Observation of inverse Compton emission from a long γ-ray burst.

Long-duration γ-ray bursts (GRBs) originate from ultra-relativistic jets launched from the collapsing cores of dying massive stars. They are characterized by an initial phase of bright and highly variable radiation in the kiloelectronvolt-to-megaelectronvolt band, which is probably produced within the jet and lasts from milliseconds to minutes, known as the prompt emission1,2. Subsequently, the interaction of the jet with the surrounding medium generates shock waves that are responsible for the afterglow emission, which lasts from days to months and occurs over a broad energy range from the radio to the gigaelectronvolt bands1-6. The afterglow emission is generally well explained as synchrotron radiation emitted by electrons accelerated by the external shock7-9. Recently, intense long-lasting emission between 0.2 and 1 teraelectronvolts was observed from GRB 190114C10,11. Here we report multi-frequency observations of GRB 190114C, and study the evolution in time of the GRB emission across 17 orders of magnitude in energy, from 5 × 10-6 to 1012 electronvolts. We find that the broadband spectral energy distribution is double-peaked, with the teraelectronvolt emission constituting a distinct spectral component with power comparable to the synchrotron component. This component is associated with the afterglow and is satisfactorily explained by inverse Compton up-scattering of synchrotron photons by high-energy electrons. We find that the conditions required to account for the observed teraelectronvolt component are typical for GRBs, supporting the possibility that inverse Compton emission is commonly produced in GRBs.

Synergies of THESEUS with the large facilities of the 2030s and guest observer opportunities.

The proposed THESEUS mission will vastly expand the capabilities to monitor the high-energy sky. It will specifically exploit large samples of gamma-ray bursts to probe the early universe back to the first generation of stars, and to advance multi-messenger astrophysics by detecting and localizing the counterparts of gravitational waves and cosmic neutrino sources. The combination and coordination of these activities with multi-wavelength, multi-messenger facilities expected to be operating in the 2030s will open new avenues of exploration in many areas of astrophysics, cosmology and fundamental physics, thus adding considerable strength to the overall scientific impact of THESEUS and these facilities. We discuss here a number of these powerful synergies and guest observer opportunities.

Relativistic jet activity from the tidal disruption of a star by a massive black hole.

Supermassive black holes have powerful gravitational fields with strong gradients that can destroy stars that get too close, producing a bright flare in ultraviolet and X-ray spectral regions from stellar debris that forms an accretion disk around the black hole. The aftermath of this process may have been seen several times over the past two decades in the form of sparsely sampled, slowly fading emission from distant galaxies, but the onset of the stellar disruption event has not hitherto been observed. Here we report observations of a bright X-ray flare from the extragalactic transient Swift J164449.3+573451. This source increased in brightness in the X-ray band by a factor of at least 10,000 since 1990 and by a factor of at least 100 since early 2010. We conclude that we have captured the onset of relativistic jet activity from a supermassive black hole. A companion paper comes to similar conclusions on the basis of radio observations. This event is probably due to the tidal disruption of a star falling into a supermassive black hole, but the detailed behaviour differs from current theoretical models of such events.

Gamma-ray bursts: huge explosion in the early Universe.

Long gamma-ray bursts (GRBs) are bright flashes of high-energy photons that can last for tens of minutes; they are generally associated with galaxies that have a high rate of star formation and probably arise from the collapsing cores of massive stars, which produce highly relativistic jets (collapsar model). Here we describe gamma- and X-ray observations of the most distant GRB ever observed (GRB 050904): its redshift (z) of 6.29 means that this explosion happened 12.8 billion years ago, corresponding to a time when the Universe was just 890 million years old, close to the reionization era. This means that not only did stars form in this short period of time after the Big Bang, but also that enough time had elapsed for them to evolve and collapse into black holes.

The association of GRB 060218 with a supernova and the evolution of the shock wave.

Although the link between long gamma-ray bursts (GRBs) and supernovae has been established, hitherto there have been no observations of the beginning of a supernova explosion and its intimate link to a GRB. In particular, we do not know how the jet that defines a gamma-ray burst emerges from the star's surface, nor how a GRB progenitor explodes. Here we report observations of the relatively nearby GRB 060218 (ref. 5) and its connection to supernova SN 2006aj (ref. 6). In addition to the classical non-thermal emission, GRB 060218 shows a thermal component in its X-ray spectrum, which cools and shifts into the optical/ultraviolet band as time passes. We interpret these features as arising from the break-out of a shock wave driven by a mildly relativistic shell into the dense wind surrounding the progenitor. We have caught a supernova in the act of exploding, directly observing the shock break-out, which indicates that the GRB progenitor was a Wolf-Rayet star.

Impact of acetaldehyde- and pyruvic acid-bound sulphur dioxide on wine lactic acid bacteria.

AIMS: To investigate the impact of acetaldehyde- and pyruvic acid-bound sulphur dioxide on wine lactic acid bacteria (LAB). METHODS AND RESULTS: Growth studies were performed where Oenococcus oeni, Pediococcus parvulus, Ped. damnosus and Lactobacillus hilgardii were inoculated into media containing various concentrations of acetaldehyde or pyruvic acid and an equimolar concentration of SO(2) at pH 3.50 and 3.70. Low concentrations of acetaldehyde- and pyruvic acid-bound SO(2) were inhibitory to the growth of all bacteria although acetaldehyde-bound SO(2) was generally more inhibitory than pyruvic acid-bound SO(2). Inhibition was greater at pH 3.50 than 3.70, and Lact. hilgardii was the most sensitive to acetaldehyde-bound SO(2), while O. oeni was the most sensitive to pyruvic acid-bound SO(2). Degradation of SO(2)-bound acetaldehyde was observed for all LAB, and aside from O. oeni, there was also complete degradation of SO(2)-bound pyruvic acid at both pH values. O. oeni only degraded pyruvic acid at pH 3.70. Degradation of SO(2)-bound acetaldehyde or pyruvic acid did not correlate with bacterial growth as inhibition was always observed in media containing bound SO(2). CONCLUSIONS: Acetaldehyde- and pyruvic acid-bound SO(2) were inhibitory to wine LAB growth at concentrations as low as 5 mg l(-1). Despite this inhibition, all wine LAB degraded SO(2)-bound acetaldehyde and pyruvic acid suggesting that bound SO(2) may have a bacteriostatic rather than bacteriocidal action. SIGNIFICANCE AND IMPACT OF THE STUDY: Sulphur dioxide bound to acetaldehyde or pyruvic acid is inhibitory to growth of wine LAB and must be considered when conducting the malolactic fermentation or controlling the growth of spoilage bacteria such as Pediococcus and Lactobacillus.

An unexpectedly rapid decline in the X-ray afterglow emission of long gamma-ray bursts.

'Long' gamma-ray bursts (GRBs) are commonly accepted to originate in the explosion of particularly massive stars, which give rise to highly relativistic jets. Inhomogeneities in the expanding flow result in internal shock waves that are believed to produce the gamma-rays we see. As the jet travels further outward into the surrounding circumstellar medium, 'external' shocks create the afterglow emission seen in the X-ray, optical and radio bands. Here we report observations of the early phases of the X-ray emission of five GRBs. Their X-ray light curves are characterised by a surprisingly rapid fall-off for the first few hundred seconds, followed by a less rapid decline lasting several hours. This steep decline, together with detailed spectral properties of two particular bursts, shows that violent shock interactions take place in the early jet outflows.

Design and implementation of electron diverters for lobster eye space-based X-ray optics.

Micropore optics have recently been implemented in a lobster eye geometry as a compact X-ray telescope. Fields generated by rare-earth magnets are used to reduce the flux of energetic electrons incident upon the focal plane detector in such a setup. We present the design and implementation of the electron diverters for X-ray telescopes of two upcoming missions: the microchannel X-ray telescope onboard the space-based multiband astronomical variable objects monitor and the soft X-ray instrument onboard the solar wind magnetosphere ionosphere link explorer. Electron diverters must be configured to conform to stringent limits on their total magnetic dipole moment and be compensated for any net moment arising from manufacturing errors. The two missions have differing designs, which are presented and evaluated in terms of the fractions of electrons reaching the detector, as determined by relativistic calculations of electron trajectories. The differential flux of electrons to the detector is calculated, and the integrated electron background is determined for both designs.

Swift and NuSTAR observations of GW170817: Detection of a blue kilonova.

With the first direct detection of merging black holes in 2015, the era of gravitational wave (GW) astrophysics began. A complete picture of compact object mergers, however, requires the detection of an electromagnetic (EM) counterpart. We report ultraviolet (UV) and x-ray observations by Swift and the Nuclear Spectroscopic Telescope Array of the EM counterpart of the binary neutron star merger GW170817. The bright, rapidly fading UV emission indicates a high mass (≈0.03 solar masses) wind-driven outflow with moderate electron fraction (Ye ≈ 0.27). Combined with the x-ray limits, we favor an observer viewing angle of ≈30° away from the orbital rotation axis, which avoids both obscuration from the heaviest elements in the orbital plane and a direct view of any ultrarelativistic, highly collimated ejecta (a γ-ray burst afterglow).

Sequence analysis of cytochrome bd oxidase suggests a revised topology for subunit I.

Numerous sequences of the cytochrome bd quinol oxidase (cytochrome bd) have recently become available for analysis. The analysis has revealed a small number of conserved residues, a new topology for subunit I and a phylogenetic tree involving extensive horizontal gene transfer. There are 20 conserved residues in subunit I and two in subunit II. Algorithms utilizing multiple sequence alignments predicted a revised topology for cytochrome bd, adding two transmembrane helices to subunit I to the seven that were previously indicated by the analysis of the sequence of the oxidase from E. coli. This revised topology has the effect of relocating the N-terminus and C-terminus to the periplasmic and cytoplasmic sides of the membrane, respectively. The new topology repositions I-H19, the putative ligand for heme b595, close to the periplasmic edge of the membrane, which suggests that the heme b595/heme d active site of the oxidase is located near the outer (periplasmic) surface of the membrane. The most highly conserved region of the sequence of subunit I contains the sequence GRQPW and is located in a predicted periplasmic loop connecting the eighth and ninth transmembrane helices. The potential importance of this region of the protein was previously unsuspected, and it may participate in the binding of either quinol or heme d. There are two very highly conserved glutamates in subunit I, E99 and E107, within the third transmembrane helix (E. coli cytochrome bd-I numbering). It is speculated that these glutamates may be part of a proton channel leading from the cytoplasmic side of the membrane to the heme d oxygen-reactive site, now placed near the periplasmic surface. The revised topology and newly revealed conserved residues provide a clear basis for further experimental tests of these hypotheses. Phylogenetic analysis of the new sequences of cytochrome bd reveals considerable deviation from the 16sRNA tree, suggesting that a large amount of horizontal gene transfer has occurred in the evolution of cytochrome bd.

Detergent-solubilized Escherichia coli cytochrome bo3 ubiquinol oxidase: a monomeric, not a dimeric complex.

The protein molecular weight, M(r), and hydrodynamic radius, R(s), of Triton X-100-solubilized Escherichia coli cytochrome bo3 were evaluated by computer fitting of sedimentation velocity data with finite element solutions to the Lamm equation. Detergent-solubilized cytochrome bo3 sediments as a homogeneous species with an S20,w of 6.75 s and a D20,w of 3.71 x 10(-7) cm2/s, corresponding to a R(s) of 5.8 nm and a M(r) of 144,000 +/- 3500. The protein molecular weight agrees very well with the value of 143,929 calculated from the four known subunit sequences and the value of 143,025 measured by MALDI mass spectrometry for the histidine-tagged enzyme. We conclude that detergent-solubilized E. coli ubiquinol oxidase is a monomeric complex of the four known subunits.

Cognitive deficits in normally intelligent patients with tuberous sclerosis.

Webb, Thomson, and Osborne [1991: Arch Dis Child 66:1375-1377] reported on the pattern of cerebral lesions found in an epidemiological sample of patients with tuberous sclerosis (TS) and clinically judged to be of normal intellect. Varying numbers of tubers and subependymal nodules were found, but clinically there appeared to be few associated neuropsychological impairments. Our objectives in this study were to conduct a detailed neuropsychological assessment to determine whether these patients were indeed free of cognitive deficits. We report the results of a detailed neuropsychological assessment in this sample and a matched comparison group. Although of average intelligence, most TS individuals had a significant cognitive deficit of one sort or another, and in a number of cases the pattern of cognitive impairments matched that seen in other neurological disorders. Additionally, the overall rate of cognitive deficits was significantly greater than in the controls. We conclude that normally intelligent individuals with TS are prone to specific cognitive difficulties. Further research will be required to clarify the nature of the links between the brain abnormalities and type of neuropsychological dysfunction. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:642-646, 1999.

Acetaldehyde metabolism by wine lactic acid bacteria.

Acetaldehyde is a volatile flavor compound present in many fermented foods and is important in the production of red and white wines. Nine strains of the genera Lactobacillus and Oenococcus were able to metabolize acetaldehyde in a resting cell system, whereas two Pediococcus strains were not. Acetic acid and ethanol were produced from its degradation. A Lactobacillus and an Oenococcus were able to degrade SO(2)-bound acetaldehyde, as well. A coincubation of resting cells of Saccharomyces bayanus Première Cuvée and Oenococcus oeni Lo111 showed that strain Lo111 metabolized acetaldehyde produced by the yeast. The ability of malolactic bacteria to degrade free and SO(2)-bound acetaldehyde has implications for sensory and color qualities and the use of SO(2) in wine.

Ophthalmic manifestations of tuberous sclerosis: a population based study.

BACKGROUND/AIMS: Tuberous sclerosis complex (TSC) has retinal and non-retinal ophthalmic manifestations. This study was designed to determine the prevalence of the ophthalmic manifestations and of refractive errors in a population of patients with TSC. METHODS: 179 patients identified were in a prevalence study of TSC in the south of England and 107 of these agreed to full ophthalmic examination which was successful in 100. Ophthalmic examination included examination of the eyelids, cover test, examination of the irides, dilation funduscopy using both direct and indirect ophthalmoscopy, and refraction using retinoscopy. Myopia was defined as a spherical equivalent <-0.5D and hyperopia as a spherical equivalent >+0.5D. RESULTS: Retinal hamartomas were seen in 44 of the 100 patients. The commonest morphological type of hamartoma seen was the flat, translucent lesion in 31 of the 44 patients (70%). The multinodular "mulberry" lesion was seen in 24 of the 44 patients (55%) and the transitional type lesion was seen in four of the 44 patients (9%). Punched out areas of retinal depigmentation were seen in 39 of the 100 patients but only six of 100 controls. 27% of eyes were myopic, 22% were hyperopic, and 27% had astigmatism >0.75D. Of the non-retinal findings, 39 patients had angiofibromas of the eyelids, five had non-paralytic strabismus, and three had colobomas. CONCLUSION: Apart from the higher prevalence of flat retinal hamartomas, the findings of this study compare closely with previous large clinic based series of TSC patients. Refractive findings were similar to previous studies of a similarly aged non-TSC population. This is the first series to document the statistically significant association of punched out chorioretinal depigmentation with TSC and the authors believe that it should be looked for as an aid to diagnosis.

Vigabatrin in the treatment of infantile spasms in tuberous sclerosis: literature review.

The purpose of this report is to review the efficacy and safety of vigabatrin in the treatment of infantile spasms in infants suffering from tuberous sclerosis complex. We reviewed all studies published in the English-language literature investigating the use of vigabatrin in the treatment of infantile spasms. Ten studies gave results for the efficacy of vigabatrin in infantile spasms for infants both with and without underlying diagnoses of tuberous sclerosis. Of the 313 patients without tuberous sclerosis complex, 170 (54%) had complete cessation of their infantile spasms; of the 77 patients with tuberous sclerosis complex, 73 (95%) had complete cessation of their seizures. We conclude that vigabatrin should be considered as first-line monotherapy for the treatment of infantile spasms in infants with either a confirmed diagnosis of tuberous sclerosis or those at high risk, ie, those with a first-degree relative with tuberous sclerosis complex. Paradoxically, in those without tuberous sclerosis complex, vigabatrin might be less efficacious than suggested by studies including patients with tuberous sclerosis complex.

Towards an international consensus on definitions and standardised outcome measures for therapeutic trials (and epidemiological studies) in West syndrome.

This paper argues for a standardized use of definitions and outcome measures in publications on West syndrome. Specific recommendations include the need for a validated definition of hypsarrhythmia, the use of the term non-symptomatic and abandoning the terms cryptogenic and idiopathic, talking about underlying disease association and not aetiology or cause and defining a clinical response to mean that no clinical evidence of a spasm has been seen for a specified time - 48 h was suggested. Patients should be followed up to report development - perhaps at 12-15 months and again at 2 and 5 years. Disease free survival should be reported. Side effects need to be seen as adverse events producing risk modification. Outcomes should be blind whenever possible. A consensus group will take these and other suggestions forward--please contact mail to: mpsjpo@bath.ac.uk if you are interested in taking part.

The treatment of West syndrome: a Cochrane review of the literature to December 2000.

BACKGROUND: West syndrome is an age dependent syndrome, which includes a peculiar type of epileptic seizure (infantile spasms), usually hypsarrhythmia and in the majority psychomotor retardation. Despite huge advances in medicine it still remains a poorly understood entity and although with newer imaging techniques we are more often able to elicit the underlying 'causes' of these spasms, still little is known about their pathophysiological basis and treatment remains problematic. OBJECTIVES: To compare the effects of single pharmaceutical therapies used to treat infantile spasms in terms of long-term psychomotor development, subsequent epilepsy, control of the spasms and side effects. METHODS: A search of the central trials register of the Cochrane Epilepsy Group, medline database, embase database and the reference lists of all retrieved articles was undertaken. Correspondence with colleagues and drug companies and appeals at international conferences were also undertaken to try and discover unpublished data. All randomised controlled trials (RCTs) on the medical treatment of infantile spasms were included. Data was then extracted independently by the three reviewers and analysed using the RevMan software package. MAIN RESULTS: We found ten small RCTs on the pharmacological treatment of infantile spasms. No unpublished trials were discovered. These ten studies looked at just 335 patients treated with a total of eight different pharmaceutical agents. Overall methodology of the studies was poor, partly because of ethical dilemmas such as giving placebo injections to children. No study considered the effects of treatment on long-term psychomotor development or onset of other seizure types. One small study found vigabatrin to be more efficacious in stopping infantile spasms in a group of patients with tuberous sclerosis than hydrocortisone. One underpowered study showed a trend for vigabatrin to be more efficacious than placebo in stopping infantile spasms, another two equally underpowered studies suggested adrenocorticotrophic hormone (ACTH) to be more efficacious than low-dose prednisone. It was not possible to compare reduction in the number of spasms between the different treatments because of differences in methods of analysis. Overall, only nine patients were reported to have been withdrawn from the trial treatments due to side effects and two deaths were reported. CONCLUSIONS: There is still little evidence available on the optimum treatment for infantile spasms. Further trials with larger number of patients, and longer follow-up are required.

Treatment of infantile spasms.

BACKGROUND: Infantile spasms (West's Syndrome) is a syndrome which includes a peculiar type of epileptic seizure, usually hypsarrhythmia and in the majority of patients, psychomotor retardation. It remains poorly understood and despite modern imaging techniques an underlying cause is often not found. Little is known about their pathophysiological basis and treatment remains problematic. OBJECTIVES: To compare the effects of single drugs used to treat infantile spasms upon long-term psychomotor development, subsequent epilepsy, control of the spasms and side effects. SEARCH STRATEGY: Our search included the Cochrane Epilepsy Group trials register, MEDLINE (1960 to 2001), EMBASE (1981 to 2001), contacting pharmaceutical companies and appeals at international conferences. SELECTION CRITERIA: Randomized controlled trials (RCTs) of the administration of drugs to people with infantile spasms. DATA COLLECTION AND ANALYSIS: Three reviewers independently selected trials for inclusion and extracted data. Study quality and potential sources of heterogeneity were assessed. Outcomes included cessation of spasms, time to cessation of spasms, participants with cessation of spasms remaining spasm free, reduction in spasms, resolution of hypsarrhythmia, subsequent epilepsy rates and side effects. MAIN RESULTS: Ten small RCTs were included. In total these studies recruited just 335 participants and tested eight different drugs. Overall, studies were of poor methodological quality. No study assessed long-term psychomotor development or the development of other seizure types. One small study found vigabatrin to be more efficacious than hydrocortisone in stopping infantile spasms in a group of people with tuberous sclerosis. One underpowered study showed a trend for vigabatrin to be more efficacious than placebo in stopping infantile spasms, two small studies when combined showed ACTH to be more efficacious than low-dose prednisone (2mg/kg). It was not possible to compare reduction in the number of spasms between the different treatments because of differences in methods of analysis. Overall, only nine participants were reported to have been withdrawn from the trial treatments due to side effects and two deaths were reported. REVIEWER'S CONCLUSIONS: We found no reliable evidence that any of the treatments assessed were more efficacious than any other. Few studies considered psychomotor development or subsequent seizure rates as outcomes and none had long term follow-up. Further trials with larger numbers of participants, and longer follow-up are required.

Perinatal mortality rates in isolated general practitioner maternity units.

OBJECTIVE: To determine the perinatal mortality rate among normally formed, singleton babies with birth weights greater than or equal to 2500 g in Bath health district based on the intended place of delivery at the time of onset of labour or at the time of diagnosis of intrauterine death. DESIGN: The numbers of live births and stillbirths were collected monthly returns from the maternity units concerned. Deaths of infants aged less than or equal to 1 week were collected in the same returns. The intended place of delivery was confirmed at the monthly perinatal mortality meeting, during which maternal and fetal factors were discussed. SETTING: A rural health district of 400,000 population where one third of all deliveries occurred in seven isolated general practitioner maternity units, 8% in the integrated general practitioner unit, and the remainder in the consultant unit. SUBJECTS: All babies of women whose deliveries were booked in the district before the onset of labour or the diagnosis of intrauterine death, excluding twins, babies with lethal congenital malformations, and those less than 2500 g. MAIN OUTCOME MEASURES: Outcome of all deliveries and parity of mothers. RESULTS: 14,415 Deliveries were analysed. The perinatal mortality rate was 2.8/1000 births in the consultant unit (7950 deliveries), 4.8 in the isolated general practitioner units (5237 deliveries), and zero in the integrated general practitioner unit (1228 deliveries). Perinatal deaths attributable to asphyxia were more common in the isolated general practitioner units (1.5 per 1000) than the consultant unit (0.6 per 1000). The perinatal mortality rate among babies born to nulliparous women was 3.2/1000 births in the consultant unit and 5.7 in the isolated general practitioner units; for those born to multigravid women it was 2.4 and 4.2 respectively. CONCLUSIONS: The outcome of delivery was not influenced by parity. Both antenatal and intrapartum care were responsible for the higher perinatal mortality rate in the isolated general practitioner units. The integrated unit, which shared midwifery staff with the consultant unit, seemed to work well. Analysis by intended place of delivery at the time of onset of labour or diagnosis of intrauterine death suggested that the care given in isolated units needs to be improved, perhaps by better training of general practitioners and consultant supervision of antenatal care.

GRB 130427A: a nearby ordinary monster.

Long-duration gamma-ray bursts (GRBs) are an extremely rare outcome of the collapse of massive stars and are typically found in the distant universe. Because of its intrinsic luminosity (L ~ 3 × 10(53) ergs per second) and its relative proximity (z = 0.34), GRB 130427A reached the highest fluence observed in the γ-ray band. Here, we present a comprehensive multiwavelength view of GRB 130427A with Swift, the 2-meter Liverpool and Faulkes telescopes, and by other ground-based facilities, highlighting the evolution of the burst emission from the prompt to the afterglow phase. The properties of GRB 130427A are similar to those of the most luminous, high-redshift GRBs, suggesting that a common central engine is responsible for producing GRBs in both the contemporary and the early universe and over the full range of GRB isotropic energies.