Multiplicity in Early Stellar Evolution

Observations from optical to centimeter wavelengths have demonstrated that multiple systems of two or more bodies is the norm at all stellar evolutionary stages. Multiple systems are widely agreed to result from the collapse and fragmentation of cloud cores, despite the inhibiting influence of magnetic fields. Surveys of Class 0 protostars with mm interferometers have revealed a very high multiplicity frequency of about 2/3, even though there are observational difficulties in resolving close protobinaries, thus supporting the possibility that all stars could be born in multiple systems. Near-infrared adaptive optics observations of Class I protostars show a lower binary frequency relative to the Class 0 phase, a declining trend that continues through the Class II/III stages to the field population. This loss of companions is a natural consequence of dynamical interplay in small multiple systems, leading to ejection of members. We discuss observational consequences of this dynamical evolution, and its influence on circumstellar disks, and we review the evolution of circumbinary disks and their role in defining binary mass ratios. Special attention is paid to eclipsing PMS binaries, which allow for observational tests of evolutionary models of early stellar evolution. Many stars are born in clusters and small groups, and we discuss how interactions in dense stellar environments can significantly alter the distribution of binary separations through dissolution of wider binaries. The binaries and multiples we find in the field are the survivors of these internal and external destructive processes, and we provide a detailed overview of the multiplicity statistics of the field, which form a boundary condition for all models of binary evolution. Finally we discuss various formation mechanisms for massive binaries, and the properties of massive trapezia.Comment: Accepted for publication as a chapter in Protostars and Planets VI, University of Arizona Press (2014), eds. H. Beuther, R. Klessen, C. Dullemond, Th. Hennin

Metamorphic Domain-Specific Languages: A Journey Into the Shapes of a Language

External or internal domain-specific languages (DSLs) or (fluent) APIs? Whoever you are -- a developer or a user of a DSL -- you usually have to choose your side; you should not! What about metamorphic DSLs that change their shape according to your needs? We report on our 4-years journey of providing the "right" support (in the domain of feature modeling), leading us to develop an external DSL, different shapes of an internal API, and maintain all these languages. A key insight is that there is no one-size-fits-all solution or no clear superiority of a solution compared to another. On the contrary, we found that it does make sense to continue the maintenance of an external and internal DSL. The vision that we foresee for the future of software languages is their ability to be self-adaptable to the most appropriate shape (including the corresponding integrated development environment) according to a particular usage or task. We call metamorphic DSL such a language, able to change from one shape to another shape

Loss of APC induces polyploidy as a result of a combination of defects in mitosis and apoptosis

Mutations in the adenomatous polyposis coli (APC) tumor suppressor gene initiate a majority of colorectal cancers. Acquisition of chromosomal instability is an early event in these tumors. We provide evidence that the loss of APC leads to a partial loss of interkinetochore tension at metaphase and alters mitotic progression. Furthermore, we show that inhibition of APC in U2OS cells compromises the mitotic spindle checkpoint. This is accompanied by a decrease in the association of the checkpoint proteins Bub1 and BubR1 with kinetochores. Additionally, APC depletion reduced apoptosis. As expected from this combination of defects, tetraploidy and polyploidy are consequences of APC inhibition in vitro and in vivo. The removal of APC produced the same defects in HCT116 cells that have constitutively active β-catenin. These data show that the loss of APC immediately induces chromosomal instability as a result of a combination of mitotic and apoptotic defects. We suggest that these defects amplify each other to increase the incidence of tetra- and polyploidy in early stages of tumorigenesis

Oral dosing for antenatal corticosteroids in the Rhesus macaque.

Antenatal corticosteroids (ACS) are standard of care for women at risk of preterm delivery, although choice of drug, dose or route have not been systematically evaluated. Further, ACS are infrequently used in low resource environments where most of the mortality from prematurity occurs. We report proof of principle experiments to test betamethasone-phosphate (Beta-P) or dexamethasone-phosphate (Dex-P) given orally in comparison to the clinical treatment with the intramuscular combination drug beta-phosphate plus beta-acetate in a Rhesus Macaque model. First, we performed pharmacokinetic studies in non-pregnant monkeys to compare blood levels of the steroids using oral dosing with Beta-P, Dex-P and an effective maternal intramuscular dose of the beta-acetate component of the clinical treatment. We then evaluated maternal and fetal blood steroid levels with limited fetal sampling under ultrasound guidance in pregnant macaques. We found that oral Beta is more slowly cleared from plasma than oral Dex. The blood levels of both drugs were lower in maternal plasma of pregnant than in non-pregnant macaques. Using the pharmacokinetic data, we treated groups of 6-8 pregnant monkeys with oral Beta-P, oral Dex-P, or the maternal intramuscular clinical treatment and saline controls and measured pressure-volume curves to assess corticosteroid effects on lung maturation at 5d. Oral Beta-P improved the pressure-volume curves similarly to the clinical treatment. Oral Dex-P gave more variable and nonsignificant responses. We then compared gene expression in the fetal lung, liver and hippocampus between oral Beta-P and the clinical treatment by RNA-sequencing. The transcriptomes were largely similar with small gene expression differences in the lung and liver, and no differences in the hippocampus between the groups. As proof of principle, ACS therapy can be effective using inexpensive and widely available oral drugs. Clinical dosing strategies must carefully consider the pharmacokinetics of oral Beta-P or Dex-P to minimize fetal exposure while achieving the desired treatment responses

Real time imaging, forecasting and management of human-induced seismicity at Preston New Road, Lancashire, England

Earthquakes induced by subsurface fluid injection pose a significant issue across a range of industries. Debate continues as to the most effective methods to mitigate the resulting seismic hazard. Observations of induced seismicity indicate that the rate of seismicity scales with the injection volume and that events follow the Gutenberg-Richter distribution. These two inferences permit us to populate statistical models of the seismicity and extrapolate them to make forecasts of the expected event magnitudes as injection continues. Here, we describe a shale gas site where this approach was used in real time to make operational decisions during hydraulic fracturing operations. Microseismic observations revealed the intersection between hydraulic fracturing and a pre-existing fault or fracture network that became seismically active. Although "red light" events, requiring a pause to the injection program, occurred on several occasions, the observed event magnitudes fell within expected levels based on the extrapolated statistical models, and the levels of seismicity remained within acceptable limits as defined by the regulator. To date, induced seismicity has typically been regulated using retroactive traffic light schemes. This study shows that the use of high-quality microseismic observations to populate statistical models that forecast expected event magnitudes can provide a more effective approach

X-Ray and UV Orbital Phase Dependence in LMC X-3

The black-hole binary LMC X-3 is known to be variable on time scales of days to years. We investigate X-ray and ultraviolet variability in the system as a function of the 1.7 day binary phase using a 6.4 day observation with the Rossi X-ray Timing Explorer (RXTE) from December 1998. An abrupt 14% flux decrease, lasting nearly an entire orbit, is followed by a return to previous flux levels. This behavior occurs twice, at nearly the same binary phase, but it is not present in consecutive orbits. When the X-ray flux is at lower intensity, a periodic amplitude modulation of 7% is evident in data folded modulo the orbital period. The higher intensity data show weaker correlation with phase. This is the first report of X-ray variability at the orbital period of LMC X-3. Archival RXTE observations of LMC X--3 during a high flux state in December 1996 show similar phase dependence. An ultraviolet light curve obtained with the High Speed Photometer aboard the Hubble Space Telescope shows orbital modulation consistent with that in the optical, caused by the ellipsoidal variation of the spatially deformed companion. The X-ray spectrum of LMC X-3 can be acceptably represented by a phenomenological disk-black-body plus a power law. Changes in the spectrum of LMC X-3 during our observations are compatible with earlier observations during which variations in the 2-10 keV flux are tracked closely by the disk geometry spectral model parameter.Comment: 11 pages, 7 figures, ApJ in pres

Subdivision of the bacterioferritin comigratory protein family of bacterial peroxiredoxins based on catalytic activity.

© American Chemical Society,2010. Post-print version of article deposited in accordance with SHERPA RoMEO guidelinesPeroxiredoxins are ubiquitous proteins that catalyze the reduction of hydroperoxides, thus conferring resistance to oxidative stress. Using high-resolution mass spectrometry, we recently reclassified one such peroxiredoxin, bacterioferritin comigratory protein (BCP) of Escherichia coli, as an atypical 2-Cys peroxiredoxin that functions through the formation of an intramolecular disulfide bond between the active and resolving cysteine. An engineered E. coli BCP, which lacked the resolving cysteine, retained enzyme activity through a novel catalytic pathway. Unlike the active cysteine, the resolving cysteine of BCP peroxiredoxins is not conserved across all members of the family. To clarify the catalytic mechanism of native BCP enzymes that lack the resolving cysteine, we have investigated the BCP homologue of Burkholderia cenocepacia. We demonstrate that the B. cenocepacia BCP (BcBCP) homologue functions through a 1-Cys catalytic pathway. During catalysis, BcBCP can utilize thioredoxin as a reductant for the sulfenic acid intermediate. However, significantly higher peroxidase activity is observed utilizing glutathione as a resolving cysteine and glutaredoxin as a redox partner. Introduction of a resolving cysteine into BcBCP changes the activity from a 1-Cys pathway to an atypical 2-Cys pathway, analogous to the E. coli enzyme. In contrast to the native B. cenocepacia enzyme, thioredoxin is the preferred redox partner for this atypical 2-Cys variant. BCP-deficient B. cenocepacia exhibit a growth-phase-dependent hypersensitivity to oxidative killing. On the basis of sequence alignments, we believe that BcBCP described herein is representative of the major class of bacterial BCP peroxiredoxins. To our knowledge, this is the first detailed characterization of their catalytic activity. These studies support the subdivision of the BCP family of peroxiredoxins into two classes based on their catalytic activity

Short and long-term clinical outcomes of use of beta-interferon or glatiramer acetate for people with clinically isolated syndrome : a systematic review of randomised controlled trials and network meta-analysis

Source of funding: This work is part of a larger report commissioned by the NIHR HTA Programme as project number ID809. A.C. and G.J.M.T. are partly supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care West Midlands at the University Hospitals Birmingham NHS Foundation Trust.Peer reviewedPublisher PD

Patient and physician preferences for surgical and adjuvant treatment options for rectal cancer

Hypothesis Patients and their clinicians hold varying preferences for surgical and adjuvant treatment therapies for rectal cancer. Design Preferences were determined using the Prospective Measure of Preference. Setting Royal Prince Alfred and St Vincent\u27s hospitals in Sydney, Australia. Participants Patients with colorectal cancer were interviewed during their postoperative hospital stay, and physicians were asked to complete a mailed survey. Main Outcome Measures The Prospective Measure of Preference method produces 2 outcome measures of preference: willingness to trade and prospective measure of preference time trade-off. Results Patients\u27 strongest preference was to avoid a stoma: more than 60% would give up a mean of 34% of their life expectancy to avoid this surgical option. This was followed by treatment options involving chemoradiotherapy, where more than 50% would give up a mean of almost 25% of their life to avoid treatment. Surgeons held stronger preferences against all adjuvant options compared with oncologists (P ≤ .01). Conclusions Patients had strong preferences against all treatment options, and these preferences frequently differed from those of physicians. These results highlight the importance of determining patients\u27 own preferences in the clinical encounter. Furthermore, the diversity of preferences of clinical subspecialists emphasizes the need for multidisciplinary treatment planning to ensure a balanced approach to treatment decision making for patients with rectal cancer