gebhart/patrepeval huggingface dataset:
Flow cytometric detection of β‐globin mRNA in murine haemopoietic tissues using fluorescent in situ hybridization (1990)

The novel method for flow cytometric detection of cellular RNA species in suspended cells by fluorescent in situ hybridization (FC-FISH) was applied in the evaluation of beta-globin expression in murine haemopoietic tissues. Normal murine bone marrow cells and regenerating bone marrow cells obtained after lethal irradiation and bone marrow transplantation as well as murine 15 d fetal liver were examined. Furthermore, spleens and bone marrow of phenylhydrazine-induced anaemic mice were studied. Biotinylated sense- and antisense single strand RNA probes, obtained by transcription of a 510 nucleotides murine beta-globin cDNA sequence subcloned into the pGEM1 plasmid were used as hybridization probes. For detection of the hybrids formed, avidin-FITC was used. Only the antisense beta-globin probe gave strongly positive fluorescence signals in a defined population of cells in each of the tissues examined, whereas the sense probe did not give signals higher than control samples. Melting characteristics of the hybrids showed the specificity of the in situ hybridization reaction. Forward light scatter distributions, reflecting cell size of the positive cells were as expected from erythroid cells. Within the erythrocyte subpopulation both beta-globin-negative and -positive cells were detected. The percentages of positive cells determined flow cytometrically correlated with the percentages observed in May-Grünwald/Giemsa stained preparations. Differences observed in fluorescence intensity between positive cells of different organs were no larger than about a factor of two, indicating a rather constant beta-globin mRNA content over the entire differentiation range. An exception was 15 d fetal liver, which was shown biochemically to contain about eight times more beta-globin RNA and which had a 2.4 times higher fluorescence intensity. We estimate that the sensitivity of the present method is such that as little as 500 copies per cell of a specific mRNA of 1 kb length would be detectable.
Distinct Strategies Are Required to Suppress Antigen-specific Responses to Genetically Modified Keratinocytes and Fibroblasts (2011)

Keratinocytes and fibroblasts are potential targets of gene/cell therapy for genodermatoses. Immune elimination of genetically modified cells, however, presents a major impediment to effective therapy. Using ex vivo approaches to gene transfer, we have previously shown that expression of an antigen by either cell type in skin induces immune rejection of transplanted cells, although the nature of immune responses induced by these two cell types are distinct. In this study, we explore the efficacy of local immunosuppressive strategies to divert destructive immune responses from genetically modified fibroblast and keratinocytes. Expression of CTLA4Ig and, to a lesser extent, PDL1, by antigenic fibroblasts protected them from immune rejection resulting in long-term graft survival (>18 weeks). Similar treatment was not effective for antigenic keratinocytes. Long-term protection of transgenic keratinocytes was achieved through transient blockade of CD40/CD154 interactions during the first 2 weeks of cell transplantation. Although neither of these strategies induced antigen-specific tolerance, they were sufficient to prevent rejection of genetically modified cells. These results indicate that different strategies are required to protect antigenic cell types even within the same tissue. Moreover, induction of antigen-specific tolerance is not a necessary requirement for long-term survival of genetically modified skin cells.
An Orange Fluorescent Protein with a Large Stokes Shift for Single-Excitation Multicolor FCCS and FRET Imaging (2012)

Multicolor imaging based on genetically encoded fluorescent proteins (FPs) is a powerful approach to study several dynamic processes in a live cell. We report a monomeric orange FP with a large Stokes shift (LSS), called LSSmOrange (excitation/emission at 437/572 nm), which fills up an existing spectral gap between the green-yellow and red LSSFPs. Brightness of LSSmOrange is five-fold larger than that of the brightest red LSSFP and similar to the green-yellow LSSFPs. LSSmOrange allows numerous multicolor applications using a single-excitation wavelength that was not possible before. Using LSSmOrange we developed four-color single-laser fluorescence cross-correlation spectroscopy, solely based on FPs. The quadruple cross-correlation combined with photon counting histogram techniques allowed quantitative single-molecule analysis of particles labeled with four FPs. LSSmOrange was further applied to simultaneously image two Förster resonance energy transfer pairs, one of which is the commonly used CFP-YFP pair, with a single-excitation laser line. The combination of LSSmOrange-mKate2 and CFP-YFP biosensors enabled imaging of apoptotic activity and calcium fluctuations in real time. The LSSmOrange mutagenesis, low-temperature, and isotope effect studies revealed a proton relay for the excited-state proton transfer responsible for the LSS phenotype.
Meningitis Due to Penicillin-Resistant Streptococcus pneumoniae in Adults (1990)

A 33-year-old woman with quiescent systemic lupus erythematosus developed meningitis due to a penicillin-resistant strain of Streptococcus pneumoniae. After an initial failure of penicillin therapy, the patient responded to cefotaxime. The meningitis was complicated by total neurosensory hearing loss. Howell-Jolly bodies noted on peripheral blood smear led to a radionuclide spleen scan, which documented functional asplenia. This woman is the second patient in the United States with meningitis caused by a strain of S. pneumoniae moderately resistant to penicillin G (minimal inhibitory concentration, 1.0 microgram/mL). The resistant isolate displayed resistance to penicillin that was not of enzymatic origin but rather was due to an alteration of penicillin-binding proteins. This experience illustrates the importance of testing the in vitro susceptibility of the pneumococcus to penicillin G.
Mitochondria as Targets for Nitric Oxide–Induced Protection During Simulated Ischemia and Reoxygenation in Isolated Neonatal Cardiomyocytes (2001)

Pretreatment with an NO donor induces a modest, sustained mitochondrial depolarization and protects cardiomyocytes from sI/R injury. The demonstrated reduction in mitochondrial Ca(2+) uptake possibly reduces cytosolic Ca(2+) overload, providing a likely mechanism for NO-induced protection.
Occurrence of N-Nonsubstituted Glucosamine Residues in Peptidoglycan of Lysozyme-resistant Cell Walls from Bacillus cereus (1972)

The occurrence of N-nonsubstituted glucosamine residues in Bacillus cereus cell wall peptidoglycan is demonstrated and accounts for resistance of the cell walls to lysozyme. Lysozyme-resistant cell walls isolated from three strains of B.cereus indicate unusually small free muramic acid contents as analyzed in an autoanalyzer after acid hydrolysis. Over 80% of the total muramic acid was recovered from the acid hydrolysates of the peptidoglycan as disaccharides, which were identified as glucosaminyl-β(1→4)-muramic acid and glucosaminyl-β(1→4)-muramic acid 6-phosphate. Analysis by dinitrophenylation techniques revealed that, in the peptidoglycan, over 70% of glucosamine residues have free amino groups. These cell walls, which remain resistant to lysozyme after removal of O-acetyl groups, polysaccharide components, and peptide components, are converted into a lysozyme-sensitive form by means of N-acetylation with acetic anhydride.
Metabolic engineering of a synergistic pathway for n-butanol production in Saccharomyces cerevisiae (2016)

n-Butanol has several favourable properties as an advanced fuel or a platform chemical. Bio-based production of n-butanol is becoming increasingly important for sustainable chemical industry. Synthesis of n-butanol can be achieved via more than one metabolic pathway. Here we report the metabolic engineering of Saccharomyces cerevisiae to produce n-butanol through a synergistic pathway: the endogenous threonine pathway and the introduced citramalate pathway. Firstly, we characterized and optimized the endogenous threonine pathway; then, a citramalate synthase (CimA) mediated pathway was introduced to construct the synergistic pathway; next, the synergistic pathway was optimized by additional overexpression of relevant genes identified previously; meanwhile, the n-butanol production was also improved by overexpression of keto-acid decarboxylases (KDC) and alcohol dehydrogenase (ADH). After combining these strategies with co-expression of LEU1 (two copies), LEU4, LEU2 (two copies), LEU5, CimA, NFS1, ADH7 and ARO10(*), we achieved an n-butanol production of 835 mg/L in the final engineered strain, which is almost 7-fold increase compared to the initial strain. Furthermore, the production showed a 3-fold of the highest titer ever reported in yeast. Therefore, the engineered yeast strain represents a promising alternative platform for n-butanol production.
A Fluorescent, Genetically-Encoded Voltage Probe Capable of Resolving Action Potentials (2012)

There is a pressing need in neuroscience for genetically-encoded, fluorescent voltage probes that can be targeted to specific neurons and circuits to allow study of neural activity using fluorescent imaging. We created 90 constructs in which the voltage sensing portion (S1-S4) of Ciona intestinalis voltage sensitive phosphatase (CiVSP) was fused to circularly permuted eGFP. This led to ElectricPk, a probe that is an order of magnitude faster (taus ~1-2 ms) than any currently published fluorescent protein-based voltage probe. ElectricPk can follow the rise and fall of neuronal action potentials with a modest decrease in fluorescence intensity (~0.7% ΔF/F). The probe has a nearly linear fluorescence/membrane potential response to both hyperpolarizing and depolarizing steps. This is the first probe based on CiVSP that captures the rapid movements of the voltage sensor, suggesting that voltage probes designed with circularly permuted fluorescent proteins may have some advantages.
Cellulite: a review (2000)

Gynoid lipodystrophy (cellulite) is an extremely controversial topic. A lack of knowledge regarding specific aetiopathogenic factors, as well as the opportunism of some professionals and the media, has fuelled debate regarding the scientific basis of this condition. This article reviews the clinical, epidemiological, histopathological and therapeutic aspects of cellulite.
The decomposition of methyl hemiacetals of benzaldehyde in aqueous solution: a study of the effect of aromatic substitution (1999)

The acid-base catalysed decomposition of hydrates and hemiacetals of carbonyl compounds are classical examples of reactions where (slow) proton transfer is coupled with heavy atom reorganization, i.e., CO bond breaking and solvent reorganization. We have studied the influence of m- and p-substitution in the carbonyl electrophile on the kinetics of the acid and base catalysis of the decomposition of methyl hemiacetals of benzaldehyde. The experimental data are well described by three-dimensional More O'Ferrall - Jencks energy contour diagrams according to principles developed by Jencks (the BEMA HAPOTHLE). Thus, for acid catalysis, a Cordes cross-interaction coefficient p xy' = δρ/δpK a = 0.15 indicates the coupled nature of the rate-limiting step in a class e mechanism, similar to conclusions reached from systematic substitution in the nucleophile. Our more extensive set of data for base catalysis permits a more rigorous analysis according to the BEMA HAPOTHLE. The data are consistent with a class n mechanism as also suggested earlier on the basis of substitution in the nucleophile. A slight upward curvature observed in the Hammett plots for the various catalysts is described by the direct correlation parameter p y = -δρ/δσ = -0.11. This second derivative demonstrates the concerted nature of the CO bond cleavage and O-H formation in the transition state, which changes with changing substituent. A class n mechanism for base catalysis is also supported by the observation of a Cordes cross-interaction parameter p xy = -δρ/δpK a = -δβ/δσ = 0.03, which describes the experimentally observed decrease in Hammett ρ with increasing pK a of the catalyst. This change may be rationalized by the movement of a saddle point on a diagonal reaction coordinate in the energy contour diagram, as a resultant of shifts parallel and perpendicular to the coordinate, when the energy along one side of the diagram is changed. It is concluded that observed rate changes as a result of substitution in the electrophile are consistent with and present further confirmation of earlier suggested mechanisms of hemiacetal decomposition reactions.Key words: methyl hemiacetals of benzaldehydes, acid-base catalysed breakdown, Hammett plots, More O'Ferrall - Jencks diagrams.
Larynx carcinoma regulates tumor-associated macrophages through PLGF signaling (2015)

Cancer neovascularization plays an essential role in the metastasis of larynx carcinoma (LC). However, the underlying molecular mechanisms are not completely understood. Recently, we reported that placental growth factor (PLGF) regulates expression of matrix metalloproteinase 3 (MMP3) through ERK/MAPK signaling pathway in LC. Here, we show that MMP9 upregulated in LC, and appeared to be mainly produced by M2 macrophages (tumor-associated macrophages (TAM)). In a transwell co-culture system, PLGF secreted by LC cells triggered macrophage polarization to a TAM subtype that releases MMP9. Moreover, MMP9 was found to be activated in the PLGF-polarized TAM via transforming growth factor β (TGFβ) receptor signaling activation. Furthermore, PLGF in LC cells induced macrophage polarization in vivo, and significantly promoted the growth of LC. Thus, together with our previous work, our study highlights a pivotal role of cross-talk between TAM and LC in regulating the metastasis of LC.
Overexpression of active Syrian golden hamster prion protein PrPc as a glutathione S-transferase fusion in heterologous systems (1995)

This article describes a procedure which permits for the first time the isolation of the prion protein PrPc from the Syrian golden hamster in heterologous systems. Using a glutathione S-transferase (GST) fusion approach, milligram amounts of stable, soluble, and homogeneous GST::PrPc protein were obtained in Escherichia coli and with baculovirus-infected insect cells. Authentic PrPc was released from the immobilized fusion protein by direct cleavage with thrombin. GST::PrPc expressed in these two expression systems and also authentic PrPc released by thrombin cleavage were recognized by a polyclonal antibody directed against amino acid 95 to 110 of the golden hamster PrPc protein. GST::PrPc was not detected by a monoclonal antibody recognizing the region encompassing amino acids 138 to 152 of the human prion protein. The fusion protein was sensitive to proteinase K digestion, demonstrating that the cellular rather than the proteinase K-resistant scrapie isoform was produced.
Visual Cluster Analysis of Trajectory Data with Interactive Kohonen Maps (2009)

Visual-interactive cluster analysis provides valuable tools for effectively analyzing large and complex data sets. Owing to desirable properties and an inherent predisposition for visualization, the Kohonen Feature Map (or Self-Organizing Map or SOM) algorithm is among the most popular and widely used visual clustering techniques. However, the unsupervised nature of the algorithm may be disadvantageous in certain applications. Depending on initialization and data characteristics, cluster maps (cluster layouts) may emerge that do not comply with user preferences, expectations or the application context. Considering SOM-based analysis of trajectory data, we propose a comprehensive visual-interactive monitoring and control framework extending the basic SOM algorithm. The framework implements the general Visual Analytics idea to effectively combine automatic data analysis with human expert supervision. It provides simple, yet effective facilities for visually monitoring and interactively controlling the trajectory clustering process at arbitrary levels of detail. The approach allows the user to leverage existing domain knowledge and user preferences, arriving at improved cluster maps. We apply the framework on several trajectory clustering problems, demonstrating its potential in combining both unsupervised (machine) and supervised (human expert) processing, in producing appropriate cluster results.
Paneth Cell α-Defensins from Rhesus Macaque Small Intestine (2004)

Antimicrobial peptides are secreted by small intestinal Paneth cells as components of innate immunity. To investigate the role of alpha-defensins in enteric host defenses in nonhuman primates, alpha-defensin cDNAs were isolated, alpha-defensin peptides were purified from rhesus macaque small bowel, and the bactericidal activities of the peptides were measured. Six rhesus enteric alpha-defensin (RED) cDNAs, RED-1 to RED-6, were identified in a jejunum cDNA library; the deduced RED peptides exhibited extensive diversity relative to the primary structures of rhesus myeloid alpha-defensins. RED-4 was purified from monkey jejunum, and N-terminal peptide sequencing of putative RED-4 peptides identified two N termini, RTCYCRTGR. and TCYCRTGRC.; these corresponded to alternative N termini for the RED-4 molecules, as deduced from their molecular masses and RED cDNAs. In situ hybridization experiments localized RED mRNAs exclusively to small intestinal Paneth cells. Recombinant RED-1 to RED-4 were purified to homogeneity and shown to be microbicidal in the low micromolar range (</=10 micro g/ml) against gram-positive and gram-negative bacteria, with individual peptides exhibiting variable target cell specificities. Thus, compared to myeloid alpha-defensins from rhesus macaques, enteric alpha-defensin peptides are highly variable in both primary structure and activity. These studies should facilitate further analyses of the role of alpha-defensins in primate enteric immunity.
Centrally tinted contact lenses. A useful visual aid for patients with achromatopsia. (1995)

Achromatopsia (rod monochromacy) is a congenital color-vision defect of autosomal recessive inheritance due to severely abnormal or totally absent cone function. The disease is characterized by markedly reduced visual acuity, nystagmus, and, often, ametropia. Even under normal daylight conditions, these patients are extremely handicapped by glare because of a lack of rod inhibition by the abnormal or deficient cones. Light-absorbing glasses (absorption > 90%) can ameliorate this visual impairment to a certain extent but are sometimes not accepted by the patient since they are felt to disfigure the face. Especially during the first few years of school, this can lead to psychological problems. A special contact lens (Hydroflex, Wöhlk Company, Kiel) with a centrally tinted area (absorption 80%) that is slightly greater in diameter than the pupil under daylight conditions can correct ametropia and reduce light exposure and dazzle in a cosmetically much better way. Our first experience with this kind of visual aid in a 9-year-old girl suffering from incomplete achromatopsia is presented.
Protein kinase inhibitors from the urea class. (2002)

Protein kinase inhibitors hold great potential as novel therapies for cancer and inflammatory disorders. While bis-aryl ureas have been reported as kinase inhibitors as early as 1996, a number of publications and patent applications appeared in the literature during the past two years. Three urea-based kinase inhibitors are currently undergoing clinical trials. The present review summarizes available data, and provides an overview of the structure-activity relationships against a variety of kinase targets, including p38, Raf-1 and cyclin-dependent kinases.
Modified polyriboinosinic-polyribocytidylic acid, an immunological adjuvant (1976)

Stabilization of polyriboinosinic-polyribocytidylic acid against enzymatic hydrolysis by addition of poly-1-lysine and carboxymethylcellulose (PICLC) resulted in a compound with marked adjuvanticity. The primary antibody response of rhesus monkeys to formalin-inactivated Venezuelan equine encephalomyelitis virus vaccine was significantly potentiated if the vaccine was combined with PICLC prior to vaccination. The antibody response was maintained at a significantly higher level than controls for 2.5 months postvaccination and paralleled immunological responses reported for live, attenuated (TC-83) vaccine.
Non-intrusive tongue machine interface (2014)

There has been recent interest in designing systems that use the tongue as an input interface. Prior work however either require surgical procedures or in-mouth sensor placements. In this paper, we introduce TongueSee, a non-intrusive tongue machine interface that can recognize a rich set of tongue gestures using electromyography (EMG) signals from the surface of the skin. We demonstrate the feasibility and robustness of TongueSee with experimental studies to classify six tongue gestures across eight participants. TongueSee achieves a classification accuracy of 94.17% and a false positive probability of 0.000358 per second using three-protrusion preamble design.
ChemInform Abstract: Synthesis of 4‐Substituted 4‐Arylpiperidines. (2001)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Comparative toxicities of 3 platinum‐containing chemotherapy regimens in relapsed/refractory lymphoma patients (2016)

Optimal salvage chemotherapy regimen for patients with relapsed or refractory Hodgkin and non-Hodgkin lymphoma remains unclear but often based on platinum regimens. This retrospective study assesses in real life the toxicities profiles of patients with relapsed or refractory lymphoma treated with DHA (dexamethasone, high dose aracytine cytarabine) plus platinum salt (dexamethasone-High dose aracytine (cis)platin (DHAP), dexamethasone-High dose aracytine carboplatin (DHAC), or dexamethasone-High dose aracytine Oxaliplatin (DHAOX)), from February 2007 to May 2013 in 2 French hospitals. Toxicities were recorded from medical files and assessed according to the National Cancer Institute Common Toxicity Criteria version 3.0. Potential risk factors of renal insufficiency were tested by univariate analyses. A total of 276 patients were treated: 168 with DHAP (60.9%), 79 with DHAOX (28.6%), and 29 with DHAC (10.5%). Rituximab was associated in 80.1% of patients (n = 221). Renal failure was reported in 97 patients, mainly with cisplatin regimen (86.6%) leading to 8.9% grade III to IV renal failure (P = .001). Renal insufficiency was reversible in most patients but remained persistent in 24, with all of them being treated with DHAP except 1. Cisplatin-based regimen (50.0% versus 12.0%, P < .05) and female (44.6% versus 29.7%, P < .05) appeared to be at higher risks of renal failure. Platinum cumulative dose is a significant risk factor of nephrotoxicity. Hematologic toxicity was more frequent with carboplatin and cisplatin with at least 1 event (all toxicity grade) respectively in 79.3% and 71.4% of patients treated (P < .005). Auditory toxicity was mainly reported with cisplatin (n = 19; 4 grade I-II and 15 grade III-IV). Oxaliplatin was implicated in 77.6% of neurotoxicity (n = 59), mainly moderate (grade I-II). In conclusion, DHAOX and DHAC regimens have more favorable toxicity profile than DHAP regimen. Their lack of renal toxicity makes them attractive regimens, which may be interesting for patients eligible for autologous stem cell transplantation. Nevertheless, these results have to be confirmed by the therapeutic efficacy of these 3 regimens.