cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
Inductance of Circuit Structures for MIT LL Superconductor Electronics Fabrication Process with 8 Niobium Layers
Creators: name: Tolpygo, Sergey K.
name: Bolkhovsky, Vladimir
name: Weir, T. J.
name: Galbraith, C. J.
name: Johnson, Leonard M.
name: Gouker, Mark A.
name: Semenov, Vasili K.
Publisher: name: arXiv
Year: 2014
Subjects: subject: Superconductivity (cond-mat.supr-con)
subject: Instrumentation and Detectors (physics.ins-det)
subject: FOS: Physical sciences

description: Inductance of superconducting thin-film inductors and structures with linewidth down to 250 nm has been experimentally evaluated. The inductors include various striplines and microstrips, their 90-degree bends and meanders, interlayer vias, etc., typically used in superconducting digital circuits. The circuits have been fabricated by a fully planarized process with 8 niobium layers, developed at MIT Lincoln Laboratory for very-large-scale superconducting integrated circuits. Excellent run-to-run reproducibility and inductance uniformity of better than 1% across 200-mm wafers have been found. It has been found that the inductance per unit length of stripline and microstrip line inductors continues to grow as the inductor linewidth is reduced deep into the submicron range to the widths comparable to the film thickness and magnetic field penetration depth. It is shown that the linewidth reduction does not lead to widening of the parameter spread due to diminishing sensitivity of the inductance to the linewidth and dielectric thickness. The experimental results were compared with numeric inductance extraction using commercial software and freeware, and a good agreement was found for 3-D inductance extractors. Methods of further miniaturization of circuit inductors for achieving circuit densities > 10^6 Josephson junctions per cm^2 are discussed.
description: 5 pages, 7 figures, 31 references. Presented at Applied Superconductivity Conference, ASC 2014, Charlotte, NC, USA, August 10-15, 2014
Dynamic Dysfunction in Dihydrofolate Reductase Results from Antifolate Drug Binding: Modulation of Dynamics within a Structural State
Creators: name: Carroll, Mary J.
name: Lee, Andrew L.
name: Mauldin, Randall V.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2009

description: The arduous task of rationally designing small molecule enzyme inhibitors is complicated by the inherent flexibility of the protein scaffold. To gain insight into the changes in dynamics associated with small molecule based inhibition, we have characterized, using NMR spectroscopy, E. coli dihydrofolate reductase in complex with two drugs: methotrexate and trimethoprim. The complexes allowed the intrinsic dynamic effects of drug binding to be revealed within the context of the “closed” structural ensemble. Binding of both drugs results in an identical decoupling of global motion on the micro- to millisecond timescale. Consistent with a change in overall dynamic character, the drugs’ perturbations to pico- to nanosecond backbone and side-chain methyl dynamics are also highly similar. These data show that the inhibitors simultaneously modulate slow concerted switching and fast motions at distal regions of DHFR, providing a dynamic link between the substrate binding site and distal loop residues known to affect catalysis.
D2.1 Needs and Opportunities Definition Report for Renovation based on IDDS Framework.
Creators: name: Several Authors
Publisher: name: Zenodo
Year: 2023

description: Description of work generate a general IDDS framework for the development of the renovation solutions for building residential projects covering: i) Potential and needs of improvements in the construction and renovation. Focus will be given to the core objectives of the SPHERE methodology that aim to deliver the impact of the project. Opportunities delivered by the SPHERE concept and how the digital twin can enable the needs will be addressed, such as improved sustainability, shortened project life span , improved information exchange among stakeholders and social acceptance, improved project management, results monitoring and improved holistic benefits to the end users which will be the exploitable results of the project. ii) Identification of Process Scenarios utilizing the Digital Twin. Based on the identified opportunities and how the digital twin concept can address them, workflow scenarios on the process needs and the role of the SPHERE platform services will be identified. This will be carried out in collaboration with the administrative and technical acceptance analyses carried out in the task, ensuring the delivery of useable and scalable workflow scenarios. The relevant user types and actors will be identified, in close collaboration with the stakeholder and advisory board members, end user and demo support partners of the project consortium, to provide the usability and replicability of the workflows. iii) Assessment of Barriers and need for Change Management. Known barriers for the implementation of digitized ICT solutions in the renovation domain will be identified, as an essential aspect of the IDDS approach. Regulatory and technical compliance will be assessed. Behavioural and operational change requirements will be identified and solutions will be proposed. Emerging technologies in the sector which will be integrated into the digital twin approach, and the adoption and acceptance of the process stakeholders will be analysed. Social acceptance needs and their monitoring and collaboration methodology will be identified.
Effects of doxorubicin and apigenin on chronic myeloid leukemia cells (K562) in vitro: anti-proliferative and apoptosis induction assessments
Creators: name: Noorian, Maryam
name: Chamani, Elham
name: Salmani, Fatemeh
name: Rezaei, Zohreh
name: Khorsandi, Khatereh
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biochemistry
subject: Cell Biology
subject: Genetics
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Physiology
subject: Pharmacology
subject: Biotechnology
subject: Chemical Sciences not elsewhere classified
subject: Developmental Biology
subject: Cancer
subject: Hematology

description: In this study, we aimed to investigate the effect of the co-treatment with apigenin and doxorubicin (DOX) on K562 cells. Our results show that apigenin (0, 40, 60, 80 ,100 µM) and DOX (0–10 µM) as single therapy, could decrease K562 cell viability (after 24 h of treatment) in a dose-dependent manner. Additionally, the co-treatment with apigenin (60, 80 µM) and 10 µM of DOX led to a greater reduction in cell growth (CI: 0.92 and 0.97) after 24 h of treatment compared to the single DOX treatment (p < 0.05). Consequently, apigenin and DOX, either as single or as co-treatment (24 h of treatment), were indicated to induce apoptosis in K562 cells through morphological studies, RT-qPCR, and western-blot analysis. Eventually, the expressions of Caspase 3, 6, 7, and 9 genes in the single treatment with DOX had higher alteration compared to the co-treatment with DOX and apigenin (p < 0.05).
Mg2+-Assisted Catalysis by B. Stearothermophilus TrpRS Is Promoted by Allosteric Effects
Creators: name: Li, Li
name: Kaguni, Laurie S.
name: Weinreb, Violetta
name: Carter, Charles W.
name: Campbell, Cassandra L.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2009

description: Mn2+-assisted catalysis by B. stearothermophilus TrpRS parallels that in polymerases and reduces specificity in amino acid activation. As predicted by non-equilibrium molecular dynamics simulations, multi-variant thermodynamic cycles with [ATP]-dependent Michaelis-Menten kinetics and Mn2+ for Mg2+ substitution demonstrate energetic coupling of ATP affinities to the metal; to lysines K111 and K192, which interact via the PPi leaving group; and to K195, which couples differently to the metal via the α–phosphate. However, net coupling to the metal opposes catalysis in both ground (Km) and transition (kcat) states. The 105-fold rate acceleration by Mg2+-protein interactions therefore requires additional favorable protein-metal couplings. Examples include longer-range, i.e., allosteric, interactions previously illustrated by the remote F37I mutation, which both reduces kcat and enhances catalytic assist by Mn2+, relative to that by Mg2+. These data support a model linking metal-assisted phosphoryl transfer catalysis to domain movement, and hence to free-energy transduction in a broad range of enzymes.
Structures of Get3, Get4, and Get5 Provide New Models for TA Membrane Protein Targeting
Creators: name: Dohlman, Henrik G.
name: Schwappach, Blanche
name: Simpson, Peter J.
name: Isaacson, Rivka L.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2010

description: The GET pathway, using several proteins (Gets 1–5 and probably Sgt2), posttranslationally conducts tail-anchored (TA) proteins to the endoplasmic reticulum (ER). At the ER, TA proteins are inserted into the lipid bilayer and then sorted and directed to their respective destinations in the secretory pathway. Until last year, there was no structural information on any of the GET components but now there are ten crystal structures of Get3 in a variety of nucleotide-bound states and conformations. The structures of Get4 and a portion of Get5 also emerged in 2010. This minireview provides a detailed comparison of the GET structures and discusses their mechanistic relevance to TA protein insertion. It also addresses the outstanding gaps in detailed molecular information on this system, including the structures of Get5, Sgt2, and the transmembrane complex comprising Get1 and Get2.
Probing cluster environments of blazars through gamma-gamma absorption
Creators: name: Sushch, Iurii
name: Böttcher, Markus
Publisher: name: arXiv
Year: 2014
Subjects: subject: High Energy Astrophysical Phenomena (astro-ph.HE)
subject: FOS: Physical sciences

description: Most blazars are known to be hosted in giant elliptic galaxies, but their cluster environments have not been thoroughly investigated. Cluster environments may contain radiation fields of low-energy photons created by nearby galaxies and/or stars in the intracluster medium that produce diffuse intracluster light. These radiation fields may absorb very high energy gamma rays ($E\gtrsim100$ GeV; VHE) and trigger pair cascades with further production of subsequent generations of gamma rays with lower energies via inverse Compton scattering on surrounding radiation fields leaving a characteristic imprint in the observed spectral shape. The change of the spectral shape of the blazar reflects the properties of its ambient medium. We show, however, that neither intracluster light nor the radiation field of an individual nearby galaxy can cause substantial gamma-gamma absorption. Substantial gamma-gamma absorption is possible only in the case of multiple, $\gtrsim5$, luminous nearby galaxies. This situation is not found in the local Universe, but may be possible at larger redshifts ($z\gtrsim2$). Since VHE gamma rays from such distances are expected to be strongly absorbed by the extragalactic background light, we consider possible signatures of gamma-ray induced pair cascades by calculating the expected GeV flux which appears to be below the Fermi sensitivity even for $\sim10$ nearby galaxies.
description: 5 pages, 5 figures, accepted for publication in A&A
Two new triterpenes from Commicarpus grandiflorus (A. Rich.) Standl. aerial parts exudate
Creators: name: Di Stasi, Mauro
name: Donadio, Giuliana
name: Bader, Ammar
name: De Leo, Marinella
name: Braca, Alessandra
Publisher: name: Taylor & Francis
Year: 2022
Subjects: subject: Biophysics
subject: Biochemistry
subject: Molecular Biology
subject: Environmental Sciences not elsewhere classified
subject: Chemical Sciences not elsewhere classified
subject: Ecology
subject: FOS: Biological sciences
subject: Sociology
subject: FOS: Sociology
subject: Biological Sciences not elsewhere classified
subject: Inorganic Chemistry
subject: FOS: Chemical sciences

description: The exudate of Commicarpus grandiflorus (A. Rich.) Standl. flowering aerial parts was investigated for its chemical composition. Nine compounds were isolated, five triterpenes and four methylated flavones, of which two were new natural triterpenes, 2α,3β,11α-olean-18-en-2,3,11-triol (1) and 2α,3β-olean-12-en-2,3-diol-11-one (2) that were named commicarpotriol and commicarpodiol, respectively. Structural characterization was carried out using 1D, 2D NMR, and MS techniques and the antimicrobial activity of all isolates was evaluated.
Structural and Dynamic Determinants of Protein-Peptide Recognition
Creators: name: Proctor, Elizabeth A.
name: Dagliyan, Onur
name: Ding, Feng
name: Dokholyan, Nikolay V.
name: D'Auria, Kevin M.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2011

description: Protein-peptide interactions play important roles in many cellular processes, including signal transduction, trafficking, and immune recognition. Protein conformational changes upon binding, an ill-defined peptide binding surface, and the large number of peptide degrees of freedom make the prediction of protein-peptide interactions particularly challenging. To address these challenges, we perform rapid molecular dynamics simulations in order to examine the energetic and dynamic aspects of protein-peptide binding. We find that, in most cases, we recapitulate the native binding sites and native-like poses of protein-peptide complexes. Inclusion of electrostatic interactions in simulations significantly improves the prediction accuracy. Our results also highlight the importance of protein conformational flexibility, especially side-chain movement, which allows the peptide to optimize its conformation. Our findings not only demonstrate the importance of sufficient sampling of the protein and peptide conformations, but also reveal the possible effects of electrostatics and conformational flexibility on peptide recognition.
GALEX Diffuse Observations of the Sky: The Data
Creators: name: Murthy, Jayant
Publisher: name: arXiv
Year: 2014
Subjects: subject: Astrophysics of Galaxies (astro-ph.GA)
subject: Instrumentation and Methods for Astrophysics (astro-ph.IM)
subject: FOS: Physical sciences

description: I present tabulations of the diffuse observations made by the GALEX spacecraft in two UV bands (FUV: 1539 A and NUV: 2316 A) from the (almost) final data release of the GALEX spacecraft (GR6/GR7). This data release includes all the FUV observations and the majority of the NUV observations. I discuss overall trends in the data but the primary purpose is to make the data available to the public. These data files described in this paper are hosted by the Mikulski Archive for Space Telescopes (MAST) at the Space Telescope Science Insitutute from whence they may be downloaded. For ease of use, I have also created maps of the diffuse radiation in both bands over the entire observed sky at 6' resolution.
description: 24 pages, ApJS (accepted); Links are now active
Structural Basis for μ-Opioid Receptor Binding and Activation
Creators: name: Gauthier, Josee
name: Diatchenko, Luda
name: Maixner, William
name: Dokholyan, Nikolay V.
name: Serohijos, Adrian W.R.
name: Ding, Feng
name: Yin, Shuangye
name: Gibson, Dustin G.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2011

description: Opioids that stimulate the μ-opioid receptor (MOR1) are the most frequently prescribed and effective analgesics. Here we present a structural model of MOR1. Molecular dynamics simulations show a ligand-dependent increase in the conformational flexibility of the third intracellular loop that couples with the G-protein complex. These simulations likewise identified residues that form frequent contacts with ligands. We validated the binding residues using site-directed mutagenesis coupled with radioligand binding and functional assays. The model was used to blindly screen a library of ~1.2 million compounds. From the thirty-four compounds predicted to be strong binders, the top three candidates were examined using biochemical assays. One compound showed high efficacy and potency. Post hoc testing revealed this compound to be nalmefene, a potent clinically used antagonist, thus further validating the model. In summary, the MOR1 model provides a tool for elucidating the structural mechanism of ligand-initiated cell signaling and screening for novel analgesics.
Synthesis of novel naphthalene-chimonanthine scaffolds hybrids with potent antibacterial or antifungal activity
Creators: name: Zheng, Shaojun
name: Wu, Wenbin
name: Jiang, Qiaoju
name: Lin, Chuansong
name: Fang, Yue
name: Dai, Huihui
name: Tang, Bing
name: Tan, Yi
Publisher: name: Taylor & Francis
Year: 2022
Subjects: subject: Biochemistry
subject: Microbiology
subject: FOS: Biological sciences
subject: Pharmacology
subject: Biotechnology
subject: Environmental Sciences not elsewhere classified
subject: Chemical Sciences not elsewhere classified
subject: Ecology
subject: Biological Sciences not elsewhere classified
subject: Infectious Diseases
subject: FOS: Health sciences
subject: Plant Biology

description: In this work, a total of 19 novel naphthalene hybrids with chimonanthine scaffolds were efficiently synthesised from indole-3-acetonitrile in good yields. The prepared compounds were evaluated for biological activity against Cryptococcus neoformans, Escherichia coli, Shigella spp, Candida albicans, Salmonella spp, and Staphylococcus aureus. The preliminary bioassays showed that most of the synthesised compounds exhibited significant antibacterial or antifungal activity. Notably, compound 8 showed potent activity against Cryptococcus neofonmans, Escherichia coli, Shigella spp, and Candida albicans than the positive control, all with the same MIC value of 3.53 µM. Compound 8 had a broad spectrum of antibacterial or antifungal activity, and will be studied further.
Fabrication Process and Properties of Fully-Planarized Deep-Submicron Nb/Al-AlOx/Nb Josephson Junctions for VLSI Circuits
Creators: name: Tolpygo, Sergey K.
name: Bolkhovsky, Vladimir
name: Weir, Terence J.
name: Johnson, Leonard M.
name: Gouker, Mark A.
name: Oliver, William D.
Publisher: name: arXiv
Year: 2014
Subjects: subject: Superconductivity (cond-mat.supr-con)
subject: FOS: Physical sciences

description: A fabrication process for Nb/Al-AlOx/Nb Josephson junctions (JJs) with sizes down to 200 nm has been developed on a 200-mm-wafer tool set typical for CMOS foundry. This process is the core of several nodes of a roadmap for fully-planarized fabrication processes for superconductor integrated circuits with 4, 8, and 10 niobium layers developed at MIT Lincoln Laboratory. The process utilizes 248 nm photolithography, anodization, high-density plasma etching, and chemical mechanical polishing (CMP) for planarization of SiO$_2$ interlayer dielectric. JJ electric properties and statistics such as on-chip and wafer spreads of critical current, $I_c$, normal-state conductance, $G_N$, and run-to-run reproducibility have been measured on 200-mm wafers over a broad range of JJ diameters from 200 nm to 1500 nm and critical current densities, $J_c$, from 10 kA/$cm^2$ to 50 kA/$cm^2$ where the JJs become self-shunted. Diffraction-limited photolithography of JJs is discussed. A relationship between JJ mask size, JJ size on wafer, and the minimum printable size for coherent and partially coherent illumination has been worked out. The $G_N$ and $I_c$ spreads obtained have been found to be mainly caused by variations of the JJ areas and agree with the model accounting for an enhancement of mask errors near the diffraction-limited minimum printable size of JJs. $I_c$ and $G_N$ spreads from 0.8% to 3% have been obtained for JJs with sizes from 1500 nm down to 500 nm. The spreads increase to about 8% for 200-nm JJs. Prospects for circuit densities > $10^6$ JJ/$cm^2$ and 193-nm photolithography for JJ definition are discussed.
description: 13 pages, 16 figures, 62 references. Presented at Applied Superconductivity Conference, ASC 2014, Charlotte, NC, USA, August 10-15, 2014
A Master Switch Couples Mg2+-Assisted Catalysis to Domain Motion in B. Stearothermophilus Tryptophanyl-tRNA Synthetase
Creators: name: Weinreb, Violetta
name: Li, Li
name: Carter, Charles W.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2012

description: We demonstrate how Tryptophanyl-tRNA synthetase (TrpRS) uses conformation-dependent Mg2+ activation to couple catalysis of tryptophan activation to specific, functional domain movements. Rate acceleration by Mg2+ requires ~ -6.0 kcal/mole in protein•Mg2+ interaction energy, none of which arises from the active site. A highly cooperative interaction between Mg2+ and four residues from a remote, conserved motif that mediates the shear of domain movement: (i) destabilizes the pre-transition state conformation, thereby (ii) inducing the Mg2+ to stabilize the transition state for kcat by ~ -5.0 kcal/mole. Cooperative, long-range conformational effects on the metal therefore convert an inactive Mg2+ coordination into one that can stabilize the transition state if, and only if, domain motion occurs. Transient, conformation-dependent Mg2+ activation, analogous to the escapement in mechanical clocks, explains vectorial coupling.
Amenable Invariant Random Subgroups
Creators: name: Bader, Uri
name: Duchesne, Bruno
name: Lecureux, Jean
Publisher: name: arXiv
Year: 2014
Subjects: subject: Group Theory (math.GR)
subject: FOS: Mathematics

description: We show that an amenable Invariant Random Subgroup of a locally compact second countable group lives in the amenable radical. This answers a question raised in the introduction of the paper "Kesten's Theorem for Invariant Random Subgroup" by Abert, Glasner and Virag. We also consider, in the opposite direction, property (T), and prove a similar statement for this property. The Appendix by Phillip Wesolek proves that the set of amenable subgroups is a Borel subset in the Chabauty topology.
description: We added an Appendix by Phillip Wesolek
Segmental Motions, Not a Two-State Concerted Switch, Underlie Allostery in CheY
Creators: name: Lee, Andrew L.
name: Boyer, Joshua A.
name: McDonald, Leanna R.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2012

description: The switch between an inactive and active conformation is an important transition for signaling proteins, yet the mechanisms underlying such switches are not clearly understood. Escherichia coli CheY, a response regulator protein from the two-component signal transduction system that regulates bacterial chemotaxis, is an ideal protein for the study of allosteric mechanisms. By utilizing 15N CPMG relaxation dispersion experiments, we monitored the inherent dynamic switching of unphosphorylated CheY. We show that CheY does not undergo a two-state concerted switch between the inactive and active conformations. Interestingly, partial saturation of Mg2+ enhances the intrinsic allosteric motions. Taken together with chemical shift perturbations, these data indicate that the µs-ms timescale motions underlying CheY allostery are segmental in nature. We propose an expanded allosteric network of residues, including W58, that undergo asynchronous, local switching between inactive and active-like conformations as the primary basis for the allosteric mechanism.
The Structure of the Plk4 Cryptic Polo Box Reveals Two Tandem Polo Boxes Required for Centriole Duplication
Creators: name: Slep, Kevin C.
name: Pinkerton, Derek C.
name: Nye, Jonathan
name: Slevin, Lauren K.
name: Rogers, Gregory C.
name: Buster, Daniel W.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2012

description: Centrioles are key microtubule polarity determinants. Centriole duplication is tightly controlled to prevent cells from developing multipolar spindles, a situation that promotes chromosomal instability. A conserved component in the duplication pathway is Plk4, a polo kinase family member that localizes to centrioles in M/G1. To limit centriole duplication, Plk4 levels are controlled through trans-autophosphorylation that primes ubiquitination. In contrast to Plks 1–3, Plk4 possesses a unique central region called the “cryptic polo box”. Here, we present the crystal structure of this region at 2.3 Å resolution. Surprisingly, the structure reveals two tandem, homodimerized polo boxes, PB1-PB2, that form a unique, winged architecture. The full PB1-PB2 cassette is required for binding the centriolar protein Asterless as well as robust centriole targeting. Thus, with its C-terminal polo box (PB3), Plk4 has a triple polo box architecture that facilitates oligomerization, targeting, and promotes trans-autophosphorylation, limiting centriole duplication to once per cell cycle.
Collaborating and Managing Tension Within Multi-Professional Teams Supporting Children With Autism at Risk of Exclusion
Creators: name: McCartney, A.
Publisher: name: School of Psychology, University of East London
Year: 2022

description: Multi-professional collaborative working is central to developing effective solutions that support children with autism who are at risk of exclusion. This article explores and presents the tensions and collaborative processes present within multi-professional collaborative working. The study took a two-phased approach to understand the contextual and professional issues affecting multi-professional collaborative working. Four professional groups participated: educational psychologists (EPs), special educational needs co-ordinators (SENCos), communication and interaction team workers (CIT) and speech and language therapists (SALT). Phase one used within-profession focus groups to explore the contemporary, contextual and professional issues that affect the identity and application of one’s professional role. Phase two used cross-professional discussion groups to document the collaborative practices that navigate professional roles and contextual tensions. The findings identified key issues that affect professional identity, role and practice. The study also unveiled how professionals manage tensions and professional roles to maximise their capacity in developing an intervention to support children with autism who are at risk of exclusion.
Effects of doxorubicin and apigenin on chronic myeloid leukemia cells (K562) in vitro: anti-proliferative and apoptosis induction assessments
Creators: name: Noorian, Maryam
name: Chamani, Elham
name: Salmani, Fatemeh
name: Rezaei, Zohreh
name: Khorsandi, Khatereh
Publisher: name: Taylor & Francis
Year: 2022
Subjects: subject: Biochemistry
subject: Cell Biology
subject: Genetics
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Physiology
subject: Pharmacology
subject: Biotechnology
subject: Chemical Sciences not elsewhere classified
subject: Developmental Biology
subject: Cancer
subject: Hematology

description: In this study, we aimed to investigate the effect of the co-treatment with apigenin and doxorubicin (DOX) on K562 cells. Our results show that apigenin (0, 40, 60, 80 ,100 µM) and DOX (0–10 µM) as single therapy, could decrease K562 cell viability (after 24 h of treatment) in a dose-dependent manner. Additionally, the co-treatment with apigenin (60, 80 µM) and 10 µM of DOX led to a greater reduction in cell growth (CI: 0.92 and 0.97) after 24 h of treatment compared to the single DOX treatment (p < 0.05). Consequently, apigenin and DOX, either as single or as co-treatment (24 h of treatment), were indicated to induce apoptosis in K562 cells through morphological studies, RT-qPCR, and western-blot analysis. Eventually, the expressions of Caspase 3, 6, 7, and 9 genes in the single treatment with DOX had higher alteration compared to the co-treatment with DOX and apigenin (p < 0.05).
A Cryptic TOG Domain with a Distinct Architecture Underlies CLASP-Dependent Bipolar Spindle Formation
Creators: name: Rogers, Stephen L.
name: Slep, Kevin C.
name: Leano, Jonathan B.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2013

description: CLASP is a key regulator of microtubule (MT) dynamics and bipolar mitotic spindle structure with CLASP mutants displaying a distinctive monopolar spindle phenotype. It has been postulated that cryptic TOG domains underlie CLASP’s ability regulate MT dynamics. Here, we report the crystal structure of the first cryptic TOG domain (TOG2) from human CLASP1, revealing the existence of a bona fide TOG array in the CLASP family. Strikingly, CLASP1 TOG2 exhibits a unique, convex architecture across the tubulin-binding surface that contrasts with the flat tubulin-binding surface of XMAP215 family TOG domains. Mutations in key, conserved TOG2 determinants abrogate the ability of CLASP mutants to rescue bipolar spindle formation in Drosophila cells depleted of endogenous CLASP. These findings highlight the common mechanistic use of TOG domains in XMAP215 and CLASP families to regulate MT dynamics, and suggest that differential TOG domain architecture may confer distinct functions to these critical cytoskeletal regulators.
What sparks a guide on the side? A qualitative study to explore motivations and approaches of mentors in health professions education
Creators: name: Ramani, Subha
name: Kusurkar, Rashmi A.
name: Papageorgiou, Evangelos
name: van Schalkwyk, Susan
Publisher: name: Taylor & Francis
Year: 2022
Subjects: Biological Sciences not elsewhere classified
Science Policy

description: Despite abundant research emphasising the value of mentoring for healthcare professionals, little is known about what motivates mentors. This study aimed to explore what motivated a group of internationally renowned health professions educators to accept informal, international and mostly online mentoring roles, and their approaches to that mentoring. Using a qualitative approach, we interviewed ten global educational leaders, who volunteered to serve as mentors in an initiative implemented by the Association for Medical Education in Europe in 2019, via Zoom. The hour-long interviews, conducted between May and October 2019, were audiotaped and transcribed on Zoom. De-identified transcripts were analysed for key themes. The key themes identified could be mapped to three categories, Motivations – Why; Approaches – How, and Global and virtual mentoring – What. Themes under motivations included: (1) Nurturing relationships focussed on mentees’ growth; (2) Pass on the benefit of one’s experience; (3) For one’s own continued growth. Themes under approaches included: (1) Provide a safe space; (2) Encourage mentees to take ownership of their professional development. Themes under global and virtual mentoring included: (1) Mentoring across geographical borders is still about relationships; (2) Virtual mentoring is not a barrier to relationship building. Though mentors also saw own growth and ongoing professional development as an important benefit of mentoring, altruism or the desire to benefit others, appeared to be a key motivating factor for them. Finding ways in which to identify mentors who are passionate about strengthening the field in this way – for example through reflective narratives and critical conversations – could be key when implementing mentoring initiatives.
Role of Electrostatic Repulsion in Controlling pH-Dependent Conformational Changes of Viral Fusion Proteins
Creators: name: Higgins, Chelsea D.
name: Harrison, Joseph S.
name: Koellhoffer, Jayne F.
name: Lai, Jonathan R.
name: O’Meara, Matthew J.
name: Kuhlman, Brian A.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2013

description: Viral fusion proteins undergo dramatic conformational transitions during membrane fusion. For viruses that enter through the endosome, these conformational rearrangements are typically pH sensitive. Here we provide a comprehensive review of the molecular interactions that govern pH-dependent rearrangements and introduce a novel paradigm for electrostatic residue pairings that regulate progress through the viral fusion coordinate. Analysis of structural data demonstrates a significant role for side chain protonation in triggering conformational change. To characterize this behavior we identify two distinct residue pairings, which we define as Histidine-Cation (HisCat) and Anion-Anion (AniAni) interactions. These side chain pairings destabilize a particular conformation via electrostatic repulsion through side chain protonation. Furthermore, two energetic control mechanisms, thermodynamic and kinetic, regulate these structural transitions. This review expands on the current literature by identification of these residue clusters, discussion of data demonstrating their function, and speculation of how these residue pairings contribute to the energetic controls.
Identification of an Actin Binding Surface on Vinculin that Mediates Mechanical Cell and Focal Adhesion Properties
Creators: name: Burridge, Keith
name: Campbell, Sharon L.
name: Shen, Kai
name: Palmer, Sean M.
name: Plevock, Karen M.
name: Tolbert, Caitlin E.
name: Dokholyan, Nikolay V.
name: Galkin, Vitold E.
name: Orlova, Albina
name: Thompson, Peter M.
name: Kota, Pradeep
name: Egelman, Edward H.
name: Superfine, Richard
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2014

description: Vinculin, a cytoskeletal scaffold protein essential for embryogenesis and cardiovascular function, localizes to focal adhesions and adherens junctions, connecting cell surface receptors to the actin cytoskeleton. While vinculin interacts with many adhesion proteins, its interaction with filamentous actin regulates cell morphology, motility, and mechanotransduction. Disruption of this interaction lowers cell traction forces and enhances actin flow rates. Although a model for the vinculin:actin complex exists, we recently identified actin-binding deficient mutants of vinculin outside sites predicted to bind actin, and developed an alternative model to better define this novel actin-binding surface, using negative-stain EM, discrete molecular dynamics, and mutagenesis. Actin-binding deficient vinculin variants expressed in vinculin knockout fibroblasts fail to rescue cell-spreading defects and reduce cellular response to external force. These findings highlight the importance of this new actin-binding surface and provide the molecular basis for elucidating additional roles of this interaction, including actin-induced conformational changes which promote actin bundling.
“What is the mechanism?”: Cues, barriers, and opportunities to discuss foundational science during internal medicine rounds
Creators: name: Pai, Jonathan S.
name: Kirsch, Heidi E.
name: O’Sullivan, Patricia S.
name: Cornett, Patricia A.
Publisher: name: Taylor & Francis
Year: 2022
Subjects: Medicine
Biotechnology
Science Policy
Mental Health

description: Repeated application of foundational science (FS) during medical reasoning results in encapsulation of knowledge needed to develop clinical expertise. Despite proven benefit of educating learners using a FS framework to anchor clinical decision making, how FS is integrated on clinical rotations has not been well characterized. This study examines how and when FS discussion occurs on internal medicine teaching rounds. We performed a convergent mixed method study. Six internal medicine teams at a quaternary hospital were observed during rounds and team members interviewed. Transcripts were analyzed using thematic analysis. Descriptive statistics provided a summary of the observations. Our study revealed that rounds used a teacher-centered model where FS knowledge was transmitted as pearls external to the clinical context. FS content arose primarily when the patient was complex. Barriers preventing FS discussion were lack of time and perceived lack of personal FS knowledge. Our study describes scenarios that commonly elicit discussion of FS on inpatient medicine rounds highlighting a ‘transmission’ model of FS knowledge. We suggest a learner-centered model that engages students in the practice of integrating FS into clinical reasoning.
The TLQP-21 Peptide Activates the G-Protein-Coupled Receptor C3aR1 via a Folding-upon-Binding Mechanism
Creators: name: Possenti, Roberta
name: Vulchanova, Lucy
name: Bartolomucci, Alessandro
name: Sassano, Maria F.
name: Severini, Cinzia
name: Verardi, Raffaello
name: Vostrikov, Vitaly V.
name: Braun, Patrick D.
name: Gurney, Allison
name: Cero, Cheryl
name: Gopinath, Tata
name: Roth, Bryan L.
name: Veglia, Gianluigi
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2014

description: TLQP-21, a VGF-encoded peptide is emerging as a novel target for obesity-associated disorders. TLQP-21 is found in the sympathetic nerve terminals in the adipose tissue and targets the G-protein-coupled-receptor (GPCR) Complement-3a-Receptor1 (C3aR1). So far, the mechanisms of TLQP-21-induced receptor activation remained unexplored. Here, we report that TLQP-21 is intrinsically disordered and undergoes a disorder-to-order transition, adopting an α-helical conformation, upon targeting cells expressing the C3aR1. We determined that the hot spots for TLQP-21 are located at the C-terminus, with mutations in the last four amino acids progressively reducing the bioactivity and, a single site mutation (R21A) or C-terminal amidation abolishing its function completely. Interestingly, the human TLQP-21 sequence carrying a S20A substitution activates the human C3aR1 receptor with lower potency compared to the rodent sequence. These studies reveal the mechanism of action of TLQP-21 and provide molecular templates for designing agonists and antagonists to modulate C3aR1 functions.
Community engagement by faculties of medicine: A scoping review of current practices and practical recommendations
Creators: name: Boone, Hannah
name: Snow, Nicholas Jacob
name: Allison, Jill
name: Sparkes, Carolyn Sturge
name: Dawe, Russell
Publisher: name: Taylor & Francis
Year: 2022
Subjects: subject: Pharmacology
subject: Environmental Sciences not elsewhere classified
subject: Ecology
subject: FOS: Biological sciences
subject: Biological Sciences not elsewhere classified
subject: Science Policy

description: Social accountability (SA) is the responsibility of faculties of medicine (FoMs) to address the health priorities of the communities they serve. Community engagement (CE) is a vital, but often ambiguous, component of SA. Practical guidance on how to engage community partners (CPs) is key for meaningful CE. We conducted a systematic scoping review of CE involving FoMs to map out how FoMs engage their communities, to provide practical recommendations for FoMs to take part in CE, and to highlight gaps in the literature. We searched electronic databases for articles describing projects or programs involving FoMs and CPs. Descriptive information was analyzed thematically. Thirty-eight of 1406 articles were included, revealing three themes: (1) Partners (Who to Engage)—deciding who to engage establishes the basis for responsibility and creates space for communities to engage FoMs; (2) Partnerships (How to Engage)—fostering creative and authentic collaboration, enabling meaningful community contributions; and (3) Projects and Programs (With What to Engage)—identifying opportunities for communities to have a voice in many spaces within FoMs. Under these themes emerged 32 practical recommendations. Practical guidance facilitates meaningful commitments to communities. The literature is rich with examples of community-FoM partnerships. We provide recommendations for CE that are clear, evidence-based, and responsive.
"ins1262319_resources.tar.gz" of "Measurement of the differential and double-differential Drell-Yan cross sections in proton-proton collisions at 7 TeV"
Creators: name: CMS Collaboration
Publisher: name: HEPData
Year: 2013

description: ins1262319_resources.tar.gz (unpack then view insert.html)
description: CERN-LHC. Measurements of the differential and double-differential Drell-Yan cross sections are presented using an integrated luminosity of 4.5 (4.8) inverse femtobarns in the dimuon (dielectron) channel of proton-proton collision data recorded in 2011 with the CMS detector at the LHC at sqrt(s) = 7 TeV. Various covariance matrices are provided in addition to the tables given in the paper.
An Acetyl-Methyl Switch Drives a Conformational Change in p53
Creators: name: Jenkins, Lisa
name: Mer, Georges
name: Cui, Gaofeng
name: Gete, Yantenew
name: Kutateladze, Tatiana G.
name: Rothbart, Scott B.
name: Tong, Qiong
name: Strahl, Brian D.
name: Rincon-Arano, Hector
name: Kutateladze, Andrei G.
name: Mazur, Sharlyn J.
name: Kuznetsov, Dmitry M.
name: Klein, Brianna J.
name: Groudine, Mark
name: Appella, Ettore
name: Liu, Wallace H.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2015

description: Individual posttranslational modifications (PTMs) of p53 mediate diverse p53-dependent responses, however much less is known about the combinatorial action of adjacent modifications. Here, we describe crosstalk between the early DNA damage response mark p53K382me2 and the surrounding PTMs that modulate binding of p53 co-factors, including 53BP1 and p300. The 1.8 Å resolution crystal structure of the tandem Tudor domain (TTD) of 53BP1 in complex with p53 peptide acetylated at K381 and dimethylated at K382 (p53K381acK382me2) reveals that the dual PTM induces a conformational change in p53. The α-helical fold of p53K381acK382me2 positions the side chains of R379, K381ac, and K382me2 to interact with TTD concurrently, reinforcing a modular design of double PTM mimetics. Biochemical and NMR analyses show that other surrounding PTMs, including phosphorylation of serine/threonine residues of p53, affect association with TTD. Our findings suggest a novel PTM-driven conformation switch-like mechanism that may regulate p53 interactions with binding partners.
Structural Plasticity of Methyllysine Recognition by the Tandem Tudor Domain of 53BP1
Creators: name: Kutateladze, Tatiana G.
name: Singh, Namit
name: Hayashi, Ryo
name: Botuyan, Maria Victoria
name: Cui, Gaofeng
name: Appella, Ettore
name: Rothbart, Scott B.
name: Tong, Qiong
name: Strahl, Brian D.
name: Mer, Georges
name: Musselman, Catherine A.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2015

description: p53 is dynamically regulated through various posttranslational modifications (PTMs), which differentially modulate its function and stability. The dimethylated marks p53K370me2 and p53K382me2 are associated with p53 activation or stabilization and both are recognized by the tandem Tudor domain (TTD) of 53BP1, a p53 co-factor. Here we detail the molecular mechanisms for the recognition of p53K370me2 and p53K382me2 by 53BP1. The solution structures of TTD in complex with the p53K370me2 and p53K382me2 peptides show a remarkable plasticity of 53BP1 in accommodating these diverse dimethyllysine-containing sequences. We demonstrate that dimeric TTDs are capable of interacting with the two PTMs on a single p53K370me2K382me2 peptide, greatly strengthening the 53BP1-p53 interaction. Analysis of binding affinities of TTD toward methylated p53 and histones reveals strong preference of 53BP1 for p53K382me2, H4K20me2, and H3K36me2 and suggests a possible role of multivalent contacts of 53BP1 in p53 targeting to and accumulation at the sites of DNA damage.
Using Multiple Sampling Approaches to Measure Sexual Risk-taking Among Young People in Haiti: Programmatic Implications
Creators: name: Roussel, Barbara
name: Outlaw, Theresa Finn
name: Speizer, Ilene S.
name: GÃ³mez, Anu Manchikanti
name: Beauvais, Harry
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2009

description: No previous published research has examined the applicability of varying methods for identifying young people who are at high risk of experiencing unintended pregnancy and acquiring HIV infection. This study compares three surveys of young people aged 15-24 in Port-au-Prince, Haiti, in terms of their sociodemographic characteristics and sexual behaviors and the surveys' usefulness for identifying young people at high risk and for program planning. The surveys consist of responses from: a representative sample of young people in the 2005-06 Haiti Demographic and Health Survey (HDHS), a 2004 facility-based study, and a 2006-07 venue-based study that used the Priorities for Local AIDS Control Efforts (PLACE) method. The facility-based and PLACE studies included larger proportions of single, sexually experienced young people and people who knew someone with HIV/AIDS than did the HDHS. More respondents in the PLACE sample had multiple sex partners in the past year and received money or gifts in return for sex, compared with respondents in the facility study. At first and last sex, more PLACE respondents used contraceptives, including condoms. Experience of pregnancy was most commonly reported in the data from the facility-based sample; however, more ever-pregnant PLACE respondents than others reported ever having terminated a pregnancy. Program managers seeking to implement prevention activities should consider using facility- or venue-based methods to identify and understand the behaviors of young people at high risk.
CNN: Single-label to Multi-label
Creators: name: Wei, Yunchao
name: Xia, Wei
name: Huang, Junshi
name: Ni, Bingbing
name: Dong, Jian
name: Zhao, Yao
name: Yan, Shuicheng
Publisher: name: arXiv
Year: 2014
Subjects: subject: Computer Vision and Pattern Recognition (cs.CV)
subject: FOS: Computer and information sciences

description: Convolutional Neural Network (CNN) has demonstrated promising performance in single-label image classification tasks. However, how CNN best copes with multi-label images still remains an open problem, mainly due to the complex underlying object layouts and insufficient multi-label training images. In this work, we propose a flexible deep CNN infrastructure, called Hypotheses-CNN-Pooling (HCP), where an arbitrary number of object segment hypotheses are taken as the inputs, then a shared CNN is connected with each hypothesis, and finally the CNN output results from different hypotheses are aggregated with max pooling to produce the ultimate multi-label predictions. Some unique characteristics of this flexible deep CNN infrastructure include: 1) no ground truth bounding box information is required for training; 2) the whole HCP infrastructure is robust to possibly noisy and/or redundant hypotheses; 3) no explicit hypothesis label is required; 4) the shared CNN may be well pre-trained with a large-scale single-label image dataset, e.g. ImageNet; and 5) it may naturally output multi-label prediction results. Experimental results on Pascal VOC2007 and VOC2012 multi-label image datasets well demonstrate the superiority of the proposed HCP infrastructure over other state-of-the-arts. In particular, the mAP reaches 84.2% by HCP only and 90.3% after the fusion with our complementary result in [47] based on hand-crafted features on the VOC2012 dataset, which significantly outperforms the state-of-the-arts with a large margin of more than 7%.
description: 13 pages, 10 figures, 3 tables