gebhart/patrepeval huggingface dataset:
Passive leg raising as an indicator of fluid responsiveness in patients with severe sepsis (2012)

Changes in ΔSVI and ΔCVPm induced by PLR are accurate indices for predicting fluid responsiveness in mechanically ventilated patients with severe sepsis.
SIMULATION OF DNA-NANOTUBE INTERACTIONS (2004)

▪ Abstract Carbon nanotubes functionalized with biological molecules (such as protein peptides and nucleic acids) show great potential for application in bioengineering and nanotechnology. Fundamental understanding, description, and regulation of such bio-nano-systems will ultimately lead to a new generation of integrated systems that combine unique properties of the carbon nanotube (CNT) with biological recognition capabilities. In this review, we describe recent advances in understanding the interactions between deoxyribonucleic acids (DNA) and CNT, as well as relevant simulation techniques. We also review progress in simulating DNA noncovalent interactions with CNTs in an aqueous environment. Molecular dynamics simulations indicate that DNA molecules may be encapsulated inside or wrap around CNT owing to van der Waals attraction between DNA and CNT. We focus on the dynamics and energetics of DNA encapsulation inside nanotubes and discuss the mechanism of encapsulation and the effects of nanotube size, nanotube end-group, DNA base sequence, solvent temperature and pressure on the encapsulation process. Finally, we discuss the likely impact of DNA encapsulation on bioengineering and nanotechnology, as well as other potential applications.
Contribution of SARS-CoV-2 Accessory Proteins to Viral Pathogenicity in K18 Human ACE2 Transgenic Mice (2021)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the viral pathogen responsible for the current coronavirus disease 2019 (COVID-19) pandemic. As of 19 May 2021, John Hopkins University's COVID-19 tracking platform reported 3.3 million deaths associated with SARS-CoV-2 infection. Currently, the World Health Organization has granted emergency use listing (EUL) to six COVID-19 vaccine candidates. However, much of the pathogenesis observed during SARS-CoV-2 infection remains elusive. To gain insight into the contribution of individual accessory open reading frame (ORF) proteins in SARS-CoV-2 pathogenesis, we used our recently described reverse-genetics system approach to successfully engineer recombinant SARS-CoV-2 (rSARS-CoV-2) constructs; we removed individual viral ORF3a, -6, -7a, -7b, and -8 proteins from them, and we characterized the resulting recombinant viruses <i>in vitro</i> and <i>in vivo</i>. Our results indicate differences in plaque morphology, with ORF-deficient (ΔORF) viruses producing smaller plaques than those of the wild type (rSARS-CoV-2/WT). However, growth kinetics of ΔORF viruses were like those of rSARS-CoV-2/WT. Interestingly, infection of K18 human angiotensin-converting enzyme 2 (hACE2) transgenic mice with the ΔORF rSARS-CoV-2s identified ORF3a and ORF6 as the major contributors of viral pathogenesis, while ΔORF7a, ΔORF7b, and ΔORF8 rSARS-CoV-2s induced pathology comparable to that of rSARS-CoV-2/WT. This study demonstrates the robustness of our reverse-genetics system to generate rSARS-CoV-2 constructs and the major role for ORF3a and ORF6 in viral pathogenesis, providing important information for the generation of attenuated forms of SARS-CoV-2 for their implementation as live attenuated vaccines for the treatment of SARS-CoV-2 infection and associated COVID-19. <b>IMPORTANCE</b> Despite great efforts put forward worldwide to combat the current coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a human health and socioeconomic threat. Insights into the pathogenesis of SARS-CoV-2 and the contribution of viral proteins to disease outcome remain elusive. Our study aims (i) to determine the contribution of SARS-CoV-2 accessory open reading frame (ORF) proteins to viral pathogenesis and disease outcome and (ii) to develop a synergistic platform combining our robust reverse-genetics system to generate recombinant SARS-CoV-2 constructs with a validated rodent model of infection and disease. We demonstrate that SARS-CoV-2 ORF3a and ORF6 contribute to lung pathology and ultimately disease outcome in K18 hACE2 transgenic mice, while ORF7a, ORF7b, and ORF8 have little impact on disease outcome. Moreover, our combinatory platform serves as a foundation for generating attenuated forms of the virus to develop live attenuated vaccines for the treatment of SARS-CoV-2.
Screening an expression library with a ligand probe: isolation and sequence of a cDNA corresponding to a brain calmodulin-binding protein. (1987)

The use of cloning vectors that express inserted cDNA as fusion protein has led to the isolation of genes encoding a variety of eukaryotic proteins. In these instances antisera or monoclonal antibodies were used as probes to screen expression libraries. Since fusion proteins sometimes display biological activity reflective of the insert-specified portion, we tested the possibility that ligand-binding sites might exist in fusion proteins. Specifically we used 125I-labeled calmodulin as a probe to screen a mouse brain lambda gt11 library. One clone, lambda ICM-1 isolated using this approach, produces fusion protein that binds calmodulin with high affinity (Kd, 3-10 nM) in a Ca2+-dependent manner. Molecular genetic mapping experiments and deduction of the predicted higher-order structure from sequence data indicate the binding site is, or is within, a basic, amphiphilic alpha-helical domain composed of approximately 20 amino acids. lambda ICM-1 hybridizes with brain mRNA of 2.1 and 3.5 kb but not with mRNA from liver or kidney, suggesting possible restriction of the protein to brain. We discuss several observations that suggest lambda ICM-1 corresponds to Ca2+/calmodulin-dependent protein kinase II, an enzyme that phosphorylates several neuronal proteins, some of which apparently play a role in synaptic function. Our results suggest certain types of ligands may be useful probes to isolate genes encoding various receptor proteins, particularly when the protein is very rare or when it is difficult to obtain antibodies suitable for screening libraries.
On a class of optimal rateless codes (2008)

In this paper we analyze a class of systematic fountain/rateless codes constructed using Bernoulli(1/2) random variables. Using simple bounds we then show that this class of codes stochastically minimizes the number of coded packets receptions needed to successfully decode all the information packets. This optimality holds over a large class of random codes that includes Bernoulli(q) random codes with q les 1/2 and LT codes. We then conclude by demonstrating asymptotic optimality for intermediate decoding of the same codes.
Task and Motion Analyses in Endoscopic Surgery (1996)

Abstract We present here task and motion analyses, part of a larger study on users, tasks and tools in endoscopic surgery. Expert and novice surgeons’ performance of laparoscopic surgery in training workshops was captured on video and analyzed. Four basic surgical tasks were identified: dissecting tissue, suturing, tying knots, and cutting suture. Each task was decomposed into subtasks with operational beginnings and endings. Subtasks were further analyzed into component motions. Here we discuss: differences between novice and expert surgeons; task constraints that might account for the pattern of results across the different tasks, including precision and safety constraints; differences in manipulation of the same endoscopic tool as a function of the target object; the large number of “additional” motions; difficulties in positioning and orientation of tools to perform the surgical tasks; and the serial execution of reach and grasp movements in endoscopic surgery, compared to their parallel execution in natural prehension.
Dynamic shim updating: A new approach towards optimized whole brain shimming (1996)

The static magnetic field within two widely spaced axial slices of the human brain was mapped in five subjects following global shimming. This revealed a first order field shift in the anterior-posterior direction between the cerebellum and cerebrum, which has implications for functional and spectroscopic magnetic resonance imaging. A new method is described called dynamic shim updating (DSU) to compensate for these field differences whereby the shim correction fields are updated in real time during multislice data acquisition to match the current imaging or spectroscopy slice. A hardware unit is presented to demonstrate the method using the first order shim corrections, which can be updated virtually instantaneously between slice acquisitions to give optimal shimming of each slice. The efficiency of the approach is demonstrated using field mapping and high speed MR imaging (echo-planar imaging), which are sensitive to field inhomogeneity.
In vivo measures of dopaminergic radioligands in the rat brain: Equilibrium infusion studies (2001)

The application of an equilibrium infusion method for measuring specific in vivo radioligand binding in the conscious rat brain was evaluated for two ligands of the dopaminergic system, (+)-alpha-[(11)C]dihydrotetrabenazine (DTBZ) and d-threo-[(11)C]methylphenidate (MePhen). Both radioligands can be successfully utilized to reach equilibrium distributions in rat brain within 1 h; combinations of tritiated and carbon-11-labeled radiotracers can furthermore be used to obtain simultaneous measures of the neuronal membrane dopamine transporter (using [(3)H]MePhen) and vesicular monoamine transporter (using [(11)C]DTBZ) in the same animal. These studies provided quantitative measures of distribution volume ratios, which represent specific radioligand binding. Stereospecificity of in vivo binding was demonstrated using equilibrium infusions of the low-affinity isomers of each ligand, (-)-alpha-[(11)C]dihydrotetrabenazine (DTBZ) and l-threo-[(11)C]methylphenidate, both of which produced uniform brain distributions and no specific binding. Specific binding of (+)-alpha-[(11)C]dihydrotetrabenazine was blocked by co-infusion of tetrabenazine, but was unaffected by administration of methylphenidate, haloperidol, or apomorphine. Specific binding of d-threo-[(11)C]methylphenidate, conversely, was blocked with unlabeled methylphenidate but not affected by tetrabenazine or the dopamine receptor ligands. Equilibrium measures of in vivo radioligand binding, as utilized in this study, offer a quantitative means to evaluate acute and chronic drug effects on in vivo radioligand binding in the rat brain.
Pleural subxyphoid drain confers better pulmonary function and clinical outcomes in chronic obstructive pulmonary disease after off-pump coronary artery bypass grafting: a randomized controlled trial (2014)

Subxyphoid pleural drainage in severe Chronic obstructive pulmonary disease patients determined better preservation and recovery of pulmonary capacity and volumes with lower pulmonary shunt fraction and better clinical outcomes on early postoperative off-pump coronary artery bypass grafting.
Natural and Synthetic Allatotoxins: Suicide Substrates for Juvenile Hormone Biosynthesis (1982)

Cytotoxic agents with antijuvenile hormone activity in insects have been discovered. Their mechanism of action may involve an oxidative bioactivation into a reactive quinone methide.
Interaction of a novel red-region fluorescent probe, Nile Blue, with DNA and its application to nucleic acids assay (1999)

A novel fluorimetric method was developed for the rapid determination of DNA and RNA based on their quenching effect on the cationic red-region fluorescent dye Nile Blue (NB). In the investigation of the interaction of NB with DNA by steady-state polarization measurements, thermal denaturing study, determination of absorption and fluorescence characteristics, salt effect study and electrophoresis experiments, the results supported the suggestion that NB served as an intercalator to the stack base pairs of nucleic acids. Further evidence showed that the quenching could be ascribed to the static quenching mode. A binding constant of about 10(6) M-1 and a binding site size of about three base pairs were obtained by spectral methods. Under optimum conditions, the calibration curves for the determination of calf thymus DNA (CT DNA) and yeast RNA were linear over the ranges 3.0 ng mL-1-2.0 micrograms mL-1 and 27 ng mL-1-10 micrograms mL-1, respectively. The detection limits were 3.0 ng mL-1 for CT DNA and 27 ng mL-1 for RNA. The relative standard deviation (n = 6) was within 2.1% in the middle of the linear range. Interferences from some interesting co-existing substances in the determination of DNA were also examined.
Depressed index cladding graded barrier separate confinement single quantum well heterostructure laser (1991)

In this letter, we present data for a novel depressed index cladding laser structure which provides reduced perpendicular far-field divergence angle with acceptable low-threshold current densities. Narrow perpendicular divergence angles of 27° full width at half maximum for a nearly perfect Gaussian beam shape have been measured, with a corresponding near-field spot size of 1.30 μm. Threshold current densities of 309 A/cm2 are observed for 150 μm stripewidth, 780 μm long devices with 0.80 μm transverse spot sizes. Pulsed output powers for unmounted devices are greater than 0.9 W/uncoated facet.
Role of B7-H1 and B7-H4 molecules in down-regulating effector phase of T-cell immunity: novel cancer escaping mechanisms (2005)

The majority of human and rodent cancers display various antigens which could elicit cellular and humoral immune responses. Such immunity, however, often fails to prevent progressive growth of cancers. It has long been speculated that tumor antigens may not be presented in appropriate fashion, which subsequently fails to elicit a strong immune response. Recent studies, however, indicate that immunization by formulated tumor antigens or even transfer of pre-activated T lymphocytes also have limited impact on cancer growth despite the fact that these methods could often enhance immune responses in cancer patients. These findings imply that even afferent arm of immunity are strengthen, it is not necessarily being translated to tumor regression. It is possible that the development of evasion mechanisms in tumor microenvironment play a critical role in the resistance of therapeutic immune responses. Recent studies provide compelling evidence that human and rodent cancers develop evasion mechanisms by aberrantly expressing normal proteins, which are required for normal tissue homeostasis, to either build a microenvironment locally or reach other organs systemically. In this review, we will focus our discussion on two recently described molecules, B7-H1 and B7-H4, in the context of their roles in the evasion of tumor immunity and possible approaches for therapeutic manipulation.
Molecular Cloning of N-methylputrescine Oxidase from Tobacco (2007)

Nicotine biosynthesis in Nicotiana species requires an oxidative deamination of N-methylputrescine, catalyzed by N-methylputrescine oxidase (MPO). In a screen for tobacco genes that were down-regulated in a tobacco mutant with altered regulation of nicotine biosynthesis, we identified two homologous MPO cDNAs which encode diamine oxidases of a particular subclass. Tobacco MPO genes were expressed specifically in the root, and up-regulated by jasmonate treatment. Recombinant MPO protein expressed in Escherichia coli formed a homodimer and deaminated N-methylputrescine more efficiently than symmetrical diamines. These results indicate that MPO evolved from general diamine oxidases to function effectively in nicotine biosynthesis.
Structure of the DNA-Eco RI Endonuclease Recognition Complex at 3 Å Resolution (1986)

The crystal structure of the complex between Eco RI endonuclease and the cognate oligonucleotide TCGCGAATTCGCG provides a detailed example of the structural basis of sequence-specific DNA-protein interactions. The structure was determined, to 3 Å resolution, by the ISIR (iterative single isomorphous replacement) method with a platinum isomorphous derivative. The complex has twofold symmetry. Each subunit of the endonuclease is organized into an α/β domain consisting a five-stranded β sheet, α helices, and an extension, called the "arm," which wraps around the DNA. The large β sheet consists of antiparallel and parallel motifs that form the foundations for the loops and α helices responsible for DNA strand scission and sequence-specific recognition, respectively. The DNA cleavage site is located in a cleft that binds the DNA backbone in the vicinity of the scissile bond. Sequence specificity is mediated by 12 hydrogen bonds originating from α helical recognition modules. Arg 200 forms two hydrogen bonds with guanine while Glu 144 and Arg 145 form four hydrogen bonds to adjacent adenine residues. These interactions discriminate the Eco RI hexanucleotide GAATTC from all other hexanucleotides because any base substitution would require rupture of at least one of these hydrogen bonds.
Synthesis of Aluminum Oxide/Gradient Copolymer Composites by Atom Transfer Radical Polymerization (2002)

ADVERTISEMENT RETURN TO ISSUEPREVNoteSynthesis of Aluminum Oxide/Gradient Copolymer Composites by Atom Transfer Radical PolymerizationBin Gu and Ayusman SenView Author Information Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802 Cite this: Macromolecules 2002, 35, 23, 8913–8916Publication Date (Web):October 4, 2002Publication History Received24 May 2002Revised20 August 2002Published online4 October 2002Published inissue 1 November 2002https://pubs.acs.org/doi/10.1021/ma020809rhttps://doi.org/10.1021/ma020809rbrief-reportACS PublicationsCopyright © 2002 American Chemical SocietyRequest reuse permissionsArticle Views662Altmetric-Citations44LEARN 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:Copolymers,Monomers,Oxides,Polymer particles,Radical polymerization Get e-Alerts
Pyridin‐2(1H)‐ones: A Promising Class of HIV‐1 Non‐nucleoside Reverse Transcriptase Inhibitors (2007)

The HIV-1 reverse transcriptase (RT) is an attractive target in the treatment of AIDS. This minireview focuses on the advances in the development of non-nucleoside RT inhibitors of the pyridin-2(1H)-one class. Representative molecules, covering several subclasses are presented. Computational studies, including automated docking and QSAR, are also discussed.
Critical Role for Lysines 21 and 22 in Signal-induced, Ubiquitin-mediated Proteolysis of IkB-α (1996)

The NF-kappa B transcription factor induces rapid transcription of many genes in response to a variety of extracellular signals. NF-kappa B is readily activated from normally inhibited cytoplasmic stores by induced proteolytic degradation of I kappa B-alpha, a principal inhibitor of this transcription factor. Following the inhibitor's degradation, NF-kappa B is free to translocate to the nucleus and induce gene transcription. The I kappa B-alpha inhibitor is targeted for degradation by signal-induced phosphorylation of two closely spaced serines in its NH2 terminus (Ser32 and Ser36). Proteolytic degradation appears to be carried out by proteasomes which can recognize ubiquitinated intermediates of the I kappa B-alpha inhibitor. We provide evidence which supports a ubiquitin-mediated mechanism. Amino acid substitutions of two adjacent potential ubiquitination sites in the NH2 terminus of I kappa B-alpha (Lys21 and Lys22) almost completely block the rapid, signal-induced degradation of the mutant protein, while they do not interfere with induced phosphorylation. The mutant I kappa B-alpha also does not permit signal-induced activation of NF-kappa B bound to it. The data suggest that ubiquitination at either of the two adjacent lysines (21 and 22) is required for degradation following induced phosphorylation at nearby serines 32 and 36. Such dependence on ubiquitination of specific sites for protein degradation is unusual. This mechanism of degradation may also apply to I kappa B-beta, an inhibitor related to and functionally overlapping with I kappa B-alpha, as well as to cactus, an I kappa B homolog of Drosophila.
Peak External Photocurrent Quantum Efficiency Exceeding 100% via MEG in a Quantum Dot Solar Cell (2011)

Multiple exciton generation (MEG) is a process that can occur in semiconductor nanocrystals, or quantum dots (QDs), whereby absorption of a photon bearing at least twice the bandgap energy produces two or more electron-hole pairs. Here, we report on photocurrent enhancement arising from MEG in lead selenide (PbSe) QD-based solar cells, as manifested by an external quantum efficiency (the spectrally resolved ratio of collected charge carriers to incident photons) that peaked at 114 ± 1% in the best device measured. The associated internal quantum efficiency (corrected for reflection and absorption losses) was 130%. We compare our results with transient absorption measurements of MEG in isolated PbSe QDs and find reasonable agreement. Our findings demonstrate that MEG charge carriers can be collected in suitably designed QD solar cells, providing ample incentive to better understand MEG within isolated and coupled QDs as a research path to enhancing the efficiency of solar light harvesting technologies.
High-Throughput Permeability pH Profile and High-Throughput Alkane/Water logPwith Artificial Membranes (2001)

This study reports on a novel, high-throughput assay, designed to predict passive, transcellular permeability in early drug discovery. The assay is carried out in 96-well microtiterplates and measures the ability of compounds to diffuse from a donor to an acceptor compartment which are separated by a 9-10 microm hexadecane liquid layer. A set of 32 well-characterized, chemically diverse drugs was used to validate the method. The permeability values derived from the flux factors between donor and acceptor compartments show a good correlation with gastrointestinal absorption in humans. For comparison, correlations based on experimental or calculated octanol/water distribution coefficients (log D(o/w,6.8)) were significantly lower. In addition, this simple and robust assay allows determination of pH permeability profiles, critical information to predict gastrointestinal absorption of ionizable drugs and difficult to obtain from cell culture experiments. Correction for the unstirred water layer effect allows to differentiate between effective and intrinsic membrane permeability and opens up the dynamic range of the method. In addition, alkane/water partition coefficients can be derived from intrinsic membrane permeabilities, making this assay the first high-throughput method able to measure alkane/water log P in the microtiterplate format.