Miracle-dz/UniFAR-FTUs huggingface dataset:
The Crystal Structure of an Integral Membrane Fatty Acid α-Hydroxylase*

Neuronal electrical impulse propagation is facilitated by the myelin sheath, a compact membrane surrounding the axon. The myelin sheath is highly enriched in galactosylceramide (GalCer) and its sulfated derivative sulfatide. Over 50% of GalCer and sulfatide in myelin is hydroxylated by the integral membrane enzyme fatty acid 2-hydroxylase (FA2H). GalCer hydroxylation contributes to the compact nature of the myelin membrane, and mutations in FA2H result in debilitating leukodystrophies and spastic paraparesis. We report here the 2.6 Å crystal structure of sphingolipid α-hydroxylase (Scs7p), a yeast homolog of FA2H. The Scs7p core is composed of a helical catalytic cap domain that sits atop four transmembrane helices that anchor the enzyme in the endoplasmic reticulum. The structure contains two zinc atoms coordinated by the side chains of 10 highly conserved histidines within a dimetal center located near the plane of the cytosolic membrane. We used a yeast genetic approach to confirm the important role of the dimetal-binding histidines in catalysis and identified Tyr-322 and Asp-323 as critical determinants involved in the hydroxylase reaction. Examination of the Scs7p structure, coupled with molecular dynamics simulations, allowed for the generation of a model of ceramide binding to Scs7p. Comparison of the Scs7p structure and substrate-binding model to the structure of steroyl-CoA desaturase revealed significant differences in the architecture of the catalytic cap domain and location of the dimetal centers with respect to the membrane. These observations provide insight into the different mechanisms of substrate binding and recognition of substrates by the hydroxylase and desaturase enzymes.
Recognizing and Curating Photo Albums via Event-Specific Image Importance

Automatic organization of personal photos is a problem with many real world ap- plications, and can be divided into two main tasks: recognizing the event type of the photo collection, and selecting interesting images from the collection. In this paper, we attempt to simultaneously solve both tasks: album-wise event recognition and image- wise importance prediction. We collected an album dataset with both event type labels and image importance labels, refined from an existing CUFED dataset. We propose a hybrid system consisting of three parts: A siamese network-based event-specific image importance prediction, a Convolutional Neural Network (CNN) that recognizes the event type, and a Long Short-Term Memory (LSTM)-based sequence level event recognizer. We propose an iterative updating procedure for event type and image importance score prediction. We experimentally verified that image importance score prediction and event type recognition can each help the performance of the other.
Integrating BDI reasoning into agent based modeling and simulation

Agent Based modeling (ABM) platforms such as Repast and its predecessors are popular for developing simulations to understand complex phenomenon and interactions. Such simulations are increasingly used as support tools for policy and planning. This work takes a Belief Desire Intention (BDI) agent platform and embeds it into Repast, to support more powerful modeling of human behavior. We describe the issues faced in integrating the two paradigms, and how we addressed these issues to leverage the relevant advantages of the two approaches for real world applications.
Succinct Trees in Practice

We implement and compare the major current techniques for representing general trees in succinct form. This is important because a general tree of n nodes is usually represented in pointer form, requiring O(n log n) bits, whereas the succinct representations we study require just 2n + o(n) bits and carry out many sophisticated operations in constant time. Yet, there is no exhaustive study in the literature comparing the practical magnitudes of the o(n)-space and the O(1)-time terms. The techniques can be classified into three broad trends: those based on BP (balanced parentheses in preorder), those based on DFUDS (depth-first unary degree sequence), and those based on LOUDS (level-ordered unary degree sequence). BP and DFUDS require a balanced parentheses representation that supports the core operations findopen, findclose, and enclose, for which we implement and compare three major algorithmic proposals. All the tree representations require also core operations rank and select on bitmaps, which are already well studied in the literature. We show how to predict the time and space performance of most variants via combining these core operations, and also study some tree operations for which specialized implementations exist. This is especially relevant for a recent proposal (K. Sadakane and G. Navarro, SODA'10) which, although belonging to class BP, deviates from the main techniques in some cases in order to achieve constant time for the widest range of operations. We experiment over various types of real-life trees and of traversals, and conclude that the latter technique stands out as an excellent practical combination of space occupancy, time performance, and functionality, whereas others, particularly LOUDS, are still interesting in some limited-functionality niches.
Design and performance parameters of an ultra-low voltage, single supply 32bit processor implemented in 28nm FDSOI technology

This work presents a single-supply SPARC 32b V8 microprocessor designed with Ultra Low Voltage (ULV) adapted standard cells and memories, aiming at low energy operation and stand by power. The microprocessor, equipped with 10 Transistors ULV bitcell 8KB SRAM cache, has been fabricated in Fully Depleted Silicon On Insulator (FDSOI) 28nm technology. A comparative analysis with similar implementations has been provided highlighting the performance gain and power savings that are achieved by our design methodology and implementation technology. Wafer-level tests showed that our ULV adapted microprocessor has an operating range that is functional down to 0.33V and that the ULV able cache can save from 30% to 62% energy.
Region-based image querying

Retrieving images from large and varied collections using image content as a key is a challenging and important problem. In this paper, we present a new image representation which provides a transformation from the raw pixel data to a small set of localized coherent regions in color and texture space. This so-called &ldquo;blobworld&rdquo; representation is based on segmentation using the expectation-maximization algorithm on combined color and texture features. The texture features we use for the segmentation arise from a new approach to texture description and scale selection. We describe a system that uses the blobworld representation to retrieve images. An important and unique aspect of the system is that, in the context of similarity-based querying, the user is allowed to view the internal representation of the submitted image and the query results. Similar systems do not offer the user this view into the workings of the system; consequently, the outcome of many queries on these systems can be quite inexplicable, despite the availability of knobs for adjusting the similarity metric
Connexin30.2: In Vitro Interaction with Connexin36 in HeLa Cells and Expression in AII Amacrine Cells and Intrinsically Photosensitive Ganglion Cells in the Mouse Retina

Electrical coupling via gap junctions is an abundant phenomenon in the mammalian retina and occurs in all major cell types. Gap junction channels are assembled from different connexin subunits, and the connexin composition of the channel confers specific properties to the electrical synapse. In the mouse retina, gap junctions were demonstrated between intrinsically photosensitive ganglion cells and displaced amacrine cells but the underlying connexin remained undetermined. In the primary rod pathway, gap junctions play a crucial role, coupling AII amacrine cells among each other and to ON cone bipolar cells. Although it has long been known that connexin36 and connexin45 are necessary for the proper functioning of this most sensitive rod pathway, differences between homocellular AII/AII gap junctions and AII/ON bipolar cell gap junctions suggested the presence of an additional connexin in AII amacrine cells. Here, we used a connexin30.2-lacZ mouse line to study the expression of connexin30.2 in the retina. We show that connexin30.2 is expressed in intrinsically photosensitive ganglion cells and AII amacrine cells. Moreover, we tested whether connexin30.2 and connexin36—both expressed in AII amacrine cells—are able to interact with each other and are deposited in the same gap junctional plaques. Using newly generated anti-connexin30.2 antibodies, we show in HeLa cells that both connexins are indeed able to interact and may form heteromeric channels: both connexins were co-immunoprecipitated from transiently transfected HeLa cells and connexin30.2 gap junction plaques became significantly larger when co-expressed with connexin36. These data suggest that connexin36 is able to form heteromeric gap junctions with another connexin. We hypothesize that co-expression of connexin30.2 and connexin36 may endow AII amacrine cells with the means to differentially regulate its electrical coupling to different synaptic partners.
A fuzzier approach to machine translation evaluation: A pilot study on post-editing productivity and automated metrics in commercial settings

Machine Translation (MT) quality is typically assessed using automatic evaluation metrics such as BLEU and TER. Despite being generally used in the industry for evaluating the usefulness of Translation Memory (TM) matches based on text similarity, fuzzy match values are not as widely used for this purpose in MT evaluation. We designed an experiment to test if this fuzzy score applied to MT output stands up against traditional methods of MT evaluation. The results obtained seem to confirm that this metric performs at least as well as traditional methods for MT evaluation.
Higher order Markov random fields for independent sets

It is well-known that if one samples from the independent sets of a large regular graph of large girth using a pairwise Markov random field (i.e. hardcore model) in the uniqueness regime, each excluded node has a binomially distributed number of included neighbors in the limit. In this paper, motivated by applications to the design of communication networks, we pose the question of how to sample from the independent sets of such a graph so that the number of included neighbors of each excluded node has a different distribution of our choosing. We observe that higher order Markov random fields are well-suited to this task, and investigate the properties of these models. For the family of so-called reverse ultra log-concave distributions, which includes the truncated Poisson and geometric, we give necessary and sufficient conditions for the natural higher order Markov random field which induces the desired distribution to be in the uniqueness regime, in terms of the set of solutions to a certain system of equations. We also show that these Markov random fields undergo a phase transition, and give explicit bounds on the associated critical activity, which we prove to exhibit a certain robustness. For distributions which are small perturbations around the binomial distribution realized by the hardcore model at critical activity, we give a description of the corresponding uniqueness regime in terms of a simple polyhedral cone. Our analysis reveals an interesting non-monotonicity with regards to biasing towards excluded nodes with no included neighbors. We conclude with a broader discussion of the potential use of higher order Markov random fields for analyzing independent sets in graphs.
Visual Representation of Searched Results using Tree Diagram

This paper presents a new search method and the representation of results via tree diagram. As the reliance on computers increases, so will the volume of data and information stored in them. Storing of data and information on the computer is not a difficult task, but what is more daunting is searching for the file that you have stored. Currently on a Windows Operating System File Search method, users are able to search for a file and the results are displayed immediately with no structure. A prototype was built in this research to enable users to search a file based on its contents followed by a recommendation to display results via tree diagram for returned search results. It was found that search result that is visually displayed via tree diagram offered users a visual representation of where the relative location of the file is stored. Future work should enhance the ability of the tree diagram display to be interactive.
Stabilizing column generation using Lagrangean/surrogate relaxation: an application to p-median location problems

The Lagrangean/surrogate relaxation was explored recently as a faster computational alternative to traditional Lagrangean heuristics. We combine the Lagrangean/surrogate and the traditional column generation approaches to accelerate and stabilize primal and dual bounds obtained using the reduced cost selection. The Lagrangean/surrogate multiplier modifies the reduced cost criterion, providing the selection of new productive columns. The p-median problem is the problem of locating p facilities (medians) on a network such as the sum of all the distances from each demand point to its nearest facility is minimized. Computational tests running p-median instances taken from the literature are presented.
Micronucleus-specific histone H1 is required for micronuclear chromosome integrity in Tetrahymena thermophila

Histone H1 molecules play a key role in establishing and maintaining higher order chromatin structures. They can bind to linker DNA entering and exiting the nucleosome and regulate transcriptional activity. Tetrahymena thermophila has two histone H1, namely, macronuclear histone H1 and micronuclear histone H1 (Mlh1). Mlh1 is specifically localized at micronuclei during growth and starvation stages. Moreover, Mlh1 is localized around micronuclei and forms a specific structure during the conjugation stage. It co-localizes partially with spindle apparatus during micronuclear meiosis. Analysis of MLH1 knock-out revealed that Mlh1 was required for the micronuclear integrity and development during conjugation stage. Overexpression of Mlh1 led to abnormal conjugation progression. RT-PCR analysis indicated that the expression level of HMGB3 increased in ΔMLH1 strains, while the expression level of MLH1 increased in ΔHMGB3 cells during conjugation. These results indicate that micronuclear integrity and sexual development require normal expression level of Mlh1 and that HmgB3 and Mlh1 may functionally compensate each other in regulating micronuclear structure in T. thermophila.
Spatially localized hippocampal shape analysis in late‐life cognitive decline

We present a method for generating data‐driven, concise, and spatially localized parameterizations of hippocampal (HP) shape, and use the method to analyze HP atrophy in late‐life cognitive decline. The method optimizes a set of shape basis vectors (shape components) that strike a balance between spatial locality and compact representation of population shape characteristics. The method can be used for exploratory analysis of localized shape deformations in any population of HP on which point‐to‐point correspondence mappings have been established via anatomical landmarking or high‐dimensional warping. Experiments combine the method with an automated HP to HP mapping method to analyze tracings of 101 elderly subjects with normal cognition, mild cognitive impairment, and Alzheimer's Disease (AD) from an AD Center population. Results suggest that shape components corresponding to atrophy to the CA1 and subiculum HP fields—where early AD pathology is located—correlate strongly with robust measures of the cognitive dysfunction that is typical of early AD. Furthermore, the energy function minimized by the shape component optimization technique is shown to be smooth with few local minima, suggesting that the method may be relatively easy to apply in practice. © 2009 Wiley‐Liss, Inc.
Human-network-based filtering: the information propagation model based on word-of-mouth communication

In the real world, people get filtered information through word-of-mouth communication. This type of information is "filtered" because the information from one user to another is filtered by the people who pass the information to other people. We propose an Information Propagation Model, which simulates word-of-mouth communication on a computer network. In this model, certain information of interest to a user is automatically distributed to neighboring users. Therefore, this model works as an information filtering system filtered by a human network. In this paper we describe the concepts of this model, the features found in this model, and the preliminary experiment, which was carried out by real users. Results of the experiment show both the effectiveness of filtering in our model, and also that the value of information correlates closely with the distance from which the information was transferred.
A Novel JAK2 Exon 12 Mutation Identified in the Retrospective Analysis of Paraffin-embedded Tissues of Polycythemia Vera Patients

The aim of the study was to screen formalin-fixed, paraffin-embedded tissues of polycythemia vera patients for the presence of JAK2V617F and JAK2 exon 12 mutations. Of 64 cases, 60 were positive for JAK2V617F mutation using allele-specific polymerase chain reaction (PCR). Using modified allele-specific PCR, samples of 4 JAK2V617F-negative patients were analyzed for the presence of JAK2 exon 12 mutations. In one case, we found a PCR product matching with allele-specific primer, which was designed to detect the N542-E543del mutation. Surprisingly, in the result sequence we have detected another recently described mutation, R541-E543delinsK. In the other 3 JAK2V617F-negative patients, allele-specific PCR for the detection of JAK2 exon 12 mutations did not yield any product. However, in 1 case, the sequencing of JAK2 exon 12 PCR product revealed a novel mutation, H538-K539delinsF. We confirmed that paraffin-embedded tissues represent a valuable source of DNA, which can be used in diagnostics of both JAK2 exon 12 and exon 14 mutations and we described 1 novel JAK2 exon 12 mutation.
Elucidation of Motifs in Ribosomal Protein S9 That Mediate Its Nucleolar Localization and Binding to NPM1/Nucleophosmin

Biogenesis of eukaryotic ribosomes occurs mainly in a specific subnuclear compartment, the nucleolus, and involves the coordinated assembly of ribosomal RNA and ribosomal proteins. Identification of amino acid sequences mediating nucleolar localization of ribosomal proteins may provide important clues to understand the early steps in ribosome biogenesis. Human ribosomal protein S9 (RPS9), known in prokaryotes as RPS4, plays a critical role in ribosome biogenesis and directly binds to ribosomal RNA. RPS9 is targeted to the nucleolus but the regions in the protein that determine its localization remains unknown. Cellular expression of RPS9 deletion mutants revealed that it has three regions capable of driving nuclear localization of a fused enhanced green fluorescent protein (EGFP). The first region was mapped to the RPS9 N-terminus while the second one was located in the proteins C-terminus. The central and third region in RPS9 also behaved as a strong nucleolar localization signal and was hence sufficient to cause accumulation of EGFP in the nucleolus. RPS9 was previously shown to interact with the abundant nucleolar chaperone NPM1 (nucleophosmin). Evaluating different RPS9 fragments for their ability to bind NPM1 indicated that there are two binding sites for NPM1 on RPS9. Enforced expression of NPM1 resulted in nucleolar accumulation of a predominantly nucleoplasmic RPS9 mutant. Moreover, it was found that expression of a subset of RPS9 deletion mutants resulted in altered nucleolar morphology as evidenced by changes in the localization patterns of NPM1, fibrillarin and the silver stained nucleolar organizer regions. In conclusion, RPS9 has three regions that each are competent for nuclear localization, but only the central region acted as a potent nucleolar localization signal. Interestingly, the RPS9 nucleolar localization signal is residing in a highly conserved domain corresponding to a ribosomal RNA binding site.
Challenges in power-ground integrity

With the advance of semiconductor manufacturing, EDA, and VLSI design technologies, circuits with increasingly higher speed are being integrated at an increasingly higher density. This trend causes correspondingly larger voltage fluctuations in the on-chip power distribution network due to IR-drop, L di/dt noise, or LC resonance. Therefore, power-ground integrity becomes a serious challenge in designing future high-performance circuits. In this paper, we introduce power-ground integrity, addressing its importance, verification methodology, and problem solution.
Hierarchical Ethernet-PON Design with QoS Supporting by Eligible Reporting

Ethernet passive optical network (EPON) can be seen as a hierarchical service model. In this respect, it should have a proper media access control (MAC) protocol to allocate bandwidth effectively and fairly among ONUs. Moreover, it should be able to support quality of service (QoS) on a per-queue basis. To address these issues, we develop a dynamic bandwidth allocation (DBA) scheme and a scheduling algorithm called eligible reporting. The eligible reporting is composed of a simple rate-controller and the priority reporting. It endows EPON with the ability to support priority service in the sense that delay and bandwidth allocations are decoupled. Also, our DBA scheme achieves high network utilization in the weighted max-min fair sense. Simulation results are presented to evaluate the proposed algorithm
Mobility and routing management for heterogeneous multi-hop wireless networks

This paper proposes a new heterogeneous multi-hop cellular IP (MCIP) network that integrates multi-hop communication with cellular IP. MCIP increases the coverage of the wireless network and improves the network robustness against adverse propagation phenomena by supporting communication in dead zones and areas with poor radio coverage. MCIP includes three components: location management, connection management and route reconfiguration. Location management is responsible for maintaining the location information for mobile stations (MSs) in a local domain. Connection management establishes an initial path for data transmission and a route reconfiguration mechanism is proposed to take advantage of various multi-hop connection alternatives available based on terminal interfaces, network accessibility and topology. Our simulation results show that MCIP performs well in networks of various sizes
Novel +90G>A Intronic Polymorphism of CYP2D6

Objective CYP2D6, an enzyme, metabolizes a large number of commonly prescribed drugs. Variations in CYP2D6 gene encoding this enzyme have been associated with individual differences in drug metabolism rates. The purpose of our study was to identify some allelic variants of CYP2D6 gene and to detect defective CYP2D6 alleles, as part of a pharmacogenetic screening program. Materials and Methods A prospective study was done on 120 participants referred to Royan Institute in 2013. Allele and genotype frequencies for polymorphism of CYP2D6 gene in exons 1 and 4 were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and sequencing on PCR products, respectively. Results We identified a novel variant of the gene encoding cytochrome P450 2D6 (CYP2D6) at position +90 of intron 4 by sequencing method. This novel polymorphism of CYP2D6 has been deposited in GeneBank® under the accession number KF225465 in Jun 2013. Conclusion In the current study, we identified novel polymorphism in intron 4. This single nucleotide polymorphism (SNP) is known as +90G>A in the fourth intron.