An Altered Derivatives Marketplace: Clearing Swaps Under Dodd-Frank

Though over a year has passed, the impact of the Dodd Frank Act remains unclear. This Note examines the provisions of the Act that relate to swap transactions within the context of pre-reform and postreform markets. In order to reduce the uncertainties inherent in unregulated swap transactions, the Act employs a comprehensive framework, which includes mandatory clearing through derivative clearing organizations, extensive reporting requirements, margin requirements, and position limits. This Note argues that, in doing so, the Dodd Frank Act addresses the fundamental failures of pre-reform derivative markets. However, the importance of the role for derivative clearing organizations under this framework creates a risk that these organizations will become systemically significant, mirroring problems with under-capitalized and over-exposed financial institutions in the downturn

PD-1 Blockade in Chronically HIV-1-Infected Humanized Mice Suppresses Viral Loads

An estimated 34 million people are living with HIV worldwide (UNAIDS, 2012), with the number of infected persons rising every year. Increases in HIV prevalence have resulted not only from new infections, but also from increases in the survival of HIV-infected persons produced by effective anti-retroviral therapies. Augmentation of anti-viral immune responses may be able to further increase the survival of HIV-infected persons. One strategy to augment these responses is to reinvigorate exhausted anti-HIV immune cells present in chronically infected persons. The PD-1-PD-L1 pathway has been implicated in the exhaustion of virus-specific T cells during chronic HIV infection. Inhibition of PD-1 signaling using blocking anti-PD-1 antibodies has been shown to reduce simian immunodeficiency virus (SIV) loads in monkeys. We now show that PD-1 blockade can improve control of HIV replication in vivo in an animal model. BLT (Bone marrow-Liver-Thymus) humanized mice chronically infected with HIV-1 were treated with an anti-PD-1 antibody over a 10-day period. The PD-1 blockade resulted in a very significant 45-fold reduction in HIV viral loads in humanized mice with high CD8+ T cell expression of PD-1, compared to controls at 4 weeks post-treatment. The anti-PD-1 antibody treatment also resulted in a significant increase in CD8+ T cells. PD-1 blockade did not affect T cell expression of other inhibitory receptors co-expressed with PD-1, including CD244, CD160 and LAG-3, and did not appear to affect virus-specific humoral immune responses. These data demonstrate that inhibiting PD-1 signaling can reduce HIV viral loads in vivo in the humanized BLT mouse model, suggesting that blockade of the PD-1-PD-L1 pathway may have therapeutic potential in the treatment of patients already infected with the AIDS virus

Nitrate leaching from short-hydroperiod floodplain soils

Numerous studies have shown the importance of riparian zones to reduce nitrate (NO<sub>3</sub><sup>−</sup>) contamination coming from adjacent agricultural land. Much less is known about nitrogen (N) transformations and nitrate fluxes in riparian soils with short hydroperiods (1–3 days of inundation) and there is no study that could show whether these soils are a N sink or source. Within a restored section of the Thur River in NE Switzerland, we measured nitrate concentrations in soil solutions as an indicator of the net nitrate production. Samples were collected along a quasi-successional gradient from frequently inundated gravel bars to an alluvial forest, at three different depths (10, 50 and 100 cm) over a one-year period. Along this gradient we quantified N input (atmospheric deposition and sedimentation) and N output (leaching) to create a nitrogen balance and assess the risk of nitrate leaching from the unsaturated soil to the groundwater. Overall, the main factor explaining the differences in nitrate concentrations was the field capacity (FC). In subsoils with high FCs and VWC near FC, high nitrate concentrations were observed, often exceeding the Swiss and EU groundwater quality criterions of 400 and 800 μmol L<sup>−1</sup>, respectively. High sedimentation rates of river-derived nitrogen led to apparent N retention up to 200 kg N ha<sup>−1</sup> yr<sup>−1</sup> in the frequently inundated zones. By contrast, in the mature alluvial forest, nitrate leaching exceeded total N input most of the time. As a result of the large soil N pools, high amounts of nitrate were produced by nitrification and up to 94 kg N-NO<sub>3</sub><sup>−</sup> ha<sup>−1</sup> yr<sup>−1</sup> were leached into the groundwater. Thus, during flooding when water fluxes are high, nitrate from soils can contribute up to 11% to the total nitrate load in groundwater

Targeted therapy in nuclear medicine—current status and future prospects

In recent years, a number of new developments in targeted therapies using radiolabeled compounds have emerged. New developments and insights in radioiodine treatment of thyroid cancer, treatment of lymphoma and solid tumors with radiolabeled monoclonal antibodies (mAbs), the developments in the application of radiolabeled small receptor-specific molecules such as meta-iodobenzylguanidine and peptides and the position of locoregional treatment in malignant involvement of the liver are reviewed. The introduction of recombinant human thyroid-stimulating hormone and the possibility to enhance iodine uptake with retinoids has changed the radioiodine treatment protocol of patients with thyroid cancer. Introduction of radiolabeled mAbs has provided additional treatment options in patients with malignant lymphoma, while a similar approach proves to be cumbersome in patients with solid tumors. With radiolabeled small molecules that target specific receptors on tumor cells, high radiation doses can be directed to tumors in patients with disseminated disease. Radiolabeled somatostatin derivatives for the treatment of neuroendocrine tumors are the role model for this approach. Locoregional treatment with radiopharmaceuticals of patients with hepatocellular carcinoma or metastases to the liver may be used in inoperable cases, but may also be of benefit in a neo-adjuvant or adjuvant setting. Significant developments in the application of targeted radionuclide therapy have taken place. New treatment modalities have been introduced in the clinic. The concept of combining therapeutic radiopharmaceuticals with other treatment modalities is more extensively explore

Comprehensive analysis of draft genomes of two closely related pseudomonas syringae phylogroup 2b strains infecting mono- and dicotyledon host plants

Comparison of the prophage region in Pseudomonas syringae strain SM (A) with the corresponding regions in strains 1845 (B) and 2507 (C) using MAUVE software (Darling et al. 2010). (PNG 2118 kb

Pedunculopontine nucleus gamma band activity-preconscious awareness, waking, and REM sleep

The pedunculopontine nucleus (PPN) is a major component of the reticular activating system (RAS) that regulates waking and REM sleep, states of high-frequency EEG activity. Recently,we described the presence of high threshold, voltage-dependent N- and P/Q-type calcium channels in RAS nuclei that subserve gamma band oscillations in the mesopontine PPN, intralaminar parafascicular nucleus (Pf), and pontine subcoeruleus nucleus dorsalis (SubCD). Cortical gamma band activity participates in sensory perception, problem solving, and memory. Rather than participating in the temporal binding of sensory events as in the cortex, gamma band activity in the RAS may participate in the processes of preconscious awareness, and provide the essential stream of information for the formulation of many of our actions.That is, the RAS may play an early permissive role in volition. Our latest results suggest that (1) the manifestation of gamma band activity during waking may employ a separate intracellular pathway compared to that during REM sleep, (2) neuronal calcium sensor (NCS-1) protein, which is over expressed in schizophrenia and bipolar disorder, modulates gamma band oscillations in the PPN in a concentration-dependent manner, (3) leptin, which undergoes resistance in obesity resulting in sleep dysregulation, decreases sodium currents in PPN neurons, accounting for its normal attenuation of waking, and (4) following our discovery of electrical coupling in the RAS, we Hypothesize that there are cell clusters within the PPN that may act in concert. These results provide novel information on the mechanisms controlling high-frequency activity related to waking and REM sleep by elements of the RAS.Fil: Urbano Suarez, Francisco Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas (i); ArgentinaFil: Donofrio, Stasia M.. University Of Arkansas For Medical Sciences; Estados UnidosFil: Luster, Brennon R.. University Of Arkansas For Medical Sciences; Estados UnidosFil: Beck, Paige B.. University Of Arkansas For Medical Sciences; Estados UnidosFil: Hyde, James Robert. University Of Arkansas For Medical Sciences; Estados UnidosFil: Bisagno, Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas (i); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Garcia Rill, Edgar. University Of Arkansas For Medical Sciences; Estados Unido

Colonic Patch and colonic SILT development are independent and differentially-regulated events

Intestinal lymphoid tissues have to simultaneously ensure protection against pathogens and tolerance towards commensals. Despite such vital functions, their development in the colon is poorly understood. Here, we show that the two distinct lymphoid tissues of the colon–colonic patches and colonic SILTs–can easily be distinguished based on anatomical location, developmental timeframe and cellular organization. Furthermore, whereas colonic patch development depended on CXCL13-mediated LTi cell clustering followed by LTα-mediated consolidation, early LTi clustering at SILT anlagen did not require CXCL13, CCR6 or CXCR3. Subsequent dendritic cell recruitment to and gp38+VCAM-1+ lymphoid stromal cell differentiation within SILTs required LTα; B cell recruitment and follicular dendritic cell differentiation depended on MyD88-mediated signalling, but not the microflora. In conclusion, our data demonstrate that different mechanisms, mediated mainly by programmed stimuli, induce the formation of distinct colonic lymphoid tissues, therefore suggesting that these tissues may have different functions

Functional diversity of chemokines and chemokine receptors in response to viral infection of the central nervous system.

Encounters with neurotropic viruses result in varied outcomes ranging from encephalitis, paralytic poliomyelitis or other serious consequences to relatively benign infection. One of the principal factors that control the outcome of infection is the localized tissue response and subsequent immune response directed against the invading toxic agent. It is the role of the immune system to contain and control the spread of virus infection in the central nervous system (CNS), and paradoxically, this response may also be pathologic. Chemokines are potent proinflammatory molecules whose expression within virally infected tissues is often associated with protection and/or pathology which correlates with migration and accumulation of immune cells. Indeed, studies with a neurotropic murine coronavirus, mouse hepatitis virus (MHV), have provided important insight into the functional roles of chemokines and chemokine receptors in participating in various aspects of host defense as well as disease development within the CNS. This chapter will highlight recent discoveries that have provided insight into the diverse biologic roles of chemokines and their receptors in coordinating immune responses following viral infection of the CNS