242 results on '"Alexander Berg"'
Search Results
2. Fertility-preserving myeloablative conditioning using single-dose CD117 antibody-drug conjugate in a rhesus gene therapy model
- Author
-
Naoya Uchida, Ulana Stasula, Selami Demirci, Paula Germino-Watnick, Malikiya Hinds, Anh Le, Rebecca Chu, Alexander Berg, Xiong Liu, Ling Su, Xiaolin Wu, Allen E. Krouse, N. Seth Linde, Aylin Bonifacino, So Gun Hong, Cynthia E. Dunbar, Leanne Lanieri, Anjali Bhat, Rahul Palchaudhuri, Bindu Bennet, Megan Hoban, Kirk Bertelsen, Lisa M. Olson, Robert E. Donahue, and John F. Tisdale
- Subjects
Science - Abstract
Abstract Hematopoietic stem cell (HSC) gene therapy has curative potential; however, its use is limited by the morbidity and mortality associated with current chemotherapy-based conditioning. Targeted conditioning using antibody-drug conjugates (ADC) holds promise for reduced toxicity in HSC gene therapy. Here we test the ability of an antibody-drug conjugate targeting CD117 (CD117-ADC) to enable engraftment in a non-human primate lentiviral gene therapy model of hemoglobinopathies. Following single-dose CD117-ADC, a >99% depletion of bone marrow CD34 + CD90 + CD45RA- cells without lymphocyte reduction is observed, which results are not inferior to multi-day myeloablative busulfan conditioning. CD117-ADC, similarly to busulfan, allows efficient engraftment, gene marking, and vector-derived fetal hemoglobin induction. Importantly, ADC treatment is associated with minimal toxicity, and CD117-ADC-conditioned animals maintain fertility. In contrast, busulfan treatment commonly causes severe toxicities and infertility in humans. Thus, the myeloablative capacity of single-dose CD117-ADC is sufficient for efficient engraftment of gene-modified HSCs while preserving fertility and reducing adverse effects related to toxicity in non-human primates. This targeted conditioning approach thus provides the proof-of-principle to improve risk-benefit ratio in a variety of HSC-based gene therapy products in humans.
- Published
- 2023
- Full Text
- View/download PDF
3. Kommission für forschungsnahe Dienste
- Author
-
Alexander Berg-Weiß, Elke Bongartz, Sibylle Hermann, Miriam Kötter, Caroline Leiß, and Christoph Müller
- Subjects
Forschungsnahe Dienste ,VDB-Kommissionen ,Jahresbericht ,Bibliography. Library science. Information resources - Published
- 2023
- Full Text
- View/download PDF
4. Sputum lipoarabinomannan (LAM) as a biomarker to determine sputum mycobacterial load: exploratory and model-based analyses of integrated data from four cohorts
- Author
-
Aksana Jones, Jay Saini, Belinda Kriel, Laura E. Via, Yin Cai, Devon Allies, Debra Hanna, David Hermann, Andre G. Loxton, Gerhard Walzl, Andreas H. Diacon, Klaus Romero, Ryo Higashiyama, Yongge Liu, and Alexander Berg
- Subjects
Tuberculosis ,Lipoarabinomannan ,LAM ,Biomarker ,Mycobacterium ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Despite the high global disease burden of tuberculosis (TB), the disease caused by Mycobacterium tuberculosis (Mtb) infection, novel treatments remain an urgent medical need. Development efforts continue to be hampered by the reliance on culture-based methods, which often take weeks to obtain due to the slow growth rate of Mtb. The availability of a “real-time” measure of treatment efficacy could accelerate TB drug development. Sputum lipoarabinomannan (LAM; an Mtb cell wall glycolipid) has promise as a pharmacodynamic biomarker of mycobacterial sputum load. Methods The present analysis evaluates LAM as a surrogate for Mtb burden in the sputum samples from 4 cohorts of a total of 776 participants. These include those from 2 cohorts of 558 non-TB and TB participants prior to the initiation of treatment (558 sputum samples), 1 cohort of 178 TB patients under a 14-day bactericidal activity trial with various mono- or multi-TB drug therapies, and 1 cohort of 40 TB patients with data from the first 56-day treatment of a standard 4-drug regimen. Results Regression analysis demonstrated that LAM was a predictor of colony-forming unit (CFU)/mL values obtained from the 14-day treatment cohort, with well-estimated model parameters (relative standard error ≤ 22.2%). Moreover, no changes in the relationship between LAM and CFU/mL were observed across the different treatments, suggesting that sputum LAM can be used to reasonably estimate the CFU/mL in the presence of treatment. The integrated analysis showed that sputum LAM also appears to be as good a predictor of time to Mycobacteria Growth Incubator Tube (MGIT) positivity as CFU/mL. As a binary readout, sputum LAM positivity is a strong predictor of solid media or MGIT culture positivity with an area-under-the-curve value of 0.979 and 0.976, respectively, from receiver-operator curve analysis. Conclusions Our results indicate that sputum LAM performs as a pharmacodynamic biomarker for rapid measurement of Mtb burden in sputum, and thereby may enable more efficient early phase clinical trial designs (e.g., adaptive designs) to compare candidate anti-TB regimens and streamline dose selection for use in pivotal trials. Trial registration NexGen EBA study (NCT02371681)
- Published
- 2022
- Full Text
- View/download PDF
5. Development of physiologically‐based pharmacokinetic models for standard of care and newer tuberculosis drugs
- Author
-
Helen Humphries, Lisa Almond, Alexander Berg, Iain Gardner, Oliver Hatley, Xian Pan, Ben Small, Mian Zhang, Masoud Jamei, and Klaus Romero
- Subjects
Therapeutics. Pharmacology ,RM1-950 - Abstract
Abstract Tuberculosis (TB) remains a global health problem and there is an ongoing effort to develop more effective therapies and new combination regimes that can reduce duration of treatment. The purpose of this study was to demonstrate utility of a physiologically‐based pharmacokinetic modeling approach to predict plasma and lung concentrations of 11 compounds used or under development as TB therapies (bedaquiline [and N‐desmethyl bedaquiline], clofazimine, cycloserine, ethambutol, ethionamide, isoniazid, kanamycin, linezolid, pyrazinamide, rifampicin, and rifapentine). Model accuracy was assessed by comparison of simulated plasma pharmacokinetic parameters with healthy volunteer data for compounds administered alone or in combination. Eighty‐four percent (area under the curve [AUC]) and 91% (maximum concentration [Cmax]) of simulated mean values were within 1.5‐fold of the observed data and the simulated drug‐drug interaction ratios were within 1.5‐fold (AUC) and twofold (Cmax) of the observed data for nine (AUC) and eight (Cmax) of the 10 cases. Following satisfactory recovery of plasma concentrations in healthy volunteers, model accuracy was assessed further (where patients’ with TB data were available) by comparing clinical data with simulated lung concentrations (9 compounds) and simulated lung: plasma concentration ratios (7 compounds). The 5th–95th percentiles for the simulated lung concentration data recovered between 13% (isoniazid and pyrazinamide) and 88% (pyrazinamide) of the observed data points (Am J Respir Crit Care Med, 198, 2018, 1208; Nat Med, 21, 2015, 1223; PLoS Med, 16, 2019, e1002773). The impact of uncertain model parameters, such as the fraction of drug unbound in lung tissue mass (fumass), is discussed. Additionally, the variability associated with the patient lung concentration data, which was sparse and included extensive within‐subject, interlaboratory, and experimental variability (as well interindividual variability) is reviewed. All presented models are transparently documented and are available as open‐source to aid further research.
- Published
- 2021
- Full Text
- View/download PDF
6. Potentiale nutzen und Verbindungen herstellen
- Author
-
Benjamin Auberer, Alexander Berg-Weiß, Vanessa Gabriel, and Martin Spenger
- Subjects
Fachreferat ,Forschungsdaten ,Forschungsdatenmanagement ,Datenkompetenz ,Data Literacy ,Bibliography. Library science. Information resources - Abstract
In diesem Artikel werden Handlungsoptionen und -spielräume wissenschaftlicher Bibliotheken im Kontext eines sich durch die Digitalisierung verändernden Aufgaben- und Anforderungsspektrums thematisiert. Dieses Themenfeld wird durch die Linse der Berufsgruppe der wissenschaftlichen Bibliothekar*innen bzw. Fachreferent*innen betrachtet. Bestehenden Strukturen, insbesondere den Fachreferaten, kommt in diesem Prozess eine besondere Rolle zu, bieten sie doch Chancen, neue Themen effizient und gezielt an der eigenen Einrichtung einzubinden. Durch die Übernahme neuer Aufgaben durch die Fachreferent*innen besteht jedoch der Bedarf einer Selbstvergewisserung, um adäquat auf neue Situationen reagieren zu können. Anhand des Beispiels Forschungsdatenmanagement (FDM) an der Universitätsbibliothek der LMU (UB der LMU) werden Möglichkeiten aufgezeigt, wie eine Kooperation zwischen FDM-Beratung, Fachreferaten und Forschenden aussehen kann. Welche Rolle spielen dabei Konzepte wie „Embedded Librarian“ oder „Data Literacy“? Und wie können Fachreferent*innen einbezogen werden, um die FDM-Strukturen der eigenen Einrichtung erfolgreich weiterzuentwickeln?
- Published
- 2022
- Full Text
- View/download PDF
7. Openness in Libraries
- Author
-
Alexander Berg-Weiß, Sibylle Hermann, Miriam Kötter, Caroline Leiß, Christoph Müller, and Annette Strauch-Davey
- Subjects
Openness ,Change Management ,Open Science ,Research Support Services ,Commission for Research-Related Services ,Bibliography. Library science. Information resources - Published
- 2022
- Full Text
- View/download PDF
8. Openness in Bibliotheken
- Author
-
Alexander Berg-Weiß, Sibylle Hermann, Miriam Kötter, Caroline Leiß, Christoph Müller, and Annette Strauch-Davey
- Subjects
Openness ,Change Management ,Open Science ,Forschungsnahe Dienste ,Kommission für forschungsnahe Dienste ,Bibliography. Library science. Information resources - Published
- 2022
- Full Text
- View/download PDF
9. Bericht der Kommission für forschungsnahe Dienste 2021
- Author
-
Alexander Berg-Weiß, Sibylle Hermann, Miriam Kötter, Caroline Leiß, Christoph Müller, and Annette Strauch-Davey
- Subjects
Forschungsnahe Dienste ,VDB-Kommissionen ,Jahresbericht ,Bibliography. Library science. Information resources - Published
- 2022
- Full Text
- View/download PDF
10. Kommission für forschungsnahe Dienste
- Author
-
Miriam Kötter, Alexander Berg-Weiß, and Christoph Müller
- Subjects
Kommission für forschungsnahe Dienste ,Bibliography. Library science. Information resources - Published
- 2021
- Full Text
- View/download PDF
11. Bayerisches Modellprojekt eHumanities – interdisziplinär zur Stärkung des Forschungsdatenmanagements in den digitalen Geistes- und Sozialwissenschaften
- Author
-
Alexander Berg-Weiß, Anna Daudrich, Sonja Kümmet, Markus Putnings, Jürgen Rohrwild, Julian Schulz, and Martin Spenger
- Subjects
Bayern ,Best Practice ,Inhaltserschließung ,DataCite Metadata Generator ,RDMO ,Open Educational Resources ,Technology - Abstract
Das vom Bayerischen Staatsministerium für Wissenschaft und Kunst geförderte Projekt eHumanities – interdisziplinär entwickelt Tools und Best-Practice-Empfehlungen für das Forschungsdatenmanagement in den digitalen Geistes- und Sozialwissenschaften und darüber hinaus. Resultate sind u.a. ein Best-Practice-Guide für das Metadatenschema DataCite, eine aktualisierte und funktional erweiterte Version des DataCite-Metadatengenerators, DMP-Fragenkataloge für RDMO, Schulungs- und Lehrinhalte (z. B. Video-Tutorials, Lernmodule als Open Educational Resources) sowie eine Modellkooperation zwischen Informationsinfrastruktureinrichtungen. In diesem Kontext wurden eine technische Lösung zur Dateneinspeisung und -indexierung in einen Data Discovery Service sowie Best-Practice-Prozessabläufe zur Erschließung und Verfügbarhaltung der Daten geschaffen.
- Published
- 2021
- Full Text
- View/download PDF
12. Ultrafast Dynamics of Sb-Corroles: A Combined Vis-Pump Supercontinuum Probe and Broadband Fluorescence Up-Conversion Study
- Author
-
Clark Zahn, Till Stensitzki, Mario Gerecke, Alexander Berg, Atif Mahammed, Zeev Gross, and Karsten Heyne
- Subjects
photoreaction ,triplet formation ,femtosecond spectroscopy ,fluorescence up-conversion ,corrole dynamics ,tetrapyrrole ,ultrafast relaxation ,intersystem crossing ,Organic chemistry ,QD241-441 - Abstract
Corroles are a developing class of tetrapyrrole-based molecules with significant chemical potential and relatively unexplored photophysical properties. We combined femtosecond broadband fluorescence up-conversion and fs broadband Vis-pump Vis-probe spectroscopy to comprehensively characterize the photoreaction of 5,10,15-tris-pentafluorophenyl-corrolato-antimony(V)-trans-difluoride (Sb-tpfc-F2). Upon fs Soret band excitation at ~400 nm, the energy relaxed almost completely to Q band electronic excited states with a time constant of 500 ± 100 fs; this is evident from the decay of Soret band fluorescence at around 430 nm and the rise time of Q band fluorescence, as well as from Q band stimulated emission signals at 600 and 650 nm with the same time constant. Relaxation processes on a time scale of 10 and 20 ps were observed in the fluorescence and absorption signals. Triplet formation showed a time constant of 400 ps, with an intersystem crossing yield from the Q band to the triplet manifold of between 95% and 99%. This efficient triplet formation is due to the spin-orbit coupling of the antimony ion.
- Published
- 2017
- Full Text
- View/download PDF
13. Axonal regeneration after sciatic nerve lesion is delayed but complete in GFAP- and vimentin-deficient mice.
- Author
-
Alexander Berg, Johan Zelano, Marcela Pekna, Ulrika Wilhelmsson, Milos Pekny, and Staffan Cullheim
- Subjects
Medicine ,Science - Abstract
Peripheral axotomy of motoneurons triggers Wallerian degeneration of injured axons distal to the lesion, followed by axon regeneration. Centrally, axotomy induces loss of synapses (synaptic stripping) from the surface of lesioned motoneurons in the spinal cord. At the lesion site, reactive Schwann cells provide trophic support and guidance for outgrowing axons. The mechanisms of synaptic stripping remain elusive, but reactive astrocytes and microglia appear to be important in this process. We studied axonal regeneration and synaptic stripping of motoneurons after a sciatic nerve lesion in mice lacking the intermediate filament (nanofilament) proteins glial fibrillary acidic protein (GFAP) and vimentin, which are upregulated in reactive astrocytes and Schwann cells. Seven days after sciatic nerve transection, ultrastructural analysis of synaptic density on the somata of injured motoneurons revealed more remaining boutons covering injured somata in GFAP(-/-)Vim(-/-) mice. After sciatic nerve crush in GFAP(-/-)Vim(-/-) mice, the fraction of reinnervated motor endplates on muscle fibers of the gastrocnemius muscle was reduced 13 days after the injury, and axonal regeneration and functional recovery were delayed but complete. Thus, the absence of GFAP and vimentin in glial cells does not seem to affect the outcome after peripheral motoneuron injury but may have an important effect on the response dynamics.
- Published
- 2013
- Full Text
- View/download PDF
14. The extent of synaptic stripping of motoneurons after axotomy is not correlated to activation of surrounding glia or downregulation of postsynaptic adhesion molecules.
- Author
-
Alexander Berg, Johan Zelano, Sebastian Thams, and Staffan Cullheim
- Subjects
Medicine ,Science - Abstract
Synapse elimination in the adult central nervous system can be modelled by axotomy of spinal motoneurons which triggers removal of synapses from the cell surface of lesioned motoneurons by processes that remain elusive. Proposed candidate mechanisms are removal of synapses by reactive microglia and astrocytes, based on the remarkable activation of these cell types in the vicinity of motoneurons following axon lesion, and/or decreased expression of synaptic adhesion molecules in lesioned motoneurons. In the present study, we investigated glia activation and adhesion molecule expression in motoneurons in two mouse strains with deviant patterns of synapse elimination following axotomy. Mice deficient in complement protein C3 display a markedly reduced loss of synapses from axotomized motoneurons, whereas mice with impaired function of major histocompatibility complex (MHC) class Ia display an augmented degree of stripping after axotomy. Activation of microglia and astrocytes was assessed by semiquantative immunohistochemistry for Iba 1 (microglia) and GFAP (astrocytes), while expression of synaptic adhesion molecules was determined by in situ hybridization. In spite of the fact that the two mouse strains display very different degrees of synapse elimination, no differences in terms of glial activation or in the downregulation of the studied adhesion molecules (SynCAM1, neuroligin-2,-3 and netrin G-2 ligand) could be detected. We conclude that neither glia activation nor downregulation of synaptic adhesion molecules are correlated to the different extent of the synaptic stripping in the two studied strains. Instead the magnitude of the stripping event is most likely a consequence of a precise molecular signaling, which at least in part is mediated by immune molecules.
- Published
- 2013
- Full Text
- View/download PDF
15. [Untitled]
- Author
-
Alexander Berg and Ralf Stockmann
- Subjects
e-learning ,Learnmanagement ,Lernplattform ,Open Source ,Kursverwaltung ,virtuelle Lernumgebung ,virtueller Campus ,virtuelle Universität ,blended learning ,seminarbegleitend ,Kursplattform ,information management ,higher education ,data mining ,Education - Abstract
Dieser Beitrag beschreibt die Konzeption, den Funktionsumfang und Erfahrungswerte der Open-Source-eLearning-Plattform Stud.IP. Der Funktionsumfang umfasst für jede einzelne Veranstaltung Ablaufpläne, das Hochladen von Hausarbeiten, Diskussionsforen, persönliche Homepages, Chaträume u.v.a. Ziel ist es hierbei, eine Infrastruktur des Lehrens und Lernens anzubieten, die dem Stand der Technik entspricht. Wissenschaftliche Einrichtungen finden zudem eine leistungsstarke Umgebung zur Verwaltung ihres Personals, Pflege ihrer Webseiten und der automatischer Erstellung von Veranstaltungs- oder Personallisten vor. Betreiber können auf ein verlässliches Supportsystem zugreifen, dass sie an der Weiterentwicklung durch die Entwickler- und Betreiber-Community teilhaben lässt.This article provides information about the concept design, features and experience values of the E-Learning software ”Stud.IP” (open source). The functional range covers timetables, upload of documents, discussion boards, personal homepages, chatrooms etc.The goal is to offer an up to date infrastructure of both instruction and learning. In addition, scientists get a high performance environment for the administration of its personnel, care of their web pages and the automatic generation of meeting- or personnel lists. Operators can access a reliable support system and may take part in a widespread developer community.
- Published
- 2005
16. Wittgenstein and Hegel: Reevaluation of Difference
- Author
-
Jakub Mácha, Alexander Berg, Jakub Mácha, Alexander Berg and Jakub Mácha, Alexander Berg, Jakub Mácha, Alexander Berg
- Published
- 2019
17. Hollow-fibre system model of tuberculosis reproducibility and performance specifications for best practice in drug and combination therapy development
- Author
-
Tawanda Gumbo, Shashikant Srivastava, Devyani Deshpande, Jotam G Pasipanodya, Alexander Berg, Klaus Romero, David Hermann, and Debra Hanna
- Subjects
Pharmacology ,Microbiology (medical) ,Infectious Diseases ,Pharmacology (medical) - Abstract
Background The hollow-fibre system model of tuberculosis (HFS-TB) has been endorsed by regulators; however, application of HFS-TB requires a thorough understanding of intra- and inter-team variability, statistical power and quality controls. Methods Three teams evaluated regimens matching those in the Rapid Evaluation of Moxifloxacin in Tuberculosis (REMoxTB) study, plus two high-dose rifampicin/pyrazinamide/moxifloxacin regimens, administered daily for up to 28 or 56 days against Mycobacterium tuberculosis (Mtb) under log-phase growth, intracellular growth or semidormant growth under acidic conditions. Target inoculum and pharmacokinetic parameters were pre-specified, and the accuracy and bias at achieving these calculated using percent coefficient of variation (%CV) at each sampling point and two-way analysis of variance (ANOVA). Results A total of 10 530 individual drug concentrations, and 1026 individual cfu counts were measured. The accuracy in achieving intended inoculum was >98%, and >88% for pharmacokinetic exposures. The 95% CI for the bias crossed zero in all cases. ANOVA revealed that the team effect accounted for 20% difference in slope, with a power of >99%. Conclusions HFS-TB is a highly tractable tool for choosing combination regimens with little variability between teams, and between replicates.
- Published
- 2023
18. A prognostic classification system for uveal melanoma based on a combination of patient age and sex, the American Joint Committee on Cancer and the Cancer Genome Atlas models
- Author
-
Viktor T. Gill, Shiva Sabazade, Christina Herrspiegel, Kathryn G. Ewens, Adrianna Opalko, Nicole Dan, Tinna Christersdottir, Alexander Berg Rendahl, Carol L. Shields, Stefan Seregard, Arupa Ganguly, and Gustav Stålhammar
- Subjects
Ophthalmology ,General Medicine - Abstract
To revisit the independent importance of ciliary body involvement (CBI), monosomy 3 (M3), tumour size, histological and clinical factors in uveal melanoma (UM) and to devise a new prognostic classification based on a combination of the American Joint Committee on Cancer (AJCC) and the Cancer Genome Atlas (TCGA) models.Two cohorts with a total of 1796 patients were included. Clinicopathological factors were compared between patients with and without CBI and M3. Development of the prognostic classification was performed in a training cohort and was then tested in two independent validation cohorts.Tumours with CBI were more common in women, had greater apical thickness, greater basal tumour diameter, greater rates of vasculogenic mimicry and greater rates of M3, were more often asymptomatic at diagnosis and had poorer 5- and 10-year globe conservation rates (p 0.023). In multivariate logistic regression, patient age at diagnosis, tumour diameter and CBI were independent predictors of M3 (p 0.001). In multivariate Cox regression, male sex, age at diagnosis, tumour diameter, M3 and CBI were independent predictors of metastasis. The proposed prognostic classification combined patient age, sex, CBI, extraocular extension, M3, 8q (optional) and tumour size, and demonstrated greater prognostic acumen than both AJCC 4 T categories and TCGA groups A to D in validation cohorts.Tumour size does not confound the prognostic implication of CBI, M3, male sex and age at diagnosis in UM. These factors were included in a new prognostic classification that outperforms AJCC T category and TCGA groups.
- Published
- 2022
19. Development of physiologically‐based pharmacokinetic models for standard of care and newer tuberculosis drugs
- Author
-
Iain Gardner, Oliver Hatley, Lisa Almond, Ben G Small, Klaus Romero, Mian Zhang, Helen Humphries, Xian Pan, Masoud Jamei, and Alexander Berg
- Subjects
medicine.medical_specialty ,Antitubercular Agents ,Cmax ,RM1-950 ,Gastroenterology ,Article ,chemistry.chemical_compound ,Pharmacokinetics ,Internal medicine ,Isoniazid ,medicine ,Humans ,Tuberculosis ,Pharmacology (medical) ,Ethambutol ,business.industry ,Research ,Area under the curve ,Standard of Care ,Articles ,Pyrazinamide ,Rifapentine ,chemistry ,Modeling and Simulation ,Ethionamide ,Therapeutics. Pharmacology ,Bedaquiline ,business ,medicine.drug - Abstract
Tuberculosis (TB) remains a global health problem and there is an ongoing effort to develop more effective therapies and new combination regimes that can reduce duration of treatment. The purpose of this study was to demonstrate utility of a physiologically‐based pharmacokinetic modeling approach to predict plasma and lung concentrations of 11 compounds used or under development as TB therapies (bedaquiline [and N‐desmethyl bedaquiline], clofazimine, cycloserine, ethambutol, ethionamide, isoniazid, kanamycin, linezolid, pyrazinamide, rifampicin, and rifapentine). Model accuracy was assessed by comparison of simulated plasma pharmacokinetic parameters with healthy volunteer data for compounds administered alone or in combination. Eighty‐four percent (area under the curve [AUC]) and 91% (maximum concentration [C max]) of simulated mean values were within 1.5‐fold of the observed data and the simulated drug‐drug interaction ratios were within 1.5‐fold (AUC) and twofold (C max) of the observed data for nine (AUC) and eight (C max) of the 10 cases. Following satisfactory recovery of plasma concentrations in healthy volunteers, model accuracy was assessed further (where patients’ with TB data were available) by comparing clinical data with simulated lung concentrations (9 compounds) and simulated lung: plasma concentration ratios (7 compounds). The 5th–95th percentiles for the simulated lung concentration data recovered between 13% (isoniazid and pyrazinamide) and 88% (pyrazinamide) of the observed data points (Am J Respir Crit Care Med, 198, 2018, 1208; Nat Med, 21, 2015, 1223; PLoS Med, 16, 2019, e1002773). The impact of uncertain model parameters, such as the fraction of drug unbound in lung tissue mass (fumass), is discussed. Additionally, the variability associated with the patient lung concentration data, which was sparse and included extensive within‐subject, interlaboratory, and experimental variability (as well interindividual variability) is reviewed. All presented models are transparently documented and are available as open‐source to aid further research.
- Published
- 2021
20. Comparison of the dietary omega-3 fatty acids impact on murine psoriasis-like skin inflammation and associated lipid dysfunction
- Author
-
Alexander V. Sorokin, Hildur Arnardottir, Maryia Svirydava, Qimin Ng, Yvonne Baumer, Alexander Berg, Carla J. Pantoja, Elizabeth M. Florida, Heather L. Teague, Zhi-Hong Yang, Pradeep K. Dagur, Tiffany M. Powell-Wiley, Zu-Xi Yu, Martin P. Playford, Alan T. Remaley, and Nehal N. Mehta
- Subjects
Nutrition and Dietetics ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Molecular Biology ,Biochemistry - Published
- 2023
21. Sputum lipoarabinomannan (LAM) as a biomarker to determine sputum mycobacterial load: exploratory and model-based analyses of integrated data from four cohorts
- Author
-
Aksana, Jones, Jay, Saini, Belinda, Kriel, Laura E, Via, Yin, Cai, Devon, Allies, Debra, Hanna, David, Hermann, Andre G, Loxton, Gerhard, Walzl, Andreas H, Diacon, Klaus, Romero, Ryo, Higashiyama, Yongge, Liu, Alexander, Berg, Institute of Infectious Disease and Molecular Medicine, and Faculty of Health Sciences
- Subjects
Lipopolysaccharides ,Infectious Diseases ,Lipoarabinomannan ,Sputum ,Humans ,Tuberculosis ,Mycobacterium tuberculosis ,Biomarker ,LAM ,bacterial infections and mycoses ,Biomarkers ,Mycobacterium - Abstract
Background Despite the high global disease burden of tuberculosis (TB), the disease caused by Mycobacterium tuberculosis (Mtb) infection, novel treatments remain an urgent medical need. Development efforts continue to be hampered by the reliance on culture-based methods, which often take weeks to obtain due to the slow growth rate of Mtb. The availability of a “real-time” measure of treatment efficacy could accelerate TB drug development. Sputum lipoarabinomannan (LAM; an Mtb cell wall glycolipid) has promise as a pharmacodynamic biomarker of mycobacterial sputum load. Methods The present analysis evaluates LAM as a surrogate for Mtb burden in the sputum samples from 4 cohorts of a total of 776 participants. These include those from 2 cohorts of 558 non-TB and TB participants prior to the initiation of treatment (558 sputum samples), 1 cohort of 178 TB patients under a 14-day bactericidal activity trial with various mono- or multi-TB drug therapies, and 1 cohort of 40 TB patients with data from the first 56-day treatment of a standard 4-drug regimen. Results Regression analysis demonstrated that LAM was a predictor of colony-forming unit (CFU)/mL values obtained from the 14-day treatment cohort, with well-estimated model parameters (relative standard error ≤ 22.2%). Moreover, no changes in the relationship between LAM and CFU/mL were observed across the different treatments, suggesting that sputum LAM can be used to reasonably estimate the CFU/mL in the presence of treatment. The integrated analysis showed that sputum LAM also appears to be as good a predictor of time to Mycobacteria Growth Incubator Tube (MGIT) positivity as CFU/mL. As a binary readout, sputum LAM positivity is a strong predictor of solid media or MGIT culture positivity with an area-under-the-curve value of 0.979 and 0.976, respectively, from receiver-operator curve analysis. Conclusions Our results indicate that sputum LAM performs as a pharmacodynamic biomarker for rapid measurement of Mtb burden in sputum, and thereby may enable more efficient early phase clinical trial designs (e.g., adaptive designs) to compare candidate anti-TB regimens and streamline dose selection for use in pivotal trials. Trial registration NexGen EBA study (NCT02371681)
- Published
- 2022
22. Model-Based Meta-Analysis of Relapsing Mouse Model Studies from the Critical Path to Tuberculosis Drug Regimens Initiative Database
- Author
-
Alexander Berg, James Clary, Debra Hanna, Eric Nuermberger, Anne Lenaerts, Nicole Ammerman, Michelle Ramey, Dan Hartley, David Hermann, and Medical Microbiology & Infectious Diseases
- Subjects
Pharmacology ,Mice ,Infectious Diseases ,SDG 3 - Good Health and Well-being ,Recurrence ,Antitubercular Agents ,Critical Pathways ,Animals ,Tuberculosis ,Pharmacology (medical) ,Mycobacterium tuberculosis - Abstract
Tuberculosis (TB), the disease caused by Mycobacterium tuberculosis (Mtb), remains a leading infectious disease-related cause of death worldwide, necessitating the development of new and improved treatment regimens. Nonclinical evaluation of candidate drug combinations via the relapsing mouse model (RMM) is an important step in regimen development, through which candidate regimens that provide the greatest decrease in the probability of relapse following treatment in mice may be identified for further development. Although RMM studies are a critical tool to evaluate regimen efficacy, making comprehensive "apples to apples" comparisons of regimen performance in the RMM has been a challenge in large part due to the need to evaluate and adjust for variability across studies arising from differences in design and execution. To address this knowledge gap, we performed a model-based meta-analysis on data for 17 unique regimens obtained from a total of 1592 mice across 28 RMM studies. Specifically, a mixed-effects logistic regression model was developed that described the treatment duration- dependent probability of relapse for each regimen and identified relevant covariates contributing to interstudy variability. Using the model, covariate-normalized metrics of interest, namely, treatment duration required to reach 50% and 10% relapse probability, were derived and used to compare relative regimen performance. Overall, the model-based meta-analysis approach presented herein enabled cross-study comparison of efficacy in the RMM and provided a framework whereby data from emerging studies may be analyzed in the context of historical data to aid in selecting candidate drug combinations for clinical evaluation as TB drug regimens.
- Published
- 2022
23. Cohort Profile:COVIDMENT: COVID-19 cohorts on mental health across six nations
- Author
-
Unnarsdóttir, Anna Bára, Lovik, Anikó, Fawns-Ritchie, Chloe, Ask, Helga, Kõiv, Kadri, Hagen, Kristen, Didriksen, Maria, Christoffersen, Lea Arregui Nordahl, Garðarsson, Alexander Berg, McIntosh, Andrew, Kähler, Anna K, Campbell, Archie, Hauksdóttir, Arna, Erikstrup, Christian, Mikkelsen, Dorte Helenius, Altschul, Drew, Thordardottir, Edda Bjork, Frans, Emma Maria, Kvale, Gerd, Tómasson, Gunnar, Kariis, Hanna Maria, Jónsdóttir, Harpa Lind, Rúnarsdóttir, Harpa, Magnúsdóttir, Ingibjörg, Eid, Jarle, Jakobsdóttir, Jóhanna, Nielsen, Kaspar René, Kaspersen, Kathrine Agergård, Milani, Lili, Trogstad, Lill-Iren Schou, Yi, Lu, Bruun, Mie Topholm, Sullivan, Patrick F, Magnus, Per Minor, Shen, Qing, Nesvåg, Ragnar, Brandlistuen, Ragnhild E, Mägi, Reedik, Ostrowski, Sisse Rye, Løkhammer, Solveig, Solem, Stian, Reichborn-Kjennerud, Ted, Hansen, Thomas Folkmann, Werge, Thomas, Aspelund, Thor, Porteous, David J, Fang, Fang, Lehto, Kelli, Andreassen, Ole A, Pedersen, Ole Birger Vesterager, Hellard, Stephanie Le, Valdimarsdóttir, Unnur A, Unnarsdóttir, Anna Bára, Lovik, Anikó, Fawns-Ritchie, Chloe, Ask, Helga, Kõiv, Kadri, Hagen, Kristen, Didriksen, Maria, Christoffersen, Lea Arregui Nordahl, Garðarsson, Alexander Berg, McIntosh, Andrew, Kähler, Anna K, Campbell, Archie, Hauksdóttir, Arna, Erikstrup, Christian, Mikkelsen, Dorte Helenius, Altschul, Drew, Thordardottir, Edda Bjork, Frans, Emma Maria, Kvale, Gerd, Tómasson, Gunnar, Kariis, Hanna Maria, Jónsdóttir, Harpa Lind, Rúnarsdóttir, Harpa, Magnúsdóttir, Ingibjörg, Eid, Jarle, Jakobsdóttir, Jóhanna, Nielsen, Kaspar René, Kaspersen, Kathrine Agergård, Milani, Lili, Trogstad, Lill-Iren Schou, Yi, Lu, Bruun, Mie Topholm, Sullivan, Patrick F, Magnus, Per Minor, Shen, Qing, Nesvåg, Ragnar, Brandlistuen, Ragnhild E, Mägi, Reedik, Ostrowski, Sisse Rye, Løkhammer, Solveig, Solem, Stian, Reichborn-Kjennerud, Ted, Hansen, Thomas Folkmann, Werge, Thomas, Aspelund, Thor, Porteous, David J, Fang, Fang, Lehto, Kelli, Andreassen, Ole A, Pedersen, Ole Birger Vesterager, Hellard, Stephanie Le, and Valdimarsdóttir, Unnur A
- Published
- 2022
24. FlexSensor: Automated measurement software for rapid photonic circuits capturing
- Author
-
Christoph Schmidt, Jakob Wilhelm Hinum-Wagner, Reinhard Klambauer, and Alexander Bergmann
- Subjects
Silicon photonics ,Wafer-level measurements ,Measurement automation ,Graphical user interface ,Computer software ,QA76.75-76.765 - Abstract
This paper introduces the automation measurement software FlexSensor for capturing resonant spectra, an innovative and extensible software program developed explicitly for measuring and evaluating wafer-level Silicon Photonic (SiPh) circuits. Wafer-level Silicon Photonics allows the integration of numerous optical components and structures on a single wafer. However, researchers and engineers need precise and repeatable measurements to characterize them and face significant challenges when dealing with large numbers of complex systems on a single wafer. A toolchain gap hampers the measuring of such highly integrated photonic structures: While the setup necessitates the integration of an optimized hardware and software toolchain, there is neither software nor a standardized way to implement a reproducible measurement routine for a massive set of measurements.FlexSensor allows integration and control of external hardware (tunable lasers, analog–digital converters) and supports measurement data storage and evaluation. The software enables researchers and engineers to efficiently analyze the spectral response of photonic structures and facilitate rapid measuring.
- Published
- 2024
- Full Text
- View/download PDF
25. Wittgenstein und die Begriffe des Psychischen bei Hegel
- Author
-
Alexander Berg
- Subjects
Philosophy of language ,Philosophy ,General Engineering ,Modern philosophy ,Theology ,History of philosophy - Abstract
Wittgenstein and the Concepts of Mind in Hegel. Hegel distinguishes three main forms of the (subjective) mind – the soul, the consciousness and the spirit. He seeks to use these concepts to rediscover the meaning of Aristotle’s works on the soul (Περὶ ψυχῆς) and, at the same time, to counteract certain scientistic tendencies within the philosophy of mind. Although Wittgenstein (most likely) was not aware of these Hegelian distinctions, his own use of the concepts of mind exhibits some remarkable similarities to Hegel’s, and Wittgenstein too develops his understanding of mind by first examining the scientific psychology of his time and delineating his own position by way of contrast with it.This article examines three areas in which Wittgenstein substantially developed his understanding of the concepts of mind. The sequence of the investigation follows the order in which these areas became significant for Wittgenstein’s thinking, and compares them in each case with the three main Hegelian forms of the concepts of mind.
- Published
- 2020
26. A qualitative study on music teachers' perceptions of digital composition for pupils in primary school
- Author
-
Hansson, Alexander Berg and Eidsvaag, Fritz Flåmo
- Subjects
iPad ,Musikk ,Musikkinstrumenter ,Musikk på iPad ,Improvisasjon ,Digital komponering ,GarageBand ,Barneskolen ,Musikklærere - Abstract
Denne masteroppgaven er basert på fire musikklæreres utsagn om hvordan de oppfatter at bruk av iPad bidrar til å heve kvaliteten på sine elevers arbeidsprosess og produkter når de skal lage musikk. Det fokuseres både på positive og negative aspekter ved dette. Informantene er norske lærere på ulike barneskoler i Bærum. Hovedproblemstillingen i denne masteroppgaven er: Hvordan oppfatter musikklærere at bruk av digitale verktøy kan virke hemmende eller fremmende for elevers arbeid med komponering på barneskolen, sammenlignet med tradisjonelle musikkinstrumenter? I læreplanen (LK20) for musikkfaget er digitale ferdigheter og det å lage musikk to viktige elementer. Data fra studien viser at lærerne mener det er mange gode grunner til at vi må bruke de digitale ressursene skolen har tilgjengelig når elever skal komponere og improvisere. Disse funnene støttes av tidligere forskning på digital komponering i skolen. Lærerne mener også at det er viktig å ta vare på tradisjonen med akustiske instrumenter og lydkilder, og kan med fordel kombineres med de mange lydene som finnes på iPaden, i GarageBand spesielt. This master's thesis is based on statements from four music teachers of how they perceive the use of iPad helps to raise the quality of their students' work process and musical products when they make music in school. It focuses on both positive and negative aspects of this. The informants are Norwegian teachers at various primary schools in Bærum. The main research question in this master's thesis is: How do music teachers perceive that the use of digital tools can have an inhibiting or promoting effect on students' engagement in composition in primary school, in relation to traditional musical instruments? In the Norwegian curriculum (LK20) for music, digital skills and making music are two important elements. Data in the study shows that the teachers believe there are many good reasons why we must use the digital resources at the school when students compose and improvise music. These findings are supported by previous research on digital composition in schools. The teachers also believe that it is important to hold on to the tradition of acoustic instruments and sound sources, and can be combined with the many sounds found on the iPad, in GarageBand in particular.
- Published
- 2022
27. Duration of pretomanid/moxifloxacin/pyrazinamide therapy compared with standard therapy based on time-to-extinction mathematics
- Author
-
Kayle N Cirrincione, Johanna S. van Zyl, Shashikant Srivastava, Alexander Berg, Klaus Romero, Dave Hermann, Katherine Riley Martin, Gesham Magombedze, Paula Bendet, Debra Hanna, Tawanda Gumbo, and Devyani Deshpande
- Subjects
Pharmacology ,Microbiology (medical) ,Combination therapy ,Moxifloxacin ,Antitubercular Agents ,Phases of clinical research ,Mycobacterium tuberculosis ,Pyrazinamide ,Clinical trial ,Regimen ,Infectious Diseases ,Nitroimidazoles ,Anesthesia ,medicine ,Credible interval ,Humans ,Tuberculosis ,Combined Modality Therapy ,Drug Therapy, Combination ,Pharmacology (medical) ,Mathematics ,Original Research ,medicine.drug - Abstract
ObjectivesAnimal models have suggested that the combination of pretomanid with pyrazinamide and moxifloxacin (PaMZ) may shorten TB therapy duration to 3–4 months. Here, we tested that in the hollow-fibre system model of TB (HFS-TB).MethodsA series of HFS-TB experiments were performed to compare the kill rates of the PaMZ regimen with the standard three-drug combination therapy. HFS-TB experiments were performed with bacilli in log-phase growth treated for 28 days, intracellular bacilli treated daily for 28 days and semi-dormant Mycobacterium tuberculosis treated with daily therapy for 56 days for sterilizing effect. Next, time-to-extinction equations were employed, followed by morphism transformation and Latin hypercube sampling, to determine the proportion of patients who achieved a time to extinction of 3, 4 or 6 months with each regimen.ResultsUsing linear regression, the HFS-TB sterilizing effect rates of the PaMZ regimen versus the standard-therapy regimen during the 56 days were 0.18 (95% credible interval=0.13–0.23) versus 0.15 (95% credible interval=0.08–0.21) log10 cfu/mL/day, compared with 0.16 (95% credible interval=0.13–0.18) versus 0.11 (95% credible interval=0.09–0.13) log10 cfu/mL/day in the Phase II clinical trial, respectively. Using time-to-extinction and Latin hypercube sampling modelling, the expected percentages of patients in which the PaMZ regimen would achieve sterilization were 40.37% (95% credible interval=39.1–41.34) and 72.30% (95% credible interval=71.41–73.17) at 3 and 4 months duration of therapy, respectively, versus 93.67% (95% credible interval=93.18–94.13) at 6 months for standard therapy.ConclusionsThe kill rates of the PaMZ regimen were predicted to be insufficient to achieve cure in less than 6 months in most patients.
- Published
- 2019
28. Cohort Profile:COVIDMENT: COVID-19 cohorts on mental health across six nations
- Author
-
Anna Bára Unnarsdóttir, Anikó Lovik, Chloe Fawns-Ritchie, Helga Ask, Kadri Kõiv, Kristen Hagen, Maria Didriksen, Lea Arregui Nordahl Christoffersen, Alexander Berg Garðarsson, Andrew McIntosh, Anna K Kähler, Archie Campbell, Arna Hauksdóttir, Christian Erikstrup, Dorte Helenius Mikkelsen, Drew Altschul, Edda Bjork Thordardottir, Emma Maria Frans, Gerd Kvale, Gunnar Tómasson, Hanna Maria Kariis, Harpa Lind Jónsdóttir, Harpa Rúnarsdóttir, Ingibjörg Magnúsdóttir, Jarle Eid, Jóhanna Jakobsdóttir, Kaspar René Nielsen, Kathrine Agergård Kaspersen, Lili Milani, Lill-Iren Schou Trogstad, Lu Yi, Mie Topholm Bruun, Patrick F Sullivan, Per Minor Magnus, Qing Shen, Ragnar Nesvåg, Ragnhild E Brandlistuen, Reedik Mägi, Sisse Rye Ostrowski, Solveig Løkhammer, Stian Solem, Ted Reichborn-Kjennerud, Thomas Folkmann Hansen, Thomas Werge, Thor Aspelund, David J Porteous, Fang Fang, Kelli Lehto, Ole A Andreassen, Ole Birger Vesterager Pedersen, Stephanie Le Hellard, and Unnur A Valdimarsdóttir
- Subjects
Cohort Profile ,Epidemiology ,Mental Disorders ,QUESTIONNAIRE ,COVID-19 ,General Medicine ,DEPRESSION ,Cohort Studies ,Mental Health ,ANXIETY ,Humans ,AcademicSubjects/MED00860 ,SCALE ,Mental Disorders/epidemiology - Abstract
Key features • COVIDMENT [www.covidment.is] is a NordForsk-funded research collaboration across six nations, with the overarching aim to significantly advance current knowledge on mental morbidity trajectories associated with the coronavirus disease 2019 (COVID-19) in the general population and in specific risk groups. • From March 2020 through August 2021, 392 817 individuals have been recruited to the seven COVIDMENT cohorts: the Danish Blood Donor Study (N ¼ 71 562), the Estonian Biobank COVID-19 and Mental Health Data Collection cohorts (N ¼ 13 329 and N ¼ 86 116, respectively), the Icelandic COVID-19 National Resilience Cohort (N ¼ 22 849), the Norwegian BRY.DEG2020 (N ¼ 19 343), the Norwegian Mother, Father and Child Cohort Study (N ¼ 132 486), the Scottish Generation Scotland/CovidLife (N ¼ 18 518) and the Swedish Omtanke2020 (N ¼ 28 614). Semi-harmonized questionnaire data have been collected across all COVIDMENT cohorts with longitudinal data available, e.g. through linkage to the national registers. • The average age of participants ranged from 31.8 to 58.5 years across cohorts. The prevalence of depressive symptoms above cut-off point varied considerably across cohorts (4.2–20.8%). The prevalence of depressive symptoms was highest at COVID-19 incidence of 30 cases per week per 100 000 persons, i.e. 14.3% [95% confidence interval (CI): 9.4–21.8%], which was 61.0% (95% CI: 34.0–94.1%) higher than the prevalence at COVID-19 incidence of 0 cases per week per 100 000 persons (P ¼ 1.1 x 10 ^( 6)). •
- Published
- 2021
29. Transzendenz bei Hegel und Heidegger
- Author
-
Alexander Berg and Alexander Berg
- Published
- 2012
30. Cohort Profile: COVIDMENT: COVID-19 cohorts on mental health across six nations
- Author
-
Unnarsdóttir, Anna Bára, primary, Lovik, Anikó , additional, Fawns-Ritchie, Chloe, additional, Ask, Helga, additional, Kõiv, Kadri, additional, Hagen, Kristen, additional, Didriksen, Maria, additional, Christoffersen, Lea Arregui Nordahl, additional, Garðarsson, Alexander Berg, additional, McIntosh, Andrew, additional, Kähler, Anna K, additional, Campbell, Archie, additional, Hauksdóttir, Arna, additional, Erikstrup, Christian, additional, Mikkelsen, Dorte Helenius, additional, Altschul, Drew, additional, Thordardottir, Edda Bjork, additional, Frans, Emma Maria, additional, Kvale, Gerd, additional, Tómasson, Gunnar, additional, Kariis, Hanna Maria, additional, Jónsdóttir, Harpa Lind, additional, Rúnarsdóttir, Harpa, additional, Magnúsdóttir, Ingibjörg, additional, Eid, Jarle, additional, Jakobsdóttir, Jóhanna, additional, Nielsen, Kaspar René, additional, Kaspersen, Kathrine Agergård, additional, Milani, Lili, additional, Trogstad, Lill-Iren Schou, additional, Yi, Lu, additional, Bruun, Mie Topholm, additional, Sullivan, Patrick F, additional, Magnus, Per Minor, additional, Shen, Qing, additional, Nesvåg, Ragnar, additional, Brandlistuen, Ragnhild E, additional, Mägi, Reedik, additional, Ostrowski, Sisse Rye, additional, Løkhammer, Solveig, additional, Solem, Stian, additional, Reichborn-Kjennerud, Ted, additional, Hansen, Thomas Folkmann, additional, Werge, Thomas, additional, Aspelund, Thor, additional, Porteous, David J, additional, Fang, Fang, additional, Lehto, Kelli, additional, Andreassen, Ole A, additional, Pedersen, Ole Birger Vesterager, additional, Hellard, Stephanie Le, additional, and Valdimarsdóttir, Unnur A, additional
- Published
- 2021
- Full Text
- View/download PDF
31. Ultrafast electron transfer in a self-assembling sulfonated aluminum corrole–methylviologen complex
- Author
-
Zeev Gross, Karsten Heyne, Till Stensitzki, Alexander Berg, Clark Zahn, Atif Mahammed, and Angelica Zacarias
- Subjects
Photosynthetic reaction centre ,Paraquat ,Materials science ,Porphyrins ,Electrons ,Photoinduced electron transfer ,Surfaces, Coatings and Films ,Electron Transport ,chemistry.chemical_compound ,Electron transfer ,chemistry ,Photoinduced charge separation ,Chemical physics ,Ultrafast laser spectroscopy ,Materials Chemistry ,Physical and Theoretical Chemistry ,Corrole ,Absorption (electromagnetic radiation) ,Spectroscopy ,Aluminum - Abstract
Photoinduced electron transfer systems can mimic certain features of natural photosynthetic reaction centers, which are crucial for solar energy production. Among other tetra-pyrroles, the versatile chemical and photophysical properties of corroles make them very promising donors applicable in donor–acceptor complexes. Here, we present a first comprehensive study of ultrafast photoinduced electron transfer in a self-assembling sulfonated aluminum corrole–methylviologen complex combining visible and mid-IR transient absorption spectroscopy. The noncovalent D–A association of the corrole–methylviologen complex has the great advantage that photoinduced charge separation becomes possible even though the back electron transfer (BET) rate is large. Initial forward electron transfer from corrole to methylviologen is observed on an ∼130 fs time scale. Subsequent back electron transfer takes place with τBET = (1.8 ± 0.5) ps, revealing very complex relaxation dynamics. Direct probing in the mid-IR allows us to unravel the back electron transfer and cooling dynamics/electronic reorganization. Upon tracing the dynamics of the methylviologen-radical marker band at 1640 cm–1 and the C═C stretching of corrole at around 1500 cm–1, we observe that large amounts of excess energy survive the back transfer, leading to the formation of hot ground state absorption. A closer examination of the signal after 300 ps, surviving the back transfer, exhibits a charge-separation yield of 10–15%.
- Published
- 2021
32. Dynamics of task preparation processes revealed by effect course analysis on response times and error rates
- Author
-
Alexander Berger, Wilfried Kunde, and Markus Kiefer
- Subjects
Medicine ,Science - Abstract
Abstract Cuing or executing a task impacts processing pathways for task-relevant information. While there is ample evidence that processing associated with task execution changes with practice, such evidence regarding cue-induced task preparation is scarce. Here we explored practice-related changes of processing pathways by task cuing in order to assess the plasticity of task preparation. We first developed and validated a new method for the study of practice-related changes, the effect course analysis. The effect course analysis is a model-free, non-parametric method designed to reveal effect changes within an experimental session on a continuous time scale. Then we applied this method to a new study in which cued task sets were supposed to remain activated during assessment of task-relevant pathways, as potential task execution was postponed at the end of the trial. The results showed that, with little practice, task cuing amplified task-relevant pathways, whereas this effect vanished with practice, suggesting that practice prompts fundamental changes of how task cues are used for task preparation. Hence, if one cannot be certain that cognitive processing is stationary, investigating the time course of experimental effects appears to be crucial to determine how cognitive processing is influenced by practice.
- Published
- 2024
- Full Text
- View/download PDF
33. Wittgenstein and Classical German Philosophy
- Author
-
Alexander Berg, Denys Kaidalov, Alexander Berg, and Denys Kaidalov
- Abstract
The contributors in this volume situate Wittgenstein's philosophy within the context of Kant, Hegel, Fichte, and Schelling. They show how his philosophy both stands in the tradition of German idealism while breaking new ground. The topics of logic and language make this tension especially palpable and allow the authors to reveal new connections and offer critical perspectives.
- Published
- 2025
34. Cuticular hydrocarbons on old museum specimens of the spiny mason wasp, Odynerus spinipes (Hymenoptera: Vespidae: Eumeninae), shed light on the distribution and on regional frequencies of distinct chemotypes
- Author
-
Sergey A. Belokobylskij, Aline Wirtgen, Villu Soon, Alexander Berg, Katharina Christmann, Thomas Schmitt, Victoria C. Moris, Oliver Niehuis, Wolf‑Harald Liebig, and Hannes Baur
- Subjects
0106 biological sciences ,0301 basic medicine ,Entomology ,Range (biology) ,Population ,Zoology ,Hymenoptera ,010603 evolutionary biology ,01 natural sciences ,Biochemistry ,03 medical and health sciences ,Odynerus spinipes ,education ,Ecology, Evolution, Behavior and Systematics ,education.field_of_study ,Ecology ,Vespidae ,biology ,Chemotype ,Biochemistry and Molecular Biology ,500 Science ,biology.organism_classification ,Sexual dimorphism ,030104 developmental biology ,Biological dispersal ,570 Life sciences - Abstract
The mason wasp Odynerus spinipes shows an exceptional case of intrasexual cuticular hydrocarbon (CHC) profile dimorphism. Females of this species display one of two CHC profiles (chemotypes) that differ qualitatively and quantitatively from each other. The ratio of the two chemotypes was previously shown to be close to 1:1 at three sites in Southern Germany, which might not be representative given the Palearctic distribution of the species. To infer the frequency of the two chemotypes across the entire distributional range of the species, we analyzed with GC–MS the CHC profile of 1042 dry-mounted specimens stored in private and museum collections. We complemented our sampling by including 324 samples collected and preserved specifically for studying their CHCs. We were capable of reliably identifying the chemotypes in 91% of dry-mounted samples, some of which collected almost 200 years ago. We found both chemotypes to occur in the Far East, the presumed glacial refuge of the species, and their frequency to differ considerably between sites and geographic regions. The geographic structure in the chemotype frequencies could be the result of differential selection regimes and/or different dispersal routes during the colonization of the Western Palearctic. The presented data pave the route for disentangling these factors by providing information where to geographically sample O. spinipes for population genetic analyses. They also form the much-needed basis for future studies aiming to understand the evolutionary and geographic origin as well as the genetics of the astounding CHC profile dimorphism that O. spinipes females exhibit.
- Published
- 2021
35. MODL-25. Radiation and focused ultrasound–mediated blood–brain barrier opening for DMG: safety and feasibility of combinatorial therapy
- Author
-
Nicholas McQuillan, Masih Tazhibi, Hong-Jian Wei, Antonios Pouliopoulos, Ethan Bendau, Andrea Webster Carrion, Alexander Berg, Danae Kokossis, Xu Zhang, Zhiguo Zhang, Zachary Englander, Nina Yoh, Chia-Ing Jan, Robyn D Gartrell, James Garvin, Luca Szalontay, Elisa Konofagou, Stergios Zacharoulis, and Cheng-Chia Wu
- Subjects
Cancer Research ,Oncology ,Neurology (clinical) - Abstract
Diffuse midline glioma (DMG) is a pediatric tumor with dismal prognosis. Systemic therapeutic strategies have been unsuccessful to date and radiotherapy (RT) remains the standard of care. A central impediment to systemic therapy is the blood-brain barrier (BBB), which precludes drug delivery to the tumor site. Focused ultrasound (FUS) with intravenous microbubbles can transiently and non-invasively circumvent the BBB to enhance drug delivery. Nevertheless, it remains unclear whether FUS is safe at the brainstem in combination with clinical doses of RT. In this study, we hypothesized that FUS-mediated BBB-opening (BBBO) is safe and feasible with 39 Gy RT. To establish a safety timeline, we administered FUS to the brainstem of nontumor bearing mice concurrent with or adjuvant to radiation; then, we validated our findings in a syngeneic orthotopic xenograft DMG model which received repeated sonication concurrent with RT. Male B6 (Cg)-Tyrc-2J/J albino mice received intracranial injection of 4423 mouse DMG cells (PDGFB+, H3.3K27M, p53−/−) at a location posterior and lateral to the lambda. A clinical RT dose of 39 Gy in 13 fractions was delivered to the brainstem with the Small Animal Radiation Research Platform (SARRP) or the XRAD-320 irradiator. FUS was administered with a 0.5 MHz transducer, and both BBBO and tumor volume were monitored with MRI. FUS-mediated BBBO in nontumor bearing mice receiving RT did not affect cardiorespiratory rate, motor function, and tissue integrity. Moreover, tumor bearing mice tolerated repeated brainstem BBBO concurrent with RT. 39 Gy over 13 fractions offered local control, although disease progression occurred in all animals approximately 3-4 weeks post-RT. Ultimately, repeated FUS-mediated BBB opening concurrent with RT is safe and feasible. In our brainstem DMG model, relapse occurs, making it ideal for future tests of combinatorial RT and FUS-mediated drug delivery.
- Published
- 2022
36. Ultraschallunterstützter Schmelzklebstoffauftrag
- Author
-
Alexander Berg, Markus Schleser, Artem Delidovich, and Alexander Houben
- Subjects
Polymers and Plastics ,General Chemical Engineering ,General Chemistry - Published
- 2018
37. Nahrungsbeziehungen als Wechselwirkungen verstehen - Eine explorative Studie zur Wirkung von Conceptual Change-Stories
- Author
-
Cornelia Averdunk, Jörg Zabel, and Alexander Bergmann-Gering
- Subjects
Conceptual Change Story ,Conceptual Change ,Nahrungsbeziehungen ,Wechselwirkung ,Sekundarstufe I ,Special aspects of education ,LC8-6691 - Abstract
Wechselwirkung ist ein zentrales, übergreifendes Konzept im Bereich Ökologie. Nahrungsbeziehungen in Ökosystemen eignen sich besonders, um das Konzept Wechselwirkung in der Sekundarstufe I beispielhaft einzuführen. Studien zeigen, dass Lernenden die elaborierte Beschreibung von Nahrungsbeziehungen schwerfällt und sie oftmals nur direkte Wechselwirkungen beschreiben. In der Forschungsliteratur wird ein Bedarf an unterrichtlichen Strategien benannt, mit deren Hilfe Schüler:innen aufbauend auf ihre bisherigen Konzepte fachlich angemessenere entwickeln können und dabei Nahrungsbeziehungen auch als indirekte und zyklische Wechselwirkungen erklären. Das Projekt entwickelt auf Basis von Conceptual Change-Texts ein innovatives Lernmedium: Conceptual Change-Stories. Diese greifen Konstruktionsprinzipien von Conceptual Change-Texts auf, bieten aber durch die narrative Textgestaltung vereinfachte Zugänge zum Verstehen von Nahrungsbeziehungen als Wechsel-wirkungen. In der vorliegenden Studie wird die Wirkung der Conceptual Change-Stories auf die Beschreibungen von Nah-rungsbeziehungen bei Schüler:innen der Klassenstufe 6 untersucht. Die Ergebnisse liefern Anhaltspunkte zur (Weiter-) Entwicklung von Conceptual Change-Stories. Erste Ergebnisse deuten an, dass Conceptual Change-Stories ein geeignetes Lern-medium darstellen können, um Wechselwirkungen im Nahrungsnetz verstehbar zu machen.
- Published
- 2024
- Full Text
- View/download PDF
38. Wittgensteins Hegel
- Author
-
Alexander Berg and Reiner Roos
- Published
- 2021
39. Analysis of RNA-Seq, DNA Target Enrichment, and Sanger Nucleotide Sequence Data Resolves Deep Splits in the Phylogeny of Cuckoo Wasps (Hymenoptera: Chrysididae)
- Author
-
Carlo Polidori, Yolanda Ballesteros, Eric P. van den Berghe, Paolo Rosa, Jeroen de Rond, Massimo Olmi, Bernhard Misof, Thomas Schmitt, Lars Podsiadlowski, Adalgisa Guglielmino, Thomas Pauli, Karen Meusemann, Franco Strumia, Ralph S. Peters, Hermes E. Escalona, Christoph Mayer, Xin Zhou, Manfred Niehuis, Alexander Berg, Jan Philip Oeyen, Mareike Wurdack, Alexander Donath, Shanlin Liu, Manuela Sann, Oliver Niehuis, and Sandra Kukowka
- Subjects
0106 biological sciences ,0301 basic medicine ,biology ,Nucleic acid sequence ,RNA-Seq ,Hymenoptera ,biology.organism_classification ,010603 evolutionary biology ,01 natural sciences ,Target enrichment ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,chemistry ,Phylogenetics ,Evolutionary biology ,Insect Science ,Animal Science and Zoology ,Cuckoo ,Ecology, Evolution, Behavior and Systematics ,DNA ,Developmental Biology - Abstract
The wasp family Chrysididae (cuckoo wasps, gold wasps) comprises exclusively parasitoid and kleptoparasitic species, many of which feature a stunning iridescent coloration and phenotypic adaptations to their parasitic life style. Previous attempts to infer phylogenetic relationships among the family’s major lineages (subfamilies, tribes, genera) based on Sanger sequence data were insufficient to statistically resolve the monophyly and the phylogenetic position of the subfamily Amiseginae and the phylogenetic relationships among the tribes Allocoeliini, Chrysidini, Elampini, and Parnopini (Chrysidinae). Here, we present a phylogeny inferred from nucleotide sequence data of 492 nuclear single-copy genes (230,915 aligned amino acid sites) from 94 species of Chrysidoidea (representing Bethylidae, Chrysididae, Dryinidae, Plumariidae) and 45 outgroup species by combining RNA-seq and DNA target enrichment data. We find support for Amiseginae being more closely related to Cleptinae than to Chrysidinae. Furthermore, we find strong support for Allocoeliini being the sister lineage of all remaining Chrysidinae, whereas Elampini represent the sister lineage of Chrysidini and Parnopini. Our study corroborates results from a recent phylogenomic investigation, which revealed Chrysidoidea as likely paraphyletic.
- Published
- 2021
40. Cumulative Fraction of Response for Once- and Twice-Daily Delamanid in Patients with Pulmonary Multidrug-Resistant Tuberculosis
- Author
-
Tomohiro Sasaki, Hirota Kuniko, Shashikant Srivastava, Tawanda Gumbo, Moti L. Chapagain, Yusuke Inoue, Makoto Matsumoto, Lawrence Geiter, Jeffrey Hafkin, Devyani Deshpande, Norimitsu Hariguchi, Yongge Liu, Xiaofeng Wang, Alexander Berg, and Suresh Mallikaarjun
- Subjects
Tuberculosis ,PK-PD target ,Antitubercular Agents ,Pharmacology ,delamanid ,Mycobacterium tuberculosis ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Tuberculosis, Multidrug-Resistant ,medicine ,Animals ,Humans ,Pharmacology (medical) ,PK-PD index ,030212 general & internal medicine ,Dosing ,Oxazoles ,0303 health sciences ,biology ,030306 microbiology ,business.industry ,QTcF Prolongation ,hollow-fiber system model of tuberculosis ,biology.organism_classification ,medicine.disease ,Infectious Diseases ,cumulative fraction of response ,Nitroimidazoles ,Pharmacodynamics ,Sputum ,Delamanid ,medicine.symptom ,business ,medicine.drug - Abstract
Pharmacokinetic (PK) and pharmacodynamic (PD) analyses were conducted to determine the cumulative fraction of response (CFR) for 100 mg twice-daily (BID) and 200 mg once-daily (QD) delamanid in patients with multidrug-resistant tuberculosis (MDR-TB), using a pharmacodynamic target (PDT) that achieves 80% of maximum efficacy. First, in the mouse model of chronic TB, the PK/PD index for delamanid efficacy was determined to be area under the drug concentration-time curve over 24 h divided by MIC (AUC0–24/MIC), with a PDT of 252., Pharmacokinetic (PK) and pharmacodynamic (PD) analyses were conducted to determine the cumulative fraction of response (CFR) for 100 mg twice-daily (BID) and 200 mg once-daily (QD) delamanid in patients with multidrug-resistant tuberculosis (MDR-TB), using a pharmacodynamic target (PDT) that achieves 80% of maximum efficacy. First, in the mouse model of chronic TB, the PK/PD index for delamanid efficacy was determined to be area under the drug concentration-time curve over 24 h divided by MIC (AUC0–24/MIC), with a PDT of 252. Second, in the hollow-fiber system model of tuberculosis, plasma-equivalent PDTs were identified as an AUC0–24/MIC of 195 in log-phase bacteria and 201 in pH 5.8 cultures. Third, delamanid plasma AUC0–24/MIC and sputum bacterial decline data from two early bactericidal activity trials identified a clinical PDT of AUC0–24/MIC of 171. Finally, the CFRs for the currently approved 100-mg BID dose were determined to be above 95% in two MDR-TB clinical trials. The CFR for the 200-mg QD dose, evaluated in a trial in which delamanid was administered as 100 mg BID for 8 weeks plus 200 mg QD for 18 weeks, was 89.3% based on the mouse PDT and >90% on the other PDTs. QTcF (QTc interval corrected for heart rate by Fridericia’s formula) prolongation was approximately 50% lower for the 200 mg QD dose than the 100 mg BID dose. In conclusion, while CFRs of 100 mg BID and 200 mg QD delamanid were close to or above 90% in patients with MDR-TB, more-convenient once-daily dosing of delamanid is feasible and likely to have less effect on QTcF prolongation.
- Published
- 2020
41. Rigorous Design Optimization of a Fiber-Enabled Polarimetric Waveguide Interferometer for Biosensing
- Author
-
Samuel M. Hormann, Gandolf Feigl, Jakob W. Hinum-Wagner, and Alexander Bergmann
- Subjects
Integrated photonics ,silicon nitride ,interferometer ,polarimeter ,biosensing ,point-of-care ,Applied optics. Photonics ,TA1501-1820 ,Optics. Light ,QC350-467 - Abstract
Integrated photonic sensors have gained significant attention for biosensing applications. An especially potent design is the polarimetric waveguide interferometer, which utilizes polarization diversity for effective self-referencing. However, its implementations are held back by the need for bulky free-space optics or unreliable waveguide junctions for polarization handling. To overcome these limitations, we propose a novel concept for a compact photonic system that employs edge couplers to excite both polarizations from an optical fiber and an in-line polarizer to obtain the phase information in the fiber-based readout. Additionally, we improve the waveguide design methodology to minimize the limit of detection through balancing sensitivity with optical loss. To this end, we create a unified perturbative approach based on atomic force microscopy and ellipsometry data to model sensitivity, surface-roughness-induced scattering, absorption, and radiation. We then incorporate the coupling efficiency into a figure of merit for the combined system. Thus, we optimize the geometry of a strip waveguide on a CMOS-foundry-sourced silicon nitride platform for biosensing. Through exhaustive screening of the design space, we discover that polarization diversity simultaneously leverages high sensitivity and low overlap with sidewall roughness. Further, we present designs that eliminate the phase signal from two major noise sources: thermal and bulk refractive index fluctuations. Finally, we provide design recommendations and achieve a 5.2-fold improvement over a comparable bimodal waveguide interferometer. Thus, our aim is to design a robust, compact, sensitive, and cost-effective polarimetric waveguide interferometer through an efficient concept and an optimized design.
- Published
- 2024
- Full Text
- View/download PDF
42. Cohort Profile: COVIDMENT: COVID-19 cohorts on mental health across six nations.
- Author
-
Unnarsdóttir, Anna Bára, Lovik, Anikó, Fawns-Ritchie, Chloe, Ask, Helga, Kõiv, Kadri, Hagen, Kristen, Didriksen, Maria, Christoffersen, Lea Arregui Nordahl, Garðarsson, Alexander Berg, McIntosh, Andrew, Kähler, Anna K, Campbell, Archie, Hauksdóttir, Arna, Erikstrup, Christian, Mikkelsen, Dorte Helenius, Altschul, Drew, Thordardottir, Edda Bjork, Frans, Emma Maria, Kvale, Gerd, and Tómasson, Gunnar
- Published
- 2022
- Full Text
- View/download PDF
43. Qualitative and Quantitative Analyses of Automotive Exhaust Plumes for Remote Emission Sensing Application Using Gas Schlieren Imaging Sensor System
- Author
-
Hafiz Hashim Imtiaz, Paul Schaffer, Yingjie Liu, Paul Hesse, Alexander Bergmann, and Martin Kupper
- Subjects
remote emission sensing ,synthetic schlieren imaging ,background-oriented schlieren imaging ,optical gas imaging ,exhaust detection ,exhaust plume size measurement ,Meteorology. Climatology ,QC851-999 - Abstract
Remote emission sensing (RES) is a state-of-the-art technique for monitoring thousands of vehicles on the road every day to detect high emitters. Modern commercial RES systems use absorption spectroscopy to measure the ratio of pollutants to CO2 from vehicle exhaust gases. In this work, we present an approach to enable direct concentration measurements by spectroscopic techniques in RES through measurement of the absorption path length. Our gas schlieren imaging sensor (GSIS) system operates on the principle of background-oriented schlieren (BOS) imaging in combination with advanced image processing and deep learning techniques to calculate detected exhaust plume sizes. We performed a qualitative as well as a quantitative analysis of vehicle exhaust and plume dimensions with the GSIS system. We present the system details and results from the GSIS system in the lab in comparison to a BOS model based on flow simulations, the results from characterization measurements in the lab with defined gas mixtures and temperatures, and the results from measurements on the road from different vehicles.
- Published
- 2024
- Full Text
- View/download PDF
44. Vorüberlegungen
- Author
-
Alexander Berg
- Published
- 2020
45. Die Bedeutung von Wittgensteins Phoenix-Park-Satz
- Author
-
Alexander Berg
- Published
- 2020
46. Literatur
- Author
-
Alexander Berg
- Published
- 2020
47. Danksagung
- Author
-
Alexander Berg
- Published
- 2020
48. Philosophische Eso- und Exoterik
- Author
-
Alexander Berg
- Published
- 2020
49. Familienähnlichkeit und Sprachspiel
- Author
-
Alexander Berg
- Published
- 2020
50. Was ist Philosophie?
- Author
-
Alexander Berg
- Published
- 2020
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.