Star Formation in Disk Galaxies. I. Formation and Evolution of Giant Molecular Clouds via Gravitational Instability and Cloud Collisions

We investigate the formation and evolution of giant molecular clouds (GMCs) in a Milky-Way-like disk galaxy with a flat rotation curve. We perform a series of 3D adaptive mesh refinement (AMR) numerical simulations that follow both the global evolution on scales of ~20kpc and resolve down to scales ~<10pc with a multiphase atomic interstellar medium (ISM). In this first study, we omit star formation and feedback, and focus on the processes of gravitational instability and cloud collisions and interactions. We define clouds as regions with n_H>=100cm^-3 and track the evolution of individual clouds as they orbit through the galaxy from their birth to their eventual destruction via merger or via destructive collision with another cloud. After ~140Myr a large fraction of the gas in the disk has fragmented into clouds with masses ~10^6 Msun and a mass spectrum similar to that of Galactic GMCs. The disk settles into a quasi steady state in which gravitational scattering of clouds keeps the disk near the threshold of global gravitational instability. The cloud collision time is found to be a small fraction, ~1/5, of the orbital time, and this is an efficient mechanism to inject turbulence into the clouds. This helps to keep clouds only moderately gravitationally bound, with virial parameters of order unity. Many other observed GMC properties, such as mass surface density, angular momentum, velocity dispersion, and vertical distribution, can be accounted for in this simple model with no stellar feedback.Comment: 21 pages ApJ format, including 16 figures, accepted to Ap

Kiloparsec-scale simulations of star formation in disk galaxies. I. the unmagnetized and zero-feedback limit

We present hydrodynamic simulations of the evolution of self-gravitating dense gas on scales of 1 kpc down to ≲ parsec in a galactic disk, designed to study dense clump formation from giant molecular clouds (GMCs). These structures are expected to be the precursors to star clusters and this process may be the rate limiting step controlling star formation rates in galactic systems as described by the Kennicutt-Schmidt relation. We follow the thermal evolution of the gas down to 5 K using extinction-dependent heating and cooling functions. We do not yet include magnetic fields or localized stellar feedback, so the evolution of the GMCs and clumps is determined solely by self-gravity balanced by thermal and turbulent pressure support and the large-scale galactic shear. While cloud structures and densities change significantly during the simulation, GMC virial parameters remain mostly above unity for timescales exceeding the free-fall time of GMCs indicating that energy from galactic shear and large-scale cloud motions continuously cascades down to and within the GMCs. We implement star formation at a slow, inefficient rate of 2% per local free-fall time, but even this yields global star formation rates that are about two orders of magnitude larger than the observed Kennicutt-Schmidt relation due to overproduction of dense gas clumps. We expect a combination of magnetic support and localized stellar feedback is required to inhibit dense clump formation to 1% of the rate that results from the nonmagnetic, zero-feedback limit

Distinct plasma metabolomic signatures differentiate autoimmune encephalitis from drug‐resistant epilepsy

Objective: Differentiating forms of autoimmune encephalitis (AE) from other causes of seizures helps expedite immunotherapies in AE patients and informs studies regarding their contrasting pathophysiology. We aimed to investigate whether and how Nuclear Magnetic Resonance (NMR)‐based metabolomics could differentiate AE from drug‐resistant epilepsy (DRE), and stratify AE subtypes. Methods: This study recruited 238 patients: 162 with DRE and 76 AE, including 27 with contactin‐associated protein‐like 2 (CASPR2), 29 with leucine‐rich glioma inactivated 1 (LGI1) and 20 with N‐methyl‐d‐aspartate receptor (NMDAR) antibodies. Plasma samples across the groups were analyzed using NMR spectroscopy and compared with multivariate statistical techniques, such as orthogonal partial least squares discriminant analysis (OPLS‐DA). Results: The OPLS‐DA model successfully distinguished AE from DRE patients with a high predictive accuracy of 87.0 ± 3.1% (87.9 ± 3.4% sensitivity and 86.3 ± 3.6% specificity). Further, pairwise OPLS‐DA models were able to stratify the three AE subtypes. Plasma metabolomic signatures of AE included decreased high‐density lipoprotein (HDL, −(CH2)n−, –CH3), phosphatidylcholine and albumin (lysyl moiety). AE subtype‐specific metabolomic signatures were also observed, with increased lactate in CASPR2, increased lactate, glucose, and decreased unsaturated fatty acids (UFA, –CH2CH=) in LGI1, and increased glycoprotein A (GlycA) in NMDAR‐antibody patients. Interpretation: This study presents the first non‐antibody‐based biomarker for differentiating DRE, AE and AE subtypes. These metabolomics signatures underscore the potential relevance of lipid metabolism and glucose regulation in these neurological disorders, offering a promising adjunct to facilitate the diagnosis and therapeutics

Thirty- and ninety-day outcomes after sublobar resection with and without brachytherapy for non–small cell lung cancer: Results from a multicenter phase III study

ObjectiveSublobar resection (SR) is commonly used for patients considered high risk for lobectomy. Nonoperative therapies are increasingly being reported for patients with similar risk because of perceived lower morbidity. We report 30- and 90-day adverse events (AEs) from American College of Surgeons Oncology Group Z4032, a multicenter phase III study for high-risk patients with stage I non–small cell lung cancer.MethodsData from 222 evaluable patients randomized to SR (n = 114) or SR with brachytherapy (n = 108) are reported. AEs were recorded using the Common Terminology Criteria for Adverse Events, Version 3.0, at 30 and 90 days after surgery. Risk factors (age, percent baseline carbon monoxide diffusion in the lung [DLCO%], percent forced expiratory volume in 1 second [FEV1%], upper lobe vs lower lobe resections, performance status, surgery approach, video-assisted thoracic surgery vs open and extent, and wedge vs segmentectomy) were analyzed using a multivariable logistic model for their impact on the incidence of grade 3 or higher (G3+) AEs. Respiratory AEs were also specifically analyzed.ResultsMedian age, FEV1%, and DLCO% were similar in the 2 treatment groups. There was no difference in the location of resection (upper vs lower lobe) or the use of segmental or wedge resections. There were no differences between the groups with respect to “respiratory” G3+ AEs (30 days: 14.9% vs 19.4%, P = .35; 0–90 days: 19.3% vs 25%, P = .31) and “any” G3+ AEs (30 days: 25.4% vs 30.6%, P = .37; 0–90 days: 29.8% vs 37%, P = .25). Further analysis combined the 2 groups. Mortality occurred in 3 patients (1.4%) by 30 days and in 6 patients (2.7%) by 90 days. Four of the 6 deaths were thought to be due to surgery. When considered as continuous variables, FEV1% was associated with “any” G3+ AE at days 0 to 30 (P = .03; odds ratio [OR] = 0.98) and days 0 to 90 (P = .05; OR = 0.98), and DLCO% was associated with “respiratory” G3+ AE at days 0 to 30 (P = .03; OR = 0.97) and days 0 to 90 (P = .05; OR = 0.98). Segmental resection was associated with a higher incidence of any G3+ AE compared with wedge resection at days 0 to 30 (40.3% vs 22.7%; OR = 2.56; P < .01) and days 0 to 90 (41.5% vs 29.7%; OR = 1.96; P = .04). The median FEV1% was 50%, and the median DLCO% was 46%. By using these median values as potential cutpoints, only a DLCO% of less than 46% was significantly associated with an increased risk of “respiratory” and “any” G3+ AE for days 0 to 30 and 0 to 90.ConclusionsIn a multicenter setting, SR with brachytherapy was not associated with increased morbidity compared with SR alone. SR/SR with brachytherapy can be performed safely in high-risk patients with non–small cell lung cancer with low 30- and 90-day mortality and acceptable morbidity. Segmental resection was associated with increased “any” G3+ AE, and DLCO% less than 46% was associated with “any” G3+ AE and “respiratory” G3+ AE at both 30 and 90 days

The second set of pulsar discoveries by CHIME/FRB/Pulsar: 14 Rotating Radio Transients and 7 pulsars

The Canadian Hydrogen Mapping Experiment (CHIME) is a radio telescope located in British Columbia, Canada. The large field of view (FOV) of $\sim$ 200 square degrees has enabled the CHIME/FRB instrument to produce the largest FRB catalog to date. The large FOV also allows CHIME/FRB to be an exceptional pulsar and Rotating Radio Transient (RRAT) finding machine, despite saving only the metadata information of incoming Galactic events. We have developed a pipeline to search for pulsars/RRATs using DBSCAN, a clustering algorithm. Output clusters are then inspected by a human for pulsar/RRAT candidates and follow-up observations are scheduled with the more sensitive CHIME/Pulsar instrument. The CHIME/Pulsar instrument is capable of a near-daily search mode observation cadence. We have thus developed the CHIME/Pulsar Single Pulse Pipeline to automate the processing of CHIME/Pulsar search mode data. We report the discovery of 21 new Galactic sources, with 14 RRATs, 6 regular slow pulsars and 1 binary system. Owing to CHIME/Pulsar's daily observations we have obtained timing solutions for 8 of the 14 RRATs along with all the regular pulsars. This demonstrates CHIME/Pulsar's ability at finding timing solutions for transient sources

GMC Collisions as Triggers of Star Formation. II. 3D Turbulent, Magnetized Simulations

We investigate giant molecular cloud (GMCs) collisions and their ability to induce gravitational instability and thus star formation. This mechanism may be a major driver of star formation activity in galactic disks. We carry out a series of three dimensional, magnetohydrodynamics (MHD), adaptive mesh refinement (AMR) simulations to study how cloud collisions trigger formation of dense filaments and clumps. Heating and cooling functions are implemented based on photo-dissociation region (PDR) models that span the atomic to molecular transition and can return detailed diagnostic information. The clouds are initialized with supersonic turbulence and a range of magnetic field strengths and orientations. Collisions at various velocities and impact parameters are investigated. Comparing and contrasting colliding and non-colliding cases, we characterize morphologies of dense gas, magnetic field structure, cloud kinematic signatures, and cloud dynamics. We present key observational diagnostics of cloud collisions, especially: relative orientations between magnetic fields and density structures, like filaments; 13CO(J=2-1), 13CO(J=3-2), and 12CO(J=8-7) integrated intensity maps and spectra; and cloud virial parameters. We compare these results to observed Galactic clouds

Single-Cell Analysis of Blood-Brain Barrier Response to Pericyte Loss

Rationale: Pericytes are capillary mural cells playing a role in stabilizing newly formed blood vessels during development and tissue repair. Loss of pericytes has been described in several brain disorders, and genetically induced pericyte deficiency in the brain leads to increased macromolecular leakage across the blood-brain barrier (BBB). However, the molecular details of the endothelial response to pericyte deficiency remain elusive. Objective: To map the transcriptional changes in brain endothelial cells resulting from lack of pericyte contact at single-cell level, and to correlate them with regional heterogeneities in BBB function and vascular phenotype. Methods and Results: We reveal transcriptional, morphological and functional consequences of pericyte absence for brain endothelial cells using a combination of methodologies, including single-cell RNA sequencing, tracer analyses and immunofluorescent detection of protein expression in pericyte-deficient adult Pdgfbret/ret mice. We find that endothelial cells without pericyte contact retain a general BBB-specific gene expression profile, however, they acquire a venous-shifted molecular pattern and become transformed regarding the expression of numerous growth factors and regulatory proteins. Adult Pdgfbret/ret brains display ongoing angiogenic sprouting without concomitant cell proliferation providing unique insights into the endothelial tip cell transcriptome. We also reveal heterogeneous modes of pericyte-deficient BBB impairment, where hotspot leakage sites display arteriolar-shifted identity and pinpoint putative BBB regulators. By testing the causal involvement of some of these using reverse genetics, we uncover a reinforcing role for angiopoietin 2 at the BBB. Conclusions: By elucidating the complexity of endothelial response to pericyte deficiency at cellular resolution, our study provides insight into the importance of brain pericytes for endothelial arterio-venous zonation, angiogenic quiescence and a limited set of BBB functions. The BBB-reinforcing role of ANGPT2 is paradoxical given its wider role as TIE2 receptor antagonist and may suggest a unique and context-dependent function of ANGPT2 in the brain

GMC Collisions as Triggers of Star Formation. III. Density and Magnetically Regulated Star Formation

We study giant molecular cloud (GMC) collisions and their ability to trigger star cluster formation. We further develop our three dimensional magnetized, turbulent, colliding GMC simulations by implementing star formation sub-grid models. Two such models are explored: (1) Density-Regulated, i.e., fixed efficiency per free-fall time above a set density threshold; (2) Magnetically- Regulated, i.e., fixed efficiency per free-fall time in regions that are magnetically supercritical. Variations of parameters associated with these models are also explored. In the non-colliding simulations, the overall level of star formation is sensitive to model parameter choices that relate to effective density thresholds. In the GMC collision simulations, the final star formation rates and efficiencies are relatively independent of these parameters. Between non-colliding and colliding cases, we compare the morphologies of the resulting star clusters, properties of star-forming gas, time evolution of the star formation rate (SFR), spatial clustering of the stars, and resulting kinematics of the stars in comparison to the natal gas. We find that typical collisions, by creating larger amounts of dense gas, trigger earlier and enhanced star formation, resulting in 10 times higher SFRs and efficiencies. The star clusters formed from GMC collisions show greater spatial sub-structure and more disturbed kinematics