Background-Inhibitory control or regulatory difficulties have been explored in major depressive disorder (MDD) but typically in the context of affectively salient information. Inhibitory control is addressed specifically by using a task devoid of affectively-laden stimuli, to disentangle the effects of altered affect and altered inhibitory processes in MDD.
The electron microscope (EM) provides exquisitely detailed information about structural arrangements of matter through its high native resolution, contrast and wide variety of available signals. This enables broad application across numerous fields, including physics, materials science, medicine, and biology. In some fields, especially biology, there is increasing need for quantification at smaller length scales and simultaneous demand for structural data from larger volumes. While new digital automated tools make it possible in some cases to investigate most of a 3 mm transmission EM sample, they remain ineffective for significantly larger volumes, for example whole-genome patterned DNA [1], neural circuits [2], silicon wafers, and histological arrays. This is due in large part to operating costmeasured in both dollars and hours-arising from extensive sample preparation / handling and dependence on skilled operators [3]. For this reason, applicability of high-resolution EM beyond laboratory research is mostly limited to niche areas (for example, nephrology and ciliary dyskinesia in clinical medicine). Further, researchers and clinicians increasingly turn to methods that take ensemble measurements such as low-cost genetic sequencing and mass spectrometry despite the richness and spatial precision of information available from EM. Published EM results are generally cherry-picked from dozens to hundreds of images of painstakingly-prepared samples taken over weeks to months. What if EM's were optimized such that every image coming from the machine was scientifically significant and "publication-ready"? High throughput requires new ways of looking at EM imaging. The EM imaging process is a packet system, and throughput can be defined as the amount of useful data retrieved from the system during the packet divided by the time taken to do so. To be an honest throughput number, the time taken should include all aspects of the experiment, including sample preparation and loading, machine setup time (and any downtime experienced), as well as the time spent in the microscope itself. Generally the time spent actually examining the sample in the microscope is tiny compared to these other steps, and the time spent acquiring scientifically significant data is an even smaller fraction. Microscopy needs to significantly change to meet the throughput needs of modern biology: high resolution imaging may transition from a seldom-used relatively small part of a lengthy process to an always-on, always available part of a long term, continuous acquisition chain lasting weeks, months or even years. In this paradigm, collecting scientifically significant images becomes the majority of the process, rather than a small part of an arduous march dominated by sample preparation, sample handling, and experiment design. For a microscope to operate efficiently in this paradigm, it needs to offer robust and reliable performance over very long timescales. Such automation has begun with scanning EM [4] and work in EM-based gene sequencing [5,6]. T...
Electron microscopy is widely regarded as a high-end laboratory science tool, where substantial resources are pooled to collect image data of exquisite quality. Electron microscopes (EM's) are uniquely able to produce detailed structural images that support discoveries from basic science to monitoring of industrial process. The strong scattering, large depth of focus, and unique blend of signals including elemental analysis are attractive in many applications. Being difficult to operate relative to many other common laboratory tools, EM's are traditionally housed in centers at universities and large research institutions where ample laboratory space, support staff, supplies, and skilled operators come together, or at industrial sites for organizations with research or quality control needs that justify the substantial cost. For those who do not have access to an on-site EM, many larger institutions and service centers accept samples sent in to be imaged, at great expense and often delay of weeks to months for complex analyses. The complexity, high cost, and significant maintenance associated with collecting EM image data has until now severely limited the fields in which EM can be realistically used [1]. This is exemplified in the number of EM instruments deployed (in the tens of thousands) to the number of deployed light microscopes (in the hundreds of millions) [2].A new, smaller, more reliable and user-friendly personal EM --the Mochii TM scanning electron microscope -has been developed by us at Voxa in Seattle, WA (Fig. 1). This low voltage microscope has features that bring accessible and on-demand EM imaging into fields and laboratories where EM was previously hindered by form factor, complexity, and cost. Among these features are small size and light weight (0.25m tall, light enough to carry in a suitcase); user-friendly native wireless tablet interface; multi-and distance-user capabilities (connection to unlimited client nodes), exceedingly low power consumption (by virtue of lowpower magnetic-electrostatic optics), and an integrated metal evaporator for easy sample preparation (only one pump-down cycle to image). We expect the cost to own and operate a Mochii TM microscope to be a fraction of the cost of typical EM's with similar imaging performance due to its low power consumption, simple design, and commoditized user-replaceable consumables.The improved tablet interface and reduced cost compared to existing benchtop systems significantly lowers the barrier of entry to EM imaging in fields where money, space, and/or operational expertise were limited. Learners and scientists in schools and community science centers can begin using EM imaging to explore scientific phenomena at below light-diffraction-limit resolutions for the first time (Fig. 2). We also expect that smaller research labs and new labs or startup companies can easily begin accessing image data without the enormous investment that would be required for a typical EM.Novel miniaturization features also open up access to EM imaging in scientif...
Electron microscopy (EM) is a highly attractive tool for many applications due to its unique blend of strong optical scattering, high native resolution, large depth of focus, and variety of signals including characteristic Xray emission, enabling high-magnification structural imaging and chemical analysis. Despite high optical performance and versatility supporting a wide variety of industries from basic science research to industrial process monitoring, EM has through its ~100-year history been widely regarded as a high-end tool with limited reach outside the laboratory, in particular due to inherent complexity and need for vacuum. Making EM accessible outside constrained laboratory environments will bring EM's performance and versatility to a much broader range of scientific and engineering endeavors.EM's are traditionally housed in centers at universities and large research institutions where those without access to on-site EM typically send samples to be imaged, at great expense and often with delay of weeks to months for complex analyses. For current field work, samples must be sent back to a facility where they can experience chemical or morphological changes over time and/or may be damaged in transit and cannot be reliably analyzed. On-site EM -defined here as EM for immediate portable use in remote or extreme environments at or near the site of sample collection -has historically been impractical.Mochii™ is a portable commercial scanning EM developed by the coauthors at Voxa in Seattle, WA to address the need for EM outside the laboratory (Fig. 1) [1]. This tiny low voltage microscope, which fits in the overhead bin of an airplane, has features that bring accessible and on-demand EM imaging to new applications previously hindered by size, complexity, and cost. Among these features are hand-carryable form-factor and low power consumption (0.25m tall, <12 kg, <80 W), user-friendly native wireless tablet interface, multi-user and remote capabilities, an integrated metal evaporator for easy sample preparation, and optional energy-dispersive X-ray analyzer for chemical identification [2]. The cost to own and operate a Mochii microscope is a fraction of the cost of typical EM's possessing similar imaging performance due to its low power consumption, simple design, and commoditized user-replaceable consumables. At the meeting we will report on use of EM and considerations for use in extreme field environments, such as outdoors under battery power, on moving vehicles such as ocean vessels, and perhaps the most extreme of environments: space (low earth orbit (LEO) and deep space).We are in process to prepare Mochii for manned spaceflight. Ground-based versions of EM's have been essential in NASA research for many years. In mineralogy and petrology, for example, EM is used to understand the origin and evolution of the solar system, particularly rocky bodies, through detailed study of asteroidal and cometary samples. In microbiology, EM has been used to visualize the architecture of tissues and cells to understand ...
Learners in K-12 schools and informal learning environments have historically had significantly less access to critical technologies than practicing scientists. They can observe pollen grains in basic light microscopes while studying plants, but cannot observe the surface structures that affect the pollens' dispersal. They can learn about structure-function relationships in insect anatomy, but not observe mechanosensory bristles on the eye of a fly they caught in their own classroom or learning space, nor the nanostructures enabling moths to hang upside-down on the ceiling. While today's student scientists have access to a great wealth of micro-and nano-scale images via the internet, they have so far been unable to take those images themselves. For K-12 student scientists and informal learners, direct observation of a great range of scientific phenomena has been impossible.
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