Hot dense capsule implosion cores produced by z-pinch dynamic hohlraum radiation

Hot dense capsule implosions driven by z-pinch x-rays have been measured for the first time. A ~220 eV dynamic hohlraum imploded 1.7-2.1 mm diameter gas-filled CH capsules which absorbed up to ~20 kJ of x-rays. Argon tracer atom spectra were used to measure the Te~ 1keV electron temperature and the ne ~ 1-4 x10^23 cm-3 electron density. Spectra from multiple directions provide core symmetry estimates. Computer simulations agree well with the peak compression values of Te, ne, and symmetry, indicating reasonable understanding of the hohlraum and implosion physics.Comment: submitted to Phys. Rev. Let

Review of high convergence implosion experiments with single and double shell targets

Experiments have been been performed in recent years at the Omega laser studying double shell capsules as an a1 teinative, 11011 cryogenic, path towards ignition at NTF. Double shell capsules designed to mitigate the Au M-band radiation asymmetries, were experimentally found to perform well in both spherical and cylindrical hohlraums, achieving near 1-D (-90 %) clean calculated yield at convergence comparable to that required for NIF ignition. Near-term plans include directly driven double shell experiments at Omega, which eliminates Au M-band radiation as a yield degradation m ec h an i s in

Validation of the Thai version of the family reported outcome measure (FROM-16)© to assess the impact of disease on the partner or family members of patients with cancer

© The Author(s). 2019Background: Cancer not only impairs a patient's physical and psychosocial functional behaviour, but also contributes to negative impact on family members' health related quality of life. Currently, there is an absence of a relevant tool in Thai with which to measure such impact. The aim of this study was to translate and validate the Family Reported Outcome Measure (FROM-16) in Thai cancer patients' family members. Methods: Thai version of FROM-16 was generated by interactive forward-backward translation process following standard guidelines. This was tested for psychometric properties including reliability and validity, namely content validity, concurrent validity, known group validity, internal consistency, exploratory and confirmatory factor analysis. Construct validity was examined by comparing the Thai FROM-16 version with the WHOQOL-BREF-THAI. Results: The internal consistency reliability was strong (Cronbach's alpha = 0.86). A Negative moderate correlation between the Thai FROM-16 and WHOQOL-BREF-THAI was observed (r = - 0.4545, p < 0.00), and known group validity was proved by a statistically significant higher score in family members with high burden of care and insufficient income. The factor analysis supported both 3-factor and 2-factor loading model with slight difference when compared with the original version. Conclusions: The Thai FROM-16 showed good reliability and validity in Thai family members of patients with cancer. A slight difference in factor analysis results compared to the original version could be due to cross-culture application.Peer reviewedFinal Published versio

Capsule design for the National Ignition Facility

Several choices exist in the design and production of capsules intended to ignite and propagate fusion burn of the DT fuel when imploded by indirect drive at the National Ignition Facility. These choices include ablator material, ablator dopant concentration and distribution, capsule dimensions, and x-ray drive profile (shock timings and strengths). The choice of ablator material must also include fabrication and material characteristics, such as attainable surface finishes, permeability, strength, transparency to radio frequency and infrared radiation, thermal conductivity, and material homogeneity. Understanding the advantages and/or limitations of these choices is an ongoing effort for LLNL and LANL designers. At this time, simulations in one- two- and three- dimensions show that capsules with either a copper doped beryllium or a polyimide (C22H10N2O4) ablator material have both the least sensitivity to initial surface roughnesses and favorable fabrication qualities. Simulations also indicate the existence of capsule designs based on these ablator materials which ignite and burn when imploded by less than nominal laser performance (900 kJ energy, 250 TW power, producing 250 eV peak radiation temperature). We will describe and compare these reduced scale capsules, in addition to several designs which use the expected 300 eV peak x-ray drive obtained from the nominal NIF laser (1.3 MJ, 500 TW)

Growth arrest-specific gene 6 expression in human breast cancer

Growth arrest-specific gene 6 (Gas6), identified in 1995, acts as the ligand to the Axl/Tyro3 family of tyrosine kinase receptors and exerts mitogenic activity when bound to these receptors. Overexpression of the Axl/Tyro3 receptor family has been found in breast, ovarian and lung tumours. Gas6 is upregulated 23-fold by progesterone acting through the progesterone receptor B (PRB). Recently, Gas6 has been shown to be a target for overexpression and amplification in breast cancer. Quantitative real-time PCR analysis was used to determine the levels of Gas6 mRNA expression in 49 primary breast carcinomas. Expression of PRB protein was evaluated immunohistochemically with a commercially available PRB antibody. The results showed a positive association between PRB protein and Gas6 mRNA levels (P=0.04). Gas6 correlated positively with a number of favourable prognostic variables including lymph node negativity (P=0.0002), younger age at diagnosis (P=0.04), smaller size of tumours (P=0.02), low Nottingham prognostic index scores (P=0.03) and low nuclear morphology (P=0.03). This study verifies for the first time the association between PRB and Gas6 in breast cancer tissue

Reduced Distractibility in a Remote Culture

Background In visual processing, there are marked cultural differences in the tendency to adopt either a global or local processing style. A remote culture (the Himba) has recently been reported to have a greater local bias in visual processing than Westerners. Here we give the first evidence that a greater, and remarkable, attentional selectivity provides the basis for this local bias. Methodology/Principal Findings In Experiment 1, Eriksen-type flanker interference was measured in the Himba and in Western controls. In both groups, responses to the direction of a task-relevant target arrow were affected by the compatibility of task-irrelevant distractor arrows. However, the Himba showed a marked reduction in overall flanker interference compared to Westerners. The smaller interference effect in the Himba occurred despite their overall slower performance than Westerners, and was evident even at a low level of perceptual load of the displays. In Experiment 2, the attentional selectivity of the Himba was further demonstrated by showing that their attention was not even captured by a moving singleton distractor. Conclusions/Significance We argue that the reduced distractibility in the Himba is clearly consistent with their tendency to prioritize the analysis of local details in visual processing

A “Coiled-Coil” Motif Is Important for Oligomerization and DNA Binding Properties of Human Cytomegalovirus Protein UL77

Human cytomegalovirus (HCMV) UL77 gene encodes the essential protein UL77, its function is characterized in the present study. Immunoprecipitation identified monomeric and oligomeric pUL77 in HCMV infected cells. Immunostaining of purified virions and subviral fractions showed that pUL77 is a structural protein associated with capsids. In silico analysis revealed the presence of a coiled-coil motif (CCM) at the N-terminus of pUL77. Chemical cross-linking of either wild-type pUL77 or CCM deletion mutant (pUL77ΔCCM) implicated that CCM is critical for oligomerization of pUL77. Furthermore, co-immunoprecipitations of infected and transfected cells demonstrated that pUL77 interacts with the capsid-associated DNA packaging motor components, pUL56 and pUL104, as well as the major capsid protein. The ability of pUL77 to bind dsDNA was shown by an in vitro assay. Binding to certain DNA was further confirmed by an assay using biotinylated 36-, 250-, 500-, 1000-meric dsDNA and 966-meric HCMV-specific dsDNA designed for this study. The binding efficiency (BE) was determined by image processing program defining values above 1.0 as positive. While the BE of the pUL56 binding to the 36-mer bio-pac1 containing a packaging signal was 10.0±0.63, the one for pUL77 was only 0.2±0.03. In contrast to this observation the BE of pUL77 binding to bio-500 bp or bio-1000 bp was 2.2±0.41 and 4.9±0.71, respectively. By using pUL77ΔCCM it was demonstrated that this protein could not bind to dsDNA. These data indicated that pUL77 (i) could form homodimers, (ii) CCM of pUL77 is crucial for oligomerization and (iii) could bind to dsDNA in a sequence independent manner

BST2/Tetherin Enhances Entry of Human Cytomegalovirus

Interferon-induced BST2/Tetherin prevents budding of vpu-deficient HIV-1 by tethering mature viral particles to the plasma membrane. BST2 also inhibits release of other enveloped viruses including Ebola virus and Kaposi's sarcoma associated herpesvirus (KSHV), indicating that BST2 is a broadly acting antiviral host protein. Unexpectedly however, recovery of human cytomegalovirus (HCMV) from supernatants of BST2-expressing human fibroblasts was increased rather than decreased. Furthermore, BST2 seemed to enhance viral entry into cells since more virion proteins were released into BST2-expressing cells and subsequent viral gene expression was elevated. A significant increase in viral entry was also observed upon induction of endogenous BST2 during differentiation of the pro-monocytic cell line THP-1. Moreover, treatment of primary human monocytes with siRNA to BST2 reduced HCMV infection, suggesting that BST2 facilitates entry of HCMV into cells expressing high levels of BST2 either constitutively or in response to exogenous stimuli. Since BST2 is present in HCMV particles we propose that HCMV entry is enhanced via a reverse-tethering mechanism with BST2 in the viral envelope interacting with BST2 in the target cell membrane. Our data suggest that HCMV not only counteracts the well-established function of BST2 as inhibitor of viral egress but also employs this anti-viral protein to gain entry into BST2-expressing hematopoietic cells, a process that might play a role in hematogenous dissemination of HCMV

Attomolar Detection of Botulinum Toxin Type A in Complex Biological Matrices

BACKGROUND: A highly sensitive, rapid and cost efficient method that can detect active botulinum neurotoxin (BoNT) in complex biological samples such as foods or serum is desired in order to 1) counter the potential bioterrorist threat 2) enhance food safety 3) enable future pharmacokinetic studies in medical applications that utilize BoNTs. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a botulinum neurotoxin serotype A assay with a large immuno-sorbent surface area (BoNT/A ALISSA) that captures a low number of toxin molecules and measures their intrinsic metalloprotease activity with a fluorogenic substrate. In direct comparison with the "gold standard" mouse bioassay, the ALISSA is four to five orders of magnitudes more sensitive and considerably faster. Our method reaches attomolar sensitivities in serum, milk, carrot juice, and in the diluent fluid used in the mouse assay. ALISSA has high specificity for the targeted type A toxin when tested against alternative proteases including other BoNT serotypes and trypsin, and it detects the holotoxin as well as the multi-protein complex form of BoNT/A. The assay was optimized for temperature, substrate concentration, size and volume proportions of the immuno-sorbent matrix, enrichment and reaction times. Finally, a kinetic model is presented that is consistent with the observed improvement in sensitivity. CONCLUSIONS/SIGNIFICANCE: The sensitivity, specificity, speed and simplicity of the BoNT ALISSA should make this method attractive for diagnostic, biodefense and pharmacological applications

Asynchronous combinatorial action of four regulatory factors activates Bcl11b for T cell commitment

During T cell development, multipotent progenitors relinquish competence for other fates and commit to the T cell lineage by turning on Bcl11b, which encodes a transcription factor. To clarify lineage commitment mechanisms, we followed developing T cells at the single-cell level using Bcl11b knock-in fluorescent reporter mice. Notch signaling and Notch-activated transcription factors collaborate to activate Bcl11b expression irrespectively of Notch-dependent proliferation. These inputs work via three distinct, asynchronous mechanisms: an early locus 'poising' function dependent on TCF-1 and GATA-3, a stochastic-permissivity function dependent on Notch signaling, and a separate amplitude-control function dependent on Runx1, a factor already present in multipotent progenitors. Despite their necessity for Bcl11b expression, these inputs act in a stage-specific manner, providing a multitiered mechanism for developmental gene regulation