gebhart/patrepeval huggingface dataset:
Epidermal growth factor receptor, but not c-erbB-2, activation prevents lactogenic hormone induction of the beta-casein gene in mouse mammary epithelial cells. (1990)

The HC11 cell line was isolated from mammary gland cells of pregnant mice. The cells displayed a normal phenotype and retained some characteristics of mammary epithelial cell differentiation. After treatment with the lactogenic hormones prolactin and glucocorticoids, the HC11 cells expressed the milk protein beta-casein. Various oncogenes were transfected and expressed in HC11 cells. The oncogenes were tested for their transformation ability and for their effects upon the differentiation of the HC11 cells. All of the oncogenes tested, including activated human Ha-ras, human transforming growth factor-alpha, activated rat neuT, and human c-erbB-2 activated by a point mutation in the transmembrane domain, caused transformation of the HC11 cells, as shown by tumor formation in nude mice. HC11 cells expressing the neuT and activated c-erbB-2 genes synthesized beta-casein in response to lactogenic hormones, whereas those expressing the Ha-ras or transforming growth factor-alpha oncogenes were no longer able to respond to the lactogenic hormones. This inhibition of beta-casein production occurs at the transcriptional level and in the transforming growth factor-alpha-transformed cells is due to an autocrine mechanism involving the activation of the epidermal growth factor receptor. This suggests that, although the c-erbB-2 and epidermal growth factor receptors are structurally quite similar, their activation has different effects upon mammary epithelial cell differentiation.
Effect of TNF-α Antisense Oligomers on Cytokine Production by Primary Murine Alveolar Macrophages (1998)

Antisense oligomers can inhibit expression of a single gene in a sequence-specific manner. As a result, these sequences are being developed both as powerful experimental tools in the laboratory and as a novel class of therapeutic agents. In this study, we evaluated a panel of morpholino antisense (M-AS) oligomers for their ability to inhibit tumor necrosis factor-alpha (TNF-alpha) production by primary murine alveolar macrophages (AMs) and compared them with the more commonly used phosphorothioate oligonucleotides (S-AS). We found that 25 microM of morpholino oligomers whose sequence spanned the AUG (M-AS 2, M-AS 2me, and M-AS 5) start codon of TNF-alpha significantly inhibited TNF production on stimulation by both lipopolysaccharides (LPS) (36.6 +/- 3.2%, 27.3 +/- 3.0%, and 37.7 +/- 2.0% inhibition, respectively), whereas S-AS targeted toward the same region were ineffective. M-AS 2 and M-AS 2me also significantly inhibited TNF production in AMs stimulated by adherence to a solid substrate (28.7 +/- 2.2% and 29.4 +/- 8.3% inhibition, respectively). Increasing the concentration of M-AS 2 and M-AS 2me to 50 microM improved their efficacy in both LPS-stimulated (42.7 +/- 1.5% and 45.9 +/- 2.1% inhibition, respectively) and adherence-stimulated (52.6 +/- 0.7% and 41.7 +/- 2.9% inhibition, respectively) AMs. In contrast, we showed that neither an antisense sequence targeted to a region upstream of the AUG site (M-AS 4) nor the nonsense control sequences M-NS 1 and M-NS 2 significantly inhibited TNF-alpha production by AMs on exposure to either stimulus. The data indicate that morpholino oligomers inhibit TNF-alpha production by murine AMs in a sequence-dependent and dose-dependent manner.
Overcoming Antigenic Competition to Produce Multispecific Cytotoxic T Lymphocyte Lines for Adoptive Transfer (2009)

for different epitopes and the doses required to eradicate disease are lacking.We have developed an in-vivo model to assess specificity and efficacy of CMV-CTL and establish TC doses required for treatment using colon carcinoma cells transduced with CMVpp65 as a surrogate system.HLA A0201 1 human colon carcinoma cells transduced with CMVpp65 and GFP-firefly luciferase (CoCa-pp65) were injected subcutaneously (s.c.) into NOD/Scid-IL2Rgc-KO/J mice (NSG) at doses ranging from 10 4 -10 6 (4 mice /group) and tumor growth followed for 4 weeks using bio-luminescent imaging and tumor measurements.Consistent engraftment was observed with 3 Â 10 5 cells.Groups of NSG mice were then injected s.c with CoCa-pp65 (3 Â 10 5 ) mixed with HLA A0201-restricted CMV-CTL (A2-CMV-CTLs) at E:T ratios of 50:1, 10:1, 2:1 and 0.4:1.To ascertain antigen specificity of A2-CMV-CTLs, groups of 4 NSG mice were subsequently co-injected s.c. with 3 tumor-TC combinations (E:T 5 1:1) as follows: (i) A2-CMV-CTLs 1 3 Â 10 5 CoCa-pp65 (ii) A2-CMV-CTLs 1 A2 tumor without CMVpp65 (iii) A2-Flu-CTLs 1 3 Â 10 5 CoCa-pp65.Control animals were injected with the 2 tumors without TC.IL-2 (2000 U i.p) was given 2 Â a week, growth followed by imaging x 4 weeks.No growth of CoCa-pp65 was detected in any animal co-injected with A2-CMV-CTL at any E:T ratio, with consistent tumor growth over 4 weeks in controls.Current experiments are assessing E:T ratios lower than 0.4:1.Tumor growth was observed in control groups (ii) and (iii) with no detectable growth in (i) by imaging or examination of autopsied tissues.These studies demonstrate that CMV-CTL can eradicate clonogenic tumor cells expressing an immunogenic viral antigen in-vivo at E:T ratios that are significantly lower than those required in-vitro.This model also allows for comparison of cytotoxic activity of TC directed against different immunogenic epitopes and permits comparisons of virus-specific and tumor specific TC for their immunotherapeutic potential.
Linear radio frequency power amplifier design using nonlinear feedback linearization techniques (2005)

This paper presents the results of the research conducted on the feedback linearization of radio frequency (RF) power amplifiers (PA) used in digital communication applications. The proposed design takes into account not only the nonlinear behavior of the power amplifier but also its dynamic behavior. First, a faithful mathematical model of the voltage I/O characteristic of the PA is developed, i.e., a sigmoidal function model which closely describes its nonlinear gain behavior is derived and a multiplicative nonlinear feedback controller is applied to it to render the overall amplifier's response linear. Simulation results obtained using Matlab/Simulink are presented, and power amplifier linearity properties are quantified in terms of the output power spectrum when the input is a BPSK waveform, the classic two-tone test, the white noise test, and the AM/AM and AM/PM conversion curves.
Avoiding Proppant Flowback in Tight-Gas Completions with Improved Fracture Design (2003)

Abstract In this paper we describe the possibility and benefits of incorporating the stability analysis of the proppant pack during the design stage of hydraulic fracturing treatments. After the well is treated and cleaned up, the flowback of proppant from a fracture-treated formation is highly undesirable for several reasons, including possible damage to the wellhead and flowlines, operational complications, and last but not least, decrease in well-productivity. The issue has been studied on an empirical basis and the most important factors have been determined. Nevertheless, qualitative models suggested so far seem to work only under limited conditions and currently there is no clear methodology for predicting the occurrence of proppant flowback while designing the treatment. In this work we review previously suggested prediction methods and analyze the proppant flowback patterns experienced in 24 South-Texas tight-gas completions. As a result of the study we conclude that the predictive power of the available models is not satisfactory and the implications for "proppant stability control agents" are not based on convincing evidence. A new semi-mechanistic model is proposed that shows reasonable agreement with both laboratory and field data. A methodology is suggested to incorporate the proppant flowback prediction at the fracture design stage. The suggested methodology is based on the concept of "minimum necessary departure from optimality to satisfy technical constraints", in this case the constraint being to keep the likelihood of proppant flowback under a certain threshold.
Identification, classification, and analysis of beta‐bulges in proteins (1993)

A beta-bulge is a region of irregularity in a beta-sheet involving two beta-strands. It usually involves two or more residues in the bulged strand opposite to a single residue on the adjacent strand. These irregularities in beta-sheets were identified and classified automatically, extending the definition of beta-bulges given by Richardson et al. (Richardson, J.S., Getzoff, E.D., & Richardson, D.C., 1978, Proc. Natl. Acad. Sci. USA 75, 2574-2578). A set of 182 protein chains (170 proteins) was used, and a total of 362 bulges were extracted. Five types of beta-bulges were found: classic, G1, wide, bent, and special. Their characteristic amino acid preferences were found for most classes of bulges. Basically, bulges occur frequently in proteins; on average there are more than two bulges per protein. In general, beta-bulges produce two main changes in the structure of a beta-sheet: (1) disrupt the normal alternation of side-chain direction; (2) accentuate the twist of the sheet, altering the direction of the surrounding strands.
Combined anti‐PDGFRα and PDGFRβ targeting in non‐small cell lung cancer (2008)

Activation of the platelet-derived growth factor (PDGF)-receptors is critically involved into various stromal cell functions including recruitment of stromal cells and vascular endothelial growth factor (VEGF) induction in tumor and perivascular cells. To evaluate the effects of combined PDGFRalpha and -beta inhibition in a non-small cell lung cancer model, we stably transfected A549 lung cancer cells with the PDGF-A mutant PDGF-0. PDGF-0 has been generated by substituting amino acids in the binding region of PDGF-A with the corresponding VEGF-A region, leading to a decreased receptor-binding affinity and activation. Compared with control vector transfected cells, transfection with PDGF-0 had no impact on monolayer growth and apoptosis in vitro, but significantly impaired the number of colony formation in soft agar. After subcutaneous injections, all mice developed tumors within 5 days. While control vector transfected A549 cells were characterized by constant tumor growth, PDGF-0 transfected A549 revealed a reduced tumor mass (p < 0.001) with no further growth beyond 14 days (2 months observation time) and complete regressions in 7 of 13 cases. Immunohistochemical analyses revealed that PDGF-0 transfected tumors demonstrated decreased recruitment of periendothelial cells, while the tumor invasion zone was similar to control vector transfectants. Similarly, conditioned medium from PDGF-0 transfected cells induced significantly less migration of smooth muscle cells and fibroblasts in vitro. Interestingly, in PDGF-0 transfectants, neither total vessel count nor VEGF expression were significantly altered. These studies demonstrate that combined inhibition of PDGFRalpha and -beta results in markedly decreased tumor growth in vivo because of impaired recruitment of periendothelial cells.
Intestinal IgA: novel views on its function in the defence of the largest mucosal surface (1999)

The intestine is undoubtedly the most misunderstood and under-appreciated lymphoid organ in the body. Yet, in the eyes of mucosal immunologists, the gut exemplifies finely tuned, extensively interacting populations of cells and their products involved in innate and specific defence of the body’s largest surface area, a surface exposed to the heaviest burden of environmental antigens. As the largest lymphoepithelial organ, it contains cells that absorb, process, and present antigen, B and T cells of various types, and antibody producing cells.1 Every day intestinal plasma cells produce more antibodies than do all other lymphoid organs (spleen, lymph nodes, and the bone marrow) combined.2 Although the remarkable dominance of IgA producing cells in the intestine and of IgA in the intestinal fluid has been known for decades, fine details of the migration or “homing” of IgA plasma cell precursors, their terminal differentiation, the mechanisms mediating and regulating the selective transepithelial transport of IgA, and the functional advantages of this molecule in the gut continue to emerge with impressive rapidity.

One feature unique to the mucosal immune system is the crucial role of epithelial cells of various morphological forms and phenotypes in mucosal defences.3 Functional interdependence of epithelial and lymphoid cells in the intestine has been amply documented. In addition to production of inflammatory cytokines (e.g. interleukin (IL) 8 and macrophage inflammatory protein (MIP) 1α and anti-inflammatory cytokines (e.g. transforming growth factor (TGF) β and IL-10), epithelial cells are also a source of cytokines that regulate the terminal differentiation of arriving lymphocytes into IgA producing plasma cells (e.g. TGF-β, IL-6, IL-10).3Lymphocytes resident in the lamina propria and in the intraepithelial compartment, mostly of T cell lineage, participate directly and indirectly in the protection of the mucosa,4 and provide stimuli (e.g. interferon (IFN) γ) for the maintenance …
External beam radiation enhances antibody mediated radiocytotoxicity in human glioma cells in vitro. (1997)

Enhanced accumulation of monoclonal antibodies in tumor tissue has been observed as a result of external beam irradiation (EBR). This effect was mainly attributed to increased vascular leakage due to unspecific radiation damage of vascular endothelial cells. The aim of this study was to investigate the effects of EBR on expression and antibody-binding of epidermal growth-factor receptor (EGF-R) in human glioma cells in-vitro. High-grade glioma cells were irradiated with conventional x-rays (0-3600 Rad) and surface binding, internalization and radiocytotoxicity of 125I-labeled monoclonal antibody (MAb) 425, specific for human EGF-R, was tested. EBR showed a short-term dose and time dependent increase of specific MAb 425 binding and internalization in receptor positive cell lines U87-MG and A1207. This effect was probably due to a mitotic block and an increase in cellular volume. Combination of EBR and 125I-425 showed additive effects on cell vitality/survival and was more pronounced in contact inhibited cells as compared to cells growing in a log-phase. We assume that cells exposed to 125I-labeled MAb 425 are only able to accumulate a critical number of DNA double-strand breaks when the doubling-time is prolonged e.g. under contact-inhibition or radiation induced mitotic blockade. We conclude that EBR has no negative effects on EGF-R expression, MAb-binding and internalization. The combination of EBR and 125I-MAb 425 enhances cytotoxic efficacy and thus supports adjuvant use in the clinical management of high-grade glioma.
Cutting Edge: STAT1 Is Required for IL-6–Mediated Bcl6 Induction for Early Follicular Helper Cell Differentiation (2013)

Bcl6 is required for CD4 T cell differentiation into T follicular helper cells (Tfh). In this study, we examined the role of IL-6 in early processes of in vivo Tfh differentiation, because the timing and mechanism of action of IL-6 in Tfh differentiation have been controversial in vivo. We found that early Bcl6(+)CXCR5(+) Tfh differentiation was severely impaired in the absence of IL-6; however, STAT3 deficiency failed to recapitulate that defect. IL-6R signaling activates the transcription factor STAT1 specifically in CD4 T cells. Strikingly, we found that STAT1 activity was required for Bcl6 induction and early Tfh differentiation in vivo. IL-6 mediated STAT3 activation is important for downregulation of IL-2Rα to limit Th1 cell differentiation in an acute viral infection. Thus, IL-6 signaling is a major early inducer of the Tfh differentiation program unexpectedly mediated by both STAT3 and STAT1 transcription factors.
Hepatoma‐derived growth factor involved in the carcinogenesis of gastric epithelial cells through promotion of cell proliferation by Erk1/2 activation (2008)

Hepatoma-derived growth factor (HDGF) is related to tumorigenesis and the development of cancer; it is an independent factor associated with the prognosis of liver cancer, non-small cell lung cancer and pancreatic cancer. However, the molecular mechanism by which HDGF participates in gastric carcinogenesis and development as well as its functional regulation during the development of gastric precancerous lesions needs to be further analyzed. In the present study, we analyzed the effect of HDGF transfection on the proliferation and on the changes of mitogen-activated protein kinase (MAPK), Akt, and nuclear factor-kB (NF-kB) pathways in gastric cancer AGS cells. HDGF transfection significantly activated Erk1/2 in AGS cells and promoted anchorage-independent growth. Further studies showed that HDGF expression gradually increased in the gastric carcinogenesis process and HDGF showed a high expression in poorly differentiated adenocarcinoma prone to lymphoid metastasis; these findings suggest that HDGF is involved in the gastric carcinogenesis process and promotes proliferation and metastasis via Erk1/2 activation.
CRISPR/Cas9-mediated genome engineering and the promise of designer flies on demand (2013)

The CRISPR/Cas9 system has attracted significant attention for its potential to transform genome engineering. We and others have recently shown that the RNA-guided Cas9 nuclease can be employed to engineer the Drosophila genome, and that these modifications are efficiently transmitted through the germline. A single targeting RNA can guide Cas9 to a specific genomic sequence where it induces double-strand breaks that, when imperfectly repaired, yield mutations. We have also demonstrated that 2 targeting RNAs can be used to generate large defined deletions and that Cas9 can catalyze gene replacement by homologous recombination. Zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) have shown similar promise in Drosophila. However, the ease of producing targeting RNAs over the generation of unique sequence-directed nucleases to guide site-specific modifications makes the CRISPR/Cas9 system an appealingly accessible method for genome editing. From the initial planning stages, engineered flies can be obtained within a month. Here we highlight the variety of genome modifications facilitated by the CRISPR/Cas9 system along with key considerations for starting your own CRISPR genome engineering project.
Dietary antioxidant curcumin inhibits microtubule assembly through tubulin binding (2006)

Curcumin, a component of turmeric, has potent antitumor activity against several tumor types. However, its molecular target and mechanism of antiproliferative activity are not clear. Here, we identified curcumin as a novel antimicrotubule agent. We have examined the effects of curcumin on cellular microtubules and on reconstituted microtubules in vitro. Curcumin inhibited HeLa and MCF-7 cell proliferation in a concentration-dependent manner with IC(50) of 13.8 +/- 0.7 microm and 12 +/- 0.6 microm, respectively. At higher inhibitory concentrations (> 10 microm), curcumin induced significant depolymerization of interphase microtubules and mitotic spindle microtubules of HeLa and MCF-7 cells. However, at low inhibitory concentrations there were minimal effects on cellular microtubules. It disrupted microtubule assembly in vitro, reduced GTPase activity, and induced tubulin aggregation. Curcumin bound to tubulin at a single site with a dissociation constant of 2.4 +/- 0.4 microm and the binding of curcumin to tubulin induced conformational changes in tubulin. Colchicine and podophyllotoxin partly inhibited the binding of curcumin to tubulin, while vinblastine had no effect on the curcumin-tubulin interactions. The data together suggested that curcumin may inhibit cancer cells proliferation by perturbing microtubule assembly dynamics and may be used to develop efficacious curcumin analogues for cancer chemotherapy.
Investigation of Dual Circulation Control Surfaces for Flight Control (2004)

*† An experimental investigation into the application of circulation control on a full span test configuration with a delta wing planform has been performed in a closed return wind tunnel at 25m/s. The circulation was controlled using jets of air, ejected from a plenum, attaching to a cylindrical trailing edge. It was found that large lift augmentations were possible, to the order of 20 (cf. existing flap systems ≈ 0.1). The effect of circulation control was used to investigate the concept as a means of trimming an aircraft. It was found that only low values for jet momentum coefficient, Cµ’s up to 0.002, would be required to trim the aircraft at the range of angle of attack investigated. Only small variations in pitching moment were noted indicating that the increase in lift would not be compromised by other control concerns. An investigation into roll control was also conducted, using differential blowing on either side of the full span model. The results indicated that the roll control varied linearly with Cµ, with the presence of the leading edge vortex augmented the effect in a pro-roll capacity.
Prediction of angiographic change in native human coronary arteries and aortocoronary bypass grafts. Lipid and nonlipid factors. (1990)

A within-group risk factor analysis was conducted to predict angiographic change in the Cholesterol Lowering Atherosclerosis Study, a randomized, placebo-controlled trial of colestipol plus niacin therapy in men with previous coronary bypass surgery. Global angiographic change, including both native coronary arteries and bypass grafts after 2 treatment years, was the end point. Risk factors included on-trial clinical measures, plasma lipids, lipoproteins, and apolipoproteins. Univariate analysis indicated that risk factors previously observed by others in epidemiologic investigation of ischemic heart disease--total cholesterol, LDL cholesterol, non-HDL cholesterol, triglycerides, apolipoprotein B, and diastolic blood pressure--had significant effects in the placebo-treated group. Univariate analysis indicated significant effects of apolipoprotein C-III in drug- and placebo-treated groups. Multivariate analysis indicated the predominant risk factor predicting the probability of global coronary progression was non-HDL cholesterol in placebo-treated subjects and the content of apolipoprotein C-III in high density lipoproteins of drug-treated subjects. Both drug- and placebo-treated group findings point to an important role for triglyceride-rich lipoproteins in progression and regression of human atherosclerosis.
Efficient Dense and Sparse Matrix Multiplication on GP-SIMD (2014)

We present efficient Dense and Sparse Matrix Multiplication on GP-SIMD, a hybrid general purpose SIMD computer architecture that eliminates synchronization by in-memory computing, combining data storage and massively parallel processing. Cycle-accurate simulation of on a large set of matrices shows enhanced power efficiency relative to conventional architectures.
Design and Implementation of Components to Represent the 3-Dimensional+Temporal Objects (2004)

As geographic object is consisted of 3-dimensional, it must be appropriated use the 3-dimensional coordinate system to express for exact representation. To define 3-dimensional+temporal object model we extended 3-dimensional space and valid time from object model of OpenGIS consortium that is limited to 2-dimensional space. This methodology guarantees compatibility with other systems to construct with the open model. Also, it permitted administration for two kinds of object by considering both objects whose position and shape changes discretely over time and objects whose position changes continuously. 3-dimensional+temporal object model was implemented by 3-dimensional+temporal object component using OLE/COM techniques. The interfaces of the component defined based on 3-dimensional+temporal object model. To use this component, we implement the data consumer for 3-dimensional+temporal data.