Modeling of the hydrogen Lyman lines in solar flares

The hydrogen Lyman lines (91.2 nm < λ < 121.6 nm) are significant contributors to the radiative losses of the solar chromosphere, and they are enhanced during flares. We have shown previously that the Lyman lines observed by the Extreme Ultraviolet Variability instrument onboard the Solar Dynamics Observatory exhibit Doppler motions equivalent to speeds on the order of 30 km s−1. However, contrary to expectations, both redshifts and blueshifts were present and no dominant flow direction was observed. To understand the formation of the Lyman lines, particularly their Doppler motions, we have used the radiative hydrodynamic code, RADYN, along with the radiative transfer code, RH, to simulate the evolution of the flaring chromosphere and the response of the Lyman lines during solar flares. We find that upflows in the simulated atmospheres lead to blueshifts in the line cores, which exhibit central reversals. We then model the effects of the instrument on the profiles, using the Extreme Ultraviolet Variability Experiment (EVE) instrument's properties. What may be interpreted as downflows (redshifted emission) in the lines, after they have been convolved with the instrumental line profile, may not necessarily correspond to actual downflows. Dynamic features in the atmosphere can introduce complex features in the line profiles that will not be detected by instruments with the spectral resolution of EVE, but which leave more of a signature at the resolution of the Spectral Investigation of the Coronal Environment instrument onboard the Solar Orbiter

CXD101 and nivolumab in patients with metastatic microsatellite-stable colorectal cancer (CAROSELL): a multicentre, open-label, single-arm, phase II trial.

BACKGROUND: Patients with microsatellite stable (MSS) colorectal carcinoma (CRC) do not respond to immune checkpoint inhibitors. Preclinical models suggested synergistic anti-tumour activity combining CXD101 and anti-programmed cell death protein 1 treatment; therefore, we assessed the clinical combination of CXD101 and nivolumab in heavily pre-treated patients with MSS metastatic CRC (mCRC). PATIENTS AND METHODS: This single-arm, open-label study enrolled patients aged 18 years or older with biopsy-confirmed MSS CRC; at least two lines of systemic anticancer therapies (including oxaliplatin and irinotecan); at least one measurable lesion; Eastern Cooperative Oncology Group performance status of 0, 1 or 2; predicted life expectancy above 3 months; and adequate organ and bone marrow function. Nine patients were enrolled in a safety run-in study to define a tolerable combination schedule of CXD101 and nivolumab, followed by 46 patients in the efficacy assessment phase. Patients in the efficacy assessment cohort were treated orally with 20 mg CXD101 twice daily for 5 consecutive days every 3 weeks, and intravenously with 240 mg nivolumab every 2 weeks. The primary endpoint was immune disease control rate (iDCR). RESULTS: Between 2018 and 2020, 55 patients were treated with CXD101 and nivolumab. The combination therapy was well tolerated with the most frequent grade 3 or 4 adverse events being neutropenia (18%) and anaemia (7%). Immune-related adverse reactions commonly ascribed to checkpoint inhibitors were surprisingly rare although we did see single cases of pneumonitis, hypothyroidism and hypopituitarism. There were no treatment-related deaths. Of 46 patients assessable for efficacy, 4 (9%) achieved partial response and 18 (39%) achieved stable disease, translating to an immune disease control rate of 48%. The median overall survival (OS) was 7.0 months (95% confidence interval 5.13-10.22 months). CONCLUSIONS: The primary endpoint was met in this phase II study, which showed that the combination of CXD101 and nivolumab, at full individual doses in the treatment of advanced or metastatic MSS CRC, was both well tolerated and efficacious

Areas of natural occurrence of melipona scutellaris Latreille, 1811(Hymenoptera: Apidae) in the state of Bahia, Brazil.

The bee Melipona scutellaris is considered the reared meliponine species with the largest distribution in the North and Northeast regions of Brazil, with records from the state of Rio Grande do Norte down to the state of Bahia. Considering the importance of this species in the generation of income for family agriculture and in the preservation of areas with natural vegetation, this study aimed at providing knowledge on the distribution of natural colonies of M. scutellaris in the state of Bahia. Literature information, interviews with stinglessbee beekeepers, and expeditions were conducted to confirm the natural occurrence of the species. A total of 102 municipalities showed records for M. scutellaris, whose occurrence was observed in areas ranging from sea level up to 1,200-meter height. The occurrence of this species in the state of Bahia is considered to be restricted to municipalities on the coastal area and the Chapada Diamantina with its rainforests. Geographic coordinates, elevation, climate and vegetation data were obtained, which allowed a map to be prepared for the area of occurrence in order to support conservation and management policies for the species

Dynamic changes in the brain protein interaction network correlates with progression of Aβ42 pathology in Drosophila

Alzheimer’s disease (AD), the most prevalent form of dementia, is a progressive and devastating neurodegenerative condition for which there are no effective treatments. Understanding the molecular pathology of AD during disease progression may identify new ways to reduce neuronal damage. Here, we present a longitudinal study tracking dynamic proteomic alterations in the brains of an inducible Drosophila melanogaster model of AD expressing the Arctic mutant Aβ42 gene. We identified 3093 proteins from flies that were induced to express Aβ42 and age-matched healthy controls using label-free quantitative ion-mobility data independent analysis mass spectrometry. Of these, 228 proteins were significantly altered by Aβ42 accumulation and were enriched for AD-associated processes. Network analyses further revealed that these proteins have distinct hub and bottleneck properties in the brain protein interaction network, suggesting that several may have significant effects on brain function. Our unbiased analysis provides useful insights into the key processes governing the progression of amyloid toxicity and forms a basis for further functional analyses in model organisms and translation to mammalian systems

Arecibo HI Absorption Measurements of Pulsars and the Electron Density at Intermediate Longitudes in the First Galactic Quadrant

We have used the Arecibo telescope to measure the HI absorption spectra of eight pulsars. We show how kinematic distance measurements depend upon the values of the galactic constants R_o and Theta_o, and we select our preferred current values from the literature. We then derive kinematic distances for the low-latitude pulsars in our sample and electron densities along their lines of sight. We combine these measurements with all others in the inner galactic plane visible from Arecibo to study the electron density in this region. The electron density in the interarm range 48 degrees < l < 70 degrees is [0.017 (-0.007,+0.012) (68% c.l.)] cm^(-3). This is 0.75 (-0.22,+0.49) (68% c.l.) of the value calculated by the Cordes & Lazio (2002) galactic electron density model. The model agrees more closely with electron density measurements toward Arecibo pulsars lying closer to the galactic center, at 30 degrees<l<48 degrees. Our analysis leads to the best current estimate of the distance of the relativistic binary pulsar B1913+16: d=(9.0 +/- 3) kpc. We use the high-latitude pulsars to search for small-scale structure in the interstellar hydrogen observed in absorption over multiple epochs. PSR B0301+19 exhibited significant changes in its absorption spectrum over 22 yr, indicating HI structure on a ~500 AU scale.Comment: Accepted by Astrophysical Journal September 200

Does the revised cardiac risk index predict cardiac complications following elective lung resection?

Background: Revised Cardiac Risk Index (RCRI) score and Thoracic Revised Cardiac Risk Index (ThRCRI) score were developed to predict the risks of postoperative major cardiac complications in generic surgical population and thoracic surgery respectively. This study aims to determine the accuracy of these scores in predicting the risk of developing cardiac complications including atrial arrhythmias after lung resection surgery in adults. Methods: We studied 703 patients undergoing lung resection surgery in a tertiary thoracic surgery centre. Observed outcome measures of postoperative cardiac morbidity and mortality were compared against those predicted by risk. Results: Postoperative major cardiac complications and supraventricular arrhythmias occurred in 4.8% of patients. Both index scores had poor discriminative ability for predicting postoperative cardiac complications with an area under receiver operating characteristic (ROC) curve of 0.59 (95% CI 0.51-0.67) for the RCRI score and 0.57 (95% CI 0.49-0.66) for the ThRCRI score. Conclusions: In our cohort, RCRI and ThRCRI scores failed to accurately predict the risk of cardiac complications in patients undergoing elective resection of lung cancer. The British Thoracic Society (BTS) recommendation to seek a cardiology referral for all asymptomatic pre-operative lung resection patients with > 3 RCRI risk factors is thus unlikely to be of clinical benefit

Photometry and membership for low mass stars in the young open cluster NGC 2516

We present the results of a 0.86 square degree CCD photometric survey of the open cluster NGC 2516, which has an age of about 150 Myr and may have a much lower metallicity than the similarly-aged Pleiades. We select a preliminary catalogue of 1254 low mass (between 0.2 and 2.0M_{sun}) cluster candidates, of which about 70--80 percent are expected to be genuine. The mass function is metallicity dependent, but consistent with a Salpeter-like law (dN/dlog M ~ M^{-alpha}, alpha=+1.47+/-0.11 or alpha=+1.67+/-0.11 for solar and half-solar metallicities) between 0.7 and 3.0M_{sun}. At lower masses (between 0.3 and 0.7M_{sun}) there is a sharp fall in the mass function, with alpha=-0.75+/-0.20 (solar metallicity) or alpha=-0.49+/-0.13 (half-solar metallicity), which seems inconsistent with the much flatter mass functions seen in the Pleiades and field populations. We explain this by demonstrating that mass segregation has been at work in NGC 2516 -- more than half the cluster low mass stars are expected to lie outside out survey. The mass of NGC 2516 stars with mass greater than 0.3M_{sun} inside our survey is 950-1200M_{sun}, depending on metallicity and what corrections are applied for unresolved binarity. Correcting for mass segregation increases this to ~1240-1560M_{sun}, about twice the total mass of the Pleiades.Comment: 27 pages, accepted for Astronomy & Astrophysic

ESA’s Soil Moisture and Ocean Salinity Mission - An overview on the mission’s performance and scientific results

European Geosciences Union General Assembly 2014 (EGU2014), 27 april - 2 may 2014, Vienna, Austria.-- 1 pageThe Soil Moisture and Ocean Salinity (SMOS) mission, launched on 2 November 2009, is the European Space Agency’s (ESA) second Earth Explorer Opportunity mission. The scientific objectives of the SMOS mission directly respond to the need for global observations of soil moisture and ocean salinity, two key variables used in predictive hydrological, oceanographic and atmospheric models. SMOS observations also provide information on the characterisation of ice and snow covered surfaces and the sea ice effect on ocean-atmosphere heat fluxes and dynamics, which affects large-scale processes of the Earth’s climate system. This paper will provide an overview on the various aspects of the SMOS mission, such as 1. The performance of the mission after more than 5 years in orbit: The SMOS mission has been in routine operations since May 2010, following the successful completion of the 6-months commissioning phase. The paper will summarise the technical and scientific status of the mission, including the status of the RFI detection and mitigation and its effect on the data products. SMOS has so far provided very reliable instrument operations, data processing and dissemination to users. The paper will also provide an overview on the MIRAS instrument performance, including the instrument calibration and level 1 brightness temperature data processing. 2. An overview on the SMOS data products: SMOS provides continuously level 1 (brightness temperature) and level 2 (soil moisture and ocean salinity) to its scientific user community since summer 2010. SMOS also provides brightness temperature data (level 1 data) to ECMWF in near-real time (NRT), who assimilates the data into their forecasting system. New services have been established to deliver a tailored NRT data product via the WMO’s GTS and EUMETSAT’s EUMETCast data dissemination systems to other operational agencies. This will open up new operational applications for SMOS data. Other data products are under development, responding to the requirements of the science community in particular in the area of hydrology, climate, land use and ship routing, namely a frozen soil indicator, data products for freeze/thaw periods, sea ice thickness and vegetation water content. 3. Provide an update on the overall validation approach and recent activities: SMOS data products are continuously improved and approach the scientific mission objectives. Validation activities are essential to ensure high data quality. ESA in collaboration with national agencies and institutions maintains a frame for validation activities such as reference sites, ground based observations as well as campaigns. The paper will provide an update on recent activities, such as the activities at DOME-C. 4. Summarise the collaboration with other space-borne L-band sensors, such as NASA’s Aquarius and SMAP missionsPeer Reviewe

A synthetic cyclized antimicrobial peptide with potent effects against drug resistant skin pathogens

Acknowledgments We would like to thank Anna Blasi-Romero for helping with the set-up of the initial scanning electron microscopy experiments. This project was partially supported by the Stiftelsen Olle Engkvist Byggmästare (AB 186 678), Region Stockholm (AB, ALF project 995080), a fellowship grant from the EPSRC (no. EP/S027246/1, W.E.H.), the Bo Rydin Foundation (no. F30/20; NF), the Swedish Research Council (# no. 2011-3403; UG); and Postdoctoral scholarship by Elisabeth and Alfred Ahlqvists Stiftelse, Apotekarsocieteten (TM). The graphical abstract was created with a BioRender standard academic license.Peer reviewedPublisher PD

Recent advances in the structural and molecular biology of type IV secretion systems

Bacteria use type IV secretion (T4S) systems to deliver DNA and protein substrates to a diverse range of prokaryotic and eukaryotic target cells. T4S systems have great impact on human health, as they are a major source of antibiotic resistance spread among bacteria and are central to infection processes of many pathogens. Therefore, deciphering the structure and underlying translocation mechanism of T4S systems is crucial to facilitate development of new drugs. The last five years have witnessed considerable progress in unraveling the structure of T4S system subassemblies, notably that of the T4S system core complex, a large 1 MegaDalton (MDa) structure embedded in the double membrane of Gram-negative bacteria and made of 3 of the 12 T4S system components. However, the recent determination of the structure of ∼3 MDa assembly of 8 of these components has revolutionized our views of T4S system architecture and opened up new avenues of research, which are discussed in this review