gebhart/patrepeval huggingface dataset:
NO-mediated cytoprotection: Instant adaptation to oxidative stress in bacteria (2005)

Numerous sophisticated systems have been described that protect bacteria from increased levels of reactive oxygen species. Although indispensable during prolonged oxidative stress, these response systems depend on newly synthesized proteins, and are hence both time and energy consuming. Here, we describe an "express" cytoprotective system in Bacillus subtilis which depends on nitric oxide (NO). We show that NO immediately protects bacterial cells from reactive oxygen species by two independent mechanisms. NO transiently suppresses the enzymatic reduction of free cysteine that fuels the damaging Fenton reaction. In addition, NO directly reactivates catalase, a major antioxidant enzyme that has been inhibited in vivo by endogenous cysteine. Our data also reveal a critical role for bacterial NO-synthase in adaptation to oxidative stress associated with fast metabolic changes, and suggest a possible role for NO in defending pathogens against immune oxidative attack.
N-terminal galanin-(1-16) fragment is an agonist at the hippocampal galanin receptor. (1989)

The galanin N-terminal fragment [galanin-(1-16)] has been prepared by solid-phase synthesis and by enzymic cleavage of galanin by endoproteinase Asp-N. This peptide fragment displaced 125I-labeled galanin in receptor autoradiography experiments on rat forebrain and spinal cord and in equilibrium binding experiments from high-affinity binding sites in the ventral hippocampus with an IC50 of approximately 3 nM. In tissue slices of the same brain area, galanin-(1-16), similarly to galanin, inhibited the muscarinic agonist-stimulated breakdown of inositol phospholipids. Upon intracerebroventricular administration, galanin-(1-16) (10 micrograms/15 microliters) also inhibited the scopolamine (0.3 mg/kg, s.c.)-evoked release of acetylcholine, as studied in vivo by microdialysis. Substitution of [L-Trp2] for [D-Trp2] resulted in a 500-fold loss in affinity as compared with galanin-(1-16). It is concluded that, in the ventral hippocampus, the N-terminal galanin fragment [galanin-(1-16)] is recognized by the galanin receptors controlling acetylcholine release and muscarinic agonist-stimulated inositol phospholipid breakdown as a high-affinity agonist and that amino acid residue [Trp2] plays an important role in the receptor-ligand interactions.
Profile of energy metabolism in a murine hybridoma: Glucose and glutamine utilization (1994)

The antibody-secreting murine hybridoma, CC9C10, was grown in batch culture in a medium containing 20 mM glucose and 2 mM glutamine. After 2 days of exponential growth, the glutamine content of the medium was completely depleted, whereas the glucose content was reduced to 60% of the original concentration. The glucose and glutamine metabolism was analyzed at midexponential phase by use of radioactively labelled substrates. Glycolysis accounted for the metabolism of most of the glucose utilized (> 96%) with flux through the pentose phosphate pathway (3.6%) and the TCA cycle (0.6%) accounting for the remainder. Glutamine was partially oxidised via glutaminolysis to alanine (55%), aspartate (3%), glutamate (4%), lactate (9%), and CO2 (22%). Calculation of the theoretical ATP production from these pathways indicated that glucose could provide 59% and glutamine 41% of the energy requirement of the cells.
Genetic and Functional Analysis of Full-Length Human Immunodeficiency Virus Type 1 env Genes Derived from Brain and Blood of Patients with AIDS (2003)

The genetic evolution of human immunodeficiency virus type 1 (HIV-1) in the brain is distinct from that in lymphoid tissues, indicating tissue-specific compartmentalization of the virus. Few primary HIV-1 envelope glycoproteins (Envs) from uncultured brain tissues have been biologically well characterized. In this study, we analyzed 37 full-length env genes from uncultured brain biopsy and blood samples from four patients with AIDS. Phylogenetic analysis of intrapatient sequence sets showed distinct clustering of brain relative to blood env sequences. However, no brain-specific signature sequence was identified. Furthermore, there was no significant difference in the number or positions of N-linked glycosylation sites between brain and blood env sequences. The patterns of coreceptor usage were heterogeneous, with no clear distinction between brain and blood env clones. Nine Envs used CCR5 as a coreceptor, one used CXCR4, and two used both CCR5 and CXCR4 in cell-to-cell fusion assays. Eight Envs could also use CCR3, CCR8, GPR15, STRL33, Apj, and/or GPR1, but these coreceptors did not play a major role in virus entry into microglia. Recognition of epitopes by the 2F5, T30, AG10H9, F105, 17b, and C11 monoclonal antibodies varied among env clones, reflecting genetic and conformational heterogeneity. Envs from two patients contained 28 to 32 N-glycosylation sites in gp120, compared to around 25 in lab strains and well-characterized primary isolates. These results suggest that HIV-1 Envs in brain cannot be distinguished from those in blood on the basis of coreceptor usage or the number or positions of N-glycosylation sites, indicating that other properties underlie neurotropism. The study also demonstrates characteristics of primary HIV-1 Envs from uncultured tissues and implies that Env variants that are glycosylated more extensively than lab strains and well-characterized primary isolates should be considered during development of vaccines and neutralizing antibodies.
Real-time observation of single molecules by confocal fluorescence microscopy (1995)

The ability to detect, identify, and manipulate individual molecules offer exciting possibilities in many fields, including chemical analysis, materials research, and the biological sciences. A particularly powerful approach is to combine the exquisite sensitivity of laser-induced fluorescence and the spatial localization and imaging capabilities of diffraction-limited or near-field optical microscopes. Unlike scanning tunneling microscopy (STM) and atomic force microscopy (AFM), which lack molecular specificity, optical spectroscopy and microscopy techniques can be used for real-time monitoring and molecular identification at nanometer dimensions or in ultrasmall volumes. We report the use of confocal fluorescence microscopy coupled with a diffraction-limit laser beam and a high-efficiency photodiode for real-time detection of single fluorescent molecules in solution at room temperature. Rigler and Eigen have also demonstrated single-molecule detection with a confocal microscope and fluorescence correlation spectroscopy. The probe (or sampling) volume is effectively an elongated cylinder, with its radius being determined by optical diffraction and length by spherical aberration.
Antimicrobial susceptibility patterns of enterococci in intensive care units in Sweden evaluated by different MIC breakpoint systems (2001)

Three hundred and twenty-two (322) clinical isolates were collected from patients admitted to intensive care units (ICUs) at eight Swedish hospitals between December 1996 and December 1998. Of the isolates, 244 (76%) were Enterococcus faecalis, 74 (23%) were Enterococcus faecium and four (1%) were other Enterococcus spp. MICs of ampicillin, imipenem, meropenem, piperacillin/tazobactam, ciprofloxacin, trovafloxacin, clinafloxacin, gentamicin, streptomycin, vancomycin, teicoplanin, quinupristin/dalfopristin, linezolid and evernimicin were determined by Etest. Susceptible and resistant isolates were defined according to the species-related MIC breakpoints of the British Society for Antimicrobial Chemotherapy (BSAC), the National Committee for Clinical Laboratory Standards (NCCLS) and the Swedish Reference Group for Antibiotics (SRGA). Tentative breakpoints were applied for new/experimental antibiotics. Multidrug resistance among enterococci in ICUs is not uncommon in Sweden, particularly among E. faecium, and includes ampicillin resistance and concomitant resistance to fluoroquinolones. Almost 20% of E. faecalis isolates showed high-level resistance to gentamicin and concomitant resistance to fluoroquinolones. Vancomycin-resistant enterococci were only found sporadically. Among the new antimicrobial agents, linezolid and evernimicin showed the best activity against all enterococcal isolates. There was good concordance between the BSAC, NCCLS and SRGA breakpoints in detecting resistance. When applying the SRGA breakpoints for susceptibility, isolates were more frequently interpreted as intermediate. This might indicate earlier detection of emerging resistance using the SRGA breakpoint when the native population is considered susceptible, but with the risk that isolates belonging to the native susceptible population will be incorrectly interpreted as intermediate.
Automated Insufflation of Carbon Dioxide for MDCT Colonography: Distension and Patient Experience Compared with Manual Insufflation (2005)

Automated carbon dioxide insufflation significantly improves colonic distention compared with manual insufflation. Benefit is greatest in the left colon, particularly when the patient is supine. Patient acceptance is similar to that for manual insufflation.
The Effects of Hearing Aid Directional Microphone and Noise Reduction Processing on Listening Effort in Older Adults with Hearing Loss (2015)

Directional microphone processing effectively reduced the cognitive load of listening to speech in background noise. This is significant because it is likely that listeners with hearing impairment will frequently encounter noisy speech in their everyday communications.
Association with the SRC Family Tyrosyl Kinase LYN Triggers a Conformational Change in the Catalytic Region of Human cAMP-specific Phosphodiesterase HSPDE4A4B (1999)

The cAMP-specific phosphodiesterase (PDE) HSPDE 4A4B(pde46) selectively bound SH3 domains of SRC family tyrosyl kinases. Such an interaction profoundly changed the inhibition of PDE4 activity caused by the PDE4-selective inhibitor rolipram and mimicked the enhanced rolipram inhibition seen for particulate, compared with cytosolic pde46 expressed in COS7 cells. Particulate pde46 co-localized with LYN kinase in COS7 cells. The unique N-terminal and LR2 regions of pde46 contained the sites for SH3 binding. Altered rolipram inhibition was triggered by SH3 domain interaction with the LR2 region. Purified LYN SH3 and human PDE4A LR2 could be co-immunoprecipitated, indicating a direct interaction. Protein kinase A-phosphorylated pde46 remained able to bind LYN SH3. pde46 was found to be associated with SRC kinase in the cytosol of COS1 cells, leading to aberrant kinetics of rolipram inhibition. It is suggested that pde46 may be associated with SRC family tyrosyl kinases in intact cells and that the ensuing SH3 domain interaction with the LR2 region of pde46 alters the conformation of the PDE catalytic unit, as detected by altered rolipram inhibition. Interaction between pde46 and SRC family tyrosyl kinases highlights a potentially novel regulatory system and point of signaling system cross-talk.
G120R, a Human Growth Hormone Antagonist, Shows Zinc-dependent Agonist and Antagonist Activity on Nb2 Cells (1995)

Substitution of arginine for glycine at position 120 in native 22-kDa human growth hormone (hGH) results in an analogue, G120R, which is unable to dimerize the GH receptor and is widely used to probe the molecular mechanism of action of hGH. When acting on human GH receptors, G120R antagonizes several biological effects of hGH, but is itself inactive as an agonist. It has been reported that this mutant also antagonizes hGH activation of the rat or human prolactin (PRL) receptor in cell-based assays, with no agonist activity. We have now tested this mutant in a sensitive MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)-ESTA (eluted stain assay) bioassay using rat PRL receptors in the Nb2 cell line. We confirm that G120R acts as an efficient antagonist of native hGH, but show that it can also act as an agonist to generate intracellular signals leading to metabolic activation and proliferation of Nb2 cells. We have demonstrated an unusual sensitivity to the presence of zinc (Zn2+). In the absence of added Zn2+, G120R shows weak but full agonist activity in the bioassay, and this can be blocked by co-incubation with recombinant hGH-binding protein. G120R can therefore be utilized to discriminate between the molecular mechanisms of hGH interactions with its somatogenic and lactogenic receptors. Future studies with G120R in the rat may need to take account of its significant agonist effects on PRL receptors.
TRANSCRIPTION BY RNA POLYMERASE III (1988)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Distinct Roles of Ephrin-B2 Forward and EphB4 Reverse Signaling in Endothelial Cells (2003)

Ephrin-B2 forward signaling and EphB4 reverse signaling differentially affect cell adhesion and migration between arterial and venous endothelial cells.
Intraoral 3D scanner (2007)

Here a new set-up of a 3D-scanning system for CAD/CAM in dental industry is proposed. The system is designed for direct scanning of the dental preparations within the mouth. The measuring process is based on phase correlation technique in combination with fast fringe projection in a stereo arrangement. The novelty in the approach is characterized by the following features: A phase correlation between the phase values of the images of two cameras is used for the co-ordinate calculation. This works contrary to the usage of only phase values (phasogrammetry) or classical triangulation (phase values and camera image co-ordinate values) for the determination of the co-ordinates. The main advantage of the method is that the absolute value of the phase at each point does not directly determine the coordinate. Thus errors in the determination of the co-ordinates are prevented. Furthermore, using the epipolar geometry of the stereo-like arrangement the phase unwrapping problem of fringe analysis can be solved. The endoscope like measurement system contains one projection and two camera channels for illumination and observation of the object, respectively. The new system has a measurement field of nearly 25mm &times; 15mm. The user can measure two or three teeth at one time. So the system can by used for scanning of single tooth up to bridges preparations. In the paper the first realization of the intraoral scanner is described.
3 Year simvastatin treatment and lens nuclear back scattering (2000)

Although no significant difference was found between the simvastatin and placebo groups, the currently available data are insufficient for exclusion of the possibility that taking simvastatin during a 3 year period increases nuclear back scattering. However, a possible minor increase of nuclear back scattering is clinically irrelevant considering known beneficial effects of simvastatin on coronary heart disease.
Studies of the Expression of Epidermal Growth Factor Receptor in Human Renal Cell Carcinoma: A Comparison of Immunohistochemical Method versus Ligand Binding Assay (1997)

We evaluated the expression of epidermal growth factor receptor (EGFR) in 21 patients with renal cell carcinoma (RCC) by immunohistochemical staining of frozen tumor sections using a monoclonal antibody for EGFR and by a ligand binding method using radiolabeled epidermal growth factor. EGFR was detected in 16 of the 21 cases by ligand binding, while 11 of the 21 cases were detected by immunohistochemical staining. A significant correlation was observed between the two methods in detecting EGFR (p < 0.0001). EGFR was detected by the ligand binding method in all patients who died of RCC. Four cases that were graded as EGFR-negative on immunohistochemistry died of RCC. Observations suggest the ligand binding method was more sensitive than the immunohistochemical method in detecting EGFR and forecasting patient survival.
Qualitative and Quantitative DNA and RNA Analysis by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (2006)

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) gives extremely precise reading of mass-to-charge ratios (two analytes differ by 1 Da can be distinguished) and provides high sensitivity (less than 1 fmole of a DNA oligonucleotide can be detected), allowing DNA quantifications with single base specificity and single DNA molecule sensitivity (coupled with polymerase chain reaction [PCR]). To quantify a DNA sequence of interest, a competitive synthetic (60-80 bases) oligonucleotide standard with an artificial single base mutation in the middle is introduced, and these two virtually identical sequences are co-amplified by PCR. A third primer (extension primer) is designed to anneal to the region immediately upstream of the mutation site. Depending on the specific mutation introduced and the ddNTP/dNTP mixtures used, either one or two bases are added to the extension primer to produce two extension products from the two templates. Last, the two extension products are detected and quantified by high-throughput MALDI-TOF MS. In addition, with an improved primer extension method called single allele base extension reaction (SABER), rare mutant DNA can be robustly detected even when normal DNA is present at 50-fold or more than the DNA mutants.
BAFF, a Novel Ligand of the Tumor Necrosis Factor Family, Stimulates B Cell Growth (1999)

Members of the tumor necrosis factor (TNF) family induce pleiotropic biological responses, including cell growth, differentiation, and even death. Here we describe a novel member of the TNF family, designated BAFF (for B cell activating factor belonging to the TNF family), which is expressed by T cells and dendritic cells. Human BAFF was mapped to chromosome 13q32-34. Membrane-bound BAFF was processed and secreted through the action of a protease whose specificity matches that of the furin family of proprotein convertases. The expression of BAFF receptor appeared to be restricted to B cells. Both membrane-bound and soluble BAFF induced proliferation of anti-immunoglobulin M-stimulated peripheral blood B lymphocytes. Moreover, increased amounts of immunoglobulins were found in supernatants of germinal center-like B cells costimulated with BAFF. These results suggest that BAFF plays an important role as costimulator of B cell proliferation and function.
Induction of interleukin-8 synthesis from monocytes by human C5a anaphylatoxin. (1994)

Interleukin-8 (IL-8) is an important mediator of inflammation and has been shown to be a potent chemotactic/cell activator for polymorphonuclear neutrophils (PMNs). T lymphocytes, and basophils. Cellular sources of IL-8 include monocytes, PMNs, endothelial cells, epithelial cells, and keratinocytes when stimulated by factors such as lipopolysaccharide, IL-1, and tumor necrosis factor-alpha. This report demonstrates that C5a, in addition to being a direct mediator of inflammation, can induce both IL-8 synthesis and high levels of release from monocytes. Natural human C5a and a synthetic C-terminal analogue peptide of C5a each induced IL-8 synthesis and release from CD14+ human peripheral blood mononuclear cells. Antigenic reactivity based on enzyme-linked immunosorbent assay gave evidence that IL-8 was present in the culture supernatants of stimulated peripheral blood mononuclear cells. Proof that supernatant levels of IL-8 attain biologically significant quantities was provided by human PMN chemotaxis assays. The quantity of IL-8 recovered from C5a-activated monocytes in peripheral blood mononuclear cells is up to 1,000-fold greater than that released from comparable numbers of PMNs under similar conditions. Therefore, IL-8 released from C5a-activated monocytes may play a significant role in expanding and prolonging cellular infiltration and activation at sites of infection, inflammation, or tissue injury. This observation suggests an important humoral amplification loop for inflammatory events involving both complement activation and cytokine release.
In Vivo Biodistribution of Dendrimers and Dendrimer Nanocomposites — Implications for Cancer Imaging and Therapy (2005)

Our results indicate that the surface chemistry, composition, and 3-D structure of nanoparticles are critical in determining their in vivo biodistribution, and therefore the efficacy of nanodevice imaging and therapies. We demonstrate that gold/dendrimer nanocomposites in vivo, present biodistribution characteristics different from PAMAM dendrimers in a B16 mouse tumor model system. We review important chemical and biologic uses of these nanodevices and discuss the potential of nanocomposite devices to greatly improve cancer imaging and therapy, in particular radiation therapy. We also discuss major issues confronting the use of nanoparticles in the near future, with consideration of toxicity analysis and whether biodegradable devices are needed or even desirable.
Abstract 857: Development of a Bruton's tyrosine kinase (Btk) inhibitor - ONO-WG-307, a potential treatment for B-cell malignancies (2012)

Abstract Purpose: Signals from B cell receptors (BCR) play a central role in signal transduction pathways regulating survival, activation, proliferation, and differentiation of B-lineage lymphoid cells. BCR signaling is implicated in the survival of malignant B cells and recent studies indicate that targeting Btk, an essential component of the BCR pathway, may be effective in the treatment of B-cell lymphoma. ONO-WG-307 is a highly potent and selective Btk inhibitor with an IC50 in the sub-nmol/L range. We evaluated the inhibitory effect of ONO-WG-307 alone and in combination with the chimeric type I anti-CD20 antibody rituximab, using in vitro tumor growth assays and mouse xenograft models. Methods: Two types of tumor cell lines (follicular lymphoma (FL) and activated B-cell-like (ABC) sub-type of diffuse large B cell lymphoma (DLBCL)) wereplated on to micro-titration plates (at doses up to 200 umol/L for ONO-WG-307 and 100 ug/mL for rituximab) for in vitro cytotoxic assays. The same cells were also implanted subcutaneously (SC) into female SCID mice to explore ONO-WG-307 anti-tumor activity in vivo (orally at doses up to 50 mg/kg, bid for ONO-WG-307 and intraperitoneally at doses up to 10 mg/kg, q7d). The IC50 of the in vitro cytotoxic activity was determined using a MTS assay 72 and 96 hours after incubation. Anti-tumor activity was defined as the ratio of the median tumor volume of treatment groups versus control group. The determination of combination index (CI) was calculated by the median-effect method. The CI was used to express synergism (&amp;lt;1), additivity (=1) or antagonism (&amp;gt;1). Results: In the MTS assay, ABC-DLBCL cells were much more sensitive to ONO-WG-307 given as single agent compared with FL cell lines, however, the activity of rituximab single agent had no impact on ABC-DLBCL cell lines in contrast to its inhibitory activity against FL cell lines. When ONO-WG-307 was combined with rituximab, a moderate antagonism was observed in vitro on FL cell lines. In an ABC-DLBCL xenograft model, treatment with single agent ONO-WG-307 resulted in a dose-dependent inhibition of tumor growth and also showed moderate anti-tumor activity in a FL xenograft model. Conclusion: ONO-WG-307 is a highly potent and selective oral Btk inhibitor with evidence of efficacy in both the ABC-DLBCL and the FL cell lines and in xenograft models. These preliminary results suggest that ONO-WG-307 may be an effective therapy in the treatment of B-cell malignancies. To determine whether combination of ONO-WG-307 and rituximab is more efficacious, additional in vivo combination work is underway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 857. doi:1538-7445.AM2012-857