3,289 research outputs found
DScentTrail: A new way of viewing deception
The DScentTrail System has been created to support and demonstrate research theories in the joint disciplines of computational inference, forensic psychology and expert decision-making in the area of counter-terrorism. DScentTrail is a decision support system, incorporating artificial intelligence, and is intended to be used by investigators. The investigator is presented with a visual representation of a suspect‟s behaviour over time, allowing them to present multiple challenges from which they may prove the suspect guilty outright or receive cognitive or emotional clues of deception. There are links into a neural network, which attempts to identify deceptive behaviour of individuals; the results are fed back into DScentTrail hence giving further enrichment to the information available to the investigator
World Spinors - Construction and Some Applications
The existence of a topological double-covering for the and
diffeomorphism groups is reviewed. These groups do not have finite-dimensional
faithful representations. An explicit construction and the classification of
all , unitary irreducible representations is presented.
Infinite-component spinorial and tensorial fields,
"manifields", are introduced. Particle content of the ladder manifields, as
given by the "little" group is determined. The manifields are
lifted to the corresponding world spinorial and tensorial manifields by making
use of generalized infinite-component frame fields. World manifields transform
w.r.t. corresponding representations, that are constructed
explicitly.Comment: 19 pages, Te
Potent antiviral agents fail to elicit genetically-stable resistance mutations in either enterovirus 71 or Coxsackievirus A16
Enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) are the two major causative agents 13 of hand, foot and mouth disease (HFMD), for which there are currently no licenced 14 treatments. Here, the acquisition of resistance towards two novel capsid-binding compounds, 15 NLD and ALD, was studied and compared to the analogous compound GPP3. During serial 16 passage, EV71 rapidly became resistant to each compound and mutations at residues I113 17 and V123 in VP1 were identified. A mutation at residue 113 was also identified in CVA16 18 after passage with GPP3. The mutations were associated with reduced thermostability and 19 were rapidly lost in the absence of inhibitors. In silico modelling suggested that the mutations 20 prevented the compounds from binding the VP1 pocket in the capsid. Although both viruses 21 developed resistance to these potent pocket-binding compounds, the acquired mutations were 22 associated with large fitness costs and reverted to WT phenotype and sequence rapidly in the 23 absence of inhibitors. The most effective inhibitor, NLD, had a very large selectivity index, 24 showing interesting pharmacological properties as a novel anti-EV71 agent
Cometary ions detected by the Cassini spacecraft 6.5 au downstream of Comet 153P/Ikeya-Zhang
During March-April 2002, while between the orbits of Jupiter and Saturn, the Cassini spacecraft detected a significant enhancement in pickup proton flux. The most likely explanation for this enhancement was the addition of protons to the solar wind by the ionization of neutral hydrogen in the corona of comet 153P/Ikeya-Zhang. This comet passed relatively close to the Sun-Cassini line during that period, allowing pickup ions to be carried to Cassini by the solar wind. This pickup proton flux could have been further modulated by the passage of the interplanetary counterparts of coronal mass ejections past the comet and spacecraft. The radial distance of 6.5 Astronomical Units (au) traveled by the pickup protons, and the implied total tail length of 7.5 au make this cometary ion tail the longest yet measured
Epithelial specific splicing regulator proteins as emerging oncogenes in aggressive prostate cancer
Computer simulation of syringomyelia in dogs
Syringomyelia is a pathological condition in which fluid-filled cavities (syringes) form and expand in the spinal cord. Syringomyelia is often linked with obstruction of the craniocervical junction and a Chiari malformation, which is similar in both humans and animals. Some brachycephalic toy breed dogs such as Cavalier King Charles Spaniels (CKCS) are particularly predisposed. The exact mechanism of the formation of syringomyelia is undetermined and consequently with the lack of clinical explanation, engineers and mathematicians have resorted to computer models to identify possible physical mechanisms that can lead to syringes. We developed a computer model of the spinal cavity of a CKCS suffering from a large syrinx. The model was excited at the cranial end to simulate the movement of the cerebrospinal fluid (CSF) and the spinal cord due to the shift of blood volume in the cranium related to the cardiac cycle. To simulate the normal condition, the movement was prescribed to the CSF. To simulate the pathological condition, the movement of CSF was blocked
Sizing subwavelength defects with ultrasonic imagery: an assessment of super-resolution imaging on simulated rough defects
There is a constant drive within the nuclear power industry to improve upon the characterization capabilities of current ultrasonic inspection techniques in order to improve safety and reduce costs. Particular emphasis has been placed on the ability to characterize very small defects which could result in extended component lifespan and help reduce the frequency of in-service inspections. Super-resolution (SR) algorithms, also known as sampling methods, have been shown to demonstrate the capability to resolve scatterers separated by less than the diffraction limit when deployed in representative inspections and therefore could be used to tackle this issue. In this paper, the factorization method (FM) and the Time Reversal Multiple-Signal-Classification (TR-MUSIC) algorithms are applied to the simulated ultrasonic array inspection of small rough embedded planar defects to establish their characterization capabilities. Their performance was compared to the conventional total focusing method (TFM). A full 2-D finite-element (FE) Monte Carlo modeling study was conducted for defects with a range of sizes, orientations, and magnitude of surface roughness. The results presented show that for subwavelength defects, both the FM and TR-MUSIC algorithms were able to size and estimate defect orientation accurately for smooth cases and, for rough defects, up to a roughness of 100 μm. This level of roughness is representative of the thermal fatigue defects encountered in the nuclear power sector. This contrasted with the relatively poor performance of TFM in these cases which consistently oversized these defects and could not be used to estimate the defect orientation, making through-wall sizing with this method impossible
Long-Term Survival With Tafamidis in Patients With Transthyretin Amyloid Cardiomyopathy
BACKGROUND: Tafamidis is approved in many countries for the treatment of transthyretin amyloid cardiomyopathy. This study reports data on the long-term efficacy of tafamidis from an ongoing long-term extension (LTE) to the pivotal ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial). METHODS: Patients with transthyretin amyloid cardiomyopathy who completed ATTR-ACT could enroll in an LTE, continuing with the same tafamidis dose or, if previously treated with placebo, randomized (2:1) to tafamidis meglumine 80 or 20 mg. All patients in the LTE transitioned to tafamidis free acid 61 mg (bioequivalent to tafamidis meglumine 80 mg) following a protocol amendment. In this interim analysis, all-cause mortality was assessed in patients treated with tafamidis meglumine 80 mg in ATTR-ACT continuing in the LTE, compared with those receiving placebo in ATTR-ACT transitioning to tafamidis in the LTE. RESULTS: Median follow-up was 58.5 months in the continuous tafamidis group (n=176) and 57.1 months in the placebo to tafamidis group (n=177). There were 79 (44.9%) deaths with continuous tafamidis and 111 (62.7%) with placebo to tafamidis (hazard ratio, 0.59 [95% CI, 0.44-0.79]; P<0.001). Mortality was also reduced in the continuous tafamidis (versus placebo to tafamidis) subgroups of: variant transthyretin amyloidosis (0.57 [0.33-0.99]; P=0.05) and wild-type transthyretin amyloidosis (0.61 [0.43-0.87]; P=0.006); and baseline New York Heart Association class I and II (0.56 [0.38-0.82]; P=0.003) and class III (0.65 [0.41-1.01]; P=0.06). CONCLUSIONS: In the LTE, patients initially treated with tafamidis in ATTR-ACT had substantially better survival than those first treated with placebo, highlighting the importance of early diagnosis and treatment in transthyretin amyloid cardiomyopathy. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01994889 and NCT02791230
The Germ Cell Nuclear Proteins hnRNP G-T and RBMY Activate a Testis-Specific Exon
The human testis has almost as high a frequency of alternative splicing events as brain. While not as extensively studied as brain, a few candidate testis-specific splicing regulator proteins have been identified, including the nuclear RNA binding proteins RBMY and hnRNP G-T, which are germ cell-specific versions of the somatically expressed hnRNP G protein and are highly conserved in mammals. The splicing activator protein Tra2β is also highly expressed in the testis and physically interacts with these hnRNP G family proteins. In this study, we identified a novel testis-specific cassette exon TLE4-T within intron 6 of the human transducing-like enhancer of split 4 (TLE4) gene which makes a more transcriptionally repressive TLE4 protein isoform. TLE4-T splicing is normally repressed in somatic cells because of a weak 5′ splice site and surrounding splicing-repressive intronic regions. TLE4-T RNA pulls down Tra2β and hnRNP G proteins which activate its inclusion. The germ cell-specific RBMY and hnRNP G-T proteins were more efficient in stimulating TLE4-T incorporation than somatically expressed hnRNP G protein. Tra2b bound moderately to TLE4-T RNA, but more strongly to upstream sites to potently activate an alternative 3′ splice site normally weakly selected in the testis. Co-expression of Tra2β with either hnRNP G-T or RBMY re-established the normal testis physiological splicing pattern of this exon. Although they can directly bind pre-mRNA sequences around the TLE4-T exon, RBMY and hnRNP G-T function as efficient germ cell-specific splicing co-activators of TLE4-T. Our study indicates a delicate balance between the activity of positive and negative splicing regulators combinatorially controls physiological splicing inclusion of exon TLE4-T and leads to modulation of signalling pathways in the testis. In addition, we identified a high-affinity binding site for hnRNP G-T protein, showing it is also a sequence-specific RNA binding protein
- …