An Improved Algorithm for Generating Database Transactions from Relational Algebra Specifications

Alloy is a lightweight modeling formalism based on relational algebra. In prior work with Fisler, Giannakopoulos, Krishnamurthi, and Yoo, we have presented a tool, Alchemy, that compiles Alloy specifications into implementations that execute against persistent databases. The foundation of Alchemy is an algorithm for rewriting relational algebra formulas into code for database transactions. In this paper we report on recent progress in improving the robustness and efficiency of this transformation

Integrative analysis identifies candidate tumor microenvironment and intracellular signaling pathways that define tumor heterogeneity in NF1

Neurofibromatosis type 1 (NF1) is a monogenic syndrome that gives rise to numerous symptoms including cognitive impairment, skeletal abnormalities, and growth of benign nerve sheath tumors. Nearly all NF1 patients develop cutaneous neurofibromas (cNFs), which occur on the skin surface, whereas 40-60% of patients develop plexiform neurofibromas (pNFs), which are deeply embedded in the peripheral nerves. Patients with pNFs have a ~10% lifetime chance of these tumors becoming malignant peripheral nerve sheath tumors (MPNSTs). These tumors have a severe prognosis and few treatment options other than surgery. Given the lack of therapeutic options available to patients with these tumors, identification of druggable pathways or other key molecular features could aid ongoing therapeutic discovery studies. In this work, we used statistical and machine learning methods to analyze 77 NF1 tumors with genomic data to characterize key signaling pathways that distinguish these tumors and identify candidates for drug development. We identified subsets of latent gene expression variables that may be important in the identification and etiology of cNFs, pNFs, other neurofibromas, and MPNSTs. Furthermore, we characterized the association between these latent variables and genetic variants, immune deconvolution predictions, and protein activity predictions

Neutron cryo-crystallography captures the protonation state of ferryl heme in a peroxidase

Heme enzymes activate oxygen through formation of transient iron-oxo (ferryl) intermediates of the heme iron. A long-standing question has been the nature of the iron-oxygen bond and, in particular, the protonation state. We present neutron structures of the ferric derivative of cytochrome c peroxidase and its ferryl intermediate; these allow direct visualization of protonation states. We demonstrate that the ferryl heme is an Fe(IV)=O species and is not protonated. Comparison of the structures shows that the distal histidine becomes protonated on formation of the ferryl intermediate, which has implications for the understanding of O–O bond cleavage in heme enzymes. The structures highlight the advantages of neutron cryo-crystallography in probing reaction mechanisms and visualizing protonation states in enzyme intermediates

High-resolution neutron and X-ray diffraction room-temperature studies of an H-FABP-oleic acid complex: study of the internal water cluster and ligand binding by a transferred multipolar electron-density distribution

Crystal diffraction data of heart fatty acid binding protein (H-FABP) in complex with oleic acid were measured at room temperature with high-resolution X-ray and neutron protein crystallography (0.98 and 1.90 Å resolution, respectively). These data provided very detailed information about the cluster of water molecules and the bound oleic acid in the H-FABP large internal cavity. The jointly refined X-ray/neutron structure of H-FABP was complemented by a transferred multipolar electron-density distribution using the parameters of the ELMAMII library. The resulting electron density allowed a precise determination of the electrostatic potential in the fatty acid (FA) binding pocket. Bader's quantum theory of atoms in molecules was then used to study interactions involving the internal water molecules, the FA and the protein. This approach showed H···H contacts of the FA with highly conserved hydrophobic residues known to play a role in the stabilization of long-chain FAs in the binding cavity. The determination of water hydrogen (deuterium) positions allowed the analysis of the orientation and electrostatic properties of the water molecules in the very ordered cluster. As a result, a significant alignment of the permanent dipoles of the water molecules with the protein electrostatic field was observed. This can be related to the dielectric properties of hydration layers around proteins, where the shielding of electrostatic interactions depends directly on the rotational degrees of freedom of the water molecules in the interface.Facultad de Ciencias ExactasInstituto de Física de Líquidos y Sistemas Biológico

Anatomic MR Imaging and Functional Diffusion Tensor Imaging of Peripheral Nerve Tumors and Tumorlike Conditions

ABSTRACT BACKGROUND AND PURPOSE: A number of benign and malignant peripheral nerve tumor and tumorlike conditions produce similar imaging features on conventional anatomic MR imaging. Functional MR imaging using DTI can increment the diagnostic performance in differentiation of these lesions. Our aim was to evaluate the role of 3T anatomic MR imaging and DTI in the characterization of peripheral nerve tumor and tumorlike conditions

British Torture in the 'War on Terror'

Despite longstanding allegations of UK involvement in prisoner abuse during counterterrorism operations as part of the US-led ‘war on terror’, a consistent narrative emanating from British government officials is that Britain neither uses, condones nor facilitates torture or other cruel, inhuman, degrading treatment and punishment. We argue that such denials are untenable. We have established beyond reasonable doubt that Britain has been deeply involved in post-9/11 prisoner abuse, and we can now provide the most detailed account to date of the depth of this involvement. We argue that it is possible to identify a peculiarly British approach to torture in the ‘war on terror’, which is particularly well-suited to sustaining a narrative of denial. To explain the nature of UK involvement, we argue that it can be best understood within the context of how law and sovereign power have come to operate during the ‘war on terror’. We turn here to the work of Judith Butler, and explore the role of Britain as a ‘petty sovereign’, operating under the state of exception established by the US Executive. UK authorities have not themselves suspended the rule of law so overtly, and indeed have repeatedly insisted on their commitment to it. They have nevertheless been able to construct a rhetorical, legal and policy ‘scaffold’ that has enabled them to demonstrate at least procedural adherence to human rights norms, while at the same time allowing UK officials to acquiesce in the arbitrary exercise of sovereignty over individuals who are denied any access to appropriate representation or redress in compliance with the rule of law

Fiscal Year 2014

Report regarding the annual defense authorization process and the interest Congress members have in the military

Heritage language anxiety and majority language anxiety among Turkish immigrants in the Netherlands

Aims and objectives: This study examines the language anxiety that occurs in immigrants’ daily lives when speaking the heritage language and the majority language, both in their host country and during visits to their home country. It compares the levels of heritage language anxiety and majority language anxiety across three generations of the Turkish immigrant community in the Netherlands and explores the link between immigrants’ language anxiety, and sociobiographical (i.e. generation, gender, education) and language background variables (i.e. age of acquisition, self-perceived proficiency, frequency of language use). Design: A Likert scale-based questionnaire was administered to 116 participants across three generations who reported their language anxiety levels when speaking the heritage language and the majority language in three social contexts (i.e. family, friendship and speaking with native speakers). Findings: Statistical analyses revealed that heritage language anxiety and majority language anxiety were prevalent in immigrants’ daily life, and that levels of both forms of anxiety differed across generations, and in different daily life situations. First- and second-generation immigrants typically experienced majority language anxiety, while second- and predominantly third-generation immigrants suffered from heritage language anxiety. Relationships emerged between language background variables and both forms of anxiety, but only in certain situations. These findings suggest that language background variables on their own may be insufficient to explain immigrant language anxiety in certain social contexts (i.e. within family). Rather than merely language background factors, a variety of other issues within social, cultural and national currents must be considered when examining language anxiety in the immigrant context. Implications: Taking an interdisciplinary approach that combines language contact and foreign language anxiety/second language anxiety research, this study suggests that the concept of foreign language anxiety/second language anxiety should be expanded beyond the confines of the classroom in order to include daily interactions immigrant or minority communities. Originality: This study contributes to the limited body of evidence on the topic of language anxiety in immigrant contexts and presents a new construct ‘majority language anxiety’