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A new paradigm for diagnosis of neurodegenerative diseases: peripheral exosomes of brain origin

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Translational Neurodegeneration 2022年第1期11卷 532-546页

作者： Neelam Younas Leticia Camila Fernandez Flores Franziska Hopfner Günter U.Höglinger inga Zerr Prion Research Group Department of NeurologyNational Reference Center for Surveillance of TSEUniversitätsklinikum Göttingen:Universitätsmedizin GöttingenGeorg-August UniversityGöttingenGermanyRobert-Koch-Strasse 4037075 GöttingenGermany Hannover Medical School Medizinische Hochschule HannoverHannoverGermany German Center for Neurodegenerative Diseases(DZNe) MunichGermany German Center for Neurodegenerative Diseases(DZNe) GöttingenGermany.

Neurodegenerative diseases are a heterogeneous group of maladies, characterized by progressive loss of neurons. These diseases involve an intricate pattern of cross-talk between different types of cells to maintain specific signaling pathways. A component of such intercellular cross-talk is the exchange of various types of extracellular vesicles (eVs). exosomes are a subset of eVs, which are increasingly being known for the role they play in the pathogenesis and progression of neurodegenerative diseases, e.g., synucleinopathies and tauopathies. The ability of the central nervous system exosomes to cross the blood-brain barrier into blood has generated enthusiasm in their study as potential biomarkers. However, the lack of standardized, efficient, and ultra-sensitive methods for the isolation and detection of brain-derived exosomes has hampered the development of effective biomarkers. exosomes mirror heterogeneous biological changes that occur during the progression of these incurable illnesses, potentially offering a more comprehensive outlook of neurodegenerative disease diagnosis, progression and treatment. In this review, we aim to discuss the challenges and opportunities of peripheral biofluid-based brain-exosomes in the diagnosis and biomarker discovery of Alzheimer’s and Parkinson’s diseases. In the later part, we discuss the traditional and emerging methods used for the isolation of exosomes and compare their advantages and disadvantages in clinical settings.

关键词： Alzheimer’s disease Central nervous system Diagnosis exosomes Blood-brain barrier Parkinson’s disease

Microindentation as a perspective method for determination of mechanical properties of ribbon metallic glasses

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广东有色金属学报 2005年第2期15卷 185-187页

作者： Victor A.Feodorov inga Y.permyakova Andrey N. Kapustin Depart ment of General Physics Derzhavin Tambov State University Tambov 392622 Russia

Conditions of gauging of true microhardness of thin ribbons metallic glasses (MG) with the count of their depth are established. For the first time the method of a indentation was approved for an assessment of crack resistance of MG. The behavior of parameterK_ Ic is found in a interval of temperature of viscous-brittle transition down to the beginning of volumetric crystallization of MG. The estimation method of temperature of viscous - brittle transition is offered at the microindentation of annealing ribbon on an elastic substrate.

关键词：玻璃金属材料结构参数结晶化

Feature selection for energy system modeling: Identification of relevant time series information

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能源与人工智能(英文) 2021年第2期4卷 16-29页

作者： inga M.Muller Chair of Renewable and Sustainable energy Systems Technical University of MunichAccisstrasse 21Munich 80333Germany

Heuristic or clustering based time series aggregation methods are often used to reduce temporal complexity of energy system models by selecting representative ***,these methods potentially neglect relevant information of time series(e.g.,distribution parameters).To identify relevant time series parameters,feature selection algorithms can be *** present research contributes by(a)developing a new feature selection approach based on clustering,nested modeling and regression(CNR)which is designed for applications requiring high selectivity and using different data sets,(b)comparing and evaluating CNR with feature selection methods available from the literature(e.g.,LASSO)and(c)identifying relevant information of the time series applied in energy system models,in particular those of demand,photovoltaic and *** show that CNR achieves on average up to 101%lower mean absolute errors when methods are directly ***,CNR better identifies relevant information when the number of selected features is *** disadvantage of CNR,however,is its high computational effort.A potential remedy to counter this is the combination with another method(e.g.,as pre-feature selection).In terms of relevant information,energy systems including photovoltaic are mainly characterized by the correlation between demand and photovoltaic time series as well as the range and the 35%quantile of *** energy systems include wind power,the minimum and mean of wind as well as the correlation between demand and wind time series are relevant *** implications of these findings are discussed.

关键词： energy system modeling Feature selection Time series analysis Nested modeling Clustering Regression Intermittent renewable energies

Higher education For Sustainability:A Global Perspective

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Geography and Sustainability 2021年第2期2卷 99-106页

作者： ingaŽalėnienė Paulo Pereira Mykolas Romeris University Ateities s.20VilniusLithuania environmental Management Laboratory Mykolas Romeris UniversityAteities s.20VilniusLithuania

Higher education institutions have an essential role in *** are key agents in the education of future leaders that will contribute to the successful United Nations Sustainable Development Goals(SDGs)*** geography of SDGs this implementation is very heterogeneous,but it is clear that higher education institutions contribute decisively to creating a mindset that facilitates the dissemination of SDGs *** perspective paper analyses the impacts of higher education on sustainability and the challenges and barriers as-sociated with this *** education contributes decisively to the SDGs implementation,but especially to Goal 1(end poverty in all its forms everywhere),Goal 3(ensure healthy lives and promote well-being for all at all ages),Goal 5(gender equality),Goal 8(decent work and economic growth),Goal 12(responsible consumption and production),Goal 13(climate change)and Goal 16(peace,justice and strong institutions).As a transfor-mational agent,the higher education sector has a tremendous impact on students’habit and contribution to a prosperous ***,to establish the required change in education,sustainability principles need to be at the heart of higher institutions strategy(e.g.,curricula,modus operandi)and is key to be incorporated in the organisational *** by leading by example,the external influence in the society will be possible(e.g.,implementing SDGs key aspects such as gender quality,reduce waste reduction and energy consumption).For this to be a reality,different communication methods with students are needed(e.g.,different student academic levels).Nevertheless,critical challenges need to be tackled in the institutions inside and outside the institution environment,such as incorporating sustainability principles,political environment and stakeholders’interest.

关键词： Higher education institutions Sustainability Organisational culture Communication

The Impact of a Bicuspid Aortic Valve on Aortic Geometry and Function in Patients with Aortic Coarctation:A Comprehensive CMR Study

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Congenital Heart Disease 2021年第6期16卷 551-560页

作者： Laura Schweikert Dominik Gabbert Sylvia Krupickova inga Voges Department of Congenital Heart Disease and Paediatric Cardiology University Hospital Schleswig-HolsteinKielGermany Royal Brompton Hospital LondonUK

Background:An isolated bicuspid aortic valve(BAV)is associated with structural and functional abnormalities of the aorta and the left ventricle(LV).Although~50%of patients with aortic coarctation(CoA)have a BAV,less is known about its impact on LV function and aortic geometry and function in CoA *** this cardiovascular magnetic resonance imaging(CMR)study,we analysed markers of LV and aortic function as well as aortic geometry in a large cohort of CoA patients with a BAVand compared them with CoA patients with a tricuspid aortic valve(TAV).Methods:We included 48 patients with a BAV(18.4±9.3 years)and 45 patients with TAV(20.7±9.9 years).LV volumes,mass and ejection fraction as well as aortic distensibilty,pulse wave velocity(PWV)were measured from standard cine CMR and phase-contrast CMR images.2-dimensional CMR feature tracking(2DCMR-FT)was performed to measure longitudinal,circumferential and radial strain and strain rate of the *** arch geometry was classified as romanic,gothic and ***:LV volumes,mass and ejection fraction as well as aortic distensibility and PWV did not significantly differ between the BAV and the TAV *** was also no significant difference for LV global longitudinal,radial and circumferential strain and strain rate between both *** with a BAV had more commonly a gothic aortic arch compared to TAV patients,but this difference was not statistically significant(22 vs.14,p=0.2).Ascending and descending aortic distensibility correlated with LV mass in the entire patient group(perential and radial strain(GLS,GCS,GRS)and global longitudinal and circumferential strain rate(GLSR,GCSR)correlated with LV ejection fraction(pest that the presence of a BAV does not adversely impact LV and aortic function in children and young adults with *** correlation of global circumferential,longitudinal and radial strain values with LV ejection fraction dem

关键词： Aortic coarctation bicuspid aortic valve cardiovascular magnetic resonance feature tracking

No evidence for increased cell entry or antibody evasion by Delta sublineage AY.4.2

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Cellular & Molecular Immunology 2022年第3期19卷 449-452页

作者： Prerna Arora Amy Kempf inga Nehlmeier Luise Graichen Martin S.Winkler Martin Lier Sebastian Schulz Hans-Martin Jäck Stefan Pöhlmann Markus Hoffmann Infection Biology Unit German Primate CenterKellnerweg 437077GöttingenGermany Faculty of Biology and Psychology Georg-August-University GöttingenWilhelmsplatz 137073GöttingenGermany Department of Anesthesiology University of Göttingen Medical CenterGeorg-August University GöttingenRobert-Koch-Straße 4037075GöttingenGermany Division of Molecular Immunology Department of Internal Medicine 3Friedrich-Alexander University Erlangen-NürnbergGlückstraße 691054ErlangenGermany

Since the beginning of the COVID-19 pandemic,multiple SARS-CoV-2 variants have *** some variants spread only locally,others,referred to as variants of concern,disseminated globally and became drivers of the *** SARS-CoV-2 variants harbor mutations relative to the virus circulating early in the pandemic,and mutations in the viral spike(S)protein are considered of particular relevance since the S protein mediates host cell entry and constitutes the key target of the neutralizing antibody *** a consequence,mutations in the S protein may increase SARS-CoV-2 infectivity and enable its evasion of neutralizing ***,mutations in the S protein can modulate viral transmissibility and pathogenicity.

关键词： SARS-CoV-2 AY.4.2 Delta Host cell entry Antibody evasion

efficient antibody evasion but reduced ACe2 binding by the emerging SARS-CoV-2 variant B.1.640.2

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Cellular & Molecular Immunology 2022年第9期19卷 1067-1069页

作者： Prerna Arora Amy Kempf inga Nehlmeier Luise Graichen Sebastian Schulz Anne Cossmann Alexandra Dopfer-Jablonka Martin S.Winkler Hans-Martin Jäck Georg M.N.Behrens Stefan Pöhlmann Markus Hoffmann Infection Biology Unit German Primate CenterKellnerweg 437077GöttingenGermany Faculty of Biology and Psychology Georg-August-University GöttingenWilhelmsplatz 137073GöttingenGermany Division of Molecular Immunology Department of Internal Medicine 3Friedrich-Alexander University of Erlangen-NürnbergGlückstraße 691054ErlangenGermany Department for Rheumatology and Immunology Hannover Medical SchoolCarl-Neuberg-Straße 130625HannoverGermany German Centre for Infection Research(DZIF) Partner Site Hannover-BraunschweigHannoverGermany Centre for Individualised Infection Medicine(CiiM) HannoverGermany Department of Anesthesiology University of Göttingen Medical CenterGöttingenGeorg-August University of GöttingenRobert-Koch-Straße 4037075GöttingenGermany

The SARS-CoV-2 spike(S)protein engages ACe2 for cell entry,and the S protein/ACe2 interface is an important target for neutralizing *** the course of the COVID-19 pandemic,SARS-CoV-2 variants have emerged that harbor mutations in the S protein,which confer neutralization resistance and allow viral spread in immunologically nonnaive *** most prominent example is the highly mutated Omicron variant,which infects convalescent or vaccinated individuals with unprecedented efficiency[1,2].

关键词： ACe2 harbor neutral

Profound neutralization evasion and augmented host cell entry are hallmarks of the fast-spreading SARS-CoV-2 lineage XBB.1.5

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Cellular & Molecular Immunology 2023年第4期20卷 419-422页

作者： Markus Hoffmann Prerna Arora inga Nehlmeier Amy Kempf Anne Cossmann Sebastian R.Schulz Gema Morillas Ramos Luis A.Manthey Hans-Martin Jäck Georg M.N.Behrens Stefan Pöhlmann Infection Biology Unit German Primate CenterKellnerweg 437077 GöttingenGermany Faculty of Biology and Psychology Georg-August-University GöttingenWilhelmsplatz 137073 GöttingenGermany Department for Rheumatology and Immunology Hannover Medical SchoolCarl-Neuberg-Straße 130625 HannoverGermany Division of Molecular Immunology Department of Internal Medicine 3Friedrich-Alexander University of Erlangen-NürnbergGlückstraße 691054 ErlangenGermany German Centre for Infection Research(DZIF) partner site Hannover-BraunschweigCarl-Neuberg-Straße 130625 HannoverGermany Centre for Individualized Infection Medicine(CiiM) FeodorLynen-Straße730625 HannoverGermany

Since late 2022, the share of infections caused by the SARS-CoV2 lineage XBB.1.5 has gradually increased in the United States,resulting in XBB.1.5 becoming the dominating SARS-CoV-2lineage in the United States and a similar trend is likely to soontake place also in european countries. However, information onthe virological properties of XBB.1.5 is scarce. Here, weconducted an initial virological assessment of the SARS-CoV-2XBB.1.5 lineage.

关键词： becoming likely lineage

Host cell entry and neutralisation sensitivity of the SARS-CoV-2 XBB.1.16 lineage

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Cellular & Molecular Immunology 2023年第8期20卷 969-971页

作者： inga Nehlmeier Amy Kempf Prerna Arora Anne Cossmann Alexandra Dopfer-Jablonka Metodi V.Stankov Sebastian R.Schulz Hans-Martin Jäck Georg M.N.Behrens Stefan Pöhlmann Markus Hoffmann Infection Biology Unit German Primate Center—Leibniz Institute for Primate ResearchKellnerweg 437077GöttingenGermany Faculty of Biology and Psychology Georg-August-University GöttingenWilhelmsplatz 137073GöttingenGermany Department of Rheumatology and Immunology Hannover Medical SchoolCarl-Neuberg-Straße 130625HannoverGermany German Centre for Infection Research(DZIF) Partner Site Hannover-BraunschweigCarl-Neuberg-Straße 130625HannoverGermany Division of Molecular Immunology Department of Internal Medicine 3Friedrich-Alexander University of Erlangen-NürnbergGlückstraße 691054ErlangenGermany Centre for Individualized Infection Medicine(CiiM) Feodor-Lynen-Straße 730625HannoverGermany

Despite previous circulation of the highly transmissible and antibody evasive BA.2.75, BQ.1, XBB.1 and XBB.1.5 lineages, the share of infections caused by the SARS-CoV-2 lineage XBB.1.16 has gradually increased in India in early 2023, resulting in XBB.1.16 being the dominating SARS-CoV-2 lineage in India today. Since a similar trend may also take place in other countries and information on the biological properties of the XBB.1.16 lineage is scarce, we conducted a rapid assessment of the SARS-CoV-2 XBB.1.16 lineage with respect to its ability to enter cells and evade neutralisation by antibodies.

关键词： lineage neutral spite