gebhart/patrepeval huggingface dataset:
Regulation of targeted chemotherapy with cytotoxic lutenizing hormone-releasing hormone analogue by epidermal growth factor. (2000)

Targeting chemotherapy selectively to cancers can reduce the toxic side effects. AN-152, a conjugate of doxorubicin and [D-Lys6]-luteinizing hormone-releasing hormone (LH-RH), is more potent against LH-RH receptor-bearing cancers and produces less peripheral toxicity than doxorubicin. Many cancers, e.g., 50% of breast cancers, but few normal tissues express these receptors, providing a selective target for this cytotoxic conjugate. In this study, the effectiveness of AN-152 was heightened by receptor up-regulation. The cytotoxic effect of AN-152 can be regulated by the number of active LH-RH receptors on cancer cells. LH-RH receptor-positive (MCF-7) and -negative (UCI-107) cancer cells were treated with epidermal growth factor (EGF) or the somatostatin analogue, RC-160. EGF and RC-160 have been shown previously to regulate LH-RH receptors through phosphorylation. The effect of receptor regulation, by hormone exposure, on the cytotoxicity of AN-152 and doxorubicin and on the cellular uptake of AN-152, [D-Lys6]LH-RH, or doxorubicin was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and by two-photon laser scanning microscopy. The results demonstrated that the cellular entry of the conjugate was: (a) specific for cancers with LH-RH receptors; (b) up-regulated by EGF; (c) down-regulated by RC-160; and (d) the cytotoxicity of the AN-152 paralleled the efficiency of entry. This study illustrates the potential use of receptor regulation for increasing the efficacy of chemotherapeutic approaches that are directed to cell surface receptors.
REDUCTION OF THE OCCURRENCE OF ACUTE CELLULAR REJECTION AMONG RENAL ALLOGRAFT RECIPIENTS TREATED WITH BASILIXIMAB, A CHIMERIC ANTI-INTERLEUKIN-2-RECEPTOR MONOCLONAL ANTIBODY1,2 (1999)

Prophylactic basiliximab therapy is well tolerated, has an adverse event profile comparable to placebo, and significantly reduces the number of acute rejection episodes in renal allograft patients within the first year after transplantation.
Characterization of a 34-Kilodalton Protein of Mycobacterium leprae That Is Isologous to the Immunodominant 34-Kilodalton Antigen of Mycobacterium paratuberculosis (1998)

During DNA sequence analysis of cosmid L373 from the Mycobacterium leprae genome, an open reading frame of 1.4 kb encoding a protein with some homology to the immunodominant 34-kDa protein of Mycobacterium paratuberculosis, but lacking significant serological activity, was detected. The DNA sequence predicted a signal peptide with a modified lipoprotein consensus sequence, but the protein proved to be devoid of lipid attachment.
Radial basis function interpolation for 3-D ultrasound (1998)

3-D freehand ultrasound imaging produces a set of irregularly spaced B-scans, which are typically reconstructed on a regular grid for visualisation and data analysis. Most standard reconstruction algorithms are designed to minimise computational requirements and do not exploit the underlying shape of the data. We investigate whether approximation with splines holds any promise as a better reconstruction method. A radial basis function (RBF) approximation method is implemented and compared with three standard methods. The RBF&amp;apos;s are shown to accommodate both dense, overlapping data and sparse data, without introducing the kind of reconstruction artifacts common with the standard methods. The other potential advantages of RBF&amp;apos;s, such as the direct computation of derivatives, make further investigation worthwhile.
Surface-Enhanced Raman Gene Probes (1994)

We report for the first time a new type of DNA gene probe based on surface-enhanced Raman scattering (SERS) label detection. The surface-enhanced Raman gene (SERG) probes do not require the use of radioactive labels and have great potential to provide both sensitivity and selectivity. The SERG probe can be used to detect DNA biotargets (e.g., gene sequences, bacteria, viral DNA fragments) via hybridization to DNA sequences complementary to that probe. The analytical figures of merit and its applications in environmental and biomedical areas are discussed.
Multiple Promoters Exist in the Human GR Gene, One of Which Is Activated by Glucocorticoids (2001)

A new human GR gene sequence (hGR 1Ap/e), which is distinct from the previously identified human GR promoter and coding sequences, has been isolated and characterized. The hGR 1Ap/e sequence is approximately 31 kbp upstream of the human GR coding sequence. This sequence (2,056 bp) contains a novel promoter (the hGR 1A promoter; 1,075 bp) and untranslated exon sequence (hGR exon 1A sequence; 981 bp). Alternative splicing produces three different hGR 1A-containing transcripts, 1A1, 1A2, and 1A3. GR transcripts containing exon 1A1, 1A2, 1B, and 1C are expressed at various levels in many cancer cell lines, while the exon 1A3-containing GR transcript is expressed most abundantly in blood cell cancer cell lines. Glucocorticoid hormone treatment causes an up-regulation of exon 1A3-containing GR transcripts in CEM-C7 T-lymphoblast cells and a down-regulation of exon 1A3-containing transcripts in IM-9 B-lymphoma cells. Deoxyribonuclease I footprinting using CEM-C7 cell nuclear extract reveals four footprints in the promoter region and two intraexonic footprints. Much of the basal promoter-activating function is found in the +41/+269 sequence, which contains two deoxyribonuclease I footprints (FP5 and FP6). When this sequence is cloned into the pXP-1 luciferase reporter gene, hormone treatment causes a significant increase in luciferase activity in Jurkat T cells that are cotransfected with a GR expression vector. FP5 is an interferon regulatory factor-binding element, and it contributes significantly to basal transcription rate, but it is not activated by steroid. FP6 resembles a glucocorticoid response element and can bind GRbeta. This novel hGR 1Ap/e sequence may have future applications for the diagnosis, prognosis, and treatment of T-cell leukemia and lymphoma.
TRPV4 mediates myofibroblast differentiation and pulmonary fibrosis in mice (2014)

Idiopathic pulmonary fibrosis (IPF) is a fatal fibrotic lung disorder with no effective medical treatments available. The generation of myofibroblasts, which are critical for fibrogenesis, requires both a mechanical signal and activated TGF-β; however, it is not clear how fibroblasts sense and transmit the mechanical signal(s) that promote differentiation into myofibroblasts. As transient receptor potential vanilloid 4 (TRPV4) channels are activated in response to changes in plasma membrane stretch/matrix stiffness, we investigated whether TRPV4 contributes to generation of myofibroblasts and/or experimental lung fibrosis. We determined that TRPV4 activity is upregulated in lung fibroblasts derived from patients with IPF. Moreover, TRPV4-deficient mice were protected from fibrosis. Furthermore, genetic ablation or pharmacological inhibition of TRPV4 function abrogated myofibroblast differentiation, which was restored by TRPV4 reintroduction. TRPV4 channel activity was elevated when cells were plated on matrices of increasing stiffness or on fibrotic lung tissue, and matrix stiffness-dependent myofibroblast differentiation was reduced in response to TRVP4 inhibition. TRPV4 activity modulated TGF-β1-dependent actions in a SMAD-independent manner, enhanced actomyosin remodeling, and increased nuclear translocation of the α-SMA transcription coactivator (MRTF-A). Together, these data indicate that TRPV4 activity mediates pulmonary fibrogenesis and suggest that manipulation of TRPV4 channel activity has potential as a therapeutic approach for fibrotic diseases.
Myogenic differentiation of mesenchymal stem cells for muscle regeneration in urinary tract. (2013)

Smooth or skeletal myogenic differentiation of mesenchymal stem cells with regenerative medicine technology may provide a novel approach for muscle regeneration and tissue repair in urinary tract. The long-term effect and safety of mesenchymal stem cell transplantation should be further evaluated before this approach becomes widely used in patients.
HIV-1 Tat-Mediated Apoptosis in Human Brain Microvascular Endothelial Cells (2003)

The integrity of the blood-brain barrier (BBB) is critical for normal brain function. Neuropathological abnormalities in AIDS patients have been associated with perivascular HIV-infected macrophages, gliosis, and abnormalities in the permeability of the BBB. The processes by which HIV causes these pathological conditions are not well understood. To characterize the mechanism by which HIV-1 Tat protein modulates human brain microvascular endothelial cell (HBMEC) functions, we studied the effects of HIV-1 Tat in modulating HBMEC apoptosis and permeability. Treatment of HBMEC with HIV-1 Tat led to Flk-1/KDR and Flt-4 receptor activation and the release of NO. The protein levels of endothelial NO synthase (NOS) and inducible NOS were increased by HIV-1 Tat stimulation. Importantly, HIV-1 Tat caused apoptosis of HBMEC, as evidenced by changes in the cleavage of poly(A)DP-ribose polymerase, DNA laddering, and incorporation of fluorescein into the nicked chromosomal DNA (TUNEL assay). HIV-1 Tat-mediated apoptosis in HBMEC was significantly inhibited in the presence of N-nitro-L-arginine methyl ester (an inhibitor of NOS) and wortmannin (a phosphoinositol 3-kinase inhibitor). Furthermore, HIV-1 Tat treatment significantly increased HBMEC permeability, and pretreatment with both N-nitro-L-arginine methyl ester and wortmannin inhibited the Tat-induced permeability. Taken together, these results indicate that dysregulated production of NO by HIV-1 Tat plays a pivotal role in brain endothelial injury, resulting in the irreversible loss of BBB integrity, which may lead to enhanced infiltration of virus-carrying cells across the BBB.
Effect of Glycerol and Glucose on the Enhancement of Biomass, Lipid and Soluble Carbohydrate Production by Chlorella vulgaris in Mixotrophic Culture (2013)

Biodiesel-derived glycerol is a promising substrate for mixotrophic cultivation of oleaginous microalgae, which can also reduce the cost of microalgal biodiesel. The objective of this study is to investigate the potential of using glycerol and glucose as a complex carbon substrate to produce microalgal biomass and biochemical components, such as photosynthetic pigments, lipids, soluble carbohydrates and proteins by Chlorella vulgaris. The results show that C. vulgaris can utilize glycerol as a sole carbon substrate, but its effect is inferior to that of the mixture of glycerol and glucose. The effect of glycerol and glucose could enhance the algal cell growth rate, biomass content and volumetric productivity, and overcome the lower biomass production on glycerol as the sole organic carbon source in mixotrophic culture medium. The utilization of complex organic carbon substrate can stimulate the biosynthesis of lipids and soluble carbohydrates as the raw materials for biodiesel and bioethanol production, and reduce the anabolism of photosynthetic pigments and proteins. This study provides a promising niche for reducing the overall cost of biodiesel and bioethanol production from microalgae as it investigates the by-products of algal biodiesel production and algal cell hydrolysis as possible raw materials (lipids and carbohydrates) and organic carbon substrates (soluble carbohydrates and glycerol) for mixotrophic cultivation of microalgae.
Shared antigens between bacteria and guinea pig line 10 hepatocarcinoma cells. (1976)

This study was undertaken to investigate the possibility that Listeria monocytogenes, Brucella abortus, and Salmonella typhimurium share antigenic components with guinea pig line 10 hepatocarcinoma cells. Rabbits were immunized with sonicates of these bacteria or line 10 tumor cells. Other rabbits were immunized with line 1 cells, a tumor with antigenic characteristics different from those of line 10. The binding of antibodies to radiolabeled antigens prepared from extracts of bacteria and line 10 cells was studied by precipitation of radiolabeled antigen-antibody complexes with anti-rabbit immunoglobulin. Antibodies in sera from rabbits immunized with these bacteria and line 10 cells bound both the labeled bacteria and line 10 antigens. Antibodies in sera from rabbits immunized with line 1 cells did not bind the bacterial antigens. Inhibition studies involving reactions between radiolabeled Listeria and line 10 antigens and antibodies to Listeria and line 10 cells confirmed that the binding reactions were specific and that line 10 cells shared antigens with Listeria cells. The possibility that B. abortus and S. typhimurium also shared antigens with line 10 cells was suggested. Whether antigens shared by these bacteria and line 10 cells are identical with tumor-specific antigens was not determined.
Identification of two common regions of allelic loss in chromosome arm 12q in human pancreatic cancer. (1998)

Using the method of microsatellite analysis, we studied 40 tissues with pancreatic ductal adenocarcinoma and identified two commonly deleted regions on the long arm of chromosome 12. One (region A) was found between D12S81 and D12S1719 at 12q21 at a frequency of 67.5%, and the other (region B) was located between D12S360 and D12S78 at 12q22-q23.1 at a frequency of 60%; the latter was reported previously (M. Kimura, et al. Genes Chromosomes Cancer, 17: 88-93, 1996). The results of microsatellite analyses were verified by fluorescence in situ hybridization. We further analyzed 19 pancreatic cancer cell lines by fluorescence in situ hybridization and found that 10 of them showed allelic loss at D12S81 and 6 showed allelic loss at D12S360. Yeast artificial chromosome contigs were constructed to cover the deleted regions. Region B was completely covered by a 650-kb yeast artificial chromosome clone. The frequently deleted regions in chromosome 12q in pancreatic cancer that were identified here may provide new avenues for isolating novel tumor suppressor genes.
The IL-6 Signal Transducer, gp130: an Pncostatin M Receptor and Affinity Converter for the LIF Receptor (1992)

Leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) are multifunctional cytokines with many similar activities. LIF is structurally and functionally related to another cytokine, Oncostatin M (OSM), that binds to the high-affinity LIF receptor but not to the low-affinity LIF receptor. A complementary DNA was isolated that encodes the high-affinity converting subunit of the LIF receptor. The converter conferred high-affinity binding of both LIF and OSM when expressed with the low-affinity LIF receptor and is identical to the signal transducing subunit of the IL-6 receptor, gp130. The gp130 subunit alone confers low-affinity binding of OSM when expressed in COS-7 cells. This receptor system resembles the high-affinity receptors for granulocyte-macrophage colony-stimulating factor, IL-3, and IL-5, which share a common subunit.
Crosswell electromagnetic tomography; system design considerations and field results (1995)

Abstract Electrical conductivity is an important petroleum reservoir parameter because of its sensitivity to porosity, pore fluid type, and saturation. Although induction logs are widely used to obtain the conductivity near boreholes, the poor resolution offered by surface-based electrical and electromagnetic (EM) field systems has thus far limited obtaining this information in the region between boreholes. Low-frequency crosswell EM offers the promise of providing subsurface conductivity information at a much higher resolution than was previously possible. Researchers at Lawrence Livermore National Lab (LLNL) and Lawrence Berkeley Laboratories (LBL), together with an industrial consortium, recently began a program to conduct low-frequency crosswell EM surveys and develop suitable inversion techniques for interpreting the data.In developing the field instrumentation we used off-the-shelf components whenever possible, but custom-designed induction coil transmitters and receivers were built for the field experiments. The assembled field system has adequate power for moderate to high-resolution imaging, using boreholes spaced up to 500 m apart. The initial field experiment was undertaken in flat lying terrain at the British Petroleum test site in Devine, Texas. Using wells spaced 100 m apart, we collected a complete crosswell EM data set encompassing a 30 m thick, 10 ohm-m limestone layer at a depth of 600 m. The resulting profiles were repeatable to within 1% and showed an excellent sensitivity to the layered structure, closely matching the borehole induction resisitivity log. At the UC Richmond field station, crosswell EM measurements were made to track an injected slug of salt water. Conductivity images of data collected before and after injection showed a clear anomaly as a result of the salt water plume and indicated that the plume had migrated in a northerly direction from the injection borehole.
Multidisciplinary team working: Collaboration and conflict (2006)

The aim of this paper is to report on findings identifying some of the difficulties encountered by the multidisciplinary team in the development and implementation of a care pathway for patients diagnosed with schizophrenia. Policy direction has shifted towards greater team working and blurring of professional boundaries. Moreover, there is greater need to deliver care according to set standards and for patients to reach particular outcomes of care. Care pathways are relatively new for psychiatry and will potentially uncover tensions within the team. Data were collected by participant observation and semistructured interviews over a period of 12 months on an acute psychiatric unit. The care team developed the care pathway and the process of development and implementation was observed through action research. Cross-sectional indexing was used to analyse the data, and themes were developed using interview and observational data collection methods. Clinicians argued strongly for clear role boundaries but also defended their perceived control over health care from other professions. The findings indicate that designing a care pathway for people with schizophrenia may produce conflicting perceptions from the team. Conflict may arise through professions being unwilling to accept plurality over roles, which may hinder progress in meeting the needs of patients. The findings also counter the impression that care pathways can be implemented with little impact on the team.
Prox1 Is Required for Granule Cell Maturation and Intermediate Progenitor Maintenance During Brain Neurogenesis (2010)

The dentate gyrus has an important role in learning and memory, and adult neurogenesis in the subgranular zone of the dentate gyrus may play a role in the acquisition of new memories. The homeobox gene Prox1 is expressed in the dentate gyrus during embryonic development and adult neurogenesis. Here we show that Prox1 is necessary for the maturation of granule cells in the dentate gyrus during development and for the maintenance of intermediate progenitors during adult neurogenesis. We also demonstrate that Prox1-expressing intermediate progenitors are required for adult neural stem cell self-maintenance in the subgranular zone; thus, we have identified a previously unknown non-cell autonomous regulatory feedback mechanism that controls adult neurogenesis in this region of the mammalian brain. Finally, we show that the ectopic expression of Prox1 induces premature differentiation of neural stem cells.
Spatial control of the GEN1 Holliday junction resolvase ensures genome stability (2014)

Holliday junction (HJ) resolvases are necessary for the processing of persistent recombination intermediates before cell division. Their actions, however, need to be restricted to the late stages of the cell cycle to avoid the inappropriate cleavage of replication intermediates. Control of the yeast HJ resolvase, Yen1, involves phosphorylation changes that modulate its catalytic activity and nuclear import. Here, we show that GEN1, the human ortholog of Yen1, is regulated by a different mechanism that is independent of phosphorylation. GEN1 is controlled exclusively by nuclear exclusion, driven by a nuclear export signal (NES) that restricts GEN1 actions to mitosis when the nuclear membrane breaks down. Construction of a nuclear-localized version of GEN1 revealed that its premature actions partially suppress phenotypes associated with loss of BLM and MUS81, but cause elevated crossover formation. The spatial control of GEN1 therefore contributes to genome stability, by avoiding competition with non-crossover promoting repair pathways.
Metabolizable and Non-Metabolizable Sugars Activate Different Signal Transduction Pathways in Tomato (2002)

To gain insight into the regulatory mechanisms of sugar signaling in plants, the effect of derivatives of the transport sugar sucrose (Suc), the Suc isomers palatinose and turanose, and the Suc analog fluoro-Suc were tested. Photo-autotrophic suspension culture cells of tomato (Lycopersicon peruvianum) were used to study their effect on the regulation of marker genes of source and sink metabolism, photosynthesis, and the activation of mitogen-activated protein kinases (MAPKs). Suc and glucose (Glc) resulted in reverse regulation of source and sink metabolism. Whereas the mRNA level of extracellular invertase (Lin6) was induced, the transcript level of small subunit of ribulose bisphosphate carboxylase (RbcS) was repressed. In contrast, turanose, palatinose, and fluoro-Suc only rapidly induced Lin6 mRNA level, whereas the transcript level of RbcS was not affected. The differential effect of the metabolizable and non-metabolizable sugars on RbcS mRNA regulation was reflected by the fact that only Suc and Glc inhibited photosynthesis and chlorophyll fluorescence. The activation of different signal transduction pathways by sugars was further supported by the analysis of the activation of MAPKs. MAPK activity was found to be strongly activated by turanose, palatinose, and fluoro-Suc, but not by Suc and Glc. To analyze the role of sugars in relation to pathogen perception, an elicitor preparation of Fusarium oxysporum lycopersici was used. The strong activation of MAPKs and the fast and transient induction of Lin6 expresssion by the fungal elicitor resembles the effect of turanose, palatinose, and fluoro-Suc and indicates that non-metabolizable sugars are sensed as stress-related stimuli.
Precise Equilibrium Constants from Spectrophotometric Data:  BrCl in Br2/Cl2 Gas Mixtures (2003)

The equilibrium constant for the reaction, Br2(g) + Cl2(g) ⇄ BrCl(g), is estimated using the classic spectrophotometric method with precise data and a multispectrum fitting approach. Analysis of spectra for 18 Cl2:Br2 mixing ratios yields K° = 9.1 at 22 °C, with a nominal statistical error (1 σ) of 0.04. This error translates into a remarkable precision of 0.4 cm-1 in the dissociation energy of BrCl, easily beating that for the current best spectroscopic estimate (±5 cm-1). However, a sensitivity analysis shows that K° is susceptible to small systematic errors and minor changes in the least-squares fit model, leading to a more conservative estimate of 2% error. The derived K° is consistent with statistical mechanical estimates that employ the current value for the BrCl dissociation energy, but it differs considerably from some recently measured and used values, which range from 6.4 to 10.4. The revised estimate of the BrCl dissociation energy is 𝒟e = 18 248 ± 2 cm-1.
Diagnosis and Initial Management of Musculoskeletal Coccidioidomycosis in Children (2014)

IV (case series).
Neuron Number in the Entorhinal Cortex and CA1 in Preclinical Alzheimer Disease (2001)

There is little or no neuronal loss in aging or preclinical AD but substantial loss in very mild AD. The findings indicate that AD results in clinical deficits only when it produces significant neuronal loss.