The rapid onset of stellar bars in the baryon-dominated centers of disk galaxies

Recent observations of high-redshift galactic disks ($z\approx 1-3$) show a strong negative trend in the dark matter fraction $f_{DM}$ with increasing baryonic surface density. For this to be true, the inner baryons must dominate over dark matter in early massive galaxies, as observed in the Milky Way today. If disks are dominant at early times, we show that stellar bars form promptly within these disks, leading to a high bar fraction at early times. New JWST observations provide the best evidence to date for mature stellar bars in this redshift range. The disk mass fraction $f_{disk}$ within $R_s=2.2 R_{disk}$ is the dominant factor in determining how rapidly a bar forms. Using 3D hydro simulations of halo-disk-bulge galaxies, we confirm the "Fujii relation" for the exponential dependence of the bar formation time $\tau_{bar}$ as a function of $f_{disk}$. For $f_{disk} > 0.3$, the bar formation time declines exponentially fast with increasing $f_{disk}$. This relation is a challenge to simulators - barred models with inadequate resolution fall off this curve. Instead of Fujii's arbitrary threshold for when a bar forms, for the first time, we exploit the exponential growth timescale associated with a positive feedback cycle as the bar emerges from the underlying disk. A modified, mass-dependent trend is observed for halos relevant to systems at cosmic noon ($10.5 < \log M_{halo} < 12$), where the bar onset is slower for higher mass halos at a fixed $f_{disk}$. If baryons dominate over dark matter within $R \approx R_s$, we predict that a high fraction of bars will be found in high-redshift disks long before $z = 1$. Due to its widespread use in simulations, we investigate the Efstathiou-Lake-Negroponte criterion for bar instability: this sub-optimal parameter is inversely related to $f_{disk}$, with a secondary dependence on $M_{halo}$.Comment: 27 pages, 8 figures, 1 table - Astrophysical Journal, accepted (9 March 2023

Prospective dark matter annihilation signals from the Sagittarius Dwarf Spheroidal

The Sagittarius Dwarf Spheroidal galaxy (Sgr) is investigated as a target for dark matter (DM) annihilation searches utilizing J-factor distributions calculated directly from a high-resolution hydrodynamic simulation of the infall and tidal disruption of Sgr around the Milky Way. In contrast to past studies, the simulation incorporates DM, stellar and gaseous components for both the Milky Way and the Sgr progenitor galaxy. The simulated distributions account for significant tidal disruption affecting the DM density profile. Our estimate of the J-factor value for Sgr, JSgr = 1.48 × 1010 M2☉ kpc−5 (6.46 × 1016 GeV cm−5), is significantly lower than found in prior studies. This value, while formally a lower limit, is likely close to the true J-factor value for Sgr. It implies a DM cross-section incompatibly large in comparison with existing constraints would be required to attribute recently observed gamma-ray emission from Sgr to DM annihilation. We also calculate a J-factor value using a NFW profile fitted to the simulated DM density distribution to facilitate comparison with past studies. This NFW J-factor value supports the conclusion that most past studies have overestimated the dark matter density of Sgr on small scales. This, together with the fact that the Sgr has recently been shown to emit gamma-rays of astrophysical origin, complicate the use of Sgr in indirect DM detection searches

Non-Markovian modeling of protein folding.

We extract the folding free energy landscape and the time-dependent friction function, the two ingredients of the generalized Langevin equation (GLE), from explicit-water molecular dynamics (MD) simulations of the α-helix forming polypeptide [Formula: see text] for a one-dimensional reaction coordinate based on the sum of the native H-bond distances. Folding and unfolding times from numerical integration of the GLE agree accurately with MD results, which demonstrate the robustness of our GLE-based non-Markovian model. In contrast, Markovian models do not accurately describe the peptide kinetics and in particular, cannot reproduce the folding and unfolding kinetics simultaneously, even if a spatially dependent friction profile is used. Analysis of the GLE demonstrates that memory effects in the friction significantly speed up peptide folding and unfolding kinetics, as predicted by the Grote-Hynes theory, and are the cause of anomalous diffusion in configuration space. Our methods are applicable to any reaction coordinate and in principle, also to experimental trajectories from single-molecule experiments. Our results demonstrate that a consistent description of protein-folding dynamics must account for memory friction effects

Statistical strategies to improve the efficiency of molecular studies of colorectal cancer prognosis

The evaluation of tumour molecular markers may be beneficial in prognosis and predictive in therapy. We develop a stopping rule approach to assist in the efficient utilisation of resources and samples involved in such evaluations. This approach has application in determining whether a specific molecular marker has sufficient variability to yield meaningful results after the evaluation of molecular markers in the first n patients in a study of sample size N (n⩽N). We evaluated colorectal tumours for mutations (microsatellite instability, K-ras, B-raf, PI3 kinase, and TGFβR-II) by PCR and protein markers (Bcl2, cyclin D1, E-cadherin, hMLH1, ki67, MDM2, and P53) by immunohistochemistry. Using this method, we identified and abandoned potentially uninformative molecular markers in favour of more promising candidates. This approach conserves tissue resources, time, and money, and may be applicable to other studies

Restriction of AID activity and somatic hypermutation by PARP-1

Affinity maturation of the humoral immune response depends on somatic hypermutation (SHM) of immunoglobulin (Ig) genes, which is initiated by targeted lesion introduction by activation-induced deaminase (AID), followed by error-prone DNA repair. Stringent regulation of this process is essential to prevent genetic instability, but no negative feedback control has been identified to date. Here we show that poly(ADP-ribose) polymerase-1 (PARP-1) is a key factor restricting AID activity during somatic hypermutation. Poly(ADP-ribose) (PAR) chains formed at DNA breaks trigger AID-PAR association, thus preventing excessive DNA damage induction at sites of AID action. Accordingly, AID activity and somatic hypermutation at the Ig variable region is decreased by PARP-1 activity. In addition, PARP-1 regulates DNA lesion processing by affecting strand biased A:T mutagenesis. Our study establishes a novel function of the ancestral genome maintenance factor PARP-1 as a critical local feedback regulator of both AID activity and DNA repair during Ig gene diversification

Tumoral calcinosis: radiologic-pathologic correlation

Tumoral calcinosis is a frequently misdiagnosed disorder. This study details the radiologic and pathologic characteristics of tumoral calcinosis that distinguish it from most other entities.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46807/1/256_2004_Article_BF00204854.pd

On reminder effects, drop-outs and dominance: evidence from an online experiment on charitable giving

We present the results of an experiment that (a) shows the usefulness of screening out drop-outs and (b) tests whether different methods of payment and reminder intervals affect charitable giving. Following a lab session, participants could make online donations to charity for a total duration of three months. Our procedure justifying the exclusion of drop-outs consists in requiring participants to collect payments in person flexibly and as known in advance and as highlighted to them later. Our interpretation is that participants who failed to collect their positive payments under these circumstances are likely not to satisfy dominance. If we restrict the sample to subjects who did not drop out, but not otherwise, reminders significantly increase the overall amount of charitable giving. We also find that weekly reminders are no more effective than monthly reminders in increasing charitable giving, and that, in our three months duration experiment, standing orders do not increase giving relative to one-off donations

Practice Patterns and Long-Term Survival for Early-Stage Rectal Cancer

Standard of care treatment for most stage I rectal cancers is total mesorectal excision (TME). Given the morbidity associated with TME, local excision (LE) for early-stage rectal cancer has been explored. This study examines practice patterns and overall survival (OS) for early-stage rectal cancer

Evaluation of commercially available RNA amplification kits for RNA sequencing using very low input amounts of total RNA

This article includes supplemental data. Please visit http://www.fasebj.org to obtain this information.Multiple recent publications on RNA sequencing (RNA-seq) have demonstrated the power of next-generation sequencing technologies in whole-transcriptome analysis. Vendor-specific protocols used for RNA library construction often require at least 100 ng total RNA. However, under certain conditions, much less RNA is available for library construction. In these cases, effective transcriptome profiling requires amplification of subnanogram amounts of RNA. Several commercial RNA amplification kits are available for amplification prior to library construction for next-generation sequencing, but these kits have not been comprehensively field evaluated for accuracy and performance of RNA-seq for picogram amounts of RNA. To address this, 4 types of amplification kits were tested with 3 different concentrations, from 5 ng to 50 pg, of a commercially available RNA. Kits were tested at multiple sites to assess reproducibility and ease of use. The human total reference RNA used was spiked with a control pool of RNA molecules in order to further evaluate quantitative recovery of input material. Additional control data sets were generated from libraries constructed following polyA selection or ribosomal depletion using established kits and protocols. cDNA was collected from the different sites, and libraries were synthesized at a single site using established protocols. Sequencing runs were carried out on the Illumina platform. Numerous metrics were compared among the kits and dilutions used. Overall, no single kit appeared to meet all the challenges of small input material. However, it is encouraging that excellent data can be recovered with even the 50 pg input total RNA

Treatment of active lupus nephritis with the novel immunosuppressant 15-deoxyspergualin: an open-label dose escalation study

Introduction: As the immunosuppressive potency of 15-deoxyspergualin (DSG) has been shown in the therapy of renal transplant rejection and Wegener's granulomatosis, the intention of this study was to evaluate the safety of DSG in the therapy of lupus nephritis (LN). Methods: Patients with histologically proven active LN after prior treatment with at least one immunosuppressant were treated with 0.5 mg/kg normal body weight/day DSG, injected subcutaneously for 14 days, followed by a break of one week. These cycles were repeated to a maximum of 9 times. Doses of oral corticosteroids were gradually reduced to 7.5 mg/day or lower by cycle 4. Response was measured according to a predefined decision pattern. The dose of DSG was adjusted depending on the efficacy and side effects. Results: 21 patients were included in this phase-I/II study. After the first DSG injection, one patient was excluded from the study due to renal failure. 5 patients dropped out due to adverse events or serious adverse events including fever, leukopenia, oral candidiasis, herpes zoster or pneumonia. 11/20 patients achieved partial (4) or complete responses (7), 8 were judged as treatment failures and one patient was not assessable. 12 patients completed all 9 cycles; in those patients, proteinuria decreased from 5.88g/day to 3.37g/day (P = 0.028), Selena-SLEDAI decreased from 17.6 to 11.7. In 13/20 patients, proteinuria decreased by at least 50%; in 7 patients to less than 1g/day. Conclusions: Although the number of patients was small, we could demonstrate that DSG provides a tolerably safe treatment for LN. The improvement in proteinuria encourages larger controlled trials