gebhart/patrepeval huggingface dataset:
Application of neural networks to flow cytometry data analysis and real‐time cell classification (1996)

Conventional analysis of flow cytometric data requires that population identification be performed graphically after a sample has been run using two- parameter scatter plots.As more parameters are measured, the number of possible two-parameter plots increases geometrically, making data analysis increasingly cumbersome.Artificial Neural Systems (ANS), also known as neural networks, are a powerful and convenient method for overcoming this data bottleneck.ANS "learn" to make classifications using all of the measured parameters simultaneously.Mathematical models and programming expertise are not required.A N S are inherently parallel so that high processing speed can be achieved.Because A N S are nonlinear, curved class boundaries and other nonlinearities can emerge naturally.Here, we present biomedical and oceanographic data to demonstrate the useful properties of neural networks for processing and analyzing flow cytometry data.We show that ANS are equally useful for human leukocytes and marine plankton data.They can easily accommodate nonlinear variations in data, detect subtle changes in measurements, interpolate and classify cells they were not trained on, and analyze multiparameter cell data in real time.Real-time classification of a mixture of six cyanobacteria strains was achieved with an average accuracy of 98%.
Current Understanding of Sepsis (1996)

Sepsis and septic shock represent the thirteenth leading cause of death in the United States. It has been estimated that there are 500,000 new episodes each year, with an associated crude mortality of 35% [1]. Over the last 4 decades the age-adjusted mortality has climbed steadily from 0.5 to 7 per 100,000 episodes [2]. Approximately one-third to one-half of patients who are septic have culture-positive blood, and much of our understanding of this clinical syndrome derives from studies of nosocomial bacteremia and candidemia.
Molecular Characterization of a Carbon Transporter in Plastids from Heterotrophic Tissues: The Glucose 6-Phosphate/Phosphate Antiporter (1998)

Plastids of nongreen tissues import carbon as a source of biosynthetic pathways and energy. Within plastids, carbon can be used in the biosynthesis of starch or as a substrate for the oxidative pentose phosphate pathway, for example. We have used maize endosperm to purify a plastidic glucose 6-phosphate/phosphate translocator (GPT). The corresponding cDNA was isolated from maize endosperm as well as from tissues of pea roots and potato tubers. Analysis of the primary sequences of the cDNAs revealed that the GPT proteins have a high degree of identity with each other but share only approximately 38% identical amino acids with members of both the triose phosphate/phosphate translocator (TPT) and the phosphoenolpyruvate/phosphate translocator (PPT) families. Thus, the GPTs represent a third group of plastidic phosphate antiporters. All three classes of phosphate translocator genes show differential patterns of expression. Whereas the TPT gene is predominantly present in tissues that perform photosynthetic carbon metabolism and the PPT gene appears to be ubiquitously expressed, the expression of the GPT gene is mainly restricted to heterotrophic tissues. Expression of the coding region of the GPT in transformed yeast cells and subsequent transport experiments with the purified protein demonstrated that the GPT protein mediates a 1:1 exchange of glucose 6-phosphate mainly with inorganic phosphate and triose phosphates. Glucose 6-phosphate imported via the GPT can thus be used either for starch biosynthesis, during which process inorganic phosphate is released, or as a substrate for the oxidative pentose phosphate pathway, yielding triose phosphates.
Overexpression of Both CXC Chemokine Receptor 4 and Vascular Endothelial Growth Factor Proteins Predicts Early Distant Relapse in Stage II-III Colorectal Cancer Patients (2006)

We have shown that concomitant and high expression of CXCR4 and VEGF is a strong and independent predictor of early distant relapse in colorectal cancer. CXCR4 triggers a plethora of phenomena, including stimulation of clonogenic growth, induction of VEGF release, and ICAM-1 up-regulation. These data support the inhibition of CXCR4 to prevent the development of colorectal cancer metastasis.
Thermoresponsive Artificial Extracellular Matrix for Tissue Engineering:  Hyaluronic Acid Bioconjugated with Poly(N-isopropylacrylamide) Grafts (2001)

Thermoresponsive hyaluronans (HAs) were prepared by graft polymerization of N-isopropylacrylamide (NIPAM) on HA (number-averaged molecular weight, Ma, ca. 1.5 x 10(5) and 5.0 x 10(5)) using dithiocarbamate which is a kind of iniferter (initiator, transfer agent and terminator). The degree of dithiocarbamylation (DD) as an iniferter ranged from 0.4 to 11.4% per disaccharide unit of HA. The estimated Mn of the grafted polyNIPAM (PNIPAM) ranged from approximately 5.0 x 10(3) to 8.4 x 10(4). The PNIPAM-grafted HAs (PNIPAM-HAs) were water-soluble at room temperature, while they precipitated at temperatures above approximately 34 degrees C in water. The temperature at the onset of precipitation (lower critical solution temperature: LCST) was independent of parameters of molecular architecture such as Mn of HA, degree of grafting of PNIPAM, and Mn of PNIPAM. Equilibrium transmittance of the aqueous solution above LCST decreased with an increase in both degree of grafting and Mn of PNIPAM. At physiological temperature, the PNIPAM-HA film cast from a cold solution was very wettable with water. A markedly reduced adhesion of endothelial cells to the film was observed, indicating that the PNIPAM-HA film may serve as a non-cell-adhesive matrix. Scanning electron microscopic observation appeared to differentiate supramolecular structures between rapidly freeze-dried PNIPAM-HA and nongrafted HA:PNIPAM-HA exhibited a nonuniform fibrous network, whereas the morphology of which is markedly different from that of a nongrafted HA gel exhibited a mixture of sharp needle- and platelike structures.
Increase in Community-Acquired Methicillin-Resistant Staphylococcus aureus at a Naval Medical Center (2000)

A retrospective review of methicillin-resistant Staphylococcus aureus isolates from the Naval Medical Center, San Diego, for the years 1994 through 1997, found that the annual number of community-acquired MRSA isolates increased during the period. These outpatient isolates were more likely than inpatient isolates to be sensitive to a greater number of antibiotics.
Histochemical Localization of Cell Proliferation Using <i>In Situ</i> Hybridization for Histone mRNA (2006)

Monoclonal antibodies to proliferation associated antigens have long been used to histologically localize mitogenesis. However, techniques that distinguish cells in the synthetic or S phase have tended to rely on the in vivo incorporation of tritiated thymidine or thymidine analogs such as bromodeoxyuridine. The necessity to pulse with these labels before retrieving tissue means that they cannot be used in humans and are not available retrospectively. Measuring expression of histones serves as a useful adjunct to these techniques. As expression of histone proteins (H2A, H2B, H3, H4) are restricted to the synthetic phase of the cell cycle, hybridization for histone mRNA precisely distinguishes those cells in the S phase. Measuring their expression can easily be applied to the histological localization of proliferation, and can be used both prospectively and with archived tissue specimens. Several histone in situ hybridization probes and nonradioactive detection systems are now available commercially. A generalized protocol for their use in measuring in situ proliferation is provided in this chapter.
Molecular Design of a Chiral Lewis Acid for the Asymmetric Claisen Rearrangement (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMolecular Design of a Chiral Lewis Acid for the Asymmetric Claisen RearrangementKeiji Maruoka, Susumu Saito, and Hisashi YamamotoCite this: J. Am. Chem. Soc. 1995, 117, 3, 1165–1166Publication Date (Print):January 1, 1995Publication History Published online1 May 2002Published inissue 1 January 1995https://pubs.acs.org/doi/10.1021/ja00108a048https://doi.org/10.1021/ja00108a048research-articleACS PublicationsRequest reuse permissionsArticle Views1317Altmetric-Citations89LEARN 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 Get e-Alerts
Lipoic acid - the drug of the future? (2006)

Numerous experimental and clinical studies proved efficiency of treatment with lipoic acid-containing drugs in diseases, in which pro- and antioxidant balance is disrupted (diabetes, neurodegenerative diseases, acquired immune deficiency syndrome (AIDS), tumors, etc.). Efficiency of lipoate has been attributed to unique antioxidant properties of lipoate/dihydrolipoate system, its reactive oxygen species (ROS) scavenging ability and significant effect on the tissue concentrations of reduced forms of other antioxidants, including one of the most powerful, glutathione (thus lipoate is called an antioxidant of antioxidants). Moreover, analysis of literature data suggests participation of lipoic acid in processes of cell growth and differentiation. This fact can be crucial to clinical practice, however, this problem requires further studies.
[Absence of a close linkage between Alzheimer's disease and the polymorphic probe coding for superoxide dismutase 1]. (1988)

The hypothesis of a tight linkage between Alzheimer's disease (AD), a presenile dementia, and the probe coding for superoxide dismutase 1 (SOD 1), located on chromosome 21 at 21q22, has been investigated in a large family originating from Calabria, in which AD is transmitted as an autosomal dominant mendelian trait. Analysis of the Msp I restriction polymorphism, after molecular hybridization with the probe of DNAs coming from 22 subjects of the pedigree, allowed to the demonstrate that there wasn't any tight linkage between AD and the marker studied.
Hybridization Enhancement Using Cavitation Microstreaming (2003)

Conventional DNA microarray hybridization relies on diffusion of target to surface-bound probes, and thus is a rate-limited process. In this paper, a micromixing technique based on cavitation microstreaming principle that was developed to accelerate hybridization process is explained. Fluidic experiments showed that air bubbles resting on a solid surface and set into vibration by a sound field generated steady circulatory flows, resulting in global convection flows and, thus, rapid mixing. The time to fully mix dyed solutions in a 50-microL chamber using cavitation microstreaming was significantly reduced from hours (a pure diffusion-based mixing) to 6 s. Cavitation microstreaming was implemented to enhance DNA hybridization in both fluorescence-detection-based and electrochemical-detection-based DNA microarray chips. The former showed that cavitation microstreaming results in up to 5-fold hybridization signal enhancement with significantly improved signal uniformity, as compared to the results obtained in conventional diffusion-based biochips for a given time (2 h). Hybridization kinetics study in the electrochemical detection-based chips showed that acoustic microstreaming results in up to 5-fold kinetics acceleration. Acoustic microstreaming has many advantages over most existing techniques used for hybridization enhancement, including a simple apparatus, ease of implementation, low power consumption (approximately 2 mW), and low cost.
Random insertion of GFP into the cAMP-dependent protein kinase regulatory subunit from Dictyostelium discoideum (1998)

The green fluorescent protein (GFP) is currently being used for diverse cellular biology approaches, mainly as a protein tag or to monitor gene expression. Recently it has been shown that GFP can also be used to monitor the activation of second messenger pathways by the use of fluorescence resonance energy transfer (FRET) between two different GFP mutants fused to a Ca2+ sensor. We show here that GFP fusions can also be used to obtain information on regions essential for protein function. As FRET requires the two GFPs to be very close, N- or C-terminal fusion proteins will not generally produce FRET between two interacting proteins. In order to increase the probability of FRET, we decided to study the effect of random insertion of two GFP mutants into a protein of interest. We describe here a methodology for random insertion of GFP into the cAMP-dependent protein kinase regulatory subunit using a bacterial expression vector. The selection and analysis of 120 green fluorescent colonies revealed that the insertions were distributed throughout the R coding region. 14 R/GFP fusion proteins were partially purified and characterized for cAMP binding, fluorescence and ability to inhibit PKA catalytic activity. This study reveals that GFP insertion only moderately disturbed the overall folding of the protein or the proper folding of another domain of the protein, as tested by cAMP binding capacity. Furthermore, three R subunits out of 14, which harbour a GFP inserted in the cAMP binding site B, inhibit PKA catalytic subunit in a cAMP-dependent manner. Random insertion of GFP within the R subunit sets the path to develop two-component FRET with the C subunit.
Functional Characterization of the Internal Ribosome Entry Site of eIF4G mRNA (1998)

The eIF4 group initiation factors are required for cap-dependent translation initiation. Infection of mammalian cells by picornaviruses results in proteolytic cleavage of one of these factors, eIF4G, which severely restricts cap-dependent initiation but permits cap-independent initiation to proceed from an internal ribosome entry site (IRES) in picornaviral RNAs. The first 357 nucleotides (nt) of the 5'-untranslated region of eIF4G mRNA also contains an IRES. Using bicistronic constructs for expression in K562 cells, we have now shown that progressive deletions of the 5'-untranslated region can have either stimulatory or inhibitory effects. Furthermore, a 101-nt segment exhibits full IRES activity, and an 81-nt segment exhibits detectable IRES activity. A polypyrimidine tract (PPT) at the 3' terminus is essential for internal initiation, a property which is characteristic of picornaviral IRESs but not the other host cellular IRESs studied to date. IRES activity does not require sequences beyond 357 nt. Out-of-frame AUGs have no effect on IRES-driven luciferase expression when introduced upstream of the PPT but markedly decrease expression when introduced at sites between the PPT and the authentic initiation codon at nt 369. These results suggest that the ribosomal subunit enters at or near the PPT and then scans downstream for the initiation codon.
Atrial pacing from the coronary vein. Ten-year experience in 50 patients with implanted pervenous pacemakers. (1978)

During the past ten years, pervenous atrial pacemakers have been implanted in 50 patients (mean age 68 years, 60% males) using an electrode positioned in the coronary vein. The indications for atrial pacing were symptomatic sinus bradycardia (72%), atrial brady-tachy syndrome (20%), and recurrent tachyarrhythmias (8%). Atrial pacemakers have been implanted for a total of 1531 pacing months, average 31 months per patient, median 26 months and range 3-97 months. Effective atrial pacing has been achieved with Medtronic model 5818 and 6904 electrodes. Unipolar or bipolar atrial pacing has been equally effective, and commercially available Medtronic 5950, Cordis 162 and CPI 602 pulse generators have been utilized without difficulty. A total of 11 electrode related malpacing events occurred in the ten-year period with a malpacing event rate of 10% in the first pacing month, 1.1% per paced month during the next six months, and 0.25% per paced month thereafter. Life table analysis reveals that effective atrial pacing was achieved in 76% of the patients during a follow-up of more than five years. This experience substantiates the long-term safety and effectiveness of atrial pacing from the coronary vein using standard pacemaker electrodes and generators.
A Phase II Study of Moderate Hypothermia in Severe Brain Injury (1993)

Forty-six patients with severe nonpenetrating brain injury [Glasgow Coma Scale (GCS) 4-7] were randomized to standard management at 37 degrees C (n = 22) and to standard management with systemic hypothermia to 32 to 33 degrees C (n = 24). The two groups were balanced in terms of age (Wilcoxon's rank sum test, p > 0.95), randomizing GCS (chi-square test, p = 0.54), and primary diagnosis. Cooling was begun within 6 h of injury by use of cooling blankets. Metocurine and morphine were given hourly during induction and maintenance of hypothermia. Rewarming was at a rate of 1 degree C per 4 h beginning 48 h after intravascular temperature had reached 33 degrees C. Muscle relaxants and sedation were continued until core temperature reached 35 degrees C. There were no cardiac or coagulopathy-related complications. Seizure incidence was lower in the hypothermia group (Fisher's exact text, p = 0.019). Sepsis was seen more commonly in the hypothermia group, but difference was not statistically significant (chi-square test). Mean Glasgow Outcome Scale (GOS) score at 3 months after injury showed an absolute increase of 16% (i.e., 36.4-52.2%) in the number of patients in the Good Recovery/Moderate Disability (GR/MD) category as compared with Severe Disability/Vegetative/Dead (SD/V/D) (chi-square test, p > 0.287). Based on evidence of improved neurologic outcome with minimal toxicity, we believe that phase III testing of moderate systemic hypothermia in patients with severe head injury is warranted.
A Monoclonal Antibody that Binds Anionic Phospholipids on Tumor Blood Vessels Enhances the Antitumor Effect of Docetaxel on Human Breast Tumors in Mice (2005)

Anionic phospholipids, principally phosphatidylserine, become exposed on the external surface of viable vascular endothelial cells in tumors, providing an excellent marker for tumor vascular targeting. We recently raised an IgG monoclonal antibody, 3G4, which binds to anionic phospholipids in a beta2-glycoprotein I-dependent manner. It inhibited tumor growth in a variety of rodent tumor models by stimulating antibody-dependent cellular cytotoxicity toward tumor vessels. In the present study, we tested the hypothesis that docetaxel, which is known to have antivascular effects on tumors, might induce exposure of anionic phospholipids on tumor vasculature and, thus, enhance the antitumor activity of 3G4. Treatment of human umbilical vascular endothelial cells with subtoxic concentrations of docetaxel (20 pmol/L) in vitro caused anionic phospholipids to be externalized without inducing apoptosis. Docetaxel treatment of mice increased the percentage of tumor vessels that expose anionic phospholipids from 35% to 60%. No induction of phosphatidylserine was observed on vessels in normal tissues even after systemic treatment with docetaxel. Treatment of mice bearing orthotopic MDA-MB-435 human breast tumors with 3G4 plus docetaxel inhibited tumor growth by 93%. Treatment of mice bearing disseminated MDA-MB-435 tumors with 3G4 plus docetaxel reduced the average number of tumor colonies in the lungs by 93% and half the animals did not develop tumors. In both tumor models, the antitumor effect of the combination was statistically superior (P < 0.01) to that of docetaxel or 3G4 alone. Combination therapy reduced the tumor vessel density and plasma volume in tumors to a greater extent than did the individual drugs. The combination therapy was no more toxic to the mice than was docetaxel alone. These results indicate that, as an adjuvant therapy, 3G4 could enhance the therapeutic efficacy of docetaxel in breast cancer patients.
Production of unique immunotoxin cancer therapeutics in algal chloroplasts (2012)

The idea of targeted therapy, whereby drug or protein molecules are delivered to specific cells, is a compelling approach to treating disease. Immunotoxins are one such targeted therapeutic, consisting of an antibody domain for binding target cells and molecules of a toxin that inhibits the proliferation of the targeted cell. One major hurdle preventing these therapies from reaching the market has been the lack of a suitable production platform that allows the cost-effective production of these highly complex molecules. The chloroplast of the green alga Chlamydomonas reinhardtii has been shown to contain the machinery necessary to fold and assemble complex eukaryotic proteins. However, the translational apparatus of chloroplasts resembles that of a prokaryote, allowing them to accumulate eukaryotic toxins that otherwise would kill a eukaryotic host. Here we show expression and accumulation of monomeric and dimeric immunotoxin proteins in algal chloroplasts. These fusion proteins contain an antibody domain targeting CD22, a B-cell surface epitope, and the enzymatic domain of exotoxin A from Pseudomonas aeruginosa . We demonstrated that algal-produced immunotoxins accumulate as soluble and enzymatically active proteins that bind target B cells and efficiently kill them in vitro. We also show that treatment with either the mono- or dimeric immunotoxins significantly prolongs the survival of mice with implanted human B-cell tumors.