gebhart/patrepeval huggingface dataset:
Granulocyte colony-stimulating factor rapidly activates a distinct STAT- like protein in normal myeloid cells (1995)

Binding of granulocyte colony-stimulating factor (G-CSF) to normal myeloid cells activates the protein tyrosine kinases Lyn and Syk and results in the immediate early upregulation of G-CSF receptor (R) mRNA. In our studies of the signaling pathways activated by G-CSF that are coupled to proliferation and differentiation of myeloid cells, we examined whether G-CSF activated a latent transcription factor belonging to the STAT protein family. Electrophoretic mobility shift assays (EMSAs) of nuclear extracts from G-CSF-stimulated human myeloid cells showed the rapid activation of a DNA-binding protein that bound to the high-affinity serum-inducible element (hSIE) and migrated with mobility similar to serum inducible factor (SIF)-A (Stat3 homodimer). The G-CSF-stimulated SIF-A complex (G-SIF-A) did not bind to duplex oligonucleotides used to purify and characterize other Stat proteins (Stat1-6). In addition, antibodies raised against Stat1-6 failed to supershift the G-SIF-A complex or interfere with its formation. Based on its binding to the hSIE and lack of antigenic cross-reactivity with other known STAT proteins that bind to this element, it is likely that G-SIF-A is composed of a distinct member of the STAT protein family. EMSAs of whole-cell extracts prepared from cell lines containing full-length and truncated mutants of the G-CSFR showed that activation of G-SIF-A did not correlate with proliferation; rather, optimal activation requires the distal half of the cytosolic domain of the G-CSFR that is essential for differentiation. Activation of G-SIF-A, therefore, may be an early G-CSFR-coupled event that is critical for myeloid maturation.
[Coenzyme Q10 in cancer chemotherapy--experimental studies on augmentation of the effects of masked compounds, especially in the combined chemotherapy with immunopotentiators]. (1983)

Immunopotentiators may mitigate the depression of immunological function caused by the cancer itself or by chemotherapeutics. However, it has been found that these immunopotentiators reduce the metabolic activity of the host against drugs, including "masked" chemotherapeutics, which might be activated by metabolization in the body. Reported here is the result of serial experiments carried out on the activation of cyclophosphamide (CPM) in tumor-bearing animals, pretreated with phenobarbital, a drug-metabolizing enzyme inducer, and coenzyme Q10, a physiological activator of the electron transfer system in mitochondrias, in combination with immunopotentiators. Female Donryu rats (120 g body weight) implanted with Yoshida Sarcoma cells (YS) (2.5 X 10(6) i.p.) were treated with CPM (160 mg/kg X 1 i.p.), 84 hrs after implantation; the levels of the normustard-like substances (active metabolites of CPM) were serially measured. Some of the animals were also treated with PSK (125 mg/kg X 5 i.p.), a proteinpolysaccharide immunopotentiator obtained from mycelia of the Coriolus vesicolor, or with OK-432 (10 KE/kg X 5 i.m.), a streptococcal immunopotentiator. The results obtained were as follows: The blood levels of the normustard-like substances were lowered, i.e. the CPM activation was depressed in the YS-bearing rats and the depression was markedly intensified by PSK or OK-432 administration. Phenobarbital (40 mg/kg X 3 i.p.) or coenzyme Q10 (5 mg/rat X 5 i.p.) administration could mitigate the depression of the blood levels caused by the immunopotentiators, and the combination of phenobarbital with coenzyme Q10 could recover the blood levels up to those of the YS-bearing control rats, or even higher. YS-implanted (i.p.) rats treated with CPM+ immunopotentiators+coenzyme Q10 survived longer than those treated with CPM+immunopotentiators. These findings suggest the usefulness of coenzyme Q10 for the enhancement of cancer immunochemotherapy using masked compounds combined with immunopotentiators; all the more so, because coenzyme Q10 has also an immuno-stimulating effect, moreover, it presents almost no side effects in clinical application.
Immunomagnetic Enrichment, Genomic Characterization, and Prognostic Impact of Circulating Melanoma Cells (2004)

Immunomagnetic enrichment enables isolation and genomic characterization of circulating melanoma cells. The prognostic impact on survival of metastatic patients apparently reflects the aggressiveness of an ongoing tumor spread. Direct genomic analysis of the enriched and isolated cells will help to clarify the molecular-genetic basis of the establishment of generalized melanoma.
Expression of the polyalanine expansion mutant of nuclear poly(A)‐binding protein induces apoptosis via the p53 pathway (2012)

The PABPN1 [nuclear poly(A)-binding protein 1] is ubiquitous, binds to the nascent mRNA transcript and controls the poly(A) tract elongation process in multicellular organisms. Expansion of GCG repeats that encode first 6 of the 10 alanine residues of a polyalanine tract at the N-terminus of wild-type PABPN1 to 12-17 alanine residues causes aggregation of the protein and cell death. Patients with the adult onset autosomal dominant OPMD (oculopharyngeal muscular dystrophy) carry the GCG expansion mutation in their PABPN1 gene. The symptoms of OPMD include drooping eye lids and difficulty swallowing. The severity of symptoms increases with the length of the expansion. We have investigated the mechanism of cell death in HeLa and HEK-293 (human embryonic kidney) cultured cells expressing the mutant PABPN1 with a polyalanine tract containing 17 alanine residues (PABPN1-A17). In cells expressing PABPN1-A17, the abundance of pro-apoptotic proteins, p53, PUMA (p53 up-regulated modulator of apoptosis) and Noxa, are up-regulated. This was associated with the redistribution of p53 to the nucleus and mitochondria. Concomitantly Bax was translocated to the mitochondria, followed by the release of cytochrome c and the cleavage of caspase 3. Furthermore, blocking p53-mediated transcription using pifithrin significantly reduced apoptosis. Our findings suggest a key role of p53-mediated apoptosis in death of cells expressing the polyalanine expansion mutant of PABPN1.
CCKA and CCKB receptors are expressed in small cell lung cancer lines and mediate Ca2+ mobilization and clonal growth. (1993)

Gastrin, cholecystokinin (CCK), and CCK-related peptides comprise a hormonal family characterized by an identical carboxy-terminal amino acid sequence, a domain critical for receptor binding. The addition of gastrin to small cell lung cancer (SCLC) cells causes a rapid and transient increase in the intracellular concentration of calcium ([Ca2+]i). Furthermore, gastrin acts as a direct growth factor through CCKB/gastrin receptors. We report here that the expression of the mRNA coding for CCKB/gastrin receptors correlates with the responsiveness of SCLC cells to gastrin in terms of Ca2+ mobilization and stimulation of clonal growth in semisolid medium. The GLC19 SCLC cell line had no detectable expression of CCKB/gastrin receptor mRNA. Accordingly, gastrin (1-100 nM) did not cause any measurable increase in [Ca2+]i. In contrast, the addition of cholecystokinin residues 26-33 (CCK-8) caused a rapid and transient increase in [Ca2+]i in this cell line. CCK-8 mobilized Ca2+ in a dose-dependent manner in the nanomolar range (half-maximal stimulatory concentration = 12 nM). Furthermore, the selective CCKA antagonist CAM-1481 inhibited the increase in [Ca2+]i induced by CCK-8 (half-maximal inhibitory concentration = 3 nM) in GLC19 but not in H510 cells. The selective CCKB/gastrin antagonist blocked the increase in [Ca2+]i induced by CCK-8 (half-maximal inhibitory concentration = 80 pM) in H510 but not in GLC19 cells. Thus, the effects of CCK-8 are mediated through CCKA receptors in GLC19 cells and via CCKB/gastrin receptors in H510 cells. CCK-8 markedly stimulated colony formation in GLC19 cells in a dose-dependent manner in the nanomolar range, whereas over the same concentration range, gastrin had no effect on clonal growth. CAM-1481 inhibited the CCK-stimulated colony formation in GLC19 but not in H510 cells. Our results show, for the first time, that CCKA receptors can mediate Ca2+ mobilization and growth in SCLC cells and that SCLC cells express two distinct functional CCK receptor subtypes.
Carbohydrate Reserves and Reproductive Development at Low Leaf Water Potentials in Maize1 (1985)

Low water potentials (ψ w ) during anthesis and early grain fill can decrease yields in grain crops. If photosynthesis is inhibited under these conditions, carbohydrate reserves may become limiting for grain growth. We measured the mobilization of stored nonstructural carbohydrates in the maize plant ( Zea mays L.) during low ψ w , imposed at silk emergence (T1), early grain fill (T2), and mid‐grain fill (T3) and maintained to maturity. low leaf ψ w , completely inhibited photosynthesis, and reproductive development depended entirely on reserves. The control yield was equivalent to 9910 kg ha −1 . Mean yields on a per‐plant basis were 139, 89, 25, and 0 g for the control, T3, T2, and T1 treatments, respectively. Yield losses resulted from decreased seed size in T3, decreased seed size and number in T2, and a cessation of silk and ear development in T1. After anthesis, dry matter accumulated in the stems and leaves and was mobilized to the ear at low ψ w in T3 and T2 but not in T1. All the mobilized dry matter from the stems and a sizable fraction from the leaves was carbohydrate. By maturity, the mobilized carbohydrates had been depleted to the level at anthesis. In T1, there was no mobilization and the carbohydrates remained at the low anthesis levels until maturity. The low carbohydrate at T1 indicates that reserves were not sufficient to support reproductive development when photosynthesis was inhibited at low ψ w . The lack of reserves may explain the high sensitivity of anthesis and early grain fill to low ψ w , as well as previous reports of the inability of silks to maintain turgor by osmotic adjustment. The decreasing sensitivity of grain development to low ψ w as reproduction progresses may result from an increasing availability of reserves.
Beta 3-endonexin, a novel polypeptide that interacts specifically with the cytoplasmic tail of the integrin beta 3 subunit. (1995)

The adhesive and signaling functions of integrins are regulated through their cytoplasmic domains. We identified a novel 111 residue polypeptide, designated beta 3-endonexin, that interacted with the cytoplasmic tail of the beta 3 integrin subunit in a yeast two-hybrid system. This interaction is structurally specific, since it was reduced by 64% by a point mutation in the beta 3 cytoplasmic tail (S752-->P) that disrupts integrin signaling. Moreover, this interaction is integrin subunit specific since it was not observed with the cytoplasmic tails of the alpha IIb, beta 1, or beta 2 subunits. beta 3-Endonexin fusion proteins bound selectively to detergent-solubilized beta 3 from platelets and human umbilical vein endothelial cells, and beta 3-endonexin mRNA and protein were detected in platelets and other tissues. A related mRNA encoded a larger polypeptide that failed to bind to beta integrin tails. The apparent specificity of beta 3-endonexin for the beta 3 integrin subunit suggests potential mechanisms for selective modulation of integrin functions.
A dimensional analysis of creativity and mental illness: Do anxiety and depression symptoms predict creative cognition, creative accomplishments, and creative self-concepts? (2010)

The link, if any, between creativity and mental illness is one of the most controversial topics in modern creativity research. The present research assessed the relationships between anxiety and depression symptom dimensions and several facets of creativity: divergent thinking, creative self-concepts, everyday creative behaviors, and creative accomplishments. Latent variable models estimated effect sizes and their confidence intervals. Overall, measures of anxiety, depression, and social anxiety predicted little variance in creativity. Few models explained more than 3% of the variance, and the effect sizes were small and inconsistent in direction.
Evidence of deep ultraviolet amplified spontaneous emission in electron beam pumped AlGaN multiple-quantum-well-based structures (2012)

In this paper we report detailed cathodoluminescence (CL) studies of deep UV emitting AlGaN multiple quantum wells (MQWs) embedded in AlN cladding layers to simulate a deep UV laser structure. These structures were produced by plasma-assisted molecular beam epitaxy (MBE) on 6H-SiC substrates. The AlGaN QWs were grown under excess gallium conditions, a growth mode consistent with liquid phase epitaxy rather than physical vapor phase epitaxy. This growth mode leads to AlGaN films with compositional inhomogeneities and thus band structure potential fluctuations. The degree of such compositional inhomogeneities depends on the amount of excess gallium and employment of indium as a surfactant during growth. The structure and microstructure of these MQWs were investigated by x-ray diffraction and TEM/STEM. Their optical properties were investigated with spatially-resolved CL spectroscopy and mapping. E-beam pumping experiments were performed by irradiating the top surface and collecting the luminescence from the cleaved edge. The observed superlinear dependence of the QW CL intensity on beam current together with linewidth narrowing strongly suggests light amplification by stimulated emission.
A Test for Measuring Growth Responses of Mollicutes to Serum and Polyoxyethylene Sorbitan (1993)

A test is described that is useful for characterizing mollicutes in terms of the ability to maintain growth in medium containing 15 to 20% fetal bovine serum or in serum-free media with or without 0.04% Tween 80 (polyoxyethylene sorbitan). Representative Acholeplasma species maintained growth in serum-free medium, and about half of the strains tested grew well in Tween 80-supplemented medium. Representative Mycoplasma and Entomoplasma species did not maintain growth in either serum-free medium alone or when Tween 80 was added. Spiroplasma species and group representatives generally failed to sustain growth in serum-free medium with or without Tween 80, but at least four of the spiroplasmas tested maintained growth in serum-free medium. The representative Mesoplasma species grew in serum-free media only when Tween 80 was added, as did Mycoplasma lactucae. Although the test has obvious determinative uses for members of the class Mollicutes, it does not supplant the conventional methodology for assaying the cholesterol requirements of these organisms.
Biomaterials (2002)

Biomaterials: Principles and Applications offers a comprehensive review of all the major biomaterials in this rapidly growing field. In recent years, the role of biomaterials has been influenced considerably by advances in many areas of biotechnology and science, as well as advances in surgical techniques and instruments. Comprising chapters
High aspect ratio polyimide etching using an oxygen plasma generated by electron cyclotron resonance source (1994)

High aspect ratio etching of polyimide in an O2 plasma generated by an electron cyclotron resonance (ECR) source was investigated. The dependence of etch rate, profile, and selectivity on microwave power, rf power, pressure, etch time, and gas composition were characterized. Etch rate was found to increase with microwave and rf power. Etch anisotropy increases with rf power but decreases with pressure and etch time. With 750 W microwave power, 300 W rf power, and 0.5 mTorr pressure, the polyimide etch rate was 0.91 μm/min and the anisotropy was 0.92. Etch selectivity between polyimide and the Ti mask was 3150:1 at 50 W and 536:1 at 300 W rf power. Compared to reactive ion etching, etching using an ECR source provides etch rate that is typically 10× faster and etch selectivity that is 4–6× higher. High aspect ratio (≳15:1) structures in polyimide that were 50 μm deep and 3 μm wide have been obtained using an O2 plasma generated by an ECR source.
Progressive Islet Graft Failure Occurs Significantly Earlier in Autoantibody-Positive Than in Autoantibody-Negative IDDM Recipients of Intrahepatic Islet Allografts (1997)

Alloimmunity has been uncovered to be a cause of graft loss representing a major barrier for clinical islet transplantation, and several studies are designed to evaluate new strategies for immunosuppression to prevent alloimmunity. In contrast, the significance for autoimmune destruction of transplanted beta-cells has remained somewhat controversial. Recently, two case reports based on histological findings have suggested recurrent autoimmune insulitis despite immunosuppressive therapy both in clinical pancreas and in islet transplantation. In the present study, in 23 islet-grafted patients with IDDM receiving standard immunosuppressive therapy, we demonstrate that progressive impairment of islet graft function occurs significantly earlier in those individuals positive for autoantibodies as a typical stigma of diabetes-associated autoimmunity that is well established in the prediabetic periods of IDDM. Intraportal infusion of allogeneic islets was performed in 23 C-peptide-negative IDDM patients, according to the clinical transplantation categories defined as islet after kidney (IAK) or simultaneous islet and kidney (SIK). Complete islet graft failure was defined as the 1st day of permanent C-peptide negativity in the serum (<0.2 ng/ml) and C-peptide negativity in the urine (<2 microg/dl). The median observation period following islet transplantation was 12 months (range 1-50) with a cumulative follow-up of 336 months. Islet cell antibodies (ICAs) and GAD65 antibodies were monitored before and regularly after islet transplantation. Kaplan-Meier survival analysis and log-rank statistics revealed a significant (P < 0.05) difference in cumulative islet graft survival depending on the presence of islet cell and/or GAD65 antibodies. These results strongly suggest that recurrent autoimmunity directed to transplanted beta-cells contributes to islet graft failure despite sustained immunosuppression. For successful clinical islet transplantation in the future, new immunosuppressive therapies are needed to prevent both alloimmunity and autoimmunity.
A Bivalent Ligand (KDN-21) Reveals Spinal δ and κ Opioid Receptors Are Organized as Heterodimers That Give Rise to δ1 and κ2 Phenotypes. Selective Targeting of δ−κ Heterodimers (2004)

In view of recent pharmacological studies suggesting the existence of delta-kappa opioid receptor heterodimers/oligomers in the spinal cord, we have synthesized and evaluated (intrathecally in mice) a series of bivalent ligands (KDN series) containing kappa and delta antagonist pharmacophores. Pharmacological and binding data have provided evidence for the bridging of spinal delta-kappa receptor heterodimers by KDN-21 and for their identification as delta(1) and kappa(2). The selectivity profile of KDN-21 and the apparent absence of coupled delta(1)-kappa(2) phenotypes in the brain suggest a new approach for targeting receptors.
Laboratory Correlates of Protection against Haemophilus influenzae Type b Disease (1995)

The concentration of serum antibody to the Haemophilus influenzae type b polysaccharide sufficient to confer protection against Hib disease has been estimated to range from 0.15 to 1.0 microgram/ml as measured by conventional antigen binding assays. However, the ability of these serologic tests to predict vaccine equivalence and/or protective efficacy is limited since there are important qualitative differences in vaccine-induced anti-PRP antibody, such as isotype, variable region usage, and antibody avidity. These differences may profoundly affect the biologic activity of the antibody. Also, Hib conjugate vaccination primes infants for memory antibody responses to a subsequent encounter with PRP, and immunologic priming can occur in infants with very low serum anti-PRP antibody responses to conjugate vaccination, or in those whose antibody concentrations have declined after vaccination. Primed infants are likely to be protected against Hib disease in the absence of "protective" serum antibody concentrations because priming permits a rapid serum anti-PRP antibody response upon encountering the organism. Thus, quantitative assessment of immunogenicity, by itself, is insufficient to predict vaccine equivalence or protective efficacy. In defining surrogate serologic tests for prediction of vaccine efficacy, assessments of antibody avidity and induction of immunologic memory should be included. Ideally, these assessments should be supplemented with antibody functional assays such as complement-mediated bactericidal activity, opsonic activity, or passive protection in animal models of disease.
Nitric Oxide Induces the Synthesis of Vascular Endothelial Growth Factor by Rat Vascular Smooth Muscle Cells (2000)

Vascular endothelial growth factor (VEGF) is known to induce the release of nitric oxide (NO) from endothelial cells. However, the effect of NO on VEGF synthesis is not clear. Accordingly, the effect of endogenous and exogenous NO on VEGF synthesis by rat vascular smooth muscle cells (VSMCs) was investigated. Two in vitro models were used: (1) VSMCs stimulated to produce NO by treatment with interleukin (IL)-1beta (10 ng/mL) and (2) VSMCs lipotransfected with pKecNOS plasmid, containing the endothelial constitutive NO synthase (ecNOS) cDNA. The synthesis of NO was inhibited by N(omega)-nitro-L-arginine methyl ester (L-NAME, 2 to 5 mmol/L) or diaminohydroxypyrimidine (DAHP, 2.5 to 5 mmol/L), inhibitors of NOS and GTP cyclohydrolase I, respectively. Some cells treated with L-NAME or DAHP were supplemented with L-arginine (10 mmol/L) or tetrahydrobiopterin (BH(4); 100 micromol/L), respectively. In addition, we studied the effect of sodium nitroprusside (SNP; 10 and 100 micromol/L) and chemically related compounds, potassium ferrocyanide and ferricyanide, on VEGF generation. IL-1beta induced iNOS expression and NO generation and significantly upregulated VEGF mRNA expression and protein synthesis. L-NAME and DAHP totally inhibited NO generation and decreased the IL-1beta-upregulated VEGF synthesis by 30% to 40%. Supplementation with L-arginine or BH(4) increased NO generation by L-NAME- or DAHP-treated cells, and VEGF synthesis was augmented by addition of BH(4). The cells generating NO after pKecNOS transfection released significantly higher amounts of VEGF than cells transfected with control plasmids. Inhibition of NO generation by L-NAME decreased VEGF synthesis. In contrast to the effect of endogenous NO, we observed the inhibition of VEGF synthesis in the presence of high (10 or 100 micromol/L) concentrations of SNP. This effect was mimicked by chemically related ferricyanide and ferrocyanide compounds, suggesting that the inhibitory effect of sodium nitroprusside may be mediated by an NO-independent mechanism. The results indicate that endogenous NO enhances VEGF synthesis. The positive interaction between endogenous NO and VEGF may have implications for endothelial regeneration after balloon angioplasty and for angiogenesis.
Microbial and Enzymatic Processes for the Production of Biologically and Chemically Useful Compounds [New Synthetic Methods (69)] (1988)

Abstract In recent years, the most significant development in the field of synthetic organic chemistry has been the application of biological systems to chemical reactions. Reactions catalyzed by enzymes and enzyme systems display far greater specificities than more conventional organic reactions. Biological and/or enzymatic syntheses and transformations, that is, “microbial transformations,” have great potential. Some of these reactions have already been shown to have useful applications in the fields of synthetic organic chemistry and biotechnology. This article reviews the current status of the rapidly developing field of microbial transformation, the methodology, available technological procedures, and fields of application being described especially in relation to conventional organic synthesis methods.