gebhart/patrepeval huggingface dataset:
A Novel Iminosugar UV-12 with Activity against the Diverse Viruses Influenza and Dengue (Novel Iminosugar Antiviral for Influenza and Dengue) (2015)

Iminosugars are capable of targeting the life cycles of multiple viruses by blocking host endoplasmic reticulum α-glucosidase enzymes that are required for competent replication of a variety of enveloped, glycosylated viruses. Iminosugars as a class are approved for use in humans with diseases such as diabetes and Gaucher's disease, providing evidence for safety of this class of compounds. The in vitro antiviral activity of iminosugars has been described in several publications with a subset of these demonstrating in vivo activity against flaviviruses, herpesviruses, retroviruses and filoviruses. Although there is compelling non-clinical in vivo evidence of antiviral efficacy, the efficacy of iminosugars as antivirals has yet to be demonstrated in humans. In the current study, we report a novel iminosugar, UV-12, which has efficacy against dengue and influenza in mouse models. UV-12 exhibits drug-like properties including oral bioavailability and good safety profile in mice and guinea pigs. UV-12 is an example of an iminosugar with activity against multiple virus families that should be investigated in further safety and efficacy studies and demonstrates potential value of this drug class as antiviral therapeutics.
MOFganic Chemistry: Challenges and Opportunities for Metal–Organic Frameworks in Synthetic Organic Chemistry (2023)

Metal-organic frameworks (MOFs) are porous, crystalline solids constructed from organic linkers and inorganic nodes that have been widely studied for applications in gas storage, chemical separations, and drug delivery. Owing to their highly modular structures and tunable pore environments, we propose that MOFs have significant untapped potential as catalysts and reagents relevant to the synthesis of next-generation therapeutics. Herein, we outline the properties of MOFs that make them promising for applications in synthetic organic chemistry, including new reactivity and selectivity, enhanced robustness, and user-friendly preparation. In addition, we outline the challenges facing the field and propose new directions to maximize the utility of MOFs for drug synthesis. This perspective aims to bring together the organic and MOF communities to develop new heterogeneous platforms capable of achieving synthetic transformations that cannot be replicated by homogeneous systems.
Reverse-Phase Protein Microarrays for Theranostics and Patient Tailored Therapy (2009)

Analysis of the genome provides important information about the somatic genetic changes existing in the tissue; however, it is the proteins that do the work of the cell. Diseases such as cancer are caused by derangements in cellular protein molecular networks and cell signaling pathways. These pathways contain a large and growing collection drug targets, governing cellular survival, proliferation, invasion, and cell death. The clinical utility of reverse-phase protein microarrays (RPPA), a new technology invented in our laboratory, lies in its ability to generate a functional map of known cell signaling networks or pathways for an individual patient obtained directly from a biopsy specimen. Coupled with laser capture microdissection (LCM), the RPPA platform, the entire cellular proteome is immobilized on a substratum with subsequent immunodetection of the total levels and phosphorylated, or activated, state of cell signaling proteins. The results of which pathways are "in use" can then be correlated with biological and clinical information and serve as both a diagnostic and a therapeutic guide, thus providing a "theranostic" endpoint.
Modulating electrolytic tissue ablation with reversible electroporation pulses (2015)

Electrolytic ablation is a minimally invasive tissue ablation technique that operates by delivering low magnitude direct current to the target region over long periods of time, generating electrolytic products that destroy cells. Our study seeks to examine the hypothesis that permeabilizing the cell membrane with reversible electroporation will reduce the electrolytic dose required for tissue ablation, by exposing the interior of the cell to the electrolytic products. The hypothesis is examined by evaluating the extent of tissue damage when electrolytic and reversible electroporation sequences are delivered separately and in combination, it in vivo, to rat liver tissue. The study shows that combining reversible electroporation with electrolysis produces a substantial increase in the extent of tissue ablation compared to that achieved by electrolysis alone.
Introduction of Two Prolines and Removal of the Polybasic Cleavage Site Lead to Higher Efficacy of a Recombinant Spike-Based SARS-CoV-2 Vaccine in the Mouse Model (2021)

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as the prime target for vaccine development. The spike protein mediates both binding to host cells and membrane fusion and is also so far the only known viral target of neutralizing antibodies. Coronavirus spike proteins are large trimers that are relatively unstable, a feature that might be enhanced by the presence of a polybasic cleavage site in SARS-CoV-2 spike. Exchange of K986 and V987 for prolines has been shown to stabilize the trimers of SARS-CoV-1 and the Middle East respiratory syndrome coronavirus spike proteins. Here, we test multiple versions of a soluble spike protein for their immunogenicity and protective effect against SARS-CoV-2 challenge in a mouse model that transiently expresses human angiotensin-converting enzyme 2 via adenovirus transduction. Variants tested include spike proteins with a deleted polybasic cleavage site, proline mutations, or a combination thereof, besides the wild-type protein. While all versions of the protein were able to induce neutralizing antibodies, only the antigen with both a deleted cleavage site and the K986P and V987P (PP) mutations completely protected from challenge in this mouse model.<b>IMPORTANCE</b> A vaccine for SARS-CoV-2 is urgently needed. A better understanding of antigen design and attributes that vaccine candidates need to have to induce protective immunity is of high importance. The data presented here validate the choice of antigens that contain the PP mutations and suggest that deletion of the polybasic cleavage site may lead to a further-optimized design.
Development of a robust DNA quality and quantity assessment qPCR assay for targeted next-generation sequencing library preparation (2016)

Next-generation sequencing (NGS) is becoming a standard for genetic analyses of clinical samples. DNAs retrieved from formalin-fixed, paraffin-embedded (FFPE) tissue specimens are commonly degraded, and specimens such as core biopsies are sometimes too small to obtain enough DNA for NGS applications. Thus, it is important to measure both the DNA quantity and quality accurately from clinical samples. However, there is no standard method for DNA quantity and quality analyses for NGS library preparation. We tested four different methods (PicoGreen, Qubit® fluorometry, TaqMan and SYBR-Green-based qPCR assay) and compared each to RNase P TaqMan as a reference control. We found that SYBR-Green-based qPCR assay provides a consistent and accurate DNA quantification while keeping its cost relatively low and the throughput high. We designed a dual-probe SYBR-Green qPCR assay for DNA quantity and quality assessment for targeted NGS library preparation. This assay provides a Dscore (degradation score) of the interrogated DNA by analyzing two different sizes of amplicons. We show an example of a clinical sample with a very high Dscore (high degradation). With a regular DNA quantification, without considering the degradation status, no correct NGS libraries were obtained. However, after optimizing the library condition by considering its poor DNA quality, a reasonably good library and sequencing results were obtained. In summary, we developed and presented a new DNA quantity and quality analysis qPCR assay for the targeted NGS library preparation. This assay may be mostly efficient for the clinical samples with high degradation and poor DNA quality.
Cover Picture: When are Two Waters Worse Than One? Doubling the Hydration Number of a Gd–DTPA Derivative Decreases Relaxivity (Chem. Eur. J. 20/2005) (2005)

MRI contrast agents act by relaxing water protons. When an acetate group on the MRI angiography contrast agent MS‐325 is replaced with a methyl group, it opens up a coordination site for a second water ligand. The additional water is expected to improve the relaxivity of the new complex, and this is observed in buffer solution. However, in the presence of the plasma protein serum albumin the relaxivity is only about half that of MS‐325, making the new compound less attractive for blood vessel imaging. On page 5866 ff., P. Caravan et al. describe the synthesis of this novel gadolinium complex and report mechanistic studies indicating that slow water exchange limits relaxivity. The artwork was created by Vincent Jacques.
Auditory brain stem responses in patients after radiation therapy for nasopharyngeal carcinoma (1992)

The results emphasize the importance of protecting the brain stem from high-dose radiation when possible. The results also demonstrate the usefulness of ABR as a supplement to the clinical examination of patients with possible myelopathy occurring after radiation exposure.
Surfactants and their role in wound cleansing and biofilm management (2017)

Surfactants are widely used as detergents, emulsifiers, wetting agents, foaming agents and dispersants in the cosmetics, hygiene, food and oil industries. Their use in a clinical setting is also common, particularly within the field of wound care. Many wound cleansers contain surfactants and subsequently there is available data that shows the growing potential of these wound cleansers in the enhancement of wound closure. The presence of microorganisms in wounds has been recognised as a significant factor that delay healing. In complex or chronic wounds that are complicated by biofilms, persistent inflammation or the production of non-viable tissue and slough, the use of surfactants has been shown to aid in the removal of these barriers to wound healing. The use of concentrated surfactant(poloxamer) based wound dressings represent an important component of wound management. Consequently, this article will discuss the effect of clinically used surfactants, with specific focus on a concentrated poloxamer for use against wound biofilm.
Diffraction efficiency of deep volume holograms (1989)

The coupled mode analysis of volume holograms established by Kogelnik 1 predicts a periodic functional behavior for the diffraction efficiency as a function of the index perturbation length product. With absorption constant α, the diffraction efficiency η from a volume index grating is given by where d is the thickness of the hologram, Δ n is the amplitude of the index perturbation, and θ is the angle of incidence of the readout beam with respect to the normal to the surface of the hologram (we assume an unslanted grating). Typically, the amplitude of Δ nd is such that the increasing part of the first period of η is observed. The theory predicts that as Δ nd is increased beyond this region, the diffraction efficiency should drop. Photorefractive crystals, due to their real time holographic feature, are ideal media for observing such a phenomenon. In a photorefractive crystal, Δ n is proportional to the modulation depth intensity interference pattern responsible for writing the hologram. Hence, by merely manipulating the intensities of the writing beams, one can examine the functional behavior of the diffraction efficiency. We show experiments that verify this periodic diffraction efficiency function and hence demonstrate the large Δ nd product achievable with BaTiO 3 .
Analysis of branching tubular structures in 3D digital images (2003)

Accurate definition of a three-dimensional (3D) branching tree structures from large 3D medical images, has become a common problem over several imaging modalities. For example, 3D computed-tomography (CT) images of the airways as well as micro-CT images of vasculature employ new paradigms that require detailed definitions of tree structures. Manual definition is impossible for images of this scale. Existing techniques lack features necessary for navigational or quantitative analysis or fail to recover paths. We present a generic tree analysis technique that is applicable to arbitrary segmented images of branching structures for both of these purposes. The method has been tested on over 30 human, animal, phantom, and micro-CT images. An initial comparison with a previous method demonstrates its ability to capture more paths, especially in peripheral regions.
Unified theory of ripple transport in stellarators (1987)

The distribution function for ripple-trapped particles has been found in a series form valid for all low collision frequencies, for standard and transport-optimized stellarators. The diffusion coefficient obtained with this distribution function shows excellent agreement with the results of Monte Carlo and Fokker-Planck computer codes, in the cases studied.
Moneda y Nación (2016)

Uno de los procesos mas interesantes del siglo XIX fue la organizacion y diferenciacion
de los distintos grupos politicos que definirian posteriormente los
modelos de organizacion social colombianos. Esta no fue una tarea facil, ni trasego
un camino despejado, sino mas bien fue un recorrido que estuvo marcado
por contradicciones, aprendizajes dificiles, guerras civiles de todos los tenores y
profundas crisis politicas que en varias ocasiones fueron saldadas en el patibulo,
el exilio, las expropiaciones y la carcel. Fue un periodo de definiciones.
Utilisation du motif diazabicyclo3,2,1octane et valorisation de la fonction dithiocarbamate en synthese supportee etude de la reactivite d'un nouveau sel d'iminium (1999)

Une strategie de synthese sur support solide basee sur l'utilisation d'un repartiteur a ete developpee pour generer une collection de molecules a structures definies. Le choix du repartiteur s'est oriente vers un squelette bicyclique de type diazabicyclo3,2,1octane de structure proche d'une molecule naturelle, la quinocarcine connue pour ses activites biologiques. L'etape cle de la synthese est une reaction de cycloaddition 1,3 dipolaire. Ce repartiteur possede trois fonctions derivatisables qui ont ete etudiees dans des reactions de derivatisations. La sequence de derivatisation du repartiteur sur support solide mise au point est compatible avec un grand nombre de blocs fonctionnels, et parfaitement transposable a la synthese a haut debit. De nouvelles methodologies de synthese sur support solide permettant de generer la diversite par enchainement de reactions ont ete developpees. La fonction dithiocarbamate n-monosubstituee a ete utilisee comme point d'ancrage au support solide. Ce precurseur peut agir comme un electrophile, biselectrophile ou nucleophile. L'etude a consiste a exploiter toutes ces proprietes pour acceder a differentes structures fonctionnalisees. Des syntheses de thiourees, de guanidines, d'imino 4-thiazolines et de 4-imidazole-2-thiones ont ete developpees sur support solide. L'utilisation de ce traceless linker a permis de liberer proprement les molecules du support solide par un clivage fonctionnalisant. La reactivite d'un sel de chlorosulfanyl iminium a ete etudiee. Ce sel permet d'halogener selectivement des alcools primaires en presence de secondaires. Une etude des conditions reactionnelles a conduit a l'utiliser comme agent doux pour la formation de liaisons ester et amide. La synthese de ce sel d'iminium sur support solide a ete effectuee. Cette etude a necessite la preparation d'une nouvelle resine polystyrene thiol.
An Antibody to a 17 Amino Acid Synthetic Peptide of the Type I Interleukin-1 Receptor Preferentially Blocks Interleukin-1β Binding (1996)

On the basis of their relative hydropathy and alpha-helical structure, we prepared antibodies to four synthetic peptides with amino acid sequences homolgous to four hydrophilic, extracellular regions of the murine 80 kDa type I interleukin-1 receptor (IL-1RI). Antibodies to each of the four peptides recognized their specific immunogen. Human [125I]-IL-1 alpha or -beta was crosslinked to murine EL4 and D10S cells. Antiserum to peptide 150-166 precipitated the IL-1/IL-1R complex, whereas antibodies to peptide 66-84, 190-200, or 266-285 did not. Antibody to peptide 150-166 did not precipitate the type II IL-1R. Anti-IL-1RI150-166 blocked 71% of the binding of radiolabeled human IL-1 beta to EL4 cells and 50% of the binding to D10S cells. Using affinity-purified anti-IL-1RI150-166, we compared the ability of this antibody to inhibit the binding of murine or human IL-1 alpha to that of murine or human IL-1 beta. At a concentration of 20 ng/ml, affinity-purified anti-IL-1RI150-166 blocked 50% binding of murine IL-1 beta. At 1 microgram/ml, 90% blockage was observed. In contrast, no significant blockade of IL-1 alpha binding was observed at concentrations as high as 3 micrograms/ml of anti-IL-1RI150-166. The selective blockade of IL-1 beta forms was not due to differences in the affinities of these ligands for receptors on these cells. The antibody also blocked the binding of human IL-1 beta but not human IL-1 alpha to EL4 cells. The biologic activity of murine IL-1 beta but not IL-1 alpha on EL4 cells was also inhibited by this antibody. These data suggest (1) that antibody to a specific epitope on the extracellular domain interferes with the binding of IL-1 beta but not IL-1 alpha, (2) the differential inhibition of binding of IL-1 beta but not IL-1 alpha by anti-IL-1RI150-166 also blocks biologic activity, and (3) IL-1 alpha and IL-1 beta may transduce different signals by binding to separate loci on the IL-1RI.
Eye Dominance Columns from an Isogenic Double-Nasal Frog Eye (1983)

Removing the posterior (temporal) two-thirds of the Xenopus eye bud produces a remaining fragment, which becomes round and grows to a normal adult size eye. Electrophysiological and anatomical analyses showed that each of the two halves of this eye projected across the entire optic tectum in mirror image (double-nasal) fashion, and that fibers from each half-eye sorted out to form eye dominance stripes on the tectum. That both halves of the mirror-symmetric map were derived from only one animal, and from only one side of the head, rules out global markers such as right versus left and histocompatibility differences as causing the formation of these stripes.
Application of the van Everdingen-Meyer Method for Analyzing Variable-Rate Well Tests (1990)

Summary This paper discusses application of superposition to pressure-transient analysis when rate varies significantly before and during pressure measurements. To apply rigorous superposition, use of conventional pressure-transient and rate-time methods is recommended to estimate permeability, skin, and in some cases, drainage area. These properties allow calculation of the dimensionless time constant used in superposition calculations on the basis of rate change and dimensionless pressure. As van Everdingen and Meyer proposed, the time constant is varied until a linear fit of the pressure variable is made vs. superposition time. An important step is to use all available rate data, even though pressures may not be measured during periods of rate change. Our work shows the use of full superposition to check the consistency of standard well-test analysis based on the constant-rate or constant-pressure assumption. Data from two gas wells and results from a gas-well simulator provide the basis for our discussion. Problems covered are choosing the dimensionless pressure solution, estimating initial pressure by extrapolation of the superposition plot, and analyzing rate-dependent effects.
ADVANTAGES AND DISADVANTAGES OF DIFFERENT SAMPLING TECHNIQUES FOR SAMPLING VOLATILE ORGANIC HYDROCARBONS IN AIR (2000)

The sampling and analysis of volatile organic compounds (VOC) in air are a great challenge. Air is a matrix very difficult to handle, the pollutants are usually present at very low concentration, so their detection and quantitation require precise sampling, sample preparation, analysis and data evaluation. VOC air samples are almost never sufficiently concentrated to be directly introduced into a capillary GC system via a standard gas-sampling valve. The respective advantages and limitations of these different sampling methods will be reviewed. The observations are based on the results of two sampling campaign, namely in February-May 1998, in Veszprem, where diffusive samplers were used for the determination of BTEX compounds, and July-August 1998, in Berlin (Germany), where pumped sorbent tubes, passivated canisters and on-line air stream samplers were used for the determination of 54 VOC compounds. VOC measurements contribute to improving our current understanding and will help to clarify what if any remedial action is required.
Agricultural workers in meatpacking plants presenting to an emergency department with suspected COVID‐19 infection are disproportionately Black and Hispanic (2021)

Workers in meatpacking plants in Iowa had a higher rate of testing positive for COVID-19 but were not more likely to be hospitalized for their illness. These patients were disproportionately Black and Hispanic.
OFDM-based analog multiband: A scalable design for indoor mm-wave wireless communication (2014)

We propose an approach to scaling communication bandwidths over dispersive channels that preserves the advantage of DSP-centric receiver design, while sidestepping the difficulty of scaling analog-to-digital conversion (ADC) to higher and higher bandwidths. This is accomplished by channelizing the available bandwidth into contiguous subbands in the analog domain, with the width of a subband chosen so that digitization is possible at reasonable cost and power using existing ADC technology. We illustrate these ideas for multiGigabit indoor mm-wave communication, with GHz bandwidth divided into subbands of width 250-500 MHz. The channel delay spread even after beamforming can be as large as 20 ns, hence the channel seen within subbands is dispersive. Further, the contiguity of subbands and the sloppy analog channelization implies that adjacent subbands interfere with each other. We show that OFDM within subbands is an attractive approach in these settings: the channel dispersion within subbands can be handled with a moderate cyclic prefix, while the inter-band interference manifests itself only on the edge subcarriers. We clarify the structure of the inter-band interference, and show that it is effectively suppressed by adaptive linear Minimum Mean Squared Error (MMSE) techniques for joint detection across adjacent subbands. Our performance evaluation is carried out using channel models developed for the IEEE 802.1 lad 60 GHz standard.
Efficient electrospray deposition of surfaces smaller than the spray plume (2022)

Electrospray deposition (ESD) uses charged droplets at the micro- and nano-scale to create a wide variety of particles and coatings. In ESD, an electrostatic force is applied to a solution, which then disperses charged droplets loaded with the materials to be deposited on a grounded target. Because the droplets carry charge, repulsive effects due to accumulation of charge in a coating (self-limiting electrospray) or “crowding” of the spray droplets can reduce the efficiency of the approach. This is especially the case when the targets are smaller than the characteristic size of the spray plume. For this reason, while many studies have presumed high efficiency in ESD, the actual measured efficiencies for small targets are much lower. Here, it is shown how architecting the local “charge landscape” can lead to ESD coatings approaching 100% deposition efficiency on both flat and microneedle array targets composed of multiple model materials, including biocompatible polymers, proteins, and bioactive small molecules. In this way, ESD can be considered a viable alternative to other conformal approaches, such as dip or inkjet coating.