Improving the Pipeline for Developing and Testing Pharmacological Treatments in Pregnancy

In a Perspective, Lucy Chappell and Anna David discuss ways to develop and test pharmacological treatments in pregnancy

Past carbonate preservation events in the deep Southeast Atlantic Ocean (Cape Basin) and their implications for Atlantic overturning dynamics and marine carbon cycling

Micropaleontological and geochemical analyses reveal distinct millennial-scale increases in carbonate preservation in the deep Southeast Atlantic (Cape Basin) during strong and prolonged Greenland interstadials that are superimposed on long-term (orbital-scale) changes in carbonate burial. These data suggest carbonate oversaturation of the deep Atlantic and a strengthened Atlantic Meridional Overturning Circulation (AMOC) during the most intense Greenland interstadials. However, proxy evidence from outside the Cape Basin indicate that AMOC changes also occurred during weaker and shorter Greenland interstadials. Here we revisit the link between AMOC dynamics and carbonate saturation in the deep Cape Basin over the last 400 kyr (sediment cores TN057-21, TN057-10 and ODP Site 1089) by reconstructing centennial changes in carbonate preservation using mm-scale X-ray fluorescence (XRF) scanning data. We observe close agreement between variations in XRF Ca/Ti, sedimentary carbonate content and foraminiferal shell fragmentation, reflecting a common control primarily through changing deep-water carbonate saturation. We suggest that the high-frequency (sub-orbital) component of the XRF Ca/Ti records indicates the fast and recurrent redistribution of carbonate ions in the Atlantic basin via the AMOC during both long/strong- and short/weak North Atlantic climate anomalies. In contrast, the low- frequency (orbital) XRF Ca/Ti component is interpreted to reflect slow adjustments through carbonate compensation, and/or changes in the deep-ocean respired carbon content. Our findings emphasize the recurrent influence of rapid AMOC variations on the marine carbonate system during past glacial periods, providing a mechanism for transferring the impacts of North Atlantic climate anomalies to the global carbon cycle via the Southern Ocean.J.G. acknowledges support from the Swiss National Science Foundation (grant 200021_163003), the German Research Foundation (grant GO 2294/2-1) and the Gates Cambridge Trust. L.C.S. acknowledges the Royal Society, the Cambridge Isaac Newton Trust and NERC grant NE/J010545/1. S.L.J was funded by the Swiss National Science Foundation (grants PP00P2-144811 and PP002_172915)

Measurement of the Gluino Mass via Cascade Decays for SPS 1a

If R-parity conserving supersymmetry is realised with masses below the TeV scale, sparticles will be produced and decay in cascades at the LHC. In the case of a neutral LSP, which will not be detected, decay chains cannot be fully reconstructed, complicating the mass determination of the new particles. In this paper we extend the method of obtaining masses from kinematical endpoints to include a gluino at the head of a five-sparticle decay chain. This represents a non-trivial extension of the corresponding method for the squark decay chain. We calculate the endpoints of the new distributions and assess their applicability by examining the theoretical distributions for a variety of mass scenarios. The precision with which the gluino mass can be determined by this method is investigated for the mSUGRA point SPS 1a. Finally we estimate the improvement obtained from adding a Linear Collider measurement of the LSP mass.Comment: 40 pages; extended discussion of error

Nef does not contribute to replication differences between R5 pre-AIDS and AIDS HIV-1 clones from patient ACH142

AIDS-associated, CCR5-tropic (R5) HIV-1 clones, isolated from a patient that never developed CXCR4-tropic HIV-1, replicate to a greater extent and cause greater cytopathic effects than R5 HIV-1 clones isolated before the onset of AIDS. Previously, we showed that HIV-1 Env substantially contributed to the enhanced replication of an AIDS clone. In order to determine if Nef makes a similar contribution, we cloned and phenotypically analyzed nef genes from a series of patient ACH142 derived R5 HIV-1 clones. The AIDS-associated Nef contains a series of residues found in Nef proteins from progressors [1]. In contrast to other reports [1-3], this AIDS-associated Nef downmodulated MHC-I to a greater extent and CD4 less than pre-AIDS Nef proteins. Additionally, all Nef proteins enhanced infectivity similarly in a single round of replication. Combined with our previous study, these data show that evolution of the HIV-1 env gene, but not the nef gene, within patient ACH142 significantly contributed to the enhanced replication and cytopathic effects of the AIDS-associated R5 HIV-1 clone

Concurrent codes:a holographic-type encoding robust against noise and loss

Concurrent coding is an encoding scheme with 'holographic' type properties that are shown here to be robust against a significant amount of noise and signal loss. This single encoding scheme is able to correct for random errors and burst errors simultaneously, but does not rely on cyclic codes. A simple and practical scheme has been tested that displays perfect decoding when the signal to noise ratio is of order -18dB. The same scheme also displays perfect reconstruction when a contiguous block of 40% of the transmission is missing. In addition this scheme is 50% more efficient in terms of transmitted power requirements than equivalent cyclic codes. A simple model is presented that describes the process of decoding and can determine the computational load that would be expected, as well as describing the critical levels of noise and missing data at which false messages begin to be generated

Accurate Liability Estimation Improves Power in Ascertained Case Control Studies

Linear mixed models (LMMs) have emerged as the method of choice for confounded genome-wide association studies. However, the performance of LMMs in non-randomly ascertained case-control studies deteriorates with increasing sample size. We propose a framework called LEAP (Liability Estimator As a Phenotype, https://github.com/omerwe/LEAP) that tests for association with estimated latent values corresponding to severity of phenotype, and demonstrate that this can lead to a substantial power increase

Rossby wave dynamics of the North Pacific extra-tropical response to El Niño: importance of the basic state in coupled GCMs

The extra-tropical response to El Nino in a "low" horizontal resolution coupled climate model, typical of the Intergovernmental Panel on Climate Change fourth assessment report simulations, is shown to have serious systematic errors. A high resolution configuration of the same model has a much improved response that is similar to observations. The errors in the low resolution model are traced to an incorrect representation of the atmospheric teleconnection mechanism that controls the extra-tropical sea surface temperatures (SSTs) during El Nino. This is due to an unrealistic atmospheric mean state, which changes the propagation characteristics of Rossby waves. These erroneous upper tropospheric circulation anomalies then induce erroneous surface circulation features over the North Pacific. The associated surface wind speed and direction errors create erroneous surface flux and upwelling anomalies which finally lead to the incorrect extra-tropical SST response to El Nino in the low resolution model. This highlights the sensitivity of the climate response to a single link in a chain of complex climatic processes. The correct representation of these processes in the high resolution model indicates the importance of horizontal resolution in resolving such processes