High resolution electron microscopy study of a high Cu variant of Weldalite (tm) 049 and a high strength Al-Cu-Ag-Mg-Zr alloy

Weldalite (trademark) 049 is an Al-Cu-Li-Ag-Mg alloy that is strengthened in artificially aged tempers primarily by very thin plate-like precipitates lying on the set of (111) matrix planes. This precipitate might be expected to be the T(sub 1) phase, Al2CuLi, which has been observed in Al-Cu-Li alloys. However, in several ways this precipitate is similar to the omega phase which also appears as the set of (111) planes plates and is found in Al-Cu-Ag-Mg alloys. The study was undertaken to identify the set of (111) planes precipitate or precipitates in Weldalite (trademark) 049 in the T8 (stretched and artificially aged) temper, and to determine whether T(sub 1), omega, or some other phase is primarily responsible for the high strength (i.e., 700 MPa tensile strength) in this Al-Cu-Li-Ag-Mg alloy

Natural aging and reversion behavior of Al-Cu-Li-Ag-Mg alloy Weldalite (tm) 049

This study was initiated to understand the natural aging and reversion behavior of Weldalite (trademark) 049 in tempers without cold work. Of particular interest are: (1) the microstructural basis for the high strength in the T4 condition; (2) an explanation of the reversion phenomenon; and (3) the effect of re-aging at room temperature after a reversion treatment. Mechanical properties were measured and transmission electron microscopy (TEM) analysis performed at various stages of microstructural development during aging, reversion, and subsequent re-aging

Structure and properties during aging of an Al-Cu-Li-Ag-Mg alloy, Weldalite (tm) 049

An Al-Cu-Li-Ag-Mg alloy, Weldalite (trademark) 049, was recently introduced as an ultra-high strength alloy (7000 MPa yield strength in artificially aged tempers) with good weldability. In addition, the alloy exhibits an extraordinary natural aging response (440 MPa yield strength (YS) in the unstretch condition) and a high ductility reversion condition which may be useful as a cold-forming temper. In contrast to other Al-Li alloys, these properties can essentially be obtained with or without a stretch or other coldworking operation prior to aging. Preliminary studies have revealed that the T4 temper (no stretch, natural age) is strengthened by a combination of GP zones and delta prime (Al3Li). The T6 temper (no stretch, aged at 180 C to peak strength) was reported to be strengthened primarily by T(sub 1) phase (Al2CuLi) with a minor presence of a theta prime like (Al2Cu) phase. On the other hand, a similar but lower solute containing alloy was reported to contain omega, (stoichiometry unknown), theta prime, and S prime in the peak strength condition. The purpose of this study is to further elucidate the strengthening phases in Weldalite (trademark) 049 in the unstretched tempers, and to follow the development of the microstructure from the T4 temper through reversion (180 C for 5 to 45 minutes) to the T6 temper

Evaluation of the microstructure of Al-Cu-Li-Ag-Mg Weldalite (tm) alloys, part 4

Weldalite (trademark) 049 is an Al-Cu-Li-Ag-Mg alloy designed to have ultrahigh strength and to serve in aerospace applications. The alloy displays significantly higher strength than competitive alloys in both naturally aged and artificially aged tempers. The strengthening phases in such tempers have been identified to, in part, explain the mechanical properties attained. In general, the alloy is strengthened by delta prime Al3Li and Guinier-Preston (GP) zones in the naturally aged tempers. In artificially aged tempers in slightly underaged conditions, strengthening is provided by several phases including GP zones, theta prime Al2Cu, S prime Al2CuMg, T(sub 1) Al2CuLi, and possibly a new phase. In the peak strength artificially aged tempers, T(sub 1) is the predominant strengthening phase

Primary and malignant cholangiocytes undergo CD40 mediated Fas dependent Apoptosis, but are insensitive to direct activation with exogenous fas ligand

Introduction Cholangiocarcinoma is a rare malignancy of the biliary tract, the incidence of which is rising, but the pathogenesis of which remains uncertain. No common genetic defects have been described but it is accepted that chronic inflammation is an important contributing factor. We have shown that primary human cholangiocyte and hepatocyte survival is tightly regulated via co-operative interactions between two tumour necrosis family (TNF) receptor family members; CD40 and Fas (CD95). Functional deficiency of CD154, the ligand for CD40, leads to a failure of clearance of biliary tract infections and a predisposition to cholangiocarcinoma implying a direct link between TNF receptor-mediated apoptosis and the development of cholangiocarcinoma. Aims To determine whether malignant cholangiocytes display defects in CD40 mediated apoptosis. By comparing CD40 and Fas-mediated apoptosis and intracellular signalling in primary human cholangiocytes and three cholangiocyte cell lines. Results Primary cholangiocytes and cholangiocyte cell lines were relatively insensitive to direct Fas-mediated killing with exogenous FasL when compared with Jurkat cells, which readily underwent Fas-mediated apoptosis, but were extremely sensitive to CD154 stimulation. The sensitivity of cells to CD40 activation was similar in magnitude in both primary and malignant cells and was STAT-3 and AP-1 dependent in both. Conclusions 1) Both primary and malignant cholangiocytes are relatively resistant to Fas–mediated killing but show exquisite sensitivity to CD154, suggesting that the CD40 pathway is intact and fully functional in both primary and malignant cholangiocytes 2) The relative insensitivity of cholangiocytes to Fas activation demonstrates the importance of CD40 augmentation of Fas dependent death in these cells. Agonistic therapies which target CD40 and associated intracellular signalling pathways may be effective in promoting apoptosis of malignant cholangiocytes

HST/WFPC2 and VLA Observations of the Ionized Gas in the Dwarf Starburst Galaxy NGC 4214

We present new H alpha and [O III] 5007 narrow band images of the starbursting dwarf galaxy NGC 4214, obtained with the WFPC2 onboard HST, together with VLA observations of the same galaxy. The HST images resolve features down to physical scales of 2-5 pc, revealing several young (<10 Myr) star forming complexes of various ionized gas morphologies (compact knots, complete or fragmentary shells) and sizes (10-200 pc). Our results are consistent with a uniform set of evolutionary trends: The youngest, smaller, filled regions that presumably are those just emerging from dense star forming clouds, tend to be of high excitation and are highly obscured. Evolved, larger shell-like regions have lower excitation and are less extincted due of the action of stellar winds and supernovae. In at least one case we find evidence for induced star formation which has led to a two-stage starburst. Age estimates based on W(H alpha) measurements do not agree with those inferred from wind-driven shell models of expanding H II regions. The most likely explanation for this effect is the existence of a 2 Myr delay in the formation of superbubbles caused by the pressure exerted by the high density medium in which massive stars are born. We report the detection of a supernova remnant embedded in one of the two large H II complexes of NGC 4214. The dust in NGC 4214 is not located in a foreground screen but is physically associated with the warm ionized gas.Comment: 41 pages, including 9 figures and 7 tables. To appear in the November issue of the Astronomical Journa

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

The association between gestational weight gain z-score and stillbirth: a case-control study

Background There is limited information on potentially modifiable risk factors for stillbirth, such as gestational weight gain (GWG). Our purpose was to explore the association between GWG and stillbirth using the GWG z−score. Methods We analyzed 479 stillbirths and 1601 live births from the Stillbirth Collaborative Research Network case−control study. Women with triplets or monochorionic twins were excluded from analysis. We evaluated the association between GWG z−score (modeled as a restricted cubic spline with knots at the 5th, 50th, and 95th percentiles) and stillbirth using multivariable logistic regression with generalized estimating equations, adjusting for pre − pregnancy body mass index (BMI) and other confounders. In addition, we conducted analyses stratified by pre − pregnancy BMI category (normal weight, overweight, obese). Results Mean GWG was 18.95 (SD 17.6) lb. among mothers of stillbirths and 30.89 (SD 13.3) lb. among mothers of live births; mean GWG z−score was − 0.39 (SD 1.5) among mothers of cases and − 0.17 (SD 0.9) among control mothers. In adjusted analyses, the odds of stillbirth were elevated for women with very low GWG z−scores (e.g., adjusted odds ratio (aOR) and 95% Confidence Interval (CI) for z−score − 1.5 SD versus 0 SD: 1.52 (1.30, 1.78); aOR (95% CI) for z−score − 2.5 SD versus 0 SD: 2.36 (1.74, 3.20)). Results differed slightly by pre − pregnancy BMI. The odds of stillbirth were slightly elevated among women with overweight BMI and GWG z−scores ≥1 SD (e.g., aOR (95% CI) for z−score of 1.5 SD versus 0 SD: 1.84 (0.97, 3.50)). Conclusions GWG z−scores below − 1.5 SD are associated with increased odds of stillbirth

Bacterial toxin inhibitors based on multivalent scaffolds.

Protein toxins released by certain intestinal bacteria are the cause of many diarrhoeal diseases including cholera and travellers' diarrhoea. The toxins enter their target cells by first binding to specific glycolipids in the cell membrane. Inhibition of these protein-carbohydrate interactions has the potential to prevent the toxins from reaching their site of action, and thus avoid the ensuing diarrhoea. Simple oligosaccharides typically have low affinities for the protein toxins, therefore inhibitor design has focussed on exploiting the principles of multivalency: multiple weak interactions acting in concert can enhance the overall binding interaction. The major classes of multivalent inhibitors investigated to date will be discussed; these include glycopolymers, glycodendrimers, tailored glycoclusters and inhibitors exploiting templated assembly