ALMA Compact Array observations of the Fried Egg nebula: Evidence for large-scale asymmetric mass-loss from the yellow hypergiant IRAS 17163-3907.

Yellow hypergiants are rare and represent a fast evolutionary stage of massive evolved stars. That evolutionary phase is characterised by a very intense mass loss, the understanding of which is still very limited. Here we report ALMA Compact Array observations of a 50″-mosaic toward the Fried Egg nebula, around one of the few Galactic yellow hypergiants IRAS 17163-3907. The emission from the 12CO J=2-1 line, H30α recombination line, and continuum is imaged at a resolution of ~8″, revealing the morphology of the molecular environment around the star. The continuum emission is unresolved and peaks at the position of the star. The radio recombination line H30α shows unresolved emission at the star, with an approximately gaussian spectrum centered on a velocity of 21±3 km s-1 with a width of 57±6 km s-1. In contrast, the CO 2-1 emission is complex and decomposes into several components beyond the contamination from interstellar gas in the line of sight. The CO spectrum toward the star is a broad plateau, centered at the systemic velocity of +18 km s-1 and with an expansion velocity of 100±10 km s-1. Assuming isotropic and constant mass-loss, we estimate a mass-loss rate of 8±1.5 ×10-5 M⊙ yr-1. At a radius of 25″ from the star, we detect CO emission associated with the dust ring previously imaged by Herschel. The kinematics of this ring, however, is not consistent with an expanding shell, but show a velocity gradient of vsys ±20 km s-1. In addition, we find a puzzling bright feature radially connecting the star to the CO ring, at a velocity of +40 km s-1 relative to the star. This spur feature may trace a unidirectional ejection event from the star. Our ACA observations reveal the complex morphology around IRAS 17163 and illustrate the breakthroughs that ALMA will bring to the field of massive stellar evolution.

VELOCITY-RESOLVED [C ii] EMISSION AND [C ii]/FIR MAPPING ALONG ORION WITH HERSCHEL.

We present the first ~7.5'×11.5' velocity-resolved (~0.2 km s-1) map of the [C ii] 158 µm line toward the Orion molecular cloud 1 (OMC 1) taken with the Herschel/HIFI instrument. In combination with far-infrared (FIR) photometric images and velocity-resolved maps of the H41α hydrogen recombination and CO J=2-1 lines, this data set provides an unprecedented view of the intricate small-scale kinematics of the ionized/PDR/molecular gas interfaces and of the radiative feedback from massive stars. The main contribution to the [C ii] luminosity (~85 %) is from the extended, FUV-illuminated face of the cloud (G0>500, nH>5×103 cm-3) and from dense PDRs (G≳104, nH≳105 cm-3) at the interface between OMC 1 and the H ii region surrounding the Trapezium cluster. Around ~15 % of the [C ii] emission arises from a different gas component without CO counterpart. The [C ii] excitation, PDR gas turbulence, line opacity (from [13C ii]) and role of the geometry of the illuminating stars with respect to the cloud are investigated. We construct maps of the L[C ii]/LFIR and LFIR/MGas ratios and show that L[C ii]/LFIR decreases from the extended cloud component (~10-2-10-3) to the more opaque star-forming cores (~10-3-10-4). The lowest values are reminiscent of the "[C ii] deficit" seen in local ultra-luminous IR galaxies hosting vigorous star formation. Spatial correlation analysis shows that the decreasing L[C ii]/LFIR ratio correlates better with the column density of dust through the molecular cloud than with LFIR/MGas. We conclude that the [C ii] emitting column relative to the total dust column along each line of sight is responsible for the observed L[C ii]/LFIR variations through the cloud.

Evaluation and management of blunt traumatic aortic injury: a practice management guideline from the Eastern Association for the Surgery of Trauma

BACKGROUND: Blunt traumatic aortic injury (BTAI) is the second most common cause of death in trauma patients. Eighty percent of patients with BTAI will die before reaching a trauma center. The issues of how to diagnose, treat, and manage BTAI were first addressed by the Eastern Association for the Surgery of Trauma (EAST) in the practice management guidelines on this topic published in 2000. Since that time, there have been advances in the management of BTAI. As a result, the EAST guidelines committee decided to develop updated guidelines for this topic using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework recently adopted by EAST. METHODS: A systematic review of the MEDLINE database using PubMed was performed. The search retrieved English language articles regarding BTAI from 1998 to 2013. Letters to the editor, case reports, book chapters, and review articles were excluded. Topics of investigation included imaging to diagnose BTAI, type of operative repair, and timing of operative repair. RESULTS: Sixty articles were identified. Of these, 51 articles were selected to construct the guidelines. CONCLUSION: There have been changes in practice since the publication of the previous guidelines in 2000. Computed tomography of the chest with intravenous contrast is strongly recommended to diagnose clinically significant BTAI. Endovascular repair is strongly recommended for patients without contraindications. Delayed repair of BTAI is suggested, with the stipulation that effective blood pressure control must be used in these patients.(AU)

Hydride spectroscopy of the diffuse interstellar medium: new clues on the gas fraction in molecular form and cosmic ray ionization rate in relation to H3+.

The Herschel-guaranteed time key programme PRobing InterStellar Molecules with Absorption line Studies (PRISMAS)(1) is providing a survey of the interstellar hydrides containing the elements C, O, N, F and Cl. As the building blocks of interstellar molecules, hydrides provide key information on their formation pathways. They can also be used as tracers of important physical and chemical properties of the interstellar gas that are difficult to measure otherwise. This paper presents an analysis of two sight-lines investigated by the PRISMAS project, towards the star-forming regions W49N and W51. By combining the information extracted from the detected spectral lines, we present an analysis of the physical properties of the diffuse interstellar gas, including the electron abundance, the fraction of gas in molecular form, and constraints on the cosmic ray ionization rate and the gas density.

Diphtheria toxin-interleukin-3 fusion protein (DT(388)IL3) prolongs disease-free survival of leukemic immunocompromised mice.

The novel fusion protein DT(388)IL3, composed of the catalytic and translocation domains of diphtheria toxin (DT(388)) fused with a Met-His linker to human interleukin 3 (IL-3), was tested for anti-leukemia efficacy in an in vivo model of differentiated human acute myeloid leukemia (AML). Six-week-old female SCID mice were irradiated with 350 cGy, inoculated 24 h later with 20 million (i.v., i.p., or s.c.) TF1 cells transfected with the v-SRC oncogene, and treated i.p., starting 24 h later, with up to five daily injections of saline, DT(388)IL3 (2 microg), DT(388)GMCSF (2 microg), DAB(389)IL2 (2 microg), or cytarabine (80 microg) or two weekly injections of anti-CD33-calicheamicin conjugate (5 microg). Animals were monitored twice daily, and moribund animals killed and necropsied. Control animals had a median disease-free survival (DFS) of 37 days (i.v., n = 45), 35 days (i.p., n = 20), and 21 days (s.c., n = 20), respectively. Only 5/49 (10%) of the DT(388)IL3 treated i.v. inoculated animals died with leukemia. Median DFS with i.v., i.p. and s.c. tumor inoculated animals was prolonged by fusion protein treatment to >120 days, 66 days and 31 days (P < 0.001, = 0.0003, and = 0.0006), respectively. Median DFS with s.c. tumor inoculated animals was also prolonged by other active anti-leukemia agents (DT(388)GMCSF, cytarabine and anti-CD33-calicheamicin) relative to controls by 67%, 172% and 47% (P < 0.0001, <0.0001, and =0.0004), respectively. In contrast, median DFS with s.c. tumor inoculated animals treated with DAB(389)IL2 non-significantly reduced by 13% relative to controls (P = 0.21). Thus, DT(388)IL3 fusion protein demonstrates in vivo anti-leukemia efficacy and warrants further preclinical development for treatment of chemo-resistant, IL-3 receptor positive AML patients.

An analysis of the results of myringoplasty in children.

An analysis of the results of 100 temporalis fascia underlay myringoplasties in children between the ages of 2-17 years is presented. The follow-up period in this retrospective review was from 6 to 24 months. There was no statistically significant correlation between the age of patient, a history of previous ear surgery, previous general anaesthesia, previous adenotonsillar surgery, preoperative otorrhoea, impaired eustachian tubal function, individual surgeon performing the surgery, size of perforation or operative technique and the outcome of the surgery with respect to graft take rate. The overall graft take rate was 75.3% of the 93 patients that returned for follow-up. The seniority of the surgeon and by implication the degree of operative experience of the surgeon is found to be significantly correlated with the graft take rate (P < 0.05). On audiometric testing, the mean pre-operative air conduction threshold improved significantly (P < 0.0001) from 32.0 dBHL (S.D. 11.22) to 20.18 dBHL (S.D. 15.54) while the speech reception threshold improved from a mean of 25.34 dBHL (S.D. 12.88) to 18.79 (S.D. 15.5) (P < 0.0005). Although not statistically significant, patients under the age of 8 years were found to have a low graft take rate (56%) when compared to the mean. The audiometric results in this age group were comparable to the rest of the group. The findings in this study suggest that myringoplasty is a beneficial procedure in the pediatric population in the hands of a skilled and experienced surgeon. The learning curve seen in the surgeons in this study suggests that suitable cases for junior surgeons should be carefully selected.

Myringoplasty--effects on hearing and contributing factors.

Indications for myringoplasty are chronic otorrhoea and hearing impairment. Some authors have described poor postoperative hearing results and sensorineural hearing loss associated with the surgery, and question the indication for myringoplasty on an ear with normal hearing (< 25 dB). This study of 211 consecutive myringoplasties performed over 1 year details the 'take rate,' hearing gains and losses, and factors found to influence the above. The take rate of 78% is comparable with figures in the literature. The most significant factors influencing this are the grade of the surgeon and the size of the perforation. The average pre-operative air-bone gap was closed from 23.7 dB to 13.9 dB with a 4.5% incidence of postoperative sensorineural hearing loss. Postoperatively 77.9% of patients had an air-bone gap of less than 20 dB. We conclude that myringoplasty is a beneficial procedure, closing the tympanic membrane and improving the hearing.

Analysis of the oligosaccharides on androgen-binding proteins: implications concerning their role in structure/function relationships.

Rat androgen-binding protein (rABP), human testosterone-binding globulin (hTeBG) and rabbit (rb) TeBG are heterodimeric proteins. The source of the heterogeneity arises from the differential glycosylation of a common protein core. This glycosylation results in a heavy subunit (more glycosylation) and a light subunit (less glycosylation). Glycosylation is one factor responsible for multiple charged species seen when rABP, hTeBG, and rbTeBG are analyzed by two-dimensional gel electrophoresis. Enzymatic digestion with the endoglycosidase, peptide: N-glycosidase F indicated that all three proteins have asparagine (Asn)-linked oligosaccharides as their major glycan substituent. Treatment with exoglycosidases provided evidence for terminal sialic acid, galactose and mannose and N-acetylglucosamine residues. About 16-22% of the mass of the heavy subunit and about 8-14% of the mass of the light subunit is contributed by carbohydrate. Serial lectin chromatography indicated that rABP is glycosylated differently from hTeBG and rbTeBG. About 40% of the rABP contains tri and tetraantennary complex oligosaccharides, while only about 20% of the hTeBG and TeBG from pregnant rabbits contains these types of glycans. About 9% of the TeBG from male rabbits bears these types of oligosaccharides. All of the biantennary complex oligosaccharides on rABP are fucosylated on the chitobiose core, but only 8% of those on hTeBG and none of those on rbTeBG are fucosylated in this manner. All three proteins are glycosylated at more than one site. The data indicate that the proteins may have more than one type of oligosaccharide on them. It is likely that differences in glycosylation are responsible for different physiological roles of the proteins.

Cystic hygroma: massive recurrence in adult life.

Cystic hygroma is considered a disease of childhood. It may appear for the first time in adult life but recurrence by that stage is rare and may present difficulties in diagnosis due to previous treatment. The authors present a case where early pharmacological intervention may have prevented a potentially life threatening situation. The world literature is also reviewed.

Analysis of the oligosaccharides on rat androgen-binding protein using serial lectin chromatography.

The microheterogeneity seen when rat androgen-binding protein (rABP) is analyzed by two-dimensional polyacrylamide gel electrophoresis is attributable, at least in part, to the differential glycosylation of a single promoter. Further insight into the chemical nature of the oligosaccharide units on rABP was obtained by serial lectin chromatography. When rABP was chromatographed on immobilized Concanavalin A (Con-A), it was fractionated into three classes: (1) one that did not bind to the lectin (about 44% of the rABP), (2) one that was bound and could be eluted with 10 mM 1-O-methyl alpha-D-glucopyranoside (glucoside), about 34%, and (3) one that could be eluted with 0.5 M methyl alpha-D-mannopyranoside (mannoside), about 23%. Binding to Con-A indicates the presence of asparagine-linked oligosaccharides. Chromatography of the glucoside-eluted peak on lentil lectin (LcH) indicated that the rABP in that fraction contained a fucose residue on the chitobiose core. Chromatography of the mannoside-eluted peak on wheat germ agglutinin (WGA) indicated the presence of rABP with high mannose- (44%) and hybrid-type (56%) glycans attached. Chromatography on Ricinus communis I (RCA-I) lectin indicated a species containing galactosylated complex-type oligosaccharide chains. Treatment of rABP forms with exoglycosidases confirmed the presence of externally disposed fucose, sialic acid, mannose, and galactose residues. LcH chromatography indicated that about 30% of the rABP that did not bind to Con-A possessed triantennary oligosaccharides with fucose on the chitobiose core. About 28% of the rABP was retarded when it was chromatographed on Phaseolus vulgaris E lectin, suggesting the presence of bisected biantennary chains with terminal galactose residues. We were unable to detect rABP species with serine- or threonine-linked oligosaccharide chains in this fraction. Other forms of rABP in the nonretained fraction of Con-A were not resolved. Western blotting did not reveal major differences in relative molecular weight (Mr) among the rABP species; some differences in the ratio of the heavy to the light subunit of the molecule were detectable.

Structure of asparagine-linked oligosaccharides on human and rabbit testosterone-binding globulin.

We have previously demonstrated, using two-dimensional polyacrylamide gel electrophoresis, that much of the microheterogeneity of human (h) and rabbit (rb) testosterone-binding globulin (TeBG) is due to differential glycosylation of a single protomer. Since glycosylation has been shown to be a physiologically important modification of proteins, we have examined the structure of the oligosaccharide chains attached to hTeBG and rbTeBG to facilitate future studies on the mechanisms of action of the proteins. The structures of the oligosaccharides attached to TeBG were determined by using serial lectin chromatography. About 10% of the TeBG from castrated male rabbits and about 20% of the TeBG from pregnant rabbits and from a human sample were not retained on a column of immobilized concanavalin-A (Con-A). This fraction would consist of TeBG with attached asparagine (Asn)-linked tri- and tetraantennary complex and serine/threonine (O)-linked oligosaccharides as well as non-glycosylated forms. None of the lectins used to subfractionate these species was effective. Forty to 50% of the TeBG applied to Con-A possessed biantennary complex oligosaccharides as indicated by the fact that it could be eluted with 10 mM 1-O-methyl-alpha-D-glucopyranoside and by its retention on wheat germ agglutinin (WGA). About 8% of the biantennary complex oligosaccharides on hTeBG and none of those on rbTeBG were fucosylated on the chitobiose core, as determined by chromatography on Lens culinaris lectin (LcH). Galactosylated oligosaccharides were also present on the TeBG in this fraction as indicated by its interaction with Ricinus communis-I (RCA-I). Thirty to 40% of the TeBG applied to Con-A was retained and could be eluted with 0.5 M methyl-alpha-D-mannopyranoside. This fraction contains TeBG possessing high mannose-type, hybrid-type, and complex galactosylated glycans as determined by chromatography on Con-A, WGA, and RCA-I. Evidence based on the binding of mannoside-eluted TeBG to Con-A, WGA, and RCA-I indicated that at least the TeBG in this fraction contained two glycosylation sites and that the sites were differentially glycosylated.

The microheterogeneity of rabbit testosterone-binding globulin is due to differential glycosylation of its single protomer.

Affinity-purified rabbit testosterone-binding globulin (rbTeBG) is a homodimer with a molecular weight (Mr) of about 92,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of the chemically cross-linked protein. When noncross-linked rbTeBG is subjected to SDS-PAGE, individual protomers (Mr approximately equal to 44,400 +/- 400 and Mr approximately equal to 42,000 +/- 1300) are resolved. The protomers are present in a ratio of approximately 2 (heavy):1 (light). Enzymatic deglycosylation of native rbTeBG or of rbTeBG that had been photoaffinity-labeled with [1,2-3H]17 beta-hydroxy-4,6-androstadien-3-one was conducted. The products were then identified on immunoblots using a monoclonal antibody that cross-reacts with rbTeBG, or by fluorography. These analyses indicated that rbTeBG contained sialic acid and asparagine (Asn)-linked oligosaccharides and provided evidence for the presence of serine/threonine (O)-linked glycans on the molecule. The presumptive removal of all oligosaccharides by enzymatic or chemical means resulted in the appearance of a single subunit (Mr approximately equal to 37,150 +/- 1200). On the basis of this monomeric molecular weight, carbohydrate would contribute 16% and 11% to the relative molecular mass of the nondeglycosylated heavy and light subunits, respectively. Therefore, the size heterogeneity of the nondeglycosylated rbTeBG subunits is a result of their differential glycosylation. In addition to size heterogeneity, the rbTeBG subunits are composed of multiple-charge variants. Although enzymatic and chemical methods of glycan removal altered the isoelectric points of the isoforms, none of the treatments yielded a single isoform. Thus, it is possible that moieties other than oligosaccharides are contributing charge to the isoelectric variants of rbTeBG.

Human testosterone-binding globulin is a dimer composed of two identical protomers that are differentially glycosylated.

Affinity-purified human testosterone-binding globulin (hTeBG) is composed of two subunits [mol wt (Mr), 52,200 and 48,600], as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), electrophoretic transfer, and immunochemical localization with a monoclonal antibody raised against rat androgen-binding protein. Fluorography of SDS-PAGE gels on which photoaffinity-labeled hTeBG was analyzed yielded essentially identical results. Enzymatic deglycosylation of hTeBG with neuraminidase to remove sialic acid led to the production of two subunits of 50,800 and 47,300 Mr when assessed by SDS-PAGE. Treatment of hTeBG with an optimal concentration of N-glycanase to remove Asn-linked oligosaccharides produced a single subunit of 44,100 Mr. When hTeBG was treated with neuraminidase and O-glycanase to remove O-linked oligosaccharides, three subunits were seen, two of which had Mr not clearly different from those obtained with neuraminidase treatment alone plus a subunit of 40,900 Mr. Treatment of hTeBG with a combination of all three enzymes produced a single subunit of 42,900 Mr. Chemical deglycosylation with trifluoromethane-sulfonic acid produced a single subunit with a Mr identical to that produced by treatment with all three enzymes. We concluded that this is the Mr of completely deglycosylated hTeBG. Based on this Mr, carbohydrates contribute 18% and 12% to the apparent Mr of the heavy and light subunits of hTeBG, respectively. Two-dimensional PAGE analysis of hTeBG with its oligosaccharides intact indicated that the heavy subunit was composed of seven isoelectric variants with pI values of 5.87-6.55, while the light subunit was composed of four charge variants with pI values of 6.14-6.55. Treatment of hTeBG with the enzymes resulted in a shift in the pH values to a more basic pH range, indicating that carbohydrate removal also removed charged species from the protein. The greatest cathodal shift occurred when hTeBG was treated with a combination of the three enzymes (pI 7.33-7.77) or when it was chemically deglycosylated (pI 6.37-7.02). Despite the apparent removal of all carbohydrates, the single subunit was still composed of multiple isoforms. This finding suggests that other charged species remain on the hTeBG molecule.