cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
Assessing the Use of Influenza Forecasts and Epidemiological Modeling in Public Health Decision Making in the United States
Creators: name: Doms, Colin
name: Kramer, Sarah Corinne
name: Shaman, Jeffrey L.
Publisher: name: Columbia University
Year: 2018
Subjects: Influenza
Epidemiology--Mathematical models
Health planning

description: Although forecasts and other mathematical models have the potential to play an important role in mitigating the impact of infectious disease outbreaks, the extent to which these tools are used in public health decision making in the United States is unclear. Throughout 2015, we invited public health practitioners belonging to three national public health organizations to complete a cross-sectional survey containing questions on model awareness, model use, and communication with modelers. Of 39 respondents, 46.15% used models in their work, and 20.51% reported direct communication with those who create models. Over half (64.10%) were aware that influenza forecasts exist. The need for improved communication between practitioners and modelers was overwhelmingly endorsed, with over 50% of participants indicating the need for models more relevant to public health questions, increased frequency of telecommunication, and more plain language in discussing models. Model use for public health decision making must be improved if models are to reach their full potential as public health tools. Increased quality and frequency of communication between practitioners and modelers could be particularly useful in achieving this goal. It is important that improvements be made now, rather than waiting for the next public health crisis to occur.
Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits
Creators: name: Randall, Joshua C.
name: Winkler, Thomas W.
name: Heid, Iris M.
Publisher: name: Universität Regensburg
Year: 2013
Subjects: subject: 610 Medizin

description: Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were genome-wide significant in women (P<5×10(-8)), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits.
Fermat's principle of least time predicts refraction of ant trails at substrate borders
Creators: name: Oettler, Jan
name: Schmid, Volker S.
name: Zankl, Niko
name: Rey, Olivier
name: Dress, Andreas
name: Heinze, Jürgen
Publisher: name: Universität Regensburg
Year: 2013
Subjects: subject: 590 Tiere (Zoologie)

description: Fermat's principle of least time states that light rays passing through different media follow the fastest (and not the most direct) path between two points, leading to refraction at medium borders. Humans intuitively employ this rule, e.g., when a lifeguard has to infer the fastest way to traverse both beach and water to reach a swimmer in need. Here, we tested whether foraging ants also follow Fermat's principle when forced to travel on two surfaces that differentially affected the ants' walking speed. Workers of the little fire ant, Wasmannia auropunctata, established "refracted" pheromone trails to a food source. These trails deviated from the most direct path, but were not different to paths predicted by Fermat's principle. Our results demonstrate a new aspect of decentralized optimization and underline the versatility of the simple yet robust rules governing the self-organization of group-living animals.
Structure and nucleic acid binding properties of KOW domains 4 and 6–7 of human transcription elongation factor DSIF
Creators: name: Zuber, Philipp K.
name: Hahn, Lukas
name: Reinl, Anne
name: Schweimer, Kristian
name: Knauer, Stefan H.
name: Gottesman, Maxwell E.
name: Rösch, Paul
name: Wöhrl, Birgitta M.
Publisher: name: Columbia University
Year: 2018
Subjects: Nucleic acids
RNA-protein interactions
Transcription factors

description: The human transcription elongation factor DSIF is highly conserved throughout all kingdoms of life and plays multiple roles during transcription. DSIF is a heterodimer, consisting of Spt4 and Spt5 that interacts with RNA polymerase II (RNAP II). DSIF binds to the elongation complex and induces promoter-proximal pausing of RNAP II. Human Spt5 consists of a NusG N-terminal (NGN) domain motif, which is followed by several KOW domains. We determined the solution structures of the human Spt5 KOW4 and the C-terminal domain by nuclear magnetic resonance spectroscopy. In addition to the typical KOW fold, the solution structure of KOW4 revealed an N-terminal four-stranded β-sheet, previously designated as the KOW3-KOW4 linker. In solution, the C-terminus of Spt5 consists of two β-barrel folds typical for KOW domains, designated KOW6 and KOW7. We also analysed the nucleic acid and RNAP II binding properties of the KOW domains. KOW4 variants interacted with nucleic acids, preferentially single stranded RNA, whereas no nucleic acid binding could be detected for KOW6-7. Weak binding of KOW4 to the RNAP II stalk, which is comprised of Rpb4/7, was also detected, consistent with transient interactions between Spt5 and these RNAP II subunits.
title: "Testa colossale di Apollo su busto moderno", arte romana, inv. CXX (ITA/EN)
title: Scheda catalogo digitale Borghese
titleType: AlternativeTitle
Creators: name: Clementi, Jessica
name: Galleria Borghese
Publisher: name: Galleria Borghese
Year: 2024

description: Pubblicazione delle schede delle opere conservate nel museo ed estratte dal catalogo digitale di

Galleria Borghese, nelle due versioni esistenti online, in italiano e inglese.

Collegamento al catalogo digitale:

ITA: https://www.collezionegalleriaborghese.it/

EN: https://www.collezionegalleriaborghese.it/en
Insights into myalgic encephalomyelitis/chronic fatigue syndrome phenotypes through comprehensive metabolomics
Creators: name: Nagy-Szakal, Dorottya
name: Barupal, Dinesh K.
name: Lee, Bohyun
name: Che, Xiaoyu
name: Williams, Brent L.
name: Kahn, Ellie J. R.
name: Ukaigwe, Joy E.
name: Bateman, Lucinda
name: Klimas, Nancy G.
name: Komaroff, Anthony L.
name: Levine, Susan
name: Montoya, José G.
name: Peterson, Daniel L.
name: Levin, Bruce
name: Hornig, Mady
name: Fiehn, Oliver
name: Lipkin, W. Ian
Publisher: name: Columbia University
Year: 2018
Subjects: Chronic fatigue syndrome
Metabolites
Molecular biology
Nervous system--Diseases

description: The pathogenesis of ME/CFS, a disease characterized by fatigue, cognitive dysfunction, sleep disturbances, orthostatic intolerance, fever, irritable bowel syndrome (IBS), and lymphadenopathy, is poorly understood. We report biomarker discovery and topological analysis of plasma metabolomic, fecal bacterial metagenomic, and clinical data from 50 ME/CFS patients and 50 healthy controls. We confirm reports of altered plasma levels of choline, carnitine and complex lipid metabolites and demonstrate that patients with ME/CFS and IBS have increased plasma levels of ceramide. Integration of fecal metagenomic and plasma metabolomic data resulted in a stronger predictive model of ME/CFS (cross-validated AUC = 0.836) than either metagenomic (cross-validated AUC = 0.745) or metabolomic (cross-validated AUC = 0.820) analysis alone. Our findings may provide insights into the pathogenesis of ME/CFS and its subtypes and suggest pathways for the development of diagnostic and therapeutic strategies.
Thermal Transition Design and Beam Heat-load Estimation for the COLDDIAG Refurbishment
Creators: name: Cha, Hyuk Jin
name: Glamann, Nicole
name: Grau, Andreas Wolfgang
name: Saez De Jauregui, David
name: Müller, Anke-Susanne
Publisher: name: Joint Accelerator Conferences Website (JACoW)
Year: 2021

description: The COLDDIAG (cold vacuum chamber for beam heat load diagnostics) developed at Karlsruhe Institute of Technology has been modified for more studies at cryogenic temperatures different from the previous operations at 4 K in a cold bore and at 50 K in a thermal shield. The key components in this campaign are two thermal transitions connecting both ends of the bore at 50 K with the shield at the same or higher temperature. In this paper, we present design efforts for the compact transitions, allowed heat intakes to the cooling power margin and mechanical robustness in the cryogenic environment. A manufacture scheme for the transition and its peripheral is also given. In addition, the beam heat loads in the refurbished COLDDIAG are estimated in terms of the accelerator beam parameters.
Necessity of Superposition of Macroscopically Distinct States for Quantum Computational Speedup
Creators: name: Shimizu, Akira
name: Matsuzaki, Yuichiro
name: Ukena, Akihisa
Publisher: name: arXiv
Year: 2010
Subjects: subject: Quantum Physics (quant-ph)
subject: Mesoscale and Nanoscale Physics (cond-mat.mes-hall)
subject: FOS: Physical sciences

description: For quantum computation, we investigate the conjecture that the superposition of macroscopically distinct states is necessary for a large quantum speedup. Although this conjecture was supported for a circuit-based quantum computer performing Shor's factoring algorithm [A. Ukena and A. Shimizu, Phys. Rev. A69 (2004) 022301], it needs to be generalized for it to be applicable to a large class of algorithms and/or other models such as measurement-based quantum computers. To treat such general cases, we first generalize the indices for the superposition of macroscopically distinct states. We then generalize the conjecture, using the generalized indices, in such a way that it is unambiguously applicable to general models if a quantum algorithm achieves exponential speedup. On the basis of this generalized conjecture, we further extend the conjecture to Grover's quantum search algorithm, whose speedup is large but quadratic. It is shown that this extended conjecture is also correct. Since Grover's algorithm is a representative algorithm for unstructured problems, the present result further supports the conjecture.
description: 18 pages, 5 figures. Fixed typos throughout the manuscript. This version has been published
Estrogen Promotes Mandibular Condylar Fibrocartilage Chondrogenesis and Inhibits Degeneration via Estrogen Receptor Alpha in Female Mice
Creators: name: Robinson, Jennifer L.
name: Soria, Paola
name: Xu, Manshan
name: Vrana, Mark Ziggy
name: Luchetti, Jeffrey M
name: Lu, Helen H.
name: Chen, Jing
name: Wadhwa, Sunil
Publisher: name: Columbia University
Year: 2018
Subjects: Estrogen--Receptors
Temporomandibular joint--Diseases
Mandibular condyle
Medicine

description: Temporomandibular joint degenerative disease (TMJ-DD) is a chronic form of TMJ disorder that specifically afflicts people over the age of 40 and targets women at a higher rate than men. Prevalence of TMJ-DD in this population suggests that estrogen loss plays a role in the disease pathogenesis. Thus, the goal of the present study was to determine the role of estrogen on chondrogenesis and homeostasis via estrogen receptor alpha (ERα) during growth and maturity of the joint. Young and mature WT and ERαKO female mice were subjected to ovariectomy procedures and then given placebo or estradiol treatment. The effect of estrogen via ERα on fibrocartilage morphology, matrix production, and protease activity was assessed. In the young mice, estrogen via ERα promoted mandibular condylar fibrocartilage chondrogenesis partly by inhibiting the canonical Wnt signaling pathway through upregulation of sclerostin (Sost). In the mature mice, protease activity was partly inhibited with estrogen treatment via the upregulation and activity of protease inhibitor 15 (Pi15) and alpha-2-macroglobulin (A2m). The results from this work provide a mechanistic understanding of estradiol on TMJ growth and homeostasis and can be utilized for development of therapeutic targets to promote regeneration and inhibit degeneration of the mandibular condylar fibrocartilage.
Somatosensory innervation of the oral mucosa of adult and aging mice
Creators: name: Moayedi-Esfahani, Yalda
name: Duenas-Bianchi, Lucia F.
name: Lumpkin, Ellen A.
Publisher: name: Columbia University
Year: 2018
Subjects: Oral mucosa
Sensory neurons
Somatosensory cortex

description: Oral mechanoreception is implicated in fundamental functions including speech, food intake and swallowing; yet, the neuroanatomical substrates that encode mechanical stimuli are not well understood. Tactile perception is initiated by intricate mechanosensitive machinery involving dedicated cells and neurons. This signal transduction setup is coupled with the topology and mechanical properties of surrounding epithelium, thereby providing a sensitive and accurate system to detect stress fluctuations from the external environment. We mapped the distribution of anatomically distinct neuronal endings in mouse oral cavity using transgenic reporters, molecular markers and quantitative histomorphometry. We found that the tongue is equipped with an array of putative mechanoreceptors that express the principal mechanosensory channel Piezo2, including end bulbs of Krause innervating individual filiform papillae and a novel class of neuronal fibers innervating the epithelium surrounding taste buds. The hard palate and gums are densely populated with three classes of sensory afferents organized in discrete patterns including Merkel cell-neurite complexes, Meissner’s corpuscles and glomerular corpuscles. In aged mice, we find that palatal Merkel cells reduce in number at key time-points that correlate with impaired oral abilities, such as swallowing and mastication. Collectively, this work identifies the mechanosensory architecture of oral tissues involved in feeding.
Ratio Estimation in SIMS Analysis
Creators: name: Ogliore, R. C.
name: Huss, G. R.
name: Nagashima, K.
Publisher: name: arXiv
Year: 2011
Subjects: subject: Instrumentation and Methods for Astrophysics (astro-ph.IM)
subject: Earth and Planetary Astrophysics (astro-ph.EP)
subject: Data Analysis, Statistics and Probability (physics.data-an)
subject: FOS: Physical sciences

description: The determination of an isotope ratio by secondary ion mass spectrometry (SIMS) traditionally involves averaging a number of ratios collected over the course of a measurement. We show that this method leads to an additive positive bias in the expectation value of the estimated ratio that is approximately equal to the true ratio divided by the counts of the denominator isotope of an individual ratio. This bias does not decrease as the number of ratios used in the average increases. By summing all counts in the numerator isotope, then dividing by the sum of counts in the denominator isotope, the estimated ratio is less biased: the bias is approximately equal to the ratio divided by the summed counts of the denominator isotope over the entire measurement. We propose a third ratio estimator (Beale's estimator) that can be used when the bias from the summed counts is unacceptably large for the hypothesis being tested. We derive expressions for the variance of these ratio estimators as well as the conditions under which they are normally distributed. Finally, we investigate a SIMS dataset showing the effects of ratio bias, and discuss proper ratio estimation for SIMS analysis.
Engineered Healing of Avascular Meniscus Tears by Stem Cell Recruitment
Creators: name: Tarafder, Solaiman
name: Gulko, Joseph Andrew
name: Sim, Kun Hee
name: Yang, Jian
name: Cook, James L.
name: Lee, Chang H.
Publisher: name: Columbia University
Year: 2018
Subjects: Meniscus (Anatomy)--Wounds and injuries
Stem cells
Regenerative medicine

description: Meniscus injuries are extremely common with approximately one million patients undergoing surgical treatment annually in the U.S. alone. Upon injury, the outer zone of the meniscus can be repaired and expected to functionally heal but tears in the inner avascular region are unlikely to heal. To date, no regenerative therapy has been proven successful for consistently promoting healing in inner-zone meniscus tears. Here, we show that controlled applications of connective tissue growth factor (CTGF) and transforming growth factor beta 3 (TGFβ3) can induce seamless healing of avascular meniscus tears by inducing recruitment and step-wise differentiation of synovial mesenchymal stem/progenitor cells (syMSCs). A short-term release of CTGF, a selected chemotactic and profibrogenic cue, successfully recruited syMSCs into the incision site and formed an integrated fibrous matrix. Sustain-released TGFβ3 then led to a remodeling of the intermediate fibrous matrix into fibrocartilaginous matrix, fully integrating incised meniscal tissues with improved functional properties. Our data may represent a novel clinically relevant strategy to improve healing of avascular meniscus tears by recruiting endogenous stem/progenitor cells.
Genetic engineering of Pyrococcus furiosus to use chitin as a carbon source
Creators: name: Kreuzer, Martina
name: Schmutzler, Karolin
name: Waege, Ingrid
name: Thomm, Michael
name: Hausner, Winfried
Publisher: name: Universität Regensburg
Year: 2013
Subjects: subject: 570 Biowissenschaften, Biologie
subject: Amino Acid Sequence
subject: Carbon/metabolism
subject: Chitin/metabolism
subject: Chitinase/metabolism
subject: Computational Biology
subject: Frameshift Mutation
subject: Gene Expression/drug effects
subject: Genetic Engineering
subject: Hypoxanthine Phosphoribosyltransferase/metabolism
subject: Molecular Sequence Data
subject: Protein Structure, Tertiary
subject: Purines/pharmacology
subject: Pyrococcus furiosus/metabolism
subject: Sequence Alignment
subject: Simvastatin/pharmacology
subject: Thermococcus/enzymology

description: BACKGROUND: Bioinformatic analysis of the genes coding for the chitinase in Pyrococcus furiosus and Thermococcus kodakarensis revealed that most likely a one nucleotide insertion in Pyrococcus caused a frame shift in the chitinase gene. This splits the enzyme into two separate genes, PF1233 and PF1234, in comparison to Thermococcus kodakarensis. Furthermore, our attempts to grow the wild type strain of Pyrococcus furiosus on chitin were negative. From these data we assume that Pyrococcus furiosus is most likely unable to use chitin as a carbon source. The aim of this study was to analyze in vivo if the one nucleotide insertion is responsible for the inability to grow on chitin, using a recently described genetic system for Pyrococcus furiosus. RESULTS: A marker-less genetic system for Pyrococcus furiosus was developed using simvastatin for positive selection and 6-methylpurine for negative selection. Resistance against simvastatin was achieved by overexpression of the hydroxymethylglutaryl coenzyme A reductase gene. For the resistance to 6-methylpurine the hypoxanthine-guanine phosphoribosyltransferase gene was deleted. This system was used to delete the additional nucleotide at position 1006 in PF1234. The resulting chitinase in the mutant strain was a single subunit enzyme and aligns perfectly to the enzyme from Thermococcus kodakarensis. A detailed analysis of the wild type and the mutant using counted cell numbers as well as ATP and acetate production as growth indicators revealed that only the mutant is able to use chitin as a carbon source. An additional mutant strain containing a reduced chitinase version containing just one catalytic and one chitin-binding domain showed diminished growth on chitin in comparison to the mutant containing the single large enzyme. CONCLUSIONS: Wild type Pyrococcus furiosus is most likely unable to grow on chitin in the natural biotope due to a nucleotide insertion which separates the chitinase gene into two ORFs, whereas a genetically engineered strain with the deleted nucleotide is able to grow on chitin. The overall high sequence identity of the two chitinases between P. furiosus and T. kodakarensis indicates that this mutation occurred very recently or there is still some kind of selection pressure for a functional enzyme using programmed +/-1 frameshifting.
Complex prospective memory in adults with attention deficit hyperactivity disorder
Creators: name: Fuermaier, Anselm B. M.
name: Tucha, Lara
name: Koerts, Janneke
name: Aschenbrenner, Steffen
name: Westermann, Celina
name: Weisbrod, Matthias
name: Lange, Klaus W.
name: Tucha, Oliver
Publisher: name: Universität Regensburg
Year: 2013
Subjects: subject: 150 Psychologie
subject: Adult
subject: Analysis of Variance
subject: Attention/physiology
subject: Attention Deficit Disorder with Hyperactivity/physiopathology
subject: Cognition/physiology
subject: Female
subject: Humans
subject: Male
subject: Memory, Episodic
subject: Neuropsychological Tests

description: OBJECTIVES: Attention deficit hyperactivity disorder (ADHD) in adults has been associated with disturbances of attention and executive functions. Furthermore, impairments of verbal and figural retrospective memory were reported. However, little is known about the effects of ADHD on prospective memory, the execution of delayed intentions in the future. METHODS: The present study compared the performance of 45 adult patients with ADHD not treated with stimulant medication with the performance of 45 matched healthy individuals on a paradigm of complex prospective memory which measured task planning, plan recall, self-initiation and execution. Furthermore, the contribution of other cognitive functions to prospective memory functioning was assessed, including measures of attention, executive functions and memory. RESULTS: A large-scale impairment could be observed in task planning abilities in patients with ADHD. Only negligible to small effects were found for plan recall, self-initiation and execution. Inhibition was identified to contribute significantly to performance on task planning. CONCLUSIONS: The present findings suggest that four cognitive components contribute to the performance of prospective memory. Impairments of prospective memory mainly emerged from deficient planning abilities in adults with ADHD. Implications on behavioral based intervention strategies are discussed.
Efficient Blood-Brain Barrier Opening in Primates with Neuronavigation-Guided Ultrasound and Real-Time Acoustic Mapping
Creators: name: Wu, Shih-Ying
name: Aurup, Christian
name: Sierra Sanchez, Carlos Jose
name: Grondin, Julien Louis Philippe
name: Zheng, Wenlan
name: Salles Kamimura, Hermes Arytto
name: Ferrera, Vincent P.
name: Konofagou, Elisa E.
Publisher: name: Columbia University
Year: 2018
Subjects: Blood-brain barrier
Brain--Diseases--Treatment
High-intensity focused ultrasound
Therapeutics

description: Brain diseases including neurological disorders and tumors remain under treated due to the challenge to access the brain, and blood-brain barrier (BBB) restricting drug delivery which, also profoundly limits the development of pharmacological treatment. Focused ultrasound (FUS) with microbubbles is the sole method to open the BBB noninvasively, locally, and transiently and facilitate drug delivery, while translation to the clinic is challenging due to long procedure, targeting limitations, or invasiveness of current systems. In order to provide rapid, flexible yet precise applications, we have designed a noninvasive FUS and monitoring system with the protocol tested in monkeys (from in silico preplanning and simulation, real-time targeting and acoustic mapping, to post-treatment assessment). With a short procedure (30 min) similar to current clinical imaging duration or radiation therapy, the achieved targeting (both cerebral cortex and subcortical structures) and monitoring accuracy was close to the predicted 2-mm lower limit. This system would enable rapid clinical transcranial FUS applications outside of the MRI system without a stereotactic frame, thereby benefiting patients especially in the elderly population.
A direct tissue-grafting approach to increasing endogenous brown fat
Creators: name: Blumenfeld, Nicole R.
name: Kang, Hwan June
name: Fenzl, Anna
name: Song, Ziwei
name: Chung, Janice Juho
name: Singh, Ranjodh
name: Johnson, Roshawn
name: Karakecili, Ayse
name: Feranil, Jun B.
name: Rossen, Ninna S.
name: Zhang, Vivian
name: Jaggi, Sahir
name: McCarty, Bret
name: Bessler, Steven
name: Schwartz, Gary J.
name: Grant, Robert T.
name: Korner, Judith
name: Kiefer, Florian W.
name: Gillette, Brian M.
name: Sia, Samuel K.
Publisher: name: Columbia University
Year: 2018
Subjects: Grafting
Brown adipose tissue
Diabetes--Alternative treatment
Obesity--Treatment

description: There is widespread evidence that increasing functional mass of brown adipose tissue (BAT) via browning of white adipose tissue (WAT) could potentially counter obesity and diabetes. However, most current approaches focus on administration of pharmacological compounds which expose patients to highly undesirable side effects. Here, we describe a simple and direct tissue-grafting approach to increase BAT mass through ex vivo browning of subcutaneous WAT, followed by re-implantation into the host; this cell-therapy approach could potentially act synergistically with existing pharmacological approaches. With this process, entitled “exBAT”, we identified conditions, in both mouse and human tissue, that convert whole fragments of WAT to BAT via a single step and without unwanted off-target pharmacological effects. We show that ex vivo, exBAT exhibited UCP1 immunostaining, lipid droplet formation, and mitochondrial metabolic activity consistent with native BAT. In mice, exBAT exhibited a highly durable phenotype for at least 8 weeks. Overall, these results enable a simple and scalable tissue-grafting strategy, rather than pharmacological approaches, for increasing endogenous BAT and studying its effect on host weight and metabolism.
Ultracold and dense samples of ground-state molecules in lattice potentials
Creators: name: Nägerl, Hanns-Christoph
name: Mark, Manfred J.
name: Haller, Elmar
name: Gustavsson, Mattias
name: Hart, Russell
name: Danzl, Johann G.
Publisher: name: arXiv
Year: 2010
Subjects: subject: Quantum Gases (cond-mat.quant-gas)
subject: FOS: Physical sciences

description: We produce an ultracold and dense sample of rovibronic ground state Cs_2 molecules close to the regime of quantum degeneracy, in a single hyperfine level, in the presence of an optical lattice. The molecules are individually trapped, in the motional ground state of an optical lattice well, with a lifetime of 8 s. For preparation, we start with a zero-temperature atomic Mott-insulator state with optimized double-site occupancy and efficiently associate weakly-bound dimer molecules on a Feshbach resonance. Despite extremely weak Franck-Condon wavefunction overlap, the molecules are subsequently transferred with >50% efficiency to the rovibronic ground state by a stimulated four-photon process. Our results present a crucial step towards the generation of Bose-Einstein condensates of ground-state molecules and, when suitably generalized to polar heteronuclear molecules such as RbCs, the realization of dipolar many-body quantum-gas phases in periodic potentials.
description: 10 pages, 4 figures
Evaluation of an mHealth app : a pilot trial of "Destressify" on university student mental health
Creators: name: Lee, Rebecca Anne
Publisher: name: University of British Columbia
Year: 2017

description: Background: One in five Canadians experience mental health issues with university students showing significantly higher rates of mental health problems than the general public. Current university support services are limited by factors such as available staff and finances, and social stigma has frequently been identified as an additional barrier that prevents students from accessing these resources. Mobile health (mHealth) apps are one form of alternative health support that is discrete and accessible to students, and while they are recognized as a promising alternative, there is limited research demonstrating their efficacy. Objective: To evaluate a mindfulness-based app’s (“DeStressify”) efficacy on stress, anxiety, depressive symptomology, sleep behaviour, work/class absenteeism, work/school productivity, and quality of life among university students. Methods: Full-time undergraduate students at a Canadian university with smartphones and internet access were recruited through in-class announcements and on-campus posters. Participants randomized into an experimental condition were given and instructed to use the Destressify app five days a week for four weeks. Control condition participants were wait-listed. All participants completed pre- and post-intervention online surveys to self-assess stress, anxiety, depressive symptomatology, sleep quality, and health-related quality of life. Results: 206 responses were collected at baseline with 163 participants completing the study (86 control, 77 experimental). Using Destressify was shown to reduce trait anxiety (P = .005) and improve general health (P = .001), energy (P = .005), and emotional wellbeing (P = .005) in university students, and more participants than expected by chance in the experimental condition believed their productivity improved between baseline and post-intervention measurements (P = ￼iii .01). The app did not significantly improve stress, state anxiety, physical and social functioning, role limitations due to physical or emotional health problems, or pain (P > .05). Conclusions: Mindfulness-based apps may provide an effective alternative support for university student mental health. Universities and other institutions may benefit from promoting the use of Destressify or other mindfulness-based mHealth apps among students who are interested in methods of anxiety management or mindfulness-based self-driven health support. Future steps include examining Destressify and similar mHealth apps over a longer time period and in university staff and faculty.
Evidence for Regulation of Hemoglobin Metabolism and Intracellular Ionic Flux by the Plasmodium falciparum Chloroquine Resistance Transporter
Creators: name: Lee, Andrew H.
name: Dhingra, Satish Kumar
name: Lewis, Ian A.
name: Singh, Maneesh K.
name: Siriwardana, Amila
name: Dalal, Seema
name: Rubiano, Kelly
name: Klein, Matthias S.
name: Baska, Katelynn S.
name: Krishna, Sanjeev
name: Klemba, Michael
name: Roepe, Paul D.
name: Llinás, Manuel
name: Garcia, Celia R. S.
name: Fidock, David Armand
Publisher: name: Columbia University
Year: 2018
Subjects: Hemoglobin
Malaria--Prevention
Chloroquine
Plasmodium falciparum

description: Plasmodium falciparum multidrug resistance constitutes a major obstacle to the global malaria elimination campaign. Specific mutations in the Plasmodium falciparum chloroquine resistance transporter (PfCRT) mediate resistance to the 4-aminoquinoline drug chloroquine and impact parasite susceptibility to several partner agents used in current artemisinin-based combination therapies, including amodiaquine. By examining gene-edited parasites, we report that the ability of the wide-spread Dd2 PfCRT isoform to mediate chloroquine and amodiaquine resistance is substantially reduced by the addition of the PfCRT L272F mutation, which arose under blasticidin selection. We also provide evidence that L272F confers a significant fitness cost to asexual blood stage parasites. Studies with amino acid-restricted media identify this mutant as a methionine auxotroph. Metabolomic analysis also reveals an accumulation of short, hemoglobin-derived peptides in the Dd2 + L272F and Dd2 isoforms, compared with parasites expressing wild-type PfCRT. Physiologic studies with the ionophores monensin and nigericin support an impact of PfCRT isoforms on Ca2+ release, with substantially reduced Ca2+ levels observed in Dd2 + L272F parasites. Our data reveal a central role for PfCRT in regulating hemoglobin catabolism, amino acid availability, and ionic balance in P. falciparum, in addition to its role in determining parasite susceptibility to heme-binding 4-aminoquinoline drugs.
Dual Inhibition of Bcl-2/Bcl-xL and XPO1 is synthetically lethal in glioblastoma model systems
Creators: name: Shang, Enyuan
name: Zhang, Yiru
name: Shu, Chang
name: Ishida, Chiaki Tsuge
name: Bianchetti, Elena
name: Westhoff, Mike-Andrew
name: Karpel-Massler, Georg
name: Siegelin, Markus D.
Publisher: name: Columbia University
Year: 2018
Subjects: Glioblastoma multiforme
Tumors--Treatment
Neuroglia
Cell death
Cancer--Treatment

description: XPO1 has recently emerged as a viable treatment target for solid malignancies, including glioblastoma (GBM), the most common primary malignant brain tumor in adults. However, given that tumors become commonly resistant to single treatments, the identification of combination therapies is critical. Therefore, we tested the hypothesis that inhibition of anti-apoptotic Bcl-2 family members and XPO1 are synthetically lethal. To this purpose, two clinically validated drug compounds, the BH3-mimetic, ABT263, and the XPO1 inhibitor, Selinexor, were used in preclinical GBM model systems. Our results show that inhibition of XPO1 reduces cellular viability in glioblastoma cell cultures. Moreover, addition of ABT263 significantly enhances the efficacy of XPO1 inhibition on the reduction of cellular viability, which occurs in a synergistic manner. While selinexor inhibits the proliferation of glioblastoma cells, the combination treatment of ABT263 and selinexor results in substantial induction of cell death, which is accompanied by activation of effector- initiator caspases and cleavage of PARP. Mechanistically we find that XPO1 inhibition results in down-regulation of anti-apoptotic Mcl-1 and attenuates ABT263 driven Mcl-1 up-regulation. Consistently, siRNA mediated silencing of Mcl-1 sensitizes for ABT263 mediated cell death and partially for the combination treatment. By using a human patient-derived xenograft model of glioblastoma in mice, we demonstrate that the combination treatment of ABT263 and Selinexor reduces tumor growth significantly more than each compound alone. Collectively, these results suggest that inhibition of XPO1 and Bcl-2/Bcl-xL might be a potential strategy for the treatment of malignant glial tumors.
Correlated Light-Serial Scanning Electron Microscopy (CoLSSEM) for ultrastructural visualization of single neurons in vivo
Creators: name: Hirabayashi, Yusuke
name: Tapia, Juan Carlos
name: Polleux, Franck
Publisher: name: Columbia University
Year: 2018
Subjects: Scanning electron microscopy
Neurons
Imaging systems in medicine
Brain mapping
Neural circuitry

description: A challenging aspect of neuroscience revolves around mapping the synaptic connections within neural circuits (connectomics) over scales spanning several orders of magnitude (nanometers to meters). Despite significant improvements in serial section electron microscopy (SSEM) technologies, several major roadblocks have impaired its general applicability to mammalian neural circuits. In the present study, we introduce a new approach that circumvents some of these roadblocks by adapting a genetically-encoded ascorbate peroxidase (APEX2) as a fusion protein to a membrane-targeted fluorescent reporter (CAAX-Venus), and introduce it in single pyramidal neurons in vivo using extremely sparse in utero cortical electroporation. This approach allows us to perform Correlated Light-SSEM (CoLSSEM), a variant of Correlated Light-EM (CLEM), on individual neurons, reconstructing their dendritic and axonal arborization in a targeted way via combination of high-resolution confocal microscopy, and subsequent imaging of its ultrastructural features and synaptic connections with ATUM-SEM (automated tape-collecting ultramicrotome - scanning electron microscopy) technology. Our method significantly will improve the feasibility of large-scale reconstructions of neurons within a circuit, and permits the description of some ultrastructural features of identified neurons with their functional and/or structural connectivity, one of the main goal of connectomics.
Studies on the Assembly Characteristics of Large Subunit Ribosomal Proteins in S. cerevisae
Creators: name: Ohmayer, Uli
name: Gamalinda, Michael
name: Sauert, Martina
name: Ossowski, Julius
name: Pöll, Gisela
name: Linnemann, Jan
name: Hierlmeier, Thomas
name: Perez-Fernandez, Jorge
name: Kumcuoglu, Beril
name: Leger-Silvestre, Isabelle
name: Faubladier, Marlène
name: Griesenbeck, Joachim
name: Woolford, John
name: Tschochner, Herbert
name: Milkereit, Philipp
Publisher: name: Universität Regensburg
Year: 2013
Subjects: subject: 570 Biowissenschaften, Biologie

description: During the assembly process of ribosomal subunits, their structural components, the ribosomal RNAs (rRNAs) and the ribosomal proteins (r-proteins) have to join together in a highly dynamic and defined manner to enable the efficient formation of functional ribosomes. In this work, the assembly of large ribosomal subunit (LSU) r-proteins from the eukaryote S. cerevisiae was systematically investigated. Groups of LSU r-proteins with specific assembly characteristics were detected by comparing the protein composition of affinity purified early, middle, late or mature LSU (precursor) particles by semi-quantitative mass spectrometry. The impact of yeast LSU r-proteins rpL25, rpL2, rpL43, and rpL21 on the composition of intermediate to late nuclear LSU precursors was analyzed in more detail. Effects of these proteins on the assembly states of other r-proteins and on the transient LSU precursor association of several ribosome biogenesis factors, including Nog2, Rsa4 and Nop53, are discussed.
Attentional set to safety recruits the ventral medial prefrontal cortex
Creators: name: Yao, Shuxia
name: Qi, Song
name: Kendrick, Keith M.
name: Mobbs, Dean
Publisher: name: Columbia University
Year: 2018
Subjects: Prefrontal cortex
Attention--Physiological aspects
Threat (Psychology)
Survival--Psychological aspects
Neural circuitry

description: Early detection of danger is highly adaptive, yet fast orientation towards safety is also key to survival. This study aimed to explore how human brain searches for safety by manipulating subjects’ attentional set. Subjects were asked to judge random dots motion (RDM) direction and could be shocked for incorrect responses (RDM trials) while keeping alert in detecting shock probability cues (cue detection trials). Relative to safe condition, where attention was set to search cues associated with no shock, incorrect responses to ‘dangerous+’ cues would increase and correct responses to ‘dangerous−’ cues would decrease shock probability. In RDM trials, relative to the ‘dangerous+’, the safe and ‘dangerous−’ attentional set induced stronger activation in the ventral medial prefrontal cortex (vmPFC), a core region involved in flexible threat assessment and safety signalling. In cue detection trials, shorter response times and greater accuracy were observed for ‘dangerous+’ than ‘dangerous−’ and safe cues. At neural level ‘dangerous+’ cues induced stronger activity in the frontoparietal attention network than safe cues. Overall, our findings demonstrate that attentional set for searching safety recruits the vmPFC, while detection of threat-related cues elicits activity in the frontoparietal attention network, suggesting new roles for these regions in human defensive survival circuitry.
Fabrication of FeSe1-x superconducting films with bulk properties
Creators: name: Jung, Soon-Gil
name: Lee, Nam Hoon
name: Choi, Eun-Mi
name: Kang, Won Nam
name: Lee, Sung-Ik
name: Hwang, Tae-Jong
name: Kim, Dong Ho
Publisher: name: arXiv
Year: 2010
Subjects: subject: Superconductivity (cond-mat.supr-con)
subject: FOS: Physical sciences

description: We have fabricated high-quality FeSe1-x superconducting films with a bulk Tc of 11-12 K on different substrates, Al2O3(0001), SrTiO3(100), MgO(100), and LaAlO3(100), by using a pulsed laser deposition technique. All the films were grown at a high substrate temperature of 610 oC, and were preferentially oriented along the (101) direction, the latter being to be a key to fabricating of FeSe1-x superconducting thin films with high Tc. According to the energy dispersive spectroscopy data, the Fe:Se composition ratio was 1:0.90+-0.02. The FeSe1-x film grown on a SrTiO3 substrate showed the best quality with a high upper critical magnetic field [Hc2(0)] of 56 T.
Archaea on human skin
Creators: name: Probst, Alexander J.
name: Auerbach, Anna K.
name: Moissl-Eichinger, Christine
Publisher: name: Universität Regensburg
Year: 2013
Subjects: subject: 570 Biowissenschaften, Biologie

description: The recent era of exploring the human microbiome has provided valuable information on microbial inhabitants, beneficials and pathogens. Screening efforts based on DNA sequencing identified thousands of bacterial lineages associated with human skin but provided only incomplete and crude information on Archaea. Here, we report for the first time the quantification and visualization of Archaea from human skin. Based on 16 S rRNA gene copies Archaea comprised up to 4.2% of the prokaryotic skin microbiome. Most of the gene signatures analyzed belonged to the Thaumarchaeota, a group of Archaea we also found in hospitals and clean room facilities. The metabolic potential for ammonia oxidation of the skin-associated Archaea was supported by the successful detection of thaumarchaeal amoA genes in human skin samples. However, the activity and possible interaction with human epithelial cells of these associated Archaea remains an open question. Nevertheless, in this study we provide evidence that Archaea are part of the human skin microbiome and discuss their potential for ammonia turnover on human skin.
The structure of invariant tori in a 3D galactic potential
Creators: name: Katsanikas, M.
name: Patsis, P. A.
Publisher: name: arXiv
Year: 2010
Subjects: subject: Chaotic Dynamics (nlin.CD)
subject: Cosmology and Nongalactic Astrophysics (astro-ph.CO)
subject: Astrophysics of Galaxies (astro-ph.GA)
subject: Mathematical Physics (math-ph)
subject: Dynamical Systems (math.DS)
subject: FOS: Physical sciences
subject: FOS: Mathematics
subject: 70H08, 70H12, 70H14, 37J20, 37J35, 37J40, 85A05

description: We study in detail the structure of phase space in the neighborhood of stable periodic orbits in a rotating 3D potential of galactic type. We have used the color and rotation method to investigate the properties of the invariant tori in the 4D spaces of section. We compare our results with those of previous works and we describe the morphology of the rotational, as well as of the tube tori in the 4D space. We find sticky chaotic orbits in the immediate neighborhood of sets of invariant tori surrounding 3D stable periodic orbits. Particularly useful for galactic dynamics is the behavior of chaotic orbits trapped for long time between 4D invariant tori. We find that they support during this time the same structure as the quasi-periodic orbits around the stable periodic orbits, contributing however to a local increase of the dispersion of velocities. Finally we find that the tube tori do not appear in the 3D projections of the spaces of section in the axisymmetric Hamiltonian we examined.
description: 26 pages, 34 figures, accepted for publication in the International Journal of Bifurcation and Chaos
Deep impact: unintended consequences of journal rank
Creators: name: Brembs, Björn
name: Button, Katherine
name: Munafò, Marcus
Publisher: name: Universität Regensburg
Year: 2013
Subjects: subject: impact factor, journal ranking, statistics as topic, publishing, open access, scholarly communication, libraries, library services
subject: 000 Allgemeines, Wissenschaft
subject: 020 Bibliotheks- und Informationswissenschaft

description: Most researchers acknowledge an intrinsic hierarchy in the scholarly journals (“journal rank”) that they submit their work to, and adjust not only their submission but also their reading strategies accordingly. On the other hand, much has been written about the negative effects of institutionalizing journal rank as an impact measure. So far, contributions to the debate concerning the limitations of journal rank as a scientific impact assessment tool have either lacked data, or relied on only a few studies. In this review, we present the most recent and pertinent data on the consequences of our current scholarly communication system with respect to various measures of scientific quality (such as utility/citations, methodological soundness, expert ratings or retractions). These data corroborate previous hypotheses: using journal rank as an assessment tool is bad scientific practice. Moreover, the data lead us to argue that any journal rank (not only the currently-favored Impact Factor) would have this negative impact. Therefore, we suggest that abandoning journals altogether, in favor of a library-based scholarly communication system, will ultimately be necessary. This new system will use modern information technology to vastly improve the filter, sort and discovery functions of the current journal system.
Synthesis and pharmacological characterization of new tetrahydrofuran based compounds as conformationally constrained histamine receptor ligands
Creators: name: Bodensteiner, Julian
name: Baumeister, Paul
name: Geyer, Roland
name: Buschauer, Armin
name: Reiser, Oliver
Publisher: name: Universität Regensburg
Year: 2013
Subjects: subject: 540 Chemie
subject: 615 Pharmazie

description: A series of tetrahydrofuran based compounds with a bicyclic core that provides conformational restriction were synthesized and investigated by radioligand displacement studies and functional [(35)S]GTPγS binding assays at the human histamine receptor (hHR) subtypes. The amines and ((1S,3R,5S,6R)- and ((1S,3S,5S,6R)-3-(1H-imidazol-5-yl)-2-oxabicyclo[3.1.0]hexan-6-yl)methanamine), exhibited submicromolar Ki values at the hH3R with 10-fold higher affinities than their corresponding (6S)-epimers and 25- and >34-fold selectivity over the hH4R, respectively. Both compounds act as neutral antagonists at the hH3R with KB values of 181 and 32 nM, respectively. The cyanoguanidines of the imidazole series and the oxazole analogues turned out to be inactive at all hHR subtypes.