Solomonoff Induction Violates Nicod's Criterion

Nicod's criterion states that observing a black raven is evidence for the hypothesis H that all ravens are black. We show that Solomonoff induction does not satisfy Nicod's criterion: there are time steps in which observing black ravens decreases the belief in H. Moreover, while observing any computable infinite string compatible with H, the belief in H decreases infinitely often when using the unnormalized Solomonoff prior, but only finitely often when using the normalized Solomonoff prior. We argue that the fault is not with Solomonoff induction; instead we should reject Nicod's criterion.Comment: ALT 201

Novel semiconducting iron–quinizarin metal–organic framework for application in supercapacitors^*

We present conductivity data for a newly synthesised metal organic framework FeQ, Fe(C14H6O4).H2O demonstrating significant electronic transport. The electrical conductivity of the material is expected to be through the π-π interaction of the ligand- quinizarin and is measured to be 1.73 × 10-2 Scm-1. Its potential role as supercapacitor electrodes is discussed

Human C4orf14 interacts with the mitochondrial nucleoid and is involved in the biogenesis of the small mitochondrial ribosomal subunit.

The bacterial homologue of C4orf14, YqeH, has been linked to assembly of the small ribosomal subunit. Here, recombinant C4orf14 isolated from human cells, co-purified with the small, 28S subunit of the mitochondrial ribosome and the endogenous protein co-fractionated with the 28S subunit in sucrose gradients. Gene silencing of C4orf14 specifically affected components of the small subunit, leading to decreased protein synthesis in the organelle. The GTPase of C4orf14 was critical to its interaction with the 28S subunit, as was GTP. Therefore, we propose that C4orf14, with bound GTP, binds to components of the 28S subunit facilitating its assembly, and GTP hydrolysis acts as the release mechanism. C4orf14 was also found to be associated with human mitochondrial nucleoids, and C4orf14 gene silencing caused mitochondrial DNA depletion. In vitro C4orf14 is capable of binding to DNA. The association of C4orf14 with mitochondrial translation factors and the mitochondrial nucleoid suggests that the 28S subunit is assembled at the mitochondrial nucleoid, enabling the direct transfer of messenger RNA from the nucleoid to the ribosome in the organelle.Medical Research Council (MRC); Biotechnology and Biological Sciences Research Council (BBSRC); European Union; Academy of Finland (to H.M.C.). Funding for open access charge: MRC

The functional outcome of total knee replacements in young patients : A 10-year matched case control study

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PFC Sigma Cobalt Chrome total knee replacements : early outcomes demonstrate no significant early failures at the three-year mark

The PFC Sigma Cobalt Chrome Sigma (PFCSCC) was introduced in 2006, and represents further development of the PFC Sigma design aiming at reducing the problem of backside wear. To ensure that there were no significant early failures following the introduction of this knee system to our hospital in 2006, we prospectively identified all patients undergoing TKA with the PFCSCC over a one-year period. Clinical and demographic patient data, American Knee Society scores, Oxford Knee scores, SF-12 scores and radiographic data were recorded preoperatively and at three-year post surgery. 233 patients underwent 249 primary knee arthroplasties with the PFCSCC. Seven patients (eight TKAs) died before the last review and eight cases were lost to follow up. Mean age was 66.7 (range 34 - 80) with 47.6% male. Mean follow-up days were 1109 (range 741 to 1591). 5 (2.2%) were revised for infection with 1 revised for pain. The 3-year survival rate was 97.6% and 99.6% for aseptic failure. AKS 46.2 (0 - 95) was preoperatively 88.3 (17 - 100) with 3 years P < 0.001. OKS 39.0 (22 - 53) was preoperatively 22.6 (12 - 53) with 3 years P < 0.001. 17 of the 219 who had x-rays (8%) had radiolucent zones on x-ray. Our results demonstrate a good early aseptic survivorship of the PFCSCC at three years of 99.6%, combined with a good functional and objective improvement in our patients in three years.Publisher PDFPeer reviewe

Transcript availability dictates the balance between strand-asynchronous and strand-coupled mitochondrial DNA replication

Mammalian mitochondria operate multiple mechanisms of DNA replication. In many cells and tissues a strand-asynchronous mechanism predominates over coupled leading and lagging-strand DNA synthesis. However, little is known of the factors that control or influence the different mechanisms of replication, and the idea that strand-asynchronous replication entails transient incorporation of transcripts (aka bootlaces) is controversial. A firm prediction of the bootlace model is that it depends on mitochondrial transcripts. Here, we show that elevated expression of Twinkle DNA helicase in human mitochondria induces bidirectional, coupled leading and lagging-strand DNA synthesis, at the expense of strand-asynchronous replication; and this switch is accompanied by decreases in the steady-state level of some mitochondrial transcripts. However, in the so-called minor arc of mitochondrial DNA where transcript levels remain high, the strand-asynchronous replication mechanism is instated. Hence, replication switches to a strand-coupled mechanism only where transcripts are scarce, thereby establishing a direct correlation between transcript availability and the mechanism of replication. Thus, these findings support a critical role of mitochondrial transcripts in the strand-asynchronous mechanism of mitochondrial DNA replication; and, as a corollary, mitochondrial RNA availability and RNA/DNA hybrid formation offer means of regulating the mechanisms of DNA replication in the organelle

Identification of the REST regulon reveals extensive transposable element-mediated binding site duplication

The genome-wide mapping of gene-regulatory motifs remains a major goal that will facilitate the modelling of gene-regulatory networks and their evolution. The repressor element 1 is a long, conserved transcription factor-binding site which recruits the transcriptional repressor REST to numerous neuron-specific target genes. REST plays important roles in multiple biological processes and disease states. To map RE1 sites and target genes, we created a position specific scoring matrix representing the RE1 and used it to search the human and mouse genomes. We identified 1301 and 997 RE1s inhuman and mouse genomes, respectively, of which >40% are novel. By employing an ontological analysis we show that REST target genes are significantly enriched in a number of functional classes. Taking the novel REST target gene CACNA1A as an experimental model, we show that it can be regulated by multiple RE1s of different binding affinities, which are only partially conserved between human and mouse. A novel BLAST methodology indicated that many RE1s belong to closely related families. Most of these sequences are associated with transposable elements, leading us to propose that transposon-mediated duplication and insertion of RE1s has led to the acquisition of novel target genes by REST during evolution

Cognitive ability and physical health:A Mendelian randomization study

Causes of the association between cognitive ability and health remain unknown, but may reflect a shared genetic aetiology. This study examines the causal genetic associations between cognitive ability and physical health. We carried out two-sample Mendelian randomization analyses using the inverse-variance weighted method to test for causality between later life cognitive ability, educational attainment (as a proxy for cognitive ability in youth), BMI, height, systolic blood pressure, coronary artery disease, and type 2 diabetes using data from six independent GWAS consortia and the UK Biobank sample (N = 112 151). BMI, systolic blood pressure, coronary artery disease and type 2 diabetes showed negative associations with cognitive ability; height was positively associated with cognitive ability. The analyses provided no evidence for casual associations from health to cognitive ability. In the other direction, higher educational attainment predicted lower BMI, systolic blood pressure, coronary artery disease, type 2 diabetes, and taller stature. The analyses indicated no causal association from educational attainment to physical health. The lack of evidence for causal associations between cognitive ability, educational attainment, and physical health could be explained by weak instrumental variables, poorly measured outcomes, or the small number of disease cases

31P magnetic resonance spectroscopy as a predictor of efficacy in photodynamic therapy using differently charged zinc phthalocyanines

Photodynamic therapy (PDT) is a developing approach to the treatment of solid tumours which requires the combined action of light and a photosensitizing drug in the presence of adequate levels of molecular oxygen. We have developed a novel series of photosensitizers based on zinc phthalocyanine which are water-soluble and contain neutral (TDEPC), positive (PPC) and negative (TCPC) side-chains. The PDT effects of these sensitizers have been studied in a mouse model bearing the RIF-1 murine fibrosarcoma line studying tumour regrowth delay, phosphate metabolism by magnetic resonance spectroscopy (MRS) and blood flow, using D2O uptake and MRS. The two main aims of the study were to determine if MRS measurements made at the time of PDT treatment could potentially be predictive of ultimate PDT efficacy and to assess the effects of sensitizer charge on PDT in this model. It was clearly demonstrated that there is a relationship between MRS measurements during and immediately following PDT and the ultimate effect on the tumour. For all three drugs, tumour regrowth delay was greater with a 1-h time interval between drug and light administration than with a 24-h interval. In both cases, the order of tumour regrowth delay was PPC > TDEPC = TCPC (though the data at 24 h were not statistically significant). Correspondingly, there were greater effects on phosphate metabolism (measured at the time of PDT or soon after) for the 1-h than for the 24-h time interval. Again effects were greatest with the cationic PPC, with the sequence being PPC > TDEPC > TCPC. A parallel sequence was observed for the blood flow effects, demonstrating that reduction in blood flow is an important factor in PDT with these sensitizers. © 1999 Cancer Research Campaig