bluuebunny/crossref_metadata_2025 huggingface dataset:
A study of coFeB magnetic yoke based on planar electromagnet
Authors: Qin L. , Li Q. , Yuan Yong J.
Published: May 2017

This paper studies the fabrication of a novel planar electromagnet consisting of a planar copper coil and a magnetic yoke. CoFeB was used as the magnetic yoke material instead of the traditional permanent magnets. The planar electromagnet was fabricated and optimized to maximize the electromagnetic force, especially with varying CoFeB thickness. The micro-planar electromagnet was fabricated successfully by the traditional micro-electro-mechanical-system (MEMS) techniques and XRD, VSM were used to characterize the performance of the electromagnet. The planar electromagnet exhibits superior perpendicular magnetic anisotropy (PMA) and 0.006 emu of [Formula: see text] was achieved following 2 min deposition of CoFeB thin film. By integrating with other micro apparatuses, it is anticipated that the planar electromagnet will have potential applications in areas such as biosensors, biological medicine, drug delivery, chemical analysis and environmental monitoring.
ON HADAMARD FRACTIONAL CALCULUS
Authors: MA LI , LI CHANGPIN
Published: May 2017

This paper is devoted to the investigation of the Hadamard fractional calculus in three aspects. First, we study the semigroup and reciprocal properties of the Hadamard-type fractional operators. Then, the definite conditions of certain class of Hadamard-type fractional differential equations (HTFDEs) are proposed through the Banach contraction mapping principle. Finally, we prove a novel Gronwall inequality with weak singularity and analyze the dependence of solutions of HTFDEs on the derivative order and the perturbation terms along with the proposed initial value conditions. The illustrative examples are presented as well.
Advanced Economic Control of Electricity-Based Space Heating Systems in Domestic Coalitions with Shared Intermittent Energy Resources
Authors: Panagopoulos Athanasios Aris , Maleki Sasan , Rogers Alex , Venanzi Matteo , Jennings Nicholas R.
Published: May 2017

Over the past few years, Domestic Heating Automation Systems (DHASs) that optimize the domestic space heating control process with minimum user input, utilizing appropriate occupancy prediction technology, have emerged as commercial products (e.g., the smart thermostats from Nest and Honeywell). At the same time, many houses are being equipped with, potentially grid-connected, Intermittent Energy Resources (IERs), such as rooftop photovoltaic systems and/or small wind turbine generators. Now, in many regions of the world, such houses can sell energy to the grid but at a lower price than the price of buying it. In this context, and given the anticipated increase in electrification of heating, the next generation DHASs need to incorporate Advanced Economic Control (AEC). Such AEC can exploit the energy buffer that heating loads provide, in order to shift the consumption of electricity-based heating systems to follow the intermittent energy generation of the house. By so doing, the energy imported from the grid can be minimized and considerable monetary gains for the household can be achieved, without affecting the occupants’ schedule. These benefits can be amplified still further in domestic coalitions, where a number of houses come together and share their IER generation to minimize their cumulative grid energy import.

Given the above, in this work we extend a state-of-the-art DHAS, to propose AdaHeat+, a practical DHAS, that, for the first time, incorporates AEC. Our work is applicable to both individual houses and domestic coalitions and comes complete with an allocation mechanism to share the coalition gains. Importantly, we propose an effective heuristic heating schedule planning approach for collective AEC that (i) has a complexity that scales in a linear and parallelizable manner with the coalition size, and (ii) enables AdaHeat+ to handle the distinct preferences, in balancing heating cost and thermal discomfort, of the households. Our approach relies on stochastic IER power output predictions. In this context, we propose a simple and effective formulation for the site-specific calibration of such predictions based on adaptive Gaussian process modeling. Finally, we demonstrate the effectiveness of AdaHeat+ through real data evaluation, to show that collective AEC can improve heating cost-efficiency by up to 60%, compared to independent AEC (and even more when compared to no-AEC).
Protecting Caches from Soft Errors
Authors: Ko Yohan , Jeyapaul Reiley , Kim Youngbin , Lee Kyoungwoo , Shrivastava Aviral
Published: May 2017

Soft error is one of the most important design concerns in modern embedded systems with aggressive technology scaling. Among various microarchitectural components in a processor, cache is the most susceptible component to soft errors. Error detection and correction codes are common protection techniques for cache memory due to their design simplicity. In order to design effective protection techniques for caches, it is important to quantitatively estimate the susceptibility of caches without and even with protections. At the architectural level, vulnerability is the metric to quantify the susceptibility of data in caches. However, existing tools and techniques calculate the vulnerability of data in caches through coarse-grained block-level estimation. Further, they ignore common cache protection techniques such as error detection and correction codes. In this article, we demonstrate that our word-level vulnerability estimation is accurate through intensive fault injection campaigns as compared to block-level one. Further, our extensive experiments over benchmark suites reveal several counter-intuitive and interesting results. Parity checking when performed over just reads provides reliable and power-efficient protection than that when performed over both reads and writes. On the other hand, checking error correcting codes only at reads alone can be vulnerable even for single-bit soft errors, while that at both reads and writes provides the perfect reliability.
Real-Time Simulation Support for Runtime Verification of Cyber-Physical Systems
Authors: Zheng Xi , Julien Christine , Chen Hongxu , Podorozhny Rodion , Cassez Franck
Published: May 2017

In Cyber-Physical Systems (CPS), cyber and physical components must work seamlessly in tandem. Runtime verification of CPS is essential yet very difficult, due to deployment environments that are expensive, dangerous, or simply impossible to use for verification tasks. A key enabling factor of runtime verification of CPS is the ability to integrate real-time simulations of portions of the CPS into live running systems. We propose a verification approach that allows CPS application developers to opportunistically leverage real-time simulation to support runtime verification. Our approach, termed B
race
B
ind
, allows selecting, at runtime, between actual physical processes or simulations of them to support a running CPS application. To build B
race
B
ind
, we create a real-time simulation architecture to generate and manage multiple real-time simulation environments based on existing simulation models in a manner that ensures sufficient accuracy for verifying a CPS application. Specifically, B
race
B
ind
aims to both improve simulation speed and minimize latency, thereby making it feasible to integrate simulations of physical processes into the running CPS application. B
race
B
ind
then integrates this real-time simulation architecture with an existing runtime verification approach that has low computational overhead and high accuracy. This integration uses an aspect-oriented adapter architecture that connects the variables in the cyber portion of the CPS application with either sensors and actuators in the physical world or the automatically generated real-time simulation. Our experimental results show that, with a negligible performance penalty, our approach is both efficient and effective in detecting program errors that are otherwise only detectable in a physical deployment.
Dynamic Power and Energy Management for Energy Harvesting Nonvolatile Processor Systems
Authors: Ma Kaisheng , Li Xueqing , Liu Huichu , Sheng Xiao , Wang Yiqun , Swaminathan Karthik , Liu Yongpan , Xie Yuan , Sampson John , Narayanan Vijaykrishnan
Published: May 2017

Self-powered systems running on scavenged energy will be a key enabler for pervasive computing across the Internet of Things. The variability of input power in energy-harvesting systems limits the effectiveness of static optimizations aimed at maximizing the input-energy-to-computation ratio. We show that the resultant gap between available and exploitable energy is significant, and that energy storage optimizations alone do not significantly close the gap. We characterize these effects on a real, fabricated energy-harvesting system based on a nonvolatile processor. We introduce a unified energy-oriented approach to first optimize the number of backups, by more aggressively using the stored energy available when power failure occurs, and then optimize forward progress via improving the rate of input energy to computation via dynamic voltage and frequency scaling and self-learning techniques. We evaluate combining these schemes and show capture of up to 75.5% of all input energy toward processor computation, an average of 1.54 × increase over the best static “Forward Progress” baseline system. Notably, our energy-optimizing policy combinations simultaneously improve both the rate of forward progress and the rate of backup events (by up to 60.7% and 79.2% for RF power, respectively, and up to 231.2% and reduced to zero, respectively, for solar power). This contrasts with static frequency optimization approaches in which these two metrics are antagonistic.
Analysis and Design of Safety-critical, Cyber-Physical Systems
Authors: McGregor John D. , Gluch David P. , Feiler Peter H.
Published: May 2017

The list of applications classified as safety critical is growing due to emerging contexts such as the Internet of Things that touch the everyday activities of millions of people through smart devices like home automation systems and connected vehicles. These consumer products require high reliability but must be priced competitively. Traditional system development strategies are costly, in part, because traditional verification activities find only a small percentage of defects early in a project and because when discovered late in the development life cycle their repair requires changes to dependent code as well. Our development approach leverages early system architecture knowledge to jump start an architecture-centric development strategy that iteratively establishes traceability among the requirements, architecture, and verification artifacts. A virtual integration strategy makes the current state of the system under development available for analysis early in the product development life cycle. The approach is implemented using the Architecture Analysis and Design Language (AADL) embodied in the Open Source AADL Tool Environment (OSATE). The Architecture-Led Incremental System Assurance (ALISA) toolkit, the latest contribution of our team at the Software Engineering Institute, builds on AADL to provide the constructs and tools for an engineer to specify the integrated system, and to define verification activities that ensure satisfaction of the specification. The results from using the languages and techniques in pilot projects have shown very large cost and time savings, important to holding down costs for consumer-level Internet of Things systems. In this paper we focus on the architecture-led development process and illustrate the support given by ALISA.
Simulation of AADL models with software-in-the-loop execution
Authors: Buzdalov Denis
Published: May 2017

In this paper we consider a problem of simulation of avionics models with heterogeneously specified behaviours of components. In particular, we consider a situation when some software components of a model are specified by a program code of ARINC653 partitions but the rest of a model is defined in a very abstract way. One approach of behavioural and time analysis of such models is described in this paper.
Debugging Embedded Systems Requirements Before The Design Begins
Authors: Gaucher Fabien , Génevaux Yves
Published: May 2017

Over the last two decades, there has been a real movement towards requirements engineering [1]. However, the various tools that have been developed with the aim of improving the specifications development are mostly focused on requirements management and traceability, and there was no easy-to-use requirements validation tool available for checking their functional consistency before any design or coding takes place. As a result, 40 to 60% of design bugs are caused by faulty requirements that generate costly iterations of the development process.

Argosim's ambition is to change this situation by providing STIMULUS [2], the very first requirements simulation tool for real-time embedded systems. STIMULUS combines the ability to write requirements into a formal yet simple textual language, but also and even more importantly, to simulate them by generating the possible behaviours of the specified system in the form of execution plots. The analysis of simulation results allows for the quick and early detection of ambiguous, incorrect, incomplete or even conflicting requirements.

In practice, STIMULUS integrates seamlessly into the agile development processes [3]. It allows for the concurrent development and validation of both the requirements and their test scenarios in a very incremental way.

Once validated at the specification level, both requirements and test scenarios can be reused to validate the design implementation.Test scenarios make it possible to generate many test vectors automatically, while requirements are reused as test observers, or test oracles, in order to automatically check that the system satisfies its requirements.

This paper describes the major innovation offered by STIMULUS in the field of requirements engineering. It will first present its operating principles and then briefly illustrate both the requirements validation and software validation workflows with an example from the automotive domain.
Information, Uncertainty, and War
Authors: Ramsay Kristopher W.
Published: May 2017

Uncertainty about capabilities, intent, or resolve has long been linked to war. More recently, the bargaining model of war has established uncertainty, also referred to as asymmetric information, as one of the two major causes of costly conflict, the other being the dynamics of commitment in anarchy. A growing theoretical literature has made significant strides in fleshing out causal mechanisms and expanding our understanding of the role of information in conflict onset and how it relates to crisis bargaining and arms races. This article reviews these theoretical developments and describes current efforts to better understand the relationships between information, uncertainty, and war.
Social Movement Theory and the Prospects for Climate Change Activism in the United States
Authors: McAdam Doug
Published: May 2017

The issue of climate change poses something of a puzzle. For all the attention accorded the issue, climate change/global warming has spawned surprisingly little grassroots activism in the contemporary United States. Drawing on social movement theory, the author seeks to explain this puzzle. The prevailing consensus among movement scholars is that the prospect for movement emergence is facilitated by the confluence of three factors: the expansion of political opportunities, the availability of mobilizing structures, and cognitive and affective mobilization through framing processes. The author then applies each of these factors to the case of climate change, arguing that (a) awareness of the issue developed during an especially inopportune period in American politics, (b) the organizations that arose to address the issue were ill suited to the kind of grassroots mobilization characteristic of successful movements, and (c) the amorphous nature of the issue played havoc with efforts at strategic framing.
ATP-citrate lyase is essential for high glucose-induced histone hyperacetylation and fibrogenic gene upregulation in mesangial cells
Authors: Deb Dilip K. , Chen Yinyin , Sun Jian , Wang Youli , Li Yan Chun
Published: May 2017

The goal of this study was to address the role of ATP-citrate lyase (ACL), an enzyme that converts citrate to acetyl-CoA, in high glucose (HG)-induced histone acetylation and profibrotic gene expression. Our recent ChIP-Seq studies have demonstrated that HG induces genome-wide histone hyperacetylation in mesangial cells (MCs). Here, we showed that exposure of MCs to HG markedly increased histone acetylation at the H3K9/14 and H3K18 marks and induced the expression of potent profibrotic factors TGF-β1, TGF-β3, and connective tissue growth factor (CTGF). The induction of these profibrotic factors was further enhanced by histone deacetylase inhibitor but suppressed by histone acetyl-transferase inhibitor, confirming the importance of histone acetylation in this regulation. Interestingly, HG not only upregulated ACL expression but also promoted ACL nuclear translocation, evidenced by increased ACL concentration and activity in the nuclear extracts. Consistent with this observation, transfection of MCs with a plasmid-carrying green fluorescent protein (GFP)-ACL fusion protein led to GFP nuclear accumulation when cultured in HG condition. Silencing ACL with siRNAs alleviated HG-induced histone hyperacetylation, as well as upregulation of TGF-β1, TGF-β3, CTGF, and extracellular matrix (ECM) proteins fibronectin and collagen type IV, whereas ACL overexpression further enhanced HG induction of histone acetylation, as well as these profibrotic factors and ECM proteins. Collectively, these observations demonstrate that HG promotes ACL expression and translocation into the nucleus, where ACL converts citrate to acetyl-CoA to provide the substrate for histone acetylation, leading to upregulation of fibrogenic genes. Therefore, ACL plays a critical role in epigenetic regulation of diabetic renal fibrosis.
The tryptophan/kynurenine pathway, systemic inflammation, and long-term outcome after kidney transplantation
Authors: de Vries Laura V. , Minović Isidor , Franssen Casper F.M. , van Faassen Martijn , Sanders Jan-Stephan F. , Berger Stefan P. , Navis Gerjan , Kema Ido P. , Bakker Stephan J. L.
Published: May 2017

Tryptophan is metabolized along the kynurenine pathway, initially to kynurenine, and subsequently to cytotoxic 3-hydroxykynurenine. There is increasing interest in this pathway because of its proinflammatory nature, and drugs interfering in it have received increasing attention. We aimed to investigate whether serum and urinary parameters of the tryptophan/kynurenine pathway, and particularly cytotoxic 3-hydroxykynurenine, are associated with systemic inflammation and long-term outcome in renal transplant recipients (RTR). Data were collected in outpatient RTR with a functioning graft for >1 yr. Tryptophan, kynurenine, and 3-hydroxykynurenine in serum and urine were measured using LC-MS/MS. A total of 561 RTR (age: 51 ± 12 yr; 56% male) were included at a median of 6.0 (2.6–11.6) yr posttransplantation. Baseline median serum tryptophan was 40.0 (34.5–46.0) µmol/l, serum kynurenine was 1.8 (1.4–2.2) µmol/l, and serum 3-hydroxykynurenine was 42.2 (31.0–61.7) nmol/l. Serum kynurenine and 3-hydroxykynurenine were strongly associated with parameters of systemic inflammation. During follow-up for 7.0 (6.2–7.5) yr, 51 RTR (9%) developed graft failure and 120 RTR (21%) died. Both serum kynurenine and 3-hydroxykynurenine were independently associated with graft failure [HR 1.72 (1.23–2.41), P = 0.002; and HR 2.03 (1.42–2.90), P < 0.001]. Serum 3-hydroxykynurenine was also independently associated with mortality [HR 1.37 (1.08–1.73), P = 0.01], whereas serum kynurenine was not. Urinary tryptophan/kynurenine pathway parameters were not associated with outcome. Of tryptophan metabolites, serum 3-hydroxykynurenine is cross-sectionally most strongly and consistently associated with systemic inflammation and prospectively with adverse long-term outcome after kidney transplantation. Serum 3-hydroxykynurenine may be an interesting biomarker and target for the evaluation of drugs interfering in the tryptophan/kynurenine pathway.
Dispelling the myth that habitual caffeine consumption influences the performance response to acute caffeine supplementation
Authors: Gonçalves Lívia de Souza , Painelli Vitor de Salles , Yamaguchi Guilherme , Oliveira Luana Farias de , Saunders Bryan , da Silva Rafael Pires , Maciel Erika , Artioli Guilherme Giannini , Roschel Hamilton , Gualano Bruno
Published: May 2017

This study investigates the influence of habitual caffeine intake on aerobic exercise-performance responses to acute caffeine supplementation. A double-blind, crossover, counterbalanced study was performed. Forty male endurance-trained cyclists were allocated into tertiles, according to their daily caffeine intake: low (58 ± 29 mg/d), moderate (143 ± 25 mg/d), and high (351 ± 139 mg/d) consumers. Participants completed three trials in which they performed simulated cycling time trials (TTs) in the fastest time possible following ingestion of the following: caffeine (CAF: 6 mg/kg body mass), placebo (PLA), and no supplement (CON). A mixed-model analysis revealed that TT performance was significantly improved in CAF compared with PLA and CON (29.92 ± 2.18 vs. 30.81 ± 2.67 and 31.14 ± 2.71 min, respectively; P = 0.0002). Analysis of covariance revealed no influence of habitual caffeine intake as a covariate on exercise performance ( P = 0.47). TT performance was not significantly different among tertiles ( P = 0.75). No correlation was observed between habitual caffeine intake and absolute changes (CAF − CON) in TT performance with caffeine ( P = 0.524). Individual analysis showed that eight, seven, and five individuals improved above the variation of the test in CAF in the low, moderate, and high tertiles, respectively. A Fisher’s exact test did not show any significant differences in the number of individuals who improved in CAF among the tertiles ( P > 0.05). Blood lactate and ratings of perceived exertion were not different between trials and tertiles ( P > 0.05). Performance effects of acute caffeine supplementation during an ~30-min cycling TT performance were not influenced by the level of habitual caffeine consumption.

NEW & NOTEWORTHY There has been a long-standing paradigm that habitual caffeine intake may influence the ergogenicity of caffeine supplementation. Low, moderate, and high caffeine consumers showed similar absolute and relative improvements in cycling time-trial performance following acute supplementation of 6 mg/kg body mass caffeine. Performance effects of acute caffeine were not influenced by the level of habitual caffeine consumption, suggesting that high habitual caffeine intake does not negate the benefits of acute caffeine supplementation.
Physical activity modulates corticospinal excitability of the lower limb in young and old adults
Authors: Hassanlouei Hamidollah , Sundberg Christopher W. , Smith Ashleigh E. , Kuplic Andrew , Hunter Sandra K.
Published: May 2017

Aging is associated with reduced neuromuscular function, which may be due in part to altered corticospinal excitability. Regular physical activity (PA) may ameliorate these age-related declines, but the influence of PA on corticospinal excitability is unknown. The purpose of this study was to determine the influence of age, sex, and PA on corticospinal excitability by comparing the stimulus-response curves of motor evoked potentials (MEP) in 28 young (22.4 ± 2.2 yr; 14 women and 14 men) and 50 old adults (70.2 ± 6.1 yr; 22 women and 28 men) who varied in activity levels. Transcranial magnetic stimulation was used to elicit MEPs in the active vastus lateralis muscle (10% maximal voluntary contraction) with 5% increments in stimulator intensity until the maximum MEP amplitude. Stimulus-response curves of MEP amplitudes were fit with a four-parameter sigmoidal curve and the maximal slope calculated (slopemax). Habitual PA was assessed with tri-axial accelerometry and participants categorized into either those meeting the recommended PA guidelines for optimal health benefits (>10,000 steps/day, high-PA; n = 21) or those not meeting the guidelines (<10,000 steps/day, low-PA; n = 41). The MEP amplitudes and slopemax were greater in the low-PA compared with the high-PA group ( P < 0.05). Neither age nor sex influenced the stimulus-response curve parameters ( P > 0.05), suggesting that habitual PA influenced the excitability of the corticospinal tract projecting to the lower limb similarly in both young and old adults. These findings provide evidence that achieving the recommended PA guidelines for optimal health may mediate its effects on the nervous system by decreasing corticospinal excitability.

NEW & NOTEWORTHY Transcranial magnetic stimulation was used to determine whether achieving the recommended 10,000 steps/day for optimal health influenced the excitability of the corticospinal tract projecting to the knee extensor muscles. Irrespective of age and sex, individuals who achieved >10,000 steps/day had lower corticospinal excitability than those who performed <10,000 steps/day, possibly representing greater control of inhibitory and excitatory networks. Physical activity involving >10,000 steps/day may mediate its effects on the nervous system by decreasing corticospinal excitability.
Transcribing the connectome: roles for transcription factors and chromatin regulators in activity-dependent synapse development
Authors: Chen Liang-Fu , Zhou Allen S. , West Anne E.
Published: May 2017

The wiring of synaptic connections in the developing mammalian brain is shaped by both intrinsic and extrinsic signals. One point where these regulatory pathways converge is via the sensory experience-dependent regulation of new gene transcription. Recent studies have elucidated a number of molecular mechanisms that allow nuclear transcription factors and chromatin regulatory proteins to encode aspects of specificity in experience-dependent synapse development. Here we review the evidence for the transcriptional mechanisms that sculpt activity-dependent aspects of synaptic connectivity during postnatal development and discuss how disruption of these processes is associated with aberrant brain development in autism and intellectual disability.
Evidence of adaptations of locomotor neural drive in response to enhanced intermuscular connectivity between the triceps surae muscles of the rat
Authors: Bernabei Michel , van Dieën Jaap H. , Maas Huub
Published: May 2017

The aims of this study were to investigate changes 1) in the coordination of activation of the triceps surae muscle group, and 2) in muscle belly length of soleus (SO) and lateral gastrocnemius (LG) during locomotion (trotting) in response to increased stiffness of intermuscular connective tissues in the rat. We measured muscle activation and muscle belly lengths, as well as hindlimb kinematics, before and after an artificial enhancement of the connectivity between SO and LG muscles obtained by implanting a tissue-integrating surgical mesh at the muscles’ interface. We found that SO muscle activation decreased to 62%, while activation of LG and medial gastrocnemius muscles increased to 134 and 125%, respectively, compared with the levels measured preintervention. Although secondary additional or amplified activation bursts were observed with enhanced connectivity, the primary pattern of activation over the stride and the burst duration were not affected by the intervention. Similar muscle length changes after manipulation were observed, suggesting that length feedback from spindle receptors within SO and LG was not affected by the connectivity enhancement. We conclude that peripheral mechanical constraints given by morphological (re)organization of connective tissues linking synergists are taken into account by the central nervous system. The observed shift in activity toward the gastrocnemius muscles after the intervention suggests that these larger muscles are preferentially recruited when the soleus has a similar mechanical disadvantage in that it produces an unwanted flexion moment around the knee.

NEW & NOTEWORTHY Connective tissue linkages between muscle-tendon units may act as an additional mechanical constraint on the musculoskeletal system, thereby reducing the spectrum of solutions for performing a motor task. We found that intermuscular coordination changes following intermuscular connectivity enhancement. Besides showing that the extent of such connectivity is taken into account by the central nervous system, our results suggest that recruitment of triceps surae muscles is governed by the moments produced at the ankle-knee joints.
Decoronation: An Alternative Treatment for Replacement Root Resorption
Authors: Sala Marianne , Mendoza-Mendoza Asunción , Yañez-Vico Rosa-María
Published: May 2017

Introduction. Ankylosis and disrupted or altered root development are frequent complications associated with intrusive luxation and tooth avulsion lesions. Various forms of treatment have been described according to the severity of the trauma and root development. The literature shows that decoronation is an ideal treatment in cases where replacement resorption occurs.Methods. Two clinical cases are presented: involving intrusive luxation [15-year-old female patient with an affected maxillary left lateral incisor (2.2)] and a replanted avulsed tooth [8-year-old male patient with avulsion of the right maxillary central incisor (1.1)]; both cases presented advanced root resorption so that decoronation with a prosthetic tooth replacement was decided as the final treatment option.Results. In the short-term follow-up, patients were asymptomatic and had no functional problems. Radiographs showed that crestal bone height had been preserved.Conclusions. Preserving the decoronated root in the alveolar process not only helps to maintain bone volume but also enables vertical bone growth and facilitates the future insertion of an implant.
Apigenin Inhibits Human SW620 Cell Growth by Targeting Polyamine Catabolism
Authors: Wang Jing , Li TongMing , Zang Linquan , Pan Xuediao , Wang Sujun , Wu Yanyan , Wang Guixiang
Published: May 2017

Apigenin is a nonmutagenic flavonoid that has antitumor properties. Polyamines are ubiquitous cellular polycations, which play an important role in the proliferation and differentiation of cancer cells. Highly regulated pathways control the biosynthesis and degradation of polyamines. Ornithine decarboxylase (ODC) is the rate‐limiting enzyme in the metabolism, and spermidine/spermine‐N1‐Acetyl transferase (SSAT) is the rate‐limiting enzyme in the catabolism of polyamines. In the current study, the effect of increasing concentrations of apigenin on polyamine levels, ODC and SSAT protein expression, mRNA expression, cell proliferation and apoptosis, and the production of reactive oxygen species (ROS) was investigated in SW620 colon cancer cells. The results showed that apigenin significantly reduced cell proliferation, decreased the levels of spermidine and spermine, and increased previously downregulated putrescine contents. Apigenin also enhanced SSAT protein and mRNA levels and the production of reactive oxygen species in SW620 cells, though it had no significant effect on the levels of ODC protein or mRNA. Apigenin appears to decrease the proliferation rate of human SW620 cells by facilitating SSAT expression to induce polyamine catabolism and increasing ROS levels to induce cell apoptosis.
Methylprednisolone Administration Following Spinal Cord Injury Reduces Aquaporin 4 Expression and Exacerbates Edema
Authors: Cabrera-Aldana Eibar Ernesto , Ruelas Fernando , Aranda Cristina , Rincon-Heredia Ruth , Martínez-Cruz Angelina , Reyes-Sánchez Alejandro , Guizar-Sahagún Gabriel , Tovar-y-Romo Luis B.
Published: May 2017

Spinal cord injury (SCI) is an incapacitating condition that affects motor, sensory, and autonomic functions. Since 1990, the only treatment administered in the acute phase of SCI has been methylprednisolone (MP), a synthetic corticosteroid that has anti-inflammatory effects; however, its efficacy remains controversial. Although MP has been thought to help in the resolution of edema, there are no scientific grounds to support this assertion. Aquaporin 4 (AQP4), the most abundant component of water channels in the CNS, participates in the formation and elimination of edema, but it is not clear whether the modulation of AQP4 expression by MP plays any role in the physiopathology of SCI. We studied the functional expression of AQP4 modulated by MP following SCI in an experimental model in rats along with the associated changes in the permeability of the blood-spinal cord barrier. We analyzed these effects in male and female rats and found that SCI increased AQP4 expression in the spinal cord white matter and that MP diminished such increase to baseline levels. Moreover, MP increased the extravasation of plasma components after SCI and enhanced tissue swelling and edema. Our results lend scientific support to the increasing motion to avoid MP treatment after SCI.
Melatonin Secretion Pattern in Critically Ill Patients: A Pilot Descriptive Study
Authors: Boyko Yuliya , Holst René , Jennum Poul , Oerding Helle , Nikolic Miki , Toft Palle
Published: May 2017

Critically ill patients have abnormal circadian and sleep homeostasis. This may be associated with higher morbidity and mortality. The aims of this pilot study were (1) to describe melatonin secretion in conscious critically ill mechanically ventilated patients and (2) to describe whether melatonin secretion and sleep patterns differed in these patients with and without remifentanil infusion. Eight patients were included. Blood-melatonin was taken every 4th hour, and polysomnography was carried out continually during a 48-hour period. American Academy of Sleep Medicine criteria were used for sleep scoring if sleep patterns were identified; otherwise, Watson’s classification was applied. As remifentanil was periodically administered during the study, its effect on melatonin and sleep was assessed. Melatonin secretion in these patients followed a phase-delayed diurnal curve. We did not observe any effect of remifentanil on melatonin secretion. We found that the risk of atypical sleep compared to normal sleep was significantly lower (p<0.001) under remifentanil infusion. Rapid Eye Movement (REM) sleep was only observed during the nonsedation period. We found preserved diurnal pattern of melatonin secretion in these patients. Remifentanil did not affect melatonin secretion but was associated with lower risk of atypical sleep pattern. REM sleep was only registered during the period of nonsedation.
Humoral Hypercalcemia of Malignancy with a Parathyroid Hormone-Related Peptide-Secreting Intrahepatic Cholangiocarcinoma Accompanied by a Gastric Cancer
Authors: Takeda Katsushi , Kimura Ryosuke , Nishigaki Nobuhiro , Sato Shinya , Okamoto Asami , Watanabe Kumiko , Yasui Sachie
Published: May 2017

Humoral hypercalcemia of malignancy (HHM) is caused by the oversecretion of parathyroid hormone-related peptide (PTHrP) from malignant tumors. Although any tumor may cause HHM, that induced by intrahepatic cholangiocarcinoma (ICC) or gastric cancer (GC) is rare. We report here a 74-year-old male who displayed HHM with both ICC and GC and showed an elevated serum PTHrP level. Treatment of the hypercalcemia with saline, furosemide, elcatonin, and zoledronic acid corrected his serum calcium level and improved symptoms. Because treatment of ICC should precede that of GC, we chose chemotherapy with cisplatin (CDDP) and gemcitabine (GEM). Chemotherapy reduced the size of the ICC and decreased the serum PTHrP level. One year after diagnosis, the patient was alive in the face of a poor prognosis for an ICC that produced PTHrP. Immunohistochemical staining for PTHrP was positive for the ICC and negative for the GC, leading us to believe that the cause of the HHM was a PTHrP-secreting ICC. In conclusion, immunohistochemical staining for PTHrP may be useful in discovering the cause of HHM in the case of two cancers accompanied by an elevated serum PHTrP level. Chemotherapy with CDDP and GEM may be the most appropriate treatment for a PTHrP-secreting ICC.
Frequent Symptom Sets Identification from Uncertain Medical Data in Differentially Private Way
Authors: Ding Zhe , Qin Zhen , Qin Zhiguang
Published: May 2017

Data mining techniques are applied to identify hidden patterns in large amounts of patient data. These patterns can assist physicians in making more accurate diagnosis. For different physical conditions of patients, the same physiological index corresponds to a different symptom association probability for each patient. Data mining technologies based on certain data cannot be directly applied to these patients’ data. Patient data are sensitive data. An adversary with sufficient background information can make use of the patterns mined from uncertain medical data to obtain the sensitive information of patients. In this paper, a new algorithm is presented to determine the top K most frequent itemsets from uncertain medical data and to protect data privacy. Based on traditional algorithms for mining frequent itemsets from uncertain data, our algorithm applies sparse vector algorithm and the Laplace mechanism to ensure differential privacy for the top K most frequent itemsets for uncertain medical data and the expected supports of these frequent itemsets. We prove that our algorithm can guarantee differential privacy in theory. Moreover, we carry out experiments with four real-world scenario datasets and two synthetic datasets. The experimental results demonstrate the performance of our algorithm.
Keratoacanthoma of the Nasal Septum Secondary to Ranibizumab Use
Authors: Cohn Jason E. , Caruso Sales Hilary M. , Nguyen Giang Huong , Spector Harvey , Briskin Kenneth
Published: May 2017

Keratoacanthoma (KA) is a benign epithelial tumor that typically presents as a firm, cone-shaped, flesh-colored nodule with a central horn-filled crater. KA is considered to be a low-grade variant of squamous cell carcinoma (SCC). We report a rare case of a 72-year-old male who presented with a KA involving the nasal septum, possibly related to ranibizumab use. A flesh-colored lesion on the right anterior nasal septum lesion was visualized on examination. Histologic examination revealed a well-circumscribed, dome-shaped central crater filled with keratin, well-differentiated squamous epithelium with ground-glass cytoplasm with pushing margins, and intraepithelial microabscesses establishing the diagnosis of KA. KA of the nasal septum has only been reported once in the literature. This case is unusual because it normally presents on sun-exposed areas. Additionally, this patient was taking ranibizumab, a vascular endothelial growth factor (VEGF) inhibitor for macular degeneration. Despite ranibizumab not being directly linked to precancerous and cancerous skin lesions, agents in this medication class have been. Although it is difficult to prove associations in this isolated case, the role of ranibizumab causing cutaneous lesions should be further investigated.
Advances in the Diagnosis and Treatment of Acute Kidney Injury in Cirrhosis Patients
Authors: Lei Lei , Li Liangping , Zhang Hu
Published: May 2017

Liver cirrhosis is a common progressive and chronic clinical liver disease. Due to the strong compensation ability of the liver, no obvious symptoms develop in the early stage. However, multiple systems are involved in decompensation of the liver. Acute kidney injury (AKI) is one of the most serious complications, characterized by a sharp drop in the glomerular filtration rate (GFR); a rapid increase in Scr and BUN, as well as sodium and water storage; and a disturbance of acid-base balance. The mortality rate is high, and the prognosis is very poor. Thus, it is important to make a definite diagnosis and initiate treatment in the early stage to decrease mortality and improve the prognosis. Although diagnosing liver cirrhosis with serum creatinine has many shortcomings, a dynamic change in this marker is still the main diagnostic criterion for AKI. Identifying new markers of kidney injury with clinical value has also become an increasing focus of research. In this text, we review recent changes regarding categorization of AKI diagnostic criteria as well as new markers of AKI and treatments for cirrhosis-related AKI.
Sensory Eye Dominance in Treated Anisometropic Amblyopia
Authors: Chen Yao , Wang Jiafeng , Shi Hongmei , Wang Xiaoxiao , Feng Lixia
Published: May 2017

Amblyopia results from inadequate visual experience during the critical period of visual development. Abnormal binocular interactions are believed to play a critical role in amblyopia. These binocular deficits can often be resolved, owing to the residual visual plasticity in amblyopes. In this study, we quantitatively measured the sensory eye dominance in treated anisometropic amblyopes to determine whether they had fully recovered. Fourteen treated anisometropic amblyopes with normal or corrected to normal visual acuity participated, and their sensory eye dominance was assessed by using a binocular phase combination paradigm. We found that the two eyes were unequal in binocular combination in most (11 out of 14) of our treated anisometropic amblyopes, but none of the controls. We concluded that the treated anisometropic amblyopes, even those with a normal range of visual acuity, exhibited abnormal binocular processing. Our results thus suggest that there is potential for improvement in treated anisometropic amblyopes that may further enhance their binocular visual functioning.
Dual Inhibition of EZH2 and EZH1 Sensitizes PRC2-Dependent Tumors to Proteasome Inhibition
Authors: Rizq Ola , Mimura Naoya , Oshima Motohiko , Saraya Atsunori , Koide Shuhei , Kato Yuko , Aoyama Kazumasa , Nakajima-Takagi Yaeko , Wang Changshan , Chiba Tetsuhiro , Ma Anqi , Jin Jian , Iseki Tohru , Nakaseko Chiaki , Iwama Atsushi
Published: May 2017

Purpose: EZH2 and EZH1, the catalytic components of polycomb repressive complex 2 (PRC2), trigger trimethylation of H3K27 (H3K27me3) to repress the transcription of target genes and are implicated in the pathogenesis of various cancers including multiple myeloma and prostate cancer. Here, we investigated the preclinical effects of UNC1999, a dual inhibitor of EZH2 and EZH1, in combination with proteasome inhibitors on multiple myeloma and prostate cancer.

Experimental Design: In vitro and in vivo efficacy of UNC1999 and the combination with proteasome inhibitors was evaluated in multiple myeloma cell lines, primary patient cells, and in a xenograft model. RNA-seq and ChIP-seq were performed to uncover the targets of UNC1999 in multiple myeloma. The efficacy of the combination therapy was validated in prostate cancer cell lines.

Results: Proteasome inhibitors repressed EZH2 transcription via abrogation of the RB-E2F pathway, thereby sensitizing EZH2-dependent multiple myeloma cells to EZH1 inhibition by UNC1999. Correspondingly, combination of proteasome inhibitors with UNC1999, but not with an EZH2-specific inhibitor, induced synergistic antimyeloma activity in vitro. Bortezomib combined with UNC1999 remarkably inhibited the growth of myeloma cells in vivo. Comprehensive analyses revealed several direct targets of UNC1999 including the tumor suppressor gene NR4A1. Derepression of NR4A1 by UNC1999 resulted in suppression of MYC, which was enhanced by the combination with bortezomib, suggesting the cooperative blockade of PRC2 function. Notably, this combination also exhibited strong synergy in prostate cancer cells.

Conclusions: Our results identify dual inhibition of EZH2 and EZH1 together with proteasome inhibition as a promising epigenetics-based therapy for PRC2-dependent cancers. Clin Cancer Res; 23(16); 4817–30. ©2017 AACR.
A Novel Ataxic Mutant Mouse Line Having Sensory Neuropathy Shows Heavy Iron Deposition in Kidney
Authors: Hashimoto Hisashi , Kawabe Tomonori , Fukuda Takahiro , Kusakabe Moriaki
Published: May 2017

Background/Aims: A novel ataxic mouse line was established from the offspring of a male mouse administered cyclophosphamide in a juvenile period. Methods: We have attempted to examine the phenotype and histopathological changes of affected mice. Furthermore, linkage analysis and sequencing of the mutant was performed to reveal the causative gene locus. Results and Conclusion: The affected mouse was characterized by heavy hind limb ataxia with gait disorder, which was first recognized at about 4 weeks of age and slowly progressed with advancing age. The phenotype was inherited in an autosomal recessive pattern. The genetic locus associated with the phenotype was named hak and mapped to 107,305,356-108,637,615 on chromosome 2qE3, non-coding sequences in the vicinity of Bdnf gene. Many spheroids were noticed in the cerebellar medulla and the brain stem. In the peripheral nerves, some sensory ganglionic cells showed deposition of NF-200 in the perikaryon and NF-200-positive spheroids in nerve fibers. No inflammatory cell infiltration was observed. In addition, the adult affected mouse had distinct iron deposition in the kidney and the liver, but not in the heart, the skeletal muscle and the central nervous system. These results suggest that the hak mouse has a tissue-specific impairment in the expression of a type of Bdnf transcripts.
Adenoid Cystic Carcinoma of the Larynx Presenting as a Thyroid Mass and Brief Literature Review
Authors: Shirian Sadegh , Maghbool Maryam , Aledavood Azita , Negahban Shahrzad , Khademi Bijan , Daneshbod Yahya
Published: May 2017

Background: Adenoid cystic carcinoma (ACC) of the larynx and trachea is very rare. Case: A 45-year-old man with ACC of the larynx presenting as a thyroid mass is reported in this study. Physical examination revealed a large solid thyroid nodule in the left lobe without any lymphadenopathy. A technetium thyroid scan showed multinodular goiter with cold nodules in the left lobe, isthmus, and functioning nodules in the right lobe. A large thyroid mass originating from the left side of the larynx, mostly the left vocal cord and the infraglottic part, was seen using enhanced magnetic resonance imaging after rupture of the thyroid cartilage on the left side. Ultrasound-guided fine needle aspiration smears and cell blocks of the thyroid nodule showed highly cellular smears composed of large tissue fragments, three-dimensional clusters, and sheets of neoplastic cells with slightly enlarged round and hyperchromatic nuclei. Immunohistochemical study showed that the cell block expressed C-kit and CK 7 on the cribriform growth pattern of the tumoral cells. However, protein expression of thyroglobulin and thyroid transcription factor-1 was not detectable. Conclusion: To approach a thyroid nodule, direct invasion or metastatic tumors of other organs must be borne in mind.