gebhart/patrepeval huggingface dataset:
Compromised Humoral and Delayed-Type Hypersensitivity Responses in IL-23-Deficient Mice (2004)

The heterodimeric cytokine IL-23 consists of a private cytokine-like p19 subunit and a cytokine receptor-like subunit, p40, which is shared with IL-12. Previously reported IL-12p40-deficient mice have profound immune defects resulting from combined deficiency in both IL-12 and IL-23. To address the effects of specific IL-23 deficiency, we generated mice lacking p19 by gene targeting. These mice display no overt abnormalities but mount severely compromised T-dependent humoral immune responses. IL-23p19(-/-) mice produce strongly reduced levels of Ag-specific Igs of all isotypes, but mount normal T-independent B cell responses. In addition, delayed type hypersensitivity responses are strongly impaired in the absence of IL-23, indicating a defect at the level of memory T cells. T cells stimulated with IL-23-deficient APCs secrete significantly reduced amounts of the proinflammatory cytokine IL-17, and IL-23-deficient mice phenotypically resemble IL-17-deficient animals. Thus, IL-23 plays a critical role in T cell-dependent immune responses, and our data provide further support for the existence of an IL-23/IL-17 axis of communication between the adaptive and innate parts of the immune system.
Phosphorylation of ERK1/2 mitogen-activated protein kinase is associated with poor response to anti-hormonal therapy and decreased patient survival in clinical breast cancer (2001)

It is believed that growth factor phosphorylation cascades interact closely with oestrogen receptor (ER) signaling to regulate breast cancer growth, and that alterations in these pathways may underlie resistance to anti-hormones such as tamoxifen. There is an increasing body of experimental evidence implicating the mitogen-activated protein kinase extracellular signal-regulated-kinases ERK1 and ERK2 (ERK1/2 MAPK) in these events. The present study is the first to address the relationship between ERK1/2 MAPK phosphorylation (p-MAPK) and response to anti-hormonal agents in clinical breast cancer (n = 90). Immunocytochemical analysis using a phosphorylation state-specific ERK1/2 MAPK antibody revealed 72% of breast tumors to have considerable nuclear p-MAPK immunostaining (designated p-MAPK positive), whereas staining was barely detectable or absent in the remaining 28% (designated p-MAPK negative). Comparison with staining in normal breast material obtained from reduction mammoplasty patients (n = 10) demonstrated an increased frequency of higher intensity p-MAPK immunostaining cells within carcinomas (p = 0.002). Significant relationships were revealed between p-MAPK positivity and poorer quality (p = 0.001) and shortened duration (p = 0.006) of anti-hormonal response, as well as with decreased survival time from the initiation of therapy (p = 0.022). These associations were retained in ER positive disease (p = 0.013, p = 0.037 and p = 0.048 respectively), where multivariate analysis demonstrated p-MAPK status to be a significantly independent predictor for response duration (p = 0.034) and patient survival (p = 0.029). Phosphorylated ERK1/2 MAP kinase is thus potentially prognostic for prediction of response to anti-hormonal agents and survival, data providing further evidence that ERK1/2 MAP kinase plays a role in circumvention of anti-hormonal response in breast cancer.
Syndecan-1 expression in mammary epithelial tumor cells is E-cadherin-dependent (1996)

E-cadherin is a Ca(2+)-dependent cell-cell adhesion molecule, which is mainly expressed in epithelial cells. Recent studies have shown that E-cadherin has an important role as an invasion suppressor molecule in epithelial tumor cells. Syndecan-1 is a cell surface proteoglycan that has been implicated in a number of cellular functions including cell-cell adhesion, cell-matrix anchorage and growth factor presentation for signalling receptors. Its suppression has also been shown to be associated with malignant transformation of epithelial cells. In order to better understand the coordinated regulation of cell-cell and cell-matrix interactions during malignant transformation, we have studied the expression of syndecan-1 in malignant mammary tumor cells genetically manipulated for E-cadherin expression. In invasive NM-e-ras-MAC1 cells, where E-cadherin was partially downregulated by specific antisense RNA, syndecan-1 expression was suppressed. Furthermore, transfection of E-cadherin cDNA into invasive NM-f-ras-TD cells resulted in the upregulation of syndecan-1 expression in association with decreased invasiveness. In both cases, regulation of syndecan-1 occurred post-transcriptionally, since syndecan-1 mRNA levels remained unchanged. Instead, a translational regulation is suggested, since syndecan-1 core protein synthesis was E-cadherin dependent. Another cell adhesion protein, beta 1-integrin was not affected by E-cadherin expression. The data provide an example of coordinated changes in the expression of two cell adhesion molecules, syndecan-1 and E-cadherin during epithelial cell transformation.
Inactivation of gene expression in plants as a consequence of specific sequence duplication. (1994)

Numerous examples now exist in plants where the insertion of multiple copies of a transgene leads to loss of expression of some or all copies of the transgene. Where the transgene contains sequences homologous to an endogenous gene, expression of both transgene and endogenous gene is sometimes found to be impaired. Several examples of these phenomena displaying different features are reviewed. Possible explanations for the observed phenomena are outlined, drawing on known cellular processes in Drosophila, fungi, and mammals as well as plants. It is hypothesized that duplicated sequences can, under certain circumstances, become involved in cycles of hybrid chromatin formation or other processes that generate the potential for modification of inherited chromatin structure and cytosine methylation patterns. These epigenetic changes could lead to altered transcription rates or altered efficiencies of mRNA maturation and export from the nucleus. Where the loss of gene expression is posttranscriptional, antisense RNA could be formed on accumulated, inefficiently processed RNAs by an RNA-dependent RNA polymerase or from a chromosomal promoter and cause the observed loss of homologous mRNAs and possibly the modification of homologous genes. It is suggested that the mechanisms evolved to help silence the many copies of transposable elements in plants. Multicopy genes that are part of the normal gene catalog of a plant species must have evolved to avoid these silencing mechanisms or their consequences.
Single-molecule fluorescence in situ hybridization: Quantitative imaging of single RNA molecules (2013)

In situ detection of RNAs is becoming increasingly important for analysis of gene expression within and between intact cells in tissues. International genomics efforts are now cataloging patterns of RNA transcription that play roles in cell function, differentiation, and disease formation, and they are demonstrating the importance of coding and noncoding RNA transcripts in these processes. However, these techniques typically provide ensemble averages of transcription across many cells. In situ hybridization-based analysis methods complement these studies by providing information about how expression levels change between cells within normal and diseased tissues, and they provide information about the localization of transcripts within cells, which is important in understanding mechanisms of gene regulation. Multi-color, single-molecule fluorescence in situ hybridization (smFISH) is particularly useful since it enables analysis of several different transcripts simultaneously. Combining smFISH with immunofluorescent protein detection provides additional information about the association between transcription level, cellular localization, and protein expression in individual cells.
The Effect of 2 Different Custom-Molded Corrective Orthotics on Plantar Pressure (2006)

Context: Because of research variability and the increasing use of orthotics to manage lower extremity problems, further research is warranted. Objective: To investigate the effect of rear-foot- and forefoot-posted (PAL) and mediolongitu-dinal arch-supported (SOLE) orthotics on plantar pressure (PP) during walking. Design: Repeated measures. Setting: Laboratory. Participants: 17 subjects with forefoot varus. Intervention: Data were collected at 0 and 6 weeks for no-orthotic and orthotic conditions. Measurements: PPs were collected with the EMED Pedar measurement system. Results: Zero weeks: PAL increased PP in lateral forefoot (LFF), middle toes (MT), and lateral toes (LT) and decreased PP in lateral heel (LH), medial forefoot (MFF), and central forefoot (CFF). SOLE increased PP for midfoot (MF) and LT and decreased PP in medial heel (MH), LH, and CFF. 6 weeks: PAL increased PP in LFF, MT, and LT and decreased PP in LH, MFF, and CFF. SOLE increased PP in MF and decreased PP in MH, LH, and LFF. Conclusion: The SOLE orthotic appeared to be more effective in attaining the goals of custom-molded-orthotic intervention.
Antibodies as cytotoxic therapy. (1994)

At present, there are no unconjugated monoclonal antibodies that have proven therapeutic benefit in hematologic malignancies or solid tumors. The most active areas of current interest relate to antibodies to various growth factor receptors and the testing of humanized antibodies.
Fully automated determination of solid fat content by pulsed NMR (1974)

Abstract Pulsed NMR has been developed into a quick, accurate fully automated method for the determination of the solid fat content in partially crystallized fats. Accepting a standard deviation of 0.3% solids, the percentage of solids is displayed on a digital voltmeter or printed out 6 sec after placing the sample into the sample holder. To allow for the dead time of the receiver, a correction factor has been introduced giving rise to only small errors (&lt;1%) in the solid fat content. Due to the short measuring time, no temperature control of the sample holder is needed between 10–45 C. Pulsed NMR values can be converted into dilatations and vice versa.
Angiopoietin-1 Inhibits Endothelial Cell Apoptosis via the Akt/Survivin Pathway (2000)

A productive angiogenic response must couple to the survival machinery of endothelial cells to preserve the integrity of newly formed vessels. Angiopoietin-1 (Ang-1) is an endothelium-specific ligand essential for embryonic vascular stabilization, branching morphogenesis, and post-natal angiogenesis, but its contribution to endothelial cell survival has not been completely elucidated. Here we show that Ang-1 acting via the Tie 2 receptor induces phosphorylation of the survival serine-threonine kinase, Akt (or protein kinase B). This is associated with up-regulation of the apoptosis inhibitor, survivin, in endothelial cells and protection of endothelium from death-inducing stimuli. Moreover, dominant negative survivin negates the ability of Ang-1 to protect cells from undergoing apoptosis. The activation of anti-apoptotic pathways mediated by Akt and survivin in endothelial cells may contribute to Ang-1 stabilization of vascular structures during angiogenesis, in vivo.
7-(N-substituted)amino-2,3-polymethylene benzofurane derivatives with tracheal relaxant activity. (1996)

A set of twelve 7-(N-substituted)amino-2,3-polymethylenebenzofuranes (1-12) together with three related compounds (13-15) was prepared. Ten selected compounds were tested for tracheal relaxant activity in vitro and two of them (6,7) were also subjected to a broad pharmacological screening. Five compounds (2,7,9,12,14) at the concentration of 30 micrograms/ml exhibited high tracheal relaxant activity (73-94% tone reduction) that was superior than that of theophylline at the same concentration. The 7-(N-trifluoromethylsulfonyl)amino-2,3-tetramethylenebenzofuran e (9) was highly active till the concentration of 1 microgram/ml giving a stronger tracheal relaxation than amrinone at 3 micrograms/ml. On the other hand the general screening did not show any other major activity. The benzofurane derivatives 1-13 were obtained through obvious steps from the corresponding 7-nitrobenzofuranes, which were prepared by a Fischer indole-like cyclization of O-[(2-nitro)phenyl] ketone oximes. In one case two peculiar side products were isolated.
Triptolide, an Inhibitor of the Human Heat Shock Response That Enhances Stress-induced Cell Death (2006)

Molecular chaperones, inducible by heat shock and a variety of other stresses, have critical roles in protein homeostasis, balancing cell stress with adaptation, survival, and cell death mechanisms. In transformed cells and tumors, chaperones are frequently overexpressed, with constitutive activation of the heat shock transcription factor HSF1 implicated in tumor formation. Here, we describe the activity of triptolide, a diterpene triepoxide from the plant Triptergium wilfordii, as an inhibitor of the human heat shock response. Triptolide treatment of human tissue culture cells prevented the inducible expression of heat shock genes, shown by suppression of an HSP70 promoter-reporter construct and by suppression of endogenous HSP70 gene expression. Upon examining the steps in the HSF1 activation pathway, we found that triptolide abrogates the transactivation function of HSF1 without interfering in the early events of trimer formation, hyperphosphorylation, and DNA binding. The ability of triptolide to inhibit the heat shock response renders these cells sensitive to stress-induced cell death, which may be of great relevance to cancer treatments.
Recombinant Newcastle Disease Virus as a Vaccine Vector for Cancer Therapy (2008)

Naturally occurring strains of Newcastle disease virus (NDV) are currently being investigated in multiple clinical trials for oncolytic cancer therapy in the United States and abroad. We have previously reported, for the first time, the development of recombinant NDVs designed for enhanced cancer therapeutic efficacy. Specifically, we have shown that NDV engineered to express interleukin-2 (IL-2) generates a robust therapeutic response associated with increased tumor-specific T-cell infiltration after intratumoral administration in mice. We have now demonstrated that this therapeutic response is dependent on T cells and we have investigated the potential to focus the NDV-induced immune response toward a tumor-associated antigen (TAA) to enhance the inherent therapeutic efficacy of NDV further. We found that intratumoral treatments of tumor-bearing mice with recombinant NDV expressing a model TAA elicited an enhanced tumor-specific response, resulting in a significant increase in the number of complete tumor regressions compared with control NDV. Additionally, coadministration of NDV expressing a model TAA with NDV expressing IL-2 enhanced the TAA-directed response and led to more complete tumor regressions. Our results show that TAA-directed immunotherapy by oncolytic recombinant NDV alone or in combination with IL-2 results in an enhanced therapeutic efficacy and warrant consideration in the development of cancer therapies based on the use of oncolytic NDV.
A magnetic manipulator for studying local rheology and micromechanical properties of biological systems (1996)

A magnetic micromanipulator capable of generating two-dimensional translational and rotational motions on a microscope stage is described. With 3 μm-diam paramagnetic beads, forces in the piconewton range and torques on the order of 10−14 N m are obtained and can be modulated in time at moderate frequencies (&amp;lt;5 Hz). Typical magnetic fields between 0.1 and 0.2 T, and gradients between 10 and 20 T m−1 are created by four independent feedback-controlled electromagnets. Video microscopy and computerized image analysis are used to locate the beads on each image with a resolution of 0.1 pixel (20 nm). The device is primarily designed to study, at a microscopic scale, the local mechanical properties of biological polymers such as actin in solution, and of cell cytoplasm. Possible applications include the in situ manipulation of intracellular organelles.
A local image reconstruction algorithm for stochastic rendering (2011)

Stochastic renderers produce unbiased but noisy images of scenes that include the advanced camera effects of motion and defocus blur and possibly other effects such as transparency. We present a simple algorithm that selectively adds bias in the form of image space blur to pixels that are unlikely to have high frequency content in the final image. For each pixel, we sweep once through a fixed neighborhood of samples in front to back order, using a simple accumulation scheme. We achieve good quality images with only 16 samples per pixel, making the algorithm potentially practical for interactive stochastic rendering in the near future.
Selective tumor killing based on specific DNA-damage response deficiencies (2012)

Organisms constantly undergo various stresses within their life span, which can damage their DNA. In order to maintain genomic stability and counteract the development of unwanted genomic mutations, organisms have evolved a DNA-damage response (DDR) to protect their genome. Due to the critical roles played by DDR in genomic stability, its defects can lead to cellular transformation and potentially tumorigenesis. Consequently, this also provides the opportunity to specifically target tumor cells due to a weakened ability to tolerate genotoxic stresses. In this lies a treatment strategy in which the inhibition of remaining DDR pathways can hyper-sensitize tumors to chemotherapeutic agents while minimizing deleterious effects to healthy cells. Therefore it is important to understand the genotypic background of specific tumors to determine which DDR pathways remain and can be targeted for inhibition. Tumor therapies based on the DDR are ideal not only as a means of increasing the effectiveness of current chemotherapies but also as a means to selectively target tumor cells while leaving healthy cells unharmed. Thus, targeting DDR components as a means of increasing effectiveness and discrimination of current chemotherapeutic tumor treatments is currently the focus of many studies and clinical trials.
Solid-phase synthesis of oligopurine deoxynucleic guanidine (DNG) and analysis of binding with DNA oligomers (2001)

The first stepwise solid-phase synthesis of deoxynucleic guanidine (DNG), a positively charged DNA analog, using controlled pore glass as the solid support is reported. For the first time, purine bases have been incorporated into the DNG oligomer and DNG has been synthesized using a solid-phase method, proceeding in the 3'-->5' direction, that is compatible with the cleavage conditions used in the solid-phase synthesis of DNA. A DNG sequence containing a pentameric tract of adenosine nucleosides has been synthesized and the thermal denaturation temperature of its complexes with complementary thymidyl DNA oligomers was 79 degrees C. Binding of thymidyl DNA oligomers to adenyl DNG oligomers is 2:1, as seen in thymidyl and adenyl DNA triplexes. No binding of adenyl DNG with octameric cytidyl DNA was observed, indicating that the positive charge does not overcome base pairing fidelity.
Possible genetic association between interleukin-1alpha gene polymorphism and the severity of chronic polyarthritis. (1999)

Interleukin-1 (IL-1) has been implicated in the pathogenesis of rheumatoid arthritis (RA). IL-1alpha gene polymorphism was analysed for the exon V and promoter region in 51 patients with destructive and 47 with non-destructive RA, as well as in 94 controls. The two biallelic polymorphisms in the promoter region and the exon V were 100% linked. The rare IL-1A2 allele carriage rate was 45% in the control population. It was increased in destructive (54.4%) and decreased in non-destructive RA (26.8%, destructive versus non-destructive, p < 0.007). All indices of disease activity and joint destruction were significantly lower in the patients positive for IL-1A1, and higher in those positive for IL-1A2. The present findings suggest that this IL-1alpha gene polymorphism may contribute to the pathogenesis of chronic polyarthritis. The presence of the IL-1A2 allele could constitute a risk factor for the development of destructive arthritis and could be used early in the course of the disease as a prognostic marker.
The pCL vector system: rapid production of helper-free, high-titer, recombinant retroviruses (1996)

We describe the construction and characterization of retroviral vectors and packaging plasmids that produce helper-free retrovirus with titers of 1 X 10(6) to 5 X 10(6) within 48 h. These vectors contain the immediate early region of the human cytomegalovirus enhancer-promoter fused to the Moloney murine leukemia virus long terminal repeat at the TATA box in the 5' U3 region, yielding the pCL promoter. By selecting vectors designed to express genes from one of four promoters (dihydrofolate reductase, Rous sarcoma virus, long terminal repeat, or cytomegalovirus), the pCL system permits the investigator to control the level of gene expression in target cells over a 100-fold range, while maintaining uniformly high titers of virus from transiently transfected producer cells. The pCL packaging plasmids lack a packaging signal (delta-psi) and include an added safety modification that renders them self-inactivating through the deletion of the 3' U3 enhancer. Ecotropic, amphotropic (4070A), and amphotropic-mink cell focus-forming hybrid (10A1) envelope constructions have been prepared and tested, permitting flexible selection of vector pseudotype in accordance with experimental needs. Vector supernatants are free of helper virus and are of sufficiently high titer within 2 days of transient transfection in 293 cells to permit infection of more than 50% of randomly cycling target cells in culture. We demonstrated the efficacy of these vectors by using them to transfer three potent cell cycle control genes (the p16(INK4A), p53, and Rb1 genes) into human glioblastoma cells.
Reactivation Kineties of diethylphosphoryl acetylcholine esterase (1985)

The kinetics of reactivation of diethylphosphorylated acetylcholine esterase by pyridine-2-aldoxime methochloride has been studied using the approach of following the course of the hydrolysis of acetylcholine during the reactivation of the phosphorylated enzyme by the reactivator [Tsou, C.-L. (1965) Acta Biochem. Biophys. Sin. 5, 398-417]. Equations are derived based on the scheme of the formation of a complex between the phosphorylated enzyme and the reactivator and the rate of dissociation of this complex is not necessarily faster than the dephosphorylation and regeneration of the active enzyme. The regenerated enzyme then reacts with the substrate through an acetyl-enzyme intermediate as generally depicted. The equation obtained for product formation during the course of reactivation contains two exponential terms and this is in accord with the experimentally observed biphasic reaction. By making the assumption that the dissociation of the phosphorylated enzyme-reactivator complex is much faster than the dephosphorylation reaction, the above equation can be simplified to a form containing only one exponential term. By following the course of the reactivation reaction with the conventional approach of taking aliquots and assaying for enzyme activity recovery, it would appear likely that one would miss the initial stage of this biphasic reaction.