bluuebunny/crossref_metadata_2025 huggingface dataset:
Outward Influence and Cascade Size Estimation in Billion-scale Networks
Authors: Nguyen Hung T. , Nguyen Tri P. , Vu Tam N. , Dinh Thang N.
Published: September 2017

Estimating cascade size and nodes' influence is a fundamental task in social, technological, and biological networks. Yet this task is extremely challenging due to the sheer size and the structural heterogeneity of networks. We investigate a new influence measure, termed outward influence (OI), defined as the (expected) number of nodes that a subset of nodes S will activate, excluding the nodes in S. Thus, OI equals, the de facto standard measure, influence spread of S minus |S|. OI is not only more informative for nodes with small influence, but also, critical in designing new effective sampling and statistical estimation methods. Based on OI, we propose SIEA/SOIEA, novel methods to estimate influence spread/outward influence at scale and with rigorous theoretical guarantees. The proposed methods are built on two novel components 1) IICP an important sampling method for outward influence; and 2) RSA, a robust mean estimation method that minimize the number of samples through analyzing variance and range of random variables. Compared to the state-of-the art for influence estimation, SIEA is Ω(log
4
n) times faster in theory and up to several orders of magnitude faster in practice. For the first time, influence of nodes in the networks of billions of edges can be estimated with high accuracy within a few minutes. Our comprehensive experiments on real-world networks also give evidence against the popular practice of using a fixed number, e.g. 10K or 20K, of samples to compute the ``ground truth'' for influence spread.
Pseudo-Separation for Assessment of Structural Vulnerability of a Network
Authors: Kuhnle Alan , Pan Tianyi , Crawford Victoria G. , Alim Md Abdul , Thai My T.
Published: September 2017

Based upon the idea that network functionality is impaired if two nodes in a network are sufficiently separated in terms of a given metric, we introduce two combinatorial pseudocut problems generalizing the classical min-cut and multi-cut problems. We expect the pseudocut problems will find broad relevance to the study of network reliability. We comprehensively analyze the computational complexity of the pseudocut problems and provide three approximation algorithms for these problems. Motivated by applications in communication networks with strict Quality-of-Service (QoS) requirements, we demonstrate the utility of the pseudocut problems by proposing a targeted vulnerability assessment for the structure of communication networks using QoS metrics; we perform experimental evaluations of our proposed approximation algorithms in this context.
Optimizing Speculative Execution of Deadline-Sensitive Jobs in Cloud
Authors: Xu Maotong , Alamro Sultan , Lan Tian , Subramaniam Suresh
Published: September 2017

In this paper, we bring various speculative scheduling strategies together under a unifying optimization framework, which defines a new metric, Probability of Completion before Deadlines (PoCD), to measure the probability that MapReduce jobs meet their desired deadlines. We propose an optimization problem to jointly optimize PoCD and execution cost in different strategies. Three strategies are prototyped on Hadoop MapReduce and evaluated against two baseline strategies using experiments. A 78% net utility increase with up to 94% PoCD and 12% cost improvement is achieved.
ECF
Authors: Lim Yeon-sup , Nahum Erich M. , Towsley Don , Gibbens Richard J.
Published: September 2017

Multi-Path TCP (MPTCP) is a new standardized transport protocol that enables devices to utilize multiple network interfaces. The default MPTCP path scheduler prioritizes paths with the smallest round trip time (RTT). In this work, we examine whether the default MPTCP path scheduler can provide applications the ideal aggregate bandwidth, i.e., the sum of available bandwidths of all paths. Our experimental results show that heterogeneous paths cause under-utilization of the fast path, resulting in undesirable application behaviors such as lower video streaming quality than can be obtained using the available aggregate bandwidth. To solve this problem, we propose and implement a new MPTCP path scheduler, ECF (Earliest Completion First), that utilizes all relevant information about a path, not just RTT. Our results show that ECF consistently utilizes all available paths more efficiently than other approaches under path heterogeneity, particularly for streaming video.
A Fast, Small, and Dynamic Forwarding Information Base
Authors: Yu Ye , Belazzougui Djamal , Qian Chen , Zhang Qin
Published: September 2017

Concise is a Forwarding information base (FIB) design that uses very little memory to support fast query of a large number of dynamic network names or flow IDs. Concise makes use of minimal perfect hashing and the SDN framework to design and implement the data structure, protocols, and system. Experimental results show that Concise uses significantly smaller memory to achieve faster query speed compared to existing FIB solutions and it can be updated very efficiently.
Stein's Method for Mean-Field Approximations in Light and Heavy Traffic Regimes
Authors: Ying Lei
Published: September 2017

Mean-field analysis is an analytical method for understanding large-scale stochastic systems such as large-scale data centers and communication networks. The idea is to approximate the stationary distribution of a large-scale stochastic system using the equilibrium point (called the mean-field limit) of a dynamical system (called the mean-field model). This approximation is often justified by proving the weak convergence of stationary distributions to its mean-field limit. Most existing mean-field models concerned the light-traffic regime where the load of the system, denote by ρ, is strictly less than one and is independent of the size of the system. This is because a traditional mean-field model represents the limit of the corresponding stochastic system. Therefore, the load of the mean-field model is ρ=lim
N-> ∞
ρ
(N)
, where ρ
(N)
is the load of the stochastic system of size N. Now if ρ
(N)
-> 1 as N -> ∞ (i.e., in the heavy-traffic regime), then ρ=1. For most systems, the mean-field limits when ρ=1 are trivial and meaningless. To overcome this difficulty of traditional mean-field models, this paper takes a different point of view on mean-field models. Instead of regarding a mean-field model as the limiting system of large-scale stochastic system, it views the equilibrium point of the mean-field model, called a mean-field solution, simply as an approximation of the stationary distribution of the finite-size system. Therefore both mean-field models and solutions can be functions of N. The proposed method focuses on quantifying the approximation error. If the approximation error is small (as we will show in two applications), then we can conclude that the mean-field solution is a good approximation of the stationary distribution.
Fluid-Model-Based Car Routing for Modern Ridesharing Systems
Authors: Braverman Anton , Dai J.G. , Liu Xin , Ying Lei
Published: September 2017

We consider a closed queueing network model of ridesharing systems such as Didi Chuxing, Lyft, and Uber. We focus on empty-car routing, a mechanism by which we control car flow in the network to optimize system-wide utility functions, e.g. the availability of empty cars when a passenger arrives. We establish both process-level and steady-state convergence of the queueing network to a fluid limit in a large market regime where demand for rides and supply of cars tend to infinity, and use this limit to study a fluid-based optimization problem. We prove that the optimal network utility obtained from the fluid-based optimization is an upper bound on the utility in the finite car system for any routing policy, both static and dynamic, under which the closed queueing network has a stationary distribution. This upper bound is achieved asymptotically under the fluid-based optimal routing policy. Simulation results with real-word data released by Didi Chuxing demonstrate that the utility under the fluid-based optimal routing policy converges to the upper bound with a rate of 1/√N, where N is the number of cars in the network.
Matrix Factorization at the Frontier of Non-convex Optimizations
Authors: Oh Sewoong
Published: September 2017

Principal Component Analysis (PCA) and Canonical Component Analysis (CCA) are two of the few examples of non-convex optimization problems that can be solved efficiently with sharp guarantees. This is achieved by the classical and well-established understanding of matrix factorizations. Recently, several new theoretical and algorithmic challenges have arisen in statistical learning over matrix factorizations, motivated by various real-world applications. Despite the inherent non-convex nature of these problem, efficient algorithms are being discovered with provable guarantees, extending the frontier of our understanding of non-convex optimization problems. I will present several recent results in this area in applications to matrix completion and sensing, crowdsourcing, ranking, and tensor factorization.
A mitohormetic response to pro-oxidant exposure in the house mouse
Authors: Zhang Yufeng , Humes Frances , Almond Gregory , Kavazis Andreas N. , Hood Wendy R.
Published: September 2017

Mitochondria are hypothesized to display a biphasic response to reactive oxygen species (ROS) exposure. In this study, we evaluated the time course changes in mitochondrial performance and oxidative stress in house mice following X-irradiation. Forty-eight mice were equally divided among six groups, including a nonirradiated control and five experimental groups that varied in time between X-ray exposure and euthanasia (1 h and 1, 4, 7, and 10 days after X-irradiation). We measured parameters associated with mitochondrial respiratory function and ROS emission from isolated liver and skeletal muscle mitochondria and levels of oxidative damage and antioxidants in liver, skeletal muscle, and heart tissues. Mitochondrial function dropped initially after X-irradiation but recovered quickly and was elevated 10 days after the exposure. Hydrogen peroxide production, lipid peroxidation, and protein carbonylation showed inverse U-shaped curves, with levels returning to control or lower than control, 10 days after X-irradiation. Enzymatic antioxidants and markers for mitochondrial biogenesis exhibited a tissue-specific response after irradiation. These data provide the first chronological description of the mitohormetic response after a mild dose of irradiation and highlight the protective response that cells display to ROS exposure. This study also provides valuable information and application for future mitochondrial and oxidative stress studies in numerous physiological settings.
The plateau in the NIRS-derived [HHb] signal near the end of a ramp incremental test does not indicate the upper limit of O2 extraction in the vastus lateralis
Authors: Inglis Erin Calaine , Iannetta Danilo , Murias Juan M.
Published: September 2017

This study aimed to examine, at the level of the active muscles, whether the plateau in oxygen (O2) extraction normally observed near the end of a ramp incremental (RI) exercise test to exhaustion is caused by the achievement of an upper limit in O2 extraction. Eleven healthy men (27.3 ± 3.0 yr, 81.6 ± 8.1 kg, 183.9 ± 6.3 cm) performed a RI cycling test to exhaustion. O2 extraction of the vastus lateralis (VL) was measured continuously throughout the test using the near-infrared spectroscopy (NIRS)-derived deoxygenated hemoglobin [HHb] signal. A leg blood flow occlusion was performed at rest (LBFOCC1) and immediately after the RI test (LBFOCC2). The [HHb] values during the resting occlusion (108.1 ± 21.7%; LBFOCC1) and the peak values during exercise (100 ± 0%; [HHb]plateau) were significantly greater than those observed at baseline (0.84 ± 10.6% at baseline 1 and 0 ± 0% at baseline 2) ( P < 0.05). No significant difference was found between LBFOCC1 and [HHb]plateau ( P > 0.05) or between the baseline measurements ( P > 0.05). [HHb] values at LBFOCC2 (130.5 ± 19.7%) were significantly greater than all other time points ( P < 0.05). These results support the existence of an O2 extraction reserve in the VL muscle at the end of a RI cycling test and suggest that the observed plateau in the [HHb] signal toward the end of a RI test is not representative of an upper limit in O2 extraction.
Fluid replacement modulates oxidative stress- but not nitric oxide-mediated cutaneous vasodilation and sweating during prolonged exercise in the heat
Authors: McNeely Brendan D. , Meade Robert D. , Fujii Naoto , Seely Andrew J. E. , Sigal Ronald J. , Kenny Glen P.
Published: September 2017

The roles of nitric oxide synthase (NOS), reactive oxygen species (ROS), and angiotensin II type 1 receptor (AT1R) activation in regulating cutaneous vasodilation and sweating during prolonged (≥60 min) exercise are currently unclear. Moreover, it remains to be determined whether fluid replacement (FR) modulates the above thermoeffector responses. To investigate, 11 young men completed 90 min of continuous moderate intensity (46% V̇o2peak) cycling performed at a fixed rate of metabolic heat production of 600 W (No FR condition). On a separate day, participants completed a second session of the same protocol while receiving FR to offset sweat losses (FR condition). Cutaneous vascular conductance (CVC) and local sweat rate (LSR) were measured at four intradermal microdialysis forearm sites perfused with: 1) lactated Ringer (Control); 2) 10 mM NG-nitro-l-arginine methyl ester (l-NAME, NOS inhibition); 3) 10 mM ascorbate (nonselective antioxidant); or 4) 4.34 nM losartan (AT1R inhibition). Relative to Control (71% CVCmax at both time points), CVC with ascorbate (80% and 83% CVCmax) was elevated at 60 and 90 min of exercise during FR (both P < 0.02) but not at any time during No FR (all P > 0.31). In both conditions, CVC was reduced at end exercise with l-NAME (60% CVCmax; both P < 0.02) but was not different relative to Control at the losartan site (76% CVCmax; both P > 0.19). LSR did not differ between sites in either condition (all P > 0.10). We conclude that NOS regulates cutaneous vasodilation, but not sweating, irrespective of FR, and that ROS influence cutaneous vasodilation during prolonged exercise with FR.
Variation in Akt protein kinases in human populations
Authors: Rotwein Peter
Published: September 2017

The three Akt kinases are related proteins that are essential for normal growth and metabolic regulation and are implicated as key signaling mediators in many physiological and pathophysiological processes. Each Akt is activated by common biochemical signals that act downstream of growth factor and hormone receptors via phosphatidylinositol-3 kinase, and each controls several downstream pathways. The importance of Akt actions in human physiology is strengthened by the rarity of modifying mutations in their genes and by the devastating impact caused by these mutations on growth and development and in disorders such as cancer. Recent advances in genomics present unique opportunities for enhancing our understanding of human physiology and disease predisposition through the lens of population genetics, and the availability of DNA sequence data from 60,706 people in the Exome Aggregation Consortium has prompted this analysis. Results reveal a cohort of potential missense and other alterations in the coding regions of each AKT gene, but with nearly all changes being uncommon. The total number of different alleles per gene varied over an approximately threefold range, from 52 for AKT3 to 158 for AKT2, with variants distributed throughout all Akt protein domains. Previously characterized disease-causing mutations were found rarely in the general population. In contrast, a fairly prevalent amino acid substitution in AKT2 appears to be linked to increased predisposition for type 2 diabetes. Further analysis of variant Akt molecules as identified here will provide opportunities to understand the intricacies of Akt signaling and actions at a population level in human physiology and pathology.
Nonuniform surround suppression of visual responses in mouse V1
Authors: Samonds Jason M. , Feese Berquin D. , Lee Tai Sing , Kuhlman Sandra J.
Published: September 2017

Complex receptive field characteristics, distributed across a population of neurons, are thought to be critical for solving perceptual inference problems that arise during motion and image segmentation. For example, in a class of neurons referred to as “end-stopped,” increasing the length of stimuli outside of the bar-responsive region into the surround suppresses responsiveness. It is unknown whether these properties exist for receptive field surrounds in the mouse. We examined surround modulation in layer 2/3 neurons of the primary visual cortex in mice using two-photon calcium imaging. We found that surround suppression was significantly asymmetric in 17% of the visually responsive neurons examined. Furthermore, the magnitude of asymmetry was correlated with orientation selectivity. Our results demonstrate that neurons in mouse primary visual cortex are differentially sensitive to the addition of elements in the surround and that individual neurons can be described as being either uniformly suppressed by the surround, end-stopped, or side-stopped.

NEW & NOTEWORTHY Perception of visual scenes requires active integration of both local and global features to successfully segment objects from the background. Although the underlying circuitry and development of perceptual inference is not well understood, converging evidence indicates that asymmetry and diversity in surround modulation are likely fundamental for these computations. We determined that these key features are present in the mouse. Our results support the mouse as a model to explore the neural basis and development of surround modulation as it relates to perceptual inference.
Coupling of synaptic inputs to local cortical activity differs among neurons and adapts after stimulus onset
Authors: Wright Nathaniel C. , Hoseini Mahmood S. , Yasar Tansel Baran , Wessel Ralf
Published: September 2017

Cortical activity contributes significantly to the high variability of sensory responses of interconnected pyramidal neurons, which has crucial implications for sensory coding. Yet, largely because of technical limitations of in vivo intracellular recordings, the coupling of a pyramidal neuron’s synaptic inputs to the local cortical activity has evaded full understanding. Here we obtained excitatory synaptic conductance ( g) measurements from putative pyramidal neurons and local field potential (LFP) recordings from adjacent cortical circuits during visual processing in the turtle whole brain ex vivo preparation. We found a range of g-LFP coupling across neurons. Importantly, for a given neuron, g-LFP coupling increased at stimulus onset and then relaxed toward intermediate values during continued visual stimulation. A model network with clustered connectivity and synaptic depression reproduced both the diversity and the dynamics of g-LFP coupling. In conclusion, these results establish a rich dependence of single-neuron responses on anatomical, synaptic, and emergent network properties.

NEW & NOTEWORTHY Cortical neurons are strongly influenced by the networks in which they are embedded. To understand sensory processing, we must identify the nature of this influence and its underlying mechanisms. Here we investigate synaptic inputs to cortical neurons, and the nearby local field potential, during visual processing. We find a range of neuron-to-network coupling across cortical neurons. This coupling is dynamically modulated during visual processing via biophysical and emergent network properties.
Comparison of the Feasibility and Safety of First- versus Second-Generation AMPLATZER™ Occluders for Left Atrial Appendage Closure
Authors: Al-Kassou Baravan , Omran Heyder
Published: September 2017

Introduction. Left atrial appendage closure (LAAC) is considered an alternative to oral anticoagulation therapy in patients with atrial fibrillation (AF). The aim of this study was to compare the safety and efficacy of the first- and second-generation AMPLATZER Devices for LAAC, AMPLATZER Cardiac Plug (ACP) versus AMPLATZER Amulet™. Methods. Procedural data, such as fluoroscopy time, radiation dose, and contrast-dye, as well as VARC criteria and major adverse events (MAEs) were assessed for both devices. The rate of peridevice leaks was analyzed at echocardiographic follow-up. Results. A total of 196 patients with AF underwent LAAC with the ACP (n=99) or Amulet device (n=97). The use of Amulet was associated with significantly lower fluoroscopy time (14.8 ± 7.4 min versus 10.6 ± 4.1 min; p<0.001), lower radiation dose (4833 ± 3360 cGy⁎cm2 versus 3206 ± 2169 cGy⁎cm2; p<0.001), and reduced amount of contrast-dye (150.2 ± 83.9 ml versus 128.8 ± 46.0 ml; p=0.03). Furthermore, LAAC with Amulet devices resulted in lower device-resizing rates (3 versus 16 cases; p=0.001). Peridevice leaks were less frequent in the Amulet group (12 versus 4; p=0.03). MAE occurred in 6 ACP and 4 Amulet patients (p=0.58). Conclusions. The Amulet device is associated with shorter fluoroscopy times and radiation dosages, reduced use of contrast-dye, lower recapture rates, and less peridevice leaks as compared to the ACP.
Electroacupuncture Improves Gastric Emptying in Critically Ill Neurosurgical Patients: A Pilot Study
Authors: Kao Man-Ling , Chen Yao-Li , Lee Shu-Ching , Huang Sung-Yen , Lin Ping-Yi
Published: September 2017

Objective. To compare the efficacy of combined electroacupuncture and metoclopramide treatment with that of metoclopramide only in improving gastric emptying in critically ill neurosurgical patients. Methods. In this prospective case‐control pilot study, a total of 16 adult critically ill mechanically ventilated patients who were treated in the surgical intensive care unit were enrolled. Electrical stimulation was applied to 4 pairs of points (maximum intensity < 9.8 mA at 2 Hz). Patients in the control group received standard treatment with intravenous metoclopramide only. Patients in the experimental group received intravenous metoclopramide plus electroacupuncture treatment once daily for 6 consecutive days. Results. Gastric residual volume in the experimental group (n = 7) reduced gradually until the fourth day after treatment with electroacupuncture combined with routine metoclopramide administration. Beginning on the fourth day, residual volume was maintained at less than 200 ml per day for the following two days. In the control group (n = 9), there was a gradual reduction in residual volume during the first four days followed by a rebounding increase over the next two days. Conclusions. Electroacupuncture combined with intravenous metoclopramide is a more effective treatment for gastric emptying than metoclopramide alone in adult critically ill patients with impaired brain function.
Complete Response to Sorafenib Rechallenge in a Patient with Metastatic Renal Cell Carcinoma
Authors: Kasahara Ryo , Nakaigawa Noboru , Kobayashi Kazuki
Published: September 2017

A 79-year-old Japanese man underwent a medical examination for hoarseness. Computed tomography revealed a left renal tumor, and radical nephrectomy was performed. The tumor was a clear cell carcinoma. Fourteen months after the operation, the tumor had metastasized to the spleen, right lung, and retroperitoneal lymph nodes. We initiated molecular targeted therapy sequentially with sorafenib, sunitinib, and axitinib and then conducted a rechallenge with sorafenib. His metastatic lesions had completely vanished 5 months after initiation of the rechallenge. Ten months after the rechallenge, lumbar vertebral body metastasis appeared. However, we consider that the sorafenib rechallenge was effective because of the very slow growth of the metastatic lesion, with no other metastasis for 30 months, at the time of writing this report. Approximately 7 years after the first local recurrence, he remained alive, with relatively normal daily functioning.
VLDL Induced Modulation of Nitric Oxide Signalling and Cell Redox Homeostasis in HUVEC
Authors: Magnifico Maria Chiara , Oberkersch Roxana Elena , Mollo Azzurra , Giambelli Luca , Grooten Yasmine , Sarti Paolo , Calabrese Graciela Cristina , Arese Marzia
Published: September 2017

High levels of circulating lipoprotein constitute a risk factor for cardiovascular diseases, and in this context, the specific role of the very‐low‐density lipoproteins (VLDL) is poorly understood. The response of human umbilical vein endothelial cells (HUVEC) to VLDL exposure was studied, especially focusing on the pathways involved in alteration of redox homeostasis and nitric oxide (NO) bioavailability. The results obtained by the analysis of the expression level of genes implicated in the NO metabolism and oxidative stress response indicated a strong activation of inducible NO synthase (iNOS) upon 24 h exposure to VLDL, particularly if these have been preventively oxidised. Simultaneously, both mRNA and protein expression of endothelial NO synthase (eNOS) were decreased and its phosphorylation pattern, at the key residues Tyr495 and Ser1177, strongly suggested the occurrence of the eNOS uncoupling. The results are consistent with the observed increased production of nitrites and nitrates (NOx), reactive oxygen species (ROS), 3‐nitrotyrosine (3‐NT), and, at mitochondrial level, a deficit in mitochondrial O2 consumption. Altogether, these data suggest that the VLDL, particularly if oxidised, when allowed to persist in contact with endothelial cells, strongly alter NO bioavailability, affecting redox homeostasis and mitochondrial function.
An Entropy for Groups of Intermediate Growth
Authors: Kalogeropoulos Nikolaos
Published: September 2017

One of the few accepted dynamical foundations of nonadditive (“nonextensive”) statistical mechanics is that the choice of the appropriate entropy functional describing a system with many degrees of freedom should reflect the rate of growth of its configuration or phase space volume. We present an example of a group, as a metric space, that may be used as the phase space of a system whose ergodic behavior is statistically described by the recently proposedδ-entropy. This entropy is a one-parameter variation of the Boltzmann/Gibbs/Shannon functional and is quite different, in form, from the power-law entropies that have been recently studied. We use the first Grigorchuk group for our purposes. We comment on the connections of the above construction with the conjectured evolution of the underlying system in phase space.
MicroRNA‐34a: A Key Regulator in the Hallmarks of Renal Cell Carcinoma
Authors: Toraih Eman A. , Ibrahiem Afaf T. , Fawzy Manal S. , Hussein Mohammad H. , Al-Qahtani Saeed Awad M. , Shaalan Aly A. M.
Published: September 2017

Renal cell carcinoma (RCC) incidence has increased over the past two decades. Recent studies reported microRNAs as promising biomarkers for early cancer detection, accurate prognosis, and molecular targets for future treatment. This study aimed to evaluate the expression levels of miR‐34a and 11 of its bioinformatically selected target genes and proteins to test their potential dysregulation in RCC. Quantitative real‐time PCR for miR‐34a and its targets; MET oncogene; gene‐regulating apoptosis (TP53INP2 and DFFA); cell proliferation (E2F3); and cell differentiation (SOX2 and TGFB3) as well as immunohistochemical assay for VEGFA, TP53, Bcl2, TGFB1, and Ki67 protein expression have been performed in 85 FFPE RCC tumor specimens. Clinicopathological parameter correlation and in silico network analysis have also implicated. We found RCC tissues displayed significantly higher miR‐34a expression level than their corresponding noncancerous tissues, particularly in chromophobic subtype. MET and E2F3 were significantly upregulated, while TP53INP2 and SOX2 were downregulated. ROC analysis showed high diagnostic performance of miR‐34a (AUC = 0.854), MET (AUC = 0.765), and E2F3 (AUC = 0.761). The advanced pathological grade was associated with strong TGFB1, VEGFA, and Ki67 protein expression and absent Tp53 staining. These findings indicate miR‐34a along with its putative target genes could play a role in RCC tumorigenesis and progression.
Efficacy Study of Carrageenan as an Alternative Infused Material (Filler) in Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Porous 3D Scaffold
Authors: Che Johari Nor Syamimi , Aizad Syazwan , Zubairi Saiful Irwan
Published: September 2017

Polymeric porous 3D scaffold plays an important role in culturing mammalian cells asex vivomodel. However, the scaffold used is ineffective due to its structural and cell acceptability weaknesses. Therefore, this research attempts to overcome the weaknesses by using carrageenan from red seaweedKappaphycus alvareziias an alternative infused material (filler) of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) porous 3D scaffold. The 3D scaffold was conventionally fabricated using the solvent-casting particulate-leaching (SCPL) method. Carrageenan was later infused into 3D porous scaffolds under vacuum pressure and freeze-drying process. Five carrageenan concentrations were prepared and its physicochemical properties such as pH and viscosity were carried out on each concentration to determine the best solutions to produce a new composite 3D structure. The preliminary result shows that carrageenan concentrations of 2, 4, and 6% (w/v) were considered the best solutions for the infusion process due to its stable rheology properties. The pH and viscosity profiles of three selected carrageenan solutions were exhibited in the range of 9.00–9.20 and 0.047–1.144 Pa·s, respectively. Moreover, the incorporated carrageenan gel fraction was in the range of 4.30% to 14.95% (w/w) which was determined by gravimetric analysis and dye staining method (visual assessment). The well-infused carrageenan 3D scaffold was further characterized based on its internal morphology and degradability study. The vertical cross-sections of the scaffolds revealed homogeneous accumulation of dried gelatinous carrageenan which was covered throughout its pores wall. The degradation rate (K) of the carrageenan infused 3D scaffold was between0.01±1.66(mg/day) and0.03±3.23(mg/day). The higher the carrageenan concentration used, the faster the degradation rate occurring (p<0.05). The 3D infused scaffold of 4% (w/v) carrageenan concentration (S2) produced a moderate degradation rate of0.02±1.55(mg/day) with a sustained structural integrity up to 28 days. The carrageenan infused scaffold of 4% (w/v) was demonstrated to be the best 3D structure for a long-term cell culture (>2 weeks). In conclusion, the usage of carrageenan as a composite material exhibits its great potential to be used in tissue engineering application and 3D cell culture model.
Discrete Models of Disease and Competition
Authors: Bravo de la Parra R. , Marvá M. , Sánchez E. , Sanz L.
Published: September 2017

The aim of this work is to analyze the influence of the fast development of a disease on competition dynamics. To this end we present two discrete time ecoepidemic models. The first one corresponds to the case of one parasite affecting demography and intraspecific competition in a single host, whereas the second one contemplates the more complex case of competition between two different species, one of which is infected by the parasite. We carry out a complete mathematical analysis of the asymptotic behavior of the solutions of the corresponding systems of difference equations and derive interesting ecological information about the influence of a disease in competition dynamics. This includes an assessment of the impact of the disease on the equilibrium population of both species as well as some counterintuitive behaviors in which although we would expect the outbreak of the disease to negatively affect the infected species, the contrary happens.
Five Regioisomers of Dimethyl Dodecahedrane Derivatives: A Hybrid DFT B3LYP Study
Authors: Lee Seol , Cho YongJae , Lee Kee Hag
Published: September 2017

The hybrid density functional (B3LYP/6-31G(d, p)) method was used to understand why 1,2-dimethyl dodecahedrane has not been reported yet. From the direct dimethyl substitution of the dodecahedrane cage, we could have five C20H18(CH3)2 derivatives which were geometrically optimized without constraints. The results suggest that 1,16-dimethyl dodecahedrane derivative is the most stable, whereas the 1,2-dimethyl derivative is the most unstable; this implies that the distortion due to steric hindrance interactions would be a crucial effect on the relative energies of the dimethyl dodecahedranes. It would be disadvantaged thermodynamically for 1,2-dimethyl derivative that, in the experimental results, was not synthesized yet. The LUMO of each of the derivatives was equivalently delocalized over the void within the cage, implying that dimethyl derivatives are able to encapsulate atoms at the center of the cage. The HOMO was limitedly delocalized on the cage. The characteristics of the HOMO of derivatives show three patterns, implying that each derivative might undergo one of three entirely different sets of characteristic chemical reactions with electrophilic reagents.
Curcumin Attenuation of Wear Particle-Induced Osteolysis via RANKL Signaling Pathway Suppression in Mouse Calvarial Model
Authors: Cheng Tao , Zhao Yaochao , Li Bin , Cheng Mengqi , Wang Jiaxing , Zhang Xianlong
Published: September 2017

Wear particle-induced chronic inflammation and osteoclastogenesis are two critical factors in the osteolytic process. Curcumin (CUR) is an active compound of the medicinal herb Curcuma longa and has anti-inflammatory and antiosteoclastogenic properties. Our study tested the hypothesis that CUR might attenuate polymethylmethacrylate- (PMMA-) induced inflammatory osteolysis using mouse calvaria osteolysis model in vivo and in vitro. The mice were divided into four groups: phosphate-buffered saline group, CUR, PMMA, and PMMA + CUR groups. Three days before PMMA particle implantation, the mice were intraperitoneally injected with CUR (25 mg/kg/day). Ten days after the operation, the mouse calvaria was harvested for microcomputed tomography, histomorphometry, and molecular biology analysis. As expected, CUR markedly reduced the secretion of tumor necrosis factor-α, interleukin- (IL-) 1β, and IL-6 in the calvarial organ culture. Moreover, CUR suppressed osteoclastogenesis and decreased bone resorption in vivo compared with PMMA-stimulated calvaria. Furthermore, CUR downregulated the osteoclast-specific gene expression and reversed the receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin messenger RNA and protein ratio in PMMA particle-stimulated mice. These results suggest that CUR attenuated PMMA particle-induced inflammatory osteolysis by suppressing the RANKL signaling pathway in the murine calvarium, which could be a candidate compound to prevent and treat AL.
Stabilization of Stochastic Markovian Jump Systems with Partially Unknown Transition Probabilities and Multiplicative Noise
Authors: Zhao Yong , Fu You
Published: September 2017

We are concerned with the problems of stability and stabilization for stochastic Markovian jump systems subject to partially unknown transition probabilities and multiplicative noise, including the continuous‐ and discrete‐time cases. Sufficient conditions guaranteeing systems considered to be asymptotically stable in the mean square are presented in the form of LMIs. Furthermore, the desired state feedback controllers are designed. It is shown that, by introducing the free‐weighing matrix method, the results we have obtained not only are less conservative than the existing ones but also can be regarded as extensions of the corresponding results of Markovian jump systems without noise. Numerical examples are finally provided to illustrate the effectiveness of the proposed theoretical results.
Transient Ischemic Attack and Ischemic Stroke in Danon Disease with Formation of Left Ventricular Apical Thrombus despite Normal Systolic Function
Authors: Tsuda Takeshi , Shillingford Amanda J. , Vetter Jane , Kandula Vinay , Jain Badal , Temple Joel
Published: September 2017

Danon disease is a rare X-linked dominant skeletal and cardiac muscle disorder presenting with hypertrophic cardiomyopathy, Wolf-Parkinson-White syndrome, skeletal myopathy, and mild intellectual disability. Early morbidity and mortality due to heart failure or sudden death are known in Danon disease, more in males than in females. Here, we present a 17-year-old female adolescent with Danon disease and severe concentric hypertrophy with normal left ventricular (LV) systolic function, who has been complaining of intermittent headache and weakness for about 3 years, initially diagnosed with hemiplegic migraine. Subsequently, her neurological manifestation progressed to transient ischemic attack (TIA) and eventually to ischemic stroke confirmed by CT scan with 1-day history of expressive aphasia followed by persistent left side weakness and numbness. Detailed echocardiogram for the first time revealed a small LV apical thrombus with unchanged severe biventricular hypertrophy and normal systolic function. This unexpected LV apical thrombus may be associated with a wide spectrum of neurological deficits ranging from TIA to ischemic stroke in Danon disease. Possibility of cerebral ischemic events should be suspected in Danon disease when presenting with neurological deficits even with normal systolic function. Careful assessment for LV apical thrombus is warranted in such cases.
Existence of Mild Solutions and Controllability of Fractional Impulsive Integrodifferential Systems with Nonlocal Conditions
Authors: Qin Haiyong , Gu Zhenyun , Fu Youliang , Li Tongxing
Published: September 2017

This paper is concerned with the existence results of nonlocal problems for a class of fractional impulsive integrodifferential equations in Banach spaces. We define a piecewise continuous control function to obtain the results on controllability of the corresponding fractional impulsive integrodifferential control systems. The results are obtained by means of fixed point methods. An example to illustrate the applications of our main results is given.
BMP4/LIF or RA/Forskolin Suppresses the Proliferation of Neural Stem Cells Derived from Adult Monkey Brain
Authors: Han Xinxin , Yu Liming , Chen Qingqing , Wang Min , Ren Jie , Wang Guangming , Chen Yihong , Lu Lixia , Tian Haibin , Chen Li , Zhang Ying , Liu Yuehua , He Hua , Gao Zhengliang
Published: September 2017

Monkeys are much closer to human and are the most common nonhuman primates which are used in biomedical studies. Neural progenitor cells can originate from the hippocampus of adult monkeys. Despite a few reports, the detailed properties of monkey neural stem cells (NSCs) and their responses to cytokine are still unclear. Here, we derive NSCs from an adult monkey brain and demonstrate that BMP4 inhibits cell proliferation and affects cell morphology of monkey NSCs. Combined treatment of BMP4 and LIF or RA and Forskolin represses the proliferation of monkey NSCs. We also show that BMP4 may promote monkey NSC quiescence. Our study therefore provides implications for NSC-based cell therapy of brain injury in the future.
Effects of Drought on Morphological Traits in Some Cowpea Genotypes by Evaluating Their Combining Abilities
Authors: Olajide Amos Afolarin , Ilori Christopher Olumuyiwa
Published: September 2017

An evaluation was conducted to understand the genetic effects of combining ability for four different morphological traits, on 42 hybrids in randomized complete block design with three replications in water-stressed and well-watered environments. The significance of the additive variance (D) and dominance variance (H1) indicated the presence of both additive and nonadditive gene actions in both environments. Among the parents, there was asymmetrical distribution of positive and negative dominant genes and the preponderance of overdominance gene action for all the traits in both environments. This study also indicated a minimum of ten genes for plant height in water-stressed environment and minimum of three and eight genes for terminal leaflet area and number of leaves per plant in both environments, respectively. Estimates of narrow-sense heritability ranged from 13.0% for number of branches per plant in water-stressed to 95.0% in well-watered environment for terminal leaflet area. The study revealed that Danilla, IT93K-432-1, and IT97K-499-35 were the best general combiners for all traits, Danilla × IT97K-499-35, and Danilla × IT93K-432-1 were found to be the best specific combiners for all traits in water-stressed environment. Genetic interactions, additive × additive and additive × dominance, were more pronounced in the inheritance of the traits. This indicated that the selection for these traits should be delayed till advanced generations.
Understanding the Resistive Switching Phenomena of Stacked Al/Al2O3/Al Thin Films from the Dynamics of Conductive Filaments
Authors: Molina-Reyes Joel , Hernandez-Martinez Luis
Published: September 2017

We present the resistive switching characteristics of Metal-Insulator-Metal (MIM) devices based on amorphous Al2O3which is deposited by Atomic Layer Deposition (ALD). A maximum processing temperature for this memory device is 300°C, making it ideal for Back-End-of-Line (BEOL) processing. Although some variations in the forming, set, and reset voltages (VFORM,VSET, andVRESET) are obtained for many of the measured MIM devices (mainly due to roughness variations of the MIM interfaces as observed after atomic-force microscopy analysis), thememristoreffect has been obtained after cyclicI-Vmeasurements. These resistive transitions in the metal oxide occur for bothbipolarandunipolarconditions, while theIOFF/IONratio is around 4–6 orders of magnitude and is formed at gate voltages ofVg<4 V. In unipolar mode, a gradual reduction inVSETis observed and is related to combined (a) incomplete dissolution of conductive filaments (made of oxygen vacancies and metal ions) which leaves some residuals and (b) thickening of chemically reduced Al2O3during localized Joule heating. This is important because, by analyzing the macroscopic resistive switching behavior of this MIM structure, we could indirectly relate it to microscopic and/or nanoscopic phenomena responsible for the physical mechanism upon which most of these devices operate.
Nutritional Value and Potential Chemical Food Safety Hazards of Selected Traditional and Conventional Pork Hams from Poland
Authors: Halagarda Michał , Kędzior Władysław , Pyrzyńska Ewa
Published: September 2017

Consumers no longer look for food characterized only by health safety and proper nutritional value. As a result, an increased interest in traditional and regional food can be observed. The aim of this paper is to analyze the results of a comparative analysis of three types of hams: traditional products registered on the List of Traditional Products of the Polish Ministry of Agriculture and Rural Development, then products whose names, retail prices, appearance, and manufacturer’s description suggest traditional methods of production, and finally conventional hams. The results show that traditional hams are characterized by the highest nutritional value among the analyzed groups of products. They have the lowest water and a high protein content. In addition, traditional hams are distinguished by a low concentration of sodium chloride and no addition of phosphates. The residues of nitrites and nitrates indicate their moderate use in manufacturing processes.
T Cells Deficient in Diacylglycerol Kinase ζ Are Resistant to PD-1 Inhibition and Help Create Persistent Host Immunity to Leukemia
Authors: Jing Weiqing , Gershan Jill A. , Holzhauer Sandra , Weber James , Palen Katie , McOlash Laura , Pulakanti Kirthi , Wesley Erin , Rao Sridhar , Johnson Bryon D. , Riese Matthew J.
Published: September 2017

Efforts to improve the efficacy of adoptive T-cell therapies and immune checkpoint therapies in myelogenous leukemia are desired. In this study, we evaluated the antileukemia activity of adoptively transferred polyclonal cancer antigen-reactive T cells deficient in the regulator diacylglycerol kinase zeta (DGKζ) with or without PD-1/PD-L1 blockade. In the C1498 mouse model of myeloid leukemia, we showed that leukemia was eradicated more effectively in DGKζ-deficient (DGKζ−/−) mice than wild-type mice. T cells transferred from DGKζ-deficient mice to wild-type tumor-bearing recipients conferred this benefit. Leukemia clearance was similar to mice treated with anti-PD-L1. Strikingly, we found that the activity of adoptively transferred DGKζ−/− T cells relied partly on induction of sustainable host T-cell immunity. Transferring DGKζ-deficient T cells increased the levels of IFNγ and other cytokines in recipient mice, especially with coadministration of anti-PD-L1. Overall, our results offered evidence that targeting DGKζ may leverage the efficacy of adoptive T-cell and immune checkpoint therapies in leukemia treatment. Furthermore, they suggest that DGKζ targeting might decrease risks of antigen escape or resistance to immune checkpoint blockade. Cancer Res; 77(20); 5676–86. ©2017 AACR.
Characterization of the Immune Microenvironment in Hepatocellular Carcinoma
Authors: Yarchoan Mark , Xing Dongmei , Luan Lan , Xu Haiying , Sharma Rajni B. , Popovic Aleksandra , Pawlik Timothy M. , Kim Amy K. , Zhu Qingfeng , Jaffee Elizabeth M. , Taube Janis M. , Anders Robert A.
Published: September 2017

Purpose: Hepatocellular carcinoma (HCC) often arises in the setting of chronic liver inflammation and may be responsive to novel immunotherapies.

Experimental Design: To characterize the immune microenvironment in HCC, IHC staining was performed for CD8-positive T lymphocytes, PD-1–positive, and LAG-3–positive lymphocytes, CD163-positive macrophages, and PD-L1 expression in tumor and liver background from 29 cases of resected HCC.

Results: Expression of CD8 was reduced in tumor, and expression of CD163 was reduced at the tumor interface. Positive clusters of PD-L1 expression were identified in 24 of 29 cases (83%), and positive expression of LAG-3 on tumor-infiltrating lymphocytes was identified in 19 of 29 cases (65%). The expression of both PD-L1 and LAG-3 was increased in tumor relative to liver background. No association between viral status or other clinicopathologic features and expression of any of the IHC markers investigated was noted.

Conclusions: LAG-3 and PD-L1, two inhibitory molecules implicated in CD8 T-cell tolerance, are increased in most HCC tumors, providing a basis for investigating combinatorial checkpoint blockade with a LAG-3 and PD-L1 inhibitor in HCC. Clin Cancer Res; 23(23); 7333–9. ©2017 AACR.