Pricing Upward-Only Adjusting Leases

This paper presents a stochastic pricing model of a unique, path-dependent lease instrument common in the United Kingdom and numerous commonwealth countries, the upward-only adjusting lease. In this lease, the rental rate is fixed at lease commencement but will be reset to the market rate at predetermined intervals (usually every five years) if it exceeds the contract rent. Numerical results indicate how the initial coupon rate should be set relative to that on a symmetric up-and-downward adjusting variable rate' lease under various economic conditions (level of real interest rates and expected drift and volatility of the underlying rental service flow). We also consider the calculation of effective rents when free rent periods are given during either a market collapse or a steady-state drift.

Modifying the Schwarz Bayesian information criterion to locate multiple interacting quantitative trait loci

The problem of locating multiple interacting quantitative trait loci (QTL) can be addressed as a multiple regression problem, with marker genotypes being the regressor variables. An important and difficult part in fitting such a regression model is the estimation of the QTL number and respective interactions. Among the many model selection criteria that can be used to estimate the number of regressor variables, none are used to estimate the number of interactions. Our simulations demonstrate that epistatic terms appearing in a model without the related main effects cause the standard model selection criteria to have a strong tendency to overestimate the number of interactions, and so the QTL number. With this as our motivation we investigate the behavior of the Schwarz Bayesian information criterion (BIC) by explaining the phenomenon of the overestimation and proposing a novel modification of BIC that allows the detection of main effects and pairwise interactions in a backcross population. Results of an extensive simulation study demonstrate that our modified version of BIC performs very well in practice. Our methodology can be extended to general populations and higher-order interactions

The dual role of tumor lymphatic vessels in dissemination of metastases and immune response development

Lymphatic vasculature plays a crucial role in the immune response, enabling transport of dendritic cells (DCs) and antigens (Ags) into the lymph nodes. Unfortunately, the lymphatic system has also a negative role in the progression of cancer diseases, by facilitating the metastatic spread of many carcinomas to the draining lymph nodes. The lymphatics can promote antitumor immune response as well as tumor tolerance. Here, we review the role of lymphatic endothelial cells (LECs) in tumor progression and immunity and mechanism of action in the newest anti-lymphatic therapies, including photodynamic therapy (PDT)

Polyclonal antibody cocktails generated using DNA vaccine technology protect in murine models of orthopoxvirus disease

<p>Abstract</p> <p>Background</p> <p>Previously we demonstrated that DNA vaccination of nonhuman primates (NHP) with a small subset of vaccinia virus (VACV) immunogens (L1, A27, A33, B5) protects against lethal monkeypox virus challenge. The L1 and A27 components of this vaccine target the mature virion (MV) whereas A33 and B5 target the enveloped virion (EV).</p> <p>Results</p> <p>Here, we demonstrated that the antibodies produced in vaccinated NHPs were sufficient to confer protection in a murine model of lethal <it>Orthopoxvirus </it>infection. We further explored the concept of using DNA vaccine technology to produce immunogen-specific polyclonal antibodies that could then be combined into cocktails as potential immunoprophylactic/therapeutics. Specifically, we used DNA vaccines delivered by muscle electroporation to produce polyclonal antibodies against the L1, A27, A33, and B5 in New Zealand white rabbits. The polyclonal antibodies neutralized both MV and EV in cell culture. The ability of antibody cocktails consisting of anti-MV, anti-EV, or a combination of anti-MV/EV to protect BALB/c mice was evaluated as was the efficacy of the anti-MV/EV mixture in a mouse model of progressive vaccinia. In addition to evaluating weight loss and lethality, bioimaging technology was used to characterize the spread of the VACV infections in mice. We found that the anti-EV cocktail, but not the anti-MV cocktail, limited virus spread and lethality.</p> <p>Conclusions</p> <p>A combination of anti-MV/EV antibodies was significantly more protective than anti-EV antibodies alone. These data suggest that DNA vaccine technology could be used to produce a polyclonal antibody cocktail as a possible product to replace vaccinia immune globulin.</p

A Versatile, Portable Intravital Microscopy Platform for Studying Beta-cell Biology In Vivo

The pancreatic islet is a complex micro-organ containing numerous cell types, including endocrine, immune, and endothelial cells. The communication of these systems is lost upon isolation of the islets, and therefore the pathogenesis of diabetes can only be fully understood by studying this organized, multicellular environment in vivo. We have developed several adaptable tools to create a versatile platform to interrogate β-cell function in vivo. Specifically, we developed β-cell-selective virally-encoded fluorescent protein biosensors that can be rapidly and easily introduced into any mouse. We then coupled the use of these biosensors with intravital microscopy, a powerful tool that can be used to collect cellular and subcellular data from living tissues. Together, these approaches allowed the observation of in vivo β-cell-specific ROS dynamics using the Grx1-roGFP2 biosensor and calcium signaling using the GcAMP6s biosensor. Next, we utilized abdominal imaging windows (AIW) to extend our in vivo observations beyond single-point terminal measurements to collect longitudinal physiological and biosensor data through repeated imaging of the same mice over time. This platform represents a significant advancement in our ability to study β-cell structure and signaling in vivo, and its portability for use in virtually any mouse model will enable meaningful studies of β-cell physiology in the endogenous islet niche

A Stochastic Fluid Model Approach to the Stationary Distribution of the Maximum Priority Process

In traditional priority queues, we assume that every customer upon arrival has a fixed, class-dependent priority, and that a customer may not commence service if a customer with a higher priority is present in the queue. However, in situations where a performance target in terms of the tails of the class-dependent waiting time distributions has to be met, such models of priority queueing may not be satisfactory. In fact, there could be situations where high priority classes easily meet their performance target for the maximum waiting time, while lower classes do not. Here, we are interested in the stationary distribution at the times of commencement of service of this maximum priority process. Until now, there has been no explicit expression for this distribution. We construct a mapping of the maximum priority process to a tandem fluid queue, which enables us to find expressions for this stationary distribution. We derive the results for the stationary distribution of the maximum priority process at the times of the commencement of service.Comment: The Eleventh International Conference on Matrix-Analytic Methods in Stochastic Models (MAM11), 2022, Seoul, Republic of Kore

Indiana Center for Biological Microscopy

poster abstractThe Indiana Center for Biological Microscopy “ICBM” has provided imaging capabilities since 1996. The primary objective of the Center is to provide state-of-the-art microscopy facility to Indiana University researchers. In 2002 the ICBM was designated as an NIDDK George O'Brien Center for Advanced Microscopic Analysis, whose objective is to develop methods of intravital multiphoton microscopy and 3-dimentional microscopy for renal research. Since that time, the ICBM has worked with various IU investigators to develop methods for intravital microscopy of various organs. One of the recent goals of the Center is to develop an intravital microscopy service for Cancer Center investigators by establishing the Optical Microscopy Core for the CEMH. The Center is available to anyone at the Indiana University and researchers from outside the institution. We are organized around the principle of providing researchers with access to and training on the latest instruments in optical microscopy. We emphasize hands-on access to instruments for individual investigators and unparalleled assistance from on-staff imaging experts