gebhart/patrepeval huggingface dataset:
Metabolic Engineering for the Production of Copolyesters Consisting of 3‐Hydroxybutyrate and 3‐Hydroxyhexanoate by Aeromonas hydrophila (2004)

Aeromonas hydrophila 4AK4 was able to synthesize copolyesters consisting of 3-hydroxybutyrate (3HB) and about 15 mol-% 3-hydroxyhexanoate (3HHx) (PHBHHx) when grown in long chain fatty acids such as dodecanoate regardless of growth conditions. To regulate the unit fraction in PHBHHx, phbA and phbB genes encoding beta-ketothiolase and acetoacetyl-CoA reductase in Ralstonia eutropha, were introduced into A. hydrophila 4AK4. When gluconate was used as cosubstrate of dodecanoate, the recombinant produced PHBHHx containing 3-12 mol-% 3HHx, depending on the gluconate concentration in media. Vitreoscilla hemoglobin gene, vgb, was also introduced into the above recombinant, resulting in improved PHBHHx content from 38 to 48 wt.-% in shake flask study. Fermentor studies also showed that increased gluconate concentration in medium containing dodecanoate promoted the recombinant strain harboring phbA and phbB genes to incorporate more 3HB unit into PHBHHx, resulting in reduced 3HHx fraction. Recombinant A. hydrophila harboring phbA, phbB and vgb genes demonstrated better PHBHHx productivity and higher conversion efficiency from dodecanoate to PHBHHx than those of the recombinant without vgb in fermentation study. Combined with the robust growth property and simple growth requirement, A. hydrophila 4AK4 appeared to be a useful organism for metabolic engineering.
Relationship of Plasma Leptin to Plasma Cytokines and Human Survivalin Sepsis and Septic Shock (1999)

Leptin production is increased in rodents by administration of endotoxin or cytokines. To investigate whether circulating leptin is related to cytokine release and survival in human sepsis, plasma concentrations of leptin, interleukin (IL)-6, IL-1beta, tumor necrosis factor (TNF)-alpha, soluble TNF receptor type I, IL-1 receptor antagonist (IL-1ra), and the inflammatory modulator IL-10 were measured as soon as severe sepsis (n=28) or septic shock (n=14) developed and every 6 h for 24 h. Patients with sepsis or septic shock had leptin concentrations 2.3- and 4.2-fold greater, respectively, than the control group. There was an independent association for leptin with IL-1ra and IL-10 in both patient groups. By discriminant analysis, leptin and IL-6 were independent predictors of death. These findings suggest that increases in leptin levels may be a host defense mechanism during sepsis.
A Potent Anti-CD70 Antibody–Drug Conjugate Combining a Dimeric Pyrrolobenzodiazepine Drug with Site-Specific Conjugation Technology (2013)

A highly cytotoxic DNA cross-linking pyrrolobenzodiazepine (PBD) dimer with a valine-alanine dipeptide linker was conjugated to the anti-CD70 h1F6 mAb either through endogenous interchain cysteines or, site-specifically, through engineered cysteines at position 239 of the heavy chains. The h1F6239C-PBD conjugation strategy proved to be superior to interchain cysteine conjugation, affording an antibody-drug conjugate (ADC) with high uniformity in drug-loading and low levels of aggregation. In vitro cytotoxicity experiments demonstrated that the h1F6239C-PBD was potent and immunologically specific on CD70-positive renal cell carcinoma (RCC) and non-Hodgkin lymphoma (NHL) cell lines. The conjugate was resistant to drug loss in plasma and in circulation, and had a pharmacokinetic profile closely matching that of the parental h1F6239C antibody capped with N-ethylmaleimide (NEM). Evaluation in CD70-positive RCC and NHL mouse xenograft models showed pronounced antitumor activities at single or weekly doses as low as 0.1 mg/kg of ADC. The ADC was tolerated at 2.5 mg/kg. These results demonstrate that PBDs can be effectively used for antibody-targeted therapy.
Vitreous treatment of cultured human RPE cells results in differential expression of 10 new genes. (2002)

Vitreous treatment of cultured RPE cells induces the differential expression of a variety of genes with functions in transcription, mediation of signal transduction and inflammation, glycosylation, ubiquitination and protein-protein interaction. Further examination of these genes may locate additional targets for treatment of diseases caused by contact of RPE cells with vitreous, typical in proliferative vitreoretinopathy.
Primary Polyclonal Human T Lymphocytes Targeted to Carcino-Embryonic Antigens and Neural Cell Adhesion Molecule Tumor Antigens by CD3ζ-Based Chimeric Immune Receptors (2002)

Antigen-specific T lymphocytes are attractive as potential anticancer agents. The generation of large numbers of antigen-specific T cells is possible through the use of gene therapy to express targeting receptors on the T lymphocyte. Activated T lymphocytes were transduced to express carcino-embryonic antigen or neural cell adhesion molecule targeted CD3zeta chimeric immune receptors. The chimeric receptors were expressed as homodimers and also as heterodimers with the native CD3zeta. T lymphocyte populations were expanded in the absence of selection for the modified cells and were shown to produce cytokines when cultured in the presence of immobilized purified protein antigen. These lymphocytes also responded by cytokine production and cytolytic activity when challenged with tumor-cell lines expressing the antigen recognized by the chimeric immune receptor. The cytolytic activity appears to be largely perforin mediated. Furthermore, soluble carcino-embryonic antigen did not interfere with the functional activity of the carcino-embryonic antigen-targeted lymphocytes. Long-term (5-day) stimulation of the modified lymphocytes by protein antigen resulted in reduced viability similar to that induced by anti-CD3 antibodies alone. Viability was improved by a costimulatory signal indicating that such signals may be vital in the maintenance of long-term functional activity of receptor modified T lymphocytes.
Modeling Combined Braking and Steering Tire Forces (2000)

&lt;div class="section abstract"&gt;&lt;div class="htmlview paragraph"&gt;The force distributed over the contact patch between a tire and a road surface is typically modeled in component form for dynamic simulations. The two components in the plane of the contact patch are the braking, or traction force, and the steering, or side or cornering force. A third force distributed over the contacts patch is the normal force, perpendicular to the road surface. The two tangential components in the plane of the road are usually modeled separately since they depend primarily on independent parameters, wheel slip and sideslip. Mathematical expressions found in the literature for each component include exponential functions, piecewise linear functions and the Bakker-Nyborg-Pacejka equations, among others. Because braking and steering frequently occur simultaneously and their resultant tangential force is limited by friction, the two components must be properly combined for a full range of the wheel slip and sideslip parameters. This paper examines the way in which these two components are combined for an existing approach known as the Nicolas-Comstock model.&lt;/div&gt;&lt;div class="htmlview paragraph"&gt;First, performance criteria for tire modeling are proposed. Then the Nicolas-Comstock model is examined relative to the criteria. As originally proposed, this model falls short of meeting the criteria over the full range of transverse and longitudinal wheel slip values and sideslip angles. A modified version of the Nicolas-Comstock model is presented that satisfies these performance criteria. Finally, comparisons are made of the Modified Nicolas-Comstock model to other combined tire force models and to existing tire force measurements.&lt;/div&gt;&lt;/div&gt;
Growth of adult rat retinal ganglion cell neurites on astrocytes (1990)

Astrocytes, as well as Schwann cells (SC), can provide suitable substrata for embryonic neurites during development, but their abilities to support adult regenerating neurites have not been directly compared. The aim of the present study was to determine the ability of astrocytes to promote adult rat retinal ganglion cell (RGC) regeneration in vitro and to compare this to previously determined growth on the surface of Schwann cells. We prepared Type I astrocytes (Raff et al: J. Neurosci. 3:1289-1300, 1983) from perinatal rats. These were subcultured and maintained in either a serum-free medium for at least 2 weeks (stellate astrocytes with little immunoreactivity for laminin) or in serum containing medium for 7 to 10 days (flat and polygonal astrocytes with immunoreactivity for laminin). Stellate astrocytes might therefore represent mature astrocytes in vivo (Ard and Bunge: J. Neurosci. 8:2844-2858, 1988), while flat astrocytes might resemble immature brain astrocytes (Liesi et al: J. Cell Biol. 96:920-924, 1983). Adult RGC survival and axonal regrowth on these glia populations was compared to that observed on different SC populations, as previously reported (Baehr and Bunge: Exp. Neurol. 106:27-40, 1989). Both astrocyte populations (either flat or stellate astrocytes) did not enhance RGC survival. Stellate astrocytes were less effective in supporting RGC axon regeneration than flat astrocytes. When these date were compared to RGC survival and axon growth on SC (Baehr and Bunge: Exp. Neurol. 106:27-40, 1989) only "activated" mature SC populations were superior to astrocytes in enhancing RGC survival and neurite regrowth.(ABSTRACT TRUNCATED AT 250 WORDS)
Ribavirin Treatment of Respiratory Syncytial Viral Infection in Infants With Underlying Cardiopulmonary Disease (1985)

Aerosolized ribavirin was evaluated in the treatment of respiratory syncytial virus lower respiratory tract disease in 53 infants, 36 of whom had underlying diseases. Of the total infants, 26 were studied in a double-blind, placebo-controlled manner; 14 received ribavirin and 12 received placebo, a water aerosol, for an average of five days. When the infants with bronchopulmonary dysplasia and congenital heart disease treated with ribavirin were compared with those receiving placebo, the treated infants showed a significantly faster rate of improvement in their illness severity score. The degree of improvement in the total group of infants receiving ribavirin compared with those receiving placebo was similarly greater, and at the end of therapy significantly greater improvement was also demonstrated in their arterial blood gas values and in the amount of virus shed from their nasal washes. No toxic or adverse effects of the aerosol therapy were observed in any of the 53 infants studied, and resistance to ribavirin did not develop in any of the respiratory syncytial virus strains isolated, despite prolonged treatment in some of the more ill infants.
First Report on the Abnormal Dearylation/Alkylation Reaction in One‐Pot Hantzch Synthesis with 6‐Amino‐1,3‐Dimethyl Uracil (2004)

Abstract First report on the abnormal dearylation/dealkylation reaction occurring during dehydrogenation in one‐pot, three‐component condensation of dihydropyrido[2,3‐d]pyrimidines.
Rhodium-Catalyzed Conjugate Addition of Aryl- or 1-Alkenylboronic Acids to Enones (1997)

The rhodium(I)-catalyzed conjugate addition of aryl- or 1-alkenylboronic acids to enones was carried out in high yields at 50 °C in an aqueous solvent. A combination of (acac)Rh(CO)2 and dppb was recognized to be highly effective for the addition to acyclic and cyclic enones.
Synthesis and Biological Evaluation of 1′-C-Cyano-Pyrimidine Nucleosides (1996)

Abstract 2′-Deoxy-, 2′-bromo-, and arabino-1′-C-cyano-pyrimidine nucleosides were synthesized from O2 ,2′-cyclouridine. Incorporation of cyano group at the anomeric position was achieved by treatment of 1′,2′-unsaturated uridine with NBS in the presence of pivalic acid followed by TMS-cyanide and stannic chloride. Antineoplastic and antiviral activities of those compounds are also discussed.
Cytoskeletal regulation of pulmonary vascular permeability (2001)

The endothelial cell (EC) lining of the pulmonary vasculature forms a semipermeable barrier between the blood and the interstitium of the lung. Disruption of this barrier occurs during inflammatory disease states such as acute lung injury and acute respiratory distress syndrome and results in the movement of fluid and macromolecules into the interstitium and pulmonary air spaces. These processes significantly contribute to the high morbidity and mortality of patients afflicted with acute lung injury. The critical importance of pulmonary vascular barrier function is shown by the balance between competing EC contractile forces, which generate centripetal tension, and adhesive cell-cell and cell-matrix tethering forces, which regulate cell shape. Both competing forces in this model are intimately linked through the endothelial cytoskeleton, a complex network of actin microfilaments, microtubules, and intermediate filaments, which combine to regulate shape change and transduce signals within and between EC. A key EC contractile event in several models of agonist-induced barrier dysfunction is the phosphorylation of regulatory myosin light chains catalyzed by Ca(2+)/calmodulin-dependent myosin light chain kinase and/or through the activity of the Rho/Rho kinase pathway. Intercellular contacts along the endothelial monolayer consist primarily of two types of complexes (adherens junctions and tight junctions), which link to the actin cytoskeleton to provide both mechanical stability and transduction of extracellular signals into the cell. Focal adhesions provide additional adhesive forces in barrier regulation by forming a critical bridge for bidirectional signal transduction between the actin cytoskeleton and the cell-matrix interface. Increasingly, the effects of mechanical forces such as shear stress and ventilator-induced stretch on EC barrier function are being recognized. The critical role of the endothelial cytoskeleton in integrating these multiple aspects of pulmonary vascular permeability provides a fertile area for the development of clinically important barrier-modulating therapies.
Negative Symptoms in Schizophrenia: Avolition and Occam's Razor (2008)

The identification of schizophrenia's negative symptoms dates back to the earliest descriptions of Kraepelin and Bleuler, who each highlighted the central role of avolition in the phenomenology and course of this illness. Since, there have been numerous advances in our understanding of schizophrenia, and the present review tracks the changes that have taken place in our understanding of negative symptoms, their description and measurement. That these symptoms represent a distinct domain of the illness is discussed in the context of their ties to other symptoms and functional outcome. The underlying structure of the negative symptom construct is explored, including several lines of investigation that point towards diminished expression and amotivation as key underlying subdomains. We also discuss findings of intact emotional experience and consummatory pleasure in individuals with schizophrenia, calling into question the presence of anhedonia in this illness. We conclude with a reconceptualization of the negative symptoms, suggesting amotivation (ie, avolition) represents the critical component, particularly in regard to functional outcome. Further exploration and clarification of this core deficit will ultimately enhance our neurobiological understanding of schizophrenia, as well as strategies that may improve outcome.
Thermostability of Firefly Luciferases Affects Efficiency of Detection by In Vivo Bioluminescence (2004)

Luciferase from the North American firefly (Photinis pyralis) is a useful reporter gene in vivo, allowing noninvasive imaging of tumor growth, metastasis, gene transfer, drug treatment, and gene expression. Luciferase is heat labile with an in vitro halflife of approximately 3 min at 37 degrees C. We have characterized wild type and six thermostabilized mutant luciferases. In vitro, mutants showed half-lives between 2- and 25-fold higher than wild type. Luciferase transfected mammalian cells were used to determine in vivo half-lives following cycloheximide inhibition of de novo protein synthesis. This showed increased in vivo thermostability in both wild-type and mutant luciferases. This may be due to a variety of factors, including chaperone activity, as steady-state luciferase levels were reduced by geldanamycin, an Hsp90 inhibitor. Mice inoculated with tumor cells stably transfected with mutant or wild-type luciferases were imaged. Increased light production and sensitivity were observed in the tumors bearing thermostable luciferase. Thermostable proteins increase imaging sensitivity. Presumably, as more active protein accumulates, detection is possible from a smaller number of mutant transfected cells compared to wild-type transfected cells.
DNA sequencing separations in capillary gels on a modified commercial DNA sequencing instrument. (1990)

DNA sequencing separations of standard DNA fragments of known sequence have been achieved in small diameter capillary gels electrophoresed and analyzed in parallel in a modified commercial DNA sequencer instrument. DNA sequencing in terms of base-calling accuracy is comparable to conventional slab gels; however, the separations in the capillary were performed somewhat faster and required less sample than those in the slab gel. Advantages of this approach vs. separations on conventional slab gels are discussed.
Histopathological Reactions of Calcium Phosphate Cement (1992)

Calcium phosphate cement (CPC) consisting of Ca4 (PO4)2O and CaHPO4 (2H2O) was recently developed. This study evaluated in vivo aspects of CPC and CPC mixtures compared to those of commercial hydroxyapatite (HP) and several endodontic materials: Grossman's cement (GC), calcium hydroxide-iodine paste (CHP) and gutta-percha plate (GP). Biocompatibility of subcutaneous implants in Donryu rats was evaluated after one month. Results showed very slight inflammatory reactions from CPC, CPC mixtures and HP. The materials were surrounded by thin fibrous connective tissues with a small number of lymphocytes and plasma cells. Severe inflammatory reactions were provoked by GC. Granulation tissues induced by CHP resembled those of pseudoxanthomatous granuloma. The GP material was encapsulated by relatively thick fibrous connective tissues with little inflammatory reactions.
Logic Operations at the Molecular Level. An XOR Gate Based on a Molecular Machine (1997)

A pseudorotaxane formed in solution by self-assembly of a wire-type electron acceptor (2,7-dibenzyldiazapyrenium dication) and a macrocyclic electron donor (2,3-dinaphtho-30-crown-10) can be unthreaded and rethreaded by chemical inputs. Unthreading can be obtained by addition of stoichiometric amounts of acids or amines. After the unthreading process caused by addition of acid, rethreading can be obtained by addition of amine, and vice versa. The threading/unthreading processes are accompanied (and therefore can be monitored) by strong changes in the fluorescence properties of the system. The input (chemical)/output (fluorescence) characteristics of this molecular-level system correspond to those of an XOR logic gate.
Neuronal Sensitization for Histamine-Induced Itch in Lesional Skin of Patients With Atopic Dermatitis (2003)

As the area of axon reflex flare is an indirect measure of activity in primary afferent neurons, our results suggest a decreased activation of peripheral pruriceptors in patients with AD. The massively increased itch in lesional skin of patients with AD might therefore be based on sensitization for itch in the spinal cord rather than in primary afferent neurons. This sensitization does not appear to be simply based on skin inflammation because histamine-induced itch was not augmented in lesional skin of psoriasis.
Polymeric Crowding Agents Improve Passive Biomacromolecule Encapsulation in Lipid Vesicles (2010)

Large solutes such as high molecular weight proteins can be difficult to encapsulate in lipid vesicles. Passive trapping of these macromolecular solutes during vesicle formation typically results in concentrations inside the vesicles that are much lower than in the external solution. Here, we investigated the effect of macromolecular crowding on passive encapsulation of biological macromolecules with molecular weights ranging from 52 kDa to 660 kDa within both individual giant lipid vesicles (GVs, > 3 microm diameter) and populations of 200 nm diameter large unilamellar vesicles (LUVs). Fluorescently labeled biomacromolecules were encapsulated during vesicle formation in the presence or absence of three weight percent poly(ethylene glycol) (PEG; 8 kDa) or dextran 500 kDa, which served as crowding agents. Encapsulation efficiency of the labeled biomolecules was higher for the lower molecular weight solutes, with internal concentrations essentially equal to external concentrations for labeled biomacromolecules with hydrodynamic radii (r(h)) less than 10 nm. In contrast, internal concentrations were reduced markedly for larger solutes with r(h) > or = 10 nm. Addition of PEG or dextran during vesicle formation improved encapsulation of these larger proteins up to the same levels as observed for the smaller proteins, such that internal and external concentrations were equal. This observation is consistent with PEG and dextran acting as volume excluders, reducing the hydrodynamic radius of the biomacromolecules and increasing their encapsulation. This work demonstrates a simple and general route to improved encapsulation of otherwise poorly encapsulated macromolecular solutes in both GV and LUVs up to their concentration in the solution present during vesicle formation.
Specific Isolation of Placenta‐Derived Exosomes from the Circulation of Pregnant Women and Their Immunoregulatory Consequences1 (2006)

Placental exosomes suppressed T-cell signaling components; however, while exosomal FasL is an important contributor, it does not appear to be the sole mediator. The additional expression of PD-L1 may explain immunoregulatory consequences of exosomes with low or absent FasL.
Expression of p53, bcl-2, E-cadherin, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinases-1 in paired primary tumors and brain metastasis. (1999)

The objectives of this study were to: (a) characterize the immunohistochemical expression of p53, bcl-2, E-cadherin (EC), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinases-1 (TIMP-1) in brain metastases; (b) compare immunohistochemical (IHC) expression of brain metastases with their primary tumors; and (c) assess the prognostic value of expression of these markers. Tumors from 35 patients with brain metastasis were studied for IHC expression of p53, bcl-2, EC, MMP-9, and TIMP-1. In 17 cases, primary tumors were also available for study. In brain metastases, p53 was positive in 91% of cases and intermediate in 9%, MMP-9 was positive in all cases, TIMP-1 was intermediate in 6% and negative in 94% of cases, EC expression was positive in 86% of cases and intermediate in 14%, and bcl-2 was variable. All primary tumors were positive for p53 and MMP-9, 3% were intermediate for TIMP-1 and 97% were negative, 65% were positive for EC and 35% were intermediate, whereas bcl-2 expression was variable. Neither p53, bcl-2, TIMP-1, or EC staining correlated with overall survival or survival with brain metastases. No assessment of survival differences could be made for MMP-9 because of its overexpression in all tissues. This study found that MMP-9 and p53 were markedly overexpressed in primary tumors and matched brain metastasis, TIMP-1 expression was negative in the majority of specimens, whereas EC expression was maintained in both primary tumors and brain metastases and bcl-2 expression was variable. This study suggests that the functional balance of MMP-9 and TIMP-1 is shifted toward extracellular matrix degradation in brain metastases and that deregulation of cell cycle control by p53 also exists in brain metastases. The high expression of EC may indicate the importance of adherence at late stages of metastasis but requires further study.