bluuebunny/crossref_metadata_2025 huggingface dataset:
Homocysteine and homocysteine-related compounds: an overview of the roles in the pathology of the cardiovascular and nervous systems
Authors: Djuric Dragan , Jakovljevic Vladimir , Zivkovic Vladimir , Srejovic Ivan
Published: August 2018

Homocysteine, an amino acid containing a sulfhydryl group, is an intermediate product during metabolism of the amino acids methionine and cysteine. Hyperhomocysteinemia is used as a predictive risk factor for cardiovascular disorders, the stroke progression, screening for inborn errors of methionine metabolism, and as a supplementary test for vitamin B12deficiency. Two organic systems in which homocysteine has the most harmful effects are the cardiovascular and nervous system. The adverse effects of homocysteine are achieved by the action of several different mechanisms, such as overactivation of N-methyl-d-aspartate receptors, activation of Toll-like receptor 4, disturbance in Ca2+handling, increased activity of nicotinamide adenine dinucleotide phosphate-oxidase and subsequent increase of production of reactive oxygen species, increased activity of nitric oxide synthase and nitric oxide synthase uncoupling and consequent impairment in nitric oxide and reactive oxygen species synthesis. Increased production of reactive species during hyperhomocysteinemia is related with increased expression of several proinflammatory cytokines, including IL-1β, IL-6, TNF-α, MCP-1, and intracellular adhesion molecule-1. All these mechanisms contribute to the emergence of diseases like atherosclerosis and related complications such as myocardial infarction, stroke, aortic aneurysm, as well as Alzheimer disease and epilepsy. This review provides evidence that supports the causal role for hyperhomocysteinemia in the development of cardiovascular disease and nervous system disorders.
Rigidity and Substitutive Dendric Words
Authors: Berthé V. , Dolce F. , Durand F. , Leroy J. , Perrin D.
Published: August 2018

Dendric words are infinite words that are defined in terms of extension graphs. These are bipartite graphs that describe the left and right extensions of factors. Dendric words are such that all their extension graphs are trees. They are also called tree words. This class of words includes classical families of words such as Sturmian words, codings of interval exchanges, or else, Arnoux–Rauzy words. We investigate here the properties of substitutive dendric words and prove some rigidity properties, that is, algebraic properties on the set of substitutions that fix a dendric word. We also prove that aperiodic minimal dendric subshifts (generated by dendric words) cannot have rational topological eigenvalues, and thus, cannot be generated by constant length substitutions.
On the Complexity of Solving Restricted Word Equations
Authors: Manea Florin , Nowotka Dirk , Schmid Markus L.
Published: August 2018

We investigate the complexity of the solvability problem for restricted classes of word equations with and without regular constraints. The solvability problem for unrestricted word equations remains [Formula: see text]-hard, even if, on both sides, between any two occurrences of the same variable no other different variable occurs; for word equations with regular constraints, the solvability problems remains [Formula: see text]-hard for equations whose two sides share no variables or with two variables, only one of which is repeated. On the other hand, word equations with only one repeated variable (but an arbitrary number of variables) and at least one non-repeated variable on each side, can be solved in polynomial-time.
On the Strength of Unambiguous Tree Automata
Authors: Michalewski Henryk , Skrzypczak Michał
Published: August 2018

This work is a study of the class of non-deterministic automata on infinite trees that are unambiguous i.e. have at most one accepting run on every tree. The motivating question asks if the fact that an automaton is unambiguous implies some drop in the descriptive complexity of the language recognised by the automaton. As it turns out, such a drop occurs for the parity index and does not occur for the weak parity index.

More precisely, given an unambiguous parity automaton [Formula: see text] of index [Formula: see text], we show how to construct an alternating automaton [Formula: see text] which accepts the same language, but is simpler in terms of the acceptance condition. In particular, if [Formula: see text] is a Büchi automaton ([Formula: see text]) then [Formula: see text] is a weak alternating automaton. In general, [Formula: see text] belongs to the class [Formula: see text], what implies that it is simultaneously of alternating index [Formula: see text] and of the dual index [Formula: see text]. The transformation algorithm is based on a separation procedure of Arnold and Santocanale (2005).

In the case of non-deterministic automata with the weak parity condition, we provide a separation procedure analogous to the one used above. However, as illustrated by examples, this separation procedure cannot be used to prove a complexity drop in the weak case, as there is no such drop.
Analytical forms of the deuteron wave function for Nijmegen group potentials and polarization characteristics of A(d,d′)X reactions
Authors: Zhaba Viktor Ivanovich
Published: August 2018

Polarization observables of the [Formula: see text] reactions have been calculated according to the received coefficients of the analytical form for deuteron wave function (DWF) in coordinate space for the nucleon–nucleon Nijmegen group potentials (NijmI, NijmII and Nijm93). The obtained values of tensor [Formula: see text] and vector [Formula: see text] analyzing powers have been compared with the published experimental data at [Formula: see text]-scaling for the inelastic scattering of deuterons on hydrogen, carbon and beryllium. Theoretical values of tensor–tensor [Formula: see text] and vector–vector [Formula: see text] polarization transfers have also been evaluated in the plane-wave impulse approximation.
Quantum gravity effect on the tunneling particles from Warped-AdS3 black hole
Authors: Gecim Ganim , Sucu Yusuf
Published: August 2018

In this study, using the Hamilton–Jacobi approach, we investigated the Hawking temperature of the (2 + 1)-dimensional Warped-AdS3 black hole by considering the generalized uncertainty principle (GUP) effect. In this connection, we calculated quantum mechanical tunneling probabilities of the scalar spin-0 and Dirac spin-[Formula: see text] particles from the black hole by using the modified Klein–Gordon and Dirac equations, respectively. Then, we observed that the Hawking temperature of the black hole depends not only on radius and angular velocity of the outer horizon of the black hole, but also on the angular velocity of the inner horizon of the black hole and the total angular momentum, energy and mass of a tunneling particle. In this case, the Hawking radiation of Dirac particle is different from that of the scalar particle. Moreover, this situation shows that the Hawking temperature calculated under the GUP may give us information about which sort of particle is tunneling. And, the direct dependence of the Hawking temperature to the inner horizon’s angular velocity makes the effect of the Chandrasekhar–Friedman–Schutz (CFS) mechanism more clear in the black hole physics.
Acceleration of cosmic expansion through huge cosmological constant progressively reduced by submicroscopic information transfer
Authors: Rebhan E.
Published: August 2018

In a previous paper (Ref. 1), the presence of dark energy in our universe was explained as the fingerprint of a comprehensive, much older and expanding multiverse with positive spatial curvature, whose space–time is spanned by this energy, and which was created out of nothing. This concept is expanded by the addition of a model for explaining the decay of the mass density [Formula: see text] of dark energy from its origin until now by a factor of approximately [Formula: see text].

Elementary particles contain information about which laws of nature they obey, but not what exactly these are. Most likely, the laws are not followed by obedience to a categorical imperative. Rather, it is assumed, that from the very beginning the information about them is coded in submicroscopic patches of the space–time. The initial density [Formula: see text] is supposed to belong to the unimpaired cosmological constant obtained from elementary particle theory. Due to its huge value, it causes an extremely fast spatial expansion by which continuously new space–time elements are created. To them, the information about the physical laws must be transmitted from the already present space–time. This process needs time which with ever-increasing expansion velocity is getting scarcer and scarcer. It is concluded that this impedes the expansion through a friction-like process which can be described by a term proportional to the expansion velocity. This term is subtracted from the expansion acceleration. It is shown that the solutions thus obtained are also solutions of the cosmological standard equations employing a scalar field [Formula: see text]. In consequence, the present model can be considered as a reinterpretation of results which can be obtained with acknowledged methods.
Experts EEG Cognitive Analysis and Substance Classification in Security Inspection
Authors: Yuan Yue , Wang Hong , Yuan Peixin
Published: August 2018

In recent years, the workload of security offers has increased along with the requirement of anti-terrorism. In the paper, a series of evaluation index of security inspection based on the EEG signals of the security officers were proposed to improve the accuracy of dangerous instances detection and decrease the workload of the officers. We performed an experiment to record the EEG data of security officers when they were watching the picture with or without the dangerous item in the uncovered and obscured scenes. Brain network analysis based on graph theory was applied to generate the indexes from the EEG induced by the parcel picture of security inspection, and is a new perspective on the classification of the parcel composition. The paper studied the low-frequency, multi-channel experts EEG signals, calculated the phase locking value (PLV) between every two channels to construct the topological functional brain network (FBN). The appropriate binary FBNs were obtained by setting the thresholds, and then the complex brain network parameters were estimated by the graph-theoretic methods, which were used for classification with 10-fold cross-validation and the average accuracy was 83.3[Formula: see text][Formula: see text][Formula: see text]97.78%. The method was effectively applied to the substance classification and would further improve the recognition accuracy of the target by combining this method with the existing detection technology.
Mixed Encoding of Collections of Output Variables for LUT-Based Mealy FSMs
Authors: Barkalov Alexander , Titarenko Larysa , Chmielewski Sławomir
Published: August 2018

A method is proposed targeting the decrease of the number of look-up tables (LUTs) in logic circuits of field programmable gate arrays (FPGA)-based Mealy finite state machines. The method is based on constructing a partition for the set of output variables. It diminishes the number of additional variables encoding the collections of output variables (COVs). A formal method is proposed for finding the partition. An example of synthesis is given, as well as the results of investigations. The investigations were conducted for standard benchmarks.
Developing an Offline Persian Automatic Lip Reader as a New Human–Mobile Interaction Method in Android Smart Phones
Authors: Lesani Fatemeh Sadat , Fotouhi Ghazvini Faranak , Dianat Rouhollah
Published: August 2018

In this paper, a new method to communicate with mobile phones is introduced. A camera phone can track the user’s lip motions using the lip reading algorithms. They recognize the words and sentences to run the appropriate application automatically. However, two of the challenges when implementing these algorithms in mobile phones are the changing ambient’s light and the limited resources such as memory and CPU. In this research, two methods are introduced to solve these problems. An offline lip reading application is implemented for Android phones which tracks the user’s lips in the Persian language. The application recognizes Persian words using visual features extraction from the user’s lips. The significance of this paper lies in the fact that it reports one of the first systems ever developed for offline lip reading. The whole process takes place completely on the device without the support of a dedicated server for the execution of the algorithms. In addition, this research is one of the first studies conducted on Persian mobile lip reading systems. Finally, the application was tested by disabled people who suffer from hand disabilities. The application satisfied them more than other applications which use sound, touch or text as an interface.
EFFECTS OF ECLIPSE PHASE AND DELAY ON THE DYNAMICS OF HIV INFECTION
Authors: SAHANI SAROJ KUMAR , YASHI
Published: August 2018

In this paper, an HIV infection model with eclipse phase, humoral immune response and immunological delay has been discussed. By studying the characteristic equations of the model, the local stability analysis of various equilibrium points has been explored. Treating the delay as the bifurcation parameter, it has been shown that the delay can destabilize the stability of the infected steady-state leading to Hopf bifurcation and periodic solutions. By using Lyapunov functionals and LaSalle’s invariance principle, the global stability analysis of the boundary equilibrium points has also been explored. It has also been shown numerically that the inclusion of the drug therapy in the model generates sporadic outbursts of virus called viral blips. In the end, numerical simulations have been employed to justify the analytical results proved in the paper. Biologically, the proposed model can explain the presence of viral blips in the system, during the introduction of HAART, as observed in the HIV-infected patient. These blips could mark the viral advancement in the system, thus resulting in complete immunological failure. One of the reasons for these viral blips can be the presence of delay in the activation of immunological response. But the development of drug-resistive virus could also be the reason for this sudden rise in viral loads. Moreover, the incorporation of the delay in the model generates oscillations and periodicity in the model, thus validating the long latency period seen in most HIV-infected patients. Also, a longer delay in the activation of immune response marks a viral advancement in the viral timeline resulting in viral blips, which signify the evolution of the virus.
Anticipated backward SDEs with jumps and quadratic-exponential growth drivers
Authors: Fujii Masaaki , Takahashi Akihiko
Published: August 2018

In this paper, we study a class of Anticipated Backward Stochastic Differential Equations (ABSDE) with jumps. The solution of the ABSDE is a triple [Formula: see text] where [Formula: see text] is a semimartingale, and [Formula: see text] are the diffusion and jump coefficients. We allow the driver of the ABSDE to have linear growth on the uniform norm of [Formula: see text]’s future paths, as well as quadratic and exponential growth on the spot values of [Formula: see text], respectively. The existence of the unique solution is proved for Markovian and non-Markovian settings with different structural assumptions on the driver. In the former case, some regularities on [Formula: see text] with respect to the forward process are also obtained.
Necessary and sufficient conditions for ergodicity of CIR type SDEs with Markov switching
Authors: Zhang Zhenzhong , Yang Hongqian , Tong Jinying , Hu Liangjian
Published: August 2018

In this paper, we consider the ergodicity and transience of the Cox–Ingersoll–Ross (CIR) interest rate model with Markov switching. Using the theory of [Formula: see text]-matrices, we give some necessary and sufficient conditions for ergodicity of the CIR interest rate model with Markov switching. Besides, we show that the transition semigroup converges to the stationary distribution at an exponential rate in the Wasserstein distance. Finally, two examples are presented to illustrate our theory.
Some subgroups of symmetric groups determined using signed Brauer diagrams
Authors: Sharma Ram Parkash , Parmar Rajni
Published: August 2018

A class of subgroups of order [Formula: see text], [Formula: see text] [Formula: see text] of even permutations is obtained for symmetric group [Formula: see text] using the set [Formula: see text] of signed Brauer diagrams. Consequently, every group of order [Formula: see text] has a Sylow [Formula: see text]-subgroup of order [Formula: see text].
Quandle rings
Authors: Bardakov Valeriy G. , Passi Inder Bir S. , Singh Mahender
Published: August 2018

In this paper, a theory of quandle rings is proposed for quandles analogous to the classical theory of group rings for groups, and interconnections between quandles and associated quandle rings are explored.
Innovation Ecosystem in Sergipe State: The Difficulties Faced by Startups
Authors: Felizola Matheus Pereira Mattos , de Aragão Gomes Iracema Machado , Prata de Almeida Maria Beatriz Filgueiras
Published: August 2018

The founders of startups in Sergipe state, Brazil, began to unite in 2012, with a purpose of strengthening the innovation ecosystem in the state. The aim of this paper was to deepen the knowledge about the entrepreneurs’ movement entitled “Caju Valley”, in order to propose measures to strengthen the group. From the analysis realized, it was possible to observe that the Caju Valley group, although being important to the startups’ ecosystem, still suffers due to the lack of balance between the various stakeholders, and also faces the lack of maturity of the entrepreneurs, timid or suspicious investors, accelerators without effective action and incubators with low effectivity.
Innovation and Performance: The Impact of Investments in R&D According to the Different Levels of Productivity of Firms
Authors: Soares de Almeida Carlos Alano , Del Corso Jansen Maia , Rocha Leonardo Andrade , da Silva Wesley Vieira , da Veiga Claudimar Pereira
Published: August 2018

The objective of this paper is to verify how investments in R&D influence the measures of performance (sales and operating profit) of companies. Based on the EU Industrial R&D Investment Scoreboard, a 2003–2013 information panel was developed for 548 companies. Regression with panel data and Quantile Regression were used. The results indicate that investments in R&D positively influence sales and operating profit of companies as a whole, varies according to the R&D intensity when companies are analyzed in groups and that the distance from the frontier influences the relationship between R&D and performance. The companies of the upper quantiles have better relation R&D and profit than the companies more distant from the frontier. Companies with higher profit can transform R&D investments more efficiently into profit.
Cu2O Nanoparticles and Multi-Branched Nanowires as Anodes for Lithium-Ion Batteries
Authors: Chen Xu , Yu Chunxin , Guo Xiaojiao , Bi Qinsong , Sajjad Muhammad , Ren Yang , Zhou Xiaowei , Liu Zhu
Published: August 2018

Novelty Cu2O multi-branched nanowires and nanoparticles with size ranging from [Formula: see text]15[Formula: see text]nm to [Formula: see text]60[Formula: see text]nm have been synthesized by one-step hydrothermal process. These Cu2O nanostructures when used as anode materials for lithium-ion batteries exhibit the excellent electrochemical cycling stability and reduced polarization during the repeated charge/discharge process. The specific capacity of the Cu2O nanoparticles, multi-branched nanowires and microscale are maintained at 201.2[Formula: see text]mAh/g, 259.6[Formula: see text]mAh/g and 127.4[Formula: see text]mAh/g, respectively, under the current density of 0.1[Formula: see text]A/g after 50 cycles. The enhanced electrochemical performance of the Cu2O nanostructures compared with microscale counterpart can be attributed to the larger contact area between active Cu2O nanostructures/electrolyte interface, shorter diffusion length of Li[Formula: see text] within nanostructures and the improved stress release upon lithiation/delithiation.
Fabrication and Field-Emission Properties of Vertically-Aligned Tapered [110]Si Nanowire Arrays Prepared by Nanosphere Lithography and Electroless Ag-Catalyzed Etching
Authors: Feng Z. , Lin K. Q. , Chen Y. C. , Cheng S. L.
Published: August 2018

In this study, the controllable fabrication of a variety of vertically aligned, single-crystalline [110]-oriented Si nanowire arrays with sharp tips on (110)Si substrates is achieved using a combined self-assembled nanosphere lithography and multiple electroless Ag-catalyzed Si etching processes. All of the experiments were performed at room temperature. The morphological evolution and formation mechanism of long tapered [110]Si nanowire arrays during the multiple tip-sharpening cycle processes have been investigated by scanning electron microscopy, transmission electron microscopy and water contact angle measurements. Field emission measurements demonstrate that the field-emission behaviors of all nanowire samples produced in this study agree well with the Fowler–Nordheim theory, and the produced long tapered [110]Si nanowire array possesses superior electron emission characteristics, with a very low turn-on field of 1.4[Formula: see text]V/[Formula: see text]m and a high field enhancement factor of 3816. The simple and room temperature fabrication of the well-ordered long tapered [110]Si nanowire array and its excellent electron field emission performance suggest that it can serve as a good candidate for applications in high-performance Si-based vacuum electronic nanodevices.
Study of an epidemic model with Z-type control
Authors: Samanta Sudip
Published: August 2018

In the present paper, an epidemic model with Z-type control mechanism has been proposed and analyzed to explore the disease control strategy on an infectious disease outbreak. The uncontrolled model can have a disease-free equilibrium and an endemic equilibrium. The expression of the basic reproduction number and the conditions for the stability of the equilibria are derived. It is also observed that the disease-free equilibrium is globally asymptotically stable if [Formula: see text], whereas the endemic equilibrium is globally asymptotically stable if [Formula: see text]. The model is further improved by considering Z-control mechanism and investigated. Disease can be controlled by using Z-control while the basic reproduction of the uncontrolled system is greater than unity. The positivity conditions of the solutions are derived and the basin of attraction for successful implementation of Z-control mechanism is also investigated. To verify the analytical findings, extensive numerical simulations on the model are carried out.
Threshold conditions for a family of epidemic dynamic models for malaria with distributed delays in a non-random environment
Authors: Wanduku Divine
Published: August 2018

A family of deterministic SEIRS epidemic dynamic models for malaria is presented. The family type is determined by a general functional response for the nonlinear incidence rate of the disease. Furthermore, the malaria models exhibit three random delays — the incubation periods of the plasmodium inside the female mosquito and human hosts, and also the period of effective acquired natural immunity against the disease. Insights about the effects of the delays and the nonlinear incidence rate of the disease on (1) eradication and (2) persistence of malaria in the human population are obtained via analyzing and interpreting the global asymptotic stability results of the disease-free and endemic equilibrium of the system. The basic reproduction numbers and other threshold values for malaria are calculated, and superior threshold conditions for the stability of the equilibria are found. Numerical simulation results are presented.
Analytically depicting the calcium diffusion for Alzheimer’s affected cell
Authors: Dave Devanshi D. , Jha Brajesh Kumar
Published: August 2018

Brain is the most complex structure of the human body. The processes going inside the brain and the mechanisms behind it have been unrevealed up to certain extent only. Out of the various physiological phenomena carried out by the brain, calcium signalling can be considered as one of the most important. Calcium being a second messenger plays an important role in transformation of various information. In view of above, an attempt has been made here to study calcium signalling in presence of buffers, i.e. one kind of proteins and endoplasmic reticulum (ER), which is also known as store house of the cell. Being the store house of the cell, it has very high amount of calcium, whereas buffers decrease the level of free calcium ions by binding calcium ions to it. A two-dimensional mathematical model has been developed to see the impact of these parameters on cytosolic calcium concentration. This mathematical model is solved analytically using Laplace transforms and similarity transforms. The simulations are carried out using MATLAB. It is observed that the impact of buffer and ER is significant on calcium signalling. The obtained results are interpreted with the Alzheimeric condition of the nerve cells.
Many Haken Heegaard splittings
Authors: Sisto Alessandro
Published: August 2018

We give a simple criterion for a Heegaard splitting to yield a Haken manifold. As a consequence, we construct many Haken manifolds, in particular homology spheres, with prescribed properties, namely Heegaard genus, Heegaard distance and Casson invariant.

Along the way we give simpler and shorter proofs of the existence of splittings with specified Heegaard distance, originally proven by Ido–Jang–Kobayashi, of the existence of hyperbolic manifolds with prescribed Casson invariant, originally due to Lubotzky–Maher–Wu, and of a result about subsurface projections of disc sets (for which we even get better constants), originally due to Masur–Schleimer.
A recurrent composite loess landslide in southwestern China
Authors: Zhu Yuxuan , Dai Fuchu , Gao Jingxian , Yao Xin
Published: August 2018

A loess landslide occurred in southwestern China on 21 September 2016. The field investigation performed 2 months after this event revealed that this slope failure was a partial reactivation of a landslide initiated in 1995, with a first-time failure in 1975. This landslide has been triggered three times, each having a distinct mode. This study suggests that the high groundwater table was a critical factor in this landslide occurrence.
The Dependent Doors Problem
Authors: Korman Amos , Rodeh Yoav
Published: August 2018

We introduce the
dependent doors problem
as an abstraction for situations in which one must perform a sequence of dependent decisions, without receiving feedback information on the effectiveness of previously made actions. Informally, the problem considers a set of
d
doors that are initially closed, and the aim is to open all of them as fast as possible. To open a door, the algorithm knocks on it, and it might open or not according to some probability distribution. This distribution may depend on which other doors are currently open, as well as on which other doors were open during each of the previous knocks on that door. The algorithm aims to minimize the expected time until all doors open. Crucially, it must act at any time without knowing whether or which other doors have already opened. In this work, we focus on scenarios where dependencies between doors are both positively correlated and acyclic.

The fundamental distribution of a door describes the probability it opens in the best of conditions (with respect to other doors being open or closed). We show that if in two configurations of
d
doors corresponding doors share the same fundamental distribution, then these configurations have the same optimal running time up to a universal constant, no matter what the dependencies between doors and what the distributions. We also identify algorithms that are optimal up to a universal constant factor. For the case in which all doors share the same fundamental distribution, we additionally provide a simpler algorithm and a formula to calculate its running time. We furthermore analyse the price of lacking feedback for several configurations governed by standard fundamental distributions. In particular, we show that the price is logarithmic in
d
for memoryless doors but can potentially grow to be linear in
d
for other distributions.

We then turn our attention to investigate precise bounds. Even for the case of two doors, identifying the optimal sequence is an intriguing combinatorial question. Here, we study the case of two cascading memoryless doors. That is, the first door opens on each knock independently with probability
p
1
. The second door can only open if the first door is open, in which case it will open on each knock independently with probability
p
2
. We solve this problem almost completely by identifying algorithms that are optimal up to an additive term of 1.
An Efficient Representation for Filtrations of Simplicial Complexes
Authors: Boissonnat Jean-Daniel , C. S. Karthik
Published: August 2018

A filtration over a simplicial complex
K
is an ordering of the simplices of
K
such that all prefixes in the ordering are subcomplexes of
K
. Filtrations are at the core of Persistent Homology, a major tool in Topological Data Analysis. To represent the filtration of a simplicial complex, the entire filtration can be appended to any data structure that explicitly stores all the simplices of the complex such as the Hasse diagram or the recently introduced Simplex Tree [Algorithmica’14]. However, with the popularity of various computational methods that need to handle simplicial complexes, and with the rapidly increasing size of the complexes, the task of finding a compact data structure that can still support efficient queries is of great interest.

This direction has been recently pursued for the case of maintaining simplicial complexes. For instance, Boissonnat et al. [Algorithmica’17] considered storing the simplices that are maximal with respect to inclusion and Attali et al. [IJCGA’12] considered storing the simplices that block the expansion of the complex. Nevertheless, so far there has been no data structure that compactly stores the
filtration
of a simplicial complex, while also allowing the efficient implementation of basic operations on the complex.

In this article, we propose a new data structure called the Critical Simplex Diagram (CSD), which is a variant of the Simplex Array List [Algorithmica’17]. Our data structure allows one to store in a compact way the filtration of a simplicial complex and allows for the efficient implementation of a large range of basic operations. Moreover, we prove that our data structure is essentially optimal with respect to the requisite storage space. Finally, we show that the CSD representation admits fast construction algorithms for Flag complexes and relaxed Delaunay complexes.
K-Regret Queries Using Multiplicative Utility Functions
Authors: Qi Jianzhong , Zuo Fei , Samet Hanan , Yao Jia Cheng
Published: August 2018

The
k
-regret query aims to return a size-
k
subset
S
of a database
D
such that, for any query user that selects a data object from this size-
k
subset
S
rather than from database
D
, her regret ratio is minimized. The regret ratio here is modeled by the relative difference in the optimality between the locally optimal object in
S
and the globally optimal object in
D
. The optimality of a data object in turn is modeled by a utility function of the query user. Unlike traditional top-
k
queries, the
k
-regret query does not minimize the regret ratio for a specific utility function. Instead, it considers a family of infinite utility functions
F
, and aims to find a size-
k
subset that minimizes the maximum regret ratio of any utility function in
F
.

Studies on
k
-regret queries have focused on the family of additive utility functions, which have limitations in modeling individuals’ preferences and decision-making processes, especially for a common observation called the diminishing marginal rate of substitution (DMRS). We introduce
k
-regret queries with multiplicative utility functions, which are more expressive in modeling the DMRS, to overcome those limitations. We propose a query algorithm with bounded regret ratios. To showcase the applicability of the algorithm, we apply it to a special family of multiplicative utility functions, the Cobb-Douglas family of utility functions, and a closely related family of utility functions, the Constant Elasticity of Substitution family of utility functions, both of which are frequently used utility functions in microeconomics. After a further study of the query properties, we propose a heuristic algorithm that produces even smaller regret ratios in practice. Extensive experiments on the proposed algorithms confirm that they consistently achieve small maximum regret ratios.
An Efficient Algorithm for Computing High-Quality Paths amid Polygonal Obstacles
Authors: Agarwal Pankaj K. , Fox Kyle , Salzman Oren
Published: August 2018

We study a path-planning problem amid a set O of obstacles in R
2
, in which we wish to compute a short path between two points while also maintaining a high clearance from O; the clearance of a point is its distance from a nearest obstacle in O. Specifically, the problem asks for a path minimizing the reciprocal of the clearance integrated over the length of the path. We present the first polynomial-time approximation scheme for this problem. Let
n
be the total number of obstacle vertices and let ε ∈ (0, 1]. Our algorithm computes in time
O
(
n
2
/ε
2
log
n
/ε) a path of total cost at most (1 + ε) times the cost of the optimal path.
Application validation on RTDroid
Authors: Yan Yin , Ziarek Lukasz
Published: August 2018

Android is becoming used more frequently in domains that expect some real-time guarantees. To facilitate the adoption of Android for programming real-time systems, this work presents a first effort to apply real-time scheduling theories to a real-time extension on Android, RTDroid. We integrate real-time properties specified in RT-Droid's application manifest with an existing real-time scheduling framework, Cheddar. We leverage Cheddar to perform schedulability analysis and feasibility tests, based on the properties of RTDroid application components specified in the application manifest. This paper details our integration process and reports our experience of validating real-time properties in a real-time application developed on RTDroid.
Dietary Nitrate and Physical Performance
Authors: Jones Andrew M. , Thompson Christopher , Wylie Lee J. , Vanhatalo Anni
Published: August 2018

Nitric oxide (NO) plays a plethora of important roles in the human body. Insufficient production of NO (for example, during older age and in various disease conditions) can adversely impact health and physical performance. In addition to its endogenous production through the oxidation of l-arginine, NO can be formed nonenzymatically via the reduction of nitrate and nitrite, and the storage of these anions can be augmented by the consumption of nitrate-rich foodstuffs such as green leafy vegetables. Recent studies indicate that dietary nitrate supplementation, administered most commonly in the form of beetroot juice, can ( a) improve muscle efficiency by reducing the O2 cost of submaximal exercise and thereby improve endurance exercise performance and ( b) enhance skeletal muscle contractile function and thereby improve muscle power and sprint exercise performance. This review describes the physiological mechanisms potentially responsible for these effects, outlines the circumstances in which ergogenic effects are most likely to be evident, and discusses the effects of dietary nitrate supplementation on physical performance in a range of human populations.
Iron and Cancer
Authors: Torti Suzy V. , Manz David H. , Paul Bibbin T. , Blanchette-Farra Nicole , Torti Frank M.
Published: August 2018

This review explores the multifaceted role that iron has in cancer biology. Epidemiological studies have demonstrated an association between excess iron and increased cancer incidence and risk, while experimental studies have implicated iron in cancer initiation, tumor growth, and metastasis. The roles of iron in proliferation, metabolism, and metastasis underpin the association of iron with tumor growth and progression. Cancer cells exhibit an iron-seeking phenotype achieved through dysregulation of iron metabolic proteins. These changes are mediated, at least in part, by oncogenes and tumor suppressors. The dependence of cancer cells on iron has implications in a number of cell death pathways, including ferroptosis, an iron-dependent form of cell death. Uniquely, both iron excess and iron depletion can be utilized in anticancer therapies. Investigating the efficacy of these therapeutic approaches is an area of active research that promises substantial clinical impact.
Postexercise improvement in glucose uptake occurs concomitant with greater γ3-AMPK activation and AS160 phosphorylation in rat skeletal muscle
Authors: Wang Haiyan , Arias Edward B. , Pataky Mark W. , Goodyear Laurie J. , Cartee Gregory D.
Published: August 2018

A single exercise session can increase insulin-stimulated glucose uptake (GU) by skeletal muscle, concomitant with greater Akt substrate of 160 kDa (AS160) phosphorylation on Akt-phosphosites (Thr642and Ser588) that regulate insulin-stimulated GU. Recent research using mouse skeletal muscle suggested that ex vivo 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) or electrically stimulated contractile activity-inducing increased γ3-AMPK activity and AS160 phosphorylation on a consensus AMPK-motif (Ser704) resulted in greater AS160 Thr642phosphorylation and GU by insulin-stimulated muscle. Our primary goal was to determine whether in vivo exercise that increases insulin-stimulated GU in rat skeletal muscle would also increase γ3-AMPK activity and AS160 site-selective phosphorylation (Ser588, Thr642, and Ser704) immediately postexercise (IPEX) and/or 3 h postexercise (3hPEX). Epitrochlearis muscles isolated from sedentary and exercised (2-h swim exercise; studied IPEX and 3hPEX) rats were incubated with 2-deoxyglucose to determine GU (without insulin at IPEX; without or with insulin at 3hPEX). Muscles were also assessed for γ1-AMPK activity, γ3-AMPK activity, phosphorylated AMPK (pAMPK), and phosphorylated AS160 (pAS160). IPEX versus sedentary had greater γ3-AMPK activity, pAS160 (Ser588, Thr642, Ser704), and GU with unaltered γ1-AMPK activity. 3hPEX versus sedentary had greater γ3-AMPK activity, pAS160 Ser704, and GU with or without insulin; greater pAS160 Thr642only with insulin; and unaltered γ1-AMPK activity. These results using an in vivo exercise protocol that increased insulin-stimulated GU in rat skeletal muscle are consistent with the hypothesis that in vivo exercise-induced enhancement of γ3-AMPK activation and AS160 Ser704IPEX and 3hPEX are important for greater pAS160 Thr642and enhanced insulin-stimulated GU by skeletal muscle.
Considerations for best practices in studies of fiber or other dietary components and the intestinal microbiome
Authors: Klurfeld David M. , Davis Cindy D. , Karp Robert W. , Allen-Vercoe Emma , Chang Eugene B. , Chassaing Benoit , Fahey George C. , Hamaker Bruce R. , Holscher Hannah D. , Lampe Johanna W. , Marette Andre , Martens Eric , O’Keefe Stephen J. , Rose Devin J. , Saarela Maria , Schneeman Barbara O. , Slavin Joanne L. , Sonnenburg Justin L. , Swanson Kelly S. , Wu Gary D. , Lynch Christopher J.
Published: August 2018

A 2-day workshop organized by the National Institutes of Health and U.S. Department of Agriculture included 16 presentations focused on the role of diet in alterations of the gastrointestinal microbiome, primarily that of the colon. Although thousands of research projects have been funded by U.S. federal agencies to study the intestinal microbiome of humans and a variety of animal models, only a minority addresses dietary effects, and a small subset is described in sufficient detail to allow reproduction of a study. Whereas there are standards being developed for many aspects of microbiome studies, such as sample collection, nucleic acid extraction, data handling, etc., none has been proposed for the dietary component; thus this workshop focused on the latter specific point. It is important to foster rigor in design and reproducibility of published studies to maintain high quality and enable designs that can be compared in systematic reviews. Speakers addressed the influence of the structure of the fermentable carbohydrate on the microbiota and the variables to consider in design of studies using animals, in vitro models, and human subjects. For all types of studies, strengths and weaknesses of various designs were highlighted, and for human studies, comparisons between controlled feeding and observational designs were discussed. Because of the lack of published, best-diet formulations for specific research questions, the main recommendation is to describe dietary ingredients and treatments in as much detail as possible to allow reproduction by other scientists.
Abemaciclib Is Active in Preclinical Models of Ewing Sarcoma via Multipronged Regulation of Cell Cycle, DNA Methylation, and Interferon Pathway Signaling
Authors: Dowless Michele , Lowery Caitlin D. , Shackleford Terry , Renschler Matthew , Stephens Jennifer , Flack Robert , Blosser Wayne , Gupta Simone , Stewart Julie , Webster Yue , Dempsey Jack , VanWye Alle B. , Ebert Philip , Iversen Philip , Olsen Jonathan B. , Gong Xueqian , Buchanan Sean , Houghton Peter , Stancato Louis
Published: August 2018

Purpose:

Ewing sarcoma (ES) is a rare and highly malignant cancer that occurs in the bone and surrounding tissue of children and adolescents. The EWS/ETS fusion transcription factor that drives ES pathobiology was previously demonstrated to modulate cyclin D1 expression. In this study, we evaluated abemaciclib, a small-molecule CDK4 and CDK6 (CDK4 and 6) inhibitor currently under clinical investigation in pediatric solid tumors, in preclinical models of ES.

Experimental Design:

Using Western blot, high-content imaging, flow cytometry, ELISA, RNA sequencing, and CpG methylation assays, we characterized the in vitro response of ES cell lines to abemaciclib. We then evaluated abemaciclib in vivo in cell line–derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models of ES as either a monotherapy or in combination with chemotherapy.

Results:

Abemaciclib induced quiescence in ES cell lines via a G1 cell-cycle block, characterized by decreased proliferation and reduction of Ki-67 and FOXM1 expression and retinoblastoma protein (RB) phosphorylation. In addition, abemaciclib reduced DNMT1 expression and promoted an inflammatory immune response as measured by cytokine secretion, antigen presentation, and interferon pathway upregulation. Single-agent abemaciclib reduced ES tumor volume in preclinical mouse models and, when given in combination with doxorubicin or temozolomide plus irinotecan, durable disease control was observed.

Conclusions:

Collectively, our data demonstrate that the antitumor effects of abemaciclib in preclinical ES models are multifaceted and include cell-cycle inhibition, DNA demethylation, and immunogenic changes.
Integrative Epigenetic and Gene Expression Analysis of Renal Tumor Progression to Metastasis
Authors: Nam Hye-Young , Chandrashekar Darshan S. , Kundu Anirban , Shelar Sandeep , Kho Eun-Young , Sonpavde Guru , Naik Gurudatta , Ghatalia Pooja , Livi Carolina B. , Varambally Sooryanarayana , Sudarshan Sunil
Published: August 2018

The Cancer Genome Atlas (TCGA) and other large-scale genomic data pipelines have been integral to the current understanding of the molecular events underlying renal cell carcinoma (RCC). These data networks have focused mostly on primary RCC, which often demonstrates indolent behavior. However, metastatic disease is the major cause of mortality associated with RCC and data sets examining metastatic tumors are sparse. Therefore, a more comprehensive analysis of gene expression and DNA methylome profiling of metastatic RCC in addition to primary RCC and normal kidney was performed. Integrative analysis of the methylome and transcriptome identified over 30 RCC-specific genes whose mRNA expression inversely correlated with promoter methylation, including several known targets of hypoxia inducible factors. Notably, genes encoding several metabolism-related proteins were identified as differentially regulated via methylation including hexokinase 2, aldolase C, stearoyl-CoA desaturase, and estrogen-related receptor-γ (ESRRG), which has a known role in the regulation of nuclear-encoded mitochondrial metabolism genes. Several gene expression changes could portend prognosis in the TCGA cohort. Mechanistically, ESRRG loss occurs via DNA methylation and histone repressive silencing mediated by the polycomb repressor complex 2. Restoration of ESRRG in RCC lines suppresses migratory and invasive phenotypes independently of its canonical role in mitochondrial metabolism.

Implications:

Collectively, these data provide significant insight into the biology of aggressive RCC and demonstrate a novel role for DNA methylation in the promotion of HIF signaling and invasive phenotypes in renal cancer.
Endothelial Cells Promote Colorectal Cancer Cell Survival by Activating the HER3-AKT Pathway in a Paracrine Fashion
Authors: Wang Rui , Bhattacharya Rajat , Ye Xiangcang , Fan Fan , Boulbes Delphine R. , Ellis Lee M.
Published: August 2018

The regulation of colorectal cancer cell survival pathways remains to be elucidated. Previously, it was demonstrated that endothelial cells (EC) from the liver (liver parenchymal ECs or LPEC), the most common site of colorectal cancer metastases, secrete soluble factors in the conditioned medium (CM) that, in turn, increase the cancer stem cell phenotype in colorectal cancer cells. However, the paracrine effects of LPECs on other colorectal cancer cellular functions have not been investigated. Here, results showed that CM from LPECs increased cell growth and chemoresistance by activating AKT in colorectal cancer cells in vitro. Using an unbiased receptor tyrosine kinase array, it was determined that human epidermal growth factor receptor 3 (ERBB3/HER3) was activated by CM from LPECs, and it mediated AKT activation, cell growth, and chemoresistance in colorectal cancer cells. Inhibition of HER3, either by an inhibitor AZD8931 or an antibody MM-121, blocked LPEC-induced HER3-AKT activation and cell survival in colorectal cancer cells. In addition, CM from LPECs increased in vivo tumor growth in a xenograft mouse model. Furthermore, inhibiting HER3 with AZD8931 significantly blocked tumor growth induced by EC CM. These results demonstrated a paracrine role of liver ECs in promoting cell growth and chemoresistance via activating HER3-AKT in colorectal cancer cells.

Implications:

This study suggested a potential of treating patients with metastatic colorectal cancer with HER3 antibodies/inhibitors that are currently being assessed in clinical trials for various cancer types.