The nuclear factor-kB (NF-kB) signaling cascade is comprised of two branches, the canonical and alternative NF-kB pathways. Signaling through the alternative NF-kB pathway culminates in the activation of the downstream transcription factor subunits, RELB and NF-kB2. The biological roles of RELB and NF-kB2 within the B cell lineage have been obscured in constitutional knockout mice by the diverse functions of these subunits in non-B cell types. To overcome these limitations, conditional alleles were generated to investigate the roles of RELB and NF-kB2 in B cell development. These alleles allowed the identification of complex functional requirements for RELB and/or NF-kB2 in naïve B cells, germinal center (GC) B cells and plasma cells (PCs). These functional requirements may have implications for B cell malignancies that display mutations that constitutively activate the alternative NF-kB pathway. A large body of work has demonstrated that B cell activating factor (BAFF) signaling is critical for the maintenance of mature B cells. However, the contribution of the alternative NF-kB subunits that are activated downstream of BAFF remained unclear, especially in regards to their specific target genes. We have identified critical, B cell-intrinsic roles for RELB and NF-kB2 in the maintenance of mature B cells. In response to BAFF, these subunits were found to control the expression of anti-apoptotic genes, genes that ensure correct positioning within the B cell niche, and genes involved in promoting B–T cell interactions that allow effective antigen-mediated activation. During the GC B cell reaction, light zone (LZ) B cells undergo affinity-based selection mediated by T follicular helper (Tfh) cells. A subset of LZ B cells show activation of the NF-kB signaling cascade, suggesting a critical role for NF-kB in the selection of high-affinity GC B cells. We here report that GC B cell development occurred normally in mice with conditional deletion of either relb (RELB) or nfkb2 (NF-kB2) in GC B cells. In contrast, the simultaneous ablation of both subunits caused rapid involution of established GCs, similar to what has been observed for ablation of the canonical NF-kB transcription factor subunit c-REL. Intriguingly, RNA-sequencing analysis of relb/nfkb2-deleted GC B cells revealed no overlap between the genes controlled by RELB/p52 and c-REL within GC B cells. This suggests that signaling through the separate NF-kB pathways in GC B cells results in the expression of different biological programs that are independently required for the maintenance of the GC reaction. In addition, we observed that human PCs and PC precursors within the LZ showed high protein levels of NF-kB2 compared to surrounding lymphocytes, suggesting a biological role for this subunit in PCs. Indeed, ablation of nfkb2 alone in GC B cells led to a dramatic decrease in antigen-specific serum IgG1 and antigen-specific IgG1-secreting cells. Interestingly however, the mice developed normal frequencies of PCs, suggesting a role for NF-kB2 in PC physiology rather than differentiation.

Finally, based on theoretical calculations and experiments, we present a development model (DDRA model) to describe the interaction between the protein and its solvent molecule. The parameters derived from this model provide good fits to the experimentally determined complex dielectric constant, making it of the model valuable benchmarks for other theoretical treatments of bio-molecular system. / Secondly, we focus our aims on investigating protein molecules due to the possibility of being able to explain the mechanism of molecular interactions more clearly. Two lands of labeled immunoglobulin G were investigated using a reflective THz-IDS system. The dielectric properties were sensitive to the conjugation of the antibody. Additionally, terahertz spectroscopy is able to evaluate the depth of the hydrogen shell and shows that the hydrogen-bonded networks of charged protein solutions play an important role in determining the dielectric. / The bio-molecular interaction has been one of the most challenging subjects to probe due to its complexity. In the thesis, we have been attempting to answer fundamental questions about bio-molecular interactions in the terahertz (THz) region from the macroscopic to microscopic level. Terahertz radiation (defined as 0.1--10 THz) can excite intermolecular interactions such as the librational and vibrational modes. These attributes make it feasible to probe the dynamic characteristics of the bio-molecular system. Furthermore, it is worth investigating whether terahertz technology could potentially be used as a novel tool in the biomedical diagnosis field in the near future. / Thirdly, using a transmission THz-TDS system we investigated a biomarker protein and observed distinct spectral differences at various temperatures. This work demonstrates that terahertz spectroscopy can be used to evaluate the anharmonicity of the vibrational potential. By comparing the absorption spectra of the THz-TDS and Synchrotron results it is possible to deduce the approximate localization of the vibrational modes within the molecular chain. / We develop a controlled study to investigate the effects of formalin fixing on the THz properties of two different tissue types. The optical properties are measured using THz reflection spectroscopy. The results present how the fixing process can affect image contrast in THz images of biological samples. / Sun, Yiwen. / Advisers: Emma MacPherson; Yuan-ting Zhang. / Source: Dissertation Abstracts International, Volume: 73-03, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 120-140). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Gene expression knockdown using RNA interference has dramatically altered the ability to silence target genes without the need for a creation of a genetic knockout. The pitfalls surrounding successful siRNA gene expression knockdown fall in the broad category of delivery. This work focuses on the use of N-isopropyl-acrylamide conjugated polyglycerol (PGNIPAM) as a novel cationic vector of in vitro and possible in vivo delivery of siRNA. The hyper-branched structure of the PGNIPAM molecule bears a biocompatible core with cationic subunits on the surface, providing a less toxic alternative to other cationic polymers used in the past. Further PGNIPAM shows excellent binding and release characteristics over other comparable molecules and systems. Activity of the siRNA requires access to the cell cytoplasm, which in turn requires passage of the siRNA through the cell membrane and release into the internal environment with no degradation. PGNIPAM has shown the ability to traverse the endocytic pathway and release the siRNA directly into the cytoplasm where it can interact with cellular machinery. Knockdown of known oncogene survivin was observed in vitro both through mRNA expression reduction as well as through protein reduction in MDA-MB-231 human breast cancer cells. Additionally, early stage animal work with a human breast cancer model shows positive results for coupled treatment of tumors using siRNA against survivin and doxorubicin, an anticancer drug. PGNIPAM offers a safer alternative to other cationic delivery systems and has shown improvement over standard modes of knockdown from commercial products.

No description available.

Typescript. / Thesis (Ph. D.)--University of Hawaii. 1967. / Bibliography: leaves 211-218. / xi, 218 l illus., maps, tables

The mussel bed and its multitude of inhabitants form a life community typical of our intertidal, rocky, open-coast areas. These animals are essentially immobile, are conveniently available at low tide, and have been well defined in their consumer order. Certain main members from this community were chosen with the intention that they would represent an index of heavy metal pollution for a given area under different seasonal and other variable conditions. Samples for monitoring were collected from two different sites. The first site was immediately outside the entrance to San Francisco Bay and located between Seal Rocks and Phelan Beach State Parks. This location was chosen to represent a water mass of supposed maximum pollution. The Golden Gate can be assumed to be the funnel through which flows all waters from the San Joaquin and Sacramento River drainages and from the San Francisco Bay area itself. The second site, immediately north of the Dillon Beach township, located at the juncture of Bodega and Tomales Bays, was chosen since it might represent a water mass of minimum pollution. This area is not immediately near any large urban influence, industrial activity or subject to heavy auto traffic. Therefore, at the outset it was hoped that the “immobile” consumer order within the mussel bed community would reflect the relative pollution of two supposedly different water masses.

This paper investigates a means of detecting the reaction of aquatic vertebrates to environmental change by recording behavioral patterns within the diurnal activity. An apparatus measuring the activity of Jordanella floridae, Goode and Bean, using a photoelectric sensor system is described. Individual sensors monitored specific areas of the test aquarium that had special significance to the fish in the way of a particular behavioral category. An event recorder documented the breakage of light beams, giving continuous and accurately timed data of activity. Two distinct patterns of activity were recognized; a control, or typical, pattern, and a pattern resulting from the administration of a large (10°C) change in environmental temperature. Modifications in the diurnal behavior were consistent with reactions that could be adaptive for the species under similar conditions in nature.

Indiana University-Purdue University Indianapolis (IUPUI) / Biomedical research has produced vast amounts of new information in the last decade but has been slow to find its use in clinical applications. Data from disparate sources such as genetic studies and summary data from published literature have been amassed, but there is a significant gap, primarily due to a lack of normative methods, in combining such information for inference and knowledge discovery. In this research using Bayesian Networks (BN), a probabilistic framework is built to address this gap. BN are a relatively new method of representing uncertain relationships among variables using probabilities and graph theory. Despite their computational complexity of inference, BN represent domain knowledge concisely. In this work, strategies using BN have been developed to incorporate a range of available information from both raw data sources and statistical and summary measures in a coherent framework. As an example of this framework, a prototype model (In-silico Bayesian Integration of GWAS or IsBIG) has been developed. IsBIG integrates summary and statistical measures from the NIH catalog of genome wide association studies (GWAS) and the database of human genome variations from the international HapMap project. IsBIG produces a map of disease to disease associations as inferred by genetic linkages in the population. Quantitative evaluation of the IsBIG model shows correlation with empiric results from our Electronic Medical Record (EMR) – The Regenstrief Medical Record System (RMRS). Only a small fraction of disease to disease associations in the population can be explained by the linking of a genetic variation to a disease association as studied in the GWAS. None the less, the model appears to have found novel associations among some diseases that are not described in the literature but are confirmed in our EMR. Thus, in conclusion, our results demonstrate the potential use of a probabilistic modeling approach for combining data from disparate sources for inference and knowledge discovery purposes in biomedical research.

The theme of the diploma thesis is allergens in the teaching of natural science, biology and chemistry. The subject and its aim is to find out the presence of allergens in selected classes of natural sciences (natural sciences, biology, chemistry) as well as the level of awareness of problems of allergies and allergens from teachers and pupils of elementary schools and grammar schools and to compare whether teachers of selected subjects take into account Creating climate climate for allergic pupils. The thesis consists of theoretical and practical part. The first part summarizes all theoretical knowledge, including the theme of allergies and allergens. It deals with the concept of allergy from the historical point of view, it characterizes the general importance of allergies and its connection with the immune system, it presents individual risk factors influencing the origin and development of allergic disease. A large part of the theoretical part describes allergic diseases including their manifestations, diagnosis and follow-up treatment, and also the individual types of allergens that are classified according to their effects on the organism. Last but not least, the chapter deals with the presence of allergens in the school environment. Also in this part the pedagogical documents - RVP and ŠVP...

The purpose of this project was to develop a Web site that would facilitate students' use of the Internet to research topics relating to the study of biology. This Web site serves as a bridge to link classroom topics to real world scientific information and research available on the Internet. Methods of preventing plagiarism and focusing Internet research were incorporated into the overall Web site design.