The genetic code is the cellular translation table for the conversion of nucleotide sequences into amino acid sequences. Changes to the meaning of sense codons would introduce errors into almost every translated message and are expected to be highly detrimental. However, reassignment of single or multiple codons in mitochondria and nuclear genomes, although extremely rare, demonstrates that the...

The spatial dependence structure of climate extremes may be represented by the class of max-stable distributions. When the domain is very large, describing the spatial dependence between and within subdomains is particularly challenging and requires very flexible, yet interpretable, models. In this work, we use the inherent hierarchical dependence structure of the (max-stable) nested logistic d...

We develop a biased Monte Carlo algorithm to measure probabilities of rare events in cluster-cluster aggregation for arbitrary collision kernels. Given trajectory with fixed number collisions, the modifies both waiting times between as well sequence using local moves. show that is ergodic by giving protocol transforms an standard valid The can sample order $10^{-40}$ and lower. algorithm's effe...

Codon usage tends to be optimized in highly expressed genes. A plausible explanation for this phenomenon is that translational accuracy is increased in highly expressed genes with infrequent use of rare codons. Besides structural domains (SDs), eukaryotic proteins generally have intrinsically disordered regions (IDRs) that by themselves do not assume unique three-dimensional structures. As IDRs...

Various carcinogenic metabolites, including catechol estrogens, play a role in malignant transformation. An enzyme that is capable of neutralizing the genotoxic effects of these compounds is catechol-O-methyltransferase (COMT). A variant form of this enzyme has been shown to reduce its activity by up to 4-fold; thus, we hypothesize that single nucleotide polymorphisms of the COMT gene can be a ...

p53 tumor suppressor gene, also known as “genome guardian” is mutated in more than half of allkind of cancers. in this study we have investigated the controls of environmental ph for p53 genemutation in point of specific sequence which is prone to mutagenesis. the most probable cancerousmutations occur as point mutations in exons 5-8 of p53 gene. the 175th codon of p53 is the thirdmost mutated ...

Pigment epithelium-derived factor (PEDF) is widely known for its neurotrophic and antiangiogenic functions. Efficacy studies of PEDF in animal models are limited because of poor heterologous protein yields. Here, we redesigned the human PEDF gene to preferentially match codon frequencies of E coli without altering the amino acid sequence. Following de novo synthesis, codon optimized PEDF (coPED...

common and potentially deleterious rare variation in this pathway would be associated with severe asthma based on SARP cluster designation. Methods: To evaluate common variants (minor allele frequency or MAF .5%), 419 SARP non-Hispanic white participants with a cluster assignment were genotyped for 182 single nucleotide polymorphisms (SNPs) in Th2 pathway genes using whole-genome SNP data. Indi...

common and potentially deleterious rare variation in this pathway would be associated with severe asthma based on SARP cluster designation. Methods: To evaluate common variants (minor allele frequency or MAF .5%), 419 SARP non-Hispanic white participants with a cluster assignment were genotyped for 182 single nucleotide polymorphisms (SNPs) in Th2 pathway genes using whole-genome SNP data. Indi...

Megalencephalic leukoencephalopathy (MLC) is a rare neurological disorder with an autosomal recessive pattern. Clinical diagnosis was based on macrocephaly, recurrent seizure, and magnetic resonance imaging (MRI). Here we report first finding of a novel homozygous single base deletion in the MLC1 gene in an affected Iranian child causing a premature stop codon (p.L150fs.160X).