Ambiguous Codes Research Articles

Contracts of Intellectual Gratification A Louisiana-Scotland Discovery

The study of contracts of intellectual gratification in Scotland and Louisiana shows that moral damages ex contractu play an unappreciated role in the protection of personality interests. Historically, tort law has been more closely identified with protecting personality interests, and to be sure it remains the dominant way these rights are thought about. Through a tort prism we see personality rights as rights erga omnes, namely, as absolute subjective rights that others must not invade. This is quite different from a contractual viewpoint. A contractual vision of personality interests allows an individual the freedom to stipulate for those interests he or she wishes to create, secure or enjoy, even if no legislator or judge has thought fit to declare such interests worthy of protection. These need not be particularised categories like privacy, honour and dignity, but relative interests of various weights. In this sense contract concerns the pro-active personality creating interests through the agreements parties enter into. Here we may think of personality rights as plastic and varied as the parties may conceive. Both Louisiana and Scotland have steered a middle course in creating an exceptional category of contract in which these personality interests receive protection. Louisiana created the exception in the early nineteenth century, while Scotland created it through a decisional breakthrough in the 1970s. It is interesting to observe, however, how little difference these starting points made in the final analysis. The judges labouring with an old code text arrived, despite a seriously mistranslated code, at approximately the same position as their distant brethren reached operating without any text at all. The latter found a gap in the “common law” of Scotland and filled it with a series of precedents, while the former encountered gaps in an ambiguous code and poured in new meaning. Yet the Scottish judge might not have not recognised the existence of any gap unless he was already informed, at a deeper level, by the liberal Scottish tradition on solatium, and the Louisiana judge might never have perceived the gaps in the text without the context provided by the code and the tradition. The judges in both systems next faced the issue of stating the boundaries of the exception with clarity and of keeping the category stable and within reasonable limits. Both employed the “object” of the contract as the basis for recognising contracts of intellectual gratification. In Louisiana the object evokes the wider connotation of “the cause” of the contract, while in Scotland it would not have that overtone, yet this produced little or no divergence in approach. A common problem was to settle upon the exact qualifiers shaping the parameters of the exception. The reasoning was almost identical. The judges realised that the object of a contract is typically of mixed purpose, and it would be overly restrictive to require the plaintiff to prove that his or her exclusive, sole or entire purpose was to seek intellectual gratification. Accordingly, the Scottish and English cases say it is sufficient if “a major or important object” of the contract is to give pleasure, relaxation or peace of mind. The Louisiana judges say it is enough if plaintiff seeks to gratify “a significant” interest of that type. The Louisiana judges found the qualifier in the guise of interpreting the legislative will; the Scottish and English judges found theirs in the course of an inductive search for the correct principle. What we seem to have witnessed is the creative process in two mixed jurisdictions which balanced their dual traditions in similar ways and with similar results.

A Standard Method for Abbreviating the Names of Fishes of the United States, Canada, and Mexico

Abbreviations for fish names are used by fisheries biologists throughout the data life cycle, especially field data collection and entry, sharing, and reporting. However, use of nonstandard abbreviation systems across North America hinders data collection, sharing, and communication among agencies, programs, universities, and other data providers. An ideal abbreviation system would yield unique codes for all species, while being intuitive, memorable, and stable over time, as well as providing for a wide range of scenarios such as naming subspecies, hybrids, and unidentified species of a known taxon. A standard abbreviation system that meets these ideals was developed using a defined rule set and implemented for fishes of the continental United States, Canada, and Mexico. Standard abbreviations were developed for 3,875 species, in addition to their respective genera and families. Use of the standard abbreviation system can improve data integrity by reducing worker training, use of ambiguous codes, and misinterpretation of shared data. Abbreviations facilitate faster data recording and entry, as well as brevity in writing reports and creating tables. The standard abbreviation system will be made available online for widespread use.

Quantum code for quantum error characterization

A quantum error correcting code is a subspace $\mathcal{C}$ such that allowed errors acting on any state in $\mathcal{C}$ can be corrected. A quantum code for which state recovery is only required up to a logical rotation within $\mathcal{C}$, can be used for detection of errors, but not for quantum error correction. Such a code with stabilizer structure, which we call an "ambiguous stabilizer code" (ASC), can nevertheless be useful for the characterization of quantum dynamics (CQD). The use of ASCs can help lower the size of CQD probe states used, but at the cost of increased number of operations.

At Home in the Realm of Enchantment: The Queer Enticements of the Grimms' “Frau Holle”

Queemess is longing that propels us onward, beyond romances of the negative and toiling in the present. Queemess is that thing that lets us feel that this world is not enough, that indeed something is missing. Often we can glimpse the worlds proposed and promised by queemess in the realm of the aesthetic.Jose E. Munoz, Cruising Utopia, 1Prologue: Reading QueerlyBefore we fall down the well that brings us to Frau Holle, let's spend some time at our local gay bar involved in serious discussion about the merits and limits of queering the fairy tale. We're an eclectic bunch of scholars drinking beer and talking queer. First, we toast our debt to feminism: any queer interpretation further elaborates, even it departs from, rethinking of the fairy tale through feminism begun forty years ago. Second, we admit happily our tendencies toward what Bonnie Zimmerman calls the willful appropriations of mode of lesbian engagement with literature (139). For us perverse reading is an act of desire exciting meeting between our queer world of difference and the marvelous world of fairy-tale enchantments. By working through intuition and decipherment to draw out homoerotic traces and by finding pleasure in the text by actively listening to and speaking back to it, our perverse reading queers Mikhail Bakhtin's unfinalizable dialogic, expanding networks of expression.The works of certain colleagues gathered here at Club Shescape tonight adumbrate the queer potential of dialogism for fairy-tale readings. Cristina Bacchilega articulated the feminist recognition of fairy tales as sites of competing, historically and socially framed desires (10) that could be especially well understood in intertextual and interdiscursive readings of postmodern tales, exemplified in recent books by Jessica Tiffin and Vanessa Joosen. Pauline Greenhill, in her work on ballads, illuminated sexual scripts in floating verses; and the early work of Donald Haase cleared the path in claiming with some defiance that tales consist of highly ambiguous symbolic codes having no inherent, immutable, and clearly defined meaning and asserting the value of diverse responses reflecting a recipient's experience, perspective or predisposition (Reception 235). Haase distinguished but saw place for both responsible sociohistorical-geographic scholarship and irresponsible privately controlled reception and interpretation (243).At the same time (and again in 2004 in Fairy Tales and Feminism), Haase decried the dearth of reception studies, calling for more interview-based studies akin to Kay Stone's Romantic Heroines and Things Walt Disney Never Told Us. Among her discoveries, Haase says, she found that adult women's memory of fairy-tale characters was selective in remaking docile figures into active ones. This attested ultimately not only to the variability of interpretation but also to woman's ongoing and potentially liberating engagement with fairy tales over the course of her lifetime (Haase, Fairy Tales, 26). Few followed in Stone's footsteps, and none, to my knowledge, followed her queerly. We desperately need well-considered queer reception studies, especially in this era of children and teenagers who identify early on gay or queer. However, with none currently in hand, we can still call on belated interpretive practices. My own experience of reading, and that of number of my students and colleagues, consciously and inevitably yokes our reception to queer interpretation. We are among the growing legions of Haase's presciently termed irresponsible recipients of the fairy tale.Our concern is not so much with textual history it is with story's affecting potentialities, although feminist recovery scholarship rooted in carefully considered, if sometimes anecdotal, archive evidence adds sociohistorical benefits. Shawn Jarvis and Jeannine Blackwell open up our understanding of the German woman's social landscape during the initial reception period of the Grimms' tales. …

A validated algorithm to ascertain colorectal cancer recurrence using registry resources in Denmark.

Colorectal cancer recurrences are difficult to ascertain accurately and efficiently. We developed and validated an algorithm to identify recurrences that uses Danish medical registries. The algorithm uses metastasis and chemotherapy codes in the Danish National Patient Registry and codes indicating cancer recurrence in the Danish Pathology Registry. We applied the algorithm to a cohort (n = 21,246) of colorectal cancer patients diagnosed 2001-2011 and followed through 2012. In a cohort (n = 355) of two groups of actively followed patients, we compared the imputed recurrence data with recurrences diagnosed by regular follow-up. We compared cumulative incidence curves of imputed recurrence in local and regional stage patients from the large cohort, and of imputed and diagnosed recurrences in the actively followed cohort. In the 355 members of the actively followed cohort, our algorithm correctly identified 60 of 63 recurrences [sensitivity = 95%; 95% confidence interval (CI) 87-99%] and misclassified only 10 of 292 without recurrence (specificity = 97%; 95% CI 94-98%). Cumulative incidence curves showed that members of the large cohort with regional disease had much higher incidence of imputed recurrence than those with local disease. In the actively followed cohort, the cumulative incidence of recurrence overlapped substantially when recurrence was imputed by our algorithm or using the follow-up data. Despite some limitations regarding ambiguous pathology codes, our algorithm showed excellent performance against actively followed recurrence data, and the expected relation between recurrence risk and cancer stage. It can be used in the Danish registries and adapted to similar registries elsewhere.

Phylogenomics of the carrot genus (Daucus, Apiaceae).

• We explored the utility of multiple nuclear orthologs for the taxonomic resolution of wild and cultivated carrot, Daucus species.• We studied the phylogeny of 92 accessions of 13 species and two subspecies of Daucus and 15 accessions of related genera (107 accessions total) with DNA sequences of 94 nuclear orthologs. Reiterative analyses examined data of both alleles using ambiguity codes or a single allele with the highest coverage, trimmed vs. untrimmed homopolymers; pure exonic vs. pure intronic data; the use of all 94 markers vs. a reduced subset of markers; and analysis of a concatenated data set vs. a coalescent (species tree) approach.• Our maximum parsimony and maximum likelihood trees were highly resolved, with 100% bootstrap support for most of the external and many of the internal clades. They resolved multiple accessions of many different species as monophyletic with strong support, but failed to support other species. The single allele analysis gave slightly better topological resolution; trimming homopolymers failed to increase taxonomic resolution; the exonic data had a smaller proportion of parsimony-informative characters. Similar results demonstrating the same dominant topology can be obtained with many fewer markers. A Bayesian concordance analysis provided an overall similar phylogeny, but the coalescent analysis provided drastic changes in topology to all the above.• Our research highlights some difficult species groups in Daucus and misidentifications in germplasm collections. It highlights a useful subset of markers and approaches for future studies of dominant topologies in Daucus.

Evolution of the genetic code through progressive symmetry breaking

Evolution of the genetic code in an early RNA world is dependent on the steadily improving specificity of the coevolving protein synthesis machinery for codons, anticodons, tRNAs and amino acids. In the beginning, there is RNA but the machinery does not distinguish yet between the codons, which therefore all encode the same information. Synonymous codons are equivalent under a symmetry group that exchanges (permutes) the codons without affecting the code. The initial group changes any codon into any other by permuting the order of the bases in the triplet as well as by replacing the four RNA bases with each other at every codon position. This group preserves the differences between codons, known as Hamming distances, with a 1-distance corresponding to a single point mutation. Stepwise breaking of the group into subgroups divides the 64 codons into progressively smaller subsets – blocks of equivalent codons under the smaller symmetry groups, with each block able to encode a different message. This formalism prescribes how the evolving machinery increasingly differentiates between codons. The model indicates that primitive ribosomes first identified a unique mRNA reading frame to break the group permuting the order of the bases and subsequently enforced increasingly stringent codon–anticodon basepairing rules to break the subgroups permuting the four bases at each codon position. The modern basepairing rules evolve in five steps and at each step the number of codon blocks doubles. The fourth step generates 16 codon blocks corresponding with the 16 family boxes of the standard code and the last step splits these boxes into 32 blocks of commonly two, but rarely one or three, synonymous codons. The evolving codes transmit at most one message per codon block and as the number of messages increases so does the specificity of the code and of protein synthesis. The selective advantage conferred by better functioning proteins drives the symmetry breaking process. Over time paralogous tRNA evolution expands the anticodon repertoire, which is divided into anticodon blocks matching the codon blocks under the stage-specific ribosomal basepairing rules. Contemporaneously an expanding family of primitive aminoacyl-tRNA synthetases (aaRSs) divides the tRNA diversities into various different and overlapping subsets: each aaRS accepts some tRNAs but rejects all others and several aaRSs may accept the same tRNA species. Selection favoring less ambiguous codes eliminates these overlaps and also imposes the ribosomal anticodon block division as ambiguity arises when different aaRSs accept tRNAs of the same anticodon block. Only when the tRNAs of one or several anticodon blocks are accepted by a unique aaRS does the code become specific. This coding pattern is observed in the standard code and the evolution of amino acid assignments by primitive aaRSs onto tRNAs is traced back via tRNA trees that picture a gradual division of tRNA diversities into blocks with increasingly specific amino acid assignments. Symmetry breaking combined with continuous selection for codes carrying more information evolves increasingly specific codes and efficiently traverses an immense space of all possible codes (>1084) to give rise to the standard code.

COSMID: A Web-based Tool for Identifying and Validating CRISPR/Cas Off-target Sites.

Precise genome editing using engineered nucleases can significantly facilitate biological studies and disease treatment. In particular, clustered regularly interspaced short palindromic repeats (CRISPR) with CRISPR-associated (Cas) proteins are a potentially powerful tool for modifying a genome by targeted cleavage of DNA sequences complementary to designed guide strand RNAs. Although CRISPR/Cas systems can have on-target cleavage rates close to the transfection rates, they may also have relatively high off-target cleavage at similar genomic sites that contain one or more base pair mismatches, and insertions or deletions relative to the guide strand. We have developed a bioinformatics-based tool, COSMID (CRISPR Off-target Sites with Mismatches, Insertions, and Deletions) that searches genomes for potential off-target sites (http://crispr.bme.gatech.edu). Based on the user-supplied guide strand and input parameters, COSMID identifies potential off-target sites with the specified number of mismatched bases and insertions or deletions when compared with the guide strand. For each site, amplification primers optimal for the chosen application are also given as output. This ranked-list of potential off-target sites assists the choice and evaluation of intended target sites, thus helping the design of CRISPR/Cas systems with minimal off-target effects, as well as the identification and quantification of CRISPR/Cas induced off-target cleavage in cells.

A legal analysis of advertising of unhealthy foods to children: a case for regulatory reform?

BackgroundGrowing calls for restrictions on marketing of unhealthy food and drink to children over recent years have culminated in the development of a set of global recommendations by WHO to limit the power of food advertising and reduce children's overall exposure to promotion of unhealthy food and drink. There is also increasing criticism from health advocates in the UK and elsewhere on the effectiveness of existing regulation and the continued reliance on self-regulation of advertising over state-led regulation. We aimed to map the legal framework of regulation of food advertising to children in the European Union (EU) and UK and examine it for gaps in coverage of foods, ages, channels, and techniques; and to assess strengths and weaknesses of the regulatory regimen by principles of better regulation and aspects of regulatory theory, to develop implications for reform. MethodsRelevant law and regulation was identified by legal research techniques. Analysis of the framework included close textual consideration of legislation and other regulations. Published work and reports were searched for commentary on the effectiveness of the regulation. Broader assessment of the regulatory regimen was by analysis for compliance with principles of better regulation and aspects of regulatory theory. FindingsThe EU framework of regulation sets some minimum standards for the protection of children from unhealthy marketing, including limits on false health claims, misleading statements, and direct encouragement of children to buy food or pester others to do so. However, the EU's approach is potentially weakened by the exemption from regulation of exaggerated statements, the failure to allow member states to develop stronger regulation for food labelling, and the encouragement of voluntary self-regulation over state-led action in broadcast media. The UK has adopted some strong restrictions of unhealthy (high in fat, salt, or sugar) food and drink marketing in broadcast media but has not adopted a strategic approach to reduce unhealthy marketing to children more widely. The UK Government has endorsed the development of ambiguous and uncertain codes, with interpretation—even of health consequences—left to the self-regulatory agency. This factor has led to a complex and incoherent system. Moreover, many forms of advertising and marketing are left uncovered by industry-led self-regulation, creating gaps that ignore the nature of modern integrated marketing. UK regulation does not meet the UK Government's own standards of good regulation and the central players, UK Government sanctioned co-regulatory and self-regulatory industries, are also missing key qualities that may be necessary to secure legitimacy in the eyes of both public health advocates and the public. InterpretationGaps and inconsistencies in the regulatory framework suggest that there is a clear case for reform of existing industry-led regulation of advertising to children. However, much study of regulation suggests that there is no binary distinction between state-led regulation and self-regulation. Instead, there are a range of positions between the two. The state is able to influence self-regulators by indirect means; for example, the oversight of industry codes by other regulators or the development of competing regulatory bodies. Advocacy that highlights the flaws in self-regulation is justified. However, theoretical approaches, such as systems-theoretical views of regulation suggest that an indirect approach might be more likely to succeed than attempts to end self-regulation, and more desirable than piecemeal adjustments that are likely to only displace, rather than reduce, unhealthy advertising to children. FundingNone.

On the Origin of Ambiguity in Efficient Communication

This article studies the emergence of ambiguity in communication through the concept of logical irreversibility and within the framework of Shannon’s information theory. This leads us to a precise and general expression of the intuition behind Zipf’s vocabulary balance in terms of a symmetry equation between the complexities of the coding and the decoding processes that imposes an unavoidable amount of logical uncertainty in natural communication. Accordingly, the emergence of irreversible computations is required if the complexities of the coding and the decoding processes are balanced in a symmetric scenario, which means that the emergence of ambiguous codes is a necessary condition for natural communication to succeed.

The nature and scope of gambling in Canada

This paper provides a historical review of gambling in Canada and examines the benefits and shortcomings of present-day Canadian gambling policies and practices. This includes a discussion of provincial and federal government roles in gambling regulation and an overview of problem gambling prevention and treatment initiatives. The gambling studies literature was probed for pertinent information on factors such as historical development, legislative changes, economic conditions and cultural influences that have affected gambling participation and social responsibility strategies in Canada. Two major Criminal Code of Canada amendments (in 1969 and 1985) were pivotal in Canadian gambling expansion. The first decriminalized lotteries and casinos, while the second allowed electronic gambling devices and authorized provinces to operate and regulate gambling. These changes resulted in a radical gambling expansion which, in addition to raising provincial revenues, created public policy concerns. Varying provincial government interpretations of the ambiguous Criminal Code gambling statutes led to a lack of uniformity in how provinces regulate and operate gambling; when gambling expanded, there were no legislative safeguards in place to deal with the personal and societal effects of problem gambling. Subsequent programs designed to prevent and treat problem gambling have not been overly effective. Canadian provinces have a monopoly on gambling within their borders and treat the activity as a profit-driven business enterprise. Problems associated with widespread gambling such as addiction, increased crime, bankruptcy and suicide are seen as minor concerns and not addressed in an aggressive fashion. Given the Canadian federal government's detachment from gambling policy and Canadian provinces' heavy reliance on gambling revenues, little change in the Canadian gambling landscape is anticipated in the near future.

Bioinformatic Databases and Resources in the public domain to aid HLA research

Research in HLA as in any other field depends on information. Different groups have generated generic and specific resources and tools to support this research. The present review describes a qualified subset of these resources, which should cover the most important starting points for research in the HLA field. It discusses access to HLA allele sequences, allele frequencies, continues with general support to access to literature, DNA and protein sequence information, structural models, teaching books, databases with phenotypic datasets, alignment tools, peptide binding, statistical tools, guidelines and ambiguity coding. Following functionalities and databases have been included: IMGT/HLA, Immuno Polymorphism Database (IPD), allele frequencies*.net, a detailed look into NCBI (National Center of Biotechnology Information) with a subset of databases and tools, focusing on literature research, sequences, user-specific support tools and applications (PubMed, GenBank, MyNCBI, blast, Gene, MapViewer, Structure, CN3D, WorkBench, and dbMHC). This is followed by a brief survey of EBI-EMBL/Ensemble, the sequence alignment tool Clustal, the peptide and ligand databases SYFPEITHI and Immune Epitope Database, and last but not least statistical packages and HLA allele coding resources PyPop, the Immuno-genomics Data Analysis Working Group and the NMDP informatics section. All databases and tools can be freely accessed. Data linked to individuals, however, might require authorization by a data access committee.

Algorithms for enhancing public health utility of national causes-of-death data

BackgroundCoverage and quality of cause-of-death (CoD) data varies across countries and time. Valid, reliable, and comparable assessments of trends in causes of death from even the best systems are limited by three problems: a) changes in the International Statistical Classification of Diseases and Related Health Problems (ICD) over time; b) the use of tabulation lists where substantial detail on causes of death is lost; and c) many deaths assigned to causes that cannot or should not be considered underlying causes of death, often called garbage codes (GCs). The Global Burden of Disease Study and the World Health Organization have developed various methods to enhance comparability of CoD data. In this study, we attempt to build on these approaches to enhance the utility of national cause-of-death data for public health analysis.MethodsBased on careful consideration of 4,434 country-years of CoD data from 145 countries from 1901 to 2008, encompassing 743 million deaths in ICD versions 1 to 10 as well as country-specific cause lists, we have developed a public health-oriented cause-of-death list. These 56 causes are organized hierarchically and encompass all deaths. Each cause has been mapped from ICD-6 to ICD-10 and, where possible, they have also been mapped to the International List of Causes of Death 1-5. We developed a typology of different classes of GCs. In each ICD revision, GCs have been identified. Target causes to which these GCs should be redistributed have been identified based on certification practice and/or pathophysiology. Proportionate redistribution, statistical models, and expert algorithms have been developed to redistribute GCs to target codes for each age-sex group.ResultsThe fraction of all deaths assigned to GCs varies tremendously across countries and revisions of the ICD. In general, across all country-years of data available, GCs have declined from more than 43% in ICD-7 to 24% in ICD-10. In some regions, such as Australasia, GCs in 2005 are as low as 11%, while in some developing countries, such as Thailand, they are greater than 50%. Across different age groups, the composition of GCs varies tremendously - three classes of GCs steadily increase with age, but ambiguous codes within a particular disease chapter are also common for injuries at younger ages. The impact of redistribution is to change the number of deaths assigned to particular causes for a given age-sex group. These changes alter ranks across countries for any given year by a number of different causes, change time trends, and alter the rank order of causes within a country.ConclusionsBy mapping CoD through different ICD versions and redistributing GCs, we believe the public health utility of CoD data can be substantially enhanced, leading to an increased demand for higher quality CoD data from health sector decision-makers.

Evaluation of pre-screening methods for the identification of HIV-1 superinfection

The aim of this study was to compare sensitivity thresholds of two pre-screening methods – the heteroduplex mobility assay (HMA) and the presence of ambiguity codes in population-based sequences – applied for detection of HIV-1 superinfection. HIV-1 env C2-C4 PCR products generated from 48 serum samples isolated from 24 HIV-1 positive and therapy-naïve homosexual men at seroconversion and at approximately 1 year thereafter were subjected to HMA and population sequencing. Clonal sequence analysis was used to determine the sensitivity of each method to detect sequence variability. Results from HMA were compared to pairwise genetic distance of clonal sequences; heteroduplexes resulted from as little as 1.4% pairwise distance between two sequences and were detected even when only 1.5% of the pairwise distance comparisons exceeded this distance threshold. By contrast, the ambiguity code approach using population-based sequencing detected only 20.1% of existing sequence variation and was less sensitive to minority populations ≤20%, resulting in an underestimation of HIV-1 diversity. Thus, HMA was found to be more sensitive for detection of sequence variations than the ambiguity code approach, suggesting that HMA would be a more appropriate method to pre-screen for HIV-1 superinfection.

Quality control despite mistranslation caused by an ambiguous genetic code

A high level of accuracy during protein synthesis is considered essential for life. Aminoacyl-tRNA synthetases (aaRSs) translate the genetic code by ensuring the correct pairing of amino acids with their cognate tRNAs. Because some aaRSs also produce misacylated aminoacyl-tRNA (aa-tRNA) in vivo, we addressed the question of protein quality within the context of missense suppression by Cys-tRNA(Pro), Ser-tRNA(Thr), Glu-tRNA(Gln), and Asp-tRNA(Asn). Suppression of an active-site missense mutation leads to a mixture of inactive mutant protein (from translation with correctly acylated aa-tRNA) and active enzyme indistinguishable from the wild-type protein (from translation with misacylated aa-tRNA). Here, we provide genetic and biochemical evidence that under selective pressure, Escherichia coli not only tolerates the presence of misacylated aa-tRNA, but can even require it for growth. Furthermore, by using mass spectrometry of a reporter protein not subject to selection, we show that E. coli can survive the ambiguous genetic code imposed by misacylated aa-tRNA tolerating up to 10% of mismade protein. The editing function of aaRSs to hydrolyze misacylated aa-tRNA is not essential for survival, and the EF-Tu barrier against misacylated aa-tRNA is not absolute. Rather, E. coli copes with mistranslation by triggering the heat shock response that stimulates nonoptimized polypeptides to achieve a native conformation or to be degraded. In this way, E. coli ensures the presence of sufficient functional protein albeit at a considerable energetic cost.

Probabilistic base calling of Solexa sequencing data

BackgroundSolexa/Illumina short-read ultra-high throughput DNA sequencing technology produces millions of short tags (up to 36 bases) by parallel sequencing-by-synthesis of DNA colonies. The processing and statistical analysis of such high-throughput data poses new challenges; currently a fair proportion of the tags are routinely discarded due to an inability to match them to a reference sequence, thereby reducing the effective throughput of the technology.ResultsWe propose a novel base calling algorithm using model-based clustering and probability theory to identify ambiguous bases and code them with IUPAC symbols. We also select optimal sub-tags using a score based on information content to remove uncertain bases towards the ends of the reads.ConclusionWe show that the method improves genome coverage and number of usable tags as compared with Solexa's data processing pipeline by an average of 15%. An R package is provided which allows fast and accurate base calling of Solexa's fluorescence intensity files and the production of informative diagnostic plots.

PatMaN: rapid alignment of short sequences to large databases

Summary: We present a tool suited for searching for many short nucleotide sequences in large databases, allowing for a predefined number of gaps and mismatches. The commandline-driven program implements a non-deterministic automata matching algorithm on a keyword tree of the search strings. Both queries with and without ambiguity codes can be searched. Search time is short for perfect matches, and retrieval time rises exponentially with the number of edits allowed.Availability: The C++ source code for PatMaN is distributed under the GNU General Public License and has been tested on the GNU/Linux operating system. It is available from http://bioinf.eva.mpg.de/patman.Contact: pruefer@eva.mpg.deSupplementary information: Supplementary data are available at Bioinformatics online.

Analysis of the full-length genome of hepatitis B virus in the serum and cerebrospinal fluid of a patient with acute hepatitis B and transverse myelitis

Although many extrahepatic manifestations have been described in patients with acute or chronic hepatitis B, there are few reports about neurological disorders. We describe a 55-year-old man who contracted acute hepatitis B virus (HBV) infection and transverse myelitis. His neurological findings were gradually reduced along with the recovery from hepatitis. The cerebrospinal fluid (CSF) was revealed to be positive for HBsAg and HBV DNA. Full-length sequences of HBV in his serum and CSF were determined, and it was revealed that these two isolates had mutations at nucleotide (nt) 1762/1764 in the core promoter region and nt 1896 in the precore region. They were identical to each other except for two ambiguous codes at nt 2020 and 2631 in the CSF isolate. After cloning of the amplicons, substitutions at nt 2020 and 2631 were found in 6 (38%) of the 16 CSF clones. One clone of the 6 CSF clones had an additional substitution at nt 2119. These substitutions were not found in 16 serum clones. The presence of HBV clones unique to CSF suggests that HBV was a possible causative agent of the myelitis.

Incidence of Cutaneous T-Cell Lymphoma in the United States, 1973-2002

To describe incidence trends for cutaneous T-cell lymphoma (CTCL) in the United States. Population-based study. Data were obtained from 13 population-based cancer registries of the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute from 1973 through 2002. A total of 4783 cases of CTCL were identified for the period 1973 through 2002. Diagnosis of CTCL. The overall annual age-adjusted incidence of CTCL was 6.4 per million persons. Annual incidence increased by 2.9 x 10(-6) per decade over the study period. Incidence was higher among blacks (9.0 x 10(-6)) than among whites (6.1 x 10(-6)) and was higher among men (8.7 x 10(-6)) than among women (4.6 x 10(-6)). The racial differences in incidence decreased with age, while the sex differences increased with age and decreased over time. Substantial geographic variation in incidence was found. Incidence was correlated with high physician density, high family income, high percentage of population with a bachelor's degree or higher, and high home values. Changes in International Classification of Diseases for Oncology (ICD-O) morphologic definitions have resulted in the redistribution of the cases of CTCL among specific subclassifications. The continued rise in incidence of CTCL is substantial, and the cause of this increase is unknown. The racial, ethnic, sex, and geographic differences in incidence may be of etiologic importance. Changes in ICD-O definitions have made it difficult to evaluate incidence trends for subclassifications of CTCL such as mycosis fungoides. In addition, these changes resulted in the creation of ambiguous histologic codes, which may have caused coding errors. These errors along with the lack of independent verification are limitations of our study. An epidemiological investigation using population-based data is important to better understand this disorder.

A Nuclear Ribosomal DNA Phylogeny of Acer Inferred with Maximum Likelihood, Splits Graphs, and Motif Analysis of 606 Sequences

The multi-copy internal transcribed spacer (ITS) region of nuclear ribosomal DNA is widely used to infer phylogenetic relationships among closely related taxa. Here we use maximum likelihood (ML) and splits graph analyses to extract phylogenetic information from ~ 600 mostly cloned ITS sequences, representing 81 species and subspecies of Acer, and both species of its sister Dipteronia. Additional analyses compared sequence motifs in Acer and several hundred Ana-cardiaceae, Burseraceae, Meliaceae, Rutaceae, and Sapindaceae ITS sequences in GenBank. We also assessed the effects of using smaller data sets of consensus sequences with ambiguity coding (accounting for within-species variation) instead of the full (partly redundant) original sequences. Neighbor-nets and bipartition networks were used to visualize conflict among character state patterns. Species clusters observed in the trees and networks largely agree with morphology-based classifications; of de Jong's (1994) 16 sections, nine are supported in neighbor-net and bipartition networks, and ten by sequence motifs and the ML tree; of his 19 series, 14 are supported in networks, motifs, and the ML tree. Most nodes had higher bootstrap support with matrices of 105 or 40 consensus sequences than with the original matrix. Within-taxon ITS divergence did not differ between diploid and polyploid Acer, and there was little evidence of differentiated parental ITS haplotypes, suggesting that concerted evolution in Acer acts rapidly.