bluuebunny/crossref_metadata_2025 huggingface dataset:
Bounded expectations: resource analysis for probabilistic programs
Authors: Ngo Van Chan , Carbonneaux Quentin , Hoffmann Jan
Published: December 2018

This paper presents a new static analysis for deriving upper bounds on the expected resource consumption of probabilistic programs. The analysis is fully automatic and derives symbolic bounds that are multivariate polynomials in the inputs. The new technique combines manual state-of-the-art reasoning techniques for probabilistic programs with an effective method for automatic resource-bound analysis of deterministic programs. It can be seen as both, an extension of automatic amortized resource analysis (AARA) to probabilistic programs and an automation of manual reasoning for probabilistic programs that is based on weakest preconditions. An advantage of the technique is that it combines the clarity and compositionality of a weakest-precondition calculus with the efficient automation of AARA. As a result, bound inference can be reduced to off-the-shelf LP solving in many cases and automatically-derived bounds can be interactively extended with standard program logics if the automation fails. Building on existing work, the soundness of the analysis is proved with respect to an operational semantics that is based on Markov decision processes. The effectiveness of the technique is demonstrated with a prototype implementation that is used to automatically analyze 39 challenging probabilistic programs and randomized algorithms. Experiments indicate that the derived constant factors in the bounds are very precise and even optimal for some programs.
Incremental inference for probabilistic programs
Authors: Cusumano-Towner Marco , Bichsel Benjamin , Gehr Timon , Vechev Martin , Mansinghka Vikash K.
Published: December 2018

We present a novel approach for approximate sampling in probabilistic programs based on incremental inference. The key idea is to adapt the samples for a program
P
into samples for a program
Q
, thereby avoiding the expensive sampling computation for program
Q
. To enable incremental inference in probabilistic programming, our work: (i) introduces the concept of a trace translator which adapts samples from
P
into samples of
Q
, (ii) phrases this translation approach in the context of sequential Monte Carlo (SMC), which gives theoretical guarantees that the adapted samples converge to the distribution induced by
Q
, and (iii) shows how to obtain a concrete trace translator by establishing a correspondence between the random choices of the two probabilistic programs. We implemented our approach in two different probabilistic programming systems and showed that, compared to methods that sample the program
Q
from scratch, incremental inference can lead to orders of magnitude increase in efficiency, depending on how closely related
P
and
Q
are.
Polyhedral auto-transformation with no integer linear programming
Authors: Acharya Aravind , Bondhugula Uday , Cohen Albert
Published: December 2018

State-of-the-art algorithms used in automatic polyhedral transformation for parallelization and locality optimization typically rely on Integer Linear Programming (ILP). This poses a scalability issue when scaling to tens or hundreds of statements, and may be disconcerting in production compiler settings. In this work, we consider relaxing integrality in the ILP formulation of the Pluto algorithm, a popular algorithm used to find good affine transformations. We show that the rational solutions obtained from the relaxed LP formulation can easily be scaled to valid integral ones to obtain desired solutions, although with some caveats. We first present formal results connecting the solution of the relaxed LP to the original Pluto ILP. We then show that there are difficulties in realizing the above theoretical results in practice, and propose an alternate approach to overcome those while still leveraging linear programming. Our new approach obtains dramatic compile-time speedups for a range of large benchmarks. While achieving these compile-time improvements, we show that the performance of the transformed code is not sacrificed. Our approach to automatic transformation provides a mean compilation time improvement of 5.6× over state-of-the-art on relevant challenging benchmarks from the NAS PB, SPEC CPU 2006, and PolyBench suites. We also came across situations where prior frameworks failed to find a transformation in a reasonable amount of time, while our new approach did so instantaneously.
1000 Bull Genomes Project to Map Simple and Complex Genetic Traits in Cattle: Applications and Outcomes
Authors: Hayes Ben J. , Daetwyler Hans D.
Published: December 2018

The 1000 Bull Genomes Project is a collection of whole-genome sequences from 2,703 individuals capturing a significant proportion of the world's cattle diversity. So far, 84 million single-nucleotide polymorphisms (SNPs) and 2.5 million small insertion deletions have been identified in the collection, a very high level of genetic diversity. The project has greatly accelerated the identification of deleterious mutations for a range of genetic diseases, as well as for embryonic lethals. The rate of identification of causal mutations for complex traits has been slower, reflecting the typically small effect size of these mutations and the fact that many are likely in as-yet-unannotated regulatory regions. Both the deleterious mutations that have been identified and the mutations associated with complex trait variation have been included in low-cost SNP array designs, and these arrays are being genotyped in tens of thousands of dairy and beef cattle, enabling management of deleterious mutations in these populations as well as genomic selection.
From Stochastic Thermodynamics to Thermodynamic Inference
Authors: Seifert Udo
Published: December 2018

For a large class of nonequilibrium systems, thermodynamic notions like work, heat, and, in particular, entropy production can be identified on the level of fluctuating dynamical trajectories. Within stochastic thermodynamics various fluctuation theorems relating these quantities have been proven. Their application to experimental systems requires that all relevant mesostates are accessible. Recent advances address the typical situation that only partial, or coarse-grained, information about a system is available. Thermodynamic inference as a general strategy uses consistency constraints derived from stochastic thermodynamics to infer otherwise hidden properties of nonequilibrium systems. An important class in this respect are active particles, for which we resolve the conflicting strategies that have been proposed to identify entropy production. As a paradigm for thermodynamic inference, the thermodynamic uncertainty relation provides a lower bound on the entropy production through measurements of the dispersion of any current in the system. Likewise, it quantifies the cost of precision for biomolecular processes. Generalizations and ramifications allow the inference of, inter alia, model-free upper bounds on the efficiency of molecular motors and of the minimal number of intermediate states in enzymatic networks.
Involvement of the STAT5-cyclin D/CDK4-pRb pathway in β-cell proliferation stimulated by prolactin during pregnancy
Authors: Zhao Xin , Xu Yili , Wu Ya , Zhang Hui , Shi Houxia , Zhu Hui , Woo Minna , Wu Xiaohong
Published: December 2018

During pregnancy, maternal pancreatic β-cells undergo a compensatory expansion in response to the state of insulin resistance, where prolactin (PRL) plays a major role. Retinoblastoma protein (Rb) has been shown to critically regulate islet proliferation and function. The aim of the study was to explore the role of Rb in β-cell mass expansion during pregnancy. Expression of pocket protein family and E2Fs were examined in mouse islets during pregnancy and in insulinoma cells (INS-1) stimulated by PRL. PRL-stimulated INS-1 cells were used to explore the signaling pathway that regulates Rb downstream of the PRL receptor. Pancreas-specific Rb-knockout (Rb-KO) mice were assessed to evaluate the in vivo function of Rb in β-cell proliferation during pregnancy. During pregnancy, expression of Rb, phospho-Rb (p-Rb), p107, and E2F1 increased, while p130 decreased in maternal islets. With PRL stimulation, induction of Rb expression occurred mainly in the nucleus, while p-Rb was predominantly in the cytoplasm. Inhibition of STAT5 significantly restrained the expression of CDK4, Rb, p-Rb, and E2F1 in PRL-stimulated INS-1 cells with attenuation in cell cycle progression. Reduction of Rb phosphorylation by CDK4 inhibition blocked PRL-mediated proliferation of INS-1 cells. On the other hand, knockdown of Rb using siRNA led to an induction in E2F1 leading to cell cycle progression from G1 to S and G2/M phase, similar to the effects of PRL-mediated induction of p-Rb that led to cell proliferation. With Rb knockdown, PRL did not lead to further increase in cell cycle progression. Similarly, while Rb-KO pregnant mice displayed better glucose tolerance and higher insulin secretion, they had similar β-cell mass and proliferation to wild-type pregnant controls, supporting the essential role of Rb suppression in augmenting β-cell proliferation during pregnancy. Rb-E2F1 regulation plays a pivotal role in PRL-stimulated β-cell proliferation. PRL promotes Rb phosphorylation and E2F1 upregulation via STAT5-cyclin D/CDK4 pathway during pregnancy.
Estrogen receptor-α signaling maintains immunometabolic function in males and is obligatory for exercise-induced amelioration of nonalcoholic fatty liver
Authors: Winn Nathan C. , Jurrissen Thomas J. , Grunewald Zachary I. , Cunningham Rory P. , Woodford Makenzie L. , Kanaley Jill A. , Lubahn Dennis B. , Manrique-Acevedo Camila , Rector R. Scott , Vieira-Potter Victoria J. , Padilla Jaume
Published: December 2018

The role of estrogen receptor-α (ERα) signaling in immunometabolic function is established in females. However, its necessity in males, while appreciated, requires further study. Accordingly, we first determined whether lower metabolic function in male mice compared with females is related to reduced ERα expression. ERα protein expression in metabolically active tissues was lower in males than in females, and this lower expression was associated with worse glucose tolerance. Second, we determined whether ERα is required for optimal immunometabolic function in male mice consuming a chow diet. Despite lower expression of ERα in males, its genetic ablation (KO) caused an insulin-resistant phenotype characterized by enhanced adiposity, glucose intolerance, hepatic steatosis, and metaflammation in adipose tissue and liver. Last, we determined whether ERα is essential for exercise-induced metabolic adaptations. Twelve-week-old wild-type (WT) and ERα KO mice either remained sedentary (SED) or were given access to running wheels (WR) for 10 wk while fed an obesogenic diet. Body weight and fat mass were lower in WR mice regardless of genotype. Daily exercise obliterated immune cell infiltration and inflammatory gene transcripts in adipose tissue in both genotypes. In the liver, however, wheel running suppressed hepatic steatosis and inflammatory gene transcripts in WT but not in KO mice. In conclusion, the present findings indicate that ERα is required for optimal immunometabolic function in male mice despite their reduced ERα protein expression in metabolically active tissues. Furthermore, for the first time, we show that ERα signaling appears to be obligatory for exercise-induced prevention of hepatic steatosis.
Postexercise skeletal muscle signaling responses to moderate- to high-intensity steady-state exercise in the fed or fasted state
Authors: Stocks Ben , Dent Jessica R. , Ogden Henry B. , Zemp Martina , Philp Andrew
Published: December 2018

Exercise performed in the fasted state acutely increases fatty acid availability and utilization. Furthermore, activation of energy-sensing pathways and fatty acid metabolic genes can be augmented by fasting and fasted exercise. However, whether a similar effect occurs at higher exercise intensities remains poorly understood. This study aimed to assess the effect of fed and fasted exercise upon postexercise signaling and mRNA responses during moderate- to high-intensity steady-state exercise. Eight male participants [age: 25 (SD 2) yr, V̇o2peak: 47.9 (SD 3.8) ml·kg−1·min−1] performed 1 h of cycling at 70% Wmaxin the fasted (FAST) state or 2 h following ingestion of a carbohydrate-rich mixed-macronutrient breakfast (FED). Muscle biopsies were collected pre-, immediately, and 3 h postexercise from the medial vastus lateralis, while venous blood samples were collected throughout the trial. Plasma, nonesterified fatty acid, and glycerol concentrations were elevated during FAST compared with FED, although substrate utilization during exercise was similar. AMPKThr172phosphorylation was ~2.5-fold elevated postexercise in both trials and was significantly augmented by ~30% during FAST. CREBSer133phosphorylation was elevated approximately twofold during FAST, although CREBSer133phosphorylation acutely decreased by ~50% immediately postexercise. mRNA expression of PDK4 was approximately three- to fourfold augmented by exercise and approximately twofold elevated throughout FAST, while expression of PPARGC1A mRNA was similarly activated (~10-fold) by exercise in both FED and FAST. In summary, performing moderate- to high-intensity steady-state exercise in the fasted state increases systemic lipid availability, elevates phosphorylation of AMPKThr172and CREBSer133, and augments PDK4 mRNA expression without corresponding increases in whole body fat oxidation and the mRNA expression of PPARGC1A.
Cannabis sativa L. and Nonpsychoactive Cannabinoids: Their Chemistry and Role against Oxidative Stress, Inflammation, and Cancer
Authors: Pellati Federica , Borgonetti Vittoria , Brighenti Virginia , Biagi Marco , Benvenuti Stefania , Corsi Lorenzo
Published: December 2018

In the last decades, a lot of attention has been paid to the compounds present in medicinal Cannabis sativa L., such as Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), and their effects on inflammation and cancer-related pain. The National Cancer Institute (NCI) currently recognizes medicinal C. sativa as an effective treatment for providing relief in a number of symptoms associated with cancer, including pain, loss of appetite, nausea and vomiting, and anxiety. Several studies have described CBD as a multitarget molecule, acting as an adaptogen, and as a modulator, in different ways, depending on the type and location of disequilibrium both in the brain and in the body, mainly interacting with specific receptor proteins CB1 and CB2. CBD is present in both medicinal and fibre-type C. sativa plants, but, unlike Δ9-THC, it is completely nonpsychoactive. Fibre-type C. sativa (hemp) differs from medicinal C. sativa, since it contains only few levels of Δ9-THC and high levels of CBD and related nonpsychoactive compounds. In recent years, a number of preclinical researches have been focused on the role of CBD as an anticancer molecule, suggesting CBD (and CBD-like molecules present in the hemp extract) as a possible candidate for future clinical trials. CBD has been found to possess antioxidant activity in many studies, thus suggesting a possible role in the prevention of both neurodegenerative and cardiovascular diseases. In animal models, CBD has been shown to inhibit the progression of several cancer types. Moreover, it has been found that coadministration of CBD and Δ9-THC, followed by radiation therapy, causes an increase of autophagy and apoptosis in cancer cells. In addition, CBD is able to inhibit cell proliferation and to increase apoptosis in different types of cancer models. These activities seem to involve also alternative pathways, such as the interactions with TRPV and GRP55 receptor complexes. Moreover, the finding that the acidic precursor of CBD (cannabidiolic acid, CBDA) is able to inhibit the migration of breast cancer cells and to downregulate the proto-oncogene c-fos and the cyclooxygenase-2 (COX-2) highlights the possibility that CBDA might act on a common pathway of inflammation and cancer mechanisms, which might be responsible for its anticancer activity. In the light of all these findings, in this review we explore the effects and the molecular mechanisms of CBD on inflammation and cancer processes, highlighting also the role of minor cannabinoids and noncannabinoids constituents of Δ9-THC deprived hemp.
Dynamic Modeling of a Vibrating Screen Considering the Ore Inertia and Force of the Ore over the Screen Calculated with Discrete Element Method
Authors: Moncada M. Manuel , Rodríguez Cristian G.
Published: December 2018

Vibrating screens are critical machines used for size classification in mineral processing. Their proper operation, including accurate vibration movement and slope angle, can provide the benefits of energy savings and cost reductions in the screening process and the whole mining process. Dynamic models of the vibrating screen movement available in the literature do not simulate ore motion or its interaction with screen decks. The discrete element method (DEM) allows for the calculation of the dynamic of the ore. In this paper, two 2D three‐degrees‐of‐freedom dynamic models for a vibrating screen are tested, using linear and nonlinear approaches for angular displacement. These models consider the inertia of the ore and the ore force calculated with DEM. A double‐deck linear motion vibrating screen is simulated using the DEM software LIGGGTHS. DEM is used to obtain the ore parameters in the steady state and the force on the screen decks. Two cases are compared: Case 1 considers the ore as moving together with the vibrating screen, and Case 2 considers the ore force on the screen deck as calculated by DEM. Simulations are carried out with data for an industrial vibrating screen used in copper mining. The force over the screen is significantly different between the cases. Case 1 produces a force that is unrealistic because the ore cannot produce a high‐amplitude adhesion force over the screen decks. In Case 2, no adhesion force acts between the ore and deck. It is concluded that the linear dynamic model used in Case 2 is adequate to evaluate the influence of the ore on the movement of the vibrating screen. The linear dynamic model considering the force as in Case 1 can be used to simulate a vibrating screen, as long as a correct calibration parameter is included to obtain an accurate motion amplitude.
Design of Analog Signal Processing Applications Using Carbon Nanotube Field Effect Transistor-Based Low-Power Folded Cascode Operational Amplifier
Authors: Bendre Varsha S. , Kureshi A. K. , Waykole Saurabh
Published: December 2018

Carbon nanotube (CNT) is one of the embryonic technologies within recent inventions towards miniaturization of semiconductor devices and is gaining much attention due to very high throughput and very extensive series of applications in various analog/mixed signal applications of today’s high-speed era. The carbon nanotube field effect transistors (CNFETs) have been reconnoitred as the stimulating aspirant for the future generations of integrated circuit (IC) devices. CNFETs are being widely deliberated as probable replacement to silicon MOSFETs also. In this paper, different analog signal processing applications such as inverting amplifier, noninverting amplifier, summer, subtractor, differentiator, integrator, half-wave and full-wave rectifiers, clipper, clamper, inverting and noninverting comparators, peak detector, and zero crossing detector are implemented using low-power folded cascode operational amplifier (op-amp) implemented using CNFET. The proposed CNFET-based analog signal processing applications are instigated at 32 nm technology node. Simulation results show that the proposed applications are properly implemented using novel folded cascode operational amplifier (FCOA) implemented using CNFET.
Neuroprotective Effects of Gagam‐Sipjeondaebo‐Tang, a Novel Herbal Formula, against MPTP‐Induced Parkinsonian Mice and MPP+‐Induced Cell Death in SH‐SY5Y Cells
Authors: Ko Jade Heejae , Lee Ju-Hee , Choi Bobin , Park Ju-Yeon , Kwon Young-Won , Jeon Songhee , Park Sun-Dong , Kim Seung-Nam
Published: December 2018

Parkinson’s disease is a neurodegenerative disease characterized by progressive cell death of dopaminergic neuron and following neurological disorders. Gagam‐Sipjeondaebo‐Tang (GST) is a novel herbal formula made of twelve medicinal herbs derived from Sipjeondaebo‐Tang, which has been broadly used in a traditional herbal medicine. In the present study, we investigated the effects of GST against 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced motor abnormalities in mice and 1‐methyl‐4‐phenylpyridinium (MPP+)‐induced neurotoxicity in SH‐SY5Y cell. First, we found that GST alleviated motor dysfunction induced by MPTP, and the result showed dopaminergic neurons recovery in substantia nigra. In the cell experiment, pretreatment with GST increased the cell viability and attenuated apoptotic cell death in MPP+‐treated SH‐SY5Y cells. GST also inhibited reactive oxygen species production and restored the mitochondrial membrane potential loss, which were induced by MPP+. Furthermore, GST extract significantly activated ERK and Akt, cell survival‐related proteins, in SH‐SY5Y cells. The effect of GST preventing mitochondrial dysfunction was antagonized by pretreatment of PD98059 and LY294002, selective inhibitors of ERK and Akt, respectively. Taken together, GST alleviated abnormal motor functions and recovered neuronal cell death, mitochondrial dysfunction, possibly via ERK and Akt activation. Therefore, we suggest that GST may be a candidate for the treatment and prevention of Parkinson’s disease.
Multiobjective Glowworm Swarm Optimization-Based Dynamic Replication Algorithm for Real-Time Distributed Databases
Authors: Thalij Saadi Hamad , Hakkoymaz Veli
Published: December 2018

Distributed systems offer resources to be accessed geographically for large-scale data requests of different users. In many cases, replication of the vital data files and storing their replica in multiple locations accessible to the requesting clients is vital in improving the data availability, reliability, security, and reduction of the execution time. It is important that real-time distributed databases maintain the consistency constraints and also guarantee the time constraints required by the client requests. However, when the size of the distributed system increases, the user access time also tends to increase, which in turn increases the vitality of the replica placement. Thus, the primary issues that emerge are deciding upon an optimal replication number and identifying perfect locations to store the replicated data. These open challenges have been considered in this study, which turns to develop a dynamic data replication algorithm for real-time distributed databases using a multiobjective glowworm swarm optimization (MGSO) strategy. The proposed algorithm adapts the random patterns of the read-write requests and employs a dynamic window mechanism for replication. It also models the replica number and placement problem as a multiobjective optimization problem and utilizes MGSO for resolving it. The cost models are presented to ensure the time constraint satisfaction in servicing user requests. The performance of the MGSO dynamic data replication algorithm has been studied using competitive analysis, and the results show the efficiency of the proposed algorithm for the distributed databases.
Identification of Fasciola Species Isolates from Nghe An Province, Vietnam, Based on ITS1 Sequence of Ribosomal DNA Using a Simple PCR-RFLP Method
Authors: Anh Do Ngoc , Anh Le Tran , Tuan Le Quoc , Bac Nguyen Duy , Tien Tran Viet , Phuong Vu Thi Binh , Duong Tran Thanh , Luc Nguyen Khac , Quang Nguyen Ba
Published: December 2018

Fascioliasis—a disease caused by Fasciola spp. (Platyhelminthes: Trematoda: Digenea)—is considered as the most important helminthic infection of bovine, sheep, and buffalo in Vietnam. The aim of this study is to detect the genotype of Fasciola spp. isolated from bovine and buffalo in the Nghe An province, central Vietnam, using PCR-RFLP and sequence analysis of the first nuclear ribosomal internal transcribed spacer (ITS1). Adult Fasciola spp. were isolated from bile ducts of bovine and buffalo in Nghe An province, Vietnam. Overall, 96 adult flukes from livers of slaughtered animals were collected from abattoirs of different areas. They included 7 samples from infected bovine and 89 samples from infected buffalo. 96/96 samples were identified as Fasciola species by ITS1 of rDNA. In this study, a PCR-RFLP method was used to distinguish between F. hepatica and F. gigantica in ITS1 of rDNA (680 bp) with RsaI restriction enzyme. RFLP pattern with RsaI produced a consistent pattern of 360, 100, and 60 bp fragments in F. hepatica, whereas F. gigantica worms had a profile of 360, 170, and 60 bp in size, respectively. The results showed that using PCR-RFLP based on the first internal transcribed spacers (ITS1) of the ribosomal RNA revealed that 93 out of 96 isolates were of Fasciola gigantica type, whereas three isolates presented an intermediate Fasciola. In the present study, F. gigantica and intermediate form were coexisting in bovine and buffalo in the Nghe An province of central Vietnam, whereas F. hepatica was not detected.
Speed Improvement in Image Stitching for Panoramic Dynamic Images during Minimally Invasive Surgery
Authors: Kim Dinh Thai , Nguyen Van Thang , Cheng Ching-Hwa , Liu Don-Gey , Liu Kai Che Jack , Huang Kai Che Jack
Published: December 2018

Minimally invasive surgery (MIS) minimizes the surgical incisions that need to be made and hence reduces the physical trauma involved during the surgical process. The ultimate goal is to reduce postoperative pain and blood loss as well as to limit the scarring area and hence accelerate recovery. It is therefore of great interest to both the surgeon and the patient. However, a major problem with MIS is that the field of vision of the surgeon is very narrow. We had previously developed and tested an MIS panoramic endoscope (MISPE) that provides the surgeon with a broader field of view. However, one issue with the MISPE was its low rate of video stitching. Therefore, in this paper, we propose using the region of interest in combination with the downsizing technique to improve the image-stitching performance of the MISPE. Experimental results confirm that, by using the proposed method, the image size can be increased by more than 160%, with the image resolution also improving. For instance, we could achieve performance improvements of 10× (CPU) and 23× (GPU) as compared to that of the original method.
A Sensitive Resonance Rayleigh Scattering Method for Na+ Based on Graphene Oxide Nanoribbon Catalysis
Authors: Wang Haidong , Li Chongning , Luo Yanghe , Jiang Zhiliang
Published: December 2018

The gold nanoparticle reaction of HAuCl4-H2O2 was very slow under 60°C, and the as-prepared graphene oxide nanoribbons (GONRs) exhibited strong catalysis of the reaction to form gold nanoparticles (AuNP) that appeared a resonance Rayleigh scattering (RRS) peak at 550 nm. Upon addition of potassium pyroantimonate (PA) ligand, it was adsorbed on the GONRs surface to inhibit the catalysis to cause the RRS peak decreasing. When the analyte of Na+ was added, the coordination reaction between PA and Na+ took place to form the stable complexes of [Na2(PA)] to release free GONRs catalyst that resulted in the RRS peak increasing linearly. Accordingly, a new and sensitive RRS method for Na+ was established, with a linear range of 0.69-25.8 nmol/L and a detection limit of 0.35 nmol/L Na+.
SIRT7 Regulates the Vascular Smooth Muscle Cells Proliferation and Migration via Wnt/β-Catenin Signaling Pathway
Authors: Zheng Jianghua , Chen Kai , Wang Haifei , Chen Zhilong , Xi Yong , Yin Hongshun , Lai Kun , Liu Yujuan
Published: December 2018

A huge amount of evidence indicates that sirtuin 7 (SIRT7), a key mediator of many cellular activities, plays a crucial role in the pathogenesis of various diseases. However, little is known about the role of SIRT7 in atherosclerosis. This study investigated the potential role of SIRT7 in regulating the proliferation and migration of human vascular smooth muscle cells (HAVSMCs) and its possible molecular mechanism. In this study, human vascular smooth muscle cells (HAVSMCs) were induced by oxidized low-density lipoprotein (ox-LDL) to establish atherosclerosis (AS) cell model. Immunofluorescence staining and Western blot were used to detect the level of α-SMA expression, which was a marker protein in AS. In addition, RT-qPCR and Western blot assay were applied for exploring the mRNA and protein expression levels of SIRT7, Wnt, β-catenin, and cyclin D1 after knockdown or overexpression of SIRT7. And, furthermore, Cell Counting Kit-8 assay, flow cytometry, and wound-healing assay were used to assess HAVSMCs proliferation, cell cycle, and migration. Dickkopf-1 (DKK-1), a secretory glycoprotein that can block Wnt/β-catenin pathway, was used in SIRT7 overexpression HAVSMCs; subsequently cells proliferation and migration were assessed by Cell Counting Kit-8 assay, flow cytometry analysis, and wound-healing assay. We found that knockdown of SIRT7 significantly promoted cell proliferation and migration, decreased the percentages of cells in the G1 and G2 phases, and increased those in the S phase and downregulated the protein expression levels of Wnt, β-catenin, and cyclin D1, while overexpression of SIRT7 had reverse results. After treatment with Wnt/beta-catenin pathway inhibitor DKK-1 in SIRT7 overexpression HAVSMCs, cell proliferation and migration were increased, respectively. In conclusion, SIRT7 inhibited HAVSMCs proliferation and migration via enhancing Wnt/β-catenin activation, which provided a novel therapeutic strategy for antiatherosclerosis.
Spatial Distribution and Temporal Trend of Tropospheric NO2 over the Wanjiang City Belt of China
Authors: Xie Yu , Wang Wei , Wang Qinglong
Published: December 2018

We utilize the tropospheric NO2 columns derived from the observations of Ozone Monitoring Instrument (OMI) onboard AURA to analyze the spatial distributions and temporal trends of NO2 in Wanjiang City Belt (WCB) of China from 2005 to 2016. The aim of this study is to assess the effect of industrial transfer policy on the air quality in WCB. Firstly, we used the surface in situ NO2 concentrations to compare with the OMI-retrieved tropospheric NO2 columns in order to verify the accuracy of the satellite data over the WCB area. Although it is difficult to compare the two datasets directly, the comparison results prove the accuracy of the OMI-retrieved tropospheric NO2 columns in cities of WCB. Then, the spatial distributions of the annual averaged tropospheric NO2 total columns over Anhui Province show that NO2 columns were considerably higher in WCB than those in other areas of Anhui. Also, we compared the spatial distributions of the total NO2 columns in 2005 through 2010 and in 2011 through 2016 and found that the total NO2 columns in WCB increased by 19.9%, while the corresponding value increased only 13.9% in other Anhui areas except the WCB area. Furthermore, the temporal variations of NO2 columns show that although the NO2 columns over WCB and Anhui increased significantly from 2005 to 2011, they decreased sharply from 2011 to 2016 due to the strict emission reduction measures in China. Finally, the HYSPLIT model was used to analyze the origins of NO2 and transport pathways of air masses in a typical city, Ma’anshan city.
Effects of Valproate Monotherapy on the Oxidant‐Antioxidant Status in Mexican Epileptic Children: A Longitudinal Study
Authors: Beltrán-Sarmiento Eduardo , Arregoitia-Sarabia Cindy K. , Floriano-Sánchez Esaú , Sandoval-Pacheco Roberto , Galván-Hernández Diana E. , Coballase-Urrutia Elvia , Carmona-Aparicio Liliana , Ramos-Reyna Eduardo , Rodríguez-Silverio Juan , Cárdenas-Rodríguez Noemí
Published: December 2018

Epilepsy is a neurological disorder that can produce brain injury and neuronal death. Several factors such as oxidative stress have been implicated in epileptogenesis. Valproic acid (VPA) is a widely used drug for the treatment of epilepsy, but the mechanisms underlying these benefits are complex and still not fully understood. The objective of this study was to evaluate, for the first time, the effects of VPA on the oxidant‐antioxidant status in Mexican epileptic children before and after 6 or 12 months of treatment with VPA by determining the activities of several plasmatic antioxidant enzymes (glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT)) and oxidant marker (malondialdehyde (MDA), hydrogen peroxide (H2O2), 8‐hydroxy‐2‐deoxyguanosine (8‐OHdG), and 3‐nitrotyrosine (3‐NT) levels) profiles. The possible relationships between these markers and some clinicopathological factors were also evaluated. Plasma samples were obtained from the peripheral blood of 16 healthy children and 32 patients diagnosed with epilepsy, and antioxidant/oxidant markers were measured spectrometrically. Significant decreases in all antioxidant enzyme activities, with the exception of GPx, and increases in all oxidant markers in epileptic subjects versus healthy children were observed. Interestingly, all these effects reverted after VPA monotherapy, although the results were different depending on the treatment period (6 or 12 months). These changes were contingent upon brain imaging findings, type of epilepsy, etiology of epilepsy, and the efficacy of 6 months of VPA monotherapy. Significant and positive correlations of GPx and SOD activities and H2O2 and 8‐OHdG levels with the age of children at the beginning of treatment were observed. H2O2 levels were also positively correlated with number of seizures before VPA monotherapy. VPA showed significant antioxidant effects decreasing seizure activity, possibly depending on the presence of cerebral structural alterations, treatment time, and age.
Stepanov-Like Asymptotical Almost Periodic Functions and an Application
Authors: Li Yongkun , Wang Yaolu , Xiang Jianglian
Published: December 2018

In this paper, we first study some basic properties of Stepanov-like asymptotical almost periodic functions including the completeness of the space of Stepanov-like asymptotical almost periodic functions. Then, as an application, based on these and the contraction mapping principle, we obtain sufficient conditions for the existence and uniqueness of Stepanov-like asymptotical almost periodic solutions for a class of semilinear delay differential equations.
Detection Method for Distributed Web-Crawlers: A Long-Tail Threshold Model
Authors: Ro Inwoo , Han Joong Soo , Im Eul Gyu
Published: December 2018

This paper proposes an advanced countermeasure against distributed web-crawlers. We investigated other methods for crawler detection and analyzed how distributed crawlers can bypass these methods. Our method can detect distributed crawlers by focusing on the property that web traffic follows the power distribution. When we sort web pages by the number of requests, most of requests are concentrated on the most frequently requested web pages. In addition, there will be some web pages that normal users do not generally request. But crawlers will request for these web pages because their algorithms are intended to request iteratively by parsing web pages to collect every item the crawlers encounter. Therefore, we can assume that if some IP addresses are frequently used to request the web pages that are located in the long-tail area of a power distribution graph, those IP addresses can be classified as crawler nodes. The experimental results with NASA web traffic data showed that our method was effective in identifying distributed crawlers with 0.0275% false positives when a conventional frequency-based detection method shows 2.882% false positives with an equal access threshold.
Analysis of Noise Characteristics of Multichannel Systems of the Formation of Signals of Georadars with Synthesized Aperture
Authors: Kuzichkin Oleg R. , Surzhik Dmitriy I. , Vasiliev Gleb S. , Kurilov Igor A. , Dorofeev Nikolai V.
Published: December 2018

The noise characteristics of multichannel systems of forming signals based on hybrid frequency synthesizers with automatic compensation of phase distortions of direct digital synthesizers, which are used in the composition of georadars with synthesized aperture, are investigated. It is established that the phase noise of the output signals of the formers at the 1 kHz detuning from the carrier oscillation at the output frequencies of the devices in the range from 500 to 3500 MHz is characterized by a level of minus 100 - minus 130 dB. In this case, the circuit of the signal former based on a hybrid frequency synthesizer with direct digital synthesizer as a reference oscillator of a phase locked loop is characterized by the worst noise characteristics but with the highest degree of autocompensation (about 13 dB). Conversely, the circuit of the signal former based on a hybrid frequency synthesizer with direct digital synthesizer as a support generator of the phase-locked loop has the best phase noises level from the considered variants of devices and least degree of autocompensation (about 6 dB).
Indicators of Male Gout Patients’ Comorbidities with the Theory on Traditional Chinese Medicine
Authors: Zhang Jianyong , Zhang Siyang , Xie Jingjing , Tang Li , Qiu Xia , Xiao Yuya , Zhang Yanying , Jia Ertao , Ma Xu , Wang Binbin
Published: December 2018

Gout, typically manifesting as acute burning pain and swelling in a joint, has a high frequency of comorbidities. Based on Traditional Chinese Medicine syndrome (TCMS) theory, obstruction of dampness and heat syndrome (ODHS) and intermingled phlegm‐stasis blood syndrome (IPSBS) were the two main TCMS subtypes in Chinese suffering from acute gout. In this study, we did a retrospective study enrolling 4,417 ODHS male gout cases and 1,413 IPSBS male gout cases, to investigate the comorbidities distribution difference between the two subtype groups and seek the potential indicators of male gout with some comorbidities. Interestingly, we found male ODHS group with higher prevalence of possible kidney damage (ODHS: 4.34%; IPSBS: 0.78%), lower prevalence of cardiac‐cerebral vascular diseases (ODHS: 0.52%, IPSBS: 0.85%) and diabetes (ODHS: 1.06%; IPSBS: 1.63%) than male IPSBS group. And cystatin C is the only index reflecting that renal function showed significant difference between the two groups and the average levels were out of the normal range (1.09 ± 0.28 versus 1.17 ± 0.31, p=0.001). Further, we also observed significance difference on abnormality rates of cystatin C between the two groups. (χ2=5.543, p= 0.019). Besides, the comparison between the two subtypes also showed significant difference on hematocrit (43.12 ± 3.60 versus 42.26 ± 4.17%, p=0.007), mean corpuscular volume (89.52 ± 6.07 versus 86.81 ± 7.11fL, p=0.001), and mean corpuscular hemoglobin concentration (338.00 ± 11.67 versus 334.86 ± 13.58g/L, p=0.004). In general, we put forward that male gout patients with ODHS should be more vigilant of damage of renal function, and those with IPSBS should pay more attention to prevent cardiac‐cerebral vascular diseases and diabetes. Increased Cys C level might be correlated with risk of comorbidities, especially diabetes . Thus, it is of significance to diagnose the TCMS in acute gout accurately and monitored related indices to prevent comorbidities.
CML Hematopoietic Stem Cells Expressing IL1RAP Can Be Targeted by Chimeric Antigen Receptor–Engineered T Cells
Authors: Warda Walid , Larosa Fabrice , Neto Da Rocha Mathieu , Trad Rim , Deconinck Eric , Fajloun Ziad , Faure Cyril , Caillot Denis , Moldovan Marius , Valmary-Degano Severine , Biichle Sabeha , Daguindau Etienne , Garnache-Ottou Francine , Tabruyn Sebastien , Adotevi Olivier , Deschamps Marina , Ferrand Christophe
Published: December 2018

Chronic myeloid leukemia (CML) is a chronic disease resulting in myeloid cell expansion through expression of the BCR-ABL1 fusion transcript. Tyrosine kinase inhibitors (TKI) have significantly increased survival of patients with CML, and deep responders may consider stopping the treatment. However, more than 50% of patients relapse and restart TKI, subsequently suffering unknown toxicity. Because CML is a model immune system–sensitive disease, we hypothesize that chimeric antigen receptor (CAR) T cells targeting IL1 receptor-associated protein (IL1RAP) in quiescent CML stem cells may offer an opportunity for a permanent cure. In this study, we produced and molecularly characterized a specific monoclonal anti-IL1RAP antibody from which fragment antigen-binding nucleotide coding sequences were cloned as a single chain into a lentiviral backbone and secured with the suicide gene iCASP9/rimiducid system. Our CAR T-cell therapy exhibited cytotoxicity against both leukemic stem cells and, to a lesser extent, monocytes expressing IL1RAP, with no apparent effect on the hematopoietic system, including CD34+ stem cells. This suggests IL1RAP as a tumor-associated antigen for immunotherapy cell targeting. IL1RAP CAR T cells were activated in the presence of IL1RAP+ cell lines or primary CML cells, resulting in secretion of proinflammatory cytokines and specifically killing in vitro and in a xenograft murine model. Overall, we demonstrate the proof of concept of a CAR T-cell immunotherapy approach in the context of CML that is applicable for young patients and primary TKI-resistant, intolerant, or allograft candidate patients.

Significance:

These findings present the first characterization and proof of concept of a chimeric antigen receptor directed against IL1RAP expressed by leukemic stem cells in the context of CML.
Mantle Cell Lymphoma Case Report
Authors: Podzolkov V.I. , Vargina T.S. , Pokrovskaya A.E. , Safronova T.A. , Abramova A.A.
Published: December 2018

Introduction: Due to the beginning of the use of immunophenotypic and cytogenetic techniques, new nosological forms of lymphoproliferative diseases have appeared over the past few decades. According to the WHO classification (2008), today there are more than 50 known lymphoproliferative diseases. Case Presentation: We present the case of a 51-year-old man with lymphoproliferative syndrome. Our patient underwent morphological and immunohistochemical investigations of biopsy materials from the right inguinal lymph node. The morphological picture was characteristic for small cell lymphoma. Immunophenotypically, tumor proliferate cells expressed CD20, CD76b, CD5, and cyclin D, and the tumor immunophenotype matched mantle cell lymphoma. Discussion: At the present stage of the development of medicine, the diagnosis of lymphoproliferative diseases is based on the clinical picture of the disease with the definition of localization and characteristics of the tumor process, morphological study of tumor tissue and cells, and immunophenotypic and/or cytogenetic analyses are mandatory to determine the final diagnosis.
Evidence for Incomplete Neutralization in Chilean Spanish
Authors: Bolyanatz Mariška A.
Published: December 2018

Background/Aims:In Chilean Spanish, syllable- and word-final /s/ are frequently weakened to an [h]-like segment or completely deleted. In word-final position, /s/ serves as the plural morpheme, so its deletion renders a site for potential neutralization with singular items. Chilean scholars have previously described differences in the vowel preceding weakened or deleted /s/ distinguishing it from non-/s/-final words, but this putative incomplete neutralization has not yet been acoustically verified, nor have its conditioning factors been explored. The primary purpose of this study was to assess via phonetic analysis of spontaneous speech whether neutralization of final vowels in singular words and plural words in Chilean Spanish is indeed incomplete, as hypothesized by scholars during the 20th century. Additionally, these vowels were also compared to the vowels of monomorphemic /s/-final words in order to ensure that the attested singular-versus-plural differences were not simply indicative of closed syllable laxing processes.Methods:Vowels were extracted from the spontaneous speech of 20 Chilean Spanish speakers and acoustically analyzed via VoiceSauce.Results:The results revealed that final /a/ vowels of plural words were found to be breathier than singular vowels but less breathy than the final vowels of monomorphemic words, and that plural /o/ was significantly fronted. They also demonstrated increased breathiness on /e/ vowels closed by /s/, regardless of morphological status.Conclusion:These results provide the first account of incomplete neutralization of plural vowel correlates in spontaneous speech in Chilean Spanish, and they offer evidence for closed syllable processes in this particular dialect, in alignment with an exemplar-theoretic approach.
An Investigation of Reliability of the Sunderland Tracheosophageal Voice Perceptual Scale
Authors: Coffey Margaret M. , Tolley Neil , Howard David , Hickson Mary
Published: December 2018

Background: The Sunderland Tracheosophageal Voice Perceptual scale (SToPS) is the only perceptual rating scale designed specifically for tracheosophageal voice [Hurren et al.: Clin Otolaryngol. 2009 Dec; 34(6): 533–8]. Objective: To investigate the inter rater reliability of the SToPS when analyzing alaryngeal voice. Methods: Prospective evaluation of inter rater reliability of the SToPS based on audio recordings of 230 voice samples from 41 laryngectomy patients rated by 3 experts. Interval data were analyzed using intraclass correlation coefficients (ICC) while categorical data were analyzed using Kappa. Results: ICC of above 0.6 was observed between raters for each prosthesis on a majority of parameters demonstrating a good level of reliability. Reliability was fair (ICC of between 0.40 and 0.59) on Q11 (Articulatory precision) and Q12 (Paralinguistics). Reliability was also fair (0.21–0.40) or slight (0.00–0.20) for Q2 (Tonicity), which was analyzed using Kappa. Kappa above 0.61 signified a good level of reliability. Conclusions: This study demonstrates good rater reliability for the majority of parameters on the SToPS scale, supporting the use of this tool within the clinical realm. However, further research is required to ascertain if any methods of increasing inter rater reliability on those parameters which did not reach good reliability can be identified.
The Tubular Damage Markers: Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 in Newborns with Intrauterine Growth Restriction
Authors: Kamianowska Monika , Szczepański Marek , Kulikowska Elżbieta Ewa , Bebko Barbara , Wasilewska Anna
Published: December 2018

Background: Intrauterine growth restriction (IUGR) is a poorly understood complication of pregnancy. It may be associated with various diseases in adulthood, such as hypertension, cardiovascular disease, insulin resistance, and end-stage renal disease. Objectives: The aim of this study was to check whether IUGR affects the function of renal tubules, as assessed by the tubular damage markers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1). Methods: The study included 126 term neonates. Thirty-eight newborns were the result of pregnancies complicated by IUGR. Eighty-eight healthy newborns were the result of normal pregnancies with no prenatal or perinatal complications. The concentrations of urinary NGAL and KIM-1 were determined with a commercially available ELISA kit and were normalized for urinary creatinine (Cr) concentration. Results: We found a significantly higher urinary concentration of NGAL and NGAL/Cr ratio in newborns from pregnancies complicated by IUGR when compared to the reference group. We found that female gender was associated with a higher concentration of urinary NGAL and also urinary NGAL/Cr. Conclusions: This is the first work that demonstrates that urinary NGAL concentration and urinary NGAL/Cr are significantly higher in infants that are small for gestational age than in appropriate-for-gestational-age infants. This might indicate subclinical kidney damage in newborns with IUGR.