Miracle-dz/UniFAR-FTUs huggingface dataset:
Membrane Associated Progesterone Receptors: Promiscuous Proteins with Pleiotropic Functions – Focus on Interactions with Cytochromes P450

Membrane-associated progesterone receptors (MAPR) are a group of four rather small, partially homologous proteins, which share a similar non-covalent heme-binding domain that is related to cytochrome b5, a well-known functional interaction partner of microsomal cytochrome P450 (CYP) monooxygenase systems. Apart from their structural similarities the four proteins progesterone membrane component 1 (PGRMC1, also referred to as IZA, sigma-2 receptor, Dap1), PGRMC2, neudesin (NENF) and neuferricin (CYB5D2) display surprisingly divergent and multifunctional physiological properties related to cholesterol/steroid biosynthesis, drug metabolism and response, iron homeostasis, heme trafficking, energy metabolism, autophagy, apoptosis, cell cycle regulation, cell migration, neural functions, and tumorigenesis and cancer progression. The purpose of this mini-review is to briefly summarize the structural and functional properties of MAPRs with particular focus on their interactions with the CYP system. For PGRMC1, originally identified as a non-canonical progesterone-binding protein that mediates some immediate non-genomic actions of progesterone, available evidence indicates mainly activating interactions with steroidogenic CYPs including CYP11A1, CYP21A2, CYP17, CYP19, CYP51A1, and CYP61A1, while interactions with drug metabolizing CYPs including CYP2C2, CYP2C8, CYP2C9, CYP2E1, and CYP3A4 were either ineffective or slightly inhibitory. For the other MAPRs the evidence is so far less conclusive. We also point out that experimental limitations question some of the previous conclusions. Use of appropriate model systems should help to further clarify the true impact of these proteins on CYP-mediated metabolic pathways.
Querying Big Data by Accessing Small Data

This paper investigates the feasibility of querying big data by accessing a bounded amount of the data. We study boundedly evaluable queries under a form of access constraints, when their evaluation cost is determined by the queries and constraints only. While it is undecidable to determine whether FO queries are boundedly evaluable, we show that for several classes of FO queries, the bounded evaluability problem is decidable. We also provide characterization and effective syntax for their boundedly evaluable queries. When a query Q is not boundedly evaluable, we study two approaches to approximately answering Q under access constraints. (1) We search for upper and lower envelopes of Q that are boundedly evaluable and warrant a constant accuracy bound. (2) We instantiate a minimum set of variables (parameters) in Q such that the specialized query is boundedly evaluable. We study problems for deciding the existence of envelopes and bounded specialized queries, and establish their complexity for various classes of FO queries.
Cryptic Neogene vicariance and Quaternary dispersal of the red‐spotted toad (Bufo punctatus): insights on the evolution of North American warm desert biotas

We define the geographical distributions of mitochondrial DNA (mtDNA) lineages embedded within a broadly distributed, arid‐dwelling toad, Bufo punctatus. These patterns were evaluated as they relate to hypothesized vicariant events leading to the formation of desert biotas within western North America. We assessed mtDNA sequence variation among 191 samples from 82 sites located throughout much of the species’ range. Parsimony‐based haplotype networks of major identified lineages were used in nested clade analysis (NCA) to further elucidate and evaluate shallow phylogeographic patterns potentially associated with Quaternary (Pleistocene–Holocene) vicariance and dispersal. Phylogenetic analyses provided strong support for three monophyletic lineages (clades) within B. punctatus. The geographical distributions of the clades showed little overlap and corresponded to the general boundaries of the Peninsular Desert, and two continental desert regions, Eastern (Chihuahuan Desert–Colorado Plateau) and Western (Mojave–Sonoran deserts), geographically separated along the Rocky Mountains and Sierra Madre Occidental. The observed divergence levels and congruence with postulated events in earth history implicate a late Neogene (latest Miocene–early Pliocene) time frame for separation of the major mtDNA lineages. Evaluation of nucleotide and haplotype diversity and interpretations from NCA reveal that populations on the Colorado Plateau resulted from a recent, likely post‐Pleistocene, range expansion from the Chihuahuan Desert. Dispersal across historical barriers separating major continental clades appear to be recent, resulting in secondary contacts in at least two areas. Given the observed contact between major clades, we speculated as to why the observed deep phylogeographic structure has not been eroded during the multiple previous interglacials of the Pleistocene.
Stochastic Hierarchical Multiobjective Routing Model in MPLS Networks with Two Service Classes - Report on a robustness analysis experiment ∗‡

The report begins by reviewing a two-level hierarchical multicriteria routing model for MPLS networks with two service classes (Quality of Service and Best Effort services) and alternative routing, previously proposed by the authors. Some key issues raised by its great complexity are discussed, as well as the major factors that constitute the sources of imprecision, inaccuracy and uncertainty of the model and the way in which they are dealt with in the adopted resolution approach. Analytic and stochastic simulation experiments, for a benchmarking case study, are performed in order to evaluate the inaccuracies intrinsic to the analytic/numerical resolution procedures. Furthermore, various experiments are executed for evaluating the effects in the model results of the uncertainty associated with the estimates of the mean of the stochastic traffic flows, in a dynamic version of the routing method. In this form, a robustness analysis focused on key robustness aspects of the model was carried out.
Behavioral modeling of Si LDMOS pre-matched devices with application to Doherty power amplifiers

Development of an experimental behavioral model to describe the non-linear characteristics of high power internally pre-matched LDMOS power transistors is presented. The model is developed by characterizing the device with swept power load-pull measurements across a large load impedance plane with the input impedance set at a pre-determined state. Based on measurements of complex input and output voltages at the device's package terminals, a functional representation is adopted to express the device's complex gain with respect to RF input voltage (or available source power) and the device's load terminating impedance. It is further shown that this approach can be used to independently model high power LDMOS pre-matched devices biased at Class-A/B and -C for use in simulating a complete Doherty power amplifier circuit. Simulations of a 300W Doherty power amplifier using this approach are contrasted to more conventional compact device models with excellent agreement noted across a large output power range. Hence, when compact models are unavailable, a behavioral one can be formulated from load pull measurements on the devices of interest.
Investigations Into Internal and External Aspects of Dynamic Agent-Environment Couplings

This paper originates from my work on`social agents'. An important issue in this kind of research is the dynamic coupling of an agent with its social and non-social environment. Additionally I considerìnternal dynamics' inside an agents as a basic step towards understanding. The paper therefore focusses on the internal and external dynamics which couple an agent to its environment. The rst part of this paper discusses the issue of embodiment in animals and artifacts and its relation tòsocial dynamics. ' I argue that embodiment is linked to a concept of a body and is not necessarily given when running a control program on robot hardware. For this purpose I introduce the concept of`body image'. Additionally, I stress the individual characteristics of an embodied cog-nitive system, as well as its social embeddedness. I outline the framework of a physical-psychological state-space which changes dynamically in a self-modifying way as a holistic approach towards embodied human and artiicial cognition. This framework is meant to discuss internal and external dynamics of an embodied , natural or artiicial agent. In order to stress the importance of a dynamic memory I introduce the concept of anàutobiographical agent'. The second part of the paper gives an example of the implementation of a physical agent, a robot, which is dynamically coupled to its environment by balancing on a seesaw. For the control of the robot a behavior-oriented approach using the dynamical systems metaphor is used. The problem is studied through building a complete and co-adapted robot-environment system. A seesaw which varies its orientation with one or two degrees of freedom is used as the artiiciaìhabitat'. The problem of stabilizing the body axis by active motion on a seesaw is solved by using two inclination sensors and a parallel, behavior-oriented control architecture. Some experiments are described which demonstrate the exploitation of the dynamics of the robot-environment system.
Real-time single-molecule studies of the motions of DNA polymerase fingers illuminate DNA synthesis mechanisms

DNA polymerases maintain genomic integrity by copying DNA with high fidelity. A conformational change important for fidelity is the motion of the polymerase fingers subdomain from an open to a closed conformation upon binding of a complementary nucleotide. We previously employed intra-protein single-molecule FRET on diffusing molecules to observe fingers conformations in polymerase–DNA complexes. Here, we used the same FRET ruler on surface-immobilized complexes to observe fingers-opening and closing of individual polymerase molecules in real time. Our results revealed the presence of intrinsic dynamics in the binary complex, characterized by slow fingers-closing and fast fingers-opening. When binary complexes were incubated with increasing concentrations of complementary nucleotide, the fingers-closing rate increased, strongly supporting an induced-fit model for nucleotide recognition. Meanwhile, the opening rate in ternary complexes with complementary nucleotide was 6 s−1, much slower than either fingers closing or the rate-limiting step in the forward direction; this rate balance ensures that, after nucleotide binding and fingers-closing, nucleotide incorporation is overwhelmingly likely to occur. Our results for ternary complexes with a non-complementary dNTP confirmed the presence of a state corresponding to partially closed fingers and suggested a radically different rate balance regarding fingers transitions, which allows polymerase to achieve high fidelity.
Metabotropic Glutamate Receptor Activation Enhances the Activities of Two Types of Ca2+-Activated K+Channels in Rat Hippocampal Astrocytes

The influence of activation of glutamate receptor (GluR) on outward K+ current in cultured neonate rat hippocampal astrocytes was investigated. Patch-clamp analysis of K+ channel currents in cultured astrocytes identified the existence of 71 ± 6 and 161 ± 11 pS single-channel K+ currents that were sensitive to changes in voltage and [Ca2+]i and blocked by external TEA but not by charybdotoxin, iberiotoxin, apamin, or 4-aminopyridine. Reverse transcriptase (RT)-PCR and Northern blot analysis revealed transcripts of the Ca2+-activated K+ channel (KCa) β4-subunit (β4) (KCNMB4) in cultured astrocytes. Expression of the metabotropic glutamate receptor (mGluR) subtypes mGluR1 and mGluR5 and the ionotropic glutamate receptor (iGluR) subtypes iGluR1 and iGluR4 were detected by RT-PCR and immunofluorescence analysis in cultured astrocytes. The mGluR agonistsl-glutamate and quisqualate increased the open state probability (NPo) of the 71 and 161 pS K+ channel currents that were prevented by the mGluR receptor antagonists 1-aminoindan-1,5-dicarboxylic acid orl-(+)-2-amino-3-phosphonopropionic acid and not by the iGluR antagonists (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate or CNQX. Activation of the two types of K+ channel currents by mGluR agonists was attenuated by pertussis toxin and by inhibition of phospholipase C (PLC) or cytochrome P450 arachidonate epoxygenase. These results indicate that brain astrocytes contain the KCNMB4 transcript and express two novel types of KCa channels that are gated by activation of a G-protein coupled metabotropic glutamate receptor functionally linked to PLC and cytochrome P450 arachidonate epoxygenase activity.
A lesion detection observer study comparing 2-dimensional versus fully 3-dimensional whole-body PET imaging protocols.

UNLABELLED We compared the impact of 2-dimensional (2D) and fully 3-dimensional (3D) acquisition modes on the performance of human observers in detecting and localizing tumors in whole-body (18)F-FDG images. METHODS We selected protocols based on noise equivalent count (NEC) rates derived from a series of 2D and fully 3D whole-body patient and phantom acquisitions on a dual-mode PET scanner. The fully 3D peak NEC value for a standard 70-kg patient was achieved for an injected dose of approximately 444 MBq (12 mCi) assuming a 90-min delay before acquisition, whereas the 2D peak value was never reached. The protocols were therefore set to those corresponding to a 444-MBq injected dose in fully 3D and 2D and a 740-MBq (20 mCi) injected dose in 2D that was considered as the maximum allowable dose. We used a non-Monte Carlo simulator to generate multiple realizations of whole-body PET data based on the geometry of the mathematic cardiac torso phantom (MCAT) with accurate noise properties. Two-dimensional and fully 3D acquisition times were set to 5 min per bed position. Spherical 1-cm-diameter lesions (targets) with random locations and contrasts were distributed in different organs. The simulated 2D datasets were reconstructed using attenuation-weighted ordered-subsets expectation maximization ((AW)OSEM) and the fully 3D datasets were reconstructed with FORE+(AW)OSEM (FORE = Fourier rebinning). Five human observers located and ranked the targets using a volumetric display of the whole-body PET data to replicate the clinical practice. An alternate free-response operating characteristic (AFROC) analysis of the human observer reports was performed for each protocol and each organ separately. RESULTS The 2D protocol corresponding to 740-MBq injected dose allowed the overall best detection performance. It was followed by the fully 3D acquisition at the peak fully 3D NEC rate from a 444-MBq injected dose. A 2D acquisition corresponding to a 444-MBq injected dose was ranked last. Differences in detection performance were organ specific. CONCLUSION This study showed that, for this patient size and scanner type, the fully 3D acquisition mode allowed better or equivalent detection performance than the 2D mode for an injected dose corresponding to the peak fully 3D NEC rate. The 2D acquisition protocol combined with a higher injected dose resulted in the highest detectabilities.
Influence of School Location within Districts of Terengganu on Body Weight Status among School Adolescents

Rapid development in the urbanisation process is linked to a shift in dietary intake and lifestyle. The locality may also determine the differences in socio-demographic and environmental factors related to nutrition between the rural and urban populations. The present study aimed to determine prevalence of obesity and to compare the body weight status on body weight status among school adolescents aged 10 to 17 years within districts of Terengganu. A cross sectional survey involving school adolescents aged 10 to 17 years from all government school in seven districts in Terengganu were carried out. Anthropometrics data were obtained from National Fitness Standard (SEGAK) assessment which was uploaded into specific developed database Health Monitoring System (HEMS) and BMI were classified using WHO BMI-for-age zscore. A total of 62,567 school adolescents were involved in this study. Girls had significantly higher BMI than boys in age groups of 13 to 15 and 16 to 17 years old. There were significant differences in mean BMI between rural and urban school locations school adolescents in all age groups (P <0.001) among boys and girls. Significant differences were also found between rural and urban school location in 10 to 12 years old in Dungun and Marang, whilst Kemaman and Kuala Terengganu districts had significant difference between rural and urban in 16 to 17 years old age group. Marang had the highest obesity prevalence within urban 15.3% school location whilst rural school location within Kuala Terengganu had the highest prevalence of obesity (14.1%). The obesity prevalence increased substantially regardless of school locations International Journal of Academic Research in Business and Social Sciences 2017, Vol. 7, No. 6
Examining sleep as a protective mechanism for executive functioning in children from low-income homes

ABSTRACT For young children, sleep is essential for healthy development. Inadequate sleep can affect emotional, behavioural, cognitive, and health outcomes. Low family income and resources can put children at risk for poor sleep quality, impairing their subsequent cognitive abilities. The current study examined low socioeconomic status (SES) as a factor that increases vulnerability to the negative effects of poor sleep quality on young children’s executive functioning (EF). It was hypothesized that sleep quality would be more strongly associated with EF skills for children from low-SES homes than for children from high-SES home. Results indicated that low family income predicted poorer performances in working memory. In addition, sleep quality was associated with working memory, but only for children from low-SES homes. These results suggest that sleep quality may be especially important for EF skills for children from low-SES homes.
Rates of flow and patterns of fluid circulation

11.1 Significance of fluid circulation rates and patterns The rates and patterns of fluid circulation in seafloor hydrothermal systems control the efficiency of lithospheric heat extraction, the nature of fluid-rock interaction, and the extent of seafloor and sub-seafloor biospheres supported by fluid, energy, and solute fluxes. It has been challenging to determine the patterns and rates of fluid flow within seafloor hydrothermal systems for several reasons. Active systems are remote and measurements are often difficult to make. Although newly developed tools have led to important advances in in situ characterization (Chapter 8), considerable challenges remain in determining where and how quickly fluids move through the sub-seafloor environment. Fossil systems provide an integrated record of fluid flow (Chapter 9), but system heterogeneity and overprinting of multiple generations of activity make quantitative interpretation difficult. Exposures are limited within both active and fossil systems, with the former often restricted to widely spaced or isolated boreholes and seafloor outcrops, and the latter comprising mainly ophi- olites and rare seafloor exposures (for example, along fracture zones or rifts, e.g. Karson, 2002). Fluid flow within seafloor hydrothermal systems is transient on a range of time scales, and some of these systems operate over lateral and vertical distances of kilometers or more. Additional complexities arise due to the scaling of rock properties within heterogeneous, fractured crust (Chapter 7). A more subtle difficulty is the influence of assumptions and ideas that became embedded in the literature at an early stage of research. Even after some of these ideas have been found to conflict with observations, they continue to influence interpretations. In this chapter, rates of fluid flow in hydrothermal systems, the lateral extent of circula- tion, preferred directions of fluid flow, and the "shapes" of fluid pathways are discussed. Techniques applied to resolve these parameters include use of thermal and chemical tracers, seafloor and borehole observations, and coupled modeling. Considerably more is known about apparent rates of fluid flow than is known about overall patterns of fluid circulation, bu te ven estimates of rates should be viewed with caution because estimates are gener- ally based on fundamental assumptions regarding the primary direction of flow, nature of
Mobility Prediction Based on Machine Learning

Mobile applications are required to operate in highly dynamic pervasive computing environments of dynamic nature and predict the location of mobile users in order to act proactively. We focus on the location prediction and propose a new model/framework. Our model is used for the classification of the spatial trajectories through the adoption of Machine Learning (ML) techniques. Predicting location is treated as a classification problem through supervised learning. We perform the performance assessment of our model through synthetic and real-world data. We monitor the important metrics of prediction accuracy and training sample size.
Human Embryonic and Fetal Mesenchymal Stem Cells Differentiate toward Three Different Cardiac Lineages in Contrast to Their Adult Counterparts

Mesenchymal stem cells (MSCs) show unexplained differences in differentiation potential. In this study, differentiation of human (h) MSCs derived from embryonic, fetal and adult sources toward cardiomyocytes, endothelial and smooth muscle cells was investigated. Labeled hMSCs derived from embryonic stem cells (hESC-MSCs), fetal umbilical cord, bone marrow, amniotic membrane and adult bone marrow and adipose tissue were co-cultured with neonatal rat cardiomyocytes (nrCMCs) or cardiac fibroblasts (nrCFBs) for 10 days, and also cultured under angiogenic conditions. Cardiomyogenesis was assessed by human-specific immunocytological analysis, whole-cell current-clamp recordings, human-specific qRT-PCR and optical mapping. After co-culture with nrCMCs, significantly more hESC-MSCs than fetal hMSCs stained positive for α-actinin, whereas adult hMSCs stained negative. Furthermore, functional cardiomyogenic differentiation, based on action potential recordings, was shown to occur, but not in adult hMSCs. Of all sources, hESC-MSCs expressed most cardiac-specific genes. hESC-MSCs and fetal hMSCs contained significantly higher basal levels of connexin43 than adult hMSCs and co-culture with nrCMCs increased expression. After co-culture with nrCFBs, hESC-MSCs and fetal hMSCs did not express α-actinin and connexin43 expression was decreased. Conduction velocity (CV) in co-cultures of nrCMCs and hESC-MSCs was significantly higher than in co-cultures with fetal or adult hMSCs. In angiogenesis bioassays, only hESC-MSCs and fetal hMSCs were able to form capillary-like structures, which stained for smooth muscle and endothelial cell markers.Human embryonic and fetal MSCs differentiate toward three different cardiac lineages, in contrast to adult MSCs. Cardiomyogenesis is determined by stimuli from the cellular microenvironment, where connexin43 may play an important role.