bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving Dynamically-Generated Code Performance on Dynamic Binary Translators
Authors: Wang Wenwen , Wu Jiacheng , Gong Xiaoli , Li Tao , Yew Pen-Chung
Published: December 2018

The recent transition in the software industry toward dynamically generated code poses a new challenge to existing dynamic binary translation (DBT) systems. A significant re-translation overhead could be introduced due to the maintenance of the consistency between the dynamically-generated guest code and the corresponding translated host code. To address this issue, this paper presents a novel approach to optimize DBT systems for guest applications with dynamically-generated code. The proposed approach can maximize the reuse of previously translated host code to mitigate the re-translation overhead. A prototype based on such an approach has been implemented on an existing DBT system HQEMU. Experimental results on a set of JavaScript applications show that it can achieve a 1.24X performance speedup on average compared to the original HQEMU.
gMig
Authors: Ma Jiacheng , Zheng Xiao , Dong Yaozu , Li Wentai , Qi Zhengwei , He Bingsheng , Guan Haibing
Published: December 2018

This paper introduces gMig, an open-source and practical GPU live migration solution for full virtualization. By taking advantage of the dirty pattern of GPU workloads, gMig presents the One-Shot Pre-Copy combined with the hashing based Software Dirty Page technique to achieve efficient GPU live migration. Particularly, we propose three approaches for gMig: 1) Dynamic Graphics Address Remapping, which parses and manipulates GPU commands to adjust the address mapping to adapt to a different environment after migration, 2) Software Dirty Page, which utilizes a hashing based approach to detect page modification, overcomes the commodity GPU's hardware limitation, and speeds up the migration by only sending the dirtied pages, 3) One-Shot Pre-Copy, which greatly reduces the rounds of pre-copy of graphics memory. Our evaluation shows that gMig achieves GPU live migration with an average downtime of 302 ms on Windows and 119 ms on Linux. With the help of Software Dirty Page, the number of GPU pages transferred during the downtime is effectively reduced by 80.0%.
Fast PokeEMU
Authors: Yan Qiuchen , McCamant Stephen
Published: December 2018

Software that emulates a CPU has many applications, but is difficult to implement correctly and requires extensive testing. Since a large number of test cases are required for full coverage, it is important that the tests execute efficiently. We explore techniques for combining many instruction tests into one program to amortize overheads such as booting an emulator. To ensure the results of each test are reflected in a final result, we use the outputs of one instruction test as an input to the next, and adopt the "Feistel network" construction from cryptography so that each step is invertible. We evaluate this approach by applying it to PokeEMU, a tool that generates emulator tests using symbolic execution. The combined tests run much faster, but still reveal most of the same behavior differences as when run individually.
CURD: a dynamic CUDA race detector
Authors: Peng Yuanfeng , Grover Vinod , Devietti Joseph
Published: December 2018

As GPUs have become an integral part of nearly every pro- cessor, GPU programming has become increasingly popular. GPU programming requires a combination of extreme levels of parallelism and low-level programming, making it easy for concurrency bugs such as data races to arise. These con- currency bugs can be extremely subtle and di cult to debug due to the massive numbers of threads running concurrently on a modern GPU. While some tools exist to detect data races in GPU pro- grams, they are often prohibitively slow or focused only on a small class of data races in shared memory. Compared to prior work, our race detector, CURD, can detect data races precisely on both shared and global memory, selects an appropriate race detection algorithm based on the synchronization used in a program, and utilizes efficient compiler instrumentation to reduce performance overheads. Across 53 benchmarks, we find that using CURD incurs an aver- age slowdown of just 2.88x over native execution. CURD is 2.1x faster than Nvidia’s CUDA-Racecheck race detector, de- spite detecting a much broader class of races. CURD finds 35 races across our benchmarks, including bugs in established benchmark suites and in sample programs from Nvidia.
Ryū: fast float-to-string conversion
Authors: Adams Ulf
Published: December 2018

We present Ryū, a new routine to convert binary floating point numbers to their decimal representations using only fixed-size integer operations, and prove its correctness. Ryū is simpler and approximately three times faster than the previously fastest implementation.
Mapping spiking neural networks onto a manycore neuromorphic architecture
Authors: Lin Chit-Kwan , Wild Andreas , Chinya Gautham N. , Lin Tsung-Han , Davies Mike , Wang Hong
Published: December 2018

We present a compiler for Loihi, a novel manycore neuromorphic processor that features a programmable, on-chip learning engine for training and executing spiking neural networks (SNNs). An SNN is distinguished from other neural networks in that (1) its independent computing units, or "neurons", communicate with others only through spike messages; and (2) each neuron evaluates local learning rules, which are functions of spike arrival and departure timings, to modify its local state. The collective neuronal state dynamics of an SNN form a nonlinear dynamical system that can be cast as an unconventional model of computation. To realize such an SNN on Loihi requires each constituent neuron to locally store and independently update its own spike timing information. However, each Loihi core has limited resources for this purpose and these must be shared by neurons assigned to the same core. In this work, we present a compiler for Loihi that maps the neurons of an SNN onto and across Loihi's cores efficiently. We show that a poor neuron-to-core mapping can incur significant energy costs and address this with a greedy algorithm that compiles SNNs onto Loihi in a power-efficient manner. In so doing, we highlight the need for further development of compilers for this new, emerging class of architectures.
BLeak: automatically debugging memory leaks in web applications
Authors: Vilk John , Berger Emery D.
Published: December 2018

Despite the presence of garbage collection in managed languages like JavaScript, memory leaks remain a serious problem. In the context of web applications, these leaks are especially pervasive and difficult to debug. Web application memory leaks can take many forms, including failing to dispose of unneeded event listeners, repeatedly injecting iframes and CSS files, and failing to call cleanup routines in third-party libraries. Leaks degrade responsiveness by increasing GC frequency and overhead, and can even lead to browser tab crashes by exhausting available memory. Because previous leak detection approaches designed for conventional C, C++ or Java applications are ineffective in the browser environment, tracking down leaks currently requires intensive manual effort by web developers.

This paper introduces BLeak (Browser Leak debugger), the first system for automatically debugging memory leaks in web applications. BLeak's algorithms leverage the observation that in modern web applications, users often repeatedly return to the same (approximate) visual state (e.g., the inbox view in Gmail). Sustained growth between round trips is a strong indicator of a memory leak. To use BLeak, a developer writes a short script (17-73 LOC on our benchmarks) to drive a web application in round trips to the same visual state. BLeak then automatically generates a list of leaks found along with their root causes, ranked by return on investment. Guided by BLeak, we identify and fix over 50 memory leaks in popular libraries and apps including Airbnb, AngularJS, Google Analytics, Google Maps SDK, and jQuery. BLeak's median precision is 100%; fixing the leaks it identifies reduces heap growth by an average of 94%, saving from 0.5 MB to 8 MB per round trip. We believe BLeak's approach to be broadly applicable beyond web applications, including to GUI applications on desktop and mobile platforms.
Calling-to-reference context translation via constraint-guided CFL-reachability
Authors: Cai Cheng , Zhang Qirun , Zuo Zhiqiang , Nguyen Khanh , Xu Guoqing , Su Zhendong
Published: December 2018

A calling context is an important piece of information used widely to help developers understand program executions (e.g., for debugging). While calling contexts offer useful control information, information regarding data involved in a bug (e.g., what data structure holds a leaking object), in many cases, can bring developers closer to the bug's root cause. Such data information, often exhibited as heap reference paths, has already been needed by many tools.

The only way for a dynamic analysis to record complete reference paths is to perform heap dumping, which incurs huge runtime overhead and renders the analysis impractical. This paper presents a novel static analysis that can precisely infer, from a calling context of a method that contains a use (e.g., read or write) of an object, the heap reference paths leading to the object at the time the use occurs. Since calling context recording is much less expensive, our technique provides benefits for all dynamic techniques that need heap information, significantly reducing their overhead.
iReplayer: in-situ and identical record-and-replay for multithreaded applications
Authors: Liu Hongyu , Silvestro Sam , Wang Wei , Tian Chen , Liu Tongping
Published: December 2018

Reproducing executions of multithreaded programs is very challenging due to many intrinsic and external non-deterministic factors. Existing RnR systems achieve significant progress in terms of performance overhead, but none targets the in-situ setting, in which replay occurs within the same process as the recording process. Also, most existing work cannot achieve identical replay, which may prevent the reproduction of some errors.

This paper presents iReplayer, which aims to identically replay multithreaded programs in the original process (under the "in-situ" setting). The novel in-situ and identical replay of iReplayer makes it more likely to reproduce errors, and allows it to directly employ debugging mechanisms (e.g. watchpoints) to aid failure diagnosis. Currently, iReplayer only incurs 3% performance overhead on average, which allows it to be always enabled in the production environment. iReplayer enables a range of possibilities, and this paper presents three examples: two automatic tools for detecting buffer overflows and use-after-free bugs, and one interactive debugging tool that is integrated with GDB.
D4: fast concurrency debugging with parallel differential analysis
Authors: Liu Bozhen , Huang Jeff
Published: December 2018

We present D4, a fast concurrency analysis framework that detects concurrency bugs (e.g., data races and deadlocks) interactively in the programming phase. As developers add, modify, and remove statements, the code changes are sent to D4 to detect concurrency bugs in real time, which in turn provides immediate feedback to the developer of the new bugs. The cornerstone of D4 includes a novel system design and two novel parallel differential algorithms that embrace both change and parallelization for fundamental static analyses of concurrent programs. Both algorithms react to program changes by memoizing the analysis results and only recomputing the impact of a change in parallel. Our evaluation on an extensive collection of large real-world applications shows that D4 efficiently pinpoints concurrency bugs within 100ms on average after a code change, several orders of magnitude faster than both the exhaustive analysis and the state-of-the-art incremental techniques.
Symbolic reasoning for automatic signal placement
Authors: Ferles Kostas , Van Geffen Jacob , Dillig Isil , Smaragdakis Yannis
Published: December 2018

Explicit signaling between threads is a perennial cause of bugs in concurrent programs. While there are several run-time techniques to
automatically
notify threads upon the availability of some shared resource, such techniques are not widely-adopted due to their run-time overhead. This paper proposes a new solution based on static analysis for automatically generating a performant
explicit-signal
program from its corresponding
implicit-signal
implementation. The key idea is to generate verification conditions that allow us to minimize the number of required signals and unnecessary context switches, while guaranteeing semantic equivalence between the source and target programs. We have implemented our method in a tool called Expresso and evaluate it on challenging benchmarks from prior papers and open-source software. Expresso-generated code significantly outperforms past automatic signaling mechanisms (avg. 1.56x speedup) and closely matches the performance of hand-optimized explicit-signal code.
GPU code optimization using abstract kernel emulation and sensitivity analysis
Authors: Hong Changwan , Sukumaran-Rajam Aravind , Kim Jinsung , Rawat Prashant Singh , Krishnamoorthy Sriram , Pouchet Louis-Noël , Rastello Fabrice , Sadayappan P.
Published: December 2018

In this paper, we develop an approach to GPU kernel optimization by focusing on identification of bottleneck resources and determining optimization parameters that can alleviate the bottleneck. Performance modeling for GPUs is done by abstract kernel emulation along with latency/gap modeling of resources. Sensitivity analysis with respect to resource latency/gap parameters is used to predict the bottleneck resource for a given kernel's execution. The utility of the bottleneck analysis is demonstrated in two contexts: 1) Coupling the new bottleneck-driven optimization strategy with the OpenTuner auto-tuner: experimental results on all kernels from the Rodinia suite and GPU tensor contraction kernels from the NWChem computational chemistry suite demonstrate effectiveness. 2) Manual code optimization: two case studies illustrate the use of the bottleneck analysis to iteratively improve the performance of code from state-of-the-art domain-specific code generators.
Bayonet: probabilistic inference for networks
Authors: Gehr Timon , Misailovic Sasa , Tsankov Petar , Vanbever Laurent , Wiesmann Pascal , Vechev Martin
Published: December 2018

Network operators often need to ensure that important probabilistic properties are met, such as that the probability of network congestion is below a certain threshold. Ensuring such properties is challenging and requires both a suitable language for probabilistic networks and an automated procedure for answering probabilistic inference queries.

We present Bayonet, a novel approach that consists of: (i) a probabilistic network programming language and (ii) a system that performs probabilistic inference on Bayonet programs. The key insight behind Bayonet is to phrase the problem of probabilistic network reasoning as inference in existing probabilistic languages. As a result, Bayonet directly leverages existing probabilistic inference systems and offers a flexible and expressive interface to operators.

We present a detailed evaluation of Bayonet on common network scenarios, such as network congestion, reliability of packet delivery, and others. Our results indicate that Bayonet can express such practical scenarios and answer queries for realistic topology sizes (with up to 30 nodes).
Advanced automata-based algorithms for program termination checking
Authors: Chen Yu-Fang , Heizmann Matthias , Lengál Ondřej , Li Yong , Tsai Ming-Hsien , Turrini Andrea , Zhang Lijun
Published: December 2018

In 2014, Heizmann et al. proposed a novel framework for program termination analysis. The analysis starts with a termination proof of a sample path. The path is generalized to a Büchi automaton (BA) whose language (by construction) represents a set of terminating paths. All these paths can be safely removed from the program. The removal of paths is done using automata difference, implemented via BA complementation and intersection. The analysis constructs in this way a set of BAs that jointly "cover" the behavior of the program, thus proving its termination. An implementation of the approach in Ultimate Automizer won the 1st place in the Termination category of SV-COMP 2017.

In this paper, we exploit advanced automata-based algorithms and propose several non-trivial improvements of the framework. To alleviate the complementation computation for BAs---one of the most expensive operations in the framework---, we propose a multi-stage generalization construction. We start with generalizations producing subclasses of BAs (such as deterministic BAs) for which efficient complementation algorithms are known, and proceed to more general classes only if necessary. Particularly, we focus on the quite expressive subclass of semideterministic BAs and provide an improved complementation algorithm for this class. Our experimental evaluation shows that the proposed approach significantly improves the power of termination checking within the Ultimate Automizer framework.
VeriPhy: verified controller executables from verified cyber-physical system models
Authors: Bohrer Rose , Tan Yong Kiam , Mitsch Stefan , Myreen Magnus O. , Platzer André
Published: December 2018

We present VeriPhy, a verified pipeline which automatically transforms verified high-level models of safety-critical cyber-physical systems (CPSs) in differential dynamic logic (dL) to verified controller executables. VeriPhy proves that all safety results are preserved end-to-end as it bridges abstraction gaps, including: i) the gap between mathematical reals in physical models and machine arithmetic in the implementation, ii) the gap between real physics and its differential-equation models, and iii) the gap between nondeterministic controller models and machine code. VeriPhy reduces CPS safety to the faithfulness of the physical environment, which is checked at runtime by synthesized, verified monitors. We use three provers in this effort: KeYmaera X, HOL4, and Isabelle/HOL. To minimize the trusted base, we cross-verify KeYmaeraX in Isabelle/HOL. We evaluate the resulting controller and monitors on commodity robotics hardware.
A general path-based representation for predicting program properties
Authors: Alon Uri , Zilberstein Meital , Levy Omer , Yahav Eran
Published: December 2018

Predicting program properties such as names or expression types has a wide range of applications. It can ease the task of programming, and increase programmer productivity. A major challenge when learning from programs is
how to represent programs in a way that facilitates effective learning
.

We present a
general path-based representation
for learning from programs. Our representation is purely syntactic and extracted automatically. The main idea is to represent a program using paths in its abstract syntax tree (AST). This allows a learning model to leverage the structured nature of code rather than treating it as a flat sequence of tokens.

We show that this representation is general and can: (i) cover different prediction tasks, (ii) drive different learning algorithms (for both generative and discriminative models), and (iii) work across different programming languages.

We evaluate our approach on the tasks of predicting variable names, method names, and full types. We use our representation to drive both CRF-based and word2vec-based learning, for programs of four languages: JavaScript, Java, Python and C#. Our evaluation shows that our approach obtains better results than task-specific handcrafted representations across different tasks and programming languages.
Partial control-flow linearization
Authors: Moll Simon , Hack Sebastian
Published: December 2018

If-conversion is a fundamental technique for vectorization. It accounts for the fact that in a SIMD program, several targets of a branch might be executed because of divergence. Especially for irregular data-parallel workloads, it is crucial to avoid if-converting non-divergent branches to increase SIMD utilization. In this paper, we present partial linearization, a simple and efficient if-conversion algorithm that overcomes several limitations of existing if-conversion techniques. In contrast to prior work, it has provable guarantees on which non-divergent branches are retained and will never duplicate code or insert additional branches. We show how our algorithm can be used in a classic loop vectorizer as well as to implement data-parallel languages such as ISPC or OpenCL. Furthermore, we implement prior vectorizer optimizations on top of partial linearization in a more general way. We evaluate the implementation of our algorithm in LLVM on a range of irregular data analytics kernels, a neutronics simulation benchmark and NAB, a molecular dynamics benchmark from SPEC2017 on AVX2, AVX512, and ARM Advanced SIMD machines and report speedups of up to 146 % over ICC, GCC and Clang O3.
Pinpoint: fast and precise sparse value flow analysis for million lines of code
Authors: Shi Qingkai , Xiao Xiao , Wu Rongxin , Zhou Jinguo , Fan Gang , Zhang Charles
Published: December 2018

When dealing with millions of lines of code, we still cannot have the cake and eat it: sparse value-flow analysis is powerful in checking source-sink problems, but existing work cannot escape from the “pointer trap” – a precise points-to analysis limits its scalability and an imprecise one seriously undermines its precision. We present Pinpoint, a holistic approach that decomposes the cost of high-precision points-to analysis by precisely discovering local data dependence and delaying the expensive inter-procedural analysis through memorization. Such memorization enables the on-demand slicing of only the necessary inter-procedural data dependence and path feasibility queries, which are then solved by a costly SMT solver. Experiments show that Pinpoint can check programs such as MySQL (around 2 million lines of code) within 1.5 hours. The overall false positive rate is also very low (14.3% - 23.6%). Pinpoint has discovered over forty real bugs in mature and extensively checked open source systems. And the implementation of Pinpoint and all experimental results are freely available.
To-many or to-one? all-in-one! efficient purely functional multi-maps with type-heterogeneous hash-tries
Authors: Steindorfer Michael J. , Vinju Jurgen J.
Published: December 2018

An immutable multi-map is a many-to-many map data structure with expected fast insert and lookup operations. This data structure is used for applications processing graphs or many-to-many relations as applied in compilers, runtimes of programming languages, or in static analysis of object-oriented systems. Collection data structures are assumed to carefully balance execution time of operations with memory consumption characteristics and need to scale gracefully from a few elements to multiple gigabytes at least. When processing larger in-memory data sets the overhead of the data structure encoding itself becomes a memory usage bottleneck, dominating the overall performance.

In this paper we propose AXIOM, a novel hash-trie data structure that allows for a highly efficient and type-safe multi-map encoding by distinguishing inlined values of singleton sets from nested sets of multi-mappings. AXIOM strictly generalizes over previous hash-trie data structures by supporting the processing of fine-grained type-heterogeneous content on the implementation level (while API and language support for type-heterogeneity are not scope of this paper). We detail the design and optimizations of AXIOM and further compare it against state-of-the-art immutable maps and multi-maps in Java, Scala and Clojure. We isolate key differences using microbenchmarks and validate the resulting conclusions on a case study in static analysis. AXIOM reduces the key-value storage overhead by 1.87x; with specializing and inlining across collection boundaries it improves by 5.1x.
Mechanisms of Cotranslational Maturation of Newly Synthesized Proteins
Authors: Kramer Günter , Shiber Ayala , Bukau Bernd
Published: December 2018

The timely production of functional proteins is of critical importance for the biological activity of cells. To reach the functional state, newly synthesized polypeptides have to become enzymatically processed, folded, and assembled into oligomeric complexes and, for noncytosolic proteins, translocated across membranes. Key activities of these processes occur cotranslationally, assisted by a network of machineries that transiently engage nascent polypeptides at distinct phases of translation. The sequence of events is tuned by intrinsic features of the nascent polypeptides and timely association of factors with the translating ribosome. Considering the dynamics of translation, the heterogeneity of cellular proteins, and the diversity of interaction partners, it is a major cellular achievement that these processes are temporally and spatially so precisely coordinated, minimizing the generation of damaged proteins. This review summarizes the current progress we have made toward a comprehensive understanding of the cotranslational interactions of nascent chains, which pave the way to their functional state.
Microrobotics and Microorganisms: Biohybrid Autonomous Cellular Robots
Authors: Alapan Yunus , Yasa Oncay , Yigit Berk , Yasa I. Ceren , Erkoc Pelin , Sitti Metin
Published: December 2018

Biohybrid microrobots, composed of a living organism integrated with an artificial carrier, offer great advantages for the miniaturization of devices with onboard actuation, sensing, and control functionalities and can perform multiple tasks, including manipulation, cargo delivery, and targeting, at nano- and microscales. Over the past decade, various microorganisms and artificial carriers have been integrated to develop unique biohybrid microrobots that can swim or crawl inside the body, in order to overcome the challenges encountered by the current cargo delivery systems. Here, we first focus on the locomotion mechanisms of microorganisms at the microscale, crucial criteria for the selection of biohybrid microrobot components, and the integration of the selected artificial and biological components using various physical and chemical techniques. We then critically review biohybrid microrobots that have been designed and used to perform specific tasks in vivo. Finally, we discuss key challenges, including fabrication efficiency, swarm manipulation, in vivo imaging, and immunogenicity, that should be overcome before biohybrid microrobots transition to clinical use.
Embracing Complexity: Reviewing the Past Decade of Team Effectiveness Research
Authors: Mathieu John E. , Gallagher Peter T. , Domingo Monique A. , Klock Elizabeth A.
Published: December 2018

We conceptualize organizational teams as dynamic systems evolving in response to their environments. We then review the past 10 years of team effectiveness research and summarize its implications by categorizing studies under three main overlapping and coevolving dimensions: compositional features, structural features, and mediating mechanisms. We highlight prominent work that focused on variables in each of these dimensions and discuss their key relationships with team outcomes. Furthermore, we review how contextual factors impact team effectiveness. On the basis of this review, we advocate that future research seek to examine team relationships through a dynamic, multilevel perspective, while incorporating new and novel measurement techniques. We submit that the future of teams research may benefit from a conceptualization of them as dynamic networks and modeling them as small complex systems.
On the Statistical Formalism of Uncertainty Quantification
Authors: Berger James O. , Smith Leonard A.
Published: December 2018

The use of models to try to better understand reality is ubiquitous. Models have proven useful in testing our current understanding of reality; for instance, climate models of the 1980s were built for science discovery, to achieve a better understanding of the general dynamics of climate systems. Scientific insights often take the form of general qualitative predictions (i.e., “under these conditions, the Earth's poles will warm more than the rest of the planet”); such use of models differs from making quantitative forecasts of specific events (i.e. “high winds at noon tomorrow at London's Heathrow Airport”). It is sometimes hoped that, after sufficient model development, any model can be used to make quantitative forecasts for any target system. Even if that were the case, there would always be some uncertainty in the prediction. Uncertainty quantification aims to provide a framework within which that uncertainty can be discussed and, ideally, quantified, in a manner relevant to practitioners using the forecast system. A statistical formalism has developed that claims to be able to accurately assess the uncertainty in prediction. This article is a discussion of if and when this formalism can do so. The article arose from an ongoing discussion between the authors concerning this issue, the second author generally being considerably more skeptical concerning the utility of the formalism in providing quantitative decision-relevant information.
Statistical Models of Key Components of Wildfire Risk
Authors: Xi Dexen D.Z. , Taylor Stephen W. , Woolford Douglas G. , Dean C.B.
Published: December 2018

Fire danger systems have evolved from qualitative indices, to process-driven deterministic models of fire behavior and growth, to data-driven stochastic models of fire occurrence and simulation systems. However, there has often been little overlap or connectivity in these frameworks, and validation has not been common in deterministic models. Yet, marked increases in annual fire costs, losses, and fatality costs over the past decade draw attention to the need for better understanding of fire risk to support fire management decision making through the use of science-backed, data-driven tools. Contemporary risk modeling systems provide a useful integrative framework. This article discusses a variety of important contributions for modeling fire risk components over recent decades, certain key fire characteristics that have been overlooked, and areas of recent research that may enhance risk models.
Effects of Newer Antidiabetic Drugs on Endothelial Function and Arterial Stiffness: A Systematic Review and Meta-Analysis
Authors: Batzias Konstantinos , Antonopoulos Alexios S. , Oikonomou Evangelos , Siasos Gerasimos , Bletsa Evanthia , Stampouloglou Panagiota K. , Mistakidi Chara-Vasiliki , Noutsou Marina , Katsiki Niki , Karopoulos Periklis , Charalambous Georgios , Thanopoulou Anastasia , Tentolouris Nicholas , Tousoulis Dimitris
Published: December 2018

Background. Newer antidiabetic drugs, i.e., dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may exert distinct cardiovascular effects. We sought to explore their impact on vascular function. Methods. Published literature was systematically searched up to January 2018 for clinical studies assessing the effects of DPP-4 inhibitors, GLP-1 RAs, and SGLT-2 inhibitors on endothelial function and arterial stiffness, assessed by flow-mediated dilation (FMD) of the brachial artery and pulse wave velocity (PWV), respectively. For each eligible study, we used the mean difference (MD) with 95% confidence intervals (CIs) for FMD and PWV. The pooled MD for FMD and PWV were calculated by using a random-effect model. The presence of heterogeneity among studies was evaluated by the I2 statistic. Results. A total of 26 eligible studies (n=668 patients) were included in the present meta-analysis. Among newer antidiabetic drugs, only SGLT-2 inhibitors significantly improved FMD (pooled MD 1.14%, 95% CI: 0.18 to 1.73, p=0.016), but not DPP-4 inhibitors (pooled MD = 0.86%, 95% CI: -0.15 to 1.86, p=0.095) or GLP-1 RA (pooled MD = 2.37%, 95% CI: -0.51 to 5.25, p=0.107). Both GLP-1 RA (pooled MD = −1.97, 95% CI: -2.65 to -1.30, p<0.001) and, to a lesser extent, DPP-4 inhibitors (pooled MD = -0.18, 95% CI: -0.30 to -0.07, p=0.002) significantly decreased PWV. Conclusions. Newer antidiabetic drugs differentially affect endothelial function and arterial stiffness, as assessed by FMD and PWV, respectively. These findings could explain the distinct effects of these drugs on cardiovascular risk of patients with type 2 diabetes.
Similarity Statistics for Clusterability Analysis with the Application of Cell Formation Problem
Authors: Zhu Yingyu , Li Simon
Published: December 2018

This paper proposes the use of the statistics of similarity values to evaluate the clusterability or structuredness associated with a cell formation (CF) problem. Typically, the structuredness of a CF solution cannot be known until the CF problem is solved. In this context, this paper investigates the similarity statistics of machine pairs to estimate the potential structuredness of a given CF problem without solving it. One key observation is that a well-structured CF solution matrix has a relatively high percentage of high-similarity machine pairs. Then, histograms are used as a statistical tool to study the statistical distributions of similarity values. This study leads to the development of the U-shape criteria and the criterion based on the Kolmogorov-Smirnov test. Accordingly, a procedure is developed to classify whether an input CF problem can potentially lead to a well-structured or ill-structured CF matrix. In the numerical study, 20 matrices were initially used to determine the threshold values of the criteria, and 40 additional matrices were used to verify the results. Further, these matrix examples show that genetic algorithm cannot effectively improve the well-structured CF solutions (of high grouping efficacy values) that are obtained by hierarchical clustering (as one type of heuristics). This result supports the relevance of similarity statistics to preexamine an input CF problem instance and suggest a proper solution approach for problem solving.
Existence of Uniqueness and Nonexistence Results of Positive Solution for Fractional Differential Equations Integral Boundary Value Problems
Authors: Wang Yongqing
Published: December 2018

In this paper, we consider a class of fractional differential equations with conjugate type integral conditions. Both the existence of uniqueness and nonexistence of positive solution are obtained by means of the iterative technique. The interesting point lies in that the assumption on nonlinearity is closely associated with the spectral radius corresponding to the relevant linear operator.
Fluid‐Induced Vibration Elimination of a Rotor/Seal System with the Dynamic Vibration Absorber
Authors: Xu Qi , Niu Junkai , Yao Hongliang , Zhao Lichao , Wen Bangchun
Published: December 2018

The dynamic vibration absorbers have been applied to attenuate the rotor unbalance and torsional vibrations. The major purpose of this paper is to research the elimination of the fluid‐induced vibration in the rotor/seal system using the absorber. The simplified rotor model with the absorber is established, and the Muszynska fluid force model is employed for the nonlinear seal force. The numerical method is used for the solutions of the nonlinear differential equations. The nonlinear responses of the rotor/seal system without and with the absorber are obtained, and then the rotating speed ranges by which the fluid‐induced instability can be eliminated completely and partially are presented, respectively. The absorber parameters ranges by which the instability vibration can be eliminated completely and partially are obtained. The results show that the natural frequency vibration due to the fluid‐induced instability in the rotor/seal system can be eliminated efficiently using the absorber. The appropriate natural frequency and damping ratio of the absorber can extend the complete elimination region of the instability vibration and postpone the occurrence of the instability vibration.
Lineage-Specific Chiral Biases of Human Embryonic Stem Cells during Differentiation
Authors: Worley Kathryn E. , Chin Amanda S. , Wan Leo Q.
Published: December 2018

Left-right symmetry breaking is a complex developmental process and an important part of embryonic axis development. As of yet, the biophysical mechanism behind LR asymmetry establishment remains elusive for the overall asymmetry of embryos as well as for the organ-specific asymmetry. Here, we demonstrate that inherent cellular chirality is observable in the cells of early embryonic stages using a 3D Matrigel bilayer system. Differentiation of human embryonic stem cells to three lineages corresponding to heart, intestine, and neural tissues demonstrates phenotype-specific inherent chiral biases, complementing the current knowledge regarding organ development. The existence of inherent cellular chirality early in development and its correlation with organ asymmetry implicate cell chirality as a possible regulator in LR symmetry breaking.
Numerical Method for Solving Nonhomogeneous Backward Heat Conduction Problem
Authors: Su LingDe , Jiang TongSong
Published: December 2018

In this paper we consider a numerical method for solving nonhomogeneous backward heat conduction problem. Coupled with the likewise Crank Nicolson scheme and an intermediate variable, the backward problem is transformed to a nonhomogeneous Helmholtz type problem; the unknown initial temperature can be obtained by solving this Helmholtz type problem. To illustrate the effectiveness and accuracy of the proposed method, we solve several problems in both two and three dimensions. The results show that this numerical method can solve nonhomogeneous backward heat conduction problem effectively and precisely, even though the final temperature is disturbed by significant noise.
Coping Strategies for Adverse Effects of Antiretroviral Therapy among Adult HIV Patients Attending University of Gondar Referral Hospital, Gondar, Northwest Ethiopia: A Cross-Sectional Study
Authors: Gelaw Yitayih Kefale , Adugna Boressa , Tsegaye Adino Tesfahun , Melaku Tadesse , Kefale Belayneh
Published: December 2018

Background. Adverse effects from antiretroviral therapy (ART) have an impact on quality of life and medication adherence. There is no clear understanding of how people manage the adverse effects of ART. The individual taking medications which cause serious adverse effects may choose to stop or reduce the medications to relieve the adverse effects. Hence, this study was aimed at assessing coping strategies for adverse effects of ART among adult human immunodeficiency virus (HIV) patients. Methods. A cross-sectional study was conducted at HIV clinic of University of Gondar Referral Hospital (UoGRH). A total of 394 study participants were recruited by systematic random sampling. Data were collected through interviewing patients. Data were entered to Epi-Info 3.5.4 and analyzed using SPSS-20.0. Descriptive statistics were used to summarize patient’s sociodemographic data and the adverse effects of their ART regimen. Binary and multivariate logistic regressions were used to investigate the potential predictors of nonadherence coping strategies. Results. The majorities of study participants were females (66%) and aged between 35 and 44 years (38.1%). The major adverse effects reported by the participants were headache (48.2%) followed by fatigability (18%) and loss of appetite (17.5%). Coping strategies used by HIV patients for adverse effect of ART were positive emotion coping strategy (91.1%), social support seeking (76.6%), taking other medications (76.6%), information seeking (48.7%), and nonadherence (35.5%). Younger age (AOR = 29.54, 95% CI = 2.49–35.25, p = 0.007), low level of education (AOR = 5.70, 95% CI = 2.16-15.05, p < 0.001), and living far from the health institution (AOR = 2.68, 95% CI = 1.29–5.57, p = 0.008) were associated with nonadherence coping strategy to relieve the adverse effects of ART. Conclusion. The present study revealed that positive emotion coping was the most commonly used strategy. Age, level of education, and distance from health institution were the predictors of nonadherence coping strategy.
Efficacy of Immunotherapy in Patients with Metastatic Mucosal or Uveal Melanoma
Authors: Mignard Claire , Deschamps Huvier Aurélie , Gillibert André , Duval Modeste Anne Bénédicte , Dutriaux Caroline , Khammari Amir , Avril Marie-Françoise , Kramkimel Nora , Mortier Laurent , Marcant Pierre , Lesimple Thierry , Gaudy-Marqueste Caroline , Lesage Candice , Machet Laurent , Aubin François , Meyer Nicolas , Beneton Nathalie , Jeudy Géraldine , Montaudié Henri , Arnault Jean-Philippe , Visseaux Laetitia , Trabelsi Sabiha , Amini-Adle Mona , Maubec Eve , Le Corre Yannick , Lipsker Dan , Wierzbicka-Hainaut Ewa , Litrowski Noémie , Stefan Andreea , Brunet-Possenti Florence , Leccia Marie-Thérèse , Joly Pascal
Published: December 2018

Background. The objective was to assess the response rate and survival of patients with metastatic mucosal melanoma (MM) and uveal melanoma (UM) treated with anti-CTLA-4 or anti-PD-1 monoclonal antibodies (mAbs). Methods. A multicenter retrospective study was performed in 25 dermatology departments in France. All patients with stage III-C to IV MM or UM who were treated with anti-CTLA-4 or anti-PD-1 mAbs between 2008 and 2016 were included and compared after adjustment for main prognostic factors with a second cohort of patients treated with chemotherapy. Tumor response was evaluated according to RECIST v. 1.1 criteria at Week 12. Results. Four-hundred-and-thirty-nine patients were included, 229 MM (151 immunotherapy, 78 chemotherapy) and 210 UM (100 immunotherapy, 110 chemotherapy). Response rates of MM patients treated with immunotherapy were 18/151 (11.9%; 95% CI:7.2%-18.2%), versus 11/78 (14.1%, 95% CI:7.3%-23.8%) in patients treated with chemotherapy (p=0.87). No tumor response was observed in UM patients treated with immunotherapy, versus 4/110 responses (3.6%, 95% CI:1.0-9.0%) in patients treated with chemotherapy (p=0.15). The adjusted overall survival (OS) of MM patients treated with immunotherapy was longer than that of patients treated with chemotherapy HR=0.62 (95% CI: 0.43-0.91), p=0.014, with an unadjusted median OS of 15.97 months [interquartile range (IQR)=6.89-27.11] and 8.82 months [IQR=5.02-14.92], respectively. The adjusted OS of UM patients treated with immunotherapy was not significantly different from that of patients treated with chemotherapy (HR=0.98, 95% CI: 0.66–1.44) p=0.92, with an unadjusted median OS of 13.38 months [IQR=6.03-29.57] and 11.02 months [IQR=6.13-23.93], respectively. Conclusion. Immunotherapy significantly improves OS for MM. The prognosis of metastatic UM remains poor.
Efficacy and Safety of Hou Gu Mi Xi on Spleen Qi Deficiency in Patients with Nonorganic Gastrointestinal Disorders: Protocol for a Multicenter, Randomized, Placebo‐Controlled Trial
Authors: Chen Xiaofan , Nie Heyun , Liu Wenjun , Zhou Xu , Nie Jianhua , Xie Bin , Chen Dongping , Jiang Yiping , Zhang Kunhe , Fu Ying , Yang Deping , Xiong Yan , Zhao Zhangyang , Sun Xin , Zhu Weifeng
Published: December 2018

Background. There is a worldwide epidemic of nonorganic gastrointestinal disorders (NOGDs), which are a class of disorders that cause various discomforts and ultimately progress into organic gastrointestinal diseases. Because of the unsatisfactory efficacy of Western medical treatments, traditional Chinese medicine (TCM) is becoming a promising complementary and alternative treatment to manage NOGDs. Objectives. To investigate the efficacy and safety of Hou Gu Mi Xi (HGMX), a newly developed dietary TCM formula, on the syndrome of spleen qi deficiency (SQD) in patients with NOGDs. Methods/Design. This study is a multicenter, randomized, double‐blinded, parallel, and placebo‐controlled trial that will last for 2 years. All qualified subjects with NOGDs and SQD will be included. The study population will be divided into the HGMX and placebo groups. To assess the efficacy of HGMX, we will mainly focus on changes in SQD symptoms scored by a Spleen Qi Deficiency Symptoms Grading and Quantifying Scale and evaluate changes in gastrin‐17, the negative Helicobacter pylori conversion rate, body weight, body mass index, and gastroscopy findings. The safety of HGMX will be assessed by recording adverse events (AEs), severe AEs, treatment‐related AEs and withdrawal due to AEs. Discussion. This trial is part of our study series that intends to validate the potential of HGMX in the management of chronic gastrointestinal diseases. This series of RCTs is the first committed to the evaluation of a dietary TCM formula and will hopefully establish an evidence‐based clinical research model for dietary TCM formulas. Ethics. The protocol was approved by Ethics Committee of five research hospitals and was registered in Clinicaltrials.gov (NCT03019042).
Mass Transfer during Osmotic Dehydration of Tunisian Pomegranate Seeds and Effect of Blanching Pretreatment
Authors: Khoualdia Basma , Ben-Ali Samia , Hannachi Ahmed
Published: December 2018

In this work, the osmotic dehydration (OD) of Tunisian pomegranate seeds of “El Gabsi” variety was investigated. To optimize the process operating conditions, the effect of temperature, hypertonic solution solid content, and stirring speed was studied. The best conditions resulting in the higher water loss and the minimum of fruit damages found are 40°C, 50°Bx, and 440 rpm. In these conditions, the effect of blanching pretreatments on the solute and water transfer kinetics during the OD was investigated. The blanching pretreatments were carried out using two methods: blanching in a boiling water bath and in a microwave oven. The mass diffusion kinetic depends on time, temperature, hypertonic solution solid content, stirring speeds, and pretreatment process. Peleg’s model showed a good fit to the experimental data. By applying blanching pretreatments, the water and solute effective diffusivities passed from the order of 10−9 to the order of 10−8, and the OD equilibrium time was significantly reduced.
Bacterial Nosocomial Infections and Antimicrobial Susceptibility Pattern among Patients Admitted at Hiwot Fana Specialized University Hospital, Eastern Ethiopia
Authors: Tolera Moti , Abate Degu , Dheresa Merga , Marami Dadi
Published: December 2018

Nosocomial infections remain a major cause of mortality and morbidity worldwide. Despite the highly specialized interventions and policies, the rate of infection is still high due to the emergence of antimicrobial-resistant bacteria. This study described the prevalence of bacterial nosocomial infections and antimicrobial susceptibility pattern of isolates among patients admitted at Hiwot Fana Specialized University Hospital, Eastern Ethiopia. A hospital-based cross-sectional study was conducted among 394 nosocomial infection-suspected patients from March 2017 to July 2017. Data were collected using a structured questionnaire. Specimens from the respective site of infections were collected and examined for the presence of pathogenic bacteria and their antimicrobial susceptibility using standard culture and serological tests. Data were summarized using descriptive statistics. The prevalence of culture-confirmed bacterial nosocomial infection was 6.9% (95% CI: 4.3–7.9).Staphylococcus aureus(18.5%) was the most common isolate followed byEscherichia coli(16.7%).S. aureusshowed 80% resistance to chloramphenicol and erythromycin, and 70% to cephalexin and tetracycline, respectively. A methicillin-resistantS. aureusmade up 88.9% of allS. aureusisolates.Pseudomonas aeruginosashowed 83.7% resistance to each of ceftazidime and cephalexin, and 66.7% to chloramphenicol. The most common multidrug-resistant isolates wereP. aeruginosa(30.4%) andS. aureus(21.7%). The prevalence of nosocomial infections in this study was comparable with other findings; however, the high rates of antimicrobial resistant isolates represent a substantial threat to the patients, communities, health care providers, and modern medical practices. Bacterial nosocomial infection treatment should be supported by culture isolation and antimicrobial susceptibility testing.