In situ monitoring the effects of Ti6Al4V powder oxidation during laser powder bed fusion additive manufacturing

Making laser powder bed fusion (L-PBF) additive manufacturing process sustainable requires effective powder recycling. Recycling of Ti6Al4V powder in L-PBF can lead to powder oxidation, however, such impact on laser-matter interactions, process, and defect dynamics during L-PBF are not well understood. This study reveals and quantifies the effects of processing Ti6Al4V powders with low (0.12 wt%) and high (0.40 wt%) oxygen content during multilayer thin-wall L-PBF using in situ high speed synchrotron X-ray imaging. Our results reveal that high oxygen content Ti6Al4V powder can reduce melt ejections, surface roughness, and defect population in the built parts. With increasing oxygen content in the part, there is an increase in microhardness due to solid solution strengthening and no significant change in the microstructure is evident

In situ characterisation of surface roughness and its amplification during multilayer single-track laser powder bed fusion additive manufacturing

Surface roughness controls the mechanical performance and durability (e.g., wear and corrosion resistance) of laser powder bed fusion (LPBF) components. The evolution mechanisms of surface roughness during LPBF are not well understood due to a lack of in situ characterisation methods. Here, we quantified key processes and defect dynamics using synchrotron X-ray imaging and ex situ optical imaging and explained the evolution mechanisms of side-skin and top-skin roughness during multi-layer LPBF of Ti-6Al-4V (where down-skin roughness was out of the project scope). We found that the average surface roughness alone is not an accurate representation of surface topology of an LPBF component and that the surface topology is multimodal (e.g., containing both roughness and waviness) and multiscale (e.g., from 25 µm sintered powder features to 250 µm molten pool wavelength). Both roughness and topology are significantly affected by the formation of pre-layer humping, spatter, and rippling defects. We developed a surface topology matrix that accurately describes surface features by combining 8 different metrics: average roughness, root mean square roughness, maximum profile peak height, maximum profile valley height, mean height, mean width, skewness, and melt pool size ratio. This matrix provides a guide to determine the appropriate linear energy density to achieve the optimum surface finish of Ti-6Al-4V thin-wall builds. This work lays a foundation for surface texture control which is critical for build design, metrology, and performance in LPBF

Doping a semiconductor to create an unconventional metal

Landau Fermi liquid theory, with its pivotal assertion that electrons in metals can be simply understood as independent particles with effective masses replacing the free electron mass, has been astonishingly successful. This is true despite the Coulomb interactions an electron experiences from the host crystal lattice, its defects, and the other ~1022/cm3 electrons. An important extension to the theory accounts for the behaviour of doped semiconductors1,2. Because little in the vast literature on materials contradicts Fermi liquid theory and its extensions, exceptions have attracted great attention, and they include the high temperature superconductors3, silicon-based field effect transistors which host two-dimensional metals4, and certain rare earth compounds at the threshold of magnetism5-8. The origin of the non-Fermi liquid behaviour in all of these systems remains controversial. Here we report that an entirely different and exceedingly simple class of materials - doped small gap semiconductors near a metal-insulator transition - can also display a non-Fermi liquid state. Remarkably, a modest magnetic field functions as a switch which restores the ordinary disordered Fermi liquid. Our data suggest that we have finally found a physical realization of the only mathematically rigourous route to a non-Fermi liquid, namely the 'undercompensated Kondo effect', where there are too few mobile electrons to compensate for the spins of unpaired electrons localized on impurity atoms9-12.Comment: 17 pages 4 figures supplemental information included with 2 figure

The C-Terminal Domain of the Arabinosyltransferase Mycobacterium tuberculosis EmbC Is a Lectin-Like Carbohydrate Binding Module

The D-arabinan-containing polymers arabinogalactan (AG) and lipoarabinomannan (LAM) are essential components of the unique cell envelope of the pathogen Mycobacterium tuberculosis. Biosynthesis of AG and LAM involves a series of membrane-embedded arabinofuranosyl (Araf) transferases whose structures are largely uncharacterised, despite the fact that several of them are pharmacological targets of ethambutol, a frontline drug in tuberculosis therapy. Herein, we present the crystal structure of the C-terminal hydrophilic domain of the ethambutol-sensitive Araf transferase M. tuberculosis EmbC, which is essential for LAM synthesis. The structure of the C-terminal domain of EmbC (EmbCCT) encompasses two sub-domains of different folds, of which subdomain II shows distinct similarity to lectin-like carbohydrate-binding modules (CBM). Co-crystallisation with a cell wall-derived di-arabinoside acceptor analogue and structural comparison with ligand-bound CBMs suggest that EmbCCT contains two separate carbohydrate binding sites, associated with subdomains I and II, respectively. Single-residue substitution of conserved tryptophan residues (Trp868, Trp985) at these respective sites inhibited EmbC-catalysed extension of LAM. The same substitutions differentially abrogated binding of di- and penta-arabinofuranoside acceptor analogues to EmbCCT, linking the loss of activity to compromised acceptor substrate binding, indicating the presence of two separate carbohydrate binding sites, and demonstrating that subdomain II indeed functions as a carbohydrate-binding module. This work provides the first step towards unravelling the structure and function of a GT-C-type glycosyltransferase that is essential in M. tuberculosis. Author Summary Top Tuberculosis (TB), an infectious disease caused by the bacillus Mycobacterium tuberculosis, burdens large swaths of the world population. Treatment of active TB typically requires administration of an antibiotic cocktail over several months that includes the drug ethambutol. This front line compound inhibits a set of arabinosyltransferase enzymes, called EmbA, EmbB and EmbC, which are critical for the synthesis of arabinan, a vital polysaccharide in the pathogen's unique cell envelope. How precisely ethambutol inhibits arabinosyltransferase activity is not clear, in part because structural information of its pharmacological targets has been elusive. Here, we report the high-resolution structure of the C-terminal domain of the ethambutol-target EmbC, a 390-amino acid fragment responsible for acceptor substrate recognition. Combining the X-ray crystallographic analysis with structural comparisons, site-directed mutagenesis, activity and ligand binding assays, we identified two regions in the C-terminal domain of EmbC that are capable of binding acceptor substrate mimics and are critical for activity of the full-length enzyme. Our results begin to define structure-function relationships in a family of structurally uncharacterised membrane-embedded glycosyltransferases, which are an important target for tuberculosis therapy

Comparative study between wear of uncoated and TiAlN-coated carbide tools in milling of Ti6Al4V

As is recognized widely, tool wear is a major problem in the machining of difficult-to-cut titanium alloys. Therefore, it is of significant interest and importance to understand and determine quantitatively and qualitatively tool wear evolution and the underlying wear mechanisms. The main aim of this paper is to investigate and analyse wear, wear mechanisms and surface and chip generation of uncoated and TiAlN-coated carbide tools in a dry milling of Ti6Al4V alloys. The quantitative flank wear and roughness were measured and recorded. Optical and scanning electron microscopy (SEM) observations of the tool cutting edge, machined surface and chips were conducted. The results show that the TiAlN-coated tool exhibits an approximately 44% longer tool life than the uncoated tool at a cutting distance of 16 m. A more regular progressive abrasion between the flank face of the tool and the workpiece is found to be the underlying wear mechanism. The TiAlN-coated tool generates a smooth machined surface with 31% lower roughness than the uncoated tool. As is expected, both tools generate serrated chips. However, the burnt chips with blue color are noticed for the uncoated tool as the cutting continues further. The results are shown to be consistent with observation of other researchers, and further imply that coated tools with appropriate combinations of cutting parameters would be able to increase the tool life in cutting of titanium alloys

Evaluation of geospatial methods to generate subnational HIV prevalence estimates for local level planning

Objective: There is evidence of substantial subnational variation in the HIV epidemic. However, robust spatial HIV data are often only available at high levels of geographic aggregation and not at the finer resolution needed for decision making. Therefore, spatial analysis methods that leverage available data to provide local estimates of HIV prevalence may be useful. Such methods exist but have not been formally compared when applied to HIV. Design/methods: Six candidate methods – including those used by the Joint United Nations Programme on HIV/AIDS to generate maps and a Bayesian geostatistical approach applied to other diseases – were used to generate maps and subnational estimates of HIV prevalence across three countries using cluster level data from household surveys. Two approaches were used to assess the accuracy of predictions: internal validation, whereby a proportion of input data is held back (test dataset) to challenge predictions; and comparison with location-specific data from household surveys in earlier years. Results: Each of the methods can generate usefully accurate predictions of prevalence at unsampled locations, with the magnitude of the error in predictions similar across approaches. However, the Bayesian geostatistical approach consistently gave marginally the strongest statistical performance across countries and validation procedures. Conclusions: Available methods may be able to furnish estimates of HIV prevalence at finer spatial scales than the data currently allow. The subnational variation revealed can be integrated into planning to ensure responsiveness to the spatial features of the epidemic. The Bayesian geostatistical approach is a promising strategy for integrating HIV data to generate robust local estimates

Application of functional genomics to primate endometrium: insights into biological processes

Endometrium is a dynamic tissue that responds on a cyclic basis to circulating levels of the ovarian-derived steroid hormones, estradiol and progesterone. Functional genomics has enabled a global approach to understanding gene regulation in whole endometrial tissue in the setting of a changing hormonal milieu. The proliferative phase of the cycle, under the influence of estradiol, has a preponderance of genes involved in DNA synthesis and cell cycle regulation. Interestingly, genes encoding ion channels and cell adhesion, as well as angiogenic factors, are also highly regulated in this phase of the cycle. After the LH surge, different gene expression profiles are uniquely observed in the early secretory, mid-secretory (window of implantation), and late secretory phases. The early secretory phase is notable for up-regulation of multiple genes and gene families involved in cellular metabolism, steroid hormone metabolism, as well as some secreted glycoproteins. The mid-secretory phase is characterized by multiple biological processes, including up-regulation of genes encoding secreted glycoproteins, immune response genes with a focus on innate immunity, and genes involved in detoxification mechanisms. In the late secretory phase, as the tissue prepares for desquamation, there is a marked up-regulation of an inflammatory response, along with matrix degrading enzymes, and genes involved in hemostasis, among others. This monograph reviews hormonal regulation of gene expression in this tissue and the molecular events occurring therein throughout the cycle derived from functional genomics analysis. It also highlights challenges encountered in using human endometrial tissue in translational research in this context

The nonadaptive nature of the H1N1 2009 Swine Flu pandemic contrasts with the adaptive facilitation of transmission to a new host

<p>Abstract</p> <p>Background</p> <p>The emergence of the 2009 H1N1 Influenza pandemic followed a multiple reassortment event from viruses originally circulating in swines and humans, but the adaptive nature of this emergence is poorly understood.</p> <p>Results</p> <p>Here we base our analysis on 1180 complete genomes of H1N1 viruses sampled in North America between 2000 and 2010 in swine and human hosts. We show that while transmission to a human host might require an adaptive phase in the HA and NA antigens, the emergence of the 2009 pandemic was essentially nonadaptive. A more detailed analysis of the NA protein shows that the 2009 pandemic sequence is characterized by novel epitopes and by a particular substitution in loop 150, which is responsible for a nonadaptive structural change tightly associated with the emergence of the pandemic.</p> <p>Conclusions</p> <p>Because this substitution was not present in the 1918 H1N1 pandemic virus, we posit that the emergence of pandemics is due to epistatic interactions between sites distributed over different segments. Altogether, our results are consistent with population dynamics models that highlight the epistatic and nonadaptive rise of novel epitopes in viral populations, followed by their demise when the resulting virus is too virulent.</p

Celecoxib and acetylbritannilactone interact synergistically to suppress breast cancer cell growth via COX-2-dependent and -independent mechanisms

The use of celecoxib is associated with a significant decrease in breast cancer risk. However, the long-term use of high-dose celecoxib might be limited owing to cardiovascular side effects. In this study, we found that acetylbritannilactone (ABL), extract from a Chinese medicinal herb, could reduce celecoxib dose and potentiate the growth-inhibitory effect in breast cancer cells. ABL enhanced the apoptotic effect of celecoxib in COX-2-expressing cells, but had little effect in COX-2-negative cells. The apoptosis induced by the combination treatment disappeared when COX-2 was knocked down, whereas the lack of apoptotic effects in COX-2-negative cells was reversed after COX-2 transfection. However, the combination treatment induced a G0/G1 phase arrest independent of whether or not the cells expressed COX-2. The G0/G1 arrest was attributed to a decreased expression of cyclinD1, cyclinE, CDK2 and CDK6, especially the upregulation of p21. In addition, inhibition of Akt and p38 signaling pathways was required by the synergism, as the constitutively active Akt and p38 protected cells against apoptosis and cell cycle arrest induced by the combination treatment. In vivo, administration of celecoxib and ABL were more effective than the individual agents against xenograft tumor growth. Thus, our data suggested that the combinatorial approach of celecoxib and ABL might be helpful for breast cancer treatment

Dormancy within Staphylococcus epidermidis biofilms : a transcriptomic analysis by RNA-seq

The proportion of dormant bacteria within Staphylococcus epidermidis biofilms may determine its inflammatory profile. Previously, we have shown that S. epidermidis biofilms with higher proportions of dormant bacteria have reduced activation of murine macrophages. RNA-sequencing was used to identify the major transcriptomic differences between S. epidermidis biofilms with different proportions of dormant bacteria. To accomplish this goal, we used an in vitro model where magnesium allowed modulation of the proportion of dormant bacteria within S. epidermidis biofilms. Significant differences were found in the expression of 147 genes. A detailed analysis of the results was performed based on direct and functional gene interactions. Biological processes among the differentially expressed genes were mainly related to oxidation-reduction processes and acetyl-CoA metabolic processes. Gene set enrichment revealed that the translation process is related to the proportion of dormant bacteria. Transcription of mRNAs involved in oxidation-reduction processes was associated with higher proportions of dormant bacteria within S. epidermidis biofilm. Moreover, the pH of the culture medium did not change after the addition of magnesium, and genes related to magnesium transport did not seem to impact entrance of bacterial cells into dormancy.The authors thank Stephen Lorry at Harvard Medical School for providing CLC Genomics software. This work was funded by Fundacao para a Ciencia e a Tecnologia (FCT) and COMPETE grants PTDC/BIA-MIC/113450/2009, FCOMP-01-0124-FEDER-014309, FCOMP-01-0124-FEDER-022718 (FCT PEst-C/SAU/LA0002/2011), QOPNA research unit (project PEst-C/QUI/UI0062/2011), and CENTRO-07-ST24-FEDER-002034. The following authors had an individual FCT fellowship: VC (SFRH/BD/78235/2011) and AF (2SFRH/BD/62359/2009)