Earthquake response of steel braces and braced steel frames

This thesis consists of three parts. Chapter 2 deals with the dynamic buckling behavior of steel braces under cyclic axial end displacement. Braces under such a loading condition belong to a class of "acceleration magnifying" structural components, in which a small motion at the loading points can cause large internal acceleration and inertia. This member-level inertia is frequently ignored in current studies of braces and braced structures. This chapter shows that, under certain conditions, the inclusion of the member-level inertia can lead to brace behavior fundamentally different from that predicted by the quasi-static method. This result is to have significance in the correct use of the quasi-static, pseudo-dynamic and static condensation methods in the simulation of braces or braced structures under dynamic loading. The strain magnitude and distribution in the braces are also studied in this chapter.

Chapter 3 examines the effect of column uplift on the earthquake response of braced steel frames and explores the feasibility of flexible column-base anchoring. It is found that fully anchored braced-bay columns can induce extremely large internal forces in the braced-bay members and their connections, thus increasing the risk of failures observed in recent earthquakes. Flexible braced-bay column anchoring can significantly reduce the braced bay member force, but at the same time also introduces large story drift and column uplift. The pounding of an uplifting column with its support can result in very high compressive axial force.

Chapter 4 conducts a comparative study on the effectiveness of a proposed non-buckling bracing system and several conventional bracing systems. The non-buckling bracing system eliminates buckling and thus can be composed of small individual braces distributed widely in a structure to reduce bracing force concentration and increase redundancy. The elimination of buckling results in a significantly more effective bracing system compared with the conventional bracing systems. Among the conventional bracing systems, bracing configurations and end conditions for the bracing members affect the effectiveness.

The studies in Chapter 3 and Chapter 4 also indicate that code-designed conventionally braced steel frames can experience unacceptably severe response under the strong ground motions recorded during the recent Northridge and Kobe earthquakes.

Structural Characterization of Pro-inflammatory and Anti-inflammatory Immunoglobulin G Fc Proteins

Immunoglobulin G (IgG) is central in mediating host defense due to its ability to target and eliminate invading pathogens. The fragment antigen binding (Fab) regions are responsible for antigen recognition; however the effector responses are encoded on the Fc region of IgG. IgG Fc displays considerable glycan heterogeneity, accounting for its complex effector functions of inflammation, modulation and immune suppression. Intravenous immunoglobulin G (IVIG) is pooled serum IgG from multiple donors and is used to treat individuals with autoimmune and inflammatory disorders such as rheumatoid arthritis and Kawasaki’s disease, respectively. It contains all the subtypes of IgG (IgG1-4) and over 120 glycovariants due to variation of an Asparagine 297-linked glycan on the Fc. The species identified as the activating component of IVIG is sialylated IgG Fc. Comparisons of wild type Fc and sialylated Fc X-ray crystal structures suggests that sialylation causes an increase in conformational flexibility, which may be important for its anti-inflammatory properties.

Although glycan modifications can promote the anti-inflammatory properties of the Fc, there are amino acid substitutions that cause Fcs to initiate an enhanced immune response. Mutations in the Fc can cause up to a 100-fold increase in binding affinity to activating Fc gamma receptors located on immune cells, and have been shown to enhance antibody dependent cell-mediated cytotoxicity. This is important in developing therapeutic antibodies against cancer and infectious diseases. Structural studies of mutant Fcs in complex with activating receptors gave insight into new protein-protein interactions that lead to an enhanced binding affinity.

Together these studies show how dynamic and diverse the Fc region is and how both protein and carbohydrate modifications can alter structure, leading to IgG Fc’s switch from a pro-inflammatory to an anti-inflammatory protein.

Sensing and Actuation from Biology to Electronics

We introduce an in vitro diagnostic magnetic biosensing platform for immunoassay and nucleic acid detection. The platform has key characteristics for a point-of-use (POU) diagnostic: portability, low-power consumption, low cost, and multiplexing capability. As a demonstration of capabilities, we use this platform for the room temperature, amplification-free detection of a 31 bp DNA oligomer and interferon-gamma (a protein relevant for tuberculosis diagnosis). Reliable assay measurements down to 100 pM for the DNA and 1 pM for the protein are demonstrated. We introduce a novel "magnetic freezing" technique for baseline measurement elimination and to enable spatial multiplexing. We have created a general protocol for adapting integrated circuit (IC) sensors to any of hundreds of commercially available immunoassay kits and custom designed DNA sequences.

We also introduce a method for immunotherapy treatment of malignant gliomas. We utilize leukocytes internalized with immunostimulatory nanoparticle-oligonucleotide conjugates to localize and retain immune cells near the tumor site. As a proof-of-principle, we develop a novel cell imaging and incubation chamber for in vitro magnetic motility experiments. We use the apparatus to demonstrate the controlled movement of magnetically loaded THP-1 leukocytes.

Finally, we introduce an IC transmitter and power ampli er (PA) that utilizes electronic digital infrastructure, sensors, and actuators to self-heal and adapt to process, dynamic, and environmental variation. Traditional IC design has achieved incredible degrees of reliability by ensuring that billions of transistors on a single IC die are all simultaneously functional. Reliability becomes increasingly difficult as the size of a transistor shrinks. Self-healing can mitigate these variations.