Miracle-dz/UniFAR-FTUs huggingface dataset:
Three-dimensional structures reveal multiple ADP/ATP binding modes for a synthetic class of artificial proteins.

The creation of synthetic enzymes with predefined functions represents a major challenge in future synthetic biology applications. Here, we describe six structures of de novo proteins that have been determined using protein crystallography to address how simple enzymes perform catalysis. Three structures are of a protein, DX, selected for its stability and ability to tightly bind ATP. Despite the addition of ATP to the crystallization conditions, the presence of a bound but distorted ATP was found only under excess ATP conditions, with ADP being present under equimolar conditions or when crystallized for a prolonged period of time. A bound ADP cofactor was evident when Asp was substituted for Val at residue 65, but ATP in a linear configuration is present when Phe was substituted for Tyr at residue 43. These new structures complement previously determined structures of DX and the protein with the Phe 43 to Tyr substitution [Simmons, C. R. , et al. (2009) ACS Chem. Biol. 4, 649-658] and together demonstrate the multiple ADP/ATP binding modes from which a model emerges in which the DX protein binds ATP in a configuration that represents a transitional state for the catalysis of ATP to ADP through a slow, metal-free reaction capable of multiple turnovers. This unusual observation suggests that design-free methods can be used to generate novel protein scaffolds that are tailor-made for catalysis.
Stochastic power grid analysis considering process variations

In this paper, we investigate the impact of interconnect and device process variations on voltage fluctuations in power grids. We consider random variations in the power grid's electrical parameters as spatial stochastic processes and propose a new and efficient method to compute the stochastic voltage response of the power grid. Our approach provides an explicit analytical representation of the stochastic voltage response using orthogonal polynomials in a Hilbert space. The approach has been implemented in a prototype software called OPERA (Orthogonal Polynomial Expansions for Response Analysis). Use of OPERA on industrial power grids demonstrated speed-ups of up to two orders of magnitude. The results also show a significant variation of about /spl plusmn/35% in the nominal voltage drops at various nodes of the power grids and demonstrate the need for variation-aware power grid analysis.
The Effect of Context and Application Type on Mobile Usability: An Empirical Study

This paper discusses the effect of context on mobile usability, proposes an expanded model of mobile application context, and conducts an empirical study to test a number of hypotheses concerning the use of software implementation technology and location context in mobile applications. Four different application types (PC web based, PC device based, mobile web based and mobile device based) were tested using a within-subjects repeated-measures design. The results demonstrate that by utilising client side processing and location context, the mobile device based application is able to achieve objective performance and subjective usability measures comparable to those of the PC based versions, despite the limited input and display capabilities of the mobile device. Conversely, the mobile web based application, which was unable to take advantage of location context or client-side application code, showed the lowest quantitative performance.
Clinical and genetic characteristics of pyridoxine-dependent epilepsy: Case series report of three Chinese patients with phenotypic variability

Pyridoxine-dependent epilepsy (PDE) is a rare disorder caused by aldehyde dehydrogenase 7 family member A1 (ALDH7A1) deficiency. The present study reported on three Chinese cases of PDE with phenotypic variability for providing further insight into this disease. All three patients presented with recurrent seizures and readily responded to treatment with pyridoxine, in line with the typical symptomology of PDE. The three cases varied in their clinical manifestations with regard to the time of onset, seizure type, EEG findings and mental development. Four ALDH7A1 mutations were identified in Case 1 (c.1008+1G>A and c.871+5G>A) and Case 2 (c.977A>G and c.1463A>G). To the best of our knowledge, the present study was the first to report on the mutations c.871+5G>A and c.1463A>G. Early definitive diagnosis and timely treatment with pyridoxine was the cornerstone of management of PDE. Timely treatment was associated with excellent prognosis. A high index of suspicion in cases and early genetic testing may facilitate early diagnosis of this rare disease.
Fast Parallel SVM using Data Augmentation

As one of the most popular classifiers, linear SVMs still have challenges in dealing with very large-scale problems, even though linear or sub-linear algorithms have been developed recently on single machines. Parallel computing methods have been developed for learning large-scale SVMs. However, existing methods rely on solving local sub-optimization problems. In this paper, we develop a novel parallel algorithm for learning large-scale linear SVM. Our approach is based on a data augmentation equivalent formulation, which casts the problem of learning SVM as a Bayesian inference problem, for which we can develop very efficient parallel sampling methods. We provide empirical results for this parallel sampling SVM, and provide extensions for SVR, non-linear kernels, and provide a parallel implementation of the Crammer and Singer model. This approach is very promising in its own right, and further is a very useful technique to parallelize a broader family of general maximum-margin models.
A joint ML estimation technique for timing, CFO and channel for OFDMA uplink transmissions

This paper addresses the issue of joint maximum-likelihood (ML) estimation of carrier frequency offset (CFO), timing error and channel response for OFDMA uplink transmissions. A pilot preamble-based approach is proposed that makes use of the concept of signal decomposition. Earlier works have demonstrated that it is possible to decompose the multidimensional optimization involved in this joint estimation into a series of one-dimensional searches. The alternating projection (AP) algorithm is effectively used to determine the ML solution to this problem in many earlier works. In this work, we propose a new method of signal decomposition that can be combined with the conventional AP method to arrive at better parameter estimates. It achieves better performance in lesser number of estimation cycles and hence with lesser computational load. Another advantage is that it offers the flexibility of application to any generalized subcarrier assignment scheme in OFDMA systems. The performance advantages of this new method are substantiated through simulation studies.
Human Embryonic Stem Cells as an In Vitro Model for Human Vascular Development and the Induction of Vascular Differentiation

Early embryonic blood vessels are typically composed of fragile tubes of endothelial cells encircled by vascular smooth muscle cells. Early human vasculogenesis was explored in spontaneous and directed differentiation models derived from human embryonic stem (HES) cells. In a 3-dimensional (3D) model, HES cells were studied for their potential for vascular differentiation during the spontaneous formation of embryoid bodies. Directed differentiation was investigated by means of a 2-dimensional (2D) differentiation method to promote vascular differentiation from HES cells (without the formation of embryoid bodies). Using this latter approach, up-regulation of early lineage markers of endothelial progenitors were induced. Additional culture under strict conditions and exposure to angiogenic growth factors resulted in a prolonged differentiation pathway into mature endothelial cells and up-regulation of vascular smooth muscle cell markers. The use of 3D collagen gels and Matrigel assays for the induction and inhibition of human vascular sprouting in vitro further established the vascular potential of the cells generated by the 2D differentiation system. Our study shows that HES cells can provide useful models to study early differentiation and development of blood vessels. Moreover, the 2D differentiation model facilitates both the production of vascular lineage cells from HES cells for various potential therapeutic applications and also provides a model for studying the mechanisms involved in early human embryonic blood vessel development.
Performance analysis of the V-BLAST algorithm: an analytical approach

A geometrically based analytical approach to the performance analysis of the V-BLAST algorithm is presented in this paper, which is based on the analytical model of the Gramm-Schmidt process. This approach presents a new geometrical view of the V-BLAST and explains some of its properties in a complete and rigorous form, including a statistical analysis of postprocessing signal-to-noise ratios for a 2/spl times/n system (where n is the number of receive antennas). Closed-form analytical expressions of the vector signal at ith processing step and its power are presented. A rigorous proof that the diversity order at ith step (without optimal ordering) is (n-m+i) is given (where m is the number of transmit antennas). It is shown that the optimal ordering is based on the least correlation criterion and that the after-processing signal power is determined by the channel correlation matrices in a fashion similar to the channel capacity. Closed-form analytical expressions are derived for outage probabilities and average BER of a 2/spl times/n system. The effect of the optimal ordering is shown to be to increase the first step SNR by 3 dB (rather than to increase the diversity order as one might intuitively expect based on the selection combining argument) and to increase the second step outage probability twice.
Aragonite Precipitation by “Proto-Polyps” in Coral Cell Cultures

The mechanisms of coral calcification at the molecular, cellular and tissue levels are poorly understood. In this study, we examine calcium carbonate precipitation using novel coral tissue cultures that aggregate to form “proto-polyps”. Our goal is to establish an experimental system in which calcification is facilitated at the cellular level, while simultaneously allowing in vitro manipulations of the calcifying fluid. This novel coral culturing technique enables us to study the mechanisms of biomineralization and their implications for geochemical proxies. Viable cell cultures of the hermatypic, zooxanthellate coral, Stylophora pistillata, have been maintained for 6 to 8 weeks. Using an enriched seawater medium with aragonite saturation state similar to open ocean surface waters (Ωarag∼4), the primary cell cultures assemble into “proto-polyps” which form an extracellular organic matrix (ECM) and precipitate aragonite crystals. These extracellular aragonite crystals, about 10 µm in length, are formed on the external face of the proto-polyps and are identified by their distinctive elongated crystallography and X-ray diffraction pattern. The precipitation of aragonite is independent of photosynthesis by the zooxanthellae, and does not occur in control experiments lacking coral cells or when the coral cells are poisoned with sodium azide. Our results demonstrate that proto-polyps, aggregated from primary coral tissue culture, function (from a biomineralization perspective) similarly to whole corals. This approach provides a novel tool for investigating the biophysical mechanism of calcification in these organisms.
Quantum Gravity, or The Art of Building Spacetime

The method of four-dimensional Causal Dynamical Triangulations provides a background-independent definition of the sum over geometries in quantum gravity, in the presence of a positive cosmological constant. We present the evidence accumulated to date that a macroscopic four-dimensional world can emerge from this theory dynamically. Using computer simulations we observe in the Euclidean sector a universe whose scale factor exhibits the same dynamics as that of the simplest mini-superspace models in quantum cosmology, with the distinction that in the case of causal dynamical triangulations the effective action for the scale factor is not put in by hand but obtained by integrating out {\it in the quantum theory} the full set of dynamical degrees of freedom except for the scale factor itself.
Fluorescence Intrinsic Characterization of Excitation-Emission Matrix Using Multi-Dimensional Ensemble Empirical Mode Decomposition

Excitation-emission matrix (EEM) fluorescence spectroscopy is a noninvasive method for tissue diagnosis and has become important in clinical use. However, the intrinsic characterization of EEM fluorescence remains unclear. Photobleaching and the complexity of the chemical compounds make it difficult to distinguish individual compounds due to overlapping features. Conventional studies use principal component analysis (PCA) for EEM fluorescence analysis, and the relationship between the EEM features extracted by PCA and diseases has been examined. The spectral features of different tissue constituents are not fully separable or clearly defined. Recently, a non-stationary method called multi-dimensional ensemble empirical mode decomposition (MEEMD) was introduced; this method can extract the intrinsic oscillations on multiple spatial scales without loss of information. The aim of this study was to propose a fluorescence spectroscopy system for EEM measurements and to describe a method for extracting the intrinsic characteristics of EEM by MEEMD. The results indicate that, although PCA provides the principal factor for the spectral features associated with chemical compounds, MEEMD can provide additional intrinsic features with more reliable mapping of the chemical compounds. MEEMD has the potential to extract intrinsic fluorescence features and improve the detection of biochemical changes.
SNAT3‐mediated glutamine transport in perisynaptic astrocytes in situ is regulated by intracellular sodium

The release of glutamine from astrocytes adjacent to synapses in the central nervous system is thought to play a vital role in the mechanism of glutamate recycling and is therefore important for maintaining excitatory neurotransmission. Here we investigate the nature of astrocytic membrane transport of glutamine in rat brainstem slices, using electrophysiological recording and fluorescent imaging of pHi and Nai+ . Glutamine application to perisynaptic astrocytes induced a membrane current, caused by activation of system A (SA) family transporters. A significant electroneutral component was also observed, which was mediated by the system N (SN) family transporters. This response was stimulated by glutamine (KM of 1.57 mM), histidine, and asparagine, but not by leucine or serine, indicating activation of the SNAT3 isoform of SN. We hypothesized that increasing the [Na+]i would alter the SNAT3 transporter equilibrium, thereby stimulating glutamine release. In support of this hypothesis, we show that SNAT3 transport can be driven by changing cation concentration and that manipulations to raise [Na+]i (activation of excitatory amino acid transporters (EAATs), SA transporters or AMPA receptors) all directly influence SNAT3 transport rate. A kinetic model of glutamine fluxes is presented, which shows that EAAT activation causes the release of glutamine, driven mainly by the increased [Na+]i. These data demonstrate that SNAT3 is functionally active in perisynaptic astrocytes in situ. As a result, astrocytic Nai+ signaling, as would be stimulated by neighboring synaptic activity, has the capacity to stimulate astrocytic glutamine release to support glutamate recycling.
Determination of Effective Parameters of Gas Injection in Naturally Fractured Reservoirs by Combination of Reservoir Simulation and Design of Experiment Techniques

Screening analysis is a useful guideline which helps us with proper field selection for different enhanced oil recovery processes. In this work, reservoir simulation is combined with experimental design to estimate main effects and possible interactions of reservoir rock and fluid properties on performance of different gas injection processes in naturally fractured reservoirs (NFRs). Studied parameters include reservoir thickness (h), oil viscosity μo), pore size distribution (λ), horizontal permeability (Kh), storage capacity (ω), reservoir dip, critical water saturation (Swc) and threshold capillary pressure (pct). The recovery factors of different simulation designs are analyzed by use of fractional factorial design (FFD) approach. Finally, the statistical significance of results are evaluated by hypothesis testing and ANOVA, and presented by Pareto and tornado plots. Main effect analysis showed that effective parameters are ordered with respect to their importance as follows: For Methane and nitrogen injection: Kh, dip, Swc, ω, h, μo and λ; threshold capillary pressure showed a minor effect on recovery factor. For Carbon dioxide injection: μo, dip, Swc, ω, h and Kh; Pore size distribution (λ) and threshold pressure were not shown to be statistically significant in this process. Likeness of main effects and parameter interactions for methane and nitrogen injection prove the similarity of dominant mechanisms and characteristics of these processes compared to CO2 injection which seems almost different.
Hydrophobized triphenyl phosphonium derivatives for the preparation of mitochondriotropic liposomes: choice of hydrophobic anchor influences cytotoxicity but not mitochondriotropic effect

Abstract Context: Nanocarrier-based strategies to achieve delivery of bioactives specifically to the mitochondria are being increasingly explored due to the importance of mitochondria in critical cellular processes. Objective: To test the ability of liposomes modified with newly synthesized triphenylphosphonium (TPP)–phospholipid conjugates and to test their use in overcoming the cytotoxicity of stearyl triphenylphosphonium (STPP)-modified liposomes when used for delivery of therapeutic molecules to the mitochondria. Methods: TPP–phospholipid conjugates with the dioleoyl, dimyristoyl or dipalmitoyl lipid moieties were synthesized and liposomes were prepared with these conjugates in a 1 mol% ratio. The subcellular distribution of the liposomes was tested by confocal microscopy. Furthermore, the liposomes were tested for their effect on cell viability using a MTS assay, on cell membrane integrity using a lactate dehydrogenase assay and on mitochondrial membrane integrity using a modified JC-1 assay. Results: The liposomes modified with the new TPP–phospholipid conjugates exhibited similar mitochondriotropism as STPP-liposomes but they were more biocompatible as compared to the STPP liposomes. While the STPP-liposomes had a destabilizing effect on cell and mitochondrial membranes, the liposomes modified with the TPP–phospholipid conjugates did not demonstrate any such effect on biomembranes. Conclusions: Using phospholipid anchors in the synthesis of TPP–lipid conjugates can provide liposomes that exhibit the same mitochondrial targeting ability as STPP but with much higher biocompatibility.
Joint Voxel and Coordinate Regression for Accurate 3D Facial Landmark Localization

3D face shape is more expressive and viewpoint-consistent than its 2D counterpart. However, 3D facial landmark localization in a single image is challenging due to the ambiguous nature of landmarks under 3D perspective. Existing approaches typically adopt a suboptimal two-step strategy, performing 2D landmark localization followed by depth estimation. In this paper, we propose the Joint Voxel and Coordinate Regression (JVCR) method for 3D facial landmark localization, addressing it more effectively in an end-to-end fashion. First, a compact volumetric representation is proposed to encode the per-voxel likelihood of positions being the 3D landmarks. The dimensionality of such a representation is fixed regardless of the number of target landmarks, so that the curse of dimensionality could be avoided. Then, a stacked hourglass network is adopted to estimate the volumetric representation from coarse to fine, followed by a 3D convolution network that takes the estimated volume as input and regresses 3D coordinates of the face shape. In this way, the 3D structural constraints between landmarks could be learned by the neural network in a more efficient manner. Moreover, the proposed pipeline enables end-to-end training and improves the robustness and accuracy of 3D facial landmark localization. The effectiveness of our approach is validated on the 3DFAW and AFLW2000-3D datasets. Experimental results show that the proposed method achieves state-of-the-art performance in comparison with existing methods.
Visual servoing of a wheeled mobile robot for intercepting a moving object

We present a vision-based scheme for driving a nonholonomic mobile robot to intercept a moving target. Our method relies on a two-level approach. On the lower level, the pan-tilt platform which carries the on-board camera is controlled so as to keep the target at the center of the image plane. On the higher level, the robot operates under the assumption that the camera system achieves perfect tracking. In particular, the relative position of the ball is retrieved from the pan/tilt angles through simple geometry, and used to compute a control law driving the robot to the target. Various possible choices are discussed for the high-level robot controller. The proposed visual interception method is validated through simulations as well as experiments on the mobile robot MagellanPro.