gebhart/patrepeval huggingface dataset:
High-Efficiency Transfection of Primary Human and Mouse T Lymphocytes Using RNA Electroporation (2005)

The use of nonviral gene transfer methods in primary lymphocytes has been hampered by low gene transfer efficiency and high transfection-related toxicity. In this report, high gene transfection efficiency with low transfection-related toxicity was achieved by electroporation using in vitro-transcribed mRNA. Using these methods, >90% transgene expression with >80% viable cells was observed in stimulated primary human and murine T lymphocytes transfected with GFP or mCD62L. Electroporation of unstimulated human PBMCs or murine splenocytes with GFP RNA yielded 95 and 56% GFP+ cells, respectively. Electroporation of mRNA for NY-ESO-1, MART-1, and p53 antigen-specific TCRs into human T lymphocytes redirected these lymphocytes to recognize melanoma cell lines in an MHC-restricted manner. The onset of gene expression was rapid (within 30 min) and durable (up to 7 days postelectroporation) using both GFP and TCR-mediated recognition of target cells. There was no adverse effect observed on the T lymphocytes subjected to RNA electroporation evaluated by cell growth rate, annexin-V staining of apoptotic cells, BrdU incorporation, tumor antigen-specific recognition or antigen-specific TCR affinity. The results of this study indicate that mRNA electroporation provides a powerful tool to introduce genes into both human and murine primary T lymphocytes.
Prediction of intradialytic hypotension using PPG and ECG (2013)

Intradialytic hypotension (IDH) is the most common complication during hemodialysis; early prediction and prevention of IDH would dramatically improve the living conditions for patients with end stage renal disease. A recently published study suggests that a decrease in the envelope of the photoplethysmograpy (PPG) signal can be used for predicting acute symptomatic IDH. In the present study, the PPG based method is extended by introducing a patient dependent detection threshold, which involves information on heart rate variability (HRV) and heart rate turbulence (HRT) from the current dialysis session. This is motivated since several studies have found significant differences in HRV and HRT between hypotension-prone and hypotension-resistant patients. Recordings from 15 patients during 38 hemodialysis sessions were used to evaluate the method. Symptomatic IDH was correctly predicted in 9 out of 14 cases, while 5 out of 24 cases were falsely predicted. The performance was better for acute symptomatic IDH, 5 out of 5 cases were correctly predicted. The present method represents a novel approach to combining information derived from ECG and PPG signals.
Effect of Hypophysectomy on the Formation and Maintenance of Corpora Lutea in the Ewe (1968)

Complete hypophysectomy on the day of ovulation in the ewe invariably prevented the formation of corpora lutea, and luteal regression occurred by day 12 in ewes completely hypophysectomized on day 5. Luteal function was also destroyed in approximately half of the incompletely hypophysectomized animals. Normal cyclic animals with spontaneous ovulations and anestrous animals in which ovulations were induced responded to hypophysectomy in a similar manner. It was concluded that pituitary support is necessary throughout the estrous cycle for normal formation and maintenance of corpora lutea in the ewe. (Endocrinology82: 753, 1968)
Effects of AV Sequential Versus Asynchronous AV Pacing on Pulmonary Hemodynamics (1986)

We studied the effects of various pacing modes on cardiac hemodynamics and pulmonary gas alterations in chronic heart blocked dogs. Changing the pacing mode from an atrioventricular interval of 100 ms (AV100) to a ventriculo-atrial interval of 100 ms (VA100) caused a significant fall in left ventricular pressure (117.64 +/- 11.91 to 95.60 +/- 16.58 mmHg) and cardiac output from 2.18 +/- 0.24 to 1.46 +/- 0.20 L/min. Following the change in pacing mode from AV100 to VA100, there was an increase in the alveolar-arterial O2 gradient from 23.28 +/- 6.97 to 28.74 +/- 8.43 mmHg and a decrease in the arterial CO2 tension from 32.42 +/- 3.22 to 29.42 +/- 3.22 mmHg. There was also a decrease in arterial CO2 tension when the AV100 pacing mode was compared to asynchronous ventricular pacing (32.42 +/- 3.22 versus 30.56 +/- 2.82 mmHg). The minute volume of O2 also decreased when the pacing mode was changed from AV100 to asynchronous ventricular pacing (0.134 +/- 0.01 versus 0.126 +/- 0.01 L/min) and decreased further at VA100 to 0.114 +/- 0.01 L/min. Other significant changes were also observed: the percent of expired CO2 decreased when the pacing mode was changed from AV100 to VA100 (3.68 +/- 0.13 versus 3.37 +/- 0.26%) or to asynchronous ventricular pacing (3.40 +/- 0.31%). The end-expiratory O2 increased and CO2 decreased when the pacing mode was changed from AV100 to VA100. The breath-by-breath correlation of end-expiratory O2 and CO2 with left ventricular systolic pressure showed an almost immediate increase in O2 and reduction in CO2 concentration associated with decreasing systolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Biophysical and Biological Studies of End-Group-Modified Derivatives of Pep-1 (2005)

Pep-1 is a tryptophane-rich cell-penetrating peptide (CPP) that has been previously proposed to bind protein cargoes by hydrophobic assembly and translocate them across cellular membranes. To date, however, the molecular mechanisms responsible for cargo binding and translocation have not been clearly identified. This study was conducted to gain insight into the interaction between Pep-1 with its cargo and the biological membrane to identify the thereby involved structural elements crucial for translocation. We studied three peptides differing in their N- and C-termini: (i) Pep-1, carrying an acetylated N-terminus and a C-terminal cysteamine elongation, (ii) AcPepWAmide, with an acetylated N-terminus and an amidated C-terminus, and (iii) PepW, with two free termini. Thioredoxin (TRX) and beta-galactosidase were used as protein cargoes. To study CPP-membrane interactions, we performed biophysical as well as biological assays. To mimic biological membranes, we used phospholipid liposomes in a dye leakage assay and surfactant micelles for high-resolution NMR studies. In addition, membrane integrity, cell viability, and translocation efficiency were analyzed in HeLa cells. An alpha-helical structure was found for all peptides in the hydrophobic N-terminal region encompassing residues 4-13, whereas the hydrophilic region remained unstructured in the presence of micelles. Our results show that the investigated peptides interacted with the micelles as well as with the protein cargo via their tryptophan-rich domain. All peptides displayed an orientation parallel to the micelle surface. The C-terminal cysteamine group formed an additional membrane anchor, leading to more efficient translocation properties in cells. No membrane permeabilization was observed, and our data were largely compatible with an endocytic pathway for cellular uptake.
In Vivo Bioluminescence Imaging for the Study of Intestinal Colonization by Escherichia coli in Mice (2009)

Bioluminescence imaging (BLI) is emerging as a powerful tool for real-time monitoring of infections in living animals. However, since luciferases are oxygenases, it has been suggested that the requirement for oxygen may limit the use of BLI in anaerobic environments, such as the lumen of the gut. Strains of Escherichia coli harboring the genes for either the bacterial luciferase from Photorhabdus luminescens or the PpyRE-TS and PpyGR-TS firefly luciferase mutants of Photinus pyralis (red and green thermostable P. pyralis luciferase mutants, respectively) have been engineered and used to monitor intestinal colonization in the streptomycin-treated mouse model. There was excellent correlation between the bioluminescence signal measured in the feces (R2=0.98) or transcutaneously in the abdominal region of whole animals (R2=0.99) and the CFU counts in the feces of bacteria harboring the luxABCDE operon. Stability in vivo of the bioluminescence signal was achieved by constructing plasmid pAT881(pGB2OmegaPamiluxABCDE), which allowed long-term monitoring of intestinal colonization without the need for antibiotic selection for plasmid maintenance. Levels of intestinal colonization by various strains of E. coli could be compared directly by simple recording of the bioluminescence signal in living animals. The difference in spectra of light emission of the PpyRE-TS and PpyGR-TS firefly luciferase mutants and dual bioluminescence detection allowed direct in vitro and in vivo quantification of two bacterial populations by measurement of red and green emitted signals and thus monitoring of the two populations simultaneously. This system offers a simple and direct method to study in vitro and in vivo competition between mutants and the parental strain. BLI is a useful tool to study intestinal colonization.
Glutathione and N-Acetylcysteine Suppression of Human Immunodeficiency Virus Replication in Human Monocyte/Macrophages In Vitro (1992)

Glutathione (GSH), its derivatives and N-acetylcysteine (NAC) inhibit the induction of HIV-1 expression in a chronically HIV-1-infected promonocytic cell line (U1/HIV) and peripheral blood mononuclear cells (PBMC). We have examined the effects of GSH and NAC on HIV-1 replication in human primary monocyte/macrophages cultured in vitro. Ficoll-gradient purified human monocytes were cultivated in vitro for 7-10 days and then infected with HIV-1 (Bal and Ada-M). Infection was blocked or substantially reduced by GSH or NAC (5-20 mM). Significant reduction (greater than or equal to 90%) in the amount of virus released, as determined by measuring supernatant reverse transcriptase activity and secreted p24 protein, was obtained when the cells were treated for 4 h with greater than or equal to 10 mM of GSH or NAC. The inhibitory effects of GSH and NAC were concentration dependent. This anti-HIV-1 effect persisted in these cultures for at least 35 days without evidence of significant increase in HIV-1 expression. Thus, a single pulse exposure of HIV-1-infected monocyte/macrophages with GSH or NAC led to a sustained, concentration-dependent decrease in HIV-1 p24 antigen levels, as well as, reverse transcriptase activity without producing detectable cellular toxicity in monocyte/macrophages.
Mitogen-activated protein kinase phosphatase 1 is overexpressed in prostate cancers and is inversely related to apoptosis. (1997)

Several oncogenes involved in prostate carcinogenesis activate mitogen-activated protein (MAP) kinases, which can relay both proliferative (via extracellular regulated kinases (ERK)) and apoptotic signals (via jun N-terminal protein kinases (JNK)) to the nucleus. Mitogen-activated protein kinase phosphatase 1 (MKP-1) is induced by several oncogenes in the ras-dependent pathway and can inactivate both MAP kinase pathways. The role of MKP-1 in proliferation and apoptosis is, however, still controversial. A series of 51 prostate cancers, including a subset (n = 13) that had been previously treated by androgen ablation, was used to examine whether MKP-1 mRNA and protein expression correlated with that of ERK-1, JNK-1, bcl-2, which confers resistance to apoptosis, and apoptotic index measured by in situ end-labeling of fragmented DNA. In a subset of tumors, MKP-1 expression was assessed by semiquantitative RT-PCR and was compared with both ERK-1 and JNK-1 enzymatic activity. In cases not treated by androgen ablation, MKP-1 was overexpressed in the preinvasive stage of prostate cancer, but its expression decreased with higher histologic grade and advanced disease stage. There was coexpression of MKP-1, ERK-1, and JNK-1 proteins. In addition, MKP-1 expression was inversely correlated to JNK-1 but not to ERK-1 enzymatic activity. Finally, MKP-1 and bcl-2 were inversely related to apoptotic indices. In cases treated by total androgen ablation, MKP-1 and bcl-2 were both down-regulated, whereas JNK-1 was up-regulated. Subpopulations of cells that did not undergo apoptosis maintained expression of both MKP-1 and bcl-2. These results suggest that MKP-1 overexpression is associated with the early phases of neoplastic transformation in prostate tissue. The enzymatic data on MKP-1 kinase substrates and the inverse correlation between MKP-1 and parameters of programmed cell death support the hypothesis that MKP-1 inhibits apoptosis in human prostate tumors, perhaps through the JNK pathway.
Comparison of Intravenous Ethanol Versus Diazepam for Alcohol Withdrawal Prophylaxis in the Trauma ICU: Results of a Randomized Trial (2008)

Concerning the prophylaxis of AWS, intravenous ethanol offers no advantage over diazepam with respect to efficacy or adverse sedative effects. The purported benefit of intravenous ethanol as a prophylactic agent against AWS was not evident.
Carnitine Palmitoyltransferase (CPT) Modulators: A Medicinal Chemistry Perspective on 35 Years of Research (2011)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTCarnitine Palmitoyltransferase (CPT) Modulators: A Medicinal Chemistry Perspective on 35 Years of ResearchSimona M. Ceccarelli*†, Odile Chomienne†, Marcel Gubler†, and Arduino Arduini‡View Author Information† Pharmaceuticals Division, F. Hoffmann-La Roche Ltd., CH- 4070 Basel, Switzerland‡ CoreQuest Sagl, Tecnopolo, CH-6934 Bioggio, Switzerland*Phone: (+41) 61-688-4437. Fax: (+41) 61-688-6459. E-mail: [email protected]Cite this: J. Med. Chem. 2011, 54, 9, 3109–3152Publication Date (Web):April 19, 2011Publication History Received30 June 2010Published online19 April 2011Published inissue 12 May 2011https://pubs.acs.org/doi/10.1021/jm100809ghttps://doi.org/10.1021/jm100809greview-articleACS PublicationsCopyright © 2011 American Chemical SocietyRequest reuse permissionsArticle Views3385Altmetric-Citations73LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Anatomy,Carbohydrates,Inhibition,Inhibitors,Rodent models Get e-Alerts
A rapid and non‐invasive selection of transgenic embryos before implantation using green fluorescent protein (GFP) (1995)

Non-invasive selection of transgenic mice was performed at the stage of preimplantation embryos. The morulae collected from wild female mated with hemizygous transgenic male expressing Aequorea victoria green fluorescent protein (GFP) under chicken beta-actin promoter could be classified as green or non-green under a fluorescent microscope. All the green embryos were shown to carry the transgene by PCR analysis. Taking advantage of the detection of GFP expression can be done non-invasively, the selected embryos were demonstrated to be able to developed to term with 100% of accuracy of the selection.
Single-molecule FRET reveals sugar-induced conformational dynamics in LacY (2007)

The N- and C-terminal six-helix bundles of lactose permease (LacY) form a large internal cavity open on the cytoplasmic side and closed on the periplasmic side with a single sugar-binding site at the apex of the cavity near the middle of the molecule. During sugar/H(+) symport, an outward-facing cavity is thought to open with closing of the inward-facing cavity so that the sugar-binding site is alternately accessible to either face of the membrane. In this communication, single-molecule fluorescence (Förster) resonance energy transfer is used to test this model with wild-type LacY and a conformationally restricted mutant. Pairs of Cys residues at the ends of two helices on the cytoplasmic or periplasmic sides of wild-type LacY and the mutant were labeled with appropriate donor and acceptor fluorophores, single-molecule fluorescence resonance energy transfer was determined in the absence and presence of sugar, and distance changes were calculated. With wild-type LacY, binding of a galactopyranoside, but not a glucopyranoside, results in a decrease in distance on the cytoplasmic side and an increase in distance on the periplasmic side. In contrast, with the mutant, a more pronounced decrease in distance and in distance distribution is observed on the cytoplasmic side, but there is no change on the periplasmic side. The results are consistent with the alternating access model and indicate that the defect in the mutant is due to impaired ligand-induced flexibility on the periplasmic side.
Ligands for insulin receptor isolation (1984)

Biotinylated insulins are bivalent molecules having the ability to bind to insulin receptors on the one hand and to "avidins" on the other. In order to be useful as ligands for insulin receptor isolation, biotinylated insulins must be developed that have the capacity to bind simultaneously to both and insulin receptor. The present investigation addresses this problem. A series of biotinylated and dethiobiotinylated insulins has been prepared in which the distance between the biotin carboxyl group and the insulin varies from 7 to 20 atoms. These compounds form complexes with succinoylavidin. The dissociation rates (K-1) of these complexes have been determined from the [14C]biotin exchange assay. The dissociation kinetics of most of these complexes are biphasic, and the kinetic constants reported are those corresponding to the slow rate. Ligands containing dethiobiotin dissociate more rapidly than the corresponding biotin derivatives. The interposition of a spacer arm substantially decreases the rate of dissociation. The [14C]biotin exchange assay could not be used with streptavidin complexes of the above ligand since biotin dissociates more rapidly from streptavidin than from succinoylavidin. However, the relative dissociation rates of a series of ligands could be determined and were as follows: 6-(dethiobiotinylamido)-hexanoic acid greater than dethiobiotinyl-A1-insulin greater than biotinylinsulin greater than biotinyl-A1-insulin greater than biotinyl-A2-insulin. Dethiobiotin and its amide failed to form complexes with streptavidin. The affinity of the ligands for insulin receptors was determined by measuring their ability to stimulate 14CO2 formation from [1-14C]glucose in rat epididymal adipocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Precision of Hyaline Cartilage Thickness Measurements (1992)

Measurement of cartilage thickness in vivo is an important indicator of the status of a joint as the various degenerative and inflammatory arthritides directly affect the condition of the cartilage. In order to assess the precision of thickness measurements of hyaline articular cartilage, we undertook a pilot study using MR imaging, plain radiography, and ultrasonography (US). We measured the cartilage of the hip and knee joints in 10 persons (4 healthy volunteers and 6 patients). The joints in each patient were examined on two separate occasions using each modality. In the hips as well as the knee joints, the most precise measuring method was plain film radiography. For radiographs of the knees obtained in the standing position, the coefficient of variation was 6.5%; in the hips this figure was 6.34%. US of the knees and MR imaging of the hips were the second best modalities in the measurement of cartilage thickness. In addition, MR imaging enabled the most complete visualization of the joint cartilage.
Synthesis of 2-(7-Indolyl)-benzimidazoles via 7-Formylindoles (1986)

4,6-Dimethoxyindoles undergo Vilsmeier formylation to give 7-formylindoles which can be converted into 2-(7-indolyl)-benzimidazoles on reaction with 1,2-diaminobenzene.
Intracavitary treatment of soft tissue sarcomas in dogs using cisplatin in a biodegradable polymer. (1998)

The rate of recurrence appeared to be similar using intracavitary cisplatin compared to previous reports of STS treated by marginal surgery followed by radiotherapy. The complication rate indicates the need for further refinement of the polymer/cisplatin system.
Selective Ion Filtering by Digital Thresholding:  A Method To Unwind Complex ESI-Mass Spectra and Eliminate Signals from Low Molecular Weight Chemical Noise (2005)

In this work, we present a simple method by which to preferentially detect either high molecular weight or low molecular weight ions generated by electrospray ionization. This approach, termed selective ion filtering by digital thresholding (SIFdT) is demonstrated on a commercial ESI-TOF instrument that employs a fast digitizer coupled to a microchannel plate detector. The digital representation of each individual scan is digitally filtered prior to spectral coaddition. As larger, more highly charged ions induce a more intense response than low molecular weight singly charged species, a digital threshold can be set that precludes the detection of singly charged species yet permits the efficient detection of larger, more highly charged species. In this work, we demonstrate the applicability of this approach to eliminate low molecular weight chemical noise in ESI-TOF spectra of oligonucleotide and protein ions, demonstrate improved dynamic range for analyte solutions containing high levels of low MW constituents, and show that spectra acquired at different digital thresholds can be subtracted to yield spectra of low molecular weight constituents with improved mass measurement accuracies. A notional scheme is presented in which an alternative digitization approach is employed using multiple differentially thresholded data streams to allow improved internal mass calibration and higher resolution ion partitioning.
Size Effect in Heterogeneous Nucleation (1958)

Assuming a spherical nucleating particle, the effect of particle size and surface properties upon nucleation efficiency is investigated. A general result is derived which is then applied to the condensation, sublimation, and freezing of water on foreign nuclei. The size effect is found to become important in the range 100–1000 A of particle radius. For particles larger than this, nucleation efficiency is substantially independent of size, while for smaller particles the efficiency is very greatly reduced.
Design, Synthesis, and Testing of Non-Nephrotoxic Desazadesferrithiocin Polyether Analogues (2008)

A series of iron-clearing efficiencies (ICEs), ferrokinetics, and toxicity studies for ( S)-2-(2,4-dihydroxyphenyl)-4,5-dihydro-4-methyl-4-thiazolecarboxylic acid (deferitrin, 1), ( S)-4,5-dihydro-2-[2-hydroxy-4-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid ( 2), and (S)-4,5-dihydro-2-[2-hydroxy-3-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid ( 3) are reported. The ICEs in rodents are shown to be dose-dependent and saturable for ligands 2 and 3 and superior to 1. Both polyether analogues in subcutaneous (sc) versus oral (po) administration in rodents and primates demonstrated excellent bioavailability. Finally, in a series of toxicity studies of ligands 1- 3, the dosing regimen was shown to have a profound effect in animals treated with ligand 1. When ligand 1 was given at doses of 237 micromol/kg/day twice a day (b.i.d.), there was serious proximal tubule damage versus 474 micromol/kg/day once daily (s.i.d.). With 2 and 3, in iron-overloaded and/or non-iron-loaded rodents, kidney histopathologies remained normal.