Möglichkeiten und Grenzen der Digitalisierung im Bildungsbereich und der gegenwärtigen Herausforderung in Zeiten der Pandemie

In der gegenwärtigen gesellschaftlichen digitalen Transformation verändern sich Orte und Räume. Lehr- und Lerninhalte können zeitunabhängig bearbeitet werden, d. h. der klassische (Präsenz-)Unterricht muss in der digitalen Welt neu gedacht werden. Was aber nicht bedeutet, dass dieser aus unserer Bildungslandschaft verschwindet bzw. verschwinden soll. Es braucht pädagogisch und didaktisch gut durchdachte Konzepte und Überlegungen, wann es klüger erscheint eine Präsenzveranstaltung anzusetzen oder digitale Räume für den Unterricht bzw. Unterrichtsertrag genutzt werden können. Dafür braucht es nicht nur Pädagoginnen und Pädagogen, die über eine fachdidaktische Expertise verfügen, sondern auch medienkompetent aufbereitete Inhalte, um virtuelle Räume wirkmächtig für den Unterricht nutzen zu können. Wie in dem vorliegenden Beitrag dargelegt sind im humanistischen Bildungsverständnis soziale Interaktionen und ein Miteinander wesentliche Faktoren, die in der Schule oder an Hochschulen neben der fachlichen Expertise Lernenden vermittelt werden. Im "Distance Learning" haben die befragten Lehrerinnen und Lehrer festgehalten, dass die von der Hochschule angebotenen Online-Formate sowohl inhaltlich als auch persönlich als bereichernd empfunden wurden und zukünftig Fortbildungen sowohl in Präsenz als auch in digitaler Form wünschenswert wären. Was wiederum einen klaren Auftrag für die Hochschulen darstellt, damit Schule sich weiterentwickeln kann und junge Menschen für die aktive Teilhabe an der Gesellschaft von morgen gerüstet sind

Value of large scale expansion of tumor infiltrating lymphocytes in a compartmentalised gas-permeable bag: interests for adoptive immunotherapy

<p>Abstract</p> <p>Background</p> <p>Adoptive cell therapy (ACT) has emerged as an effective treatment for patients with metastatic melanoma. However, there are several logistical and safety concerns associated with large-scale <it>ex vivo </it>expansion of tumour-specific T lymphocytes for widespread availability of ACT for cancer patients. To address these problems we developed a specific compartmentalised bag allowing efficient expansion of tumour-specific T lymphocytes in an easy handling, closed system.</p> <p>Methods</p> <p>Starting from lymph nodes from eight melanoma patients, we performed a side-by-side comparison of Tumour-Infiltrating Lymphocytes (TIL) produced after expansion in the compartmentalised bag versus TIL produced using the standard process in plates. Proliferation yield, viability, phenotype and IFNγ secretion were comparatively studied.</p> <p>Results</p> <p>We found no differences in proliferation yield and cell viability between both TIL production systems. Moreover, each of the cell products complied with our defined release criteria before being administered to the patient. The phenotype analysis indicated that the compartmentalised bag favours the expansion of CD8+ cells. Finally, we found that TIL stimulated in bags were enriched in reactive CD8+ T cells when co-cultured with the autologous melanoma cell line.</p> <p>Conclusions</p> <p>The stimulation of TIL with feeder cells in the specifically designed compartmentalised bag can advantageously replace the conventional protocol using plates. In particular, the higher expansion rate of reactive CD8+ T cells could have a significant impact for ACT.</p

Individual based model links thermodynamics, chemical speciation and environmental conditions to microbial growth

Individual based Models (IbM) must transition from research tools to engineering tools. To make the transition we must aspire to develop large, three dimensional and physically and biologically credible models. Biological credibility can be promoted by grounding, as far as possible, the biology in thermodynamics. Thermodynamic principles are known to have predictive power in microbial ecology. However, this in turn requires a model that incorporates pH and chemical speciation. Physical credibility implies plausible mechanics and a connection with the wider environment. Here, we propose a step toward that ideal by presenting an individual based model connecting thermodynamics, pH and chemical speciation and environmental conditions to microbial growth for 5·105 individuals. We have showcased the model in two scenarios: a two functional group nitrification model and a three functional group anaerobic community. In the former, pH and connection to the environment had an important effect on the outcomes simulated. Whilst in the latter pH was less important but the spatial arrangements and community productivity (that is, methane production) were highly dependent on thermodynamic and reactor coupling. We conclude that if IbM are to attain their potential as tools to evaluate the emergent properties of engineered biological systems it will be necessary to combine the chemical, physical, mechanical and biological along the lines we have proposed. We have still fallen short of our ideals because we cannot (yet) calculate specific uptake rates and must develop the capacity for longer runs in larger models. However, we believe such advances are attainable. Ideally in a common, fast and modular platform. For future innovations in IbM will only be of use if they can be coupled with all the previous advances

Loss of migratory traditions makes the endangered patagonian Huemul deer a year-round refugee in its summer habitat

The huemul (Hippocamelus bisulcus) is endangered, with 1500 deer split into >100 subpopulations along 2000 km of the Andes. Currently occupied areas are claimed-erroneously-to be critical prime habitats. We analyzed historical spatiotemporal behavior since current patterns represent only a fraction of pre-Columbian ones. Given the limited knowledge, the first group (n = 6) in Argentina was radio-marked to examine spatial behavior. Historically, huemul resided year-round in winter ranges, while some migrated seasonally, some using grasslands >200 km east of their current presence, reaching the Atlantic. Moreover, huemul anatomy is adapted to open unforested habitats, also corroborated by spotless fawns. Extreme naivety towards humans resulted in early extirpation on many winter ranges—preferentially occupied by humans, resulting in refugee huemul on surrounding mountain summer ranges. Radio-marked huemul remained in small ranges with minimal altitudinal movements, as known from other subpopulations. However, these resident areas documented here are typical summer ranges as evidenced by past migrations, and current usage for livestock. The huemul is the only cervid known to use mountain summer ranges year-round in reaction to anthropogenic activities. Losing migratory traditions is a major threat, and may explain their presently prevalent skeletal diseases, reduced longevity, and lacking recolonizations for most remaining huemul subpopulations.Fil: Fluck, Werner Thomas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina. Universidad de Basilea; Suiza. Administración de Parques Nacionales; ArgentinaFil: Smith Flueck, Jo Anne M.. Universidad Nacional del Comahue; Argentina. Parque Protegido Shoonem; Argentina. Deer Lab; ArgentinaFil: Escobar, Miguel E.. Parque Protegido Shoonem; ArgentinaFil: Zuliani, Melina Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina. Fundación Bariloche; ArgentinaFil: Fuchs, Beat. Deer Lab; ArgentinaFil: Geist, Valerius. University of Calgary; CanadáFil: Heffelfinger, James R.. Arizona Game and Fish Department; Estados UnidosFil: Black de Decima, Patricia Ann. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; ArgentinaFil: Gizejewski, Zygmunt. Polish Academy of Sciences; ArgentinaFil: Vidal, Fernando. Univerdidad Santo Tomas; Chile. Centro de Conservacion y Manejo de Vida Silvestre; ChileFil: Barrio, Javier. Centro de Ornitología y Biodiversidad; PerúFil: Molinuevo, María Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Agrarias y Forestales. Departamento de Ciencias Biológicas; ArgentinaFil: Monjeau, Jorge Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina. Fundación Bariloche; ArgentinaFil: Hoby, Stefan. Berne Animal Park; SuizaFil: Jiménez, Jaime M.. University of North Texas; Estados Unido

Multi-site genetic analysis of diffusion images and voxelwise heritability analysis : a pilot project of the ENIGMA–DTI working group

The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium was set up to analyze brain measures and genotypes from multiple sites across the world to improve the power to detect genetic variants that influence the brain. Diffusion tensor imaging (DTI) yields quantitative measures sensitive to brain development and degeneration, and some common genetic variants may be associated with white matter integrity or connectivity. DTI measures, such as the fractional anisotropy (FA) of water diffusion, may be useful for identifying genetic variants that influence brain microstructure. However, genome-wide association studies (GWAS) require large populations to obtain sufficient power to detect and replicate significant effects, motivating a multi-site consortium effort. As part of an ENIGMA–DTI working group, we analyzed high-resolution FA images from multiple imaging sites across North America, Australia, and Europe, to address the challenge of harmonizing imaging data collected at multiple sites. Four hundred images of healthy adults aged 18–85 from four sites were used to create a template and corresponding skeletonized FA image as a common reference space. Using twin and pedigree samples of different ethnicities, we used our common template to evaluate the heritability of tract-derived FA measures. We show that our template is reliable for integrating multiple datasets by combining results through meta-analysis and unifying the data through exploratory mega-analyses. Our results may help prioritize regions of the FA map that are consistently influenced by additive genetic factors for future genetic discovery studies. Protocols and templates are publicly available at (http://enigma.loni.ucla.edu/ongoing/dti-working-group/)

Characteristics of Nondisabled Older Patients Developing New Disability Associated with Medical Illnesses and Hospitalization

OBJECTIVE: To identify demographic, clinical, and biological characteristics of older nondisabled patients who develop new disability in basic activities of daily living (BADL) during medical illnesses requiring hospitalization. DESIGN: Longitudinal observational study. SETTING: Geriatric and Internal Medicine acute care units. PARTICIPANTS: Data are from 1,686 patients aged 65 and older who independent in BADL 2 weeks before hospital admission, enrolled in the 1998 survey of the Italian Group of Pharmacoepidemiology in the Elderly Study. MEASUREMENTS: Study outcome was new BADL disability at time of hospital discharge. Sociodemographic, functional status, and clinical characteristics were collected at hospital admission; acute and chronic conditions were classified according to the International Classification of Disease, ninth revision; fasting blood samples were obtained and processed with standard methods. RESULTS: At the time of hospital discharge 113 patients (6.7%) presented new BADL disability. Functional decline was strongly related to patients’ age and preadmission instrumental activities of daily living status. In a multivariate analysis, older age, nursing home residency, low body mass index, elevated erythrocyte sedimentation rate, acute stroke, high level of comorbidity expressed as Cumulative Illness Rating Scale score, polypharmacotherapy, cognitive decline, and history of fall in the previous year were independent and significant predictors of BADL disability. CONCLUSION: Several factors might contribute to loss of physical independence in hospitalized older persons. Preexisting conditions associated with the frailty syndrome, including physical and cognitive function, comorbidity, body composition, and inflammatory markers, characterize patients at high risk of functional decline

Impact of SARS-CoV-2 ORF6 and its variant polymorphisms on host responses and viral pathogenesis

: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes several proteins that inhibit host interferon responses. Among these, ORF6 antagonizes interferon signaling by disrupting nucleocytoplasmic trafficking through interactions with the nuclear pore complex components Nup98-Rae1. However, the roles and contributions of ORF6 during physiological infection remain unexplored. We assessed the role of ORF6 during infection using recombinant viruses carrying a deletion or loss-of-function (LoF) mutation in ORF6. ORF6 plays key roles in interferon antagonism and viral pathogenesis by interfering with nuclear import and specifically the translocation of IRF and STAT transcription factors. Additionally, ORF6 inhibits cellular mRNA export, resulting in the remodeling of the host cell proteome, and regulates viral protein expression. Interestingly, the ORF6:D61L mutation that emerged in the Omicron BA.2 and BA.4 variants exhibits reduced interactions with Nup98-Rae1 and consequently impairs immune evasion. Our findings highlight the role of ORF6 in antagonizing innate immunity and emphasize the importance of studying the immune evasion strategies of SARS-CoV-2

Multidifferential study of identified charged hadron distributions in ZZ-tagged jets in proton-proton collisions at s=\sqrt{s}=13 TeV

Jet fragmentation functions are measured for the first time in proton-proton collisions for charged pions, kaons, and protons within jets recoiling against a $Z$ boson. The charged-hadron distributions are studied longitudinally and transversely to the jet direction for jets with transverse momentum 20 $< p_{\textrm{T}} < 100$ GeV and in the pseudorapidity range $2.5 < \eta < 4$. The data sample was collected with the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.64 fb$^{-1}$. Triple differential distributions as a function of the hadron longitudinal momentum fraction, hadron transverse momentum, and jet transverse momentum are also measured for the first time. This helps constrain transverse-momentum-dependent fragmentation functions. Differences in the shapes and magnitudes of the measured distributions for the different hadron species provide insights into the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb public pages

Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

The decay $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ is studied in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=13$ TeV using data corresponding to an integrated luminosity of 5 $\mathrm{fb}^{-1}$ collected by the LHCb experiment. In the $\Lambda_{c}^+ K^{-}$ system, the $\Xi_{c}(2930)^{0}$ state observed at the BaBar and Belle experiments is resolved into two narrower states, $\Xi_{c}(2923)^{0}$ and $\Xi_{c}(2939)^{0}$, whose masses and widths are measured to be $$m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV},$$ where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt $\Lambda_{c}^{+} K^{-}$ sample. Evidence of a new $\Xi_{c}(2880)^{0}$ state is found with a local significance of $3.8\,\sigma$, whose mass and width are measured to be $2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV}$ and $12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}$, respectively. In addition, evidence of a new decay mode $\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-}$ is found with a significance of $3.7\,\sigma$. The relative branching fraction of $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ with respect to the $B^{-} \to D^{+} D^{-} K^{-}$ decay is measured to be $2.36 \pm 0.11 \pm 0.22 \pm 0.25$, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages

Measurement of the ratios of branching fractions R(D∗)\mathcal{R}(D^{*}) and R(D0)\mathcal{R}(D^{0})

The ratios of branching fractions $\mathcal{R}(D^{*})\equiv\mathcal{B}(\bar{B}\to D^{*}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(\bar{B}\to D^{*}\mu^{-}\bar{\nu}_{\mu})$ and $\mathcal{R}(D^{0})\equiv\mathcal{B}(B^{-}\to D^{0}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(B^{-}\to D^{0}\mu^{-}\bar{\nu}_{\mu})$ are measured, assuming isospin symmetry, using a sample of proton-proton collision data corresponding to 3.0 fb${ }^{-1}$ of integrated luminosity recorded by the LHCb experiment during 2011 and 2012. The tau lepton is identified in the decay mode $\tau^{-}\to\mu^{-}\nu_{\tau}\bar{\nu}_{\mu}$. The measured values are $\mathcal{R}(D^{*})=0.281\pm0.018\pm0.024$ and $\mathcal{R}(D^{0})=0.441\pm0.060\pm0.066$, where the first uncertainty is statistical and the second is systematic. The correlation between these measurements is $\rho=-0.43$. Results are consistent with the current average of these quantities and are at a combined 1.9 standard deviations from the predictions based on lepton flavor universality in the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-039.html (LHCb public pages