Emission Line Metallicities From The Faint Infrared Grism Survey and VLT/MUSE

We derive direct measurement gas-phase metallicities of $7.4 < 12 + \log(O/H) < 8.4$ for 14 low-mass Emission Line Galaxies (ELGs) at $0.3 < z < 0.8$ identified in the Faint Infrared Grism Survey (FIGS). We use deep slitless G102 grism spectroscopy of the Hubble Ultra Deep Field (HUDF), dispersing light from all objects in the field at wavelengths between 0.85 and 1.15 microns. We run an automatic search routine on these spectra to robustly identify 71 emission line sources, using archival data from VLT/MUSE to measure additional lines and confirm redshifts. We identify 14 objects with $0.3 < z < 0.8$ with measurable O[III]$\lambda$4363 \AA\ emission lines in matching VLT/MUSE spectra. For these galaxies, we derive direct electron-temperature gas-phase metallicities with a range of $7.4 < 12 + \log(O/H) < 8.4$. With matching stellar masses in the range of $10^{7.9} M_{\odot} < M_{\star} < 10^{10.4} M_{\odot}$, we construct a mass-metallicity (MZ) relation and find that the relation is offset to lower metallicities compared to metallicities derived from alternative methods (e.g.,$R_{23}$, O3N2, N2O2) and continuum selected samples. Using star formation rates (SFR) derived from the $H\alpha$ emission line, we calculate our galaxies' position on the Fundamental Metallicity Relation (FMR), where we also find an offset toward lower metallicities. This demonstrates that this emission-line-selected sample probes objects of low stellar masses but even lower metallicities than many comparable surveys. We detect a trend suggesting galaxies with higher Specific Star Formation (SSFR) are more likely to have lower metallicity. This could be due to cold accretion of metal-poor gas that drives star formation, or could be because outflows of metal-rich stellar winds and SNe ejecta are more common in galaxies with higher SSFR.Comment: 14 pages, 11 figures, accepted in Ap

FIGS -- Faint Infrared Grism Survey: Description and Data Reduction

The Faint Infrared Grism Survey (FIGS) is a deep Hubble Space Telescope (HST) WFC3/IR (Wide Field Camera 3 Infrared) slitless spectroscopic survey of four deep fields. Two fields are located in the Great Observatories Origins Deep Survey-North (GOODS-N) area and two fields are located in the Great Observatories Origins Deep Survey-South (GOODS-S) area. One of the southern fields selected is the Hubble Ultra Deep Field. Each of these four fields were observed using the WFC3/G102 grism (0.8$\mu m$-1.15$\mu m$ continuous coverage) with a total exposure time of 40 orbits (~ 100 kilo-seconds) per field. This reaches a 3 sigma continuum depth of ~26 AB magnitudes and probes emission lines to $\approx 10^{-17}\ erg\ s^{-1} \ cm^{-2}$. This paper details the four FIGS fields and the overall observational strategy of the project. A detailed description of the Simulation Based Extraction (SBE) method used to extract and combine over 10000 spectra of over 2000 distinct sources brighter than m_F105W=26.5 mag is provided. High fidelity simulations of the observations is shown to significantly improve the background subtraction process, the spectral contamination estimates, and the final flux calibration. This allows for the combination of multiple spectra to produce a final high quality, deep, 1D-spectra for each object in the survey.Comment: 21 Pages. 17 Figures. To appear in Ap

RNA Sequencing of Human Peripheral Nerve in Response to Injury: Distinctive Analysis of the Nerve Repair Pathways

The development of regenerative therapies for central nervous system diseases can likely benefit from an understanding of the peripheral nervous system repair process, particularly in identifying potential gene pathways involved in human nerve repair. This study employed RNA sequencing (RNA-seq) technology to analyze the whole transcriptome profile of the human peripheral nerve in response to an injury. The distal sural nerve was exposed, completely transected, and a 1 to 2 cm section of nerve fascicles was collected for RNA-seq from six participants with Parkinson\u27s disease, ranging in age between 53 and 70 yr. Two weeks after the initial injury, another section of the nerve fascicles of the distal and pre-degenerated stump of the nerve was dissected and processed for RNA-seq studies. An initial analysis between the pre-lesion status and the postinjury gene expression revealed 3,641 genes that were significantly differentially expressed. In addition, the results support a clear transdifferentiation process that occurred by the end of the 2-wk postinjury. Gene ontology (GO) and hierarchical clustering were used to identify the major signaling pathways affected by the injury. In contrast to previous nonclinical studies, important changes were observed in molecular pathways related to antiapoptotic signaling, neurotrophic factor processes, cell motility, and immune cell chemotactic signaling. The results of our current study provide new insights regarding the essential interactions of different molecular pathways that drive neuronal repair and axonal regeneration in humans

Single‐cell profiling and zebrafish avatars reveal LGALS1 as immunomodulating target in glioblastoma

Glioblastoma (GBM) remains the most malignant primary brain tumor, with a median survival rarely exceeding 2 years. Tumor heterogeneity and an immunosuppressive microenvironment are key factors contributing to the poor response rates of current therapeutic approaches. GBM‐associated macrophages (GAMs) often exhibit immunosuppressive features that promote tumor progression. However, their dynamic interactions with GBM tumor cells remain poorly understood. Here, we used patient‐derived GBM stem cell cultures and combined single‐cell RNA sequencing of GAM‐GBM co‐cultures and real‐time in vivo monitoring of GAM‐GBM interactions in orthotopic zebrafish xenograft models to provide insight into the cellular, molecular, and spatial heterogeneity. Our analyses revealed substantial heterogeneity across GBM patients in GBM‐induced GAM polarization and the ability to attract and activate GAMs—features that correlated with patient survival. Differential gene expression analysis, immunohistochemistry on original tumor samples, and knock‐out experiments in zebrafish subsequently identified LGALS1 as a primary regulator of immunosuppression. Overall, our work highlights that GAM‐GBM interactions can be studied in a clinically relevant way using co‐cultures and avatar models, while offering new opportunities to identify promising immune‐modulating targets.Deutsche Forschungsgemeinschaft (DFG)Fondation Leducq (Leducq Foundation) http://dx.doi.org/10.13039/501100001674Fonds Wetenschappelijk Onderzoek (FWO) http://dx.doi.org/10.13039/501100003130Helmholtz ImagingHHS ¦ National Institutes of Health (NIH) http://dx.doi.org/10.13039/100000002iNAMES (Imaging from NAno to MESo)Kom op tegen Kanker (Fight Cancer) http://dx.doi.org/10.13039/501100011851KU Leuven (Katholieke Universiteit Leuven) http://dx.doi.org/10.13039/501100004040Vlaamse Overheid (Government of Flanders) http://dx.doi.org/10.13039/501100002913VSC (Vlaams Supercomputer Centrum/Flemish Supercomputer Center)Peer Reviewe

Neuropilin-2 mediates VEGF-C–induced lymphatic sprouting together with VEGFR3

If neuropilin-2 and the growth factor VEGF-C don’t come together, lymphatic vessels don’t branch apart

Assessment of the safety of glucocorticoid regimens in combination with abiraterone acetate for metastatic castration-resistant prostate cancer:a randomized, open-label phase 2 study

Importance: Abiraterone acetate is combined with prednisone, 5 mg, twice daily for metastatic castration-resistant prostate cancer (mCRPC) and with prednisone, 5 mg, once daily for newly diagnosed, high-risk, metastatic castration-sensitive prostate cancer. Understanding the physiological effects of these and other regimens is important. Objective: To evaluate the safety of abiraterone acetate with 4 glucocorticoid regimens. Design, Setting, and Participants: Open-label, randomized clinical trial (1:1:1:1) of 164 men with mCRPC from 22 hospitals in 5 countries who were randomly assigned to 1 of 4 intervention groups between June 2013 and October 2014. Analyses were conducted from August 2017 to June 2018. Interventions: Abiraterone acetate, 1000 mg, once daily with prednisone, 5 mg, twice daily (n = 41), 5 mg once daily (n = 41), 2.5 mg twice daily (n = 40), or dexamethasone, 0.5 mg, once daily (n = 42). Main Outcomes and Measures: Primary end point was no mineralocorticoid excess (grade ≥1 hypokalemia or grade ≥2 hypertension) through 24 weeks (6 cycles) from treatment. Results: Of 164 men (median [range] age, 70 [50-90] years) randomized to receive abiraterone acetate, 1000 mg, daily with prednisone, 5 mg, twice daily, once daily, or 2.5 mg twice daily, or dexamethasone, 0.5 mg, once daily, 24 (70.6%) of 34 patients (95% CI, 53.8%-83.2%), 14 (36.8%) of 38 patients (95% CI, 23.4%-52.7%), 21 (60.0%) of 35 patients (95% CI, 43.6%-74.4%), and 26 (70.3%) of 37 patients (95% CI, 54.2%-82.5%), respectively, had no mineralocorticoid excess. Plasma adrenocorticotrophic hormone and urinary mineralocorticoid metabolites after 8 weeks were higher with prednisone, 2.5 mg, twice daily and 5 mg once daily than with 5 mg twice daily or dexamethasone, 0.5 mg, once daily. The level of urinary glucocorticoid metabolites appeared higher in patients who did not meet the primary end point, regardless of glucocorticoid regimen. Total lean body mass decreased in the prednisone groups and total body fat increased in the prednisone, 5 mg, twice daily and dexamethasone groups. In the dexamethasone group, there was an increase in serum insulin and homeostatic model assessment of insulin resistance, while total bone mineral density decreased. In the prednisone, 5 mg, twice daily, 5 mg once daily, 2.5 mg twice daily, and dexamethasone groups, median radiographic progression-free survival was 18.5, 15.3, 12.8, and 26.6 months, respectively. Conclusions and Relevance: Abiraterone acetate with prednisone, 5 mg, twice daily or dexamethasone, 0.5 mg, once daily met the prespecified threshold for the primary end point (95% CI excluded 50% mineralocorticoid excess); abiraterone acetate with prednisone, 5 mg, once daily or 2.5 mg twice daily did not meet the threshold. Abiraterone acetate in combination with dexamethasone appeared to be particularly active but may be associated with adverse metabolic consequences

Platelet rich plasma injection grafts for musculoskeletal injuries: a review

In Europe and the United States, there is an increasing prevalence of the use of autologous blood products to facilitate healing in a variety of applications. Recently, we have learned more about specific growth factors, which play a crucial role in the healing process. With that knowledge there is abundant enthusiasm in the application of concentrated platelets, which release a supra-maximal quantity of these growth factors to stimulate recovery in non-healing injuries. For 20 years, the application of autologous PRP has been safely used and documented in many fields including; orthopedics, sports medicine, dentistry, ENT, neurosurgery, ophthalmology, urology, wound healing, cosmetic, cardiothoracic, and maxillofacial surgery. This article introduces the reader to PRP therapy and reviews the current literature on this emerging treatment modality. In summary, PRP provides a promising alternative to surgery by promoting safe and natural healing. However, there are few controlled trials, and mostly anecdotal or case reports. Additionally the sample sizes are frequently small, limiting the generalization of the findings. Recently, there is emerging literature on the beneficial effects of PRP for chronic non-healing tendon injuries including lateral epicondylitis and plantar fasciitis and cartilage degeneration (Mishra and Pavelko, The American Journal of Sports Medicine 10(10):1–5, 2006; Barrett and Erredge, Podiatry Today 17:37–42, 2004). However, as clinical use increases, more controlled studies are needed to further understand this treatment

Integration fluktuierender erneuerbarer Energien durch konvergente Nutzung von Strom- und Gasnetzen - Konvergenz Strom- und Gasnetze (KonStGas) - Abschlussbericht

Für die Energiewende in Deutschland ist zeitnah ein nennenswerter Ausbau der Stromnetze auf Transport- und Verteilnetzebene erforderlich. Mittel- bis langfristig werden für die Umstellung der Strom- und Energieversorgung auf erneuerbaren Energien (EE) zusätzlich große Speicherkapazitäten benötigt. Dabei sind kostengünstige und mit minimalen Energieverlusten verbundene Speicher- und Erzeugungstechnologien anzustreben. Lösungsansätze dafür werden bisher überwiegend auf der Stromseite diskutiert. Chancen, die sich aus der Kopplung von Strom- und Gasnetzen ergeben, werden kaum wahrgenommen. Das erhebliche Lösungspotential der vorhandenen Gasinfrastruktur und -Anwendungstechnologien mittels Power-to-Gas sowie die damit verbundenen Auswirkungen auf eine nachhaltige Gestaltung der Energiewende finden zu wenig Beachtung. Vor diesem Hintergrund hatte das Forschungsvorhaben "Integration fluktuierender erneuerbarer Energien durch konvergente Nutzung von Strom und Gasnetzen - Konvergenz Strom- und Gasnetze" zum Ziel, unter Berücksichtigung der Kopplung von Strom- und Gasnetzen, (1) die Potenziale zur Aufnahme, Speicherung und Verteilung von EE zu bestimmen, (2) die dynamischen Energieströme aus Angebot und Nachfrage in der gesamten Energieversorgungsstruktur zu modellieren, (3) die Kopplung volkswirtschaftlich zu analysieren und (4) Handlungsempfehlungen für den Ausbau der Netzinfrastrukturen und die Entwicklung eines zukünftigen Energiemarktes abzuleiten

Sensitivity of the IceCube-Gen2 Surface Array for Cosmic-Ray Anisotropy Studies

The energy of the transition from Galactic to extra-galactic origin of cosmic rays is one of the major unresolved issues of cosmic-ray physics. However, strong constraints can be obtained from studying the anisotropy in the arrival directions of cosmic rays. The sensitivity to cosmic-ray anisotropy is, in particular, a matter of statistics. Recently, the cosmic ray anisotropy measurements in the TeV to PeV energy range were updated from IceCube using 11 years of data. The IceCube-Gen2 surface array will cover an area about 8 times larger than the existing IceTop surface array with a corresponding increase in statistics and capability to investigate cosmic-ray anisotropy with higher sensitivity. In this contribution, we present details on the performed simulation studies and sensitivity to the cosmic-ray anisotropy signal for the IceCube-Gen2 surface array

Estimating the coincidence rate between the optical and radio array of IceCube-Gen2

The IceCube-Gen2 Neutrino Observatory is proposed to extend the all-flavour energy range of IceCube beyond PeV energies. It will comprise two key components: I) An enlarged 8km3 in-ice optical Cherenkov array to measure the continuation of the IceCube astrophysical neutrino flux and improve IceCube\u27s point source sensitivity above ∼100TeV; and II) A very large in-ice radio array with a surface area of about 500km2. Radio waves propagate through ice with a kilometer-long attenuation length, hence a sparse radio array allows us to instrument a huge volume of ice to achieve a sufficient sensitivity to detect neutrinos with energies above tens of PeV. The different signal topologies for neutrino-induced events measured by the optical and in-ice radio detector - the radio detector is mostly sensitive to the cascades produced in the neutrino interaction, while the optical detector can detect long-ranging muon and tau leptons with high accuracy - yield highly complementary information. When detected in coincidence, these signals will allow us to reconstruct the neutrino energy and arrival direction with high fidelity. Furthermore, if events are detected in coincidence with a sufficient rate, they resemble the unique opportunity to study systematic uncertainties and to cross-calibrate both detector components