gebhart/patrepeval huggingface dataset:
Combinatorial Methods, Automated Synthesis and High‐Throughput Screening in Polymer Research: The Evolution Continues (2003)

Abstract Summary: For speeding‐up preparation as well as investigating new polymeric materials, combinatorial techniques, parallel experimentation, and high‐throughput screening methods represent a very promising approach in polymer chemistry: a large variety of parameters can be screened simultaneously resulting in new structure–property relationships. As previously described, polymer chemistry seems to be perfectly suited for combinatorial approaches since it is relatively easy to vary many parameters during the synthesis, processing, blending, or compounding. Moreover, the development and application of high‐throughput screening techniques for polymer properties can accelerate the development of new materials and can result in new structure–property relationships. Therefore, these screening tools, together with parallel preparation techniques, will significantly decrease the time to market of new products. Here we provide an update of our recent overview covering new developments in the field of combinatorial and parallel polymer synthesis and high‐throughput screening. Development of high‐throughput screening techniques for polymer properties. magnified image Development of high‐throughput screening techniques for polymer properties.
Reduction of radioantibody-induced myelotoxicity in hamsters by recombinant interleukin-1. (1988)

Recombinant human interleukin 1 (IL-1) administered i.p. to tumor-bearing hamsters results in a dose-dependent 2- to 5-fold increase in total peripheral white blood cells. These levels remain elevated for 2 to 3 wk and then decline to base-line levels. Pretreatment of animals with similar doses of IL-1 prevents radioimmunotherapy-induced destruction of the radiosensitive hematopoietic system. Furthermore, recovery from radio-immunotherapy-induced myelosuppression is possible if animals are given IL-1 1 wk after radioimmunotherapy treatment. Thus, both protection and rescue from the hematopoietic damage associated with radioantibody treatment are feasible by pre- or posttreatment with IL-1.
Histone Deacetylase Inhibitors: Overview and Perspectives (2007)

Histone deacetylase inhibitors (HDACi) comprise structurally diverse compounds that are a group of targeted anticancer agents. The first of these new HDACi, vorinostat (suberoylanilide hydroxamic acid), has received Food and Drug Administration approval for treating patients with cutaneous T-cell lymphoma. This review focuses on the activities of the 11 zinc-containing HDACs, their histone and nonhistone protein substrates, and the different pathways by which HDACi induce transformed cell death. A hypothesis is presented to explain the relative resistance of normal cells to HDACi-induced cell death.
Adaptive acidification tolerance response of Salmonella typhimurium (1990)

Salmonella typhimurium can encounter a wide variety of environments during its life cycle. One component of the environment which will fluctuate widely is pH. In nature, S. typhimurium can experience and survive dramatic acid stresses that occur in diverse ecological niches ranging from pond water to phagolysosomes. However, in vitro the organism is very sensitive to acid. To provide an explanation for how this organism survives acid in natural environments, the adaptive ability of S. typhimurium to become acid tolerant was tested. Logarithmically grown cells (pH 7.6) shifted to mild acid (pH 5.8) for one doubling as an adaptive procedure were 100 to 1,000 times more resistant to subsequent strong acid challenge (pH 3.3) than were unadapted cells shifted directly from pH 7.6 to 3.3. This acidification tolerance response required protein synthesis and appears to be a specific defense mechanism for acid. No cross protection was noted for hydrogen peroxide, SOS, or heat shock. Two-dimensional polyacrylamide gel electrophoretic analysis of acid-regulated polypeptides revealed 18 proteins with altered expression, 6 of which were repressed while 12 were induced by mild acid shifts. An avirulent phoP mutant was 1,000-fold more sensitive to acid than its virulent phoP+ parent, suggesting a correlation between acid tolerance and virulence. The Mg2(+)-dependent proton-translocating ATPase was also found to play an important role in acid tolerance. Mutants (unc) lacking this activity were unable to mount an acid tolerance response and were extremely acid sensitive. In contrast to these acid-sensitive mutants, a constitutively acid-tolerant mutant (atr) was isolated from wild-type LT2 after prolonged acid exposure. This mutant overexpressed several acidification tolerance response polypeptides. The data presented reveal an important acidification defense modulon with broad significance toward survival in biologically hostile environments.
Fetal Globin Induction in β-thalassemia (2009)

Thalassemia patients with persistently high levels of fetal globin typically have less severe anemia, have milder clinical syndromes, and are often transfusion independent. Therefore, the search for molecules exhibiting the property of inducing gamma-globin gene expression and fetal hemoglobin (HbF) production is of great interest. Different pharmacological agents have been studied, namely erythropoietin, short chain fatty acids and cytotoxic agents, azacytidine, and hydroxycarbamide. Hemoglobin F inducers from natural plants, such as angelicin and resveratrol, are powerful inducers of erythroid differentiation and increase HbF in erythroid progenitors of thalassemia patients. Induction of HbF in beta-thalassemia patients is expected to be crucial for developing countries unable to sustain the high cost of clinical management of beta-thalassemia patients.
Induction of mRNA for a serine protease and a beta-thromboglobulin-like protein in mitogen-stimulated human leukocytes. (1987)

Two cDNA clones corresponding to genes that are induced at least 10-fold in peripheral human blood leukocytes by staphylococcal enterotoxin A were isolated and sequenced. Clone 1-3E encodes a 247-residue protein that comprises a putative signal sequence, and resembles a serine protease; the cognate mRNA is expressed in T lymphocyte clones but in none of the other human cell lines tested. The deduced protein sequence is most closely related (68% homology) to that of the postulated protease CCPI from activated murine cytotoxic T lymphocytes and to that of rat mast cell protease II (47% homology). The other cDNA, 3-10C, encodes a protein of 99 residues that resembles human beta-thromboglobulin (42% homology); the cognate mRNA was also found in SEA-stimulated U937 cells, a histiocytic lymphoma-derived cell line.
Activating Protein-1, Nuclear Factor-κB, and Serum Response Factor as Novel Target Molecules of the Cancer-Amplified Transcription Coactivator ASC-2 (2000)

ASC-2 was recently discovered as a cancer-amplified transcription coactivator molecule of nuclear receptors, which interacts with multifunctional transcription integrators steroid receptor coactivator-1 (SRC-1) and CREB-binding protein (CBP)/p300. Herein, we report the identification of three mitogenic transcription factors as novel target molecules of ASC-2. First, the C-terminal transactivation domain of serum response factor (SRF) was identified among a series of ASC-2-interacting proteins from the yeast two-hybrid screening. Second, ASC-2 specifically interacted with the activating protein-1 (AP-1) components c-Jun and c-Fos as well as the nuclear factor-kappaB (NFkappaB) components p50 and p65, as demonstrated by the glutathione S-transferase pull-down assays as well as the yeast two-hybrid tests. In cotransfection of mammalian cells, ASC-2 potentiated transactivations by SRF, AP-1, and NFkappaB in a dose-dependent manner, either alone or in conjunction with SRC-1 and p300. In addition, ASC-2 efficiently relieved the previously described transrepression between nuclear receptors and either AP-1 or NFkappaB. Overall, these results suggest that the nuclear receptor coactivator ASC-2 also mediates transactivations by SRF, AP-1, and NFkappaB, which may contribute to the putative, ASC-2-mediated tumorigenesis.
Biochemical and functional properties of a pyruvate formate‐lyase (PFL)‐activating system in Streptococcus mutans (2003)

Streptococcus mutans has an oxygen-sensitive enzyme, pyruvate formate-lyase (PFL), which is a key enzyme in anaerobic sugar fermentation. We have shown that S. mutans has an activating system, including a PFL-activating enzyme (PFL-activase) and an electron transport system; the latter transfers an electron from NADPH to PFL-activase, as occurs in Escherichia coli. NADPH was a physiological electron donor for the electron transport system and as little as 0.02 mM NADPH activated over 80% of PFL of S. mutans. The optimum pH of the PFL-activating system was around 6.8, whereas the optimum of the E. coli system is at alkaline pH. In addition, small dialyzable molecules in cell-free extracts participated in keeping PFL active in S. mutans. These results suggest that, in dental plaque under anaerobic conditions where sugar supply is often limited or pH frequently falls below neutrality, S. mutans always keeps PFL active through the activating system.
By Hook or by Crook? Morphometry, Competition and Cooperation in Rodent Sperm (2007)

Our results suggest that in rodents sperm cooperation is more widespread than assumed so far and highlight the importance of diploid versus haploid selection in the evolution of sperm design and function.
HIF hydroxylation and the mammalian oxygen-sensing pathway (2003)

Hypoxia refers to below-normal levels of oxygen in air, blood, or tissue. Tissue hypoxia leads to cellular dysfunction and ultimately can lead to cell death. Causes of tissue hypoxia include (a) decreased blood oxygenation (such as occurs in certain pulmonary disorders), (b) altered oxygen release from hemoglobin (associated with some hemoglobinopathies), and (c) impaired blood delivery leading to localized anemia (i.e., ischemia) as a result of low cardiac output or vascular obstruction. In order to adapt to hypoxia, mammals use a number of physiological responses. These include (a) increased production of erythropoietin (EPO), which augments the production of red blood cells; (b) induction of tyrosine hydroxylase, which facilitates the control of ventilation through the carotid body; and (c) the stimulation of new blood vessels by upregulation of VEGF (1). At the cellular level, hypoxia induces a number of metabolic changes that allow for continued energy generation despite decreased oxygen availability.
DNA nicking favors PCR recombination (1991)

We attempted to use the polymerase chain reaction (PCR) to monitor in vitro recombination in a plasmid containing directly repeated sequences. Some of the plasmid preparations which had not been exposed to recombination conditions were however found to behave in the PCR test as if they had undergone homologous recombination. We show here that such false positives are attributable to a small degree of nicking and/or breaking of the DNA template. Presumably, such damage allows the formation of hybrid parental duplexes containing at least one truncated strand, the 3' end of which maps within the homology; extension of this 3' end by the polymerase then results in a linkage of sequences identical to that arising from homologous recombination.
An animal model in sheep for biocompatibility testing of biomaterials in cancellous bones (2006)

This experimental animal model serves an excellent basis for testing the biocompatibility of novel biomaterials to be used as bone replacement or new bone formation enhancing materials.
Authentication of mobile users (1994)

The goal of the paper is to propose a general approach for the authentication of users in remote domains while maintaining strict separation of security domains. The article begins with a discussion of security issues specific to user mobility, with identification of authentication requirements. Authentication solutions in existing mobile-user environments are summarized, the authors' solution to authentication of mobile users is presented, then some variations on the theme are introduced.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Analysis and optimization of intermodulation in high-T/sub c/ superconducting microwave filter design (1998)

The authors present a numerically efficient way to determine the intermodulation power arising in a weakly nonlinear N-resonator high-T/sub c/ superconducting microwave filter. This is used to analyze a given filter configuration in order to locate the resonators which are contributing most to the intermodulation power and give a means for reducing intermodulation. Using simulated annealing, the different parameters of a filter are optimized in order to reduce intermodulation within given constraints on the shape of the linear filter response. The possibilities of these methods are discussed. Calculations of this kind are useful in high-T/sub c/ microwave filter design, where nonlinearities can pose a problem.
Analysis of the murine leukemia virus R peptide: delineation of the molecular determinants which are important for its fusion inhibition activity (1997)

In previous studies, the C-terminal R peptide of the murine leukemia virus (MuLV) Env protein was shown to be a potent inhibitor of viral fusion activity. In the present study, we investigated the molecular determinants in the MuLV Env protein cytoplasmic tail which are important for the fusion inhibition activity of the R peptide. We constructed a series of mutant MuLV env genes which express Env proteins with serial truncations, internal deletions, or amino acid substitutions in the cytoplasmic tail. To analyze their cell fusion activity, we employed a quantitative fusion assay. We found that truncations of up to 7 amino acids from the C terminus of the cytoplasmic tail had no detectable effect on the lack of fusion activity of the full-length Env protein; however, further truncations resulted in a progressive increase in cell fusion activity. Studies of mutant proteins with amino acid substitutions in the cytoplasmic tail showed that Leu-627 plays an important role in fusion inhibition by the R peptide, while most of the other amino acids in the R peptide were not essential for fusion inhibition. Studies of mutant proteins with internal deletions upstream of the cleavage site in the cytoplasmic tail showed that this region is also involved in fusion inhibition by the R peptide, although only to a limited extent. The results are consistent with a model in which the MuLV R peptide exhibits its fusion inhibition activity through interaction with a cellular factor(s).
Cyclic AMP Inhibits the Proliferation of Thyroid Carcinoma Cell Lines through Regulation of CDK4 Phosphorylation (2008)

How cyclic AMP (cAMP) could positively or negatively regulate G1 phase progression in different cell types or in cancer cells versus normal differentiated counterparts has remained an intriguing question for decades. At variance with the cAMP-dependent mitogenesis of normal thyroid epithelial cells, we show here that cAMP and cAMP-dependent protein kinase activation inhibit S-phase entry in four thyroid carcinoma cell lines that harbor a permanent activation of the Raf/ERK pathway by different oncogenes. Only in Ret/PTC1-positive TPC-1 cells did cAMP markedly inhibit the Raf/ERK cascade, leading to mTOR pathway inhibition, repression of cyclin D1 and p21 and p27 accumulation. p27 knockdown did not prevent the DNA synthesis inhibition. In the other cells, cAMP little affected these signaling cascades and levels of cyclins D or CDK inhibitors. However, cAMP differentially inhibited the pRb-kinase activity and T172-phosphorylation of CDK4 complexed to cyclin D1 or cyclin D3, whereas CDK-activating kinase activity remained unaffected. At variance with current conceptions, our studies in thyroid carcinoma cell lines and previously in normal thyrocytes identify the activating phosphorylation of CDK4 as a common target of opposite cell cycle regulations by cAMP, irrespective of its impact on classical mitogenic signaling cascades and expression of CDK4 regulatory partners.
A prospective study of simplified omeprazole suspension for the prophylaxis of stress-related mucosal damage (1996)

Simplified omeprazole suspension prevented clinically significant upper gastrointestinal bleeding and maintained gastric pH of > 5.5 in mechanically ventilated critical care patients without producing toxicity.
TNF/TNFR FAMILY MEMBERS IN COSTIMULATION OF T CELL RESPONSES (2004)

Several members of the tumor necrosis factor receptor (TNFR) family function after initial T cell activation to sustain T cell responses. This review focuses on CD27, 4-1BB (CD137), OX40 (CD134), HVEM, CD30, and GITR, all of which can have costimulatory effects on T cells. The effects of these costimulatory TNFR family members can often be functionally, temporally, or spatially segregated from those of CD28 and from each other. The sequential and transient regulation of T cell activation/survival signals by different costimulators may function to allow longevity of the response while maintaining tight control of T cell survival. Depending on the disease condition, stimulation via costimulatory TNF family members can exacerbate or ameliorate disease. Despite these complexities, stimulation or blockade of TNFR family costimulators shows promise for several therapeutic applications, including cancer, infectious disease, transplantation, and autoimmunity.
The novel anti-MEK small molecule AZD6244 induces BIM-dependent and AKT-independent apoptosis in diffuse large B-cell lymphoma (2011)

The RAS/RAF/MEK/ERK signaling pathway has been largely unexplored as a potential therapeutic target in lymphoma. The novel 2nd generation anti-MEK small molecule, AZD6244, down-regulated its direct downstream target, phospho-ERK (pERK) in germinal center and nongerminal center diffuse large B-cell lymphoma (DLBCL) cell lines and primary cells. Similar decreased pERK levels were noted despite constitutive activation (CA) of MEK. Consequently, several lymphoma-related ERK substrates were down-regulated by AZD6244 including MCT-1, c-Myc, Bcl-2, Mcl-1, and CDK1/2. AZD6244 induced time- and dose-dependent antiproliferation and apoptosis in all DLBCL cell lines and fresh/primary cells (IC(50) 100nM-300nM). Furthermore, AZD6244 resulted in significantly less tumor compared with control in an in vivo DLBCL SCID xenograft model. Cell death was associated with cleaved PARP, caspases-8, -9, and -3, and apoptosis was caspase-dependent. In addition, there was stabilization of FoxO3a, activation of BIM and PUMA, and a significant decrease in c-Myc transcripts. Moreover, siRNA knockdown of BIM abrogated AZD6244-related apoptosis, while shRNA knockdown of ERK minimally sensitized cells. Finally, manipulation of AKT with transfection of OCI-LY3 cells with CA-AKT or through chemical inhibition (LY294002) had minimal effect on AZD6244-induced cell death. Altogether, these findings show that the novel anti-MEK agent, AZD6244, induced apoptosis in DLBCL and that cell death was BIM-dependent.
Effective particle-mediated vaccination against mouse melanoma by coadministration of plasmid DNA encoding Gp100 and granulocyte-macrophage colony-stimulating factor. (2001)

Particle-mediated gene delivery was used to immunize mice against melanoma. Mice were immunized with a plasmid cDNA coding for the human melanoma-associated antigen, gp100. Murine B16 melanoma, stably transfected with human gp100 expression plasmid, was used as a tumor model. Particle-mediated delivery of gp100 plasmid into the skin of naïve mice resulted in significant protection from a subsequent tumor challenge. Co-delivery of murine granulocyte-macrophage colony-stimulating factor (GM-CSF) expression plasmid together with the gp100 plasmid consistently resulted in a greater level of protection from tumor challenge. The inclusion of the GM-CSF plasmid with the gp100 DNA vaccine allowed a reduction in the gp100 plasmid dose required for antitumor efficacy. Protection from tumor challenge was achieved with as little as 62.5 ng of gp100 DNA per vaccination. Tumor protection induced by the gp100 + GM-CSF gene combination was T cell mediated, because it was abrogated in vaccinated mice treated with anti-CD4 and anti-CD8 monoclonal antibodies. In addition, administration of the gp100 + GM-CSF DNA vaccine to mice bearing established 7-day tumors resulted in significant suppression of tumor growth. These results indicate that inclusion of GM-CSF DNA augments the efficacy of particle-mediated vaccination with gp100 DNA, and this form of combined gp100 + GM-CSF DNA vaccine warrants clinical evaluation in melanoma patients.
Effects of Polymer Matrices on Calibration Functions of Luminescent Oxygen Sensors Based on Porphyrin Ketone Complexes (1996)

The design of luminescent oxygen sensors is guided by optimizing sensitivity and/or the form of the calibration function. Both qualities are governed by the molecular processes of luminescence quenching. To evaluate the influence of matrix effects, we prepared membranes based on oxygen-sensitive phosphorescent complexes of porphyrin ketones dissolved in plasticizer-free poly(vinyl chloride) (PVC) and polystyrene (PS). In a PVC matrix, both platinum(II) and palladium(II) octaethylporphyrin ketones exhibited perfectly linear Stern-Volmer intensity plots and almost single-exponential excited state decays. In a PS matrix, the sensitivity of palladium(II) octaethylporphyrin ketone was among the highest reported to date. Yet, slightly nonlinear Stern-Volmer plots and nonexponential decays illustrate the significance of matrix effects of PS. Addition of plasticizers to PVC-based sensors allowed tuning of the oxygen sensitivity in a wide range, while the Stern-Volmer plots became pronouncedly nonlinear. For the plasticizer bis(2-ethylhexyl) adipate, the decay profile was single-exponential in the absence but nonexponential in the presence of oxygen, which is attributed to a distribution of quenching rate constants.
Antiserum raised against an epitope of the cholecystokinin B/gastrin receptor inhibits hepatic invasion of a human colon tumor. (2000)

Serum gastrin is known to be elevated in patients with liver-metastasizing colon cancer; thus, cholecystokinin (CCK) B/gastrin receptors may also be up-regulated. A liver-invasive model of colon cancer was established with the human colonic cell line C170HM2, which expresses the CCKB/gastrin receptor at both the gene and protein level. An antiserum has been derived that is directed against the NH2-terminal 17 amino acids of the human CCKB/gastrin receptor coupled to diphtheria toxoid. The peptide was denoted gastrin receptor protein (GRP) 1. The therapeutic effect of GRP1 antiserum was evaluated on the liver invasion of C170HM2 tumors. Biodistribution studies revealed that GRP1 antiserum localized preferentially within the liver tumors when compared with normal liver tissue (1.5-fold increase after 24 h; P < 0.05). Antiserum against GRP1 inhibited both tumor take rate and final liver tumor weight when compared with treatment with control serum in mice with an increasing tumor burden. Liver tumor weights were reduced from 0.37 to 0.10 gram (P = 0.0155), 1.25 grams to 0.76 gram (P = 0.003) and 1.89 grams to 0.76 gram (P = 0.0068, all Mann-Whitney nonparametric U test). Necrosis and apoptosis were increased in the GRP1 antiserum-treated tumors when compared with control serum-treated tumors. As shown by Western blotting, CCKB/gastrin receptor expression of C170HM2 xenografts after treatment with GRP1 antiserum shifted to a predominantly lower molecular weight form (Mr 45,000) that is known to be an internalized form of the receptor. In conclusion, targeting of the CCKB/gastrin receptor may yield a valuable therapeutic modality for the treatment of advanced colon cancer.