The Origin and Universality of the Stellar Initial Mass Function

We review current theories for the origin of the Stellar Initial Mass Function (IMF) with particular focus on the extent to which the IMF can be considered universal across various environments. To place the issue in an observational context, we summarize the techniques used to determine the IMF for different stellar populations, the uncertainties affecting the results, and the evidence for systematic departures from universality under extreme circumstances. We next consider theories for the formation of prestellar cores by turbulent fragmentation and the possible impact of various thermal, hydrodynamic and magneto-hydrodynamic instabilities. We address the conversion of prestellar cores into stars and evaluate the roles played by different processes: competitive accretion, dynamical fragmentation, ejection and starvation, filament fragmentation and filamentary accretion flows, disk formation and fragmentation, critical scales imposed by thermodynamics, and magnetic braking. We present explanations for the characteristic shapes of the Present-Day Prestellar Core Mass Function and the IMF and consider what significance can be attached to their apparent similarity. Substantial computational advances have occurred in recent years, and we review the numerical simulations that have been performed to predict the IMF directly and discuss the influence of dynamics, time-dependent phenomena, and initial conditions.Comment: 24 pages, 6 figures. Accepted for publication as a chapter in Protostars and Planets VI, University of Arizona Press (2014), eds. H. Beuther, R. S. Klessen, C. P. Dullemond, Th. Hennin

Long-term efficacy and safety of first-line ibrutinib treatment for patients with CLL/SLL: 5 years of follow-up from the phase 3 RESONATE-2 study.

RESONATE-2 is a phase 3 study of first-line ibrutinib versus chlorambucil in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Patients aged ≥65 years (n = 269) were randomized 1:1 to once-daily ibrutinib 420 mg continuously or chlorambucil 0.5-0.8 mg/kg for ≤12 cycles. With a median (range) follow-up of 60 months (0.1-66), progression-free survival (PFS) and overall survival (OS) benefits for ibrutinib versus chlorambucil were sustained (PFS estimates at 5 years: 70% vs 12%; HR [95% CI]: 0.146 [0.098-0.218]; OS estimates at 5 years: 83% vs 68%; HR [95% CI]: 0.450 [0.266-0.761]). Ibrutinib benefit was also consistent in patients with high prognostic risk (TP53 mutation, 11q deletion, and/or unmutated IGHV) (PFS: HR [95% CI]: 0.083 [0.047-0.145]; OS: HR [95% CI]: 0.366 [0.181-0.736]). Investigator-assessed overall response rate was 92% with ibrutinib (complete response, 30%; 11% at primary analysis). Common grade ≥3 adverse events (AEs) included neutropenia (13%), pneumonia (12%), hypertension (8%), anemia (7%), and hyponatremia (6%); occurrence of most events as well as discontinuations due to AEs decreased over time. Fifty-eight percent of patients continue to receive ibrutinib. Single-agent ibrutinib demonstrated sustained PFS and OS benefit versus chlorambucil and increased depth of response over time

Externally Fed Accretion onto Protostars

The asymmetric molecular emission lines from dense cores reveal slow, inward motion in the clouds' outer regions. This motion is present both before and after the formation of a central star. Motivated by these observations, we revisit the classic problem of steady, spherical accretion of gas onto a gravitating point mass, but now include self-gravity of the gas and impose a finite, subsonic velocity as the outer boundary condition. We find that the accretion rate onto the protostar is lower than values obtained for isolated, collapsing clouds, by a factor that is the Mach number of the outer flow. Moreover, the region of infall surrounding the protostar spreads out more slowly, at a speed close to the subsonic, incoming velocity. Our calculation, while highly idealized, provides insight into two longstanding problems -- the surprisingly low accretion luminosities of even the most deeply embedded stellar sources, and the failure so far to detect spatially extended, supersonic infall within their parent dense cores. Indeed, the observed subsonic contraction in the outer regions of dense cores following star formation appears to rule out a purely hydrodynamic origin for these clouds.Comment: accepted by MNRA

13CO Cores in Taurus Molecular Cloud

Young stars form in molecular cores, which are dense condensations within molecular clouds. We have searched for molecular cores traced by $^{13}$CO $J=1\to 0$ emission in the Taurus molecular cloud and studied their properties. Our data set has a spatial dynamic range (the ratio of linear map size to the pixel size) of about 1000 and spectrally resolved velocity information, which together allow a systematic examination of the distribution and dynamic state of $^{13}$CO cores in a large contiguous region. We use empirical fit to the CO and CO$_2$ ice to correct for depletion of gas-phase CO. The $^{13}$CO core mass function ($^{13}$CO CMF) can be fitted better with a log-normal function than with a power law function. We also extract cores and calculate the $^{13}$CO CMF based on the integrated intensity of $^{13}$CO and the CMF from 2MASS. We demonstrate that there exists core blending, i.e.\ combined structures that are incoherent in velocity but continuous in column density. The core velocity dispersion (CVD), which is the variance of the core velocity difference $\delta v$, exhibits a power-law behavior as a function of the apparent separation $L$:\ CVD (km/s) $\propto L ({\rm pc})^{0.7}$. This is similar to Larson's law for the velocity dispersion of the gas. The peak velocities of $^{13}$CO cores do not deviate from the centroid velocities of the ambient $^{12}$CO gas by more than half of the line width. The low velocity dispersion among cores, the close similarity between CVD and Larson's law, and the small separation between core centroid velocities and the ambient gas all suggest that molecular cores condense out of the diffuse gas without additional energy from star formation or significant impact from converging flows.Comment: 46 pages, 23 figures, accepted by Ap

High Velocity Molecular Outflows In Massive Cluster Forming Region G10.6-0.4

We report the arcsecond resolution SMA observations of the $^{12}$CO (2-1) transition in the massive cluster forming region G10.6-0.4. In these observations, the high velocity $^{12}$CO emission is resolved into individual outflow systems, which have a typical size scale of a few arcseconds. These molecular outflows are energetic, and are interacting with the ambient molecular gas. By inspecting the shock signatures traced by CH$_{3}$OH, SiO, and HCN emissions, we suggest that abundant star formation activities are distributed over the entire 0.5 pc scale dense molecular envelope. The star formation efficiency over one global free-fall timescale (of the 0.5 pc molecular envelope, $\sim10^{5}$ years) is about a few percent. The total energy feedback of these high velocity outflows is higher than 10$^{47}$ erg, which is comparable to the total kinetic energy in the rotational motion of the dense molecular envelope. From order-of-magnitude estimations, we suggest that the energy injected from the protostellar outflows is capable of balancing the turbulent energy dissipation. No high velocity bipolar molecular outflow associated with the central OB cluster is directly detected, which can be due to the photo-ionization.Comment: 42 pages, 14 figures, accepted by Ap

Stellar and substellar initial mass function: a model that implements gravoturbulent fragmentation and accretion

In this work, we derive the stellar initial mass function (IMF) from the superposition of mass distributions of dense cores, generated through gravoturbulent fragmentation of unstable clumps in molecular clouds (MCs) and growing through competitive accretion. MCs are formed by the turbulent cascade in the interstellar medium at scales L from 100 down to ~0.1 pc. Their internal turbulence is essentially supersonic and creates clumps with a lognormal distribution of densities n. Our model is based on the assumption of a power-law relationship between clump mass and clump density: n~m^x, where x is a scale-free parameter. Gravitationally unstable clumps are assumed to undergo isothermal fragmentation and produce protostellar cores with a lognormal mass distribution, centred around the clump Jeans mass. Masses of individual cores are then assumed to grow further through competitive accretion until the rest of the gas within the clump is being exhausted. The observed IMF is best reproduced for a choice of x=0.25, for a characteristic star formation timescale of ~5 Myr, and for a low star formation efficiency of ~10 %.Comment: 11 pages, 7 figures; accepted for publication in MNRA

Protostellar collapse and fragmentation using an MHD GADGET

Although the influence of magnetic fields is regarded as vital in the star formation process, only a few magnetohydrodynamics (MHD) simulations have been performed on this subject within the smoothed particle hydrodynamics (SPH) method. This is largely due to the unsatisfactory treatment of non-vanishing divergence of the magnetic field. Recently smoothed particle magnetohydrodynamics (SPMHD) simulations based on Euler potentials have proven to be successful in treating MHD collapse and fragmentation problems, however these methods are known to have some intrinsical difficulties. We have performed SPMHD simulations based on a traditional approach evolving the magnetic field itself using the induction equation. To account for the numerical divergence, we have chosen an approach that subtracts the effects of numerical divergence from the force equation, and additionally we employ artificial magnetic dissipation as a regularization scheme. We apply this realization of SPMHD to a widely known setup, a variation of the 'Boss & Bodenheimer standard isothermal test case', to study the impact of the magnetic fields on collapse and fragmentation. In our simulations, we concentrate on setups, where the initial magnetic field is parallel to the rotation axis. We examine different field strengths and compare our results to other findings reported in the literature. We are able to confirm specific results found elsewhere, namely the delayed onset of star formation for strong fields, accompanied by the tendency to form only single stars. We also find that the 'magnetic cushioning effect', where the magnetic field is wound up to form a 'cushion' between the binary, aids binary fragmentation in a case, where previously only formation of a single protostar was expected.Comment: 18 pages, 11 figures. Final version (with revisions). Accepted to MNRA

Long-term efficacy and safety of first-line ibrutinib treatment for patients with CLL/SLL: 5 years of follow-up from the phase 3 RESONATE-2 study

RESONATE-2 is a phase 3 study of first-line ibrutinib versus chlorambucil in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Patients aged >= 65 years (n = 269) were randomized 1:1 to once-daily ibrutinib 420 mg continuously or chlorambucil 0.5-0.8 mg/kg for = 3 adverse events (AEs) included neutropenia (13%), pneumonia (12%), hypertension (8%), anemia (7%), and hyponatremia (6%); occurrence of most events as well as discontinuations due to AEs decreased over time. Fifty-eight percent of patients continue to receive ibrutinib. Single-agent ibrutinib demonstrated sustained PFS and OS benefit versus chlorambucil and increased depth of response over time

Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia

Background: chronic lymphocytic leukemia (CLL) primarily affects older persons who often have coexisting conditions in addition to disease-related immunosuppression and myelosuppression. We conducted an international, open-label, randomized phase 3 trial to compare two oral agents, ibrutinib and chlorambucil, in previously untreated older patients with CLL or small lymphocytic lymphoma. Methods: we randomly assigned 269 previously untreated patients who were 65 years of age or older and had CLL or small lymphocytic lymphoma to receive ibrutinib or chlorambucil. The primary end point was progression-free survival as assessed by an independent review committee. Results: the median age of the patients was 73 years. During a median follow-up period of 18.4 months, ibrutinib resulted in significantly longer progression-free survival than did chlorambucil (median, not reached vs. 18.9 months), with a risk of progression or death that was 84% lower with ibrutinib than that with chlorambucil (hazard ratio, 0.16; P<0.001). Ibrutinib significantly prolonged overall survival; the estimated survival rate at 24 months was 98% with ibrutinib versus 85% with chlorambucil, with a relative risk of death that was 84% lower in the ibrutinib group than in the chlorambucil group (hazard ratio, 0.16; P=0.001). The overall response rate was higher with ibrutinib than with chlorambucil (86% vs. 35%, P<0.001). The rates of sustained increases from baseline values in the hemoglobin and platelet levels were higher with ibrutinib. Adverse events of any grade that occurred in at least 20% of the patients receiving ibrutinib included diarrhea, fatigue, cough, and nausea; adverse events occurring in at least 20% of those receiving chlorambucil included nausea, fatigue, neutropenia, anemia, and vomiting. In the ibrutinib group, four patients had a grade 3 hemorrhage and one had a grade 4 hemorrhage. A total of 87% of the patients in the ibrutinib group are continuing to take ibrutinib. Conclusions: ibrutinib was superior to chlorambucil in previously untreated patients with CLL or small lymphocytic lymphoma, as assessed by progression-free survival, overall survival, response rate, and improvement in hematologic variables. (Funded by Pharmacyclics and others; RESONATE-2 ClinicalTrials.gov number, NCT01722487.)

Antigen-Specific Blocking of CD4-Specific Immunological Synapse Formation Using BPI and Current Therapies for Autoimmune Diseases

This is the peer reviewed version of the following article: Manikwar, P., Kiptoo, P., Badawi, A. H., Büyüktimkin, B. and Siahaan, T. J. (2012), Antigen-specific blocking of CD4-Specific immunological synapse formation using BPI and current therapies for autoimmune diseases. Med Res Rev, 32: 727–764. doi:10.1002/med.20243, which has been published in final form at http://doi.org/10.1002/med.20243. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.In this review, we discuss T-cell activation, etiology, and the current therapies of autoimmune diseases (i.e., MS, T1D, and RA). T-cells are activated upon interaction with antigen-presenting cells (APC) followed by a “bull’s eye”-like formation of the immunological synapse (IS) at the T-cell–APC interface. Although the various disease-modifying therapies developed so far have been shown to modulate the IS and thus help in the management of these diseases, they are also known to present some undesirable side effects. In this study, we describe a novel and selective way to suppress autoimmunity by using a bifunctional peptide inhibitor (BPI). BPI uses an intercellular adhesion molecule-1 (ICAM-1)-binding peptide to target antigenic peptides (e.g., proteolipid peptide, glutamic acid decarboxylase, and type II collagen) to the APC and therefore modulate the immune response. The central hypothesis is that BPI blocks the IS formation by simultaneously binding to major histocompatibility complex-II and ICAM-1 on the APC and selectively alters the activation of T cells from TH1 to Treg and/or TH2 phenotypes, leading to tolerance