LENS® and SFF: Enabling Technologies for Optimized Structures

Optimized, lightweight, high-strength structures are needed in many applications from aerospace to automotive. In pursuit of such structures, there have been proposed analytical solutions and some specialized FEA solutions for specific structures such as automobile frames. However, generalized 3D optimization methods have been unavailable for use by most designers. Moreover, in the cases where optimized structural solutions are available, they are often hollow, curving, thin wall structures that cannot be fabricated by conventional manufacturing methods. Researchers at Sandia National Laboratories and the University of Rhode Island teamed to solve these problems. The team has been pursuing two methods of optimizing models for generalized loading conditions, and also has been investigating the methods needed to fabricate these structures using Laser Engineered Net Shaping™ (LENS®) and other rapid prototyping methods. These solid freeform fabrication (SFF) methods offer the unique ability to make hollow, high aspect ratio features out of many materials. The manufacturing development required for LENS to make these complex structures has included the addition of rotational axes to Sandia’s LENS machine bringing the total to 5 controlled axes. The additional axes have required new efforts in process planning. Several of the unique structures that are only now possible through the use of SFF technology are shown as part of the discussion of this exciting new application for SFF.Mechanical Engineerin

Passive tracer reconstruction as a least-squares problem with a semi-Lagrangian constraint: An application to fish eggs and larvae

A variational, data assimilation, algorithm was developed for reconstruction of a two-dimensional, nonstationary, passive tracer field in the ocean with open boundaries and a known velocity field. The observations, spatial smoothing terms and passive tracer conservation equation were included as weak constraints. The algorithm was tested with simulated, nonstationary, pseudo-oceanographic data integrated for a 7-day period. Simulations were run to determine the robustness of the algorithm and the effect of theoretical, simulated \u27sampling events,\u27 mimicking the standard oceanographic survey. We explored the sensitivity of the reconstructed tracer fields to the distribution of the pseudo-oceanographic sampling strategy, essentially an antenna problem, and to errors in the velocity field and the observations. The algorithm was applied to observations of silver hake ( Merluccius bilinearis) eggs and larvae obtained in August 1998 on the Scotian Shelf. Finally, the evolution of fish eggs and larvae concentration was found. The corresponding mortality rate of fish eggs and larvae was determined to be 0.28 day-1, with errors of 0.03 day-1. The approach, which is quite general and could be applied to many different problems requiring minimization subject to constraints, allows for error analysis of the results

Fecundity variation in Icelandic summer-spawning herring and implications for reproductive potential

An exploration of fish fecundity aimed at estimating the reproductive potential of a stock requires comprehensive and quantitative examinations of the influencing factors. Here, Icelandic summer-spawning herring (Clupea harengus) are used to quantify potential fecundity (F P , number of eggs) and relative fecundity [RF P ¼ F P (body weight ÿ ovary weight) ÿ1 ] as functions of length (L) and weight (W ) in mature prespawning herring. Using a coupled examination of atresia (oocyte degeneration in the ovary) and the maturation stage of oocytes as characterized by size, we show that atresia has no meaningful effect on fecundity estimates if determined near the spawning time. Among prespawning herring, F P is a strong function of L or W (r 2 ¼ 0.84 in either case). Fulton's condition factor K

Measurement of the 18Ne(a,p_0)21Na reaction cross section in the burning energy region for X-ray bursts

The 18Ne(a,p)21Na reaction provides one of the main HCNO-breakout routes into the rp-process in X-ray bursts. The 18Ne(a,p_0)21Na reaction cross section has been determined for the first time in the Gamow energy region for peak temperatures T=2GK by measuring its time-reversal reaction 21Na(p,a)18Ne in inverse kinematics. The astrophysical rate for ground-state to ground-state transitions was found to be a factor of 2 lower than Hauser-Feshbach theoretical predictions. Our reduced rate will affect the physical conditions under which breakout from the HCNO cycles occurs via the 18Ne(a,p)21Na reaction.Comment: 5 pages, 3 figures, accepted for publication on Physical Review Letter

Inhibition of inflammatory changes in human myometrial cells by cell penetrating peptide and small molecule inhibitors of NFκB

Complications arising from Preterm Birth are the leading causes of neonatal death globally. Current therapeutic strategies to prevent Preterm Birth are yet to demonstrate success in terms of reducing this neonatal disease burden. Upregulation of intracellular inflammatory pathways in uterine cells, including those involving nuclear factor kappa-B (NFκB), have been causally linked to both human term and preterm labor, but the barrier presented by the cell membrane presents an obstacle to interventions aimed at dampening these inflammatory responses. Cell penetrating peptides (CPPs) are novel vectors that can traverse cell membranes without the need for recognition by cell surface receptors and offer the ability to deliver therapeutic cargo internal to cell membranes. Using a human uterine cell culture inflammatory model, this study aimed to test the effectiveness of CPP-cargo delivery to inhibit inflammatory responses, comparing this effect with a small molecule inhibitor (Sc514) that has a similar intracellular target of action within the NFκB pathway (the IKK complex). The CPP Penetratin, conjugated to rhodamine, was able to enter uterine cells within a 60 min timeframe as assessed by live confocal microscopy, this phenomena was not observed with the use of a rhodamine-conjugated inert control peptide (GC(GS)4). Penetratin CPP conjugated to an IKK-inhibitory peptide (Pen-NBD) demonstrated ability to inhibit both the IL1β-induced expression of the inflammatory protein COX2 and dampen the expression of a bespoke array of inflammatory genes. Truncation of the CPP vector rendered the CPP-cargo conjugate much less effective, demonstrating the importance of careful vector selection. The small molecule inhibitor Sc514 also demonstrated ability to inhibit COX2 protein responses and a broad down-regulatory effect on uterine cell inflammatory gene expression. These results support the further exploration of either CPP-based or small molecular treatment strategies to dampen gestational cell inflammatory responses in the context of preterm birth. The work underlines both the importance of careful selection of CPP vector-cargo combinations and basic testing over a broad time and concentration range to ensure effective responses. Further work should demonstrate the effectiveness of CPP-linked cargos to dampen alternative pathways of inflammation linked to Preterm Birth such as MAP Kinase or AP

Predictors of Caregiver Communication About Reproductive and Sexual Health and Sensitive Sex Topics

Numerous studies examining parent–teen communication about sex (PTCS) have focused on reproductive and sexual health information (i.e., pregnancy, physical development, contraception), with significantly fewer addressing communication about sensitive sex topics (i.e., sexual pleasure, masturbation). This study compares predictors of communication about reproductive and sexual health to those of sensitive sex topics with early adolescents. Participants were 465 rural caregivers and their African American youth. Positive attitudes and self-efficacy for PTCS, open communication style, and older youth age predicted caregiver reports of communication about reproductive and sexual health topics. Open communication style and self-efficacy for PTCS predicted caregiver reports of communication about sensitive sex topics. For youth, only older age and being female predicted communication about reproductive and sexual health, while only being female predicted communication about sensitive sex topics. This study may inform interventions that seek to increase PTCS by highlighting strategies for improving communication about both reproductive and sensitive sex topics

Greece in crisis: austerity, populism and the politics of blame

Within the broader debate on the Greek crisis, the theory of ‘populist democracy’ postulates that populism is fundamental to the sustenance of the Greek political system and is at the heart of Greece's endemic domestic weaknesses. This article tests this assumption empirically through the use of a sophisticated framing analysis of speeches delivered by the leaders of the five parties in the Greek parliament in the period 2009–11. The findings confirm that populism: (a) is expressed through the narratives of political actors; (b) is observed across the party system; (c) is expressed in the forms of blame-shifting and exclusivity; and (d) differs depending on position in the party system. The article contributes to the debate by testing and building on the theory of democratic populism, providing a novel way of measuring and operationalizing populism and identifying a new typology that distinguishes between mainstream and fringe populism

Hematopoietic stem cell gene therapy for brain metastases using myeloid cell-specific gene promoters

Background: Brain metastases (BrM) develop in 20-40% of cancer patients and represent an unmet clinical need. Limited access of drugs into the brain due to the blood-brain barrier is at least partially responsible for therapeutic failure, necessitating improved drug delivery systems. Methods: Green fluorescent protein (GFP)-transduced murine and non-transduced human hematopoietic stem cells (HSCs) were administered into mice (n = 10 and 3). The HSC progeny in mouse BrM and in patient-derived BrM tissue (n = 6) was characterized by flow cytometry and immunofluorescence. Promoters driving gene expression, specifically within the BrM-infiltrating HSC progeny, were identified through differential gene expression analysis and subsequent validation of a series of promoter-GFP-reporter constructs in mice (n = 5). One of the promoters was used to deliver TNF-related apoptosis-inducing ligand (TRAIL) to BrM in mice (n = 17/21 for TRAIL versus control group). Results: HSC progeny (consisting mostly of macrophages) efficiently homed to macrometastases (37.6% [SD = 7.2%] of all infiltrating cells for murine HSC progeny; 27.9% [SD = 4.9%] of infiltrating CD45+ hematopoietic cells for human HSC progeny) and micrometastases in mice (19.3-53.3% of all macrophages for murine HSCs). Macrophages were also abundant in patient-derived BrM tissue (8.8%, SD = 7.8%). Collectively, this provided a rationale to optimize the delivery of gene therapy to BrM within myeloid cells. MMP14 promoter emerged as the strongest promoter construct capable of limiting gene expression to BrM-infiltrating myeloid cells in mice TRAIL delivered under MMP14 promoter statistically significantly prolonged survival in mice (19.0 [SD = 3.4] versus 15.0 [SD = 2.0] days for TRAIL versus control group; two-sided p = 0.006), demonstrating therapeutic and translational potential of our approach. Conclusions: Our study establishes HSC gene therapy using a myeloid cell-specific promoter as a new strategy to target BrM. This approach, with strong translational value, has potential to overcome the blood-brain barrier, target micrometastases, and control multifocal lesions