Diffusion-weighted MRI characteristics of the cerebral metastasis to brain boundary predicts patient outcomes.

DWI demonstrates changes in the tumor, across the tumor edge and in the peritumoral region which may not be visible on conventional MRI and this may be useful in predicting patient outcomes for operated cerebral metastases

Increasing the detectability of external influence on precipitation by correcting feature location in GCMs

Understanding how precipitation varies as the climate changes is essential to determining the true impact of global warming. This is a difficult task not only due to the large internal variability observed in precipitation but also because of a limited historical record and large biases in simulations of precipitation by general circulation models (GCMs). Here we make use of a technique that spatially and seasonally transforms GCM fields to reduce location biases and investigate the potential of this bias correction to study historical changes. We use two versions of this bias correction—one that conserves intensities and another that conserves integrated precipitation over transformed areas. Focussing on multimodel ensemble means, we find that both versions reduce RMS error in the historical trend by approximately 11% relative to the Global Precipitation Climatology Project (GPCP) data set. By regressing GCMs' historical simulations of precipitation onto radiative forcings, we decompose these simulations into anthropogenic and natural time series. We then perform a simple detection and attribution study to investigate the impact of reducing location biases on detectability. A multiple ordinary least squares regression of GPCP onto the anthropogenic and natural time series, with the assumptions made, finds anthropogenic detectability only when spatial corrections are applied. The result is the same regardless of which form of conservation is used and without reducing the dimensionality of the fields beyond taking zonal means. While “detectability” is dependent both on the exact methodology and the confidence required, this nevertheless demonstrates the potential benefits of correcting location biases in GCMs when studying historical precipitation, especially in cases where a signal was previously undetectable

Quantitative Susceptibility Mapping by Inversion of a Perturbation Field Model: Correlation With Brain Iron in Normal Aging

There is increasing evidence that iron deposition occurs in specific regions of the brain in normal aging and neurodegenerative disorders such as Parkinson's, Huntington's, and Alzheimer's disease. Iron deposition changes the magnetic susceptibility of tissue, which alters the MR signal phase, and allows estimation of susceptibility differences using quantitative susceptibility mapping (QSM). We present a method for quantifying susceptibility by inversion of a perturbation model, or “QSIP.” The perturbation model relates phase to susceptibility using a kernel calculated in the spatial domain, in contrast to previous Fourier-based techniques. A tissue/air susceptibility atlas is used to estimate B[subscript 0] inhomogeneity. QSIP estimates in young and elderly subjects are compared to postmortem iron estimates, maps of the Field-Dependent Relaxation Rate Increase, and the L1-QSM method. Results for both groups showed excellent agreement with published postmortem data and in vivo FDRI: statistically significant Spearman correlations ranging from Rho=0.905 to Rho=1.00 were obtained. QSIP also showed improvement over FDRI and L1-QSM: reduced variance in susceptibility estimates and statistically significant group differences were detected in striatal and brainstem nuclei, consistent with age-dependent iron accumulation in these regions.National Institutes of Health (U.S.) (Grant P41EB015902)National Institutes of Health (U.S.) (Grant P41RR013218)National Institutes of Health (U.S.) (Grant P41EB015898)National Institutes of Health (U.S.) (Grant P41RR019703)National Institutes of Health (U.S.) (Grant T32EB0011680-06)National Institutes of Health (U.S.) (Grant K05AA017168)National Institutes of Health (U.S.) (Grant R01AA012388

6-Deoxyhexoses froml-Rhamnose in the Search for Inducers of the Rhamnose Operon: Synergy of Chemistry and Biotechnology

In the search for alternative non‐metabolizable inducers in the l ‐rhamnose promoter system, the synthesis of fifteen 6‐deoxyhexoses from l ‐rhamnose demonstrates the value of synergy between biotechnology and chemistry. The readily available 2,3‐acetonide of rhamnonolactone allows inversion of configuration at C4 and/or C5 of rhamnose to give 6‐deoxy‐d ‐allose, 6‐deoxy‐d ‐gulose and 6‐deoxy‐l ‐talose. Highly crystalline 3,5‐benzylidene rhamnonolactone gives easy access to l ‐quinovose (6‐deoxy‐l ‐glucose), l ‐olivose and rhamnose analogue with C2 azido, amino and acetamido substituents. Electrophilic fluorination of rhamnal gives a mixture of 2‐deoxy‐2‐fluoro‐l ‐rhamnose and 2‐deoxy‐2‐fluoro‐l ‐quinovose. Biotechnology provides access to 6‐deoxy‐l ‐altrose and 1‐deoxy‐l ‐fructose

O-mannosylation in Candida albicans enables development of interkingdom biofilm communities

Peer reviewedPublisher PD

Composition and activity of the non-canonical Gram-positive SecY2 complex

The accessory Sec system in Streptococcus gordonii DL1 is a specialized export system that transports a large serine-rich repeat protein, Hsa, to the bacterial surface. The system is composed of core proteins SecA2 and SecY2 and accessory Sec proteins Asp1–Asp5. Similar to canonical SecYEG, SecY2 forms a channel for translocation of the Hsa adhesin across the cytoplasmic membrane. Accessory Sec proteins Asp4 and Asp5 have been suggested to work alongside SecY2 to form the translocon, similar to the associated SecY, SecE, and SecG of the canonical system (SecYEG). To test this theory, S. gordonii secY2, asp4, and asp5 were co-expressed in Escherichia coli. The resultant complex was subsequently purified, and its composition was confirmed by mass spectrometry to be SecY2-Asp4-Asp5. Like SecYEG, the non-canonical complex activates the ATPase activity of the SecA motor (SecA2). This study also shows that Asp4 and Asp5 are necessary for optimal adhesion of S. gordonii to glycoproteins gp340 and fibronectin, known Hsa binding partners, as well as for early stage biofilm formation. This work opens new avenues for understanding the structure and function of the accessory Sec system

Informatics and data mining tools and strategies for the Human Connectome Project

The Human Connectome Project (HCP) is a major endeavor that will acquire and analyze connectivity data plus other neuroimaging, behavioral, and genetic data from 1,200 healthy adults. It will serve as a key resource for the neuroscience research community, enabling discoveries of how the brain is wired and how it functions in different individuals. To fulfill its potential, the HCP consortium is developing an informatics platform that will handle: 1) storage of primary and processed data, 2) systematic processing and analysis of the data, 3) open access data sharing, and 4) mining and exploration of the data. This informatics platform will include two primary components. ConnectomeDB will provide database services for storing and distributing the data, as well as data analysis pipelines. Connectome Workbench will provide visualization and exploration capabilities. The platform will be based on standard data formats and provide an open set of application programming interfaces (APIs) that will facilitate broad utilization of the data and integration of HCP services into a variety of external applications. Primary and processed data generated by the HCP will be openly shared with the scientific community, and the informatics platform will be available under an open source license. This paper describes the HCP informatics platform as currently envisioned and places it into the context of the overall HCP vision and agenda

Does transparency overcome conflicts of interest? Evidence from investment managers and their brokers.

The relationship between investment managers and brokers has been identified by regulators in Europe and the US as a potentially important source of con icts of interest. Little systematic evidence is available, however, on this complex relationship, which involves trade execution, sell-side research, and a variety of bundled services. This paper reports the outcome of a landmark ruling under the UK Freedom of Information Act, which allowed us to obtain, from UK pension funds, information on commissions, trading activity, payments for research and other variables. We find that following recent regulatory changes in the UK to increase transparency, average commission rates have fallen. However, trading has increased signicantly, resulting in total commission payments to brokers more than doubling between 2003 and 2007

Uncertainty categories in medical image segmentation: a study of source-related diversity

Measuring uncertainties in the output of a deep learning method is useful in several ways, such as in assisting with interpretation of the outputs, helping build confidence with end users, and for improving the training and performance of the networks. Several different methods have been proposed to estimate uncertainties, including those from epistemic (relating to the model used) and aleatoric (relating to the data) sources using test-time dropout and augmentation, respectively. Not only are these uncertainty sources different, but they are governed by parameter settings (e.g., dropout rate or type and level of augmentation) that establish even more distinct uncertainty categories. This work investigates how different the uncertainties are from these categories, for magnitude and spatial pattern, to empirically address the question of whether they provide usefully distinct information that should be captured whenever uncertainties are used. We take the well characterised BraTS challenge dataset to demonstrate that there are substantial differences in both magnitude and spatial pattern of uncertainties from the different categories, and discuss the implications of these in various use cases