Miracle-dz/UniFAR-FTUs huggingface dataset:
Metabolic networks and bioenergetics of Aurantiochytrium sp. B-072 during storage lipid formation

Baffled shake flask cultivation of Aurantiochytrium sp. B-072 was carried out at in a glucose-monosodium glutamate mineral medium at different C/N-ratios (30–165) with glucose fixed at 90 g/L. With increasing C/N-ratio, a modest increase in lipid content (60 to 73 % w/w) was observed whereas fat-free biomass decreased but overall biomass showed little variation. FA-profiles were not affected to a large extent by C/N-ratio and absolute docosahexaenoic (DHA)-levels fell in narrow range (5–6 g/L). However at C/N > 64 a rapid decrease in lipid synthetic rate and/or incomplete glucose utilization occurred. Glucose and FA-fluxes based on fat-free biomass peaked at a C/N ratio of 56. This condition was chosen for calculation of the redox balance (NAD(P)H) and energy (ATP) requirement and to estimate the in vivo P/O ratio during the main period of fatty acid biosynthesis. Several models with different routes for NADPH, acetyl-CoA formation and re-oxidation of OAA formed via ATP-citrate lyase were considered as these influence the redox- and energy balance. As an example, using a commonly shown scheme whereby NADPH is supplied by a cytosolic “transhydrogenase cycle” (pyruvate-OAA-malate-pyruvate) and OAA formed by ATP-citrate lyase is recycled via import into the mitochondria as malate, the calculated NADPH-requirement amounted to 5.5 with an ATP-demand of 10.5 mmol/(g fat-free biomass x h) and an in vivo P/O-ratio (not including non-growth associated maintenance) of 1.6. The lowest ATP requirement is found when acetyl-CoA would be transported directly from the mitochondria to the cytosol by carnitine acetyltransferase. Assay of some enzymes critical for NADPH supply indicates that activity of glucose-6-phosphate dehydrogenase, the first enzyme in the HMP pathway, is far insufficient for the required NADPH-flux and malic enzyme must be a major source. Activity of the latter (ca. 300 mU/mg protein) far exceeds that in oleaginous fungi and yeast.
Self-Protection against Gliotoxin—A Component of the Gliotoxin Biosynthetic Cluster, GliT, Completely Protects Aspergillus fumigatus Against Exogenous Gliotoxin

Gliotoxin, and other related molecules, are encoded by multi-gene clusters and biosynthesized by fungi using non-ribosomal biosynthetic mechanisms. Almost universally described in terms of its toxicity towards mammalian cells, gliotoxin has come to be considered as a component of the virulence arsenal of Aspergillus fumigatus. Here we show that deletion of a single gene, gliT, in the gliotoxin biosynthetic cluster of two A. fumigatus strains, rendered the organism highly sensitive to exogenous gliotoxin and completely disrupted gliotoxin secretion. Addition of glutathione to both A. fumigatus ΔgliT strains relieved gliotoxin inhibition. Moreover, expression of gliT appears to be independently regulated compared to all other cluster components and is up-regulated by exogenous gliotoxin presence, at both the transcript and protein level. Upon gliotoxin exposure, gliT is also expressed in A. fumigatus ΔgliZ, which cannot express any other genes in the gliotoxin biosynthetic cluster, indicating that gliT is primarily responsible for protecting this strain against exogenous gliotoxin. GliT exhibits a gliotoxin reductase activity up to 9 µM gliotoxin and appears to prevent irreversible depletion of intracellular glutathione stores by reduction of the oxidized form of gliotoxin. Cross-species resistance to exogenous gliotoxin is acquired by A. nidulans and Saccharomyces cerevisiae, respectively, when transformed with gliT. We hypothesise that the primary role of gliotoxin may be as an antioxidant and that in addition to GliT functionality, gliotoxin secretion may be a component of an auto-protective mechanism, deployed by A. fumigatus to protect itself against this potent biomolecule.
Future sparse interactions : a MARL approach

Recent research has demonstrated that considering local interactions among agents in specific parts of the state space, is a successful way of simplifying the multi-agent learning process. By taking into account other agents only when a conflict is possible, an agent can significantly reduce the state-action space in which it learns. Current approaches, however, consider only the immediate rewards for detecting conflicts. In this paper, we contribute a reinforcement learning algorithm that learns when a strategic interaction among agents is needed, several time-steps before the conflict is reflected by the (immediate) reward signal.
Performance analysis of differential receivers in synchronous shared environments

This paper proposes a general framework for analyzing the performance of ultra wide band (UWB) communication systems in a synchronous reference scenario. In this context the information flows, produced by various sources, are synchronously multiplexed to share the common radio resource. The analysis in mainly devoted to investigate the performance of differential UWB receiver architectures, with the signal plus (multiplexing) interference to noise ratio (SINR) and bit error rate (BER) being the parameters of interest. While the obtained results point out that typical channelization codes (i.e. Hadamard) do not seem to be adequate to mitigate multiplexing interference (MI), we identified exact expressions to completely remove MI. In this perspective, the developed framework turns out to be a fundamental setup to identify efficient code families that aims at optimizing the overall system performance
The role of linguistic cues in bilingual negation processing

Aims and objectives: A vast body of research has dealt with negation processing. There are many differences between negations across languages, which could influence negation processing in bilingual speakers. However, bilingual negation processing has rarely been experimentally investigated. This study aims at exploring whether highly proficient Croatian-English bilinguals are able to adequately adopt English negations, and whether linguistic cues from both languages have similar effect on negation processing. Methodology: A sentence–picture verification task was used to investigate the processing of affirmative sentences, sentential and constituent negations, Croatian negative concord and English sentences with negated subject. Data and analysis: 2 (language) × 4 (sentence type) × 2 (congruency) ANOVA with repeated measures was used to analyze the data. Findings: The results showed that the effect of language was not significant, except in the case of constituent negations which were processed faster in English. There was a significant difference between the processing of affirmative and negative sentences, as affirmatives were processed faster than negatives in both languages. Constituent negations in both languages were processed slower compared with other types of negations. Originality: The results suggest that strong linguistic cues, such as word order and quantifiers, influence negation processing in both languages, resulting in differences between different types of negations. The results are discussed in the light of two existing models of negation and sentence processing. A new model, as a combination of these two models, is proposed. Implications: The fact that there was no significant difference in negation processing between the bilinguals’ two languages supports the view that highly proficient successive bilinguals are able to adequately adopt negations in both their languages.
Translocation of a Bak C-Terminus Mutant from Cytosol to Mitochondria to Mediate Cytochrome c Release: Implications for Bak and Bax Apoptotic Function

Background One of two proapoptotic Bcl-2 proteins, Bak or Bax, is required to permeabilize the mitochondrial outer membrane during apoptosis. While Bax is mostly cytosolic and translocates to mitochondria following an apoptotic stimulus, Bak is constitutively integrated within the outer membrane. Membrane anchorage occurs via a C-terminal transmembrane domain that has been studied in Bax but not in Bak, therefore what governs their distinct subcellular distribution is uncertain. In addition, whether the distinct subcellular distributions of Bak and Bax contributes to their differential regulation during apoptosis remains unclear. Methodology/Principal Findings To gain insight into Bak and Bax targeting to mitochondria, elements of the Bak C-terminus were mutated, or swapped with those of Bax. Truncation of the C-terminal six residues (C-segment) or substitution of three basic residues within the C-segment destabilized Bak. Replacing the Bak C-segment with that from Bax rescued stability and function, but unexpectedly resulted in a semi-cytosolic protein, termed Bak/BaxCS. When in the cytosol, both Bax and Bak/BaxCS sequestered their hydrophobic transmembrane domains in their hydrophobic surface groove. Upon apoptotic signalling, Bak/BaxCS translocated to the mitochondrial outer membrane, inserted its transmembrane domain, oligomerized, and released cytochrome c. Despite this Bax-like subcellular distribution, Bak/BaxCS retained Bak-like regulation following targeting of Mcl-1. Conclusions/Significance Residues in the C-segment of Bak and of Bax contribute to their distinct subcellular localizations. That a semi-cytosolic form of Bak, Bak/BaxCS, could translocate to mitochondria and release cytochrome c indicates that Bak and Bax share a conserved mode of activation. In addition, the differential regulation of Bak and Bax by Mcl-1 is predominantly independent of the initial subcellular localizations of Bak and Bax.
Sketch based image retrieval using a soft computation of the histogram of edge local orientations (S-HELO)

This paper introduces S-HELO (Soft-Histogram of Edge Local Orientations), an outperforming method for describing images in the context of sketch based image retrieval (SBIR). This proposal exploits the advantages provided by the HELO descriptor for describing sketches, and improves significantly its performance by using a soft computation of local orientations and taking into account spatial information. We experimentally demonstrate that a soft computation process together with a local estimation of orientations are very suitable for describing sketches in the context of image retrieval. Indeed, our results show that S-HELO significantly outperforms not only HELO but also classical orientation-based descriptors as HOG. We also show that S-HELO performs very close to the optimal when what we want to retrieve are target images. Moreover, our proposal also shows an outstanding performance for similarity search, i.e., retrieving images that belong to the same category of the query sketch.
SNP-SNP Interaction Network in Angiogenesis Genes Associated with Prostate Cancer Aggressiveness

Angiogenesis has been shown to be associated with prostate cancer development. The majority of prostate cancer studies focused on individual single nucleotide polymorphisms (SNPs) while SNP-SNP interactions are suggested having a great impact on unveiling the underlying mechanism of complex disease. Using 1,151 prostate cancer patients in the Cancer Genetic Markers of Susceptibility (CGEMS) dataset, 2,651 SNPs in the angiogenesis genes associated with prostate cancer aggressiveness were evaluated. SNP-SNP interactions were primarily assessed using the two-stage Random Forests plus Multivariate Adaptive Regression Splines (TRM) approach in the CGEMS group, and were then re-evaluated in the Moffitt group with 1,040 patients. For the identified gene pairs, cross-evaluation was applied to evaluate SNP interactions in both study groups. Five SNP-SNP interactions in three gene pairs (MMP16+ ROBO1, MMP16+ CSF1, and MMP16+ EGFR) were identified to be associated with aggressive prostate cancer in both groups. Three pairs of SNPs (rs1477908+ rs1387665, rs1467251+ rs7625555, and rs1824717+ rs7625555) were in MMP16 and ROBO1, one pair (rs2176771+ rs333970) in MMP16 and CSF1, and one pair (rs1401862+ rs6964705) in MMP16 and EGFR. The results suggest that MMP16 may play an important role in prostate cancer aggressiveness. By integrating our novel findings and available biomedical literature, a hypothetical gene interaction network was proposed. This network demonstrates that our identified SNP-SNP interactions are biologically relevant and shows that EGFR may be the hub for the interactions. The findings provide valuable information to identify genotype combinations at risk of developing aggressive prostate cancer and improve understanding on the genetic etiology of angiogenesis associated with prostate cancer aggressiveness.
Distributed, integrated and interactive traffic simulations

Mainstream discourse in urban planning is in transition, due to shifts from a technical to a communicative perspective, and increased scrutiny and criticism of models and simulations. The cognizance of complexity in urban systems is imposing limitations on modeling. The added benefits of today's data and computational power make simulations harder to validate and understand. Reconciling the movements towards a communicative and exploratory approach as compared to a technical and predictive approach requires new methods for planning process and posits new requirements and functions for simulations. Based on distributed simulation and gaming simulation, the paper presents a framework to support the exploration of simulated and realistic virtual worlds in a participatory fashion, enabling new approaches to urban planning. The development and evaluation of the framework casts simulations in a new perspective and explores the context of use of simulations in planning and design.
A standardized method for measuring intracranial arterial stenosis.

BACKGROUND AND PURPOSE Atherosclerosis of the major intracranial arteries is an important cause of ischemic stroke. We established measurement criteria to assess percent stenosis of a major intracranial artery (carotid, middle cerebral, vertebral, basilar) and determined the interobserver/intraobserver agreements and interclass/intraclass correlations of these measurements. METHODS We defined percent stenosis of an intracranial artery as follows: percent stenosis = [(1 - (D(stenosis)/D(normal)))] x 100, where D(stenosis) = the diameter of the artery at the site of the most severe stenosis and D(normal) = the diameter of the proximal normal artery. If the proximal segment was diseased, contingency sites were chosen to measure D(normal): distal artery (second choice), feeding artery (third choice). Using a hand-held digital caliper, three neuroradiologists independently measured D(stenosis) and D(normal) of 24 stenotic intracranial arteries. Each observer repeated the readings 4 weeks later. We determined how frequently two observers' measurements of percent stenosis of each of the 24 diseased arteries differed by 10% or less. RESULTS Among the three pairs of observers, interobserver agreements were 88% (observer 1 versus observer 2), 79% (observer 1 versus observer 3), 75% (observer 2 versus observer 3) for the first reading and were 75% (observer 1 versus observer 2), 100% (observer 1 versus observer 3), and 71% (observer 2 versus observer 3) for the second reading. Intraobserver agreement for each of the observers was 88%, 83%, and 100%. Interclass correlation was 85% (first reading) and 87% (second reading). Intraclass correlation was 92% (first and second readings combined). CONCLUSION This method shows good interobserver and intraobserver agreements for the measurement of intracranial stenosis of a major artery. If validated in subsequent studies, this method may serve as a standard for the measurement of percent stenosis of an intracranial artery.
Application of Metabolic 13C Labeling in Conjunction with High-Field Nuclear Magnetic Resonance Spectroscopy for Comparative Conformational Analysis of High Mannose-Type Oligosaccharides

High mannose-type oligosaccharides are enzymatically trimmed in the endoplasmic reticulum, resulting in various processing intermediates with exposed glycotopes that are recognized by a series of lectins involved in glycoprotein fate determination in cells. Although recent crystallographic data have provided the structural basis for the carbohydrate recognition of intracellular lectins, atomic information of dynamic oligosaccharide conformations is essential for a quantitative understanding of the energetics of carbohydrate–lectin interactions. Carbohydrate NMR spectroscopy is useful for characterizing such conformational dynamics, but often hampered by poor spectral resolution and lack of recombinant techniques required to produce homogeneous glycoforms. To overcome these difficulties, we have recently developed a methodology for the preparation of a homogeneous high mannose-type oligosaccharide with 13C labeling using a genetically engineered yeast strain. We herein successfully extended this method to result in the overexpression of 13C-labeled Man9GlcNAc2 (M9) with a newly engineered yeast strain with the deletion of four genes involved in N-glycan processing. This enabled high-field NMR analyses of 13C-labeled M9 in comparison with its processing product lacking the terminal mannose residue ManD2. Long-range NOE data indicated that the outer branches interact with the core in both glycoforms, and such foldback conformations are enhanced upon the removal of ManD2. The observed conformational variabilities might be significantly associated with lectins and glycan-trimming enzymes.
A Graph Theoretic Linkage Attack on Microdata in a Metric Space

Certain methods of analysis require the knowledge of the spatial distances between entities whose data are stored in a microdata table. For instance, such knowledge is necessary and sufficient to perform data mining tasks such as nearest neighbour searches or clustering. However, when inter-record distances are published in addition to the microdata for research purposes, the risk of identity disclosure has to be taken into consideration. In order to tackle this problem, we introduce a flexible graph model for microdata in a metric space and propose a linkage attack based on realistic assumptions of a data snooper's background knowledge. This attack is based on the idea of finding a maximum approximate common subgraph of two vertex-labelled and edgeweighted graphs. By adapting a standard argument from algorithmic graph theory to our setup, this task is transformed to the maximum clique detection problem in a corresponding product graph. A toy example and experimental results show that publishing even approximate distances could increase the risk of identity disclosure unreasonably. We will concentrate on the perturbation of the distances; the anonymization of the vertex labels will play only a minor role in our simulations. Since the current version of our attack is not scalable, it can be launched only on datasets of sizes up to few thousands records. In the future we intend to explore possible ways of pushing further the limits of our approach.
Multicasting in energy-limited ad-hoc wireless networks

We address the problem of multicasting in military "ad-hoc" wireless networks. Since such networks lack a fixed cellular infrastructure, multicast algorithms that are based on the availability of fixed, known topologies cannot be used effectively. Even when the locations of the nodes are fixed and known, the properties of the wireless medium create a networking environment that is vastly different from that of wired networks, and for which the multicasting problem has scarcely been addressed. Specifically, the broadcast nature of wireless transmission and the dependence of range on the transmission power create new opportunities for multicasting that need to be traded off against the interference caused by such transmissions. We address the ways in which the wireless network characteristics, as well as the constraints of limited energy, affect the multicast protocol operation. Preliminary trade-offs are provided, and future research directions are outlined.
Delta-oriented architectural variability using MontiCore

Modeling of software architectures is a fundamental part of software development processes. Reuse of software components and early analysis of software topologies allow the reduction of development costs and increases software quality. Integrating variability modeling concepts into architecture description languages (ADLs) is essential for the development of diverse software systems with high demands on software quality. In this paper, we present the integration of delta modeling into the existing ADL MontiArc. Delta modeling is a language-independent variability modeling approach supporting proactive, reactive and extractive product line development. We show how Δ-MontiArc, a language for explicit modeling of architectural variability based on delta modeling, is implemented as domain-specific language (DSL) using the DSL development framework MontiCore. We also demonstrate how MontiCore's language reuse mechanisms provide efficient means to derive an implementation of Δ-MontiArc tool implementation. We evaluate Δ-MontiArc by comparing it with annotative variability modeling.
MoCA, ACE-R, and MMSE Versus the National Institute of Neurological Disorders and Stroke–Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards Neuropsychological Battery After TIA and Stroke

Background and Purpose— The Montreal Cognitive Assessment (MoCA) and Addenbrooke's Cognitive Examination–Revised (ACE-R) are proposed as short cognitive tests for use after stroke, but there are few published validations against a neuropsychological battery. We studied the relationship between MoCA, ACE-R, Mini-Mental State Examination (MMSE) and mild cognitive impairment (MCI) in patients with cerebrovascular disease and mild cognitive impairment (MCI). Methods— One hundred consecutive non-institutionalized patients had the MMSE, MoCA, ACE-R, and National Institute of Neurological Disorders and Stroke–Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards Neuropsychological Battery ≥1 year after transient ischemic attack or stroke in a population-based study. MCI was diagnosed using modified Petersen criteria in which subjective cognitive complaint is not required (equivalent to cognitive impairment–no dementia) and subtyped by number and type of cognitive domains affected. Results— Among 91 nondemented subjects completing neuropsychological testing (mean/SD age, 73.4/11.6 years; 44% female; 56% stroke), 39 (42%) had MCI (amnestic multiple domain=10, nonamnestic multiple domain=9, nonamnestic single domain=19, amnestic single domain=1). Sensitivity and specificity for MCI were optimal with MoCA <25 (sensitivity=77%, specificity=83%) and ACE-R <94 (sensitivity=83%, specificity=73%). Both tests detected amnestic MCI better than nonamnestic single-domain impairment. MMSE only achieved sensitivity >70% at a cutoff of <29, mainly due to relative insensitivity to single-domain impairment. Conclusions— The MoCA and ACE-R had good sensitivity and specificity for MCI defined using the Neurological Disorders and Stroke–Canadian Stroke Network Vascular Cognitive Impairment Battery ≥1 year after transient ischemic attack and stroke, whereas the MMSE showed a ceiling effect. However, optimal cutoffs will depend on use for screening (high sensitivity) or diagnosis (high specificity). Lack of timed measures of processing speed may explain the relative insensitivity of the MoCA and ACE-R to single nonmemory domain impairment.