Open questions in the study of population III star formation

The first stars were key drivers of early cosmic evolution. We review the main physical elements of the current consensus view, positing that the first stars were predominantly very massive. We continue with a discussion of important open questions that confront the standard model. Among them are uncertainties in the atomic and molecular physics of the hydrogen and helium gas, the multiplicity of stars that form in minihalos, and the possible existence of two separate modes of metal-free star formation.Comment: 15 pages, 2 figures. To appear in the conference proceedings for IAU Symposium 255: Low-Metallicity Star Formation: From the First Stars to Dwarf Galaxie

A simple double-focusing electrostatic ion beam deflector

We have developed an electrostatic, double-focusing 90° deflector for fast ion beams consisting of concentric cylindrical plates of differing heights. In contrast to standard cylindrical deflectors, our design allows for focusing of an incoming parallel beam not only in the plane of deflection but also in the orthogonal direction. The optical properties of our design resemble those of a spherical capacitor deflector while it is much easier and more cost effective to manufacture

Can Deep Altruism Sustain Space Settlement?

Space settlement represents a long-term human effort that requires unprecedented coordination across successive generations. In this chapter, I develop a comparative hierarchy for the value of long-term projects based upon their benefits to culture, their development of infrastructure, and their contributions to lasting information. I next draw upon the concept of the time capsule as an analogy, which enables a comparison of historical examples of projects across generational, intergenerational, and deep time. The concept of deep altruism can then be defined as the selfless pursuit of informational value for the well-being of others in the distant future. The first steps toward supporting an effort like space settlement through deep altruism would establish governance and funding models that begin to support ambitions with intergenerational succession.Comment: To be published in The Human Factor in a Mission to Mars: An Interdisciplinary Approach, K. Szocik (Ed.), Springe

Molecular Hydrogen Formation in the Early Universe: New Implications From Laboratory Measurements

We have performed the first energy-resolved measurement of the associative detachment (AD) reaction H- + H → H2 + e-: This reaction is the dominant formation pathway for H2 during the epoch of first star formation in the early universe. Despite being the most fundamental anion-neutral chemical reaction, experiment and theory have failed to converge in both magnitude and energy dependence. The uncertainty in this rate coefficient severely limits our under- standing of the formation of the first stars and protogalaxies

Molecular Hydrogen Formation in the Early Universe: New Implications From Laboratory Measurements

We have performed the first energy-resolved measurement of the associative detachment (AD) reaction H- + H → H2 + e-: This reaction is the dominant formation pathway for H2 during the epoch of first star formation in the early universe. Despite being the most fundamental anion-neutral chemical reaction, experiment and theory have failed to converge in both magnitude and energy dependence. The uncertainty in this rate coefficient severely limits our under- standing of the formation of the first stars and protogalaxies

Publisher Correction: An engineered human Fc domain that behaves like a pH-toggle switch for ultra-long circulation persistence.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

A dose-finding Phase 2 study of single agent isatuximab (anti-CD38 mAb) in relapsed/refractory multiple myeloma

A Phase 2 dose-finding study evaluated isatuximab, an anti-CD38 monoclonal antibody, in relapsed/refractory multiple myeloma (RRMM; NCT01084252). Patients with ?3 prior lines or refractory to both immunomodulatory drugs and proteasome inhibitors (dual refractory) were randomized to isatuximab 3 mg/kg every 2 weeks (Q2W), 10 mg/kg Q2W(2 cycles)/Q4W, or 10 mg/kg Q2W. A fourth arm evaluated 20 mg/kg QW(1 cycle)/Q2W. Patients (N = 97) had a median (range) age of 62 years (38-85), 5 (2-14) prior therapy lines, and 85% were double refractory. The overall response rate (ORR) was 4.3, 20.0, 29.2, and 24.0% with isatuximab 3 mg/kg Q2W, 10 mg/kg Q2W/Q4W, 10 mg/kg Q2W, and 20 mg/kg QW/Q2W, respectively. At doses ?10 mg/kg, median progression-free survival and overall survival were 4.6 and 18.7 months, respectively, and the ORR was 40.9% (9/22) in patients with high-risk cytogenetics. CD38 receptor density was similar in responders and non-responders. The most common non-hematologic adverse events (typically grade ?2) were nausea (34.0%), fatigue (32.0%), and upper respiratory tract infections (28.9%). Infusion reactions (typically with first infusion and grade ?2) occurred in 51.5% of patients. In conclusion, isatuximab is active and generally well tolerated in heavily pretreated RRMM, with greatest efficacy at doses ?10 mg/kg

Neutralization of (NK-cell-derived) B-cell activating factor by Belimumab restores sensitivity of chronic lymphoid leukemia cells to direct and Rituximab-induced NK lysis.

Natural killer (NK) cells are cytotoxic lymphocytes that substantially contribute to the therapeutic benefit of antitumor antibodies like Rituximab, a crucial component in the treatment of B-cell malignancies. In chronic lymphocytic leukemia (CLL), the ability of NK cells to lyse the malignant cells and to mediate antibody-dependent cellular cytotoxicity upon Fc receptor stimulation is compromised, but the underlying mechanisms are largely unclear. We report here that NK-cells activation-dependently produce the tumor necrosis factor family member 'B-cell activating factor' (BAFF) in soluble form with no detectable surface expression, also in response to Fc receptor triggering by therapeutic CD20-antibodies. BAFF in turn enhanced the metabolic activity of primary CLL cells and impaired direct and Rituximab-induced lysis of CLL cells without affecting NK reactivity per se. The neutralizing BAFF antibody Belimumab, which is approved for treatment of systemic lupus erythematosus, prevented the effects of BAFF on the metabolism of CLL cells and restored their susceptibility to direct and Rituximab-induced NK-cell killing in allogeneic and autologous experimental systems. Our findings unravel the involvement of BAFF in the resistance of CLL cells to NK-cell antitumor immunity and Rituximab treatment and point to a benefit of combinatory approaches employing BAFF-neutralizing drugs in B-cell malignancies

FcγRIIb Inhibits Allergic Lung Inflammation in a Murine Model of Allergic Asthma

Allergic asthma is characterized by airway eosinophilia, increased mucin production and allergen-specific IgE. Fc gamma receptor IIb (FcγRIIb), an inhibitory IgG receptor, has recently emerged as a negative regulator of allergic diseases like anaphylaxis and allergic rhinitis. However, no studies to date have evaluated its role in allergic asthma. Our main objective was to study the role of FcγRIIb in allergic lung inflammation. We used a murine model of allergic airway inflammation. Inflammation was quantified by BAL inflammatory cells and airway mucin production. FcγRIIb expression was measured by qPCR and flow cytometry and the cytokines were quantified by ELISA. Compared to wild type animals, FcγRIIb deficient mice mount a vigorous allergic lung inflammation characterized by increased bronchoalveolar lavage fluid cellularity, eosinophilia and mucin content upon ragweed extract (RWE) challenge. RWE challenge in sensitized mice upregulated FcγRIIb in the lungs. Disruption of IFN-γ gene abrogated this upregulation. Treatment of naïve mice with the Th1-inducing agent CpG DNA increased FcγRIIb expression in the lungs. Furthermore, treatment of sensitized mice with CpG DNA prior to RWE challenge induced greater upregulation of FcγRIIb than RWE challenge alone. These observations indicated that RWE challenge upregulated FcγRIIb in the lungs by IFN-γ- and Th1-dependent mechanisms. RWE challenge upregulated FcγRIIb on pulmonary CD14+/MHC II+ mononuclear cells and CD11c+ cells. FcγRIIb deficient mice also exhibited an exaggerated RWE-specific IgE response upon sensitization when compared to wild type mice. We propose that FcγRIIb physiologically regulates allergic airway inflammation by two mechanisms: 1) allergen challenge mediates upregulation of FcγRIIb on pulmonary CD14+/MHC II+ mononuclear cells and CD11c+ cells by an IFN-γ dependent mechanism; and 2) by attenuating the allergen specific IgE response during sensitization. Thus, stimulating FcγRIIb may be a therapeutic strategy in allergic airway disorders