On the Interface Between LENS® Deposited Stainless Steel 304L Repair Geometry and Cast or Machined Components

Laser Engineered Net Shaping™ (LENS®) is being evaluated for use as a metal component repair/modification process. A component of the evaluation is to better understand the characteristics of the interface between LENS deposited material and the substrate on which it is deposited. A processing and metallurgical evaluation was made on LENS processed material fabricated for component qualification tests. A process parameter evaluation was used to determine optimum build parameters and these parameters were used in the fabrication of tensile test specimens to study the characteristics of the interface between LENS deposited material and several types of substrates. Analyses of the interface included mechanical properties, microstructure, and metallurgical integrity. Test samples were determined for a variety of geometric configurations associated with interfaces between LENS deposited material and both wrought base material or previously deposited LENS material. Thirteen different interface configurations were fabricated for evaluation representing a spectrum of deposition conditions from complete part build, to hybrid substrate-LENS builds, to repair builds for damaged or re-designed housings. Good mechanical properties and full density were observed for all configurations. When tested to failure, fracture occurred by ductile microvoid coalescence. The repair and hybrid interfaces showed the same metallurgical integrity as, and had properties similar to, monolithic LENS deposits.Mechanical Engineerin

Thermal Behavior in the Lens Process

Direct laser metal deposition processing is a promising manufacturing technology which could significantly impact the length oftime between initial concept and finished part. For adoption ofthis technology in the manufacturing environment, further understanding is required to ensure robust components with appropriate properties are routinelyfabricated. This requires a complete understanding ofthe thermal history.during part fabrication and control ofthis behavior. This paper will describe our research to understand the thermal behavior for the Laser Engineered Net Shaping (LENS) process!, where a component is fabricated by focusing a laser beam onto a substrate to create a molten pool in which powder particles are simultaneously injected to build each layer. The substrate is moved beneath the l~ser beam to deposit a thin cross section, thereby creating the desired geometry for each layer. After deposition of each layer, the powder delivery nozzle and focusing lens assembly is incremented in the positive Z-direction, thereby building a three dimensional component layer additively. It is important to control the thermal behavior to reproducibly fabricate parts. The ultimate intent is to monitor the thermal signatures and to incorporate sensors and feedback algorithms to control part fabrication. With appropriate control, the geometric properties (accuracy, surface finish, low warpage) as well as the materials' properties (e.g. strength, ductility) of a component can be dialed into the part through the fabrication parameters. Thermal monitoring techniques will be described, and their particular benefits highlighted. Preliminary details in correlating thermal behavior with processing results will be discussed.Mechanical Engineerin

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Targeting deficiencies in the TLR5 mediated vaginal response to treat female recurrent urinary tract infection

Abstract The identification of the host defence peptides as target effectors in the innate defence of the uro-genital tract creates new translational possibilities for immunomodulatory therapies, specifically vaginal therapies to treat women suffering from rUTI, particularly those carrying the TLR5_C1174T SNP. Urinary tract infections (UTIs) are a microbial disease reported worldwide. Women are particularly susceptible with many suffering debilitating recurrent (r) infections. Treatment is by antibiotics, but such therapy is linked to antibiotic resistance and re-infection. This study explored the innate protective mechanisms of the urogenital tract with the aim of boosting such defences therapeutically. Modelling UTIs in vitro, human vaginal and bladder epithelial cells were challenged with uropathogenic Escherichia coli (CFT073) and microbial PAMPs including flagellin, LPS and peptidoglycan. Flagellin functioning via the TLR5/NFκB pathway was identified as the key UPEC virulence factor causing a significant increase (P < 0.05) in the production of the host-defence peptide (HDP), BD2. BD2-depleted urine samples from bladder infected mice supported increased UPEC growth, strengthening the significance of the HDPs in protecting the urogenital tissues from infection. Clinically, vaginal-douche BD2 concentrations were reduced (p < 0.05) in women suffering rUTIs, compared to age-matched healthy controls with concentrations further decreased (p < 0.05) in a TLR5392Stop SNP rUTI subgroup. Topical vaginal estrogen treatment increased (p < 0.001) BD2 concentrations in all women, including those carrying the SNP. These data identify therapeutic and antibiotic sparing roles for vaginal immunomodulatory agents that specifically target HDP induction, facilitate bacterial killing and disrupt the UPEC infection cycle

LTF and DEFB1 polymorphisms are associated with susceptibility toward chronic periodontitis development

Objectives: Chronic periodontitis is a common pathological condition that affects the supporting tissue of the teeth, leading to progressive alveolar bone destruction and teeth loss. The disease is caused by bacteria and derives from an altered host immune and inflammatory response, also involving different factors such as the oral hygiene, smoking, and genetic background. The innate immune response, the first line of host defense, could also play an important role in the susceptibility to chronic periodontitis. In this study, we evaluated the possible association between periodontal disease and seven genetic variations within DEFB1 and LTF genes, encoding for \u3b2-defensins 1 and lactoferrin (two members of oral innate immune system), in an Italian isolated population. Subjects and Methods: DEFB1 5\u2032UTR g. -52G>A (rs1799946), g. -44C>G (rs1800972), g. -20G>A (rs11362), 3\u2032UTR c*5G>A (rs1047031), c*87A>G (rs1800971), LTF p.Ala29Thr (rs1126477), and p.Lys47Arg (rs1126478) single nucleotide polymor- phisms (SNPs) were analyzed in 155 healthy individuals and 439 chronic periodontitis patients from North-East Italy. Results: Significant associations were found between periodontitis and g. -20G>A (rs11362) and g. -44C>G (rs1800972) SNPs in DEFB1 gene as well as p.Ala29Thr (rs1126477) and p.Lys47Arg (rs1126478) SNPs in LTF gene. Discussion: Our results suggest the involvement of DEFB1 and LTF genetic variations in the susceptibility toward development of periodontitis

2D Cu-TCNQ Metal-Organic Networks Induced by Surface Alloying

We have studied the self-assembly of 7,7,8,8-tetracyanoquinodimethane molecules on the (3√2 × √2)R45° reconstruction of the SnCu(001) surface alloy by means of X-ray photoemission spectroscopy, scanning tunneling microscopy, near-edge X-ray absorption fine structure spectroscopy, and density functional theory calculations. Our results show that surface alloying strongly attenuates the chemical interaction of the molecule with the surface, but it does not inhibit the charge transfer from the substrate to the molecules. The assembly mechanism of the molecules is completely modified with respect to the bare Cu(001) surface. We show that, on the SnCu(100) surface alloy, the strong CN-Cu interaction drives the formation of different coordination structures with native Cu adatoms. We found that the flexible coordination chemistry of Cu allows the formation of three different stable phases, each one with the Cu ions in a different coordination geometry (coordinations 4, 3, and 2). Moreover, we show that both the formation of lateral H bonds between adjacent molecules and the interaction of the Cu ion with the substrate play determinant roles in the stabilization of the structures.Fil: Fuhr, Javier Daniel. Universidad Nacional de Cuyo; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Robino, L.I.. Universidad Nacional de Cuyo; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; ArgentinaFil: Rodríguez, L.M.. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Verdini, A.. No especifíca;Fil: Floreano, L.. No especifíca;Fil: Ascolani, Hugo del Lujan. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología - Nodo Bariloche | Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología - Nodo Bariloche; ArgentinaFil: Gayone, Julio Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología - Nodo Bariloche | Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología - Nodo Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentin

Rare coding variants and X-linked loci associated with age at menarche

More than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only similar to 3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency proteincoding variants and X-chromosome variants. Five missense/nonsense variants (in ALMS1/LAMB2/TNRC6A/TACR3/PRKAG1) are associated with age at menarche (minor allele frequencies 0.08-4.6%; effect sizes 0.08-1.25 years per allele; P&lt;5 x 10(-8)). In addition, we identify common X-chromosome loci at IGSF1 (rs762080, P = 9.4 x 10(-13)) and FAAH2 (rs5914101, P = 4.9 x 10(-10)). Highlighted genes implicate cellular energy homeostasis, post-transcriptional gene silencing and fatty-acid amide signalling. A frequently reported mutation in TACR3 for idiopathic hypogonatrophic hypogonadism (p.W275X) is associated with 1.25-year-later menarche (P = 2.8 x 10(-11)), illustrating the utility of population studies to estimate the penetrance of reportedly pathogenic mutations. Collectively, these novel variants explain similar to 0.5% variance, indicating that these overlooked sources of variation do not substantially explain the &apos;missing heritability&apos; of this complex trait