The Caledonian face test: A new test of face discrimination

yesThis study aimed to develop a clinical test of face perception which is applicable to a wide range of patients and can capture normal variability. The Caledonian face test utilises synthetic faces which combine simplicity with sufficient realism to permit individual identification. Face discrimination thresholds (i.e. minimum difference between faces required for accurate discrimination) were determined in an "odd-one-out" task. The difference between faces was controlled by an adaptive QUEST procedure. A broad range of face discrimination sensitivity was determined from a group (N=52) of young adults (mean 5.75%; SD 1.18; range 3.33-8.84%). The test is fast (3-4min), repeatable (test-re-test r2=0.795) and demonstrates a significant inversion effect. The potential to identify impairments of face discrimination was evaluated by testing LM who reported a lifelong difficulty with face perception. While LM's impairment for two established face tests was close to the criterion for significance (Z-scores of -2.20 and -2.27) for the Caledonian face test, her Z-score was -7.26, implying a more than threefold higher sensitivity. The new face test provides a quantifiable and repeatable assessment of face discrimination ability. The enhanced sensitivity suggests that the Caledonian face test may be capable of detecting more subtle impairments of face perception than available tests.Non

Multi-Granular Trend Detection for Time-Series Analysis

Time series (such as stock prices) and ensembles (such as model runs for weather forecasts) are two important types of one-dimensional time-varying data. Such data is readily available in large quantities but visual analysis of the raw data quickly becomes infeasible, even for moderately sized data sets. Trend detection is an effective way to simplify time-varying data and to summarize salient information for visual display and interactive analysis. We propose a geometric model for trend-detection in one-dimensional time-varying data, inspired by topological grouping structures for moving objects in two- or higher-dimensional space. Our model gives provable guarantees on the trends detected and uses three natural parameters: granularity, support-size, and duration. These parameters can be changed on-demand. Our system also supports a variety of selection brushes and a time-sweep to facilitate refined searches and interactive visualization of (sub-)trends. We explore different visual styles and interactions through which trends, their persistence, and evolution can be explored

Conditional inactivation of the Men1 gene leads to pancreatic and pituitary tumorigenesis but does not affect normal development of these tissues

Mutations of the MEN1 gene, encoding the tumor suppressor menin, predispose individuals to the cancer syndrome multiple endocrine neoplasia type 1, characterized by the development of tumors of the endocrine pancreas and anterior pituitary and parathyroid glands. We have targeted the murine Men1 gene by using Cre recombinase-loxP technology to develop both total and tissue-specific knockouts of the gene. Conditional homozygous inactivation of the Men1 gene in the pituitary gland and endocrine pancreas bypasses the embryonic lethality associated with a constitutional Men1(-/-) genotype and leads to beta-cell hyperplasia in less than 4 months and insulinomas and prolactinomas starting at 9 months. The pituitary gland and pancreas develop normally in the conditional absence of menin, but loss of this transcriptional cofactor is sufficient to cause beta-cell hyperplasia in some islets; however, such loss is not sufficient to initiate pituitary gland tumorigenesis, suggesting that additional genetic events are necessary for the latter

Advancement of Nucleic Acid-Based Tools for Monitoring in Situ Reductive Dechlorination

Regulatory protocols generally recognize that destructive processes are the most effective mechanisms that support natural attenuation of chlorinated solvents. In many cases, these destructive processes will be biological processes and, for chlorinated compounds, will often be reductive processes that occur under anaerobic conditions. The existing EPA guidance (EPA, 1998) provides a list of parameters that provide indirect evidence of reductive dechlorination processes. In an effort to gather direct evidence of these processes, scientists have identified key microorganisms and are currently developing tools to measure the abundance and activity of these organisms in subsurface systems. Drs. Edwards and Luffler are two recognized leaders in this field. The research described herein continues their development efforts to provide a suite of tools to enable direct measures of biological processes related to the reductive dechlorination of TCE and PCE. This study investigated the strengths and weaknesses of the 16S rRNA gene-based approach to characterizing the natural attenuation capabilities in samples. The results suggested that an approach based solely on 16S rRNA may not provide sufficient information to document the natural attenuation capabilities in a system because it does not distinguish between strains of organisms that have different biodegradation capabilities. The results of the investigations provided evidence that tools focusing on relevant enzymes for functionally desired characteristics may be useful adjuncts to the 16SrRNA methods

Fnr (EtrA) acts as a fine-tuning regulator of anaerobic metabolism in \u3cem\u3eShewanella oneidensis\u3c/em\u3e MR-1

Background EtrA in Shewanella oneidensis MR-1, a model organism for study of adaptation to varied redox niches, shares 73.6% and 50.8% amino acid sequence identity with the oxygen-sensing regulators Fnr in E. coli and Anr in Pseudomonas aeruginosa, respectively; however, its regulatory role of anaerobic metabolism in Shewanella spp. is complex and not well understood. Results The expression of the nap genes, nrfA, cymA and hcp was significantly reduced in etrA deletion mutant EtrA7-1; however, limited anaerobic growth and nitrate reduction occurred, suggesting that multiple regulators control nitrate reduction in this strain. Dimethyl sulfoxide (DMSO) and fumarate reductase gene expression was down-regulated at least 2-fold in the mutant, which, showed lower or no reduction of these electron acceptors when compared to the wild type, suggesting both respiratory pathways are under EtrA control. Transcript analysis further suggested a role of EtrA in prophage activation and down-regulation of genes implicated in aerobic metabolism. Conclusion In contrast to previous studies that attributed a minor regulatory role to EtrA in Shewanella spp., this study demonstrates that EtrA acts as a global transcriptional regulator and, in conjunction with other regulators, fine-tunes the expression of genes involved in anaerobic metabolism in S. oneidensis strain MR-1. Transcriptomic and sequence analyses of the genes differentially expressed showed that those mostly affected by the mutation belonged to the Energy metabolism category, while stress-related genes were indirectly regulated in the mutant possibly as a result of a secondary perturbation (e.g. oxidative stress, starvation). We also conclude based on sequence, physiological and expression analyses that this regulator is more appropriately termed Fnr and recommend this descriptor be used in future publications

Evolution of a periodic eight-black-hole lattice in numerical relativity

The idea of black-hole lattices as models for the large-scale structure of the universe has been under scrutiny for several decades, and some of the properties of these systems have been elucidated recently in the context of the problem of cosmological backreaction. The complete, three-dimensional and fully relativistic evolution of these system has, however, never been tackled. We explicitly construct the first of these solutions by numerically integrating Einstein's equation in the case of an eight-black-hole lattice with the topology of S3.Comment: 21 pages, 13 figures. Corrected and clarified discussio

Magnetic Behavior of a Mixed Ising Ferrimagnetic Model in an Oscillating Magnetic Field

The magnetic behavior of a mixed Ising ferrimagnetic system on a square lattice, in which the two interpenetrating square sublattices have spins +- 1/2 and spins +-1,0, in the presence of an oscillating magnetic field has been studied with Monte Carlo techniques. The model includes nearest and next-nearest neighbor interactions, a crystal field and the oscillating external field. By studying the hysteretic response of this model to an oscillating field we found that it qualitatively reproduces the increasing of the coercive field at the compensation temperature observed in real ferrimagnets, a crucial feature for magneto-optical applications. This behavior is basically independent of the frequency of the field and the size of the system. The magnetic response of the system is related to a dynamical transition from a paramagnetic to a ferromagnetic phase and to the different temperature dependence of the relaxation times of both sublattices.Comment: 10 figures. To be published in Phys.Rev

Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling

Large brain size is one of the defining characteristics of modern humans. Seckel syndrome (MIM 210600), a disorder of markedly reduced brain and body size, is associated with defective ATR-dependent DNA damage signaling. Only a single hypomorphic mutation of ATR has been identified in this genetically heterogeneous condition. We now report that mutations in the gene encoding pericentrin (PCNT)--resulting in the loss of pericentrin from the centrosome, where it has key functions anchoring both structural and regulatory proteins--also cause Seckel syndrome. Furthermore, we find that cells of individuals with Seckel syndrome due to mutations in PCNT (PCNT-Seckel) have defects in ATR-dependent checkpoint signaling, providing the first evidence linking a structural centrosomal protein with DNA damage signaling. These findings also suggest that other known microcephaly genes implicated in either DNA repair responses or centrosomal function may act in common developmental pathways determining human brain and body size

Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis

Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-offunction mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n¼40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC

Complex structural rearrangements are present in high-grade dysplastic Barrett\u27s oesophagus samples

Background: Oesophageal adenocarcinoma (EAC) incidence is increasing and has a poor survival rate. Barrett’s oesophagus (BE) is a precursor condition that is associated with EAC and often occurs in conjunction with chronic gastro-oesophageal reflux, however many individuals diagnosed with BE never progress to cancer. An understanding of the genomic features of BE and EAC may help with the early identification of at-risk individuals. Methods: In this study, we assessed the genomic features of 16 BE samples using whole-genome sequencing. These included non-dysplastic samples collected at two time-points from two BE patients who had not progressed to EAC over several years. Seven other non-dysplastic samples and five dysplastic BE samples with high-grade dysplasia were also examined. We compared the genome profiles of these 16 BE samples with 22 EAC samples. Results: We observed that samples from the two non-progressor individuals had low numbers of somatic single nucleotide variants, indels and structural variation events compared to dysplastic and the remaining non-dysplastic BE. EAC had the highest level of somatic genomic variations. Mutational signature 17, which is common in EAC, was also present in non-dysplastic and dysplastic BE, but was not present in the non-progressors. Many dysplastic samples had mutations in genes previously reported in EAC, whereas only mutations in CDKN2A or in the fragile site genes appeared common in non-dysplastic samples. Rearrangement signatures were used to identify a signature associated with localised complex events such as chromothripsis and breakage fusion-bridge that are characteristic of EACs. Two dysplastic BE samples had a high contribution of this signature and contained evidence of localised rearrangements. Two other dysplastic samples also had regions of localised structural rearrangements. There was no evidence for complex events in non-dysplastic samples. Conclusions: The presence of complex localised rearrangements in dysplastic samples indicates a need for further investigations into the role such events play in the progression from BE to EAC