Effects of Process Variables and Size Scale on Solidification Microstructure in Laser-Based Solid Freeform Fabrication of Ti-6Al-4V

Mechanical Engineerin

Novel pharmacological actions of Trequinsin Hydrochloride improve human sperm cell motility and function

Background and purposeAsthenozoospermia is a leading cause of male infertility, but the development of pharmaceuticals to improve sperm motility has been hindered by the lack of effective screening platforms and knowledge of suitable molecular targets. We have demonstrated that a high throughput screening (HTS) strategy in conjunction with established in vitro tests can identify and characterise the action of compounds that improve sperm motility. The study aimed to apply HTS to identify new compounds from a novel small molecule library that increase intracellular calcium, [Ca2+]I, promote human sperm cell motility and systemically determine the mechanism of action. Experimental approach A validated HTS fluorometric [Ca2+]i assay was used to screen an in-house library of compounds. Trequinsin hydrochloride (a phosphodiesterase 3 inhibitor) was selected for detailed molecular (plate reader assays, electrophysiology and cyclic nucleotide measurement) and functional (motility and acrosome reaction) testing in sperm from healthy volunteer donors and, where possible, patients.   Key resultsThe fluorometric analysis identified Trequinsin as an efficacious agonist of [Ca2+]i, although less potent than progesterone (P4). Functionally, Trequinsin significantly increased cell hyperactivation and penetration into viscous medium in all donor sperm samples and cell hyperactivation in 22/25 (88%) patient sperm samples. The Trequinsin-induced [Ca2+]i response was cross-desensitised consistently by prostaglandin E1 but not with P4. Whole-cell patch clamp electrophysiology confirmed that Trequinsin activates CatSper and partially inhibits potassium channel activity. Trequinsin also increases intracellular cGMP.   Conclusion and Implications Trequinsin exhibits a novel pharmacological profile in human sperm and may be a suitable lead compound for the development of new pharmaceuticals to improve patient sperm function and fertilisation potential

Prediction of Microstructure in Laser Deposition of Titanium Alloys

Laser deposition of titanium alloys is under consideration for aerospace applications, and offers significant increases in efficiency and flexibility compared to conventional manufacturing methods. However, its ultimate success will depend on the ability to predict and control the microstructure and resulting mechanical properties of the deposit. In this study, both 2-D continuum finite element modeling and 3-D cellular automaton finite element modeling of a thinwall geometry are used to investigate the effects of deposition process variables on microstructure in laser deposited Ti-6Al-4V. Numerical results for cooling rate and thermal gradient obtained from the 2-D models are used to provide insight into grain size and morphology, while the 3-D cellular automaton models are used to provide direct predictions of deposited microstructure. The numerical model predictions are subsequently compared with observed microstructures in LENSTM deposited Ti-6Al-4V.This work was supported by the Joint AFRL/DAGSI Research Program, project number ML-WSU-01-11, as well as by a grant from Wright State University and the Ohio Board of Regents.Mechanical Engineerin

Making meaningful musical experiences accessible using the iPad

In this paper we report on our experiences using ubiquitous computing devices to introduce music-based creative activities into an Australian school. The use of music applications on mobile tablet computers (iPads) made these activities accessible to students with a limited range of prior musical background and in a general purpose classroom setting. The activities were designed to be meaningful and contribute toward personalresilience in the students. We describe the approach to meeting these objectives and discuss results of the project. The paper includes an overview of the ongoing project including its aims, objectives and utilisation of mobile technologies and software with generative and networkable capabilities. Two theoretical frameworks inform the research design; the meaningful engagement matrix and personal resilience. We describe these frameworks and how they inform the activity planning. We report on the activities undertaken to date and share results from questionnaires, interviews, musical outcomes, and observation

The effect of 14 weeks of vitamin D3 supplementation on antimicrobial peptides and proteins in athletes

Heavy training is associated with increased respiratory infection risk and antimicrobial proteins are important in defence against oral and respiratory tract infections. We examined the effect of 14 weeks of vitamin D3 supplementation (5000 IU/day) on the resting plasma cathelicidin concentration and the salivary secretion rates of secretory immunoglobulin A (SIgA), cathelicidin, lactoferrin and lysozyme in athletes during a winter training period. Blood and saliva were obtained at the start of the study from 39 healthy men who were randomly allocated to vitamin D3 supplement or placebo. Blood samples were also collected at the end of the study; saliva samples were collected after 7 and 14 weeks. Plasma total 25(OH)D concentration increased by 130% in the vitamin D3 group and decreased by 43% in the placebo group (both P=0.001). The percentage change of plasma cathelicidin concentration in the vitamin D3 group was higher than in the placebo group (P=0.025). Only in the vitamin D3 group, the saliva SIgA and cathelicidin secretion rates increased over time (both P=0.03). A daily 5000 IU vitamin D3 supplement has a beneficial effect in up-regulating the expression of SIgA and cathelicidin in athletes during a winter training period which could improve resistance to respiratory infections

A Photometric System for Detection of Water and Methane Ices on Kuiper Belt Objects

We present a new near-infrared photometric system for detection of water ice and methane ice in the solar system. The system consists of two medium-band filters in the K-band region of the near-infrared, which are sensitive to water ice and methane ice, plus continuum observations in the J-band and Y-band. The primary purpose of this system is to distinguish between three basic types of Kuiper Belt Objects (KBOs) --- those rich in water ice, those rich in methane ice, and those with little absorbance. In this work, we present proof-of-concept observations of 51 KBOs using our filter system, 21 of which have never been observed in the near-IR spectroscopically. We show that our custom photometric system is consistent with previous spectroscopic observations while reducing telescope observing time by a factor of 3. We use our filters to identify Haumea collisional family members, which are thought to be collisional remnants of a much larger body and are characterized by large fractions of water ice on their surfaces. We add 2009 YE7 to the Haumea collisional family based on our water ice band observations(J-H2O = -1.03 +/- 0.27) which indicate a high amount of water ice absorption, our calculated proper orbital elements, and the neutral optical colors we measured, V-R = 0.38 +/- 0.04, which are all consistent with the rest of the Haumea family. We identify several objects dynamically similar to Haumea as being distinct from the Haumea family as they do not have water ice on their surfaces. In addition, we find that only the largest KBOs have methane ice, and we find that Haumea itself has significantly less water ice absorption than the smaller Haumea family members. We find no evidence for other families in the Kuiper Belt.Comment: 38 pages, 7 figure

Kuiper Belt Object Occultations: Expected Rates, False Positives, and Survey Design

A novel method of generating artificial scintillation noise is developed and used to evaluate occultation rates and false positive rates for surveys probing the Kuiper Belt with the method of serendipitous stellar occultations. A thorough examination of survey design shows that: (1) diffraction-dominated occultations are critically (Nyquist) sampled at a rate of 2 Fsu^{-1}, corresponding to 40 s^{-1} for objects at 40 AU, (2) occultation detection rates are maximized when targets are observed at solar opposition, (3) Main Belt Asteroids will produce occultations lightcurves identical to those of Kuiper Belt Objects if target stars are observed at solar elongations of: 116 deg < epsilon < 125 deg, or 131 deg < epsilon < 141 deg, and (4) genuine KBO occultations are likely to be so rare that a detection threshold of >7-8 sigma should be adopted to ensure that viable candidate events can be disentangled from false positives.Comment: Accepted AJ, 12 pages, 12 figure

CirC: Compiler infrastructure for proof systems, software verification, and more

Cryptographic tools like proof systems, multi-party computation, and fully homomorphic encryption are usually applied to computations expressed as systems of arithmetic constraints. In practice, this means that these applications rely on compilers from high-level programming languages (like C) to such constraints. This compilation task is challenging, but not entirely new: the software verification community has a rich literature on compiling programs to logical constraints (like SAT or SMT). In this work, we show that building shared compiler infrastructure for compiling to constraint representations is possible, because these representations share a common abstraction: stateless, non-uniform, non-deterministic computations that we call existentially quantified circuits, or EQCs. Moreover, we show that this shared infrastructure is useful, because it allows compilers for proof systems to benefit from decades of work on constraint compilation techniques for software verification. To make our approach concrete we create CirC, an infrastructure for building compilers to EQCs. CirC makes it easy to compile to new EQCs: we build support for three, R1CS (used for proof systems), SMT (used for verification and bug-finding), and ILP (used for optimization), in ≈2000 LOC. It\u27s also easy to extend CirC to support new source languages: we build a feature-complete compiler for a cryptographic language in one week and ≈900 LOC, whereas the reference compiler for the same language took years to write, comprises ≈24000 LOC, and produces worse-performing output than our compiler. Finally, CirC enables novel applications that combine multiple EQCs. For example, we build the first pipeline that (1) automatically identifies bugs in programs, then (2) automatically constructs cryptographic proofs of the bugs\u27 existence

Inference for bounded parameters

The estimation of signal frequency count in the presence of background noise has had much discussion in the recent physics literature, and Mandelkern [1] brings the central issues to the statistical community, leading in turn to extensive discussion by statisticians. The primary focus however in [1] and the accompanying discussion is on the construction of a confidence interval. We argue that the likelihood function and $p$-value function provide a comprehensive presentation of the information available from the model and the data. This is illustrated for Gaussian and Poisson models with lower bounds for the mean parameter

Applying laboratory thermal desorption data in an interstellar context: sublimation of methanol thin films

Methods by which experimental measurements of thermal desorption can be applied in astrophysical environments have been developed, using the sublimation of solid methanol as an example. The temperature programmed desorption of methanol from graphitic, amorphous silica and polycrystalline gold substrates was compared, with the kinetic parameters of desorption extracted by either a leading edge analysis or by fitting using a stochastic integration method. At low coverages, the desorption shows a substrate-dependent fractional order. However, at higher coverages methanol desorption is zeroth order with kinetic parameters independent of substrate. Using a kinetic model based on the stochastic integration analyses, desorption under astrophysically relevant conditions can be simulated. We find that the chemical and morphological nature of the substrate has relatively little impact on the desorption temperature of solid methanol, and that the substrate independent zeroth-order kinetics can provide a satisfactory model for desorption in astrophysical environments. Uncertainties in the heating rate and the distribution of grain sizes will have the largest influence on the range of desorption temperature. These conclusions are likely to be generally applicable to all species in dust grain ice mantles