Thesis (M.P.H.)--University of Michigan, 1946.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1939. / Typescript. Includes abstract and vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 100-109).

Thesis (D.P.H.)--University of Michigan.

Thesis (Ph. D.)--Ohio State University, 2005. / Available online via OhioLINK's ETD Center; full text release delayed at author's request until 2008 Jun 1

Dissertation (D.P.H.)--University of Michigan.

Human APOBEC3 proteins are host-encoded intrinsic restriction factors that can prevent the replication of a broad range of human and animal retroviruses such as HIV, SIV, FIV, MLVs and XMRV. The main pathway of the restriction is believed to occur as a result of the cytidine deaminase activity of these proteins that converts cytidines into uridines in single-stranded DNA retroviral replication intermediates. Uridines in these DNA intermediates disrupt the viral replication cycle and also alter retrovirus infectivity because of the C-to-T transition mutations generated as a result of the deaminase activity on the minus strand DNA. In addition, human APOBEC3 proteins also exhibit a deamination-independent pathway to restrict retroviruses that is not currently well understood. Although the restriction of retroviruses by human APOBEC3 proteins has been intensely studied in vitro, our understanding of how the murine APOBEC3 (mA3) protein restricts retroviruses and/or prevents zoonotic infections in vivo is very limited. In contrast to humans and primates that have 7 APOBEC3 genes, mice have but a single copy. My study of the function and structure of mA3 revealed that it has an inverted functional organization for cytidine deamination in comparison to the human A3G catalytic sites. I have also found that disruption of the integrity of either of these catalytic sites substantially impedes restriction of HIV and MLV. Interestingly, our data shows that mA3 induces a significant decrease in retroviral activity of HIV and MLVs by exploiting both deamination-dependent and -independent pathways. However, the deaminase activity of mA3 is essential to confer long-term restriction of retroviral infection. My observations suggest that mA3 has dual activities, both deamination-dependent and -independent, that work cooperatively to restrict a broad range of human and animal retroviral pathogens. In the context of the intrinsic immune system, APOBEC3 proteins provide a powerful block to the transmission of retroviral pathogens that very few have found ways to evade.

Previous studies with conjugates containing the NH2-terminal and COOH-terminal antigenic determinants of oxidized ferredoxin from C. pasteurianum indicated a need for at least two determinants to stimulate DNA synthesis in sensitized lymphocytes. This suggested a mechanism involving cell cooperation, a possibility which has been investigated here by selectively inactivating cells binding one or the other of the determinants. Cells from immunized guinea pigs were tested in vitro for their capacity to bind antigen or to be stimulated by it before and after "antigen suicide" with radioiodinated conjugates containing the NH2-terminal or COOH-terminal determinants of oxidized ferredoxin. A microculture system for assessing antigen induced stimulation of 3H-thymidine uptake by lymphocytes was developed for this work. The data show that: 1) Lymphocytes from unimmunized guinea pigs bind both NH2-terminal and COOH-terminal determinants at a frequency of about 10-4. In immune animals the proportion of antigen binding cells increased about 4-6 fold. The frequency of cells binding the determinants depends markedly on the specific activity of antigens employed. 2) Both T and B lymphocytes bind the antigenic determinants from oxidized ferredoxin. 3) Specific inactivation of cells binding either determinant was achieved by antigen suicide with ¹²⁵I-NH₂-terminal or ¹²⁵I COOH-terminal s-BSA conjugates. Synergy occurs between the NH2-terminal binding cells and COOH-terminal binding cells in the proliferative response of sensitized lymph node cells challenged with oxidized ferredoxin in vitro. Evidence from B cell depletion studies indicates that this is a T cell-T cell interaction. / Science, Faculty of / Microbiology and Immunology, Department of / Graduate

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The People’s Republic of China (“China”) claims absolute immunity for itself but embraces a concept of state for immunity purposes that excludes state-owned enterprises (“SOEs”). This position has led to confusion and frustration in international litigation against China and Chinese SOEs, particularly when massive Chinese foreign investments are led by SOEs, including those made under China’s Belt and Road Initiative. Yet, the immunity status of Chinese SOEs is unclear. Against this backdrop, this thesis examines Chinese SOEs’ ability to claim sovereign immunity under the customary international law of restrictive immunity as expressed and built on in the 2004 United Nations Convention on Jurisdictional Immunities of States and Their Property (“UNCSI”), the 1976 United States Foreign Sovereign Immunities Act (“US FSIA”) and the 1978 United Kingdom State Immunity Act (“UK SIA”). In investigating the immunity status of the 97 SOEs in which the Chinese central government has direct and full/majority ownership, this thesis answers two questions: (1) under what circumstances would these 97 Chinese SOEs be treated as part of the state for immunity purposes under the UNCSI, the US FSIA and the UK SIA; and (2) under what circumstances would these 97 Chinese SOEs attract jurisdictional and execution immunities thereunder. A critical part of this analysis involves developing an understanding of Chinese SOEs’ dual identity as defined by the Chinese political economy. Chinese SOEs’ dual identity has two levels of meaning. First, it reflects the fact that some Chinese SOEs are categorized as commercial SOEs and others are categorized as public welfare SOEs in the current SOE reform. Secondly, commercial Chinese SOEs have a dual identity, i.e., a commercial and a sovereign aspect in their operations. While commercial SOEs’ primary goal is to pursue commercial interests, they also implement the state’s social, political, and economic policy goals. This sovereign aspect—primarily reflected as the sovereign purpose in their commercial transactions—adds complexity, but is necessary, to our assessment of Chinese SOEs’ “state” status and immunity under the customary international law of sovereign immunity. The three regimes studied in this thesis—the UNCSI, the US FSIA, and the UK SIA—not only take distinctive approaches toward the definition of the state, but also to the commercial exceptions to jurisdictional immunity and execution immunity. Their different analytical frameworks take us to different conclusions about Chinese SOEs’ “state” status and immunity in some cases. Under the UNCSI and the UK SIA, in principle, Chinese SOEs are unlikely to acquire “state” status to claim immunity in their commercial capacity, and consequently, unable to attract jurisdictional immunity and execution immunity for their assets as separate entities. But public welfare SOEs and some commercial SOEs can potentially attract jurisdictional immunity and execution immunity for their assets because to the extent that the purposes of their conduct—which are often related to inherently sovereign functions like the military or the public welfare—are considered in the overall context, the nature of the commercial transaction could be converted into a sovereign one. Under the US FSIA, Chinese SOEs—either commercial or public welfare ones—are state agencies/instrumentalities for immunity purposes, thus, have “state” status. But, in contrast with the UNCSI and the UK SIA, Chinese SOEs are less likely to attract jurisdictional immunity for their commercial activities or execution immunity for their assets under the US FSIA because the US statute applies a broad commercial exception that only considers the nature of the conduct in characterizing whether a transaction is a commercial one. This thesis’s investigations and conclusions have commercial, sovereign, and policy implications for Chinese SOEs’ international business transactions, China’s sovereign immunity position, and litigation involving China and Chinese SOEs in jurisdictions where restrictive immunity is upheld. First, in commercial terms, the analysis in this thesis will better enable commercial parties and states that have commercial relations with Chinese SOEs to understand the dual identity of Chinese SOEs defined by the Chinese political economy and understand under what circumstances Chinese SOEs can potentially attract jurisdictional and execution immunities. Second, in sovereign terms, my research enables states to assess their diplomatic and economic relationships with China from a foreign relations law perspective as China asserts absolute immunity in foreign domestic courts. As this thesis suggests, litigation against China and its emanations and execution against their assets in states where restrictive immunity is applied could give rise to sensitive political clashes in light of China’s absolute immunity position. The ongoing pandemic litigation between the State of Missouri and China in the US court is an example. In line with its practice, China refused to appear in this and other similar cases. My thesis work could provide legal researchers and practitioners with a better informed legal perspective on these highly political disputes. Third, in policy terms, my Chapter on China’s sovereign immunity and my findings that some commercial and public welfare SOEs can potentially attract jurisdictional and execution immunities under the UNCSI and the UK SIA provide China some reasons to not only embrace restrictive immunity but to clarify the definition of the state for immunity purposes thereunder. Ratifying the UNCSI, in my view, would allow China’s position to conform to international law on the one hand; and allow China to contribute to the development of the law of sovereign immunity on the other hand.

Outer membrane proteins (OMPs) were recovered from eleven strains (eight serogroups) of Legionella pneumophila by sequential treatment with Tris buffer (pH 8), citrate buffer(pH 2.75) and Tris buffer (pH 8). Transmission electron microscopy revealed clearly the separation of the outer membrane from the bacteria. The development of delayed hypersensitivity was also noted by measuring the area of arythema and induration produced by intradermal injections of the MPSs from Chicago 8 strain. The adjuvants enhanced greatly both active and cell-meditated immunity (CMI). Transient lymphocytopenia with a slight rise in neutrophils was noted in each of the immunized groups. Intraperitoneal challenge, seven days after the OMP booster, of one LD (1.5 x10^6) of legionellae resulted in lymphocytopenia with elevated neutrophils. All immunized rats survived the challenge, although those in the saline-OMP group were clearly the sickest. Post-challenge, legionella antibody titers rose greatly and CMI was heightened. Passive immunization (homologous and heterologous) was found to protect the rats from a challenge of on LD. Actively-immunized rats retained their immunity for at least six months as determined by their resistance to a second challenge.