REVIEW OF THE NEGOTIATION OF THE MODEL PROTOCOL ADDITIONAL TO THE AGREEMENT(S) BETWEEN STATE(S) AND THE INTERNATIONAL ATOMIC ENERGY AGENCY FOR THE APPLICATION OF SAFEGUARDS,INFCIRC/540 (Corrected) VOLUME I/III SETTING THE STAGE: 1991-1996.

Events in Iraq at the beginning of the 1990s demonstrated that the safeguards system of the International Atomic Energy Agency (IAEA) needed to be improved. It had failed, after all, to detect Iraq's clandestine nuclear weapon program even though some of Iraq's's activities had been pursued at inspected facilities in buildings adjacent to ones being inspected by the IAEA. Although there were aspects of the implementation of safeguards where the IAEA needed to improve, the primary limitations were considered to be part of the safeguards system itself. That system was based on the Nuclear Nonproliferation Treaty of 1970, to which Iraq was a party, and implemented on the basis of a model NPT safeguards agreement, published by the IAEA 1972 as INFCIRC/153 (corrected). The agreement calls for states to accept and for the IAEA to apply safeguards to all nuclear material in the state. Iraq was a party to such an agreement, but it violated the agreement by concealing nuclear material and other nuclear activities from the IAEA. Although the IAEA was inspecting in Iraq, it was hindered by aspects of the agreement that essentially limited its access to points in declared facilities and provided the IAEA with little information about nuclear activities anywhere else in Iraq. As a result, a major review of the NPT safeguards system was initiated by its Director General and Member States with the objective of finding the best means to enable the IAEA to detect both diversions from declared stocks and any undeclared nuclear material or activities in the state. Significant improvements that could be made within existing legal authority were taken quickly, most importantly a change in 1992 in how and when and what design information would be reported to the IAEA. During 1991-1996, the IAEA pursued intensive study, legal and technical analysis, and field trials and held numerous consultations with Member States. The Board of Governors discussed the issue of strengthening safeguards at almost all of its meeting

Regulation of Class-Switch Recombination and Plasma Cell Differentiation by Phosphatidylinositol 3-Kinase Signaling

SummaryClass-switch recombination (CSR) is essential for humoral immunity. However, the regulation of CSR is not completely understood. Here we demonstrate that phosphatidylinositol 3-kinase (PI3K) actively suppressed the onset and frequency of CSR in primary B cells. Consistently, mice lacking the lipid phosphatase, PTEN, in B cells exhibited a hyper-IgM condition due to impaired CSR, which could be restored in vitro by specific inhibition of PI3Kδ. Inhibition of CSR by PI3K was partially dependent on the transcription factor, BLIMP1, linking plasma cell commitment and cessation of CSR. PI3K-dependent activation of the serine-threonine kinase, Akt, suppressed CSR, in part, through the inactivation of the Forkhead Box family (Foxo) of transcription factors. Reduced PI3K signaling enhanced the expression of AID (activation-induced cytidine deaminase) and accelerated CSR. However, ectopic expression of AID could not fully overcome inhibition of CSR by PI3K, suggesting that PI3K regulates both the expression and function of AID

Coordinate suppression of B cell lymphoma by PTEN and SHIP phosphatases

Mice lacking both PTEN and SHIP phosphatases develop spontaneous B cell lymphoma

B Cells Participate in Thymic Negative Selection of Murine Auto-reactive CD4+ T Cells

It is well documented that thymic epithelial cells participate in the process of negative selection in the thymus. In recent years it was reported that also dendritic cells enter the thymus and contribute to this process, thus allowing for the depletion of thymocytes that are specific to peripherally expressed self-antigens. Here we report that also B cells may take part in the elimination of auto-reactive thymocytes. Using a unique mouse model we show that B cells induce negative selection of self-reactive thymocytes in a process that leads to the deletion of these cells whereas regulatory T cells are spared. These findings have direct implication in autoimmunity, as expression of a myelin antigen by B cells in the thymus renders the mice resistant to autoimmune inflammation of the CNS

Gαq-containing G proteins regulate B cell selection and survival and are required to prevent B cell–dependent autoimmunity

Survival of mature B cells is regulated by B cell receptor and BAFFR-dependent signals. We show that B cells from mice lacking the Gαq subunit of trimeric G proteins (Gnaq−/− mice) have an intrinsic survival advantage over normal B cells, even in the absence of BAFF. Gnaq−/− B cells develop normally in the bone marrow but inappropriately survive peripheral tolerance checkpoints, leading to the accumulation of transitional, marginal zone, and follicular B cells, many of which are autoreactive. Gnaq−/− chimeric mice rapidly develop arthritis as well as other manifestations of systemic autoimmune disease. Importantly, we demonstrate that the development of the autoreactive B cell compartment is the result of an intrinsic defect in Gnaq−/− B cells, resulting in the aberrant activation of the prosurvival factor Akt. Together, these data show for the first time that signaling through trimeric G proteins is critically important for maintaining control of peripheral B cell tolerance induction and repressing autoimmunity

Crucial Role for BAFF-BAFF-R Signaling in the Survival and Maintenance of Mature B Cells

Defects in the expression of either BAFF (B cell activating factor) or BAFF-R impairs B cell development beyond the immature, transitional type-1 stage and thus, prevents the formation of follicular and marginal zone B cells, whereas B-1 B cells remain unaffected. The expression of BAFF-R on all mature B cells might suggest a role for BAFF-R signaling also for their in vivo maintenance. Here, we show that, 14 days following a single injection of an anti-BAFF-R mAb that prevents BAFF binding, both follicular and marginal zone B cell numbers are drastically reduced, whereas B-1 cells are not affected. Injection of control, isotype-matched but non-blocking anti-BAFF-R mAbs does not result in B cell depletion. We also show that this depletion is neither due to antibody-dependent cellular cytotoxicity nor to complement-mediated lysis. Moreover, prevention of BAFF binding leads to a decrease in the size of the B cell follicles, an impairment of a T cell dependent humoral immune response and a reduction in the formation of memory B cells. Collectively, these results establish a central role for BAFF-BAFF-R signaling in the in vivo survival and maintenance of both follicular and marginal zone B cell pools

Predicting Perceptions of Inmate Sexual Violence in Female Correctional Institutions: Individual Factors Versus Social Climate Factors

Although there has been a lot of research conducted on inmate sexual violence in male correctional institutions, there is a scarcity of published literature on perceptions of inmate sexual violence in female institutions, and in recognizing the differences between individual-related factors and social climate related factors. In this study, survey data from a recent National Institute of Justice funded PREA study were used in classifying several independent variables into two predictive models that were representative of both individual-related factors, such as race, gender, criminal history, etc., as well as a social climate-related factors, such as verbal conflict, economic conflict, staff sexual misconduct, etc. We then examined the predictive abilities of both models on female inmate perceptions of inmate sexual violence in both prison and jail housing units. Results showed social climate factors to be a much better predictor of inmate perceptions of sexual violence. These results suggest that all of the expense and effort to profile and classify inmates is not as critical as attempts to improve the social climate or environment of the institution

Real-time computer analysis for nuclear material detection. Part 3. Nuclear instrumentation interface

An electronic interface between a Digital Equipment Corporation (DEC) LSI-11 microcomputer and a LeCroy Research Systems model 3001 qVt multichannel analyzer is described in detail. This interface provides for 16-bit parallel data transfer from the memory of the analyzer to the memory of the computer. An unusual feature of the interface is a provision that allows storage of counts of logic pulses (e.g., from radiation detector discriminators) in the first 16 channels of the analyzer's memory. A further provision allows use of a LeCroy printer and display interface that is designed specifically as a companion module to the qVt analyzer

REVIEW OF THE NEGOTIATION OF THE MODEL PROTOCOL ADDITIONAL TO THE AGREEMENT(S) BETWEEN STATE(S) AND THE INTERNATIONAL ATOMIC ENERGY AGENCY FOR THE APPLICATION OF SAFEGUARDS,INFCIRC/540 (Corrected) VOLUME I/III SETTING THE STAGE: 1991-1996.

Events in Iraq at the beginning of the 1990s demonstrated that the safeguards system of the International Atomic Energy Agency (IAEA) needed to be improved. It had failed, after all, to detect Iraq's clandestine nuclear weapon program even though some of Iraq's's activities had been pursued at inspected facilities in buildings adjacent to ones being inspected by the IAEA. Although there were aspects of the implementation of safeguards where the IAEA needed to improve, the primary limitations were considered to be part of the safeguards system itself. That system was based on the Nuclear Nonproliferation Treaty of 1970, to which Iraq was a party, and implemented on the basis of a model NPT safeguards agreement, published by the IAEA 1972 as INFCIRC/153 (corrected). The agreement calls for states to accept and for the IAEA to apply safeguards to all nuclear material in the state. Iraq was a party to such an agreement, but it violated the agreement by concealing nuclear material and other nuclear activities from the IAEA. Although the IAEA was inspecting in Iraq, it was hindered by aspects of the agreement that essentially limited its access to points in declared facilities and provided the IAEA with little information about nuclear activities anywhere else in Iraq. As a result, a major review of the NPT safeguards system was initiated by its Director General and Member States with the objective of finding the best means to enable the IAEA to detect both diversions from declared stocks and any undeclared nuclear material or activities in the state. Significant improvements that could be made within existing legal authority were taken quickly, most importantly a change in 1992 in how and when and what design information would be reported to the IAEA. During 1991-1996, the IAEA pursued intensive study, legal and technical analysis, and field trials and held numerous consultations with Member States. The Board of Governors discussed the issue of strengthening safeguards at almost all of its meeting