61 results on '"Peter Meyn"'
Search Results
2. Data from Ontogeny and Vulnerabilities of Drug-Tolerant Persisters in HER2+ Breast Cancer
- Author
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Benjamin G. Neel, Alireza Khodadadi-Jamayran, Benjamin Haibe-Kains, Abhyudai Singh, Jason Moffat, Beatrix Ueberheide, Aristotelis Tsirigos, Jane A. Skok, Adriana Heguy, Peter Meyn, Sylvia Adams, Kwok-kin Wong, Jiehui Deng, Christos Sotiriou, David Venet, Kwan Ho Tang, Avantika Dhabaria, Allison M.L. Nixon, Kevin R. Brown, Arvind Singh Mer, Azin Sayad, Shaowen Jiang, Jayu Jen, and Chewei Anderson Chang
- Abstract
Resistance to targeted therapies is an important clinical problem in HER2-positive (HER2+) breast cancer. “Drug-tolerant persisters” (DTP), a subpopulation of cancer cells that survive via reversible, nongenetic mechanisms, are implicated in resistance to tyrosine kinase inhibitors (TKI) in other malignancies, but DTPs following HER2 TKI exposure have not been well characterized. We found that HER2 TKIs evoke DTPs with a luminal-like or a mesenchymal-like transcriptome. Lentiviral barcoding/single-cell RNA sequencing reveals that HER2+ breast cancer cells cycle stochastically through a “pre-DTP” state, characterized by a G0-like expression signature and enriched for diapause and/or senescence genes. Trajectory analysis/cell sorting shows that pre-DTPs preferentially yield DTPs upon HER2 TKI exposure. Cells with similar transcriptomes are present in HER2+ breast tumors and are associated with poor TKI response. Finally, biochemical experiments indicate that luminal-like DTPs survive via estrogen receptor–dependent induction of SGK3, leading to rewiring of the PI3K/AKT/mTORC1 pathway to enable AKT-independent mTORC1 activation.Significance:DTPs are implicated in resistance to anticancer therapies, but their ontogeny and vulnerabilities remain unclear. We find that HER2 TKI-DTPs emerge from stochastically arising primed cells (“pre-DTPs”) that engage either of two distinct transcriptional programs upon TKI exposure. Our results provide new insights into DTP ontogeny and potential therapeutic vulnerabilities.This article is highlighted in the In This Issue feature, p. 873
- Published
- 2023
3. Supplementary Table from Ontogeny and Vulnerabilities of Drug-Tolerant Persisters in HER2+ Breast Cancer
- Author
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Benjamin G. Neel, Alireza Khodadadi-Jamayran, Benjamin Haibe-Kains, Abhyudai Singh, Jason Moffat, Beatrix Ueberheide, Aristotelis Tsirigos, Jane A. Skok, Adriana Heguy, Peter Meyn, Sylvia Adams, Kwok-kin Wong, Jiehui Deng, Christos Sotiriou, David Venet, Kwan Ho Tang, Avantika Dhabaria, Allison M.L. Nixon, Kevin R. Brown, Arvind Singh Mer, Azin Sayad, Shaowen Jiang, Jayu Jen, and Chewei Anderson Chang
- Abstract
Supplementary Table from Ontogeny and Vulnerabilities of Drug-Tolerant Persisters in HER2+ Breast Cancer
- Published
- 2023
4. Supplementary Figure All from Lower Airway Dysbiosis Affects Lung Cancer Progression
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Leopoldo N. Segal, Thales Papagiannakopoulos, Kwok-Kin Wong, Richard Bonneau, Huilin Li, Jose C. Clemente, Harvey I. Pass, Daniel H. Sterman, William N. Rom, Adriana Heguy, Aristotelis Tsirigos, William Moore, Andre L. Moreira, Cynthia A. Loomis, Valeria Mezzano, Sergei B. Koralov, Anastasia-Maria Zavitsanou, Ray Pillai, Kevin Felner, Harald Sauthoff, Robert L. Smith, Jamie L. Bessich, Samaan Rafeq, Gaetane Michaud, Linchen He, Nan Shen, James T. Morton, Michelle Badri, Mariam El-Ashmawy, Tadasu Iizumi, Joseph Carpenito, Brendan Franca, Luisannay Perez, Evan Olsen, Peter Meyn, Ting-An Yie, Yonghua Li, Rosemary Schluger, Katherine Gershner, Imran Sulaiman, Benjamin G. Wu, and Jun-Chieh J. Tsay
- Abstract
Supplementary Figure 1-23
- Published
- 2023
5. Data from Lower Airway Dysbiosis Affects Lung Cancer Progression
- Author
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Leopoldo N. Segal, Thales Papagiannakopoulos, Kwok-Kin Wong, Richard Bonneau, Huilin Li, Jose C. Clemente, Harvey I. Pass, Daniel H. Sterman, William N. Rom, Adriana Heguy, Aristotelis Tsirigos, William Moore, Andre L. Moreira, Cynthia A. Loomis, Valeria Mezzano, Sergei B. Koralov, Anastasia-Maria Zavitsanou, Ray Pillai, Kevin Felner, Harald Sauthoff, Robert L. Smith, Jamie L. Bessich, Samaan Rafeq, Gaetane Michaud, Linchen He, Nan Shen, James T. Morton, Michelle Badri, Mariam El-Ashmawy, Tadasu Iizumi, Joseph Carpenito, Brendan Franca, Luisannay Perez, Evan Olsen, Peter Meyn, Ting-An Yie, Yonghua Li, Rosemary Schluger, Katherine Gershner, Imran Sulaiman, Benjamin G. Wu, and Jun-Chieh J. Tsay
- Abstract
In lung cancer, enrichment of the lower airway microbiota with oral commensals commonly occurs, and ex vivo models support that some of these bacteria can trigger host transcriptomic signatures associated with carcinogenesis. Here, we show that this lower airway dysbiotic signature was more prevalent in the stage IIIB–IV tumor–node–metastasis lung cancer group and is associated with poor prognosis, as shown by decreased survival among subjects with early-stage disease (I–IIIA) and worse tumor progression as measured by RECIST scores among subjects with stage IIIB–IV disease. In addition, this lower airway microbiota signature was associated with upregulation of the IL17, PI3K, MAPK, and ERK pathways in airway transcriptome, and we identified Veillonella parvula as the most abundant taxon driving this association. In a KP lung cancer model, lower airway dysbiosis with V. parvula led to decreased survival, increased tumor burden, IL17 inflammatory phenotype, and activation of checkpoint inhibitor markers.Significance:Multiple lines of investigation have shown that the gut microbiota affects host immune response to immunotherapy in cancer. Here, we support that the local airway microbiota modulates the host immune tone in lung cancer, affecting tumor progression and prognosis.See related commentary by Zitvogel and Kroemer, p. 224.This article is highlighted in the In This Issue feature, p. 211
- Published
- 2023
6. Supplementary File Table All (excel) from Lower Airway Dysbiosis Affects Lung Cancer Progression
- Author
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Leopoldo N. Segal, Thales Papagiannakopoulos, Kwok-Kin Wong, Richard Bonneau, Huilin Li, Jose C. Clemente, Harvey I. Pass, Daniel H. Sterman, William N. Rom, Adriana Heguy, Aristotelis Tsirigos, William Moore, Andre L. Moreira, Cynthia A. Loomis, Valeria Mezzano, Sergei B. Koralov, Anastasia-Maria Zavitsanou, Ray Pillai, Kevin Felner, Harald Sauthoff, Robert L. Smith, Jamie L. Bessich, Samaan Rafeq, Gaetane Michaud, Linchen He, Nan Shen, James T. Morton, Michelle Badri, Mariam El-Ashmawy, Tadasu Iizumi, Joseph Carpenito, Brendan Franca, Luisannay Perez, Evan Olsen, Peter Meyn, Ting-An Yie, Yonghua Li, Rosemary Schluger, Katherine Gershner, Imran Sulaiman, Benjamin G. Wu, and Jun-Chieh J. Tsay
- Abstract
Supplementary File Table 1-10
- Published
- 2023
7. Supplementary Table from Lower Airway Dysbiosis Affects Lung Cancer Progression
- Author
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Leopoldo N. Segal, Thales Papagiannakopoulos, Kwok-Kin Wong, Richard Bonneau, Huilin Li, Jose C. Clemente, Harvey I. Pass, Daniel H. Sterman, William N. Rom, Adriana Heguy, Aristotelis Tsirigos, William Moore, Andre L. Moreira, Cynthia A. Loomis, Valeria Mezzano, Sergei B. Koralov, Anastasia-Maria Zavitsanou, Ray Pillai, Kevin Felner, Harald Sauthoff, Robert L. Smith, Jamie L. Bessich, Samaan Rafeq, Gaetane Michaud, Linchen He, Nan Shen, James T. Morton, Michelle Badri, Mariam El-Ashmawy, Tadasu Iizumi, Joseph Carpenito, Brendan Franca, Luisannay Perez, Evan Olsen, Peter Meyn, Ting-An Yie, Yonghua Li, Rosemary Schluger, Katherine Gershner, Imran Sulaiman, Benjamin G. Wu, and Jun-Chieh J. Tsay
- Abstract
Supplementary Table
- Published
- 2023
8. Assessing Engineering Students’ Conceptual Understanding of Introductory Quantum Optics
- Author
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Joaquin Veith, Boris Girnat, Philipp Bitzenbauer, and Jan-Peter Meyn
- Subjects
quantum optics ,concept inventory ,Rasch scaling ,quantum technology ,General Physics and Astronomy ,ddc:530 - Abstract
Quantum technologies have outgrown mere fundamental research in laboratories over recent years, and will facilitate more and more potentially disruptive applications in a wide range of fields in the future. In foresight, qualification opportunities need to be implemented in order to train qualified specialists, referred to as the future quantum workforce, in various fields. Universities world-wide have launched qualification programmes for engineers focusing on quantum optics and photonics. In many of these programmes, students attend courses on quantum physics contextualized via quantum optics experiments with heralded photons, because: (1) their experimental and physical foundations may be directly leveraged to teaching a number of quantum technology applications, and (2) physics education research has provided empirical evidence, according to which such quantum optics-based approaches are conducive to learning about quantum concepts. While many teachers are confident about the effectiveness of their concepts, there is little empirical evidence due to the lack of content-area-specific research tools. We present a 16-item concept inventory to assess students’ conceptual understanding of quantum optics concepts in the context of experiments with heralded photons adopted from a test instrument published in the literature. We have administered this Quantum Optics Concept Inventory as a post-test to N=216 students after instruction on quantum optics as part of an undergraduate engineering course. We evaluated the instruments’ psychometric quality, both in terms of classical test theory, and using a Rasch scaling approach. The Quantum Optics Concept Inventory enables a reliable measure (α=0.74), and the data gathered show a good fit to the Rasch model. The students’ scores suggest that fundamental quantum effects pose striking learning hurdles to the engineering students. In contrast, most of the students are able to cope with the experimental and technical foundations of quantum optics experiments with heralded photons and their underlying principles, such as the coincidence technique used for the preparation of single-photon states. These findings are in accordance with prior research, and hence, the Quantum Optics Concept Inventory may serve as a fruitful starting point for future empirical research with regard to the education of the future quantum workforce.
- Published
- 2022
- Full Text
- View/download PDF
9. Evidence for Environmental–Human Microbiota Transfer at a Manufacturing Facility with Novel Work-related Respiratory Disease
- Author
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Bianca Kapoor, Timothy C. Borbet, Thomas V. Colby, Peter Meyn, Jose C. Clemente, Jean M. Cox-Ganser, Zhan Gao, Douglas Wendland, Francis H. Y. Green, Martin J. Blaser, Randall J. Nett, Benjamin G. Wu, Randy Boylstein, Marc Veillette, Caroline Duchaine, Marcia L. Stanton, Soma Sanyal, Angela Franko, Imran Sulaiman, Vance D. Bachelder, Adriana Heguy, Maryaline Coffre, Sergei B. Koralov, Robert J. Tallaksen, Kristin J. Cummings, M. Abbas Virji, Leopoldo N. Segal, Kathleen Kreiss, Ju-Hyeong Park, Sarah Lundeen, Nicole T Edwards, Yonghua Li, Krista Warren, Jerrold L. Abraham, and Judith A. Crawford
- Subjects
Pulmonary and Respiratory Medicine ,Lung ,business.industry ,Indoor bioaerosol ,Respiratory disease ,Human microbiome ,Occupational disease ,Critical Care and Intensive Care Medicine ,medicine.disease ,Work related ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,030228 respiratory system ,Immunology ,medicine ,030212 general & internal medicine ,Microbiome ,Respiratory system ,business - Abstract
Rationale: Workers' exposure to metalworking fluid (MWF) has been associated with respiratory disease.Objectives: As part of a public health investigation of a manufacturing facility, we performed a cross-sectional study using paired environmental and human sampling to evaluate the cross-pollination of microbes between the environment and the host and possible effects on lung pathology present among workers.Methods: Workplace environmental microbiota were evaluated in air and MWF samples. Human microbiota were evaluated in lung tissue samples from workers with respiratory symptoms found to have lymphocytic bronchiolitis and alveolar ductitis with B-cell follicles and emphysema, in lung tissue samples from control subjects, and in skin, nasal, and oral samples from 302 workers from different areas of the facility. In vitro effects of MWF exposure on murine B cells were assessed.Measurements and Main Results: An increased similarity of microbial composition was found between MWF samples and lung tissue samples of case workers compared with control subjects. Among workers in different locations within the facility, those that worked in the machine shop area had skin, nasal, and oral microbiota more closely related to the microbiota present in the MWF samples. Lung samples from four index cases and skin and nasal samples from workers in the machine shop area were enriched with Pseudomonas, the dominant taxa in MWF. Exposure to used MWF stimulated murine B-cell proliferation in vitro, a hallmark cell subtype found in the pathology of index cases.Conclusions: Evaluation of a manufacturing facility with a cluster of workers with respiratory disease supports cross-pollination of microbes from MWF to humans and suggests the potential for exposure to these microbes to be a health hazard.
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- 2020
10. Toward Types of Students’ Conceptions About Photons: Results of an Interview Study
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Philipp Bitzenbauer and Jan-Peter Meyn
- Published
- 2022
11. Serial single-cell profiling analysis of metastatic TNBC during Nab-paclitaxel and pembrolizumab treatment
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Kwok-Kin Wong, Jiehui Deng, Natalie Klar, Peter Meyn, Charles M. Perou, Yutong Zhang, Christina Almonte, Ece Bagdatlioglu, Michelle Krogsgaard, Kristen E. Labbe, Adriana Heguy, Aatish Thennavan, Christian Marier, Suhagi Shah, and Sylvia Adams
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Myeloid ,Paclitaxel ,medicine.medical_treatment ,Population ,Triple Negative Breast Neoplasms ,Pembrolizumab ,Antibodies, Monoclonal, Humanized ,Article ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Albumins ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Tumor Microenvironment ,medicine ,Humans ,Prospective Studies ,education ,Chemotherapy ,education.field_of_study ,Tumor microenvironment ,Taxane ,business.industry ,Immunotherapy ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Single-Cell Analysis ,business - Abstract
PURPOSE: Immunotherapy has recently been shown to improve outcomes for advanced PD-L1-positive triple-negative breast cancer (TNBC) in the Impassion130 trial, leading to FDA approval of the first immune checkpoint inhibitor in combination with taxane chemotherapy. To further develop predictive biomarkers and improve therapeutic efficacy of the combination, interrogation of the tumor immune microenvironment before therapy as well as during each component of treatment is crucial. Here we use single-cell RNA sequencing (scRNA-seq) on tumor biopsies to assess immune cell changes from two patients with advanced TNBC treated in a prospective trial at predefined serial time points, before treatment, on taxane chemotherapy and on chemo-immunotherapy. METHODS: Both patients (one responder and one progressor) received the trial therapy, in cycle 1 nab-paclitaxel given as single agent, in cycle 2 nab-paclitaxel in combination with pembrolizumab. Tumor core biopsies were obtained at baseline, 3 weeks (after cycle 1, chemotherapy alone) and 6 weeks (after cycle 2, chemo-immunotherapy). Single-cell RNA sequencing (scRNA-seq) of both cancer cells and infiltrating immune cells isolated were performed from fresh tumor core biopsy specimens by 10x chromium sequencing. RESULTS: ScRNA-seq analysis showed significant baseline heterogeneity of tumor-infiltrating immune cell populations between the two patients as well as modulation of the tumor microenvironment by chemotherapy and immunotherapy. In the responding patient there was a population of PD-1(high) expressing T cells which significantly decreased after nab-paclitaxel plus pembrolizumab treatment as well as a presence of tissue-resident memory T cells (T(RM)). In contrast, tumors from the patient with rapid disease progression showed a prevalent and persistent myeloid compartment. CONCLUSIONS: Our study provides a deep cellular analysis of on-treatment changes during chemo-immunotherapy for advanced TNBC, demonstrating not only feasibility of single cell analyses on serial tumor biopsies but also the heterogeneity of TNBC and differences in on-treatment changes in responder versus progressor.
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- 2020
12. Fostering experimental competences of prospective physics teachers
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Philipp Bitzenbauer and Jan-Peter Meyn
- Subjects
Science instruction ,Mathematics education ,ComputingMilieux_COMPUTERSANDEDUCATION ,General Physics and Astronomy ,ddc:530 ,Science teachers ,Education - Abstract
Physics teachers are often faced with the challenge of having to set up difficult experiments, or they have to consciously manipulate parameters in order to be able to demonstrate a phenomenon convincingly. Comprehensive laboratory courses are standard procedure in any study program for prospective physics teachers. However, many students, even after completing standard laboratory courses, show difficulties in standard experimental situations, such as measuring an electric current. We report on a new seminar concept for students in physics teacher study programs. This concept is based on the current state of research in physics education, on the teachers’ professional competences, and on the modelling of experimental competence, justifying its embedding in teacher training. We present first results of a pilot study carried out to evaluate the seminar.
- Published
- 2021
13. Airway Microbiota Is Associated with Upregulation of the PI3K Pathway in Lung Cancer
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Daniel H. Sterman, Richard Bonneau, E. Olsen, Jose C. Clemente, Martin J. Blaser, Peter Meyn, Adriana Heguy, Benjamin G. Wu, Jun Chieh J. Tsay, Nan Shen, Leopoldo N. Segal, Michael D. Weiden, Aristotelis Tsirigos, Michelle H. Badri, Yonghua Li, Vivek Murthy, Ting An Yie, Imran Sulaiman, William N. Rom, Harvey I. Pass, Tenzin Lhakhang, and Gaetane Michaud
- Subjects
Adult ,Male ,0301 basic medicine ,Pulmonary and Respiratory Medicine ,Lung Neoplasms ,Respiratory System ,Critical Care and Intensive Care Medicine ,Phosphatidylinositol 3-Kinases ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Bronchoscopy ,medicine ,Humans ,Prospective Studies ,Microbiome ,Lung cancer ,PI3K/AKT/mTOR pathway ,Aged ,Original Research ,business.industry ,Cell growth ,Microbiota ,Middle Aged ,respiratory system ,medicine.disease ,respiratory tract diseases ,Up-Regulation ,Cross-Sectional Studies ,030104 developmental biology ,030220 oncology & carcinogenesis ,Host-Pathogen Interactions ,Cancer research ,Tissue invasion ,Female ,business ,Airway - Abstract
Rationale: In lung cancer, upregulation of the PI3K (phosphoinositide 3-kinase) pathway is an early event that contributes to cell proliferation, survival, and tissue invasion. Upregulation of this pathway was recently described as associated with enrichment of the lower airways with bacteria identified as oral commensals. Objectives: We hypothesize that host–microbe interactions in the lower airways of subjects with lung cancer affect known cancer pathways. Methods: Airway brushings were collected prospectively from subjects with lung nodules at time of diagnostic bronchoscopy, including 39 subjects with final lung cancer diagnoses and 36 subjects with noncancer diagnoses. In addition, samples from 10 healthy control subjects were included. 16S ribosomal RNA gene amplicon sequencing and paired transcriptome sequencing were performed on all airway samples. In addition, an in vitro model with airway epithelial cells exposed to bacteria/bacterial products was performed. Measurements and Main Results: The composition of the lower airway transcriptome in the patients with cancer was significantly different from the control subjects, which included up-regulation of ERK (extracellular signal–regulated kinase) and PI3K signaling pathways. The lower airways of patients with lung cancer were enriched for oral taxa (Streptococcus and Veillonella), which was associated with up-regulation of the ERK and PI3K signaling pathways. In vitro exposure of airway epithelial cells to Veillonella, Prevotella, and Streptococcus led to upregulation of these same signaling pathways. Conclusions: The data presented here show that several transcriptomic signatures previously identified as relevant to lung cancer pathogenesis are associated with enrichment of the lower airway microbiota with oral commensals.
- Published
- 2018
14. Microbial signatures in the lower airways of mechanically ventilated COVID19 patients associated with poor clinical outcome
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Yonghua Li, David Kaufman, Peter Meyn, Nancy Amoroso, Huilin Li, Clea Barnett, Stephen T. Yeung, Bo Shopsin, Laura Evans, Luis Angel, Imran Sulaiman, Jan Bakker, Ann Marie Schmidt, Deepak Pradhan, Christian V. Forst, Ralf Duerr, Timothy M. Uyeki, Kenneth A. Stapleford, Sara A Thannickal, J. Carpenito, Vikramjit Mukherjee, Jose C. Clemente, Anthony Lubinsky, Michael D. Weiden, Guomiao Shen, Shari B. Brosnahan, Kun Ji, Lizzette Pérez-Pérez, R. Schluger, Daniel H. Sterman, Adriana Hegu, Stephanie Banakis, Xiuxiu Liu, Chang Wang, Bin Zhang, Chan Wang, Leopoldo N. Segal, Benjamin G. Wu, Destiny Collazo, Jun-Chieh J. Tsay, Radu Postelnicu, Matthew Chung, George Jour, Kamal M. Khanna, Elodie Ghedin, Emmie de Wit, Kelsey Krolikowski, Ludovic Desvignes, Samaan Rafeq, Anthony Labarbiera, Akiko Koide, and Shohei Koide
- Subjects
Microbiology (medical) ,Adult ,Male ,medicine.medical_specialty ,viruses ,medicine.medical_treatment ,Critical Illness ,Immunology ,Respiratory System ,Adaptive Immunity ,Applied Microbiology and Biotechnology ,Microbiology ,Article ,Immune system ,Bronchoscopy ,Internal medicine ,Genetics ,medicine ,Odds Ratio ,Humans ,Microbiome ,Prospective Studies ,Respiratory system ,Prospective cohort study ,Aged ,Mechanical ventilation ,medicine.diagnostic_test ,Bacteria ,business.industry ,SARS-CoV-2 ,Microbiota ,COVID-19 ,Cell Biology ,Middle Aged ,Viral Load ,Prognosis ,Respiration, Artificial ,Bacterial Load ,Immunity, Innate ,Hospitalization ,medicine.anatomical_structure ,Respiratory failure ,Female ,Airway ,business ,Viral load ,Bronchoalveolar Lavage Fluid ,Respiratory tract - Abstract
Mortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation. On a subset of the subjects that underwent bronchoscopy, we also quantified SARS-CoV-2 viral load, analyzed the microbiome of the lower airways by metagenome and metatranscriptome analyses and profiled the host immune response. We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal (Mycoplasma salivarium), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality. Collectively, these data support the hypothesis that 1) the extent of viral infectivity drives mortality in severe COVID-19, and therefore 2) clinical management strategies targeting viral replication and host responses to SARS-CoV-2 should be prioritized.
- Published
- 2021
15. Lower airway dysbiosis affects lung cancer progression
- Author
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Daniel H. Sterman, Jose C. Clemente, Peter Meyn, Sergei B. Koralov, Kevin Felner, R. Schluger, Luisannay Perez, Linchen He, Adriana Heguy, J. Carpenito, Richard Bonneau, Mariam El-Ashmawy, Yonghua Li, B. Franca, William N. Rom, Ting An Yie, Imran Sulaiman, James T. Morton, Anastasia Maria Zavitsanou, Valeria Mezzano, Benjamin G. Wu, Katherine Gershner, Cynthia Loomis, Robert L. Smith, Samaan Rafeq, Andre L. Moreira, Gaetane Michaud, Huilin Li, Leopoldo N. Segal, Harald Sauthoff, William Moore, Tadasu Iizumi, Ray Pillai, Aristotelis Tsirigos, Harvey I. Pass, Jamie L. Bessich, Thales Papagiannakopoulos, E. Olsen, Kwok-Kin Wong, Jun Chieh J. Tsay, Michelle H. Badri, and Nan Shen
- Subjects
0301 basic medicine ,Lung Neoplasms ,medicine.medical_treatment ,New York ,Mice, Transgenic ,Adenocarcinoma ,Gut flora ,medicine.disease_cause ,Article ,Cohort Studies ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,medicine ,Animals ,Humans ,Neoplasm Metastasis ,Lung cancer ,Lung ,Neoplasm Staging ,Proportional Hazards Models ,biology ,business.industry ,Microbiota ,Cancer ,Immunotherapy ,respiratory system ,medicine.disease ,biology.organism_classification ,Survival Analysis ,respiratory tract diseases ,Gastrointestinal Microbiome ,Disease Models, Animal ,030104 developmental biology ,Oncology ,Tumor progression ,030220 oncology & carcinogenesis ,Immunology ,Disease Progression ,Dysbiosis ,Female ,Carcinogenesis ,business - Abstract
In lung cancer, enrichment of the lower airway microbiota with oral commensals commonly occurs, and ex vivo models support that some of these bacteria can trigger host transcriptomic signatures associated with carcinogenesis. Here, we show that this lower airway dysbiotic signature was more prevalent in the stage IIIB–IV tumor–node–metastasis lung cancer group and is associated with poor prognosis, as shown by decreased survival among subjects with early-stage disease (I–IIIA) and worse tumor progression as measured by RECIST scores among subjects with stage IIIB–IV disease. In addition, this lower airway microbiota signature was associated with upregulation of the IL17, PI3K, MAPK, and ERK pathways in airway transcriptome, and we identified Veillonella parvula as the most abundant taxon driving this association. In a KP lung cancer model, lower airway dysbiosis with V. parvula led to decreased survival, increased tumor burden, IL17 inflammatory phenotype, and activation of checkpoint inhibitor markers. Significance: Multiple lines of investigation have shown that the gut microbiota affects host immune response to immunotherapy in cancer. Here, we support that the local airway microbiota modulates the host immune tone in lung cancer, affecting tumor progression and prognosis. See related commentary by Zitvogel and Kroemer, p. 224. This article is highlighted in the In This Issue feature, p. 211
- Published
- 2020
16. Wärme und Energie
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Jan-Peter Meyn
- Published
- 2020
17. Ontogeny and Vulnerabilities of Drug-Tolerant Persisters in HER2+ Breast Cancer
- Author
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Chewei Anderson Chang, Jayu Jen, Shaowen Jiang, Azin Sayad, Arvind Singh Mer, Kevin R. Brown, Allison M.L. Nixon, Avantika Dhabaria, Kwan Ho Tang, David Venet, Christos Sotiriou, Jiehui Deng, Kwok-kin Wong, Sylvia Adams, Peter Meyn, Adriana Heguy, Jane A. Skok, Aristotelis Tsirigos, Beatrix Ueberheide, Jason Moffat, Abhyudai Singh, Benjamin Haibe-Kains, Alireza Khodadadi-Jamayran, and Benjamin G. Neel
- Subjects
Receptor, ErbB-2 ,Breast Neoplasms ,mTORC1 ,Biology ,Lapatinib ,Article ,Metastasis ,Phosphatidylinositol 3-Kinases ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Cell Line, Tumor ,medicine ,Humans ,Protein kinase B ,PI3K/AKT/mTOR pathway ,030304 developmental biology ,0303 health sciences ,Cancer ,medicine.disease ,respiratory tract diseases ,3. Good health ,Oncology ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research ,Female ,Signal Transduction ,medicine.drug - Abstract
Resistance to targeted therapies is an important clinical problem in HER2-positive (HER2+) breast cancer. “Drug-tolerant persisters” (DTP), a subpopulation of cancer cells that survive via reversible, nongenetic mechanisms, are implicated in resistance to tyrosine kinase inhibitors (TKI) in other malignancies, but DTPs following HER2 TKI exposure have not been well characterized. We found that HER2 TKIs evoke DTPs with a luminal-like or a mesenchymal-like transcriptome. Lentiviral barcoding/single-cell RNA sequencing reveals that HER2+ breast cancer cells cycle stochastically through a “pre-DTP” state, characterized by a G0-like expression signature and enriched for diapause and/or senescence genes. Trajectory analysis/cell sorting shows that pre-DTPs preferentially yield DTPs upon HER2 TKI exposure. Cells with similar transcriptomes are present in HER2+ breast tumors and are associated with poor TKI response. Finally, biochemical experiments indicate that luminal-like DTPs survive via estrogen receptor–dependent induction of SGK3, leading to rewiring of the PI3K/AKT/mTORC1 pathway to enable AKT-independent mTORC1 activation. Significance: DTPs are implicated in resistance to anticancer therapies, but their ontogeny and vulnerabilities remain unclear. We find that HER2 TKI-DTPs emerge from stochastically arising primed cells (“pre-DTPs”) that engage either of two distinct transcriptional programs upon TKI exposure. Our results provide new insights into DTP ontogeny and potential therapeutic vulnerabilities. This article is highlighted in the In This Issue feature, p. 873
- Published
- 2020
18. Lung Cancer Survival and Prognosis Is Affected by Lower Airway Oral Commensal Enrichment
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R. Schluger, Jose C. Clemente, Linchen He, Kevin Felner, Michelle H. Badri, Jamie Morton, Richard Bonneau, E. Olsen, Mariam El-Ashmawy, Benjamin G. Wu, A.S. Scott, A. Imperato, Daniel H. Sterman, Leopoldo N. Segal, K. Gershner, Harald Sauthoff, Thales Papagiannakopoulos, Yi Li, Ting-An Yie, Gaetane Michaud, Huilin Li, Peter Meyn, Harvey I. Pass, Nan Shen, Robert L. Smith, B. Franca, Samaan Rafeq, L. Perez, Jun-Chieh J. Tsay, Jamie L. Bessich, William Moore, Kwok K. Wong, and Imran Sulaiman
- Subjects
medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Airway ,business ,Lung cancer ,medicine.disease ,Gastroenterology - Published
- 2020
19. Sequencing identifies multiple early introductions of SARS-CoV-2 to the New York City Region
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Manon Ragonnet-Cronin, John Cadley, Lawrence Hsu Lin, Megan S. Hogan, Ludovic Boytard, Antonio Serrano, Dacia Dimartino, Marie I. Samanovic, Melissa Call, Iman Osman, Matija Snuderl, Vanessa Raabe, Mark J. Mulligan, Brendan Belovarac, Xiaojun Feng, Christian Marier, George Jour, Maria E Aguero-Rosenfeld, Amy Rapkiewicz, Peter Meyn, Raquel Ordoñez, Nicholas A. Vulpescu, Carolina Arguelles-Grande, Jared Pinnell, Paul Zappile, Lily Geidelberg, Kimon V. Argyropoulos, Tatyana Gindin, Theodore Vougiouklakis, Guomiao Shen, André M. Ribeiro-dos-Santos, Andrew Lytle, Emily P. Huang, Min Jae Kim, Margaret Black, Adriana Heguy, Gael Westby, Paolo Cotzia, Erik M. Volz, Raven Luther, John J. Chen, Yutong Zhang, Emily Guzman, Matthew T. Maurano, and Sitharam Ramaswami
- Subjects
Male ,medicine.medical_specialty ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Genome, Viral ,Biology ,Article ,DNA sequencing ,03 medical and health sciences ,0302 clinical medicine ,Epidemiology ,Pandemic ,Genetics ,medicine ,Humans ,Genetics(clinical) ,Pandemics ,Genetics (clinical) ,Phylogeny ,030304 developmental biology ,Whole genome sequencing ,0303 health sciences ,Whole Genome Sequencing ,SARS-CoV-2 ,Transmission (medicine) ,Research ,COVID-19 ,Outbreak ,Metropolitan area ,3. Good health ,City region ,Geography ,Evolutionary biology ,Female ,New York City ,030217 neurology & neurosurgery - Abstract
Effective public response to a pandemic relies upon accurate measurement of the extent and dynamics of an outbreak. Viral genome sequencing has emerged as a powerful approach to link seemingly unrelated cases, and large-scale sequencing surveillance can inform on critical epidemiological parameters. Here, we report the analysis of 236 SARS-CoV2 sequences from cases in the New York City metropolitan area during the initial stages of the 2020 COVID-19 outbreak. The majority of cases throughout the region had no recent travel history or known exposure, and genetically linked cases were spread throughout the region. Comparison to global viral sequences showed that the majority were most related to cases from Europe. Our data are consistent with numerous seed transmissions from multiple sources and a prolonged period of unrecognized community spreading. This work highlights the complementary role of real-time genomic surveillance in addition to traditional epidemiological indicators.
- Published
- 2020
20. Quantum physics ≠ quantum physics. A survey of researchers’ associations
- Author
-
Bianca Winkler, Philipp Bitzenbauer, and Jan-Peter Meyn
- Subjects
Computer science ,Quantum mechanics ,General Physics and Astronomy ,ddc:530 ,Education - Abstract
No consensus has been reached so far concerning the key topics on quantum physics suitable for secondary school teaching, despite comprehensive research. We identified the the variety of associations with quantum physics among professionals as a potential cause. From an explorative mind map study with N = 29 physics researchers, we derive six subject-specific focal points in the associations that researchers have with quantum physics.
- Published
- 2021
21. Lower Airway Dysbiosis Leads to A Pro-Tumor Inflammatory State and Worsens Non-Small Cell Lung Cancer Prognosis in a Preclinical Model
- Author
-
K. Yie, Kwok K. Wong, S. Ma, L. Perez, Peter Meyn, Benjamin G. Wu, Harvey I. Pass, E. Olsen, Adriana Heguy, Yi Li, Mariam El-Ashmawy, Thales Papagiannakopoulos, Ting-An Yie, Imran Sulaiman, Daniel H. Sterman, Jun-Chieh J. Tsay, Leopoldo N. Segal, B. Franca, and A. Gonzalez
- Subjects
business.industry ,medicine ,Cancer research ,Non small cell ,medicine.disease ,Lung cancer ,Airway ,business ,Dysbiosis - Published
- 2019
22. A new teaching concept on quantum physics in secondary schools
- Author
-
Philipp Bitzenbauer and Jan-Peter Meyn
- Subjects
Quantum optics ,Science instruction ,Engineering ,business.industry ,Concept learning ,Mathematics education ,Educational technology ,General Physics and Astronomy ,ddc:530 ,business ,Education - Abstract
In this article, an approach to integrate contemporary quantum physics into secondary school teaching is presented. The Erlanger concept on quantum optics provides an experimental-based guideway to aspects of modern quantum physics. We avoid the traditional historical approach in order to overcome the lack of modern concepts of quantum physics. In an acceptance survey, initial empirical evidence for the acceptance of the developed explanatory approaches was evaluated.
- Published
- 2020
23. A safe and effective modification of Thomson’s jumping ring experiment
- Author
-
Felix Waschke, Andreas Strunz, and Jan-Peter Meyn
- Subjects
Physics ,Science instruction ,Ring (mathematics) ,business.industry ,SCOOP ,Electrical engineering ,General Physics and Astronomy ,medicine.disease_cause ,law.invention ,Capacitor ,Jumping ,law ,Electrical network ,medicine ,business ,computer ,computer.programming_language - Abstract
The electrical circuit of the jumping ring experiment based on discharging a capacitor is optimized. The setup is scoop proof at 46?V and yet the ring jumps more than 9?m high. The setup is suitable for both lectures and student laboratory work in higher education.
- Published
- 2012
24. Renewable energy sources in terms of entropy
- Author
-
Jan-Peter Meyn
- Subjects
Physics ,Energy recovery ,Primary energy ,business.industry ,Entropy production ,General Physics and Astronomy ,Thermodynamics ,Energy consumption ,Energy accounting ,Renewable energy ,Energy flow ,Entropy (energy dispersal) ,Process engineering ,business - Abstract
A high standard of living causes a large number of irreversible processes, which generate entropy. Energy flow is necessary to remove entropy from the location of generation; commonly this is called energy consumption. The usefulness of an energy flow is defined by its capability of removing entropy from an irreversible process. Fossil energy sources are limited and their use causes ecological damage and conflicts about distribution. As a long-term alternative, energy needs to be obtained from the incoming stream of solar radiation, or indirectly by replacing natural heat engines with artificial ones. Due to the environmental side effects of this replacement, unnecessary artificial entropy production has to be minimized.
- Published
- 2010
25. An ultra-capacitor-based current source for magnetic field demonstration
- Author
-
Jan-Peter Meyn
- Subjects
Physics ,Supercapacitor ,Electrical current ,Iron filings ,Hardware_GENERAL ,Hardware_INTEGRATEDCIRCUITS ,General Physics and Astronomy ,Champ magnetique ,Current source ,Low resistance ,Engineering physics ,Power (physics) ,Magnetic field - Abstract
An ultra-capacitor in parallel with the output of a dc power supply reduces the source resistance and yields an electrical current of up to 900A through a low resistance load. The magnetic field of wires is made visible with iron filings over a large area.
- Published
- 2009
26. Demonstrating quantum random with single photons
- Author
-
Christine Silberhorn, Jan-Peter Meyn, Patrick Bronner, and Andreas Strunz
- Subjects
Physics ,Photon ,Undergraduate education ,Physics::Physics Education ,General Physics and Astronomy ,Quantum entanglement ,Polarization (waves) ,law.invention ,law ,Quantum mechanics ,Photon beams ,Quantum ,Beam splitter ,Randomness - Abstract
We present an experiment for education which demonstrates random transmission or reflection of heralded single photons on beam splitters. With our set-up, we can realize different quantum random experiments by appropriate settings of polarization rotators. The concept of entanglement is motivated by correlated randomness. The experiments are suitable for undergraduate education and are available as interactive screen experiments.
- Published
- 2009
27. Interactive screen experiments with single photons
- Author
-
Jan-Peter Meyn, Andreas Strunz, Patrick Bronner, and Christine Silberhorn
- Subjects
Physics ,Quantum optics ,Science instruction ,Focus (computing) ,Photon ,Higher education ,Multimedia ,business.industry ,Undergraduate education ,Physics::Physics Education ,General Physics and Astronomy ,Multimedia instruction ,computer.software_genre ,Engineering physics ,ComputingMilieux_COMPUTERSANDEDUCATION ,business ,computer - Abstract
Single photons are used for fundamental quantum physics experiments as well as for applications. Originally being a topic of advance courses, such experiments are increasingly a subject of undergraduate courses. We provide interactive screen experiments (ISE) for supporting the work in a real laboratory, and for students who do not have access to a quantum optics laboratory. The main focus of the ISE is on undergraduate education, but some of the experiments are suitable for other levels of higher education as well.
- Published
- 2009
28. Observation of planetary motion using a digital camera
- Author
-
Jan-Peter Meyn
- Subjects
Physics ,business.product_category ,business.industry ,media_common.quotation_subject ,Photography ,Tripod (photography) ,General Physics and Astronomy ,Education ,Stars ,Optics ,Apparent magnitude ,Sky ,Focal length ,business ,Angle of view ,Digital camera ,media_common - Abstract
A digital SLR camera with a standard lens (50 mm focal length, f/1.4) on a fixed tripod is used to obtain photographs of the sky which contain stars up to 8m apparent magnitude. The angle of view is large enough to ensure visual identification of the photograph with a large sky region in a stellar map. The resolution is sufficient to observe the motion of Saturn, and of the satellites of Jupiter, within 24 h.
- Published
- 2008
29. Musician's and physicist's view on tuning keyboard instruments
- Author
-
Martin Lubenow and Jan-Peter Meyn
- Subjects
Physics ,Science instruction ,Human–computer interaction ,media_common.quotation_subject ,Compromise ,Piano ,General Physics and Astronomy ,Equal temperament ,Musical composition ,Temperament ,Variation (game tree) ,media_common - Abstract
The simultaneous sound of several voices or instruments requires proper tuning to achieve consonance for certain intervals and chords. Most instruments allow enough frequency variation to enable pure tuning while being played. Keyboard instruments such as organ and piano have given frequencies for individual notes and the tuning must be based on a compromise. The equal temperament is not the only solution, but a special choice. Unequal temperaments produce better results in many cases, because important major thirds and triads are improved. Equal temperament was not propagated by Johann Sebastian Bach, as is often stated in introductory literature on this topic.
- Published
- 2006
30. A 9.5-W 82-MHz-repetition-rate picosecond optical parametric generator with cw diode laser injection seeding
- Author
-
U. Bäder, R. Wallenstein, Jan-Peter Meyn, B. Köhler, and A. Nebel
- Subjects
Quasi-phase-matching ,Materials science ,Physics and Astronomy (miscellaneous) ,business.industry ,Lithium niobate ,Energy conversion efficiency ,General Engineering ,General Physics and Astronomy ,Pulse duration ,Laser pumping ,Laser ,law.invention ,chemistry.chemical_compound ,chemistry ,law ,Picosecond ,Optoelectronics ,business ,Diode - Abstract
We report on an injection-seeded 9.5-W 82-MHz-repetition-rate picosecond optical parametric generator (OPG) based on a 55 mm long crystal of periodically poled lithium niobate (PPLN) with a quasi-phase-matching (QPM) grating period of 29.75 μm. The OPG is excited by a continuously diode pumped mode-locked picosecond Nd:YVO4 oscillator-amplifier system. The laser system generates 7 ps pulses with a repetition rate of 82.3 MHz and an average power of 24 W. Without injection-seeding the total average output power of the OPG is 8.9 W, which corresponds to an internal conversion efficiency of 50%. The wavelengths of the signal and idler waves were tuned in the range 1.57–1.64 μm and 3.03–3.3 μm, respectively, by changing the crystal temperature from 150 °C to 250 °C. Injection seeding of the OPG at 1.58 μm with 4 mW of single frequency continuous-wave radiation of a distributed-feedback (DFB) diode laser increases the OPG output to 9.5 W (53% conversion efficiency). The injection seeding increases the pulse duration and reduces the spectral bandwidth. When pumped by 10 W of 1.06 μm laser radiation, the duration of the signal pulses increased from 3.6 ps to 5.5 ps while the spectral bandwidth is reduced from 4.5 nm to 0.85 nm. Seeding thus improved the time-bandwidth product from 1.98 to a value of 0.56, much closer to the Fourier limit.
- Published
- 2002
31. Pulse-to-pulse wavelength tuning of an injection seeded nanosecond optical parametric generator with 10 kHz repetition rate
- Author
-
U. Bäder, G. Anstett, Jan-Peter Meyn, A. Borsutzky, R. Wallenstein, and Marco Rahm
- Subjects
Materials science ,Physics and Astronomy (miscellaneous) ,business.industry ,Lithium niobate ,General Engineering ,General Physics and Astronomy ,Laser pumping ,Nanosecond ,Laser ,law.invention ,chemistry.chemical_compound ,Laser linewidth ,Optics ,chemistry ,law ,Spectral width ,Laser beam quality ,business ,Diode - Abstract
This paper reports on the pulse-to-pulse wavelength tuning of a multiwatt narrow-linewidth nanosecond optical parametric generator (OPG). The OPG consists of a 55 mm long periodically poled lithium niobate (PPLN) crystal with a domain period of 29.75 μm. Excited by 5.7 W of 1064 nm laser pulses (duration: 10 ns, repetition rate: 10 kHz, spatial beam quality M2=1.2) the OPG generates 1.78 W of signal radiation and 0.79 W of idler radiation. The total output of 2.57 W corresponds to a crystal internal efficiency of 64%. The wavelength and spectral width of the OPG is controlled by injecting the cw single mode radiation of a 1580.2 nm DFB diode laser. A seed power as low as 20 μW is sufficient for complete control of the wavelength and the (90 MHz) linewidth of the OPG output. Fast tuning of the diode laser frequency is possible with a rate of up to 6×107 GHz/s by changing the diode current. This allows pulse-to-pulse wavelength tuning of the 10 kHz OPG over a range of 25 GHz limited only by the maximum variation of the current (of 60 mA) allowed for the DFB diode laser used. Increasing the current from 35 mA to 95 mA changed the diode power from 0.3 mW to 5.7 mW. Since these power levels are well above the required minimum seed power, the change of the diode current changes the wavelength of the OPG, but not its linewidth or its output power.
- Published
- 2002
32. Fourier-transform external cavity lasers
- Author
-
Martin R. Hofmann, M. Breede, P. Knobloch, J Zimmermann, Thomas Kleine-Ostmann, M. Matus, Jerome V. Moloney, Jens Struckmeier, Jan-Peter Meyn, S. W. Koch, Martin Koch, and S. Hoffmann
- Subjects
Materials science ,Laser diode ,business.industry ,Far-infrared laser ,Physics::Optics ,Second-harmonic generation ,Laser ,Atomic and Molecular Physics, and Optics ,Electronic, Optical and Magnetic Materials ,Semiconductor laser theory ,law.invention ,Optics ,law ,Optical cavity ,Fiber laser ,Optoelectronics ,Electrical and Electronic Engineering ,Physical and Theoretical Chemistry ,business ,Tunable laser - Abstract
We explore the potential of a new laser resonator design that uses an intracavity Fourier transformation and allows for multi-color operation, gain extension and intracavity second harmonic generation (SHG). First, purely electronically controlled wavelength tuning is demonstrated using liquid crystal displays (LCDs) and digital mirror devices. Moreover, the new design can be applied to different lasers as shown on the examples of a laser diode and a Thulium-doped fiber laser in the mid-infrared. Furthermore, we demonstrate the simultaneous control of multiple gain media within one single external cavity. In addition, tunable emission in the 490 nm range is obtained using intracavity SHG with one single control parameter. Finally, we unambiguously prove simultaneous multi-wavelength operation with variable wavelength spacings and apply it to the generation of THz difference frequencies.
- Published
- 2002
33. Demonstrating the Barkhausen effect with high signal-to-noise ratio
- Author
-
Jan-Peter Meyn
- Subjects
Physics ,Preamplifier ,Ground ,Acoustics ,05 social sciences ,Bandwidth (signal processing) ,050301 education ,General Physics and Astronomy ,01 natural sciences ,law.invention ,Inductance ,symbols.namesake ,Electromagnetic coil ,law ,0103 physical sciences ,symbols ,Resistor ,010306 general physics ,0503 education ,Barkhausen effect - Abstract
The Barkhausen effect can be impaired by various noise sources. These are avoided by a hum-bucking coil, earthing, a preamplifier with carefully chosen bandwidth, and matching the input resistor to the inductance of the coil. The present setup is suitable for lecture hall demonstration in higher education institutes.
- Published
- 2017
34. Discovery and optimization of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1
- Author
-
Darlene Romashko, James G. Tarrant, Felix Weng, Keith R. Hornberger, Matthew R. Medeiros, Andrew Kleinberg, Peter Meyn, Dan Maarten Berger, Mark Albertella, William Peick, An-Hu Li, Mark Bittner, Jing Wang, Hanqing Dong, Paul Maresca, Mark J. Mulvihill, Earl W. May, Wilde Victoria Lynn, Kam W. Siu, Brianna Tokar, Michael Tanowitz, Michael J. Gray, Andrew P. Crew, and Andrew Cooke
- Subjects
Stereochemistry ,Pyridines ,Clinical Biochemistry ,Pharmaceutical Science ,Crystallography, X-Ray ,Biochemistry ,chemistry.chemical_compound ,Inhibitory Concentration 50 ,Mice ,Structure-Activity Relationship ,Neoplasms ,Drug Discovery ,Pyridine ,Potency ,Animals ,Humans ,Amines ,Enzyme Inhibitors ,Furans ,Molecular Biology ,Molecular Structure ,Chemistry ,Organic Chemistry ,MAP Kinase Kinase Kinases ,Xenograft Model Antitumor Assays ,Enzyme Activation ,Drug Design ,Molecular Medicine - Abstract
The discovery and potency optimization of a series of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1 is described. Micromolar hits taken from high-throughput screening were optimized for biochemical and cellular mechanistic potency to ∼10 nM, as exemplified by compound 12az. Application of structure-based drug design aided by co-crystal structures of TAK1 with inhibitors significantly shortened the number of iterations required for the optimization.
- Published
- 2013
35. The kinematic advantage of electric cars
- Author
-
Jan-Peter Meyn
- Subjects
Physics ,Rest (physics) ,Engine power ,Electric motor ,General Physics and Astronomy ,Kinematics ,Naturwissenschaftliche Fakultät ,Diesel engine ,Automotive engineering ,Acceleration ,Three-phase ,ddc:530 ,Turbocharger - Abstract
Acceleration of a common car with with a turbocharged diesel engine is compared to the same type with an electric motor in terms of kinematics. Starting from a state of rest, the electric car reaches a distant spot earlier than the diesel car, even though the latter has a better specification for engine power and average acceleration from 0 to 100 km h−1. A three phase model of acceleration as a function of time fits the data of the electric car accurately. The first phase is a quadratic growth of acceleration in time. It is shown that the tenfold higher coefficient for the first phase accounts for most of the kinematic advantage of the electric car.
- Published
- 2015
36. Grundlegende Experimentiertechnik im Physikunterricht
- Author
-
Jan-Peter Meyn
- Published
- 2011
37. Recognition and destruction of Bacillus Calmette-Guerin-infected human monocytes
- Author
-
K. D. Smith, Peter Meyn, A Molloy, and Gilla Kaplan
- Subjects
Antigens, Differentiation, T-Lymphocyte ,Cytotoxicity, Immunologic ,Interleukin 2 ,Immunology ,chemical and pharmacologic phenomena ,Monocytes ,Microbiology ,Antigens, CD ,medicine ,Animals ,Humans ,Immunology and Allergy ,Cytotoxic T cell ,Killer Cells, Lymphokine-Activated ,Cytotoxicity ,Cells, Cultured ,Antigens, Bacterial ,Sheep ,Lymphokine-activated killer cell ,biology ,Monocyte ,hemic and immune systems ,Articles ,biology.organism_classification ,Mycobacterium bovis ,Virology ,CD56 Antigen ,Cytolysis ,medicine.anatomical_structure ,Interleukin-2 ,Intracellular ,Mycobacterium ,medicine.drug - Abstract
We have established a long-term culture system to study macrophages chronically infected with mycobacteria. Monocytes are infected with Bacillus Calmette-Guerin (BCG) and support exponential intracellular replication without profound perturbation of normal host cell function. We have used this system to investigate lymphokine-activated killer (LAK)-mediated cytolysis. We have found that interleukin 2 stimulation of peripheral blood lymphocytes generates a cytotoxic activity against human monocytes. A CD56- subpopulation of LAK cells specifically recognizes and lyses BCG-infected cells. Lysis of the host cell has no effect on parasite viability and results in the liberation of bacteria capable of infecting more cells.
- Published
- 1993
38. Prolonged immunostimulatory effect of low-dose polyethylene glycol interleukin 2 in patients with human immunodeficiency virus type 1 infection
- Author
-
Antonia L. Montana, Kendall A. Smith, Gilla Kaplan, Zanvil A. Cohn, Hedy Teppler, and Peter Meyn
- Subjects
Adult ,CD4-Positive T-Lymphocytes ,Male ,Interleukin 2 ,T cell ,Immunology ,HIV Infections ,Lymphocyte Activation ,Polyethylene Glycols ,Natural killer cell ,Leukocyte Count ,Immune system ,Aldesleukin ,Humans ,Immunology and Allergy ,Medicine ,Hypersensitivity, Delayed ,Immunity, Cellular ,Lymphokine-activated killer cell ,Dose-Response Relationship, Drug ,business.industry ,Articles ,Middle Aged ,medicine.anatomical_structure ,Evaluation Studies as Topic ,Toxicity ,Interleukin-2 ,Female ,business ,Viral load ,medicine.drug - Abstract
13 patients with human immunodeficiency virus type 1 infection class II-IV, but without opportunistic infection or neoplasm, received 6 micrograms (3.6 x 10(4) IU) of polyethylene glycol recombinant human interleukin 2 (PEG IL-2) intradermally twice a week for 4 mo were then followed for an additional 6 mo. Clinical, immunological, and viral parameters were monitored in the patients, all of whom were taking zidovudine. The cutaneous administration of PEG IL-2 resulted in an indurated zone resembling a delayed-type hypersensitivity response of 26 +/- 1 mm diameter (676 mm2) at 72-96 h after injection throughout the 4 mo of administration. This dose, which was appreciably lower than in most previous trials, was not associated with local or systemic toxicity. No increase in the viral burden of circulating leukocytes or plasma occurred. A number of immunological functions were stimulated by this course of therapy. All patients demonstrated high levels of lymphokine-activated killer cell activity by cells freshly removed from the circulation and in the absence of in vitro exposure to IL-2. Natural killer cell activity was also enhanced. Limiting dilution analysis revealed an increase in the frequency of IL-2-responsive cells from abnormally low to levels above normal during the course of injections. In a subgroup of four patients with > or = 400 CD4+ T cells/microliter at entry, there was a trend to sustained increases in CD4+ T cell numbers. However, this increase did not reach statistical significance. This subset of patients also exhibited higher proliferative responses to phytohemagglutinin as mitogen. Several of these effects persisted for 3-6 mo after cessation of therapy. In conclusion, low-dose IL-2 regimens lead to sustained immune enhancement in the absence of toxicity. We suggest pursuit of this approach for further clinical trials both as prophylaxis and therapy.
- Published
- 1993
39. Efficacy of Low Doses of the Polyethylene Glycol Derivative of Interleukin-2 in Modulating the Immune Response of Patients with Human Immunodeficiency Virus Type 1 Infection
- Author
-
Paul U. Cameron, Hedy Teppler, Zanvil A. Cohn, Antonia L. Montana, Peter Meyn, Kendall A. Smith, and Gilla Kaplan
- Subjects
Adult ,Male ,Interleukin 2 ,Cellular immunity ,Injections, Intradermal ,Opportunistic infection ,HIV Infections ,Biology ,Lymphocyte Activation ,Polyethylene Glycols ,Leukocyte Count ,Immune system ,Immunity ,Aldesleukin ,Immunopathology ,medicine ,Humans ,Immunology and Allergy ,Hypersensitivity, Delayed ,Killer Cells, Lymphokine-Activated ,Immunity, Cellular ,Middle Aged ,medicine.disease ,Recombinant Proteins ,Killer Cells, Natural ,Infectious Diseases ,Delayed hypersensitivity ,Immunology ,HIV-1 ,Leukocytes, Mononuclear ,Interleukin-2 ,Zidovudine ,medicine.drug - Abstract
Interleukin-2 (IL-2) is a key cytokine in cellular immunity. Human immunodeficiency virus type 1 (HIV-1)-infected individuals lack IL-2 because of low CD4+ T lymphocyte numbers. In an attempt to enhance cellular immunity, low-dose recombinant human (rh) IL-2 at 10 micrograms or 180,000 units or its polyethylene glycol (PEG) derivative at 9 micrograms or 36,000 units was given by intracutaneous injection to 8 HIV-1-infected men for 30 days. Participants had no evidence of opportunistic infection and received concurrent zidovudine. IL-2 treatment was nontoxic and elicited a local cellular response resembling classic delayed-type hypersensitivity (DTH) with local interferon-gamma production, even in anergic patients. Systemic responses included enhanced DTH responses to recall antigens, improved in vitro proliferative responses to mitogen, and enhanced NK cell activity. Peripheral leukocyte phenotype and virus titers were unchanged. Long-term studies of low-dose IL-2 are warranted to determine whether immunoenhancing effects can be sustained and if they are associated with improved clinical course.
- Published
- 1993
40. Novel responses of human skin to intradermal recombinant granulocyte/macrophage-colony-stimulating factor: Langerhans cell recruitment, keratinocyte growth, and enhanced wound healing
- Author
-
P A Frindt, R Celona, Gerald P. Walsh, R A Burkhardt, L S Guido, R M Abalos, J Barker, T T Fajardo, Peter Meyn, and Gilla Kaplan
- Subjects
Adult ,Keratinocytes ,Male ,Pathology ,medicine.medical_specialty ,Time Factors ,Langerhans cell ,Adolescent ,Injections, Intradermal ,Injections, Subcutaneous ,Immunology ,CD1 ,Human skin ,CHO Cells ,Biology ,Dermis ,Cricetinae ,Escherichia coli ,Leukocytes ,medicine ,Animals ,Humans ,Leprosy, Borderline ,Immunology and Allergy ,Intradermal injection ,Skin ,Wound Healing ,Granulocyte-Macrophage Colony-Stimulating Factor ,Articles ,Middle Aged ,Molecular biology ,Recombinant Proteins ,Leprosy, Lepromatous ,Microscopy, Electron ,medicine.anatomical_structure ,Granulocyte macrophage colony-stimulating factor ,Langerhans Cells ,Female ,Keratinocyte ,Wound healing ,medicine.drug - Abstract
Recombinant granulocyte/macrophage-colony-stimulating factor (rGM-CSF), prepared from Chinese hamster ovary (CHO) cells and Escherichia coli, was administered to 35 patients with the borderline and polar lepromatous forms of leprosy by the intradermal and subcutaneous routes at doses of 7.5-45.0 micrograms/d for 10 d. With each of these doses and routes, increases in the number of circulating eosinophils were noted. After the intradermal injection, the local skin sites demonstrated zones of roughening and micronodularity that appeared within 24-48 h and persisted for more than 6 d. Reinjection of sites led to enhanced areas of epidermal reaction. GM-CSF prepared from CHO cells was a more potent inducer of this effect. GM-CSF given by the subcutaneous route, at higher doses, failed to initiate these changes. At the microscopic level, the epidermis became thickened (+75%) with increased numbers and layers of enlarged keratinocytes. These contained increased numbers of ribosomes and prominent nucleoli, and were imbedded in a looser meshwork of the zona Pellucida. The modified keratinocytes remained MHC class II antigen negative throughout the course of the response. A major change in the dermis was the progressive accumulation of CD1+, Birbeck granule-positive cells. These Langerhans were recognizable at 48 h after intradermal injection and reached maximum numbers by 4 d. During this period the number of epidermal Langerhans cells remained relatively constant. No increment in dermal Langerhans cells occurred when GLM-CSF was injected by the subcutaneous route. No appreciable increase in the numbers of T cells and monocytes was noted, and granulocytes and eosinophils were largely present within the dermal microvasculature. 4-mm punch biopsies taken from injected sites and adjacent controls were compared in terms of the rapidity of wound healing. 22 of 26 sites demonstrated more rapid filling and hemostasis, whereas four were equivalent to controls. We conclude that rGM-CSF, when introduced into the skin, leads to enhanced keratinocyte growth, the selective recruitment of Langerhans cells into the dermis, and enhanced wound healing of the prepared site. There was no evidence of an enhanced cell-mediated response to Mycobacterium leprae, and bacillary numbers remained unchanged.
- Published
- 1992
41. Self-injection-locking of a CW-OPO by intracavity frequency-doubling the idler wave
- Author
-
P. Grob, M.E. Klein, R. Wallenstein, Jan-Peter Meyn, D.-H. Lee, and Klaus J. Boller
- Subjects
Physics ,business.industry ,Physics::Optics ,Second-harmonic generation ,Beat (acoustics) ,Self injection ,Grating ,Atomic and Molecular Physics, and Optics ,Optics ,Cross-polarized wave generation ,Phase noise ,Optical parametric oscillator ,business ,Diode - Abstract
We report on the observation of self-injection-locking of the signal wave of an optical parametric oscillator (OPO) with the intracavity frequency doubled idler wave. The two-mirror OPO is based on a periodically poled LiNbO3 (PPLN) crystal and pumped with a grating stabilized, continuous-wave (CW) single-frequency diode master-oscillator power-amplifier (MOPA) system. Simultaneous quasi-phase-matching (QPM) of OPO and second harmonic generation (SHG) is provided in the same crystal which carries two different domain gratings. The beat of the signal wave and the frequency-doubled idler wave is suppressed within a 500-kHz wide frequency range centered around zero as expected for self-injection- locking. The measurements prove the feasibility of optically phase-stabilized by-three-division of an optical frequency with CW-OPOs using cascaded nonlinearities.
- Published
- 2009
42. Diode-pumped continuous-wave widely tunable optical parametric oscillator based on periodically poled lithium tantalate
- Author
-
Klaus J. Boller, M.E. Klein, B. Beier, Jan-Peter Meyn, R. Wallenstein, and D.-H. Lee
- Subjects
Materials science ,business.industry ,Amplifier ,Optical parametric amplifier ,Atomic and Molecular Physics, and Optics ,Wavelength ,chemistry.chemical_compound ,Optics ,chemistry ,Lithium tantalate ,Optical parametric oscillator ,Continuous wave ,Parametric oscillator ,business ,Diode - Abstract
We report on a diode-laser pumped cw optical parametric oscillator (OPO) based on quasi-phase-matched periodically poled lithium tantalate. Pumped by the 2.3-W single-frequency, nearly diffraction-limited 925-nm output of an InGaAs diode master-oscillator power amplifier, the pump and signal resonant OPO generates a single-frequency idler wave with an output of as much as 244 mW. The wavelengths of the signal and idler waves are widely tunable in the range 1.55-2.3mum by use of different poling periods (27.3 to 27.9mum) and by variation of the crystal temperature in the range 70-190 degrees C.
- Published
- 2007
43. Single-frequency continuous-wave radiation from 0.77 to 1.73 microm generated by a green-pumped optical parametric oscillator with periodically poled LiTaO3
- Author
-
U. Strossner, Stephan Schiller, Richard Wallenstein, Jan-Peter Meyn, Achim Peters, and J. Mlynek
- Subjects
Materials science ,business.industry ,Low frequency ,Radiation ,Laser ,Signal ,Atomic and Molecular Physics, and Optics ,law.invention ,Wavelength ,Optics ,law ,Optical parametric oscillator ,Continuous wave ,business ,Visible spectrum - Abstract
We describe a cw optical parametric oscillator (OPO) with multigrating periodically poled LiTaO(3) . Pumped by a single-frequency 532-nm laser, the OPO emits single-frequency radiation at wavelengths from 0.77 to 1.73 microm with as much as 60 mW of output power. Mode-hop-free operation for as long as 50 min, a low frequency drift (70 MHz/h), and as much as 700-MHz continuous frequency tuning of signal and idler are demonstrated.
- Published
- 2007
44. Singly resonant continuous-wave optical parametric oscillator pumped by a diode laser
- Author
-
D.-H. Lee, Klaus J. Boller, Jan-Peter Meyn, M.E. Klein, and Richard Wallenstein
- Subjects
Materials science ,business.industry ,Potassium titanyl phosphate ,Laser ,Optical parametric amplifier ,Atomic and Molecular Physics, and Optics ,law.invention ,chemistry.chemical_compound ,Optics ,chemistry ,law ,Ultrafast laser spectroscopy ,Optical parametric oscillator ,Continuous wave ,Optoelectronics ,Parametric oscillator ,business ,Diode - Abstract
We report on what is believed to be the first singly resonant cw optical parametric oscillator (SRO) that is directly pumped by a diode laser. The SRO consists of a 38-mm-long periodically poled LiNbO(3) crystal in a four-mirror signal-resonant ring cavity. Pumped by 2.5 W of 925-nm diode-laser radiation, the SRO generates 480 mW of single-frequency idler radiation at 2.1mum . The wavelengths of the signal and the idler output are tuned in the ranges of 1.55 to 1.70mum and 2.03 to 2.29mum, respectively, by tuning the wavelength of the diode laser from 924.0 to 925.4 nm.
- Published
- 2007
45. Generation of sub-6-fs blue pulses by frequency doubling with quasi-phase-matching gratings
- Author
-
Ursula Keller, Lukas Gallmann, Günter Steinmeyer, Gennady Imeshev, Jan-Peter Meyn, and Martin M. Fejer
- Subjects
Quasi-phase-matching ,Materials science ,business.industry ,Physics::Optics ,Second-harmonic generation ,Grating ,Laser ,Pulse shaping ,Atomic and Molecular Physics, and Optics ,law.invention ,chemistry.chemical_compound ,Optics ,chemistry ,law ,Pulse compression ,Lithium tantalate ,Optoelectronics ,business ,Bandwidth-limited pulse - Abstract
We demonstrate the generation of sub-6-fs pulses centered at 405 nm by frequency doubling of 8.6-fs Ti:sapphire laser pulses. The frequency doubling is carried out in a nonlinearly chirped quasi-phase-matching grating fabricated in a lithium tantalate substrate. This device simultaneously provides frequency conversion and pulse compression of the positively prechirped fundamental pulses. The second-harmonic pulses are characterized in a cross-correlation setup, and their pulse shapes are retrieved by two iterative phase-reconstruction algorithms. The generated second-harmonic spectrum spans a bandwidth of 220 THz. To our knowledge, these are the shortest pulses ever generated in the blue spectral region.
- Published
- 2007
46. Quantitative analysis of a wind energy conversion model
- Author
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Andreas Strunz, Anna Gräbner, Florian Zucker, and Jan-Peter Meyn
- Subjects
Electric motor ,Physics ,Wind power ,Maximum power principle ,business.industry ,Rotor (electric) ,General Physics and Astronomy ,Turbine ,law.invention ,Power optimizer ,Wind profile power law ,law ,business ,Wind tunnel ,Marine engineering - Abstract
A rotor of 12 cm diameter is attached to a precision electric motor, used as a generator, to make a model wind turbine. Output power of the generator is measured in a wind tunnel with up to 15 m s−1 air velocity. The maximum power is 3.4 W, the power conversion factor from kinetic to electric energy is cp = 0.15. The v3 power law is confirmed. The model illustrates several technically important features of industrial wind turbines quantitatively.
- Published
- 2015
47. Pulsed Noncollinear Optical Parametric Oscillator with tilted Periodically Poled Grating Structure
- Author
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X Liang, U. Bäder, Jan-Peter Meyn, R. Wallenstein, M. Peltz, Jürgen Bartschke, and A. Borsutzky
- Subjects
Materials science ,Quality (physics) ,Optics ,Signal beam ,business.industry ,Reflection (physics) ,Optical parametric oscillator ,Optoelectronics ,Nonlinear optics ,Grating ,business ,Pulse shaping ,Power (physics) - Abstract
We report on a 1064nm pumped, 10kHz noncollinear PPLN-OPO. It generates 5.8ns pulses at 1566nm with an average power of 3.6W. The tilted QPM grating improves substancially the signal beam quality (M2 < 1.2).
- Published
- 2004
48. Phase-coherent all-optical frequency division by three
- Author
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Jan-Peter Meyn, R. Wallenstein, Petra Gross, D.-H. Lee, Klaus-Jochen Boller, M.E. Klein, Laser Physics & Nonlinear Optics, and Faculty of Science and Technology
- Subjects
METIS-208557 ,Physics ,business.industry ,Phase (waves) ,Physics::Optics ,Laser ,Interference (wave propagation) ,Atomic and Molecular Physics, and Optics ,law.invention ,Injection locking ,Frequency divider ,Wavelength ,Optics ,law ,IR-40382 ,Optical parametric oscillator ,High harmonic generation ,business - Abstract
The properties of all-optical phase-coherent frequency division by 3, based on a self-phase-locked continuous-wave (cw) optical parametric oscillator (OPO), are investigated theoretically and experimentally. The frequency to be divided is provided by a diode laser master-oscillator power-amplifier system operated at a wavelength of 812 nm and used as the pump source of the OPO. Optical self-phase-locking of the OPO signal and idler waves is achieved by mutual injection locking of the signal wave and the intracavity frequency-doubled idler wave. The OPO process and the second-harmonic generation of the idler wave are simultaneously phase matched through quasi-phase-matching using two periodically poled sections of different period manufactured within the same LiNbO3 crystal. An optical self-phase-locking range of up to 1 MHz is experimentally observed. The phase coherence of frequency division by three is measured via the phase stability of an interference pattern formed by the input and output waves of the OPO. The fractional frequency instability of the divider is measured to be smaller than 7.6×10-14 for a measurement time of 10 s (resolution limited). The self-phase-locking characteristics of the cw OPO are theoretically investigated by analytically solving the coupled field equations in the steady-state regime. For the experimental parameters of the OPO, the calculations predict a locking range of 1.3 MHz and a fractional frequency instability of 1.6×10-15, in good agreement with the experimental results.
- Published
- 2003
49. Single pass blue light generation in bulk periodically poled LiTaO/sub 3/ with a passively mode-locked Nd:YAlO/sub 3/ laser at 930 nm
- Author
-
U. Keller, Jan-Peter Meyn, François Morier-Genoud, C. Hönninger, T. Kellner, G. Huber, and R. Wallenstein
- Subjects
Single pass ,Materials science ,business.industry ,chemistry.chemical_element ,Second-harmonic generation ,Laser ,Ferroelectricity ,Neodymium ,law.invention ,Crystal ,Optics ,chemistry ,law ,Optoelectronics ,business ,Tunable laser ,Blue light - Abstract
Summary form only given. We investigated the single pass second harmonic generation of a passively mode-locked Nd:YAlO/sub 3/ laser operating at /spl lambda/ = 930 nm in a bulk periodically poled LiTaO/sub 3/ (PPLT) crystal. The Nd:YAlO/sub 3/ laser was passively mode-locked with a semiconductor saturable absorber mirror (SESAM) in a V-shaped cavity.
- Published
- 2003
50. Singly-resonant continuous-wave optical parametric oscillator pumped by a diode laser
- Author
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D.-H. Lee, Richard Wallenstein, M.E. Klein, Klaus J. Boller, and Jan-Peter Meyn
- Subjects
OPOS ,Materials science ,business.industry ,Lithium niobate ,Physics::Optics ,Nonlinear optics ,Laser ,law.invention ,Optical pumping ,chemistry.chemical_compound ,Optics ,chemistry ,law ,Optical parametric oscillator ,Continuous wave ,Optoelectronics ,business ,Diode - Abstract
Summary form only given. Singly-resonant continuous-wave (CW) optical parametric oscillators (SROs) have favourable properties in respect to power stability and wavelength tunability. A disadvantage is, however, the high pump power at threshold. The operation of singly resonant CW OPOs thus requires multiwatt laser radiation in a beam of good spectral and spatial quality. For this reason the CW SROs reported so far used high power solid-state lasers as pump sources. In the paper we present, to our knowledge, the first singly-resonant CW OPO which is directly pumped by a high power diode laser. The OPO is based on periodically poled lithium niobate (PPLN).
- Published
- 2003
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