Miracle-dz/UniFAR-FTUs huggingface dataset:
MUSTANG-MR Structural Sieving Server: Applications in Protein Structural Analysis and Crystallography

Background A central tenet of structural biology is that related proteins of common function share structural similarity. This has key practical consequences for the derivation and analysis of protein structures, and is exploited by the process of “molecular sieving” whereby a common core is progressively distilled from a comparison of two or more protein structures. This paper reports a novel web server for “sieving” of protein structures, based on the multiple structural alignment program MUSTANG. Methodology/Principal Findings “Sieved” models are generated from MUSTANG-generated multiple alignment and superpositions by iteratively filtering out noisy residue-residue correspondences, until the resultant correspondences in the models are optimally “superposable” under a threshold of RMSD. This residue-level sieving is also accompanied by iterative elimination of the poorly fitting structures from the input ensemble. Therefore, by varying the thresholds of RMSD and the cardinality of the ensemble, multiple sieved models are generated for a given multiple alignment and superposition from MUSTANG. To aid the identification of structurally conserved regions of functional importance in an ensemble of protein structures, Lesk-Hubbard graphs are generated, plotting the number of residue correspondences in a superposition as a function of its corresponding RMSD. The conserved “core” (or typically active site) shows a linear trend, which becomes exponential as divergent parts of the structure are included into the superposition. Conclusions The application addresses two fundamental problems in structural biology: First, the identification of common substructures among structurally related proteins—an important problem in characterization and prediction of function; second, generation of sieved models with demonstrated uses in protein crystallographic structure determination using the technique of Molecular Replacement.
Security Requirements Engineering for Evolving Software Systems: A Survey

Long-lived software systems often undergo evolution over an extended period. Evolution of these systems is inevitable as they need to continue to satisfy changing business needs, new regulations and standards, and introduction of novel technologies. Such evolution may involve changes that add, remove, or modify features; or that migrate the system from one operating platform to another. These changes may result in requirements that were satisfied in a previous release of a system not being satisfied in subsequent versions. When evolutionary changes violate security requirements, a system may be left vulnerable to attacks. In this article we review current approaches to security requirements engineering and conclude that they lack explicit support for managing the effects of software evolution. We then suggest that a cross fertilization of the areas of software evolution and security engineering would address the problem of maintaining compliance to security requirements of software systems as they evolve.
Power of the wingbeat: modelling the effects of flapping wings in vertebrate flight

Animal flight performance has been studied using models developed for man-made aircraft. For an aeroplane with fixed wings, the energetic cost as a function of flight speed can be expressed in terms of weight, wing span, wing area and body area, where more details are included in proportionality coefficients. Flying animals flap their wings to produce thrust. Adopting the fixed wing flight model implicitly incorporates the effects of wing flapping in the coefficients. However, in practice, these effects have been ignored. In this paper, the effects of reciprocating wing motion on the coefficients of the fixed wing aerodynamic power model for forward flight are explicitly formulated in terms of thrust requirement, wingbeat frequency and stroke-plane angle, for optimized wingbeat amplitudes. The expressions are obtained by simulating flights over a large parameter range using an optimal vortex wake method combined with a low-level blade element method. The results imply that previously assumed acceptable values for the induced power factor might be strongly underestimated. The results also show the dependence of profile power on wing kinematics. The expressions introduced in this paper can be used to significantly improve animal flight models.
Invasion of endothelial cells by Neisseria meningitidis requires cortactin recruitment by a phosphoinositide-3-kinase/Rac1 signalling pathway triggered by the lipo-oligosaccharide

Type-IV-pilus-mediated adhesion of Neisseria meningitidis (also known as meningococcus) to human endothelial cells induces the formation of membrane protrusions leading to bacterial uptake. We have previously shown that these protrusions result from a Rho- and Cdc42-dependent cortical actin polymerization, and from the activation of the ErbB2 tyrosine-kinase receptor and the Src kinase, leading to tyrosine phosphorylation of cortactin. We report here that N. meningitidis mutants expressing a deglycosylated lipo-oligosaccharide are poorly invasive. These mutants show structurally altered actin polymerization. Moreover, although they efficiently recruit and activate ErbB2 and Src, these mutants are defective in the recruitment and phosphorylation of cortactin. We demonstrate that phosphorylated cortactin controls the cortical actin polymerization, which leads to membrane protrusion formation. In addition, we show that cortactin recruitment is dependent on the activation of a phosphoinositide-3-kinase/Rac1-GTPase signalling pathway, which is required for actin polymerization and internalization of N. meningitidis, and is not activated by the mutant strains. Altogether, these results define a new role for the lipo-oligosaccharide in triggering a phosphoinositide-3-kinase/Rac1 signalling required to elicit an efficient uptake of N. meningitidis in non-phagocytic cells.
Tits Alternative for Maximal Subgroups of Skew Linear Groups

Let D be a noncommutative finite dimensional F-central division algebra, and let N be a normal subgroup of GL n (D) with n ≥ 1. Given a maximal subgroup M of N, it is proved that either M contains a noncyclic free subgroup, or there exists an abelian subgroup A and a finite family of fields properly containing F with for all 1 ≤ i ≤ r such that M/A is finite if Char F = 0 and M/A is locally finite if Char F = p > 0, where .
On the Pseudo-Hermiticity of General PT-Symmetric Standard Hamiltonians in One Dimension

For a given standard Hamiltonian H with arbitrary complex scalar and vector potentials in one-dimension, we construct an invertible antilinear operator τ such that H is τ -anti-pseudo-Hermitian, i.e., H = τHτ−1. We use this result to give the explicit form of a linear Hermitian invertible operator with respect to which any standard PT symmetric Hamiltonian with a real degree of freedom is pseudo-Hermitian. In a recent series of papers [1, 2, 3] we have revealed the basic mathematical structure responsible for the intriguing spectral properties of PT -symmetric systems [4]. The main ingredient leading to the results of [1, 2, 3] and their ramifications [5, 6, 7, 8, 9] is the concept of a pseudo-Hermitian operator. By definition, a linear operator H acting in a Hilbert space is pseudo-Hermitian if there is a linear Hermitian invertible operator η satisfying H = ηHη, (1) ∗E-mail address: amostafazadeh@ku.edu. tr
(Mis)Conceptions Regarding Teacher-Generated Preemptive Attention to Form

Preemptive focus on form (FonF) is perhaps the most under-researched area in the field of incidental focus on form. However, between the two subsets of preemptive focus on form, teacher-initiated preemptive FonF seems to be the least favored one. To put this stance into a test, 18 sessions of an intermediate EFL class were observed, audio-recorded and analyzed for the instances of learner- and teacher-initiated focus on form episodes (FFEs), as well as the rate of uptake moves following them. To triangulate the observational data on uptake, an elicitation instrument, namely, a think-aloud incidental focus on form sheet was also devised to collect on-the-spot, written instances of learner and teacher generated FFES. The quantitative results derived both from the audio-data and the sheets demonstrated that teacher-initiated FFEs strongly came first regarding their frequency and the rate of follow-up uptake moves. An in-depth qualitative analysis of the uptake sheets also revealed that after certain teacher-initiated FFEs, some learners produced multiple uptake moves, while after some others no one or just a single learner produced uptake. The findings from uptake sheets indicate that specific teacher-initiated FFEs are highly effective in tapping the linguistic holes of all or majority of EFL learners in a given class. Based on the quantitative and qualitative results, the researchers call for a reconsideration of the role and effectiveness of teacher-generated attention to form as an important component of communicative classes.
Potential of stem/progenitor cells in treating stroke: the missing steps in translating cell therapy from laboratory to clinic.

Cesar V Borlongan1,2†, Michael Chopp3, Gary K Steinberg4, Tonya M Bliss4, Yi Li3, Mei Lu3, David C Hess1 & Douglas Kondziolka5 †Author for correspondence 1Medical College of Georgia and Augusta VA Medical Center, Department of Neurology, 1120 15th Street Augusta, GA 30904, USA 2Tel. : +1 706 721 2145; Fax: +1 706 721 7619; E-mail: cborlongan@ mail.mcg. edu 3Henry Ford Hospital, Department of Neurology, 2799 West Grand Blvd., Detroit, MI 48202, USA 4Stanford University School of Medicine, Department of Neurosurgery, R281, 300 Pasteur Drive, Stanford, CA, 94305, USA 5University of Pittsburgh, Department of Neurological Surgery, Suite B-400, UPMC, 200 Lothrop Street Pittsburgh, PA 15213, USA ‘. it is imperative for clinical translation that these cells be tested in multiple models of focal stroke, in two species, in both genders and in multiple laboratories. ’
Task-dependent representations in rat hippocampal place neurons.

It is suggested that the hippocampal formation is essential to spatial representations by flexible encoding of diverse information during navigation, which includes not only externally generated sensory information such as visual and auditory sensation but also ideothetic information concerning locomotion (i.e., internally generated information such as proprioceptive and vestibular sensation) as well as information concerning reward. In the present study, we investigated how various types of information are represented in the hippocampal formation, by recording hippocampal complex-spike cells from rats that performed three types of place learning tasks in a circular open field with the use of intracranial self-stimulation as reward. The intracranial self-stimulation reward was delivered in the following three contexts: if the rat 1) entered an experimenter-determined reward place within the open field, and this place was randomly varied in sequential trials; 2) entered two specific places, one within and one outside the place field (an area identified by change in activity of a place neuron); or 3) entered an experimenter-specified place outside the place field. Because the behavioral trails during navigation were more constant in the second task than in the first task, ideothetic information concerning locomotion was more relevant to acquiring reward in the second task than in the first task. Of 43 complex-spike cells recorded, 37 displayed place fields under the first task. Of these 37 place neurons, 34 also had significant reward correlates only inside the place field. Although reward and place correlates of the place neuron activity did not change between the first and second tasks, neuronal correlates to behavioral variables for locomotion such as movement speed, direction, and turning angle significantly increased in the second task. Furthermore, 6 of 31 place neurons tested with the third task, in which the reward place was located outside the original place field, shifted place fields. The results indicated that neuronal correlates of most place neurons flexibly increased their sensitivity to relevant information in a given context and environment, and some place neurons changed the place field per se with place reward association. These results suggest two strategies for how hippocampal neurons incorporate an incredible variety of perceptions into a unified representation of the environment: through flexible use of information and the creation of new representations.
Computational Insights into Binding of Bisphosphates to Farnesyl Pyrophosphate Synthase

Bisphosphonates (BPs) are the most widely used and effective treatment for osteoporosis and Paget's disease. Non-nitrogen containing BPs (non-N-BPs), namely etidronate, clodronate, tiludronate, as well as nitrogen-containing BPs (N-BPs), namely pamidronate, alendronate, ibandronate, risedronate, zoledronate and minodronate have been launched on the market to date. N-BPs act by inhibiting the enzyme farnesyl pyrophosphate synthase (FPPS), and several crystal structures of complexes between FPPS and N-BPs have been revealed. Understanding the physical basis of the binding between protein and small molecules is an important goal in both medicinal chemistry and structural biology. In this review, we analyze in detail the energetic basis of molecular recognition between FPPS and N-BPs. First, we summarize the interactions between ligands and proteins observed in N-BPs-FPPS complexes in the Protein Data Bank (PDB). Second, we present an interaction energy analysis on the basis of full quantum mechanical calculation of FPPS and N-BP complexes using the fragment molecular orbital (FMO) method. The FMO result revealed that not only hydrogen bond and electrostatic interaction but also CH-O and π-π interaction with FPPS are important for N-BP’s potency. Third, we describe a binding site analysis of FPPS on the basis of the inhomogeneous solvation theory which, by clustering the results from an explicit solvent molecular dynamics simulation (MD), is capable of describing the entropic and enthalpic contributions to the free energies of individual hydration sites. Finally, we also discuss the structure-activity relationship (SAR) of the series of minodronate derivatives.
An Edge-Bundling Layout for Interactive Parallel Coordinates

Parallel Coordinates is an often used visualization method for multidimensional data sets. Its main challenges for large data sets are visual clutter and over plotting which hamper the recognition of patterns in the data. We present an edge-bundling method using density-based clustering for each dimension. This reduces clutter and provides a faster overview of clusters and trends. Moreover, it allows rendering the clustered lines using polygons, decreasing rendering time remarkably. In addition, we design interactions to support multidimensional clustering with this method. A user study shows improvements over the classic parallel coordinates plot in two user tasks: correlation estimation and subset tracing.
The role of high-school duration for university students' motivation, abilities and achievements

ABSTRACT We study the effects of learning intensity and duration of high school on students' motivation, abilities and achievements at university. The empirical analysis is based on primary panel data from an education reform in the German state of Saxony-Anhalt that reduced university preparatory schooling from 13 to 12 years but left the curriculum unchanged. The estimates show some impacts on students' perceptions of learning abilities, but the probability of university drop-out and the final grade remain unchanged. By and large, the findings indicate that students affected by the reform are similarly motivated and skilled compared to the counterfactual situation.
The nuclear basket proteins Mlp1p and Mlp2p are part of a dynamic interactome including Esc1p and the proteasome

Mlp1p and Mlp2p form the basket of the yeast nuclear pore complex (NPC) and contribute to NPC positioning, nuclear stability, and nuclear envelope morphology. The Mlps also embed the NPC within an extended interactome, which includes protein complexes involved in mRNP biogenesis, silencing, spindle organization, and protein degradation.
A one-pass resource-allocating codebook for patch-based visual object recognition

Frequencies of occurrence of low-level image features is the representation of choice in the design of state-of-the-art visual object recognition systems. A crucial step in this process is the construction of a codebook of visual features, which is usually done by cluster analysis of a large number of low-level image features detected as interest points. However, clustering is a process that retains regions of high density in a distribution and it follows that the resulting codebook need not have discriminant properties. Here we extend our recent work on constructing a one-pass discriminant codebook design procedure inspired by the resource allocating network model from the artificial neural networks literature. Unlike clustering, this approach retains data spread out more widely in the input space, thereby including rare low-level features in the codebook. It simultaneously achieves increased discrimination and a drastic reduction in the computational needs. We illustrate some properties of our-method and compare it to a closely related approach.
Toxicokinetics/Toxicodynamics of γ-Hydroxybutyrate-Ethanol Intoxication: Evaluation of Potential Treatment Strategies

γ-Hydroxybutyrate (GHB), a common drug of abuse, is often coingested with ethanol. Increasing renal clearance via monocarboxylate transporter (MCT) inhibition represents a potential therapeutic strategy in GHB overdose, as does inhibition of GABAB receptors. In this study, we investigate toxicokinetic/toxicodynamic interactions between GHB-ethanol and efficacy of treatment options for GHB-ethanol intoxication in rats. Sedation was assessed using the endpoint of return-to-righting reflex. Respiration was assessed using plethysmography. Coadministration of 2.0 g/kg ethanol i.v. with 600 mg/kg GHB i.v. increased sleep time compared with GHB alone. Administration of ethanol to steady-state concentrations of 0.1–0.2% and 0.3–0.4% (w/v) did not affect toxicokinetics of 600 mg/kg GHB i.v. , or respiratory rate, but did result in significantly lower peak tidal volumes compared with GHB alone. Oral administration of 2.5 g/kg ethanol had no significant effect on toxicokinetics of 1500 mg/kg orally administered GHB. Pretreatment with specific receptor inhibitors indicated no effect of GABAA receptor inhibition on sleep time or respiratory depression in GHB-ethanol intoxication. GABAB receptor inhibition partially prevented sedation and completely prevented respiratory depression. Ethanol increased fatality when administered at 0.1–0.2% (4 of 10) and 0.3–0.4% (9 of 10) versus 1500 mg/kg GHB i.v. alone (0 of 10). Treatment with the MCT inhibitor, l-lactate, significantly decreased sleep time after GHB-ethanol and decreased fatality at 0.1–0.2% (0 of 10) and 0.3–0.4% ethanol (5 of 10). Treatment with a GABAB receptor antagonist completely prevented fatality at 0.3–0.4% (0 of 10). These data indicate that ethanol potentiates the sedative and respiratory depressant effects of GHB, increasing the risk of fatality. MCT and GABAB receptor inhibition represent potentially effective treatments in GHB-ethanol intoxication.
Growth Management and Sustainable Transport: Do Growth Management Policies Promote Transit Use?

Although the concept of sustainability is somewhat elusive in the sense that it is defined and understood differently in different contexts, transit is typically considered a more sustainable transport mode. One critical question regarding urban transit is how do we encourage its use? In this paper, the authors focus on the effects of growth management policies on mode choice and transit use. WThe authors discuss and empirically analyze whether or not state-level growth management efforts contribute to promoting transit use and through what causal mechanisms. The authors argue that theoretically, state-level growth management policies should effectively increase transit use in two critical ways: first, by limiting core abandonment and accommodating potential increases in population (potentially avoiding unnecessary or fringe development); and second, by directing new development into areas where transit systems are already well established. The authors test this idea by analyzing 95 metropolitan areas across the U.S.; 16 within growth management jurisdiction, and 79 outside of growth management jurisdiction. The authors find that metropolitan areas that were contained within growth management program jurisdiction showed a statistically significant improvement in the percentage of commuters using transit. The results of this empirical analysis on causality however, suggest that the improvement is more likely due to an increase in occupancy rates (limiting core abandonment and potentially avoiding unnecessary development) rather than in shifting the location of new development to transit areas.
The importance of coparenting quality when parenting a child with an Autism Spectrum Disorder: a mixed method investigation

xvi : Introduction . 2 Chapter 1 1.1 Background . 2 1.2 Primary Hypothesis . 4 1.3 Overview of Research Design . 4 1.4 Method . 6 1.5 Measures. 6 1.6 Results . 7 1.7 Conclusion . 8
Factors Associated with Late Presentation of HIV and Estimation of Antiretroviral Treatment Need according to CD4 Lymphocyte Count in a Resource-Limited Setting: Data from an HIV Cohort Study in India

We describe the CD4 lymphocyte count at HIV presentation in an HIV cohort from a rural district of India. The majority of patients were diagnosed for their HIV-related symptoms, although a sizeable proportion of women were diagnosed because of antenatal screening or for having an HIV-positive partner. Patients diagnosed of HIV for antenatal screening or having an HIV-positive sexual partner had higher CD4 lymphocyte count than patients having tuberculosis or HIV-related symptoms. The proportion of patients diagnosed with CD4 count <200 and <350 cells/mm3 were 46% and 68.7%, respectively, and these figures did not change during the five years of the study. Factors associated with late presentations were male sex, older age, not having a permanent house, and, in women, lower education and being a widow or separated. With the implementation of 2010 WHO guidelines, the number of newly diagnosed patients who will require HIV treatment will increase 13.8%. If the CD4 count threshold for initiating HIV treatment is increased from 350 to 500 cells/mm3, the number of patients in need of treatment would increase 15.7%. Therefore, new strategies for avoiding HIV late presentation are urgently needed in developing countries.
Conditional mean embeddings as regressors

We demonstrate an equivalence between reproducing kernel Hilbert space (RKHS) embeddings of conditional distributions and vector-valued regressors. This connection introduces a natural regularized loss function which the RKHS embeddings minimise, providing an intuitive understanding of the embeddings and a justification for their use. Furthermore, the equivalence allows the application of vector-valued regression methods and results to the problem of learning conditional distributions. Using this link we derive a sparse version of the embedding by considering alternative formulations. Further, by applying convergence results for vector-valued regression to the embedding problem we derive minimax convergence rates which are O(\log(n)/n) -- compared to current state of the art rates of O(n^{-1/4}) -- and are valid under milder and more intuitive assumptions. These minimax upper rates coincide with lower rates up to a logarithmic factor, showing that the embedding method achieves nearly optimal rates. We study our sparse embedding algorithm in a reinforcement learning task where the algorithm shows significant improvement in sparsity over an incomplete Cholesky decomposition.