gebhart/patrepeval huggingface dataset:
Using PCR to Engineer DNA (1989)

PCR offers a means of much more quickly and easily modifying DNA fragments to meet specific needs than was previously available. This is because of the ease of PCR itself compared to recombinant DNA techniques, because sequence changes can much more readily be made in oligonucleotide primers chemically than by manipulating DNA fragments with restriction and ligation enzymes, and because PCR products can readily accept such sequence changes as 5’ “add-on” sequences to the primers. Furthermore, the efficiency at which modified product is produced is nearly 100%.
Allele-specific silencing of a pathogenic mutant acetylcholine receptor subunit by RNA interference (2003)

Slow channel congenital myasthenic syndrome (SCCMS) is a disorder of the neuromuscular synapse caused by dominantly inherited missense mutations in genes that encode the muscle acetylcholine receptor (AChR) subunits. Here we investigate the potential of post-transcriptional gene silencing using RNA interference (RNAi) for the selective down-regulation of pathogenic mutant AChR. By transfection of both siRNA and shRNA into mammalian cells expressing wild-type or mutant AChR subunits, we show, using 125I-alpha-bungarotoxin binding and immunofluorescence to measure cell surface AChR expression, efficient discrimination between the silencing of alphaS226F AChR mutant RNA transcripts and the wild-type. In this model we find that selectivity between mutant and wild-type transcripts is optimized with the nucleotide mismatch at position 9 in the shRNA complementary sequence. We also find that allele-specific silencing using shRNA has comparable efficiency to that using siRNA, underlining the general potential of stable expression of shRNA molecules as a long term therapeutic approach for allele-specific silencing of mutant transcripts in dominant genetic disorders.
THERAPEUTIC HYPOTHERMIA IN PATIENTS WITH ANEURYSMAL SUBARACHNOID HEMORRHAGE, REFRACTORY INTRACRANIAL HYPERTENSION, OR CEREBRAL VASOSPASM (2009)

Prolonged systemic hypothermia may be considered as a last-resort option for a carefully selected group of SAH patients with intracranial hypertension or CVS resistant to conventional treatment. However, complications associated with hypothermia require elaborate protocols in general intensive care unit management.
Microalbuminuria Associated With Diabetic Neuropathy (1992)

Microalbuminuria is independently associated with diabetic neuropathy. This association lends support to the theory of a vascular etiology for diabetic distal symmetrical neuropathy.
Sulfatide, a Specific Sugar Ligand for L-Selectin, Blocks CCI4-induced Liver Inflammation in Rats (1995)

The effects of sulfatide, which is a specific sugar ligand for L-selectin (LECAM-1), on CCl4-induced liver inflammation was studied in rats. Intramuscular pretreatment with sulfatide suppressed the levels of serum glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) that were increased by CCl4 injection, but galactosylceramide, a desulfated form of sulfatide, did not. A light-microscopic analysis found that the extent and the severity of lesions of the liver cells induced by CCl4 injection were significantly less in the rats treated with sulfatide. These results show that sulfatide suppresses the CCl4-induced liver inflammation by inhibiting the attachment of L-selectin expressing lymphocytes to their native sugar ligands.
Lysyl Oxidase Regulates Breast Cancer Cell Migration and Adhesion through a Hydrogen Peroxide–Mediated Mechanism (2005)

We have previously shown that lysyl oxidase (LOX) mRNA is up-regulated in invasive breast cancer cells and that catalytically active LOX facilitates in vitro cell invasion. Here we validate our in vitro studies by showing that LOX expression is up-regulated in distant metastatic breast cancer tissues compared with primary cancer tissues. To elucidate the mechanism by which LOX facilitates cell invasion, we show that catalytically active LOX regulates in vitro motility/migration and cell-matrix adhesion formation. Treatment of the invasive breast cancer cell lines, Hs578T and MDA-MB-231, with beta-aminopropionitrile (betaAPN), an irreversible inhibitor of LOX catalytic activity, leads to a significant decrease in cell motility/migration and adhesion formation. Conversely, poorly invasive MCF-7 cells expressing LOX (MCF-7/LOX32-His) showed an increase in migration and adhesion that was reversible with the addition of betaAPN. Moreover, a decrease in activated focal adhesion kinase (FAK) and Src kinase, key proteins involved in adhesion complex turnover, was observed when invasive breast cancer cells were treated with betaAPN. Additionally, FAK and Src activation was increased in MCF-7/LOX32-His cells, which was reversible on betaAPN treatment. Hydrogen peroxide was produced as a by-product of LOX activity and the removal of hydrogen peroxide by catalase treatment in invasive breast cancer cells led to a dose-dependent loss in Src activation. These results suggest that LOX facilitates migration and cell-matrix adhesion formation in invasive breast cancer cells through a hydrogen peroxide-mediated mechanism involving the FAK/Src signaling pathway. These data show the need to target LOX for treatment of aggressive breast cancer.
Utilization of high-frequency Rayleigh waves in near-surface geophysics (2004)

Rayleigh waves, surface waves that travel along a “free” surface such as the earth-air or the earth-water interface, are usually characterized by relatively low velocity, low frequency, and high amplitude. Rayleigh waves are the result of interfering P and SV waves. Particle motion of the fundamental mode of Rayleigh waves in a homogeneous medium moving from left to right is elliptical in a counter-clockwise (retrograde) direction along the free surface. As depth increases, the particle motion becomes prograded and is still elliptical when reaching sufficient depth. The motion is constrained to a vertical plane consistent with the direction of wave propagation.
Atherogenic levels of low-density lipoprotein increase hydrogen peroxide generation in cultured human endothelial cells: Possible mechanism of heightened endocytosis (1996)

Cultured human umbilical vein endothelial cells(EC) exposed to atherogenic low-density lipoprotein (LDL) levels have augmented reactive oxygen species generation. Confluent EC were incubated with 30-330 mg/dl LDL cholesterol and cellular hydrogen peroxide (H2O2) generation measured. EC incubated with 30 and 90 mg/dl LDL cholesterol showed similar low level H2O2 production. In contrast, EC exposed to 180 and 330 mg/dl LDL cholesterol have a marked, dose-related elevation in H2O2 generation. Subsequent studies have explored if direct EC exposure to H2O2 promotes cellular functional changes similar to those induced by high LDL levels (> 160 mg/dl cholesterol). Confluent EC were incubated with 0.1-10 mM H2O2 for 30 minutes and endocytosis measured and cytoskeletal structure examined. H2O2 exposure (0.5 and 1 mM) promoted heightened EC endocytosis, which similarly occurs with high LDL exposure. Likewise, cytoskeletal examination of EC perturbed with 1 mM H2O2 reveals structural remodeling with a marked increase in stress fibers, which similarly happens with high LDL levels. The above observations that high LDL levels cause increased EC H2O2 production, and direct H2O2 exposure promotes cellular functional changes similar to those induced by high LDL concentrations, suggest a modulatory role for reactive oxygen species. Thus LDL-induced reactive oxygen species generation may contribute mechanistically to endothelial perturbation, which has been hypothesized to be a major contributing factor in the pathogenesis of atherosclerosis.
<title>Advanced fiber-grating strain sensor systems for bridges, structures, and highways</title> (1998)

Fiber Bragg grating sensor systems have wide application in the area of civil structures. The advantages of fiber grating strain sensors over electrical strain gauges such as greatly reduced size, EMI resistance, and higher temperature capability make them ideal choices for smart structure applications. Some of these fiber grating sensor systems can measure or detect multiaxis strain, transverse strain, temperature, bridge scouring, ice, and traffic flow.
Mechanical properties of biodegradable composites from poly lactic acid (PLA) and microcrystalline cellulose (MCC) (2005)

Abstract Biodegradable composites were prepared using microcrystalline cellulose (MCC) as the reinforcement and polylactic acid (PLA) as a matrix. PLA is polyester of lactic acid and MCC is cellulose derived from high quality wood pulp by acid hydrolysis to remove the amorphous regions. The composites were prepared with different MCC contents, up to 25 wt %, and wood flour (WF) and wood pulp (WP) were used as reference materials. Generally, the MCC/PLA composites showed lower mechanical properties compared to the reference materials. The dynamic mechanical thermal analysis (DMTA) showed that the storage modulus was increased with the addition of MCC. The X‐ray diffraction (XRD) studies on the materials showed that the composites were less crystalline than the pure components. However, the scanning electron microscopy (SEM) study of materials showed that the MCC was remaining as aggregates of crystalline cellulose fibrils, which explains the poor mechanical properties. Furthermore, the fracture surfaces of MCC composites were indicative of poor adhesion between MCC and the PLA matrix. Biodegradation studies in compost soil at 58°C showed that WF composites have better biodegradability compared to WP and MCC composites. The composite performances are expected to improve by separation of the cellulose aggregates to microfibrils and with improved adhesion. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 97: 2014–2025, 2005
Tunable passive colliding-pulse mode locking in a linear dye laser (1984)

We demonstrate the versatile operation of a linear femtosecond dye laser that terminates in an antiresonant ring for passive colliding-pulse mode locking. The system combines several advantages of a conventional ring laser with those of a linear laser and in addition offers the unique possibility of continuously tuning the pulse-repetition rate over a 1-GHz band. Moreover, the geometry allows a commercial linear laser to be mode locked easily without significant cavity changes.
Cancer Biomarkers: Easier Said Than Done (2002)

With the above enablers, novel cancer biomarkers may be useful, both for assessing early and established neoplasia more precisely and for contributing data toward development of novel practical concepts regarding cancer biology.
Increased Adhesion and Aggregation of Platelets Lacking Cyclic Guanosine 3′,5′-Monophosphate Kinase I (1999)

Atherosclerotic vascular lesions are considered to be a major cause of ischemic diseases, including myocardial infarction and stroke. Platelet adhesion and aggregation during ischemia-reperfusion are thought to be the initial steps leading to remodeling and reocclusion of the postischemic vasculature. Nitric oxide (NO) inhibits platelet aggregation and smooth muscle proliferation. A major downstream target of NO is cyclic guanosine 3', 5'-monophosphate kinase I (cGKI). To test the intravascular significance of the NO/cGKI signaling pathway in vivo, we have studied platelet-endothelial cell and platelet-platelet interactions during ischemia/reperfusion using cGKI-deficient (cGKI-/-) mice. Platelet cGKI but not endothelial or smooth muscle cGKI is essential to prevent intravascular adhesion and aggregation of platelets after ischemia. The defect in platelet cGKI is not compensated by the cAMP/cAMP kinase pathway supporting the essential role of cGKI in prevention of ischemia-induced platelet adhesion and aggregation.
Simulations of nuclear pore transport yield mechanistic insights and quantitative predictions (2011)

To study transport through the nuclear pore complex, we developed a computational simulation that is based on known structural elements rather than a particular transport model. Results agree with a variety of experimental data including size cutoff for cargo transport with (30-nm diameter) and without (< 10 nm) nuclear localization signals (NLS), macroscopic transport rates (hundreds per second), and single cargo transit times (milliseconds). The recently observed bimodal cargo distribution is predicted, as is the relative invariance of single cargo transit times out to large size (even as macroscopic transport rate decreases). Additional predictions concern the effects of the number of NLS tags, the RanGTP gradient, and phenylalanine-glycine nucleopore protein (FG-Nup) structure, flexibility, and cross-linking. Results are consistent with and elucidate the molecular mechanisms of some existing hypotheses (selective phase, virtual gate, and selective gate models). A model emerges that is a hybrid of a number of preexisting models as well as a Brownian ratchet model, in which a cargo-karyopherin complex remains bound to the same FG-Nups for its entire trajectory through the nuclear pore complex until RanGTP severs the cargo-Nup bonds to effect release into the nucleus.
Analysis of subunit assembly of the Na-K-ATPase (1994)

The Na-K-ATPase, or sodium pump, is comprised of two subunits, alpha and beta. Each subunit spans the lipid bilayer of the cell membrane. This review summarizes our efforts to determine how the two subunits interact to form the functional ion transporter. Our major approach has been to observe the potential for subunit assembly when one or both subunits are truncated or present as chimeras that retain only a limited region of the Na-K-ATPase. DNAs encoding these altered subunit forms of the avian Na-K-ATPase are expressed in mammalian cells. Monoclonal antibodies specific for the avian beta-subunit are then used to purify newly synthesized avian beta-subunits, and the presence of accompanying alpha-subunits indicates that subunit assembly has occurred. The ectodomain of the beta-subunit (approximately residues 62-304) is sufficient for assembly with the alpha-subunit, and a COOH-terminal truncation of the beta-subunit that lacks aminoacyl residues beyond 162 will assemble inefficiently. A maximum of 26 aminoacyl residues of the alpha-subunit are necessary for robust assembly with the beta-subunit, when this sequence replaces the COOH-terminal half of the loop between membrane spans 7 and 8 in the SERCA1 Ca-ATPase. This region of the Ca-ATPase faces the lumen of the endoplasmic reticulum. These findings encourage study of other related questions, including whether there is preferential assembly of certain subunit isoforms and how various P-type ATPases are targeted to their appropriate subcellular compartments.
An Electronic, Aptamer-Based Small-Molecule Sensor for the Rapid, Label-Free Detection of Cocaine in Adulterated Samples and Biological Fluids (2006)

Whereas spectroscopic and chromatographic techniques for the detection of small organic molecules have achieved impressive results, these methods are generally slow and cumbersome, and thus the development of a general means for the real-time, electronic detection of such targets remains a compelling goal. Here we demonstrate a potentially general, label-free electronic method for the detection of small-molecule targets by building a rapid, reagentless biosensor for the detection of cocaine. The sensor, based on the electrochemical interrogation of a structure-switching aptamer, specifically detects micromolar cocaine in seconds. Because signal generation is based on binding-induced folding, the sensor is highly selective and works directly in blood serum and in the presence of commonly employed interferents and cutting agents, and because all of the sensor components are covalently attached to the electrode surface, the sensor is also reusable: we achieve >99% signal regeneration upon a brief, room temperature aqueous wash. Given recent advances in the generation of highly specific aptamers, this detection platform may be readily adapted for the detection of other small molecules of a wide range of clinically and environmentally relevant small molecules.
Development of a pointing, acquisition, and tracking system for a CubeSat optical communication module (2015)

Miniaturized satellites such as CubeSats continue to improve their capabilities to enable missions that can produce significant amounts of data. For most CubeSat missions, data must be downlinked during short low-earth orbit ground station passes, a task currently performed using traditional radio systems. Free-space optical communications take advantage of the high gain of a narrow optical beam to achieve better link efficiency, allowing more valuable data to be downlinked over the mission lifetime. We present the Nanosatellite Optical Downlink Experiment (NODE) design, capable of providing a typical 3U (30 x 10 x 10 cm) CubeSat with a comparatively high data-rate downlink. The NODE optical communication module is designed to fit within a 5 x 10 x 10 cm volume, weigh less than 1 kg, and consume no more than 10Wof power during active communication periods. Our design incorporates a fine-steering mechanism and beacon-tracking system to achieve a 10 Mbps link rate. We describe the system-level requirements and designs for key components, including a transmitter, a beacon tracking camera, and a fast-steering mirror. We present simulation results of the uplink beacon tracking and fine steering of the downlink beam, including the effects of atmospheric fading and on-orbit environmental disturbances to demonstrate the feasibility of this approach.
Vaccination with peptide mimetics of the gp41 prehairpin fusion intermediate yields neutralizing antisera against HIV-1 isolates (2010)

Eliciting a broadly neutralizing polyclonal antibody response against HIV-1 remains a major challenge. One approach to vaccine development is prevention of HIV-1 entry into cells by blocking the fusion of viral and cell membranes. More specifically, our goal is to elicit neutralizing antibodies that target a transient viral entry intermediate (the prehairpin intermediate) formed by the HIV-1 gp41 protein. Because this intermediate is transient, a stable mimetic is required to elicit an immune response. Previously, a series of engineered peptides was used to select a mAb (denoted D5) that binds to the surface of the gp41 prehairpin intermediate, as demonstrated by x-ray crystallographic studies. D5 inhibits the replication of HIV-1 clinical isolates, providing proof-of-principle for this vaccine approach. Here, we describe a series of peptide mimetics of the gp41 prehairpin intermediate designed to permit a systematic analysis of the immune response generated in animals. To improve the chances of detecting weak neutralizing polyclonal responses, two strategies were employed in the initial screening: use of a neutralization-hypersensitive virus and concentration of the IgG fraction from immunized animal sera. This allowed incremental improvements through iterative cycles of design, which led to vaccine candidates capable of generating a polyclonal antibody response, detectable in unfractionated sera, that neutralize tier 1 HIV-1 and simian HIV primary isolates in vitro. Our findings serve as a starting point for the design of more potent immunogens to elicit a broadly neutralizing response against the gp41 prehairpin intermediate.
Protein-Resistant Polymer Coatings on Silicon Oxide by Surface-Initiated Atom Transfer Radical Polymerization (2006)

The modification of silicon oxide with poly(ethylene glycol) to effectively eliminate protein adsorption has proven to be technically challenging. In this paper, we demonstrate that surface-initiated atom transfer radical polymerization (SI-ATRP) of oligo(ethylene glycol) methyl methacrylate (OEGMA) successfully produces polymer coatings on silicon oxide that have excellent protein resistance in a biological milieu. The level of serum adsorption on these coatings is below the detection limit of ellipsometry. We also demonstrate a new soft lithography method via which SI-ATRP is integrated with microcontact printing to create micropatterns of poly(OEGMA) on glass that can spatially direct the adsorption of proteins on the bare regions of the substrate. This ensemble of methods will be useful in screening biological interactions where nonspecific binding must be suppressed to discern low probability binding events from a complex mixture and to pattern anchorage-dependent cells on glass and silicon oxide.
Adjoint Sensitivity Analysis for Shallow-Water Wave Control (2000)

An adjoint sensitivity method based on the shallow-water equations is developed for water wave control in river and estuarine systems. The method is used to compute the gradient of a user-defined objective function in the N-dimensional parameter space consisting of system control settings with just one solution of the basic problem and one solution of the associated adjoint problem. Characteristic equations are derived for the adjoint problem and a new formalism is proposed for the sensitivity of shallow-water flow to boundary changes in depth and discharge. New adjoint boundary conditions are developed for river and estuarine forecasting models with open-water inflow and outflow sections. This gives rise to new expressions for sensitivities at these sections. Characteristic analysis of the adjoint and basic problems shows that sensitivities propagate in the reverse time direction along the characteristic paths of the basic problem. The Riemann variables of the adjoint problem are shown to precisely describe the sensitivity of the objective function to changes in depth and discharge at system boundaries. The method is extended to two space dimensions by bicharacteristic analysis.
Accessing Epstein-Barr Virus-Specific T-Cell Memory with Peptide-Loaded Dendritic Cells (1999)

The conventional means of studying Epstein-Barr virus (EBV)-induced cytotoxic T-lymphocyte (CTL) memory, by in vitro stimulation with the latently infected autologous lymphoblastoid cell line (LCL), has important limitations. First, it gives no information on memory to lytic cycle antigens; second, it preferentially amplifies the dominant components of latent antigen-specific memory at the expense of key subdominant reactivities. Here we describe an alternative approach, based on in vitro stimulation with epitope peptide-loaded dendritic cells (DCs), which allows one to probe the CTL repertoire for any individual reactivity of choice; this method proved significantly more efficient than stimulation with peptide alone. Using this approach we first show that reactivities to the immunodominant and subdominant lytic cycle epitopes identified by T cells during primary EBV infection are regularly detectable in the CTL memory of virus carriers; this implies that in such carriers chronic virus replication remains under direct T-cell control. We further show that subdominant latent cycle reactivities to epitopes in the latent membrane protein LMP2, though rarely undetectable in LCL-stimulated populations, can be reactivated by DC stimulation and selectively expanded as polyclonal CTL lines; the adoptive transfer of such preparations may be of value in targeting certain EBV-positive malignancies.