bluuebunny/crossref_metadata_2025 huggingface dataset:
Do Scarce Precious Metals Equate to Safe Harbor Investments? The Case of Platinum and Palladium
Authors: Diaz John Francis T.
Published: January 2016

This research establishes the predictability and safe harbor properties of two scarce precious metals, namely, platinum and palladium. Utilizing their spot prices, the study concludes intermediate memory in the return structures of both precious metals, which implies the instability of platinum and palladium returns’ persistency in the long run. However, both the ARFIMA-FIGARCH and the ARFIMA-FIAPARCH models confirm long-memory properties in the volatility of the two spot prices. The leverage effects phenomenon is not also present based on the ARFIMA-APARCH and ARFIMA-FIAPARCH models, which may possibly conclude the resilience of both precious metals against increased volatility. However, further tests proved that only platinum has a symmetric volatility response to shocks with the presence of negative gamma parameter, which proves that only platinum can be considered a safe harbor investment, because negative and positive shocks have equal effects on their returns and volatilities. Comparing the four models utilized in this study, the combined ARFIMA-FIAPARCH models are the best fitting model to characterize both precious metals’ spot prices.
Brazilian Spotted Fever with an Approach in Veterinary Medicine and One Health Perspective
Authors: Campos Sabrina Destri Emmerick , da Cunha Nathalie Costa , Almosny Nádia Regina Pereira
Published: January 2016

There is increasing interaction between man and pathogens transmitted by arthropods, especially by ticks. It is on this background that a holistic approach stands out, for the sake of Public Health. Brazilian Spotted Fever is an endemic disease at the country’s southeast, withAmblyomma sculptumas its major contributor, followed byA. aureolatumand potentiallyRhipicephalus sanguineus. Dogs have been considered sentinels, and in some areas the disease in dogs can precede human disease. Considering the importance of this disease for human health, the serological evidence in dogs, and the transmission of ticks between dogs and their owners, this review aimed to elucidate the importance of the epidemiological investigation, the diagnosis in dogs, and the role of veterinarians in Public Health to control vector-borne zoonotic diseases. We encourage veterinarians to include this rickettsial infection in the diagnosis of febrile diseases of common occurrence in dogs.
Inverse Uniqueness in Interior Transmission Problem and Its Eigenvalue Tunneling in Simple Domain
Authors: Chen Lung-Hui
Published: January 2016

We study inverse uniqueness with a knowledge of spectral data of an interior transmission problem in a penetrable simple domain. We expand the solution in a series of one-dimensional problems in the far-fields. We define an ODE by restricting the PDE along a fixed scattered direction. Accordingly, we obtain a Sturm-Liouville problem for each scattered direction. There exists the correspondence between the ODE spectrum and the PDE spectrum. We deduce the inverse uniqueness on the index of refraction from the discussion on the uniqueness anglewise of the Strum-Liouville problem.
A Role for Notch Signalling in Breast Cancer and Endocrine Resistance
Authors: Acar Ahmet , Simões Bruno M. , Clarke Robert B. , Brennan Keith
Published: January 2016

Over the past decade, there has been growing interest in the Notch signalling pathway within the breast cancer field. This interest stemmed initially from the observation that Notch signalling is aberrantly activated in breast cancer and its effects on various cellular processes including proliferation, apoptosis, and cancer stem cell activity. However more recently, elevated Notch signalling has been correlated with therapy resistance in oestrogen receptor‐positive breast cancer. As a result, inhibiting Notch signalling with therapeutic agents is being explored as a promising treatment option for breast cancer patients.
Lasting Differential Effects on Plasticity Induced by Prenatal Stress in Dorsal and Ventral Hippocampus
Authors: Grigoryan Gayane , Segal Menahem
Published: January 2016

Early life adversaries have a profound impact on the developing brain structure and functions that persist long after the original traumatic experience has vanished. One of the extensively studied brain structures in relation to early life stress has been the hippocampus because of its unique association with cognitive processes of the brain. While the entire hippocampus shares the same intrinsic organization, it assumes different functions in its dorsal and ventral sectors (DH and VH, resp.), based on different connectivity with other brain structures. In the present review, we summarize the differences between DH and VH and discuss functional and structural effects of prenatal stress in the two sectors, with the realization that much is yet to be explored in understanding the opposite reactivity of the DH and VH to stressful stimulation.
The Use of Human Adipose‐Derived Stem Cells in the Treatment of Physiological and Pathological Vulvar Dystrophies
Authors: Giuseppina Onesti Maria , Carella Sara , Ceccarelli Simona , Marchese Cinzia , Scuderi Nicolò
Published: January 2016

“Vulvar dystrophy” is characterized by chronic alterations of vulvar trophism, occurring in both physiological (menopause) and pathological (lichen sclerosus, vulvar graft‐versus‐host disease) conditions. Associated symptoms are itching, burning, dyspareunia and vaginal dryness. Current treatments often do not imply a complete remission of symptoms. Adipose‐Derived Stem Cells (ADSCs) injection represents a valid alternative therapy to enhance trophism and tone of dystrophic tissues. We evaluated efficacy of ADSCs‐based therapy in the dystrophic areas. From February to April 2013 we enrolled 8 patients with vulvar dystrophy. A biopsy specimen was performed before and after treatment. Digital photographs were taken at baseline and during the follow‐up. Pain was detected with Visual Analogue Scale and sexual function was evaluated with Female Sexual Function Index. All patients received 2 treatments in 3 months. Follow‐up was at 1 week , 1 and 3 months, and 1 and 2 years. We obtained a significant vulvar trophism enhancement in all patients, who reported pain reduction and sexual function improvement. Objective exam with speculum was easy to perform after treatment. We believe ADSCs‐based therapy finds its application in the treatment of vulvar dystrophies, since ADSCs could induce increased vascularization due to their angiogenic properties and tissue trophism improvement thanks to their eutrophic effect.
Characterizations of N(2,2,0) Algebras
Authors: Deng Fang-an , Chen Lu , Tuo ShouHeng , Ren ShengZhang
Published: January 2016

The so-called ideal and subalgebra and some additional concepts of N(2,2,0) algebras are discussed. A partial order and congruence relations on N(2,2,0) algebras are also proposed, and some properties are investigated.
Hippocampal Dendritic Spines Are Segregated Depending on Their Actin Polymerization
Authors: Domínguez-Iturza Nuria , Calvo María , Benoist Marion , Esteban José Antonio , Morales Miguel
Published: January 2016

Dendritic spines are mushroom-shaped protrusions of the postsynaptic membrane. Spines receive the majority of glutamatergic synaptic inputs. Their morphology, dynamics, and density have been related to synaptic plasticity and learning. The main determinant of spine shape is filamentous actin. Using FRAP, we have reexamined the actin dynamics of individual spines from pyramidal hippocampal neurons, both in cultures and in hippocampal organotypic slices. Our results indicate that, in cultures, the actin mobile fraction is independently regulated at the individual spine level, and mobile fraction values do not correlate with either age or distance from the soma. The most significant factor regulating actin mobile fraction was the presence of astrocytes in the culture substrate. Spines from neurons growing in the virtual absence of astrocytes have a more stable actin cytoskeleton, while spines from neurons growing in close contact with astrocytes show a more dynamic cytoskeleton. According to their recovery time, spines were distributed into two populations with slower and faster recovery times, while spines from slice cultures were grouped into one population. Finally, employing fast lineal acquisition protocols, we confirmed the existence of loci with high polymerization rates within the spine.
Self-Organizing Adaptive Wavelet Backstepping Control Research for AC Servo System
Authors: Hou Run-min , Hou Yuan-long , Gao Qiang , Wang Chao
Published: January 2016

A novel self-organizing adaptive wavelet cerebellar model articulation controller backstepping (SOWCB) control is proposed, aiming at some nonlinear and uncertain factors that caused difficulties in controlling the AC servo system. This controller consists of self-organizing wavelet cerebellar model articulation controller (CMAC) and robust compensator. It absorbs fast learning and precise approaching advantage of self-organizing wavelet CMAC to mimic a backstepping controller, and then robust compensator is added to inhibit influence of the uncertainties on system performance effectively and realize high accuracy position tracking for AC servo system. Moreover, the stability of the control system can be guaranteed by using Lyapunov method. The results of the simulation and the prototype test prove that the proposed approach can improve the steady state performance and control accuracy and possess a strong robustness to both parameter perturbation and load disturbance.
Defining Optimal Aerobic Exercise Parameters to Affect Complex Motor and Cognitive Outcomes after Stroke: A Systematic Review and Synthesis
Authors: Hasan S. M. Mahmudul , Rancourt Samantha N. , Austin Mark W. , Ploughman Michelle
Published: January 2016

Although poststroke aerobic exercise (AE) increases markers of neuroplasticity and protects perilesional tissue, the degree to which it enhances complex motor or cognitive outcomes is unknown. Previous research suggests that timing and dosage of exercise may be important. We synthesized data from clinical and animal studies in order to determine optimal AE training parameters and recovery outcomes for future research. Using predefined criteria, we included clinical trials of stroke of any type or duration and animal studies employing any established models of stroke. Of the 5,259 titles returned, 52 articles met our criteria, measuring the effects of AE on balance, lower extremity coordination, upper limb motor skills, learning, processing speed, memory, and executive function. We found that early-initiated low-to-moderate intensity AE improved locomotor coordination in rodents. In clinical trials, AE improved balance and lower limb coordination irrespective of intervention modality or parameter. In contrast, fine upper limb recovery was relatively resistant to AE. In terms of cognitive outcomes, poststroke AE in animals improved memory and learning, except when training was too intense. However, in clinical trials, combined training protocols more consistently improved cognition. We noted a paucity of studies examining the benefits of AE on recovery beyond cessation of the intervention.
An Open and Modular Hardware Node for Wireless Sensor and Body Area Networks
Authors: Ciabattoni L. , Freddi A. , Longhi S. , Monteriù A. , Pepa L. , Prist M.
Published: January 2016

Health monitoring is nowadays one of the hottest markets due to the increasing interest in prevention and treatment of physical problems. In this context the development of wearable, wireless, open-source, and nonintrusive sensing solutions is still an open problem. Indeed, most of the existing commercial architectures are closed and provide little flexibility. In this paper, an open hardware architecture for designing a modular wireless sensor node for health monitoring is proposed. By separating the connection and sensing functions in two separate boards, compliant with the IEEE1451 standard, we add plug and play capabilities to analog transducers, while granting at the same time a high level of customization. As an additional contribution of the work, we developed a cosimulation tool which simplifies the physical connection with the hardware devices and provides support for complex systems. Finally, a wireless body area network for fall detection and health monitoring, based on wireless node prototypes realized according to the proposed architecture, is presented as an application scenario.
Transplantation of Neural Stem Cells Cotreated with Thyroid Hormone and GDNF Gene Induces Neuroprotection in Rats of Chronic Experimental Allergic Encephalomyelitis
Authors: Gao Xiaoqing , Hu Guangqiang , Deng Li , Fan Guangbi , Yang Chaoxian , Du Jie
Published: January 2016

The present study investigates whether transplantation of NSCs treated with T3 alone (T3/NSCs), or in conjunction with GDNF gene (GDNF-T3/NSCs), provides a better therapeutic effect than NSCs for chronic EAE. EAE rats were, respectively, injected with NSCs, T3/NSCs, GDNF-T3/NSCs, and saline at 10 days and sacrificed at 60 days after EAE immunization. The three cell grafted groups showed a significant reduction in clinical scores, inflammatory infiltration, and demyelination compared with the saline-injected group, and among the cell grafted groups, the reduction in GDNF-T3/NSCs group was the most notable, followed by T3/NSCs group. Grafted T3/NSCs and GDNF-T3/NSCs acquired more MAP2, GalC, and less GFAP in brain compared with grafted NSCs, and grafted GDNF-T3/NSCs acquired most MAP2 and least GalC among the cell grafted groups. Furthermore, T3/NSCs and GDNF-T3/NSCs grafting increased the expression of mRNA for PDGFαR, GalC, and MBP in lesion areas of brain compared with NSCs grafting, and the expression of mRNA for GalC and MBP in GDNF-T3/NSCs group was higher than that in T3/NSCs group. In conclusion, T3/NSCs grafting, especially GDNF-T3/NSCs grafting, provides a better neuroprotective effect for EAE than NSCs transplantation.
The Role of the Reactive Oxygen Species and Oxidative Stress in the Pathomechanism of the Age‐Related Ocular Diseases and Other Pathologies of the Anterior and Posterior Eye Segments in Adults
Authors: Nita Małgorzata , Grzybowski Andrzej
Published: January 2016

The reactive oxygen species (ROS) form under normal physiological conditions and may have both beneficial and harmful role. We search the literature and current knowledge in the aspect of ROS participation in the pathogenesis of anterior and posterior eye segment diseases in adults. ROS take part in the pathogenesis of keratoconus, Fuchs endothelial corneal dystrophy, and granular corneal dystrophy type 2, stimulating apoptosis of corneal cells. ROS play a role in the pathogenesis of glaucoma stimulating apoptotic and inflammatory pathways on the level of the trabecular meshwork and promoting retinal ganglion cells apoptosis and glial dysfunction in the posterior eye segment. ROS play a role in the pathogenesis of Leber’s hereditary optic neuropathy and traumatic optic neuropathy. ROS induce apoptosis of human lens epithelial cells. ROS promote apoptosis of vascular and neuronal cells and stimulate inflammation and pathological angiogenesis in the course of diabetic retinopathy. ROS are associated with the pathophysiological parainflammation and autophagy process in the course of the age‐related macular degeneration.
Modelling of Hysteresis in Vibration Control Systems by means of the Bouc-Wen Model
Authors: Chang Chia-Ming , Strano Salvatore , Terzo Mario
Published: January 2016

The review presents developments concerning the modelling of vibration control systems with hysteresis. In particular, the review focuses on applications of the Bouc-Wen model that describes accurate hysteretic behaviour in vibration control devices. The review consists of theoretical aspects of the Bouc-Wen model, identification procedures, and applications in vibration control.
Conserved Metabolic Changes in Nondiabetic and Type 2 Diabetic Bariatric Surgery Patients: Global Metabolomic Pilot Study
Authors: Sarosiek Konrad , Pappan Kirk L. , Gandhi Ankit V. , Saxena Shivam , Kang Christopher Y. , McMahon Heather , Chipitsyna Galina I. , Tichansky David S. , Arafat Hwyda A.
Published: January 2016

The goal of this study was to provide insight into the mechanism by which bariatric surgical procedures led to weight loss and improvement or resolution of diabetes. Global biochemical profiling was used to evaluate changes occurring in nondiabetic and type 2 diabetic (T2D) patients experiencing either less extreme sleeve gastrectomy or a full gastric bypass. We were able to identify changes in metabolism that were affected by standard preoperation liquid weight loss diet as well as by bariatric surgery itself. Preoperation weight-loss diet was associated with a strong lipid metabolism signature largely related to the consumption of adipose reserves for energy production. Glucose usage shift away from glycolytic pyruvate production toward pentose phosphate pathway, via glucose-6-phosphate, appeared to be shared across all patients regardless of T2D status or bariatric surgery procedure. Our results suggested that bariatric surgery might promote antioxidant defense and insulin sensitivity through both increased heme synthesis and HO activity or expression. Changes in histidine and its metabolites following surgery might be an indication of altered gut microbiome ecology or liver function. This initial study provided broad understanding of how metabolism changed globally in morbidly obese nondiabetic and T2D patients following weight-loss surgery.
Comparative Analysis of Human Mesenchymal Stem Cells from Umbilical Cord, Dental Pulp, and Menstrual Blood as Sources for Cell Therapy
Authors: Ren Huaijuan , Sang Yunxia , Zhang Fengli , Liu Zhaoqing , Qi Nianmin , Chen Yantian
Published: January 2016

Although mesenchymal stem cells (MSCs) based therapy has been considered as a promising tool for tissue repair and regeneration, the optimal cell source remains unknown. Umbilical cord (UC), dental pulp (DP), and menstrual blood (MB) are easily accessible sources, which make them attractive candidates for MSCs. The goal of this study was to compare the biological characteristics, including morphology, proliferation, antiapoptosis, multilineage differentiation capacity, and immunophenotype of UC‐, DP‐, and MB‐MSCs in order to provide a theoretical basis for clinical selection and application of these cells. As a result, all UC‐, DP‐, and MB‐MSCs have self‐renewal capacity and multipotentiality. However, the UC‐MSCs seemed to have higher cell proliferation ability, while DP‐MSCs may have significant advantages for osteogenic differentiation, lower cell apoptosis, and senescence. These differences may be associated with the different expression level of cytokines, including vascular endothelial growth factor, fibroblast growth factor, keratinocyte growth factor, and hepatocyte growth factor in each of the MSCs. Comprehensively, our results suggest DP‐MSCs may be a desired source for clinical applications of cell therapy.
Modification of the Sweetness and Stability of Sweet-Tasting Protein Monellin by Gene Mutation and Protein Engineering
Authors: Liu Qiulei , Li Lei , Yang Liu , Liu Tianming , Cai Chenggu , Liu Bo
Published: January 2016

Natural sweet protein monellin has a high sweetness and low calorie, suggesting its potential in food applications. However, due to its low heat and acid resistance, the application of monellin is limited. In this study, we show that the thermostability of monellin can be improved with no sweetness decrease by means of sequence, structure analysis, and site-directed mutagenesis. We analyzed residues located in theα-helix as well as an ionizable residue C41. Of the mutants investigated, the effects of E23A and C41A mutants were most remarkable. The former displayed significantly improved thermal stability, while its sweetness was not changed. The mutated protein was stable after 30 min incubation at 85°C. The latter showed increased sweetness and slight improvement of thermostability. Furthermore, we found that most mutants enhancing the thermostability of the protein were distributed at the two ends ofα-helix. Molecular biophysics analysis revealed that the state of buried ionizable residues may account for the modulated properties of mutated proteins. Our results prove that the properties of sweet protein monellin can be modified by means of bioinformatics analysis, gene manipulation, and protein modification, highlighting the possibility of designing novel effective sweet proteins based on structure-function relationships.
Stem/Progenitor Cell Niches Involved in Hepatic and Biliary Regeneration
Authors: Carpino Guido , Renzi Anastasia , Franchitto Antonio , Cardinale Vincenzo , Onori Paolo , Reid Lola , Alvaro Domenico , Gaudio Eugenio
Published: January 2016

Niches containing stem/progenitor cells are present in different anatomical locations along the human biliary tree and within liver acini. The most primitive stem/progenitors, biliary tree stem/progenitor cells (BTSCs), reside within peribiliary glands located throughout large extrahepatic and intrahepatic bile ducts. BTSCs are multipotent and can differentiate towards hepatic and pancreatic cell fates. These niches’ matrix chemistry and other characteristics are undefined. Canals of Hering (bile ductules) are found periportally and contain hepatic stem/progenitor cells (HpSCs), participating in the renewal of small intrahepatic bile ducts and being precursors to hepatocytes and cholangiocytes. The niches also contain precursors to hepatic stellate cells and endothelia, macrophages, and have a matrix chemistry rich in hyaluronans, minimally sulfated proteoglycans, fetal collagens, and laminin. The microenvironment furnishes key signals driving HpSC activation and differentiation. Newly discovered third niches are pericentral within hepatic acini, contain Axin2+ unipotent hepatocytic progenitors linked on their lateral borders to endothelia forming the central vein, and contribute to normal turnover of mature hepatocytes. Their relationship to the other stem/progenitors is undefined. Stem/progenitor niches have important implications in regenerative medicine for the liver and biliary tree and in pathogenic processes leading to diseases of these tissues.
TheHarmonic Walk: An Interactive Physical Environment to Learn Tonal Melody Accompaniment
Authors: Mandanici Marcella , Rodà Antonio , Canazza Sergio
Published: January 2016

TheHarmonic Walkis an interactive physical environment designed for learning and practicing the accompaniment of a tonal melody. Employing a highly innovative multimedia system, the application offers to the user the possibility of getting in touch with some fundamental tonal music features in a very simple and readily available way. Notwithstanding tonal music is very common in our lives, unskilled people as well as music students and even professionals are scarcely conscious of what these features actually are. TheHarmonic Walk, through the body movement in space, can provide all these users a live experience of tonal melody structure, chords progressions, melody accompaniment, and improvisation. Enactive knowledge and embodied cognition allow the user to build an inner map of these musical features, which can be acted by moving on the active surface with a simple step. Thorough assessment tests with musicians and nonmusicians high school students could prove the high communicative power and efficiency of theHarmonic Walkapplication both in improving musical knowledge and in accomplishing complex musical tasks.
Abnormal Echogenicity of the Substantia Nigra, Raphe Nuclei, and Third-Ventricle Width as Markers of Cognitive Impairment in Parkinsonian Disorders: A Cross-Sectional Study
Authors: Bouwmans Angela E. P. , Leentjens Albert F. G. , Mess Werner H. , Weber Wim E. J.
Published: January 2016

Background. Patients with Parkinson’s disease (PD) have a high risk of cognitive problems.Objective. This study assesses whether abnormal echogenicity of the substantia nigra (SN) and raphe nuclei (RN) and the diameter of third ventricle are markers of cognitive impairment in patients with PD and other forms of parkinsonism.Methods. 126 outpatients with early signs of parkinsonism underwent transcranial sonography (TCS). The scales for the outcome of Parkinson’s disease cognition (SCOPA-COG) were used as cognitive measure. Definite neurological diagnosis was established after two-year follow-up.Results. One-third of the patients with PD and half of those with APS had signs of cognitive impairment. The echogenicity of the SN was not related to cognitive impairment. The diameter of the third ventricle was significantly larger in PD patients with cognitive impairment compared to those without. In patients with APS we found a significantly higher frequency of hypoechogenic RN in patients with cognitive problems.Conclusions. Cognitive impairment is already present in a substantial proportion of patients with PD and APS at first referral. In patients with APS the frequency of hypoechogenic RN points to the direction of other pathophysiology with more emphasis on deficits in the serotonergic neurotransmitter system. The larger diameter of the third ventricle in PD patients with cognitive impairment may reflect Alzheimer like brain atrophy, as has been reported in earlier studies.
Metabolic Health Has Greater Impact on Diabetes than Simple Overweight/Obesity in Mexican Americans
Authors: Wu Shenghui , Fisher-Hoch Susan P. , Reninger Belinda , Vatcheva Kristina , McCormick Joseph B.
Published: January 2016

Purpose. To compare the risk for diabetes in each of 4 categories of metabolic health and BMI.Methods. Participants were drawn from the Cameron County Hispanic Cohort, a randomly selected Mexican American cohort in Texas on the US-Mexico border. Subjects were divided into 4 phenotypes according to metabolic health and BMI: metabolically healthy normal weight, metabolically healthy overweight/obese, metabolically unhealthy normal weight, and metabolically unhealthy overweight/obese. Metabolic health was defined as having less than 2 metabolic abnormalities. Overweight/obese status was assessed by BMI higher than 25 kg/m2. Diabetes was defined by the 2010 ADA definition or by being on a diabetic medication.Results. The odds ratio for diabetes risk was 2.25 in the metabolically healthy overweight/obese phenotype (95% CI 1.34, 3.79), 3.78 (1.57, 9.09) in the metabolically unhealthy normal weight phenotype, and 5.39 (3.16, 9.20) in metabolically unhealthy overweight/obese phenotype after adjusting for confounding factors compared with the metabolically healthy normal weight phenotype.Conclusions. Metabolic health had a greater effect on the increased risk for diabetes than overweight/obesity. Greater focus on metabolic health might be a more effective target for prevention and control of diabetes than emphasis on weight loss alone.
Development of Traveling Wave Actuators Using Waveguides of Different Geometrical Forms
Authors: Bansevicius Ramutis , Mazeika Dalius , Jurenas Vytautas , Kulvietis Genadijus , Bakanauskas Vytautas
Published: January 2016

The paper covers the research and development of piezoelectric traveling wave actuators using different types of the waveguides. The introduced piezoelectric actuators can be characterized by specific areas of application, different resolution, and torque. All presented actuators are ultrasonic resonant devices and they were developed to increase amplitudes of the traveling wave oscillations of the contact surface. Three different waveguides are introduced, that is, symmetrical, asymmetrical, and cone type waveguide. A piezoelectric ring with the sectioned electrodes is used to excite traveling wave oscillations for all actuators. Operating principle, electrode pattern, and excitation regimes of piezoelectric actuators are described. A numerical modelling of the actuators was performed to validate the operating principle and to calculate trajectories of the contact points motion. Prototype actuators were made and experimental study was performed. The results of numerical and experimental analysis are discussed.
Current Molecular Targeted Therapy in Advanced Gastric Cancer: A Comprehensive Review of Therapeutic Mechanism, Clinical Trials, and Practical Application
Authors: Li Kaichun , Li Jin
Published: January 2016

Despite the great progress in the treatment of gastric cancer, it is still the third leading cause of cancer death worldwide. Patients often miss the opportunity for a surgical cure, because the cancer has already developed into advanced cancer when identified. Compared to best supportive care, chemotherapy can improve quality of life and prolong survival time, but the overall survival is often short. Due to the molecular study of gastric cancer, new molecular targeted drugs have entered the clinical use. Trastuzumab, an antibody targeting human epidermal growth factor receptor 2 (HER2), can significantly improve survival in advanced gastric cancer patients with HER2 overexpression. Second-line treatment of advanced gastric cancer with ramucirumab, an antibody targeting VEGFR-2, alone or in combination with paclitaxel, has been proved to provide a beneficial effect. The VEGFR-2 tyrosine kinase inhibitor, apatinib, can improve the survival of advanced gastric cancer patients after second-line chemotherapy failure. Unfortunately, none of the EGFR targeting antibodies (cetuximab or panitumumab), VEGF targeting monoclonal antibodies (bevacizumab), mTOR inhibitor (everolimus), or HGF/MET pathway targeting drugs has a significant survival benefit. Many other clinical trials based on molecular markers are underway. This review will summarize targeted therapies for advanced gastric cancer.
Phenolic Rich Extract from Clinacanthus nutans Attenuates Hyperlipidemia‐Associated Oxidative Stress in Rats
Authors: Sarega Nadarajan , Imam Mustapha Umar , Ooi Der-Jiun , Chan Kim Wei , Md Esa Norhaizan , Zawawi Norhasnida , Ismail Maznah
Published: January 2016

Clinacanthus nutans is used as traditional medicine in Asia but there are limited scientific studies to support its use. In this study, the stem and leaf of C. nutans were extracted using solvents of differing polarities, and their antioxidant capacities were determined using multiple antioxidant assays. The water and aqueous methanolic leaf extracts were further fractionated and their antioxidant capacities and phenolic compositions were tested. Furthermore, the efficacies of the water and aqueous methanolic leaf extracts were tested against hyperlipidemia‐induced oxidative stress in rats. Serum and hepatic antioxidant and oxidative stress markers were tested after feeding the rats with high fat diet together with the extracts or simvastatin for 7 weeks. The results indicated that both leaf extracts attenuated oxidative stress through increasing serum antioxidant enzymes activity and upregulating the expression of hepatic antioxidant genes. Multiple phenolic compounds were detected in the extracts and fractions of C. nutans, although protocatechuic acid was one of the most abundant and may have contributed significantly towards the bioactivities of the extracts. However, synergistic effects of different phenolics may have contributed to the overall bioactivities. C. nutans can be a good source of functional ingredients for the management of oxidative stress‐related diseases.
Amyloid-Beta Induced Changes in Vesicular Transport of BDNF in Hippocampal Neurons
Authors: Seifert Bianca , Eckenstaler Robert , Rönicke Raik , Leschik Julia , Lutz Beat , Reymann Klaus , Lessmann Volkmar , Brigadski Tanja
Published: January 2016

The neurotrophin brain derived neurotrophic factor (BDNF) is an important growth factor in the CNS. Deficits in transport of this secretory protein could underlie neurodegenerative diseases. Investigation of disease-related changes in BDNF transport might provide insights into the cellular mechanism underlying, for example, Alzheimer’s disease (AD). To analyze the role of BDNF transport in AD, live cell imaging of fluorescently labeled BDNF was performed in hippocampal neurons of different AD model systems. BDNF and APP colocalized with low incidence in vesicular structures. Anterograde as well as retrograde transport of BDNF vesicles was reduced and these effects were mediated by factors released from hippocampal neurons into the extracellular medium. Transport of BDNF was altered at a very early time point after onset of human APP expression or after acute amyloid-beta(1-42) treatment, while the activity-dependent release of BDNF remained unaffected. Taken together, extracellular cleavage products of APP induced rapid changes in anterograde and retrograde transport of BDNF-containing vesicles while release of BDNF was unaffected by transgenic expression of mutated APP. These early transport deficits might lead to permanently impaired brain functions in the adult brain.
Study of Hypervelocity Projectile Impact on Thick Metal Plates
Authors: Roy Shawoon K. , Trabia Mohamed , O’Toole Brendan , Hixson Robert , Becker Steven , Pena Michael , Jennings Richard , Somasoundaram Deepak , Matthes Melissa , Daykin Edward , Machorro Eric
Published: January 2016

Hypervelocity impacts generate extreme pressure and shock waves in impacted targets that undergo severe localized deformation within a few microseconds. These impact experiments pose unique challenges in terms of obtaining accurate measurements. Similarly, simulating these experiments is not straightforward. This study proposed an approach to experimentally measure the velocity of the back surface of an A36 steel plate impacted by a projectile. All experiments used a combination of a two-stage light-gas gun and the photonic Doppler velocimetry (PDV) technique. The experimental data were used to benchmark and verify computational studies. Two different finite-element methods were used to simulate the experiments: Lagrangian-based smooth particle hydrodynamics (SPH) and Eulerian-based hydrocode. Both codes used the Johnson-Cook material model and the Mie-Grüneisen equation of state. Experiments and simulations were compared based on the physical damage area and the back surface velocity. The results of this study showed that the proposed simulation approaches could be used to reduce the need for expensive experiments.
Programming of Dopaminergic Neurons by Neonatal Sex Hormone Exposure: Effects on Dopamine Content and Tyrosine Hydroxylase Expression in Adult Male Rats
Authors: Espinosa Pedro , Silva Roxana A. , Sanguinetti Nicole K. , Venegas Francisca C. , Riquelme Raul , González Luis F. , Cruz Gonzalo , Renard Georgina M. , Moya Pablo R. , Sotomayor-Zárate Ramón
Published: January 2016

We sought to determine the long-term changes produced by neonatal sex hormone administration on the functioning of midbrain dopaminergic neurons in adult male rats. Sprague-Dawley rats were injected subcutaneously at postnatal day 1 and were assigned to the following experimental groups: TP (testosterone propionate of 1.0 mg/50 μL); DHT (dihydrotestosterone of 1.0 mg/50 μL); EV (estradiol valerate of 0.1 mg/50 μL); and control (sesame oil of 50 μL). At postnatal day 60, neurochemical studies were performed to determine dopamine content in substantia nigra-ventral tegmental area and dopamine release in nucleus accumbens. Molecular (mRNA expression of tyrosine hydroxylase) and cellular (tyrosine hydroxylase immunoreactivity) studies were also performed. We found increased dopamine content in substantia nigra-ventral tegmental area of TP and EV rats, in addition to increased dopamine release in nucleus accumbens. However, neonatal exposure to DHT, a nonaromatizable androgen, did not affect midbrain dopaminergic neurons. Correspondingly, compared to control rats, levels of tyrosine hydroxylase mRNA and protein were significantly increased in TP and EV rats but not in DHT rats, as determined by qPCR and immunohistochemistry, respectively. Our results suggest an estrogenic mechanism involving increased tyrosine hydroxylase expression, either by direct estrogenic action or by aromatization of testosterone to estradiol in substantia nigra-ventral tegmental area.
Dark Spinors Hawking Radiation in String Theory Black Holes
Authors: Cavalcanti R. T. , da Rocha Roldão
Published: January 2016

The Hawking radiation spectrum of Kerr-Sen axion-dilaton black holes is derived, in the context of dark spinors tunnelling across the horizon. Since a black hole has a well defined temperature, it should radiate in principle all the standard model particles, similar to a black body at that temperature. We investigate the tunnelling of mass dimension one spin-1/2 dark fermions, which are beyond the standard model and are prime candidates to the dark matter. Their interactions with the standard model matter and gauge fields are suppressed by at least one power of unification scale, being restricted just to the Higgs field and to the graviton likewise. The tunnelling method for the emission and absorption of mass dimension one particles across the event horizon of Kerr-Sen axion-dilaton black holes is shown here to provide further evidence for the universality of black hole radiation, further encompassing particles beyond the standard model.
Hippophae rhamnoides L. Fruits Reduce the Oxidative Stress in Human Blood Platelets and Plasma
Authors: Olas Beata , Kontek Bogdan , Malinowska Paulina , Żuchowski Jerzy , Stochmal Anna
Published: January 2016

Effects of the phenolic fraction from Hippophae rhamnoides fruits on the production of thiobarbituric acid reactive substances (TBARS, a marker of lipid peroxidation) and the generation of superoxide anion () in human blood platelets (resting platelets and platelets stimulated by a strong physiological agonist, thrombin) were studied in vitro. We also examined antioxidant properties of this fraction against human plasma lipid peroxidation and protein carbonylation induced by a strong biological oxidant, hydrogen peroxide (H2O2) or H2O2/Fe (a donor of hydroxyl radicals). The tested fraction of H. rhamnoides (0.5– 50 µg/mL; the incubation time: 15 and 60 min) inhibited lipid peroxidation induced by H2O2 or H2O2/Fe. The H. rhamnoides phenolic fraction inhibited not only plasma lipid peroxidation, but also plasma protein carbonylation stimulated by H2O2 or H2O2/Fe. Moreover, the level of in platelets significantly decreased. In comparative experiments, the H. rhamnoides fraction was a more effective antioxidant than aronia extract or grape seed extract (at the highest tested concentration, 50 µg/mL). The obtained results suggest that H. rhamnoides fruits may be a new, promising source of natural compounds with antioxidant and antiplatelet activity beneficial not only for healthy people, but also for those with oxidative stress‐associated diseases.
Interhemispheric Plasticity following Intermittent Theta Burst Stimulation in Chronic Poststroke Aphasia
Authors: Griffis Joseph C. , Nenert Rodolphe , Allendorfer Jane B. , Szaflarski Jerzy P.
Published: January 2016

The effects of noninvasive neurostimulation on brain structure and function in chronic poststroke aphasia are poorly understood. We investigated the effects of intermittent theta burst stimulation (iTBS) applied to residual language-responsive cortex in chronic patients using functional and anatomical MRI data acquired before and after iTBS. Lateralization index (LI) analyses, along with comparisons of inferior frontal gyrus (IFG) activation and connectivity during covert verb generation, were used to assess changes in cortical language function. Voxel-based morphometry (VBM) was used to assess effects on regional grey matter (GM). LI analyses revealed a leftward shift in IFG activity after treatment. While left IFG activation increased, right IFG activation decreased. Changes in right to left IFG connectivity during covert verb generation also decreased after iTBS. Behavioral correlations revealed a negative relationship between changes in right IFG activation and improvements in fluency. While anatomical analyses did not reveal statistically significant changes in grey matter volume, the fMRI results provide evidence for changes in right and left IFG function after iTBS. The negative relationship between post-iTBS changes in right IFG activity during covert verb generation and improvements in fluency suggests that iTBS applied to residual left-hemispheric language areas may reduce contralateral responses related to language production and facilitate recruitment of residual language areas after stroke.
The Androgen Receptor Bridges Stem Cell‐Associated Signaling Nodes in Prostate Stem Cells
Authors: Davies Alastair H. , Zoubeidi Amina
Published: January 2016

The therapeutic potential of stem cells relies on dissecting the complex signaling networks that are thought to regulate their pluripotency and self‐renewal. Until recently, attention has focused almost exclusively on a small set of “core” transcription factors for maintaining the stem cell state. It is now clear that stem cell regulatory networks are far more complex. In this review, we examine the role of the androgen receptor (AR) in coordinating interactions between signaling nodes that govern the balance of cell fate decisions in prostate stem cells.
Wharton’s Jelly‐Derived Mesenchymal Stromal Cells and Fibroblast‐Derived Extracellular Matrix Synergistically Activate Apoptosis in a p21‐Dependent Mechanism in WHCO1 and MDA MB 231 Cancer Cells In Vitro
Authors: Dzobo Kevin , Vogelsang Matjaz , Thomford Nicholas E. , Dandara Collet , Kallmeyer Karlien , Pepper Michael S. , Parker M. Iqbal
Published: January 2016

The tumour microenvironment plays a crucial role in tumour progression and comprises tumour stroma which is made up of different cell types and the extracellular matrix (ECM). Mesenchymal stromal cells (MSCs) are part of the tumour stroma and may have conflicting effects on tumour growth. In this study we investigated the effect of Wharton’s Jelly‐derived MSCs (WJ‐MSCs) and a fibroblast‐derived ECM (fd‐ECM) on esophageal (WHCO1) and breast (MDA MB 231) cancer cells in vitro. Both WJ‐MSCs and the fd‐ECM, alone or in combination, downregulate PCNA, cyclin D1, Bcl‐2, Bcl‐xL, and MMPs and upregulate p53 and p21. p21 induction resulted in G2 phase cell cycle arrest and induced apoptosis in vitro. Our data suggest that p21 induction is via p53‐dependent and p53‐independent mechanisms in WHCO1 and MDA MB 231 cells, respectively. Vascular endothelial growth factor, Akt, and Nodal pathways were downregulated in cancer cells cocultured with WJ‐MSCs. We also demonstrate that WJ‐MSCs effects on cancer cells appear to be short‐lived whilst the fd‐ECM effect is long‐lived. This study shows the influence of tumour microenvironment on cancer cell behaviour and provides alternative therapeutic targets for potential regulation of tumour cells.
Dynamic Response of a Rigid Pavement Plate Based on an Inertial Soil
Authors: Gibigaye Mohamed , Yabi Crespin Prudence , Alloba I. Ezéchiel
Published: January 2016

This work presents the dynamic response of a pavement plate resting on a soil whose inertia is taken into account in the design of pavements by rational methods. Thus, the pavement is modeled as a thin plate with finite dimensions, supported longitudinally by dowels and laterally by tie bars. The subgrade is modeled via Pasternak-Vlasov type (three-parameter type) foundation models and the moving traffic load is expressed as a concentrated dynamic load of harmonically varying magnitude, moving straight along the plate with a constant acceleration. The governing equation of the problem is solved using the modified Bolotin method for determining the natural frequencies and the wavenumbers of the system. The orthogonal properties of eigenfunctions are used to find the general solution of the problem. Considering the load over the center of the plate, the results showed that the deflections of the plate are maximum about the middle of the plate but are not null at its edges. It is therefore observed that the deflection decreased 18.33 percent when the inertia of the soil is taken into account. This result shows the possible economic gain when taking into account the inertia of soil in pavement dynamic design.
Evolution of Hydrological Drought in Human Disturbed Areas: A Case Study in the Laohahe Catchment, Northern China
Authors: Liu Yi , Ren Liliang , Zhu Ye , Yang Xiaoli , Yuan Fei , Jiang Shanhu , Ma Mingwei
Published: January 2016

A case study on the evolution of hydrological drought in nonstationary environments is conducted over the Laohahe catchment in northern China. Using hydrometeorological observations during 1964–2009, meteorological and hydrological droughts are firstly analyzed with the threshold level method. Then, a comprehensive analysis on the changes within the catchment is conducted on the basis of hydrological variables and socioeconomic indices, and the whole period is divided into two parts: the undisturbed period (1964–1979) and the disturbed period (1980–2009). A separating framework is further introduced to distinguish droughts induced by different causes, that is, the naturalized drought and human-induced drought. Results showed that human activities are more inclined to play a negative role in aggravating droughts. Drought duration and deficit volume in naturalized conditions are amplified two to four times and three to eight times, respectively, when human activities are involved. For the two dry decades 1980s and 2000s, human activities have caused several consecutive drought events with rather long durations (up to 29 months). These results reflect the considerable impacts of human activities on hydrological drought, which could provide some theoretical support for local drought mitigation and water resources management.
How Color Properties Can Be Used to Elicit Emotions in Video Games
Authors: Geslin Erik , Jégou Laurent , Beaudoin Danny
Published: January 2016

Classifying the many types of video games is difficult, as their genres and supports are different, but they all have in common that they seek the commitment of the player through exciting emotions and challenges. Since the income of the video game industry exceeds that of the film industry, the field of inducting emotions through video games and virtual environments is attracting more attention. Our theory, widely supported by substantial literature, is that the chromatic stimuli intensity, brightness, and saturation of a video game environment produce an emotional effect on players. We have observed a correlation between the RGB additives color spaces, HSV, HSL, and HSI components of video game images, presented ton=85participants, and the emotional statements expressed in terms of arousal and valence, recovered in a subjective semantic questionnaire. Our results show a significant correlation between luminance, saturation, lightness, and the emotions of joy, sadness, fear, and serenity experienced by participants viewing 24 video game images. We also show strong correlations between the colorimetric diversity, saliency volume, and stimuli conspicuity and the emotions expressed by the players. These results allow us to propose video game environment development methods in the form of a circumplex model. It is aimed at game designers for developing emotional color scripting.