bluuebunny/crossref_metadata_2025 huggingface dataset:
AN ASSESSMENT OF STABILITY, GAIT PERFORMANCE AND ENERGY CONSUMPTION IN INDIVIDUALS WITH TRANSFEMORAL AMPUTATION
Authors: KHIRI FATOMEH , KARIMI MOHAMMAD TAGHI , FATOYE FRANCIS , JAMSHIDI NIMA
Published: March 2015

Transfemoral amputation (TFA) results in reduced sensation, altered body image and loss of function. Energy expenditure is known to be significantly higher in individuals with TFA compared with their healthy counterparts. Kinetic and kinematics characteristics of individuals with TFA have been evaluated; however, stability during quiet standing has not been examined. This study evaluated stability, gait performance and energy consumption in individuals with TFA during standing and walking. A total of subjects (5 healthy and 5 with TFA) participated in this study. The motion of lower limb joints and the force applied on the leg were evaluated using a motion analysis system, Qualysis. Stability during standing was examined using a force plate and energy consumption during walking was evaluated based on physiological cost index (PCI). Group comparisons were made using the independent t-test. There was no significant difference in stability between subjects with TFA and normal subjects during standing. However, walking speed in subjects with TFA decreased significantly compared to normal subjects (p = 0.014). PCI of subjects with TFA was 0.525 ± 0.13 compared to 0.298 ± 0.059 beats/m in normal subjects (p < 0.05). It seems that stability in subjects with TFA was similar to their healthy counterparts. However, energy consumption was higher in the TFA group than in normal subjects, which may be due to slow walking speed. Clinicians are to be aware of these findings as they may be useful for effective management of the patients with TFA.
FINITE ELEMENT ANALYSIS OF MECHANICAL DEFORMATION OF CHONDROCYTE TO 2D SUBSTRATE AND 3D SCAFFOLD
Authors: CHEN JINJU , BADER D. L. , LEE D. A. , KNIGHT M. M.
Published: March 2015

The mechanical properties of cells are important in regulation of many aspects of cell functions. The cell may respond differently to a 2D plate and a 3D scaffold. In this study, the finite element analysis (FEA) was adopted to investigate mechanical deformation of chondrocyte on a 2D glass plate and chondrocyte seeded in a 3D scaffold. The elastic properties of the cell differ in these two different compression tests. This is because that the cell sensed different environment (2D plate and 3D construct) which can alter its structure and mechanical properties. It reveals how the apparent Poisson's ratio of a cell changes with the applied strain depends on its mechanical environment (e.g., the elastic moduli and Poisson's ratios of the scaffold and extracellular matrix) which regulates cell mechanics. In addition, the elastic modulus of the nucleus also plays a significant role in the determination of the Poisson's ratio of the cell for the cells seeded scaffold. It also reveals the intrinsic Poisson's ratio of the cell cannot be obtained by extrapolating the measured apparent Poisson's ratio to zero strain, particularly when scaffold's Poisson's ratio is quite different from the cell.
Bayesian approach to Boson sampling validation
Authors: Bentivegna Marco , Spagnolo Nicolò , Vitelli Chiara , Brod Daniel J. , Crespi Andrea , Flamini Fulvio , Ramponi Roberta , Mataloni Paolo , Osellame Roberto , Galvão Ernesto F. , Sciarrino Fabio
Published: March 2015

The Boson sampling problem consists in sampling from the output probability distribution of a bosonic Fock state, after it evolves through a linear interferometer. There is strong evidence that Boson sampling is computationally hard for classical computers, while it can be solved naturally by bosons. This has led it to draw increasing attention as a possible way to provide experimental evidence for the quantum computational supremacy. Nevertheless, the very complexity of the problem makes it hard to exclude the hypothesis that the experimental data are sampled from a different probability distribution. By exploiting integrated quantum photonics, we have carried out a set of three-photon Boson sampling experiments and analyzed the results using a Bayesian approach, showing that it represents a valid alternative to currently used methods. We adopt this approach to provide evidence that the experimental data correspond to genuine three-photon interference, validating the results against fully and partially-distinguishable photon hypotheses.
Long-term interactions with empathic social robots
Authors: Leite Iolanda
Published: March 2015

We investigated the effects of an adaptive empathic model in repeated interactions between users and social robots. The proposed model includes an online learning decision-making mechanism that allows the robot to select the most appropriate supportive behaviors based on the impact that similar behaviors had in keeping the user in a positive affective state.
Guest Column
Authors: Calude Cristian S. , Calude Elena , Dinneen Michael J.
Published: March 2015

The paper presents a brief introduction to quantum computing with focus on the adiabatic model which is illustrated with the commercial D-Wave computer. We also include new theory and experimental work done on the D-Wave computer. Finally we discuss a hybrid method of combining classical and quantum computing and a few open problems.
Blockade of the dorsomedial hypothalamus and the perifornical area inhibits respiratory responses to arousing and stressful stimuli
Authors: Bondarenko Evgeny , Beig Mirza I. , Hodgson Deborah M. , Braga Valdir A. , Nalivaiko Eugene
Published: March 2015

The dorsomedial hypothalamus (DMH) and the perifornical area (DMH/PeF) is one of the key regions of central autonomic processing. Previous studies have established that this region contains neurons that may be involved in respiratory processing; however, this has never been tested in conscious animals. The aim of our study was to investigate the involvement of the DMH/PeF area in mediating respiratory responses to stressors of various intensities and duration. Adult male Wistar rats ( n = 8) received microinjections of GABAAagonist muscimol or saline into the DMH/PeF bilaterally and were subjected to a respiratory recording using whole body plethysmography. Presentation of acoustic stimuli (500-ms white noise) evoked transient responses in respiratory rate, proportional to the stimulus intensity, ranging from +44 ± 27 to +329 ± 31 cycles/min (cpm). Blockade of the DMH/PeF almost completely abolished respiratory rate and tidal volume responses to the 40- to 70-dB stimuli and also significantly attenuated responses to the 80- to 90-dB stimuli. Also, it significantly attenuated respiratory rate during the acclimatization period (novel environment stress). The light stimulus (30-s 2,000 lux) as well as 15-min restraint stress significantly elevated respiratory rate from 95 ± 4.0 to 236 ± 29 cpm and from 117 ± 5.2 to 189 ± 13 cpm, respectively; this response was abolished after the DMH/PeF blockade. We conclude that integrity of the DMH/PeF area is essential for generation of respiratory responses to both stressful and alerting stimuli.
Sodium distribution predicts the chill tolerance ofDrosophila melanogasterraised in different thermal conditions
Authors: MacMillan Heath A. , Andersen Jonas L. , Loeschcke Volker , Overgaard Johannes
Published: March 2015

Many insects, including the model holometabolous insect Drosophila melanogaster, display remarkable plasticity in chill tolerance in response to the thermal environment experienced during development or as adults. At low temperatures, many insects lose the ability to regulate Na+balance, which is suggested to cause a secondary loss of hemolymph water to the tissues and gut lumen that concentrates the K+remaining in the hemolymph. The resultant increase in extracellular [K+] inhibits neuromuscular excitability and is proposed to cause cellular apoptosis and injury. The present study investigates whether and how variation in chill tolerance induced through developmental and adult cold acclimation is associated with changes in Na+, water, and K+balance. Developmental and adult cold acclimation improved the chilling tolerance of D. melanogaster in an additive manner. In agreement with the proposed model, these effects were intimately related to differences in Na+distribution prior to cold exposure, such that chill-tolerant flies had low hemolymph [Na+], while intracellular [Na+] was similar among treatment groups. The low hemolymph Na+of cold-acclimated flies allowed them to maintain hemolymph volume, prevent hyperkalemia, and avoid injury following chronic cold exposure. These findings extend earlier observations of hemolymph volume disruption during cold exposure to the most ubiquitous model insect ( D. melanogaster), highlight shared mechanisms of developmental and adult thermal plasticity and provide strong support for ionoregulatory failure as a central mechanism of insect chill susceptibility.
Functional roles of TRPV1 and TRPV4 in control of lower urinary tract activity: dual analysis of behavior and reflex during the micturition cycle
Authors: Yoshiyama Mitsuharu , Mochizuki Tsutomu , Nakagomi Hiroshi , Miyamoto Tatsuya , Kira Satoru , Mizumachi Ryoji , Sokabe Takaaki , Takayama Yasunori , Tominaga Makoto , Takeda Masayuki
Published: March 2015

The present study used a dual analysis of voiding behavior and reflex micturition to examine lower urinary tract function in transient receptor potential vanilloid (TRPV)1 knockout (KO) mice and TRPV4 KO mice. In metabolic cage experiments conducted under conscious conditions (i.e., voluntary voiding behavior), TRPV4 KO mice showed a markedly higher voiding frequency (VF; 19.3 ± 1.2 times/day) and a smaller urine volume/voiding (UVV; 114 ± 9 μl) compared with wild-type (WT) littermates (VF: 5.2 ± 0.5 times/day and UVV: 380 ± 34 μl). Meanwhile, TRPV1 KO mice showed a similar VF to WT littermates (6.8 ± 0.5 times/day) with a significantly smaller UVV (276 ± 20 μl). Water intake among these genotypes was the same, but TRPV4 KO mice had a larger urine output than the other two groups. In cystometrogram experiments conducted in decerebrate unanesthetized mice (i.e., reflex micturition response), no differences between the three groups were found in any cystometrogram variables, including voided volume, volume threshold for inducing micturition contraction, maximal voiding pressure, and bladder compliance. However, both TRPV1 KO and TRPV4 KO mice showed a significant number of nonvoiding bladder contractions (NVCs; 3.5 ± 0.9 and 2.8 ± 0.7 contractions, respectively) before each voiding, whereas WT mice showed virtually no NVCs. These results suggest that in the reflex micturition circuit, a lack of either channel is involved in NVCs during bladder filling, whereas in the forebrain, it is involved in the early timing of urine release, possibly in the conscious response to the bladder instability.
Precise visuotopic organization of the blind spot representation in primate V1
Authors: Azzi João C. B. , Gattass Ricardo , Lima Bruss , Soares Juliana G. M. , Fiorani Mario
Published: March 2015

The optic disk is a region of the retina consisting mainly of ganglion cell axons and blood vessels, which generates a visual scotoma known as the blind spot (BS). Information present in the surroundings of the BS can be used to complete the missing information. However, the neuronal mechanisms underlying these perceptual phenomena are poorly understood. We investigate the topography of the BS representation (BSR) in cortical area V1 of the capuchin monkey, using single and multiple electrodes. Receptive fields (RFs) of neurons inside the BSR were investigated using two distinct automatic bias-free mapping methods. The first method (local mapping) consisted of randomly flashing small white squares. For the second mapping method (global mapping), we used a single long bar that moved in one of eight directions. The latter stimulus was capable of eliciting neuronal activity inside the BSR, possibly attributable to long-range surround activity taking place outside the borders of the BSR. Importantly, we found that the neuronal activity inside the BSR is organized topographically in a manner similar to that found in other portions of V1. On average, the RFs inside the BS were larger than those outside. However, no differences in orientation or direction tuning were found between the two regions. We propose that area V1 exhibits a continuous functional topographic map, which is not interrupted in the BSR, as expected by the distribution of photoreceptors in the retina. Thus V1 topography is better described as “visuotopic” rather than as a discontinuous “retinotopic” map.
Utilization of Intraoperative TEE to Assess Supraventricular Tachycardia-Inducing Right-Sided Cardiac Compression by the Liver, Post-Liver-Transplantation Status
Authors: Stoll W. David , Hand William R. , Rohan Vinayak S. , Gaddy Parker M. , Reeves Scott T. , Chavin Kenneth D.
Published: March 2015

This unique and interesting case report involves a patient who recently underwent a combined liver and kidney transplant (due to autosomal dominant polycystic kidney disease) and subsequently suffered from episodes of supraventricular tachycardia (SVT) secondary to the new liver graft compressing the right atrium and ventricle. After this was diagnosed, the patient underwent operative plication of the right hemidiaphragm. Intraoperative transesophageal echocardiography was used to demonstrate cardiac compression from the liver and demonstrate resolution of compression after plication of the hemidiaphragm.
A Mass Loss Penetration Model to Investigate the Dynamic Response of a Projectile Penetrating Concrete considering Mass Abrasion
Authors: Zhang NianSong , Wang Dong , Peng Bei , He Yong
Published: March 2015

A study on the dynamic response of a projectile penetrating concrete is conducted. The evolutional process of projectile mass loss and the effect of mass loss on penetration resistance are investigated using theoretical methods. A projectile penetration model considering projectile mass loss is established in three stages, namely, cratering phase, mass loss penetration phase, and remainder rigid projectile penetration phase.
Estimation of Continental-Basin-Scale Sublimation in the Lena River Basin, Siberia
Authors: Suzuki Kazuyoshi , Liston Glen E. , Matsuo Koji
Published: March 2015

The Lena River basin in Siberia produces one of the largest river inflows into the Arctic Ocean. One of the most important sources of runoff to the river is spring snowmelt and therefore snow ablation processes have great importance for this basin. In this study, we simulated these processes with fine resolution at basin scale using MicroMet/SnowModel and SnowAssim. To assimilate snow water equivalent (SWE) data in SnowAssim, we used routine daily snow depth data and Sturm’s method. Following the verification of this method for SWE estimation in the basin, we evaluated the impact of snow data assimilation on basin-scale snow ablation. Through validation against MODIS snow coverage data andin situsnow survey observations, we found that SnowAssim could not improve on the original simulation by MicroMet/SnowModel because of estimation errors within the SWE data. Vegetation and accumulated snowfall control the spatial distribution of sublimation and we established that sublimation has an important effect on snow ablation. We found that the ratio of sublimation to snowfall in forests was around 26% and that interannual variation of sublimation modulated spring river runoff.
Functionalized Magnetic Nanoparticles and Their Effect on Escherichia coli and Staphylococcus aureus
Authors: Darwish Mohamed S. A. , Nguyen Nhung H. A. , Ševců Alena , Stibor Ivan
Published: March 2015

Magnetite (Fe3O4) nanoparticles were prepared using coprecipitation and subsequently surface‐functionalized with 3‐aminopropyltriethoxysilane (APTS), polyethylene glycol (PEG), and tetraethoxysilane (TEOS). Nanoparticle morphology was characterized using scanning electron microscopy, while structure and stability were assessed through infrared spectroscopy and zeta potential, respectively. Average size of the nanoparticles analysed by dynamic light scattering was 89 nm, 123 nm, 109 nm, and 130 nm for unmodified magnetite and APTS‐, PEG‐, and TEOS‐modified magnetite nanoparticles, respectively. Biological effect was studied on two bacterial strains: Gram‐negative Escherichia coli CCM 3954 and Gram‐positive Staphylococcus aureus CCM 3953. Most of modified magnetite nanoparticles had a significant effect on S. aureus and not on E. coli, whereas PEG‐magnetite nanoparticles displayed no significant effect on the growth rate of either bacteria.
The Mechanism of Melanocytes-Specific Cytotoxicity Induced by Phenol Compounds Having a Prooxidant Effect, relating to the Appearance of Leukoderma
Authors: Nagata Takeshi , Ito Shinobu , Itoga Kazuyoshi , Kanazawa Hideko , Masaki Hitoshi
Published: March 2015

Specific phenol compounds including rhododendrol (RD), a skin-brightening ingredient in cosmetics, are reported to induce leukoderma, inducing a social problem, and the elucidation of mechanism of leukoderma is strongly demanded. This study investigated the relationship among the cytotoxicities of six phenol compounds on B16F10 melanoma cells and HaCaT keratinocytes and generated reactive oxygen species (ROS). As a result, the cytotoxicity of RD on B16F10 cells was higher than that on HaCaT cells, and RD significantly increased intracellular ROS and hydrogen peroxide (H2O2) levels in B16F10 cells. Furthermore, although raspberry ketone (RK), RD derivative, also increased intracellular ROS in B16F10 cells, increase in ROS was suppressed by disodium dihydrogen ethylenediaminetetraacetate dehydrate (EDTA). The amounts of increased ROS with RK in HaCaT cells without melanocyte were further increased by tyrosinase. Therefore, tyrosinase, a metalloprotein having copper, was speculated to be one of causative agents allowing phenol compounds to work as a prooxidant. Hydroxyl radical was generated by adding a mixture of tyrosinase and H2O2to RD, and the amount of the radical was further increased by UVB, indicating that RD cytotoxicity was caused by intracellularly increased ROS, which possibly related to phenol induced prooxidants.
Pollinator Behaviour on a Food‐Deceptive Orchid Calypso bulbosa and Coflowering Species
Authors: Tuomi Juha , Lämsä Juho , Wannas Lauri , Abeli Thomas , Jäkäläniemi Anne
Published: March 2015

Food deception as a pollination strategy has inspired many studies over the last few decades. Pollinator deception has evolved in many orchids possibly to enhance outcrossing. Food‐deceptive orchids usually have low pollinator visitation rates as compared to rewarding species. They may benefit in visitations from the presence (magnet‐species hypothesis) or, alternatively, absence of coflowering rewarding species (competition hypothesis). We present data on pollinator visitations on a deceptive, terrestrial orchid Calypso bulbosa, a species with a single flower per plant and whose flowering period partly overlaps with rewarding, early flowering willows (Salix sp.) and later‐flowering bilberry (Vaccinium myrtillus). When surveying inactive bumblebee queens on willows in cool weather, about 7% of them carried Calypso pollinia. Most common bumblebee species appeared to visit and thus pollinate Calypso. Bumblebees typically visited one to three Calypso flowers before flying away, providing some support for the outcrossing hypothesis. We conclude that, regarding the pollinations strategy, both magnet‐species and competition hypotheses have a role in the pollination of Calypso, but on different spatial scales. On a large scale rewarding species are important for attracting pollinators to a given region, but on a small scale absence of competition ensures sufficient pollination rate for the deceptive orchid.
Enteropathogens Associated with Acute Diarrhea in Children from Households with High Socioeconomic Level in Uruguay
Authors: Varela Gustavo , Batthyány Lara , Bianco María Noel , Pérez Walter , Pardo Lorena , Algorta Gabriela , Robino Luciana , Suárez Ramón , Navarro Armando , Pírez María Catalina , Schelotto Felipe
Published: March 2015

Infectious diarrhea, a common disease of children, deserves permanent monitoring in all social groups. To know the etiology and clinical manifestations of acute diarrhea in children up to 5 years of age from high socioeconomic level households, we conducted a descriptive, microbiological, and clinical study. Stools from 59 children with acute community-acquired diarrhea were examined, and their parents were interviewed concerning symptoms and signs. Rotavirus, adenovirus, and norovirus were detected by commercially available qualitative immunochromatographic lateral flow rapid tests.Salmonella, Campylobacter, Yersinia, andShigellawere investigated by standard bacteriological methods and diarrheagenicE. coliby PCR assays. We identified a potential enteric pathogen in 30 children. The most frequent causes of diarrhea were enteropathogenicE. coli(EPEC), viruses,Campylobacter, Salmonella, and Shiga-toxin-producingE. coli(STEC). Only 2 patients showed mixed infections. Our data suggest that children with viral orCampylobacterdiarrhea were taken to the hospital earlier than those infected with EPEC. One child infected with STEC O26 developed “complete” HUS. The microbiological results highlight the importance of zoonotic bacteria such as atypical EPEC,Campylobacter, STEC, andSalmonellaas pathogens associated with acute diarrhea in these children. The findings also reinforce our previous communications about the regional importance of non-O157 STEC strains in severe infant food-borne diseases.
Variation of Heat Flux at Lower Frequencies of Vibration in a Vibrated Granular Bed
Authors: Sheikh Nadeem Ahmed , Manzoor Shehryar , Ali Muzaffar
Published: March 2015

Granular flows in vibrated bed exhibit various physical phenomena primarily driven by vibrating base. As the vibrating surface is the only source of energy in an otherwise dissipative flow, most of the theoretical models relate the steady state energy input to the RMS velocity of vibration. Here variation of heat flux is studied at varying frequency of vibration while keeping the RMS vibration velocity and the cell loading constant. Using single particle analysis and MD simulations, an extended version of grain-base collision is observed resulting in the reduction of heat flux at lower frequencies (<50 Hz) of vibration. The presented findings are important as most experimental studies are reported at these frequencies of excitation.
Probe-Based Confocal Laser Endomicroscopy for Indeterminate Biliary Strictures: Refinement of the Image Interpretation Classification
Authors: Kahaleh Michel , Giovannini Marc , Jamidar Priya , Gan S. Ian , Cesaro Paola , Caillol Fabrice , Filoche Bernard , Karia Kunal , Smith Ioana , Gaidhane Monica , Slivka Adam
Published: March 2015

Background. Accurate diagnosis and clinical management of indeterminate biliary strictures are often a challenge. Tissue confirmation modalities during Endoscopic Retrograde Cholangiopancreatography (ERCP) suffer from low sensitivity and poor diagnostic accuracy. Probe-based confocal laser endomicroscopy (pCLE) has been shown to be sensitive for malignant strictures characterization (98%) but lacks specificity (67%) due to inflammatory conditions inducing false positives.Methods. Six pCLE experts validated the Paris Classification, designed for diagnosing inflammatory biliary strictures, using a set of 40 pCLE sequences obtained during the prospective registry (19 inflammatory, 6 benign, and 15 malignant). The 4 criteria used included (1) multiple thin white bands, (2) dark granular pattern with scales, (3) increased space between scales, and (4) thickened reticular structures. Interobserver agreement was further calculated on a separate set of 18 pCLE sequences.Results. Overall accuracy was 82.5% (n=40retrospectively diagnosed) versus 81% (n=89prospectively collected) for the registry, resulting in a sensitivity of 81.2% (versus 98% for the prospective study) and a specificity of 83.3% (versus 67% for the prospective study). The corresponding interobserver agreement for 18 pCLE clips was fair (k=0.37).Conclusion. Specificity of pCLE using the Paris Classification for the characterization of indeterminate bile duct stricture was increased, without impacting the overall accuracy.
A Second New Choroidal Osteoma in the Same Eye: Differences between Them with New Imaging Techniques
Authors: Sambricio Javier , Fernández-Reyes Marifé , De-Lucas-Viejo Beatriz , Bengoa-González Álvaro , Mencía-Gutiérrez Enrique
Published: March 2015

The authors introduce a 42-year-old woman with a choroidal osteoma. After 10 years the patient presented a second choroidal osteoma in the same eye; this osteoma has been growing in the last years. New tests that were unavailable during the first diagnosis were performed such as Fundus Autofluorescence or Enhanced Depth Imaging-Optical Coherence Tomography (EDI-OCT). These tests show characteristics of the tumors and allow us to realize a visual prognosis for the patient.
Failure Rate of Single Dose Methotrexate in Managment of Ectopic Pregnancy
Authors: Sendy Feras , AlShehri Eman , AlAjmi Amani , Bamanie Elham , Appani Surekha , Shams Taghreed
Published: March 2015

Background. One of the treatment modalities for ectopic pregnancy is methotrexate. The purpose of this study is to identify the failure rate of methotrexate in treating patients with ectopic pregnancy as well as the risk factors leading to treatment failure.Methods. A retrospective chart review of 225 patients who received methotrexate as a primary management option for ectopic pregnancy. Failure of single dose of methotrexate was defined as drop of BHCG level less than or equal to 14% in the seventh day after administration of methotrexate.Results. 225 patients had methotrexate. Most of the patients (151 (67%)) received methotrexate based on the following formula: f 50 mg X body surface area. Single dose of methotrexate was successful in 72% (162/225) of the patients. 28% (63/225) were labeled as failure of single dose of methotrexate because of suboptimal drop in BhCG. 63% (40/63) of failure received a second dose of methotrexate, and 37% (23/63) underwent surgical treatment. Among patient who received initial dose of methotrexate, 71% had moderate or severe pain, and 58% had ectopic mass size of more than 4 cm on ultrasound.Conclusion. Liberal use of medical treatment of ectopic pregnancy results in 71% success rate.
Bee-Sensor-C: An Energy-Efficient and Scalable Multipath Routing Protocol for Wireless Sensor Networks
Authors: Cai Xuelian , Duan Yulong , He Ying , Yang Jin , Li Changle
Published: March 2015

A wireless sensor network (WSN) is composed of a large collection of sensor nodes with limited resources in terms of battery supplied energy, processing capability, and storage. Therefore, the design of an energy-efficient and scalable routing protocol is a crucial concern for WSN applications. In this paper, we propose Bee-Sensor-C, an energy-aware and scalable multipath routing protocol based on dynamic cluster and foraging behavior of a bee swarm. Bee-Sensor-C is an evolution from BeeSensor which is a bee-inspired routing protocol for WSNs. First of all, through introducing a dynamic clustering scheme, Bee-Sensor-C offers parallel data transmissions close to the event area. This evolution reduces routing overhead and improves the scalability. Moreover, Bee-Sensor-C adopts an enhanced multipath construction method in order to achieve the balance of the network energy consumption. Besides, Bee-Sensor-C can well support the multicluster scenario. Through simulations, the network performance is evaluated and the results demonstrate that Bee-Sensor-C outperforms the existing protocols in terms of energy efficiency, energy consumption balance, packet delivery rate, and scalability.
Antitumor Immunity Triggered by Melphalan Is Potentiated by Melanoma Cell Surface–Associated Calreticulin
Authors: Dudek-Perić Aleksandra M. , Ferreira Gabriela B. , Muchowicz Angelika , Wouters Jasper , Prada Nicole , Martin Shaun , Kiviluoto Santeri , Winiarska Magdalena , Boon Louis , Mathieu Chantal , van den Oord Joost , Stas Marguerite , Gougeon Marie-Lise , Golab Jakub , Garg Abhishek D. , Agostinis Patrizia
Published: March 2015

Systemic chemotherapy generally has been considered immunosuppressive, but it has become evident that certain chemotherapeutic drugs elicit immunogenic danger signals in dying cancer cells that can incite protective antitumor immunity. In this study, we investigated whether locoregionally applied therapies, such as melphalan, used in limb perfusion for melanoma (Mel-ILP) produce related immunogenic effects. In human melanoma biopsies, Mel-ILP treatment upregulated IL1B, IL8, and IL6 associated with their release in patients' locoregional sera. Although induction of apoptosis in melanoma cells by melphalan in vitro did not elicit threshold levels of endoplasmic reticulum and reactive oxygen species stress associated with danger signals, such as induction of cell-surface calreticulin, prophylactic immunization and T-cell depletion experiments showed that melphalan administration in vivo could stimulate a CD8+ T cell–dependent protective antitumor response. Interestingly, the vaccination effect was potentiated in combination with exogenous calreticulin, but not tumor necrosis factor, a cytokine often combined with Mel-ILP. Our results illustrate how melphalan triggers inflammatory cell death that can be leveraged by immunomodulators such as the danger signal calreticulin. Cancer Res; 75(8); 1603–14. ©2015 AACR.
Prevention of Chemically Induced Urinary Bladder Cancers by Naproxen: Protocols to Reduce Gastric Toxicity in Humans Do Not Alter Preventive Efficacy
Authors: Lubet Ronald A. , Scheiman James M. , Bode Ann , White Jonathan , Minasian Lori , Juliana M. Margaret , Boring Daniel L. , Steele Vernon E. , Grubbs Clinton J.
Published: March 2015

The COX inhibitors (NSAID/Coxibs) are a major focus for the chemoprevention of cancer. The COX-2–specific inhibitors have progressed to clinical trials and have shown preventive efficacy in colon and skin cancers. However, they have significant adverse cardiovascular effects. Certain NSAIDs (e.g., naproxen) have a good cardiac profile, but can cause gastric toxicity. The present study examined protocols to reduce this toxicity of naproxen. Female Fischer-344 rats were treated weekly with the urinary bladder–specific carcinogen hydroxybutyl(butyl)nitrosamine (OH-BBN) for 8 weeks. Rats were dosed daily with NPX (40 mg/kg body weight/day, gavage) or with the proton pump inhibitor omeprazole (4.0 mg/kg body weight/day) either singly or in combination beginning 2 weeks after the final OH-BBN. OH-BBN–treated rats, 96% developed urinary bladder cancers. While omeprazole alone was ineffective (97% cancers), naproxen alone or combined with omeprazole-prevented cancers, yielding 27 and 35% cancers, respectively. In a separate study, OH-BBN–treated rats were administered naproxen: (A) daily, (B) 1 week daily naproxen/1week vehicle, (C) 3 weeks daily naproxen/3 week vehicle, or (D) daily vehicle beginning 2 weeks after last OH-BBN treatment. In the intermittent dosing study, protocol A, B, C, and D resulted in palpable cancers in 27%, 22%, 19%, and 96% of rats (P < 0.01). Short-term naproxen treatment increased apoptosis, but did not alter proliferation in the urinary bladder cancers. Two different protocols that should decrease the gastric toxicity of NSAIDs in humans did not alter chemopreventive efficacy. This should encourage the use of NSAIDs (e.g., naproxen) in clinical prevention trials. Cancer Prev Res; 8(4); 296–302. ©2015 AACR.
Corrected QT in Ventricular Paced Rhythms: What Is the Validation for Commonly Practiced Assumptions?
Authors: Chakravarty Saneka , Kluger Jeffrey , Chhabra Lovely , Ramu Bhavadharini , Coleman Craig
Published: March 2015

Introduction: Ventricular pacing (VP) may impact the accuracy of QT interval measurement, as it increases the QT by increasing the QRS duration amongst other mechanisms. We aimed to investigate the accuracy of the commonly used clinical practice of subtracting 50 ms from the corrected QT (QTc) in ventricular paced rhythms. Methods: We conducted a prospective observational study on 23 consecutive pacemaker patients. Four ECGs were recorded for each subject, 2 in their native rate and 2 following an atrial paced, atrial sensed and inhibited response to sensing and then a dual pacing, dual sensing and dual response pacing of 100 bpm to allow for an intrinsic and a ventricular paced QRS, respectively. The averaged QTc in the ventricular paced rhythm was then compared with the non-ventricular-paced QTc for individual subjects. Results: At a mean spontaneous heart rate of 66 bpm (SD ±8), the mean difference in QTc between the ventricular paced and nonpaced QRS was 48.27 ms (95% CI = 32-64.6 ms, p < 0.001). At faster paced rates, the mean QTc difference was 81.3 ms (95% CI = 35.8-126.8 ms, p = 0.002). Conclusions: The QTc measurement during VP confirms the current 50-ms subtraction assumption rule within a range of ±16 ms at an average heart rate of 66 bpm. However, at faster heart rates, the 50-ms adjustment may underestimate the QTc discrepancy between a wide and normal QRS.
Primary Prevention of Congenital Anomalies: Recommendable, Feasible and Achievable
Authors: Taruscio Domenica , Mantovani Alberto , Carbone Pietro , Barisic Ingeborg , Bianchi Fabrizio , Garne Ester , Nelen Vera , Neville Amanda Julie , Wellesley Diana , Dolk Helen
Published: March 2015

Primary prevention of congenital anomalies was identified as an important action in the field of rare diseases by the European Commission in 2008, but it was not included in the Council Recommendation on an action in the field of rare diseases in 2009. However, primary prevention of congenital anomalies is feasible because scientific evidence points to several risk factors (e.g., obesity, infectious and toxic agents) and protective factors (e.g., folic acid supplementation and glycemic control in diabetic women). Evidence-based community actions targeting fertile women can be envisaged, such as risk-benefit evaluation protocols on therapies for chronic diseases, vaccination policies, regulations on workplace and environmental exposures as well as the empowerment of women in their lifestyle choices. A primary prevention plan can identify priority targets, exploit and integrate ongoing actions and optimize the use of resources, thus reducing the health burden for the new generation. The EUROCAT-EUROPLAN recommendations for the primary prevention of congenital anomalies endorsed in 2013 by the European Union Committee of Experts on Rare Diseases present an array of feasible and evidence-based measures from which national plans can adopt and implement actions based on country priorities. Primary prevention of congenital anomalies can be achieved here and now and should be an integral part of national plans on rare diseases.
Association rate constants rationalise the pharmacodynamics of apixaban and rivaroxaban
Authors: Jourdi Georges , Siguret Virginie , Martin Anne Céline , Golmard Jean-Louis , Godier Anne , Samama Charles-Marc , Gaussem Pascale , Gouin-Thibault Isabelle , Bonniec Bernard Le
Published: March 2015

Rivaroxaban and apixaban are selective direct inhibitors of free and prothrombinase-bound factor Xa (FXa). Surprisingly prothrombin time (PT) is little sensitive to clinically relevant changes in drug concentration, especially with apixaban. To investigate this pharmacodynamic discrepancy we have compared the kinetics of FXa inhibition in strictly identical conditions (pH 7.48, 37 °C, 0.15 M). KI values of 0.74 ± 0.03 and 0.47 ± 0.02 nM and kon values of 7.3 ± 1.6 106 and 2.9 ± 0.6 107 M-1 s-1 were obtained for apixaban and rivaroxaban, respectively. To investigate if these constants rationalise the inhibitor pharmacodynamics, we used numerical integration to evaluate impact of FXa inhibition on thrombin generation assay (TGA) and PT. Simulation predicted that in TGA triggered with 20 pM tissue factor, 100 ng/ml apixaban or rivaroxaban increased 1.8– or 3.0-fold the lag time and 1.4– or 2.0-fold the time to peak, whilst decreasing 1.2– or 3.1-fold the maximum thrombin and 1.7– or 3.5-fold the endogenous thrombin potential. These numbers were consistent with those obtained through the corresponding TGA triggered in plasma spiked with apixaban or rivaroxaban. Simulated PT ratios were also consistent with the corresponding plasma PT: markedly less sensitive to apixaban than to rivaroxaban. Analogous differences in TGA and PT were obtained irrespective of the drug amount added. We concluded that kon values for FXa of apixaban and rivaroxaban rationalise the unexpected lower sensitivity of PT and TGA to the former.
Differential Cardiac MicroRNA Expression Predicts the Clinical Course in Human Enterovirus Cardiomyopathy
Authors: Kuehl Uwe , Lassner Dirk , Gast Martina , Stroux Andrea , Rohde Maria , Siegismund Christine , Wang Xiaomin , Escher Felicitas , Gross Michael , Skurk Carsten , Tschoepe Carsten , Loebel Madlen , Scheibenbogen Carmen , Schultheiss Heinz-Peter , Poller Wolfgang
Published: March 2015

Background—

Investigation of disease pathogenesis confined to protein-coding regions of the genome may be incomplete because many noncoding variants are associated with disease. We aimed to identify novel predictive markers for the course of enterovirus (CVB3) cardiomyopathy by screening for noncoding elements influencing the grossly different antiviral capacity of individual patients.

Methods and Results—

Transcriptome mapping of CVB3 cardiomyopathy patients revealed distinctive cardiac microRNA (miR) patterns associated with spontaneous virus clearance and recovery (CVB3-ELIM) versus virus persistence and progressive clinical deterioration (CVB3-PERS). Profiling of protein-coding genes and 754 miRs in endomyocardial biopsies of test cohorts was performed at their initial presentation, and those spontaneously eliminating the virus were compared with those with virus persistence on follow-up. miR profiling revealed highly significant differences in cardiac levels of 16 miRs, but not of protein-coding genes. Evaluation of this primary distinctive miR pattern in validation cohorts, and multivariate receiver operating characteristic curve analysis, confirmed this pattern as highly predictive for disease course (area under the curve, 0.897±0.071; 95% confidence interval, 0.758–1.000). Eight miRs were strongly induced in CVB3-PERS (miRs 135b, 155, 190, 422a, 489, 590, 601, 1290), but undetectable in CVB3-ELIM or controls. They are predicted to target multiple immune response genes, and 2 of these were confirmed by antisense-mediated ablation of miRs 135b, 190, and 422a in the monocytic THP-1 cell line.

Conclusions—

An immediate clinical application of the data is cardiac miR profiling to assess the risk of virus persistence and progressive clinical deterioration in CVB3 cardiomyopathy. Patients at risk are eligible for immediate antiviral therapy to minimize irreversible cardiac damage.
Hypertension
Authors: te Riet Luuk , van Esch Joep H.M. , Roks Anton J.M. , van den Meiracker Anton H. , Danser A.H. Jan
Published: March 2015

Blockers of the renin–angiotensin–aldosterone system (RAAS), that is, renin inhibitors, angiotensin (Ang)-converting enzyme (ACE) inhibitors, Ang II type 1 receptor antagonists, and mineralocorticoid receptor antagonists, are a cornerstone in the treatment of hypertension. How exactly they exert their effect, in particular in patients with low circulating RAAS activity, also taking into consideration the so-called Ang II/aldosterone escape that often occurs after initial blockade, is still incompletely understood. Multiple studies have tried to find parameters that predict the response to RAAS blockade, allowing a personalized treatment approach. Consequently, the question should now be answered on what basis (eg, sex, ethnicity, age, salt intake, baseline renin, ACE or aldosterone, and genetic variance) a RAAS blocker can be chosen to treat an individual patient. Are all blockers equal? Does optimal blockade imply maximum RAAS blockade, for example, by combining ≥2 RAAS blockers or by simply increasing the dose of 1 blocker? Exciting recent investigations reveal a range of unanticipated extrarenal effects of aldosterone, as well as a detailed insight in the genetic causes of primary aldosteronism, and mineralocorticoid receptor blockers have now become an important treatment option for resistant hypertension. Finally, apart from the deleterious ACE-Ang II-Ang II type 1 receptor arm, animal studies support the existence of protective aminopeptidase A-Ang III-Ang II type 2 receptor and ACE2-Ang-(1 to 7)-Mas receptor arms, paving the way for multiple new treatment options. This review provides an update about all these aspects, critically discussing the many controversies and allowing the reader to obtain a full understanding of what we currently know about RAAS alterations in hypertension.
The Structural Factor of Hypertension
Authors: Laurent Stéphane , Boutouyrie Pierre
Published: March 2015

Pathophysiological studies have extensively investigated the structural factor in hypertension, including large and small artery remodeling and functional changes. Here, we review the recent literature on the alterations in small and large arteries in hypertension. We discuss the possible mechanisms underlying these abnormalities and we explain how they accompany and often precede hypertension. Finally, we propose an integrated pathophysiological approach to better understand how the cross-talk between large and small artery changes interacts in pressure wave transmission, exaggerates cardiac, brain and kidney damage, and lead to cardiovascular and renal complications. We focus on patients with essential hypertension because this is the most prevalent form of hypertension, and describe other forms of hypertension only for contrasting their characteristics with those of uncomplicated essential hypertension.
The Sympathetic Nervous System Alterations in Human Hypertension
Authors: Grassi Guido , Mark Allyn , Esler Murray
Published: March 2015

Several articles have dealt with the importance and mechanisms of the sympathetic nervous system alterations in experimental animal models of hypertension. This review addresses the role of the sympathetic nervous system in the pathophysiology and therapy of human hypertension. We first discuss the strengths and limitations of various techniques for assessing the sympathetic nervous system in humans, with a focus on heart rate, plasma norepinephrine, microneurographic recording of sympathetic nerve traffic, and measurements of radiolabeled norepinephrine spillover. We then examine the evidence supporting the importance of neuroadrenergic factors as promoters and amplifiers of human hypertension. We expand on the role of the sympathetic nervous system in 2 increasingly common forms of secondary hypertension, namely hypertension associated with obesity and with renal disease. With this background, we examine interventions of sympathetic deactivation as a mode of antihypertensive treatment. Particular emphasis is given to the background and results of recent therapeutic approaches based on carotid baroreceptor stimulation and radiofrequency ablation of the renal nerves.
Genetic and Molecular Aspects of Hypertension
Authors: Padmanabhan Sandosh , Caulfield Mark , Dominiczak Anna F.
Published: March 2015

Until recently, significant advances in our understanding of the mechanisms of blood pressure regulation arose from studies of monogenic forms of hypertension and hypotension, which identified rare variants that primarily alter renal salt handling. Genome-wide association and exome sequencing studies over the past 6 years have resulted in an unparalleled burst of discovery in the genetics of blood pressure regulation and hypertension. More importantly, genome-wide association studies, while expanding the list of common genetic variants associated with blood pressure and hypertension, are also uncovering novel pathways of blood pressure regulation that augur a new era of novel drug development, repurposing, and stratification in the management of hypertension. In this review, we describe the current state of the art of the genetic and molecular basis of blood pressure and hypertension.
Reduced Fetal Cerebral Oxygen Consumption Is Associated With Smaller Brain Size in Fetuses With Congenital Heart Disease
Authors: Sun Liqun , Macgowan Christopher K. , Sled John G. , Yoo Shi-Joon , Manlhiot Cedric , Porayette Prashob , Grosse-Wortmann Lars , Jaeggi Edgar , McCrindle Brian W. , Kingdom John , Hickey Edward , Miller Steven , Seed Mike
Published: March 2015

Background—

Fetal hypoxia has been implicated in the abnormal brain development seen in newborns with congenital heart disease (CHD). New magnetic resonance imaging technology now offers the potential to investigate the relationship between fetal hemodynamics and brain dysmaturation.

Methods and Results—

We measured fetal brain size, oxygen saturation, and blood flow in the major vessels of the fetal circulation in 30 late-gestation fetuses with CHD and 30 normal controls using phase-contrast magnetic resonance imaging and T2 mapping. Fetal hemodynamic parameters were calculated from a combination of magnetic resonance imaging flow and oximetry data and fetal hemoglobin concentrations estimated from population averages. In fetuses with CHD, reductions in umbilical vein oxygen content (
P
<0.001) and failure of the normal streaming of oxygenated blood from the placenta to the ascending aorta were associated with a mean reduction in ascending aortic saturation of 10% (
P
<0.001), whereas cerebral blood flow and cerebral oxygen extraction were no different from those in controls. This accounted for the mean 15% reduction in cerebral oxygen delivery (
P
=0.08) and 32% reduction cerebral V
o
2
in CHD fetuses (
P
<0.001), which were associated with a 13% reduction in fetal brain volume (
P
<0.001). Fetal brain size correlated with ascending aortic oxygen saturation and cerebral V
o
2
(
r
=0.37,
P
=0.004).

Conclusions—

This study supports a direct link between reduced cerebral oxygenation and impaired brain growth in fetuses with CHD and raises the possibility that in utero brain development could be improved with maternal oxygen therapy.