Internal visual workmanship standard for microelectronic devices /NASA STD XX-2/ and training manual, volume 2

Internal visual workmanship standards for monolithic microelectronic devices - training manua

Mammalian Sperm Motility: Observation and Theory

Mammalian spermatozoa motility is a subject of growing importance because of rising human infertility and the possibility of improving animal breeding. We highlight opportunities for fluid and continuum dynamics to provide novel insights concerning the mechanics of these specialized cells, especially during their remarkable journey to the egg. The biological structure of the motile sperm appendage, the flagellum, is described and placed in the context of the mechanics underlying the migration of mammalian sperm through the numerous environments of the female reproductive tract. This process demands certain specific changes to flagellar movement and motility for which further mechanical insight would be valuable, although this requires improved modeling capabilities, particularly to increase our understanding of sperm progression in vivo. We summarize current theoretical studies, highlighting the synergistic combination of imaging and theory in exploring sperm motility, and discuss the challenges for future observational and theoretical studies in understanding the underlying mechanics.\ud Acronyms and Definitions\ud Acrosome: the cap of the sperm head containing enzymes allowing penetration of the zona pellucida via the acrosome reaction\ud Adenosine triphosphate (ATP): the currency unit of chemical energy transfer in living cells\ud Axoneme: a phylogenetically conserved structure within the eukaryotic flagellum consisting of a ring of nine microtubule doublets and a central pair, frequently referred to as 9 + 2\ud Bending moment density: the moment per unit length associated with flagellar bending; it can be divided into a hydrodynamic moment, an elastic moment (from the flagellar bending stiffness), an active moment (generated by dyneins exerting forces between adjacent microtubule doublets), and a passive moment resisting shear\ud Capacitation: the physiological state of a sperm required for fertilization, which is accompanied by the motility patterns associated with hyperactivation, characterized in saline by high-amplitude asymmetric beating\ud Central pair: a pair of microtubules along the length of the axoneme, symmetrically and slightly offset from the axoneme centerline\ud Cumulus oophorus: the outer vestment of the mammalian egg consisting of hundreds of cells radiating out from the egg embedded within a non-Newtonian hyaluronic acid gel\ud Dynein: a molecular motor within the axoneme, attached between adjacent microtubule doublets, that exerts a shearing force to induce axonemal bending\ud Flagellum: a motile cellular appendage that drives the swimming of sperm and other cells; this article focuses on the eukaryotic flagellum\ud Microtubule doublet: a pair of proteinaceous filament structures running the length of the axoneme; dyneins drive their bending, which induces flagellar motion\ud Mid-piece: the region of a sperm flagellum with a mitochondrial sheath, where ATP is generated\ud Oocyte: the egg\ud Outer dense fibers and fibrous sheath: accessory structures reinforcing the mammalian sperm flagellum; the combined axoneme and accessory structures are referred to as 9+9+2\ud Resistive-force theory: an approximation for the local drag of a slender filament element in Stokes flow (or a viscoelastic generalization thereof)\ud Rheotaxis: directed motility in response to the influence of fluid flow\ud Shear: in the context of the flagellum, the relative movement of adjacent microtubule doublets\ud Slender-body theory: an improved approximation for the local drag on a slender filament element in Stokes flow (or a viscoelastic generalization thereof)\ud Zona pellucida: a tough glycoprotein coat between the human egg and the cumulus oophorus, which a sperm must penetrate for successful fertilizatio

Incorporating spatial correlations into multispecies mean-field models

In biology, we frequently observe different species existing within the same environment. For example, there are many cell types in a tumour, or different animal species may occupy a given habitat. In modeling interactions between such species, we often make use of the mean-field approximation, whereby spatial correlations between the locations of individuals are neglected. Whilst this approximation holds in certain situations, this is not always the case, and care must be taken to ensure the mean-field approximation is only used in appropriate settings. In circumstances where the mean-field approximation is unsuitable, we need to include information on the spatial distributions of individuals, which is not a simple task. In this paper, we provide a method that overcomes many of the failures of the mean-field approximation for an on-lattice volume-excluding birth-death-movement process with multiple species. We explicitly take into account spatial information on the distribution of individuals by including partial differential equation descriptions of lattice site occupancy correlations. We demonstrate how to derive these equations for the multispecies case and show results specific to a two-species problem. We compare averaged discrete results to both the mean-field approximation and our improved method, which incorporates spatial correlations. We note that the mean-field approximation fails dramatically in some cases, predicting very different behavior from that seen upon averaging multiple realizations of the discrete system. In contrast, our improved method provides excellent agreement with the averaged discrete behavior in all cases, thus providing a more reliable modeling framework. Furthermore, our method is tractable as the resulting partial differential equations can be solved efficiently using standard numerical techniques

Functional Imaging of the Outer Retinal Complex using High Fidelity Imaging Retinal Densitometry

We describe a new technique, high fidelity Imaging Retinal Densitometry (IRD), which probes the functional integrity of the outer retinal complex. We demonstrate the ability of the technique to map visual pigment optical density and synthesis rates in eyes with and without macular disease. A multispectral retinal imaging device obtained precise measurements of retinal reflectance over space and time. Data obtained from healthy controls and 5 patients with intermediate AMD, before and after photopigment bleaching, were used to quantify visual pigment metrics. Heat maps were plotted to summarise the topography of rod and cone pigment kinetics and descriptive statistics conducted to highlight differences between those with and without AMD. Rod and cone visual pigment synthesis rates in those with AMD (v = 0.043 SD 0.019 min-1 and v = 0.119 SD 0.046 min-1, respectively) were approximately half those observed in healthy controls (v = 0.079 SD 0.024 min-1 for rods and v = 0.206 SD 0.069 min-1 for cones). By mapping visual pigment kinetics across the central retina, high fidelity IRD provides a unique insight into outer retinal complex function. This new technique will improve the phenotypic characterisation, diagnosis and treatment monitoring of various ocular pathologies, including AMD

Sustaining Educational Reforms in Introductory Physics

While it is well known which curricular practices can improve student performance on measures of conceptual understanding, the sustaining of these practices and the role of faculty members in implementing these practices are less well understood. We present a study of the hand-off of Tutorials in Introductory Physics from initial adopters to other instructors at the University of Colorado, including traditional faculty not involved in physics education research. The study examines the impact of implementation of Tutorials on student conceptual learning across eight first-semester, and seven second-semester courses, for fifteen faculty over twelve semesters, and includes roughly 4000 students. It is possible to demonstrate consistently high, and statistically indistinguishable, student learning gains for different faculty members; however, such results are not the norm, and appear to rely on a variety of factors. Student performance varies by faculty background - faculty involved in, or informed by physics education research, consistently post higher student learning gains than less-informed faculty. Student performance in these courses also varies by curricula used - all semesters in which the research-based Tutorials and Learning Assistants are used have higher student learning gains than those semesters that rely on non-research based materials and do not employ Learning Assistants.Comment: 21 pages, 4 figures, and other essential inf

Nonlinear instability in flagellar dynamics: a notel modulation mechanism in sperm migration

Throughout biology, cells and organisms use flagella and cilia to propel fluid and achieve motility. The beating of these organelles, and the corresponding ability to sense, respond to and modulate this beat is central to many processes in health and disease. While the mechanics of flagellum–fluid interaction has been the subject of extensive mathematical studies, these models have been restricted to being geometrically linear or weakly nonlinear, despite the high curvatures observed physiologically. We study the effect of geometrical nonlinearity, focusing on the spermatozoon flagellum. For a wide range of physiologically relevant parameters, the nonlinear model predicts that flagellar compression by the internal forces initiates an effective buckling behaviour, leading to a symmetry-breaking bifurcation that causes profound and complicated changes in the waveform and swimming trajectory, as well as the breakdown of the linear theory. The emergent waveform also induces curved swimming in an otherwise symmetric system, with the swimming trajectory being sensitive to head shape—no signalling or asymmetric forces are required. We conclude that nonlinear models are essential in understanding the flagellar waveform in migratory human sperm; these models will also be invaluable in understanding motile flagella and cilia in other systems

Human sperm accumulation near surfaces: a simulation study

A hybrid boundary integral/slender body algorithm for modelling flagellar cell motility is presented. The algorithm uses the boundary element method to represent the ‘wedge-shaped’ head of the human sperm cell and a slender body theory representation of the flagellum. The head morphology is specified carefully due to its significant effect on the force and torque balance and hence movement of the free-swimming cell. The technique is used to investigate the mechanisms for the accumulation of human spermatozoa near surfaces. Sperm swimming in an infinite fluid, and near a plane boundary, with prescribed planar and three-dimensional flagellar waveforms are simulated. Both planar and ‘elliptical helicoid’ beating cells are predicted to accumulate at distances of approximately 8.5–22 μm from surfaces, for flagellar beating with angular wavenumber of 3π to 4π. Planar beating cells with wavenumber of approximately 2.4π or greater are predicted to accumulate at a finite distance, while cells with wavenumber of approximately 2π or less are predicted to escape from the surface, likely due to the breakdown of the stable swimming configuration. In the stable swimming trajectory the cell has a small angle of inclination away from the surface, no greater than approximately 0.5°. The trapping effect need not depend on specialized non-planar components of the flagellar beat but rather is a consequence of force and torque balance and the physical effect of the image systems in a no-slip plane boundary. The effect is relatively weak, so that a cell initially one body length from the surface and inclined at an angle of 4°–6° towards the surface will not be trapped but will rather be deflected from the surface. Cells performing rolling motility, where the flagellum sweeps out a ‘conical envelope’, are predicted to align with the surface provided that they approach with sufficiently steep angle. However simulation of cells swimming against a surface in such a configuration is not possible in the present framework. Simulated human sperm cells performing a planar beat with inclination between the beat plane and the plane-of-flattening of the head were not predicted to glide along surfaces, as has been observed in mouse sperm. Instead, cells initially with the head approximately 1.5–3 μm from the surface were predicted to turn away and escape. The simulation model was also used to examine rolling motility due to elliptical helicoid flagellar beating. The head was found to rotate by approximately 240° over one beat cycle and due to the time-varying torques associated with the flagellar beat was found to exhibit ‘looping’ as has been observed in cells swimming against coverslips

Metabolome-Informed Microbiome Analysis Refines Metadata Classifications and Reveals Unexpected Medication Transfer in Captive Cheetahs.

Even high-quality collection and reporting of study metadata in microbiome studies can lead to various forms of inadvertently missing or mischaracterized information that can alter the interpretation or outcome of the studies, especially with nonmodel organisms. Metabolomic profiling of fecal microbiome samples can provide empirical insight into unanticipated confounding factors that are not possible to obtain even from detailed care records. We illustrate this point using data from cheetahs from the San Diego Zoo Safari Park. The metabolomic characterization indicated that one cheetah had to be moved from the non-antibiotic-exposed group to the antibiotic-exposed group. The detection of the antibiotic in this second cheetah was likely due to grooming interactions with the cheetah that was administered antibiotics. Similarly, because transit time for stool is variable, fecal samples within the first few days of antibiotic prescription do not all contain detected antibiotics, and the microbiome is not yet affected. These insights significantly altered the way the samples were grouped for analysis (antibiotic versus no antibiotic) and the subsequent understanding of the effect of the antibiotics on the cheetah microbiome. Metabolomics also revealed information about numerous other medications and provided unexpected dietary insights that in turn improved our understanding of the molecular patterns on the impact on the community microbial structure. These results suggest that untargeted metabolomic data provide empirical evidence to correct records and aid in the monitoring of the health of nonmodel organisms in captivity, although we also expect that these methods may be appropriate for other social animals, such as cats.IMPORTANCE Metabolome-informed analyses can enhance omics studies by enabling the correct partitioning of samples by identifying hidden confounders inadvertently misrepresented or omitted from carefully curated metadata. We demonstrate here the utility of metabolomics in a study characterizing the microbiome associated with liver disease in cheetahs. Metabolome-informed reinterpretation of metagenome and metabolome profiles factored in an unexpected transfer of antibiotics, preventing misinterpretation of the data. Our work suggests that untargeted metabolomics can be used to verify, augment, and correct sample metadata to support improved grouping of sample data for microbiome analyses, here for nonmodel organisms in captivity. However, the techniques also suggest a path forward for correcting clinical information in microbiome studies more broadly to enable higher-precision analyses

Recent trends and advances in microbial electrochemical sensing technologies: An overview

Microbial electrochemical systems utilize the electrochemical interaction between microorganisms and electrode surfaces to convert chemical energy into electrical energy, offering a promise as technologies for wastewater treatment, bioremediation, and biofuel production. Recently, growing research attention has been devoted to the development of microbial electrochemical sensrs as biosensing platforms. Microbial electrochemical sensors are a type of microbial electrochemical technology (MET) capable of sensing through the anodic or the cathodic electroactive microorganisms and/or biofilms. Herein, we review and summarize the recent advances in the design of microbial electrochemical sensing approaches with a specific overview and discussion of anodic and cathodic microbial electrochemical sensor devices, highlighting both the advantages and disadvantages. Particular emphasis is given on the current trends and strategies in the design of low-cost, convenient, efficient, and high performing METs with different biosensing applications, including toxicity monitoring, pathogen detection, corrosion monitoring, as well as measurements of biological oxygen demand, chemical oxygen demand, and dissolved oxygen. The conclusion provides perspectives and an outlook to understand the shortcomings in the design, development status, and sensing applications of microbial electrochemical platforms. Namely, we discuss key challenges that limit the practical implementation of METs for sensing purposes and deliberate potential solutions, necessary developments, and improvements in the field

Political leadership and the politics of performance:France, Syria and the chemical weapons crisis of 2013

This article draws upon developments in UK research on political rhetoric and political performance in order to examine the incident in 2013 when French President François Hollande committed French forces to a US-led punitive strike against Syria, after the use of chemical weapons in a Damascus suburb on 21 August. The US-led retaliation did not take place. This article analyses Hollande's declaration on 27 July and his TV appearance on 15 September. His rhetoric and style are best understood as generic to the nature of the presidential office of the Fifth Republic. The article concludes by appraising how analysis of the French case contributes to the developing literature on rhetoric, celebrity and performance