cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
DRAFTS: A Deep, Rapid Archival Flare Transient Search in the Galactic Bulge
Creators: name: Osten, Rachel A.
name: Kowalski, Adam
name: Sahu, Kailash
name: Hawley, Suzanne
Publisher: name: arXiv
Year: 2012
Subjects: subject: Solar and Stellar Astrophysics (astro-ph.SR)
subject: FOS: Physical sciences

description: We utilize the Sagittarius Window Eclipsing Extrasolar Planet Search (SWEEPS) HST/ACS dataset for a Deep Rapid Archival Flare Transient Search (DRAFTS) to constrain the flare rate toward the older stellar population in the Galactic bulge. During 7 days of monitoring 229,293 stars brighter than V=29.5, we find evidence for flaring activity in 105 stars between V=20 and V=28. We divided the sample into non-variable stars and variable stars whose light curves contain large-scale variability. The flare rate on variable stars is \sim 700 times that of non-variable stars, with a significant correlation between the amount of underlying stellar variability and peak flare amplitude. The flare energy loss rates are generally higher than those of nearby well-studied single dMe flare stars. The distribution of proper motions is consistent with the flaring stars being at the distance and age of the Galactic bulge. If they are single dwarfs, they span a range of \approx 1.0 - 0.25M\odot. A majority of the flaring stars exhibit periodic photometric modulations with P <3d. If these are tidally locked magnetically active binary systems, their fraction in the bulge is enhanced by a factor of \sim20 compared to the local value. These stars may be useful for placing constraints on the angular momentum evolution of cool close binary stars. Our results expand the type of stars studied for flares in the optical band, and suggest that future sensitive optical time-domain studies will have to contend with a larger sample of flaring stars than the M dwarf flare stars usually considered.
description: accepted for publication in the Astrophysical Journal
Additional file 1 of Carcinogenic effect of arsenic in digestive cancers: a systematic review
Creators: name: Kasmi, Sophie
name: Moser, Laureline
name: Gonvers, Stéphanie
name: Dormond, Olivier
name: Demartines, Nicolas
name: Labgaa, Ismail
Publisher: name: figshare
Year: 2023
Subjects: subject: Medicine
subject: Biotechnology
subject: Ecology
subject: FOS: Biological sciences
subject: Immunology
subject: FOS: Clinical medicine
subject: 69999 Biological Sciences not elsewhere classified
subject: Cancer
subject: Inorganic Chemistry
subject: FOS: Chemical sciences
subject: Science Policy

description: Additional file 1. Search algorithms.
Composites of Nanoporous Gold and Polymer
Creators: name: Wang, Ke
Publisher: name: TUHH Universitätsbibliothek
Year: 2015
Subjects: classificationCode: 620
subject: Ingenieurwissenschaften

description: Nanoporöses Gold, das durch Korrosion hergestellt wurde, wurde mit unterschiedlichen Polymeren vakuumimprägniert, um interpenetrierende Phasen-Nanokomposite herzustellen, die durch ein miteinander verbundenes Netzwerk von Metall-Nanostrukturen verstärkt werden. Die interpenetrierenden Phasen-Komposite wurden hinsichtlich ihrer Mikrohärte, des Druck-Spannungs-Dehnungs-Verhaltens, der makroskopischen Zug- und Biegeverformung getestet. Mechanische Tests zeigen, dass die Imprägnierung mit Polymeren ein effizienter Weg ist, um die Dichteänderung während des plastischen Fließens unter uniaxialer Last zu verringern. Das Komposit hat eine isotrope Mikrostruktur, es ist duktil unter Zugbelastung, es ist fest und verformbar unter Druckbelastung und seine Festigkeit übertrifft die von jedem der konstituierenden Phasen. Seine elektrische Leitfähigkeit erreicht 1% der von hochreinem massivem Kupfer.
description: Nanoporous gold obtained by alloy corrosion was vacuum-impregnated with different polymers to produce interpenetrating phase nanocomposites that are reinforced by interconnected network of metal nanostructures. The interpenetrating phase composites were tested for microhardness, compressive stress-strain behavior, macroscopic tensile, and bending deformation. Mechanical tests demonstrate that impregnation with polymer is an efficient way of reducing the density change during plastic flow under uniaxial load. The composite has an isotropic microstructure, it is ductile in tension, it is strong and deformable in compression, and its strength considerably exceeds that of each of the constituent phases. Its electric conductivity reaches 1% of that of high-purity massive copper.
Ampk And Cellular Aging In Keratinocytes
Creators: name: J?Ger, Sibylle
Publisher: name: Zenodo
Year: 2015

description: The aging process is perceived as resulting from a combination of intrinsic factors such as changes in intracellular signaling and extrinsic factors, most notably environmental stressors. In skin, the relationship between intrinsic changes and keratinocyte function is not clearly understood. Previously, we found that increasing the activity of AMP-activated protein kinase (AMPK) suppressed senescence in hydrogen peroxide (H2O2)-treated human primary keratinocytes, a model of oxidative stress-induced cellular aging. Using this model in the present study, we observed that resveratrol, an agent that increases the activities of both AMPK and sirtuins, ameliorated two age-associated phenotypes: cellular senescence and proliferative dysfunction. Treatment of keratinocytes with resveratrol transactivated FOXO3 and increased the expression of its target genes including catalase. Resveratrol's effects on both senescence and proliferation disappeared when FOXO3 was knocked down. Finally, we performed an exploratory study which showed that skin from humansover 50 years old had lower AMPK activity than skin from individuals under age 20. These findings suggest that the effects of resveratrol on keratinocyte senescence and proliferation are regulated by the AMPK-FOXO3 pathway.
Additional file 2 of Carcinogenic effect of arsenic in digestive cancers: a systematic review
Creators: name: Kasmi, Sophie
name: Moser, Laureline
name: Gonvers, Stéphanie
name: Dormond, Olivier
name: Demartines, Nicolas
name: Labgaa, Ismail
Publisher: name: figshare
Year: 2023
Subjects: subject: Medicine
subject: Biotechnology
subject: Ecology
subject: FOS: Biological sciences
subject: Immunology
subject: FOS: Clinical medicine
subject: 69999 Biological Sciences not elsewhere classified
subject: Cancer
subject: Inorganic Chemistry
subject: FOS: Chemical sciences
subject: Science Policy

description: Additional file 2. Quality assessment of the selected studies.
Allostery: Abl Kinase And Trubind? Back-Scattering Interferometry
Creators: name: Lavieri, Robert R.
Publisher: name: Zenodo
Year: 2015

description: When abnormally expressed or controlled, kinase activity can cause cellular dysregulation and contribute to the onset of several diseases, including cancer. Based on the understanding of kinase malfunction, the discovery of small organic molecules to alter kinase function has culminated in the development of targeted cancer therapy. However, limited selectivity and the emergence of drug resistance remain fundamental challenges.
Most known kinase inhibitors are Type I inhibitors, ATP-competitive compounds such as dasatinib that bind to the ATP binding site. Type II inhibitors are compounds which bind partially in the ATP binding site and extend into an adjacent allosteric site that is present only in the inactive kinase conformation. Compared to Type I inhibitors, Type II inhibitors have been shown to possess advantageous pharmacological properties. As such, many Type II inhibitors currently on the market, such as imatinib, are very effective anti-cancer drugs.
Mutations resistant to Type I/II inhibitors are emerging at a rapid pace and often limit the success of targeted cancer therapies. At present, there are more than 50 mutation sites conferring different levels of imatinib resistance. Recently, a number of Type III inhibitors that function via allosteric modulation have demonstrated promise towards addressing mutation dependent drug resistance. As such, the need to identify and develop reversible inhibitors that are resistant to such mutations and bind with a high affinity is the focus of many research projects.
The binding affinity of Type I, II and III Bcr-Abl kinase inhibitors with wild type and four mutant Bcr-Abl kinases (H396P, M351T, Q252H, and T315I) were measured using TruBind? Back-Scattering Interferometry (BSI). BSI successfully demonstrated facile determination of equilibrium dissociation constants (Kd) for all systems, with a high degree of concordance with competition assay derived IC50 results. These results indicate that BSI binding studies both class I, II, and III kinase inhibitors can easily be performed, allowing for confirmation of target engagement as well as direct binding assessment of type II and III kinase inhibitors against inactive Bcr-Abl kinase. The latter makes BSI an attractive biophysical technique for the study of second and third generation kinase inhibitors to address the challenges of kinase inhibitor drug resistance.
Tbd Resistence Mechanisms And Small Molecules
Creators: name: Corneila Zumbrunn
Publisher: name: Zenodo
Year: 2015

description: The bacterial topoisomerases Gyrase and Topoisomerase IV are well validated targets in antibiotic research and discovery. Fluoroquinolones (eg. Ciprofloxacin) are potent inhibitors of these targets and are an important weapon in the battle against infections. Unfortunately their utility has lately been limited due to emerging resistance. Over the last years several companies have discovered molecules that inhibit topoisomerases by a novel mode of action and are therefore devoid of cross-resistance with clinically used antibiotics including Fluoroquinolones. Especially the Novel Bacterial Topoisomerase Inhibitors (NBTI) such as GSK214944 or NBTI 5436have shown promising properties.[1, 2] We report here the synthesis and characterization of compounds (A) containing a quinolone moiety as well as a pharmacophore contained in NBTI's. Depending on the substitution, these FQ-NBTI hybrids have different modes of action. Very intriguingly is the improved activity on Gram negative bacteria. The presentation will focus on the characterization of the compounds in terms of cellular and enzymatic activities.
Novel Ways To Identify And Nurture Healthcare Innovation
Creators: name: Hertogs, Kurt
Publisher: name: Zenodo
Year: 2015

description: Johnson & Johnson is engaged in a new strategy of partnering and cultivating external innovation that relies on strengthening the ecosystem for innovation in its areas of interest. Johnson & Johnson Innovation (JJI) has been implementing this strategy by identifying early innovation and helping to translate it into value added therapeutic solutions and portfolio products. In order to achieve transformational results in areas of high unmet medical need and risk, collaboration with different stakeholders (Organizations, Companies, (R&D) Institutes, or Investors), and leveraging their expertise and contributions is of critical importance. JJI is achieving this through various investments aimed at advancing translational research and promoting new company formation, seed investing and participation in accelerators and funds. Ultimately, Johnson & Johnson will be able to improve its level of innovation and ability to make advances for patients through its interactions and engagement with external innovators. Exposure to the diverse thinking, ideas and problem solving challenges will help Johnson & Johnson to become more open and broad in its own approach. Furthermore, as startups benefit from the expertise and/or capabilities offered by Johnson & Johnson, they are more likely to advance to a next level of maturity and success to.
Atheism, Religion And Society In Mandeville'S Thought
Creators: name: Simonazzi, Mauro
Publisher: name: Zenodo
Year: 2015

description: Starting by analyzing the atheist's character, Mandeville gets gradually closer to Bayle's thesis on virtuous atheism, but he takes a different turn, and maintains that a society without religion cannot exist because atheism goes against a natural passion, fear of invisible causes. In order to understand Mandeville's position on this last point, in the second part of this essay I will consider his reflection on the origin and on the social and political functions of religion.
The Antitumor Potential Of The Endocannabinoid-Reuptake Inhibitor Omdm-2 Alone And In Combination With Cytostatic Drugs
Creators: name: Ammar, Ramy
Publisher: name: Zenodo
Year: 2015

description: Cannabis sativa has been used as medicinal plant since ancient times. Its major psychotropic ingredient ?9-tetrahydrocannabinol (THC) was characterized about 50 years ago, but only in the 90s endogenous counterparts of THC were discovered. These endogenous counterparts are collectively termed endocannabinoids (eCBs). They are increasingly emerging as widespread, complex and highly versatile signaling molecules controlling basic biological processes including cell choice between survival and death and progenitor/stem cell proliferation and differentiation (1). This makes them interesting in the treatment of cancer. Indeed, THC potential antitumor activity has been demonstrated. Targeting the eCBs as new strategy should avoid clinical and ethical considerations which limit the use of the direct agonists. We investigated the cytotoxity of the designated endocannabinoid reuptake inhibitor OMDM-2 alone and in combination with cytotoxic drugs and with the natural anticancer agent curcumin.In-vivo experiments in the Ehrlich-Ascites mouse model provided evidence for an antitumor potential of OMDM-2. In-vitro MCF-7 (breast cancer cells) and U-87 (glioma cells) were used to test the antiproliferative activity of OMDM-2 alone and in combination with standard chemotherapeutic drugs paclitaxel and temozolomide, respectively. Our combinations were evaluated by using different methods; isobole, combination index, dose reduction index. The results indicated that the addition of OMDM-2 to the chemoresistant breast and glioma cancer cells not only increased their sensitivity but also decreased the required dose of benchmark chemotherapeutics.
Increasing evidence substantiate the notion that combination therapies utilizing both-molecules targeting the endocannabinoid system in addition to natural anticancer agents or benchmark chemotherapeutics are a worthwhile option to be systematically explored in the treatment of cancer.
Additional file 3 of Carcinogenic effect of arsenic in digestive cancers: a systematic review
Creators: name: Kasmi, Sophie
name: Moser, Laureline
name: Gonvers, Stéphanie
name: Dormond, Olivier
name: Demartines, Nicolas
name: Labgaa, Ismail
Publisher: name: figshare
Year: 2023
Subjects: subject: Medicine
subject: Biotechnology
subject: Ecology
subject: FOS: Biological sciences
subject: Immunology
subject: FOS: Clinical medicine
subject: 69999 Biological Sciences not elsewhere classified
subject: Cancer
subject: Inorganic Chemistry
subject: FOS: Chemical sciences
subject: Science Policy

description: Additional file 3. Selected studies investigating the effect of arsenic (As) in esogastric cancers.
Extending maps by injective $σ$-$Z$-maps in Hilbert manifolds
Creators: name: Niemiec, Piotr
Publisher: name: arXiv
Year: 2011
Subjects: subject: General Topology (math.GN)
subject: FOS: Mathematics
subject: 57N20, 57N35, 57N37, 54C55, 54E50, 54C20

description: The aim of the paper is to prove that if $M$ is a metrizable manifold modelled on a Hilbert space of dimension $α\geq \aleph_0$ and $F$ is its $σ$-$Z$-set, then for every completely metrizable space $X$ of weight no greater than $α$ and its closed subset $A$, for any map $f: X \to M$, each open cover $\mathcal{U}$ of $M$ and a sequnce $(A_n)_n$ of closed subsets of $X$ disjoint from $A$ there is a map $g: X \to M$ $\mathcal{U}$-homotopic to $f$ such that $g\bigr|_A = f\bigr|_A$, $g\bigr|_{A_n}$ is a closed embedding for each $n$ and $g(X \setminus A)$ is a $σ$-$Z$-set in $M$ disjoint from $F$. It is shown that if $f(\partial A)$ is contained in a locally closed $σ$-$Z$-set in $M$ or $f(X \setminus A) \cap \bar{f(\partial A)} = \empty$, the map $g$ may be taken so that $g\bigr|_{X \setminus A}$ be an embedding. If, in addition, $X \setminus A$ is a connected manifold modelled on the same Hilbert space as $M$ and $\bar{f(\partial A)}$ is a $Z$-set in $M$, then there is a $\mathcal{U}$-homotopic to $f$ map $h: X \to M$ such that $h\bigr|_A = f\bigr|_A$ and $h\bigr|_{X \setminus A}$ is an open embedding.
description: 12 pages
Additional file 4 of Carcinogenic effect of arsenic in digestive cancers: a systematic review
Creators: name: Kasmi, Sophie
name: Moser, Laureline
name: Gonvers, Stéphanie
name: Dormond, Olivier
name: Demartines, Nicolas
name: Labgaa, Ismail
Publisher: name: figshare
Year: 2023
Subjects: subject: Medicine
subject: Biotechnology
subject: Ecology
subject: FOS: Biological sciences
subject: Immunology
subject: FOS: Clinical medicine
subject: 69999 Biological Sciences not elsewhere classified
subject: Cancer
subject: Inorganic Chemistry
subject: FOS: Chemical sciences
subject: Science Policy

description: Additional file 4. Selected studies investigating the effect of arsenic (As) in hepato-pancreatico-biliary cancers [52–54].
Fractal iso-contours of passive scalar in smooth random flows
Creators: name: Vucelja, Marija
name: Falkovich, Gregory
name: Turitsyn, Konstantin S.
Publisher: name: arXiv
Year: 2011
Subjects: subject: Mathematical Physics (math-ph)
subject: Chaotic Dynamics (nlin.CD)
subject: Fluid Dynamics (physics.flu-dyn)
subject: FOS: Physical sciences

description: We consider a passive scalar field under the action of pumping, diffusion and advection by a smooth flow with a Lagrangian chaos. We present theoretical arguments showing that scalar statistics is not conformal invariant and formulate new effective semi-analytic algorithm to model the scalar turbulence. We then carry massive numerics of passive scalar turbulence with the focus on the statistics of nodal lines. The distribution of contours over sizes and perimeters is shown to depend neither on the flow realization nor on the resolution (diffusion) scale $r_d$ for scales exceeding $r_d$. The scalar isolines are found fractal/smooth at the scales larger/smaller than the pumping scale $L$. We characterize the statistics of bending of a long isoline by the driving function of the Löwner map, show that it behaves like diffusion with the diffusivity independent of resolution yet, most surprisingly, dependent on the velocity realization and the time of scalar evolution.
Additional file 5 of Carcinogenic effect of arsenic in digestive cancers: a systematic review
Creators: name: Kasmi, Sophie
name: Moser, Laureline
name: Gonvers, Stéphanie
name: Dormond, Olivier
name: Demartines, Nicolas
name: Labgaa, Ismail
Publisher: name: figshare
Year: 2023
Subjects: subject: Medicine
subject: Biotechnology
subject: Ecology
subject: FOS: Biological sciences
subject: Immunology
subject: FOS: Clinical medicine
subject: 69999 Biological Sciences not elsewhere classified
subject: Cancer
subject: Inorganic Chemistry
subject: FOS: Chemical sciences
subject: Science Policy

description: Additional file 5. Selected studies investigating the effect of arsenic (As) in colorectal cancers [55].
Harnessing Pluripotent Stem Cells Derivatives To Decipher Mechanisms And Identify Treatments For Monogenic Diseases
Creators: name: Peschanski, Mark
Publisher: name: Zenodo
Year: 2015

description: Pluripotent stem cell lines derived from donors who carry a mutant gene at the origin of a monogenic disease can be obtained currently either from embryos characterized as gene-carriers during a pre-implantation genetic diagnosis procedure, or else through genetic reprogramming of donors' sample cells. Both can be used to screen libraries of compounds, in a search for new treatments. Currently, the ES cell bank at I-Stem comprises over 30 PGD-derived cell lines, representing over 15 diseases. IPS cell lines are derived at request. Robust read-outs relevant to the pathological mechanisms should first be identified. On this basis, a screening platform either in high throughput or in high content can be implemented, as derivatives of pluripotent stem cells can be obtained at near homogeneity and are amenable to miniaturization and standardization of cell processes. At I-Stem, we have exploited this potential for several monogenic pathologies, already, including Huntington's disease, myotonic dystrophy type I, Progeria and Lesch-Nyhan disease. Several runs of our proprietary library of 22,000 chemical compounds have allowed us to identify new chemical entities with therapeutic potentials, as well as to propose re-purposing of FDA-approved drugs. In parallel, functional genomics can also be implemented on large-scale platforms, in a search for yet unknown mechanisms and proteins involved in pathological signaling pathways. Using a subset of siRNA, we have in particular been able to identify one gene, the down-expression of which tended to normalize abnormal gene splicing and functional defects associated to myotonic dystrophy type 1. We eventually found out that the protein encoded by this gene is druggable, which opened a path toward a therapeutic trial which is currently ongoing.
Claire Weeda: Ethnicity in Medieval Europe 950–1250
Creators: name: Wolever, Eric
Publisher: name: Das Mittelalter. Perspektiven mediävistischer Forschung
Year: 2022

description: Claire Weeda, Ethnicity in Medieval Europe 950–1250. Medicine, Power and Religion (Health and Healing in the Middle Ages 2). York, York Medieval Press 2021. 346 S. 5 Abb.
description: Das Mittelalter. Perspektiven mediävistischer Forschung, Bd. 27 Nr. 2 (2022): Die Materialität von Kredit. Sachüberlieferungen mittelalterlicher Schuld- und Kreditbeziehungen
Generation Of Humanized Models For The Understanding Of Health And Aging
Creators: name: Kraus, Marine
Publisher: name: Zenodo
Year: 2015

description: In the last decade, great research efforts have been devoted to identify the genetic basis of age related diseases, mostly by genome-wide association studies (GWAS). Despite their highly significant association with the trait of interest, the functional role of these genetic variants is, in most cases, still not elucidated, thus frustrating their potential clinical and pharmaceutical application.
To overcome these limitations, we and our collaborators of the European project HUMAN, aim at developing humanized models recapitulating liver and pancreatic human function in various genetic contexts. We are adapting Viacyte's newly established methods (Schulz et al. 2012 PLoS One) to generate macro-encapsulated functional beta cells in vivo from human induced pluripotent stem cells. The iPSC-derived glucose responsive implants not only regulate glucose levels, but also protect mice against STZ-induced hyperglycemia. This technology will be combined with a model of ?humanization? of the liver developed by The Karolinska Institute in which most hepatocytes are human cells deriving from a single human donor (Azuma et al., 2007; Strom et al., 2010). These animals are recapitulating human liver and pancreas function at similar levels observed in human donors, supporting the notion that mice with humanized liver and pancreas will be unique and innovative tools to study human metabolic diseases and human aging.
This innovative approach offers the unique possibility of studying the function of genetic risk variants associated with metabolic diseases in an integrated living system (the mouse body), but in human-derived organs, i.e. liver and pancreas. Our ultimate goal is to improve understanding of chronic metabolic disorders such as diabetes with the aim to develop biomarkers of health and disease and science-based nutritional interventions.
Enhancement of the retrapping current of superconducting microbridges of finite length
Creators: name: Vodolazov, D. Y.
name: Peeters, F. M.
Publisher: name: arXiv
Year: 2011
Subjects: subject: Superconductivity (cond-mat.supr-con)
subject: Mesoscale and Nanoscale Physics (cond-mat.mes-hall)
subject: FOS: Physical sciences

description: We theoretically find that the resistance of a superconducting microbridge/nanowire {\it decreases} while the retrapping current $I_r$ for the transition to the superconducting state {\it increases} when one suppresses the magnitude of the order parameter $|Δ|$ in the attached superconducting leads. This effect is a consequence of the increased energy interval for diffusion of the 'hot' nonequilibrium quasiparticles (induced by the oscillations of $|Δ|$ in the center of the microbridge) to the leads. The effect is absent in short microbridges (with length less than the coherence length) and it is relatively weak in long microbridges (with length larger than the inelastic relaxation length of the nonequilibrium distribution function). A nonmonotonous dependence of $I_r$ on the length of the microbridge is predicted. Our results are important for the explanation of the enhancement of the critical current and the appearance of negative magnetoresistance observed in many recent experiments on superconducting microbridges/nanowires.
description: 6 pages, 7 figures
Henning Siekmann: Wolf und Lamm
Creators: name: Bozkaya, Inci
Publisher: name: Das Mittelalter. Perspektiven mediävistischer Forschung
Year: 2022

description: Henning Siekmann, Wolf und Lamm. Zur Karriere einer politischen Metapher im Kontext der europäischen Fabel (Bamberger Studien zu Literatur, Kultur und Medien 21). Bamberg, University of Bamberg Press 2017. 421 S.
description: Das Mittelalter. Perspektiven mediävistischer Forschung, Bd. 27 Nr. 2 (2022): Die Materialität von Kredit. Sachüberlieferungen mittelalterlicher Schuld- und Kreditbeziehungen
Implementing Ipsc Technology: Case Studies Of Ipsc-Tissue Cell Use In Disease Modeling And Drug Discovery
Creators: name: Anson, Blake
Publisher: name: Zenodo
Year: 2015

description: Case studies on deriving iPSCs from clinical and non-clinical populations and using iPSC-tissue cells in disease modeling and drug discovery.
Induced pluripotent stem cell (iPSC) technology is having a positive impact on drug discovery efforts through recent advances in generating iPSCs from both individuals and targeted populations as well as creating relevant iPSC-based human disease models. This presentation will provide data on the progress and process of two large-scale reprogramming efforts and several iPSC-based disease models being used within the Pharmaceutical industry. Population-based reprogramming efforts through the California Institute of Regenerative Medicine (CIRM) and National Heart, Lung, and Blood Institute (NHLBI), are generating ~3000 and ~250 donor lines across healthy and disease backgrounds. These iPSC clones will be deposited into publically accessible biobanks for further use by the research community. Additional case studies will be presented illustrating the utility and implementation of iPSC-based cardiac and neuronal genetic and environmental disease models in phenotypic screens. In summary this presentation will provide an overview of how iPSC technology brings human biology and diversity into drug discovery.
Sarah Semple, Alexandra Sanmark, Frode Iversen u. Natascha Mehler: Negotiating the North
Creators: name: Steinforth, Dirk H.
Publisher: name: Das Mittelalter. Perspektiven mediävistischer Forschung
Year: 2022

description: Sarah Semple, Alexandra Sanmark, Frode Iversen u. Natascha Mehler, Negotiating the North. Meeting-Places in the Middle Ages in the North Sea Zone (Society of Medieval Archaeology Monograph 41). London, New York, Routledge 2020. XX, 349 S. 166 s/w-Abb., 65 farb. Abb.
description: Das Mittelalter. Perspektiven mediävistischer Forschung, Bd. 27 Nr. 2 (2022): Die Materialität von Kredit. Sachüberlieferungen mittelalterlicher Schuld- und Kreditbeziehungen
Kjære Papa! / Anton min!
Creators: name: Qvam, Fredrikke Marie
name: Qvam, Louise Gram
name: Qvam, Olaf Hafslo
Publisher: name: Unknown
Year: 1874

description: Fredrikke beskriver ensomheten og lengsel etter å få brev fra Anton. Ellers hverdagshistorier om barna
Profiling Of Cellular Signal Transduction For Analysis Of Primary Tumor Tissue
Creators: name: Templin, Markus
Publisher: name: Zenodo
Year: 2015

description: The analysis of cellular signaling cascades is a valuable approach for understanding the processes that underlie cellular functions. Profiling of central signal transduction pathways requires the detection of protein expression and activation. In recent years, mass spectrometry based analysis systems showed their power by allowing unbiased discovery approaches, whereas novel image-guided analysis systems have given detailed information on the localization of proteins. Nevertheless the Western blot is still the most widely employed approach. In hypothesis driven research, this tool gives reliable results with good sensitivity. With the large efforts that have been put into the generation of binding molecules for array-based proteomics, large numbers of antibodies are available and screening approaches that take advantage of these valuable resources are of interest.
Here, we present a novel approach that uses the principles of the Western blot (protein separation by SDS-PAGE; protein immobilization on a solid support; detection by specific antibodies) and combines it with a multiplexed bead array as a readout system. The system allows the generation of hundreds of bead-based Western blot equivalents from a few micrograms of protein and thereby information on the expression and modification of hundreds of proteins is obtained. This new approach combines reproducibility and good linearity with large dynamic range.
Taking advantage of our approach, we performed comprehensive signal transduction analyses of clinical ovarian tumor specimen. Whereas for ovarian cancer first-line platinum-based therapy reveals high response rates (75 %), as many as 70 % of patients develop platinum resistance and relapse. Mechanisms of cellular resistance are still unknown as well are predictive markers. Using our system we compared tumor specimen from relapsed to cured patients directly on the protein level. Hundreds of antibodies were employed to analyze the activation state of different signaling cascades. Data on changes in signal transduction during resistance development is shown.
Hans Ulrich Schmid: „Hand“ und „Hals“ in mittelalterlichen Rechtssprachen der Germania
Creators: name: Gussone, Monika
Publisher: name: Das Mittelalter. Perspektiven mediävistischer Forschung
Year: 2022

description: Hans Ulrich Schmid, Hand und Hals in mittelalterlichen Rechtssprachen der Germania (Sitzungsberichte der Sächsischen Akademie der Wissenschaften zu Leipzig. Philologisch-historische Klasse 142.5). Stuttgart, Leipzig, S. Hirzel 2021. 24 S.
description: Das Mittelalter. Perspektiven mediävistischer Forschung, Bd. 27 Nr. 2 (2022): Die Materialität von Kredit. Sachüberlieferungen mittelalterlicher Schuld- und Kreditbeziehungen
A ~60 Myr periodicity is common to marine-87Sr/86Sr, fossil biodiversity, and large-scale sedimentation: what does the periodicity reflect?
Creators: name: Melott, Adrian L.
name: Bambach, Richard K.
name: Petersen, K. D.
name: McArthur, John M.
Publisher: name: arXiv
Year: 2012
Subjects: subject: Earth and Planetary Astrophysics (astro-ph.EP)
subject: Astrophysics of Galaxies (astro-ph.GA)
subject: Biological Physics (physics.bio-ph)
subject: Geophysics (physics.geo-ph)
subject: Populations and Evolution (q-bio.PE)
subject: FOS: Physical sciences
subject: FOS: Biological sciences

description: We find that the marine 87Sr/86Sr record shows a significant periodicity of 59.3 \pm 3 Myr. The 87Sr/86Sr record is 171° \pm 12°out of phase with a 62 (\pm 3) Myr periodicity previously reported in the record of marine-animal diversity. These periodicities are close to 58 (\pm 4) Myr cycles found for the number of gap-bounded sedimentary carbonate packages of North America We propose that these periodicities reflect the operation of a periodic "pulse of the Earth" in large-scale, Earth processes. These may be linked to mantle or plate-tectonic events, possibly uplift, which affects Earth's climate and oceans, and so the geochemistry, sedimentation, and biodiversity of the marine realm. Alternately, they may be linked to oscillation of the solar system normal to the plane of the galaxy.
description: 21 pages, including supplement
Targeting Metabolic Symbiosis To Overcome Resistance To Anti-Angiogenic Therapy
Creators: name: Christofori, Gerhard
Publisher: name: Zenodo
Year: 2015

description: Despite the approval of several anti-angiogenic therapies for the treatment of cancer patients, clinical results remain unsatisfactory, and transient benefits are followed by rapid tumor recurrence. In the case of the targeted inactivation of an individual pro-angiogenic pathway, such as vascular endothelial growth factor (VEGF)-mediated signaling, tumors switch to employ other pro-angiogenic factors and signaling pathways, for example fibroblast growth factors (FGF), Bv8/Prokineticin, interleukin 33 and others. We have studied the anti-angiogenic efficacy of the anti-angiogenic multi-kinase inhibitor nintedanib in a mouse model of breast cancer. Nintedanib demonstrates a potent anti-angiogenic effect. However, after an initial repression of tumor expansion, tumors resume growth in the absence of active tumor angiogenesis, suggesting a novel mechanism of therapy resistance whereby tumor cells proliferate without proper vascularization. Gene expression profiling analysis of flow cytometry-sorted tumor cells reveals a metabolic reprogramming towards anaerobic glycolysis. Indeed, combinatorial treatment with a glycolysis inhibitor (3PO) efficiently inhibits tumor growth. Moreover, alternation between hypoxic, glycolytic areas and normoxic areas in the nintedanib-treated tumors suggests the establishment of metabolic symbiosis, further illustrated by the differential expression of MCT1 and MCT4, monocarboxylate transporters implicated in lactate exchange in glycolytic tumors. Accordingly, ablation of MCT4 expression surmounts resistance to anti-angiogenic therapy. Our results suggest a mechanism of glycolytic symbiosis to overcome a potent anti-angiogenic therapy with a multi-kinase inhibitor. Hence, targeting metabolic symbiosis may be an attractive avenue
Sequence-Defined Oligomers Containing Natural And Artificial Oligo-Amino Acids For Intracellular Drug, Protein And Nucleic Acid Delivery
Creators: name: Wagner, Ernst
Publisher: name: Zenodo
Year: 2015

description: The therapeutic perspectives of therapeutic nucleic acids and intracellularly active proteins rely on effective and safe intracellular delivery. Natural biological evolution of viruses or toxins has demonstrated how defined sequence domains can be optimized. A ?chemical evolution? process can be applied for such a carrier design, with subdomains for the various delivery steps, including improved cargo packaging, targeted cell uptake, and intracellular release to be presented in optimized sequence. Building blocks have to be identified which serve as microdomains useful in a delivery step; these units have to be assembled into defined macro sequences and topologies and be evaluated in assays; the obtained structure-activity relations can be utilized for the next round of carrier design. In our recent research, automated solid phase assisted peptide synthesis was adopted for the design of >800 precise oligomers of different topologies (linear, branched, combs). Artificial oligoamino acids were combined with natural amino acids, fatty acids, precise PEG chains and other compounds. Branching points were served by lysines, endosomal-buffering was enhanced by histidines; terminal cysteines served for nanoparticle stabilization by bioreversible disulfide bond formation. Optionally, hydrophobic domains were included for stabilization. Targeting peptides, amphipathic membrane-destabilizing peptides also were incorporated. Such carriers can be well-tolerated and potent in intracellular delivery of pDNA, siRNA, proteins or small drugs.
Dalazatide, A First-In-Class Blocker Of The Kv1.3 Potassium Channel On Effector Memory T Cells: Safety, Tolerability And Proof Of Concept Immunomodulation In Patients With Active Plaque Psoriasis
Creators: name: Iadonato, Shawn
Publisher: name: Zenodo
Year: 2015

description: Background: Effector memory T cells of both CD4 and CD8 lineages are key drivers of autoimmunity and are pathogenic in several autoimmune diseases including psoriasis, atopic dermatitis, lupus nephritis, and inflammatory bowel disease. Kv1.3 is a voltage-gated potassium channel required for sustained intracellular calcium influx, proliferation and activation of effector memory T cells. Dalazatide (ShK-186) is a potent, highly specific, first-in-class peptide blocker of Kv1.3 and effector memory T cell activation. Here we report safety, tolerability, pharmacodynamics and immunomodulating proof-of-concept data for dalazatide from a phase 1b clinical trial in patients with active plaque psoriasis.
Methods: A double blind, placebo controlled trial was conducted in patients with active mild to moderate plaque psoriasis. Subjects were randomized to receive doses of 30 mcg (n=10) or 60 mcg (n=10) of dalazatide or placebo (n=4) twice weekly by subcutaneous injection for 4 weeks with 4 weeks of follow up. Skin lesion biopsies were collected at baseline and at week 4 for gene expression and immunohistological analyses. Plasma, serum and peripheral blood mononuclear cells were collected at baseline and at several times throughout the study for cytokine and immunophenotyping studies. Target psoriatic plaques were evaluated at baseline, on day 32 following the last dose, and again on day 57 (end-of-study visit).
Results: The treatment was well tolerated with all subjects completing the study and reporting only mild adverse events. Target lesion responses were noted in subjects enrolled in both the 30 mcg and 60 mcg groups. 50% of subjects in 60 mcg group achieved a clinical improvement in their target lesion. Improvements were observed as early as day 15 and continued for up to 4 weeks following the last dose. Ongoing improvement continued during the follow-up period in some subjects. 90% of subjects in 60 mcg group had reduction in PASI score.
Conclusion: These results demonstrate that twice-weekly subcutaneous injection of Kv1.3 channel blocker dalazatide is well tolerated in psoriasis patients. Improvement in clinical disease endpoints provides proof-of-concept data for the immunomodulating mechanism of action of dalazatide in a prototypical T cell mediated autoimmune disease.
Tailoring Semisynthetic Ligands To Investigate And Regulate Erbb Receptor Family Dysregulation In Cancer
Creators: name: Kroll, Carsten
Publisher: name: Zenodo
Year: 2015

description: ErbB/HER receptors are receptor tyrosine kinases and play crucial roles in cellular processes. While critical for normal signaling processes, the overexpression and mutation of ErbB receptors is associated with the malignancy of many cancers. Activation of ErbB receptors (EGFR, ErbB2/3/4) by ligand binding induces receptor homo- or heterodimerization that activates the inherent kinases, which then leads to signaling through the PI3K/AKT or the MAP kinase pathways. Accordingly, these receptors and pathways have emerged as targets for cancer therapy. Some tumors however show resistance, for example through upregulation of ErbB3.
Recently we focused on biasing ErbB3 receptor interactions with semisynthetic bivalent neuregulin ligands. Neuregulin is the endogenous ligand for ErbB3 and the bivalent ligands are supposed to bias ErbB3 signaling by trapping ErbB3 into inactive homodimers, since ErbB3 can only signal through heterodimers. We developed a robust semisynthetic strategy that allows us access to a variety of bivalent cytokines. It relies on recombinant expression of Neuregulin, modified with short amino acid sequences for sortase mediated ligation. The ligation modifies Neuregulin with chemically-synthesized peptidic components that include either a norbornene or tetrazine moiety, which undergo a metal-free bioorthogonal ligation to link the two neuregulins. Due to the synthetic linker, modifications and tags can be easily incorporated.
This powerful approach provides a tailored set of bivalent ligands for studies on the ideal construct for sequestering ErbB3 and mitigating the deleterious effects of receptor overepression. Additionally, the semisynthetic strategy provides valuable reagents for visualizing the dynamic interactions amongst the ErbB receptors and other cell surface proteins.
ICT Interest and ICT Self-concept as Determinants of Adolescents’ Vocational Choices. Implications for Gender Segregation in the Labor Market
Creators: name: Röhlke, Leo
name: Herzing, Jessica M. E.
name: Gomensoro, Andrés
name: Krebs-Oesch, Dominique
Publisher: name: University of Bern
publisherIdentifier: https://ror.org/02k7v4d05
publisherIdentifierScheme: ROR
Year: 2024
Subjects: Adolescence
Career choice
Gender segregation
ICT interest
ICT self-concept
ICT self-efficacy
Occupations
Occupational interests
Person-environment fit
Switzerland
Task content
Technology
Vocational choice
Vocational education and training
VET

description: The use of information and communication technologies (ICT) is now an integral part of many occupational task profiles. Therefore, like mathematics and science, ICT represent an important content domain that adolescents may consider in their early vocational choices. Drawing on Eccles’ situated expectancy value theory and related theories, we hypothesize that adolescents’ ICT interest and self-concept should influence their vocational choices with respect to the intensity of ICT use in future occupations. Using longitudinal data from 1,964 Swiss adolescents transitioning into firm-based vocational education and training, we find strongly gendered patterns. Higher ICT interest predicts selection into occupations involving greater intensity of both basic and advanced ICT use, but only for girls. A more positive ICT self-concept is a significant predictor of greater occupational ICT use in future occupations only for boys, and this association is driven mainly by boys choosing careers as ICT specialists. Girls’ lower average ICT interest and their less positive ICT self-concepts explain almost half of the gender differences in the intensity of advanced ICT use. These findings emphasize that ICT are an important content domain of adolescents’ vocational choices today and highlight how gendered interests and self-concepts towards ICT perpetuate occupational gender segregation.
Additional file 1 of Polycystic ovarian syndrome awareness among females in the UAE: a cross-sectional study
Creators: name: Zaitoun, Balkis
name: Al Kubaisi, Abdullah
name: AlQattan, Noora
name: Alassouli, Yahya
name: Mohammad, Alshaima
name: Alameeri, Huriya
name: Mohammed, Ghada
Publisher: name: figshare
Year: 2023
Subjects: subject: Medicine
subject: Biotechnology
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: Sociology
subject: FOS: Sociology
subject: Cancer
subject: 111714 Mental Health
subject: FOS: Health sciences

description: Additional file 1. English and Arabic PCOS Study Questionnaires
Christoph Schanze: Tugendlehre und Wissensvermittlung; Vera Jerjen: Arbeiten an Welt- und Selbstbild im ‚Welschen Gast‘
Creators: name: Wolf, Gerhard
Publisher: name: Das Mittelalter. Perspektiven mediävistischer Forschung
Year: 2022

description: Christoph Schanze, Tugendlehre und Wissensvermittlung. Studien zum ‚Welschen Gast‘ Thomasins von Zerklære (Wissensliteratur im Mittelalter 53). Wiesbaden, Reichert 2018. XII, 508 S. 39 Abb. 32 Taf. Vera Jerjen, Arbeiten an Welt- und Selbstbild im ‚Welschen Gast‘ Thomasins von Zerclære (Scrinium Friburgense 45). Wiesbaden, Reichert 2019. 256 S. 47 Abb.
description: Das Mittelalter. Perspektiven mediävistischer Forschung, Bd. 27 Nr. 2 (2022): Die Materialität von Kredit. Sachüberlieferungen mittelalterlicher Schuld- und Kreditbeziehungen
Trends In Translational Medicine: The Value Of External Innovation
Creators: name: Khusru Asadullah
Publisher: name: Zenodo
Year: 2015

description: Collaborations between academic institutions and the diagnostics/pharmaceutical industry are increasingly being initiated and executed. It's assumed that these relationships could help to improve research and development productivity in industry, as well as enable academic institutions to better exploit the translational potential of their research. Identification and validation of targets and biomarkers, key elements of successful drug discovery, are challenging. Unfortunately according published data are frequently irreproducible. Thus we must not rely on published data only. Extensive joined efforts of multiple partners seem crucial to foster progress. Different models are used and required for different stages of the drug discovery and development process as well as for different kinds of targets and biomarkers. There isn't a ?one size fits all? solution. For the initial exploration of a new biomarker candidate, a novel technology, or a new target a project within a strategic partnership or an open innovation approach may be most suitable. For the comprehensive clinical validation, however, larger consortia may be more appropriate, as this requires high resources and complementary skills. We expect the high number of academic-industrial collaborations will further increase, in part (but not only) due to the increasingly availability of public funding. Each category of collaboration has its own needs to be successful. However, there are some general elements too.
title: Low-tech sustainable sanitation options for Ghana and Ethiopia – economic, social and technical aspects
title: Low-tech nachhaltige Sanitärversorgungsoptionen für Ghana und Äthiopien - ökonomische, soziale und technologische Aspekte
titleType: AlternativeTitle
Creators: name: Drewko, Aleksandra
Publisher: name: TUHH Universitätsbibliothek
Year: 2012
Subjects: subject: Ghana
subject: neuartige Sanitärsysteme
subject: Urin
subject: Äthiopien
subject: ökonomische Analyse
subject: ecological sanitation
subject: economic analysis
subject: Ethiopia, Ghana
subject: urine
classificationCode: 620
subject: Ingenieurwissenschaften

description: Neuartige Sanitärsysteme (NASS) werden umfassend anhand von zwei Fallstudien analysiert und bewertet. Im Rahmen einer Fallstudie für Äthiopien wird eine Geschäftsidee für die Herstellung der für NASS geeigneten Kunststofftoiletten erarbeitet. Im Rahmen einer Fallstudie für Ghana wird eine ökonomische Analyse durchgeführt. Diese umfasst den Toilettenbau oder die Anpassung der bestehenden Toiletten um eine separate Sammlung von Urin und Fäzes zu gewährleisten. Ebenso werden der Urintransport zu seinem Lagerungsstandort, die Urinlagerung und eine spätere
description: Ecological sanitation (ecosan) is analyzed from a holistic system’s perspective on the example of two case studies. In the case study Ethiopia, a business idea for the production of plastic toilet slabs applicable under the ecosan approach is drafted. In the case study Ghana, an economic analysis of building or modifying toilets for the separate collection of urine and feces, transportation of urine to its storage locations, urine storage and subsequently selling it to farmers to be applied as liquid fertilizer in agriculture is performed.