gebhart/patrepeval huggingface dataset:
Nitrosamines and Nitramines in Amine-Based Carbon Dioxide Capture Systems: Fundamentals, Engineering Implications, and Knowledge Gaps (2017)

Amine-based absorption is the primary contender for postcombustion CO<sub>2</sub> capture from fossil fuel-fired power plants. However, significant concerns have arisen regarding the formation and emission of toxic nitrosamine and nitramine byproducts from amine-based systems. This paper reviews the current knowledge regarding these byproducts in CO<sub>2</sub> capture systems. In the absorber, flue gas NO<sub>x</sub> drives nitrosamine and nitramine formation after its dissolution into the amine solvent. The reaction mechanisms are reviewed based on CO<sub>2</sub> capture literature as well as biological and atmospheric chemistry studies. In the desorber, nitrosamines are formed under high temperatures by amines reacting with nitrite (a hydrolysis product of NO<sub>x</sub>), but they can also thermally decompose following pseudo-first order kinetics. The effects of amine structure, primarily amine order, on nitrosamine formation and the corresponding mechanisms are discussed. Washwater units, although intended to control emissions from the absorber, can contribute to additional nitrosamine formation when accumulated amines react with residual NO<sub>x</sub>. Nitramines are much less studied than nitrosamines in CO<sub>2</sub> capture systems. Mitigation strategies based on the reaction mechanisms in each unit of the CO<sub>2</sub> capture systems are reviewed. Lastly, we highlight research needs in clarifying reaction mechanisms, developing analytical methods for both liquid and gas phases, and integrating different units to quantitatively predict the accumulation and emission of nitrosamines and nitramines.
Effect of gate leakage current on noise properties of AlGaN/GaN field effect transistors (2000)

The effect of the gate leakage current fluctuations on noise properties of AlGaN/GaN heterostructure field effect transistors (HFETs) has been studied in conventional HFET structures and in AlGaN/GaN metal-oxide-semiconductor heterostructure field effect transistors (MOS-HFETs). The comparison of the noise properties of conventional AlGaN/GaN HFETs and AlGaN/GaN MOS-HFETs fabricated on the same wafer, allowed us to estimate the contribution of the gate current noise to the HFET’s output noise. The effect of the gate current fluctuations on output noise properties of HFETs depends on the level of noise in the AlGaN/GaN HFETs. For the transistors with a relatively high magnitude of the Hooge parameter α∼10−3, even a relatively large leakage current Ig (Ig/Id∼10−3–10−2, where Id is the drain current) does not contribute much to the output noise. In HFETs with a relatively small values of α (α∼10−5–10−4), the contribution of the leakage current to output noise can be significant even at Ig/Id∼10−4–10−3. For such transistors, a very rapid increase of the 1/f noise with gate bias was observed. The differences in the noise behavior can be linked to the material quality of the AlGaN and GaN layers in different types of HFETs.
Angiotensin II stimulates cardiac myocyte hypertrophy via paracrine release of TGF-β1 and endothelin-1 from fibroblasts (1998)

Objective: We sought to determine whether angiotensin II (Ang II) promotes hypertrophy of cardiac myocytes directly or via paracrine mechanisms mediated by cardiac fibroblasts. Methods: We studied neonatal rat cardiac myocytes and fibroblasts in culture as a model system. Paracrine effects of Ang II were identified using conditioned medium and co-culture experiments. Results: Ang II type 1 (AT1) receptors responsible for myocyte growth localized to fibroblasts in radioligand binding, emulsion autoradiography, Western analysis, and immunofluorescence staining experiments. The bulk of AT1 receptor binding in myocyte cultures (1343±472 sites/cell) was to Ang II receptors on contaminating fibroblasts (9747±2126 sites/cell). Ang II induced significant paracrine trophic effects on myocytes in conditioned medium (40% increase in protein synthesis over control) and co-culture (4-fold increase over control) experiments. TGF-β1 and endothelin-1 were paracrine mediators of hypertrophy in neutralization experiments. Conclusions: Ang II stimulates cardiac myocyte hypertrophy via paracrine release of TGF-β1 and endothelin-1 from cardiac fibroblasts in a neonatal rat cell culture model.
How Cities Work (2001)

Do cities work anymore? How did they get to be such sprawling conglomerations of lookalike subdivisions, megafreeways, and "big box" superstores surrounded by acres of parking lots? And why, most of all, don't they feel like real communities? These are the questions that Alex Marshall tackles in this hard-hitting, highly readable look at what makes cities work. Marshall argues that urban life has broken down because of our basic ignorance of the real forces that shape cities-transportation systems, industry and business, and political decision making. He explores how these forces have built four very different urban environments-the decentralized sprawl of California's Silicon Valley, the crowded streets of New York City's Jackson Heights neighborhood, the controlled growth of Portland, Oregon, and the stage-set facades of Disney's planned community, Celebration, Florida. To build better cities, Marshall asserts, we must understand and intelligently direct the forces that shape them. Without prescribing any one solution, he defines the key issues facing all concerned citizens who are trying to control urban sprawl and build real communities. His timely book will be important reading for a wide public and professional audience
Activity and Pharmacodynamics of 21-Day Topotecan Infusion in Patients With Ovarian Cancer Previously Treated With Platinum-Based Chemotherapy (1999)

Twenty-one-day infusion is a well-tolerated method of administering topotecan. Pharmacodynamic studies demonstrate correlations between (1) the week of infusion and the PBMC topo-1 level, (2) the AUC of topotecan and the decrease in topo-1 levels, and (3) the change in topo-1 level and the neutrophil nadir. The objective response rate of 35% to 38% (95% CI, 15% to 57%) in this small multicenter study is at the upper level for topotecan therapy in previously treated ovarian cancer. Prolonged topotecan administration therefore warrants further investigation in larger, randomized studies comparing this 21-day schedule with the once-daily-for-5-days schedule.
Rap1 Regulates E-cadherin-mediated Cell-Cell Adhesion (2004)

The small GTPase Rap is best characterized as a critical regulator of integrin-mediated cell adhesion, although its mechanism of action is not understood. Rap also influences the properties of other cell-surface receptors and biological processes, although whether these are a consequence of effects on integrins is not clear. We show here that Rap also plays an important role in the regulation of cadherin-mediated cell-cell adhesion in epithelial cells. Expression of constitutively active Rap1A restored cadherin-mediated cell-cell contacts in mesenchymal Ras-transformed Madin-Darby canine kidney cells, resulting in reversion to an epithelial phenotype. Activation of endogenous Rap via the Rap exchange factor Epac1 also antagonized hepatocyte growth factor-induced disruption of adherens junctions. Inhibition of Rap signaling resulted in disruption of epithelial cell-cell contacts. Rap activity was required for adhesion of cells to recombinant E-cadherin extracellular domains, i.e. in the absence of integrin-mediated adhesion. These findings suggest that Rap signaling positively contributes to cadherin-mediated adhesion and that this occurs independently of effects on integrin-mediated adhesion. Our results imply that Rap may function in a broader manner to regulate the function of cell-surface adhesion receptors.
A Thermodynamic Study of Ligand Binding to the First Three Domains of the Human Insulin Receptor: Relationship between the Receptor α-Chain C-Terminal Peptide and the Site 1 Insulin Mimetic Peptides (2009)

The C-terminal segment of the insulin receptor (IR) alpha-chain plays a critical role in insulin binding. This 16-residue peptide together with the central beta-sheet of the receptor L1 domain forms one of the insulin binding surfaces of the IR monomer. Here we use isothermal titration calorimetry to assay directly the binding of the IR alphaCT peptide to an IR construct (IR485) consisting of the three N-terminal domains of the receptor monomer. Our measurements show further that the binding of the IR alphaCT peptide to IR485 competes with the binding of a prototypical "Site 1" insulin mimetic peptide to the same receptor fragment. The competitive nature of their binding appears to be reflected in a previously undetected sequence similarity between the IR alphaCT peptide and the Site 1 mimetic peptide. In contrast, a prototypical "Site 2" peptide has very limited affinity for IR485. Taken together, these results complement our recent observation that there is a possible structural relationship between these mimetic peptides and insulin itself. They also add support to the view that the segment of unexplained electron density lying on the surface of the central beta-sheet of the L1 domain in the IR ectodomain crystal structure arises from the IR alphaCT peptide. Finally, we show that mutation of the critical IR alphaCT peptide residue Phe714 to alanine does not affect the peptide's affinity for IR485 and conclude that the resultant loss of insulin binding with this mutation results from loss of interaction of the phenylalanine side chain with insulin.
Imbalanced Base Excision Repair Increases Spontaneous Mutation and Alkylation Sensitivity in Escherichia coli (1999)

Inappropriate expression of 3-methyladenine (3MeA) DNA glycosylases has been shown to have harmful effects on microbial and mammalian cells. To understand the underlying reasons for this phenomenon, we have determined how DNA glycosylase activity and substrate specificity modulate glycosylase effects in Escherichia coli. We compared the effects of two 3MeA DNA glycosylases with very different substrate ranges, namely, the Saccharomyces cerevisiae Mag1 and the E. coli Tag glycosylases. Both glycosylases increased spontaneous mutation, decreased cell viability, and sensitized E. coli to killing by the alkylating agent methyl methanesulfonate. However, Tag had much less harmful effects than Mag1. The difference between the two enzymes' effects may be accounted for by the fact that Tag almost exclusively excises 3MeA lesions, whereas Mag1 excises a broad range of alkylated and other purines. We infer that the DNA lesions responsible for changes in spontaneous mutation, viability, and alkylation sensitivity are abasic sites and secondary lesions resulting from processing abasic sites via the base excision repair pathway.
Mathematical model of oxygen distribution in engineered cardiac tissue with parallel channel array perfused with culture medium containing oxygen carriers (2004)

A steady-state model of oxygen distribution in a cardiac tissue construct with a parallel channel array was developed and solved for a set of parameters using the finite element method and commercial software (FEMLAB). The effects of an oxygen carrier [Oxygent; 32% volume perfluorocarbon (PFC) emulsion] were evaluated. The parallel channel array mimics the in vivo capillary tissue bed, and the PFC emulsion has a similar role as the natural oxygen carrier hemoglobin in increasing total oxygen content. The construct was divided into an array of cylindrical domains with a channel in the center and tissue space surrounding the channel. In the channel, the main modes of mass transfer were axial convection and radial diffusion. In the tissue region, mass transfer was by axial and radial diffusion, and the consumption of oxygen was by Michaelis-Menten kinetics. Neumann boundary conditions were imposed at the channel centerline and the half distance between the domains. Supplementation of culture medium by PFC emulsion improved mass transport by increasing convective term and effective diffusivity of culture medium. The model was first implemented for the following set of experimentally obtained parameters: construct thickness of 0.2 cm, channel diameter of 330 mum, channel center-to-center spacingof 700 microm, and average linear velocity per channel of 0.049 cm/s, in conjunction with PFC supplemented and unsupplemented culture medium. Subsequently, the model was used to define favorable scaffold geometry and flow conditions necessary to cultivate cardiac constructs of high cell density (10(8) cells/ml) and clinically relevant thickness (0.5 cm). In future work, the model can be utilized as a tool for optimization of scaffold geometry and flow conditions.
Nanocomposite hydrogels for biomedical applications (2013)

Hydrogels mimic native tissue microenvironment due to their porous and hydrated molecular structure. An emerging approach to reinforce polymeric hydrogels and to include multiple functionalities focuses on incorporating nanoparticles within the hydrogel network. A wide range of nanoparticles, such as carbon-based, polymeric, ceramic, and metallic nanomaterials can be integrated within the hydrogel networks to obtain nanocomposites with superior properties and tailored functionality. Nanocomposite hydrogels can be engineered to possess superior physical, chemical, electrical, and biological properties. This review focuses on the most recent developments in the field of nanocomposite hydrogels with emphasis on biomedical and pharmaceutical applications. In particular, we discuss synthesis and fabrication of nanocomposite hydrogels, examine their current limitations and conclude with future directions in designing more advanced nanocomposite hydrogels for biomedical and biotechnological applications.
Reciprocal effect of mesenchymal stem cell on experimental autoimmune encephalomyelitis is mediated by transforming growth factor-β and interleukin-6 (2009)

Mesenchymal stem cells (MSCs) have the ability to suppress T cell proliferation and modulate cytokine production. Recently, MSCs have been shown to ameliorate autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE), but in some cases shown to stimulate lymphocyte proliferation. So far, mechanisms through which MSCs modulate immune reactions are still undefined. In this report we demonstrate that MSCs have the capacity for either stimulating or inhibiting myelin basic protein-specific T lymphocytes in a dose-dependent manner and modulate antigen-stimulated T cells to differentiate into either T helper type 17 or regulatory T cells, respectively, via pathways involving transforming growth factor-beta and interleukin-6. These results may lead better utility of MSCs as a treatment for autoimmune disease.
The hollow fibre model - facilitating anti-cancer pre-clinical pharmacodynamics and improving animal welfare (2006)

We describe a modified hollow fibre assay (HFA) for investigating the potential of novel molecules as pharmaceutical agents. In particular the assay provides drug/target interaction data that can facilitate the selection of lead compounds for further evaluation in more sophisticated solid tumour models, whilst successfully implementing the 3Rs - the 'replacement' 'refinement' and 'reduction' of animals. This more ethical and rapid approach to early drug development does not compromise on the validity, sensitivity, predictivity or efficacy of preclinical evaluation. We present novel data using the standard cross-linker mitomycin C (MMC) as a positive control, and two investigational DNA interactive molecules (C1311/ SJG-136). Tumour cells were seeded in fibres and implanted into mice. Following treatment with an intraperitoneal injection, fibres were excised and cells retrieved for pharmacodynamic analysis using the comet assay/fluorescence microscopy. Microscopy results revealed nuclear uptake and localisation within cytoplasmic organelles of HT29 colorectal adenocarcinoma cells following treatment with C1311 (150 mg/kg). Following treatment with SJG-136 (0.3 mg/kg) a 27.3% (p<0.001) DNA cross-linking (s.c.) effect was observed in the HL60 acute promyelocytic leukaemia cell line. DNA cross-linking effects of 55% (i.p) and 50% (s.c.) (p<0.005) were observed in the A549 lung carcinoma cell line following administration of MMC (6 mg/kg). These data are consistent with previous activity defined using solid tumour models, and support the use of the HFA for in vivo pharmacodynamic investigation whilst significantly reducing animal numbers and the influence of tumour growth on the welfare of mice.
Functional expression of recombinant human trefoil factor 1 by Escherichia coli and Brevibacillus choshinensis (2015)

This study provides a potent tool of rTFF1 production to be applied in gastric damage protection and wound healing. The protein sources from B. choshinensis were more efficient than rTFF1 produced by E. coli.
Protective antigenic sites in respiratory syncytial virus G attachment protein outside the central conserved and cysteine noose domains (2018)

Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract disease in infants. Previously, we elucidated the antibody repertoire following primary RSV infection in infants. Whole genome-fragment phage display libraries (GFPDL) expressing linear and conformational epitopes from RSV bound 100-fold more phages within attachment protein (G) following primary RSV infection. The G-reactive epitopes spanned the N- and C-termini of G ectodomain, in addition to the central conserved domain (CCD). In the current study, we examined the contribution of antigenic regions of G outside of the CCD to RSV-specific immunity. We evaluated the immunogenicity, neutralization and protective efficacy of all RSV-G antigenic sites identified following primary RSV infection using recombinant E. coli expressed G ectodomain (REG), CCD-deleted G ectodomain (REG ΔCCD), N- and C-terminal G subdomains, and antigenic site peptides. The REG ΔCCD, N- and C-terminal subdomains and peptides generated antibody titers in rabbits and mice that bound fully glycosylated Recombinant Mammalian expressed G ectodomain (RMG) and intact RSV virion particles but minimal in vitro neutralization titers compared with the intact G ectodomain. Vaccinated mice were challenged intranasally with RSV-A2 Line 19F. Viral replication in nasal cavity and lungs was significantly reduced in vaccinated animals compared to unimmunized controls. Control of viral loads post-RSV challenge correlated with serum antibody binding to the virus particles. In addition, very low Th2/Th1 cytokine ratios were found in the lungs of REG ΔCCD vaccinated mice after challenge. These data demonstrate the presence of multiple protective sites in RSV G protein outside of the CCD that could contribute to the development of a bacterially produced unglycosylated G protein as safe and protective vaccine against RSV disease.
Macroions in Salty Water with Multivalent Ions: Giant Inversion of Charge (2000)

Screening of a strongly charged macroion by oppositely charged colloidal particles, micelles, or short polyelectrolytes is considered. Because of strong lateral repulsion such multivalent counterions form a strongly correlated liquid at the surface of the macroion. This liquid provides correlation-induced attraction of multivalent counterions to the macroion surface. As a result even a moderate concentration of multivalent counterions in the solution inverts the sign of the net macroion charge. We show that at high concentration of monovalent salt the absolute value of inverted charge can be larger than the bare one. This giant inversion of charge can be observed in electrophoresis.
Seroepidemiology of the human polyomaviruses (2003)

To assess the stability of polyomavirus antibodies in serial samples over time and the incidence and age-specific prevalence of polyomavirus infections, we established enzyme immunoassays (EIAs) using purified yeast-expressed virus-like particles (VLPs) containing the VP1 major capsid proteins of JC virus (JCV) and the AS and SB strains of BK virus (BKV). A random subsample of 150 Finnish women who had serum samples taken during the first trimester of pregnancy and had a second pregnancy during a 5 year follow-up period was selected, grouped by age of first pregnancy. The polyomavirus antibody levels were similar in samples taken during the first and second pregnancies (correlation coefficient 0.93 for BKV SB and 0.94 for JCV). Analysis of serum samples from 290 Swedish children aged 1-13 years, grouped by age in 2 year intervals, demonstrated that BKV seropositivity increased rapidly with increasing age of the children, reaching 98 % seroprevalence at 7-9 years of age, followed by a minor decrease. JCV seroprevalence increased only slowly with increasing age and reaching 72 % positivity among mothers >25 years of age. The age-specific seroprevalence of the human polyomaviruses measured using this VLP-based EIA was similar to previous serosurveys by other methods. The stability of the antibodies over time indicates that polyomavirus seropositivity is a valid marker of cumulative virus exposure, and polyoma VLP-based EIAs may therefore be useful for epidemiological studies of these viruses.
717. VCP Short Hairpin RNA Rescues ΔF508- CFTR and Suppresses IL8 Levels: Therapeutic Implications in Cystic Fibrosis (2006)

Background: Endoplasmic reticulum associated degradation (ERAD) is the major quality control pathway of the cell. The most common disease-causing protein folding mutation, ΔF508-CFTR, is destroyed by ERAD to cause cystic fibrosis (CF). Valosin containing protein (VCP) is an AAA ATPase that participates in retrograde translocation of misfolded proteins from the ER and degradation of polyubiquitinated protein by the proteasomes. We hypothesize that selective inhibition of VCP not only rescues ΔF508-CFTR but also suppresses IL8 cytokine levels, the major inflammatory cytokine in CF airways. Methods: The VCP shRNA was PCR amplified from oligo/template containing the VCP hairpin using universal primers which contain XhoI (5′ prime) and EcoRI (3′ prime) flank. The PCR fragment was then cloned into the hairpin cloning site of pSHAG-MAGIC2/pSM2 vector (Open Biosystems). IB3-1 (ΔF508/W1282X) bronchial epithelial cells were transiently transfected with VCP and gp78 shRNA/siRNA constructs for selective inhibition of ERAD. CFTR levels and chloride efflux were measured by metabolic labeling and MQAE fluorescence assay, respectively. Proteasome inhibition in IB3-1 cells was carried out using PS-341 (Bortezomib/Velcade) for 6hrs. The IL8 cytokine levels were measured in IL1-β induced IB3-1 cells after ERAD or proteasome inhibition. Findings: We show here that p97/VCP and gp78 form complexes with CFTR during translocation from the ER for degradation by the cytosolic proteasome. Interference in the VCP/CFTR complex promotes accumulation of immature CFTR in the ER and partial rescue of functional chloride channels to the cell surface. Moreover, under these conditions, the cytokine whose expression is regulated by the proteasome, IL8, is reduced. Inhibition of the proteasome with bortezomib (PS-341/Velcade) also rescues CFTR and suppresses IL8 levels, but with less efficiency. Interpretation: We propose that selective inhibition of ERAD by VCP short hairpin RNA is superior to gp78 siRNA or proteasome inhibition in the correction of the ΔF508 CFTR trafficking defect.