The Pioneer and Voyager spacecraft made close-up measurements of Saturn's ionosphere and upper atmosphere in the 1970s and 1980s that suggested a chemical interaction between the rings and ...atmosphere. Exploring this interaction provides information on ring composition and the influence on Saturn's atmosphere from infalling material. The Cassini Ion Neutral Mass Spectrometer sampled in situ the region between the D ring and Saturn during the spacecraft's Grand Finale phase. We used these measurements to characterize the atmospheric structure and material influx from the rings. The atmospheric He/H
ratio is 10 to 16%. Volatile compounds from the rings (methane; carbon monoxide and/or molecular nitrogen), as well as larger organic-bearing grains, are flowing inward at a rate of 4800 to 45,000 kilograms per second.
Compared with previous standards of care (including chemotherapy, radiotherapy, and surgery), cancer immunotherapy has brought significant improvements for patients in terms of survival and quality ...of life. Immunotherapy has now firmly established itself as a novel pillar of cancer care, from the metastatic stage to the adjuvant and neoadjuvant settings in numerous cancer types. In this review article, we highlight how the history of cancer immunotherapy paved the way for discoveries that are now part of the standard of care. We also highlight the current pitfalls and limitations of cancer checkpoint immunotherapy and how novel research in the fields of personalized cancer vaccines, autoimmunity, the microbiome, the tumour microenvironment, and metabolomics is aiming to solve those challenges.
The progression of cancers from primary tumors to invasive and metastatic stages accounts for the overwhelming majority of cancer deaths. Understanding the molecular events which promote metastasis ...is thus critical in the clinic. Translational control is emerging as an important factor in tumorigenesis. The messenger RNA (mRNA) cap-binding protein eIF4E is an oncoprotein that has an important role in cancer initiation and progression. eIF4E must be phosphorylated to promote tumor development. However, the role of eIF4E phosphorylation in metastasis is not known. Here, we show that mice in which eukaryotic translation initiation factor 4E (eIF4E) cannot be phosphorylated are resistant to lung metastases in a mammary tumor model, and that cells isolated from these mice exhibit impaired invasion. We also demonstrate that transforming growth factor-beta (TGFβ) induces eIF4E phosphorylation to promote the translation of Snail and Mmp-3 mRNAs, and the induction of epithelial-to-mesenchymal transition (EMT). Furthermore, we describe a new model wherein EMT induced by TGFβ requires translational activation via the non-canonical TGFβ signaling branch acting through eIF4E phosphorylation.
Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis with associated frontotemporal dementia (ALS/FTD) are major neurodegenerative diseases for which there are no ...cures. All are characterised by damage to several seemingly disparate cellular processes. The broad nature of this damage makes understanding pathogenic mechanisms and devising new treatments difficult. Can the different damaged functions be linked together in a common disease pathway and which damaged function should be targeted for therapy? Many functions damaged in neurodegenerative diseases are regulated by communications that mitochondria make with a specialised region of the endoplasmic reticulum (ER; mitochondria-associated ER membranes or ‘MAM’). Moreover, several recent studies have shown that disturbances to ER–mitochondria contacts occur in neurodegenerative diseases. Here, we review these findings.
Interstellar dust and starlight are modeled for the galaxies of the project "Key Insights on Nearby Galaxies: A Far-Infrared Survey with Herschel." The galaxies were observed by the Infrared Array ...Camera and the Multiband Imaging Photometer for Spitzer on Spitzer Space Telescope, and the Photodetector Array Camera and Spectrometer and the Spectral and Photometric Imaging Receiver on Herschel Space Observatory. With data from 3.6 to 500 m, dust models are strongly constrained. Using a physical dust model, for each pixel in each galaxy we estimate (1) dust surface density, (2) dust mass fraction in polycyclic aromatic hydrocarbons (PAHs), (3) distribution of starlight intensities heating the dust, (4) total infrared (IR) luminosity emitted by the dust, and (5) IR luminosity originating in subregions with high starlight intensity. The dust models successfully reproduce the observed global and resolved spectral energy distributions. With the angular resolution of Herschel, we obtain well-resolved maps (available online) for the dust properties. As in previous studies, we find the PAH fraction to be an increasing function of metallicity, with a threshold oxygen abundance Z/Z 0.1, but we find the data to be fitted best with increasing linearly with above a threshold value of 0.15(O/H) . We obtain total dust masses for each galaxy by summing the dust mass over the individual map pixels; these "resolved" dust masses are consistent with the masses inferred from a model fit to the global photometry. The global dust-to-gas ratios obtained from this study are found to correlate with galaxy metallicities. Systems with Z/Z 0.5 have most of their refractory elements locked up in dust, whereas in systems with Z/Z 0.3 most of these elements tend to remain in the gas phase. Within galaxies, we find that is suppressed in regions with unusually warm dust with . With knowledge of one long-wavelength flux density ratio (e.g., f160/f500), the minimum starlight intensity heating the dust ( ) can be estimated to within ∼50%, despite a variation in of more than two orders of magnitude. For the adopted dust model, dust masses can be estimated to within ∼0.2 dex accuracy using the f160/f500 flux ratio and the integrated dust luminosity, and to ∼0.07 dex accuracy using the 500 m luminosity alone. There are additional systematic errors arising from the choice of dust model, but these are hard to estimate. These calibrated prescriptions for estimating starlight heating intensity and dust mass may be useful for studies of high-redshift galaxies.
Biodegradable Piezoelectric Force Sensor Curry, Eli J.; Ke, Kai; Chorsi, Meysam T. ...
Proceedings of the National Academy of Sciences,
01/2018, Letnik:
115, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Measuring vital physiological pressures is important for monitoring health status, preventing the buildup of dangerous internal forces in impaired organs, and enabling novel approaches of using ...mechanical stimulation for tissue regeneration. Pressure sensors are often required to be implanted and directly integrated with native soft biological systems. Therefore, the devices should be flexible and at the same time biodegradable to avoid invasive removal surgery that can damage directly interfaced tissues. Despite recent achievements in degradable electronic devices, there is still a tremendous need to develop a force sensor which only relies on safe medical materials and requires no complex fabrication process to provide accurate information on important biophysiological forces. Here, we present a strategy for material processing, electromechanical analysis, device fabrication, and assessment of a piezoelectric Poly-L-lactide (PLLA) polymer to create a biodegradable, biocompatible piezoelectric force sensor, which only employs medical materials used commonly in Food and Drug Administration-approved implants, for the monitoring of biological forces. We show the sensor can precisely measure pressures in a wide range of 0–18 kPa and sustain a reliable performance for a period of 4 d in an aqueous environment. We also demonstrate this PLLA piezoelectric sensor can be implanted inside the abdominal cavity of a mouse to monitor the pressure of diaphragmatic contraction. This piezoelectric sensor offers an appealing alternative to present biodegradable electronic devices for the monitoring of intraorgan pressures. The sensor can be integrated with tissues and organs, forming self-sensing bionic systems to enable many exciting applications in regenerative medicine, drug delivery, and medical devices.
ABSTRACT Luminous quasars at can be studied in detail with the current generation of telescopes and provide us with unique information on the first gigayear of the universe. Thus far, these studies ...have been statistically limited by the number of quasars known at these redshifts. Such quasars are rare, and therefore, wide-field surveys are required to identify them, and multiwavelength data are required to separate them efficiently from their main contaminants, the far more numerous cool dwarfs. In this paper, we update and extend the selection for the quasars presented in Bañados et al. (2014) using the Pan-STARRS1 (PS1) survey. We present the PS1 distant quasar sample, which currently consists of 124 quasars in the redshift range that satisfy our selection criteria. Of these quasars, 77 have been discovered with PS1, and 63 of them are newly identified in this paper. We present the composite spectra of the PS1 distant quasar sample. This sample spans a factor of ∼20 in luminosity and shows a variety of emission line properties. The number of quasars at presented in this work almost doubles the previously known quasars at these redshifts, marking a transition phase from studies of individual sources to statistical studies of the high-redshift quasar population, which was impossible with earlier, smaller samples.
Experimental evidence indicates that bainitic ferrite formed by transformation at low temperatures (200–350°C) contains quantities of carbon in solid solution far beyond those expected from ...para-equilibrium. A change in the conventional symmetry of the bainitic ferrite lattice from cubic to tetragonal explains the abnormal solid solubility detected. This carbon supersaturation was measured by atom probe tomography, and the tetragonality of the bainitic ferrite, was characterized by means of X-ray diffraction analysis and high resolution transmission electron microscopy.
BACKGROUNDPembrolizumab demonstrated durable antitumor activity in 233 patients with previously treated advanced microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) advanced ...solid tumors in the phase II multicohort KEYNOTE-158 (NCT02628067) study. Herein, we report safety and efficacy outcomes with longer follow-up for more patients with previously treated advanced MSI-H/dMMR noncolorectal cancers who were included in cohort K of the KEYNOTE-158 (NCT02628067) study. PATIENTS AND METHODSEligible patients with previously treated advanced noncolorectal MSI-H/dMMR solid tumors, measurable disease as per RECIST v1.1, and Eastern Cooperative Oncology Group performance status of 0 or 1 received pembrolizumab 200 mg Q3W for 35 cycles or until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) as per RECIST v1.1 by independent central radiologic review. RESULTSThree hundred and fifty-one patients with various tumor types were enrolled in KEYNOTE-158 cohort K. The most common tumor types were endometrial (22.5%), gastric (14.5%), and small intestine (7.4%). Median time from first dose to database cut-off (5 October 2020) was 37.5 months (range, 0.2-55.6 months). ORR among 321 patients in the efficacy population (patients who received ≥1 dose of pembrolizumab enrolled ≥6 months before the data cut-off date) was 30.8% 95% confidence interval (CI) 25.8% to 36.2%. Median duration of response was 47.5 months (range, 2.1+ to 51.1+ months; '+' indicates no progressive disease by the time of last disease assessment). Median progression-free survival was 3.5 months (95% CI 2.3-4.2 months) and median overall survival was 20.1 months (95% CI 14.1-27.1 months). Treatment-related adverse events (AEs) occurred in 227 patients (64.7%). Grade 3-4 treatment-related AEs occurred in 39 patients (11.1%); 3 (0.9%) had grade 5 treatment-related AEs (myocarditis, pneumonia, and Guillain-Barre syndrome, n = 1 each). CONCLUSIONSPembrolizumab demonstrated clinically meaningful and durable benefit, with a high ORR of 30.8%, long median duration of response of 47.5 months, and manageable safety across a range of heavily pretreated, advanced MSI-H/dMMR noncolorectal cancers, providing support for use of pembrolizumab in this setting.
Ammoniated aerosols are important for urban air quality, but emissions of the key precursor NH3 are not well quantified. Mobile laboratory observations are used to characterize fleet-integrated NH3 ...emissions in six cities in the U.S. and China. Vehicle NH3:CO2 emission ratios in the U.S. are similar between cities (0.33–0.40 ppbv/ppmv, 15% uncertainty) despite differences in fleet composition, climate, and fuel composition. While Beijing, China has a comparable emission ratio (0.36 ppbv/ppmv) to the U.S. cities, less developed Chinese cities show higher emission ratios (0.44 and 0.55 ppbv/ppmv). If the vehicle CO2 inventories are accurate, NH3 emissions from U.S. vehicles (0.26 ± 0.07 Tg/yr) are more than twice those of the National Emission Inventory (0.12 Tg/yr), while Chinese NH3 vehicle emissions (0.09 ± 0.02 Tg/yr) are similar to a bottom-up inventory. Vehicle NH3 emissions are greater than agricultural emissions in counties containing near half of the U.S. population and require reconsideration in urban air quality models due to their colocation with other aerosol precursors and the uncertainties regarding NH3 losses from upwind agricultural sources. Ammonia emissions in developing cities are especially important because of their high emission ratios and rapid motorizations.
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