Mathematically optimized cryoprotectant equilibration procedures for cryopreservation of human oocytes

Background Simple and effective cryopreservation of human oocytes would have an enormous impact on the financial and ethical constraints of human assisted reproduction. Recently, studies have demonstrated the potential for cryopreservation in an ice-free glassy state by equilibrating oocytes with high concentrations of cryoprotectants (CPAs) and rapidly cooling to liquid nitrogen temperatures. A major difficulty with this approach is that the high concentrations required for the avoidance of crystal formation (vitrification) also increase the risk of osmotic and toxic damage. We recently described a mathematical optimization approach for designing CPA equilibration procedures that avoid osmotic damage and minimize toxicity, and we presented optimized procedures for human oocytes involving continuous changes in solution composition. Methods Here we adapt and refine our previous algorithm to predict piecewise-constant changes in extracellular solution concentrations in order to make the predicted procedures easier to implement. Importantly, we investigate the effects of using alternate equilibration endpoints on predicted protocol toxicity. Finally, we compare the resulting procedures to previously described experimental methods, as well as mathematically optimized procedures involving continuous changes in solution composition. Results For equilibration with CPA, our algorithm predicts an optimal first step consisting of exposure to a solution containing only water and CPA. This is predicted to cause the cells to initially shrink and then swell to the maximum cell volume limit. To reach the target intracellular CPA concentration, the cells are then induced to shrink to the minimum cell volume limit by exposure to a high CPA concentration. For post-thaw equilibration to remove CPA, the optimal procedures involve exposure to CPA-free solutions that are predicted to cause swelling to the maximum volume limit. The toxicity associated with these procedures is predicted to be much less than that of conventional procedures and comparable to that of the corresponding procedures with continuous changes in solution composition. Conclusions The piecewise-constant procedures described in this study are experimentally facile and are predicted to be less toxic than conventional procedures for human oocyte cryopreservation. Moreover, the mathematical optimization approach described here will facilitate the design of cryopreservation procedures for other cell types.This work was supported by a National Science Foundation grant (#1150861) to Adam Higgins. This article is made openly accessible in part by an award from the Northern Illinois University Libraries’ Open Access Publishing Fund

Effects of Fire in the Northern Great Plains

Fire has been used inconsistently to manage native and tame grasslands in the Northern Great Plains (NGP) of the north-central U.S. and south-central Canada, particularly the grasslands found in prairies, plains, agricultural land retirement programs, and moist soil sites. This has happened for three primary reasons: (1) the reduction of American Indian use of fire after 1875, (2) fire suppression and land use changes that put increasingly more acres under annual tillage since about the same time, and (3) a growing resistance to the use of fire since about 1940, largely due to media overemphasis of its harmful effects (e.g., Bambi and Smokey the Bear ). Little can be done to change the first two factors but there is ample opportunity to change human attitudes about fire. Attitudes change when the knowledge (or lack of it) changes. We believe that people have been reluctant to include fire in resource management programs in the NGP because of a lack of adequate information about the effects of fire on the soils, plants, and animals in the region. This document provides information concerning fire effects on the grassland biome of the NGP, with special emphasis on the use of fire for wildlife management. In several instances we have drawn from published literature outside the geographic region, but only to provide a more complete reference for readers and decision makers. In most instances, we only state or abstract the published findings of others without interpretation, either pro or con. Readers can fit the information into their specific circumstances. English and scientific names are from Flora of the Great Plains by the Great Plains Flora Association and from the Checklist of Vertebrates of the United States, the U.S. territories, and Canada by RC. Banks, R.W. McDiarmid, and A.L. Gardner

Prescribed Burning Guidelines in the Northern Great Plains

The use of fire to manage grasslands for wildlife is a relatively new management option for resource managers in the Northern Great Plains (NGP). Nearly all of the burning during the past 20-25 years has been conducted without the aid of specific guidelines for the region. This state-of-the-art set of recommendations was compiled because of this void. Records of 902 grassland fires (primarily on U.S. Fish and Wildlife lands), personal experiences, and synopses of other published fire research were used in developing the guidelines in this manual. Fifty-two percent of the 902 fires were in native prairie grasslands with lesser amounts in tame and native grass plantings, wetlands, and woodlands. Prescription grassland fires averaged 31 ha (77 acres) per burn. The personnel needed to safely conduct a grassland fire depended on the size of the burn, the kind of firebreaks, available equipment, and weather conditions. Costs and hours of effort to conduct fires were inversely related to burn area size. Cost ratios are extremely high for fires of less than 4 ha (10 acres). They are essentially the same for burns of 16 to 113 ha (40 to 280 acres). The two primary reasons for burning grasslands are wildlife habitat improvement and native prairie restoration. Fire use steadily increased between 1965 and 1984, but the greatest increase occurred following workshop instruction in 1978. These guidelines present a set of reasons, criteria, techniques, and examples of simple prescriptions which aid in the planning and execution of a safe and effective prescribed burning program for wildlife enhancement in grassland areas of the NGP

Prescribed Burning Guidelines in the Northern Great Plains

This publication provides guidelines with reasons, criteria, techniques, and examples of simple prescriptions which aid in the planning and execution of a safe and effective prescribed burning program for wildlife enhancement in grassland areas of the Northern Great Plains

Effects of Fire in the Northern Great Plains

This publication is a review of selected literature about prescribed burning in the Northern Great Plains for management of wildlife. It discusses the effect of fire on soil nutrients and minerals, upland grasses and forbs, undesirable species, shrubs, trees, certain plant species, emergent vegetation in prairie wetlands, insects, nongame birds, upland game birds, waterfowl, shorebirds, small mammals, and livestock

The Robertson v. Princeton Case: Too Important to Be Left to the Lawyers

Offers comments from eleven contributors on the Robertson family's donor rights suit against the Woodrow Wilson School of Public and International Affairs for violation of donor intent. Explores its effects on and implications for the nonprofit sector

Inflammatory Regulation of CNS Barriers After Traumatic Brain Injury: A Tale Directed by Interleukin-1

Several barriers separate the central nervous system (CNS) from the rest of the body. These barriers are essential for regulating the movement of fluid, ions, molecules, and immune cells into and out of the brain parenchyma. Each CNS barrier is unique and highly dynamic. Endothelial cells, epithelial cells, pericytes, astrocytes, and other cellular constituents each have intricate functions that are essential to sustain the brain’s health. Along with damaging neurons, a traumatic brain injury (TBI) also directly insults the CNS barrier-forming cells. Disruption to the barriers first occurs by physical damage to the cells, called the primary injury. Subsequently, during the secondary injury cascade, a further array of molecular and biochemical changes occurs at the barriers. These changes are focused on rebuilding and remodeling, as well as movement of immune cells and waste into and out of the brain. Secondary injury cascades further damage the CNS barriers. Inflammation is central to healthy remodeling of CNS barriers. However, inflammation, as a secondary pathology, also plays a role in the chronic disruption of the barriers’ functions after TBI. The goal of this paper is to review the different barriers of the brain, including (1) the blood-brain barrier, (2) the blood-cerebrospinal fluid barrier, (3) the meningeal barrier, (4) the blood-retina barrier, and (5) the brain-lesion border. We then detail the changes at these barriers due to both primary and secondary injury following TBI and indicate areas open for future research and discoveries. Finally, we describe the unique function of the pro-inflammatory cytokine interleukin-1 as a central actor in the inflammatory regulation of CNS barrier function and dysfunction after a TBI

Annotated Bibliography of Fire Literature

Natural resource managers have greatly increased the use of fire to manage grassland habitats during the past two decades in the northern Great Plains region of the United States and Canada. In support of these efforts, we have compiled this annotated bibliography to provide a condensed reference of fire literature for those managers with an interest in fire ecology. References are arranged alphabetically by author and year, numbered consecutively, and referenced by number in the author and subject indexes that follow the bibliography. The intent in compiling the bibliography and indexes is more to identify subject matter and to direct the reader to sources rather than to provide a digested interpretation of each manuscript

Alteration of Gene Expression Signatures of Cortical Differentiation and Wound Response in Lethal Clear Cell Renal Cell Carcinomas

Clear cell renal cell carcinoma (ccRCC) is the most common malignancy of the adult kidney and displays heterogeneity in clinical outcomes. Through comprehensive gene expression profiling, we have identified previously a set of transcripts that predict survival following nephrectomy independent of tumor stage, grade, and performance status. These transcripts, designated as the SPC (supervised principal components) gene set, show no apparent biological or genetic features that provide insight into renal carcinogenesis or tumor progression. We explored the relationship of this gene list to a set of genes expressed in different anatomical segments of the normal kidney including the cortex (cortex gene set) and the glomerulus (glomerulus gene set), and a gene set expressed after serum stimulation of quiescent fibroblasts (the core serum response or CSR gene set). Interestingly, the normal cortex, glomerulus (part of the normal renal cortex), and CSR gene sets captured more than 1/5 of the genes in the highly prognostic SPC gene set. Based on gene expression patterns alone, the SPC gene set could be used to sort samples from normal adult kidneys by the anatomical regions from which they were dissected. Tumors whose gene expression profiles most resembled the normal renal cortex or glomerulus showed better survival than those that did not, and those with expression features more similar to CSR showed poorer survival. While the cortex, glomerulus, and CSR signatures predicted survival independent of traditional clinical parameters, they were not independent of the SPC gene list. Our findings suggest that critical biological features of lethal ccRCC include loss of normal cortical differentiation and activation of programs associated with wound healing