Oscillations in gas-grain astrochemical kinetics Dufour, Gwenaëlle; Charnley, Steven B; Lindberg, Johan E
Monthly notices of the Royal Astronomical Society,
01/2023, Letnik:
520, Številka:
1
Journal Article
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ABSTRACT
We have studied gas-grain chemical models of interstellar clouds to search for non-linear dynamical evolution. A prescription is given for producing oscillatory solutions when a bistable ...solution exists in the gas-phase chemistry and we demonstrate the existence of limit cycle and relaxation oscillation solutions. As the autocatalytic chemical processes underlying these solutions are common to all models of interstellar chemistry, the occurrence of these solutions should be widespread. We briefly discuss the implications for interpreting molecular cloud composition with time-dependent models and some future directions for this approach.
Recent observations from Herschel allow the identification of important mechanisms responsible both for the heating of the gas that surrounds low-mass protostars and for its subsequent cooling in the ...far-infrared. Shocks are routinely invoked to reproduce some properties of the far-IR spectra, but standard models fail to reproduce the emission from key molecules, e.g., H2O. Here, we present the Herschel Photodetector Array Camera and Spectrometer (PACS) far-IR spectroscopy of 90 embedded low-mass protostars (Class 0/I). The Herschel-PACS spectral maps, covering ∼55-210 m with a field of view of ∼50″, are used to quantify the gas excitation conditions and spatial extent using rotational transitions of H2O, high-J CO, and OH, as well as O i and C ii. We confirm that a warm (∼300 K) CO reservoir is ubiquitous and that a hotter component (760 170 K) is frequently detected around protostars. The line emission is extended beyond ∼1000 au spatial scales in 40/90 objects, typically in molecular tracers in Class 0 and atomic tracers in Class I objects. High-velocity emission ( 90 km s−1) is detected in only 10 sources in the O i line, suggesting that the bulk of O i arises from gas that is moving slower than typical jets. Line flux ratios show an excellent agreement with models of C-shocks illuminated by ultraviolet (UV) photons for pre-shock densities of ∼105 cm−3 and UV fields 0.1-10 times the interstellar value. The far-IR molecular and atomic lines are a unique diagnostic of feedback from UV emission and shocks in envelopes of deeply embedded protostars.
Summary Background The prostate-specific antigen (PSA) test is used to screen for prostate cancer but has a high false-positive rate that translates into unnecessary prostate biopsies and ...overdiagnosis of low-risk prostate cancers. We aimed to develop and validate a model to identify high-risk prostate cancer (with a Gleason score of at least 7) with better test characteristics than that provided by PSA screening alone. Methods The Stockholm 3 (STHLM3) study is a prospective, population-based, paired, screen-positive, diagnostic study of men without prostate cancer aged 50–69 years randomly invited by date of birth from the Swedish Population Register kept by the Swedish Tax Agency. Men with prostate cancer at enrolment were excluded from the study. The predefined STHLM3 model (a combination of plasma protein biomarkers PSA, free PSA, intact PSA, hK2, MSMB, MIC1, genetic polymorphisms 232 SNPs, and clinical variables age, family, history, previous prostate biopsy, prostate exam), and PSA concentration were both tested in all participants enrolled. The primary aim was to increase the specificity compared with PSA without decreasing the sensitivity to diagnose high-risk prostate cancer. The primary outcomes were number of detected high-risk cancers (sensitivity) and the number of performed prostate biopsies (specificity). The STHLM3 training cohort was used to train the STHLM3 model, which was prospectively tested in the STHLM3 validation cohort. Logistic regression was used to test for associations between biomarkers and clinical variables and prostate cancer with a Gleason score of at least 7. This study is registered with ISCRTN.com , number ISRCTN84445406. Findings The STHLM3 model performed significantly better than PSA alone for detection of cancers with a Gleason score of at least 7 (p<0·0001), the area under the curve was 0·56 (95% CI 0·55–0·60) with PSA alone and 0·74 (95% CI 0·72–0·75) with the STHLM3 model. All variables used in the STHLM3 model were significantly associated with prostate cancers with a Gleason score of at least 7 (p<0·05) in a multiple logistic regression model. At the same level of sensitivity as the PSA test using a cutoff of ≥3 ng/mL to diagnose high risk prostate cancer, use of the STHLM3 model could reduce the number of biopsies by 32% (95% CI 24–39) and could avoid 44% (35–54) of benign biopsies. Interpretation The STHLM3 model could reduce unnecessary biopsies without compromising the ability to diagnose prostate cancer with a Gleason score of at least 7, and could be a step towards personalised risk-based prostate cancer diagnostic programmes. Funding Stockholm County Council (Stockholms Läns Landsting).
Low-mass protostars have been suggested to show highly variable accretion rates throughout their evolution. Such changes in accretion, and related heating of their ambient envelopes, may trigger ...significant chemical variations on different spatial scales and from source-to-source. We present images of emission from C super(17)O, H super(13)CO+, CH sub(3)OH, C super(34)S and C sub(2)H toward the low-mass protostar IRAS 15398-3359 on 0".5 (75 AU diameter) scales with the Atacama Large Millimeter/submillimeter Array at 340 GHz. The resolved images show that the emission from H super(13)CO+ is only present in a ring-like structure with a radius of about 1-1".5 (150-200 AU) whereas the CO and other high dipole moment molecules are centrally condensed toward the location of the central protostar. We propose that HCO+ is destroyed by water vapor present on small scales. The origin of this water vapor is likely an accretion burst during the last 100-1000 yr increasing the luminosity of IRAS 15398-3359 by a factor of 100 above its current luminosity. Such a burst in luminosity can also explain the centrally condensed CH sub(3)OH and extended warm carbon-chain chemistry observed in this source and furthermore be reflected in the relative faintness of its compact continuum emission compared to other protostars.
Genome-wide association studies have identified thousands of SNPs associated with predisposition to various diseases, including prostate cancer. However, the mechanistic roles of these SNPs remain ...poorly defined, particularly for noncoding polymorphisms. Here we find that the prostate cancer risk-associated SNP rs339331 at 6q22 lies within a functional HOXB13-binding site. The risk-associated T allele at rs339331 increases binding of HOXB13 to a transcriptional enhancer, conferring allele-specific upregulation of the rs339331-associated gene RFX6. Suppression of RFX6 diminishes prostate cancer cell proliferation, migration and invasion. Clinical data indicate that RFX6 upregulation in human prostate cancers correlates with tumor progression, metastasis and risk of biochemical relapse. Finally, we observe a significant association between the risk-associated T allele at rs339331 and increased RFX6 mRNA levels in human prostate tumors. Together, our results suggest that rs339331 affects prostate cancer risk by altering RFX6 expression through a functional interaction with the prostate cancer susceptibility gene HOXB13.
Abstract Background Expression of the androgen receptor splice variant 7 (AR-V7) is associated with poor response to second-line endocrine therapy in castration-resistant prostate cancer (CRPC). ...However, a large fraction of nonresponding patients are AR-V7–negative. Objective To investigate if a comprehensive liquid biopsy–based AR profile may improve patient stratification in the context of second-line endocrine therapy. Design, setting, and participants Peripheral blood was collected from patients with CRPC ( n = 30) before initiation of a new line of systemic therapy. We performed profiling of circulating tumour DNA via low-pass whole-genome sequencing and targeted sequencing of the entire AR gene, including introns. Targeted RNA sequencing was performed on enriched circulating tumour cell fractions to assess the expression levels of seven AR splice variants (ARVs). Outcome measurements and statistical analysis Somatic AR variations, including copy-number alterations, structural variations, and point mutations, were combined with ARV expression patterns and correlated to clinicopathologic parameters. Results and limitations Collectively, any AR perturbation, including ARV, was detected in 25/30 patients. Surprisingly, intra-AR structural variation was present in 15/30 patients, of whom 14 expressed ARVs. The majority of ARV-positive patients expressed multiple ARVs, with AR-V3 the most abundantly expressed. The presence of any ARV was associated with progression-free survival after second-line endocrine treatment (hazard ratio 4.53, 95% confidence interval 1.424–14.41; p = 0.0105). Six out of 17 poor responders were AR-V7–negative, but four carried other AR perturbations. Conclusions Comprehensive AR profiling, which is feasible using liquid biopsies, is necessary to increase our understanding of the mechanisms underpinning resistance to endocrine treatment. Patient summary Alterations in the androgen receptor are associated with endocrine treatment outcomes. This study demonstrates that it is possible to identify different types of alterations via simple blood draws. Follow-up studies are needed to determine the effect of such alterations on hormonal therapy.
Context. The R CrA cloud hosts a handful of Class 0/I low-mass young stellar objects. The chemistry and physics at scales >500 AU in this cloud are dominated by the irradiation from the nearby Herbig ...Be star R CrA. The luminous large-scale emission makes it necessary to use high-resolution spectral imaging to study the chemistry and dynamics of the inner envelopes and discs of the protostars. Aims. We aim to better understand the structure of the inner regions of these protostars and, in particular, the interplay between the chemistry and the presence of discs. Methods. Using Atacama Large Millimeter/submillimeter Array (ALMA) high-resolution spectral imaging interferometry observations, we study the molecular line and dust continuum emission at submillimetre wavelengths. Results. We detect dust continuum emission from four circumstellar discs around Class 0/I objects within the R CrA cloud. Towards IRS7B we detect C17O emission showing a rotation curve consistent with a Keplerian disc with a well-defined edge that gives a good estimate for the disc radius at 50 AU. We derive the central object mass to 2.3 M⊙ and the disc mass to 0.024 M⊙. The observations are also consistent with a model of material infalling under conservation of angular momentum; however, this model provides a worse fit to the data. We also report a likely detection of faint CH3OH emission towards this point source, as well as more luminous CH3OH emission in an outflow orthogonal to the major axis of the C17O emission. Conclusions. The faint CH3OH emission seen towards IRS7B can be explained by a flat density profile of the inner envelope caused by the disc with a radius ≲50 AU. We propose that the regions of the envelopes where complex organic molecules are present in Class 0/I young stellar objects can become quenched as the disc grows.
The tumor suppressor protein retinoblastoma (RB) is mechanistically linked to suppression of transcription factor E2F1-mediated cell cycle regulation. For multiple tumor types, loss of RB function is ...associated with poor clinical outcome. RB action is abrogated either by direct depletion or through inactivation of RB function; however, the basis for this selectivity is unknown. Here, analysis of tumor samples and cell-free DNA from patients with advanced prostate cancer showed that direct RB loss was the preferred pathway of disruption in human disease. While RB loss was associated with lethal disease, RB-deficient tumors had no proliferative advantage and exhibited downstream effects distinct from cell cycle control. Mechanistically, RB loss led to E2F1 cistrome expansion and different binding specificity, alterations distinct from those observed after functional RB inactivation. Additionally, identification of protumorigenic transcriptional networks specific to RB loss that were validated in clinical samples demonstrated the ability of RB loss to differentially reprogram E2F1 in human cancers. Together, these findings not only identify tumor-suppressive functions of RB that are distinct from cell cycle control, but also demonstrate that the molecular consequence of RB loss is distinct from RB inactivation. Thus, these studies provide insight into how RB loss promotes disease progression, and identify new nodes for therapeutic intervention.
We present APEX 218 GHz observations of molecular emission in a complete sample of embedded protostars in the Ophiuchus star-forming region. To study the physical properties of the cores, we ...calculate H2CO and c-C3H2 rotational temperatures, both of which are good tracers of the kinetic temperature of the molecular gas. We find that the H2CO temperatures range between 16K and 124K, with the highest H2CO temperatures toward the hot corino source IRAS 16293-2422 (69-124 K) and the sources in the rho Oph A cloud (23-49 K) located close to the luminous Herbig Be star S1, which externally irradiates the rho Oph A cores. On the other hand, the c-C3H2 rotational temperature is consistently low (7-17 K) in all sources. Our results indicate that the c-C3H2 emission is primarily tracing more shielded parts of the envelope whereas the H2CO emission (at the angular scale of the APEX beam; 3600 au in Ophiuchus) mainly traces the outer irradiated envelopes, apart from in IRAS16293-2422, where the hot corino emission dominates. In some sources, a secondary velocity component is also seen, possibly tracing the molecular outflow.
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