bluuebunny/crossref_metadata_2025 huggingface dataset:
Moving slowly is hard for humans: limitations of dynamic primitives
Authors: Park Se-Woong , Marino Hamal , Charles Steven K. , Sternad Dagmar , Hogan Neville
Published: March 2017

Mounting evidence suggests that human motor control uses dynamic primitives, attractors of dynamic neuromechanical systems that require minimal central supervision. However, advantages for control may be offset by compromised versatility. Extending recent results showing that humans could not sustain discrete movements as duration decreased, this study tested whether smoothly rhythmic movements could be maintained as duration increased. Participants performed horizontal movements between two targets, paced by sounds with intervals that increased from 1 to 6 s by 200 ms per cycle and then decreased again. The instruction emphasized smooth rhythmic movements without interspersed dwell times. We hypothesized that 1) when oscillatory motions slow down, smoothness decreases; 2) slower oscillatory motions are executed as submovements or even discrete movements; and 3) the transition between smooth oscillations and submovements shows hysteresis. An alternative hypothesis was that 4) removing visual feedback restores smoothness, indicative of visually evoked corrections causing the irregularity. Results showed that humans could not perform slow and smooth oscillatory movements. Harmonicity decreased with longer intervals, and dwell times between cycles appeared and became prominent at slower speeds. Velocity profiles showed an increase with cycle duration of the number of overlapping submovements. There was weak evidence of hysteresis in the transition between these two types of movement. Eliminating vision had no effect, suggesting that intermittent visually evoked corrections did not underlie this phenomenon. These results show that it is hard for humans to execute smooth rhythmic motions very slowly. Instead, they “default” to another dynamic primitive and compose motion as a sequence of overlapping submovements.

NEW & NOTEWORTHY Complementing a large body of prior work showing advantages of composing primitives to manage the complexity of motor control, this paper uncovers a limitation due to composition of behavior from dynamic primitives: while slower execution frequently makes a task easier, there is a limit and it is hard for humans to move very slowly. We suggest that this remarkable limitation is not due to inadequacies of muscle, nor to slow neural communication, but is a consequence of how the control of movement is organized.
Gene Feature Extraction Based on Nonnegative Dual Graph Regularized Latent Low-Rank Representation
Authors: Yang Guoliang , Hu Zhengwei
Published: March 2017

Aiming at the problem of gene expression profile’s high redundancy and heavy noise, a new feature extraction model based on nonnegative dual graph regularized latent low-rank representation (NNDGLLRR) is presented on the basis of latent low-rank representation (Lat-LRR). By introducing dual graph manifold regularized constraint, the NNDGLLRR can keep the internal spatial structure of the original data effectively and improve the final clustering accuracy while segmenting the subspace. The introduction of nonnegative constraints makes the computation with some sparsity, which enhances the robustness of the algorithm. Different from Lat-LRR, a new solution model is adopted to simplify the computational complexity. The experimental results show that the proposed algorithm has good feature extraction performance for the heavy redundancy and noise gene expression profile, which, compared with LRR and Lat-LRR, can achieve better clustering accuracy.
Design and Optimization of Elliptical Cavity Tube Receivers in the Parabolic Trough Solar Collector
Authors: Cao Fei , Wang Lei , Zhu Tianyu
Published: March 2017

The nonfragile cavity receiver is of high significance to the solar parabolic trough collector (PTC). In the present study, light distributions in the cavity under different tracking error angles and PTC configurations are analyzed. A new elliptical cavity geometry is proposed and analyzed. It is obtained from this study that light distribution on the tube receiver is asymmetrical when tracking error occurs. On increasing the tracking error angle, more lights are sheltered by the cavity outer surface. The PTC focal distance has negative correlation with the cavity open length, whereas the PTC concentration ratio has positive correlation with the cavity open length. Increasing the tracking error angle and increasing the PTC focal distance would both decrease the cavity blackness. Introducing a flat plate reflector at the elliptical cavity open inlet can largely increase the cavity darkness.
Phenolic Profile and Antioxidant Activity of Crude Extracts from Microalgae and Cyanobacteria Strains
Authors: Jerez-Martel Idaira , García-Poza Sara , Rodríguez-Martel Gara , Rico Milagros , Afonso-Olivares Cristina , Gómez-Pinchetti Juan Luis
Published: March 2017

Aqueous and methanolic extracts of several microalgae (Ankistrodesmus sp., Spirogyra sp., Euglena cantabrica, and Caespitella pascheri) and cyanobacteria (Nostoc sp., Nostoc commune, Nodularia spumigena, Leptolyngbya protospira, Phormidiochaete sp., and Arthrospira platensis) were screened for their radical scavenging activity against the stable radical 1,1-diphenyl-2-picrylhydrazyl. Despite the fact that water was a more efficient solvent to extract greater amount of extractable substances, it seems that methanol was more efficient to extract a selected group of compounds with a higher antioxidant activity. In addition, the identification of 4 simple phenolics (gallic, syringic, protocatechuic, and chlorogenic acids) and the flavonoids (+) catechin and (-) epicatechin was carried out by using reverse phase high performance liquid chromatography. The strain Euglena cantabrica showed the highest concentration of phenolic compounds, particularly gallic and protocatechuic acids (5.87 and 2.97 mg per gram of dried biomass, resp.). Aqueous and methanolic extracts of microalgae Euglena cantabrica also exhibited the highest antioxidant activity, probably due to the presence of the high contents of phenolics.
Dissect the Dynamic Molecular Circuits of Cell Cycle Control through Network Evolution Model
Authors: Peng Yang , Scott Paul , Tao Ruikang , Wang Hua , Wu Yan , Peng Guang
Published: March 2017

The molecular circuits of cell cycle control serve as a key hub to integrate from endogenous and environmental signals into a robust biological decision driving cell growth and division. Dysfunctional cell cycle control is highlighted in a wide spectrum of human cancers. More importantly the mainstay anticancer treatment such as radiation therapy and chemotherapy targets the hallmark of uncontrolled cell proliferation in cancer cells by causing DNA damage, cell cycle arrest, and cell death. Given the functional importance of cell cycle control, the regulatory mechanisms that drive the cell division have been extensively investigated in a huge number of studies by conventional single-gene approaches. However the complexity of cell cycle control renders a significant barrier to understand its function at a network level. In this study, we used mathematical modeling through modern graph theory and differential equation systems. We believe our network evolution model can help us understand the dynamic cell cycle control in tumor evolution and optimizing dosing schedules for radiation therapy and chemotherapy targeting cell cycle.
A Modified Translaminar Osseous Channel-Assisted Percutaneous Endoscopic Lumbar Discectomy for Highly Migrated and Sequestrated Disc Herniations of the Upper Lumbar: Clinical Outcomes, Surgical Indications, and Technical Considerations
Authors: Xin Zhijun , Liao Wenbo , Ao Jun , Qin Jianpu , Chen Fang , Ye Zhiyuan , Cai Yuqiang
Published: March 2017

Objective is to describe a safe and effective percutaneous endoscopic approach for removal of highly migrated and sequestrated disc herniations of the upper lumbar spine and to report the results, surgical indications, and technical considerations of the new technique. Eleven patients who had highly migrated and sequestrated disc herniations in the upper lumbar were included in this study. A retrospective study was performed for all patients after translaminar osseous channel-assisted PELD was performed. Radiologic findings were investigated, and pre-and postoperative visual analog scale (VAS) assessments for back and leg pain and Oswestry disability index (ODI) evaluations were performed. Surgical outcomes were evaluated under modified MacNab criteria. All of the patients were followed for more than 1 year. The preoperative and postoperative radiologic findings revealed that the decompression of the herniated nucleus pulposus (HNP) was complete. After surgery, the mean VAS scores for back and leg pain immediately improved from 8.64 (range, 7–10) and 8.00 (range, 6–10) to 2.91 (range, 2–4) and 2.27 (range, 1–3), respectively. The mean preoperative ODI was 65.58 (range, 52.2–86), which decreased to 7.51 (range, 1.8–18) at the 12-month postoperative follow-up. The MacNab scores at the final follow-up included nine excellent, one good, and one fair. The modified translaminar osseous channel-assisted PELD could be a safe and effective option for the treatment of highly migrated and sequestrated disc herniations of the upper lumbar.
Technoeconomic Evaluation for an Installed Small-Scale Photovoltaic Power Plant
Authors: Yaniktepe Bulent , Kara Osman , Ozalp Coskun
Published: March 2017

Solar energy production and economic evaluation are analyzed, in this study, by using daily solar radiation and average temperature data which are measured for 3 years in the Osmaniye province in Turkey. Besides, this study utilizes the photovoltaic- (PV-) based grid connected to a power plant which has an installed capacity of 1 MW investment in electricity production. Economic values show that the net present value (NPV), the first economic method in the research, is about 111941 USD, which is greater than zero. Therefore, the payback year of this investment is approximately 8.3. The second one of these methods, the payback period of the simple payback period (PBP), is 6.27 years. The last method, which is the mean value of the internal rate of return (IRR), is 10.36%. The results of this study show that Osmaniye is a considerable region for the PV investment in electricity production. As a result, investment of a PV system in Osmaniye can be applicable.
The Prevalence and Awareness of Cardiovascular Diseases Risk Factors among the Lebanese Population: A Prospective Study Comparing Urban to Rural Populations
Authors: Fahs Iqbal , Khalife Zainab , Malaeb Diana , Iskandarani Mohammad , Salameh Pascale
Published: March 2017

Introduction. CVDs are largely driven by modifiable risk factors. This study sought to determine the awareness and prevalence of the modifiable CVDs risk factors among the Lebanese population.Methods. In a cross-sectional survey, 1000 participants aged ≥ 45 years were randomly selected from pharmacies and interviewed. The data was analyzed with SPSS version 21.0 software.Results. Differences between urban and rural areas include alcohol consumption (2.8% versus 1.7%;p=0.0001), cardioprotective vegetable servings (6.1% versus 2.3%;p=0.016), sedentary hours per day (18.6% versus 15.1%;p=0.002), and hypertension (38.5% versus 25.4%;p=0.001). The prevalence of overweight and obesity (77.3% versus 75.2%;p=0.468), smoking (39.3% versus 43.3%;p=0.232), diabetes (25.4% versus 21.4%;p=0.173), and dyslipidemia (25 versus 21.2%) was reported. Measurements revealed 19.3% of undiagnosed hypertension (12.4% versus 22.4%,p=0.001), 61.7% of hypertension (59.8% versus 62.6%;p=0.203), and 7.9% of undiagnosed diabetes (6.6% versus 8.6%;p=0.323). The declared awareness of CVDs risk factors was highest for smoking (91.5% versus 89.7%;p=0.339) and lowest for diabetes (54.4 versus 55.7%;p=0.692).Conclusion. This study has shown a high prevalence of modifiable CVDs risk factors in the Lebanese population ≥ 45 years, among which hypertension is the most prominent.
Evaluation of Satellite Precipitation Products and Their Potential Influence on Hydrological Modeling over the Ganzi River Basin of the Tibetan Plateau
Authors: Alazzy Alaa Alden , Lü Haishen , Chen Rensheng , Ali Abubaker B. , Zhu Yonghua , Su Jianbin
Published: March 2017

In the last few years, satellite-based precipitation datasets are believed to be a potential source for forcing inputs in driving hydrological models, which are important especially in complex terrain areas or ungauged basins where ground gauges are generally sparse or nonexistent. This study aims to comprehensively evaluate the satellite precipitation products, CMORPH-CRT, PERSIANN-CDR, 3B42RT, and 3B42 against gauge-based datasets and to infer their relative potential impacts on hydrological processes simulation using the HEC-HMS model in the Ganzi River Basin (GRB) of the Tibetan Plateau. Results from a quantitative statistical comparison reveal that, at annual and seasonal scales, both CMORPH-CRT and 3B42 perform better than PERSIANN-CDR and 3B42RT. The CMORPH-CRT and 3B42 tend to underestimate values at the medium and high precipitation intensities ranges, whereas the opposite tendency is found for PERSIANN-CDR and 3B42RT. Overall, 3B42 exhibits the best performance for streamflow simulations over GRB and even outperforms simulation driven by gauge data during the validation period. PERSIANN-CDR shows the worst overall performance. After recalibrating with input-specific precipitation data, the performance of all satellite precipitation forced simulations is substantially improved, except for PERSIANN-CDR. Furthermore, 3B42 is more suitable to drive hydrological models and can be a potential alternative source of sparse data in Tibetan Plateau basins.
A Collusion-Resistant and Privacy-Preserving Data Aggregation Protocol in Crowdsensing System
Authors: Xu Chang , Shen Xiaodong , Zhu Liehuang , Zhang Yan
Published: March 2017

With the pervasiveness and increasing capability of smart devices, mobile crowdsensing has been applied in more and more practical scenarios and provides a more convenient solution with low costs for existing problems. In this paper, we consider an untrusted aggregator collecting a group of users’ data, in which personal private information may be contained. Most previous work either focuses on computing particular functions based on the sensing data or ignores the collusion attack between users and the aggregator. We design a new protocol to help the aggregator collect all the users’ raw data while resisting collusion attacks. Specifically, the bitwise XOR homomorphic functions and aggregate signature are explored, and a novel key system is designed to achieve collusion resistance. In our system, only the aggregator can decrypt the ciphertext. Theoretical analysis shows that our protocol can capture k-source anonymity. In addition, extensive experiments are conducted to demonstrate the feasibility and efficiency of our algorithms.
Finite Analytic Method for One-Dimensional Nonlinear Consolidation under Time-Dependent Loading
Authors: Cheng Dawei , Wang Wenke , Chen Xi , Zhang Zaiyong
Published: March 2017

For one-dimensional (1D) nonlinear consolidation, the governing partial differential equation is nonlinear. This paper develops the finite analytic method (FAM) to simulate 1D nonlinear consolidation under different time-dependent loading and initial conditions. To achieve this, the assumption of constant initial effective stress is not considered and the governing partial differential equation is transformed into the diffusion equation. Then, the finite analytic implicit scheme is established. The convergence and stability of finite analytic numerical scheme are proven by a rigorous mathematical analysis. In addition, the paper obtains three corrected semianalytical solutions undergoing suddenly imposed constant loading, single ramp loading, and trapezoidal cyclic loading, respectively. Comparisons of the results of FAM with the three semianalytical solutions and the result of FDM, respectively, show that the FAM can obtain stable and accurate numerical solutions and ensure the convergence of spatial discretization for 1D nonlinear consolidation.
Safety of Cultivated Limbal Epithelial Stem Cell Transplantation for Human Corneal Regeneration
Authors: Behaegel J. , Ní Dhubhghaill S. , Koppen C. , Zakaria N.
Published: March 2017

Ex vivo cultivated limbal stem cell transplantation is a promising technique for the treatment of limbal stem cell deficiency. While the results of the clinical trials have been extensively reported since the introduction of the technique in 1997, little has been reported regarding the potential health risks associated with production processes and transplantation techniques. Culture procedures require the use of animal and/or human-derived products, which carry the potential of introducing toxic or infectious agents through contamination with known or unknown additives. Protocols vary widely, and the risks depend on the local institutional methods. Good manufacturing practice and xeno-free culture protocols could reduce potential health risks but are not yet a common practice worldwide. In this review, we focus on the safety of both autologous- and allogeneic-cultivated limbal stem cell transplantation, with respect to culture processes, surgical approaches, and postoperative strategies.
Incidence of Urethral Stricture in Patients with Adult Acquired Buried Penis
Authors: Liaw Aron , Rickborn Lanette , McClung Christopher
Published: March 2017

Introduction. Concealed-buried penis is an acquired condition associated with obesity, challenging to both manage and repair. Urethral stricture is a more common disorder with multiple etiologies. Lichen sclerosus is a significant known cause of urethral stricture, implicated in up to 30%. We hypothesize that patients with buried penis have a higher rate of urethral stricture and lichen sclerosus than the general population.Methods. We retrospectively reviewed a single surgeon’s (CM) case logs for patients presenting with a buried penis. All patients were evaluated for urethral stricture with cystoscopy or retrograde urethrogram either prior to or at the time of repair for buried penis. Those that had surgical repair or biopsy were reviewed for presence of lichen sclerosus.Results. 39 patients met inclusion criteria. Of these, 13 (33%) had associated stricture disease. The location of the strictures was bulbar urethra (38%), penile urethra (15%), and meatus or fossa navicularis (62%). Five patients had lichen sclerosus and urethral stricture disease, while 3 had lichen sclerosus without stricture. 11/13 stricture patients were treated. Six underwent dilation, 3 underwent meatotomy, and 2 underwent urethroplasty. No significant recurrences of stricture were seen.Conclusion. Patients with a concealed penis are more likely than the general population to have a urethral stricture and/or LS. Patients presenting with concealed penis should also be evaluated for a urethral stricture.
A Review of Modern Control Strategies for Clinical Evaluation of Propofol Anesthesia Administration Employing Hypnosis Level Regulation
Authors: Ilyas Muhammad , Butt Muhammad Fasih Uddin , Bilal Muhammad , Mahmood Khalid , Khaqan Ali , Ali Riaz Raja
Published: March 2017

Regulating the depth of hypnosis during surgery is one of the major objectives of an anesthesia infusion system. Continuous administration of Propofol infusion during surgical procedures is essential but it unduly increases the load of an anesthetist working in a multitasking scenario in the operation theatre. Manual and target controlled infusion systems are not appropriate to handle instabilities like blood pressure and heart rate changes arising due to interpatient and intrapatient variability. Patient safety, large interindividual variability, and less postoperative effects are the main factors motivating automation in anesthesia administration. The idea of automated system for Propofol infusion excites control engineers to come up with more sophisticated systems that can handle optimum delivery of anesthetic drugs during surgery and avoid postoperative effects. A linear control technique is applied initially using three compartmental pharmacokinetic and pharmacodynamic models. Later on, sliding mode control and model predicative control achieve considerable results with nonlinear sigmoid model. Chattering and uncertainties are further improved by employing adaptive fuzzy control andH∞control. The proposed sliding mode control scheme can easily handle the nonlinearities and achieve an optimum hypnosis level as compared to linear control schemes, hence preventing mishaps such as underdosing and overdosing of anesthesia.
Recycled Polypropylene Improved with Thermoplastic Elastomers
Authors: Matei Ecaterina , Râpă Maria , Andras Árpád Andor , Predescu Andra Mihaela , Pantilimon Cristian , Pica Alexandra , Predescu Cristian
Published: March 2017

The use of recycled polypropylene (RPP) as raw material for various industries has been known. However, the mechanical and thermal properties of recycled products are lower than those of raw material. The objective of this study was to obtain and investigate the modified recycled polypropylene (RPP) with commercial elastomers for possible applications. The compounded RPP-based thermoplastic elastomers were investigated in order to determine their thermal properties (melt flow index (MFI), differential scanning calorimetry (DSC), VICAT softening temperature (VST), and heat deflection temperature (HDT)), structural characteristics (optical microscopy, atomic force microscopy (AFM), and X-ray diffraction (XRD)), and mechanical properties (tensile properties, density, and IZOD impact). The RPP compounded with 10% elastomer recorded higher tensile properties than the unmodified RPP. Also, IZOD impact strength increased from4.3±0.2 kJ/m2(registered for RPP) to21.7±2.5 kJ/m2for the PPR/SIS30 compound, while the degree of crystallinity decreased for all compounds. The obtained results recommend the RPP/elastomers compounds both for environmental remediation from postconsumer PP wastes and to realize new goods with high performance for various applications.
Physicochemical Characterisation of Polysaccharides from the Seeds and Leaves of Miracle Fruit (Synsepalum dulcificum) and Their Antioxidant and α-Glucosidase Inhibitory Activities In Vitro
Authors: Jian Huajun , Qiao Fang , Chen Jie , He Nongyue
Published: March 2017

Miracle fruit (Synsepalum dulcificum) has been well known and studied for its unique taste-modifying ability. In this study, the monosaccharide composition, molecular weight (Mw), and in vitro bioactivities (antioxidant, α-glucosidase inhibition) of polysaccharides from the seeds (MFP-S) and leaves (MFP-L) of miracle fruit were investigated. The results showed that MFP-S was a homogeneous polysaccharide (Mw 2804 Da) with glucose. MFP-L displayed three fractions (92093, 1496, and 237 Da) consisting of rhamnose, arabinose, galactose, glucose, and xylose. Moreover, the antioxidant and α-glucosidase inhibition of MFP-L were significantly greater than those of MFP-S. The α-glucosidase inhibition of MFP-L was remarkably better than the positive control, acarbose (an antidiabetes drug). More specifically, the 50% inhibitory concentration (IC50) values of α-glucosidase activities for MFP-S, MFP-L, and acarbose were 33, 0.01, and 1 mg mL−1, separately. Therefore, MFP-L can be developed as a functional factor with both antioxidant and antidiabetes activities in food applications.
Predictive Regression Equations of Flowmetric and Spirometric Peak Expiratory Flow in Healthy Moroccan Adults
Authors: Bouti Khalid , Maouni Iliass , Benamor Jouda , Bourkadi Jamal Eddine
Published: March 2017

Introduction. PEF has never been characterized among healthy Moroccan adults. The objective of this study is to describe the values of PEF among healthy Moroccan adults, to study its relationship with anthropometric parameters (gender, age, height, and weight), to compare spirometric and flowmetric PEF, to establish the prediction equations for PEF, and to study the correlation between PEF and FEV1.Methods. Cross-sectional study conducted between May and June 2016. It involved healthy nonsmoking volunteers living in Tetouan, Morocco, gathered through a mobile stand realization of spirometry and peak flow measurements.Results. Our final sample concerned 313 adults (143 men and 170 women). For both men and women, age and height were the main determinants of PEF, and a positive correlation was found between PEF and FEV1.Conclusion. Our study has established the PEF predictive equations in the Moroccan adult population. Our results allow us to conclude that the PEF can be a reliable alternative of FEV1 in centers not equipped with spirometry.
Aromatherapy and Aromatic Plants for the Treatment of Behavioural and Psychological Symptoms of Dementia in Patients with Alzheimer’s Disease: Clinical Evidence and Possible Mechanisms
Authors: Scuteri Damiana , Morrone Luigi Antonio , Rombolà Laura , Avato Pina Rosa , Bilia Anna Rita , Corasaniti Maria Tiziana , Sakurada Shinobu , Sakurada Tsukasa , Bagetta Giacinto
Published: March 2017

The treatment of agitation and aggression, typical Behavioural and Psychological Symptoms of Dementia (BPSDs) of Alzheimer’s Disease (AD), is one of the most complicated aspects of handling patients suffering from dementia. Currently, the management of these symptoms often associated with an increased pain perception, which notably reduces the patients’ quality of life (QoL), relies on the employment of antipsychotic drugs. Unfortunately, the use of these pharmacological agents has some limits: in the long term, they do not result in being equally effective as in the first weeks of treatment and they present important side effects. Therefore, there is growing interest, supported by clinical evidence, in aromatherapy for the control of agitation, aggression, and psychotic symptoms. Some molecular mechanisms have been proposed to explain the behavioural effects of essential oils, as the whole phytocomplex or the single components, but important basic research effort is still needed. For this reason, rigorous preclinical studies are necessary in order to understand the pharmacological basis of aromatherapy in the treatment of BPSDs and to widen the cluster of effective essential oils in pharmacotherapeutic practice.
Superelevation Calculation of Debris Flow Climbing Ascending Slopes
Authors: Zhao HaiXin , You Yong , Liu JinFeng , Yao LingKan
Published: March 2017

We present a new method for calculating the superelevation of debris flow when it encounters obstacles in the process of flowing. Our calculation method is based on the Bingham Model for debris flow determination and considers the vertical difference of debris flow velocity and characteristic parameters of debris flow on a hypothetical basis. Moreover, we conducted an indoor flume experiment to verify the accuracy and reasonability of our calculation method. The experimental results showed that our method is able to accurately calculate the superelevation of debris flow with a root‐mean‐square error (16%). Furthermore, we provide an in‐depth example of how our calculation method can be employed. Ultimately, we conclusively prove that our calculation method can be used for the superelevation calculation of debris flow climbing ascending slopes. Finally, we provide more exact parameters for debris flow protection engineering.
Miniaturized Circularly Polarized Implantable Antenna for ISM-Band Biomedical Devices
Authors: Zhang Ke , Liu Changrong , Liu Xueguan , Guo Huiping , Yang Xinmi
Published: March 2017

A compact circularly polarized antenna operating at 915 MHz industrial, scientific, and medical (ISM) band for biomedical implantable applications is presented and experimentally measured. The proposed antenna can be miniaturized to a large extent with the compact size of 15 × 15 × 1.27 mm3 by means of loading patches to a ring-shaped microstrip patch antenna. An impedance bandwidth of 10.6% (865–962 MHz) for reflection coefficient less than −10 dB can be obtained. Meanwhile, the simulated 3 dB axial-ratio (AR) bandwidth reaches 14 MHz. Finally, the optimized design was fabricated and tested, and the measured results agree well with simulated results.
Selection of MEMS Accelerometers for Tilt Measurements
Authors: Łuczak Sergiusz , Grepl Robert , Bodnicki Maciej
Published: March 2017

In order to build a tilt sensor having a desired sensitivity and measuring range, one should select an appropriate type, orientation, and initial position of an accelerometer. Various cases of tilt measurements are considered: determining exclusively pitch, axial tilt, or both pitch and roll, where Cartesian components of the gravity acceleration are measured by means of low-g uni-, bi-, tri-, or multiaxial micromachined accelerometers. 15 different orientations of such accelerometers are distinguished (each illustrated with respective graphics) and related to the relevant mathematical formulas. Results of the performed experimental study revealed inherent misalignments of the sensitive axes of micromachined accelerometers as large as 1°. Some of the proposed orientations make it possible to avoid a necessity of using the most misaligned pairs of the sensitive axes; some increase the accuracy of tilt measurements by activating all the sensitive axes or reducing the effects of anisotropic properties of micromachined triaxial accelerometers; other orientations make it possible to reduce a necessary number of the sensitive axes at full measurement range. An increase of accuracy while using multiaxial accelerometers is discussed. Practical guidelines for an optimal selection of a particular micromachined accelerometer for a specific case of tilt measurement are provided.
Cancer Immunotherapy: Whence and Whither
Authors: Stambrook Peter J. , Maher John , Farzaneh Farzin
Published: March 2017

The current concepts and practice of cancer immunotherapy evolved from classical experiments that distinguished "self" from "non-self" and the finding that humoral immunity is complemented by cellular immunity. Elucidation of the biology underlying immune checkpoints and interactions between ligands and ligand receptors that govern the immune system's ability to recognize tumor cells as foreign has led to the emergence of new strategies that mobilize the immune system to reverse this apparent tolerance. Some of these approaches have led to new therapies such as the use of mAbs to interfere with the immune checkpoint. Others have exploited molecular technologies to reengineer a subset of T cells to directly engage and kill tumor cells, particularly those of B-cell malignancies. However, before immunotherapy can become a more effective method of cancer care, there are many challenges that remain to be addressed and hurdles to overcome. Included are manipulation of tumor microenvironment (TME) to enhance T effector cell infiltration and access to the tumor, augmentation of tumor MHC expression for adequate presentation of tumor associated antigens, regulation of cytokines and their potential adverse effects, and reduced risk of secondary malignancies as a consequence of mutations generated by the various forms of genetic engineering of immune cells. Despite these challenges, the future of immunotherapy as a standard anticancer therapy is encouraging. Mol Cancer Res; 15(6); 635–50. ©2017 AACR.
High Risk of Seizures and Epilepsy after Decompressive Hemicraniectomy for Malignant Middle Cerebral Artery Stroke
Authors: Brondani Rosane , Garcia de Almeida Andrea , Abrahim Cherubini Pedro , Mandelli Mota Suelen , de Alencastro Luiz Carlos , Antunes Apio Cláudio Martins , Bianchin Muxfeldt Marino
Published: March 2017

Background: Decompressive hemicraniectomy (DHC) is a life-saving procedure for treatment of large malignant middle cerebral artery (MCA) strokes. Post-stroke epilepsy is an additional burden for these patients, but its incidence and the risk factors for its development have been poorly investigated. Objective: To report the prevalence and risk factors for post-stroke seizures and post-stroke epilepsy after DHC for treatment of large malignant MCA strokes in a cohort of 36 patients. Methods: In a retrospective cohort study of 36 patients we report the timing and incidence of post-stroke epilepsy. We analyzed if age, sex, vascular risk factors, side of ischemia, reperfusion therapy, stroke etiology, extension of stroke, hemorrhagic transformation, ECASS scores, National Institutes of Health Stroke Scale (NIHSS) scores, or modified Rankin scores were risk factors for seizure or epilepsy after DHC for treatment of large MCA strokes. Results: The mean patient follow-up time was 1,086 days (SD = 1,172). Out of 36 patients, 9 (25.0%) died before being discharged. After 1 year, a total of 11 patients (30.6%) had died, but 22 (61.1%) of them had a modified Rankin score ≤4. Thirteen patients (36.1%) developed seizures within the first week after stroke. Seizures occurred in 22 (61.1%) of 36 patients (95% CI = 45.17–77.03%). Out of 34 patients who survived the acute period, 19 (55.9%) developed epilepsy after MCA infarcts and DHC (95% CI = 39.21–72.59%). In this study, no significant differences were observed between the patients who developed seizures or epilepsy and those who remained free of seizures or epilepsy regarding age, sex, side of stroke, presence of the clinical risk factors studied, hemorrhagic transformation, time of craniectomy, and Rankin score after 1 year of stroke. Conclusion: The incidence of seizures and epilepsy after malignant MCA infarcts submitted to DHC might be very high. Seizure might occur precociously in patients who are not submitted to anticonvulsant prophylaxis. The large stroke volume and the large cortical ischemic area seem to be the main risk factors for seizure or epilepsy development in this subtype of stroke.
Chromosomal Mapping of Repetitive DNAs in Myiopsitta monachus and Amazona aestiva (Psittaciformes, Psittacidae) with Emphasis on the Sex Chromosomes
Authors: de Oliveira Furo Ivanete , Kretschmer Rafael , dos Santos Michelly S. , de Lima Carvalho Carlos A. , Gunski Ricardo J. , O'Brien Patrícia C.M. , Ferguson-Smith Malcolm A. , Cioffi Marcelo B. , de Oliveira Edivaldo H.C.
Published: March 2017

Here, for the first time, we describe the karyotype of Myiopsitta monachus (Psittacidae, Arini). We found 2n = 48, corresponding to the lowest diploid number observed in Neotropical Psittaciformes so far, with an uncommonly large W chromosome homomorphic to the Z. In order to better understand the evolution of the sex chromosomes in this species, we applied several molecular cytogenetic approaches, including C-banding, FISH mapping of repetitive DNAs (several microsatellite repeats), and whole-chromosome painting on metaphases of M. monachus. For comparison, another species belonging to the same tribe but with a smaller W chromosome (A. aestiva) was also analyzed. The results show that the constitutive heterochromatin has a very diverse distribution pattern in these species revealing heterochromatic blocks in the centromeric region of all chromosomes and in most of the length of the W chromosome in A. aestiva, while in M. monachus they were found in interstitial and telomeric regions. Concerning the microsatellites, only the sequence (CG)n produced signals on the W chromosome of A. aestiva, in the distal region of both arms. However, in M. monachus, (CAA)n, (CAG)n, and (CG)n probes were accumulated on the W chromosome, and, in addition, the sequence (CAG)n also hybridized to heterochromatic regions in macrochromosomes, as well as in microchromosomes. Based on these results, we suggest that the increase in length of the W chromosome in M. monachus is due to the amplification of repetitive elements, which highlights their significant role in the evolutionary process of sex chromosome differentiation.
Cepharanthine Induces Autophagy, Apoptosis and Cell Cycle Arrest in Breast Cancer Cells
Authors: Gao Sumei , Li Xiaoyan , Ding Xia , Qi Wenwen , Yang Qifeng
Published: March 2017

Background: Cepharanthine (CEP) is a biscoclaurine alkaloid extracted from Stephania cepharantha and has been shown to have an anti-tumour effect on different types of cancers. However, the anti-cancer effect of CEP on human breast cancer cells is still unclear. Methods: We used MTT, clone formation, in vitro scratch, invasion and migration assays to confirm the inhibitory role of CEP on the proliferation of breast cancer cells. Flow cytometry, plasmid construction and western blot analysis were used to study the detailed mechanisms. Results: Our study showed that CEP could inhibit cell proliferation by inducing autophagy, apoptosis, and G0/G1 cell cycle arrest of breast cancer cells. Furthermore, we found that CEP induced autophagy and apoptosis by inhibiting the AKT/mTOR signalling pathway. Conclusion: We found that CEP could inhibit growth and motility of MCF-7 and MDA-MB-231 breast cancer cell. Our study revealed an anti-tumour effect of CEP on breast cancer cells and suggests that CEP could be a potential new clinical therapy for breast cancer.
Reassessing Phase II Heart Failure Clinical Trials
Authors: Butler Javed , Hamo Carine E. , Udelson James E. , O’Connor Christopher , Sabbah Hani N. , Metra Marco , Shah Sanjiv J. , Kitzman Dalane W. , Teerlink John R. , Bernstein Harold S. , Brooks Gabriel , Depre Christophe , DeSouza Mary M. , Dinh Wilfried , Donovan Mark , Frische-Danielson Regina , Frost Robert J. , Garza Dahlia , Gohring Udo-Michael , Hellawell Jennifer , Hsia Judith , Ishihara Shiro , Kay-Mugford Patricia , Koglin Joerg , Kozinn Marc , Larson Christopher J. , Mayo Martha , Gan Li-Ming , Mugnier Pierrre , Mushonga Sekayi , Roessig Lothar , Russo Cesare , Salsali Afshin , Satler Carol , Shi Victor , Ticho Barry , van der Laan Michael , Yancy Clyde , Stockbridge Norman , Gheorghiade Mihai
Published: March 2017

The increasing burden and the continued suboptimal outcomes for patients with heart failure underlines the importance of continued research to develop novel therapeutics for this disorder. This can only be accomplished with successful translation of basic science discoveries into direct human application through effective clinical trial design and execution that results in a substantially improved clinical course and outcomes. In this respect, phase II clinical trials play a pivotal role in determining which of the multitude of potential basic science discoveries should move to the large and expansive registration trials in humans. A critical examination of the phase II trials in heart failure reveals multiple shortcomings in their concept, design, execution, and interpretation. To further a dialogue on the challenges and potential for improvement and the role of phase II trials in patients with heart failure, the Food and Drug Administration facilitated a meeting on October 17, 2016, represented by clinicians, researchers, industry members, and regulators. This document summarizes the discussion from this meeting and provides key recommendations for future directions.
Nicotinamide Phosphoribosyltransferase in Smooth Muscle Cells Maintains Genome Integrity, Resists Aortic Medial Degeneration, and Is Suppressed in Human Thoracic Aortic Aneurysm Disease
Authors: Watson Alanna , Nong Zengxuan , Yin Hao , O’Neil Caroline , Fox Stephanie , Balint Brittany , Guo Linrui , Leo Oberdan , Chu Michael W.A. , Gros Robert , Pickering J. Geoffrey
Published: March 2017

Rationale:

The thoracic aortic wall can degenerate over time with catastrophic consequences. Vascular smooth muscle cells (SMCs) can resist and repair artery damage, but their capacities decline with age and stress. Recently, cellular production of nicotinamide adenine dinucleotide (NAD
+
) via nicotinamide phosphoribosyltransferase (Nampt) has emerged as a mediator of cell vitality. However, a role for Nampt in aortic SMCs in vivo is unknown.

Objectives:

To determine whether a Nampt-NAD
+
control system exists within the aortic media and is required for aortic health.

Methods and Results:

Ascending aortas from patients with dilated aortopathy were immunostained for NAMPT, revealing an inverse relationship between SMC NAMPT content and aortic diameter. To determine whether a Nampt-NAD
+
control system in SMCs impacts aortic integrity, mice with
Nampt
-deficient SMCs were generated. SMC-
Nampt
knockout mice were viable but with mildly dilated aortas that had a 43% reduction in NAD
+
in the media. Infusion of angiotensin II led to aortic medial hemorrhage and dissection. SMCs were not apoptotic but displayed senescence associated-ß-galactosidase activity and upregulated p16, indicating premature senescence. Furthermore, there was evidence for oxidized DNA lesions, double-strand DNA strand breaks, and pronounced susceptibility to single-strand breakage. This was linked to suppressed poly(ADP-ribose) polymerase-1 activity and was reversible on resupplying NAD
+
with nicotinamide riboside. Remarkably, we discovered unrepaired DNA strand breaks in SMCs within the human ascending aorta, which were specifically enriched in SMCs with low NAMPT.
NAMPT
promoter analysis revealed CpG hypermethylation within the dilated human thoracic aorta and in SMCs cultured from these tissues, which inversely correlated with
NAMPT
expression.

Conclusions:

The aortic media depends on an intrinsic NAD
+
fueling system to protect against DNA damage and premature SMC senescence, with relevance to human thoracic aortopathy.
History of Periodontitis Diagnosis and Edentulism as Predictors of Cardiovascular Disease, Stroke, and Mortality in Postmenopausal Women
Authors: LaMonte Michael J. , Genco Robert J. , Hovey Kathleen M. , Wallace Robert B. , Freudenheim Jo L. , Michaud Dominique S. , Mai Xiaodan , Tinker Lesley F. , Salazar Christian R. , Andrews Christopher A. , Li Wenjun , Eaton Charles B. , Martin Lisa W. , Wactawski‐Wende Jean
Published: March 2017

Background

Few studies have reported associations between periodontitis and cardiovascular disease (
CVD
) risk in older women, which is the objective of the present investigation.

Methods and Results

Participants were 57 001 postmenopausal women ages 55 to 89 years (mean 68 years; >85% 60 and older) who were enrolled (1993–1998) in the Women's Health Initiative Observational Study, and were without known
CVD
when history of periodontitis and edentulism was assessed by questionnaire at study Year‐5 (1998–2003). There were 3589 incident
CVD
events and 3816 total deaths during a mean follow‐up of 6.7 years. In multivariable analysis, periodontitis was not associated with
CVD
events, but was associated with higher total mortality (hazard ratio (
HR
)=1.12, 95%
CI
: 1.05–1.21). Edentulism was associated with higher age‐ and smoking‐adjusted risks of
CVD
(
HR
=1.42, 95%
CI
: 1.27–1.59) and mortality (
HR
=1.47, 95%
CI
: 1.32–1.63). Further adjustment eliminated the association with
CVD
, but mortality remained significantly increased (
HR
=1.17, 95%
CI
: 1.02–1.33). Stratification on age, race‐ethnicity, smoking, and diabetes mellitus yielded comparable results; however, edentulism was more strongly associated with
CVD
in women reporting ≥1 dental visit (
HR
=1.57) compared with <1 visit (
HR
1.03, interaction
P
=0.004) annually.

Conclusions

In community‐dwelling older women, edentulism was associated with increased risks of
CVD
and total mortality, and presence of periodontitis, which is more prevalent than edentulism, was associated with 17% higher mortality rate. These findings suggest that improving periodontal condition of the general population could reduce overall mortality.
Googling Service Boundaries for Endovascular Clot Retrieval Hub Hospitals in a Metropolitan Setting
Authors: Phan Thanh G. , Beare Richard , Chen Jian , Clissold Benjamin , Ly John , Singhal Shaloo , Ma Henry , Srikanth Velandai
Published: March 2017

Background and Purpose—

There is great interest in how endovascular clot retrieval hubs provide services to a population. We applied a computational method to objectively generate service boundaries for such endovascular clot retrieval hubs, defined by traveling time to hub.

Methods—

Stroke incidence data merged with population census to estimate numbers of stroke in metropolitan Melbourne, Australia. Traveling time from randomly generated addresses to 4 endovascular clot retrieval–capable hubs (Royal Melbourne Hospital [RMH], Monash Medical Center [MMC], Alfred Hospital [ALF], and Austin Hospital [AUS]) estimated using Google Map application program interface. Boundary maps generated based on traveling time at various times of day for combinations of hubs.

Results—

In a 2-hub model, catchment was best distributed when RMH was paired with MMC (model 1a, RMH 1765 km
2
and MMC 1164 km
2
) or with AUS (model 1c, RMH 1244 km
2
and AUS 1685 km
2
), with no statistical difference between models (
P
=0.20). Catchment was poorly distributed when RMH was paired with ALF (model 1b, RMH 2252 km
2
and ALF 676 km
2
), significantly different from both models 1a and 1c (both
P
<0.05). Model 1a had the greatest proportion of patients arriving within ideal time of 30 minutes followed by model 1c (
P
<0.001). In a 3-hub model, the combination of RMH, MMC, and AUS was superior to that of RMH, MMC, and ALF in catchment distribution and travel time. The method was also successfully applied to the city of Adelaide demonstrating wider applicability.

Conclusions—

We provide proof of concept for a novel computational method to objectively designate service boundaries for endovascular clot retrieval hubs.
Dynamics of White Matter Plasticity Underlying Working Memory Training: Multimodal Evidence from Diffusion MRI and Relaxometry
Authors: Metzler-Baddeley Claudia , Foley Sonya , de Santis Silvia , Charron Cyril , Hampshire Adam , Caeyenberghs Karen , Jones Derek K.
Published: March 2017

Adaptive working memory (WM) training may lead to cognitive benefits that are associated with white matter plasticity in parietofrontal networks, but the underlying mechanisms remain poorly understood. We investigated white matter microstructural changes after adaptive WM training relative to a nonadaptive comparison group. Microstructural changes were studied in the superior longitudinal fasciculus, the main parietofrontal connection, and the cingulum bundle as a comparison pathway. MRI-based metrics were the myelin water fraction and longitudinal relaxation rate R1 from multicomponent relaxometry (captured with the mcDESPOT approach) as proxy metrics of myelin, the restricted volume fraction from the composite hindered and restricted model of diffusion as an estimate of axon morphology, and fractional anisotropy and radial diffusivity from diffusion tensor imaging. PCA was used for dimensionality reduction. Adaptive training was associated with benefits in a “WM capacity” component and increases in a microstructural component (increases in R1, restricted volume fraction, fractional anisotropy, and reduced radial diffusivity) that predominantly loaded on changes in the right dorsolateral superior longitudinal fasciculus and the left parahippocampal cingulum. In contrast, nonadaptive comparison activities were associated with the opposite pattern of reductions in WM capacity and microstructure. No group differences were observed for the myelin water fraction metric suggesting that R1 was a more sensitive “myelin” index. These results demonstrate task complexity and location-specific white matter microstructural changes that are consistent with tissue alterations underlying myelination in response to training.