Miracle-dz/UniFAR-FTUs huggingface dataset:
Automatic assessment of alignment quality

Multiple sequence alignments play a central role in the annotation of novel genomes. Given the biological and computational complexity of this task, the automatic generation of high-quality alignments remains challenging. Since multiple alignments are usually employed at the very start of data analysis pipelines, it is crucial to ensure high alignment quality. We describe a simple, yet elegant, solution to assess the biological accuracy of alignments automatically. Our approach is based on the comparison of several alignments of the same sequences. We introduce two functions to compare alignments: the average overlap score and the multiple overlap score. The former identifies difficult alignment cases by expressing the similarity among several alignments, while the latter estimates the biological correctness of individual alignments. We implemented both functions in the MUMSA program and demonstrate the overall robustness and accuracy of both functions on three large benchmark sets.
Lithium and valproate attenuate dextroamphetamine‐induced changes in brain activation

Previous studies have suggested that both lithium and valproate may decrease phosphoinositol second messenger system (PI‐cycle) activity. There is also evidence that dextroamphetamine may increase PI cycle activity. It was previously demonstrated that dextroamphetamine administration in volunteers causes a region and task dependent decrease in brain activation in healthy volunteers. The current study assessed the effect of 14 days pretreatment with lithium and valproate on these dextroamphetamine‐induced changes in regional brain activity in healthy volunteers.
Studies of adhesion molecules mediating interactions between cells of peripheral nervous system indicate a major role for L1 in mediating sensory neuron growth on Schwann cells in culture

The involvement of the adhesion molecules L1, N-CAM, and J1 in adhesion and neurite outgrowth in the peripheral nervous system was investigated. We prepared Schwann cells and fibroblasts (from sciatic nerves) and neurons (from dorsal root ganglia) from 1-d mice. These cells were allowed to interact with each other in a short-term adhesion assay. We also measured outgrowth of dorsal root ganglion neurons on Schwann cell and fibroblast monolayers. Schwann cells (which express L1, N-CAM, and J1) adhered most strongly to dorsal root ganglion neurons by an L1-dependent mechanism and less by N-CAM and J1. Schwann cell-Schwann cell adhesion was mediated by L1 and N-CAM, but not J1. Adhesion of fibroblasts (which express N-CAM, but not L1 or J1) to neurons or Schwann cells was mediated by L1 and N-CAM and not J1. However, inhibition by L1 and N-CAM antibodies was found to be less pronounced with fibroblasts than with Schwann cells. N-CAM was also strongly involved in fibroblast-fibroblast adhesion. Neurite outgrowth was most extensive on Schwann cells and less on fibroblasts. A difference in extent of neurite elongation was seen between small- (10- 20 microns) and large- (20-35 microns) diameter neurons, with the larger neurons tending to exhibit longer neurites. Fab fragments of polyclonal L1, N-CAM, and J1 antibodies exerted slightly different inhibitory effects on neurite outgrowth, depending on whether the neurites were derived from small or large neurons. L1 antibodies interfered most strikingly with neurite outgrowth on Schwann cells (inhibition of 88% for small and 76% for large neurons), while no inhibition was detectable on fibroblasts. Similarly, although to a smaller extent than L1, N-CAM appeared to be involved in neurite outgrowth on Schwann cells and not on fibroblasts. Antibodies to J1 only showed a very small effect on neurite outgrowth of large neurons on Schwann cells. These observations show for the first time that identified adhesion molecules are potent mediators of glia-dependent neurite formation and attribute to L1 a predominant role in neurite outgrowth on Schwann cells which may be instrumental in regeneration.
Representations reclaimed: Accounting for the co-emergence of concepts and experience

Understanding the relationship between concepts and experience seems necessary to specifying the content of experience, yet current theories of concepts do not seem up to the job. With Peter Gardenfors's conceptual spaces theory as a foundation and with enactivist philosophy as inspiration, we present a proposed extension to conceptual spaces theory and use it to outline a model of the emergence of concepts and experience. We conclude that neither is ultimately primary but each gives rise to the other: i.e., that they co-emerge. Such a model can then serve as the anchor to a theory of concepts more generally. Concepts are most naturally understood in symbolic and representational terms, while much of experience, in contrast, is non-symbolic and non-representational; yet the conflict between the two will, herein, be shown to be more apparent than real. The main contribution of this paper is to argue for, by means of this account of co-emergence, a continuum between "low-level" mental content that is more appropriately understood in highly context-sensitive and directly sensorimotor-based terms, and "high-level" mental content that is more appropriately understood in context-free and representational or symbolic terms. In doing so we conclude that the extreme positions of representationalism and anti-representationalism are fatally flawed. (Less)
Efficient coupling of catalysis and dynamics in the E1 component of Escherichia coli pyruvate dehydrogenase multienzyme complex

Protein motions are ubiquitous and are intrinsically coupled to catalysis. Their specific roles, however, remain largely elusive. Dynamic loops at the active center of the E1 component of Escherichia coli pyruvate dehydrogenase multienzyme complex are essential for several catalytic functions starting from a predecarboxylation event and culminating in transfer of the acetyl moiety to the E2 component. Monitoring the kinetics of E1 and its loop variants at various solution viscosities, we show that the rate of a chemical step is modulated by loop dynamics. A cysteine-free E1 construct was site-specifically labeled on the inner loop (residues 401–413), and the EPR nitroxide label revealed ligand-induced conformational dynamics of the loop and a slow “open ↔ close” conformational equilibrium in the unliganded state. An 19F NMR label placed at the same residue revealed motion on the millisecond-second time scale and suggested a quantitative correlation of E1 catalysis and loop dynamics for the 200,000-Da protein. Thermodynamic studies revealed that these motions may promote covalent addition of substrate to the enzyme-bound thiamin diphosphate by reducing the free energy of activation. Furthermore, the global dynamics of E1 presumably regulate and streamline the catalytic steps of the overall complex by inducing an entirely entropic (nonmechanical) negative cooperativity with respect to substrate binding at higher temperatures. Our results are consistent with, and reinforce the hypothesis of, coupling of catalysis and regulation with enzyme dynamics and suggest the mechanism by which it is achieved in a key branchpoint enzyme in sugar metabolism.
Pathogenesis, epidemiology, diagnosis and clinical aspects of Smith–Lemli–Opitz syndrome

Introduction: Smith–Lemli–Opitz syndrome (SLOS) is a malformation syndrome inherited in an autosomal recessive fashion. It is due to a metabolic defect in the conversion of 7-dehydrocholesterol to cholesterol, which leads to an accumulation of 7-dehydrocholesterol and frequently a deficiency of cholesterol. The syndrome is characterized by typical dysmorphic facial features, multiple malformations, and intellectual disability. Areas covered: In this paper we provide an overview of the clinical phenotype and discuss how the manifestations of the syndrome vary depending on the age of the patients. We then explore the underlying biochemical defect and pathophysiological alterations that may contribute to the many disease manifestations. Subsequently we explore the epidemiology and succinctly discuss population genetics as they relate to SLOS. The next section presents the diagnostic possibilities. Thereafter, the treatment and management as is standard of care are presented. Expert opinion: Even though the knowledge of the underlying molecular mutations and the biochemical alterations is being rapidly accumulated, there is currently no efficacious therapy addressing neurological dysfunction. We discuss the difficulty of treating this disorder, which manifests as a combination of a malformation syndrome and an inborn error of metabolism. A very important factor in developing new therapies is the need to rigorously establish efficacy in controlled trials.
Comparing Translator Acceptability of TM and SMT Outputs

This paper reports on an initial study that aims to understand whether the acceptability of translation memory (TM) among translators when contrasted with machine translation (MT) unacceptability is based on users’ ability to optimise precision in match suggestions. Seven translators were asked to rate whether 60 English-German translated segments were a usable basis for a good target translation. 30 segments were from a domain-appropriate TM without a quality threshold being set, and 30 segments were translated by a general domain statistical MT system. Participants found the MT output more useful on average, with only TM fuzzy matches of over 90% considered more useful. This result suggests that, were the MT community able to provide an accurate quality threshold to users, they would consider MT to be the more useful technology.
Multi-Agent Planning as the Process of Merging Distributed Sub-plans

The subject of multi-agent planning has been of continuing concern in Distributed Artiicial Intelligence (DAI). In this paper, we suggest an approach to multi-agent planning that contains heuristic elements. Our method makes use of subgoals, and derived sub-plans, to construct a global plan. Agents solve their individual sub-plans, which are then merged into a global plan. The suggested approach reduces overall planning time and derives a plan that approximates the optimal global plan that would have been derived, given those original subgoals.
Prediction of Multiantenna Propagation Around Regular and Chaflane Street Corners

Two microcellular environments, which are the regular and chaflane street corners, are compared using a ray-launching engine based on the uniform theory of diffraction and geometric optics. This paper includes a study on the signal-to-noise ratio (SNR), K factor, correlation, and multiple-input multiple-output capacity. Two situations, which are the line-of-sight (LoS) and the non-LoS (NLoS), are distinguished and studied separately. In NLoS, the influence of the SNR is higher than the effect of the correlation. However, in LoS, the SNR is comparable in both environments, and correlation determines capacity
The Relationship of Musical Ability, Intelligence and Socioeconomic Status to Aesthetic Sensitivity

One of man's inherent needs is to have perceptive encounters with music. How he becomes equipped to experience music with meaningfulness is contingent upon many factors. Three variables (musical ability, intelligence, and socioeconomic status) were chosen as probably being the most influential of the many that impinge on an individual's making of value judgments. Their relationship to man's valueing process constitutes the basis of this study. The competency of making value judgements (and the levels at which that discrimination functions in regard to musical stimuli), for the purposes of this study, has been termed aesthetic sensitivity.
Role of MAPK Phosphatase-1 (MKP-1) in Adipocyte Differentiation*

Both time-dependent modulation of intracellular signaling molecules and sequential induction of transcriptional regulators are essential for the differentiation of preadipocytes into adipocytes. We have now shown that the activity, but not the abundance, of p42/p44 mitogen-activated protein kinase (MAPK) is down-regulated during adipocyte differentiation. This decrease in p42/p44 MAPK activity does not appear to be a direct effect of hormonal inducers of differentiation but rather represents a characteristic event of adipocyte differentiation that is achieved through a persistent change in intracellular signaling. Although the phosphorylation or abundance of MEK, an upstream kinase for p42/p44 MAPK, was not altered during differentiation, the abundance of MAPK phosphatase-1 (MKP-1), a negative regulator of p42/p44 MAPK, was increased with a time course similar to that of the down-regulation of p42/p44 MAPK activity. Ectopic expression of MKP-1 in preadipocytes reduced and depletion of endogenous MKP-1 in mature adipocytes increased the activity of p42/p44 MAPK. Prevention of the up-regulation of MKP-1 abundance in preadipocytes by expression of Mkp-1 antisense RNA resulted in persistence of p42/p44 MAPK activation and blocked differentiation, effects that were reversed by the MEK inhibitor PD98059. These results suggest that MKP-1 plays an essential role in adipocyte differentiation through down-regulation of p42/p44 MAPK activity.
The Outcome of Trachomatous Trichiasis Surgery in Ethiopia: Risk Factors for Recurrence

Background Over 1.2 million people are blind from trachomatous trichiasis (TT). Lid rotation surgery is the mainstay of treatment, but recurrence rates can be high. We investigated the outcomes (recurrence rates and other complications) of posterior lamellar tarsal rotation (PLTR) surgery, one of the two most widely practised TT procedures in endemic settings. Methodology/Principal Findings We conducted a two-year follow-up study of 1300 participants who had PLTR surgery, conducted by one of five TT nurse surgeons. None had previously undergone TT surgery. All participants received a detailed trachoma eye examination at baseline and 6, 12, 18 and 24 months post-operatively. The study investigated the recurrence rates, other complications and factors associated with recurrence. Recurrence occurred in 207/635 (32.6%) and 108/641 (16.9%) of participants with pre-operative major (>5 trichiatic lashes) and minor (<5 lashes) TT respectively. Of the 315 recurrences, 42/315 (3.3% overall) had >5 lashes (major recurrence). Recurrence was greatest in the first six months after surgery: 172 cases (55%) occurring in this period. Recurrence was associated with major TT pre-operatively (OR 2.39, 95% CI 1.83–3.11), pre-operative entropic lashes compared to misdirected/metaplastic lashes (OR 1.99, 95% CI 1.23–3.20), age over 40 years (OR 1.59, 95% CI 1.14–2.20) and specific surgeons (surgeon recurrence risk range: 18%–53%). Granuloma occurred in 69 (5.7%) and notching in 156 (13.0%). Conclusions/Significance Risk of recurrence is high despite high volume, highly trained surgeons. However, the vast majority are minor recurrences, which may not have significant corneal or visual consequences. Inter-surgeon variation in recurrence is concerning; surgical technique, training and immediate post-operative lid position require further investigation.
Toward a Semantic Account of that-Deletion in English

Abstract The phenomenon of that-deletion in English has traditionally been taken to be one of the prime examples of syntactic free variation: it has implicitly been assumed that the language arbitrarily allows predicates to embed their propositional complements with the complementizer that (as that-clauses), or without it (as bare clauses). Different researchers, however, have demonstrated that the complementizer CANNOT be deleted under certain classes of predicates. In this article, I show that the distribution of that-deletion across the different predicate classes is determined by a single semantic property, which I call “truth claim”: that-deletion is possible under predicates which semantically entail that a cognitive agent (most often their subject) has made an epistemic claim concerning the truth of the proposition denoted by the embedded clause. In some cases, that-deletion is also possible under predicates which pragmatically approximate the meanings of real truth claim predicates. This pattern is explained on the basis of semantic compatibility. I suggest that that-clauses and bare clauses have different meanings: that-clauses denote propositions, but bare clauses denote what I call “asserted propositions. ” Only truth claim predicates, and those predicates which can be pragmatically used as such, are compatible with asserted propositions. Consequently, only they are capable of embedding bare clauses. To account for the impossibility of that-deletion in non-complement positions, the above semantic theory is supplemented with a complexity-based, adjacency-type constraint on the pronunciation of the bare clause.
Recommendations for the Management of Retarded Ejaculation: Bashh Special Interest Group for Sexual Dysfunction on Behalf of the Bashh Special Interest Group for Sexual Dysfunction

We present the British Association of Sexual Health and HIV (BASHH) special interest group in sexual dysfunction recommendations for the management of retarded ejaculation. The recommendations outline the physiology, prevalence, definitions, aetiological factors and patient assessment for this sexual problem. We suggest treatment strategies, recommendations for management and an auditable outcome.
Understanding the Relationship Between Information About College Prices and Financial Aid and Students’ College-Related Behaviors

This article proposes a conceptual model for understanding the acquisition and use of information about college prices and financial aid. The model situates the process of acquiring and using information within several layers of context. Potential roles of four nested layers of context are discussed: habitus; the school and community context; the higher education context; and the broader social, economic, and policy context. Consideration of the model in light of available research suggests several potential explanations for differences across groups in the acquisition and use of information about college costs and financial aid.
On empirical memory design, faster selection of bayesian factorizations and parameter-free gaussian EDAs

Often, Estimation-of-Distribution Algorithms (EDAs) are praised for their ability to optimize a broad class of problems. EDA applications are however still limited. Often heard criticism is that a large population size is required and that distribution estimation takes long. Here we look at possibilities for improvements in these areas. We first discuss the use of a memory to aggregate information over multiple generations and reduce the population size. The approach we take, empirical risk minimization to perform non-linear regression of memory parameters, may well be generalizable to other EDAs. We design a memory this way for a Gaussian EDA and observe smaller population size requirements and fewer evaluations used. We also speed up the selection of Bayesian factorizations for Gaussian EDAs by sorting the entries in the covariance matrix. Finally, we discuss parameter-free Gaussian EDAs for real-valued single-objective optimization. We propose to not only increase the population size in subsequent runs, but to also divide it over parallel runs across the search space. On some multimodal problems improvements are thereby obtained.
Disseminating shared information in disaster relief efforts: A communication computable model

VHF radio systems commonly used to support search and rescue activities after disasters limit the flow of information among response teams deployed in the field. It generates islands of information that jeopardizes the coordination and effectiveness of the response activities. This article proposes a communication model that uses opportunistic networks and real-time messages delivery to help address such limitation. Since the communication model is computable, it is possible to diagnose the flow of information expected for a particular work scenario. The diagnose results allow identifying elements that could help improve the information flow in such scenario. This proposal allows first responders to address the stated problem during the phases of preparedness, response and recovery from a disaster.
Further defining the critical genes for the 4q21 microdeletion disorder

4q21 microdeletion syndrome (MIM: 613509) is a new genomic disorder characterized by intellectual disability, absent or severely delayed speech, growth retardation, hypotonia, variable brain malformation, and facial dysmorphism. The critical genes had been proposed based on an overlapping 1.37 Mb genomic region. No further refinement has been done since year 2010. Here, we present three cases with 4q21 deletion identified by clinical chromosomal microarray analysis. One of the cases have a de novo 761 kb deletion which is the smallest deletion ever reported at this locus. It provides an opportunity to further define the critical regions/genes associated with specific features of the 4q21 microdeletion syndrome. The evidence support the notion that PRKG2 and RASGEF1B are critical genes for intellectual disability and speech defect, and the heterogeneous nuclear ribonucleoprotein HNRNPD and HNRNPDL (previously known as HNRPDL) genes are associated with growth retardation and hypotonia. © 2016 Wiley Periodicals, Inc.
Relevance in microblogs: enhancing tweet retrieval using hyperlinked documents

Twitter serves over 1.6 billion searches each day, ranking tweets for display to the user in reverse-chronological order. However, finding relevant tweets can be a challenging task, since the relevance of a tweet is dependant both on its content and whether it links to a useful document. In this paper, we investigate how the content of documents hyperlinked from a tweet can be used to better estimate that tweet's relevance. In particular, we propose three approaches for incorporating the content of hyperlinked documents when ranking tweets. Within the context of the TREC 2011 and 2012 Microblog Tracks, we thoroughly evaluate to what extent hyperlinked documents can aid tweet retrieval effectiveness. Our results show that the application of hyperlinked documents can improve retrieval effectiveness over using the tweet content alone as well as using the presence of a URL within the tweet as a feature.
Parameter study of microwave assisted exfoliation of graphite and its application to large deformation strain sensors

Exfoliated graphite (EG), when blended into elastomer, is a promising material for the fabrication of large deformation strain sensors that can detect large deformation up to or more than 50%. Much, however, still remains uncertain and controversial about the exfoliating nature of EG and the conductivity of polymer mixed with fragmented EG (EG/polymer), which leads to the need for parameter study on EG and EG/polymer. Here, we characterize the expansion of graphite in the microwave-assisted exfoliation where KMnO4 and HNO3 are respectively used as oxidant and intercalation agent, therefore investigating the dependence of the expanding characteristics of graphite on: (i) mixing ratio (by weight) of graphite, KMnO4, and HNO3; (ii) mixing time; (iii) graphite form (natural vs. synthetic), type (lump vs. flake), and size (10 to 40 μm in diameter). The relation between the conductivity of polydimethylsiloxane (PDMS) mixed with fragmented EG (EG/PDMS) and the wt% of the composite is also measured. Based on the experimental results, 1-axis and 3-axis large deformation strain sensors are fabricated by airbrush stencil technique for the composites where pure PDMS and pure PDMS are respectively used as insulating polymer and conducting polymer. The sensors can be used for real-time structure health monitoring of engineering structures having free curved surfaces.