gebhart/patrepeval huggingface dataset:
The Gamma Catenin/CBP Complex Maintains Survivin Transcription in &#946;-catenin Deficient/Depleted Cancer Cells (2011)

Previously, we demonstrated that survivin expression is CBP/β-catenin/TCF-dependent. Now, using NCI-H28 cells, which harbor a homozygous deletion of β-catenin, we demonstrate that survivin transcription can similarly be mediated by nuclear γ-catenin. ICG-001, a specific inhibitor of binding to the N-terminus of CBP, effectively attenuates survivin expression. We demonstrate that γ-catenin by binding to TCF family members and specifically recruiting the coactivator CBP drives survivin transcription particularly in β-catenin-deficient cells. We also examined the relative expression of γ-catenin and β-catenin in 90 cases of chronic myeloid leukemia (CML) in a published gene expression microarray data base. A statistically significant negative correlation between γ-catenin and β-catenin was found in AP/BC cases (-0.389, P = 0.006). Furthermore, in subsequent independent validation studies by qPCR in 28 CP and BC patients increased γ-catenin expression predominated in BC cases and was associated with concomitantly increased survivin expression. Gene expression was 3- and 6-fold greater in BC patients as compared to CP patients, for γ-catenin and survivin, respectively. Consistent with this observation, nuclear γ-catenin accumulation was evident in this population consistent with a potential transcriptional role. Combined treatment with imatinib mesylate (IM) and ICG-001 significantly inhibited colony formation in sorted CD34(+) CML progenitors (survivin(+)/γ-catenin(high)/β-catenin(low)) isolated from one BC and one AP patient resistant to IM. Therefore, we believe that the ability of ICG-001 to block both the CBP/γ-catenin interaction and the CBP/β-catenin interaction may have clinical significance in cancers in which γ-catenin plays a significant transcriptional role.
New generation of switched capacitor converters (2002)

This paper presents a new generation of switched capacitor power converters. These new circuits use a reduced number of switches. The new family consists of three circuit topologies: double; inverting; and half the input voltage. All the switching devices are zero-current switching and hence the converter can operate at high switching frequency. The high switching current has also been reduced.
The CD19 signal transduction molecule is a response regulator of B-lymphocyte differentiation. (1995)

The phenotypes of CD19-deficient (CD19-/-) mice, and human CD19-transgenic (hCD19TG) mice that overexpress CD19 indicate that CD19 is a response regulator of B-lymphocyte surface receptor signaling. To further characterize the function of CD19 during B-cell differentiation, humoral immune responses to a T-cell-independent type 1 [trinitrophenyl-lipopolysaccharide (TNP-LPS)], a T-cell-independent type 2 [dinitrophenyl (DNP)-Ficoll], and a T-cell-dependent [DNP-keyhole limpet hemocyanin (KLH)] antigen were assessed in CD19-/- and hCD19TG mice. B cells from CD19-/- mice differentiated and underwent immunoglobulin isotype switching in vitro in response to mitogens and cytokines. In vivo, CD19-/- mice generated humoral responses to TNP-LPS and DNP-KLH that were dramatically lower than those of wild-type littermates. Surprisingly, the humoral response to DNP-Ficoll was significantly greater in CD19-/- mice. In contrast, hCD19TG mice were hyperresponsive to TNP-LPS and DNP-KLH immunization but were hyporesponsive to DNP-Ficoll. These results demonstrate that CD19 is not required for B-cell differentiation and isotype switching but serves as a response regulator which modulates B-cell differentiation. Since humoral responses to both T-cell-dependent and T-cell-independent antigens were similarly affected by alterations in CD19 expression, these differences are most likely to result from intrinsic changes in B-cell function rather than from the selective disruption of B-cell interactions with T cells.
Amplification and Enhanced Expression of the Epidermal Growth Factor Receptor Gene in A431 Human Carcinoma Cells (1984)

The sequence of the human epidermal growth factor (EGF) receptor shows great homology with the avian erythroblastosis virus v-erb B oncogene, raising the possibility that the receptor gene is identical to the c-erb B protooncogene. Human A431 epidermoid carcinoma cells, which have an unusually high number of EGF receptors, were examined to determine whether elevated EGF receptor levels correlate with gene amplification. Southern blots of genomic DNA's from A431 and other human cell lines were probed with either a v-erb B gene fragment or a human EGF receptor complementary DNA clone (pE7), previously isolated from an A431 complementary DNA library. When either probe was used to analyze Eco RI- or Hind III-generated DNA fragments, EGF receptor DNA sequences were amplified about 30-fold in A431. Differences in the banding pattern of A431 DNA fragments relative to normal fibroblast DNA indicate the occurrence of a rearrangement in the region of the receptor gene. Furthermore, A431 cells contain a characteristic, prominent 2.9-kilobase RNA. These results are consistent with the hypothesis that, in A431 cells, gene amplification, possibly associated with a translocation event, may result in the overproduction of EGF receptor protein or the appearance of the transformed phenotype (or both).
Transplantation of Autologous Iris Pigment Epithelium After Removal of Choroidal Neovascular Membranes (2000)

In this pilot study, the transplantation of autologous IPE cells was done as an addition to conventional surgical excision of choroidal neovascular membranes. Transplanted cells were well tolerated in the subretinal space and did not adversely affect the function of the photoreceptors, since improvement or stable visual acuity was observed in 18 patients after IPE transplantation. These results suggest that autologous IPE cells may be used as a substitute for autologous RPE cells to transplant to the subretinal space to treat age-related macular degeneration.
Combination Treatment of Osteoporosis: A Clinical Review (2002)

The few trials including Food and Drug Administration (FDA)-approved medications suggest that 10 mg/day alendronate with estrogen (equivalent of 0.625 mg CEE daily) can increase BMD moreso than each medication given singly in postmenopausal osteoporotic women. Estrogen dose and type must be controlled in future trials. Long-term safety data are lacking. The utility of these combinations rests on whether bone density changes will translate into decreased fracture rates.
The synthesis of pyrazolo[3,4‐d]pyridazines. Photochemical cyclization to pyrazolo[3,4‐d]pyridazin‐4(5H)‐ones with subsequent functionalization (1984)

Abstract The synthesis of 1,3‐disubstituted and 1,3,5‐trisubstituted 1 H ‐pyrazolo[3,4‐ d ]pyridazin‐4(5 H )‐ones is conveniently performed by photochemical cyclization. Functionalization of the former compounds leading to the formation of 1,4‐disubstituted and 1,3,4‐trisubstituted 1 H ‐pyrazolo[3,4‐ d ]pyridazines is smoothly effected through pertinent nucleophilic substitutions.
Cloning and characterization of the 2B4 gene encoding a molecule associated with non-MHC-restricted killing mediated by activated natural killer cells and T cells. (1993)

We have recently described a signal transducing molecule, 2B4, expressed on all NK and T cells that mediate non-MHC-restricted killing. The gene encoding this molecule was cloned and its nucleotide sequence determined. The encoded protein of 398 amino acids has a leader peptide of 18 amino acids and a transmembrane region of 24 amino acids. The predicted protein has eight N-linked glycosylation sites, suggesting that it is highly glycosylated. Comparison of 2B4 with sequences in the databanks indicates that 2B4 is a member of Ig supergene family, and it shows homology to murine and rat CD48 and human LFA-3. Northern blot analysis has shown at least three transcripts for 2B4 in adherent lymphokine-activated killer cells of several mouse strains and TCR-gamma/delta dendritic epidermal T cell lines but not in allospecific T cell clones. These three mRNA are the products of differential splicing of heterogeneous nuclear RNA. Southern blot analysis of genomic DNA from several mouse strains revealed that 2B4 belongs to a family of closely related genes. The 2B4 gene has been mapped to mouse chromosome 1 by analysis of 2B4 expression in recombinant inbred mouse strains.
Transforming Growth Factor Peptide Antagonists and Their Conversion to Partial Agonists (1997)

Transforming growth factor beta (TGF-beta) has been implicated in the pathogenesis of various human diseases. Synthetic TGF-beta antagonists therefore could have therapeutic utility. Here we show the development of such compounds. Three synthetic pentacosapeptides designated beta125-(41-65), beta225-(41-65), and beta325-(41-65), whose amino acid sequences correspond to the 41st to 65th amino acid residues of TGF-beta1, TGF-beta2, and TGF-beta3, respectively, inhibit the binding of 125I-labeled TGF-beta isoforms to TGF-beta receptors in mink lung epithelial cells with IC50 of approximately 0.06-2 microM. beta125-(41-65) blocks TGF-beta1-induced growth inhibition and TGF-beta1-induced plasminogen activator inhibitor-1 expression in these cells. The variants designated beta125-(41-65)W52A/D55A and beta325-(41-65)R52A/D55A, in which both Trp52/Arg52 and Asp55 are replaced by alanine residues, do not have TGF-beta antagonist activity. Multiple conjugation of beta125-(41-65) to carrier proteins enhances its antagonist activity but also confers partial agonist activity as measured by DNA synthesis inhibition. These results suggest that the (W/R)XXD motif is important for the activities of these TGF-beta peptide antagonists and that this motif may be the active site sequence of TGF-beta.
Asymmetric Total Synthesis of (−)-Azaspirene, a Novel Angiogenesis Inhibitor (2002)

The asymmetric total synthesis of (-)-azaspirene, an angiogenesis inhibitor, has been accomplished, establishing its absolute stereochemistry. The key steps are a MgBr2.OEt2-mediated, diastereoselective Mukaiyama aldol reaction, a NaH-promoted, intramolecular cyclization of an alkynylamide, and the aldol reaction of a ketone containing functionalized gamma-lactam moiety without protection of tert-alcohol and amide functionalities.
Studies in mouse L-cells on the incorporation of 1-beta-D-arabinofuranosylcytosine into DNA and on inhibition of DNA polymerase by 1-beta-D-arabinofuranosylcytosine 5'-triphosphate. (1970)

Studies have been carried out in mouse L-cells on the incorporation of 1-β-d-arabinofuranosylcytosine (ara-C) into DNA and on the inhibition of DNA polymerase by the 5′-triphosphate of ara-C (ara-CTP) to determine whether either of the two current models, incorporation into DNA or inhibition of DNA polymerase, could account for ara-C action. With a modification of the McGrath-Williams technique, it was found that ara-C was initially incorporated into small (Okazaki) pieces of DNA but shifted into longer DNA strands when cells were washed and incubated in a medium free of ara-C-3H. On degradation of DNA from ara-C-3H-labeled cells with micrococcal nuclease and spleen phosphodiesterase, it was found that most of the ara-C appeared to be in internucleotide rather than terminal linkages, suggesting that chain elongation is not stopped by the addition of ara-C to a growing strand. Studies on ara-C incorporation into nucleic acids failed to show any correlation between the amount of incorporation and the degree of lethality. With crude extracts of L-cells, it was found that ara-CTP was a competitive inhibitor of DNA polymerase, and values of 9.0 ± 4.3 and 8.7 ± 5.2 × 10-6 m were obtained for the Michaelis-Menten constants of dCTP and ara-CTP, respectively. Calculations based on these values and on measured values of the dCTP and ara-CTP concentrations in vivo indicated that the predicted inhibition of DNA synthesis was significantly smaller than that actually observed in whole cells. Nevertheless, an evaluation of all of the available data suggests that the most plausible model for the action of ara-C is that DNA synthesis is inhibited by inhibition of DNA polymerase.
Isolation of functionally different human monocytes by counterflow centrifugation elutriation (1982)

Human peripheral blood monocytes were isolated by counterflow centrifugation elutriation (CCE). This technique was modified in such a way that various monocyte fractions (viability greater than 99%) could be elutriated by increasing the density of the CCE-medium in steps of 0.0027 g/ml. All monocytes showed the same size distributions as determined by electronic sizing, which indicated that they differed in their density only. Both cytoplasmic esterase and peroxidase activity increased with the density of the cells. Furthermore, the monocytes with the highest density were 2.3-4 times more active in an antibody-dependent cellular cytotoxicity (ADCC) assay than those with the lowest density. In contrast, the monocyte with the highest density were less capable to induce the proliferation of lymphocytes in mixed leukocyte cultures (MLC) than those with the lowest density. This observation could not be attributed to differences in the expression of HLA-DR determinants, since a monoclonal antibody directed against HLA-DR antigens reacted equally well with the monocytes in different fractions. These results provide evidence for the existence of functionally different subsets of monocytes or different states of differentiation or maturation.
Interaction of deuterium plasma with sputter-deposited tungsten nitride films (2015)

Abstract Magnetron-sputtered tungsten nitride (WN x ) films were used as a model system to study the behaviour of re-deposited WN x layers which could form in fusion devices with tungsten (W) wall during nitrogen seeding. The interaction of such WN x layers with deuterium (D) plasmas was investigated in dedicated laboratory experiments. D retention and N removal due to D plasma exposure (D flux: 9.9 × 10 19 D m −2 s −1 , ion energy 215 eV) at different temperatures were measured with ion beam analysis (IBA). Low-energy argon sputtering followed by IBA was applied to resolve the D distribution in the top-most surface of WN x with significantly improved depth resolution compared with the standard D depth profiling method by nuclear reaction analysis. Experimentally determined thicknesses for the penetration of D in WN x were compared with the penetration depth for D calculated in SDTrimSP simulations. Results show that D is only retained within the ion penetration range for samples exposed at 300 K. In contrast to the 300 K case, D diffuses beyond the implantation depth in a sample exposed at 600 K. However, the D penetration depth is much lower than in pure W at comparable conditions. The total amount of retained D in WN x at 600 K is by 50% lower than for implantation at 300 K with the same D fluence. Nitrogen is removed only within the D ion range.
Expression of Recombinant Bovineβ-Lactoglobulin inEscherichia coli (1990)

Bovine beta-lactoglobulin A was expressed in Escherichia coli in its mature form. The gene was constructed using a cDNA clone which coded for amino acid residues Leu-11 to Ile-162 and a synthetic oligonucleotide coding for the initial 10 amino acids preceded by a translational start. The met-beta-lactoglobulin was expressed using a tac promoter vector, pTTQ18, and accounted for approximately 15% of the total cellular protein. The recombinant met-beta-lactoglobulin migrated with the same molecular weight as native beta-lactoglobulin A on SDS-PAGE. The majority of the met-beta-lactoglobulin produced was found in an insoluble form but could be solubilized using guanidine-HCl. The renatured preparation was greater than 80% pure and migrated similarly to purified beta-lactoglobulin A under nondenaturing conditions.
Human dendritic cells transfected with renal tumor RNA stimulate polyclonal T-cell responses against antigens expressed by primary and metastatic tumors. (2001)

Although renal cell carcinoma has been shown to respond to immunotherapy, renal cell carcinoma-specific rejection antigens and their corresponding CTL epitopes have rarely been described. The use of dendritic cells (DCs) transfected with mRNA isolated from tumor cells may allow specific immunotherapy even in cancers for which potent rejection antigens have not been identified. Here we show that DCs transfected with RNA isolated from renal cancer tissue are remarkably effective in stimulating tumor-specific T-cell response in vitro but do not cross-react with normal tissue antigens including antigens expressed by renal parenchyma. In contrast, the tumor-specific CTLs lysed allogeneic tumor but not allogeneic normal tissue targets, suggesting the presence of shared albeit unidentified antigens among renal carcinomas. CTL responses against telomerase reverse transcriptase (TERT) accounted in part for the reactivities against allogeneic tumors because renal tumor RNA-transfected DCs stimulated polyclonal CTL responses, which encompassed as a subcomponent a response against TERT. Nonetheless, the tumor-specific CTLs were consistently superior to the CTLs stimulated with TERT RNA-transfected DCs in recognizing and lysing tumor targets, suggesting that tumor-specific CTLs represent a polyclonal response providing more effective antitumor activity than T-cell responses directed against a single antigen in the form of TERT. Tumor RNA-transfected DCs were capable of stimulating T-cell reactivities not only against the primary tumor but also against metastatic tumors, although discrete differences in the antigenic repertoire expressed by these tissues were apparent. Thus, total tumor RNA-transfected DCs may represent a broadly applicable vaccine strategy to induce polyclonal and potentially therapeutic T-cell responses in renal cancer patients.
Artifactual formation of 8-oxo-2'-deoxyguanosine: role of fluorescent light and inhibitors (2003)

The pro-mutagenic oxidative DNA lesion, 8-oxo-2'-deoxyguanosine (8-oxodG) has been a subject of numerous studies. However, the absolute 8-oxodG levels in tissue DNA reported by various methods have been debated due to its artifactual production during DNA isolation and/or the DNA processing. We have investigated factors that may result in such artifacts during isolation and analysis of DNA as well as means for its prevention. 8-OxodG content was measured by a recently described TLC enrichment-mediated 32P-postlabeling. Liver DNA from 3 month-old, female Sprague-Dawley rats was isolated by a standard solvent-extraction procedure (phenol, phenol:Sevag, and Sevag; 23 degrees C), a modified solvent-extraction procedure (phenol:Sevag, and Sevag; 4 degrees C; KCl-SDS-protein precipitation) or sodium iodide extraction procedure. 8-OxodG was analyzed in the DNA by the 32P-postlabeling assay using a fluorescent light box during the workup, as well as in its absence. The 8-oxodG levels, when the fluorescent light box was used, were in similar range irrespective of the DNA isolation procedure (16.4+/-1.6 to 28.7+/-6 8-oxodG/10(6) nucleotides). However, the values were significantly lower (3.1+/-0.4 to 3.4+/-0.2 8-oxodG/10(6) nucleotides) in the absence of fluorescence light box, room fluorescent light (suspended through the ceiling) and natural room light did not alter the 8-oxodG levels. Further, the addition of 0.3 mM of PBN (N-t-butyl-alpha-phenyl nitrone) or TEMPO (2,2,6,6-tetramethylpiperidine-N-oxyl), or 6.8 mM 8-hydroxy-quinoline during the DNA isolation resulted in still lower values (0.8+/-0.1 to 1.8+/-0.5 8-oxodG/10(6) nucleotides) although this reduction was not consistently observed in different experiments. These results suggest that fluorescent light is the major 'culprit' in artifactual production and variability reported in the 8-oxodG levels.
Perisynaptic surface distribution of multiple classes of nicotinic acetylcholine receptors on neurons in the chicken ciliary ganglion (1995)

Most nicotinic ACh receptors (AChRs) studied to date in the embryonic chicken ciliary ganglion are recognized either by monoclonal antibody (mAb) 35 or by alpha-bungarotoxin (alpha-Bgt). Previous studies found that mAb 35-AChRs are found at both synaptic and extrasynaptic sites, while alpha-Bgt-AChRs are found exclusively at extrasynaptic sites. To gain a three-dimensional understanding of the distribution of these two AChR classes and their spatial relationship to synaptic sites, we have visualized mAb 35-AChRs and alpha-Bgt-AChRs immunofluorescently using laser scanning confocal microscopy and have compared their distribution with that of the synaptic vesicle antigen SV2. Both mAb 35-AChR and alpha-Bgt-AChRs are found in clusters that are widely distributed over the surface of embryonic chicken ciliary ganglion neurons. Some mAb 35- AChRs are located at synaptic sites, but the bulk of them are located extrasynaptically in well-defined patches measuring 1–4 micron in diameter. alpha-Bgt-AChRs are found almost exclusively in these extrasynaptic sites, which thus contain both AChR types. These sites are often surrounded by elements of the synaptic calyx but are themselves largely free of SV2 antigen. In 14 week chickens the relationship between mAb 35-AChRs, alpha-Bgt-AChRs, and synaptic sites is similar to that in embryos except that in this instance individual synaptic boutons are often surrounded by AChR-containing patches. These results suggest that most surface AChRs in both embryonic and mature chicken ciliary neurons are perisynaptic, which raises questions about the function of these AChRs.
Exploitation of solid waste in foamed concrete challenges ahead (2005)

This paper reviews the contribution of some researchers on blended
cement and reports recent findings of a research programme focused on the exploitation
of solid wastes in foamed concrete. Solid wastes studied include rice husk and its
derivatives, paper sludge and recycled expanded polystyrene (EPS). The objective is to
develop an environmental-friendly and economical foamed concrete for construction. A
novel process for the synthesis of micronised silica for use in foamed concrete is revealed
in order to provide a unique solution to construction on soft soil. Concerted collaborative
effort by researchers and the readymix concrete industry is expected to enhance the
competitive edge of the construction industry.