gebhart/patrepeval huggingface dataset:
Limited SARS-CoV-2 diversity within hosts and following passage in cell culture (2020)

Abstract Since the first reports of pneumonia associated with a novel coronavirus (COVID-19) emerged in Wuhan, Hubei province, China, there have been considerable efforts to sequence the causative virus, SARS-CoV-2 (also referred to as hCoV-19) and to make viral genomic information available quickly on shared repositories. As of 30 March 2020, 7,680 consensus sequences have been shared on GISAID, the principal repository for SARS-CoV-2 genetic information. These sequences are primarily consensus sequences from clinical and passaged samples, but few reports have looked at diversity of virus populations within individual hosts or cultures. Understanding such diversity is essential to understanding viral evolutionary dynamics. Here, we characterize within-host viral diversity from a primary isolate and passaged samples, all originally deriving from an individual returning from Wuhan, China, who was diagnosed with COVID-19 and subsequently sampled in Wisconsin, United States. We use a metagenomic approach with Oxford Nanopore Technologies (ONT) GridION in combination with Illumina MiSeq to capture minor within-host frequency variants ≥1%. In a clinical swab obtained from the day of hospital presentation, we identify 15 single nucleotide variants (SNVs) ≥1% frequency, primarily located in the largest gene – ORF1a. While viral diversity is low overall, the dominant genetic signatures are likely secondary to population size changes, with some evidence for mild purifying selection throughout the genome. We see little to no evidence for positive selection or ongoing adaptation of SARS-CoV-2 within cell culture or in the primary isolate evaluated in this study. Author Summary Within-host variants are critical for addressing molecular evolution questions, identifying selective pressures imposed by vaccine-induced immunity and antiviral therapeutics, and characterizing interhost dynamics, including the stringency and character of transmission bottlenecks. Here, we sequenced SARS-CoV-2 viruses isolated from a human host and from cell culture on three distinct Vero cell lines using Illumina and ONT technologies. We show that SARS-CoV-2 consensus sequences can remain stable through at least two serial passages on Vero 76 cells, suggesting SARS-CoV-2 can be propagated in cell culture in preparation for in-vitro and in-vivo studies without dramatic alterations of its genotype. However, we emphasize the need to deep-sequence viral stocks prior to use in experiments to characterize sub-consensus diversity that may alter outcomes.
Multi-channel low-frequency room equalization using perceptually motivated constrained optimization (2012)

We consider the problem of multiple-loudspeaker low-frequency room equalization for a wide listening area, where the equalized loudspeaker is helped using the remaining ones. Using a spatial discretization of the listening area, we formulate the problem as a multipoint error minimization between desired and synthesized magnitude frequency responses. The desired response and cost function are formulated with a goal of capturing the room's spectral power profile, and penalizing strong resonances. Considering physical and psychoacoustical observations, we argue for the use of gain-limited, short, and well-localized equalization filters, with an additional delay for loudspeakers that help the equalized one. We propose a convex optimization framework for computing room equalization filters, where the mentioned filter requirements are incorporated as convex constraints. We verify the effectiveness of our equalization approach through simulations.
Author response: An oomycete effector subverts host vesicle trafficking to channel starvation-induced autophagy to the pathogen interface (2021)

A pathogen effector mimics starvation-induced autophagy by subverting host endomembrane trafficking to stimulate biogenesis of autophagosomes around pathogen feeding sites, revealing how pathogens interlock distinct host compartments to facilitate infection.
On-chip electro-optic frequency comb generation using a heterogeneously integrated laser (2022)

We demonstrate the first on-chip resonant electro-optic frequency comb source on thin-film lithium niobate with an electrically-pumped heterogeneously integrated laser.
Instinctual Interference-Adaptive Low-Power Receiver With Combined Feedforward and Feedback Control (2021)

Highly adaptive, instinctively interference-tolerant radio frequency (RF) receivers are in high demand today. To achieve high-interference robustness at low average power, receivers need to be dynamically configured to operate in low-power mode in the absence of interference and a high-power interference-tolerant mode as an “instinctual” response to the blocker. In this letter, we present an interference-adaptive receiver with a control loop and on-board commercial off-the-shelf (COTS) components that adapt a 2-6-GHz low-noise amplifier (LNA) from a low-power mode (-10-dBm P <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1 dB,IN</sub> and ≈ 280-mW power) to high-linearity mode (1.5-dBm P <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1 dB,IN</sub> and ≈ 1.4-W power) where the linearity is increased by 11.5 dB ( > 14×) with a 5× increase in consumed power. With no interference, the control loop automatically brings the LNA back to the low-power mode.
Nanoscale Chemical Composition Mapping with AFM-based Infrared Spectroscopy (2012)

Extended abstract of a paper presented at Microscopy and Microanalysis 2012 in Phoenix, Arizona, USA, July 29 – August 2, 2012.
Leukocyte surface expression of the endoplasmic reticulum chaperone GRP78 is increased in severe COVID-19 (2023)

Hyperinflammation present in individuals with severe COVID-19 has been associated with an exacerbated cytokine production and hyperactivated immune cells. Endoplasmic reticulum stress leading to the unfolded protein response has been recently reported as an active player in inducing inflammatory responses. Once unfolded protein response is activated, GRP78, an endoplasmic reticulum-resident chaperone, is translocated to the cell surface (sGRP78), where it is considered a cell stress marker; however, its presence has not been evaluated in immune cells during disease. Here we assessed the presence of sGRP78 on different cell subsets in blood samples from severe or convalescent COVID-19 patients. The frequency of CD45+sGRP78+ cells was higher in patients with the disease compared to convalescent patients. The latter showed similar frequencies to healthy controls. In patients with COVID-19, the lymphoid compartment showed the highest presence of sGRP78+ cells versus the myeloid compartment. CCL2, TNF-α, C-reactive protein, and international normalized ratio measurements showed a positive correlation with the frequency of CD45+sGRP78+ cells. Finally, gene expression microarray data showed that activated T and B cells increased the expression of GRP78, and peripheral blood mononuclear cells from healthy donors acquired sGRP78 upon activation with ionomycin and PMA. Thus, our data highlight the association of sGRP78 on immune cells in patients with severe COVID-19.
Morphology and Surface Relief Structures of Asymmetric Poly(styrene-block-ferrocenylsilane) Thin Films (2001)

Thin films of an asymmetric styrene-block-ferrocenyldimethylsilane copolymer were studied on solid silicon substrates as well as free-standing. In the bulk the diblock forms poly(ferrocenylsilane) cylinders in a poly(styrene) matrix. The thin films were analyzed by a variety of techniques including atomic force microscopy (AFM), transmission electron microscopy (TEM), X-ray reflectivity, secondary ion mass spectrometry (SIMS), and optical microscopy. From X-ray reflectivity measurements it was concluded that both blocks were present at the substrate, whereas poly(styrene) wetted the free surface. The formation of islands and holes was observed by optical microscopy and AFM, as a result of a mismatch between the film thickness and the equilibrium spacing between layers of cylinders. Upon longer annealing of the films, the islands disappeared due to a change of the internal morphology of the thin film. After selective removal of the organic matrix by means of oxygen reactive ion etching, the phase-separated structure could be visualized by AFM. The morphology of the films altered upon annealing from an in-plane cylindrical to a hexagonal morphology. The structure in free-standing films could be analyzed by TEM. After annealing, both types of orientations of cylinders (parallel and perpendicular with respect to the surface) were found to be stable.
Design of a planar passive MMID tag antenna (2017)

The concept of millimetre‐wave identification (MMID) extends the ultra‐high frequencies radio frequency identification towards a universal frequency band equals to 5 GHz. The study presents the design of a planar passive MMID tag antenna highlighting the requirement specification and the design methodology. Simulation and experimental results are reported which validate the design procedure until a first MMID tag prototype communicating by backscattering.
A robust model for simultaneously inducing corneal neovascularization and retinal gliosis in the mouse eye. (2011)

We have developed a mouse model for investigating retinal gliosis and corneal neovascularization. We used this model to demonstrate the simultaneous inhibitory effects of WFA on both of these disease processes. Retinal gliosis occurs in several major degenerative conditions of the eye, including age-related macular degeneration, where angiogenesis is also a prevailing pathological feature. Thus, inhibitors of both gliosis and angiogensis used as combination therapy are currently being explored for treatment of such complex diseases. The model presented here affords a very simple preclinical assay for screening combination of drugs or polypharmacological agents and reduces the numbers of animals because of the different anatomic sites of these pathologies. Finally, given that endogenous mediators elicit angiogenesis and gliosis in this model, the combination of genetics and pharmacology can be exploited to study drug mechanisms and for target validation in vivo.
Organization of the Interfacial Film of Nanoemulsions Stabilized by Porphyrin Derivatives (2023)

Photodynamic therapies combining the action of a photosensitizer (PS), molecular oxygen, and light make it possible to destroy certain infectious sites and tumors. The incorporation of photosensitizers in nanocarriers allows for better control of their distribution in tissues and increases their concentration in the area that will be then illuminated. Nanoemulsions of glyceryl trioctanoate (GTO) have been designed in which pyropheophobide <i>a</i> (Pyro-A) or its lipid conjugate (Pyro-Lipid) are both stabilizing and photostimulable agents. In this work, we studied by surface pressure measurements and Brewster angle microscopy (BAM) analysis the organization of the interfacial films of nanodroplets. Comparison of preformed porphyrin nanoemulsions and two porphyrin-GTO mixtures, one mimicking the composition of the nanoemulsions and the other that of a porphyrin-rich interfacial film, highlighted the role of GTO and porphyrin derivatives in the formation, organization, and elasticity of the interfacial films in nanoemulsions. Pyro-Lipid and GTO can mix, and some of the GTO molecules remain inserted in the interfacial film at high surface pressures. In contrast, Pyro-A and GTO do not mix well and tend to segregate, leaving Pyro-A alone in the condensed interfacial film. The results of this study demonstrate the importance of characterizing the interfacial properties of porphyrin derivatives and their interaction with the oil to design stable nanoemulsions with well-controlled optical properties.
The Medicinal Chemist’s Toolbox: An Analysis of Reactions Used in the Pursuit of Drug Candidates (2011)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTThe Medicinal Chemist's Toolbox: An Analysis of Reactions Used in the Pursuit of Drug CandidatesStephen D. Roughley*‡ and Allan M. Jordan§View Author Information‡ Vernalis (R&D) Ltd., Granta Park, Cambridge, CB21 6GB, U.K.§ Cancer Research UK Drug Discovery Unit, Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Manchester, M20 4BX, U.K.*Phone: (+44) 01223 895555. Fax: (+44) 01223 895556. E-mail: [email protected]Cite this: J. Med. Chem. 2011, 54, 10, 3451–3479Publication Date (Web):April 19, 2011Publication History Received18 February 2011Published online2 May 2011Published inissue 26 May 2011https://pubs.acs.org/doi/10.1021/jm200187yhttps://doi.org/10.1021/jm200187yreview-articleACS PublicationsCopyright © 2011 American Chemical SocietyRequest reuse permissionsArticle Views51874Altmetric-Citations2000LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Alkyls,Amides,Amines,Aromatic compounds,Chemical reactions Get e-Alerts
Portable Nanopore Sequencing for Viral Surveillance (2016)

The recent Nature article (1) entitled, “Real-Time, Portable Genome Sequencing for Ebola Surveillance,” reports nanopore sequencing of the Ebola virus from 142 subjects near the end of the outbreak in West Africa from March to October 2015. The nanopore sequencer (MinION, Oxford Nanopore Technologies) has a mass of 87 g and plugs into a laptop computer by way of a USB 3.0 interface and cable. The consumable flow cell has up to 512 channels available for sequencing, each of which can simultaneously read single strands of DNA and their ligated complementary strands as “2D” reads, providing correlated data on both strands of DNA. The nanopores are typically made up of proteins like α-hemolysin that are pore-forming bacterial toxins embedded in an electrically insulating membrane. A voltage between the 2 sides of the membrane attracts DNA to the pore in an electrolyte solution. The DNA is captured by a polymerase near the pore that paces the rate of transport to 30–280 bases/s. The passage of single-stranded DNA affects the pore current, generating electrical “squiggle signals” that are sequence-specific. In simple terms, this is the Coulter principle applied to molecules rather than cells. In half of the cases, sufficient reads (25 2D reads for each amplicon) were obtained in <1 h of instrument time with a mean passing rate of 36.3%. The mean read rate was 138 amplicons/min, and in some cases, only 15 min of sequencing was required. Custom offline acquisition software was provided by the company so that Internet communication was not initially required. Nanopore sequencing is conceptually elegant and data acquisition is fast. However…

Before sequencing, sample transport and preparation are required. To prevent delays of air transport of samples, a portable 50-kg laboratory was transported in airline luggage to Guinea. As samples became available locally, they were transported …
The accumulation of lncRNAs in hybrid with DNA in patients with psoriasis reveals a decrease in the levels of RNase HII transcripts in the skin (2021)

Abstract Long functional non-coding RNAs (lncRNAs) have been in the limelight in aging research because short telomeres are associated with higher levels of TERRA (Telomeric Repeat containing RNA). The genomic instability caused in Immune-mediated inflammatory diseases (IMID) especially in patients with psoriasis, which lead to short telomeres in psoriasis lesions, is a mechanism leading to cell aging. Research on the fraction of TERRA in hybrid with DNA offers avenues for new strategies. Skin samples were fractionated to obtain the RNA associated with DNA as a R-loop structure. TERRA analysis was performed by RT-qPCR and RNA-seq analysis. The higher amount of TERRA levels attached with each chromosome end was found with psoriasis patients. The increased levels of TERRA linked with telomeres correlate with the decrease in the RNase-HII transcript which means the unresolved DNA/RNA hybrids may ultimately facilitate the formation of skin lesions. LncRNAs have multiple molecular functions, including the regulation of heterochromatin, which controls genome stability and epigenome shaping and may be used as a trans-generational prognostic marker in patients with psoriasis.
Supplementary Table Legend from Rationale and Preclinical Efficacy of a Novel Anti-EMP2 Antibody for the Treatment of Invasive Breast Cancer (2023)

&lt;p&gt;PDF - 55K, Legends for Supplementary Tables 1 through 5.&lt;/p&gt;
Suppression of Leading Edge Separation and Tip Leakage Flow in a Transonic Centrifugal Compressor Impeller Using an Inverse Design Method Based on Meridional Viscous Flow Analysis (2020)

In this paper, a design concept for suppressing the leading edge separation and tip leakage flow is introduced in order to improve aerodynamic performance of a transonic centrifugal compressor. The aerodynamic design method used in the present study is an inverse design method based on a meridional viscous flow analysis. As the design concept, the blade loading distributions at the leading edge are reduced to decrease the incidence angles. In addition, the blade loading at the impeller tip side is suppressed to prevent the interaction between the leading edge separation and tip leakage vortex. The effectiveness of the design concept was evaluated by three-dimensional Reynolds Averaged Navier-Stokes simulations. The performance improvement was observed in the redesigned impeller compared with the conventional design impeller.
Palladium-Catalyzed Amination of Unprotected Five-Membered Heterocyclic Bromides (2014)

An efficient method for the palladium-catalyzed amination of unprotected bromoimidazoles and bromopyrazoles is presented. The transformation is facilitated by the use of our newly developed Pd precatalyst based on the bulky biarylphosphine ligand tBuBrettPhos (L4). The mild reaction conditions employed allow for the preparation of a broad scope of aminoimidazoles and aminopyrazoles in moderate to excellent yields.
Alpha plus beta annealed and aged Ti-15 Mo alloy for high strength implant applications (2016)

Management of femur fractures requires titanium alloy implants that provide a good combination of static strength and ductility plus sufficient high cycle fatigue strength to resist repetitive loading. A research program was initiated to determine whether aging treatments could increase the strength of alpha + beta Ti-15Mo while maintaining acceptable tensile ductility. A pilot heat treating study indicated the best combination of strength and ductility was obtained using an α + β annealing temperature of 705°C ± 10°C followed by an aging treatment of 482°C ± 10°C. EBSD data for four suppliers revealed that the alpha phase ratios ranged from 16.3% to 18.6% and the beta phase ratios ranged from 81.4% to 83.7%. Mean beta grain size diameters ranged between 1.42 and 1.78 µm. Tensile testing qualification data from four suppliers was statistically analyzed and reviewed. Minimum reproducible tensile values were established and incorporated into ASTM F2066-13 implant material standard. Cantilever fatigue testing was performed with proximal femoral nail implants that were fabricated into fully finished implant constructs. Fatigue results for 125°, 130°, and 135° implant constructs met the acceptance criteria regarding the fatigue runout load limits and failure modes that were identified. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2010-2018, 2017.
Receptors that couple to 2 classes of G proteins increase cAMP and activate CFTR expressed in Xenopus oocytes. (1993)

The cystic fibrosis transmembrane conductance regulator (CFTR), a Cl- channel activated by phosphorylation, was expressed in Xenopus oocytes along with various combinations of several other components of the cAMP signalling pathway. Activation of the coexpressed beta 2 adrenergic receptor increased cAMP and led to CFTR activation. The activation of CFTR (1) requires only short (15 s) exposure to isoproterenol, (2) occurs for agonist concentrations 100-1000 fold lower than those that produce cAMP increases detectable by a radioimmunoassay, (3) requires injection of only 5 pg of receptor cRNA per oocyte, and (4) can be increased further by coexpression of cRNA for adenylyl cyclase type II or III or for Gs alpha. In addition, CFTR activation and cAMP increases by beta 2 activation were enhanced by activation of the coexpressed 5HT1A receptor, which is thought to couple to Gi. The additional activation by the 5HT1A receptor was enhanced by coexpression of adenylyl cyclase type II but not with type III and may proceed via the beta gamma subunits of a G protein. The sensitivity of the assay system is also demonstrated by responses to vasoactive intestinal peptide and to pituitary adenylate cyclase-activating polypeptide in oocytes injected with cerebral cortex mRNA.
Heterogeneous effect of leucotriene CysLT1receptor antagonists on antigen‐induced motor and inflammatory responses in guinea‐pig airways (2006)

1. The effect of montelukast or MEN91507, selective leucotriene CysLT1 receptor antagonists, on antigen-induced airway inflammation and bronchoconstriction were compared in anaesthetized guinea-pigs. 2. In sensitized animals, ovalbumin (0.3 mg kg(-1), i.v.)-induced microvascular leakage in trachea, intrapulmonary airways, total lung (parenchyma and intrapulmonary airways) and urinary bladder was reduced by MEN91507 (0.01-1 micromol kg(-1), i.v.), whereas montelukast (0.01-1 micromol kg(-1), i.v.) antagonized the effect of the antigen only in the lung and urinary bladder. 3. Ovalbumin (1 mg kg(-1), i.v.)-induced bronchoconstriction was dose dependently antagonized by MEN91507 (10-30 micromol kg(-1), i.v.), whereas the effect of montelukast (0.1-30 micromol kg(-1), i.v.) was marginal (15-30% inhibition). Neither MEN91507 nor montelukast (30 micromol kg(-1), i.v.) affected the bronchoconstrictor response induced by acetylcholine (0.3 micromol kg(-1), i.v.) in sensitized animals. 4. It is concluded that montelukast and MEN91507 display a differential activity against the effect of endogenous leucotrienes, despite the fact that both compounds show a similar antagonist profile against exogenous leucotrienes acting through CysLT1 receptors.
MAGNETIC RESONANCE IMAGING OF PELVIC MUSCULOSKELETAL AND GENITOURINARY ANATOMY IN PATIENTS BEFORE AND AFTER COMPLETE PRIMARY REPAIR OF BLADDER EXSTROPHY (2005)

Comparison of the pelvic anatomy in patients before and after CPRE suggests that after CPRE patients have parameters that more closely approximate, but are still significantly different, from those of control patients. Patients with greater than 3-hour continent intervals after CPRE have anatomic parameters most similar to those of age matched controls.