Lense-Thirring precession after a supermassive black hole disrupts a star.

An accretion disk formed around a supermassive black hole after it disrupts a star is expected to be initially misaligned with respect to the equatorial plane of the black hole. This misalignment induces relativistic torques (the Lense-Thirring effect) on the disk, causing the disk to precess at early times, whereas at late times the disk aligns with the black hole and precession terminates1,2. Here we report, using high-cadence X-ray monitoring observations of a tidal disruption event (TDE), the discovery of strong, quasi-periodic X-ray flux and temperature modulations. These X-ray modulations are separated by roughly 15 days and persist for about 130 days during the early phase of the TDE. Lense-Thirring precession of the accretion flow can produce this X-ray variability, but other physical mechanisms, such as the radiation-pressure instability3,4, cannot be ruled out. Assuming typical TDE parameters, that is, a solar-like star with the resulting disk extending at most to the so-called circularization radius, and that the disk precesses as a rigid body, we constrain the disrupting dimensionless spin parameter of the black hole to be 0.05 ≲ ∣a∣ ≲ 0.5.

Seasonal evolution of Titan's stratosphere during the Cassini mission.

Titan's stratosphere exhibits significant seasonal changes, including break-up and formation of polar vortices. Here we present the first analysis of mid-infrared mapping observations from Cassini's Composite InfraRed Spectrometer (CIRS) to cover the entire mission (Ls=293-93°, 2004-2017) - mid-northern winter to northern summer solstice. The north-polar winter vortex persisted well after equinox, starting break-up around Ls∼60°, and fully dissipating by Ls∼90°. Absence of enriched polar air spreading to lower latitudes suggests large-scale circulation changes and photochemistry control chemical evolution during vortex break-up. South-polar vortex formation commenced soon after equinox and by Ls∼60° was more enriched in trace gases than the northern mid-winter vortex and had temperatures ∼20 K colder. This suggests early-winter and mid-winter vortices are dominated by different processes - radiative cooling and subsidence-induced adiabatic heating respectively. By the end of the mission (Ls=93°) south-polar conditions were approaching those observed in the north at Ls=293°, implying seasonal symmetry in Titan's vortices.

Composite infrared spectrometer (CIRS) on Cassini.

The Cassini spacecraft orbiting Saturn carries the composite infrared spectrometer (CIRS) designed to study thermal emission from Saturn and its rings and moons. CIRS, a Fourier transform spectrometer, is an indispensable part of the payload providing unique measurements and important synergies with the other instruments. It takes full advantage of Cassini's 13-year-long mission and surpasses the capabilities of previous spectrometers on Voyager 1 and 2. The instrument, consisting of two interferometers sharing a telescope and a scan mechanism, covers over a factor of 100 in wavelength in the mid and far infrared. It is used to study temperature, composition, structure, and dynamics of the atmospheres of Jupiter, Saturn, and Titan, the rings of Saturn, and surfaces of the icy moons. CIRS has returned a large volume of scientific results, the culmination of over 30 years of instrument development, operation, data calibration, and analysis. As Cassini and CIRS reach the end of their mission in 2017, we expect that archived spectra will be used by scientists for many years to come.

Composite infrared spectrometer (CIRS) on Cassini: publisher's note.

This publisher's note renumbers the reference list in Appl. Opt.56, 5274 (2017)APOPAI0003-693510.1364/AO.56.005274.

ERK5 signalling in prostate cancer promotes an invasive phenotype.

BACKGROUND: Aberrant mitogen/extracellular signal-regulated kinase 5 (MEK5)-extracellular signal-regulated protein kinase 5 (ERK5)-mediated signalling has been implicated in a number of tumour types including prostate cancer (PCa). The molecular basis of ERK5-driven carcinogenesis and its clinical relevance remain to be fully characterised. METHODS: Modulation of ERK5 expression or function in human PCa PC3 and PC3-ERK5 (stably transfected with ERK5) cells was performed using siRNA-mediated knockdown or the MEK inhibitor PD18435 respectively. In vitro significance of ERK5 signalling was assessed by assays for proliferation, motility, invasion and invadopodia. Expression of matrix metalloproteinases/tissue inhibitors of metalloproteases was determined by Q-RT-PCR. Extracellular signal-regulated protein kinase 5 expression in primary and metastatic PCa was examined using immunohistochemistry. RESULTS: Reduction of ERK5 expression or signalling significantly inhibited the motility and invasive capability of PC3 cells. Extracellular signal-regulated protein kinase 5-mediated signalling significantly promoted formation of in vivo metastasis in an orthotopic PCa model (P<0.05). Invadopodia formation was also enhanced by forced ERK5 expression in PC3 cells. Furthermore, in metastatic PCa, nuclear ERK5 immunoreactivity was significantly upregulated when compared with benign prostatic hyperplasia and primary PCa (P=0.013 and P<0.0001, respectively). CONCLUSION: Our in vitro, in vivo and clinical data support an important role for the MEK5-ERK5 signalling pathway in invasive PCa, which represents a potential target for therapy in primary and metastatic PCa.

A RAC-GEF network critical for early intestinal tumourigenesis.

RAC1 activity is critical for intestinal homeostasis, and is required for hyperproliferation driven by loss of the tumour suppressor gene Apc in the murine intestine. To avoid the impact of direct targeting upon homeostasis, we reasoned that indirect targeting of RAC1 via RAC-GEFs might be effective. Transcriptional profiling of Apc deficient intestinal tissue identified Vav3 and Tiam1 as key targets. Deletion of these indicated that while TIAM1 deficiency could suppress Apc-driven hyperproliferation, it had no impact upon tumourigenesis, while VAV3 deficiency had no effect. Intriguingly, deletion of either gene resulted in upregulation of Vav2, with subsequent targeting of all three (Vav2-/- Vav3-/- Tiam1-/-), profoundly suppressing hyperproliferation, tumourigenesis and RAC1 activity, without impacting normal homeostasis. Critically, the observed RAC-GEF dependency was negated by oncogenic KRAS mutation. Together, these data demonstrate that while targeting RAC-GEF molecules may have therapeutic impact at early stages, this benefit may be lost in late stage disease.

An intense stratospheric jet on Jupiter.

The Earth's equatorial stratosphere shows oscillations in which the east-west winds reverse direction and the temperatures change cyclically with a period of about two years. This phenomenon, called the quasi-biennial oscillation, also affects the dynamics of the mid- and high-latitude stratosphere and weather in the lower atmosphere. Ground-based observations have suggested that similar temperature oscillations (with a 4-5-yr cycle) occur on Jupiter, but these data suffer from poor vertical resolution and Jupiter's stratospheric wind velocities have not yet been determined. Here we report maps of temperatures and winds with high spatial resolution, obtained from spacecraft measurements of infrared spectra of Jupiter's stratosphere. We find an intense, high-altitude equatorial jet with a speed of approximately 140 m s(-1), whose spatial structure resembles that of a quasi-quadrennial oscillation. Wave activity in the stratosphere also appears analogous to that occurring on Earth. A strong interaction between Jupiter and its plasma environment produces hot spots in its upper atmosphere and stratosphere near its poles, and the temperature maps define the penetration of the hot spots into the stratosphere.

SEASONAL EVOLUTION OF TITAN'S STRATOSPHERE NEAR THE POLES.

In this paper we report the monitoring of seasonal evolution near Titan's poles. We find Titan's south pole to exhibit since 2010 a strong temperature decrease and a dramatic enhancement of several trace species such as complex hydrocarbons and nitriles (HC3N and C6H6 in particular) previously only observed at high northern latitudes (Coustenis et al. 2016 and references therein). This results from the seasonal change on Titan going from winter (2002) to summer (2017) in the north and, at the same time, the onset of winter in the south pole. During this transition period atmospheric components with longer chemical lifetimes linger in the north undergoing slow photochemical destruction, while those with shorter lifetimes decrease and reappear in the south. An opposite effect was expected in the north, but not observed with certainty until now. We present here an analysis of high-resolution nadir spectra acquired by Cassini/CIRS at in the past years and describe the temperature and composition variations near Titan's poles. From 2013 until 2016, the northern polar region has shown a temperature increase of 10 K, while the south has shown a more significant decrease (up to 25 K) in a similar period of time. While the south polar region is continuously enhanced since about 2012, the chemical content in the north is finally showing a clear depletion for most molecules only since 2015. This is indicative of a non-symmetrical response to the seasons in Titan's stratosphere that can set constraints on photochemical and GCM models.

Wnt ligands influence tumour initiation by controlling the number of intestinal stem cells.

Many epithelial stem cell populations follow a pattern of stochastic stem cell divisions called 'neutral drift'. It is hypothesised that neutral competition between stem cells protects against the acquisition of deleterious mutations. Here we use a Porcupine inhibitor to reduce Wnt secretion at a dose where intestinal homoeostasis is maintained despite a reduction of Lgr5+ stem cells. Functionally, there is a marked acceleration in monoclonal conversion, so that crypts become rapidly derived from a single stem cell. Stem cells located further from the base are lost and the pool of competing stem cells is reduced. We tested whether this loss of stem cell competition would modify tumorigenesis. Reduction of Wnt ligand secretion accelerates fixation of Apc-deficient cells within the crypt leading to accelerated tumorigenesis. Therefore, ligand-based Wnt signalling influences the number of stem cells, fixation speed of Apc mutations and the speed and likelihood of adenoma formation.

Less absorbed solar energy and more internal heat for Jupiter.

The radiant energy budget and internal heat are fundamental properties of giant planets, but precise determination of these properties remains a challenge. Here, we report measurements of Jupiter's radiant energy budget and internal heat based on Cassini multi-instrument observations. Our findings reveal that Jupiter's Bond albedo and internal heat, 0.503 ± 0.012 and 7.485 ± 0.160 W m-2 respectively, are significantly larger than 0.343 ± 0.032 and 5.444 ± 0.425 Wm-2, the previous best estimates. The new results help constrain and improve the current evolutionary theories and models for Jupiter. Furthermore, the significant wavelength dependency of Jupiter's albedo implies that the radiant energy budgets and internal heat of the other giant planets in our solar system should be re-examined. Finally, the data sets of Jupiter's characteristics of reflective solar spectral irradiance provide an observational basis for the models of giant exoplanets.

Evidence for the expression and enzymatic activity of haem oxygenase-1 in the lungs of horses.

The aim of this study was to characterise the expression of haem oxygenase-1 (HO-1) in healthy lung tissue from horses and to measure its activity. Samples of lung tissue were collected from six horses euthanased for reasons other than respiratory disease. HO-1 expression and activity were detected in type II alveolar epithelial cells, macrophages and neutrophils in all the samples examined. The activity was dependent on the presence of NADPH and inhibited quantitatively by the addition of increasing concentrations of a competitive inhibitor of HO-1, tin mesoporphyrin IX.

Cohort study of COX-1 and COX-2 expression in canine rectal and bladder tumours.

OBJECTIVES: To determine the role that cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) play in malignant transformation in canine transitional cell carcinoma and rectal tumours. METHODS: Histological sections of 21 canine rectal adenocarcinomas and 18 canine transitional cell carcinomas were stained for COX-1 and COX-2. Mann-Whitney non-parametric tests were applied to determine if there was any relationship between the percentage of cells expressing COX-1 or COX-2, and between COX-1 and COX-2 staining intensity and age, breed or sex. RESULTS: For rectal adenocarcinomas, 19.0 per cent of the sections were negative for COX-1 and COX-2. A further 38.1 per cent of the sections were negative for COX-2 but positive for COX-1, and 38.1 per cent of the sections had rare or occasional single cells positive for COX-2. No significant differences were found in COX staining when compared with age, breed or sex. For transitional cell carcinomas, all of the sections were positive for COX-1 and COX-2. For COX-2 staining, 16.7 per cent had more than 30 per cent positive cells. For COX-1 staining, 38.9 per cent had more than 30 per cent positive cells. There was a significant increase in the percentage of COX-1 positive cells in small breed dogs (P = 0.0337). CLINICAL SIGNIFICANCE: The variations in COX expression reported in this study may explain the differences in the clinical response of transitional cell carcinomas and rectal adenocarcinomas following treatment with non-steroidal anti-inflammatory drugs.

Measuring patient activation: The utility of the Patient Activation Measure within a UK context-Results from four exemplar studies and potential future applications.

OBJECTIVE: Patient activation can be measured using the Patient Activation Measure (PAM) developed by Hibbard et al., however, little is known about the uses of the PAM in research and in practice. This study aims to explore its differing utility in four UK exemplar sites. METHODS: Data from four exemplars in a range of health settings with people living with long-term conditions (i.e. stroke or COPD) were evaluated. PAM scores were described and explored in relation to clinical and sociodemographic variables and outcome measures. RESULTS: PAM scores illustrated that most with COPD or stroke reported PAM levels of 3 or 4, indicating that they are engaging, but may need help to sustain their scores. The exemplars illustrate the utility of, and potential issues involved in, using PAM as a process/outcome measure to predict activation and the effectiveness of interventions, and as a tool to inform tailoring of targeted interventions. CONCLUSIONS: The PAM tool has been shown to be useful as an outcome measure, a screening tool to tailor education, or a quality indicator for delivery of care. PRACTICE IMPLICATIONS: However good demographic and patient history are needed to substantiate PAM scores. Further work is needed to monitor PAM prospectively.

Respiration of 14CO2 by intact animals of various species given L-[1-14C]fucose or D-[1-14C]arabinose.

The production of 14CO2 from L-[1-14C]fucose and D-[1-14C]arabinose been studied in five mammalian species. Cats, guinea pigs, mice, and rabbits respired about 22% of the label of L-[1-14C]fucose or of D-[1-14C]arabinose within 6 h after intraperitoneal injection of the sugar. Rats respired only 1.5% of the L-fucose label and 5% of the D-arabinose label in the same time period. Liver homogenates from cat, guinea pig, and rabbit produced significantly more 14CO2 from L-[1-14C]fucose or D-[1-14C]arabinose than mouse or liver homogenates. Unlike those of the other species, guinea pig liver homogenates had very low L-fucose dehydrogenase activity. The results suggest that substantial catabolism of L-fucose and D-arabinose occurs in the tissues of some animal species. Investigators wishing to employ L-fucose as a tracer of glycoprotein metabolism must, therefore, ensure that the species that they employ does not metabolize L-fucose to products interfering with their studies.

Electromagnetic needle tracking during simulated right internal jugular cannulation.

This study used three-dimensional information from Stealth navigation technology during simulated right internal jugular vein cannulation to define the initial needle trajectory taken when using three approaches: landmark (LM), short-axis (SAX) ultrasound and long-axis (LAX) ultrasound. Nineteen volunteers indicated the entry site and needle direction (track) they would use in performing right internal jugular vein cannulation by the three approaches. The likelihood of cannulation success, arterial puncture and needle direction were recorded. Volunteers were asked to assess the suitability of the simulation system for validity and educational benefit. The SAX track crossed the jugular vein more frequently than the LAX and LM tracks (SAX: 94%; LAX: 80%; LM: 47% [SAX versus LM, P <0.01]). The mean indicated needle direction in the coronal plane for LM, SAX and LAX were -4, 13 and 11 degrees, respectively. The track associated with the LAX technique would have entered the carotid artery by 16% of volunteers. At needle depths of over 40 mm, the track crossed the vertebral artery at the following rates (LM: 11%; SAX: 16%; LAX: 16%). The use of Stealth technology to provide three-dimensional feedback of the needle path taken during simulated right internal jugular cannulation was considered realistic (16/19) and of benefit for 18 of 19 (95%) respondents. The SAX track was associated with the highest likelihood of successful jugular cannulation and the lowest cross rate of the carotid artery. The simulation model using Stealth was considered to be valuable and realistic by participants despite some limitations.

One- to three-year outcome for 14 neonatal survivors of extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation, using venoarterial or venovenous perfusion, is a safe and effective procedure in the term of near-term infant with life-threatening respiratory failure. Without extracorporeal membrane oxygenation, due to the severity of their disease, these children are at high risk for neurologic damage, chronic lung disease, and death. Because survival is not expected without extracorporeal membrane oxygenation therapy, there is no corresponding control group to which these survivors may be compared. In this report, we reviewed the outcome at 1 to 3 years in the first 14 survivors of extracorporeal membrane oxygenation treated at our institution. Seven of 14 neonatal extracorporeal membrane oxygenation survivors (50%) were normal or near normal at between 1 and 3 years of age. Ten (71%) had normal mental ability. We conclude that in neonates with high mortality risk from respiratory failure, near-normal growth and development can be expected in the majority who survive with extracorporeal membrane oxygenation treatment.

Prevalence of polycystic ovary syndrome (PCOS) in first-degree relatives of patients with PCOS.

OBJECTIVE: To determine the rate of clinically evident polycystic ovary syndrome (PCOS) among first-degree female relatives within families with a proband affected by PCOS. DESIGN: Clinical and biochemical evaluation of the mothers and sisters of 93 patients with PCOS. The diagnosis of PCOS was established by: [1] a history of oligomenorrhea, [2] clinical evidence (i.e., hirsutism) or biochemical evidence (i.e., elevated total or free T) of hyperandrogenism, and [3] the exclusion of related disorders. SETTING: Tertiary care university. PATIENT(S): Patients with PCOS and their mothers and sisters. INTERVENTION(S): Interview, physical examination, and hormonal testing on blood samples were performed for all subjects. MAIN OUTCOME MEASURE(S): The presence of hirsutism and hyperandrogenemia was determined in the mothers and sisters of the patients with PCOS. RESULT(S): Of the 78 mothers and 50 sisters evaluated clinically, 19 (24%) and 16 (32%) were affected with PCOS, respectively. A higher rate of PCOS was observed when only premenopausal women not taking hormones (i.e., untreated) were considered (i.e., 35% of mothers and 40% of sisters), consistent with amelioration of symptoms with hormonal therapy or aging. These rates of PCOS are significantly higher than that observed in our general population (approximately 4%) and suggest the involvement of a major genetic component in the disorder. CONCLUSION(S): The rates of PCOS in mothers and sisters of patients with PCOS were 24% and 32%, respectively, although the risk was higher when considering untreated premenopausal women only.

Embedding comprehensive behavioral support in family ecology: an experimental, single-case analysis.

The study evaluates a comprehensive, ecological approach to behavioral family intervention with a family of a child with severe disabilities and severe problem behaviors. A multiple-baseline design across family routines assessed the functional relationship between parent implementation of a multicomponent intervention and improvement in child behavior and successful completion of routines. Results indicate durable improvements in child behavior and routine completion. Associated outcomes included generalized improvements in child behavior and enhanced activity patterns. Results verify the efficacy of the approach for ameliorating problem behaviors and empowering parents to build successful family routines. The value of collaborative research with families is briefly discussed.

Effect of low-dose irradiation on growth of and toxin production by Staphylococcus aureus and Bacillus cereus in roast beef and gravy.

The effect of irradiation (2 kGy) on growth of and toxin production by Staphylococcus aureus and Bacillus cereus in roast beef and gravy during storage at abuse temperatures (15 and 22 degrees C) was assessed by inoculation studies. Irradiation resulted in a 3-4 log10 reduction in numbers of both pathogens. Whenever B. cereus and S. aureus numbers reached 10(6) and 10(7) cfu/g, respectively, during storage their toxins were detectable. As the time taken to attain these levels was longer in irradiated than in unirradiated samples, toxin production by both pathogens was delayed by irradiation. When samples initially containing low levels (10(2)/g) of S. aureus were irradiated no toxin was produced during subsequent storage at 15 or 22 degrees C. Diarrhoeal toxin produced by B. cereus was detected after 2 days at 22 degrees C, but not at 15 degrees C, in samples containing 10(2) cells/g prior to irradiation. When higher numbers (10(6)/g) of either pathogen were present prior to irradiation, toxins were produced by both pathogens at 22 degrees C, but not at 15 degrees C. Microbial competition had an effect on the growth of B. cereus and S. aureus after irradiation when a low initial inoculum was applied. However, when a higher inoculum was used the pathogens outnumbered their competitors and competition effects were less important. It was concluded that low-dose irradiation would improve the microbiological safety of roast beef and gravy.

Evaluation of three silicone-based materials as potential retrograde fillings in surgical endodontics.

Endodontic therapy has played an important role in maintaining the integrity of the natural dentition as a fully functional and esthetic masticatory apparatus. Although the sealing of the root canal system is usually accomplished by the conservative endodontic approach, cases which have failed or which involve perforations, broken instruments, or post-crown restorations are almost always treated surgically by using zinc-free amalgam as a retrograde filling material. However, the literature is controversial concerning the health risks and benefits of this material. For this reason, the study presented here was initiated to evaluate the potential of (a) a medical grade silicone-titanium mesh compound; (b) Endo-Fill (Lee Pharmaceuticals, El Monte, CA); and (c) an experimental expanding Endo-Fill (Lee Pharmaceuticals) as alternatives to amalgam. The three silicone-based materials and amalgam were compared for linear apical dye leakage. The leakage study involved 80 teeth which were instrumented, obturated, and prepared surgically for one of the four test materials. Either the teeth were placed immediately into 1% methylene blue dye or the material was allowed to set for 24 h before placement into the dye. Endo-Fill showed significantly less leakage than did the other materials in both the immediately placed and the 24-h set groups. On the other extreme, the experimental expanding Endo-Fill allowed significantly more dye penetration than did amalgam and the other silicone variations.