gebhart/patrepeval huggingface dataset:
Matrix-bound nanovesicles prevent ischemia-induced retinal ganglion cell axon degeneration and death and preserve visual function (2019)

Injury to retinal ganglion cells (RGC), central nervous system neurons that relay visual information to the brain, often leads to RGC axon degeneration and permanently lost visual function. Herein this study shows matrix-bound nanovesicles (MBV), a distinct class of extracellular nanovesicle localized specifically to the extracellular matrix (ECM) of healthy tissues, can neuroprotect RGCs and preserve visual function after severe, intraocular pressure (IOP) induced ischemia in rat. Intravitreal MBV injections attenuated IOP-induced RGC axon degeneration and death, protected RGC axon connectivity to visual nuclei in the brain, and prevented loss in retinal function as shown by histology, anterograde axon tracing, manganese-enhanced magnetic resonance imaging, and electroretinography. In the optic nerve, MBV also prevented IOP-induced decreases in growth associated protein-43 and IOP-induced increases in glial fibrillary acidic protein. In vitro studies showed MBV suppressed pro-inflammatory signaling by activated microglia and astrocytes, stimulated RGC neurite growth, and neuroprotected RGCs from neurotoxic media conditioned by pro-inflammatory astrocytes. Thus, MBV can positively modulate distinct signaling pathways (e.g., inflammation, cell death, and axon growth) in diverse cell types. Since MBV are naturally derived, bioactive factors present in numerous FDA approved devices, MBV may be readily useful, not only experimentally, but also clinically as immunomodulatory, neuroprotective factors for treating trauma or disease in the retina as well as other CNS tissues.
Self-localization of a mobile swarm using noise correlations with local sources of opportunity (2018)

Groups of coordinated underwater vehicles or sensors are powerful tools for monitoring the ocean. A requirement of many coordinated surveys is to determine a spatial reference between each node in a swarm. This work considers the self-localization of a swarm of independently moving vehicles using acoustic noise from a dominating incoherent source recorded by a single hydrophone onboard each vehicle. This method provides an inexpensive and infrastructure-free spatial reference between vehicles. Movement between the vehicles changes the swarm geometry and a self-localization estimate must be generated from data collected on short time scales. This challenges past self-localization approaches for acoustic arrays. To overcome this challenge, the proposed self-localization algorithm jointly estimates the vehicle geometry and the directionality of the ambient noise field, without prior knowledge of either estimate. To demonstrate this method, experimental results are provided when a boat is the main dominating source. The results demonstrate the ability to both estimate the direction of arrival of the boat and the relative positions of the vehicles in the swarm. The approach in this paper is not limited to moving vessels. Simulations are provided to examine three different factors that affect the proposed solution: inter-vehicle motion, vehicle geometry, and the azimuthal variance of the noise field.
Chimeric Antigen Receptor-T-Cell Therapy for B-Cell Hematological Malignancies: An Update of the Pivotal Clinical Trial Data (2020)

Chimeric antigen receptor (CAR)-T-cell therapy is an innovative form of adoptive cell therapy that has revolutionized the treatment of certain hematological malignancies, including B-cell non-Hodgkin lymphoma (NHL) and B-cell acute lymphoblastic leukemia (ALL). The treatment is currently also being studied in other B-cell neoplasms, including multiple myeloma (MM) and chronic lymphocytic leukemia (CLL). CD19 and B-cell maturation antigen (BCMA) have been the most popular target antigens for CAR-T-cell immunotherapy of these malignancies. This review will discuss the efficacy and toxicity data from the pivotal clinical studies of CD19- and BCMA-targeted CAR-T-cell therapies in relapsed/refractory B-cell malignancies (NHL, ALL, CLL) and MM, respectively.
Disinfection by-products and microbial contamination in the treatment of pool water with granular activated carbon (2005)

For swimming pools, it is generally agreed that free chlorine levels have to be maintained to guarantee adequate disinfection. Recommended free chlorine levels can vary between 0.3 and 0.6 mg/L in Germany and up to 3 mg/L in other countries. Bathers introduce considerable amounts of organic matter, mainly in the form of such as urine and sweat, into the pool water. As a consequence, disinfection byproducts (DBPs) are formed. Regulations in Germany recommend levels of combined chlorine of less than 0.2 mg/L and levels of trihalomethanes (THMs) of less than 20 microg/L. Haloacetic acids (HAAs), haloacetonitriles (HANs), chloropicrin and chloral hydrate are also detected in considerable amounts. However, these compounds are not regulated yet. Swimming pool staff and swimmers, especially athletes, are primarily exposed to these byproducts by inhalation and/or dermal uptake. In Germany, new regulations for swimming pool water treatment generally require the use of activated carbon. In this project, three different types of granular activated carbon (GAC) (one standard GAC, two catalytic GACs) are compared for their long time behaviour in pool water treatment. In a pilot plant operated with real swimming pool water, production and removal of disinfection byproducts (THMs, HAAs, AOXs), of biodegradable substances (AOC), of bacteria (Pseudomonas aeruginosa, Legionella, coliforms, HPC) as well as the removal of chlorine and chloramines are monitored as function of GAC bed depth. Combined chlorine penetrates deeper in the filter bed than free chlorine does. However, both, free and combined chlorine removal efficiencies decrease over the time of filter operation. The decreases of removal efficiencies are also observed for parameters such as dissolved organic carbon, spectral absorption coefficient, adsorbable organic carbon and most of the disinfection byproducts. However, THMs, especially chloroform are produced in the filter bed. The GAC beds were contaminated microbially, especially with P. aeruginosa. The contamination was not removable by backwashing with chlorine concentrations up to 2 mg/l free chlorine.
The immunology of neurodegeneration (2012)

While immune responses in neurodegeneration were regarded as little more than a curiosity a decade ago, they are now increasingly moving toward center stage. Factors driving this movement include the recognition that most of the relevant immune molecules are produced within the brain, that microglia are proficient immune cells shaping neuronal circuitry and fate, and that systemic immune responses affect brain function. We will review this complex field from the perspective of neurons, extra-neuronal brain cells, and the systemic environment and highlight the possibility that cell intrinsic innate immune molecules in neurons may function in neurodegenerative processes.
Target organ disposition and plasma pharmacokinetics of doxorubicin incorporated into albumin microspheres after intrarenal arterial administration (1988)

We synthesized doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH)-loaded human albumin microspheres (containing approximately 1% doxorubicin w/w) between 15 and 20 micron in diameter. Intrarenal arterial administration of 99mTC-labeled microspheres demonstrated a high renal entrapment ratio (97% of recovered radioactivity). The pharmacokinetics and metabolism of doxorubicin are different when it is administered in microspherical form. Peak plasma levels are lower (16 ng/ml versus 135 ng/ml) compared with treatment by a doxorubicin solution. Histologic studies showed that the microspheres were trapped within capillaries and small arterioles in the renal vascular arcade. It is apparent that chemoembolization with doxorubicin-loaded microspheres significantly reduces systemic exposure to the antineoplastic agent, and maintains intrarenal drug levels.
Synthesis and bioactivity evaluation of novel spiromesifen derivatives (2011)

The present work demonstrates that some spiromesifen derivatives can be used as potential lead compounds for developing novel insecticides and acaricides.
Non-Separable Preferences in the Statistical Analysis of Roll Call Votes (2022)

Abstract Conventional multidimensional statistical models of roll call votes assume that legislators’ preferences are additively separable over dimensions. In this article, we introduce an item response model of roll call votes that allows for non-separability over latent dimensions. Conceptually, non-separability matters if outcomes over dimensions are related rather than independent in legislators’ decisions. Monte Carlo simulations highlight that separable item response models of roll call votes capture non-separability via correlated ideal points and higher salience of a primary dimension. We apply our model to the U.S. Senate and the European Parliament. In both settings, we find that legislators’ preferences over two basic dimensions are non-separable. These results have general implications for our understanding of legislative decision-making, as well as for empirical descriptions of preferences in legislatures.
Identification of platelet proteins separated by two-dimensional gel electrophoresis and analyzed by matrix assisted laser desorption/ionization-time of flight-mass spectrometry and detection of tyrosine-phosphorylated proteins (2000)

Different search programs were compared to judge their particular efficiency in protein identification. We established a human blood platelet protein map and identified tyrosine-phosphorylated proteins. The cytosolic fraction of human blood platelets was separated by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and phosphorylated proteins were detected by Western blotting using anti-phosphotyrosine antibodies. Visualized protein spots were excised, digested with trypsin and analyzed by matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS). The obtained mass fingerprint data sets have been analyzed using ProFound, MS-Fit and Mascot. For those protein spots with no significant search results MALDI post source decay (PSD) spectra have been acquired on the same sample. For automatic interpretation of these fragment ion spectra, the SEQUEST and Mascot algorithm were applied. Another approach for the identification of phosphorylated proteins is immunoprecipitation using an anti-phosphotyrosine antibody. A method for immunoprecipitation of tyrosine-phosphorylated peptides was optimized.
Optimal Application Conditions for Steam/Solvent Coinjection (2015)

Summary Laboratory and field data, although limited in number, have shown that steam/solvent coinjection can lead to a higher oil-production rate, higher ultimate oil recovery, and lower steam/oil ratio, compared with steam-only injection in steam-assisted gravity drainage (SAGD). However, a critical question still remains unanswered: Under what circumstances can the previously mentioned benefits be obtained when steam and solvent are coinjected? To answer this question requires a detailed knowledge of the mechanisms involved in coinjection and an application of this knowledge to numerical simulation. Our earlier studies demonstrated that the determining factors for improved oil-production rates are relative positions with respect to the temperature and solvent fronts, the steam and solvent contents of the chamber at its interface with reservoir bitumen, and solvent-diluting effects on the mobilized bitumen just ahead of the chamber edge. Then, the key mechanisms for improved oil displacement are solvent propagation, solvent accumulation at the chamber edge, and phase transition. This paper deals with this unanswered question by providing some key guidelines for selecting an optimum solvent and its concentration in coinjection of a single-component solvent with steam. The optimization considers the oil-production rate, ultimate oil recovery, and solvent retention in situ. Multiphase behavior of water/hydrocarbon mixtures in the chamber is explained in detail analytically and numerically. The proposed guidelines are applied to simulation of the Senlac solvent-aided-process pilot and the Long Lake expanding-solvent SAGD pilot. Results show that an optimum volatility of solvent can be typically observed in terms of the oil-production rate for given operation conditions. This optimum volatility occurs as a result of the balance between two factors affecting the oil mobility along the chamber edge: reduction of the chamber-edge temperature and superior dilution of oil in coinjection of more-volatile solvent with steam. It is possible to maximize oil recovery and minimize solvent retention in situ by controlling the concentration of a given coinjection solvent. Beginning coinjection immediately after achieving interwell communication enables the enhancement of oil recovery early in the process. Subsequently, the solvent concentration should be gradually decreased until it becomes zero for the final period of the coinjection. Simulation case studies show the validity of the oil-recovery mechanisms described. In the final section of the paper, a limited economic analysis of SAGD and different coinjection cases is provided.
Modeling Domino Effects in Enzymes:  Molecular Basis of the Substrate Specificity of the Bacterial Metallo-β-lactamases IMP-1 and IMP-6 (2003)

Metallo-beta-lactamases can hydrolyze a broad spectrum of beta-lactam antibiotics and thus confer resistance to bacteria. For the Pseudomonas aeruginosa enzyme IMP-1, several variants have been reported. IMP-6 and IMP-1 differ by a single residue (glycine and serine at position 196, respectively), but have significantly different substrate spectra; while the catalytic efficiency toward the two cephalosporins cephalothin and cefotaxime is similar for both variants, IMP-1 is up to 10-fold more efficient than IMP-6 toward cephaloridine and ceftazidime. Interestingly, this biochemical effect is caused by a residue remote from the active site. The substrate-specific impact of residue 196 was studied by molecular dynamics simulations using a cationic dummy atom approach for the zinc ions. Substrates were docked in an intermediate structure near the transition state to the binding site of IMP-1 and IMP-6. At a simulation temperature of 100 K, most complexes were stable during 1 ns of simulation time. However, at higher temperatures, some complexes became unstable and the substrate changed to a nonactive conformation. To model stability, six molecular dynamics simulations at 100 K were carried out for all enzyme-substrate complexes. Stable structures were further heated to 200 and 300 K. By counting stable structures, we derived a stability ranking score which correlated with experimentally determined catalytic efficiency. The use of a stability score as an indicator of catalytic efficiency of metalloenzymes is novel, and the study of substrates in a near-transition state intermediate structure is superior to the modeling of Michaelis complexes. The remote effect of residue 196 can be described by a domino effect: upon replacement of serine with glycine, a hole is created and a stabilizing interaction between Ser196 and Lys33 disappears, rendering the neighboring residues more flexible; this increased flexibility is then transferred to the active site.
Contracted Gaussian basis sets for molecular calculations. I. Second row atoms, <i>Z</i>=11–18 (1980)

Contracted Gaussian basis sets for molecular calculations are derived from uncontracted (12,8) and (12,9) sets for the neutral second row atoms, Z=11–18, and for the negative ions P−, S−, and Cl−. Calculations on Na...2p63p, 2P and Mg...2p63s3p, 3P are used to derive contracted Gaussian functions to describe the 3p orbital in these atoms, necessary in molecular applications. The derived basis sets range from minimal, through double-zeta, to the largest set which has a triple-zeta basis for the 3p orbital, double-zeta for the remaining. Where necessary to avoid unacceptable energy losses in atomic wave functions expanded in the contracted Gaussians, a given uncontracted Gaussian function is used in two contracted functions. These tabulations provide a hierarchy of basis sets to be used in designing a convergent sequence of molecular computations, and to establish the reliability of the molecular properties under study.
Efficient block ciphers for smartcards (1999)

We present a family of block ciphers that can be implemented very efficiently on cheap Smartcard processors. The ciphers use a very small amount of RAM and a reasonable amount of ROM. Both cipher execution and key setup/key change are very fast. The ciphers resist theoretical and practical cryptanalytic attacks and in their design timing and power analysis attacks have been taken into account.
Assessment of Multimode Spacecraft Micropropulsion Systems (2017)

Multimode spacecraft micropropulsion systems that include a high-thrust chemical mode and high-specific impulse electric mode are assessed with specific reference to CubeSat-sized satellite applications. Both cold-gas butane propellant and ionic liquid chemical monopropellant modes are investigated alongside pulsed plasma, electrospray, and ion electric thruster modes. These systems are studied by varying electric propulsion usage percent and calculating the payload mass fraction and thruster burn time for missions requiring 250, 500, and delta-V. Systems involving chemical monopropellants have the highest payload mass fractions for a reference mission of delta-V and 6U-sized CubeSat, where 1U is a volume, for electric propulsion usage below 70% of total delta-V; whereas for higher electric propulsion usage, cold-gas thrusters deliver a higher payload mass fraction due to lower system inert mass. Due to the combination of a shared propellant for both propulsive modes, low inert mass, high electric thrust, and specific impulse near optimum for the system, the monopropellant/electrospray system has the highest mission capability in terms of delta-V for missions lasting less than 150 days.
Albumin transport and processing by the proximal tubule: physiology and pathophysiology (2007)

The currently defined mechanisms underpinning the tubular reabsorption of albumin, how these are modified by pathology and pharmacology, and the clinical implications are the subject of this review.
Getting It Right: How Public Engagement Might (and Might Not) Help Us Determine What Is Equitable in Genomics and Precision Medicine (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Rare Disease, Advocacy and Justice: Intersecting Disparities in Research and Clinical CareThe Promise and Reality of Public Engagement in the Governance of Human Genome Editing ResearchIs It Just for a Screening Program to Give People All the Information They Want?Bounded Justice, Inclusion, and the Hyper/Invisibility of Race in Precision MedicinePromoting Equality in the Governance of Heritable Human Genome Editing through Ubuntu: Reflecting on a South African Public Engagement Study ACKNOWLEDGMENTSThe authors thank their colleagues at NIH for providing critical feedback on this commentary.Additional informationFundingThis work was supported in part by the Intramural Research Programs of the National Human Genome Research Institute.
A Novel gene overexpression plasmid library and its application in mapping genetic networks by systematic dosage suppression (2012)

Increasing gene dosage provides a powerful means of probing gene function, as it tends to cause a gain-of-function effect due to increased gene activity. In the budding yeast, Saccharomyces cerevisiae, systematic gene overexpression studies have shown that in wild-type cells, overexpression of a small subset of genes results in an overt phenotype. However, examining the effects of gene overexpression in sensitized cells containing mutations in known genes is a powerful means for identifying functionally relevant genetic interactions. When a query mutant phenotype is rescued by gene overexpression, the genetic interaction is termed dosage suppression. I comprehensively investigated dosage suppression genetic interactions in yeast using three approaches. First, using one of two novel plasmid libraries cloned by two colleagues and myself, I systematically performed dosage suppression screens and identified over 130 novel dosage suppression genetic interactions for more than 25 essential yeast genes. The plasmid libraries, called the molecular barcoded yeast ORF (MoBY-ORF) 1.0 and 2.0, are designed to streamline dosage analysis by being compatible with high-throughput genomics technologies that can monitor plasmid representation, including barcode microarrays and next-generation sequencing methods. Second, I describe a detailed analysis of the novel dosage suppression interactions, as well as of literature-curated interactions, and show that the gene pairs exhibiting dosage suppression are often functionally related and can overlap with physical as well as negative genetic interactions. Third, I performed a systematic categorization of dosage suppression genetic interactions in yeast and show that the majority of the dosage suppression interactions can be assigned to one of four general mechanistic classifications. With this comprehensive analysis, I conclude that systematically identifying dosage suppression genetic interactions will allow for their integration into other genetic and physical interaction networks and should provide new insight into the global wiring diagram of the cell.
Synthesis of Dendralenes (2016)

This chapter focuses on synthesis of dendralenes that construct a carbon framework via carbon-carbon bond formation. It discusses multibond forming approaches to dendralenes. Higher dendralenes are accessible by double cross-coupling by including branched alkenes into an electrophile unit. Cross-couplings are feasible by swapping reactivity of components using a double nucleophilic ethylene or 1,3-butadiene and two alkenyl electrophiles. Alkynes are versatile starting materials to couple with alkenes or allenesin transition-metal-catalyzed processes to form dendralenes. C-H activation is an important and rapidly developing area of dendralene synthesis. Halodendralenes are valuable substrates for dendralene to dendralene transformations that preserve or extend a dendralene framework. The dendralene frameworks can be extended by uncatalyzed metathesis reactions on alkyne containing dendralenes, and olefination reactions on carbonyl-containing ones. Rearrangements and isomerizations can lead to either an extension or a reduction of the dendralene framework.