Specificity Constraint Research Articles

New Genes Interacted With Recent Whole-Genome Duplicates in the Fast Stem Growth of Bamboos.

As drivers of evolutionary innovations, new genes allow organisms to explore new niches. However, clear examples of this process remain scarce. Bamboos, the unique grass lineage diversifying into the forest, have evolved with a key innovation of fast growth of woody stem, reaching up to 1 m/day. Here, we identify 1,622 bamboo-specific orphan genes that appeared in recent 46 million years, and 19 of them evolved from noncoding ancestral sequences with entire de novo origination process reconstructed. The new genes evolved gradually in exon−intron structure, protein length, expression specificity, and evolutionary constraint. These new genes, whether or not from de novo origination, are dominantly expressed in the rapidly developing shoots, and make transcriptomes of shoots the youngest among various bamboo tissues, rather than reproductive tissue in other plants. Additionally, the particularity of bamboo shoots has also been shaped by recent whole-genome duplicates (WGDs), which evolved divergent expression patterns from ancestral states. New genes and WGDs have been evolutionarily recruited into coexpression networks to underline fast-growing trait of bamboo shoot. Our study highlights the importance of interactions between new genes and genome duplicates in generating morphological innovation.

Varieties of Sobel sequences

In this paper I provide a unified analysis of a number of pragmatic anomalies that have been discussed in the literature. The paper’s main goal is to account for Sobel sequences of conditionals and sequences of disjunctive sentences, but I will also propose that this analysis can be extended to sequences of sentences with superlatives. The starting point is the observation that, while all these sequences are felicitous in one order, they are infelicitous when the order is reversed. Previous proposals have focussed on particular types of infelicitous sequences (e.g. von Fintel, in: Kenstowicz (ed) Ken Hale: A life in language, MIT Press, Cambridge, 2001; Moss in Nous 46:516–586, 2012; Lewis in Nous 52:481–507, 2018; a.o.), or a subset of all the phenomena cited above (e.g. Singh in On competition between only and exh, 2008b; Linguist Philos 31:245–260, 2008c; Dohrn, in: Pistoia-Reda, Domaneschi (eds) Linguistic and psycholinguistic approaches on implicatures and presuppositions. Palgrave McMillan, Basingstoke, 2017; a.o.). I propose that sequences of sentences belonging to the same structured set of alternatives T are subject to a Specificity Constraint (SC): sequences are acceptable if both alternatives are dominated by the same number of nodes in the structured set of alternatives T. Violations of SC can be avoided by strengthening the weaker alternative. However, covert strengthening violates an economy condition if the overtly stronger alternative is among those made salient by the preceding utterance in the sequence (if any). I propose that the set of alternatives made salient by an utterance of a sentence s consists of s’s sisters and mother in T. I will show that the strengthening mechanism varies depending on the kind of sequence we have.

Programmable RNA Cleavage and Recognition by a Natural CRISPR-Cas9 System from Neisseria meningitidis

The microbial CRISPR systems enable adaptive defense against mobile elements and also provide formidable tools for genome engineering. The Cas9 proteins are type II CRISPR-associated, RNA-guided DNA endonucleases that identify double-stranded DNA targets by sequence complementarity and protospacer adjacent motif (PAM) recognition. Here we report that the type II-C CRISPR-Cas9 from Neisseria meningitidis (Nme) is capable of programmable, RNA-guided, site-specific cleavage and recognition of single-stranded RNA targets and that this ribonuclease activity is independent of the PAM sequence. We define the mechanistic feature and specificity constraint for RNA cleavage by NmeCas9 and also show that nuclease null dNmeCas9 binds to RNA target complementary to CRISPR RNA. Finally, we demonstrate that NmeCas9-catalyzed RNA cleavagecan be blocked by three families of type II-C anti-CRISPR proteins. These results fundamentally expand the targeting capacities of CRISPR-Cas9 and highlight the potential utility of NmeCas9 as a single platform to target both RNA and DNA.

What (not) to expect when classifying rare events.

When building classifiers, it is natural to require that the classifier correctly estimates the event probability (Constraint 1), that it has equal sensitivity and specificity (Constraint 2) or that it has equal positive and negative predictive values (Constraint 3). We prove that in the balanced case, where there is equal proportion of events and non-events, any classifier that satisfies one of these constraints will always satisfy all. Such unbiasedness of events and non-events is much more difficult to achieve in the case of rare events, i.e. the situation in which the proportion of events is (much) smaller than 0.5. Here, we prove that it is impossible to meet all three constraints unless the classifier achieves perfect predictions. Any non-perfect classifier can only satisfy at most one constraint, and satisfying one constraint implies violating the other two constraints in a specific direction. Our results have implications for classifiers optimized using g-means or F1-measure, which tend to satisfy Constraints 2 and 1, respectively. Our results are derived from basic probability theory and illustrated with simulations based on some frequently used classifiers.

Strong Enrichment of Aromatic Residues in Binding Sites from a Charge-neutralized Hyperthermostable Sso7d Scaffold Library

The Sso7d protein from the hyperthermophilic archaeon Sulfolobus solfataricus is an attractive binding scaffold because of its small size (7 kDa), high thermal stability (Tm of 98 °C), and absence of cysteines and glycosylation sites. However, as a DNA-binding protein, Sso7d is highly positively charged, introducing a strong specificity constraint for binding epitopes and leading to nonspecific interaction with mammalian cell membranes. In the present study, we report charge-neutralized variants of Sso7d that maintain high thermal stability. Yeast-displayed libraries that were based on this reduced charge Sso7d (rcSso7d) scaffold yielded binders with low nanomolar affinities against mouse serum albumin and several epitopes on human epidermal growth factor receptor. Importantly, starting from a charge-neutralized scaffold facilitated evolutionary adaptation of binders to differentially charged epitopes on mouse serum albumin and human epidermal growth factor receptor, respectively. Interestingly, the distribution of amino acids in the small and rigid binding surface of enriched rcSso7d-based binders is very different from that generally found in more flexible antibody complementarity-determining region loops but resembles the composition of antibody-binding energetic hot spots. Particularly striking was a strong enrichment of the aromatic residues Trp, Tyr, and Phe in rcSso7d-based binders. This suggests that the rigidity and small size of this scaffold determines the unusual amino acid composition of its binding sites, mimicking the energetic core of antibody paratopes. Despite the high frequency of aromatic residues, these rcSso7d-based binders are highly expressed, thermostable, and monomeric, suggesting that the hyperstability of the starting scaffold and the rigidness of the binding surface confer a high tolerance to mutation.

Encoding motion events in Chinese and the “scalar specificity constraint”

Mandarin Chinese often expresses motion events with more than one verbal motion morpheme, e.g., 退 tui ‘recede’ and 回 hui ‘return’ in 退回房間裏 tui-hui fangjian-li recede-return room-inside ‘return into the room’. Building on recent work on “scale structure”, this paper proposes a “Motion Morpheme Hierarchy” that can be used to better predict the order of co-occurring motion morphemes: specifically, Chinese motion morphemes can be classified into four types based on the scale information they lexicalize, and the order of co-occurring motion morphemes tends to be closely related to the type of scale they lexicalize. The hierarchy is then verified using two corpus studies drawing on naturally occurring Chinese data: the first study examines the order of motion morphemes found in all motion constructions from selected recent Chinese novels, and the second study investigates the order of eight highly frequently used motion morphemes with respect to their co-occurring motion morphemes in the CCL Corpus; both corpus studies show that the hierarchy holds for most Chinese motion morphemes. Furthermore, this paper proposes a semantic constraint named the “Scalar Specificity Constraint” to account for the morpheme order predicted by the hierarchy: the morpheme with more information about the path of motion tends to occur after the morphemes with less information. For instance, 回 hui ‘recede’ lexicalizes an endpoint for the path and thus, is preceded by 退 tui ‘recede’ which does not indicate any endpoint. The constraint not only provides better coverage of the data involving Chinese motion constructions, but also indicates the role that the path information a motion morpheme lexicalizes plays in the morpheme’s distribution. This study provides new insight into the distribution of motion morphemes in Chinese MMMCs and a more fine-grained analysis of the semantic relationships between the morphemes in these constructions, and thus contributes to an increased understanding of how motion events are expressed in Chinese. The findings of this study may also illuminate the distribution of motion verbs in other languages, as well as constructions in domains beyond motion.

Reassortment Networks and the evolution of pandemic H1N1 swine-origin influenza.

Prior research developed Reassortment Networks to reconstruct the evolution of segmented viruses under both reassortment and mutation. We report their application to the swine-origin pandemic H1N1 virus (S-OIV). A database of all influenza A viruses, for which complete genome sequences were available in Genbank by October 2009, was created and dynamic programming was used to compute distances between all corresponding segments. A reassortment network was created to obtain the minimum cost evolutionary paths from all viruses to the exemplar S-OIV A/California/04/2009. This analysis took 35 hours on the Cray Extreme Multithreading (XMT) supercomputer, which has special hardware to permit efficient parallelization. Six specific H1N1/H1N2 bottleneck viruses were identified that almost always lie on minimum cost paths to S-OIV. We conjecture that these viruses are crucial to S-OIV evolution and worthy of careful study from a molecular biology viewpoint. In phylogenetics, ancestors are typically medians that have no functional constraints. In our method, ancestors are not inferred, but rather chosen from previously observed viruses along a path of mutation and reassortment leading to the target virus. This specificity and functional constraint render our results actionable for further experiments in vitro and in vivo.

Questioning the IT artefact: user practices that can, could, and cannot be supported in packaged-software designs

The purchase of packaged software has brought new opportunities and challenges to the development of information systems. An important question for packaged software consumers is how a software package will support, change or inhibit practices. To address this question, our paper focuses on the decisions made by a team developing four different software prototypes, with increasingly relaxed constraints on data content and structure. Each prototype significantly enlarged the number of health promotion planners that could be supported by the software. Consistent with the literature, the software designers balanced specificity (constraint) and generality (opening) in the software to incorporate a desire to serve a broad audience, and a need to be relevant to various sub-groups within this audience. Given a detailed knowledge of the software artefact, including the data content and structural choices made by designers, we hope to enable software consumers to question IT artefacts and their spokespeople, so they can make active and informed choices about software generality and specificity. We also suggest that this questioning process is shared across both customised and packaged software, and that the inscription of technology by designers may be either deterministic and detailed, or emergent and general. The implications for packaged software research and practice are considered.

The interplay between signal processing and networking in sensor networks

This paper provides a signal processing perspective on large-scale sensor networks. It focuses on two characteristics of sensor networks: application specificity and energy constraint. The former requires that network protocols be designed for the application at hand, which is often signal processing in nature, and measured by application-specific metrics. The latter calls for novel distributed signal processing techniques to provide accurate and timely network state information that can be exploited by network protocols to ensure energy efficiency. The underlying theme is about how a principled integration of signal processing and networking can lead to an efficient and fair use of limited resources. The paper aims to demonstrate that capturing and exploiting dependencies between signal processing and networking offer design choices resulting in improved network performance.

MultiPrimer

This study presents a novel application, MultiPrimer, to assist users to design multiplex PCR primers. MultiPrimer adopts an algorithm based on a genetic algorithm and can efficiently solve the multi-objective optimisation problem. A match pattern model is proposed to speed up examination of the specificity constraint. MultiPrimer is able to find a set of primer pairs simultaneously for a set of gene family sequences and multiple targets for a single cDNA sequence. A public version of the MultiPrimer software is available from http://edith.cse.nsysu.edu.tw/new/software/MultiPrimer.htm.

GENETAG: a tagged corpus for gene/protein named entity recognition

BackgroundNamed entity recognition (NER) is an important first step for text mining the biomedical literature. Evaluating the performance of biomedical NER systems is impossible without a standardized test corpus. The annotation of such a corpus for gene/protein name NER is a difficult process due to the complexity of gene/protein names. We describe the construction and annotation of GENETAG, a corpus of 20K MEDLINE® sentences for gene/protein NER. 15K GENETAG sentences were used for the BioCreAtIvE Task 1A Competition.ResultsTo ensure heterogeneity of the corpus, MEDLINE sentences were first scored for term similarity to documents with known gene names, and 10K high- and 10K low-scoring sentences were chosen at random. The original 20K sentences were run through a gene/protein name tagger, and the results were modified manually to reflect a wide definition of gene/protein names subject to a specificity constraint, a rule that required the tagged entities to refer to specific entities. Each sentence in GENETAG was annotated with acceptable alternatives to the gene/protein names it contained, allowing for partial matching with semantic constraints. Semantic constraints are rules requiring the tagged entity to contain its true meaning in the sentence context. Application of these constraints results in a more meaningful measure of the performance of an NER system than unrestricted partial matching.ConclusionThe annotation of GENETAG required intricate manual judgments by annotators which hindered tagging consistency. The data were pre-segmented into words, to provide indices supporting comparison of system responses to the "gold standard". However, character-based indices would have been more robust than word-based indices. GENETAG Train, Test and Round1 data and ancillary programs are freely available at . A newer version of GENETAG-05, will be released later this year.

Maturational Constraints on Functional Specializations for Language Processing: ERP and Behavioral Evidence in Bilingual Speakers

Changes in several postnatal maturational processes during neural development have been implicated as potential mechanisms underlying critical period phenomena. Lenneberg hypothesized that maturational processes similar to those that govern sensory and motor development may also constrain capabilities for normal language acquisition. Our goal, using a bilingual model, was to investigate the hypothesis that maturational constraints may have different effects upon the development of the functional specializations of distinct sub within language. Subjects were 61 adult Chinese/English bilinguals who were exposed to English at different points in development: 1-3, 4-6, 7-10, 11-13, and after 16 years of age. Event-related brain potentials (ERPs) and behavioral responses were obtained as subjects read sentences that included semantic anomalies, three types of syntactic violations (phrase structure, specificity constraint, and subjacency constraint), and their controls. The accuracy in judging the grammaticality for the different types of syntactic rules and their associated ERPs was affected by delays in second language exposure as short as 1-3 years. By comparison the N400 response and the judgment accuracies in detecting semantic anomalies were altered only in subjects who were exposed to English after 11-13 and 16 years of age, respectively. Further, the type of changes occurring in ERPs with delays in exposure were qualitatively different for semantic and syntactic processing. All groups displayed a significant N400 effect in response to semantic anomalies, however, the peak latencies of the N400 elicited in bilinguals who were exposed to English between 11-13 and >16 years occurred later, suggesting a slight slowing in processing. For syntactic processing. the ERP differences associated with delays in exposure to English were observed in the morphology and distribution of components. Our findings are consistent with the view that maturational changes significantly constrain the development of the neural systems that are relevant for language and, further, that subsystems specialized for processing different aspects of language display different sensitive periods.