Evolution of complex organic molecules in hot molecular cores: Synthetic spectra at (sub-)mm wavebands

Hot molecular cores (HMCs) are intermediate stages of high-mass star formation and are also known for their rich emission line spectra at (sub-)mm wavebands. The observed spectral feature of HMCs such as total number of emission lines and associated line intensities are also found to vary with evolutionary stages. We developed various 3D models for HMCs guided by the evolutionary scenarios proposed by recent empirical and modeling studies. We then investigated the spatio-temporal variation of temperature and molecular abundances in HMCs by consistently coupling gas-grain chemical evolution with radiative transfer calculations. We explored the effects of varying physical conditions on molecular abundances including density distribution and luminosity evolution of the central protostar(s). The time-dependent temperature structure of the hot core models provides a realistic framework for investigating the spatial variation of ice mantle evaporation as a function of evolutionary timescales. With increasing protostellar luminosity, the water ice evaporation font ($\sim$100K) expands and the spatial distribution of gas phase abundances of these COMs also spreads out. We simulated the synthetic spectra for these models at different evolutionary timescales to compare with observations. A qualitative comparison of the simulated and observed spectra suggests that these self-consistent hot core models can reproduce the notable trends in hot core spectral variation within the typical hot core timescales of 10$^{5}$ year. These models predict that the spatial distribution of various emission line maps will also expand with evolutionary time. The model predictions can be compared with high resolution observation that can probe scales of a few thousand AU in high-mass star forming regions such as from ALMA.[Abridged]Comment: accepted for publication in A&

Molecular line survey of the high-mass star-forming region NGC 6334I with Herschel/HIFI and the Submillimeter Array

Aims. We aim at deriving the molecular abundances and temperatures of the hot molecular cores in the high-mass star-forming region NGC 6334I and consequently deriving their physical and astrochemical conditions. Methods. In the framework of the Herschel guaranteed time key program CHESS (Chemical HErschel Surveys of Star forming regions), NGC 6334I is investigated by using the Heterodyne Instrument for the Far-Infrared (HIFI) aboard the Herschel Space Observatory. A spectral line survey is carried out in the frequency range 480–1907 GHz, and further auxiliary interferometric data from the Submillimeter Array (SMA) in the 230 GHz band provide spatial information for disentangling the different physical components contributing to the HIFI spectrum. The spectral lines in the processed Herschel data are identified with the aid of former surveys and spectral line catalogs. The observed spectrum is then compared to a simulated synthetic spectrum, assuming local thermal equilibrium, and best fit parameters are derived using a model optimization package. Results. A total of 46 molecules are identified, with 31 isotopologues, resulting in about 4300 emission and absorption lines. High-energy levels (E_u > 1000 K) of the dominant emitter methanol and vibrationally excited HCN (ν_2 = 1) are detected. The number of unidentified lines remains low with 75, or <2% of the lines detected. The modeling suggests that several spectral features need two or more components to be fitted properly. Other components could be assigned to cold foreground clouds or to outflows, most visible in the SiO and H_(2)O emission. A chemical variation between the two embedded hot cores is found, with more N-bearing molecules identified in SMA1 and O-bearing molecules in SMA2. Conclusions. Spectral line surveys give powerful insights into the study of the interstellar medium. Different molecules trace different physical conditions like the inner hot core, the envelope, the outflows or the cold foreground clouds. The derived molecular abundances provide further constraints for astrochemical models

Molecular line survey of the high-mass star-forming region NGC 6334I with Herschel/HIFI and the SMA

We aim at deriving the molecular abundances and temperatures of the hot molecular cores in the high-mass star-forming region NGC 6334I and consequently deriving their physical and astrochemical conditions. In the framework of the Herschel guaranteed time key program CHESS, NGC 6334I is investigated by using HIFI aboard the Herschel Space Observatory. A spectral line survey is carried out in the frequency range 480-1907 GHz, and auxiliary interferometric data from the SMA in the 230 GHz band provide spatial information for disentangling the different physical components contributing to the HIFI spectrum. The spectral lines are identified with the aid of former surveys and spectral line catalogs. The observed spectrum is then compared to a simulated synthetic spectrum with XCLASS, assuming local thermal equilibrium, and best fit parameters are derived using the model optimization package MAGIX. A total of 46 molecules are identified, with 31 isotopologues, resulting in about 4300 emission and absorption lines. High- energy levels of the dominant emitter methanol and vibrationally excited HCN are detected. The number of unidentified lines remains low with 75, or less than 2 percent of the lines detected. The modeling suggests that several spectral features need two or more components to be fitted properly. Other components could be assigned to cold foreground clouds or to outflows, most visible in the SiO emission. A chemical variation between the two embedded hot cores is found, with more N-bearing molecules identified in SMA1 and O-bearing molecules in SMA2. Spectral line surveys give powerful insights into the study of the interstellar medium. Different molecules trace different physical conditions like the inner hot core, the envelope, the outflows or the cold foreground clouds. The derived molecular abundances provide further constraints for astrochemical models.Comment: 30 pages including appendix, 49 figures, accepted for publication in Astronomy and Astrophysic

Submm Observations of Massive Star Formation in the Giant Molecular Cloud NGC 6334 : Gas Kinematics with Radiative Transfer Models

Context. How massive stars (M>8 Ms) form and how they accrete gas is still an open research field, but it is known that their influence on the interstellar medium (ISM) is immense. Star formation involves the gravitational collapse of gas from scales of giant molecular clouds (GMCs) down to dense hot molecular cores (HMCs). Thus, it is important to understand the mass flows and kinematics in the ISM. Aims. This dissertation focuses on the detailed study of the region NGC 6334, located in the Galaxy at a distance of 1.7 kpc. It is aimed to trace the gas velocities in the filamentary, massive star-forming region NGC 6334 at several scales and to explain its dynamics. For that purpose, different scales are examined from 0.01–10 pc to collect information about the density, molecular abundance, temperature and velocity, and consequently to gain insights about the physio-chemical conditions of molecular clouds. The two embedded massive protostellar clusters NGC 6334I and I(N), which are at different stages of development, were selected to determine their infall velocities and mass accretion rates. Methods. This astronomical source was surveyed by a combination of different observatories, namely with the Submillimeter Array (SMA), the single-dish telescope Atacama Pathfinder Experiment (APEX), and the Herschel Space Observatory (HSO). It was mapped with APEX in carbon monoxide (13CO and C18O, J=2–1) at 220.4 GHz to study the filamentary structure and turbulent kinematics on the largest scales of 10 pc. The spectral line profiles are decomposed by Gaussian fitting and a dendrogram algorithm is applied to distinguish velocity-coherent structures and to derive statistical properties. The velocity gradient method is used to derive mass flow rates. The main filament was mapped with APEX in hydrogen cyanide (HCN) and oxomethylium (HCO+, J=3–2) at 267.6 GHz to trace the dense gas. To reproduce the position- velocity diagram (PVD), a cylindrical model with the radiative transfer code Line Modeling Engine (LIME) is created with a collapsing velocity field. Both clusters NGC 6334I and I(N) were observed with the interferometer SMA in HCN (J=4–3) at 354.5 GHz at the smallest scales of 0.01 pc. The combination of interferometric and multi-frequency single-dish data gives a wide range of rotational transitions, which probe the gas at different excitation conditions and optical depths. The molecule HCN and its isotopologues H13CN/HC15N trace radii of a HMC from 1.0–0.01 pc by a range of level energies (E=4–1067 K) and optical depths (tau=100–0.1). The HMCs, which have a rich line spectra, are analyzed by using 1D (myXCLASS) and 3D numerical radiative transfer codes (RADMC-3D and LIME) in and outside of local thermodynamic equilibrium (LTE). Multiple components and the fragmentation of the clusters are modeled with these tools. Together with the optimization package MAGIX, the data are compared and reproduced with synthetic maps and spectra from these models. Results. 1. The main filament shows a velocity gradient from the end toward its center, where the most massive clumps accumulate at both ends, in accordance to predictions of a longitudinal contraction. The 3D structure is determined by taking the inclination and curvature of the filament into account, and the free-fall time is estimated to approximately 1 Myr; 2. The total gas mass is 2.3E5 Ms and the average temperature 20 K. The majority of the velocity gradients are aligned with the magnetic field, which runs perpendicular to the filaments. The calculation of the average Mach numbers yields a turbulence which is super-sonic (M_S=5.7) and sub-Alfvénic (M_A=0.86). In general, the derived scaling relations are in agreement with Larson's relations. 3. The SMA observations reveal multiple bipolar molecular outflows, blue asymmetric infall profiles, rotating cores and an ultra compact (UC) HII region in NGC 6334I which affects the surrounding gas. The average mass accretion rates are 1E-3 Ms/yr for the envelopes and 3E-4 Ms/yr for the cores, where the latter are derived from modified Bondi-Hoyle models. The orientation of the magnetic field is in NGC 6334I(N) consistent over all scales and most outflows are aligned perpendicular to it; 4. In the line surveys of the HMCs, 20 different molecules are identified with typical temperatures of 100 K. A cruel separation between the HMCs of the clusters is determined on the basis of the relative abundances. Conclusions. The combination of single-dish with interferometric data is helpful to constrain the parameter space of a model. The envelope hinders the determination of infall velocities in HMCs via line profiles. Systematic motions as a result of gravitational attraction are diffcult to find because of the turbulent nature of the ISM. The magnetic field energy in NGC 6334 is as important as the kinetic energy and regulates partly the direction of the inflowing gas and thus the geometry and collapse of the molecular clouds. NGC 6334 is heavily affected by the HII regions (produced by the OB stars), and the free-fall time and mass surface density suggest that it classifies as a starburst system

The extreme luminosity states of Sagittarius A*

We discuss mm-wavelength radio, 2.2-11.8um NIR and 2-10 keV X-ray light curves of the super massive black hole (SMBH) counterpart of Sagittarius A* (SgrA*) near its lowest and highest observed luminosity states. The luminosity during the low state can be interpreted as synchrotron emission from a continuous or even spotted accretion disk. For the high luminosity state SSC emission from THz peaked source components can fully account for the flux density variations observed in the NIR and X-ray domain. We conclude that at near-infrared wavelengths the SSC mechanism is responsible for all emission from the lowest to the brightest flare from SgrA*. For the bright flare event of 4 April 2007 that was covered from the radio to the X-ray domain, the SSC model combined with adiabatic expansion can explain the related peak luminosities and different widths of the flare profiles obtained in the NIR and X-ray regime as well as the non detection in the radio domain.Comment: 18 pages, 13 figures, accepted by A&

Kindergastroenterologische und hepatologische Versorgung in Deutschland: Ergebnisse einer deutschlandweiten Umfrage

INTRODUCTION Children and adolescents with chronic gastrointestinal, pancreatic and liver diseases need age-appropriate and qualified treatment. A representative survey is used to analyse the structural and personnel-related outpatient and inpatient care of children with chronic gastrointestinal, pancreatic and liver diseases in Germany. METHODOLOGY 319 paediatric and adolescent medicine clinics and 50 paediatric gastroenterology practices in Germany were invited to participate in the anonymous online survey via EFS Survey. The structure of the facilities, further training authorisations, cooperations, treatment and care data and an assessment of the need for care were systematically recorded and descriptively evaluated. RESULTS 81 clinics and 10 practices participated in the survey. Almost two thirds of the clinics (n=52) provide outpatient paediatric gastroenterology services. Mostly up to 10 (25.4%) or 20 hours/week (33.8%). A quarter of the clinics do not offer consultation hours. Outpatient care needs cannot be met by two-thirds of the institutions. Half of all clinics stated that inpatient paediatric gastroenterology care needs can be met. However, one third cannot cover this and only rarely are there unused capacities. 35 clinics (43.2%) have a further training authorisation according to the state medical association (n=33) and/or are a further training centre of the Society for Paediatric Gastroenterology and Nutrition (GPGE) (n=18). CONCLUSION There is a deficit in both outpatient and inpatient care in paediatric and adolescent gastroenterology. This results, among other things, from the economic framework conditions and a lack of personnel. Well-trained specialists with specialisation in paediatric and adolescent gastroenterology are still needed to provide qualified care throughout the country. Future studies should also include the need for paediatric gastroenterological care from the perspective of other groups, such as affected patients, internal gastroenterologists and paediatricians in private practice. = Introduction: Children and adolescents with chronic gastrointestinal, pancreatic and liver diseases need age-appropriate and qualified treatment. A representative survey is used to analyse the structural and personnel-related outpatient and inpatient care of children with chronic gastrointestinal, pancreatic and liver diseases in Germany. Methodology: 319 paediatric and adolescent medicine clinics and 50 paediatric gastroenterology practices in Germany were invited to participate in the anonymous online survey via EFS Survey. The structure of the facilities, further training authorisations, cooperations, treatment and care data and an assessment of the need for care were systematically recorded and descriptively evaluated. Results: 81 clinics and 10 practices participated in the survey. Almost two thirds of the clinics (n=52) provide outpatient paediatric gastroenterology services. Mostly up to 10 (25.4%) or 20 hours/week (33.8%). A quarter of the clinics do not offer consultation hours. Outpatient care needs cannot be met by two-thirds of the institutions. Half of all clinics stated that inpatient paediatric gastroenterology care needs can be met. However, one third cannot cover this and only rarely are there unused capacities. 35 clinics (43.2%) have a further training authorisation according to the state medical association (n=33) and/or are a further training centre of the Society for Paediatric Gastroenterology and Nutrition (GPGE) (n=18). Conclusion: There is a deficit in both outpatient and inpatient care in paediatric and adolescent gastroenterology. This results, among other things, from the economic framework conditions and a lack of personnel. Well-trained specialists with specialisation in paediatric and adolescent gastroenterology are still needed to provide qualified care throughout the country. Future studies should also include the need for paediatric gastroenterological care from the perspective of other groups, such as affected patients, internal gastroenterologists and paediatricians in private practice

Serum neutralizing capacity and T-cell response against the omicron BA.1 variant in seropositive children and their parents one year after SARS-CoV-2 infection

IntroductionDurability of immune protection against reinfection with SARS-CoV-2 remains enigmatic, especially in the pediatric population and in the context of immune-evading variants of concern. Obviously, this knowledge is required for measures to contain the spread of infection and in selecting rational preventive measures.MethodsHere, we investigated the serum neutralization capacity of 36 seropositive adults and 34 children approximately one year after infection with the ancestral Wuhan strain of SARS-CoV-2 by using a pseudovirus neutralization assay.ResultsWe found that 88.9% of seropositive adult (32/36) and 94.1% of seropositive children (32/34) convalescents retained the neutralizing activity against the SARS-CoV-2 Wuhan strain (WT). Although, the neutralization effect against Omicron BA.1 (B.1.1.529.1) was significantly lower, 70.6% (24/34) of children and 41.7% (15/36) of adults possessed BA.1 cross-neutralizing antibodies. The spike 1 (S1)-specific T cell recall capacity using an activation-induced marker assay was analyzed in 18 adults and 16 children. All participants had detectable S1-specific CD4 T cells against WT, and 72.2% (13/18) adults and 81,3% (13/16) children had detectable S1 WT-specific CD8 T cells. CD4 cross-reactivity against BA.1 was demonstrated in all investigated adults (18/18), and 66.7% (12/18) adult participants had also detectable specific CD8 BA.1 T cells while we detected BA.1 S1 reactive CD4 and CD8 T cells in 81.3% (13/16) children.DiscussionTogether, our findings demonstrate that infection with the ancestral strain of SARS-CoV-2 in children as well as in adults induces robust serological as well as T cell memory responses that persist over at least 12 months. This suggests persistent immunological memory and partial cross-reactivity against Omicron BA.1

<i>Herschel</i>-HOBYS study of the earliest phases of high-mass star formation in NGC 6357

Aims: To constrain models of high-mass star formation it is important to identify the massive dense cores (MDCs) that are able to form high-mass star(s). This is one of the purposes of the Herschel/HOBYS key programme. Here, we carry out the census and characterise of the properties of the MDCs population of the NGC 6357 H II region. Methods: Our study is based on the Herschel/PACS and SPIRE 70−500 μm images of NGC 6357 complemented with (sub-)millimetre and mid-infrared data. We followed the procedure established by the Herschel/HOBYS consortium to extract ~0.1 pc massive dense cores using the getsources software. We estimated their physical parameters (temperatures, masses, luminosities) from spectral energy distribution (SED) fitting. Results: We obtain a complete census of 23 massive dense cores, amongst which one is found to be IR-quiet and twelve are starless, representing very early stages of the star-formation process. Focussing on the starless MDCs, we have considered their evolutionary status, and suggest that only five of them are likely to form a high-mass star. Conclusions: We find that, contrarily to the case in NGC 6334, the NGC 6357 region does not exhibit any ridge or hub features that are believed to be crucial to the massive star formation process. This study adds support for an empirical model in which massive dense cores and protostars simultaneously accrete mass from the surrounding filaments. In addition, the massive star formation in NGC 6357 seems to have stopped and the hottest stars in Pismis 24 have disrupted the filaments

The earliest phases of high-mass star formation, as seen in NGC 6334 by Herschel-HOBYS

To constrain models of high-mass star formation, the Herschel/HOBYS KP aims at discovering massive dense cores (MDCs) able to host the high-mass analogs of low-mass prestellar cores, which have been searched for over the past decade. We here focus on NGC 6334, one of the best-studied HOBYS molecular cloud complexes. We used Herschel PACS and SPIRE 70-500 µm images of the NGC 6334 complex complemented with (sub)millimeter and mid-infrared data. We built a complete procedure to extract ~0.1 pc dense cores with the getsources software, which simultaneously measures their far-infrared to millimeter fluxes. We carefully estimated the temperatures and masses of these dense cores from their spectral energy distributions (SEDs). We also identified the densest pc-scale cloud structures of NGC 6334, one 2 px x 1 pc ridge and two 0.8 pc x 0.8 pc hubs, with volume-averaged densities of ~105 cm-3. A cross-correlation with high-mass star formation signposts suggests a mass threshold of 75 Mʘ for MDCs in NGC 6334. MDCs have temperatures of 9.5-40K, masses of 75-1000 Mʘ, and densities of 1 x 105- 7 x 107 cm-3. Their mid-infrared emission is used to separate 6 IR-bright and 10 IR-quiet protostellar MDCs while their 70 µm emission strength, with respect to fitted SEDs, helps identify 16 starless MDC candidates. The ability of the latter to host high-mass prestellar cores is investigated here and remains questionable. An increase in mass and density from the starless to the IR-quiet and IR-bright phases suggests that the protostars and MDCs simultaneously grow in mass. The statistical lifetimes of the high-mass prestellar and protostellar core phases, estimated to be 1-7 x 104 yr and at most 3 x 105 yr respectively, suggest a dynamical scenario of high-mass star formation. The present study provides good mass estimates for a statistically significant sample, covering the earliest phases of high-mass star formation. High-mass prestellar cores may not exist in NGC 6334, favoring a scenario presented here, which simultaneously forms clouds and high-mass protostars

A synthetic lethality-based strategy for individual sensitization of lung cancer cell lines with vulnerability in the SWI/SNF complex to radiotherapy

Die vorliegende Arbeit beschäftigt sich mit dem Einfluss der Chromatin-Remodellierung durch den SWI/SNF-Komplex auf die Strahlenantwort von Zellen. Dazu wurde die ATPase Untereinheit SMARCA2/BRM in SMARCA4/Brg1-mutierten und -wildtyp Zelllinien mittels siRNA depletiert und anschließend der Einfluss auf das Überleben der Zellen untersucht. In dieser Studie wird zum ersten Mal ein signifikanter Rückgang des klonogenen Überlebens nach BRM-Depletion in Kombination mit Bestrahlung von Brg1-mutierten NSCLC Zellen, im Gegensatz zu Brg1-profizienten NSCLC Zellen und Fibroblasten, gezeigt. In einem weiteren Überlebensassay, dem Minimonolayer assay, konnte eine Verschiebung der Dosis-Wirkungskurven nach einmaliger als auch nach fraktionierter Bestrahlung mit 4 Gy/Tag in den niedrigeren Dosisbereich nach BRM knock-down in Brg1-mutierten NSCLC Zelllinien nachgewiesen werden. Minimonolayer, die mittels fraktionierter Bestrahlung zweimal am Tag mit 4 Gy bestrahlt wurden, sodass die Repopulierung verringert wird und der Einfluss der Reparatur deutlich wird, zeigen nach BRM-Depletion eine anhaltende Verschiebung der Dosis-Wirkungskurve in den niedrigeren Dosisbereich. Interessanterweise zeigen die hier untersuchten Brg1-defizienten Zelllinien, im Vergleich zu den Brg1-profizienten, eine erniedrigte Strahlensensitivität. Ob die Expression des BRG1-Proteins als Biomarker für die Strahlensensitivität von NSCLC genutzt werden kann sollte daher in weiteren klinischen Studien näher untersucht werden. Zusätzlich wurden die zugrundeliegenden Mechanismen der si-BRM induzierten Strahlensensitivierung Brg1-mutierter NSCLC Zelllinien evaluiert. Dazu wurde der Einfluss der BRM-Depletion auf die DNA-Doppelstrangbruch Reparatursignalwege NHEJ und HRR untersucht. Die Ergebnisse der γH2AX und 53BP1 Foci Analysen, die als Hinweis für NHEJ dienen, zeigen keinen signifikanten Unterschied in den Brg1-defizienten als auch in Brg1-profizienten NSCLC Zelllinien nach BRM knock-down. Die Untersuchung von HRR, die mittels Detektion von RAD51 Foci durchgeführt wurde, zeigte allerdings einen signifikanten Anstieg der residuellen RAD51 Foci in Brg1-defizienten NSCLC Zelllinien, sowohl über die gesamte Zellpopulation als auch in Cyclin B1-markierten Zellen. Da die HRR nur in der S- und G2-Phase des Zellzyklusses stattfindet, wurde die Zelllinie A549 mit mutiertem Brg1 in unterschiedlichen Wachstumsphasen (G1-Phase bzw. S-Phase angereichert) bestrahlt und das klonogene Überleben nach BRM knock-down verglichen. Die Ergebnisse zeigen im Vergleich zur konfluenten Zellkultur eine erhöhte si-BRM induzierte Strahlensensitivität der exponentiell wachsenden Zellkultur. Die zusätzliche Anreicherung der Zellen in der S-Phase mittels Aphidicolin zeigt eine weitere Steigerung der Strahlenempfindlichkeit nach si-BRM in der Brg1-mutierten Zelllinie A549. Um auszuschließen, dass die NHEJ nicht am strahlensensitivierenden Effekt nach BRM-Depletion beteiligt ist, wurde das Schlüsselenzym der NHEJ, die DNA-PK inhibiert. Die Erhöhung der Strahlensensitivität nach BRM knock-down bleibt weiterhin bestehen. Anschließend wurde untersucht, ob die HRR an dem strahlensensitivierenden Effekt nach si-BRM beteiligt ist. Dazu wurde das Schlüsselenzym der HRR, RAD51, mittels siRNA depletiert. Die Ergebnisse zeigen keinen zusätzlichen si-BRM-Effekt in Kombination mit si-RAD51. Somit lässt sich schlussfolgern, dass die si-BRM induzierte strahlensensitivierende Wirkung von RAD51 abhängig ist. Aus den vorliegenden Ergebnissen lässt sich schlussfolgern, dass die Inhibition der ATPase Untereinheit SMARCA2/BRM einen neuen zielgerichteten Ansatz für die Therapie von SMARCA4/Brg1-mutierter Lungentumore darstellt.In this study we investigated the influence of the chromatin remodeling complex SWI/SNF on the radiation response of NSCLC cell lines. In this respect the expression of the ATPase subunit SMARCA2/BRM was depleted in SMARCA4/BRG1-mutated and wildtype cell lines by siRNA to evaluate the impact on the survival. This is the first study indicating increased radiation sensitivity specifically in BRG1-mutant but not BRG1-wild-type cell lines and fibroblasts after BRM depletion. The results of the mini monolayer assay, which is a tumor population survival assay, reveal that BRM depletion specifically increases the radioresponse of BRG1-deficient NSCLC cells after fractionated (4 Gy/day) as wells as single dose-irradiation in comparison to lipofectamine and non-target siRNA control. Mini monolayers of BRG1-mutant tumor cell lines irradiated two times per day with 4 Gy, thereby decreases the repopulation and increases the effect of DNA damage repair, show a persistent increase of radio response after BRM depletion. Interestingly, the results reveal that BRG1-mutated cell lines without expression of the full length BRG1 protein are significantly more resistant to ionizing radiation than cell lines without such mutation. Thus, if expression of BRG1 could be a potential biomarker for the radiation sensitivity of NSCLC should be further analyzed in clinical series. To further analyze the underlying mechanism of the sensitizing effect after BRM depletion in BRG1-mutated NSCLC cell lines, influence on DNA double strand break repair pathways NHEJ and HRR was evaluated. The results of γH2AX and 53BP1 foci analysis, indicating DNA repair by NHEJ, show neither in BRG1-deficient nor in BRG1-proficient NSCLC cell lines significantly differences in foci formation after BRM depletion. However, a decreased resolution of Rad51 foci 24 h after BRM knockdown was found in BRG1-mutated cells regarding the whole cell population as well as Cyclin B1 (G2 phase cells) labeled cells. Because HRR is only restricted to S and G2 phase cells, the surviving fraction of BRM depleted A549 enriched G1 phase cells was compared to cells enriched in S phase after irradiation. The results indicate an increase in siBRM induced radio sensitivity in S phase enriched cell culture. BRG1-mutated A549 cells enriched in S phase with Aphidicolin reveal an additional enhancement of radiation sensitivity. Inhibition of DNA-PK, the key enzyme of NHEJ, leads to a persistent radiation sensitizing effect after BRM depletion that excludes an involvement of NHEJ in the siBRM induced radio sensitizing effect. To evaluate whether HRR, the other DSB repair pathway, is involved in radio sensitization after BRM depletion, the key enzyme RAD51 was depleted by siRNA. The results show no additional radio sensitization of siBRM in combination with siRAD51. In conclusion, the present study shows that SMARCA2/BRM depletion increases radiation responsiveness of SMARCA4/BRG1-mutated human NSCLC cell lines and thus identifies BRM as an interesting therapeutic target in SMARCA4/BRG1 mutant cancers