bluuebunny/crossref_metadata_2025 huggingface dataset:
Combining effects and coeffects via grading
Authors: Gaboardi Marco , Katsumata Shin-ya , Orchard Dominic , Breuvart Flavien , Uustalu Tarmo
Published: December 2016

Effects and coeffects are two general, complementary aspects of program behaviour. They roughly correspond to computations which change the execution context (effects) versus computations which make demands on the context (coeffects). Effectful features include partiality, non-determinism, input-output, state, and exceptions. Coeffectful features include resource demands, variable access, notions of linearity, and data input requirements. The effectful or coeffectful behaviour of a program can be captured and described via type-based analyses, with fine grained information provided by monoidal effect annotations and semiring coeffects. Various recent work has proposed models for such typed calculi in terms of graded (strong) monads for effects and graded (monoidal) comonads for coeffects. Effects and coeffects have been studied separately so far, but in practice many computations are both effectful and coeffectful, e.g., possibly throwing exceptions but with resource requirements. To remedy this, we introduce a new general calculus with a combined effect-coeffect system. This can describe both the changes and requirements that a program has on its context, as well as interactions between these effectful and coeffectful features of computation. The effect-coeffect system has a denotational model in terms of effect-graded monads and coeffect-graded comonads where interaction is expressed via the novel concept of graded distributive laws. This graded semantics unifies the syntactic type theory with the denotational model. We show that our calculus can be instantiated to describe in a natural way various different kinds of interaction between a program and its evaluation context.
Disjoint intersection types
Authors: Oliveira Bruno C. d. S. , Shi Zhiyuan , Alpuim João
Published: December 2016

Dunfield showed that a simply typed core calculus with intersection types and a merge operator is able to capture various programming language features. While his calculus is type-safe, it is not
coherent
: different derivations for the same expression can elaborate to expressions that evaluate to different values. The lack of coherence is an important disadvantage for adoption of his core calculus in implementations of programming languages, as the semantics of the programming language becomes implementation-dependent.

This paper presents λ_i: a coherent and type-safe calculus with a form of
intersection types
and a
merge operator
. Coherence is achieved by ensuring that intersection types are
disjoint
and programs are sufficiently annotated to avoid
type ambiguity
. We propose a definition of disjointness where two types A and B are disjoint only if certain set of types are common supertypes of A and B. We investigate three different variants of λ_i, with three variants of disjointness. In the simplest variant, which does not allow ⊤ types, two types are disjoint if they do not share any common supertypes at all. The other two variants introduce ⊤ types and refine the notion of disjointness to allow two types to be disjoint when the only the set of common supertypes are
top-like
. The difference between the two variants with ⊤ types is on the definition of top-like types, which has an impact on which types are allowed on intersections. We present a type system that prevents intersection types that are not disjoint, as well as an algorithmic specifications to determine whether two types are disjoint for all three variants.
An operational semantics for C/C++11 concurrency
Authors: Nienhuis Kyndylan , Memarian Kayvan , Sewell Peter
Published: December 2016

The C/C++11 concurrency model balances two goals: it is relaxed enough to be efficiently implementable and (leaving aside the ``thin-air'' problem) it is strong enough to give useful guarantees to programmers. It is mathematically precise and has been used in verification research and compiler testing. However, the model is expressed in an axiomatic style, as predicates on complete candidate executions. This suffices for computing the set of allowed executions of a small litmus test, but it does not directly support the incremental construction of executions of larger programs. It is also at odds with conventional operational semantics, as used implicitly in the rest of the C/C++ standards.

Our main contribution is the development of an operational model for C/C++11 concurrency. This covers all the features of the previous formalised axiomatic model, and we have a mechanised proof that the two are equivalent, in Isabelle/HOL. We also integrate this semantics with an operational semantics for sequential C (described elsewhere); the combined semantics can incrementally execute programs in a small fragment of C.

Doing this uncovered several new aspects of the C/C++11 model: we show that one cannot build an equivalent operational model that simply follows program order, sequential consistent order, or the synchronises-with order. The first negative result is forced by hardware-observable behaviour, but the latter two are not, and so might be ameliorated by changing C/C++11. More generally, we hope that this work, with its focus on incremental construction of executions, will inform the future design of new concurrency models.
Computing repair alternatives for malformed programs using constraint attribute grammars
Authors: Steimann Friedrich , Hagemann Jörg , Ulke Bastian
Published: December 2016

Attribute grammars decorate the nodes of a program's parse tree with attributes whose values are defined by equations encoding the (static) semantics of a programming language. We show how replacing the equations of an attribute grammar with equivalent constraints that can be solved by a constraint solver allows us to compute repairs of a malformed program solely from a specification that was originally designed for checking its well-formedness. We present two repair modes --- shallow and deep fixing --- whose computed repair alternatives are guaranteed to repair every error on which they are invoked. While shallow fixing may introduce new errors, deep fixing never does; to make it tractable, we implement it using neighborhood search. We demonstrate the feasibility of our approach by implementing it on top of ExtendJ, an attribute grammar based Java compiler, and by applying it to an example from the Java EE context, detecting and fixing well-formedness errors (both real and injected) in a body of 14 open-source subject programs.
Dependent partitioning
Authors: Treichler Sean , Bauer Michael , Sharma Rahul , Slaughter Elliott , Aiken Alex
Published: December 2016

A key problem in parallel programming is how data is
partitioned
: divided into subsets that can be operated on in parallel and, in distributed memory machines, spread across multiple address spaces.

We present a
dependent partitioning
framework that allows an application to concisely describe relationships between partitions. Applications first establish
independent partitions
, which may contain arbitrary subsets of application data, permitting the expression of arbitrary application-specific data distributions.
Dependent partitions
are then derived from these using the
dependent partitioning operations
provided by the framework. By directly capturing inter-partition relationships, our framework can soundly and precisely reason about programs to perform important program analyses crucial to ensuring correctness and achieving good performance. As an example of the reasoning made possible, we present a static analysis that discharges most consistency checks on partitioned data during compilation.

We describe an implementation of our framework within Regent, a language designed for the Legion programming model. The use of dependent partitioning constructs results in a 86-96% decrease in the lines of code required to describe the partitioning, eliminates many of the expensive dynamic checks required for soundness by the current Regent partitioning implementation, and speeds up the computation of partitions by 2.6-12.7X even on a single thread. Additionally, we show that a distributed implementation incorporated into the the Legion runtime system allows partitioning of data sets that are too large to fit on a single node and yields a further 29X speedup of partitioning operations on 64 nodes.
Makalu: fast recoverable allocation of non-volatile memory
Authors: Bhandari Kumud , Chakrabarti Dhruva R. , Boehm Hans-J.
Published: December 2016

Byte addressable non-volatile memory (NVRAM) is likely to supplement, and perhaps eventually replace, DRAM. Applications can then persist data structures directly in memory instead of serializing them and storing them onto a durable block device. However, failures during execution can leave data structures in NVRAM unreachable or corrupt. In this paper, we present Makalu, a system that addresses non-volatile memory management. Makalu offers an integrated allocator and recovery-time garbage collector that maintains internal consistency, avoids NVRAM memory leaks, and is efficient, all in the face of failures.

We show that a careful allocator design can support a less restrictive and a much more familiar programming model than existing persistent memory allocators. Our allocator significantly reduces the per allocation persistence overhead by lazily persisting non-essential metadata and by employing a post-failure recovery-time garbage collector. Experimental results show that the resulting online speed and scalability of our allocator are comparable to well-known transient allocators, and significantly better than state-of-the-art persistent allocators.
Maximal causality reduction for TSO and PSO
Authors: Huang Shiyou , Huang Jeff
Published: December 2016

Verifying concurrent programs is challenging due to the exponentially large thread interleaving space. The problem is exacerbated by relaxed memory models such as Total Store Order (TSO) and Partial Store Order (PSO) which further explode the interleaving space by reordering instructions. A recent advance, Maximal Causality Reduction (MCR), has shown great promise to improve verification effectiveness by maximally reducing redundant explorations. However, the original MCR only works for the Sequential Consistency (SC) memory model, but not for TSO and PSO. In this paper, we develop novel extensions to MCR by solving two key problems under TSO and PSO: 1) generating interleavings that can reach new states by encoding the operational semantics of TSO and PSO with first-order logical constraints and solving them with SMT solvers, and 2) enforcing TSO and PSO interleavings by developing novel replay algorithms that allow executions out of the program order. We show that our approach successfully enables MCR to effectively explore TSO and PSO interleavings. We have compared our approach with a recent Dynamic Partial Order Reduction (DPOR) algorithm for TSO and PSO and a SAT-based stateless model checking approach. Our results show that our approach is much more effective than the other approaches for both state-space exploration and bug finding – on average it explores 5-10X fewer executions and finds many bugs that the other tools cannot find.
Parsing with first-class derivatives
Authors: Brachthäuser Jonathan Immanuel , Rendel Tillmann , Ostermann Klaus
Published: December 2016

Brzozowski derivatives, well known in the context of regular expressions, have recently been rediscovered to give a simplified explanation to parsers of context-free languages. We add derivatives as a novel first-class feature to a standard parser combinator language. First-class derivatives enable an inversion of the control flow, allowing to implement modular parsers for languages that previously required separate pre-processing steps or cross-cutting modifications of the parsers. We show that our framework offers new opportunities for reuse and supports a modular definition of interesting use cases of layout-sensitive parsing.
Modeling and analysis of remote memory access programming
Authors: Dan Andrei Marian , Lam Patrick , Hoefler Torsten , Vechev Martin
Published: December 2016

Recent advances in networking hardware have led to a new generation of Remote Memory Access (RMA) networks in which processors from different machines can communicate directly, bypassing the operating system and allowing higher performance. Researchers and practitioners have proposed libraries and programming models for RMA to enable the development of applications running on these networks,

However, the memory models implied by these RMA libraries and languages are often loosely specified, poorly understood, and differ depending on the underlying network architecture and other factors. Hence, it is difficult to precisely reason about the semantics of RMA programs or how changes in the network architecture affect them.

We address this problem with the following contributions: (i) a
coreRMA
language which serves as a common foundation, formalizing the essential characteristics of RMA programming; (ii) complete axiomatic semantics for that language; (iii) integration of our semantics with an existing constraint solver, enabling us to exhaustively generate
coreRMA
programs (litmus tests) up to a specified bound and check whether the tests satisfy their specification; and (iv) extensive validation of our semantics on real-world RMA systems. We generated and ran 7441 litmus tests using each of the low-level RMA network APIs: DMAPP, VPI Verbs, and Portals 4. Our results confirmed that our model successfully captures behaviors exhibited by these networks. Moreover, we found RMA programs that behave inconsistently with existing documentation, confirmed by network experts.

Our work provides an important step towards understanding existing RMA networks, thus influencing the design of future RMA interfaces and hardware.
Probabilistic model for code with decision trees
Authors: Raychev Veselin , Bielik Pavol , Vechev Martin
Published: December 2016

In this paper we introduce a new approach for learning precise and general probabilistic models of code based on decision tree learning. Our approach directly benefits an emerging class of statistical programming tools which leverage probabilistic models of code learned over large codebases (e.g., GitHub) to make predictions about new programs (e.g., code completion, repair, etc).

The key idea is to phrase the problem of learning a probabilistic model of code as learning a decision tree in a domain specific language over abstract syntax trees (called TGen). This allows us to condition the prediction of a program element on a dynamically computed context. Further, our problem formulation enables us to easily instantiate known decision tree learning algorithms such as ID3, but also to obtain new variants we refer to as ID3+ and E13, not previously explored and ones that outperform ID3 in prediction accuracy.

Our approach is general and can be used to learn a probabilistic model of any programming language. We implemented our approach in a system called Deep3 and evaluated it for the challenging task of learning probabilistic models of JavaScript and Python. Our experimental results indicate that Deep3 predicts elements of JavaScript and Python code with precision above 82% and 69%, respectively. Further, Deep3 often significantly outperforms state-of-the-art approaches in overall prediction accuracy.
UCP1 inhibition in Cidea-overexpressing mice is physiologically counteracted by brown adipose tissue hyperrecruitment
Authors: Fischer Alexander W. , Shabalina Irina G. , Mattsson Charlotte L. , Abreu-Vieira Gustavo , Cannon Barbara , Nedergaard Jan , Petrovic Natasa
Published: December 2016

Cidea is a gene highly expressed in thermogenesis-competent (UCP1-containing) adipose cells, both brown and brite/beige. Here, we initially demonstrate a remarkable adipose-depot specific regulation of Cidea expression. In classical brown fat, Cidea mRNA is expressed continuously and invariably, irrespective of tissue recruitment. However, Cidea protein levels are regulated posttranscriptionally, being conspicuously induced in the thermogenically recruited state. In contrast, in brite fat, Cidea protein levels are regulated at the transcriptional level, and Cidea mRNA and protein levels are proportional to tissue “briteness.” Although routinely followed as a thermogenic molecular marker, Cidea function is not clarified. Here, we employed a gain-of-function approach to examine a possible role of Cidea in the regulation of thermogenesis. We utilized transgenic aP2-hCidea mice that overexpress human Cidea in all adipose tissues. We demonstrate that UCP1 activity is markedly suppressed in brown-fat mitochondria isolated from aP2-hCidea mice. However, mitochondrial UCP1 protein levels were identical in wild-type and transgenic mice. This implies a regulatory effect of Cidea on UCP1 activity, but as we demonstrate that Cidea itself is not localized to mitochondria, we propose an indirect inhibitory effect. The Cidea-induced inhibition of UCP1 activity (observed in isolated mitochondria) is physiologically relevant since the mice, through an appropriate homeostatic compensatory mechanism, increased the total amount of UCP1 in the tissue to exactly match the diminished thermogenic capacity of the UCP1 protein and retain unaltered nonshivering thermogenic capacity. Thus, we verified Cidea as being a marker of thermogenesis-competent adipose tissues, but we conclude that Cidea, unexpectedly, functions molecularly as an indirect inhibitor of thermogenesis.
Potential Role of Synaptic Activity to Inhibit LTD Induction in Rat Visual Cortex
Authors: Stewart Matthew R. , Dringenberg Hans C.
Published: December 2016

Long-term depression (LTD), a widely studied form of activity-dependent synaptic plasticity, is typically induced by prolonged low-frequency stimulation (LFS). Interestingly, LFS is highly effective in eliciting LTDin vitro, but much less so underin vivoconditions; the reasons for the resistance of the intact brain to express LTD are not well understood. We examined if levels of background electrocorticographic (ECoG) activity influence LTD induction in the thalamocortical visual system of rats under very deep urethane anesthesia, inducing a brain state of reduced spontaneous cortical activity. Under these conditions, LFS applied to the lateral geniculate nucleus resulted in LTD of field postsynaptic potentials (fPSPs) recorded in the primary visual cortex (V1). Pairing LFS with stimulation of the brainstem (pedunculopontine) reticular formation resulted in the appearance of faster, more complex activity in V1 and prevented LTD induction, an effect that did not require muscarinic or nicotinic receptors. Reticular stimulation alone (without LFS) had no effect on cortical fPSPs. These results show that excitation of the brainstem activating system blocks the induction of LTD in V1. Thus, higher levels of neural activity may inhibit depression at cortical synapses, a hypothesis that could explain discrepancies regarding LTD induction in previousin vivoandin vitrowork.
A Study of Visual Descriptors for Outdoor Navigation Using Google Street View Images
Authors: Fernández L. , Payá L. , Reinoso O. , Jiménez L. M. , Ballesta M.
Published: December 2016

A comparative analysis between several methods to describe outdoor panoramic images is presented. The main objective consists in studying the performance of these methods in the localization process of a mobile robot (vehicle) in an outdoor environment, when a visual map that contains images acquired from different positions of the environment is available. With this aim, we make use of the database provided by Google Street View, which contains spherical panoramic images captured in urban environments and their GPS position. The main benefit of using these images resides in the fact that it permits testing any novel localization algorithm in countless outdoor environments anywhere in the world and under realistic capture conditions. The main contribution of this work consists in performing a comparative evaluation of different methods to describe images to solve the localization problem in an outdoor dense map using only visual information. We have tested our algorithms using several sets of panoramic images captured in different outdoor environments. The results obtained in the work can be useful to select an appropriate description method for visual navigation tasks in outdoor environments using the Google Street View database and taking into consideration both the accuracy in localization and the computational efficiency of the algorithm.
The Changing Phenotype of Inflammatory Bowel Disease
Authors: Moran Carthage , Sheehan Donal , Shanahan Fergus
Published: December 2016

It is widely known that there have been improvements in patient care and an increased incidence of Inflammatory Bowel Disease (IBD) worldwide in recent decades. However, less well known are the phenotypic changes that have occurred; these are discussed in this review. Namely, we discuss the emergence of obesity in patients with IBD, elderly onset disease, mortality rates, colorectal cancer risk, the burden of medications and comorbidities, and the improvement in surgical treatment with a decrease in surgical rates in recent decades.
Comparison of Conventional and Advanced Concrete Technologies in terms of Construction Efficiency
Authors: Špak Matej , Kozlovská Mária , Struková Zuzana , Bašková Renáta
Published: December 2016

Nowadays, high-performance concrete (HPC) and ultra-high-performance concrete (UHPC) are ranked among advanced concrete technologies. The application of the mentioned advanced technologies may have potential to improve the construction efficiency from several points of view. For instance, reducing of construction time and construction material, construction quality improving, environmental impact minimizing, and increasing of both durability and lifetime of structures as well as reducing of total construction costs may be obtained. Particular advanced concrete technologies are described and the possibilities of their utilization in both monolithic structures and precast units are presented in the article. The main benefits of modern methods of construction (MMC) based on advanced concrete technologies application in precast elements production are presented. Regarding the selected aspects of construction efficiency assessment, a comparison of conventional and advanced concrete technologies that are applied in monolithic structures and precast units is made. The results of this comparison, estimated in semantic differential scale, are presented in the article. By the results of the comparison, the significance of applying the advanced concrete technologies in modern methods of concrete structures production is demonstrated in order to improve construction efficiency.
How Does Interleukin-22 Mediate Liver Regeneration and Prevent Injury and Fibrosis?
Authors: Khawar Muhammad Babar , Azam Fareeha , Sheikh Nadeem , Abdul Mujeeb Khawaja
Published: December 2016

Interleukin-22 (IL-22) is a pluripotent T cell-derived cytokine which is a member of IL-10 cytokine family. It is the only interleukin produced by immune cells but does not target immune system components. IL-22 is mainly produced by dendritic cells (DCs) and TH17, TH22, NK, and NKT cells and targets a number of body tissues including liver, pancreas, and other epithelial tissues. It provokes a series of downstream signaling pathways upon binding with IL-22R complex which protects liver damage through STAT3 activation. IL-22BP is an inhibitor of IL-22 which has 20–1000x more affinity to bind with IL-22 compared to IL-22R1 that inhibits IL-22 activity. Its level was found to be positively correlated with the severity of liver damage and fibrosis. So, the present review is an effort to reveal the exact mechanism lying in the hepatoprotective activity of IL-22 and some of its future therapeutic implications.
Serum Cytokinome Profile Evaluation: A Tool to Define New Diagnostic and Prognostic Markers of Cancer Using Multiplexed Bead-Based Immunoassays
Authors: Capone Francesca , Guerriero Eliana , Sorice Angela , Colonna Giovanni , Ciliberto Gennaro , Costantini Susan
Published: December 2016

In recent years, many researchers are focusing their attention on the link between inflammation and cancer. The inflammation is involved in the tumor development and suppression, by stimulating the immune response. In particular, the transition from chronic inflammation to cancer produces angiogenic and growth factors able to repair the tissue and to promote cancer cell survival, implantation, and growth. In this contest, the cytokines contribute to the development of these processes becoming active before and during the inflammatory process and playing an important function at the various disease levels. Thus, these proteins can represent specific markers of tumor development and progression. Therefore the “cytokinome” term is used to indicate the evaluation of cytokine pattern by using an “omics” approach. Newly, specific protein chips of considerable and improved sensitivity are being developed to determine simultaneously several and different cytokines. This can be achieved by a multiplex technology that, through the use of small amounts of serum or other fluids, is used to determine the presence and the levels of underrepresented cytokines. Since this method is an accurate, sensitive, and reproducible cytokine assay, it is already used in many different studies. Thus, this review focuses on the more latest aspects related to cytokinome profile evaluation in different cancers.
Ghanaians Might Be at Risk of Inadequate Dietary Intake of Potassium
Authors: Yawson David Oscar , Adu Michael Osei , Ason Benjamin , Armah Frederick Ato , Boateng Emmanuel , Quansah Reggie
Published: December 2016

Adequate dietary intake of potassium (K) helps fight noncommunicable diseases (NCDs), mainly hypertension and cardiovascular diseases. This paper (i) estimated the K intake of Ghanaian population using food supply and food composition data and (ii) compared this estimate with the WHO recommended requirement for K in order to assess if there is a risk of inadequate K intake. Food supply data (1961–2011) was obtained from the FAO Food Balance Sheet (FBS) to derive trends in food and K supply. The average food supply in the FBS for 2010 and 2011 was used in assessing the risk of inadequate dietary intake of K. The K contents of the food items were obtained from food composition databases. The mean K supply per capita per day was approximately 856 mg. The assessment suggests a potentially large risk of inadequate dietary K supply at both individual and population levels. The results suggest the need for assessing options for managing K deficiency, including assessment of K supplying power of soils and K fertilizer management in food crop production systems, as well as empirical estimates of K content of food items (including those underreported in the FBS) and mixed diets in Ghana.
Altered Brain Glucose Consumption in Cogan’s Syndrome
Authors: Mora Paolo , Ruffini Livia , Ghetti Caterina , Ghirardini Stella , Scarlattei Maura , Baldari Giorgio , Cidda Carla , Rubino Pierangela , Gandolfi Stefano A. , Orsoni Jelka G.
Published: December 2016

Purpose. Prospective, controlled cohort study to investigate possible alterations in brain glucose metabolism (CMRglc) in patients with Cogan’s syndrome (CS).Patients and Methods. Functional mapping of the CMRglc was obtained by quantitative molecular imaging positron emission tomography, combined with computed tomography (FDG-PET/CT). The patients were divided into three clinical groups: typical CS; atypical CS (ACS); autoimmune inner ear disease (AIED). The unmatched control group (CG) consisted of subjects requiring FDG-PET/CT for an extracranial pathology. Statistical mapping searched areas of significant glucose hypometabolism in all the affected patients (DG) and in each clinical subgroup. The results were compared with those of the CG.Results. 44 patients were enrolled (DG) and assigned to the three study groups: 8 patients to the CS group; 21 patients to the ACS group; and 15 to the AIED group. Sixteen subjects formed the CG group. Areas of significant brain glucose hypometabolism were identified in all the study groups, with the largest number and extension in the DG and CS.Conclusions. This study revealed areas of significantly altered CMRglc in patients with CS (any subform) without neurologic complains and normal conventional neuroimaging. Our results suggest that FDG-PET/CT may represent a very useful tool for the global assessment of patients with Cogan’s syndrome.
The Classification of Tongue Colors with Standardized Acquisition and ICC Profile Correction in Traditional Chinese Medicine
Authors: Qi Zhen , Tu Li-ping , Chen Jing-bo , Hu Xiao-juan , Xu Jia-tuo , Zhang Zhi-feng
Published: December 2016

Background and Goal. The application of digital image processing techniques and machine learning methods in tongue image classification in Traditional Chinese Medicine (TCM) has been widely studied nowadays. However, it is difficult for the outcomes to generalize because of lack of color reproducibility and image standardization. Our study aims at the exploration of tongue colors classification with a standardized tongue image acquisition process and color correction. Methods. Three traditional Chinese medical experts are chosen to identify the selected tongue pictures taken by the TDA-1 tongue imaging device in TIFF format through ICC profile correction. Then we compare the mean value of L*a*b* of different tongue colors and evaluate the effect of the tongue color classification by machine learning methods. Results. The L*a*b* values of the five tongue colors are statistically different. Random forest method has a better performance than SVM in classification. SMOTE algorithm can increase classification accuracy by solving the imbalance of the varied color samples. Conclusions. At the premise of standardized tongue acquisition and color reproduction, preliminary objectification of tongue color classification in Traditional Chinese Medicine (TCM) is feasible.
A New Approach for Chaotic Time Series Prediction Using Recurrent Neural Network
Authors: Li Qinghai , Lin Rui-Chang
Published: December 2016

A self-constructing fuzzy neural network (SCFNN) has been successfully used for chaotic time series prediction in the literature. In this paper, we propose the strategy of adding a recurrent path in each node of the hidden layer of SCFNN, resulting in a self-constructing recurrent fuzzy neural network (SCRFNN). This novel network does not increase complexity in fuzzy inference or learning process. Specifically, the structure learning is based on partition of the input space, and the parameter learning is based on the supervised gradient descent method using a delta adaptation law. This novel network can also be applied for chaotic time series prediction including Logistic and Henon time series. More significantly, it features rapider convergence and higher prediction accuracy.
Exercise Training Promotes Functional Recovery after Spinal Cord Injury
Authors: Fu Juanjuan , Wang Hongxing , Deng Lingxiao , Li Jianan
Published: December 2016

The exercise training is an effective therapy for spinal cord injury which has been applied to clinic. Traditionally, the exercise training has been considered to improve spinal cord function only through enhancement, compensation, and replacement of the remaining function of nerve and muscle. Recently, accumulating evidences indicated that exercise training can improve the function in different levels from end-effector organ such as skeletal muscle to cerebral cortex through reshaping skeletal muscle structure and muscle fiber type, regulating physiological and metabolic function of motor neurons in the spinal cord and remodeling function of the cerebral cortex. We compiled published data collected in different animal models and clinical studies into a succinct review of the current state of knowledge.
Variables That Best Differentiate In-Patient Acute Stroke from Stroke-Mimics with Acute Neurological Deficits
Authors: Natteru P. , Mohebbi M. R. , George P. , Wisco D. , Gebel J. , Newey C. R.
Published: December 2016

Introduction. Strokes and stroke-mimics have been extensively studied in the emergency department setting. Although in-hospital strokes are less studied in comparison to strokes in the emergency department, they are a source of significant direct and indirect costs. Differentiating in-hospital strokes from stroke-mimics is important. Thus, our study aimed to identify variables that can differentiate in-hospital strokes from stroke-mimics. Methods. We present here a retrospective analysis of 93 patients over a one-year period (2009 to 2010), who were evaluated for a concern of in-hospital strokes. Results. About two-thirds (57) of these patients were determined to have a stroke, and the remaining (36) were stroke-mimics. Patients with in-hospital strokes were more likely to be obese (p=0.03), have been admitted to the cardiology service (p=0.01), have atrial fibrillation (p=0.03), have a weak hand or hemiparesis (p=0.03), and have a prior history of stroke (p=0.05), whereas, when the consults were called for “altered mental status” but no other deficits (p<0.0001), it is likely a stroke-mimic. Conclusion. This study demonstrates that in-hospital strokes are a common occurrence, and knowing the variables can aid in their timely diagnosis and treatment.
The Expression of HMGB1 in Bone Marrow MSCs Is Upregulated by Hypoxia with Regulatory Effects on the Apoptosis and Adhesion
Authors: Tan Mei-Yun , Zhang Cai-Dong , Xia Bo , Guo Jiang , Fan Zhong-Wei , Wu Tian-Hao , Wang Sen , Liu Shao-Feng , Deng Li , Guo Xing , Huang Yong-Can
Published: December 2016

Background and Aims. Hypoxia regulates the survival of mesenchymal stem cells (MSCs) but the mechanism is unclear. In hypoxia, the level of high mobility group box 1 (HMGB1) was increased in many cells which may be involved in the regulation of cell biology. The aim is to determine whether hypoxia affects the expression of HMGB1 in bone marrow MSCs (BM-MSCs) and to investigate the role of HMGB1 in the apoptosis and adhesion.Methods. BM-MSCs were exposed to hypoxia (1% O2) and normoxia (20% O2) and the expression of HMGB1 was measured by RT-PCR and western blotting. The apoptosis and adhesion of BM-MSCs were evaluated after interfered by different concentrations of HMGB1.Results. Expression of HMGB1 in BM-MSCs showed a significant upregulation in hypoxia when compared to those in normoxia. The adhesion of BM-MSCs was increased by HMGB1 in a concentration-dependent manner; the apoptosis effect of HMGB1 depended on its concentrations: HMGB1 at low concentration (50 ng/mL) promoted the apoptosis of BM-MSCs while HMGB1 at high concentration (≥100 ng/mL) reduced this apoptosis.Conclusions. Hypoxia enhanced the expression of HMGB1 in BM-MSCs with influences on apoptosis and adhesion and this could have a significant effect on the regenerative potential of MSC-based strategies.
Construction Formula of Biological Age Using the Principal Component Analysis
Authors: Jia Linpei , Zhang Weiguang , Jia Rufu , Zhang Hongliang , Chen Xiangmei
Published: December 2016

The biological age (BA) equation is a prediction model that utilizes an algorithm to combine various biological markers of ageing. Different from traditional concepts, the BA equation does not emphasize the importance of a golden index but focuses on using indices of vital organs to represent the senescence of whole body. This model has been used to assess the ageing process in a more precise way and may predict possible diseases better as compared with the chronological age (CA). The principal component analysis (PCA) is applied as one of the common and frequently used methods in the construction of the BA formula. Compared with other methods, PCA has its own study procedures and features. Herein we summarize the up-to-date knowledge about the BA formula construction and discuss the influential factors, so as to give an overview of BA estimate by PCA, including composition of samples, choices of test items, and selection of ageing biomarkers. We also discussed the advantages and disadvantages of PCA with reference to the construction mechanism, accuracy, and practicability of several common methods in the construction of the BA formula.
Workflow for Genome-Wide Determination of Pre-mRNA Splicing Efficiency from Yeast RNA-seq Data
Authors: Převorovský Martin , Hálová Martina , Abrhámová Kateřina , Libus Jiří , Folk Petr
Published: December 2016

Pre-mRNA splicing represents an important regulatory layer of eukaryotic gene expression. In the simple budding yeast Saccharomyces cerevisiae, about one-third of all mRNA molecules undergo splicing, and splicing efficiency is tightly regulated, for example, during meiotic differentiation. S. cerevisiae features a streamlined, evolutionarily highly conserved splicing machinery and serves as a favourite model for studies of various aspects of splicing. RNA-seq represents a robust, versatile, and affordable technique for transcriptome interrogation, which can also be used to study splicing efficiency. However, convenient bioinformatics tools for the analysis of splicing efficiency from yeast RNA-seq data are lacking. We present a complete workflow for the calculation of genome-wide splicing efficiency in S. cerevisiae using strand-specific RNA-seq data. Our pipeline takes sequencing reads in the FASTQ format and provides splicing efficiency values for the 5′ and 3′ splice junctions of each intron. The pipeline is based on up-to-date open-source software tools and requires very limited input from the user. We provide all relevant scripts in a ready-to-use form. We demonstrate the functionality of the workflow using RNA-seq datasets from three spliceosome mutants. The workflow should prove useful for studies of yeast splicing mutants or of regulated splicing, for example, under specific growth conditions.
Awareness, Treatment, and Control of Hypertension in Primary Health Care and Secondary Referral Medical Outpatient Clinic Settings at Enugu, Southeast Nigeria
Authors: Chijioke Chioli , Anakwue Raphael , Okolo Teddy , Ekwe Esther , Eze Chukwuemeka , Agunyenwa Charles , Nwosu Nnamdi , Amah Christopher , Nwadike Kenneth , Chijioke Udunma
Published: December 2016

Essential hypertension is the most common noncommunicable disease (NCD), affecting more than half the adult population in many countries and being the major NCD contributor to the double burden of disease in developing countries. We undertook a survey of the hypertension awareness, treatment, and control in primary and secondary referral health care clinics in Enugu, Nigeria, and compared these data with those obtained in local community surveys. The prevalence of hypertension in the primary care clinic (9.2%) was lower than in a previously reported community survey (42.2%), while, in the referral clinic, 70.3% of patients attending were hypertensive. Hypertension awareness rates were 91.9%, 29.4%, and 93.2% in these respective health care settings. Treatment and control rates (89.9% and 72.9%) were better in the secondary care clinic than in the primary care centre (87.7% and 46.0%). (Chi-square analysis confirmed statistically significant differences between these rates (p<0.05).) These data may form a useful index of health care system effectiveness in Nigeria. Possible reasons for the differences observed and effective strategies to address the waxing pandemic of hypertension are discussed.
In VitroProliferation of Porcine Pancreatic Islet Cells forβ-Cell Therapy Applications
Authors: Niu Guoguang , McQuilling John P. , Zhou Yu , Opara Emmanuel C. , Orlando Giuseppe , Soker Shay
Published: December 2016

β-Cell replacement through transplantation is the only curative treatment to establish a long-term stable euglycemia in diabetic patients. Owing to the shortage of donor tissue, attempts are being made to develop alternative sources of insulin-secreting cells. Stem cells differentiation and reprograming as well as isolating pancreatic progenitors from different sources are some examples; however, no approach has yet yielded a clinically relevant solution. Dissociated islet cells that are cultured in cell numbers byin vitroproliferation provide a promising platform for redifferentiation towardsβ-cells phenotype. In this study, we cultured islet-derived cellsin vitroand examined the expression ofβ-cell genes during the proliferation. Islets were isolated from porcine pancreases and enzymatically digested to dissociate the component cells. The cells proliferated well in tissue culture plates and were subcultured for no more than 5 passages. Only 10% of insulin expression, as measured by PCR, was preserved in each passage. High glucose media enhanced insulin expression by about 4–18 fold, suggesting a glucose-dependent effect in the proliferated islet-derived cells. The islet-derived cells also expressed other pancreatic genes such as Pdx1, NeuroD, glucagon, and somatostatin. Taken together, these results indicate that pancreatic islet-derived cells, proliferatedin vitro, retained the expression capacity for key pancreatic genes, thus suggesting that the cells may be redifferentiated into insulin-secretingβ-like cells.
The Efficacy of Brucea javanica Oil Emulsion Injection as Adjunctive Therapy for Advanced Non‐Small‐Cell Lung Cancer: A Meta‐Analysis
Authors: Xu Wei , Jiang Xinchan , Xu Zhengyuan , Ye Tong , Shi Qionghua
Published: December 2016

Purpose. To evaluate the efficacy of Brucea javanica oil emulsion injection (BJOEI) in patients with advanced non‐small‐cell lung cancer (NSCLC) during chemotherapy. Method. Electronic database of EMBASE and PubMed and the conference proceeding of ASCO, CNKI, CBMdisc, VIP, and Wanfang database were searched to select RCTs comparing BJOEI plus chemotherapy with chemotherapy alone in the treatment of advanced NSCLC, until June 1, 2016. Two reviewers independently performed the analysis according to the inclusion and exclusion criteria. Review Manager 5.3 and STATA 12.0 were employed for data analysis. Result. Twenty‐one studies including 2234 cases were included. The pooled result indicated that there were significant differences in ORR (RR = 1.25; 95% CI: 1.14–1.36; P < 0.00001), improvement of QOL (RR = 1.87; 95% CI: 1.63–2.15; P < 0.00001), nausea and vomiting (RR = 0.67; 95% CI: 0.46–0.98; P = 0.04), leukopenia (RR = 0.63; 95% CI: 0.52–0.75; P < 0.00001), but there was no difference in thrombocytopenia (RR = 0.78; 95% CI: 0.49–1.23; P = 0.29). Begg’s funnel plot and Egger’s test indicated that no publication bias was found. The sensitivity analysis suggested the stability of the pooled result. Conclusion. The addition of BJOEI can enhance efficacy, improve QOL, and decrease incidence of nausea and vomiting and leukopenia for advanced NSCLC patients. However, higher quality RCTs are needed to further confirm this finding.
Acceptability and Feasibility of an Evidence-Based Requisition for Bone Mineral Density Testing in Clinical Practice
Authors: Munce Sarah E. P. , Butt Debra A. , Anantharajah Rokeni (Sumi) , Huang Susana , Allin Sonya , Bereket Tarik , Jaglal Susan B.
Published: December 2016

Introduction.The purpose of this study is to understand the experience of primary care providers (PCPs) using an evidence-based requisition for bone mineral density (BMD) testing.Methods.A qualitative descriptive approach was adopted. Participants were given 3 BMD Recommended Use Requisitions (RUR) to use over a 2-month period. Twenty-six PCPs were interviewed before using the RUR. Those who had received at least one BMD report resulting from RUR use were then interviewed again. An inductive thematic analysis was performed.Results.We identified four themes in interview data: (1) positive and negative characteristics of the RUR, (2) facilitators and barriers for implementation, (3) impact of the RUR, and (4) requisition preference. Positive characteristics of the RUR related to both its content and format. Negative characteristics related to the increased amount of time needed to complete the form. Facilitators to implementation included electronic availability and organizational endorsement. Time constraints were identified as a barrier to implementation. Participants perceived that the RUR would promote appropriate referrals and the majority of participants preferred the RUR to their current requisition.Conclusions.Findings from this study provide support for the RUR as an acceptable point-of-care tool for PCPs to promote appropriate BMD testing.
Tardive Dyskinesia, Oral Parafunction, and Implant-Supported Rehabilitation
Authors: Lumetti S. , Ghiacci G. , Macaluso G. M. , Amore M. , Galli C. , Calciolari E. , Manfredi E.
Published: December 2016

Oral movement disorders may lead to prosthesis and implant failure due to excessive loading. We report on an edentulous patient suffering from drug-induced tardive dyskinesia (TD) and oral parafunction (OP) rehabilitated with implant-supported screw-retained prostheses. The frequency and intensity of the movements were high, and no pharmacological intervention was possible. Moreover, the patient refused night-time splint therapy. A series of implant and prosthetic failures were experienced. Implant failures were all in the maxilla and stopped when a rigid titanium structure was placed to connect implants. Ad hoc designed studies are desirable to elucidate the mutual influence between oral movement disorders and implant-supported rehabilitation.
Research on the Preparation and Performance of Binary Modified Maltodextrin Water-Reducing Agent
Authors: Wu Jingzhi , Qiao Min , Lyu Zhifeng , Ran Qianping
Published: December 2016

Using maltodextrin (MD) of different dextrose equivalent (DE) values, 1,3-propanesultone, and maleic anhydride as raw materials, a novel binary modified maltodextrin (BMMD) was synthesized and further applied as a water-reducing agent. Its structure was characterized by Fourier transform infrared (FT-IR) and UV. The rheological behavior of the sample solution and strengths for concrete were also determined and the adsorption was tested by TOC. The influence of the process parameters to degree of substitution (DS) and the dosage on the fluidity of cement paste were investigated. The results show that the optimal conditions of sulfonation were the MD of DE 15, m (sulfonated agent)/m (MD) of 1.4, the catalyst amount of 1% by mass MD, and the reaction time of 12 h; the optimal conditions of esterification were m (esterified agent)/m (SMD) of 0.6, the reaction temperature of 90°C, and the reaction time of 4 h. The optimal dosages of sulfonated maltodextrin (SMD) and BMMD were 0.475% and 0.45%, respectively. In this dosage, the main dispersion capacity of BMMD attributes to two kinds of anchoring groups (SO3-  &  COO-) and the appropriate molecular weight of MD.
Leptin, Leptin Soluble Receptor, and the Free Leptin Index following a Diet and Physical Activity Lifestyle Intervention in Obese Males and Females
Authors: Herrick Jeffrey E. , Panza Gino S. , Gollie Jared M.
Published: December 2016

Leptin (LEP) is associated with appetite regulation and metabolism. Concentration is linear with adiposity, suggesting LEP resistance. LEP circulates freely and bound with its soluble receptor (sOB-r); the ratio is the free leptin index (FLI), an index of leptin resistance; lower FLI suggests reduced biological action.Purpose. The aim was to determine the effect of changes in adipose tissue distribution on LEP, sOB-r, and FLI following 6 months (6 M) of a diet/exercise weight loss program (WLP). In addition, we aim to identify predictors of the FLI.Methods. 6 M WLP consisted of diet/lifestyle interventions following ADA guidelines. Body composition was assessed by DXA. LEP and sOB-r analysis were done via ELISA.Results. 10 adults completed the WLP. Significant reductions were seen in total fat percentage (% fat), nontrunk fat, (NTF), and trunk fat (TF) from base to 3 m and 6 M (p≤0.05). The FLI were reduced at 3 M and 6 M for males and 6 M for females. Total body fat and body weight predicted the FLI in both sexes.Conclusions. LEP and FLI reductions following 6 M of WLP were achieved independent of sOB-r changes. We also demonstrate that the FLI can be predicted noninvasively through total fat mass and body weight in kilograms.