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We have studied gas-grain chemical models of interstellar clouds to search for nonlinear 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., Comment: 9 pages, 3 figures, 1 table

In this paper we derive fundamental limitations on the levels of $H_2$ and $H_\infty{}$ performance that can be achieved when controlling lossless systems. The results are applied to the swing equation power system model, where it is shown that the fundamental limit on the $H_2$ norm scales with the inverse of the harmonic mean of the inertias in the system. This indicates that power systems may see a degradation in performance as more renewables are integrated, further motivating the need for new control solutions to aid the energy transition., Comment: 6 pages, 7 figures. Accepted, but not yet published for Control Systems Letters (L-CSS)

Background: Transrectal ultrasound guided systematic biopsies of the prostate is a routine procedure to establish a prostate cancer diagnosis. However, the 10-12 prostate core biopsies only sample a relatively small volume of the prostate, and tumour lesions in regions between biopsy cores can be missed, leading to a well-known low sensitivity to detect clinically relevant cancer. As a proof-of-principle, we developed and validated a deep convolutional neural network model to distinguish between morphological patterns in benign prostate biopsy whole slide images from men with and without established cancer. Methods: This study included 14,354 hematoxylin and eosin stained whole slide images from benign prostate biopsies from 1,508 men in two groups: men without an established prostate cancer (PCa) diagnosis and men with at least one core biopsy diagnosed with PCa. 80% of the participants were assigned as training data and used for model optimization (1,211 men), and the remaining 20% (297 men) as a held-out test set used to evaluate model performance. An ensemble of 10 deep convolutional neural network models was optimized for classification of biopsies from men with and without established cancer. Hyperparameter optimization and model selection was performed by cross-validation in the training data . Results: Area under the receiver operating characteristic curve (ROC-AUC) was estimated as 0.727 (bootstrap 95% CI: 0.708-0.745) on biopsy level and 0.738 (bootstrap 95% CI: 0.682 - 0.796) on man level. At a specificity of 0.9 the model had an estimated sensitivity of 0.348. Conclusion: The developed model has the ability to detect men with risk of missed PCa due to under-sampling of the prostate. The proposed model has the potential to reduce the number of false negative cases in routine systematic prostate biopsies and to indicate men who could benefit from MRI-guided re-biopsy., Comment: 13 pages, 3 figures

Molecular phenotyping by gene expression profiling is common in contemporary cancer research and in molecular diagnostics. However, molecular profiling remains costly and resource intense to implement, and is just starting to be introduced into clinical diagnostics. Molecular changes, including genetic alterations and gene expression changes, occuring in tumors cause morphological changes in tissue, which can be observed on the microscopic level. The relationship between morphological patterns and some of the molecular phenotypes can be exploited to predict molecular phenotypes directly from routine haematoxylin and eosin (H&E) stained whole slide images (WSIs) using deep convolutional neural networks (CNNs). In this study, we propose a new, computationally efficient approach for disease specific modelling of relationships between morphology and gene expression, and we conducted the first transcriptome-wide analysis in prostate cancer, using CNNs to predict bulk RNA-sequencing estimates from WSIs of H&E stained tissue. The work is based on the TCGA PRAD study and includes both WSIs and RNA-seq data for 370 patients. Out of 15586 protein coding and sufficiently frequently expressed transcripts, 6618 had predicted expression significantly associated with RNA-seq estimates (FDR-adjusted p-value < 1*10-4) in a cross-validation. 5419 (81.9%) of these were subsequently validated in a held-out test set. We also demonstrate the ability to predict a prostate cancer specific cell cycle progression score directly from WSIs. These findings suggest that contemporary computer vision models offer an inexpensive and scalable solution for prediction of gene expression phenotypes directly from WSIs, providing opportunity for cost-effective large-scale research studies and molecular diagnostics.

Background: An increasing volume of prostate biopsies and a world-wide shortage of uro-pathologists puts a strain on pathology departments. Additionally, the high intra- and inter-observer variability in grading can result in over- and undertreatment of prostate cancer. Artificial intelligence (AI) methods may alleviate these problems by assisting pathologists to reduce workload and harmonize grading. Methods: We digitized 6,682 needle biopsies from 976 participants in the population based STHLM3 diagnostic study to train deep neural networks for assessing prostate biopsies. The networks were evaluated by predicting the presence, extent, and Gleason grade of malignant tissue for an independent test set comprising 1,631 biopsies from 245 men. We additionally evaluated grading performance on 87 biopsies individually graded by 23 experienced urological pathologists from the International Society of Urological Pathology. We assessed discriminatory performance by receiver operating characteristics (ROC) and tumor extent predictions by correlating predicted millimeter cancer length against measurements by the reporting pathologist. We quantified the concordance between grades assigned by the AI and the expert urological pathologists using Cohen's kappa. Results: The performance of the AI to detect and grade cancer in prostate needle biopsy samples was comparable to that of international experts in prostate pathology. The AI achieved an area under the ROC curve of 0.997 for distinguishing between benign and malignant biopsy cores, and 0.999 for distinguishing between men with or without prostate cancer. The correlation between millimeter cancer predicted by the AI and assigned by the reporting pathologist was 0.96. For assigning Gleason grades, the AI achieved an average pairwise kappa of 0.62. This was within the range of the corresponding values for the expert pathologists (0.60 to 0.73)., Comment: 45 pages, 11 figures

Recent observations from Herschel allow the identification of important mechanisms responsible for the heating of gas surrounding low-mass protostars and its subsequent cooling in the far-infrared (FIR). 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. H$_2$O. Here, we present the Herschel-PACS far-IR spectroscopy of 90 embedded low-mass protostars (Class 0/I). The Herschel-PACS spectral maps covering $\sim55-210$ $\mu$m with a field-of-view of $\sim$50'' are used to quantify the gas excitation conditions and spatial extent using rotational transitions of H$_{2}$O, high-$J$ CO, and OH, as well as [O I] and [C II]. We confirm that a warm ($\sim$300 K) CO reservoir is ubiquitous and that a hotter component ($760\pm170$ K) is frequently detected around protostars. The line emission is extended beyond $\sim$1000 AU spatial scales in 40/90 objects, typically in molecular tracers in Class 0 and atomic tracers in Class I objects. High-velocity emission ($\gtrsim90$ 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 UV photons for pre-shock densities of $\sim$$10^5$ 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., Comment: Accepted by ApJS, 55 pages, 170 figures

We present the results of Very Large Array NH$_{3}$ $(J,K)=(1,1)$ and $(2,2)$ observations of the HH 111/HH 121 protostellar system. HH 111, with a spectacular collimated optical jet, is one of the most well-known Herbig-Haro objects. We report the detection of a new source (NH$_{3}-$S) in the vicinity of HH 111/HH 121 ($\sim$0.03 pc from the HH 111 jet source) in two epochs of the ammonia observations. This constitutes the first detection of this source, in a region which has been thoroughly covered previously by both continuum and spectral line interferometric observations. We study the kinematic and physical properties of HH 111 and the newly discovered NH$_{3}-$S. We also use HCO$^{+}$ and HCN $(J=4-3)$ data obtained with the James Clerk Maxwell Telescope and archival Atacama Large Millimeter/submillimeter Array $^{13}$CO, $^{12}$CO, and C$^{18}$O $(J=2-1)$, N$_2$D$^{+}$ $(J=3-2)$, and $^{13}$CS $(J=5-4)$ data to gain insight into the nature of NH$_{3}-$S. The chemical structure of NH$_3-$S shows evidence for "selective freeze-out", an inherent characteristic of dense cold cores. The inner part of NH$_3-$S shows subsonic non-thermal velocity dispersions indicating a "coherent core", while they increase in the direction of the jets. Archival near- to far-infrared data show no indication of any embedded source in NH$_3-$S. The properties of NH$_3-$S and its location in the infrared dark cloud suggest that it is a starless core located in a turbulent medium with turbulence induced by Herbig-Haro jets and associated outflows. More data is needed to fully understand the physical and chemical properties of NH$_3-$S and if/how its evolution is affected by nearby jets., Comment: Accepted for publication in the Astrophysical Journal, 21 pages

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 H$_2$CO and c-C$_3$H$_2$ rotational temperatures, both of which are good tracers of the kinetic temperature of the molecular gas. We find that the H$_2$CO temperatures range between 16 K and 124 K, with the highest H$_2$CO 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 S 1, which externally irradiates the $\rho$ Oph A cores. On the other hand, the c-C$_3$H$_2$ rotational temperature is consistently low (7-17 K) in all sources. Our results indicate that the c-C$_3$H$_2$ emission is primarily tracing more shielded parts of the envelope whereas the H$_2$CO emission (at the angular scale of the APEX beam; 3600 au in Ophiuchus) mainly traces the outer irradiated envelopes, apart from in IRAS 16293-2422, where the hot corino emission dominates. In some sources, a secondary velocity component is also seen, possibly tracing the molecular outflow., Comment: 19 pages, 9 figures, accepted for publication in ApJ

The formation pathways of different types of organic molecules in protostellar envelopes and other regions of star formation are subjects of intense current interest. We here present observations of C$_4$H and CH$_3$OH, tracing two distinct groups of interstellar organic molecules, toward 16 protostars in the Ophiuchus and Corona Australis molecular clouds. Together with observations in the literature, we present C$_4$H and CH$_3$OH data from single-dish observations of 40 embedded protostars. We find no correlation between the C$_4$H and CH$_3$OH column densities in this large sample. Based on this lack of correlation, a difference in line profiles between C$_4$H and CH$_3$OH, and previous interferometric observations of similar sources, we propose that the emission from these two molecules is spatially separated, with the CH$_3$OH tracing gas that has been transiently heated to high ($\sim$70-100 K) temperatures, and the C$_4$H tracing the cooler large-scale envelope where CH$_4$ molecules have been liberated from ices. These results provide insight in the differentiation between hot corino and warm carbon-chain chemistry in embedded protostars., Comment: 7 pages, 2 figures, accepted for publication in ApJL

We present sub-millimeter spectra of HCN isotopologues on Titan, derived from publicly available ALMA flux calibration observations of Titan taken in early 2014. We report the detection of a new HCN isotopologue on Titan, H$^{13}$C$^{15}$, and confirm an earlier report of detection of DCN. We model high signal-to-noise observations of HCN, H$^{13}$CN, HC$^{15}$N, DCN, and H$^{13}$C$^{15}$ to derive abundances and infer the following isotopic ratios: $^{12}$C/$^{13}$C = 89.8 $\pm$ 2.8, $^{14}$N/$^{15}$N = 72.3 $\pm$ 2.2, D/H = (2.5 $\pm$ 0.2)$\times$10$^{-4}$, and HCN/H$^{13}$C$^{15}$ = 5800 $\pm$ 270 (1$\sigma$ errors). The carbon and nitrogen ratios are consistent with and improve on the precision of previous results, confirming a factor of $\sim$2.3 elevation in $^{14}$N/$^{15}$N in HCN compared to N$_2$ and a lack of fractionation in $^{12}$C/$^{13}$C from the protosolar value. This is the first published measurement of D/H in a nitrile species on Titan, and we find evidence for a factor of $\sim$2 deuterium enrichment in hydrogen cyanide compared to methane. The isotopic ratios we derive may be used as constraints for future models to better understand the fractionation processes occurring in Titan's atmosphere., Comment: Accepted for publication in Astrophysical Journal Letters. 14 pages, 3 figures, 2 tables

We report interferometric observations of carbon monoxide (CO) and its isotopologues in Titan's atmosphere using the Atacama Large Millimeter/submillimeter Array (ALMA). The following transitions were detected: CO (J = 1-0, 2-1, 3-2, 6-5), $^{13}$CO (J = 2-1, 3-2, 6-5), C$^{18}$O (J = 2-1, 3-2), and C$^{17}$O (J = 3-2). Molecular abundances and the vertical atmospheric temperature profile were derived by modeling the observed emission line profiles using NEMESIS, a line-by-line radiative transfer code. We present the first spectroscopic detection of $^{17}$O in the outer solar system with C$^{17}$O detected at > 8$\sigma$ confidence. The abundance of CO was determined to be 49.6 ${\pm}$ 1.8 ppm, assumed to be constant with altitude, with isotopic ratios $^{12}$C/$^{13}$C = 89.9 ${\pm}$ 3.4, $^{16}$O/$^{18}$O = 486 ${\pm}$ 22, and $^{16}$O/$^{17}$O = 2917${\pm}$359. The measurements of $^{12}$C/$^{13}$C and $^{16}$O/$^{18}$O ratios are the most precise values obtained in Titan's atmospheric CO to date. Our results are in good agreement with previous studies and suggest no significant deviations from standard terrestrial isotopic ratios., Comment: Accepted for publication in ApJ Letters

(abridged) Context: The envelopes of molecular gas around embedded low-mass protostars show different chemistries, which can be used to trace their formation history and physical conditions. The excitation of some molecular species can also be used to trace these physical conditions, making it possible to constrain e.g. sources of heating and excitation. Aims: To study the range of influence of an intermediate-mass Herbig Be protostar, and to find what chemical and physical impact feedback effects from the environment may have on embedded protostars. Methods: We follow up on an earlier line survey of the Class 0/I source R CrA IRS7B in the 0.8 mm window with an unbiased line survey of the same source in the 1.3 mm window using the APEX telescope. We also study the excitation of the key species H2CO, CH3OH, and c-C3H2 in a complete sample of the 18 embedded protostars in the Corona Australis star-forming region. Radiative transfer models are used to establish abundances of the molecular species. Results: We detect line emission from 20 molecular species (32 including isotopologues) in the two surveys. The most complex species detected are CH3OH, CH3CCH, CH3CHO, and CH3CN. Several complex organics are significantly under-abundant in comparison with "hot corino" protostars. The H2CO temperatures of the sources in the region decrease with the distance to the Herbig Be star R CrA, whereas the c-C3H2 temperatures remain constant across the star-forming region. Conclusions: The high H2CO temperatures observed towards objects close to R CrA suggest that this star has a sphere of influence of several 10000 AU in which it increases the temperature of the molecular gas to 30-50 K through irradiation. The chemistry in the IRS7B envelope differs significantly from many other embedded protostars, which could be an effect of the external irradiation from R CrA., Comment: Accepted for publication in A&A. 83 pages (main body: 19 pages, appendix: 64 pages), 66 figures

Sub-arcsecond ($0.^{\prime\prime}5$) images of H$_2$CO and CCH line emission have been obtained in the $0.8$ mm band toward the low-mass protostar IRAS 15398-3359 in the Lupus 1 cloud as one of the Cycle 0 projects of the Atacama Large Millimeter/Submillimeter Array. We have detected a compact component concentrated in the vicinity of the protostar and a well-collimated outflow cavity extending along the northeast-southwest axis. The inclination angle of the outflow is found to be about $20^\circ$, or almost edge-on, based on the kinematic structure of the outflow cavity. This is in contrast to previous suggestions of a more pole-on geometry. The centrally concentrated component is interpreted by use of a model of the infalling rotating envelope with the estimated inclination angle, and the mass of the protostar is estimated to be less than $0.09\ M_\odot$. Higher spatial resolution data are needed to infer the presence of a rotationally supported disk for this source, hinted at by a weak high-velocity H$_2$CO emission associated with the protostar.

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 C$^{17}$O 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 $2.3M_{\odot}$ and the disc mass to $0.024M_{\odot}$. 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 CH$_3$OH emission towards this point source, as well as more luminous CH$_3$OH emission in an outflow orthogonal to the major axis of the C$^{17}$O emission. Conclusions: The faint CH$_3$OH emission seen towards IRS7B can be explained by a flat density profile of the inner envelope caused by the disc with a radius $\lesssim50$ 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., Comment: Accepted for publication in A&A; 11 pages, 9 figures

Low-mass protostars have been suggested to show highly variable accretion rates through-out 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 C17O, H13CO+, CH3OH, C34S and C2H toward the low-mass protostar IRAS 15398-3359 on 0.5" (75 AU diameter) scales with the Atacama Large Millimeter/submillimeter Array (ALMA) at 340 GHz. The resolved images show that the emission from H13CO+ 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 years 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 CH3OH 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., Comment: Accepted for publication in ApJ Letters; 14 pages, 5 figures

The effects of external irradiation on the chemistry and physics in the protostellar envelope around low-mass young stellar objects are poorly understood. The Corona Australis star-forming region contains the R CrA dark cloud, comprising several low-mass protostellar cores irradiated by an intermediate-mass young star. We study the effects on the warm gas and dust in a group of low-mass young stellar objects from the irradiation by the young luminous Herbig Be star R CrA. Herschel/PACS far-infrared datacubes of two low-mass star-forming regions in the R CrA dark cloud are presented. The distribution of CO, OH, H2O, [C II], [O I], and continuum emission is investigated. We have developed a deconvolution algorithm which we use to deconvolve the maps, separating the point-source emission from the extended emission. We also construct rotational diagrams of the molecular species. By deconvolution of the Herschel data, we find large-scale (several thousand AU) dust continuum and spectral line emission not associated with the point sources. Similar rotational temperatures are found for the warm CO ($282\pm4$ K), hot CO ($890\pm84$ K), OH ($79\pm4$ K), and H2O ($197\pm7$ K) emission, respectively, in the point sources and the extended emission. The rotational temperatures are also similar to what is found in other more isolated cores. The extended dust continuum emission is found in two ridges similar in extent and temperature to molecular mm emission, indicative of external heating from the Herbig Be star R CrA. Our results show that a nearby luminous star does not increase the molecular excitation temperatures in the warm gas around a young stellar object (YSO). However, the emission from photodissociation products of H2O, such as OH and O, is enhanced in the warm gas associated with these protostars and their surroundings compared to similar objects not suffering from external irradiation., Comment: 37 pages, accepted for publication in A&A

We present 50-210 um spectral scans of 30 Class 0/I protostellar sources, obtained with Herschel-PACS, and 0.5-1000 um SEDs, as part of the Dust, Ice, and Gas in Time (DIGIT) Key Program. Some sources exhibit up to 75 H2O lines ranging in excitation energy from 100-2000 K, 12 transitions of OH, and CO rotational lines ranging from J=14-13 up to J=40-39. [O I] is detected in all but one source in the entire sample; among the sources with detectable [O I] are two Very Low Luminosity Objects (VeLLOs). The mean 63/145 um [O I] flux ratio is 17.2 +/- 9.2. The [O I] 63 um line correlates with Lbol, but not with the time-averaged outflow rate derived from low-J CO maps. [C II] emission is in general not local to the source. The sample Lbol increased by 1.25 (1.06) and Tbol decreased to 0.96 (0.96) of mean (median) values with the inclusion of the Herschel data. Most CO rotational diagrams are characterized by two optically thin components ( = (0.70 +/- 1.12) x 10^49 total particles). N_CO correlates strongly with Lbol, but neither Trot nor N_CO(warm)/N_CO(hot) correlates with Lbol, suggesting that the total excited gas is related to the current source luminosity, but that the excitation is primarily determined by the physics of the interaction (e.g., UV- heating/shocks). Rotational temperatures for H2O ( = 194 +/- 85 K) and OH ( = 183 +/- 117 K) are generally lower than for CO, and much of the scatter in the observations about the best fit is attributed to differences in excitation conditions and optical depths amongst the detected lines., Comment: 58 pages, 37 figures; accepted to ApJ

We have conducted a spectral line survey in the 332 - 364 GHz region with the ASTE 10 m telescope toward R CrA IRS7B, a low-mass protostar in the Class 0 or Class 0/I transitional stage. We have also performed some supplementary observations in the 450 GHz band. In total, 16 molecular species are identified in the 332 - 364 GHz region. Strong emission lines of CN and CCH are observed, whereas complex organic molecules and long carbon-chain molecules which are characteristics of hot corino and warm carbon-chain chemistry (WCCC) source, respectively, are not detected. The rotation temperature of CH3OH is evaluated to be 31 K, which is significantly lower than that reported for the prototypical hot corino IRAS 16293-2422 (~85 K). The deuterium fractionation ratios for CCH and H2CO are obtained to be 0.038 and 0.050, respectively, which are much lower than those in the hot corino. These results suggest a weak hot corino activity in R CrA IRS7B. On the other hand, the carbon-chain related molecules, CCH and c-C3H2, are found to be abundant. However, this source cannot be classified as a WCCC source, since long carbon-chain molecules are not detected. If WCCC and hot corino chemistry represent the two extremes in chemical compositions of low-mass Class 0 sources, R CrA IRS7B would be a source with a mixture of these two chemical characteristics. The UV radiation from the nearby Herbig Ae star R CrA may also affect the chemical composition. The present line survey demonstrates further chemical diversity in low-mass star-forming regions., Comment: 45 pages, 5 figures, accepted for publication in ApJ