bluuebunny/crossref_metadata_2025 huggingface dataset:
Αcute effects of essential amino acid gel-based and whey protein supplements on appetite and energy intake in older women
Authors: Butterworth Mathew , Lees Matthew , Harlow Paul , Hind Karen , Duckworth Lauren , Ispoglou Theocharis
Published: March 2019

Deficiencies in protein and energy intakes are partly responsible for age-related sarcopenia. We investigated the effects of supplements matched in essential amino acid (EAA) content (7.5 g) on energy intake and appetite. Ten women aged 69.2 ± 2.7 years completed 3 trials in a randomised, crossover design. Composite appetite scores, peptide-YY (PYY), and insulin responses to a 200-mL whey protein (WP) isolate (275 kJ), a 50-mL EAA gel (GEL, 478 kJ), or nothing as the control (CON) condition were investigated over 1 h, followed by an ad libitum breakfast. Energy intake at breakfast (CON, 1957 ± 713; WP, 1413 ± 623; GEL, 1963 ± 611 kJ) was higher in CON and GEL than in WP (both P = 0.006). After accounting for supplement energy content, energy intake in GEL was higher than in CON (P = 0.0006) and WP (P = 0.0008). Time-averaged area under the curve for composite appetite scores (CON, 74 ± 20; WP, 50 ± 22; GEL, 60 ± 16 mm) was higher in CON than WP (P = 0.015). Time-averaged area under the curve for PYY (CON, 87 ± 13; WP, 119 ± 27; GEL, 97 ± 22 pg·mL−1) was higher in WP than CON (P = 0.009) and GEL (P = 0.012). In conclusion, supplementation with WP facilitated an increase in protein intake, whereas supplementation with GEL increases in both energy and protein intakes, when consumed before an ad libitum breakfast. Such findings highlight potential gel-based EAA supplementation intake for addressing age-related sarcopenia.
Influence of latent attitudinal factors on the multimodality of post-secondary students in Toronto
Authors: Lin TianYang , Hasnine Sami , Habib Khandker M. Nurul
Published: March 2019

The study explores the causal relationships between latent factors and various observed external variables along with their ability to explain multimodal behaviours of post-secondary students in Toronto. Multimodality was measured by the number of unique modes used by any individual for their daily travels. As opposed to using a single mode of transportation, use of multiple modes for different trips indicates the degree and the nature of multimodality. For the empirical investigation, the study uses structural equation modelling and ordered probability modelling for a dataset collected through a large-scale travel diary survey among four major universities in Toronto representing over 180 000 post-secondary students in the region. The results of the empirical investigation reveal that latent attitudes are influential factors in determining the multimodal behaviour of post-secondary students in Toronto. The results also found that mobility tool ownership and land use characteristics have a significant influence on those latent attitudes, and are direct determinants of the degree of multimodality. In particular, the results indicate that smart fare payment cards have a considerable effect on latent attitudes for post-secondary students. These findings could have policy implication from the planning perspective and should warrant further investigations.
Descriptional Complexity of the Forever Operator
Authors: Hospodár Michal , Jirásková Galina , Mlynárčik Peter
Published: March 2019

We examine the descriptional complexity of the forever operator, which assigns the language [Formula: see text] to a regular language [Formula: see text], and we investigate the trade-offs between various models of finite automata. We consider complete and partial deterministic finite automata, nondeterministic finite automata with single or multiple initial states, alternating, and Boolean finite automata. We assume that the argument and the result of this operation are accepted by automata belonging to one of these six models. We investigate all possible trade-offs and provide a tight upper bound for 32 of 36 of them. The most interesting result is the trade-off from nondeterministic to deterministic automata given by the Dedekind number [Formula: see text]. We also prove that the nondeterministic state complexity of [Formula: see text] is [Formula: see text] which solves an open problem stated by Birget [The state complexity of [Formula: see text] and its connection with temporal logic, Inform. Process. Lett. 58 (1996) 185–188].
Vanishing shear viscosity limit and boundary layer study for the planar MHD system
Authors: Qin Xulong , Yang Tong , Yao Zheng-an , Zhou Wenshu
Published: March 2019

We consider an initial boundary problem for the planar MHD system under the general condition on the heat conductivity coefficient that depends on both the temperature and the density. Firstly, the global existence of strong solution for large initial data is obtained, and then the limit of the vanishing shear viscosity is justified. In addition, the [Formula: see text] convergence rate is obtained together with the estimation on the thickness of the boundary layer.
A FORWARD EQUATION FOR COMPUTING DERIVATIVES EXPOSURE
Authors: LAPEYRE BERNARD , TAARIT MAROUAN IBEN
Published: March 2019

We derive a forward equation for computing the expected exposure of financial derivatives. Under general assumptions about the underlying diffusion process, we give an explicit decomposition of the exposure into an intrinsic value which can be directly deduced from the term structure of the forward mark-to-market, and a time value which expresses the variability of the future mark-to-market. Our approach is inspired by Dupire’s equation for local volatility and leads to an ordinary differential equation qualifying the evolution of the expected exposure with respect to the observation dates. We show how this approach can be linked with local times theory in dimension one and to the co-area formula in a higher dimension. As for numerical considerations, we show how this approach leads to an efficient numerical method in the case of one or two risk factors. The accuracy and time-efficiency of this forward representation in small dimension are of special interest in benchmarking XVA valuation adjustments at trade level.
Germs and semigroup representation theory
Authors: Guo Junying , Guo Xiaojiang , Liu Yangqing , Shum Kar Ping
Published: March 2019

Uniform representation of semigroups is introduced. It is proved that any uniform representation of an ample semigroup can be expressed as the direct sum of some representations obtained via homogenous representations on primitive adequate semigroups. Also, we give the structure of homogenous representations of primitive adequate semigroups. In addition, we consider indecomposable uniform representations of ample semigroups and their constructions.
Interval-based memory reclamation
Authors: Wen Haosen , Izraelevitz Joseph , Cai Wentao , Beadle H. Alan , Scott Michael L.
Published: March 2019

In this paper we present
interval-based reclamation
(IBR), a new approach to safe reclamation of disconnected memory blocks in nonblocking concurrent data structures. Safe reclamation is a difficult problem: a thread, before freeing a block, must ensure that no other threads are accessing that block; the required synchronization tends to be expensive. In contrast with epoch-based reclamation, in which threads reserve all blocks created after a certain time, or pointer-based reclamation (e.g., hazard pointers), in which threads reserve individual blocks, IBR allows a thread to reserve all blocks known to have existed in a bounded
interval
of time. By comparing a thread's reserved interval with the lifetime of a detached but not yet reclaimed block, the system can determine if the block is safe to free. Like hazard pointers, IBR avoids the possibility that a single stalled thread may reserve an unbounded number of blocks; unlike hazard pointers, it avoids a memory fence on most pointer-following operations. It also avoids the need to explicitly "unreserve" a no-longer-needed pointer.

We describe three specific IBR schemes (one with several variants) that trade off performance, applicability, and space requirements. IBR requires no special hardware or OS support. In experiments with data structure microbenchmarks, it also compares favorably (in both time and space) to other state-of-the-art approaches, making it an attractive alternative for libraries of concurrent data structures.
Superneurons
Authors: Wang Linnan , Ye Jinmian , Zhao Yiyang , Wu Wei , Li Ang , Song Shuaiwen Leon , Xu Zenglin , Kraska Tim
Published: March 2019

Going deeper and wider in neural architectures improves their accuracy, while the limited GPU DRAM places an undesired restriction on the network design domain. Deep Learning (DL) practitioners either need to change to less desired network architectures, or nontrivially dissect a network across multiGPUs. These distract DL practitioners from concentrating on their original machine learning tasks. We present SuperNeurons: a dynamic GPU memory scheduling runtime to enable the network training far beyond the GPU DRAM capacity. SuperNeurons features 3 memory optimizations,
Liveness Analysis, Unified Tensor Pool
, and
Cost-Aware Recomputation
; together they effectively reduce the network-wide peak memory usage down to the maximal memory usage among layers. We also address the performance issues in these memory-saving techniques. Given the limited GPU DRAM, SuperNeurons not only provisions the necessary memory for the training, but also dynamically allocates the memory for convolution workspaces to achieve the high performance. Evaluations against Caffe, Torch, MXNet and TensorFlow have demonstrated that SuperNeurons trains at least 3.2432 deeper network than current ones with the leading performance. Particularly, SuperNeurons can train ResNet2500 that has 10
4
basic network layers on a 12GB K40c.
HPVM
Authors: Kotsifakou Maria , Srivastava Prakalp , Sinclair Matthew D. , Komuravelli Rakesh , Adve Vikram , Adve Sarita
Published: March 2019

We propose a parallel program representation for heterogeneous systems, designed to enable performance portability across a wide range of popular parallel hardware, including GPUs, vector instruction sets, multicore CPUs and potentially FPGAs. Our representation, which we call HPVM, is
a hierarchical dataflow graph with shared memory and vector instructions.
HPVM supports three important capabilities for programming heterogeneous systems: a compiler intermediate representation (IR), a virtual instruction set (ISA), and a basis for runtime scheduling; previous systems focus on only one of these capabilities. As a compiler IR, HPVM aims to enable effective code generation and optimization for heterogeneous systems. As a virtual ISA, it can be used to ship executable programs, in order to achieve both functional portability and performance portability across such systems. At runtime, HPVM enables flexible scheduling policies, both through the graph structure and the ability to compile individual nodes in a program to any of the target devices on a system. We have implemented a prototype HPVM system, defining the HPVM IR as an extension of the LLVM compiler IR, compiler optimizations that operate directly on HPVM graphs, and code generators that translate the virtual ISA to NVIDIA GPUs, Intel's AVX vector units, and to multicore X86-64 processors. Experimental results show that HPVM optimizations achieve significant performance improvements, HPVM translators achieve performance competitive with manually developed OpenCL code for both GPUs and vector hardware, and that runtime scheduling policies can make use of both program and runtime information to exploit the flexible compilation capabilities. Overall, we conclude that the HPVM representation is a promising basis for achieving performance portability and for implementing parallelizing compilers for heterogeneous parallel systems.
Lazygraph
Authors: Wang Lei , Zhuang Liangji , Chen Junhang , Cui Huimin , Lv Fang , Liu Ying , Feng Xiaobing
Published: March 2019

Replicas
1
of a vertex play an important role in existing distributed graph processing systems which make a single vertex to be parallel processed by multiple machines and access remote neighbors locally without any remote access. However, replicas of vertices introduce data coherency problem. Existing distributed graph systems treat replicas of a vertex v as an atomic and indivisible vertex, and use an eager data coherency approach to guarantee replicas atomicity. In eager data coherency approach, any changes to vertex data must be immediately communicated to all replicas of v, thus leading to frequent global synchronizations and communications.

In this paper, we propose a lazy data coherency approach, called LazyAsync, which treats replicas of a vertex as independent vertices and maintains the data coherency by computations, rather than communications in existing eager approach. Our approach automatically selects some data coherency points from the graph algorithm, and maintains all replicas to share the same global view only at such points, which means the replicas are enabled to maintain different local views between any two adjacent data coherency points. Based on PowerGraph, we develop a distributed graph processing system LazyGraph to implement the LazyAsync approach and exploit graph-aware optimizations. On a 48-node EC2-like cluster, LazyGraph outperforms PowerGraph on four widely used graph algorithms across a variety of real-world graphs, with a speedup ranging from 1.25x to 10.69x.
PAM
Authors: Sun Yihan , Ferizovic Daniel , Belloch Guy E.
Published: March 2019

Ordered (key-value) maps are an important and widely-used data type for large-scale data processing frameworks. Beyond simple search, insertion and deletion, more advanced operations such as range extraction, filtering, and bulk updates form a critical part of these frameworks.

We describe an interface for ordered maps that is augmented to support fast range queries and sums, and introduce a parallel and concurrent library called PAM (Parallel Augmented Maps) that implements the interface. The interface includes a wide variety of functions on augmented maps ranging from basic insertion and deletion to more interesting functions such as union, intersection, filtering, extracting ranges, splitting, and range-sums. We describe algorithms for these functions that are efficient both in theory and practice.

As examples of the use of the interface and the performance of PAM we apply the library to four applications: simple range sums, interval trees, 2D range trees, and ranked word index searching. The interface greatly simplifies the implementation of these data structures over direct implementations. Sequentially the code achieves performance that matches or exceeds existing libraries designed specially for a single application, and in parallel our implementation gets speedups ranging from 40 to 90 on 72 cores with 2-way hyperthreading.
Efficient parallel determinacy race detection for two-dimensional dags
Authors: Xu Yifan , Lee I-Ting Angelina , Agrawal Kunal
Published: March 2019

A program is said to have a determinacy race if logically parallel parts of a program access the same memory location and one of the accesses is a write. These races are generally bugs in the program since they lead to non-deterministic program behavior --- different schedules of the program can lead to different results. Most prior work on detecting these races focuses on a subclass of programs with fork-join parallelism.

This paper presents a race-detection algorithm, 2D-Order, for detecting races in a more general class of programs, namely programs whose dependence structure can be represented as planar dags embedded in 2D grids. Such dependence structures arise from programs that use pipelined parallelism or dynamic programming recurrences. Given a computation with
T
1
work and
T
∞
span, 2D-Order executes it while also detecting races in
O
(
T
1
/
P
+
T
∞
) time on
P
processors, which is asymptotically optimal.

We also implemented PRacer, a race-detection algorithm based on 2D-Order for Cilk-P, which is a language for expressing pipeline parallelism. Empirical results demonstrate that PRacer incurs reasonable overhead and exhibits scalability similar to the baseline (executions without race detection) when running on multiple cores.
Shared-memory parallelization of MTTKRP for dense tensors
Authors: Hayashi Koby , Ballard Grey , Jiang Yujie , Tobia Michael J.
Published: March 2019

The matricized-tensor times Khatri-Rao product (MTTKRP) is the computational bottleneck for algorithms computing CP decompositions of tensors. In this work, we develop shared-memory parallel algorithms for MTTKRP involving dense tensors. The algorithms cast nearly all of the computation as matrix operations in order to use optimized BLAS subroutines, and they avoid reordering tensor entries in memory. We use our parallel implementation to compute a CP decomposition of a neuroimaging data set and achieve a speedup of up to 7.4X over existing parallel software.
Revealing parallel scans and reductions in sequential loops through function reconstruction
Authors: Jiang Peng , Agrawal Gagan
Published: March 2019

Many sequential loops are actually scans or reductions and can be parallelized across iterations despite the loop-carried dependences. In this work, we consider the parallelization of such scan/reduction loops, and propose a practical runtime approach called
sampling-and-reconstruction
to extract the hidden scan/reduction patterns in these loops.
Performance modeling for GPUs using abstract kernel emulation
Authors: Hong Changwan , Sukumaran-Rajam Aravind , Kim Jinsung , Rawat Prashant Singh , Krishnamoorthy Sriram , Pouchet Louis-Noël , Rastello Fabrice , Sadayappan P.
Published: March 2019

Performance modeling of GPU kernels is a significant challenge. In this paper, we develop a novel approach to performance modeling for GPUs through abstract kernel emulation along with latency/gap modeling of resources. Experimental results on all benchmarks from the Rodinia suite demonstrate good accuracy in predicting execution time on multiple GPU platforms.
Two concurrent data structures for efficient datalog query processing
Authors: Jordan Herbert , Scholz Bernhard , Subotic Pavle
Published: March 2019

In recent years, Datalog has gained popularity for the implementation of advanced data analysis. Applications benefit from Datalog's high-level, declarative syntax, and availability of efficient algorithms for computing solutions. The efficiency of Datalog engines has reached a point where engines such as Soufflé have reported performance results comparable to low-level hand-crafted alternatives [3].
Transparent GPU memory management for DNNs
Authors: Park Jungho , Cho Hyungmin , Jung Wookeun , Lee Jaejin
Published: March 2019

Modern DNN frameworks exploit GPU acceleration by default to achieve high performance. The limitation of GPU memory capacity becomes a serious problem because DNNs are becoming deeper and larger. This paper proposes a purely software-based transparent solution, called tvDNN, to the GPU memory capacity problem. It is based on GPU memory swapping and memory object sectioning techniques. It also provides an efficient memory-object swapping schedule based on ILP (optimal) and heuristics (suboptimal). The experimental results show that tvDNN enables Caffe to build VGG-16 with a large batch size, such as 256 or 512, using a few GB of GPU memory without significant performance degradation.
The Political Theory of Universal Basic Income
Authors: Bidadanure Juliana Uhuru
Published: March 2019

Universal basic income (UBI) is a radical policy proposal of a monthly cash grant given to all members of a community without means test, regardless of personal desert, with no strings attached, and, under most proposals, at a sufficiently high level to enable a life free from economic insecurity. Once a utopian proposal, the policy is now widely discussed and piloted throughout the world. Among the various objections to the proposal, one concerns its moral adequacy: Isn't it fundamentally unjust to give cash to all indiscriminately rather than to those who need it and deserve it? This article reviews the variety of strategies deployed by political theorists to posit that the proposal is in fact justified, or even required, by social justice. The review focuses mainly on the contemporary normative debate on UBI—roughly dating back to Philippe Van Parijs's influential work in the 1990s—and is centered on the ideals of freedom and equality.
Moral Cultures, Reputation Work, and the Politics of Scandal
Authors: Alan Fine Gary
Published: March 2019

Status has long been a core concept motivating sociology as a discipline. As related to the positioning and valuing of individuals, status often takes the form of reputation. How is an individual treated as a cultural object with identity provided by those who have reason to judge? Reputation may be given to known individuals, to those who are widely celebrated within a society, and to those whose past achievements are worth recalling through institutionalized forms of memory. Not all reputations are positive, and individuals may be remembered for misdeeds or violations of norms as embedded in the recall of scandal, political and otherwise. Both reputation and scandal have effects within the interaction order, local group cultures, and institutional structures, including media. As consensus develops, the linkages of individuals and their known status shape shared conceptions of morality.
Physiology is hard: a replication study of students’ perceived learning difficulties
Authors: Slominski Tara , Grindberg Sarah , Momsen Jennifer
Published: March 2019

Human Anatomy and Physiology (HAP) has long been recognized as a difficult course. A 2007 study (Michael J. Adv Physiol Educ 31: 34–40, 2007) sought to better understand this difficulty by asking faculty for their perceptions of why students struggle to learn in HAP. Later research built on these findings by investigating why students find physiology difficult (Sturges D, Maurer T. Internet J Allied Health Sci Pract 11: 1–10, 2013). However, without replication, these claims are limited in their generalizability. There is a need in physiology education research to replicate studies like these across different institutions to support generalizations. We, therefore, replicated both of these studies by collecting survey responses from 466 students at 4 different institutions and 17 instructors at 15 different institutions. We found that students in our study identified similar factors as the students surveyed in the original study. Students most strongly agreed with items that attributed the difficulty of HAP to the nature of the discipline, as opposed to the way physiology is taught or the way students approach learning it. Faculty in our sample, like those in the original study by Michael, agreed most strongly with items that attributed physiology’s difficulty to discipline specific factors. Our data reinforce the results of Sturges and Maurer and Michael. We can more confidently claim that HAP students and faculty believe the difficulty in learning physiology is the result of inherent features of the discipline itself and not factors related to instruction or the students themselves.
Combining novel research and community-engaged learning in an undergraduate physiology laboratory course
Authors: Woodley Sarah K. , Freeman Peter E. , Ricketts Tiffany D.
Published: March 2019

To better prepare physiology students for 21st century careers, we incorporated classroom-based undergraduate research experiences and service learning/community-engaged learning (SLCE) into a college-level physiology laboratory course. The interventions were incorporated over 4 yr and assessed using validated surveys of student-reported learning gains related to attitudes toward science, the scientific process, and career paths. Students reported the greatest learning gains in those years when students did novel research oriented around a common theme of water quality. The gains were greater than those of a matched cohort that participated in an apprentice-style summer undergraduate research experience. With respect to the SLCE related to youth science literacy, students provided evidence of learning related to academics, personal growth, and civic mindedness. For example, many expressed discomfort about being in a new situation, often describing the differences between themselves and the youth with whom they interacted. However, students also grew in confidence about collaborating with people who were different from them and in their role as the “scientist.” Limitations of the study include the quasi-experimental design and the incorporation of multiple interventions at the same time. Future studies should examine improvement in content acquisition and competency-based learning skills. Nonetheless, these results suggest that both novel research and SLCE increase student learning in the context of an undergraduate physiology laboratory course. Many of the learning gains observed with the SLCE are particularly important for physiology students, many of whom aspire to careers in health sciences, where they will be regularly working with nonscientists.
Apelin is a novel regulator of human trophoblast amino acid transport
Authors: Vaughan O.R. , Powell T.L. , Jansson T.
Published: March 2019

Apelin is an insulin-sensitizing hormone increased in abundance with obesity. Apelin and its receptor, APJ, are expressed in the human placenta, but whether apelin regulates placental function in normal body mass index (BMI) and obese pregnant women remains unknown. We hypothesized that apelin stimulates amino acid transport in cultured primary human trophoblast (PHT) cells and that maternal circulating apelin levels are elevated in obese pregnant women delivering large babies. Treating PHT cells with physiological concentrations of the pyroglutamated form [Pyr1]apelin-13 (0.1–10.0 ng/ml) for 24 h dose-dependently increased System A amino acid transport ( P < 0.05) but did not affect System L transport activity. Mechanistic target of rapamycin (mTOR), extracellular signal-regulated kinase-1/2 (ERK1/2), and AMP-activated protein kinase-α (AMPKα) signaling were unaffected by apelin ( P > 0.05). Plasma apelin was not different in obese women (BMI 35.8 ± 0.7, n = 21) with large babies compared with normal-BMI women (23.1 ± 0.5, n = 16) delivering normal birth weight infants. Apelin was highly expressed in placental villous tissue (20-fold higher vs. adipose), and APJ was present in syncytiotrophoblast microvillous membrane, but neither differed in abundance between normal-BMI and obese women. Phosphorylation (Thr172) of placental AMPKα strongly correlated with microvillous membrane APJ expression ( P < 0.01, R = 0.63) but negatively correlated with placental apelin abundance ( P < 0.01, R = −0.62). Neither placental APJ nor apelin abundance correlated with maternal BMI, plasma insulin, birth weight, or mTOR or ERK1/2 signaling ( P > 0.05). Hence, apelin stimulates trophoblast amino acid uptake, establishing a novel mechanism regulating placental function. We found no evidence that apelin constitutes an endocrine link between maternal obesity and fetal overgrowth.
Impact of GPR1 signaling on maternal high-fat feeding and placenta metabolism in mice
Authors: Huang Binbin , Huang Chen , Zhao Huashan , Zhu Wen , Wang Baobei , Wang Hefei , Chen Jie , Xiao Tianxia , Niu Jianmin , Zhang Jian
Published: March 2019

Chemerin and G protein-coupled receptor 1 (GPR1) are increased in serum and placenta in mice during pregnancy. Interestingly, we observed increased serum chemerin levels and decreased GPR1 expression in placenta of high-fat-diet-fed mice compared with chow-fed mice at gestational day 18. GPR1 protein and gene levels were significantly decreased in gestational diabetes mellitus (GDM) patient placentas. Therefore, we hypothesized that chemerin/GPR1 signaling might participate in the pathogenic mechanism of GDM. We investigated the role of GPR1 in carbohydrate homeostasis during pregnancy using pregnant mice transfected with small interfering RNA for GPR1 or a negative control. GPR1 knockdown exacerbated glucose intolerance, disrupted lipid metabolism, and decreased β-cell proliferation and insulin levels. Glucose transport protein-3 and fatty acid binding protein-4 were downregulated with reducing GPR1 in vivo and in vitro via phosphorylated AKT pathway. Taken together, our findings first demonstrate the expression of GPR1, the characterization of its direct biological effects in humans and mice, as well as the molecular mechanism that indicates the role of GPR1 signaling in maternal metabolism during pregnancy, suggesting a novel feedback mechanism to regulate glucose balance during pregnancy, and GPR1 could be a potential target for the detection and therapy of GDM.
Evidence for a role for Sestrin1 in mediating leucine-induced activation of mTORC1 in skeletal muscle
Authors: Xu Dandan , Shimkus Kevin L. , Lacko Holly A. , Kutzler Lydia , Jefferson Leonard S. , Kimball Scot R.
Published: March 2019

Previous studies established that leucine stimulates protein synthesis in skeletal muscle to the same extent as a complete mixture of amino acids, and the effect occurs through activation of the mechanistic target of rapamycin in complex 1 (mTORC1). Recent studies using cells in culture showed that the Sestrins bind leucine and are required for leucine-dependent activation of mTORC1. However, the role they play in mediating leucine-dependent activation of the kinase in vivo has been questioned because the dissociation constant of Sestrin2 for leucine is well below circulating and intramuscular levels of the amino acid. The goal of the present study was to compare expression of the Sestrins in skeletal muscle to other tissues and to assess their relative role in mediating activation of mTORC1 by leucine. The results show that the relative expression of the Sestrin proteins varies widely among tissues and that in skeletal muscle Sestrin1 expression is higher than Sestrin3, whereas Sestrin2 expression is markedly lower. Analysis of the dissociation constants of the Sestrins for leucine as assessed by leucine-induced dissociation of the Sestrin·GAP activity toward Rags 2 (GATOR2) complex revealed that Sestrin1 has the highest affinity for leucine and that Sestrin3 has the lowest affinity. In agreement with the dissociation constants calculated using cells in culture, oral leucine administration promotes disassembly of the Sestrin1·GATOR2 complex but not the Sestrin2 or Sestrin3·GATOR2 complex. Overall, the results presented herein are consistent with a model in which leucine-induced activation of mTORC1 in skeletal muscle in vivo occurs primarily through release of Sestrin1 from GATOR2.
DHA Oral Supplementation Modulates Serum Epoxydocosapentaenoic Acid (EDP) Levels in Breast Cancer Patients
Authors: Molfino Alessio , Amabile Maria Ida , Lionetto Luana , Spagnoli Alessandra , Ramaccini Cesarina , De Luca Alessandro , Simmaco Maurizio , Monti Massimo , Muscaritoli Maurizio
Published: March 2019

Introduction. The omega-3 polyunsaturated fatty acids, as docosahexaenoic acid (DHA), are considered mediators regulating the resolution of inflammation during cancer and may be associated with better outcomes. Epoxydocosapentaenoic acids (EDPs), metabolites of the DHA, are hypothesized to be responsible for some beneficial effects. In the present study, we aimed to assess the circulating 19,20-EDP levels in breast cancer (BC) patients and in healthy controls before and after DHA oral supplementation and the potential differences in the DHA conversion in 19,20-EDPs between patients with different BC presentations. Methods. BC patients and healthy controls were supplemented with DHA (algal oil) for 10 days (2 g/day). Blood samples were collected at baseline (T0) and after supplementation (T1) to assess EDP (19,20-EDP) serum levels by liquid chromatography spectrometry. Results. 33 BC patients and 10 controls were studied. EDP values at T0 were not different between patients and controls. At T1, we found an increase in 19,20-EDP levels in BC patients (P<0.00001) and in controls (P<0.001), whereas no differences in 19,20-EDPs were present between the two groups; when considering the type of BC presentation, patients with BRCA1/2 mutation showed lower 19,20-EDPs levels with respect to BC patients without the mutation (P=0.03). According to immunohistochemical subtype, luminal A-like BC patients showed at T1 higher 19,20-EDP levels compared to nonluminal A (P=0.02). Conclusions. DHA oral supplementation was associated with increased 19,20-EDP serum levels in BC patients, independent of the type of BC presentation, and in controls. Patients carrier of BRCA1/2 mutation seem to possess lower ability of DHA epoxidation, whereas luminal A-like BC patients showed higher EDP conversion. This behavior should be tested in a larger population.
Influence Factors of the Pharmacokinetics of Herbal Resourced Compounds in Clinical Practice
Authors: Sun Shi , Wang Yifang , Wu Ailing , Ding Zhen , Liu Xinguang
Published: March 2019

Herbal medicines have been used to prevent and cure diseases in eastern countries for thousands of years. In recent decades, these phytotherapies are becoming more and more popular in the West. As being nature-derived is the essential attribute of herbal medicines, people believe that taking them for diseases treatment is safe enough and has no side-effects. However, the efficacy of herbal resourced compounds (HRC) depends on the multiple constituents absorbed in the body and their pharmacokinetics. Thus, many factors will influence the clinical practice of HRC, i.e., their absorption, distribution, metabolism, and excretion (ADME). Among these factors, herb-drug interaction has been widely discussed, as these compounds may share the same drug-metabolizing enzymes and drug transporters. Meanwhile there are many other potential factors that can also change the ADME of HRC, including herb pretreatment, herb-herb interactions, pathological status, gender, age of patient, and chemical and physical modification of certain ingredients. With the aim of ensuring the efficacy of HRC and minimizing their clinical risks, this review provides and discusses the influence factors and artificial improvement of the pharmacokinetics of HRC.
An Optimization Design Method of Combination of Steep Slope and Sharp Curve Sections for Mountain Highways
Authors: Yue Lei , Wang Hui
Published: March 2019

As it was found steep slope and sharp curve sections account for 14% of the accident‐prone sections according to the accidents data in Chongqing. Regular design indices with certain thresholds are found not enough for this kind of mountain highways. The goal of this paper is to find an optimization design method for combination of steep slope and sharp curve sections based on the analysis of vehicle driving stability. The overall safety model of steep slope and sharp curve combined section is established, and the relevant coordination relationship between design indices of the front and rear alignment unit is established by using the operating speed estimation model. Taking the maximum slope length corresponding to the specified design speed as the design condition of the front segment, the threshold values and variation rules of the design indices of the rear segment under different design speeds are calculated ensuring driving safety. The safety model is simulated by CarSim software, the trajectory offset and lateral acceleration are used to indirectly reflect the degree of lateral instability, and the results are compared to verify the effectiveness of the simplified safety model established in this paper.
Potential Role of the Resident Mesenchymal Stem-Like Cells in Renal Fibrogenesis after Ureteral Obstruction
Authors: Peng Yong-Hua , Xiao Jie , Yan Chen , Luo Lan , Li Tao-Sheng
Published: March 2019

The mechanisms of renal fibrogenesis after ureteral obstruction remain unclear. We tried to primarily expand mesenchymal stem cells from renal tissues and then investigated their role in fibrogenesis after ureteral obstruction. Unilateral ureteral obstruction was induced by ligating the left ureteral duct of adult C57BL/6 mice. We collected the kidneys for experiments at 2, 7, and 14 days after operation. Histological analysis showed obviously fibrotic changes in the left kidney at 7 days and further increased at 14 days after ureteral obstruction. To expand mesenchymal stem cells, we minced the renal tissues into small explants (about 1 mm3) and cultured onto 10 cm dishes. Interestingly, the outgrowth of cells was observed significantly earlier from the explants of the obstructed left kidney than that of the unobstructed right kidney. These expanded cells showed the potency of adipogenic, osteogenic, and chondrogenic differentiations and positively expressed with CD44 and partly expressed with CD90, CD105, and CD106, but negatively expressed with CD34, CD45, and FSP1, suggesting the phenotype of mesenchymal stem-like cells (MSLCs). The mouse fibrosis RT2 profiler PCR array showed that many genes were changed over 2-fold in the MSLCs expanded from both kidneys at 2, 7, and 14 days after operation. Interestingly, profibrotic genes were prevalently enhanced in the left kidney with ureteral obstruction. Histological analysis also showed obviously infiltration of inflammatory cells in the left kidney at 14 days after operation. Our data indicate the potential role of resident MSLCs in renal fibrogenesis after ureteral obstruction, but further experiments are required to understand the relevant mechanisms.
Convergence Rates in Homogenization of the Mixed Boundary Value Problems
Authors: Zhao Jie , Wang Juan
Published: March 2019

We will study the convergence rates of solutions for homogenization of the mixed boundary value problems. By utilizing the smoothing operator as well as duality argument, we deal with the mixed boundary conditions in a uniform fashion. As a consequence, we establish the sharp rate of convergence in H1 and L2, with no smoothness assumption on the coefficients.
GRP78/BIP/HSPA5 as a Therapeutic Target in Models of Parkinson’s Disease: A Mini Review
Authors: Enogieru Adaze Bijou , Omoruyi Sylvester Ifeanyi , Hiss Donavon Charles , Ekpo Okobi Eko
Published: March 2019

Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by selective loss of dopamine neurons in the substantia nigra pars compacta of the midbrain. Reports from postmortem studies in the human PD brain, and experimental PD models reveal that endoplasmic reticulum (ER) stress is implicated in the pathogenesis of PD. In times of stress, the unfolded or misfolded proteins overload the folding capacity of the ER to induce a condition generally known as ER stress. During ER stress, cells activate the unfolded protein response (UPR) to handle increasing amounts of abnormal proteins, and recent evidence has demonstrated the activation of the ER chaperone GRP78/BiP (78 kDa glucose-regulated protein/binding immunoglobulin protein), which is important for proper folding of newly synthesized and partly folded proteins to maintain protein homeostasis. Although the activation of this protein is essential for the initiation of the UPR in PD, there are inconsistent reports on its expression in various PD models. Consequently, this review article aims to summarize current knowledge on neuroprotective agents targeting the expression of GRP78/BiP in the regulation of ER stress in experimental PD models.
Late-Onset Neutropenia after Rituximab Treatment for Adult-Onset Nephrotic Syndrome
Authors: Yamazaki Mayuko , Sugiura Hidekazu , Iwatani Yosuke , Kyoda Mizuki , Nokiba Hirohiko , Amemiya Nobuyuki , Nitta Kosaku , Tsuchiya Ken
Published: March 2019

A 41-year-old woman developed nephrotic syndrome at the age of 32 and was diagnosed with minimal change nephrotic syndrome based on a renal biopsy. Although remission was achieved with administration of prednisolone (PSL) and cyclosporine, the nephrotic syndrome recurred. She was also started on rituximab (RTX). She developed late-onset neutropenia after RTX treatment (R-LON) and improved 17 days later. Although the majority of R-LON cases undergo spontaneous remission, cases of death have been reported. This report is intended to warn about R-LON, since the use of RTX for adult-onset nephrotic syndrome is expected to increase in the future.
Stability Analysis and Reinforcement of a High‐Steep Rock Slope with Faults: Numerical Analysis and Field Monitoring
Authors: Zhan Qibing , Sun Xinjian , Li Cheng , Zhao Yawei , Zhou Xinjie , He Yinpeng , Zhang Yuxiang
Published: March 2019

This study presents a stability analysis of a high‐steep rock slope with two faults during excavations and evaluates the effectiveness of a proposed reinforcement method using prestressed anchor cables. A 3D finite difference model was established based on the strength reduction method using FLAC3D software. The influence of various fault conditions and the effectiveness of the reinforcement on the slope stability during the excavation process were analyzed and compared to field monitoring data. The numerical analysis and field monitoring results showed that the fault close to the slope surface (f20) was prone to the local instability under external forces caused by the excavation, but a fault further away from the slope surface (f14) had insignificant influence on the stability of the slope. Based on the numerical analysis results, the proposed reinforcement measure can increase the factor of safety (FOS) of the slope by 19.2%. The field monitoring data also showed that the displacement of the monitoring point gradually decreased after the reinforcement, and the deformation of the slope was effectively controlled.
Seismic Interaction Characteristics of an Inclined Straight Alternating Pile Group‐Soil in Liquefied Ground
Authors: Kong Desen , Deng Meixu , Zhao Zhimin
Published: March 2019

In this paper, the pile‐soil interaction of a low‐rise pile cap foundation of an inclined straight alternating pile on two or three layers of a soil liquefaction site under seismic load is studied. By inputting the 0.5 g El Centro seismic wave in FLAC3D, the pile‐soil interaction rule of the pile foundation of the inclined and straight pile groups of the low‐pile cap under seismic action is simulated. By analyzing the soil acceleration, the pore pressure ratio, the horizontal displacement of the pile body, the vertical displacement, and the pile body bending moment, the law of pile‐soil interaction between the pile and soil when the lower part of the pile is embedded in the clay layer is studied, and the low‐rise pile cap inclined straight alternating group pile foundation on the two‐layer soil and the three‐layer soil free field is compared and analyzed. The results show that, under seismic load, the maximum acceleration of soil mass in the two‐layer soil and three‐layer soil model is discrete, and the pore pressure ratio of sand soil increases from bottom to top. By analyzing the displacement and bending moment of pile body, the bending moment at the joint between the pile cap and the top of pile body is the largest and the most vulnerable to damage. The maximum value of pile displacement and bending moment in the three‐layer soil is less than the maximum value of the two‐layer soil, indicating that the pile group foundation in the three‐layer soil free site model is safer.
MicroRNA-15a-5p Regulates the Development of Osteoarthritis by Targeting PTHrP in Chondrocytes
Authors: Duan Zhi-xi , Huang Peng , Tu Chao , Liu Qing , Li Shuang-qing , Long Ze-ling , Li Zhi-hong
Published: March 2019

Background and Aims. A growing body of research has demonstrated that the degeneration of chondrocytes is the primary cause of osteoarthritis (OA). Parathyroid hormone-related protein (PTHrP) can alleviate the degeneration of chondrocytes via promotion of chondrocyte proliferation and inhibition of terminal differentiation, but the underlying mechanism remains unknown. This study aimed to identify the microRNAs (miRNAs) that may target PTHrP and regulate the proliferation and terminal differentiation of chondrocytes. Methods. Bioinformatic analysis was used to predict which miRNAs target PTHrP. We collected human knee cartilage specimens to acquire the primary chondrocytes, which we then used to test the expression and function of the targeted miRNAs. To explore the effects of miR-15a-5p on the putative binding sites, specific mimics or inhibitors were transfected into the chondrocytes. Furthermore, a dual-luciferase reporter gene assay and chondrocyte degeneration-related factors were used to verify the possible mechanism. Results. The expression of PTHrP was upregulated in the OA chondrocytes, whilst miR-15a-5p was downregulated in the OA chondrocytes. A negative correlation was observed between PTHrP and miR-15a-5p. The knockdown of miR-15a-5p promoted the growth of chondrocytes and inhibited calcium deposition, whilst overexpression of miR-15a-5p reversed this trend. The effect of miR-15a-5p overexpression was neutralised by PTHrP. Dual-luciferase reporter assays revealed that PTHrP can be used as a novel targeting molecule for miR-15a-5p. Conclusions. miR-15a-5p promotes the degeneration of chondrocytes by targeting PTHrP and, in addition to helping us understand the development of OA, may be a potential biomarker of OA.
Late Treatment and Recurrence of Kawasaki Disease in a Moroccan Infant
Authors: Elqadiry R. , Louachama O. , Rada N. , Draiss G. , Bouskraoui M.
Published: March 2019

Introduction. While the diagnosis of typical form of Kawasaki disease (KD) is obvious, this multifaceted disease continues to surprise us. We report the case of a recurrent Kawasaki disease in an infant. Case. At the age of 13 months, the infant was diagnosed with complete Kawasaki disease; he presented with prolonged fever, bilateral conjunctivitis, enanthem, exanthema, edema of the lower limb, peeling, and biological inflammatory syndrome. He was treated with intravenous immunoglobulin (IVIG) associated with a high dose of aspirin and then an antiplatelet dose with a good clinical-biological evolution. The echocardiography was normal. Seven months later, the patient was again admitted, in a similar picture: a prolonged fever evolving for 7 days, bilateral conjunctivitis, enanthem, cervical adenopathy of 1.5 cm/1 cm, scarlatiniform erythema, pruriginous of the trunk and limb, and peeling of the toes, with indurated edema of the hands and feet. The rest of the examination was normal except the irritability. The diagnosis of recurrent KD was made according the five criteria of the American Heart Association. The echocardiography was normal again. The infant received IVIG with good outcome. Conclusion. Despite its rarity, the possibility of recurrence of KD should be known by clinicians, so as not to delay the specific management of vasculitis whose stakes in terms of prevention of coronary artery lesions are well known. Our case confirms the possibility of this recurrence.