Canonical Architecture Research Articles

Two Distinct Networks are Affected by Mesial Temporal Lobe Epilepsy (P2-1.008)

<h3>Objective:</h3> To define networks affected by mesial temporal lobe epilepsy (MTLE) pathology. <h3>Background:</h3> The brain is organized into a robust set of canonical networks that are detectable across imaging modalities and invariant to analytic method. The same functional architecture is reflected in pathology, vis-à-vis the Network Degeneration Hypothesis. Imaging studies of MTLE often focus on canonical network effects, reporting regional changes congruent with semiology. However, MTLE-specific networks remain ill-defined. <h3>Design/Methods:</h3> A comprehensive literature search identified 45 structural and 29 resting-state-functional imaging experiments, collectively reporting 588 coordinate-foci of pathology (n=1599 MTLE subjects). Patterns of coordinate co-occurrence (within and across experiments) were computed using independent component analysis (FSL-MELODIC.v3.14). Spatial cross-correlations (FSL.v6.0.4) were computed to assess the stability of and overlap between network-patterns. Functional interpretations were obtained by regional behavioral analysis (Mango.v4.1; http://rii.uthscsa.edu/mango/plugin_behavioralanalysis.html) of healthy task-activation data (20,998 experiments; n=103,977) from the BrainMap database (https://www.brainmap.org/). Effect modification was assessed (χ²-homogeneity). <h3>Results:</h3> Two stable (R=0.890) network-patterns were identified in the MTLE literature, bearing little resemblance to canonical architecture (R&lt;0.3). Network-patterns overlapped at the hippocampus/MDN-thalamus but were otherwise spatially distinct (R=0.042). Network-1 (supramarginal, frontal/precentral, fusiform, temporal, and occipital gyri) was associated with verbal (speech-action: Z=8.23; speech-cognition: Z=6.85), motor (Z=6.06), and visual (Z=4.30) tasks. Network-2 (frontal, temporal and cingulate cortical areas, pulvinar, anterior-nucleus, and contralesional-parahippocampus) was associated with limbic (explicit-memory: Z=5.42; positive-emotion: Z=4.54) and executive-function (attention: Z=4.65; reasoning: Z=3.15) tasks. No effect-modification was observed (p&gt;0.05); structural and functional data contributed equally to both networks. <h3>Conclusions:</h3> This study identifies two distinct networks in MTLE. Seizure propagation along these networks is congruent with ictal observations of communication deficits, stereotypic behaviors, and visual hallucinosis (Network-1) as well as dyscognitive effects, transient amnesia, and pre-/post-ictal social-emotional deficits (Network-2). These cortical networks may underlie discrete behavioral phenomena manifested in MTLE; further investigation is required to determine their precise functions as they relate to the peri-ictal continuum. <b>Disclosure:</b> The institution of Mr. Towne has received research support from NIH T32GM113896. Dr. Eslami has nothing to disclose. Mr. Fox has nothing to disclose. Dr. Cavazos has received stock or an ownership interest from Brain Sentinel . The institution of Dr. Cavazos has received research support from NIH. Dr. Fox has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wiley. The institution of Dr. Fox has received research support from NIH. Dr. Fox has received intellectual property interests from a discovery or technology relating to health care. Dr. Fox has received personal compensation in the range of $500,000-$999,999 for serving as a Reviewer with NIH.

A tool-based system architecture for a digital twin: a case study in a healthcare facility

Changes in the local and global markets are forcing A/E/C/FM (Architecture, Engineering, Construction, and Facility Management) organizations to deliver more robust and innovative operational BIMs (Building Information Models). It is hypothesized that BIMs will transform from a static 3D model to a Digital Twin providing a truly digital representation of the physical asset or the building it represents. This transformation to a dynamic Digital Twin will allow the A/E/C/FM industry to visualize, monitor, and optimize operational assets and processes to support better inspection and analysis for a more efficient facility operations and maintenance. To support the adoption and implementation of Digital Twin in A/E/C/FM, the authors have defined two clear objectives. First, we discuss requirements for a functionality-based canonical architecture to create a digital twin followed by proposing two tool-based system architecture options for its implementation. Second, we use a case study approach to develop a proof-of-concept Digital Twin of an operating room in a healthcare facility using Power BI Desktop and Azure Services. The prototype aims to monitor room air quality as per INAIL (National Institute for Insurance against Accidents at Work) and ISO (International Organization for Standards) standards. Multiple sensors connected to a Raspberry Pi 4 are used to capture real-time data for various air quality parameters including temperature, humidity, airflow, particulate contamination, and Nitrous Oxide (N2O) gas. Multiple dashboards are also created to visualize, monitor, and analyze the data harnessed from the OR sensors. The implementation addresses critical issues including security, data storage, visualization, processing, data streaming, collection, and analysis. As an initial validation, the Digital Twin prototype was presented and discussed with a healthcare BIM manager. Initial feedback from the industry expert indicated that the prototype could decrease the required time to respond to facility maintenance issues such as decreased air flow due to possible obstructions.

Molecular characterization of the cytotoxic and regulatory T cell coreceptor (CRTAM), and its ligand CADM1, in the European seabass and gilthead seabream

T cell activation is a multifaceted process that depends on the activation of the T cell receptor (TCR). However, other coreceptors are also strictly necessary to provide co-signals and modulate the immune response. However, to date, most of these coreceptors are unknown in fish or their information is very limited. Therefore, in this work, we have identified the cytotoxic and regulatory T cell molecule, CRTAM, and its ligand, the cell adhesion molecule 1, CADM1, in European seabass (Dicentrarchus labrax) and gilthead seabream (Sparus aurata); and evaluated their transcriptional levels. Both putative proteins showed the canonical architecture observed in mammals, where CRTAM exhibited two immunoglobulin domains and CADM1, both the a and b forms, exhibited three of these domains. In addition, phylogeny and synteny analyses showed their conservation throughout vertebrate evolution. We found constitutive expression of all three genes, with crtam and cadm1a being predominant in immune tissues such as spleen, thymus and head-kidney (HK), while cadm1b expression was more limited to the brain. In vitro, only the T cell mitogen phytohemagglutinin (PHA) up-regulated the transcription of crtam and cadm1a in HK leucocytes. Nodavirus (NNV) infection elicited an up-regulation of crtam and cadm1a in brain and HK, appearing earlier in seabream than in seabass, which could explain the resistance of seabream to the development of nodavirus disease. In addition, they are up-regulated during the innate cell-mediated cytotoxic response in seabream but not in seabass. Altogether, our data seem to indicate that CRTAM is more related to the innate cytotoxicity in seabream and more in the specific and T cell-mediated cytotoxicity in seabass. Our results highlight the importance of CRTAM and CADM1 as important molecules in the activation of T lymphocytes in seabass and seabream, but further studies are needed.

Representing Normal and Abnormal Physiology as Routes of Flow in ApiNATOMY.

We present (i) the ApiNATOMY workflow to build knowledge models of biological connectivity, as well as (ii) the ApiNATOMY TOO map, a topological scaffold to organize and visually inspect these connectivity models in the context of a canonical architecture of body compartments. In this work, we outline the implementation of ApiNATOMY’s knowledge representation in the context of a large-scale effort, SPARC, to map the autonomic nervous system. Within SPARC, the ApiNATOMY modeling effort has generated the SCKAN knowledge graph that combines connectivity models and TOO map. This knowledge graph models flow routes for a number of normal and disease scenarios in physiology. Calculations over SCKAN to infer routes are being leveraged to classify, navigate and search for semantically-linked metadata of multimodal experimental datasets for a number of cross-scale, cross-disciplinary projects.

An Evaluation of Communication Protocol Languages for Engineering Multiagent Systems

Communication protocols are central to engineering decentralized multiagent systems. Modern protocol languages are typically formal and address aspects of decentralization, such as asynchrony. However, modern languages differ in important ways in their basic abstractions and operational assumptions. This diversity makes a comparative evaluation of protocol languages a challenging task.&#x0D; We contribute a rich evaluation of diverse and modern protocol languages. Among the selected languages, Scribble is based on session types; Trace-C and Trace-F on trace expressions; HAPN on hierarchical state machines, and BSPL on information causality. Our contribution is four-fold. One, we contribute important criteria for evaluating protocol languages. Two, for each criterion, we compare the languages on the basis of whether they are able to specify elementary protocols that go to the heart of the criterion. Three, for each language, we map our findings to a canonical architecture style for multiagent systems, highlighting where the languages depart from the architecture. Four, we identify design principles for protocol languages as guidance for future research.

Molecular characterization of the T cell costimulatory receptors CD28 and CTLA4 in the European sea bass

For the activation of T cells, it is necessary the specific recognition of the peptide by the T cell receptors (TCR) in the surface of antigen-presenting cells (APCs) and additional signals delivered by costimulatory receptors. In fish, knowledge about the presence of these costimulatory signals is limited and functional evidence almost absent. Thus, in this study, we have identified the stimulatory CD28 and the inhibitory cytotoxic T-lymphocyte-associated protein 4 (CTLA4) coreceptors in the European sea bass (Dicentrarchus labrax), and evaluated their transcription. In parallel, the transcription encoding for the T cell markers CD8α and CD4 was also evaluated. Both coreceptors showed the canonical architecture including a signal peptide, an immunoglobulin domain, a transmembrane region and a cytosolic tail. Protein predictions and phylogenetic tree identify them as true mammalian orthologues of CD28 and CTLA4. We found these genes constitutively expressed in all studied organs of European sea bass with high expression in lymphoid organs (thymus, spleen and head-kidney) and liver. The molecular expression pattern of these genes was up-regulated in head-kidney leucocytes stimulated with T mitogens as concanavalin A and phytohemagglutinin (PHA), but not with the B cell mitogen lipopolysaccharide (LPS). Fish challenged with nodavirus (NNV) evidenced a differential and opposing regulation of the cd28 and ctla4 transcription levels in the brain, the target organ for viral replication, and head-kidney. While cd28 transcription tends to decrease over the infection time in both organs the expression of the ctla4 gene tends to increase. Interestingly, the coreceptor expression is highly and significantly correlated to the transcription of the T cell markers. Our results highlight the important role of CD28 and CTLA4 as costimulatory receptors of T cells in European sea bass but further studies are deserved.

ABC Exporters in Pathogenesis: Role of Synthetic Anti-Microbial Peptides.

ABC exporters are involved in diverse cellular processes including lipid trafficking, drug resistance, pathogenesis etc. The greatest thrust has been in the area of drug resistance that explains the underlying well-crafted canonical architecture of its structure. Interestingly, ranging from structural organisation to subsequent design and delivery aspects lays the niche of antimicrobial peptides. One of the major highlight of this paper is the role of synthetic antimicrobial peptides in current scenario.

Color Columns in Visual Area V4

SummaryModels of the cerebral cortex propose a canonical columnar architecture preserved across the brain. Evidence for this model primarily stems from observations in primary sensory areas, such as the visual cortex, where neurons in an anatomical column respond preferentially to the same stimulus features. Similar columnar feature selectivity has been described for visual area V2, visual area V3 [9, 10], the middle temporal visual area (area V5), and inferotemporal cortex. The fourth visual area (V4) features color selective neurons, organized in clusters across its surface. However, whether these color-sensitive neurons are organized in a columnar fashion is debated and uncertain due to technical limitations. Here, we utilize laminar multielectrode recordings along V4 columns to resolve rival hypotheses. Linear electrode arrays were introduced orthogonally into area V4, spanning all cortical layers. Monkeys viewed color stimuli presented to the visual receptive field of the column of neurons. We found that preference for a specific color was conserved along depth but varied across columns. Interestingly, while color preference (e.g. red or green) was consistent along depth, color selectivity was significantly greater in upper layers relative to the input layer and was weakest in the lower layers. These findings demonstrate that area V4 is organized in functional columns like other visual areas.

Nanomechanical Properties and Phase Behavior of Phenylalanine Amyloid Ribbon Assemblies and Amorphous Self-Healing Hydrogels.

Phenylalanine was the minimalistic and first of numerous nonproteinaceous building blocks to be demonstrated to form amyloid-like fibrils. This unexpected organization of such a simple building block into canonical architecture, which was previously observed only with proteins and peptides, has numerous implications for medicine and supramolecular chemistry. However, the morphology of phenylalanine fibrils and their mechanical properties was never characterized in solutions. Here, using electron and atomic force microscopy, we analyze the morphological and mechanical properties of phenylalanine fibrils in both air and fluids. The fibrils demonstrate an exceptionally high Young's modulus (up to 30 GPa) and are found to be composed of intertwined protofilaments in a helical or twisted ribbon morphology. In addition, X-ray scattering experiments provide convincing evidence of an amyloidal cross-β-like secondary structure within the nanoassemblies. Furthermore, increasing the phenylalanine concentration results in the formation of highly homogenous, noncrystalline, self-healing hydrogels that display storage and loss moduli significantly higher than similar noncovalently cross-linked biomolecular nanofibrillar scaffolds. These remarkably stiff nanofibrillar hydrogels can be harnessed for various technological and biomedical applications, such as self-healing, printable, structural, load-bearing 3D scaffolds. The properties of this simple but quite remarkable hydrogel open a possibility to utilize it in the biomaterial industry.

The first comprehensive phylogenetic and biochemical analysis of NADH diphosphatases reveals that the enzyme from Tuber melanosporum is highly active towards NAD+

Nudix (for nucleoside diphosphatases linked to other moieties, X) hydrolases are a diverse family of proteins capable of cleaving an enormous variety of substrates, ranging from nucleotide sugars to NAD+-capped RNAs. Although all the members of this superfamily share a common conserved catalytic motif, the Nudix box, their substrate specificity lies in specific sequence traits, which give rise to different subfamilies. Among them, NADH pyrophosphatases or diphosphatases (NADDs) are poorly studied and nothing is known about their distribution. To address this, we designed a Prosite-compatible pattern to identify new NADDs sequences. In silico scanning of the UniProtKB database showed that 3% of Nudix proteins were NADDs and displayed 21 different domain architectures, the canonical architecture (NUDIX-like_zf-NADH-PPase_NUDIX) being the most abundant (53%). Interestingly, NADD fungal sequences were prominent among eukaryotes, and were distributed over several Classes, including Pezizomycetes. Unexpectedly, in this last fungal Class, NADDs were found to be present from the most common recent ancestor to Tuberaceae, following a molecular phylogeny distribution similar to that previously described using two thousand single concatenated genes. Finally, when truffle-forming ectomycorrhizal Tuber melanosporum NADD was biochemically characterized, it showed the highest NAD+/NADH catalytic efficiency ratio ever described.

(1)H, (15)N and (13)C backbone and side chain resonance assignments of the RRM domain from human RBM24.

Tissue development requires the expression of a regulated subset of genes, and it is becoming clear that the process of alternative splicing also plays an important role in the production of necessary tissue-specific isoforms. However, only a few of these tissue-specific splicing factors in mammals have so far been discovered. One of these factors is the RNA-binding protein RBM24 which has been recently identified as a major regulator of alternative splicing in cardiac and skeletal muscle development. The RBM24 protein contains an RNA recognition motif (RRM) domain that presumably mediates the binding to target pre-mRNA required for regulation of the splicing patterns. Here we report (1)H, (15)N and (13)C chemical shift assignments of the backbone and sidechain atoms for the RRM domain from human RBM24. Secondary chemical shift analysis and relaxation measurement confirm the canonical architecture of the RRM domain. The data will allow for atomic level studies aimed at understanding splicing regulation of target genes in heart and muscle development and investigation into a separate role of RBM24 in modulating mRNA stability of genes involved in the p53 tumor suppressor pathway.

The 3' end prothrombin gene variants in serbian patients with idiopathic thrombophilia.

Thrombophilia is a multifactorial disorder that arises from the interaction of acquired and genetic risk factors. Despite the significant efforts made to understand the etiology of this disease, there are still a certain number of patients suffering from idiopathic thrombophilia. The aim of this study was to screen the 3′ end of the prothrombin (FII) gene, which is susceptible to gain-of-function mutations due to its non canonical architecture, in patients with idiopathic thrombophilia and to determine its eventual role in the pathogenesis of thrombophilia.This study was carried out in 100 patients with idiopathic thrombophilia and 100 healthy controls. DNA variants in the 715 bp long region of the 3′ end of the prothrombin gene were identified by sequencing. In our study, we detected two variants: A19911G and C20068T. The frequency of the A19911G gene variant was slightly increased in the group of patients compared to controls, however with no statistically significant difference compared to controls [odds ratio (OR) = 1.06; 95% confidence interval (95% CI) 0.53–2.13]. Heterozygous carriers of the FII C20068T gene variant were four times more frequent in patients (4.0%) than in controls (1.0%), but this difference did not reach statistical significance (OR = 4.12; 95% CI 0.45–37.57). Our findings suggest that variant A19911G is not a significant risk factor, while C20068T may represent a potential risk factor for idiopathic thrombophilia. To confirm our results, further studies should be conducted in a larger cohort of patients.

Crystallization and preliminary X-ray characterization of the full-length bacteriophytochrome from the plant pathogen Xanthomonas campestris pv. campestris.

Phytochromes give rise to the largest photosensor family known to date. However, they are underrepresented in the Protein Data Bank. Plant, cyanobacterial, fungal and bacterial phytochromes share a canonical architecture consisting of an N-terminal photosensory module (PAS2-GAF-PHY domains) and a C-terminal variable output module. The bacterium Xanthomonas campestris pv. campestris, a worldwide agricultural pathogen, codes for a single bacteriophytochrome (XccBphP) that has this canonical architecture, bearing a C-terminal PAS9 domain as the output module. Full-length XccBphP was cloned, expressed and purified to homogeneity by nickel-NTA affinity and size-exclusion chromatography and was then crystallized at room temperature bound to its cofactor biliverdin. A complete native X-ray diffraction data set was collected to a maximum resolution of 3.25 Å. The crystals belonged to space group P43212, with unit-cell parameters a = b = 103.94, c = 344.57 Å and a dimer in the asymmetric unit. Refinement is underway after solving the structure by molecular replacement.

Biochemical characterization of the phosphatase domain of the tumor suppressor PH domain leucine-rich repeat protein phosphatase.

PH domain leucine-rich repeat protein phosphatase (PHLPP) directly dephosphorylates and inactivates Akt and protein kinase C and is therefore a prime target for pharmacological intervention of two key signaling pathways, the phosphatidylinositol 3-kinase and diacylglycerol signaling pathways. Here we report on the first biochemical characterization of the phosphatase domain of a PHLPP family member. The human PHLPP1 and PHLPP2 phosphatase domains were expressed and purified from bacteria or insect cells and their activities compared to that of full-length proteins immunoprecipitated from mammalian cells. Biochemical analyses reveal that the PHLPP phosphatase domain effectively dephosphorylates synthetic and peptidic substrates, that its activity is modulated by metals and lipophilic compounds, and that it has relatively high thermal stability. Mutational analysis of PHLPP2 reveals an unusual active site architecture compared to the canonical architecture of PP2C phosphatases and identifies key acidic residues (Asp 806, Glu 989, and Asp 1024) and bulky aromatic residues (Phe 783 and Phe 808) whose mutation impairs activity. Consistent with a unique active site architecture, we identify inhibitors that discriminate between PHLPP2 and PP2Cα. These data establish PHLPP as a member of the PP2C family of phosphatases with a unique active site architecture.

From Vienna to Frankfurt Inside Core-House Type 7: A History of Scarcity through the Modern Kitchen

This paper traces a history of war-induced scarcity through the material and technological properties of household appliances and kitchens from 1914 to 1930. Investigating the Austrian settlement and allotment garden movement, it argues that the practices of users, self-help builders, and inhabitants who reacted to living with limited resources in the state of emergency found their way into the designs of modern homes, and into the works of canonical modern architecture, in particular the famous Frankfurt Kitchen. This paper thus investigates the design and production of the modern kitchen and its transformations, from Vienna to Frankfurt, moving from a cooperative vernacular building movement to one of the largest construction endeavors to standardize and prefabricate modern housing in Germany.

Functional mapping of cortical areas with optical imaging

Sensory areas in mammalian cortex compute sensory inputs of different modalities in order to perceive the environment. Much is known about the anatomical pattern of inter-laminar connections, which form the basis of the computational process. Nevertheless, less is known about the functional relevance of these wiring patterns. We used intrinsic optical signals (IOSs) in vitro to investigate functional properties of inter-laminar connections in cortical brain slices of rat sensory cortex. By electrical stimulation in layer VI, a columnar-shaped IOS in all cortical areas was found. We detected different laminar patterns of activation in different cortical areas. In primary sensory areas, like primary visual cortex and primary somatosensory cortex, the peak intensity of IOSs occurred in layer IV, which receives the main thalamic input. In secondary sensory areas, like the secondary visual cortex or the secondary somatosensory cortex, the maximum of IOSs amplitude was shifted to layer II/III. In motor areas, IOS peak amplitude is located in layer II/III. In the hind limb area, considered as amalgam between sensory and motor function, a mixture of the activity patterns observed in primary sensory and a motor area occurred with a peak amplitude in layers II and IV. At different stimulation sites within one cortical area, the shape of columnar IOSs remained very similar, reflecting a canonical architecture of functional micro-circuitry. We conclude that both primary and secondary sensory cortical areas display their characteristic functional activation pattern, regardless of their sensory modalities.

AN ADAPTIVE NEURAL CONTROL SYSTEM OF A DC MOTOR DRIVE.

An improved parallel recurrent neural network with canonical architecture, named Recurrent Trainable Neural Network (RTNN), and an error based back-propagation through time learning algorithm, are applied to a D.C. motor drive identification and control. The unknown nonlinear dynamics of the motor together with the load are identified by the RTNN. The trained RTNN identifier is combined with a desired reference model and a RTNN controller in a direct adaptive control scheme, so in order to achive a desired trajectory tracking of the motor speed and position. Finally, the applicability of the RTNN topology and learning is illustrated by experimental results.

On neural network design part II: Inhibition and the output map

In this two part study, we presented a new design methodology for neural classifiers. The design procedure utilizes a multiclass vector quantization, MVQ, algorithm for information extraction from the training set. The extracted information suffices to specify the hidden layer in a canonical neural network architecture. The extracted information also leads to the specification of neuron inhibition rules and subsequently to the design of the hidden layer to output map. In part I of that study, we focused attention on the MVQ algorithm and how it is used to extract information from a training set. The extracted information is used to directly specify the hidden layer. In part II, we consider the non-simplistic hidden layer to output map design. We note that the MVQ algorithm, as it extracts information, decomposes the design set into disjoint neighborhoods. For each neighborhood we identify subsets of the hidden layer neurons which are significant sensors for the neighborhood. For each subset we construct an output map. Inhibition rules are established to assure that the proper output map is activated. In benchmark simulations, the overall design exhibits performance, to the extent that we are hard pressed to identify bounds on performance, if any.

Fuzzy-Neural Model for Nonlinear Systems Identification

A state space representation of both continuous and discrete time mathematical models of Recurrent Neural Networks (RNN) are given in two layer Jordan canonical architecture, and a new improved Back-Propagation (BP) type learning method, is proposed. Some topology improvements, are suggested. The proposed RTNN model is linear in small and nonlinear in large, which permits to apply all well known state- and output linear systems design methods. The obtained RTNN model is incorporated in a rule-based fuzzy system, giving the possibility to approximate and to identify a complex nonlinear plants. Simulation results of nonlinear systems identification by the proposed fuzzy-neural system, using RNN BP learning, are given.

On neural network design ? Part I: Using the MVQ algorithm

In this two-part study we present a new design methodology for neural classifiers. The design procedure utilizes a multiclass vector quantization (MVQ) algorithm for information extraction from the training set. The extracted information suffices to specify the hidden layer in a canonical neural network architecture. The extracted information also leads to the specification of neuron inhibition rules and subsequently the design of the hidden layer-to-output map. In Part I of the study we focus attention on the MVQ algorithm and how it is used to extract information from a training set. The extracted information is referred to as thecodebook. The codebook is used to directly specify the hidden layer. This specification can take the form of a perceptron layer, a radial basis layer, or a heterogeneous layer involving a mixture of neuron types. These and otherh-layer specifications are determined directly from the same extracted information. The MVQ codebook also suffices to scale the activation function of each neuron. In Part II we consider the nonsimplistic hidden layer-to-output map design. We note that the MVQ algorithm, as it extracts information, decomposes the design set into disjoint neighborhoods. For each neighborhood we identify subsets of the hidden layer neurons, which are significant sensors for the neighborhood. For each such subset we construct an output map. Inhibition rules are established to ensure that the proper output map is activated. In benchmark simulations the overall design exhibits excellent performance, to the extent that we are hard pressed to identify bounds on performance, if any.