bluuebunny/crossref_metadata_2025 huggingface dataset:
Observed and predicted effects of climate change on Arctic caribou and reindeer
Authors: Mallory Conor D. , Boyce Mark S.
Published: June 2017

The ability of many species to adapt to the shifting environmental conditions associated with climate change will be a key determinant of their persistence in the coming decades. This is a challenge already faced by species in the Arctic, where rapid environmental change is well underway. Caribou and reindeer (Rangifer tarandus) play a key role in Arctic ecosystems and provide irreplaceable socioeconomic value to many northern peoples. Recent decades have seen declines in many Rangifer populations, and there is strong concern that climate change is threatening the viability of this iconic Arctic species. We examine the literature to provide a thorough and full consideration of the many environmental factors that limit caribou and reindeer populations, and how these might be affected by a warming climate. Our review suggests that the response of Rangifer populations to climate change is, and will continue to be, varied in large part to their broad circumpolar distribution. While caribou and reindeer could have some resilience to climate change, current global trends in abundance undermine all but the most precautionary outlooks. Ultimately, the conservation of Rangifer populations will require careful management that considers the local and regional manifestations of climate change.
Carbon Nanotube Synthesis from Block Copolymer Deposited Catalyst
Authors: Woods K. , Silliman J. , Schwendemann T. C.
Published: June 2017

A block copolymer/metal-salt solution was used to deposit metal nanoparticles on substrates, from which carbon nanotubes (CNTs) were grown in a chemical vapor deposition (CVD) chamber. Mono and hybrid catalysts of Fe, Ni, and Co-nitrates were tested, and separately Co, Ni, and Cu-chlorides. In both cases cobalt/cobalt-hybrids produced the highest density of multi-wall carbon nanotubes (MWCNTs). Slight vertical growth, though sparse, was observed after growth at 800°C from a nickel catalyst on single-crystal aluminium oxide (~130nm diameter).
Critical Layer Thickness: Theory and Experiment in the ZnSe/GaAs (001) Material System
Authors: Kujofsa Tedi , Ayers John E.
Published: June 2017

The critical layer thickness (CLT) determines the criteria for dislocation formation and the onset of lattice relaxation. Although several theoretical models have been developed for the critical layer thickness, experimentally-measured CLTs in ZnSe/GaAs (001) heterostructures are often at variance with one another as well as with established theories. In a previous work [T. Kujofsa et al., J. Vac. Sci. Technol. B, 34, 051201 (2016)], we showed that the experimentally measured CLT may be much larger than the equilibrium value when using finite experimental resolution. In this work, we apply a general dislocation flow model to determine the apparent critical layer thickness as a function of the experimental resolution for ZnSe/GaAs (001) heterostructures. More importantly, we compare the results utilizing different equilibrium theories and therefore varying driving forces for the lattice relaxation in order to determine which established models are consistent with several measured values of CLT for ZnSe/GaAs (001) once kinetically-limited relaxation and finite experimental strain resolution are taken into account.
Error analysis for pesticide detection performed on paper-based microfluidic chip devices
Authors: Yang Ning , Shen Kai , Guo Jianjiang , Tao Xinyi , Xu Peifeng , Mao Hanping
Published: June 2017

Paper chip is an efficient and inexpensive device for pesticide residues detection. However, the reasons of detection error are not clear, which is the main problem to hinder the development of pesticide residues detection. This paper focuses on error analysis for pesticide detection performed on paper-based microfluidic chip devices, which test every possible factor to build the mathematical models for detection error. In the result, double-channel structure is selected as the optimal chip structure to reduce detection error effectively. The wavelength of 599.753 nm is chosen since it is the most sensitive detection wavelength to the variation of pesticide concentration. At last, the mathematical models of detection error for detection temperature and prepared time are concluded. This research lays a theory foundation on accurate pesticide residues detection based on paper-based microfluidic chip devices.
An experimental study of dolomite dissolution kinetics at conditions relevant to CO
2
geological storage
Authors: Baritantonaki Angeliki , Bolourinejad Panteha , Herber Rien
Published: June 2017

The kinetics of dolomite dissolution have been experimentally investigated under subsurface conditions characteristic of the Rotliegend gas fields in the NE of The Netherlands. Experiments were performed in closed, stirred, batch reactors at far from equilibrium conditions, with dolomite powders of different grain sizes. The experiments were repeated for all grain sizes at 25°C and an experiment was also conducted in deionized water. The rates were derived from the measured concentrations of Mg
2+
or Ca
2+
released from dolomite dissolution and were normalized by the surface area of the minerals at each time interval.

Regression of the rates with the pH resulted in the kinetic rate constants of: log
k
1
 = −8.16 ± 0.06 at 25°C and log
k
2
 = −7.61 ± 0.05 at 100°C (300 – 350 μm), log
k
3
 = −7.88 ± 0.20 at 25°C, log
k
4
 = −7.45 at 100°C (75 – 100 μm), log
k
5
 = −6.62 ± 0.50 at 25°C and log
k
6
 = −5.96 ± 1 at 100°C (20 – 25 μm).

The results obtained in this study indicate that in an acidic regime the dissolution of dolomite in brine is a factor of 2 faster than in deionized water. It was also shown that the dissolution rates, when normalized by surface area, increase with decreasing grain size.
An Argumentation Approach for Resolving Privacy Disputes in Online Social Networks
Authors: Kökciyan Nadin , Yaglikci Nefise , Yolum Pinar
Published: June 2017

Preserving users’ privacy is important for Web systems. In systems where transactions are managed by a single user, such as e-commerce systems, preserving privacy of the transactions is merely the capability of access control. However, in online social networks, where each transaction is managed by and has effect on others, preserving privacy is difficult. In many cases, the users’ privacy constraints are distributed, expressed in a high-level manner, and would depend on information that only becomes available over interactions with others. Hence, when a content is being shared by a user, others who might be affected by the content should discuss and agree on how the content will be shared online so that none of their privacy constraints are violated. To enable this, we model users of the social networks as agents that represent their users’ privacy constraints as semantic rules. Agents argue with each other on propositions that enable their privacy rules by generating facts and assumptions from their ontology. Moreover, agents can seek help from others by requesting new information to enrich their ontology. Using assumption-based argumentation, agents decide whether a content should be shared or not. We evaluate the applicability of our approach on real-life privacy scenarios in comparison with user surveys.
IronFleet
Authors: Hawblitzel Chris , Howell Jon , Kapritsos Manos , Lorch Jacob R. , Parno Bryan , Roberts Michael L. , Setty Srinath , Zill Brian
Published: June 2017

Distributed systems are notorious for harboring subtle bugs. Verification can, in principle, eliminate these bugs, but it has historically been difficult to apply at full-program scale, much less distributed system scale. We describe a methodology for building practical and provably correct distributed systems based on a unique blend of temporal logic of actions-style state-machine refinement and Hoare-logic verification. We demonstrate the methodology on a complex implementation of a Paxos-based replicated state machine library and a lease-based sharded key-value store. We prove that each obeys a concise safety specification as well as desirable liveness requirements. Each implementation achieves performance competitive with a reference system. With our methodology and lessons learned, we aim to raise the standard for distributed systems from "tested" to "correct."
Learning to Schedule Control Fragments for Physics-Based Characters Using Deep Q-Learning
Authors: Liu Libin , Hodgins Jessica
Published: June 2017

Given a robust control system, physical simulation offers the potential for interactive human characters that move in realistic and responsive ways. In this article, we describe how to learn a scheduling scheme that reorders short control fragments as necessary at runtime to create a control system that can respond to disturbances and allows steering and other user interactions. These schedulers provide robust control of a wide range of highly dynamic behaviors, including walking on a ball, balancing on a bongo board, skateboarding, running, push-recovery, and breakdancing. We show that moderate-sized Q-networks can model the schedulers for these control tasks effectively and that those schedulers can be efficiently learned by the deep Q-learning algorithm.
Building a brain may mean going analog
Authors: Savage Neil
Published: June 2017

Analog circuits consume less power per operation than CMOS technologies, and so should prove more efficient.
The beginner's creed
Authors: Denning Peter J.
Published: June 2017

We all need to learn to be expert beginners.
The RNAi Universe in Fungi: A Varied Landscape of Small RNAs and Biological Functions
Authors: Torres-Martínez Santiago , Ruiz-Vázquez Rosa M.
Published: June 2017

RNA interference (RNAi) is a conserved eukaryotic mechanism that uses small RNA molecules to suppress gene expression through sequence-specific messenger RNA degradation, translational repression, or transcriptional inhibition. In filamentous fungi, the protective function of RNAi in the maintenance of genome integrity is well known. However, knowledge of the regulatory role of RNAi in fungi has had to wait until the recent identification of different endogenous small RNA classes, which are generated by distinct RNAi pathways. In addition, RNAi research on new fungal models has uncovered the role of small RNAs and RNAi pathways in the regulation of diverse biological functions. In this review, we give an up-to-date overview of the different classes of small RNAs and RNAi pathways in fungi and their roles in the defense of genome integrity and regulation of fungal physiology and development, as well as in the interaction of fungi with biotic and abiotic environments.
Lessons from the Environmental Antibiotic Resistome
Authors: Surette Matthew D. , Wright Gerard D.
Published: June 2017

Antibiotic resistance is a global public health issue of growing proportions. All antibiotics are susceptible to resistance. The evidence is now clear that the environment is the single largest source and reservoir of resistance. Soil, aquatic, atmospheric, animal-associated, and built ecosystems are home to microbes that harbor antibiotic resistance elements and the means to mobilize them. The diversity and abundance of resistance in the environment is consistent with the ancient origins of antibiotics and a variety of studies support a long natural history of associated resistance. The implications are clear: Understanding the evolution of resistance in the environment, its diversity, and mechanisms is essential to the management of our existing and future antibiotic resources.
p53/Drp1-dependent mitochondrial fission mediates aldosterone-induced podocyte injury and mitochondrial dysfunction
Authors: Yuan Yanggang , Zhang Aiqing , Qi Jia , Wang Hui , Liu Xi , Zhao Min , Duan Suyan , Huang Zhimin , Zhang Chengning , Wu Lin , Zhang Bo , Zhang Aihua , Xing Changying
Published: June 2017

Mitochondrial dysfunction is increasingly recognized as an important factor in glomerular diseases. Previous study has shown that mitochondrial fission contributed to mitochondrial dysfunction. However, the mechanism of mitochondrial fission on mitochondrial dysfunction in aldosterone-induced podocyte injury remains ambiguous. This study aimed to investigate the pathogenic effect of mitochondrial fission both in vivo and in vitro. In an animal model of aldosterone-induced nephropathy, inhibition of the mitochondrial fission protein dynamin-related protein 1 (Drp1) suppressed aldosterone-induced podocyte injury. In cultured podocytes, aldosterone dose dependently induced Drp1 expression. Knockdown of Drp1 inhibited aldosterone-induced mitochondrial fission, mitochondrial dysfunction, and podocyte apoptosis. Furthermore, aldosterone dose dependently induced p53 expression. Knockdown of p53 inhibited aldosterone-induced Drp1 expression, mitochondrial dysfunction, and podocyte apoptosis. These findings implicated that aldosterone induced mitochondrial dysfunction and podocyte injury mediated by p53/Drp1-dependent mitochondrial fission, which may provide opportunities for therapeutic intervention for podocyte injury.
Impaired visuomotor generalization by inconsistent attentional contexts
Authors: Wang Tony S. L. , Song Joo-Hyun
Published: June 2017

In daily life, people are constantly presented with situations in which they have to learn and acquire new motor skills in complex environments, where attention is often distracted by other events. Being able to generalize and perform the acquired motor action in different environments is a crucial part of visuomotor learning. The current study examined whether attentional distraction impairs generalization of visuomotor adaptation or whether consistent distraction can operate as an internal cue to facilitate generalization. Using a dual-task paradigm combining visuomotor rotational adaptation and an attention-demanding secondary task, we showed that switching the attentional context from training (dual-task) to generalization (single-task) reduced the range of transfer of visuomotor adaptation to untrained directions. However, when consistent distraction was present throughout training and generalization, visuomotor generalization was equivalent to without distractions at all. Furthermore, this attentional context-dependent generalization was evident even when sensory modality of distractions differed between training and generalization. Therefore, the general nature of the dual tasks, rather than the specific stimuli, is associated with visuomotor memory and serves as a critical cue for generalization. Taken together, we demonstrated that attention plays a critical role during sensorimotor adaptation in selecting and associating multisensory signals with motor memory. This finding provides insight into developing learning programs that are generalizable in complex daily environments.

NEW & NOTEWORTHY Learning novel motor actions in complex environments with attentional distraction is a critical function. Successful motor learning involves the ability to transfer the acquired skill from the trained to novel environments. Here, we demonstrate attentional distraction does not impair visuomotor adaptation. Rather, consistency in the attentional context from training to generalization modulates the degree of transfer to untrained locations. The role of attention and memory must, therefore, be incorporated into existing models of visuomotor learning.
Impact of glutamatergic and serotonergic neurotransmission on diaphragm muscle activity after cervical spinal hemisection
Authors: Mantilla Carlos B. , Gransee Heather M. , Zhan Wen-Zhi , Sieck Gary C.
Published: June 2017

Incomplete cervical spinal cord hemisection at C2 (SH) disrupts descending excitatory drive to phrenic motoneurons, paralyzing the ipsilateral diaphragm muscle. Spontaneous recovery over time is associated with increased phrenic motoneuron expression of glutamatergic N-methyl-d-aspartate (NMDA) and serotonergic 5-HT2A receptors. We hypothesized that NMDA and 5-HT2A receptor-mediated neurotransmission play a role in ipsilateral diaphragm muscle activity post-SH. Adult male Sprague-Dawley rats were implanted with bilateral diaphragm EMG electrodes for chronic EMG recordings up to 28 days post-SH (SH 28D). The extent of recovery was calculated by peak root-mean-square (RMS) EMG amplitude. In all animals, absence of ipsilateral activity was verified at 3 days post-SH. Diaphragm EMG activity was also recorded during exposure to hypoxia-hypercapnia (10% O2-5% CO2). In SH animals displaying recovery of ipsilateral diaphragm EMG activity at SH 28D, cervical spinal cord segments containing the phrenic motor nucleus (C3–C5) were surgically exposed and either the NMDA receptor antagonist d-2-amino-5-phosphonovalerate (d-AP5; 100 mM, 30 μl) or 5-HT2A receptor antagonist ketanserin (40 mM, 30 μl) was instilled intrathecally. Following d-AP5, diaphragm EMG amplitude was reduced ipsilaterally, during both eupnea (42% of pre-d-AP5 value; P = 0.007) and hypoxia-hypercapnia (31% of pre-d-AP5 value; P = 0.015), with no effect on contralateral EMG activity or in uninjured controls. Treatment with ketanserin did not change ipsilateral or contralateral RMS EMG amplitude in SH animals displaying recovery at SH 28D. Our results suggest that spinal glutamatergic NMDA receptor-mediated neurotransmission plays an important role in ipsilateral diaphragm muscle activity after cervical spinal cord injury.

NEW & NOTEWORTHY Spontaneous recovery following C2 spinal hemisection (SH) is associated with increased phrenic motoneuron expression of glutamatergic and serotonergic receptors. In this study, we show that pharmacological inhibition of glutamatergic N-methyl-d-aspartate (NMDA) receptors blunts ipsilateral diaphragm activity post-SH. In contrast, pharmacological inhibition of serotonergic 5-HT2A receptors does not change diaphragm EMG activity post-SH. Our results suggest that NMDA receptor-mediated glutamatergic neurotransmission plays an important role in enhancing rhythmic respiratory-related diaphragm activity after spinal cord injury.
Oxidative Phosphorylation System in Gastric Carcinomas and Gastritis
Authors: Feichtinger René G. , Neureiter Daniel , Skaria Tom , Wessler Silja , Cover Timothy L. , Mayr Johannes A. , Zimmermann Franz A. , Posselt Gernot , Sperl Wolfgang , Kofler Barbara
Published: June 2017

Switching of cellular energy production from oxidative phosphorylation (OXPHOS) by mitochondria to aerobic glycolysis occurs in many types of tumors. However, the significance of this switching for the development of gastric carcinoma and what connection it may have to Helicobacter pylori infection of the gut, a primary cause of gastric cancer, are poorly understood. Therefore, we investigated the expression of OXPHOS complexes in two types of human gastric carcinomas (“intestinal” and “diffuse”), bacterial gastritis with and without metaplasia, and chemically induced gastritis by using immunohistochemistry. Furthermore, we analyzed the effect of HP infection on several key mitochondrial proteins. Complex I expression was significantly reduced in intestinal type (but not diffuse) gastric carcinomas compared to adjacent control tissue, and the reduction was independent of HP infection. Significantly, higher complex I and complex II expression was present in large tumors. Furthermore, higher complex II and complex III protein levels were also obvious in grade 3 versus grade 2. No differences of OXPHOS complexes and markers of mitochondrial biogenesis were found between bacterially caused and chemically induced gastritis. Thus, intestinal gastric carcinomas, but not precancerous stages, are frequently characterized by loss of complex I, and this pathophysiology occurs independently of HP infection.
Protein Function Prediction Using Deep Restricted Boltzmann Machines
Authors: Zou Xianchun , Wang Guijun , Yu Guoxian
Published: June 2017

Accurately annotating biological functions of proteins is one of the key tasks in the postgenome era. Many machine learning based methods have been applied to predict functional annotations of proteins, but this task is rarely solved by deep learning techniques. Deep learning techniques recently have been successfully applied to a wide range of problems, such as video, images, and nature language processing. Inspired by these successful applications, we investigate deep restricted Boltzmann machines (DRBM), a representative deep learning technique, to predict the missing functional annotations of partially annotated proteins. Experimental results onHomo sapiens,Saccharomyces cerevisiae,Mus musculus,andDrosophilashow that DRBM achieves better performance than other related methods across different evaluation metrics, and it also runs faster than these comparing methods.
Photoregulation of Gold Nanoparticles Stabilized in a Diacetylenic Nanocapsule
Authors: Somjid Saowalak , Chompoosor Apiwat , Kanokmedhakul Somdej , Teerasong Saowapak
Published: June 2017

The results of releasing a drug in a burst are unpredictable and one of the inherent drawbacks of using nanocarriers. Here, photoresponsive cationic gold nanoparticles to stabilize diacetylenic nanocapsules enabling photoregulated release of payloads are reported. The fabrication of these nanocapsules relied on an electrostatic interaction of a negatively charged diacetylenic core and a positively charged gold nanoparticle shell. Gold nanoparticles with photoresponsive ligands on their surfaces act as both hydrophobic core stabilizers and gatekeepers of the nanocapsules, while their polydiacetylene cores serve as hydrophobic drug carriers that can be tuned using UV irradiation. The morphology of nanocapsules was analyzed using TEM and dynamic light scattering. The resultant nanocapsules had a spherical shape with an average diameter of 152.9 ± 6.7 nm. Upon UV irradiation, the nanocapsules lost their integrity and an encapsulated model compound was released through diffusion. The release of a hydrophobic molecule was irradiation time dependent and thereby controllable. This light-triggered release provides an alternative strategy for controlled drug delivery.
Quantitative Analysis of Macular Inner Retinal Layer Using Swept-Source Optical Coherence Tomography in Patients with Optic Tract Syndrome
Authors: Goto Katsutoshi , Miki Atsushi , Yamashita Tsutomu , Araki Syunsuke , Takizawa Go , Mizukawa Kenichi , Ieki Yoshiaki , Kiryu Junichi
Published: June 2017

Objective. To evaluate macular inner retinal layers using swept-source optical coherence tomography (SS-OCT) in patients with homonymous hemianopia due to optic tract syndrome (OTS). Methods. Sixteen eyes of 8 patients with OTS were studied. The macular retinal nerve fiber layer (mRNFL), ganglion cell layer and inner plexiform layer (GCL + IPL), and mRNFL and GCL + IPL (GCC) were measured by SS-OCT (DRI OCT-1 Atlantis®).The scanned area was divided into eight regions and two hemiretinae. Each retinal thickness of the OTS group was compared with that of the 25 control subjects. Results. The GCC thickness in the ipsilateral eyes was significantly reduced in all regions, although predominant thinning of the GCC in the contralateral eyes was found in the nasal region. The GCC + IPL thickness was preferentially reduced at the temporal regions in the ipsilateral eyes and at the nasal regions in the contralateral eyes. The reduction rate of the GCL + IPL thickness was 29.6% at the temporal hemiretina in the ipsilateral eyes and 35.2% at the nasal hemiretina in the contralateral eyes. Conclusion. We found preferential loss of the GCC + IPL thickness corresponding to the hemifield defects in each eye. Quantitative analysis by SS-OCT is capable of detecting the characteristic RGC loss due to OTS.
Vertical Distribution of Suspended Sediment under Steady Flow: Existing Theories and Fractional Derivative Model
Authors: Nie Shiqian , Sun HongGuang , Zhang Yong , Chen Dong , Chen Wen , Chen Li , Schaefer Sydney
Published: June 2017

The fractional advection-diffusion equation (fADE) model is a new approach to describe the vertical distribution of suspended sediment concentration in steady turbulent flow. However, the advantages and parameter definition of the fADE model in describing the sediment suspension distribution are still unclear. To address this knowledge gap, this study first reviews seven models, including the fADE model, for the vertical distribution of suspended sediment concentration in steady turbulent flow. The fADE model, among others, describes both Fickian and non-Fickian diffusive characteristics of suspended sediment, while the other six models assume that the vertical diffusion of suspended sediment follows Fick’s first law. Second, this study explores the sensitivity of the fractional index of the fADE model to the variation of particle sizes and sediment settling velocities, based on experimental data collected from the literatures. Finally, empirical formulas are developed to relate the fractional derivative order to particle size and sediment settling velocity. These formulas offer river engineers a substitutive way to estimate the fractional derivative order in the fADE model.
A New Method to Optimize the Wake Flow of a Vehicle: The Leading Edge Rotating Cylinder
Authors: Shao Nan , Yao Guofeng , Zhang Chang , Wang Min
Published: June 2017

The wake flow of a vehicle significantly influences its aerodynamic performance and the stability during high‐speed drive. Therefore, optimization of the vehicle wake flow is an effective way to improve its aerodynamic performance and further improve the handling stability and fuel economy. In this paper, a new method, the leading edge rotating cylinder, is used to optimize the wake flow of a vehicle. According to the results of simulations, this method can reduce the pressure drag, increase the negative lift force, and strengthen the stability of the vehicle under crosswind. Furthermore, this method optimizes not only the wake flow of the vehicle with rotating cylinders but also the interactive vehicles in the driving route in overtaking maneuvers or platoon driving. In conclusion, this method effectively optimizes the flow fields around the vehicles, and it significantly helps to improve the handling stability and fuel economy of the vehicle.
Reduction of the Electrode Overpotential of the Oxygen Evolution Reaction by Electrode Surface Modification
Authors: Lu Cian-Tong , Chiu Yen-Wen , Li Mei-Jing , Hsueh Kan-Lin , Hung Ju-Shei
Published: June 2017

Metal–air batteries exhibit high potential for grid-scale energy storage because of their high theoretical energy density, their abundance in the earth’s crust, and their low cost. In these batteries, the oxygen evolution reaction (OER) occurs on the air electrode during charging. This study proposes a method for improving the OER electrode performance. The method involves sequentially depositing a Ni underlayer, Sn whiskers, and a Ni protection layer on the metal mesh. Small and uniform gas bubbles form on the Ni/Sn/Ni mesh, leading to low overpotential and a decrease in the overall resistance of the OER electrode. The results of a simulated life cycle test indicate that the Ni/Sn/Ni mesh has a life cycle longer than 1,300 cycles when it is used as the OER electrode in 6 M KOH.
Pharmacokinetics and Pharmacodynamics-Based Mathematical Modeling Identifies an Optimal Protocol for Metronomic Chemotherapy
Authors: Ciccolini Joseph , Barbolosi Dominique , Meille Christophe , Lombard Aurélie , Serdjebi Cindy , Giacometti Sarah , Padovani Laetitia , Pasquier Eddy , André Nicolas
Published: June 2017

Metronomic chemotherapy is usually associated with better tolerance than conventional chemotherapy, and encouraging response rates have been reported in various settings. However, clinical development of metronomic chemotherapy has been hampered by a number of limitations, including the vagueness of its definition and the resulting empiricism in protocol design. In this study, we developed a pharmacokinetic/pharmacodynamic mathematical model that identifies in silico the most effective administration schedule for gemcitabine monotherapy. This model is based upon four biological assumptions regarding the mechanisms of action of metronomic chemotherapy, resulting in a set of 6 minimally parameterized differential equations. Simulations identified daily 0.5–1 mg/kg gemcitabine as an optimal protocol to maximize antitumor efficacy. Both metronomic protocols (0.5 and 1 mg/kg/day for 28 days) were evaluated in chemoresistant neuroblastoma-bearing mice and compared with the standard MTD protocol (100 mg/kg once a week for 4 weeks). Systemic exposure to gemcitabine was 14 times lower in the metronomic groups compared with the standard group. Despite this, metronomic gemcitabine significantly inhibited tumor angiogenesis and reduced tumor perfusion and inflammation in vivo, while standard gemcitabine did not. Furthermore, metronomic gemcitabine yielded a 40%–50% decrease in tumor mass at the end of treatment as compared with control mice (P = 0.002; ANOVA on ranks with Dunn test), while standard gemcitabine failed to significantly reduce tumor growth. Stable disease was maintained in the metronomic groups for up to 2 months after treatment completion (67%–72% reduction in tumor growth at study conclusion, P < 0.001; ANOVA on ranks with Dunn test). Collectively, our results confirmed the superiority of metronomic protocols in chemoresistant tumors in vivo. Cancer Res; 77(17); 4723–33. ©2017 AACR.
A Small-Molecule Inhibitor of WEE1, AZD1775, Synergizes with Olaparib by Impairing Homologous Recombination and Enhancing DNA Damage and Apoptosis in Acute Leukemia
Authors: Garcia Tamara B. , Snedeker Jonathan C. , Baturin Dmitry , Gardner Lori , Fosmire Susan P. , Zhou Chengjing , Jordan Craig T. , Venkataraman Sujatha , Vibhakar Rajeev , Porter Christopher C.
Published: June 2017

Although some patients with acute leukemia have good prognoses, the prognosis of adult and pediatric patients who relapse or cannot tolerate standard chemotherapy is poor. Inhibition of WEE1 with AZD1775 has been shown to sensitize cancer cells to genotoxic chemotherapies, including cytarabine in acute myeloid leukemia (AML) and T-ALL. Inhibition of WEE1 impairs homologous recombination by indirectly inhibiting BRCA2. Thus, we sought to determine whether AZD1775 could sensitize cells to the PARP1/2 inhibitor olaparib. We found that combined treatment with AZD1775 and olaparib was synergistic in AML and ALL cells, and this combination impaired proliferative capacity upon drug withdrawal. AZD1775 impaired homologous recombination in olaparib-treated cells, resulting in enhanced DNA damage accumulation and apoptosis induction. This combination enhanced disease control and increased survival in a murine AML model. Furthermore, we demonstrated that combined treatment with AZD1775 and olaparib reduces proliferation and colony formation and increases apoptosis in AML patient samples. In aggregate, these studies raise the possibility of rational combinations of targeted agents for leukemia in patients for whom conventional chemotherapeutics may not be effective or well tolerated. Mol Cancer Ther; 16(10); 2058–68. ©2017 AACR.
Inhibition of Androgen Receptor Nuclear Localization and Castration-Resistant Prostate Tumor Growth by Pyrroloimidazole-based Small Molecules
Authors: Masoodi Khalid Z. , Xu Yadong , Dar Javid A. , Eisermann Kurtis , Pascal Laura E. , Parrinello Erica , Ai Junkui , Johnston Paul A. , Nelson Joel B. , Wipf Peter , Wang Zhou
Published: June 2017

The androgen receptor (AR) is a ligand-dependent transcription factor that controls the expression of androgen-responsive genes. A key step in androgen action, which is amplified in castration-resistant prostate cancer (CRPC), is AR nuclear translocation. Small molecules capable of inhibiting AR nuclear localization could be developed as novel therapeutics for CRPC. We developed a high-throughput screen and identified two structurally-related pyrroloimidazoles that could block AR nuclear localization in CRPC cells. We show that these two small molecules, 3-(4-ethoxyphenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole (EPPI) and 3-(4-chlorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole (CPPI) can inhibit the nuclear localization and transcriptional activity of AR and reduce the proliferation of AR-positive but not AR-negative prostate cancer cell lines. EPPI and CPPI did not inhibit nuclear localization of the glucocorticoid receptor or the estrogen receptor, suggesting they selectively target AR. In LNCaP tumor xenografts, CPPI inhibited the proliferation of relapsed LNCaP tumors. These findings suggest that EPPI and CPPI could serve as lead structures for the development of therapeutic agents for CRPC. Mol Cancer Ther; 16(10); 2120–9. ©2017 AACR.
ADA-07 Suppresses Solar Ultraviolet–Induced Skin Carcinogenesis by Directly Inhibiting TOPK
Authors: Gao Ge , Zhang Tianshun , Wang Qiushi , Reddy Kanamata , Chen Hanyong , Yao Ke , Wang Keke , Roh Eunmiri , Zykova Tatyana , Ma Weiya , Ryu Joohyun , Curiel-Lewandrowski Clara , Alberts David , Dickinson Sally E. , Bode Ann M. , Xing Ying , Dong Zigang
Published: June 2017

Cumulative exposure to solar ultraviolet (SUV) irradiation is regarded as the major etiologic factor in the development of skin cancer. The activation of the MAPK cascades occurs rapidly and is vital in the regulation of SUV-induced cellular responses. The T-LAK cell–originated protein kinase (TOPK), an upstream activator of MAPKs, is heavily involved in inflammation, DNA damage, and tumor development. However, the chemopreventive and therapeutic effects of specific TOPK inhibitors in SUV-induced skin cancer have not yet been elucidated. In the current study, ADA-07, a novel TOPK inhibitor, was synthesized and characterized. Pull-down assay results, ATP competition, and in vitro kinase assay data revealed that ADA-07 interacted with TOPK at the ATP-binding pocket and inhibited its kinase activity. Western blot analysis showed that ADA-07 suppressed SUV-induced phosphorylation of ERK1/2, p38, and JNKs and subsequently inhibited AP-1 activity. Importantly, topical treatment with ADA-07 dramatically attenuated tumor incidence, multiplicity, and volume in SKH-1 hairless mice exposed to chronic SUV. Our findings suggest that ADA-07 is a promising chemopreventive or potential therapeutic agent against SUV-induced skin carcinogenesis that acts by specifically targeting TOPK. Mol Cancer Ther; 16(9); 1843–54. ©2017 AACR.
Revisiting Communicative Competence in Augmentative and Alternative Communication
Authors: Tsai Meng-Ju
Published: June 2017

Objective: This tutorial paper is to explore the novel nature of communicative competence in augmentative and alternative communication (AAC) practice by comparing it to communicative competence in naturally verbal dyadic communication. Patients and Methods: This paper first reviews the four domains of communicative competence in AAC practice. Second, it examines competence in dyadic communications between naturally verbal people without disabilities, deriving new insights and using these to analyze the evolution of communicative competence in AAC practice. Results: Communicative competence in AAC practice should be reconceptualized from a new perspective as dyadic, learned, co-constructed, and of relative value, ascertained through performance. Conclusion: In the past decades, the study of communicative competence in AAC practice has primarily focused on individual persons who use AAC. However, the conceptualization of communicative competence should shift away from an individualized construct toward a dyadic construct. This leads to a discussion of potential implications and future research directions. This paper might offer AAC researchers and practitioners an opportunity to deepen their understanding of communicative competence and promote more positive outcomes for people who use AAC.
Endothelial Interferon Regulatory Factor 1 Regulates Lipopolysaccharide-Induced VCAM-1 Expression Independent of NFκB
Authors: Yan Rui , van Meurs Matijs , Popa Eliane R. , Jongman Rianne M. , Zwiers Peter J. , Niemarkt Anita E. , Kuiper Timara , Kamps Jan A. , Heeringa Peter , Zijlstra Jan G. , Molema Grietje , Moser Jill
Published: June 2017

Sepsis is a severe systemic inflammatory response to infection. Endothelial activation and dysfunction play a critical role in the pathophysiology of sepsis and represent an important therapeutic target to reduce sepsis mortality. Interferon regulatory factor 1 (IRF-1) was recently identified as a downstream target of TNF-α-mediated signal transduction in endothelial cells. The aim of this study was to explore the importance of IRF-1 as a regulator of lipopolysaccharide (LPS)-induced endothelial proinflammatory activation. We found that renal IRF-1 was upregulated by LPS in vivo as well as in LPS-stimulated endothelial cells in vitro. Furthermore, we identified intracellular retinoic acid inducible gene-I (RIG-I) as a regulator of LPS-mediated IRF-1 induction. IRF-1 depletion specifically resulted in diminished induction of VCAM-1 in response to LPS, but not of E-selectin or ICAM-1, which was independent of NFκB signaling. When both IRF-1 and the RIG-I adapter protein mitochondrial antiviral signaling (MAVS) were absent, VCAM-1 induction was not additionally inhibited, suggesting that MAVS and IRF-1 reside in the same signaling pathway. Surprisingly, E-selectin and IL-6 induction were no longer inhibited by MAVS knockdown when IRF-1 was also absent, revealing a redundant endothelial activation pathway. In summary, we report an IRF-1-mediated proinflammatory signaling pathway that specifically regulates LPS-mediated VCAM-1 expression, independent of NFκB.
A Novel Homozygous SACS Mutation Identified by Whole-Exome Sequencing in a Consanguineous Family with Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay
Authors: Zeng Hui , Tang Jian-Guang , Yang Yi-Feng , Tan Zhi-Ping , Tan Jie-Qiong
Published: June 2017

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a hereditary neurological disorder mostly manifested with a classical triad: progressive early-onset cerebellar ataxia, lower limb pyramidal signs, and peripheral neuropathy. We employed whole-exome sequencing and bioinformatics to identify the genetic cause in an ARSACS patient from a consanguineous family. Based on whole-exome sequences of the patient and her healthy parents, a novel homozygous deletion variant (NM_014363: c.9495_9508del; p.F3166Tfs*9) in the SACS gene was identified in the patient. This frameshift mutation is predicted to generate a truncated sacsin protein, which results in the loss of the C-terminal 1,406 amino acids. Our study provides a potential genetic diagnosis for the patient and expands the spectrum of SACS mutations.
Similar but Different: How Reflectance Confocal Microscopy May Help in the Diagnosis of Pink Lesions
Authors: Ferrari Federica , Bassoli Sara , Pellacani Giovanni , Argenziano Giuseppe , Cesinaro Anna Maria , Longo Caterina
Published: June 2017

Background: Among skin neoplasms, solitary pink tumors represent challenging lesions in clinical practice since they can mimic melanocytic and nonmelanocytic lesions or even inflammatory ones. Objective: In this case series we described dermoscopic and confocal features of 2 couples of similar lesions in order to achieve the correct diagnosis and the best therapeutic approach. Methods: During clinical routine practice, 2 couples of clinically and dermoscopically similar lesions were examined by means of confocal microscopy. Results: All lesions revealed no clear-cut diagnostic features on dermoscopy. However, confocal microscopy revealed tumor islands with palisading cells and a dark clefting at the periphery in basal cell carcinomas. In the other “false twin” lesions, atypical cells and elongated junctional nests were observed and the diagnosis of amelanotic melanomas was rendered. Conclusions: In the current case series, the combined use of dermoscopy and reflectance confocal microscopy was an optimal workup for difficult-to-diagnose lesions such as pink tumors.
A reassessment of the vocalizations of three species of Ololygon (Anura: Hylidae) from southeastern Brazil
Authors: Bang Davi Lee , Giaretta Ariovaldo Antonio
Published: June 2017

The vocalizations of Ololygon hiemalis, O. ranki, and O. canastrensis are redescribed to provide further details on their complex vocal repertoires. The acoustic diagnosis of O. hiemalis is updated in relation to congeners, especially with respect to the morphologically similar O. ranki, for which we also evaluate the morphological diagnosis of both species. Three distinct types of notes are recognized in the vocalization of the three species (short squawk-like, long squawk-like and click-like), which are emitted in distinct acoustic organizations. The main organization of the three species is herein referred as the call Type “A”, each of which has a multi-note structure composed of a series of short squawk-like notes with note-by-note increase in amplitude along call duration. The call Type A of O. hiemalis was not described in the species original description. That of topotypes of O. ranki structurally resembles the call described in the original species description. Likewise, The call Type A of O. canastrensis matches that described in the original species description. Although O. hiemalis and O. ranki are phenotypically indistinguishable, there are quantitative differences in some call traits. Many species of Ololygon have complex vocalizations consisting of, at least, two types of notes, which can be emitted in different combinations. Despite the complexity of acoustic emissions, the call Type A of many species seems to be phylogenetically conserved. Because calls sometimes are only briefly described, we emphasize the need for, and importance of, comprehensive characterizations of anuran vocalizations to support future acoustic comparisons
Advertisement and aggressive calls of Pithecopus azureus (Anura: Phyllomedusidae) from the border of Brazil and Paraguay
Authors: Haga Isabelle Aquemi , Carvalho Thiago Ribeiro de , Andrade Felipe Silva de , Giaretta Ariovaldo Antonio
Published: June 2017

The categories of calls previously described for the closely related species Pithecopus azureus and P. hypochondrialis are reassessed. In addition, the advertisement and aggressive calls of P. azureus from Brazil-Paraguay border in southwestern state of Mato Grosso do Sul in western Brazil are redescribed. Intraspecific comparisons of call traits are made for populations of P. azureus from Argentina and Bolivia, and the vocalization of P. azureus is also compared with that of the closely related species of the P. hypochondrialis Group (subclade of lowland species). Given the similarities among the advertisement calls of P. azureus, P. hypochondrialis, and P. nordestinus, it seems that acoustic traits, at least solely, should not be employed as reliable diagnostic characters among these species
Performance and kinematics of saltation in the limbless lizard Ophisaurus attenuatus (Squamata: Anguidae)
Authors: Wass Emma D. , Gerald Gary W.
Published: June 2017

Saltation has been observed in several species of snakes and limbless lizards, and is most often used as an escape tactic during encounters with predators. However, studies examining kinematics and performance in limbless lizards are scarce and limited to observations of single individuals. We analysed 34 jump sequences from eight individual Ophisaurus attenuatus that exhibited escape saltation following minimal handling. We found that jumping is kinematically different from that described in snakes and similar to one other limbless lizard. Eight jumps resulted in the body completely leaving the ground. These jumps were characterized by larger displacement distances but were similar in speed compared to other jumps. Body mass was positively related to jump speed, but not with jump distances. This study suggests that increases in force production capabilities with increasing mass and the hindering effects of gravity interact to determine saltation performance in limbless lizards
Development of thirty-four new microsatellite loci and multiplexing of seven existing loci for Zootoca vivipara (Squamata: Lacertidae)
Authors: Horreo Jose Luis , Peláez Maria Luisa , Suárez Teresa , Heulin Benoit , Fitze Patrick Stefan
Published: June 2017

Few microsatellite loci exist for the European common lizard, Zootoca vivipara, a common model species in studies of population dynamics, sexual selection, population genetics, parity evolution, and physiology. The existing primers did not amplify in all lineages, and multiplexes were not optimized. A total of 34 new polymorphic microsatellite markers have been developed for this species and tested in 64 specimens belonging to oviparous and viviparous clades (B and D). The microsatellites were combined into seven different multiplexes. Results showed that all but one loci successfully amplified in all samples and both clades. The number of alleles detected per locus ranged 7–22 alleles and the effective number 1.58–7.82. The observed heterozygosity ranged 0.312–0.930, showing that all loci were highly variable. Oviparous and viviparous clades exhibited significant genetic differences (in FST). In addition to these new markers, the seven previously published and widely used microsatellite loci have been multiplexed and tested in oviparous clades. These innovations will allow for timesaving and robust analyses in Zootoca vivipara, boosting evolutionary and population studies and easing paternity analyses
National Differences in Trends for Heart Failure Hospitalizations by Sex and Race/Ethnicity
Authors: Ziaeian Boback , Kominski Gerald F. , Ong Michael K. , Mays Vickie M. , Brook Robert H. , Fonarow Gregg C.
Published: June 2017

Background—

National heart failure (HF) hospitalization rates have not been appropriately age standardized by sex or race/ethnicity. Reporting hospital utilization trends by subgroup is important for monitoring population health and developing interventions to eliminate disparities.

Methods and Results—

The National Inpatient Sample (NIS) was used to estimate the crude and age-standardized rates of HF hospitalization between 2002 and 2013 by sex and race/ethnicity. Direct standardization was used to age-standardize rates to the 2000 US standard population. Relative differences between subgroups were reported. The national age-adjusted HF hospitalization rate decreased 30.8% from 526.86 to 364.66 per 100 000 between 2002 and 2013. Although hospitalizations decreased for all subgroups, the ratio of the age-standardized rate for men compared with women increased from 20% greater to 39% (
P
trend=0.002) between 2002 and 2013. Black men had a rate that was 229% (
P
trend=0.141) and black women, 240% (
P
trend=0.725) with reference to whites in 2013 with no significant change between 2002 and 2013. Hispanic men had a rate that was 32% greater in 2002 and the difference narrowed to 4% (
P
trend=0.047) greater in 2013 relative to whites. For Hispanic women, the rate was 55% greater in 2002 and narrowed to 8% greater (
P
trend=0.004) in 2013 relative to whites. Asian/Pacific Islander men had a 27% lower rate in 2002 that improved to 43% (
P
trend=0.040) lower in 2013 relative to whites. For Asian/Pacific Islander women, the hospitalization rate was 24% lower in 2002 and improved to 43% (
P
trend=0.021) lower in 2013 relative to whites.

Conclusions—

National HF hospitalization rates have decreased steadily during the recent decade. Disparities in HF burden and hospital utilization by sex and race/ethnicity persist. Significant population health interventions are needed to reduce the HF hospitalization burden among blacks. An evaluation of factors explaining the improvements in the HF hospitalization rates among Hispanics and Asian/Pacific Islanders is needed.