Miracle-dz/UniFAR-FTUs huggingface dataset:
The Carnitine Transporter SLC22A5 Is Not a General Drug Transporter, but It Efficiently Translocates Mildronate

In addition to its function as carnitine transporter, novel organic cation transporter type 2 (OCTN2; human gene symbol SLC22A5) is widely recognized as a transporter of drugs. This notion is based on several reports of direct measurement of drug accumulation. However, a rigorous, comparative, and comprehensive analysis of transport efficiency of OCTN2 has not been available so far. In the present study, OCTN2 orthologs from human, rat, and chicken were expressed in 293 cells using an inducible expression system. Uptake of trans-4-[4-(dimethylamino)styryl]-1-methylpyridinium iodide (ASP+), cephaloridine, ergothioneine, gabapentin, mildronate, pyrilamine, quinidine, spironolactone, tetraethylammonium, verapamil, and vigabatrin was determined by liquid chromatography/mass spectrometry. For reference, uptake of carnitine was measured in parallel. Our results indicate that OCTN2-mediated uptake of drugs was not significantly different from zero or, with tetraethylammonium and ergothioneine, was minute relative to carnitine. The carnitine congener mildronate, by contrast, was transported very efficiently. Thus, OCTN2 is not a general drug transporter but a highly specific carrier for carnitine and closely related molecules. Transport parameters (cellular accumulation, transporter affinity, sodium dependence) were similar for mildronate and carnitine. Efficiency of transport of mildronate was even higher than that of carnitine. Hence, our results establish that OCTN2 is a key target of the cardioprotective agent mildronate because it controls, as integral protein of the plasma membrane, cellular entry of mildronate and enables efficient access to intracellular targets. The highest levels of human OCTN2 mRNA were detected by real-time reverse transcription-polymerase chain reaction in kidney, ileum, breast, small intestine, skeletal muscle, and ovary but also in some heart and central nervous system tissues.
MOCDEX: Multiprocessor on Chip Multiobjective Design Space Exploration with Direct Execution

Fully integrated system level design space exploration methodologies are essential to guarantee efficiency of future large scale system on programmable chip. Each design step in the design flow from system architecture to place and route represents an optimization problem. So far, different tools (computer architecture, design automation) are used to address each problem separately with at best estimation techniques from one level to another. This approach ignores the various and very diverse vertical relations between distinct levels parameters and provides at best local optimization solutions at each step. Due to the large scale of SoC, system level design methodologies need to tackle the system design process as a global optimization problem by fully integrating physical design in the design space exploration. We propose MOCDEX, a multiobjective design space exploration methodology, for multiprocessor on chip which closes the gap between these associated tools in a fully integrated approach and with hardware in the loop. A case study of a 4-way multiprocessor demonstrates the validity of our approach.
Type Checking in XOBE

XML is the upcoming standard for internet data. Java is the most important programming language for internet applications. Nevertheless, in today’s languages and tools there is no smooth integration of Java and XML. The XML OBjEcts project (XOBE) at the University of Lubeck addresses this mismatch by defining XML objects by XML schemas and by making them to first-class data values. In XOBE, the distinction between XML documents and XML objects no longer exists. Instead, a running XOBE program works only with XML objects. XML documents in text form with explicit tags exist only for communicating with the outside world. This approach allows to check the validity of all XML objects within a program statically at compile time. This is accomplished by XML constructors. Previously generated XML objects are inserted in these constructors such that the validity can be checked at compile time. This paper concentrates on the type checking algorithm in XOBE which is used, among others, for checking the correctness of assignment statements involving XML objects. The type checking algorithm assures that all XML objects that can occur dynamically on the right hand side of an assignment statement are objects that can be assigned to the variable on the left hand side. This type checking is done statically without running the program. The algorithm is based upon regular hedge grammars and regular hedge expressions.
Structural Connectivity of the Developing Human Amygdala

A large corpus of research suggests that there are changes in the manner and degree to which the amygdala supports cognitive and emotional function across development. One possible basis for these developmental differences could be the maturation of amygdalar connections with the rest of the brain. Recent functional connectivity studies support this conclusion, but the structural connectivity of the developing amygdala and its different nuclei remains largely unstudied. We examined age related changes in the DWI connectivity fingerprints of the amygdala to the rest of the brain in 166 individuals of ages 5-30. We also developed a model to predict age based on individual-subject amygdala connectivity, and identified the connections that were most predictive of age. Finally, we segmented the amygdala into its four main nucleus groups, and examined the developmental changes in connectivity for each nucleus. We observed that with age, amygdalar connectivity becomes increasingly sparse and localized. Age related changes were largely localized to the subregions of the amygdala that are implicated in social inference and contextual memory (the basal and lateral nuclei). The central nucleus’ connectivity also showed differences with age but these differences affected fewer target regions than the basal and lateral nuclei. The medial nucleus did not exhibit any age related changes. These findings demonstrate increasing specificity in the connectivity patterns of amygdalar nuclei across age.
QEPCAD B: a program for computing with semi-algebraic sets using CADs

This report introduces QEPCAD, B, a program for computing with real algebraic sets using cylindrical algebraic decomposition (CAD). QEPCAD B both extends and improves upon the QEPCAD system for quantifier elimination by partial cylindrical algebraic decomposition written by Hoon Hong in the early 1990s. This paper briefly discusses some of the improvements in the implementation of CAD and quantifier elimination via CAD, and provides somewhat more detail on extensions to the system that go beyond quantifier elimination. The author is responsible for most of the extended features of QEPCAD B, but improvements to the basic CAD implementation and to the SACLIB library on which QEPCAD is based are the results of many people's work, including: George E. Collins, Mark J. Encarnación, Hoon Hong, Jeremy Johnson, Werner Krandick, Richard Liska, Scott McCallum, Nicolas Robidoux, and Stanly Steinberg. Source code, documentation and installation instructions for QEPCAD B are all available at www.cs. usna.edu/~qepcad.
A comparison of different control strategies in inverter connected micro-grids

Inverter connected renewable energy sources are becoming increasingly general in micro-grids. It has brought many problems and challenges to the stability and transient of the system. Traditional constant voltage and constant frequency (CVCF) method fits for many occasions, but it can't plug and play easily because it needs communication between the micro-grid controller and energy sources. Peer to peer droop-control strategies can just solve this problem. An overview of isolated micro-grid model has been introduced firstly, then the CVCF method and two droop control strategies have been described in detail. All three control strategies are brought to the power system simulation software DigSilent PowerFactory and a comparison of them in terms of transient performance in voltage and frequency control has been made. The simulation results show that the CVCF method performs best in steady state and both two peer to peer droop-control strategies can ensure micro-grid stability in pure inverter connected system. Each strategy has its advantages as well as limitations, which depend on different occasions. Some following-up research prospects are also raised in the end of this paper.
Evidence for involvement of a limbic paraventricular hypothalamic inhibitory network in hypothalamic‐pituitary‐adrenal axis adaptations to repeated stress

Emotional stressors activate a stereotyped set of limbic forebrain cell groups implicated in constraining stress‐induced hypothalamic‐pituitary‐adrenal (HPA) axis activation by inhibiting hypophysiotropic neurons in the paraventricular hypothalamic nucleus (PVH). We previously identified a circumscribed, anterior part of the bed nuclei of the stria terminalis (aBST) that houses stress‐sensitive, PVH‐projecting, γ‐aminobutyric acid (GABA)‐ergic neurons as representing a site of convergence of stress‐inhibitory influences originating from medial prefrontal and hippocampal cortices. Here we investigate whether exaggerated HPA axis responses associated with chronic variable stress (CVS; daily exposure to different stressors at unpredictable times over 14 days, followed by restraint stress on day 15) and diminished HPA output seen following repeated (14 days) restraint‐stress exposure are associated with differential engagement of the limbic modulatory network. Relative to acutely restrained rats, animals subjected to CVS showed the expected increase (sensitization) in HPA responses and diminished levels of activation (Fos) of GABAergic neurons and glutamic acid decarboxylase (GAD) mRNA expression in the aBST. By contrast, repeated restraint stress produced habituation in HPA responses, maintained levels of activation of GABAergic neurons, and increased GAD expression in the aBST. aBST‐projecting neurons in limbic sites implicated in HPA axis inhibition tended to show diminished activational responses in both repeated‐stress paradigms, with the exception of the paraventricular thalamic nucleus, in which responsiveness was maintained in repeatedly restrained animals. The results are consistent with the view that differential engagement of HPA inhibitory mechanisms in the aBST may contribute to alterations in HPA axis responses to emotional stress in sensitization and habituation paradigms. J. Comp. Neurol. 523:2769–2787, 2015. © 2015 Wiley Periodicals, Inc.
Differences in the protein composition of bovine retinal rod outer segment disk and plasma membranes isolated by a ricin-gold-dextran density perturbation method

The plasma membrane and disk membranes of bovine retinal rod outer segments (ROS) have been purified by a novel density-gradient perturbation method for analysis of their protein compositions. Purified ROS were treated with neuraminidase to expose galactose residues on plasma membrane-specific glycoproteins and labeled with ricin-gold-dextran particles. After the ROS were lysed in hypotonic buffer, the plasma membrane was dissociated from the disks by either mild trypsin digestion or prolonged exposure to low ionic strength buffer. The dense ricin-gold-dextran-labeled plasma membrane was separated from disks by sucrose gradient centrifugation. Electron microscopy was used to follow this fractionation procedure. The dense red pellet primarily consisted of inverted plasma membrane vesicles containing gold particles; the membrane fraction of density 1.13 g/cc consisted of unlabeled intact disks and vesicles. Ricin-binding studies indicated that the plasma membrane from trypsin-treated ROS was purified between 10-15-fold. The protein composition of plasma membranes and disks was significantly different as analyzed by SDS gels and Western blots labeled with lectins and monoclonal antibodies. ROS plasma membrane exhibited three major proteins of 36 (rhodopsin), 38, and 52 kD, three ricin-binding glycoproteins of 230, 160, and 110 kD, and numerous minor proteins in the range of 14-270 kD. In disk membranes rhodopsin appeared as the only major protein. A 220-kD concanavalin A-binding glycoprotein and peripherin, a rim-specific protein, were also present along with minor proteins of 43 and 57-63 kD. Radioimmune assays indicated that the ROS plasma membrane contained about half as much rhodopsin as disk membranes.
LETTER TO THE EDITOR: Nonlinear dynamics of a continuous spring - block model of earthquake faults

The continuous one-dimensional Burridge - Knopoff model is generalized by introducing plastic creep in addition to rigid sliding. The resulting equations, for an order parameter (sliding rate) and a control parameter (driving force), exhibit a velocity-strengthening and a velocity-softening instability. In the former regime, reminiscent of self-organized criticality in continuum systems, anomalous diffusion is described by a nonlinear diffusion equation. The latter regime, characteristic of deterministic chaos, is described by a time-dependent Ginzburg - Landau equation. Implications of the model with respect to earthquake predictability are discussed.
La hacienda de los Santiago en Tecali, Puebla: un cacicazgo nahua colonial, 1520-1750

E L CACICAZGO, O HACIENDA NOBLE INDÍGENA, es u n rasgo muy conocido de la sociedad i n d í g e n a del M é x i c o colonial . A l igual que muchos aspectos de la vida indígena , el cacicazgo tenía una firme base en la ley e spañola , aunque al mismo t iempo era e x p r e s i ó n de una vigorosa tradición de poder y privilegio de la nobleza ind ígena , que evidentemente p r e c e d í a a la conquista. D e s p u é s de su establecimiento a pr incipios o mediados del siglo XVI, la historia subsiguiente del cacicazgo mexicano generalmente se ha retratado de manera lineal: p e r d u r ó por u n t iempo (desde algunas d é c a d a s hasta dos siglos o más , dependiendo de la r eg ión ) y luego entró en u n a decadencia irreversible. Gibson n o t ó las decrecientes fortunas de muchos cacicazgos del valle de México en el siglo XVII, y L ó p e z Sarrelangue p intó una imagen similar para Tara scán , Michoacán , aunque observó que allí los cacicazgos m á s poderosos permanecieron estables hasta comienzos de l siglo XVIII.2
Distributed Voronoi partitioning for multi-robot systems with limited range sensors

We consider the problem of distributed partitioning of an environment by a set of robots so that each robot performs its operations in the region within the corresponding cell. Voronoi partitioning is one of the most attractive techniques that has been used to solve this problem. It has been used in several distributed multi-robotic system and sensor network applications, such as sensor coverage, search and rescue, and coverage path planning. For a truly distributed implementation of such problems, each robot should be able to compute the corresponding Voronoi cell in a distributed manner. Further, in a practical application, the robots' sensors may have limited range, thus each robot may operate within a portion of its Voronoi cell constrained by the sensor range. We describe a distributed algorithm for computation of this range constrained Voronoi cell where each robot independently constructs chords corresponding to other robots that are within a distance of twice its sensor circle radius. A robot then uses a simple and fast technique to remove inessential chords to calculate the vertices of its Voronoi cell. We prove completeness and correctness of the proposed algorithm, and also provide the upper and lower bounds on the computational complexity of our algorithm. The theoretical results are validated with the help of experiments to show that for different values of sensor ranges, our proposed algorithm incurs a time complexity that is significantly lower than that of the existing full Voronoi partition computation algorithm. The maximum number of steps required by our algorithm is also shown to be within a constant times the lower bound given by the number of neighbors of each node.
Quality of Life and Physical Ability Changes After Hospital-Based Cardiac Rehabilitation in Patients With Myocardial Infarction

Objective To evaluate the effect of hospital-based cardiac rehabilitation (CR) on quality of life (QOL) and physical ability in patients with myocardial infarction (MI). Methods Patients with MI who were referred to the Cardiac Health and Rehabilitation Center 2 weeks after percutaneous coronary intervention were divided into CR and non-CR groups. The CR group performed supervised exercises 3 times a week for 2 months. QOL assessment, using the 36-item Short-Form Health Survey (SF-36) and physical ability evaluation were performed at the beginning and end of CR. Results The CR group demonstrated statistically significant improvements in physical functioning (PF), physical role functioning (RP), bodily pain (BP), general health perceptions (GH), vitality (VT), social role functioning (SF), emotional role functioning (RE), mental health (MH), physical component summary (PCS), and mental component summary (MCS). The non-CR group showed improvement in RP. Secondary outcomes, including resting heart rate (RHR), maximal oxygen consumption (VO2max), metabolic equivalent of task (MET), maximal exercise time (ETmax), stage 3 Borg rating of perceived exertion (3RPE), maximal Borg rating of perceived exertion (RPEmax), and stage 3 rate pressure product (3RPP), improved in the CR group. The non-CR group showed improvements in VO2max, MET, ETmax, and 3RPE. There were significant differences in improvements in PF, RP, BP, VT, SF, MH, MCS, RHR, VO2max, MET, ETmax, 3RPE, and 3RPP between the two groups. Conclusion Male patients with MI demonstrated improvements in QOL and physical ability following hospital-based CR; the impact on the mental component was greater than that on the physical component.
Evaluation of Hierarchical Sampling Strategies in 3D Human Pose Estimation

A common approach to the problem of 3D human pose estimation from video is to recursively estimate the most likely pose via particle filtering. However, standard particle filtering methods fail the task due to the high dimensionality of the 3D articulated human pose space. In this paper we present a thorough evaluation of two variants of particle filtering, namely Annealed Particle Filtering and Partitioned Sampling Particle Filtering, that have been proposed to make the problem feasible by exploiting the hierarchical structures inside the pose space. We evaluate both methods in the context of markerless model-based 3D motion capture using silhouette shapes from multiple cameras. For that we created a simulation from ground truth sequences of human motions, which enables us to focus our evaluation on the sampling capabilities of the approaches, i.e. on how efficient particles are spread towards the modes of the distribution. We show the behaviour with respect to the amount of cameras used, the amount of particles used, as well as the dimensionality of the search space. Especially the performance when using more complex human models (40 DOF and above) that are able to capture human movements with higher precision compared to previous approaches is of interest in this work. In summary, we show that both methods have complementary strengths, and propose a combined method that is able to perform the tracking task with higher robustness despite reduced computational effort.
Regimented language training. Changes to brain and behaviour following intensive non-native language learning

The influence of foreign-language acquisition on adult brain structure remains mostly unexplored. Whilst several cross-sectional studies have led to further understanding of how language can affect brain structure, only a few longitudinal studies have been conducted. We measured the effects of language acquisition on behaviour and brain structure at the Swedish Armed Forces Language School in two separate cohorts of army interpreters. Our hypothesis was that intensive language studies would lead to increases in associative memory performance, hippocampal volume, relevant cortical areas and connectivity between areas of the brain. In Study 1 we compared performance on 8 cognitive tasks before and after 3 months of language learning (n = 15) to a control group of university students (n = 19). Behavioural measures revealed increases in associative memory performance; remembering names and faces, a paired associates task, which is known to involve hippocampal processing. In Study 2 semiautomatic tracing of the hippocampus using FreeSurfer was compared to manual tracing and deemed equivalent to manual tracing in young adults (n = 44) but not in older adults (n = 47). Evaluation was based on data from earlier studies. Study 3 used FreeSurfer to measure grey matter volume in subcortical structures as well as cortical thickness in the next cohort of interpreters and university students (n = 14 and 17, respectively). Results revealed increases in hippocampal volume and cortical thickness of the left middle frontal gyrus, inferior frontal gyrus, and superior temporal gyrus. The right hippocampus and the left superior temporal gyrus, both key regions in language acquisition, increased relatively more in interpreters with higher language proficiency following training. Interpreters struggling to stay at the academy showed relatively higher increases in the middle frontal gyrus, a region that is known to be involved in processing difficult speech. In Study 4 the same group of interpreters as study 3 was measured using Diffusion Tensor Imaging. No changes in white matter microstructure were observed. A possible explanation is that interpreters had well developed tracts before starting their training at the academy. Effects in this direction could be observed as lower values of radial diffusivity in interpreters relative to controls. The combined results showed that grey matter volume in relevant language areas as well as the right hippocampus increased for interpreters compared to controls. Furthermore, increases were related to separate behavioural measures and ratings. The results indicate that grey matter plasticity is not only possible during language acquisition, but the extent and region of plastic changes varies between individuals. (Less)
Socio-technical Ontology Development for Modelling Sensemaking in Heterogeneous Domains

Sensemaking is often associated with processing large or complex amount of data obtained from diverse and distributed sources. With information explosion from the web, sensemaking is becoming ubiquitous and ever more challenging. Semantic technologies have potential to support understanding of sensemaking process with the benefits they bring (e.g. reasoning, aggregation, automation). Conceptual models of sensemaking have been developed to understand its complex processes by social and information scientist. However, these frameworks are not applicable directly to system design. This paper describes a socio-technical approach for modelling sensemaking process in order to inform the development of intelligent services to aid sensemakers. We apply an a priori ontology modularisation methodology for handling complexity of heterogeneous domains and utilise well-known sensemaking theoretical framework to guide ontology development. This approach is applied in an EU project Dicode, for the development of its sensemaking ontology.