cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
Computational exploration of natural compounds targeting Staphylococcus aureus: inhibiting AgrA promoter binding for antimicrobial intervention
Creators: name: Saha, Subhadip
name: Ghosh, Monidipa
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biophysics
subject: Biochemistry
subject: Genetics
subject: FOS: Biological sciences
subject: Pharmacology
subject: Biotechnology
subject: Chemical Sciences not elsewhere classified
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Infectious Diseases
subject: FOS: Health sciences
subject: Computational Biology

description: Staphylococcus aureus is a highly virulent nosocomial pathogen that poses a significant threat to individuals exposed to healthcare settings. Due to its sophisticated machinery for producing virulence factors, S. aureus can cause severe and potentially fatal infections in humans. This study focuses on the response regulator AgrA, which plays a crucial role in regulating the production of virulence factors in S. aureus. The objective is to identify natural compounds that can inhibit the binding of AgrA to its promoter site, thus inhibiting the expression of virulence genes. To achieve this, a pharmacophore model was generated using known drugs and applied to screen the ZINC natural product database. The resulting compounds were subjected to molecular docking-based virtual screening against the C-terminal DNA binding domain of AgrA. Three compounds, namely ZINC000077269178, ZINC000051012304, and ZINC000004266026, were shortlisted based on their strong affinity for key residues involved in DNA binding and transcription initiation. Subsequently, the unbound and ligand-bound complexes were subjected to a 200 ns molecular dynamics simulation to assess their conformational stability. Various analyses, including RMSD, RMSF, Rg, SASA, Principal Component Analysis, and Gibbs free energy landscape, were conducted on the simulation trajectory. The RMSD profile indicated similar fluctuations in both bound and unbound structures, while the Rg profile demonstrated the compactness of the protein without any unfolding during the simulation. Furthermore, Principal component analysis revealed that ligand binding reduced the overall atomic motion of the protein whereas free energy landscape suggested the energy variations obtained in complexes. Communicated by Ramaswamy H. Sarma
Finding $η$ Car Analogs in Nearby Galaxies Using Spitzer: II. Identification of An Emerging Class of Extragalactic Self-Obscured Stars
Creators: name: Khan, Rubab
name: Kochanek, C. S.
name: Stanek, K. Z.
name: Gerke, Jill
Publisher: name: arXiv
Year: 2014
Subjects: subject: Solar and Stellar Astrophysics (astro-ph.SR)
subject: FOS: Physical sciences

description: Understanding the late-stage evolution of the most massive stars such as $η$ Carinae is challenging because no true analogs of $η$ Car have been clearly identified in the Milky Way or other galaxies. In Khan et. al. (2013), we utilized Spitzer IRAC images of $7$ nearby ($\lesssim4$ Mpc) galaxies to search for such analogs, and found $34$ candidates with flat or red mid-IR spectral energy distributions. Here, in Paper II, we present our characterization of these candidates using multi-wavelength data from the optical through the far-IR. Our search detected no true analogs of $η$ Car, which implies an eruption rate that is a fraction $0.01\lesssim F \lesssim 0.19$ of the ccSN rate. This is roughly consistent with each $M_{ZAMS} \gtrsim 70M_\odot$ star undergoing $1$ or $2$ outbursts in its lifetime. However, we do identify a significant population of $18$ lower luminosity $\left(\log(L/L_\odot)\simeq5.5-6.0\right)$ dusty stars. Stars enter this phase at a rate that is fraction $0.09 \lesssim F \lesssim 0.55$ of the ccSN rate, and this is consistent with all $25 < M_{ZAMS} < 60M_\odot$ stars undergoing an obscured phase at most lasting a few thousand years once or twice. These phases constitute a negligible fraction of post-main sequence lifetimes of massive stars, which implies that these events are likely to be associated with special periods in the evolution of the stars. The mass of the obscuring material is of order $\sim M_\odot$, and we simply do not find enough heavily obscured stars for theses phases to represent more than a modest fraction ($\sim 10\%$ not $\sim 50\%$) of the total mass lost by these stars. In the long term, the sources that we identified will be prime candidates for detailed physical analysis with JWST.
description: 35 pages, 12 figures, 5 tables. Submitted to ApJ
Expression of the human apolipoprotein E gene suppresses steroidogenesis in mouse Y1 adrenal cells.
Creators: name: Gwynne, J. T.
name: Prack, M. M.
name: Williams, D. L.
name: Reyland, M. E.
name: Forgez, P.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 1991

description: The lipid transport protein, apolipoprotein E (apoE), is expressed in many peripheral tissues in vivo including the adrenal gland and testes. To investigate the role of apoE in adrenal cholesterol homeostasis, the authors have expressed a human apoE genomic clone in the Y1 mouse adrenocortical cell line. Y1 cells do not express endogenous apoE mRNA or protein. Expression of apoE in Y1 cells resulted in a dramatic decrease in basal steroidogenesis; secretion of fluorogenic steroid was reduced 7- to {gt}100-fold relative to Y1 parent cells. Addition of 5-cholesten-3{beta},25-idol failed to overcome the suppression of steroidogenesis in these cells. Cholesterol esterification under basal conditions, as measured by the production of cholesteryl ({sup 14}C)oleate, was similar in the Y1 parent and the apoE-transfected cell lines. Upon incubation with adrenocorticotropin or dibutyryl cAMP, production of cholesteryl ({sup 14}C)oleate decreased 5-fold in the Y1 parent cells but was unchanged in the apoE-transfected cell lines. These results suggest that apoE may be an important modulator of cholesterol utilization and steroidogenesis in adrenal cells.
Gene- and strand-specific repair in vitro: partial purification of a transcription-repair coupling factor.
Creators: name: Sancar, A.
name: Selby, C. P.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 1991

description: In eukaryotic and prokaryotic cells, actively transcribed genes and, in some instances, the template strand of these genes have been found to be repaired 2-10 times more rapidly than nontranscribed genes or the coding strand of transcribed genes. The authors demonstrate here gene- and template strand-specific repair synthesis in vitro by using an Escherichia coli cell-free extract and a plasmid carrying a gene with the strong tac promoter. Strand-specific repair of UV, 4{prime}-hydroxymethyl-4,5{prime}, 8-trimethylpsoralen, and cis-dicholorodiammine platinum(II) damage was dependent upon transcription and a functional nucleotide excision repair system and was stimulated by 6% (wt/vol) polyethylene glycol. A defined system consisting of the transcription and repair proteins in highly purified form did not perform strand-specific repair; however, active fractions of extract conferred strand specificity to the defined system. Transcription-repair coupling activity was partially purified from extract by successive DEAE-agarose and gel filtration chromatography. The coupling factor is heat-labile, with an estimated M{sub r} of 100,000.
A computational investigation of thymidylate synthase inhibitors through a combined approach of 3D-QSAR and pharmacophore modelling
Creators: name: Benny, Sonu
name: Krishnendu, Prayaga Rajappan
name: Kumar, Sunil
name: Bhaskar, Vaishnav
name: Manisha, Deepthi S.
name: Abdelgawad, Mohamed A.
name: Ghoneim, Mohammed M.
name: Naguib, Ibrahim A.
name: Pappachen, Leena. K.
name: Zachariah, Subin Mary
name: Mathew, Bijo
name: TP, Aneesh
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biophysics
subject: Biochemistry
subject: Genetics
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Pharmacology
subject: Chemical Sciences not elsewhere classified
subject: Biological Sciences not elsewhere classified
subject: Information Systems not elsewhere classified
subject: Cancer

description: Thymidylate synthase (TS) is a crucial target of cancer drug discovery and is mainly involved in the De novo synthesis of the DNA precursor thymine. In the present study, to generate reliable models and identify a few promising molecules, we combined QSAR modelling with the pharmacophore hypothesis-generating technique. Input molecules were clustered on their similarity, and a cluster of 74 molecules with a pyrimidine moiety was chosen as the set for 3D-QSAR and pharmacophore modelling. Atom-based and field-based 3D-QSAR models were generated and statistically validated with R2 > 0.90 and Q2 > 0.75. The common pharmacophore hypothesis(CPH) generation identified the best six-point model ADHRRR. Using these best models, a library of FDA-approved drugs was screened for activity and filtered via molecular docking, ADME profiling, and molecular dynamics simulations. The top ten promising TS-inhibiting candidates were identified, and their chemical features profitable for TS inhibitors were explored. Communicated by Ramaswamy H. Sarma
Probing an excited-state atomic transition using hyperfine quantum beat spectroscopy
Creators: name: Wade, Christopher G.
name: Šibalić, Nikola
name: Keaveney, James
name: Adams, Charles S.
name: Weatherill, Kevin J.
Publisher: name: arXiv
Year: 2014
Subjects: subject: Atomic Physics (physics.atom-ph)
subject: FOS: Physical sciences

description: We describe a method to observe the dynamics of an excited-state transition in a room temperature atomic vapor using hyperfine quantum beats. Our experiment using cesium atoms consists of a pulsed excitation of the D2 transition, and continuous-wave driving of an excited-state transition from the 6P$_{3/2}$ state to the 7S$_{1/2}$ state. We observe quantum beats in the fluorescence from the 6P$_{3/2}$ state which are modified by the driving of the excited-state transition. The Fourier spectrum of the beat signal yields evidence of Autler-Townes splitting of the 6P$_{3/2}$, F = 5 hyperfine level and Rabi oscillations on the excited-state transition. A detailed model provides qualitative agreement with the data, giving insight to the physical processes involved.
Human immunodeficiency virus type 1 Gag proteins are processed in two cellular compartments.
Creators: name: Kaplan, A. H.
name: Swanstrom, R.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 1991

description: The structural proteins of the retroviral capsid are translated as a polyprotein (the Gag precursor) that is cleaved by a virally encoded protease. Processing of the human immunodeficiency virus type 1 Gag precursor Pr55 was analyzed through a combination of pulse-chase labeling, cell fractionation, and immunoprecipitation. We observed a membrane-associated processing pathway for the Gag precursor that gives rise to virions. In addition, we found that a significant amount of processing occurs in the cytoplasm of infected cells resulting in the intracellular accumulation of appropriately processed viral proteins. This observation suggests the viral protease is active in the cytoplasmic compartment of the cell. Processing of the Gag protein was blocked in both compartments by the addition of a viral protease inhibitor. A comparison of the amount of cytoplasmic processing seen in lytically infected cells with that seen in chronically infected cells showed that cytoplasmic processing was associated with the lytic infection. These observations raise the possibility that activation of the human immunodeficiency virus type 1 protease in the cytoplasm of lytically infected cells might result in the cleavage of cellular proteins and thus contribute to cytotoxicity.
MAXI investigation into the longterm X-ray variability from the very-high-energy gamma-ray blazar Mrk 421
Creators: name: Isobe, Naoki
name: Sato, Ryosuke
name: Ueda, Yoshihiro
name: Hayashida, Masaaki
name: Shidatsu, Megumi
name: Kawamuro, Taiki
name: Ueno, Shiro
name: Sugizaki, Mutsumi
name: Sugimoto, Juri
name: Mihara, Tatehiro
name: Matsuoka, Masaru
name: Negoro, Hitoshi
name: team, the MAXI
Publisher: name: arXiv
Year: 2014
Subjects: subject: High Energy Astrophysical Phenomena (astro-ph.HE)
subject: FOS: Physical sciences

description: The archetypical very-high-energy gamma-ray blazar Mrk 421 was monitored for more than 3 years with the Gas Slit Camera onboard Monitor of All Sky X-ray Image (MAXI), and its longterm X-ray variability was investigated. The MAXI lightcurve in the 3 -- 10 keV range was transformed to the periodogram in the frequency range $f = 1 \times 10^{-8}$ -- $2 \times 10^{-6}$ Hz. The artifacts on the periodogram, resulting from data gaps in the observed lightcurve, were extensively simulated for variations with a power-law like Power Spectrum Density (PSD). By comparing the observed and simulated periodograms, the PSD index was evaluated as $α= 1.60 \pm 0.25$. This index is smaller than that obtained in the higher frequency range ($f > 1 \times 10^{-5}$ Hz), namely, $α= 2.14 \pm 0.06$ in the 1998 ASCA observation of the object. The MAXI data impose a lower limit on the PSD break at $f_{\rm b} = 5 \times 10^{-6}$ Hz, consistent with the break of $f_{\rm b} = 9.5 \times 10^{-6}$ Hz, suggested from the ASCA data. The low frequency PSD index of Mrk 421 derived with MAXI falls well within the range of the typical value among nearby Seyfert galaxies ($α= 1$ -- $2$). The physical implications from these results are briefly discussed.
description: 27 pages, 8 figures, accepted for ApJ (V797)
Identification and purification to near homogeneity of the vitamin K-dependent carboxylase.
Creators: name: Wu, S. M.
name: Stafford, D. W.
name: Morris, D. P.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 1991

description: Vitamin K-dependent carboxylase catalyzes the modification of specific glutamic acids to gamma-carboxyglutamic acid in several blood-coagulation proteins. This modification is required for the blood-clotting activity of these proteins and has thus been the subject of intense investigation. We have now identified the bovine vitamin K-dependent carboxylase and purified it to near homogeneity by an affinity procedure that uses the 59-amino acid peptide FIXQ/S (residues -18 to 41 of factor IX with mutations Arg----Gln at residue -4 and Arg----Ser at residue -1). The carboxylase as purified has a molecular weight of 94,000. It is also the major protein that can be cross-linked to iodinated FIXQ/S and is the only protein whose cross-linking is prevented by a synthetic factor IX propeptide. The degree of purification is about 7000-fold with reference to ammonium sulfate-fractionated microsomal protein from liver.
A Variable PV Broad Absorption Line and Quasar Outflow Energetics
Creators: name: Capellupo, Daniel M.
name: Hamann, Fred
name: Barlow, Tom A.
Publisher: name: arXiv
Year: 2014
Subjects: subject: Astrophysics of Galaxies (astro-ph.GA)
subject: Cosmology and Nongalactic Astrophysics (astro-ph.CO)
subject: FOS: Physical sciences

description: Broad absorption lines (BALs) in quasar spectra identify high velocity outflows that might exist in all quasars and could play a major role in feedback to galaxy evolution. The viability of BAL outflows as a feedback mechanism depends on their kinetic energies, as derived from the outflow velocities, column densities, and distances from the central quasar. We estimate these quantities for the quasar, Q1413+1143 (redshift $z_e = 2.56$), aided by the first detection of PV $λλ$1118,1128 BAL variability in a quasar. In particular, PV absorption at velocities where the CIV trough does not reach zero intensity implies that the CIV BAL is saturated and the absorber only partially covers the background continuum source (with characteristic size <0.01 pc). With the assumption of solar abundances, we estimate that the total column density in the BAL outflow is log N_H > 22.3 (cm^-2). Variability in the PV and saturated CIV BALs strongly disfavors changes in the ionization as the cause of the BAL variability, but supports models with high-column density BAL clouds moving across our lines of sight. The observed variability time of 1.6 yr in the quasar rest frame indicates crossing speeds >750 km/s and a radial distance from the central black hole of <3.5 pc, if the crossing speeds are Keplerian. The total outflow mass is ~4100 M_solar, the kinetic energy ~4x10^54 erg, and the ratio of the outflow kinetic energy luminosity to the quasar bolometric luminosity is ~0.02 (at the minimum column density and maximum distance), which might be sufficient for important feedback to the quasar's host galaxy.
description: 9 pages, 4 figures, accepted for publication in MNRAS
Mutational analysis of flavonol synthase of M. pinnata towards enhancement of binding affinity: a computational approach
Creators: name: Kumari, Garima
name: Nigam, Vinod Kumar
name: Pandey, Dev Mani
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biophysics
subject: Biochemistry
subject: Genetics
subject: FOS: Biological sciences
subject: Pharmacology
subject: Biotechnology
subject: Chemical Sciences not elsewhere classified
subject: Biological Sciences not elsewhere classified

description: Millettia pinnata is an important medicinal plant that has been used as a treatment of various diseases due to presence of wide range of pharmacological properties. The plant contains quercetin, kaempferol, karanjin, pongaglabrone, kanjone, kanugin, gammatin, pongaglabol, and other bioflavonoids. Kaempferol is a natural flavonol that shows many pharmacological properties including anti-inflammatory, antioxidant, anticancer, and antidiabetic activities etc. The enzyme flavonol synthase (FLS, EC 1.14.20.6) catalyses the conversion of dihydroflavonols to flavonols, i.e. biosynthesis of kaempferol from dihydrokaempferol. The current work examined the binding affinity-based approach to improve the enzyme catalytic activity using computational methods. Sequential site-directed mutagenesis was used to create four mutants with the goal to increase hydrogen bonds and further improving the ligand (dihydrokaempferol) binding efficiency. Simulations were done to monitor the stability of the mutants followed by molecular docking to confirm interactions with ligand. For structure validation, various dynamic analysis like RMSD, RMSF, ROG, SASA, H-bond, PCA, DCCM, and FEL were performed, which predicts the stability of wild-type (WT) proteins and mutants. The Mutant_2 and Mutant_3 showed maximum H-bonding and better stability than other mutants and WT that proved higher affinity suggesting improved catalysis. Mutant_2 and Mutant_3 exhibited binding affinities of −7.6 and −8.2 kcal/mol, respectively for the ligand. The outcome of present study will provide significant improvement in synthesis of kaempferol and other plant-based flavonoids. Communicated by Ramaswamy H. Sarma
Giant Tachyons in the Landscape
Creators: name: Bena, Iosif
name: Graña, Mariana
name: Kuperstein, Stanislav
name: Massai, Stefano
Publisher: name: arXiv
Year: 2014
Subjects: subject: High Energy Physics - Theory (hep-th)
subject: FOS: Physical sciences

description: We study the dynamics of localized and fully backreacting anti-D3 branes at the tip of the Klebanov-Strassler geometry. We use a non-supersymmetric version of the Polchinski-Strassler analysis to compute the potential for anti-D3 branes to polarize into all kinds of five-brane shells in all possible directions. We find that generically there is a direction along which the brane-brane interaction is repulsive, which implies that anti-D3 branes are tachyonic. Hence, even though anti-D3 branes can polarize into five-branes, the solution will most likely be unstable. This indicates that anti-D3 brane uplift may not result in stable de Sitter vacua.
description: 24 pages, 3 figures
Loss of heterozygosity on the short arm of chromosome 17 is associated with high proliferative capacity and DNA aneuploidy in primary human breast cancer.
Creators: name: Neubauer, A.
name: Balazs, M.
name: Goodson, W.
name: Ljung, B. M.
name: Chen, L. C.
name: Kurisu, W.
name: Moore, D.
name: Liu, E.
name: Waldman, F. M.
name: Goldman, E. S.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 1991

description: Loss of heterozygosity (LOH) on the short arm of chromosome 17 (17p) was found in 27 of 52 (52%) previously untreated primary breast cancers. There was a significant correlation between this 17p allelic loss and two parameters associated with aggressive tumor behavior: high cellular proliferative fraction and DNA aneuploidy. These correlations with high cellular proliferative fraction and DNA aneuploidy were not found in tumors with LOH at nine other chromosome locations. The p53 gene, a putative tumor suppressor gene located at 17p13, was examined for aberrations to determine whether it is the target for the 17p LOH in breast cancer. Unlike other types of human cancer, there were no homozygous deletions or rearrangements of the p53 gene, and only 2 of 13 (15%) were mutated in the conserved region where mutational "hot spots" have been previously located. Therefore, we hypothesize that, in breast cancer, either loss or inactivation of gene(s) on chromosome 17p other than the p53 gene or a different mechanism of p53 gene inactivation may be responsible for the observed high labeling index and DNA aneuploidy associated with LOH at 17p.
title: A philosophical discussion of the implications and limitations of using Virtual Reality Technology (VR) as an “Empathy Machine”
Creators: name: Bouabdeli, Sarra
Publisher: name: University of Reading
Year: 2023

description: This thesis engages in a philosophical discussion on “empathy”, “virtuality”, and the use of virtual reality (VR) technology as an “empathy machine”. Here, I define empathy as the intentional activity (or skill) of recreating aspects of another subject’s emotional experience in one’s imagination to reflectively and “experientially” understand what another is feeling. As opposed to isomorphically appropriating another’s feelings to oneself, I identify empathy as third-personally “feeling with” others. After exploring the narrow and pluralistic approaches to understanding empathy, I argue that there are compelling pragmatic reasons for adopting the pluralistic approach, the proponents of which prefer to highlight varieties of empathy instead of a sole conceptualisation of “empathy proper”. As for virtuality, I subscribe to a third view that can be located between “virtual realism” and “virtual irrealism”, in that I understand virtuality as a sui generis mode of technological actualisation, where psychophysiological illusions, of virtual presence and embodiment, coexist with veridical elements, such as virtual social objects, without causing a defect in users’ rational judgment. My main contention in this research is that VR’s multisensory affordances can be instrumentally utilised as a complementary extension (but never as a replacement) for offsetting some of the limitations in attaining interpersonal empathy through imaginative perspective-taking alone. After discussing this contention in more depth, I then attempt to address some of the recurrent challenges and criticism raised against VR’s use as an empathy machine. Finally, I highlight some of the limitations in VR technology’s capability to capture and transmit a full representation of others’ lived experiences.
Mass production of volume phase holographic gratings for the VIRUS spectrograph array
Creators: name: Chonis, Taylor S.
name: Frantz, Amy
name: Hill, Gary J.
name: Clemens, J. Christopher
name: Lee, Hanshin
name: Tuttle, Sarah E.
name: Adams, Joshua J.
name: Marshall, J. L.
name: DePoy, D. L.
name: Prochaska, Travis
Publisher: name: arXiv
Year: 2014
Subjects: subject: Instrumentation and Methods for Astrophysics (astro-ph.IM)
subject: FOS: Physical sciences

description: The Visible Integral-field Replicable Unit Spectrograph (VIRUS) is a baseline array of 150 copies of a simple, fiber-fed integral field spectrograph that will be deployed on the Hobby-Eberly Telescope (HET). VIRUS is the first optical astronomical instrument to be replicated on an industrial scale, and represents a relatively inexpensive solution for carrying out large-area spectroscopic surveys, such as the HET Dark Energy Experiment (HETDEX). Each spectrograph contains a volume phase holographic (VPH) grating with a 138 mm diameter clear aperture as its dispersing element. The instrument utilizes the grating in first-order for 350-550 nm. Including witness samples, a suite of 170 VPH gratings has been mass produced for VIRUS. Here, we present the design of the VIRUS VPH gratings and a discussion of their mass production. We additionally present the design and functionality of a custom apparatus that has been used to rapidly test the first-order diffraction efficiency of the gratings for various discrete wavelengths within the VIRUS spectral range. This device has been used to perform both in-situ tests to monitor the effects of adjustments to the production prescription as well as to carry out the final acceptance tests of the gratings' diffraction efficiency. Finally, we present the as-built performance results for the entire suite of VPH gratings.
description: 16 pages, 11 figures, 2 tables. To be published in Proc. SPIE, 2014, "Advances in Optical and Mechanical Technologies for Telescopes and Instrumentation", 9151-53. The work presented in this article follows from arXiv:1207:4487
Substrate-like novel inhibitors of prolyl specific oligo peptidase for neurodegenerative disorders
Creators: name: Khan, Majid
name: Halim, Sobia Ahsan
name: Waqas, Muhammad
name: Golmohammadi, Farhad
name: Balalaie, Saeed
name: Csuk, Rene
name: Uddin, Jalal
name: Khan, Ajmal
name: Al-Harrasi, Ahmed
Publisher: name: Taylor & Francis
Year: 2023
Subjects: Biochemistry
Pharmacology
Chemical Sciences not elsewhere classified
Biological Sciences not elsewhere classified

description: Prolyl specific oligopeptidase (POP), is one of the highly expressed enzymes in the brain and is a prime target to treat disorders related to the central nervous system. Here, we describe the structure-based design of the tacrine derivatives, selective, and brain-permeable POP inhibitors. These compounds inactivate POP in-vitro specifically and sustainably at very low concentrations (nano molar). Among this series, compound 6b (IC50 = 0.81 ± 0.04 µM) exhibited most potent inhibition. Furthermore, kinetic study revealed that these molecules target active site of POP which is further confirmed by in-silico molecular interaction analysis. The computational docking results indicates that the compounds are well fitted in the active site with high binding score (i.e., > −7 to > −4 kcal/mol) where Trp595, Arg643, Tyr473, and Ser554 plays important role in binding with the active compounds. The molecular dynamic simulation of most active compounds (6a, 6b, 6d, and 6f) displayed higher free energy binding, when compared to the standard drug in MM-PBSA based binding free energy calculation. In addition, the predicted pharmacokinetic profile suggests that these compounds can serve as excellent inhibitors upon additional optimization which makes them prime choice for further investigation. Communicated by Ramaswamy H. Sarma
Impact of artificial intelligence on colorectal polyp detection for early-career endoscopists: an international comparative study
Creators: name: Ainechi, Diba
name: Misawa, Masashi
name: Barua, Ishita
name: Larsen, Solveig Linnea Veen
name: Paulsen, Vemund
name: Garborg, Kjetil Kjeldstad
name: Aabakken, Lars
name: Tønnesen, Christer Julseth
name: Løberg, Magnus
name: Kalager, Mette
name: Kudo, Shin-Ei
name: Hotta, Kinichi
name: Ohtsuka, Kazuo
name: Saito, Shoichi
name: Ikematsu, Hiroaki
name: Saito, Yutaka
name: Matsuda, Takahisa
name: Itoh, Hayato
name: Mori, Kensaku
name: Bretthauer, Michael
name: Mori, Yuichi
Publisher: name: Taylor & Francis
Year: 2022
Subjects: subject: Microbiology
subject: FOS: Biological sciences
subject: Molecular Biology
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: Ecology
subject: Sociology
subject: FOS: Sociology
subject: 80699 Information Systems not elsewhere classified
subject: FOS: Computer and information sciences
subject: Developmental Biology
subject: Cancer

description: Artificial intelligence (AI) for polyp detection is being introduced to colonoscopy, but there is uncertainty how this affects endoscopists’ ability to detect polyps and neoplasms. We performed a video-based study to address whether AI improved the endoscopists’ performance to detect polyps. We established a dataset of 200 colonoscopy videos (length 5 s; 100 without polyps and 100 with one polyp). About 33 early-career endoscopists (50–400 colonoscopies performed) from 10 European countries classified each video as either ‘polyp present’ or ‘polyp not present’. The video assessment was performed twice with a four-week interval. The first assessment was performed without any AI tool, whereas the second was performed with an AI tool for polyp detection. The primary endpoint was early-career endoscopists’ sensitivity to detect polyps. Gold standard for presence and histology of polyps were confirmed by two expert endoscopists and pathologists, respectively. McNemar’s test was used for statistical significance. There were 86 neoplastic and 14 non-neoplastic polyps (mean size 5.6 mm) in the 100 videos with polyps. Early-career endoscopists’ sensitivity to detect polyps increased from 86.3% (95% confidence interval [CI]: 85.1–87.5%) to 91.7% (95%CI: 90.7–92.6%) with the AI aid (p < .0001). Their sensitivity to detect neoplastic polyps increased from 85.4% (95% CI: 84.0–86.7%) to 92.1% (95%CI: 91.1–93.1%) with the AI aid (p < .0001). The polyp detection AI tool helped early-career endoscopists to increase their sensitivity to identify all polyps and neoplastic polyps during colonoscopy.
Approximate N^3LO Higgs-boson production cross section using physical-kernel constraints
Creators: name: de Florian, D.
name: Mazzitelli, J.
name: Moch, S.
name: Vogt, A.
Publisher: name: arXiv
Year: 2014
Subjects: subject: High Energy Physics - Phenomenology (hep-ph)
subject: FOS: Physical sciences

description: The single-logarithmic enhancement of the physical kernel for Higgs production by gluon-gluon fusion in the heavy top-quark limit is employed to derive the leading so far unknown contributions, ln^{5,4,3}(1-z), to the N^3LO coefficient function in the threshold expansion. Also using knowledge from Higgs-exchange DIS to estimate the remaining terms not vanishing for z = m_H^2/s^hat -> 1, these results are combined with the recently completed soft + virtual contributions to provide an uncertainty band for the complete N^3LO correction. For the 2008 MSTW parton distributions these N^3LO contributions increase the cross section at 14 TeV by (10 +- 2)% and (3 +- 2.5)% for the standard choices mu_R = m_H and mu_R = m_H/2 of the renormalization scale. The remaining uncertainty arising from the hard-scattering cross sections can be quantified as no more than 5%, which is smaller than that due to the strong coupling and the parton distributions.
description: 24 pages, 6 figures. arXiv-dysfunctional LaTeX macro for beta_0 replaced. Minor text changes with 3 new references. Version to appear in JHEP
Phosphorylation of insulin-like growth factor (IGF)-binding protein 1 in cell culture and in vivo: effects on affinity for IGF-I.
Creators: name: D'Ercole, A. J.
name: Camacho-Hubner, C.
name: Jones, J. I.
name: Clemmons, D. R.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 1991

description: The insulin-like growth factors (IGF-I and IGF-II) are present in extracellular fluids bound to specific IGF-binding proteins (IGFBPs). The authors and others have reported varying biologic activity of different preparations of IGFBP-1 that appeared to have identical amino acid sequences and molecular sizes. This observation prompted them to determine whether IGFBP-1 undergoes posttranslational modifications. Immunoprecipitation was used to show that Chinese hamster ovary cells and human hepatoma (hepG2) cells secrete {sup 32}P-labeled IGFBP-1 following incubation with ({sup 32}P)orthophosphate. Phospho amino acid analysis of {sup 32}P-labeled IGFBP-1 revealed only phosphoserine residues. A method was developed that could separate nonphosphorylated IGFBP-1 from four or five phosphorylated isoforms. These observations suggest that IGFBP-1 is secreted as a phosphoprotein and is subsequently dephosphorylated in vivo. Binding studies showed that the phosphorylated IGFBP-1 secreted by HepG2 cells has a 6-fold higher affinity for IGF-I than it does after dephosphorylation. They conclude that IGFBP-1 is phosphorylated and that this phosphorylation is a physiologically important posttranslational modification.
Recognition of beta 2-microglobulin-negative (beta 2m-) T-cell blasts by natural killer cells from normal but not from beta 2m- mice: nonresponsiveness controlled by beta 2m- bone marrow in chimeric mice.
Creators: name: Ohlen, C.
name: Ljunggren, H. G.
name: Hoglund, P.
name: Koller, B.
name: Carbone, E.
name: Karre, K.
name: Franksson, L.
name: Latour, A.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 1991

description: The role of major histocompatibility complex (MHC) class I expression in control of the sensitivity of normal cells to natural killer (NK) cells was studied by the use of mutant mice made deficient for expression of beta 2-microglobulin (beta 2m) through homologous recombination in embryonal stem cells. T-cell blasts from beta 2m-deficient (beta 2m -/-) mice were killed by NK cells from normal mice in vitro, while beta 2m +/- blasts were resistant. The beta 2m defect also affected the NK effector cell repertoire: NK cells from beta 2m -/- mice failed to kill beta 2m -/- blasts, while they retained the ability to kill the prototype NK cell target lymphoma YAC-1, although at reduced levels. The inability to recognize beta 2m -/- blasts could be transferred with beta 2m -/- bone marrow to irradiated beta 2m-expressing mice. In contrast, the development of CD8+ T cells (deficient in beta 2m -/- mice) was restored in such chimera. These results indicate that loss of MHC class I/beta 2m expression is sufficient to render normal cells sensitive to NK cells, and that the same defect in the hemopoietic system of a mouse renders its NK cells tolerant to beta 2m-deficient but otherwise normal cells. In the beta 2m -/- mice, NK cells may be selected or educated by other bone marrow cells to tolerate the MHC class I deficiency. Alternatively, the specificity may be controlled directly by the class I molecules on the NK cells themselves.
Structural analysis of the AICD central 12 residue peptide stretch and its interactions with metals and polyphenols, as a potential drug target for AD
Creators: name: Senapati, Dillip K.
name: Kumar, D. Jagadeesh
name: Narayan, Priya
name: G., Nagendra H.
name: A., Venkatesha M.
name: M., Govindaraju
name: Easwaran, K. R. K.
name: Ramanathan, K. V.
name: Raghothama, S.
Publisher: name: Taylor & Francis
Year: 2023
Subjects: Biophysics
Biochemistry
Molecular Biology
Pharmacology
Environmental Sciences not elsewhere classified
Chemical Sciences not elsewhere classified
Biological Sciences not elsewhere classified
Information Systems not elsewhere classified

description: Structural analysis of the central 12 residue stretch of Amyloid precursor protein Intracellular Domain (AICD16-27: T-S-I-H-H-G-V-V-E-V-D-A) was carried out by NMR and homology modeling. Further, metal and polyphenol interactions were also carried out for these 12 residues stretch, as it contains two critical Histidine residues, which were observed to be perturbed via NMR. A full length 57 residues AICD model was generated via computational methods, to ascertain its overall conformation, as the entire structure was unavailable. An overlay of this AICD entire model with the full length Aβ-42 structure matched well, implying similar properties. Docking studies with metals and polyphenols indicated involvement of the key Histidine residues highlighting their roles towards neurodegeneration and AD pathophysiology. Communicated by Ramaswamy H. Sarma
Signal transduction by integrins: increased protein tyrosine phosphorylation caused by clustering of beta 1 integrins.
Creators: name: Juliano, R. L.
name: Prockop, C.
name: Earp, H. S.
name: Kornberg, L. J.
name: Turner, C. E.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 1991

description: The integrin family of cell adhesion receptors mediates many of the interactions between cells and the extracellular matrix. Because the extracellular matrix has profound influences on cell behavior, it seems likely that integrins transduce biochemical signals across the cell membrane. The nature of these putative signals has, thus far, remained elusive. Antibody-mediated clustering of integrin receptors was used to mimic the integrin clustering process that occurs during formation of adhesive contacts. Human epidermal carcinoma (KB) cells were incubated with an anti-beta 1 integrin monoclonal antibody for 30 min on ice followed by incubation at 37 degrees C with anti-rat IgG. This treatment, which induced integrin clustering, stimulated the phosphorylation on tyrosine residues of a 115- to 130-kDa complex of proteins termed pp130. When integrins were clustered in the presence of the phosphatase inhibitor sodium orthovanadate, pp130 showed a substantial increase in phosphorylation compared to the case in which integrins were clustered in the absence of vanadate. Maximal pp130 phosphorylation was observed 10-20 min after initiation of integrin clustering in the absence of vanadate or after 5-10 min in its presence. These time courses roughly parallel the formation of integrin clusters on the cell surface as observed by fluorescence microscopy. pp130 phosphorylation depended on the amount of anti-integrin antibody present. Additionally, the tyrosine phosphorylation of pp130 showed specificity since it was stimulated by antibodies to the integrin alpha 3 and beta 1 subunits but not by antibodies to other integrin alpha subunits or to nonintegrin cell surface proteins. Immunoprecipitation experiments clearly demonstrated that pp130 is not itself a beta 1 integrin. It is postulated, therefore, that the integrin-stimulated tyrosine phosphorylation of pp130 may reflect part of an important signal transduction process between the extracellular matrix and the cell interior.
Gastric cancer screening: a systematic review and meta-analysis
Creators: name: Faria, Lídia
name: Silva, João Carlos
name: Rodríguez-Carrasco, Marta
name: Pimentel-Nunes, Pedro
name: Dinis-Ribeiro, Mário
name: Libânio, Diogo
Publisher: name: Taylor & Francis
Year: 2022
Subjects: subject: Medicine
subject: Biotechnology
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: 69999 Biological Sciences not elsewhere classified
subject: FOS: Biological sciences
subject: Science Policy

description: Gastric cancer (GC) screening is recommended in high-risk populations, although screening methods and intervals vary. In intermediate-risk populations, screening through esophagogastroduodenoscopy (EGD) may be considered depending on local resources. The aim of this study was to compare GC screening methods regarding effect on mortality, diagnostic yield and adherence. Systematic review and meta-analysis including studies evaluating population-based GC screening. Search was conducted in three online databases (MEDLINE, Scopus and clinicaltrials.gov), along with manual search. Forty-four studies were included. Studies in upper gastrointestinal series (UGIS) demonstrated that GC screening was associated with significantly lower GC mortality rates (OR 0.63, 95% CI 0.55 − 0.73). Benefits on mortality were also found in EGD and serum pepsinogen (PG) studies. EGD was associated with significantly higher GC (0.55%, 95% CI 0.39 − 0.75%) and early-GC (EGC) detection rates (0.48%, 95% CI 0.34 − 0.65%) when compared to UGIS (GC 0.19%, 95% CI 0.10 − 0.31%; EGC 0.08%, 95% CI 0.04 − 0.13%) and PG (GC 0.10%, 95% CI 0.05 − 0.16%; EGC 0.10%, 95% CI 0.04 − 0.19%). Non-invasive methods tended to higher adherence rates when compared to EGD. Regardless of the screening method, individualized recruitment performed better. Screening positively impacted GC mortality rates. EGD was associated with higher diagnostic yield, while UGIS and PG tended to higher adherence rates. Screening uptake was predominantly impacted by recruitment strategies independently of the adopted method.
Structure and Stability of Two Dimensional Phosphorene with =O or =NH Functionalization
Creators: name: Dai, Jun
name: Zeng, Xiao Cheng
Publisher: name: arXiv
Year: 2014
Subjects: subject: Materials Science (cond-mat.mtrl-sci)
subject: Mesoscale and Nanoscale Physics (cond-mat.mes-hall)
subject: FOS: Physical sciences

description: We investigate stability and electronic properties of oxy- (=O) or imine- (=NH) functionalized monolayer phosphorene with either single-side or double-side functionalization based on density-functional theory calculations. Our thermodynamic analysis shows that oxy-functionalized phosphorene can be formed under the conditions ranging from ultrahigh vacuum to high concentrations of molecular O2, while the imide-functionalized phosphorene can be formed at relatively high concentration of molecular N2H2. In addition, our Born-Oppenheimer molecular dynamics (BOMD) simulation shows that at the ambient condition both O2 and N2H2 can etch phosphorene away.
description: appears in RSC Advances, 2014
Conceptualizing Distal Drivers in Land Use Competition
Creators: name: Niewöhner, Jörg
name: Nielsen, Jonas Østergaard
name: Gasparri, Ignacio
name: Gou, Yaqing
name: Hauge, Mads
name: Joshi, Neha
name: Schaffartzik, Anke
name: Sejersen, Frank
name: Seto, Karen C.
name: Shughrue, Chris
Publisher: name: Humboldt-Universität zu Berlin
Year: 2016
Subjects: subject: Telecoupling
subject: Social space
subject: Systemic effects
subject: Competition as process
subject: Power/knowledge
subject: 300 Sozialwissenschaften
subject: 301 Soziologie, Anthropologie
subject: 303 Gesellschaftliche Prozesse
subject: 910 Geografie, Reisen
subject: 330 Wirtschaft

description: This introductory chapter explores the notion of ‘distal drivers’ in land use competition. Research has moved beyond proximate causes of land cover and land use change to focus on the underlying drivers of these dynamics. We discuss the framework of telecoupling within human–environment systems as a first step to come to terms with the increasingly distal nature of driving forces behind land use practices. We then expand the notion of distal as mainly a measure of Euclidian space to include temporal, social, and institutional dimensions. This understanding of distal widens our analytical scope for the analysis of land use competition as a distributed process to consider the role of knowledge and power, technology, and different temporalities within a relational or systemic analysis of practices of land use competition. We conclude by pointing toward the historical and social contingency of land use competition and by acknowledging that this contingency requires a methodological–analytical approach to dynamics that goes beyond linear cause–effect relationships. A critical component of future research will be a better understanding of different types of feedback processes reaching from biophysical feedback loops to feedback produced by individual or institutional reflexivity.
Platinum (II) complex of isopentyl glycine ligand: DNA binding, molecular dynamic, and anticancer activity against breast cancer
Creators: name: Moghadam, Mahboube Eslami
name: Hafshajani, Khadijeh Tavakoli
name: Sohrabi, Nasrin
name: Rezaeisadat, Morteza
name: Oftadeh, Mohsen
Publisher: name: Taylor & Francis
Year: 2023
Subjects: Biophysics
Biochemistry
Space Science
Physical Sciences not elsewhere classified
Medicine
Molecular Biology
Chemical Sciences not elsewhere classified
Biological Sciences not elsewhere classified
Cancer

description: In this paper, we performed thorough experimental and theoretical calculations to examine the interaction between Pt derivative, as an anticancer, and ct-DNA. The mode of DNA binding with [Pt(NH3)2(Isopentylgly)]NO3, where Isopentylgly is Isopentyl glycine, was evaluated by various spectroscopic methods, docking, and molecular dynamics simulation studies. UV-Vis and fluorescence spectroscopic titration results and CD spectra of DNA-drug showed this interaction is via groove binding. Also, thermal stability studies or DNA melting temperature changes (ΔTm), as well as the quenching emissions monitoring proved it. Also, the thermodynamic parameter and binding constant displayed that complex-DNA formation is a spontaneous process, and H-binding and also groove binding were found to be the main forces. Theoretical studies stated [Pt(NH3)2(Isopentylgly)]NO3-DNA formation occurs on C-G center on DNA, along with rising DNA-compound stability. IC50 value against the human breast cell line probably is due to the Isopentyl glycine ligand in the structure of the Pt compound, and it was obtained more than cisplatin and less than carboplatin against the MCF7 cell. Communicated by Ramaswamy H. Sarma Interactions of a new anticancer Pt derivative on DNA were tested in vitro using spectroscopic methods and chemical kinetic parameters. In addition, DNA binding modes with Isopentylgly ligand and Pt derivative were investigated using computational methods including docking and MD simulation. Finally, In vitro cytotoxicity was assessed on the human breast cell line.