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Objectives: The aim of this multicenter retrospective study was to investigate safety and efficacy of direct acting antiviral (DAA) treatment in the rare subgroup of patients with HCV/HIV-coinfection and advanced liver cirrhosis on the liver transplant waiting list or after liver transplantation, respectively.
Methods: When contacting 54 German liver centers (including all 23 German liver transplant centers), 12 HCV/HIV-coinfected patients on antiretroviral combination therapy were reported having received additional DAA therapy while being on the waiting list for liver transplantation (patient characteristics: Child-Pugh A (n = 6), B (n = 5), C (n = 1); MELD range 7–21; HCC (n = 2); HCV genotype 1a (n = 8), 1b (n = 2), 4 (n = 2)). Furthermore, 2 HCV/HIV-coinfected patients were denoted having received DAA therapy after liver transplantation (characteristics: HCV genotype 1a (n = 1), 4 (n = 1)).
Results: Applied DAA regimens were SOF/DAC (n = 7), SOF/LDV/RBV (n = 3), SOF/RBV (n = 3), PTV/r/OBV/DSV (n = 1), or PTV/r/OBV/DSV/RBV (n = 1), respectively. All patients achieved SVR 12, in the end. In one patient, HCV relapse occurred after 24 weeks of SOF/DAC therapy; subsequent treatment with 12 weeks PTV/r/OBV/DSV achieved SVR 12. One patient underwent liver transplantation while on DAA treatment. Analysis of liver function revealed either stable parameters or even significant improvement during DAA therapy and in follow-up. MELD scores were found to improve in 9/13 therapies in patients on the waiting list for liver transplantation; in only 2 patients a moderate increase of MELD scores persisted at the end of follow-up.
Conclusion: DAA treatment was safe and highly effective in this nation-wide cohort of patients with HCV/HIV-coinfection awaiting liver transplantation or being transplanted.
Purpose: Collaborative care is effective in improving symptoms of patients with depression. The aims of this study were to characterize symptom trajectories in patients with major depression during one year of collaborative care and to explore associations between baseline characteristics and symptom trajectories.
Methods: We conducted a cluster-randomized controlled trial in primary care. The collaborative care intervention comprised case management and behavioral activation. We used the Patient Health Questionnaire-9 (PHQ-9) to assess symptom severity as the primary outcome. Statistical analyses comprised latent growth mixture modeling and a hierarchical binary logistic regression model.
Results: We included 74 practices and 626 patients (310 intervention and 316 control recipients) at baseline. Based on a minimum of 12 measurement points for each intervention recipient, we identified two latent trajectories, which we labeled "fast improvers" (60.5%) and "slow improvers" (39.5%). At all measurements after baseline, "fast improvers" presented higher PHQ mean values than "slow improvers". At baseline, "fast improvers" presented fewer physical conditions, higher health-related quality of life, and had made fewer suicide attempts in their history.
Conclusions: A notable proportion of 39.5% of patients improved only "slowly" and probably needed more intense treatment. The third follow-up in month two could well be a sensible time to adjust treatment to support "slow improvers".
Cervical spine injuries are frequent and often caused by a blunt trauma mechanism. They can have severe consequences, with a high mortality rate and a high rate of neurological lesions.Diagnosis is a three-step process: 1) risk assessment according to the history and clinical features, guided by a clinical decision rule such as the Canadian C-Spine rule; 2) imaging if needed; 3) classification of the injury according to different classification systems in the different regions of the cervical spine.The urgency of treatment is dependent on the presence of a neurological lesion and/or instability. The treatment strategy depends on the morphological criteria as defined by the classification.
We summarize previous work on b̅b̅ud four-quark systems in the Born-Oppenheimer approximation and discuss first steps towards an extension to the theoretically more challenging bb̅ud̅ system. Strategies to identify a possibly existing bb̅ud̅ bound state are discussed and first numerical results are presented.
We study tetraquark resonances with lattice QCD potentials computed for two static quarks and two dynamical quarks, the Born-Oppenheimer approximation and the emergent wave method of scattering theory. As a proof of concept we focus on systems with isospin I = 0, but consider different relative angular momenta l of the heavy b quarks. We compute the phase shifts and search for S and T matrix poles in the second Riemann sheet. We predict a new tetraquark resonance for l = 1, decaying into two B mesons, with quantum numbers I(JP) = 0(1−), mass MeV and decay width MeV.
Роботу «Філософія і вчитель» Теодор Адорно вперше прочитав як доповідь у Будинку студентів міста Франкфурта-на-Майні в листопаді 1961 року. У цій доповіді Адорно продовжив тему критики тих чинників тодішньої освіти Західної Німеччини, які унеможливлюють особисту боротьбу інтелектуала з культурними залишками тоталітарного суспільства. Адорно зауважив такий важливий елемент освітнього процесу, яким є іспит із філософії. Цей іспит мають складати майбутні вчителі, кандидати на посаду викладача ґімназії. Також Адорно звернув свою увагу на тенденцію формалістичного дотримання Правил складання іспитів деякими майбутніми вчителями, які не здатні зрозуміти гуманістичну, емансипаційно-духовну суть філософії, а отже й не розуміють мету проведення названого іспиту. Ушанувавши давню традицію академічної свободи німецького Університету, Адорно зауважив постать німецького філософа, охарактеризувавши його тією людиною, інтелектуальна діяльність якої вплинула на гуманізацію освіти в німецькому Університеті, що безпосередньо далося взнаки відповідним социокультурним перетворенням. Однак, на думку Адорно, в повоєнних університетах ФРН переважає тенденція дотримання засад саме наукового пізнання. Ця тенденція поєднана зі ставленням деяких майбутніх учителів до знання як до привласненого у споживацький спосіб, що зумовлено браком особистої любові до власного фаху й до своїх студентів. Адорно був переконаний у тому, що такі вчителі байдужі до свого фаху й не мають до нього покликання. Ознакою відсутності покликання в цих людях Адорно назвав інтелектуальну недбалість, провінційність мовлення і провінційну нездатність зрозуміти свободу людини як духовну цінність. Подібні вчителі неспроможні пропонувати нове знання своїм студентам як за допомогою добірного усного мовлення, так і за допомогою досконалого письмового викладу. Цілком іншою Адорно запропонував убачати людину, яка здатна засвоювати знання, що потрібні для розуміння свого професійного обов’язку. Використовуючи саморозуміння та саморефлексію, вона зможе самостійно збагнути сенс своєї педагогічної роботи. Ця людина сумлінно і терпляче виконуватиме свою роботу задля практичного впровадження в суспільство гуманістичних ідеалів попереднього філософського знання.
Using a data sample of e+e− collision data corresponding to an integrated luminosity of 2.93 fb−1 collected with the BESIII detector at a center-of-mass energy of s=3.773GeV, we search for the singly Cabibbo-suppressed decays D0→π0π0π0, π0π0η, π0ηη and ηηη using the double tag method. The absolute branching fractions are measured to be B(D0→π0π0π0)=(2.0±0.4±0.3)×10−4, B(D0→π0π0η)=(3.8±1.1±0.7)×10−4 and B(D0→π0ηη)=(7.3±1.6±1.5)×10−4 with the statistical significances of 4.8σ, 3.8σ and 5.5σ, respectively, where the first uncertainties are statistical and the second ones systematic. No significant signal of D0→ηηη is found, and the upper limit on its decay branching fraction is set to be B(D0→ηηη)<1.3×10−4 at the 90% confidence level.
Що означає «опрацювання минулого» : (переклад з німецької, анотація і післямова Віталія Брижніка)
(2018)
Роботу «Що означає «опрацювання Минулого» Адорно вперше прочитав як доповідь 6 листопада 1959 року перед Координаційною радою з питань християнсько-єврейської співпраці. У цій доповіді Адорно розглянув суть соціальної ідеології, панівної в повоєнній Німеччині, яка зумовлювала стратегії суспільного примирення з політичними злочинами колишньої націонал-соціалістичної влади. На думку філософа, соціальна ідеологія суспільства споживання використовує чималу кількість відповідних засобів, аби стабілізувати свій панівний статус у суспільстві. Й передусім вона намагається ліквідувати колективну історичну пам’ять людей про жахи воєнного періоду, прагнучи витиснути їх із колективної свідомості, зокрема й завдяки спогадам людей про «кращі часи» життя під «опікою» попередньої, тоталітарної влади. Філософ назвав суроґатною ідентичність цих людей, соціально інтеґрованих лише завдяки авторитету владної особистості. Вони не ототожнюють себе з жертвами тоталітарного режиму через уплив на їхню свідомість культурних елементів цієї соціальної ідеології. Іншим наслідком даного впливу також стає відчуження цих людей від ідеї демократії як чинника належних соціокультурних перетворень. Дієвим засобом подолання цього впливу Адорно визначив нову, «демократичну педагогіку» і просвіту як «другу освіту», що практично здійснюють у суспільстві освічені люди, які володіють знанням про минулі злочини тоталітарного режиму. Тим самим вони зумовлюють у межах освітнього процесу дієве «опрацювання Минулого» через формування особистого розуміння окремої людини соціальних причин і жахливих наслідків панування тоталітарного режиму. Це ліквідує її «політичне неповноліття» й тим самим унеможливлює історичне повторення в Європі злочинів авторитарної влади.
Fluctuations of conserved quantities such as baryon number, charge, and strangeness are sensitive to the correlation length of the hot and dense matter created in relativistic heavy-ion collisions and can be used to search for the QCD critical point. We report the first measurements of the moments of net-kaon multiplicity distributions in Au+Au collisions at √sNN = 7.7, 11.5, 14.5, 19.6, 27, 39, 62.4, and 200 GeV. The collision centrality and energy dependence of the mean (M), variance (σ 2), skewness (S), and kurtosis (κ) for net-kaon multiplicity distributions as well as the ratio σ 2/M and the products Sσ and κσ 2 are presented. Comparisons are made with Poisson and negative binomial baseline calculations as well as with UrQMD, a transport model (UrQMD) that does not include effects from the QCD critical point. Within current uncertainties, the net-kaon cumulant ratios appear to be monotonic as a function of collision energy.
New measurements of directed flow for charged hadrons, characterized by the Fourier coefficient v1, are presented for transverse momenta pT, and centrality intervals in Au+Au collisions recorded by the STAR experiment for the center-of-mass energy range √sN N = 7.7–200 GeV. The measurements underscore the importance of momentum conservation, and the characteristic dependencies on √sN N , centrality and pT are consistent with the expectations of geometric fluctuations generated in the initial stages of the collision, acting in concert with a hydrodynamic-like expansion. The centrality and pT dependencies of veven 1 , as well as an observed similarity between its excitation function and that for v3, could serve as constraints for initial-state models. The veven 1 excitation function could also provide an important supplement to the flow measurements employed for precision extraction of the temperature dependence of the specific shear viscosity.
Chamomile, parsley, and celery represent major botanical sources of apigenin, a well-known flavone with chemopreventive properties. The aim of this study was to assess the phytochemical composition, antioxidant, and anti-inflammatory potential of methanol extracts obtained from chamomile, parsley, and celery collected from Romania, as well as the biological activity against A375 human melanoma and human dendritic cells. Results have shown that all three extracts are rich in polyphenolic compounds and flavonoids, and they generate a radical scavenger capacity, iron chelation potential, as well as lipoxygenase inhibition capacity. Chamomile and celery extracts present weak antiproliferative and pro-apoptotic properties in the set experimental conditions, while parsley extract draws out significant pro-apoptotic potential against A375 human melanoma cells. Parsley and chamomile extracts affected the fibroblast-like morphology of the screened tumor cell line. On the other hand, chamomile and celery extracts abrogated the expansion of LPS-activated dendritic cells, while the metabolic activity was attenuated by stimulation with celery extract; chamomile and parsley extracts had no effect upon this parameter. Chamomile and parsley extracts incubation with naive dendritic cells did not trigger cytokine secretion (TNF-alpha, IL-6, IL-10), but celery extract stimulation significantly reduced the anti-inflammatory, cytokine IL-10.
TO MAKE PROFITABLE INVESTMENT DECISIONS, INVESTORS NEED TO ASSESS THE FINANCIAL FUTURE OF FIRMS. DUE TO INVESTORS’ LACK OF INTERNAL INFORMATION ABOUT THE FIRMS’ FUTURE PROSPECTS, THEY OFTEN HAVE TO RELY ON MANAGERS’ VERBAL STATEMENTS FOR THIS TASK. HOWEVER, AS MANAGERS MIGHT HAVE AN INCENTIVE TO PRESENT POSITIVELY BIASED INFORMATION, THE VALUE OF THEIR STATEMENTS FOR INVESTORS IS NOT CLEAR.
IN THIS REPORT, WE SHOW HOW TEXTUAL ANALYSIS TOOLS CAN BE USED TO ASSESS THE VALUE OF MANAGERS’ VERBAL STATEMENTS DURING EARNINGS CONFERENCE CALLS FOR INVESTORS. WE FIND THAT IN PARTICULAR MANAGERS’ NEGATIVE STATEMENTS SIGNI FICANTLY PREDICT LOWER FUTURE EARNINGS.
The cortical networks that underlie behavior exhibit an orderly functional organization at local and global scales, which is readily evident in the visual cortex of carnivores and primates1-6. Here, neighboring columns of neurons represent the full range of stimulus orientations and contribute to distributed networks spanning several millimeters2,7-11. However, the principles governing functional interactions that bridge this fine-scale functional architecture and distant network elements are unclear, and the emergence of these network interactions during development remains unexplored. Here, by using in vivo wide-field and 2-photon calcium imaging of spontaneous activity patterns in mature ferret visual cortex, we find widespread and specific modular correlation patterns that accurately predict the local structure of visually-evoked orientation columns from the spontaneous activity of neurons that lie several millimeters away. The large-scale networks revealed by correlated spontaneous activity show abrupt ‘fractures’ in continuity that are in tight register with evoked orientation pinwheels. Chronic in vivo imaging demonstrates that these large-scale modular correlation patterns and fractures are already present at early stages of cortical development and predictive of the mature network structure. Silencing feed-forward drive through either retinal or thalamic blockade does not affect network structure suggesting a cortical origin for this large-scale correlated activity, despite the immaturity of long-range horizontal network connections in the early cortex. Using a circuit model containing only local connections, we demonstrate that such a circuit is sufficient to generate large-scale correlated activity, while also producing correlated networks showing strong fractures, a reduced dimensionality, and an elongated local correlation structure, all in close agreement with our empirical data. These results demonstrate the precise local and global organization of cortical networks revealed through correlated spontaneous activity and suggest that local connections in early cortical circuits may generate structured long-range network correlations that underlie the subsequent formation of visually-evoked distributed functional networks.
This study will consider the various aspects of the portrayal of Sultan ʿAbd al-Ḥamīd II that were emphasized in the Arab-Islamist revisionist writings about Islamic history. The focus will be especially on the writings of Anwar al-Ǧundī (1917–2002), an Egyptian Islamist writer as it was he who first adopted the process of an “Islamic revision of Islamic history”. His main academic output consisted in responding to the “Orientalist attack on Islam”, and he wrote a number of books towards this aim as as-Sulṭān ʿAbd al-Ḥamīd wa l-ḫilāfa al-islāmiyya, al-Islām fī maʿrakat at-taġrīb and al-Istiʿmār wa l-Islām.
This will be followed by an analysis of the ideological exploitation of the historical personality, and the consequences of the contemporary historical Islamist vision for the development of religious thought.
Entstanden in einem Milieu aus exklusivistischen islamischen Bewegungen, baut die Gewalttheologie der dschihadistischen Organisationen wie der al-Qa‘ida oder des IS auf eine Geschichtstheologie, welche Verfalls- und Dekadenzdiagnosen über die Situation der islamischen Welt und der Muslime mit eschatologischen Elementen verknüpft. In der Konsequenz müsse diese Dekadenz zum Zerfall der Welt und zum Anbruch der Endzeit führen, als deren kämpfende Avantgarde und notwendige Vorbedingung sich die dschihadistischen Akteure stilisieren. Videos mit identifizierbaren erzählerischen Elementen gehören dabei zu zentralen Mitteln der dschihadistischen Kommunikation. Anhand eines Fallbeispiels untersucht der Artikel die geschichts- und gewalttheologisch geprägten Strukturen der IS-Videopropaganda. Zugleich wird auf im muslimischen Spektrum generierte Alternativen zu dieser exklusivistischen Geschichtstheologie verwiesen, die nicht von einem sich in der Geschichte enthüllenden ‘Heilsplan’ Gottes ausgehen, sondern auf der Prämisse der Unabgeschlossenheit und der offenen Bewegung menschlichen Denkens beruhen und damit eine Epistemologie anbieten, die nicht Spielarten des Identitären befördert.
Im Folgenden soll ein kurzer Überblick gegeben werden über die schiitische Sicht der frühislamischen Geschichte sowie über einige Phänomene, die sich daraus ergeben haben. Sie sind Hindernisse einer islamischen Einheit und müssten, sollte ein ernsthafter Versuch einer solchen verfolgt werden, mit deutlich mehr Mut angegangen werden. Dabei geht es hier weniger darum, alle Unterschiede zwischen Schia und Sunna aufzuzeigen, als sich auf die wirklich problematischen Felder zu konzentrieren, die nicht Folgen späterer, oft zufälliger Entwicklungen sind, sondern Weichenstellungen, die in der Frühgeschichte zu verorten sind. Bisher werden diese neuralgischen Punkte bei den Versuchen einer islamischen Ökumene, um diesen sehr christlich belegten Begriff an dieser Stelle doch einmal zu verwenden, meist umgangen, weil man um ihre Brisanz und Sprengkraft weiß. Doch müsste die Auseinandersetzung mit den unterschiedlichen Geschichtsbildern erfolgen, da sie ein wichtiges innerislamisches Differenzkriterium bilden; zumindest sollte man sich klar darüber sein, dass es unterschiedliche Geschichtsbilder gibt und sie ein Differenzkriterium bilden.
Background: A diagnosis of post-traumatic stress disorder (PTSD) requires the identification of one or more traumatic events, designated the index trauma, which serves as the basis for assessment of severity of PTSD. In patients who have experienced more than one traumatic event, severity may depend on the exact definition of the index trauma. Defining the index trauma as the worst single incident may result in PTSD severity scores that differ from what would be seen if the index trauma included multiple events.
Objective: This study aimed to investigate the impact of the definition of the index trauma on PTSD baseline severity scores and treatment outcome.
Method: A planned secondary analysis was performed on data from a subset (N = 58) of patients enrolled in a trial evaluating the efficacy of a 12 week residential dialectical behavioural therapy programme for PTSD related to childhood abuse (DBT-PTSD). Assessments of the severity of PTSD were conducted at admission, at the end of the 12 week treatment period, and at 6 and 12 weeks post-treatment, using the Clinician-Administered PTSD Scale. The index trauma was defined with respect to both the worst single incident and up to three qualitatively distinct traumatic events.
Results: When the index trauma included multiple traumas, PTSD severity scores were significantly higher and improvements from pre- to post-treatment were significantly lower than when the index trauma was defined as the worst single incident.
Conclusions: In patients with PTSD who have experienced multiple traumas, defining the index trauma as the worst single incident may miss some aspects of clinically relevant symptomatology, thereby leading to a possibly biased interpretation of treatment effects. In DBT-PTSD, treatment effects were lower when the index trauma included multiple traumatic events. More research is needed to determine the impact of the various index trauma definitions on the evaluation of other trauma-focused treatments.
Begriffsgeschichte
(2018)
Die jüngeren Aufbrüche und Umbrüche haben den Begriff 'Begriffsgeschichte' nicht unberührt gelassen: "Als undogmatische Sammelbezeichnung für die Erforschung semantischer Veränderungsprozesse hat sich mittlerweile der Terminus historische Semantik interdisziplinär etabliert." Die Ausnüchterung des Begriffs im Terminus, der Begriffsgeschichte in der historischen Semantik, hilft bei der Abwehr prekärer und vielleicht auch gar nicht mehr zeitgemäßer Fragen, zumal der notorischen nach dem 'Begriff des Begriffs' der Begriffsgeschichte. Paradoxerweise drängen sie aber wieder, wenn sich die Begriffsgeschichte selbst historisch zu werden beginnt. Und da neben Interdisziplinarität und Internationalisierung auch Historisierung unabdingbar zum Ausweis wissenschaftlicher Geltung und Aktualität gehört, kommt Begriffsgeschichte um ihre Selbsthistorisierung gerade jetzt, zu Zeiten ihres späten Ruhmes, nicht herum.
Was bei Schrott aus seiner künstlerischen Bearbeitung der Wissens-'Tradition' geworden ist, ist nicht einfach zu sagen. Jedenfalls keine Naturreligion und keine Experimentaltheologie, sondern eine Dichtung, sehr groß dimensioniert, gewiss, aber doch stets nur "Stücke eines Epos: nicht in hehrem Anspruch, sondern als Poesie, die Welt enthält". Von Freuds Epostheorie her gesehen ist der befremdliche Titel "Erste Erde. Epos" gewissenhafte Leseanleitung: Achtung, Kunst! - Nicht beantwortet ist damit die Frage, warum Schrott die 'Tradition' von Wissenschaft und Wissenschaftsgeschichte literarisch bearbeitet hat.
Am 31. Januar fand am ZfL die Verleihung des Carlo-Barck-Preises an Kevin Liggieri statt. Liggieri erhielt den Preis für seine Dissertation "Zur Kultur- und Begriffsgeschichte der 'Anthropotechnik'. Eine Untersuchung programmatischer Diskurse zwischen 'Menschenzucht' und 'Menschenbehandlung'". Wir dokumentieren hier die beiden Reden von Eva Geulen und Ernst Müller anlässlich der Preisverleihung.
Background: Dialectical behaviour therapy for posttraumatic stress disorder (DBT-PTSD), which is tailored to treat adults with PTSD and co-occurring emotion regulation difficulties, has already demonstrated its efficacy, acceptance and safety in an inpatient treatment setting. It combines elements of DBT with trauma-focused cognitive behavioural interventions.
Objective: To investigate the feasibility, acceptance and safety of DBT-PTSD in an outpatient treatment setting by therapists who were novice to the treatment, we treated 21 female patients suffering from PTSD following childhood sexual abuse (CSA) plus difficulties in emotion regulation in an uncontrolled clinical trial.
Method: The Clinician Administered PTSD Symptom Scale (CAPS), the Davidson Trauma Scale (DTS), the Borderline Section of the International Personality Disorder Examination (IPDE) and the Borderline Symptom List (BSL-23) were used as primary outcomes. For secondary outcomes, depression and dissociation were assessed. Assessments were administered at pretreatment, post-treatment and six-week follow-up.
Results: Improvement was significant for PTSD as well as for borderline personality symptomatology, with large pretreatment to follow-up effect sizes for completers based on the CAPS (Cohens d = 1.30), DTS (d = 1.50), IPDE (d = 1.60) and BSL-23 (d = 1.20).
Conclusion: The outcome suggests that outpatient DBT-PTSD can safely be used to reduce PTSD symptoms and comorbid psychopathology in adults who have experienced CSA.
Der Artikel wirft einige Schlaglichter auf die Geschichtsbilder und -vorstellungen, die im modernen muslimischen religiösen Denken seit dem späten 19. Jahrhundert zum Tragen gekommen sind. Insbesondere im Blick steht dabei die Frage nach dem Umgang mit eigener Geschichtlichkeit und mit den Konsequenzen, die sich daraus für die Ausgestaltung von Islamität ergeben. Die unterschiedlichen Gewichtungen und Verknüpfungen von Vergangenheit und Gegenwart und die Frage, ob die Bedeutung des historischen Wandels für die eigenen Erkenntnisprozesse mitreflektiert wird, entscheidet, so die These, über den Umgang des religiösen Denkens mit neuen Wissensbeständen, Epistemen und methodischen Verfahren ebenso wie darüber, ob diese als legitim angesehen werden, um als authentisch islamisch akzeptiert zu werden.
Frankfurter Zeitschrift für islamisch-theologische Studien. 4/2018. Geschichte und Geschichtlichkeit
(2018)
Das neue Jahresthema des ZfL, FORMEN DES GANZEN, knüpft an das vorangegangene Jahresthema der DIVERSITÄT in den Bereichen der Natur, des Sozialen und der Kultur mit einer gewissen Zwangsläufigkeit an. Denn wer sich mit der Vielfalt beschäftigt, kann der Frage nach der Einheit der Vielfalt und damit nach dem Ganzen nicht ausweichen. So ist etwa das Schlagwort von der Biodiversität ein absolut inkludierender Begriff und damit Chiffre eines Ganzen. Allerdings wurden Ganzheitsvorstellungen im 20. Jahrhundert von Regimen in Anspruch genommen, die nicht zufällig 'totalitär' heißen. Auch deshalb stehen die heutigen Geisteswissenschaften dem Ganzen kritisch gegenüber. Jener Geist, der sie einmal als Wissenschaften binden und von den Naturwissenschaften unterscheiden sollte, gehört ja selbst zur Sippschaft unifizierender Begriffe, die ein Ganzes meinen oder behaupten.
Eugen Helmlé, 1927–2000
(2018)
Eugen Helmlé (1927–2000) war einer der verwegensten und besessensten Übersetzer seiner Zunft, der an die 150 Bücher übersetzt hat und in ganz besonderer Weise Georges Perec verbunden war, dem herausragenden französischen Autor des 1960 gegründeten Oulipo-Kreises, der gemeinsam mit seinem Übersetzer Helmlé neue formale Wege der Literaturproduktion beschritt.
Was versteht man gemeinhin unter Indizien? Indizien (indicium: An-Zeichen) beweisen ja vermeintlich keine Tat oder Schuld, sondern verweisen nur auf diese - eine spekulative, geradezu dubiose Uneindeutigkeit wird mit dem Indiz assoziiert. Dieses noch heute verbreitete Indizienverständnis resultiert historisch aus einer strafrechtlichen Debatte, die im 18. Jahrhundert den Status von Indizien äußerst konträr diskutiert, wobei deren - vermeintliche - Objektivität (Tatsache, Faktum) gegen einen - fehleranfälligen - Interpretationsspielraum (Zeichen, Denkschluss) in Anschlag gebracht wird.
So vielfältig das Studienangebot, so vielfältig sind auch die Studierenden der Goethe-Universität: Ob Bildungsbiographie oder soziale Herkunft, kultureller Hintergrund oder Lebensumstände—die Frankfurter Studierenden sind ein Spiegel der für Stadt und Region charakteristischen Diversität. Das bietet große Chancen für wechselseitiges Lernen, stellt die Universität aber auch vor Herausforderungen. Eine der größten dieser Herausforderungen ist, bei der Weiterentwicklung von Studium und Lehre die Bedürfnisse einer in sich heterogenen Studierendenschaft konstruktiv aufzugreifen. Neben einer regelmäßigen Rückmeldung der Studierenden (etwa im Rahmen der Lehrveranstaltungs- oder Studiengangsevaluation) und studentischem Engagement in universitären Gremien bedarf es hierfür einer fundierten Datenbasis. ...
Background: Worldwide, the number of recorded human hantavirus infections as well as the number of affected countries is on the rise. In Europe, most human hantavirus infections are caused by the Puumala virus (PUUV), with bank voles (Myodes glareolus) as reservoir hosts. Generally, infection outbreaks have been related to environmental conditions, particularly climatic conditions, food supply for the reservoir species and land use. However, although attempts have been made, the insufficient availability of environmental data is often hampering accurate temporal and spatially explicit models of human hantavirus infections.
Methods: In the present study, dynamics of human PUUV infections between 2001 and 2015 were explored using ArcGIS in order to identify spatio-temporal patterns.
Results: Percentage cover of forest area was identified as an important factor for the spatial pattern, whereas beech mast was found explaining temporal patterns of human PUUV infections in Germany. High numbers of infections were recorded in 2007, 2010 and 2012 and areas with highest records were located in Baden-Wuerttemberg (southwest Germany) and North Rhine-Westphalia (western Germany).
Conclusion: More reliable data on reservoir host distribution, pathogen verification as well as an increased awareness of physicians are some of the factors that should improve future human infection risk assessments in Germany.
Due to its remote and isolated location, Antarctica is home to a unique diversity of species. The harsh conditions have shaped a primarily highly adapted endemic fauna. This includes the notothenioid family Channichthyidae. Their exceptional physiological adaptations have made this family of icefish the focus of many studies. However, studies on their ecology, especially on their parasite fauna, are comparatively rare. Parasites, directly linked to the food chain, can function as biological indicators and provide valuable information on host ecology (e.g., trophic interactions) even in remote habitats with limited accessibility, such as the Southern Ocean. In the present study, channichthyid fish (Champsocephalus gunnari: n = 25, Chaenodraco wilsoni: n = 33, Neopagetopsis ionah: n = 3, Pagetopsis macropterus: n = 4, Pseudochaenichthys georgianus: n = 15) were collected off South Shetland Island, Elephant Island, and the tip of the Antarctic Peninsula (CCAML statistical subarea 48.1). The parasite fauna consisted of 14 genera and 15 species, belonging to the six taxonomic groups including Digenea (four species), Nematoda (four), Cestoda (two), Acanthocephala (one), Hirudinea (three), and Copepoda (one). The stomach contents were less diverse with only Crustacea (Euphausiacea, Amphipoda) recovered from all examined fishes. Overall, 15 new parasite-host records could be established, and possibly a undescribed genotype or even species might exist among the nematodes.
Eastern boundary upwelling provides the conditions for high marine productivity in the Canary Current System off NW-Africa. Despite its considerable importance to fisheries, knowledge on this marine ecosystem is only limited. Here, parasites were used as indicators to gain insight into the host ecology and food web of two pelagic fish species, the commercially important species Trichiurus lepturus Linnaeus, 1758, and Nealotus tripes Johnson, 1865. Fish specimens of T. lepturus (n = 104) and N. tripes (n = 91), sampled from the Canary Current System off the Senegalese coast and Cape Verde Islands, were examined, collecting data on their biometrics, diet and parasitisation. In this study, the first parasitological data on N. tripes are presented. T. lepturus mainly preyed on small pelagic Crustacea and the diet of N. tripes was dominated by small mesopelagic Teleostei. Both host species were infested by mostly generalist parasites. The parasite fauna of T. lepturus consisted of at least nine different species belonging to six taxonomic groups, with a less diverse fauna of ectoparasites and cestodes in comparison to studies in other coastal ecosystems (Brazil Current and Kuriosho Current). The zoonotic nematode Anisakis pegreffii occurred in 23% of the samples and could pose a risk regarding food safety. The parasite fauna of N. tripes was composed of at least thirteen species from seven different taxonomic groups. Its most common parasites were digenean ovigerous metacercariae, larval cestodes and a monogenean species (Diclidophoridae). The observed patterns of parasitisation in both host species indicate their trophic relationships and are typical for mesopredators from the subtropical epi- and mesopelagic. The parasite fauna, containing few dominant species with a high abundance, represents the typical species composition of an eastern boundary upwelling ecosystem.
Landwirtschaft ist der Hauptmotor der westafrikanischen Wirtschaft und Kleinbauern liefern fast 70 % des Nahrungsmittelbedarfs. Traditionell wird hauptsächlich Regenfeldbau betrieben, der durch geringen Agrarinput und die Nutzung von einfachen Werkzeugen wie Hacke und Buschmesser gekennzeichnet ist. Die Ernteerträge sind gering und die Bodenfruchtbarkeit sinkt schnell nach einigen Anbaujahren. Infolgedessen werden Wald- und Weidefläche gerodet und die Landdegradation wird beschleunigt. Dies hat direkte Auswirkungen auf die landwirtschaftliche Produktivität und die Ernährungssicherheit der Kleinbauern.
Die vorliegende Arbeit hat sich das Ziel gesetzt, sozio-ökonomische und geo-ökologische Faktoren, die den Landnutzungswandel in zwei Agrarökosystemen der Atakora Gebirgskette steuern, aufzudecken. Schließlich sollen ortsangepasste Maßnahmen vorgeschlagen werden, um die Agrarökosysteme wiederherzustellen und ihre Dienstleistungen für Kleinbauern zu erhalten.
Haushaltsbefragungen und Gruppendiskussionen wurden während Geländeaufenthalten in den Jahren 2014 und 2015 in den Dörfern der beiden Ethnien durchgeführt. Die Landnutzung und ihr Wandel werden über knapp 30 Jahre anhand von Bildern des Satellitensystems LANDSAT aus den Jahren 1987, 2001 und 2015 ausgewertet. Eine überwachte Klassifikation nach dem „Maximum Likelihood“-Klassifkationsalgorithmus und Veränderungs-analysen wurden durchgeführt. Zum Erfassen der Variabilität der Agrarparameter der Böden wurden Bodenprofile nach dem Catena-Prinzip gegraben. Bodenproben wurden aus jedem Horizont genommen. Anschließend wurden einige physische Parameter und die Nährstoffgehalte vom Fachpersonal des bodenkundlichen Labors des Instituts für Physische Geographie (Geowissenschaften) bestimmt.
Innerhalb der knapp letzten dreißig Jahre (1987-2015) ist die natürliche Vegetation bei den beiden Ethnien zugunsten der Landwirtschaft und der bebauten bzw. vegetationsfreien Flächen zurückgegangen. Über die analysierten Zeiträume liegen mehr Flächen bei den Ditamari (47,24%) unter einer negativen Dynamik als bei den Éwé (36,41%). Die Untersuchung der Steuerungsfaktoren des Landnutzungswandels bringt heraus, dass der höhere Anteil an positiv veränderten Flächen bei den Éwé ist nicht durch bessere Landnutzungsstrategien begründet. Vielmehr stellt das Relief der begrenzende Faktor für die Ausdehnung der Ackerflächen und damit die bessere Erhaltung der natürlichen Vegetation bei den Éwé dar.
Die erste Annahme, dass Veränderungen in der Landnutzung die Landdegradation zur Folge haben, wird in den beiden Untersuchungsgebieten bestätigt. Die abnehmende Dichte der Vegetationsdecke begünstigt Prozesse der Flächen-, Rillen- und Rinnenspülung. Zudem werden die ökologischen Bodenfunktionen vermindert. Erscheinungen der Landdegradation bei den Ditamari sind die Ausdehnung von oberflächlich verkrusteten Arealen und die Verbreitung des Unkrautes Striga hermontica. Bei den Éwés tritt eine starke Profilverkürzung der Böden ein und das anstehende Gestein wird an mehreren Stellen freigelegt.
Die zweite Hypothese wird in Hinsicht auf die räumliche und ethnische Differenzierung der Folgen der Landdegradation bestätigt. Allerdings sind nicht, wie vermutet, die Ditamari verletzbarer als die Éwés. Die beiden Ethnien betreiben eine intensive Subsistenzwirtschaft und die Éwé entwickeln weniger Anpassungsstrategien als die Ditamari. Im Hinblick auf die globale Erwärmung könnte die Landdegradation in den beiden Gebieten fortschreiten und die Folgen auf der Landschaft und den Kleinbauern verschärfen. Die Éwé wären, anders als vermutet, verletzbarer als die Ditamari. Eine Fortschreitung der Landdegradation könnte bei den Kleinbauern Éwés langfristig den Zusammenbruch des Agrarökosystemen hervorrufen. Sie könnten langfristig die Grundlage ihrer Existenzsicherung verlieren.
Die Studie zeigt auf, dass traditionell, zurückgezogen lebende Völker wie die Ditamari das Agrarökosystem nachhaltiger bewirtschaften und angesichts der Landdegradation anpassungsfähiger sind als tief umgewandelte Gesellschaften wie die Éwés. Sie bringt heraus, dass Kleinbauern Westafrikas keinesfalls als eine Einheit betrachtet werden sollten. Jede Ethnie ist durch Merkmale gekennzeichnet, die ihre Gestaltung der Landschaft beeinflussen. Diese Vielfältigkeit und Besonderheiten der kleinbäuerlichen Gesellschaften müssen in der Entwicklungszusammenarbeit stärker berücksichtigt werden.
Background: Molecular hydrogen (H2) is an attractive future energy carrier to replace fossil fuels. Biologically and sustainably produced H2 could contribute significantly to the future energy mix. However, biological H2 production methods are faced with multiple barriers including substrate cost, low production rates, and low yields. The C1 compound formate is a promising substrate for biological H2 production, as it can be produced itself from various sources including electrochemical reduction of CO2 or from synthesis gas. Many microbes that can produce H2 from formate have been isolated; however, in most cases H2 production rates cannot compete with other H2 production methods.
Results: We established a formate-based H2 production method utilizing the acetogenic bacterium Acetobacterium woodii. This organism can use formate as sole energy and carbon source and possesses a novel enzyme complex, the hydrogen-dependent CO2 reductase that catalyzes oxidation of formate to H2 and CO2. Cell suspensions reached specific formate-dependent H2 production rates of 71 mmol g protein −1 h−1 (30.5 mmol g CDW −1 h−1) and maximum volumetric H2 evolution rates of 79 mmol L−1 h−1. Using growing cells in a two-step closed batch fermentation, specific H2 production rates reached 66 mmol g CDW −1 h−1 with a volumetric H2 evolution rate of 7.9 mmol L−1 h−1. Acetate was the major side product that decreased the H2 yield. We demonstrate that inhibition of the energy metabolism by addition of a sodium ionophore is suitable to completely abolish acetate formation. Under these conditions, yields up to 1 mol H2 per mol formate were achieved. The same ionophore can be used in cultures utilizing formate as specific switch from a growing phase to a H2 production phase.
Conclusions: Acetobacterium woodii reached one of the highest formate-dependent specific H2 productivity rates at ambient temperatures reported so far for an organism without genetic modification and converted the substrate exclusively to H2. This makes this organism a very promising candidate for sustainable H2 production and, because of the reversibility of the A. woodii enzyme, also a candidate for reversible H2 storage.
In the current contribution we present a comprehensive study on the heteronuclear carbonyl complex H2FeRu3(CO)13 covering its low energy electron induced fragmentation in the gas phase through dissociative electron attachment (DEA) and dissociative ionization (DI), its decomposition when adsorbed on a surface under controlled ultrahigh vacuum (UHV) conditions and exposed to irradiation with 500 eV electrons, and its performance in focused electron beam induced deposition (FEBID) at room temperature under HV conditions. The performance of this precursor in FEBID is poor, resulting in maximum metal content of 26 atom % under optimized conditions. Furthermore, the Ru/Fe ratio in the FEBID deposit (≈3.5) is higher than the 3:1 ratio predicted. This is somewhat surprising as in recent FEBID studies on a structurally similar bimetallic precursor, HFeCo3(CO)12, metal contents of about 80 atom % is achievable on a routine basis and the deposits are found to maintain the initial Co/Fe ratio. Low temperature (≈213 K) surface science studies on thin films of H2FeRu3(CO)13 demonstrate that electron stimulated decomposition leads to significant CO desorption (average of 8–9 CO groups per molecule) to form partially decarbonylated intermediates. However, once formed these intermediates are largely unaffected by either further electron irradiation or annealing to room temperature, with a predicted metal content similar to what is observed in FEBID. Furthermore, gas phase experiments indicate formation of Fe(CO)4 from H2FeRu3(CO)13 upon low energy electron interaction. This fragment could desorb at room temperature under high vacuum conditions, which may explain the slight increase in the Ru/Fe ratio of deposits in FEBID. With the combination of gas phase experiments, surface science studies and actual FEBID experiments, we can offer new insights into the low energy electron induced decomposition of this precursor and how this is reflected in the relatively poor performance of H2FeRu3(CO)13 as compared to the structurally similar HFeCo3(CO)12.
Hydrogenation of CO₂ at ambient pressure catalyzed by a highly active thermostable biocatalyst
(2018)
Background: Replacing fossil fuels as energy carrier requires alternatives that combine sustainable production, high volumetric energy density, easy and fast refueling for mobile applications, and preferably low risk of hazard. Molecular hydrogen (H2) has been considered as promising alternative; however, practical application is struggling because of the low volumetric energy density and the explosion hazard when stored in large amounts. One way to overcome these limitations is the transient conversion of H2 into other chemicals with increased volumetric energy density and lower risk hazard, for example so-called liquid organic hydrogen carriers such as formic acid/formate that is obtained by hydrogenation of CO2. Many homogenous and heterogenous chemical catalysts have been described in the past years, however, often requiring high pressures and temperatures. Recently, the first biocatalyst for this reaction has been described opening the route to a biotechnological alternative for this conversion.
Results: The hydrogen-dependent CO2 reductase (HDCR) is a highly active biocatalyst for storing H2 in the form of formic acid/formate by reversibly catalyzing the hydrogenation of CO2. We report the identification, isolation, and characterization of the first thermostable HDCR operating at temperatures up to 70 °C. The enzyme was isolated from the thermophilic acetogenic bacterium Thermoanaerobacter kivui and displays exceptionally high activities in both reaction directions, substantially exceeding known chemical catalysts. CO2 hydrogenation is catalyzed at mild conditions with a turnover frequency of 9,556,000 h−1 (specific activity of 900 µmol formate min−1 mg−1) and the reverse reaction, H2 + CO2 release from formate, is catalyzed with a turnover frequency of 9,892,000 h−1 (930 µmol H2 min−1 mg−1). The HDCR of T. kivui consists of a [FeFe] hydrogenase subunit putatively coupled to a tungsten-dependent CO2 reductase/formate dehydrogenase subunit by an array of iron–sulfur clusters.
Conclusions: The discovery of the first thermostable HDCR provides a promising biological alternative for a chemically challenging reaction and might serve as model for the better understanding of catalysts able to efficiently reduce CO2. The catalytic activity for reversible CO2 hydrogenation of this enzyme is the highest activity known for bio- and chemical catalysts and requiring only ambient temperatures and pressures. The thermostability provides more flexibility regarding the process parameters for a biotechnological application.
Challenges of FAIR phase 0
(2018)
After two-year's shutdown, the GSI accelerators plus the latest addition of storage ring CRYRING, will be back into operation in 2018 as the FAIR phase 0 with the goal to fulfill the needs of scientific community and the FAIR accelerators and detector development. Even though GSI has been well known for its operation of a variety of ion beams ranging from proton up to uranium for multi research areas such as nuclear physics, astrophysics, biophysics, material science, the upcoming beam time faces a number of challenges in re-commissioning its existing circular accelerators with brand new control system and upgrade of beam instrumentations, as well as in rising failures of dated components and systems. The cycling synchrotron SIS18 has been undergoing a set of upgrade measures for fulfilling future FAIR operation, among which many measures will also be commissioned during the upcoming beam time. This paper presents the highlights of the challenges such as re-establishing the high intensity heavy ion operation as well as parallel operation mode for serving multi users. The status of preparation including commissioning results will also be reported.
Two Norwegian uristid amphipods, obligate associates of sea anemones, have for a long time been confused sub nomine Onisimus normani Sars, 1890. In reality this species only occurs in south Norway, while the north-Norwegian material belongs to O. turgidus (Sars, 1879), described from the Barents Sea and for a long time forgotten. This paper fully illustrates both species, gives a key, and provides data on their distribution and ecology.
Zielsetzung: Beteiligung von Medizinstudierenden im Rahmen der konzeptionellen Entwicklung eines zielgruppenspezifischen und attraktiven allgemeinmedizinischen Lehrangebots im ländlichen Raum.
Methodik: Es wurde ein Fragebogen entwickelt, der die Bewertung der Studierenden hinsichtlich des aktuellen Ablaufs ihres Studiums, den späteren Berufswunsch sowie die Anforderungen an ein zu entwickelndes allgemeinmedizinisches Schwerpunktprogramm im ländlichen Raum erfasst. Mittels einer Online-Befragung wurden im Sommer 2015 alle Medizinstudierende ab dem vierten vorklinischen Semester (n=2.150) der Goethe-Universität Frankfurt einmalig befragt. Die statistische Auswertung erfolgte primär deskriptiv. Die persönliche Einstellung hinsichtlich der Bereitschaft, als Hausarzt tätig zu werden, wurde auf statistische Signifikanz überprüft. Zudem wurde erhoben, ob ein messbarer Zusammenhang zwischen der eigenen Herkunft und dem späteren Wunscharbeitsort besteht.
Ergebnisse: Von insgesamt 2.150 kontaktierten Studierenden nahmen 617 an der Befragung teil (Rücklaufquote=28,7%). Die Ergebnisse repräsentieren eine große Bandbreite an Ideen und Anregungen, die sowohl die Meinung von Befürwortern als auch eher kritisch gegenüber der Lehre in der Allgemeinmedizin eingestellten Medizinstudierenden widerspiegeln. Von dem geplanten Schwerpunktprogramm erwarten die Studierenden einen starken Praxisbezug ebenso wie das Kennenlernen administrativer sowie wirtschaftlicher Hintergründe zum Führen einer Praxis.
Schlussfolgerungen: Durch die Einbeziehung der Zielgruppe am Entwicklungsprozess bestand die Möglichkeit, das zu entwickelnde Schwerpunktprogramm auf die späteren Teilnehmer passgenauer zuzuschneiden. Zudem ist zu erwarten, dass die Beteiligung der Studierenden zu einer höheren Akzeptanz des Programms führt. Die gewonnenen Ergebnisse zur Gestaltung eines Lehrangebots können als Orientierung für die mögliche Entwicklung ähnlicher Schwerpunktprogramme an anderen medizinischen Fakultäten dienen.
Aim: Participation of medical students in the conceptual development of targeted and attractive teaching content for rural areas.
Method: A questionnaire was developed to gather information on students' views of their current medical studies, career interests, and what requirements should be met by an optional rural health program in general practice. By means of an online survey in summer 2015, all medical students from the fourth preclinical semester onwards (n=2,150) at Goethe University Frankfurt were surveyed on one occasion. Statistical analysis was mainly descriptive. Personal attitudes towards a career as a family practitioner were examined for statistical significance. Further information was gathered on whether a measurable correlation exists between personal background and desired work location.
Results: Of the 2,150 students that were contacted, 617 participated in the survey (response rate=28.7%). The results covered a wide range of ideas and recommendations and were representative both of medical students with a positive attitude toward general practice, as well as those that were rather critical of teaching in general practice. The students expected the planned health program to be of strong practical relevance and to acquaint them with the administrative and economic aspects of running a practice.
Conclusions: By including the target group in the development process, it was possible to tailor the health program to meet the needs of future participants more precisely. Student participation can also be expected to result in greater acceptance of the program. The results on teaching content may also provide other medical faculties with orientation when developing comparable programs.
α-ketoglutarate dehydrogenase inhibition counteracts breast cancer-associated lung metastasis
(2018)
Metastasis formation requires active energy production and is regulated at multiple levels by mitochondrial metabolism. The hyperactive metabolism of cancer cells supports their extreme adaptability and plasticity and facilitates resistance to common anticancer therapies. In spite the potential relevance of a metastasis metabolic control therapy, so far, limited experience is available in this direction. Here, we evaluated the effect of the recently described α-ketoglutarate dehydrogenase (KGDH) inhibitor, (S)-2-[(2,6-dichlorobenzoyl) amino] succinic acid (AA6), in an orthotopic mouse model of breast cancer 4T1 and in other human breast cancer cell lines. In all conditions, AA6 altered Krebs cycle causing intracellular α-ketoglutarate (α-KG) accumulation. Consequently, the activity of the α-KG-dependent epigenetic enzymes, including the DNA demethylation ten-eleven translocation translocation hydroxylases (TETs), was increased. In mice, AA6 injection reduced metastasis formation and increased 5hmC levels in primary tumours. Moreover, in vitro and in vivo treatment with AA6 determined an α-KG accumulation paralleled by an enhanced production of nitric oxide (NO). This epigenetically remodelled metabolic environment efficiently counteracted the initiating steps of tumour invasion inhibiting the epithelial-to-mesenchymal transition (EMT). Mechanistically, AA6 treatment could be linked to upregulation of the NO-sensitive anti-metastatic miRNA 200 family and down-modulation of EMT-associated transcription factor Zeb1 and its CtBP1 cofactor. This scenario led to a decrease of the matrix metalloproteinase 3 (MMP3) and to an impairment of 4T1 aggressiveness. Overall, our data suggest that AA6 determines an α-KG-dependent epigenetic regulation of the TET–miR200–Zeb1/CtBP1–MMP3 axis providing an anti-metastatic effect in a mouse model of breast cancer-associated metastasis.
The development of genome editing tools capable of modifying specific genomic sequences with unprecedented accuracy has opened up a wide range of new possibilities in targeted gene manipulation. In particular, the CRISPR/Cas9 system, a repurposed prokaryotic adaptive immune system, has been widely adopted because of its unmatched simplicity and flexibility.
In this review we discuss achievements and current limitations of CRISPR/Cas9 genome editing in hematopoietic cells with special emphasis on its potential use in ex vivo gene therapy of monogenic blood disorders, HIV and cancer.
A series of derivatives of the potent dual soluble epoxide hydrolase (sEH)/5-lipoxygenase-activating protein (FLAP) inhibitor diflapolin was designed, synthesized, and characterized by 1H NMR, 13C NMR, and elemental analysis. These novel compounds were biologically evaluated for their inhibitory activity against sEH and FLAP. Molecular modeling tools were applied to analyze structure–activity relationships (SAR) on both targets. Results show that even small modifications on the lead compound diflapolin markedly influence the inhibitory potential, especially on FLAP, suggesting very narrow SAR.
Background: Alternative splicing is a key regulatory mechanism in eukaryotic cells and increases the effective number of functionally distinct gene products. Using bulk RNA sequencing, splicing variation has been studied across human tissues and in genetically diverse populations. This has identified disease-relevant splicing events, as well as associations between splicing and genomic variations, including sequence composition and conservation. However, variability in splicing between single cells from the same tissue or cell type and its determinants remain poorly understood.
Results: We applied parallel DNA methylation and transcriptome sequencing to differentiating human induced pluripotent stem cells to characterize splicing variation (exon skipping) and its determinants. Our results shows that variation in single-cell splicing can be accurately predicted based on local sequence composition and genomic features. We observe moderate but consistent contributions from local DNA methylation profiles to splicing variation across cells. A combined model that is built based on sequence as well as DNA methylation information accurately predicts different splicing modes of individual cassette exons (AUC=0.85). These categories include the conventional inclusion and exclusion patterns, but also more subtle modes of cell-to-cell variation in splicing. Finally, we identified and characterized associations between DNA methylation and splicing changes during cell differentiation.
Conclusions: Our study yields new insights into alternative splicing at the single-cell level and reveals a previously underappreciated link between DNA methylation variation and splicing.
Using an 𝑒+𝑒− collision data sample of 2.93 fb−1 collected at a center-of-mass energy of 3.773 GeV by the BESIII detector at BEPCII, we report the observation of 𝐷0→𝑎0(980)−𝑒+𝜈𝑒 and evidence for 𝐷+→𝑎0(980)0𝑒+𝜈𝑒 with significances of 6.4𝜎 and 2.9𝜎, respectively. The absolute branching fractions are determined to be ℬ(𝐷0→𝑎0(980)−𝑒+𝜈𝑒)×ℬ(𝑎0(980)−→𝜂𝜋−) = [1.33+0.33−0.29(stat)±0.09(syst)]×10−4 and ℬ(𝐷+→𝑎0(980)0𝑒+𝜈𝑒)×ℬ(𝑎0(980)0→𝜂𝜋0)=[1.66+0.81
−0.66(stat)±0.11(syst)]×10−4. This is the first time the 𝑎0(980) meson has been measured in a 𝐷0 semileptonic decay, which would open one more interesting page in the investigation of the nature of the puzzling 𝑎0(980) states.
he process e+e−→pK0Sn¯K−+c.c. and its intermediate processes are studied for the first time, using data samples collected with the BESIII detector at BEPCII at center-of-mass energies of 3.773, 4.008, 4.226, 4.258, 4.358, 4.416, and 4.600 GeV, with a total integrated luminosity of 7.4 fb−1. The Born cross section of e+e−→pK0Sn¯K−+c.c. is measured at each center-of-mass energy, but no significant resonant structure in the measured cross-section line shape between 3.773 and 4.600 GeV is observed. No evident structure is detected in the pK−, nK0S, pK0S, nK+, pn¯, or K0SK− invariant mass distributions except for Λ(1520). The Born cross sections of e+e−→Λ(1520)n¯K0S+c.c. and e+e−→Λ(1520)p¯K++c.c. are measured, and the 90\% confidence level upper limits on the Born cross sections of e+e−→Λ(1520)Λ¯(1520) are determined at the seven center-of-mass energies.
An amplitude analysis of the 𝐾𝑆𝐾𝑆 system produced in radiative 𝐽/𝜓 decays is performed using the (1310.6±7.0)×106 𝐽/𝜓 decays collected by the BESIII detector. Two approaches are presented. A mass-dependent analysis is performed by parametrizing the 𝐾𝑆𝐾𝑆 invariant mass spectrum as a sum of Breit-Wigner line shapes. Additionally, a mass-independent analysis is performed to extract a piecewise function that describes the dynamics of the 𝐾𝑆𝐾𝑆 system while making minimal assumptions about the properties and number of poles in the amplitude. The dominant amplitudes in the mass-dependent analysis include the 𝑓0(1710), 𝑓0(2200), and 𝑓′2(1525). The mass-independent results, which are made available as input for further studies, are consistent with those of the mass-dependent analysis and are useful for a systematic study of hadronic interactions. The branching fraction of radiative 𝐽/𝜓 decays to 𝐾𝑆𝐾𝑆 is measured to be (8.1±0.4)×10−4, where the uncertainty is systematic and the statistical uncertainty is negligible.
We report new measurements of the cross sections for the production of Dbar D final states at the ψ(3770) resonance. Our data sample consists of an integrated luminosity of 2.93 fb−1 of e+e− annihilation data produced by the BEPCII collider and collected and analyzed with the BESIII detector. We exclusively reconstruct three D0 and six D+ hadronic decay modes and use the ratio of the yield of fully reconstructed Dbar D events ("double tags") to the yield of all reconstructed D or bar D mesons ("single tags") to determine the number of D0bar D0 and D+D− events, benefiting from the cancellation of many systematic uncertainties. Combining these yields with an independent determination of the integrated luminosity of the data sample, we find the cross sections to be σ(e+e− → D0bar D0) nb and σ(e+e− → D+D−) = (2.830 ± 0.011 ± 0.026) nb, where the uncertainties are statistical and systematic, respectively.
Using a sample of 4.48×108 ψ(3686) events collected with the BESIII detector at the BEPCII collider, we study the two-photon decays of the pseudoscalar mesons π0, η, η′, η(1405), η(1475), η(1760), and X(1835) in J/ψ radiative decays using ψ(3686)→π+π−J/ψ events. The π0, η and η′ mesons are clearly observed in the two-photon mass spectra, and the branching fractions are determined to be B(J/ψ→γπ0→3γ)=(3.57±0.12±0.16)×10−5, B(J/ψ→γη→3γ)=(4.42±0.04±0.18)×10−4, and B(J/ψ→γη′→3γ)=(1.26±0.02±0.05)×10−4, where the first errors are statistical and the second systematic. No clear signal for η(1405), η(1475), η(1760) or X(1835) is observed in the two-photon mass spectra, and upper limits at the 90% confidence level on the product branching fractions are obtained.
Transverse spin transfer to Λ and ¯Λ hyperons in polarized proton-proton collisions at √𝑠=200 GeV
(2018)
The transverse spin transfer from polarized protons to Λ and Λ¯ hyperons is expected to provide sensitivity to the transversity distribution of the nucleon and to the transversely polarized fragmentation functions. We report the first measurement of the transverse spin transfer to Λ and Λ¯ along the polarization direction of the fragmenting quark, DTT, in transversely polarized proton-proton collisions at s√=200GeV with the STAR detector at RHIC. The data correspond to an integrated luminosity of 18pb−1 and cover the pseudorapidity range |η|<1.2 and transverse momenta pT up to 8GeV/c. The dependence on pT and η are presented. The DTT results are found to be comparable with a model prediction, and are also consistent with zero within uncertainties.
Rapidity-odd directed flow measurements at midrapidity are presented for Λ, Λ¯, K±, K0s and ϕ at sNN−−−−√= 7.7, 11.5, 14.5, 19.6, 27, 39, 62.4 and 200 GeV in Au+Au collisions recorded by the STAR detector at the Relativistic Heavy Ion Collider. These measurements greatly expand the scope of data available to constrain models with differing prescriptions for the equation of state of quantum chromodynamics. Results show good sensitivity for testing a picture where flow is assumed to be imposed before hadron formation and the observed particles are assumed to form via coalescence of constituent quarks. The pattern of departure from a coalescence-inspired sum-rule can be a valuable new tool for probing the collision dynamics.
Using a low background data sample of 9.7×105 𝐽/𝜓→𝛾𝜂′, 𝜂′→𝛾𝜋+𝜋− events, which are 2 orders of magnitude larger than those from the previous experiments, recorded with the BESIII detector at BEPCII, the decay dynamics of 𝜂′→𝛾𝜋+𝜋− are studied with both model-dependent and model-independent approaches. The contributions of 𝜔 and the 𝜌(770)−𝜔 interference are observed for the first time in the decays 𝜂′→𝛾𝜋+𝜋− in both approaches. Additionally, a contribution from the box anomaly or the 𝜌(1450) resonance is required in the model-dependent approach, while the process specific part of the decay amplitude is determined in the model-independent approach.
Based on an 𝑒+𝑒− collision data sample corresponding to an integrated luminosity of 567 pb−1 taken at the center-of-mass energy of √𝑠=4.6 GeV with the BESIII detector, we measure the absolute branching fraction of the inclusive decay Λ+𝑐→Λ+𝑋 to be ℬ(Λ+𝑐→Λ+𝑋)=(38.2+2.8−2.2±0.9)% using the double-tag method, where 𝑋 refers to any possible final state particles. In addition, we search for direct 𝐶𝑃 violation in the charge asymmetry of this inclusive decay for the first time, and obtain 𝒜𝐶𝑃≡[ℬ(Λ+𝑐→Λ+𝑋)−ℬ(¯Λ−𝑐 → ¯Λ+𝑋)]/[ℬ(Λ+𝑐→Λ+𝑋)+ℬ(¯Λ−𝑐 → ¯Λ+𝑋)]=(2.1+7.0−6.6±1.6)%, a statistically limited result with no evidence of 𝐶𝑃 violation.
New geochemical data from the Malawi Rift (Chiwondo Beds, Karonga Basin) fill a major spatial gap in our knowledge of hominin adaptations on a continental scale. Oxygen (δ18O), carbon (δ13C), and clumped (Δ47) isotope data on paleosols, hominins, and selected fauna elucidate an unexpected diversity in the Pleistocene hominin diet in the various habitats of the East African Rift System (EARS). Food sources of early Homo and Paranthropus thriving in relatively cool and wet wooded savanna ecosystems along the western shore of paleolake Malawi contained a large fraction of C3 plant material. Complementary water consumption reconstructions suggest that ca. 2.4 Ma, early Homo (Homo rudolfensis) and Paranthropus (Paranthropus boisei) remained rather stationary near freshwater sources along the lake margins. Time-equivalent Paranthropus aethiopicus from the Eastern Rift further north in the EARS consumed a higher fraction of C4 resources, an adaptation that grew more pronounced with increasing openness of the savanna setting after 2 Ma, while Homo maintained a high versatility. However, southern African Paranthropus robustus had, similar to the Malawi Rift individuals, C3-dominated feeding strategies throughout the Early Pleistocene. Collectively, the stable isotope and faunal data presented here document that early Homo and Paranthropus were dietary opportunists and able to cope with a wide range of paleohabitats, which clearly demonstrates their high behavioral flexibility in the African Early Pleistocene.
Brachiopod shells are the most widely used geological archive for the reconstruction of the temperature and the oxygen isotope composition of Phanerozoic seawater. However, it is not conclusive whether brachiopods precipitate their shells in thermodynamic equilibrium. In this study, we investigated the potential impact of kinetic controls on the isotope composition of modern brachiopods by measuring the oxygen and clumped isotope compositions of their shells. Our results show that clumped and oxygen isotope compositions depart from thermodynamic equilibrium due to growth rate-induced kinetic effects. These departures are in line with incomplete hydration and hydroxylation of dissolved CO2. These findings imply that the determination of taxon-specific growth rates alongside clumped and bulk oxygen isotope analyses is essential to ensure accurate estimates of past ocean temperatures and seawater oxygen isotope compositions from brachiopods.
The decay 𝐽/𝜓→𝛾𝛾𝜙 is studied using a sample of 1.31×109 𝐽/𝜓 events collected with the BESIII detector. Two structures around 1475 MeV/𝑐2 and 1835 MeV/𝑐2 are observed in the 𝛾𝜙 invariant mass spectrum for the first time. With a fit on the 𝛾𝜙 invariant mass, which takes into account the interference between the two structures, and a simple analysis of the angular distribution, the structure around 1475 MeV/𝑐2 is found to favor an assignment as the 𝜂(1475) and the mass and width for the structure around 1835 MeV/𝑐2 are consistent with the 𝑋(1835). The statistical significances of the two structures are 13.5𝜎 and 6.3𝜎, respectively. The results indicate that both 𝜂(1475) and 𝑋(1835) contain a sizeable 𝑠¯𝑠 component.
With a notional amount outstanding of more than USD 500 trillion, the market for OTC derivatives is of vital importance for global financial stability. A growing proportion of these contracts are cleared via central counterparties (CCPs), which means that CCPs are gaining in importance as critical financial market infrastructures. At the same time, there is growing concern that a new „too big to fail" problem could arise, as the CCP industry is highly concentrated due to economies of scale. From a European perspective, it should be noted that the clearing of euro-denominated OTC derivatives mainly takes place in London, hence outside the EU in the foreseeable future. For some time there has been a controversial discussion as to whether this can remain the case post Brexit. CCPs, which clear a significant proportion of euro OTC derivatives and are systemically relevant from an EU perspective, should be subject to direct supervision by EU authorities and should be established in the EU. This would represent an important building block for a future Capital Markets Union in Europe, as regulatory or supervisory arbitrage in favour of systemically important third-country CCPs could be prevented. In addition, if a systemically relevant CCP handling a considerable portion of the euro OTC derivatives business were to run into serious difficulties, this may impact ECB monetary policy. This applies both to demand for central bank money and to the transmission of monetary policy measures, which can be significantly impaired, particularly in the event that the repo market or payment systems are disrupted. It is therefore essential for the ECB to be closely involved in the supervision of CCPs. Against this background, the draft amendment of EMIR (European Market Infrastructure Regulation) presented on 13 June 2017 is a step in the right direction. In addition, there is an urgent need to introduce a recovery and resolution mechanism for CCPs in the EU to complement the existing single resolution mechanism (SRM) for banks in the eurozone. Only then can the diverse interdependencies between banks and CCPs be adequately taken into account in the recovery and resolution programmes required in a financial crisis.
Using a data sample of 𝑒+𝑒− collisions corresponding to an integrated luminosity of 567 pb−1 collected at a center-of-mass energy of √𝑠=4.6 GeV with the BESIII detector, we measure the absolute branching fraction of the inclusive semileptonic Λ+𝑐 decay with a double-tag method. We obtain ℬ(Λ+𝑐→𝑋𝑒+𝜈𝑒)=(3.95±0.34±0.09)%, where the first uncertainty is statistical and the second systematic. Using the known Λ+𝑐 lifetime and the charge-averaged semileptonic decay width of nonstrange charmed mesons (𝐷0 and 𝐷+), we obtain the ratio of the inclusive semileptonic decay widths Γ(Λ+𝑐→𝑋𝑒+𝜈𝑒)/¯Γ(𝐷→𝑋𝑒+𝜈𝑒)=1.26±0.12.
Using a data sample of 448.1×106 𝜓(3686) events collected with the BESIII detector operating at the BEPCII, we perform search for the hadronic transition ℎ𝑐→𝜋+𝜋−𝐽/𝜓 via 𝜓(3686)→𝜋0ℎ𝑐. No signals of the transition are observed, and the upper limit on the product branching fraction ℬ(𝜓(3686)→𝜋0ℎ𝑐)ℬ(ℎ𝑐→𝜋+𝜋−𝐽/𝜓) at the 90% confidence level (C.L.) is determined to be 2.0×10−6. This is the most stringent upper limit to date.
Die Jahrestagung 2015 der Gesellschaft für Comicforschung (ComFor) stand unter dem Thema »Geschichte im Comic – Geschichte des Comics«. Ein Blick in das damalige Programm (als LINK: http://www.comicgesellschaft.de/2015/ 07/23/programm-der-10-comfor-jahrestagungin-frankfurtm/) oder den mittlerweile erschienen Tagungsband (als LINK: http://www.christianbachmann.de/b_comfor7.html) offenbart, dass der zweite titelgebende Teil deutlich unterrepräsentiert war. Geplant war die Tagung auch als Gegengewicht zu den Theoriediskursen in der Comicforschung, d.h. zur Stärkung diachroner Arbeiten. Das Desiderat historischer Comicforschung blieb damit bestehen. Ein um weitere Beiträge ergänzter Band basierend auf den wenigen gehaltenen Vorträgen ist für 2018 angekündigt; bereits 2016 ist jedoch eine erfreulich große Anzahl an Publikationen mit teilweise historischen Fragestellungen erschienen. ...
We report the first measurements of absolute branching fractions for the W -exchange-only processes + c → 0K + and + c → (1530)0K + with the double-tag technique, by analyzing an e+e− collision data sample, that corresponds to an integrated luminosity of 567 pb−1 collected at a center-of-mass energy of 4.6 GeV by the BESIII detector. The branching fractions are measured to be B(+c → 0K +) = (5.90 ± 0.86 ± 0.39) × 10−3 and B(+c → (1530)0K +) = (5.02 ± 0.99 ± 0.31) × 10−3, where the first uncertainties are statistical and the second systematic. Our results are more precise than the previous relative measurements.
Using a data sample of 448.1 × 106 ψ(3686) events collected with the BESIII detector at the BEPCII collider, we report the first observation of the electromagnetic Dalitz decay ψ(3686) → η e+e−, with significances of 7.0σ and 6.3σ when reconstructing the η meson via its decay modes η → γπ+π− and η → π+π−η (η → γγ ), respectively. The weighted average branching fraction is determined to be B(ψ(3686) → η e+e−) = (1.90 ± 0.25 ± 0.11) × 10−6, where the first uncertainty is statistical and the second systematic.
How much we trust our own decisions, knowledge or perceptions influences our behavior in many everyday situations. Normally the confidence we have in our decisions is rather accurate, but under certain circumstances the subjective evaluation of a decision and its objective quality can differ heavily. Subjectively over- or underestimating the quality of decisions can lead to disadvantageous behavior. Little is known about how this feeling of confidence about a decision is generated. Is it computed automatically with the decision or does it arise in a different process?
This thesis is based on a publication that contributed to the investigation of this question by comparing the influence of two different forms of spatial attention on decision confidence. Visual spatial attention is a cognitive mechanism that serves to select parts of the visual field, leading to more accurate decisions about the attended items. It can be either voluntarily controlled (endogenous) or reflexively driven by external events (exogenous). In an orientation-matching task participants performed better in both attentional conditions than in a control condition without directed attention. Additionally, we found that only endogenous, but not exogenous attention led the subjects to overestimate the quality of their performance. The possible implications of this “relative overconfidence” were discussed with respect to the theoretical framework of spatial attention and decision confidence. The present findings support the idea that decision confidence is generated in a distinct metacognitive process. Possible ideas for further neurophysiological research are proposed. The thesis concludes with an attempt to integrate the discussion into a broader context of medical research on certain neuropsychiatric symptoms and conditions.
Background: Alternative splicing is a key mechanism in eukaryotic cells to increase the effective number of functionally distinct gene products. Using bulk RNA sequencing, splicing variation has been studied both across human tissues and in genetically diverse individuals. This has identified disease-relevant splicing events, as well as associations between splicing and genomic variations, including sequence composition and conservation. However, variability in splicing between single cells from the same tissue and its determinants remain poorly understood.
Results: We applied parallel DNA methylation and transcriptome sequencing to differentiating human induced pluripotent stem cells to characterize splicing variation (exon skipping) and its determinants. Our results shows that splicing rates in single cells can be accurately predicted based on sequence composition and other genomic features. We also identified a moderate but significant contribution from DNA methylation to splicing variation across cells. By combining sequence information and DNA methylation, we derived an accurate model (AUC=0.85) for predicting different splicing modes of individual cassette exons. These explain conventional inclusion and exclusion patterns, but also more subtle modes of cell-to-cell variation in splicing. Finally, we identified and characterized associations between DNA methylation and splicing changes during cell differentiation.
Conclusions: Our study yields new insights into alternative splicing at the single-cell level and reveals a previously underappreciated component of DNA methylation variation on splicing.
Background: Alternative splicing is a key regulatory mechanism in eukaryotic cells and increases the effective number of functionally distinct gene products. Using bulk RNA sequencing, splicing variation has been studied across human tissues and in genetically diverse populations. This has identified disease-relevant splicing events, as well as associations between splicing and genomic features, including sequence composition and conservation. However, variability in splicing between single cells from the same tissue or cell type and its determinants remains poorly understood.
Results: We applied parallel DNA methylation and transcriptome sequencing to differentiating human induced pluripotent stem cells to characterize splicing variation (exon skipping) and its determinants. Our results show that variation in single-cell splicing can be accurately predicted based on local sequence composition and genomic features. We observe moderate but consistent contributions from local DNA methylation profiles to splicing variation across cells. A combined model that is built based on genomic features as well as DNA methylation information accurately predicts different splicing modes of individual cassette exons. These categories include the conventional inclusion and exclusion patterns, but also more subtle modes of cell-to-cell variation in splicing. Finally, we identified and characterized associations between DNA methylation and splicing changes during cell differentiation.
Conclusions: Our study yields new insights into alternative splicing at the single-cell level and reveals a previously underappreciated link between DNA methylation variation and splicing.
b̄b̄ud tetraquark resonances in the Born-Oppenheimer approximation using lattice QCD potentials
(2018)
We study tetraquark resonances using lattice QCD potentials for a pair of static antiquarks b¯b¯ in the presence of two light quarks ud. The system is treated in the Born-Oppenheimer approximation and we use the emergent wave method. We focus on the isospin I=0 channel, but consider different orbital angular momenta l of the heavy antiquarks b¯b¯. We extract the phase shifts and search for S and T matrix poles on the second Riemann sheet. For orbital angular momentum l=1 we find a tetraquark resonance with quantum numbers I(JP)=0(1−), resonance mass m=10576+4−4MeV and decay width Γ=112+90−103MeV, which can decay into two B mesons.
We present data on charged kaons (K±) and ϕ mesons in Au(1.23A GeV)+Au collisions. It is the first simultaneous measurement of K− and ϕ mesons in central heavy-ion collisions below a kinetic beam energy of 10A GeV. The ϕ/K− multiplicity ratio is found to be surprisingly high with a value of 0.52±0.16 and shows no dependence on the centrality of the collision. Consequently, the different slopes of the K+ and K− transverse-mass spectra can be explained solely by feed-down, which substantially softens the spectra of K− mesons. Hence, in contrast to the commonly adapted argumentation in literature, the different slopes do not necessarily imply diverging freeze-out temperatures of K+ and K− mesons caused by different couplings to baryons.
The production of Σ0 baryons in the nuclear reaction p (3.5 GeV) + Nb (corresponding to sNN=3.18 GeV) is studied with the detector set-up HADES at GSI, Darmstadt. Σ0s were identified via the decay Σ0→Λγ with subsequent decays Λ→pπ− in coincidence with a e+e− pair from either external (γ→e+e−) or internal (Dalitz decay γ⁎→e+e−) gamma conversions. The differential Σ0 cross section integrated over the detector acceptance, i.e. the rapidity interval 0.5<y<1.1, has been extracted as ΔσΣ0=2.3±(0.2)stat±(−0.6+0.6)sys±(0.2)norm mb, yielding the inclusive production cross section in full phase space σΣ0total=5.8±(0.5)stat±(−1.4+1.4)sys±(0.6)norm±(1.7)extrapol mb by averaging over different extrapolation methods. The Λall/Σ0 ratio within the HADES acceptance is equal to 2.3±(0.2)stat±(−0.6+0.6)sys. The obtained rapidity and momentum distributions are compared to transport model calculations. The Σ0 yield agrees with the statistical model of particle production in nuclear reactions. Keywords: Hyperons, Strangeness, Proton, Nucleus.
We explore space improvements in LRP, a polymorphically typed call-by-need functional core language. A relaxed space measure is chosen for the maximal size usage during an evaluation. It Abstracts from the details of the implementation via abstract machines, but it takes garbage collection into account and thus can be seen as a realistic approximation of space usage. The results are: a context lemma for space improving translations and for space equivalences; all but one reduction rule of the calculus are shown to be space improvements, and the exceptional one, the copy-rule, is shown to increase space only moderately.
Several further program transformations are shown to be space improvements or space equivalences, in particular the translation into machine expressions is a space equivalence. These results are a step Forward in making predictions about the change in runtime space behavior of optimizing transformations in callbyneed functional languages.
The transversity distribution, which describes transversely polarized quarks in transversely polarized nucleons, is a fundamental component of the spin structure of the nucleon, and is only loosely constrained by global fits to existing semi-inclusive deep inelastic scattering (SIDIS) data. In transversely polarized p↑+p collisions it can be accessed using transverse polarization dependent fragmentation functions which give rise to azimuthal correlations between the polarization of the struck parton and the final state scalar mesons.This letter reports on spin dependent di-hadron correlations measured by the STAR experiment. The new dataset corresponds to 25 pb−1 integrated luminosity of p↑+p collisions at s=500 GeV, an increase of more than a factor of ten compared to our previous measurement at s=200 GeV. Non-zero asymmetries sensitive to transversity are observed at a Q2 of several hundred GeV and are found to be consistent with the former measurement and a model calculation. We expect that these data will enable an extraction of transversity with comparable precision to current SIDIS datasets but at much higher momentum transfers where subleading effects are suppressed.
Background: Patients with chronic kidney disease (CKD) are at high risk of myocardial infarction. Cardiac troponins are the biomarkers of choice for the diagnosis of acute myocardial infarction (AMI) without ST‐segment elevation (NSTE). In patients with CKD, troponin levels are often chronically elevated, which reduces their diagnostic utility when NSTE‐AMI is suspected. The aim of this study was to derive a diagnostic algorithm for serial troponin measurements in patients with CKD and suspected NSTE‐AMI.
Methods and Results: Two cohorts, 1494 patients from a prospective cohort study with high‐sensitivity troponin I (hs‐cTnI) measurements and 7059 cases from a clinical registry with high‐sensitivity troponin T (hs‐cTnT ) measurements, were analyzed. The prospective cohort comprised 280 CKD patients (estimated glomerular filtration rate <60 mL/min/1.73 m2). The registry data set contained 1581 CKD patients. In both cohorts, CKD patients were more likely to have adjudicated NSTE‐AMI than non‐CKD patients. The specificities of hs‐cTnI and hs‐cTnT to detect NSTE‐AMI were reduced with CKD (0.82 versus 0.91 for hs‐cTnI and 0.26 versus 0.73 for hs‐cTnT) but could be restored by applying optimized cutoffs to either the first or a second measurement after 3 hours. The best diagnostic performance was achieved with an algorithm that incorporates serial measurements and rules in or out AMI in 69% (hs‐cTnI) and 55% (hs‐cTnT) of CKD patients.
Conclusions: The diagnostic performance of high‐sensitivity cardiac troponins in patients with CKD with suspected NSTE‐AMI is improved by use of an algorithm based on admission troponin and dynamic changes in troponin concentration.