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Chromosome organization is crucial for genome function. Here, we present a method for visualizing chromosomal DNA at super-resolution and then integrating Hi-C data to produce three-dimensional models of chromosome organization. Using the super-resolution microscopy methods of OligoSTORM and OligoDNA-PAINT, we trace 8 megabases of human chromosome 19, visualizing structures ranging in size from a few kilobases to over a megabase. Focusing on chromosomal regions that contribute to compartments, we discover distinct structures that, in spite of considerable variability, can predict whether such regions correspond to active (A-type) or inactive (B-type) compartments. Imaging through the depths of entire nuclei, we capture pairs of homologous regions in diploid cells, obtaining evidence that maternal and paternal homologous regions can be differentially organized. Finally, using restraint-based modeling to integrate imaging and Hi-C data, we implement a method-integrative modeling of genomic regions (IMGR)-to increase the genomic resolution of our traces to 10 kb.

Maintaining the integrity of cryogenically preserved biological materials is critical, as even brief, undetected temperature excursions in storage can compromise sample viability. Existing monitoring systems may miss transient thaw–refreeze events, posing serious quality risks. To address this, we developed and validated frozen indicator tubes that visually signal deviations from the frozen state, serving as a cost-effective backup to electronic monitors. Our first method uses an aqueous dye solution that immobilizes the dye when frozen; any thawing causes the dye to disperse, providing a clear, external visual cue of a partial or complete thaw. For ultra-low-temperature storage (−80 °C), we introduced a second method using an ethanol-based solution calibrated to indicate thaw events. This system detects temperature rises of 10 °C or more sustained for at least fifteen minutes—conditions that may jeopardize sample stability. When paired with standard monitoring systems, these indicator tubes offer an added layer of protection by providing simple, reliable, and immediate visual confirmation of critical temperature breaches. This innovation enhances confidence in cryogenic storage protocols and supports the long-term preservation of sensitive biological materials.

Background Dissection of specific Areas Of Interest (AOIs) of slide-mounted tumor samples is often used to enrich for cancer cells in order to generate better signal to noise ratios in subsequent biochemical characterization. Most clinical laboratories utilize manual dissection for practical reasons and to avoid the expense and difficulties of laser microdissection systems. Unfortunately, manual methods often lack resolution and process documentation. The goal of this project was to design a dissection system for slide-mounted tissue with better precision than manual methods that also provides digital image guidance and electronic process documentation. Methods An instrument that is essentially a micro tissue mill was developed. It employs a specialized disposable mill bit that simultaneously dispenses liquid, cuts tissue from the slide surface, and aspirates the liquid along with the displaced tissue fragments. A software package was also developed that is capable of transferring digitally annotated AOIs between images of serially cut tissue sections to guide dissection and generate an electronic record of the process. Results The performance of this “meso” dissection system was tested using post dissection visual examination for resolution and accuracy, fluorescence based DNA quantitation for recovery efficiency, and dissection of closely situated mouse-human tissue sections followed by PCR amplification for purity determination. The minimum resolution is a dissected circle smaller than 200 microns in diameter, edge dissection accuracy is tighter than 100 microns, recovery efficiency appears greater than 95%, and recovery purity is greater than 99% relative to a different tissue located 100 microns from the dissection boundary. The system can dissect from both paraffinized and deparaffinized FFPE tissue sections that are mounted on plain glass slides, and it is compatible with DNA, RNA, and protein isolation. Conclusions The mesodissection system is an effective alternative to manual dissection methods and is applicable for biomarker analysis of anatomical pathology samples, where enrichment of AOIs from the tissue section is helpful, but pure cell populations are not required.

Leaders face an unprecedented diversity in follower expectations and value systems as the workforce expands to four distinctly unique generations, ranging from Millennials to the Silent Generation. Rapid advances in technology have amplified the generational differences and increased the complexity of an increasingly disconnected workforce. Business sustainability and success depend upon a leader’s ability to cost-effectively deliver financial results, employee performance, and employee satisfaction given these mounting challenges. The purpose of this exploratory qualitative study was to discover leadership practices proven effective in addressing the complexities of a technologically enabled, multi-generational workforce. Eighteen insurance industry senior executives were interviewed by phone using a semi-structured process consisting of nine open-ended questions, six on leadership practices and three on influencing factors. Transformational and authentic leadership were selected as the theoretical framework for reviewing the described practices. The study’s findings supported authentic leadership as the foundation for effective practices while indicating the need to incorporate select aspects of transformational leadership. By blending the two theories into an effective framework, the importance of having a more unified theory of leadership was also reinforced. The results of study were three-pronged: confirming generational differences as a critical consideration in defining effective leadership, blending authentic and transformational leadership theory into an integrated set of effective leadership practices, and highlighting technology as an integral leadership construct with significant influence on effective communication practices.

The amount of data available from simulation and measurement is growing at an incredible rate. A major challenge for the visualization community is to develop methods that allow users to explore these data interactively. For three-dimensional scalar fields, direct volume rendering has become an important technique in research and commercial settings. Interactive volume rendering requires the efficient use of available computational resources to keep pace with the disparity, resolution, and complexity of the volumes that are commonly produced from simulations (e.g., computational fluid dynamics or structural mechanics) and measurements (e.g., environmental observation and forecasting systems). For structured grids, direct volume rendering is well-studied and sufficiently straightforward with modern graphics hardware. This is not the case with unstructured volumes, because the elements that compose the mesh do not so easily map to current hardware. These datasets may be extremely large and contain more than a single static instance. Therefore, advanced solutions are required to achieve interactive visualization of this type of data. The goal of this dissertation is to provide several new techniques to facilitate the visualization of disparate unstructured meshes. Two new methods are proposed to accelerate volume rendering for the case of static data, one of which operates in object-space and the other in image-space. Acceleration methods may not always be enough, however, to allow interactive visualization for data that are too large to fit in the main memory of a computer. Therefore, a new progressive rendering approach is proposed that adaptively refines a visualization using remote resources. These new techniques are of great assistance for a large class of static imagery. However, dynamic volumes that change over time create unique challenges because of the amount of data that needs to be transmitted at each step. To address this issue, a new method for efficiently handling time-varying unstructured volumes is also presented in this dissertation. Together, these methods for interactive visualization provide a powerful framework for analyzing large amounts of unstructured data. To demonstrate this, a final application for transfer function design that combines many of these approaches is presented. This application includes an evaluation performed by a group of expert users to elaborate on the importance of these proposed techniques for interactive visualization.

Claims operations are getting headline coverage lately, driven in no small part by recent references to Accenture's claims survey that lists core systems replacement, data and analytics, and workforce growth as the top three priorities and Celent's claims fraud report highlighting reduction in fraud as one of the key levers to near term profitability. Executives appear to be in agreement that improving combined ratios will be more easily achieved than increasing underwriting profits, at least until the economy returns to a more reasonable footing. At the same time, increased competitive intensity has executives asking their claims departments to improve their delivery of service excellence and their operational efficiency. Apparently, the previously achieved efficiencies have been quickly absorbed by increased investments in technology, putting most claims departments back where they started. The race is on to pair carriers with the solutions needed to deliver on these demands.

The life and annuity insurance industry is facing two approaching \"megatrends.\" For insurers, these shifts come paired with challenges and demands for attention, as well as a warning of likely casualties among companies that don't take action. The first trend is the coming wave of baby boomer retirements. As they reach retirement age, many will be faced with trying to meet rising health care costs and retirement lifestyle needs with inadequate funds. Another challenge in dealing with the shift to payout from accumulation is how marketing will be conducted, with particular emphasis on distribution. The second trend involves the coming changes in demographics within the consumer and employee populations. These changes will impact leadership as well as product features, servicing options and distribution channels.

Uncertainty over election results, the fiscal cliff, and economic direction appear to have been addressed, allowing industry leaders to focus on a return to competitive advantage and sustainable profitability. Even with gradual improvements in the economy, companies remain faced with increasingly costly catastrophe losses and near-term minimal investment returns. Further complicating the challenges leadership faces are continued increases in consumer expectations for products and service, an increasingly diversified market, distribution challenges, and nonstop technological advances. Bottom line, the insurance industry requires game changers to improve performance in any meaningful manner. User-based insurance (UBI) offers one possible example of a game changer, but like all shifts it comes with it is own set of challenges. Layering a strong analytics solution on top of policy admin data and other data sources allows carriers to focus on four areas where analytics can bring significantly amplified results. In priority order based on potential impact, including: 1. risk assessment, 2. claims handling, 3. agent effectiveness, and 4. customer awareness.

The property and casualty industry has not had a return on equity (ROE) better than the Fortune 500 since 1987. The last times it was even close were 1991 and 1993. Even if the Fortune 500 is not considered the right benchmark, the industry average ROE has declined from a high of 12.7 percent in 2006 to an estimated 3.9 percent in 2011. Even more relevant, the industry ROE has been measurably lower than the average cost of capital since 2008. Running a business returning less than its cost of capital is rarely a sustainable model, as evidenced by the number of property & casualty impairments occurring since 2007.