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MCMV-based vaccine vectors expressing full-length viral proteins provide long-term humoral immune protection upon a single-shot vaccination

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Cellular & Molecular Immunology 2022年第2期19卷 234-244页

作者： Yeonsu Kim Xiaoyan Zheng Kathrin Eschke M.Zeeshan Chaudhry Federico Bertoglio Adriana Tomić Astrid Krmpotić Markus Hoffmann Yotam Bar-On Julia Boehme Dunja Bruder Thomas Ebensen Linda Brunotte Stephan Ludwig Martin Messerle Carlos Guzman ofer mandelboim Michael Hust Stefan Pöhlmann Stipan Jonjić LukaČičin-Šain Department of Viral Immunology Helmholtz Centre for Infection Research(HZI)BraunschweigGermany Department of Biotechnology Institut für BiochemieBiotechnologie und BioinformatikTechnischen Universität BraunschweigBraunschweigGermany Oxford Vaccine Group University of OxfordOxfordUK Center for Proteomics University of RijekaFaculty of MedicineRijekaCroatia Infection Biology Unit German Primate CenterGöttingenGermany Faculty of Biology and Psychology Georg-August-University GöttingenGöttingenGermany Department of Immunology Rappaport Faculty of MedicineTechnion-Israel Institute of TechnologyHaifaIsrael Infection Immunology Institute for Medical Microbiology and Hospital HygieneHealth Campus ImmunologyInfectiology and InflammationOtto-von-Guericke-University MagdeburgMagdeburgGermanyImmune RegulationHelmholtz Centre for Infection ResearchBraunschweigGermany Department of Vaccinology and Applied Microbiology Helmholtz Centre for Infection ResearchBraunschweigGermany Institute of Virology Medical University MünsterMünsterGermany Institute of Virology Hannover Medical School(MHH)HannoverGermany German Centre for Infection Research(DZIF) Hannover-Braunschweig SiteHannoverGermany Centre for Individualized Infection medicine(CiiM) a joint venture of HZI and MHHHannoverGermany

Global pandemics caused by influenza or coronaviruses cause severe disruptions to public health and lead to high morbidity and mortality.There remains a medical need for vaccines against these pathogens.CMV(cytomegalovirus)is aβ-herpesvirus that induces uniquely robust immune responses in which remarkably large populations of antigen-specific CD8+T cells are maintained for a lifetime.Hence,CMV has been proposed and investigated as a novel vaccine vector for expressing antigenic peptides or proteins to elicit protective cellular immune responses against numerous pathogens.We generated two recombinant murine CMV(MCMV)vaccine vectors expressing hemagglutinin(HA)of influenza A virus(MCMV^(HA))or the spike protein of severe acute respiratory syndrome coronavirus 2(MCMV^(S)).A single injection of MCMVs expressing either viral protein induced potent neutralizing antibody responses,which strengthened over time.Importantly,MCMV^(HA)-vaccinated mice were protected from illness following challenge with the influenza virus,and we excluded that this protection was due to the effects of memory T cells.Conclusively,we show here that MCMV vectors induce not only long-term cellular immunity but also humoral responses that provide long-term immune protection against clinically relevant respiratory pathogens.

关键词： Vaccine vector SARS-CoV-2 Influenza Cytomegalovirus humoral imunity

Searching for the emotional roots of breast cancer: A cross-disciplinary analysis integrating psychology, Chinese medicine, and oncology biomarkers

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Journal of Integrative Medicine 2022年第1期20卷 57-64页

作者： ofer Baranovitch Meirav Wolff-Bar Meora Feinmesser Chen Sade-Zaltz Ilan Tsarfaty Victoria Neiman Integrative Unit Davidoff Cancer CenterRabin Medical CenterPetach Tikva 4941492Israel Maccabi Tivi(Maccabi Health Organization) Tel Aviv 6801294Israel Department of Pathology Rabin Medical CenterPetach Tikva 4941492Israel Sackler Faculty of Medicine Tel Aviv UniversityTel Aviv 6997801Israel Department of Clinical Microbiology and Immunology Sackler School of MedicineTel Aviv UniversityTel Aviv 6997801Israel Institute of Oncology Davidoff Cancer CenterRabin Medical CenterPetach Tikva 4941492Israel

Objective: We employed a multidisciplinary approach incorporating theoretical ideas, clinical experience,psychology, physiology, traditional Chinese medicine(CM), modern practice of CM, and oncology to explore the effect of patients’ repression of negative emotions and traumatic events on breast cancer(BC) pathogenesis.Methods: BC female patients, older than 18 years of age, with available pathology reports who were treated at Rabin Medical Center were recruited. All participants completed questionnaires regarding medical history, behavioral tendencies, negative emotions, trauma, symptoms, and pathology(from a CM perspective). Data on tumor characteristics were collected from the pathology reports. The associations were examined using hierarchical binary logistic regressions.Results: A total of 155 BC patients were enrolled. The median age was 52 years, with a range of 26–79;95% were mothers;28% had estrogen receptor(ER)-negative BC, 52% had progesterone receptor(PR)-negative BC, 48% had human epidermal growth factor receptor 2-negative BC, and antigen Ki-67 ≥ 20%was reported for 52% of tumors. Statistically significant associations were found between the emotional markers(sense of motherhood failure, and lack of self-fulfillment), avoidance behavior, and physical symptoms that are related to emotional repression based on CM. Significant associations were also found between variables associated with physical symptoms of emotional repression, which involves the production and accumulation of non-substantial phlegm(i.e., ‘‘high-lipid Qi-like microscopic phlegm"),avoidance behavior which unconsciously uses ‘‘high-lipid Qi-like microscopic phlegm" in order to achieve emotional repression, and tumor parameters including tumor grade, PR status, and Ki-67.Patients with higher levels of ‘‘high-lipid Qi-like microscopic phlegm" were more likely to have tumors with worse prognosis(PR-negative, higher grade, and higher Ki-67).Conclusion: We demonstrated a relationship between emotional parameters, behavioral tendencies, CM

关键词： Breast cancer Chinese medicine Negative emotions Repression Trauma Phlegm

Attosecond magnetization dynamics in non-magnetic materials driven by intense femtosecond lasers

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npj Computational Materials 2023年第1期9卷 1959-1968页

作者： ofer Neufeld Nicolas Tancogne-Dejean Umberto De Giovannini Hannes Hübener Angel Rubio Max Planck Institute for the Structure and Dynamics of Matter and Center for Free-Electron Laser Science Hamburg 22761Germany Universitàdegli Studi di Palermo Dipartimento di Fisica e Chimica—Emilio SegrèPalermo I-90123Italy Center for Computational Quantum Physics(CCQ) The Flatiron InstituteNew YorkNY 10010USA

Irradiating solids with ultrashort laser pulses is known to initiate femtosecond timescale magnetization dynamics.However,sub-femtosecond spin dynamics have not yet been observed or predicted.Here,we explore ultrafast light-driven spin dynamics in a highly nonresonant strong-field regime.Through state-of-the-art ab initio calculations,we predict that a nonmagnetic material can transiently transform into a magnetic one via dynamical extremely nonlinear spin-flipping processes,which occur on attosecond timescales and are mediated by cascaded multi-photon and spin–orbit interactions.These are nonperturbative nonresonant analogs to the inverse Faraday effect,allowing the magnetization to evolve in very high harmonics of the laser frequency(e.***.here up to the 42nd,oscillating at~100 attoseconds),and providing control over the speed of magnetization by tuning the laser power and wavelength.Remarkably,we show that even for linearly polarized driving,where one does not intuitively expect the onset of an induced magnetization,the magnetization transiently oscillates as the system interacts with light.This response is enabled by transverse light-driven currents in the solid,and typically occurs on timescales of~500 attoseconds(with the slower femtosecond response suppressed).An experimental setup capable of measuring these dynamics through pump–probe transient absorption spectroscopy is simulated.Our results pave the way for attosecond regimes of manipulation of magnetism.

关键词： tuning transient dynamics

Between Incomprehensible Evil and a Moral Code of Honor: The Rescuing of the Albanian Jews During the Holocaust

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Cultural and Religious Studies 2023年第5期11卷 233-237页

作者： ofer Muchtar Ashkelon Academic college AshkelonIsrael

The Holocaust,also known as the Shoah,was the tragic and devastating event of the genocide of European Jews during World War II.Between 1941 and 1945,Nazi Germany and its collaborators systematically murdered some six million Jews across German-occupied Europe.The Jews and other racial minorities were rounded up across Europe and slaughtered by the German Nazi regime.Little was done to save,and rescue jews during that dark period,that is why the story of Albania,a small country in the Balkans,in which the entire country protected the Jewish community is so remarkable(Savich,2002).This paper will try to examine the heroic rescuing efforts made by the people of Albania during the holocaust while focusing on the Albanian moral code of honor known as“Besa”.This paper will also provide an overview of the impacts of those action.

关键词： holocaust Muslims Albanian righteous among the nations

Tailoring bacterial taxa for immune cell modulation

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Hepatobiliary Surgery and Nutrition 2021年第5期10卷 686-688页

作者： ofer Margalit Ben Boursi Department of Oncology Sheba Medical CenterRamat GanIsrael Tel-Aviv University Tel-AvivIsrael Center for Clinical Epidemiology and Biostatistics Perelman School of Medicine at the University of PennsylvaniaPhiladelphiaPAUSA

The gut microbiota is being increasingly recognized as having a major role in modulating the immune system(1)and response to immunotherapy(2,3).Landmark preclinical studies have shown that gut microbiota transferred via fecal microbiota transplantation(FMT)from humans or mice that have responded to immunotherapy enhanced the efficacy of anti-PD-L1 and anti-CTLA-4 in recipient mice(2,3).Hence,the therapeutic efficacy of immunotherapy depends upon microbiota composition.This conclusion led to the initiation of several clinical trials in which FMT was used to overcome resistance to immunotherapy in human patients.The first two proof-of-concept clinical trials involved metastatic melanoma patients that were converted from immunotherapy-refractory to immunotherapy-responsive using FMT from durable responders to immunotherapy(4,5).

关键词： clinical immunotherapy immune

Connecting Malfunctioning Glial Cells and Brain Degenerative Disorders

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Genomics, Proteomics & Bioinformatics 2016年第3期14卷 155-165页

作者： Natalie Kaminsky ofer Bihari Sivan Kanner Ari Barzilai Department of Neurobiology George S.WiseFaculty of Life SciencesTel Aviv University Sagol School of Neuroscience Tel Aviv University

The DNA damage response（DDR） is a complex biological system activated by different types of DNA damage.Mutations in certain components of the DDR machinery can lead to genomic instability disorders that culminate in tissue degeneration,premature aging,and various types of cancers.Intriguingly,malfunctioning DDR plays a role in the etiology of late onset brain degenerative disorders such as Parkinson＇s,Alzheimer＇s,and Huntington＇s diseases.For many years,brain degenerative disorders were thought to result from aberrant neural death.Here we discuss the evidence that supports our novel hypothesis that brain degenerative diseases involve dysfunction of glial cells（astrocytes,microglia,and oligodendrocytes）.Impairment in the functionality of glial cells results in pathological neuro-glial interactions that,in turn,generate a ‘‘hostile＂ environment that impairs the functionality of neuronal cells.These events can lead to systematic neural demise on a scale that appears to be proportional to the severity of the neurological deficit.

关键词： DNA damage response Genomic instability Brain degenerative diseases Glial cells Astrocytes Microglia

Femtosecond laser-assisted fabrication of piezoelectrically actuated crystalline quartz-based MEMS resonators

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Microsystems & Nanoengineering 2023年第2期9卷 295-306页

作者： John Linden Neta Melech Igor Sakaev ofer Fogel Slava Krylov David Nuttman Zeev Zalevsky Marina Sirota Department of Engineering Bar lan UniversityRamat GanIsral Research and Incubation ERCKLAYavneIsrael School of Mechanical Engineering Faculty of EngineeringTel-Aviv UniversityTel AvivIsrael Engineering Department TAMAMIAlYehudIsrael

A novel technology for the precise fabrication of quartz resonators for MEMS applications is introduced.This approach is based on the laser-induced chemical etching of quartz.The main processing steps include femtosecond UV laser treatment of a Cr-Au-coated Z-cut alpha quartz wafer,followed by wet etching.The laser-patterned Cr-Au coating serves as an etch mask and is used to form electrodes for piezoelectric actuation.This fabrication approach does not alter the quartz's crystalline structure or its piezo-electric properties.The formation of defects,which is common in laser micromachined quartz,is prevented by optimized process parameters and by controlling the temporal behavior of the laser-matter interactions.The process does not involve any lithography and allows for high geometric design flexibility.Several configurations of piezoelectrically actuated beam-type resonators were fabricated using relatively mild wet etching conditions,and their functionality was experimentally demonstrated.The devices are distinguished from prior efforts by the reduced surface roughness and improved wall profiles of the fabricated quartz structures.

关键词： quartz Femto piezoelectric

Multipoint videoconferencing with scalable video coding

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2006年第5期7卷 696-705页

作者： ELEFTHERIADIS Alexandros CIVANLAR M.Reha SHAPIRO ofer Layered Media Inc.NJ 07662 USA

We describe a system for multipoint videoconferencing that offers extremely low end-to-end delay, low cost and complexity, and high scalability, alongside standard features associated with high-end solutions such as rate matching and per- sonal video layout. The system accommodates heterogeneous receivers and networks based on the Internet Protocol and relies on scalable video coding to provide a coded representation of a source video signal at multiple temporal and spatial resolutions as well as quality levels. These are represented by distinct bitstream components which are created at each end-user encoder. Depending on the specific conferencing environment, some or all of these components are transmitted to a Scalable Video Conferencing Server (SVCS). The SVCS redirects these components to one or more recipients depending on, e.g., the available network con- ditions and user preferences. The scalable aspect of the video coding technique allows the system to adapt to different network conditions, and also accommodates different end-user requirements (e.g., a user may elect to view another user at a high or low spatial resolution). Performance results concerning flexibility, video quality and delay of the system are presented using the Joint Scalable Video Model (JSVM) of the forthcoming SVC (H.264 Annex G) standard, demonstrating that scalable coding outper- forms existing state-of-the-art systems and offers the right platform for building next-generation multipoint videoconferencing systems.

关键词： Multipoint videoconferencing, Scalable video coding, Multipoint control

Smoke interacts with fire history to stimulate soil seed bank germination in Mediterranean woodlands

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Journal of Plant Ecology 2019年第3期12卷 419-427页

作者： Neta Manela Ella Dagon Hagai Semesh ofer Ovadia Department of Life Sciences Ben-Gurion University of the Negev84105 Beer-ShevaIsrael Department of Environmental Sciences Tel-Hai CollegeUpper GalileeIsrael

Aims Fire has important consequences on vegetation dynamics.In fire-prone areas,natural selection favors plant species,characterized by a large soil seed bank,and that their germination is stimu-lated by fire.Although seed germination stimulated by fire heat is common in the eastern Mediterranean Basin,only little is known about germination stimulation by smoke.We examined the inter-active effect of aerosol smoke and fire history on the germina-ble soil seed bank(GSSB)community in eastern Mediterranean woodlands.Methods We collected soil samples from sites that have been subjected to different fire frequencies during the last four decades and exposed them to aerosol smoke,with or without watering.By document-ing the seed germination patterns characterizing these samples,we could test for changes in the abundance and richness of the germi-nable seeds in the soil.Important Findings Total GSSB density was higher in sites that were burned more fre-quently during the last four decades.Exposure to aerosol smoke increased the GSSB density,and this pattern was more pronounced in samples originating from sites burned more frequently,as well as among annual species.Notably,exposing wet samples to aerosol smoke caused a significant reduction in GSSB density and richness.These results highlight the importance of exploring germination responses using intact soil samples,rather than synthetic seed com-munities.Moreover,our findings emphasize the important role smoke plays in shaping post-fire succession processes in the Mediterranean Basin,mainly by stimulating the germination of annual species.

关键词： aerosol smoke Anagallis arvensis annuals historic fire regime Mediterranean ecosystems