抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

THE DESIGN AND ANALYSIS OF EXPERIMENTS. By Oscar Kempthorne. New York, John Wiley and Sons, Inc., 1952. 631 pp. $8.50. This book by a teacher of statistics (as well as a consultant for \"experimenters\") is a comprehensive study of the philosophical background for the statistical design of experiment. It is necessary to have some facility with algebraic notation and manipulation to be able to use the volume intelligently. The problems are presented from the theoretical point of view, without such practical examples as would be helpful for those not acquainted with mathematics. The mathematical justification for the techniques is given. As a somewhat advanced treatment of the design and analysis of experiments, this volume will be interesting and helpful for many who approach statistics theoretically as well as practically. With emphasis on the \"why,\" and with description given broadly, the author relates the subject matter to the general theory of statistics and to the general problem of experimental inference. MARGARET J. ROBERTSON

The Design and Analysis of Experiments

The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Harrison's Principles of Internal Medicine

Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications

Rapid growth in nanotechnology is increasing the likelihood of engineered nanomaterials coming into contact with humans and the environment. Nanoparticles interacting with proteins, membranes, cells, DNA and organelles establish a series of nanoparticle/biological interfaces that depend on colloidal forces as well as dynamic biophysicochemical interactions. These interactions lead to the formation of protein coronas, particle wrapping, intracellular uptake and biocatalytic processes that could have biocompatible or bioadverse outcomes. For their part, the biomolecules may induce phase transformations, free energy releases, restructuring and dissolution at the nanomaterial surface. Probing these various interfaces allows the development of predictive relationships between structure and activity that are determined by nanomaterial properties such as size, shape, surface chemistry, roughness and surface coatings. This knowledge is important from the perspective of safe use of nanomaterials.

Understanding biophysicochemical interactions at the nano–bio interface

Macromolecular structure of coals: 8. Viscoelastic behaviour of coal networks determined by thermomechanical analysis

Particle size distribution: Assessment and characterization

In some aspects, a composition comprising a pH-sensitive crosslinked copolymer of methacrylic acid and poly(ethylene glycol) monomethyl ether methacrylate and a therapeutic protein is provided. In some embodiments, the therapeutic protein is a high molecular weight protein such as factor VIII or factor IX. In some embodiments, the composition is orally administered to a patient to treat a disease or disorder such as, e.g., hemophilia.

Polymers for delivery of factor viii and/or factor ix

Swelling equations were derived for polymeric networks that consist of two swellable but distinct phases. These equations can be used to describe the equilibrium swelling behavior of certain two-phase network systems. Using physicochemical measurements of the equilibrium polymer volume fraction, it was possible to calculate the number-average molecular weight between crosslinks, Mc, using these equations. The influence of several structural parameters on Mc was investigated. © 1992 John Wiley & Sons, Inc.

Swelling equations for confined homogeneous and heterogeneous polymeric networks: Calculation of M̄c in swellable two‐phase systems

Hydrogels made of glucose oxidase-containing graft copolymers of dimethyl aminoethyl methacrylate and ethylene glycol, or glucose oxidase-containing P(DMAEMg-EG) copolymers, have been shown to deliver insulin upon exposure to glucose. The glucose oxidase reacts with glucose to form gluconic acid. The production of gluconic acid decreases the pH, which results in the swelling of the hydrogel complex. Once the mesh size has increased, insulin is released from the complex. Previous work has shown that P(DMAEM-g-EG) hydrogels have exhibited pH sensitive swelling and deswelling. Current work focuses on the design of novel hydrogels that allow for insulin release in diabetic patients that is similar to that of healthy, non-diabetic patients. To evaluate the effectiveness of proposed hydrogels, dynamic models of glucose and insulin are being developed for both healthy patients and diabetic patients in order to compare the dynamic responses of the hydrogels to those of a healthy pancreas. In healthy patients, the models show how insulin and glucose dynamics are dependent on each other throughout the body, while in diabetics the hydrogel complex dynamics are included as the primary insulin source. Understanding glucose and insulin dynamics is necessary in order develop control strategies for hydrogels used in glucose regulation. Introduction: The main objective of this research was to contribute to the medical field by providing new therapeutic methods and improved devices for insulin delivery in diabetic patients. With the new therapies developed we should be able to: (i) determine when exactly should insulin be delivered to the patient; and (ii) avoid unnecessary and premature insulin delivery. A major goal and contribution of this research were the design and development of glucose-responsive, gel-based devices for insulin delivery that can be used over a prolonged period of time. These systems are known as self-regulated drug delivery systems. A significant distinction of our research is the reliance on robust control theory to establish performance objectives for the proposed hydrogel device, as well as optimal control theory to guide the selection of optimal parameter values for the synthesis of the gel. We have developed a series of novel self-regulated, glucoseand pH-sensitive gels for insulin delivery. We have experimented already with novel hydrogels in which the swelling ratio and the resulting mesh size change reversibly as a function of environmental parameters such as pH or temperature. These reversible changes allow for the release of drugs or the permeation of solutes depending on surrounding environmental conditions. Poly(methacrylic acid) (PMAA) exhibits interpolymer complexation with poly(ethylene glycol) (PEG) as the protons of the carboxylic acid groups on PMAA form hydrogen bonds with the ether groups on the PEG chain. This complexation forms only at pH low enough to insure substantial protonation of the carboxylic acid groups. Complexation of free chains of PMAA with PEG in solution has been studied. We have also shown that poly(dimethyl aminoethyl methacrylate) and poly(ethylene glycol) exhibit the same type of hydrogen bonding, except that the pH dependence is such that the systems decomplex at low pH and complex at high pH values. Summary of Proposed Models We developed models describing the dynamics of glucose and insulin in both healthy and diabetic patients. The models were developed by representing the body as a system consisting of several compartments. Glucose and insulin dynamics were determined by deriving mass balance equations for each individual compartment. Although compartmental models have been used in the past to describe insulin and glucose dynamics, we believe that ours is a novel contribution to the field in four ways. First, we incorporate an accurate model of a meal disturbance into both models, we incorporate an accurate model of the effects of exercise on glucose levels into both models, we attempt to characterize both interpatient and intrapatient uncertainty among model parameters such as the basal values of insulin and glucose in each compartment and we incorporate insulin release dynamics from the hydrogel systems into the diabetic patient model. The model is used to determine the structure of the hydrogel system having insulin release dynamics that most resembles the dynamics of the pancreas. In addition to the use of hydrogels, we also use the models to design effective glucose control algorithms for implantable, self-regulating insulin pumps. Results We focused on studying the effects of linearization and feedback control on existing models, most notably the model created by Bergman et al (1) and modified by Furler et al (2). ) ( ) ( 1 t D XG G G P dt dG b + − − − = (1) ) ( 3 2 b I I P X P dt dX − + − = (2)

Nicholas A. Peppas

Papers

Macromolecular structure of coals: 8. Viscoelastic behaviour of coal networks determined by thermomechanical analysis

Particle size distribution: Assessment and characterization

Polymers for delivery of factor viii and/or factor ix

Swelling equations for confined homogeneous and heterogeneous polymeric networks: Calculation of M̄c in swellable two‐phase systems

Modeling and control of the behavior of glucose sensing devices