Wheat Loads and Vertical Pressure Distribution in a Full-scale Bin Part II—Detention

The vertical loads imposed on a full-scale bin floor by wheat were measured during a storage time of 6 h. The floor loads were determined to be dependent on the length of storage time. A linear regression model was developed to predict this change in loads in relation to detention time. The linear regression equation had coefficient of determination values ranging from 0.230 to 0.817. Analysis of the model slopes also indicated that fill height and radial location affect the vertical floor loads with a statistical significance level of 0.05. The radial distribution of vertical pressure during detention was measured. The vertical pressure distribution is dependent on radial location and is not uniformly distributed. Radial location significantly influenced the vertical pressure at the 0.05 significance level. The distribution pattern is similar to the filling condition

Wheat Loads and Vertical Pressure Distribution in a Full-scale Bin Part I — Filling

Flat-bottom cylindrical grain bins are subjected to unique loads and pressures during the filling process. The vertical and lateral loads imposed on a bin wall and the vertical load on a bin floor by wheat during filling were measured. The radial distribution of vertical pressure during filling was also measured. The vertical pressure was determined to be dependent on the radial location and was not uniformly distributed. The load distribution in a bin with an H/D ratio of 3 was 83% on the floor and 17% on the walls. Three widely used prediction equations of Janssen, Reimbert, and Walker were compared to the measured loads and pressures and were determined to have similar shapes but different parameters for a best fit to observed data

On the nature of the ultraluminous X-ray transient in Cen~A (NGC 5128)

We combine 9 ROSAT, 9 Chandra, and 2 XMM-Newton observations of the Cen~A galaxy to obtain the X-ray light curve of 1RXH J132519.8-430312 (=CXOU J132519.9$-$430317) spanning 1990 to 2003. The source reached a peak 0.1-2.4 keV flux F_X>10^{-12} ergs cm^{-2} s^{-1} during a 10~day span in 1995 July. The inferred peak isotropic luminosity of the source therefore exceeded 3 10^{39} ergs s^{-1}, which places the source in the class of ultra-luminous X-ray sources. Coherent pulsations at 13.264 Hz are detected during a second bright episode (F_X >3 times 10^{-13} ergs cm^{-2} s^{-1}) in 1999 December. The source is detected and varies significantly within three additional observations but is below the detection threshold in 7 observations. The X-ray spectrum in 1999 December is best described as a cut-off power law or a disk-blackbody (multi-colored disk). We also detect an optical source, m_F555W ~ 24.1 mag, within the Chandra error circle of 1RXH J132519.8-430312 in HST images taken 195~days before the nearest X-ray observation. The optical brightness of this source is consistent with a late O or early B star at the distance of Cen A. If the optical source is the counterpart, then the X-ray and optical behavior of 1RXH J132519.8-430312 are similar to the transient Be/X-ray pulsar A 0538-66.Comment: 7 pages, 8 figures. ApJ (accepted

Correlated Optical/X-ray Long-term Variability in LMXB 4U1636-536

We have conducted a 3-month program of simultaneous optical, soft and hard X-ray monitoring of the LMXB 4U1636-536/V801 Ara using the SMARTS 1.3m telescope and archival RXTE/ASM and Swift/XRT data. 4U1636-536 has been exhibiting a large amplitude, quasi-periodic variability since 2002 when its X-ray flux dramatically declined by roughly an order of magnitude. We confirmed that the anti-correlation between soft (2-12 keV) and hard (> 20 keV) X-rays, first investigated by Shih et al. (2005), is not an isolated event but a fundamental characteristic of this source's variability properties. However, the variability itself is neither strictly stable nor changing on an even longer characteristic timescale. We also demonstrate that the optical counterpart varies on the same timescale, and is correlated with the soft, and not the hard, X-rays. This clearly shows that X-ray reprocessing in LMXB discs is mainly driven by soft X-rays. The X-ray spectra in different epochs of the variability revealed a change of spectral characteristics which resemble the state change of black hole X-ray binaries. All the evidence suggests that 4U1636-536 is frequently (~monthly) undergoing X-ray state transitions, a characteristic feature of X-ray novae with their wide range of luminosities associated with outburst events. In its current behavioural mode, this makes 4U1636-536 an ideal target for investigating the details of state changes in luminous X-ray binaries.Comment: 7 pages, 6 figures, accepted for publication in MNRA

Widespread Tau Seeding Activity at Early Braak Stages

Transcellular propagation of tau aggregates may underlie the progression of pathology in Alzheimer\u27s disease (AD) and other tauopathies. Braak staging (B1, B2, B3) is based on phospho-tau accumulation within connected brain regions: entorhinal cortex (B1); hippocampus/limbic system (B2); and frontal and parietal lobes (B3). We previously developed a specific and sensitive assay that uses flow cytometry to quantify tissue seeding activity based on fluorescence resonance energy transfer (FRET) in cells that stably express tau reporter proteins. In a tauopathy mouse model, we have detected seeding activity far in advance of histopathological changes. It remains unknown whether individuals with AD also develop seeding activity prior to accumulation of phospho-tau. We measured tau seeding activity across four brain regions (hippocampus, frontal lobe, parietal lobe, and cerebellum) in 104 fresh-frozen human AD brain samples from all Braak stages. We observed widespread seeding activity, notably in regions predicted to be free of phospho-tau deposition, and in detergent-insoluble fractions that lacked tau detectable by ELISA. Seeding activity correlated positively with Braak stage and negatively with MMSE. Our results are consistent with early transcellular propagation of tau seeds that triggers subsequent development of neuropathology. The FRET-based seeding assay may also complement standard neuropathological classification of tauopathies

Diagnosing Severe Falciparum Malaria in Parasitaemic African Children: A Prospective Evaluation of Plasma PfHRP2 Measurement.

In African children, distinguishing severe falciparum malaria from other severe febrile illnesses with coincidental Plasmodium falciparum parasitaemia is a major challenge. P. falciparum histidine-rich protein 2 (PfHRP2) is released by mature sequestered parasites and can be used to estimate the total parasite burden. We investigated the prognostic significance of plasma PfHRP2 and used it to estimate the malaria-attributable fraction in African children diagnosed with severe malaria. Admission plasma PfHRP2 was measured prospectively in African children (from Mozambique, The Gambia, Kenya, Tanzania, Uganda, Rwanda, and the Democratic Republic of the Congo) aged 1 month to 15 years with severe febrile illness and a positive P. falciparum lactate dehydrogenase (pLDH)-based rapid test in a clinical trial comparing parenteral artesunate versus quinine (the AQUAMAT trial, ISRCTN 50258054). In 3,826 severely ill children, Plasmadium falciparum PfHRP2 was higher in patients with coma (p = 0.0209), acidosis (p<0.0001), and severe anaemia (p<0.0001). Admission geometric mean (95%CI) plasma PfHRP2 was 1,611 (1,350-1,922) ng/mL in fatal cases (n = 381) versus 1,046 (991-1,104) ng/mL in survivors (n = 3,445, p<0.0001), without differences in parasitaemia as assessed by microscopy. There was a U-shaped association between log(10) plasma PfHRP2 and risk of death. Mortality increased 20% per log(10) increase in PfHRP2 above 174 ng/mL (adjusted odds ratio [AOR] 1.21, 95%CI 1.05-1.39, p = 0.009). A mechanistic model assuming a PfHRP2-independent risk of death in non-malaria illness closely fitted the observed data and showed malaria-attributable mortality less than 50% with plasma PfHRP2≤174 ng/mL. The odds ratio (OR) for death in artesunate versus quinine-treated patients was 0.61 (95%CI 0.44-0.83, p = 0.0018) in the highest PfHRP2 tertile, whereas there was no difference in the lowest tertile (OR 1.05; 95%CI 0.69-1.61; p = 0.82). A limitation of the study is that some conclusions are drawn from a mechanistic model, which is inherently dependent on certain assumptions. However, a sensitivity analysis of the model indicated that the results were robust to a plausible range of parameter estimates. Further studies are needed to validate our findings. Plasma PfHRP2 has prognostic significance in African children with severe falciparum malaria and provides a tool to stratify the risk of "true" severe malaria-attributable disease as opposed to other severe illnesses in parasitaemic African children

Periodic Variability During the X-ray Decline of 4U 1636-53

We report the onset of a large amplitude, statistically significant periodicity (~46 d) in the RXTE/ASM data of the prototype X-ray burster 4U 1636-53, the X-ray flux of which has been gradually declining over the last four years. This behaviour is remarkably similar to that observed in the neutron star LMXB KS 1731-260, which is a long-term transient. We also report on an INTEGRAL/IBIS observation of 4U 1636-53 during its decline phase, and find that the hard X-ray flux (20-100 keV) indicates an apparent anti-correlation with soft X-rays (2-12 keV). We argue that 4U 1636-53 is transiting from activity to quiescence, as occurred in KS 1731-260. We also suggest that the variability during the X-ray decline is the result of an accretion rate variability related to the X-ray irradiation of the disc.Comment: 6 pages. Accepted by MNRA

Starspot-induced optical and infrared radial velocity variability in T Tauri star Hubble 4

We report optical (6150 Ang) and K-band (2.3 micron) radial velocities obtained over two years for the pre-main sequence weak-lined T Tauri star Hubble I 4. We detect periodic and near-sinusoidal radial velocity variations at both wavelengths, with a semi-amplitude of 1395\pm94 m/s in the optical and 365\pm80 m/s in the infrared. The lower velocity amplitude at the longer wavelength, combined with bisector analysis and spot modeling, indicates that there are large, cool spots on the stellar surface that are causing the radial velocity modulation. The radial velocities maintain phase coherence over hundreds of days suggesting that the starspots are long-lived. This is one of the first active stars where the spot-induced velocity modulation has been resolved in the infrared.Comment: Accepted for publication in The Astrophysical Journa

DHODH modulates transcriptional elongation in the neural crest and melanoma

Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma1. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation