends on the level of TNF-alpha itself, the expression of the p55 and p75 cell surface receptors for TNF on target cells and the concentrations of the natural inhibitors of TNF-alpha, the soluble p55 and p75 TNF receptors (TNF-R). Interleukin (IL)-10 and IL-4 are known to inhibit TNF-alpha production by monocytes. We, therefore, investigated the effects of IL-10 and IL-4 on the cell surface expression and release of TNF-R by human monocytes to determine whether these cytokines also indirectly modulated the biological activity of TNF-alpha. Exposure to IL-10 (1-10 U/ml) for 24 or 48 h increased soluble p75 TNF-R expression and concomitantly reduced surface expression of p75 TNF-R. Further, IL-1 alpha-stimulated production of TNF-alpha was diminished by IL-10 and only a small proportion of this TNF-alpha was bioactive, consistent with increased production of inhibitory soluble TNF-R. IL-10 also induced down-regulation of surface p55 TNF-R on monocytes, and increased release of soluble p55 TNF-R. However, the expression of soluble p55 TNF-R was much lower than soluble p75 TNF-R, indicating that it contributed less importantly to neutralization of TNF-alpha under these conditions. Like IL-10, IL-4 supressed the release of TNF-alpha by monocytes. In contrast to IL-10, however, IL-4 (0.1-10 ng/ml) supressed the release of soluble p75 TNF-R from monocytes in a dose-dependent manner. Release of soluble p55 TNF-R was also supressed by IL-4. IL-10, therefore, reduces the pro-inflammatory potential of TNF in three ways: by down-regulating surface TNF-R expression whilst increasing production of soluble TNF-R and inhibiting the release of TNF-alpha itself. This suggests that IL-10 may be useful in the treatment of diseases where overexpression of TNF-alpha occurs.
Synergistic Anticancer Effects of Ganciclovir/Thymidine Kinase and 5-Fluorocytosine/Cytosine Deaminase Gene Therapies (1998)

The presence of transfected cytosine deaminase and thymidine kinase genes in 9L gliosarcoma cells reduced cell survival, both in vitro and in vivo, following treatment with the relevant prodrugs; the effects of the two components appeared to be synergistic and related mechanistically to the enhancement of ganciclovir phosphorylation by thymidine kinase following 5-fluorouracil treatment.
From Cytoskeleton to Polarity and Chemoreception in the Gut Epithelium (1998)

The membrane surface of polarized epithelial cells can be separated in apical and basolateral domains that differ in molecular composition and function. Components of the cytoskeleton obviously play an important role in both generation and maintenance of epithelial polarity. The microtubular system is uniformly aligned in enterocytes and pancreatic acinar cells with the minus ends of the microtubules located apically and the plus ends basally. Drug-induced disassembly of microtubules results in mistargeting of pancreatic zymogen granules and of apical but not basolateral membrane proteins of enterocytes. Association of zymogen granules with the minus end motor protein, cytoplasmic dynein, and components of its receptor, dynactin, indicates that microtubules are important for vectorial delivery of apical but not basolateral post-Golgi vesicles. The lateral membrane domain of the gut epithelium is scaffolded by a spectrin-based membrane cytoskeleton consisting basically of actin, spectrin, and ankyrin. Ankyrin binds to different integral membrane proteins, such as the sodium pump in glandular and kidney epithelial cells or to the anion exchanger (AE2) of gastric parietal cells, thereby probably playing a critical role in maintenance and/or generation of the polarized distribution of these basolateral membrane proteins. Scattered epithelial cells sharing apical cytoskeletal features of gustatory receptor cells were identified as brush cells (tufted cells). These cells are rich in nitric oxide synthase and contain in their apical brush border the gustatory trimeric G-protein, alpha-gustducin, indicating that brush cells are involved in chemoreceptive signaling.
Photoluminescence Spectroscopy of Single CdSe Nanocrystallite Quantum Dots (1996)

We collect and spectrally resolve photoluminescence from single CdSe nanocrystallite quantum dots. The elimination of spectral inhomogeneities reveals resolution limited spectral linewidths ( $&lt;120\ensuremath{\mu}\mathrm{eV}$ at 10 K) more than 50 times narrower than expected from ensemble measurements. Light driven spectral diffusion is observed as a form of power broadening. These studies confirm the atomiclike nature of the emitting state in CdSe nanocrystallites.
Application of a filamentous phage pVIII fusion protein system suitable for efficient production, screening, and mutagenesis of F(ab) antibody fragments (1992)

Abstract We describe the application of a novel filamentous phage vector system suitable for efficient screening and production of F(ab) antibody fragments. The vector system can concurrently produce free F(ab) fragments and F(ab) displayed on the surface of M13 bacteriophage via a VHCH1-pVIII fusion protein. When expressed in a supO (nonsuppressor) strain of Escherichia coli free F(ab) can be produced. Antibody F(ab) fragments are secreted into culture medium at concentrations up to 0.3 mg/liter and conveniently subjected to detailed analysis with little or no purification. Higher concentrations of F(ab) (approximately 10 mg/liter) were found to accumulate in the periplasmic space. In this report the vector system is shown to produce correctly folded and assembled F(ab) fragments of chimeric L6, a mAb against a tumor-associated Ag expressed by many human carcinomas.
The orphan receptor GPR55 is a novel cannabinoid receptor (2007)

These data suggest that GPR55 is a novel cannabinoid receptor, and its ligand profile with respect to CB1 and CB2 described here will permit delineation of its physiological function(s).
Some Facts and Thoughts on Cell Cycle Control in Yeast (1991)

The passage of cells through the cell cycle can be regulated either by decisions made in G1 to enter S phase or by decisions made in G2 to enter mitosis. Good examples of both types of controls can be found in the life cycles of two very different ascomycete yeasts whose cell cycles have been extensively studied by genetic means: the budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe.
Serologic Differentiation Between Antitoxin Responses to Infection with Vibrio cholerae and Enterotoxin-Producing Escherichia coli (1983)

A ganglioside enzyme-linked immunosorbent assay (ELISA) was used to study and attempt to differentiate between antitoxin responses in persons infected with either Vibrio cholerae or Escherichia coli producing heat-labile enterotoxin. In most cases (69%-94%), experimentally infected North Americans and naturally infected Bangladeshis responded to either infection with significant (greater than twofold) increases in serum antibody titer to both heat-labile enterotoxin and cholera toxin. In all but one instance, the response was higher to the homologous than to the heterologous toxin, and for the Americans the homologous antitoxin titers remained significantly higher for at least one year. Determination of levels of antibodies to purified subunits A and B of cholera toxin by an ELISA showed that V. cholerae infection in most instances induced a significant response to subunit B but rarely to subunit A. E. coli infection, on the other hand, induced only slight increases in antibody titer to either subunit.
Adoptive therapy with redirected primary regulatory T cells results in antigen-specific suppression of arthritis (2009)

Regulatory T cells (Tregs) can suppress a wide range of immune cells, making them an ideal candidate for the treatment of autoimmunity. The potential clinical translation of targeted therapy with antigen-specific Tregs is hampered by the difficulties of isolating rare specificities from the natural polyclonal T cell repertoire. Moreover, the initiating antigen is often unknown in autoimmune disease. Here we tested the ability of antigen-specific Tregs generated by retroviral gene transfer to ameliorate arthritis through linked suppression and therefore without cognate recognition of the disease-initiating antigen. We explored two distinct strategies: T cell receptor (TCR) gene transfer into purified CD4+CD25+ T cells was used to redirect the specificity of naturally occurring Tregs; and co-transfer of FoxP3 and TCR genes served to convert conventional CD4(+) T cells into antigen-specific regulators. Following adoptive transfer into recipient mice, the gene-modified T cells engrafted efficiently and retained TCR and FoxP3 expression. Using an established arthritis model, we demonstrate antigen-driven accumulation of the gene modified T cells at the site of joint inflammation, which resulted in a local reduction in the number of inflammatory Th17 cells and a significant decrease in arthritic bone destruction. Together, we describe a robust strategy to rapidly generate antigen-specific regulatory T cells capable of highly targeted inhibition of tissue damage in the absence of systemic immune suppression. This opens the possibility to target Tregs to tissue-specific antigens for the treatment of autoimmune tissue damage without the knowledge of the disease-causing autoantigens recognized by pathogenic T cells.
Asparagine-proline sequence within membrane-spanning segment of SREBP triggers intramembrane cleavage by Site-2 protease (2000)

The NH(2)-terminal domains of membrane-bound sterol regulatory element-binding proteins (SREBPs) are released into the cytosol by regulated intramembrane proteolysis, after which they enter the nucleus to activate genes encoding lipid biosynthetic enzymes. Intramembrane proteolysis is catalyzed by Site-2 protease (S2P), a hydrophobic zinc metalloprotease that cleaves SREBPs at a membrane-embedded leucine-cysteine bond. In the current study, we use domain-swapping methods to localize the residues within the SREBP-2 membrane-spanning segment that are required for cleavage by S2P. The studies reveal a requirement for an asparagine-proline sequence in the middle third of the transmembrane segment. We propose a model in which the asparagine-proline sequence serves as an NH(2)-terminal cap for a portion of the transmembrane alpha-helix of SREBP, allowing the remainder of the alpha-helix to unwind partially to expose the peptide bond for cleavage by S2P.
Physical Gels of Syndiotactic Polystyrene With Fragrant Molecules (2013)

Abstract The morphology of syndiotactic polystyrene (SPS) with several typical fragrant molecules is studied to clarify what solvent conditions can produce SPS gel, which is expected to be a material that can release fragrance for a long period of time. Eight fragrant solvent molecules are employed to dissolve SPS at high temperatures and the morphologies they show after cooling are checked. Their morphologies can be divided into three: a gel with a three‐dimensional network consisting of a fibrillar structure having the SPS δ phase, a paste‐like state consisting of a non‐lamellar spherulitic structure having the SPS γ phase, and a sherbet‐like state consisting of a lamellar structure having the SPS β phase. Finally, the necessary conditions of a solvent to be able to form an SPS gel turn out to be its molecular size being less than ≈160 Å 3 and its Fedors' solubility parameter having a value whose gap from SPS is less than 1.5 (cal/cm 3 ) 1/2 . magnified image
Lymphokine-Like Factors Produced by Human Lymphoid Cell Lines with B or T Cell Surface Markers (1976)

Abstract In the present series of experiments we examined the ability of eight continuous cell lines derived from human lymphocytes to release lymphokines into their culture media. We have demonstrated that all could produce a macrophage migration inhibitory factor and a neutrophil chemotactic factor. This ability was independent of the B or T cell origin of the cell lines. As a further extension of previous reports, we report that the migration inhibitory effect does not seem to be due to cytotoxic effects as judged by trypan blue exclusion studies, and more important by the demonstration that the inhibition is reversible. The demonstration that neutrophil chemotactic activity is removable by treatment with a previously described and characterized anti-lymphokine antiserum suggests that this factor may be chemically similar to some of the lymphokines (migration inhibitory factor or chemotactic factor for macrophages) produced by antigen-activated guinea pig lymphocyte cultures. The failure to effect similar removal or inactivation of the macrophage migration inhibitory factor may simply reflect greater interspecies heterogeneity in this factor, or more interestingly, that this does not correspond to “classic” MIF. These results extend previous observations by defining further the capacity of lymphoid cell lines in continuous culture to produce mediators and by characterizing their relationship to conventional lymphokines produced by antigen or mitogen-activated lymphocytes.
Rapid and Catalyst‐Free α‐Halogenation of Ketones usingN‐Halosuccinamides in DMSO (2007)

Abstract α‐Halogenation of various carbonyl compounds such as β‐keto‐esters, cyclic ketones, and lactams with N‐halosuccinamides (NBS, NCS, NIS) in the presence of DMSO proceeded very smoothly to give the corresponding α‐monohalogenated products in good to excellent yields with high selectivity under catalyst‐free conditions.
Protein Stability and Surface Electrostatics:  A Charged Relationship (2006)

Engineering proteins to withstand a broad range of conditions continues to be a coveted objective, holding the potential to advance biomedicine, industry, and our understanding of disease. One way of achieving this goal lies in elucidating the underlying interactions that define protein stability. It has been shown that the hydrophobic effect, hydrogen bonding, and packing interactions between residues in the protein interior are dominant factors that define protein stability. The role of surface residues in protein stability has received much less attention. It has been believed that surface residues are not important for protein stability particularly because their interactions with the solvent should be similar in the native and unfolded states. In the case of surface charged residues, it was sometimes argued that solvent exposure meant that the high dielectric of the solvent will further decrease the strength of the charge-charge interactions. In this paper, we challenge the notion that the surface charged residues are not important for protein stability. We computationally redesigned sequences of five different proteins to optimize the surface charge-charge interactions. All redesigned proteins exhibited a significant increase in stability relative to their parent proteins, as experimentally determined by circular dichroism spectroscopy and differential scanning calorimetry. These results suggest that surface charge-charge interactions are important for protein stability and that rational optimization of charge-charge interactions on the protein surface can be a viable strategy for enhancing protein stability.
Low-dose taxotere enhances the ability of sorafenib to induce apoptosis in gastric cancer models (2010)

Despite the low efficacy of conventional antitumour drugs, chemotherapy remains an essential tool in controlling advanced gastric and oesophageal cancers. We aimed to provide a biological rationale based on the sorafenib-taxotere interaction for the clinical treatment of gastric cancer. In vitro experiments were performed on four human gastric cancer cell lines (GK2, AKG, KKP and NCI-N87). Cytotoxicity was evaluated by sulforhodamine B (SRB) assay, cell cycle perturbations, apoptosis and mitotic catastrophe were assessed by flow cytometric and microscopic analyses, and protein expression was studied by Western blot. In the in vivo experiments, nude mice xenografted with the most resistant line were treated with sorafenib and docetaxel singly or in association. Sorafenib inhibited cell growth (IG(50) values ranged from 3.4 to 8.1 μM) and caused down-regulation of MAP-K/ERK phosphorylation and of mcl-1 and p-bad expression after a 48-hr exposure. Apoptosis induction was associated with caspase-3 and -9 activation and mitochondrial membrane depolarization. The drug combination enhanced apoptosis (up to 80%) and produced a synergistic interaction when low doses of the taxane preceded administration of the antityrosine kinase. This synergism was probably due to the induction of an anomalous multidiploid G0-G1 peak and to consequent mitotic catastrophe, which increased sensitivity to sorafenib. Consistent with in vitro results, the docetaxel-sorafenib sequence exhibited high therapeutic efficacy in NCI-N87 mouse xenografts producing tumour weight inhibition (> 65%), tumour growth delay (up to 25 days) and increased mouse survival (30%). Our findings suggest the potential clinical usefulness of treatment with sorafenib and docetaxel for advanced gastric cancer.
Recent advances in Veeco’s radio frequency ion sources for ion beam materials processing applications (abstract) (2002)

In this article we describe an advanced inductively coupled plasma ion source being developed at Veeco for applications in data storage and active optical device fabrication. The new source design minimizes rf capacitive coupling. Capacitive coupling is responsible for erosion of the quartz discharge chamber and high transverse ion energies. Suppression of capacitive coupling, however, can be problematic for some applications due to the fact that, without it, conductive coatings that shield the transfer of inductive power to the plasma can accumulate inside the source. The authors have developed a simple and unique protective device that when installed on the quartz hardware effectively inhibits rf losses in the deposited films, greatly extending the quartz maintenance cycle and overcoming the above problem. Reduction of capacitive coupling is achieved using a slotted Faraday shield inserted between the low-frequency 1.8 MHz rf antenna and the plasma. It is found that the rf power loss to this shield is extremely low, yet it is very effective, essentially eliminating signs of discharge chamber sputtering. Further advantages of these new design features and application to special controlled etching processes are described. Also, new performance and reliability data for Veeco’s recently developed “flangeless” self-aligned ion optics grid assembly, implemented on the RIM-210 focused beam deposition ion source is shown, demonstrating the advantages of this design.
Purification of a Cross-Protective Antigen from Pasteurella multocida Grown in vitro and in vivo (2001)

A peptone-based medium was formulated to grow Pasteurella multocida in vitro, which expressed an antigen that induces cross protection in turkeys against different serotypes. Vaccines of various chromatographic fractions obtained from P. multocida grown in the medium induced active immune cross protection in turkeys, and sera from these turkeys passively cross protected naïve poults. An antigen of approximately 39 kD molecular size was purified by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electroelution from hydroxyapatite chromatographic fractions of both in vivo- and in vitro-grown P. multocida. The purified antigen from either source induced active immune cross protection but no passive protection in one of two experiments. Increasing the dose of vaccine resulted in both active and passive immune cross protection in the second experiment.
An adenovirus prime/plasmid boost strategy for induction of equipotent immune responses to two dengue virus serotypes (2007)

Our data support the hypothesis that a DEN vaccine targeting more than one serotype may be based on a single DNA-based vector to circumvent viral interference. This work lays the foundation for developing a single Ad vector encoding EDIIIs of all four DEN serotypes to evoke a balanced immune response against each one of them. Thus, this work has implications for the development of safe and effective tetravalent dengue vaccines.
The Expression of the Regulatory T Cell–Specific Forkhead Box Transcription Factor FoxP3 Is Associated with Poor Prognosis in Ovarian Cancer (2005)

High expression levels of FoxP3 might represent a surrogate marker for an immunosuppressive milieu contributing to tumor immune escape. Strategies selectively depleting Treg might improve the antitumor activity of endogenously arising tumor-reactive T cells and immunotherapies using vaccines or antibodies.
Web-scale Data Integration: You can only afford to Pay As You Go (2007)

The World Wide Web is witnessing an increase in the amount of structured content – vast heterogeneous collections of structured data are on the rise due to the Deep Web, annotation schemes like Flickr, and sites like Google Base. While this phenomenon is creating an opportunity for structured data management, dealing with heterogeneity on the web-scale presents many new challenges. In this paper, we highlight these challenges in two scenarios – the Deep Web and Google Base. We contend that traditional data integration techniques are no longer valid in the face of such heterogeneity and scale. We propose a new data integration architecture, PAYGO, which is inspired by the concept of dataspaces and emphasizes pay-as-you-go data management as means for achieving web-scale data integration. 1.
Effectiveness of high-dose combination chemotherapy and autologous bone marrow transplantation for patients with non-Hodgkin's lymphomas who are still responsive to conventional-dose therapy. (1989)

We commenced a study in September 1981 to investigate the role of high-dose combination chemotherapy in the management of patients with non-Hodgkin's lymphomas who had failed conventional therapy. Fifty patients with diffuse intermediate- and high-grade non-Hodgkin's lymphomas were treated with high-dose combination chemotherapy with autologous bone marrow rescue (ABMT) and have a minimum follow-up of 1 year. Twenty patients had disease that was still responsive to conventional-dose chemotherapy, 15 had achieved a partial response (PR) to first-line therapy, and five were showing PR to salvage therapy after relapse. Twelve of these patients (60%) achieved complete remission (CR) (two following boost radiotherapy) and three patients have nonprogressive masses on computed tomographic (CT) scan as the only abnormality. None of these patients died during the procedure. Twenty-nine patients had disease not responsive to chemotherapy at conventional dosages: 19 had no response to first-line therapy and 10 showed no response to salvage therapy given after relapse. Only three of these patients achieved CR, all of short duration only. Only two patients in this group remain alive more than 2 years after the procedure and both have nonprogressive abnormalities on CT scan. Nine patients (31%) died of sepsis during the procedure. In those patients with disease not responsive to conventional-dose therapy, dose escalation is associated with a high procedure-related mortality and a low response rate. In those patients who still have chemotherapy-responsive disease the response rate is high and mortality is low.(ABSTRACT TRUNCATED AT 250 WORDS)