gebhart/patrepeval huggingface dataset:
Lung Disease Associated with α1-Antitrypsin Deficiency (2010)

α(1)-Antitrypsin (A1AT) is a polyvalent, acute-phase reactant with an extensive range of biological functions that go beyond those usually linked to its antiprotease (serpin) activities. Genetic mutations cause a systemic deficiency of A1AT, leading to liver and pulmonary diseases, including emphysema and chronic bronchitis. The pathogenesis of emphysema, which involves the destruction of small airway structures and alveolar units, is triggered by cigarette smoke and pollutants. The tissue damage caused by these agents is further potentiated by the mutual interactions between apoptosis, oxidative stress, and protease/antiprotease imbalance. These processes lead to the activation of endogenous mediators of tissue destruction, including the lipid ceramide, extracellular matrix proteins, and abnormal inflammatory cell signaling. In this review, we propose that A1AT has a range of actions that are not restricted to protease inhibition but rather extend to mitigate a range of these pathological processes involved in the development of emphysema. We discuss the evidence indicating that A1AT blocks apoptosis by binding and inhibiting active caspase-3 and modulates a broad range of inflammatory responses induced by neutrophils and by lipopolysaccharide and tumor necrosis factor-α signaling.
Intra‐articular bupivacaine plus adrenaline for arthroscopic surgery of the knee (1992)

The purpose of the study was to evaluate three different doses of intra-articular bupivacaine plus adrenaline in relation to per- and postoperative pain relief following arthroscopy. Sixty patients were allocated to three groups of 20 patients each scheduled for arthroscopy. They were randomized prospectively to receive bupivacaine plus adrenaline 25 mg + 50 micrograms, 50 mg + 100 micrograms, 75 mg + 150 micrograms, respectively, diluted to a volume of 30 ml. Four patients were excluded because the operation could not be carried out under intra-articular analgesia, 18 patients had a diagnostic arthroscopy and 38 patients had different arthroscopic operations performed. The number of patients scoring pain in the knee as moderate or severe was less in Group 3 than in the other two groups, i.e. the highest dose had a better pain relief. No adverse effects were registered. With respect to per- or postoperative administration of analgesics, postoperative pain occurrence, and the surgeon's acceptance of the method, there were no statistically significant differences. Ninety-two percent of the patients would prefer intraarticular analgesia if they should need to have another arthroscopy performed.
4-Amino-substituted Benzenesulfonamides as Inhibitors of Human Carbonic Anhydrases (2014)

A series of N-aryl-β-alanine derivatives and diazobenzenesulfonamides containing aliphatic rings were designed, synthesized, and their binding to carbonic anhydrases (CA) I, II, VI, VII, XII, and XIII was studied by the fluorescent thermal shift assay and isothermal titration calorimetry. The results showed that 4-substituted diazobenzenesulfonamides were more potent CA binders than N-aryl-β-alanine derivatives. Most of the N-aryl-β-alanine derivatives showed better affinity for CA II while diazobenzenesulfonamides possessed nanomolar affinities towards CA I isozyme. X-ray crystallographic structures showed the modes of binding of both compound groups.
Highly selective water channel activity measured by voltage clamp: Analysis of planar lipid bilayers reconstituted with purified AqpZ (2001)

Aquaporins are membrane channels selectively permeated by water or water plus glycerol. Conflicting reports have described ion conductance associated with some water channels, raising the question of whether ion conductance is a general property of the aquaporin family. To clarify this question, a defined system was developed to simultaneously measure water permeability and ion conductance. The Escherichia coli water channel aquaporin-Z (AqpZ) was studied, because it is a highly stable tetramer. Planar lipid bilayers were formed from unilamellar vesicles containing purified AqpZ. The hydraulic conductivity of bilayers made from the total extract of E. coli lipids increased 3-fold if reconstituted with AqpZ, but electric conductance was unchanged. No channel activity was detected under voltage-clamp conditions, indicating that less than one in 10(9) transport events is electrogenic. Microelectrode measurements were simultaneously undertaken adjacent to the membrane. Changes in sodium concentration profiles accompanying transmembrane water flow permitted calculation of the activation energies: 14 kcal/mol for protein-free lipid bilayers and 4 kcal/mol for lipid bilayers containing AqpZ. Neither the water permeability nor the electric conductivity exhibited voltage dependence. This sensitive system demonstrated that AqpZ is permeated by water but not charged ions and should permit direct analyses of putative electrogenic properties of other aquaporins.
IFN-α in the Treatment of Melanoma (2012)

Among the IFNs, IFN-α2 has been the most broadly evaluated clinically. At the molecular level, IFN-α has multiple effects in a variety of malignancies that range from antiangiogenic to potent immunoregulatory, differentiation-inducing, antiproliferative, and proapoptotic effects. A multitude of IFN-α2 regimens that may be classified as low dose, intermediate dose, and high dose have been evaluated as adjuvant therapy in melanoma. A durable impact on both relapse-free and overall survival was seen only with the regimen utilizing high-dose IFN-α2b tested in the Eastern Cooperative Oncology Group and intergroup trials E1684, E1690, and E1694 as adjuvant therapy for high-risk surgically resected melanoma (stage IIB or III). Adjuvant pegylated IFN-α2b has also been evaluated at maximally tolerable doses compared with the observation group in the European Organization for Research and Treatment of Cancer trial 18991 and has shown relapse-free survival benefits in patients with microscopic nodal disease.
Spin Torque, Tunnel-Current Spin Polarization, and Magnetoresistance in MgO Magnetic Tunnel Junctions (2006)

We employ the spin-torque response of magnetic tunnel junctions with ultrathin MgO tunnel barrier layers to investigate the relationship between spin transfer and tunnel magnetoresistance (TMR) under finite bias, and find that the spin torque per unit current exerted on the free layer decreases by < 10% over a bias range where the TMR decreases by > 40%. This is inconsistent with free-electron-like spin-polarized tunneling and reduced-surface-magnetism models of the TMR bias dependence, but is consistent with magnetic-state-dependent decay lengths in the tunnel barrier.
Functionalized Mesoporous Silica via an Aminosilane Surfactant Ion Exchange Reaction: Controlled Scaffold Design and Nitric Oxide Release (2015)

Nitric oxide-releasing mesoporous silica nanoparticles (MSNs) were prepared using an aminosilane-template surfactant ion exchange reaction. Initially, bare silica particles were synthesized under basic conditions in the presence of cetyltrimethylammonium bromide (CTAB). These particles were functionalized with nitric oxide (NO) donor precursors (i.e., secondary amines) via the addition of aminosilane directly to the particle sol and a commensurate ion exchange reaction between the cationic aminosilanes and CTAB. N-Diazeniumdiolate NO donors were formed at the secondary amines to yield NO-releasing MSNs. Tuning of the ion exchange-based MSN modification approach allowed for the preparation of monodisperse particles ranging from 30 to 1100 nm. Regardless of size, the MSNs stored appreciable levels of NO (0.4-1.5 μmol mg(-1)) with tunable NO release durations (1-33 h) dependent on the aminosilane modification. Independent control of NO release properties and particle size was achieved, demonstrating the flexibility of this novel MSN synthesis over conventional co-condensation and surface grafting strategies.
p53 can repress transcription of cell cycle genes through a p21WAF1/CIP1-dependent switch from MMB to DREAM protein complex binding at CHR promoter elements (2012)

The tumor suppressor p53 plays an important role in cell cycle arrest by downregulating transcription. Many genes repressed by p53 code for proteins with functions in G₂/M. A large portion of these genes is controlled by cell cycle-dependent elements (CDE) and cell cycle genes homology regions (CHR) in their promoters. Cyclin B2 is an example of such a gene, with a function at the transition from G₂ to mitosis. We find that p53-dependent downregulation of cyclin B2 promoter activity is dependent on an intact CHR element. In the presence of high levels of p53 or p21WAF1/CIP1, protein binding to the CHR switches from MMB to DREAM complex by shifting MuvB core-associated proteins from B-Myb to E2F4/DP1/p130. The results suggest a model for p53-dependent transcriptional repression by which p53 directly activates p21WAF1/CIP1. The inhibitor then prevents further phosphorylation of p130 by cyclin-dependent kinases. The presence of hypophosphorylated pocket proteins shifts the equilibrium for complex formation from MMB to DREAM. In the case of promoters that do not hold CDE or E2F elements, binding of DREAM and MMB solely relies on a CHR site. Thus, p53 can repress target genes indirectly through CHR elements.
Genetic and Serologic Properties of Zika Virus Associated with an Epidemic, Yap State, Micronesia, 2007 (2008)

Zika virus (ZIKV) is a mosquito-borne flavivirus first isolated in Uganda from a sentinel monkey in 1947. Mosquito and sentinel animal surveillance studies have demonstrated that ZIKV is endemic to Africa and Southeast Asia, yet reported human cases are rare, with <10 cases reported in the literature. In June 2007, an epidemic of fever and rash associated with ZIKV was detected in Yap State, Federated States of Micronesia. We report the genetic and serologic properties of the ZIKV associated with this epidemic.
xylA cloning and sequencing and biochemical characterization of xylose isomerase from Thermotoga neapolitana (1995)

The xylA gene coding for xylose isomerase from the hyperthermophile Thermotoga neapolitana 5068 was cloned, sequenced, and expressed in Escherichia coli. The gene encoded a polypeptide of 444 residues with a calculated molecular weight of 50,892. The native enzyme was a homotetramer with a molecular weight of 200,000. This xylose isomerase was a member of the family II enzymes (these differ from family I isomerases by the presence of approximately 50 additional residues at the amino terminus). The enzyme was extremely thermostable, with optimal activity above 95 degrees C. The xylose isomerase showed maximum activity at pH 7.1, but it had high relative activity over a broad pH range. The catalytic efficiency (kcat/Km) of the enzyme was essentially constant between 60 and 90 degrees C, and the catalytic efficiency decreased between 90 and 98 degrees C primarily because of a large increase in Km. The T. neapolitana xylose isomerase had a higher turnover number and a lower Km for glucose than other family II xylose isomerases. Comparisons with other xylose isomerases showed that the catalytic and cation binding regions were well conserved. Comparison of different xylose isomerase sequences showed that numbers of asparagine and glutamine residues decreased with increasing enzyme thermostability, presumably as a thermophilic strategy for diminishing the potential for chemical denaturation through deamidation at elevated temperatures.
A generalized object display processor architecture (1984)

The features and organization of a hardware architecture that is designed to facilitate the real-time display and manipulation of a single three-dimensional object on a raster-scan video display are briefly summarized. The author then outlines the major features of an extension to the architecture that will permit the high-speed display and manipulation of multiple, independent, shaded three-dimensional objects represented as a voxel (volume-element) database with gray scale. The objective is to provide many useful capabilities at or near video rates facilitating extensive real-time interaction. The architecture is highly modular, permitting a cost tradeoff to be made to achieve a given level of performance. It also includes a great deal of regularity in its structure, making it directly suitable for VLSI implementation. A key feature is that no computational operations more complex than adds, shifts, and comparisons are required in real time. The display characteristics for each object are controlled by a concise object descriptor table, which contains all of the control parameters required to process that object.
Alternative Splicing Determines the Binding of Platelet-Derived Growth Factor (PDGF-AA) to Glycosaminoglycans (1996)

We have shown previously that the platelet-derived growth factor (PDGF) and a synthetic oligopeptide, corresponding to the basic carboxyl-terminal amino acid extension of the long PDGF-A isoform, bind to heparin. Here, we have expressed the long (rA125) and the short (rA109) variants of PDGF A-chains in Escherichia coli and produced the functional homodimers. Surface plasmon resonance analyses showed that while the dimeric rA125 bound with high affinity to low molecular weight heparin, the rA109, lacking the basic extension, did not. This strongly indicated that high affinity binding is due to the carboxyl-terminal extension. Investigations of kinetics and thermodynamics suggested an allosteric binding mechanism. Thus, dimeric rA125 contains two equivalent binding sites. Following low affinity binding of heparin to one binding site, the dimer undergoes a conformational change, increasing the affinity for heparin about 40 times. This positive cooperativity requires the basic amino acid extension in both monomers of the dimeric PDGF molecule. Thermodynamics of the reaction, showing an entropy-driven endothermic process, suggest the involvement of hydrophobic interactions in this rearrangement. Three amino acids in the basic carboxyl-terminal extension were essential for the interaction: the basic residues Arg111 and Lys116, and the polar Thr125. We also found that other glycosaminoglycan species, corresponding to those produced by human arterial smooth muscle cells, bound to dimeric rA125 and that heparan sulfate showed the highest affinity.
The GATA-4 transcription factor transactivates the cardiac muscle-specific troponin C promoter-enhancer in nonmuscle cells. (1994)

The unique contractile phenotype of cardiac myocytes is determined by the expression of a set of cardiac muscle-specific genes. By analogy to other mammalian developmental systems, it is likely that the coordinate expression of cardiac genes is controlled by lineage-specific transcription factors that interact with promoter and enhancer elements in the transcriptional regulatory regions of these genes. Although previous reports have identified several cardiac muscle-specific transcriptional elements, relatively little is known about the lineage-specific transcription factors that regulate these elements. In this report, we demonstrate that the slow/cardiac muscle-specific troponin C (cTnC) enhancer contains a specific binding site for the lineage-restricted zinc finger transcription factor GATA-4. This GATA-4-binding site is required for enhancer activity in primary cardiac myocytes. Moreover, the cTnC enhancer can be transactivated by overexpression of GATA-4 in non-cardiac muscle cells such as NIH 3T3 cells. In situ hybridization studies demonstrate that GATA-4 and cTnC have overlapping patterns of expression in the hearts of postimplantation mouse embryos and that GATA-4 gene expression precedes cTnC expression. Indirect immunofluorescence reveals GATA-4 expression in cultured cardiac myocytes from neonatal rats. Taken together, these results are consistent with a model in which GATA-4 functions to direct tissue-specific gene expression during mammalian cardiac development.
Laboratory evaluations of the immediate and sustained efficacy of lotilaner (Credelio™) against four common species of ticks affecting dogs in North America (2017)

Lotilaner was completely effective against existing infestations with four common species of ticks, D. variabilis, R. sanguineus, A. americanum and I. scapularis, that affect dogs in North America, with at least 4 weeks efficacy of 98.0% or more against subsequent challenge infestations. These results show that lotilaner is a highly effective isoxazoline that offers sustained efficacy against ticks through and beyond the one-month end-of-dose treatment interval.
Mechanism of electron conduction in self-assembled alkanethiol monolayer devices (2003)

Electron tunneling through self-assembled monolayers (SAM's) of alkanethiols is investigated using nanometer-scale devices. Temperature-dependent current-voltage measurements are performed on alkanethiol SAM's to distinguish between different conduction mechanisms. Temperature-independent electron transport is observed, proving that tunneling is the dominant conduction mechanism of alkanethiols, as well as exhibiting an exponential dependence of tunneling current on the molecule length with a decay coefficient \ensuremath{\beta}. From the bias dependence of \ensuremath{\beta}, a barrier height ${\ensuremath{\Phi}}_{B}$ of $1.39\ifmmode\pm\else\textpm\fi{}0.01\mathrm{eV}$ and a zero-field decay coefficient ${\ensuremath{\beta}}_{0}$ of $0.79\ifmmode\pm\else\textpm\fi{}0.01{\AA{}}^{\ensuremath{-}1}$ are determined for alkanethiols.
The Role of Bruton's Tyrosine Kinase in Immune Cell Signaling and Systemic Autoimmunity (2018)

Bruton's tyrosine kinase (BTK) is an intracellular signaling molecule first identified as the molecule affected in X-linked agammaglobulinemia (XLA) patients, who almost completely lack peripheral B cells and serum immunoglobulins. BTK is crucial for B cell development and various B cell functions, including cytokine and natural antibody production. Importantly, it is also expressed in numerous other cells, including monocytes, macrophages, granulocytes, dendritic cells, and osteoclasts. A few rare cases of autoimmune disease in XLA patients have been described. Interestingly, increased BTK protein expression in patients with systemic autoimmune disease appears to be correlated with autoantibody production. In addition, BTK may promote autoimmunity as an important driver of an imbalance in B-T cell interaction. Because of this overwhelming evidence of a pathogenic role of BTK in autoimmunity, several clinical trials in rheumatoid arthritis and systemic lupus erythematosus patients with BTK inhibitors are currently running. Here, we review BTK function in different signaling pathways and in different cell lineages, focusing on the growing body of literature indicating a critical role for BTK in autoimmunity. We also discuss BTK and the promising results of BTK inhibition in animal models of autoimmune disease.
Modelling and robust control of fluidic thrust vectoring and circulation control for unmanned air vehicles (2008)

This paper presents actuator models for fluidic thrust vectoring and circulation control and they are used in the design of a robust controller for an unmanned air vehicle. The pitching and rolling moments for the aircraft are produced through the use of a co-flow fluidic thrust vectoring arrangement at the wing trailing edges. Experimental results for the co-flow actuators are used to derive mathematical models and their performance is compared with conventional control surfaces. For the controller design, nonlinear dynamic models are approximated by a simplified linear parameter varying (LPV) model. The polytopic nature of the controller is exploited to reformulate the LPV controller design problem into a μ-synthesis problem. The LPV controllers exhibit superior stability properties over the entire operating region, when compared to conventional gain-scheduling schemes.
Application of encapsulated cell technology for retinal degenerative diseases (2006)

Ophthalmic disorders represent a rapidly growing disease area that is associated with the ageing population. Their sight is threatened by age-related macular degeneration, diabetic retinopathy, glaucoma and/or retinitis pigmentosa (RP). Few effective treatments for these disorders are available at present, in part due to lack of effective delivery of therapeutic molecules to the retina. Encapsulated cell technology (ECT) allows the controlled, continuous and long-term administration of protein drugs in the eye, where therapeutic agents are needed, and does not subject the host to the systemic exposure. Furthermore, the implants can be retrieved, providing an added level of safety. Ciliary neurotrophic factor (CNTF) has been shown to protect the retina from degeneration in 13 animal models, and ECT-based delivery of CNTF protected photoreceptors in the rcd1 dog model of RP.
Characterization of the DNA polymerase gene of human herpesvirus 6 (1991)

The construction of a recombinant bacteriophage lambda library containing overlapping clones covering 155 kbp of the 161-kbp genome of the Ugandan U1102 isolate of human herpesvirus 6 (HHV-6) is described. The use of degenerate-primer polymerase chain reaction allowed the isolation of a DNA probe for the DNA polymerase gene of HHV-6, which was subsequently used to isolate and position the pol gene on the physical map of the viral genome. A 4.4-kbp EcoRI DNA restriction fragment containing the pol gene was isolated and sequenced. The open reading frames flanking the pol gene code for the HHV-6 glycoprotein B gene and the human cytomegalovirus UL53 homolog. This arrangement is different from that seen in the alpha and gamma herpesvirus families, lending further support to the notion that HHV-6 is a member of the beta herpesvirus group.
Dry etching for coherent refractive microlens arrays (1994)

Coherent arrays of refractive micro-optics are fabricated in the surface of silicon using a combination of lithographic and reactive-ion etching (RIE) techniques. The aspheric profile can be approximated in a stepwise manner by iterative steps of photolithography and RIE (binary optics technology), by direct etching of a preshaped polymer microlens etch mask into the substrate, or by analog etching of a lens profile directly into the substrate through a pinhole mask.
A control theoretic analysis of RED (2002)

We use a previously developed nonlinear dynamic model of TCP to analyze and design active queue management (AQM) control systems using random early detection (RED). First, we linearize the interconnection of TCP and a bottlenecked queue and discuss its feedback properties in terms of network parameters such as link capacity, load and round-trip time. Using this model, we next design an AQM control system using the RED scheme by relating its free parameters such as the low-pass filter break point and loss probability profile to the network parameters. We present guidelines for designing linearly stable systems subject to network parameters like propagation delay and load level. Robustness to variations in system loads is a prime objective. We present no simulations to support our analysis.