Miracle-dz/UniFAR-FTUs huggingface dataset:
Ion channelopathies in human induced pluripotent stem cell derived cardiomyocytes: a dynamic clamp study with virtual IK1

Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) are widely used in studying basic mechanisms of cardiac arrhythmias that are caused by ion channelopathies. Unfortunately, the action potential profile of hiPSC-CMs—and consequently the profile of individual membrane currents active during that action potential—differs substantially from that of native human cardiomyocytes, largely due to almost negligible expression of the inward rectifier potassium current (IK1). In the present study, we attempted to “normalize” the action potential profile of our hiPSC-CMs by inserting a voltage dependent in silico IK1 into our hiPSC-CMs, using the dynamic clamp configuration of the patch clamp technique. Recordings were made from single hiPSC-CMs, using the perforated patch clamp technique at physiological temperature. We assessed three different models of IK1, with different degrees of inward rectification, and systematically varied the magnitude of the inserted IK1. Also, we modified the inserted IK1 in order to assess the effects of loss- and gain-of-function mutations in the KCNJ2 gene, which encodes the Kir2.1 protein that is primarily responsible for the IK1 channel in human ventricle. For our experiments, we selected spontaneously beating hiPSC-CMs, with negligible IK1 as demonstrated in separate voltage clamp experiments, which were paced at 1 Hz. Upon addition of in silico IK1 with a peak outward density of 4–6 pA/pF, these hiPSC-CMs showed a ventricular-like action potential morphology with a stable resting membrane potential near −80 mV and a maximum upstroke velocity >150 V/s (n = 9). Proarrhythmic action potential changes were observed upon injection of both loss-of-function and gain-of-function IK1, as associated with Andersen–Tawil syndrome type 1 and short QT syndrome type 3, respectively (n = 6). We conclude that injection of in silico IK1 makes the hiPSC-CM a more reliable model for investigating mechanisms underlying cardiac arrhythmias.
Real-Time Verification of Network Properties Using Atomic Predicates

Network management will benefit from automated tools based upon formal methods. Several such tools have been published in the literature. We present a new formal method for a new tool, Atomic Predicates (AP) Verifier, which is much more time and space efficient than existing tools. Given a set of predicates representing packet filters, AP Verifier computes a set of atomic predicates, which is minimum and unique. The use of atomic predicates dramatically speeds up computation of network reachability. We evaluated the performance of AP Verifier using forwarding tables and ACLs from three large real networks. The atomic predicate sets of these networks were computed very quickly and their sizes are surprisingly small. Real networks are subject to dynamic state changes over time as a result of rule insertion and deletion by protocols and operators, failure and recovery of links and boxes, etc. In a software-defined network, the network state can be observed in real time and thus may be controlled in real time. AP Verifier includes algorithms to process such events and check compliance with network policies and properties in real time. We compare time and space costs of AP Verifier with Header Space and NetPlumber using datasets from the real networks.
Provably secure authenticated group Diffie-Hellman key exchange

Authenticated key-exchange protocols allow two participants A and B, communicating over a public network and each holding an authentication means to exchange a shared secret value. Methods designed to deal with this cryptographic problem ensure A (resp. B) that no other participants aside from B (resp. A) can learn any information about the agreed value and often also ensure A and B that their respective partner has actually computed this value. A natural extension to this cryptographic method is to consider a pool of participants exchanging a shared secret value and to provide a formal treatment for it. Starting from the famous two-party Diffie--Hellman (DH) key-exchange protocol and from its authenticated variants, security experts have extended it to the multiparty setting for over a decade and, in the past few years, completed a formal analysis in the framework of modern cryptography. The present paper synthesizes this body of work on the provably-secure authenticated group DH key exchange.
Finite State Automata Resulting from Temporal Information Maximization

We extend Linkser's Infomax principle for feedforward neural networks to a measure for stochastic interdependence that captures spatial and temporal signal properties in recurrent systems. This measure — " stochastic interaction " — quantifies the Kullback-Leibler divergence of a Markov chain from a product of split chains for the single unit processes. For unconstrained Markov chains, the maximization of stochastic interaction also called " Temporal Infomax " , has been previously shown to result in almost deterministic dynamics. The present work considers Temporal Infomax on constrained Markov chains, where part of the units are clamped to prescribed stochastic processes providing external input to the system. Surprisingly, Temporal Infomax in that case leads to finite state automata, either completely de-terministic or at most weakly non-deterministic. Transitions between internal states of these systems are almost perfectly predictable given the complete current state and the input, but the activity of each single unit alone is virtually random. The results are demonstrated by means of computer simulations and confirmed analytically. We furthermore relate them to experimental data concerning the correlation dynamics and functional connectivities observed in multiple electrode recordings.
The evolution of jaw protrusion mechanics is tightly coupled to bentho-pelagic divergence in damselfishes (Pomacentridae)

ABSTRACT Most species-rich lineages of aquatic organisms have undergone divergence between forms that feed from the substrate (benthic feeding) and forms that feed from the water column (pelagic feeding). Changes in trophic niche are frequently accompanied by changes in skull mechanics, and multiple fish lineages have evolved highly specialized biomechanical configurations that allow them to protrude their upper jaws toward the prey during feeding. Damselfishes (family Pomacentridae) are an example of a species-rich lineage with multiple trophic morphologies and feeding ecologies. We sought to determine whether bentho-pelagic divergence in the damselfishes is tightly coupled to changes in jaw protrusion ability. Using high-speed video recordings and kinematic analysis, we examined feeding performance in 10 species that include three examples of convergence on herbivory, three examples of convergence on omnivory and two examples of convergence on planktivory. We also utilized morphometrics to characterize the feeding morphology of an additional 40 species that represent all 29 damselfish genera. Comparative phylogenetic analyses were then used to examine the evolution of trophic morphology and biomechanical performance. We find that pelagic-feeding damselfishes (planktivores) are strongly differentiated from extensively benthic-feeding species (omnivores and herbivores) by their jaw protrusion ability, upper jaw morphology and the functional integration of upper jaw protrusion with lower jaw abduction. Most aspects of cranial form and function that separate these two ecological groups have evolved in correlation with each other and the evolution of the functional morphology of feeding in damselfishes has involved repeated convergence in form, function and ecology. Summary: Evolutionary analyses of both form and function in damselfishes demonstrate tight linkage between jaw protrusion ability and the repeated convergence on predominantly benthic or predominantly pelagic feeding niches.
Decomposition-Based Vectorless Toggle Rate Computation for FPGA Circuits

This paper presents a novel and accurate method of estimating the toggle rates of signals in field-programmable gate array (FPGA)-based logic circuits without the use of simulation vectors. Compared to previous vectorless techniques, our approach provides improved accuracy-of-results, especially for individual signals, which could be leveraged by computer-aided design (CAD) tools for performing power optimization of logic circuits. Increased accuracy is achieved by using stochastic methods that estimate the transition densities at FPGA logic elements while accounting for both spatial and temporal correlation of logic signals. Spatial correlation is calculated by leveraging a unique XOR-based decomposition technique that provides both accurate results and fast computation times. We also consider the delay information of implemented circuits, providing for a comprehensive treatment of glitches, including the effects of inertial limits on power dissipation. Our toggle-rate estimation approach has been tested on a commonly used set of Microelectronic Center of North Carolina circuits, as well as a set of industrial circuits targeted to Altera Stratix II FPGAs. Results show that our techniques provide a three times lower percent error, while maintaining a low processing time, when compared to two existing techniques: the vectorless estimation tool shipped with the commercial Quartus II 8.0 CAD tool, and the ACE v2.0 academic tool produced from the University of British Columbia, Vancouver, BC, Canada.
A Comparison of the Water Budgets between Clouds from AMMA and TWP-ICE

AbstractTwo field campaigns, the African Monsoon Multidisciplinary Analysis (AMMA) and the Tropical Warm Pool–International Cloud Experiment (TWP-ICE), took place in 2006 near Niamey, Niger, and Darwin, Northern Territory, Australia, providing extensive observations of mesoscale convective systems (MCSs) near a desert and a tropical coast, respectively. Under the constraint of their observations, three-dimensional cloud-resolving model simulations are carried out and presented in this paper to replicate the basic characteristics of the observed MCSs. All of the modeled MCSs exhibit a distinct structure having deep convective clouds accompanied by stratiform and anvil clouds. In contrast to the approximately 100-km-scale MCSs observed in TWP-ICE, the MCSs in AMMA have been successfully simulated with a scale of about 400 km.These modeled AMMA and TWP-ICE MCSs offer an opportunity to understand the structure and mechanism of MCSs. Comparing the water budgets between AMMA and TWP-ICE MCSs suggests that TWP-I.
Adaptive Value Normalization in the Prefrontal Cortex Is Reduced by Memory Load

Abstract Adaptation facilitates neural representation of a wide range of diverse inputs, including reward values. Adaptive value coding typically relies on contextual information either obtained from the environment or retrieved from and maintained in memory. However, it is unknown whether having to retrieve and maintain context information modulates the brain’s capacity for value adaptation. To address this issue, we measured hemodynamic responses of the prefrontal cortex (PFC) in two studies on risky decision-making. In each trial, healthy human subjects chose between a risky and a safe alternative; half of the participants had to remember the risky alternatives, whereas for the other half they were presented visually. The value of safe alternatives varied across trials. PFC responses adapted to contextual risk information, with steeper coding of safe alternative value in lower-risk contexts. Importantly, this adaptation depended on working memory load, such that response functions relating PFC activity to safe values were steeper with presented versus remembered risk. An independent second study replicated the findings of the first study and showed that similar slope reductions also arose when memory maintenance demands were increased with a secondary working memory task. Formal model comparison showed that a divisive normalization model fitted effects of both risk context and working memory demands on PFC activity better than alternative models of value adaptation, and revealed that reduced suppression of background activity was the critical parameter impairing normalization with increased memory maintenance demand. Our findings suggest that mnemonic processes can constrain normalization of neural value representations.
Sinulolides A–H, New Cyclopentenone and Butenolide Derivatives from Soft Coral Sinularia sp.

Eight new compounds, sinulolides A–H (1–8), along with two known compounds, α-methoxy-2,3-dimethyl-butenolide (9) and sinularone D (10), were isolated from the soft coral Sinularia sp. The structures of these compounds were elucidated on the basis of extensive spectroscopic analysis. The absolute configurations were determined on the basis of electronic circular dichroism (ECD) data analysis. Compounds 5 and 10 exhibited moderate effects for the inhibition of NF-κB activation.
Antarctic boundary layer parametrization in a general circulation model: 1‐D simulations facing summer observations at Dome C

The parametrization of the atmospheric boundary layer (ABL) is critical over the Antarctic Plateau for climate modelling since it affects the climatological temperature inversion and the negatively buoyant near‐surface flow over the ice‐sheet. This study challenges state‐of‐the‐art parametrizations used in general circulation models to represent the clear‐sky summertime diurnal cycle of the ABL at Dome C, Antarctic Plateau. The Laboratoire de Météorologie Dynamique‐Zoom model is run in a 1‐D configuration on the fourth Global Energy and Water Cycle Exchanges Project Atmospheric Boundary Layers Study case. Simulations are analyzed and compared to observations, giving insights into the sensitivity of one model that participates to the intercomparison exercise. Snow albedo and thermal inertia are calibrated leading to better surface temperatures. Using the so‐called “thermal plume model” improves the momentum mixing in the diurnal ABL. In stable conditions, four turbulence schemes are tested. Best simulations are those in which the turbulence cuts off above 35 m in the middle of the night, highlighting the contribution of the longwave radiation in the ABL heat budget. However, the nocturnal surface layer is not stable enough to distinguish between surface fluxes computed with different stability functions. The absence of subsidence in the forcings and an underestimation of downward longwave radiation are identified to be likely responsible for a cold bias in the nocturnal ABL. Apart from model‐specific improvements, the paper clarifies on which are the critical aspects to improve in general circulation models to correctly represent the summertime ABL over the Antarctic Plateau.
Characterization of Armillaria isolates from tea (Camellia sinensis) in Kenya

Armillaria is a primary root rot pathogen of tea (Camellia sinensis) in Kenya. The main species presently described in this country are A. mellea and A. heimii. A survey covering fourteen districts of Kenya was carried out and forty-seven isolates of Armillaria collected. Cultural morphology, rhizomorph characteristics, somatic incompatibility and features of basidiomata were used to characterize the isolates, together with molecular analysis based on randomly amplified polymorphic DNA (RAPD), inter-simple sequence repeat (ISSR), restriction fragment length polymorphism (RFLP) of the internal transcribed spacer (ITS) and the intergenic spacer (IGS) regions and sequence of the IGS region. It can be concluded that two Armillaria species were present and they were different from A. mellea. The first group was morphologically similar to A. heimii but this was contradicted by the molecular data, suggesting that A. heimii could be a complex of several species. The second group was different from the first and morphological and molecular data strongly suggest that it could be a new Armillaria species.
Epithelial Myosin Light Chain Kinase Activation Induces Mucosal Interleukin-13 Expression to Alter Tight Junction Ion Selectivity*

Intestinal barrier function is reduced in inflammatory bowel disease (IBD). Tumor necrosis factor (TNF) and interleukin (IL)-13, which are up-regulated in IBD, induce barrier defects that are associated with myosin light chain kinase (MLCK) activation and increased claudin-2 expression, respectively, in cultured intestinal epithelial monolayers. Here we report that these independent signaling pathways have distinct effects on tight junction barrier properties and interact in vivo. MLCK activation alters size selectivity to enhance paracellular flux of uncharged macromolecules without affecting charge selectivity and can be rapidly reversed by MLCK inhibition. In contrast, IL-13-dependent claudin-2 expression increases paracellular cation flux in vitro and in vivo without altering tight junction size selectivity but is unaffected by MLCK inhibition in vitro. In vivo, MLCK activation increases paracellular flux of uncharged macromolecules and also triggers IL-13 expression, claudin-2 synthesis, and increased paracellular cation flux. We conclude that reversible, MLCK-dependent permeability increases cause mucosal immune activation that, in turn, feeds back on the tight junction to establish long-lasting barrier defects. Interactions between these otherwise distinct tight junction regulatory pathways may contribute to IBD pathogenesis.
Deadlock-Free Scheduling of Automated Manufacturing Systems Using Petri Nets and Hybrid Heuristic Search

This paper focuses on the deadlock-free scheduling problem of automated manufacturing systems with shared resources and route flexibility, and develops novel scheduling methods by combining deadlock control policies and hybrid heuristic search. Place-timed Petri nets are used to model the systems and find a feasible sequence of firing transitions in the built model such that the firing time of its last transition is as small as possible. Based on the reachability graph of the net and a minimum processing time matrix, new heuristic and selection functions are designed to guide search processes. The proposed hybrid heuristic search is based on state space exploration and hence suffers from the state space explosion problem. In order to reduce the explored space, the search is restrained within a limited local search window. By embedding the deadlock-avoidance policies into the search processes, a novel deadlock-free hybrid heuristic search algorithm is developed. Experimental results indicate the effectiveness and superiority of the proposed algorithm over the state-of-the-art method.
Intracortical Infarcts in Small Vessel Disease: A Combined 7-T Postmortem MRI and Neuropathological Case Study in Cerebral Autosomal-Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy

Background and Purpose— The purpose of this study was to report the detection of infarcts of the cerebral cortex in a patient with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) using high-resolution postmortem 7-T MRI in association with pathological examination. Methods— Whole brain high-resolution MRI data were obtained postmortem at 7 T in a 53-year-old patient with CADASIL. These MRI data were used to guide the neuropathological examination of the cortex. Results— Combined with neuropathology, MRI allowed the delineation of intracortical infarcts confirmed by histological examination in this case. These lesions were not visible on the last in vivo MRI obtained at 1.5 T and were difficult to detect on neuropathological examination only. Conclusions— Postmortem high-resolution MRI may help to detect intracortical infarcts in CADASIL and possibly in other small vessel diseases of the brain.
The Cauchy problem in General Relativity

The paper revisits some of the classical and recent results on the Cauchy problem in General Relativity. Special emphasis is put on the problems concerning existence of a Cauchy development, break-down criteria and stability. The author would like to make a disclaimer that despite its general title the paper is not intended as a comprehensible survey. Due to the space-time constraints many remarkable results and developments are either mentioned briefly or not discussed at all. Most notably this concerns various work on the Einstein equations with matter and symmetry reduced problems.
Determinants of Body Mass Index in Turkey: A Quantile Regression Analysis from a Middle Income Country

This study investigates the factors that may influence the individual’s Body Mass Index (BMI) in the developing country of Turkey by implementing Quantile Regression (QR) methodology. The analysis is conducted by using the 2008, 2010 and 2012 waves of the Turkish Health Survey (THS) prepared by the Turkish Statistical Institute (TURKSTAT). QR regression results provide robust evidence that additional years of schooling are negatively correlated with an individual’s BMI and this relationship is significantly raised across different quantiles of BMI. We also find a strong negative relationship between being in the labor force and an individual’s BMI, and this relationship increases across the quantiles of BMI implying that an individual is more likely to be obese if he/ she is out of labor force. Our results suggest that other socioeconomic and demographic indicators such as gender, age, marital status and household income are also important factors to explain the variation in an individual’s BMI.
Modeling Crime Diffusion and Crime Suppression on Transportation Networks: An Initial Report

In urban transportation networks, crime diffuses as criminals travel through the networks and look for illicit opportunities. It is important to ﬁrst model this diffusion in order to recommend actions or patrol policies to control the diffusion of such crime. Previously, game theory has been used for such patrol policy recommendations, but these applications of game theory for security have not modeled the diffusion of crime that comes about due to criminals seeking opportunities; instead the focus has been on highly strategic adversaries that plan attacks in advance. To overcome this limitation of previous work, this paper provides the following key contributions. First, we provide a model of crime diffusion based on a quantal biased random movement (QBRM) of criminals opportunistically and repeatedly seeking targets. Within this model, criminals react to real-time information, rather than strategically planning their attack in advance. Second, we provide a game-theoretic approach to generate randomized patrol policies for controlling such diffusion.
Formations on two-layer pursuit systems

The paper studies hierarchical pursuit strategies for groups of mobile agents in the plane. It is shown that fascinating global patterns emerge from simple two-layer pursuit schemes, including rendezvous, uniform circular motion, complex circular motion, concentric circular motion, and concentric logarithmic spiral motion. Both rigorous analysis and simulations are provided.