bluuebunny/crossref_metadata_2025 huggingface dataset:
Achieving distributed decision-making using BDI and Coo^2 for future Distributed Tactical Decision Aids
Authors: Consoli Angela
Published: September 2016

Decision-makers in the tactical environment are cognisant of its contested, complex, unknown and dynamic nature. Traditional tactical information gathering and processing methods and decision-making processes within the current tactical environment are becoming less effective and burdensome. New tactical fighter air platforms require high-quality situation awareness and more advanced decision-making methodologies in order to deliver decision superiority. In essence, new generations of tactical air platforms require a redesign of their tactical Decision Support System (DSS), or Tactical Decision Aid (TDA). Furthermore, these new air platforms can no longer work in isolation, but are required to be part of a distributed team. Therefore not only do new techniques in distributed decision making need to be developed, but the concept of Distributed Tactical Deci-sion Aids (DisTDAs) needs to be experimented. The issue on how to implement Coordination and Cooperation (Coo^2) within DisTDAs needs to be firstly addressed.

The Future Integrated Mission System (FIMS) is a first-of-its-kind Service-Oriented Architecture (SOA)-based future integrated mission system for new tactical air strike platforms. The next step is to make FIMS and its TDA distributed - this can be achieved by integrating the Agent Coordination and Cooperation Cognitive Model (AC^3M).

AC^3M illustrates how to implement agent coordination and cooperation by means of a cognitive and Intelligent Multi-Agent System (I-MAS). The centerpiece of AC^3M is the ability to successfully show the link between Coo^2 and how beneficial the link is for enhancing team automation. Analysing the model produces three remarkable results: firstly is the Stimulate-Orient-Decide-Act methodology and secondly is how the Belief, Desire and Intention (BDI) framework, Coo^2 and Stimulate-Orient-Decide-Act (SODA) were linked and interconnected. The final result was the enhanced decision-making that utilised the benefits created from the annexation of the BDI framework, Coo^2 and SODA.
FHL1B Interacts with Lamin A/C and Emerin at the Nuclear Lamina and is Misregulated in Emery-Dreifuss Muscular Dystrophy
Authors: Ziat Esma , Mamchaoui Kamel , Beuvin Maud , Nelson Isabelle , Azibani Feriel , Spuler Simone , Bonne Gisèle , Bertrand Anne T.
Published: September 2016

Background: Emery-Dreifuss muscular dystrophy (EDMD) is associated with mutations in EMD and LMNA genes, encoding for the nuclear envelope proteins emerin and lamin A/C, indicating that EDMD is a nuclear envelope disease. We recently reported mutations in FHL1 gene in X-linked EDMD. FHL1 encodes FHL1A, and the two minor isoforms FHL1B and FHL1C. So far, none have been described at the nuclear envelope.

Objective: To gain insight into the pathophysiology of EDMD, we focused our attention on the poorly characterized FHL1B isoform.

Methods: The amount and the localisation of FHL1B were evaluated in control and diseased human primary myoblasts using immunofluorescence and western blotting.

Results: We found that in addition to a cytoplasmic localization, this isoform strongly accumulated at the nuclear envelope of primary human myoblasts, like but independently of lamin A/C and emerin. During myoblast differentiation, we observed a major reduction of FHL1B protein expression, especially in the nucleus. Interestingly, we found elevated FHL1B expression level in myoblasts from an FHL1-related EDMD patient where the FHL1 mutation only affects FHL1A, as well as in myoblasts from an LMNA-related EDMD patient.

Conclusions: Altogether, the specific localization of FHL1B and its modulation in disease-patient’s myoblasts confirmed FHL1-related EDMD as a nuclear envelope disease.
Type 0 Spinal Muscular Atrophy: Further Delineation of Prenatal and Postnatal Features in 16 Patients
Authors: Grotto Sarah , Cuisset Jean-Marie , Marret Stéphane , Drunat Séverine , Faure Patricia , Audebert-Bellanger Séverine , Desguerre Isabelle , Flurin Vincent , Grebille Anne-Gaëlle , Guerrot Anne-Marie , Journel Hubert , Morin Gilles , Plessis Ghislaine , Renolleau Sylvain , Roume Joëlle , Simon-Bouy Brigitte , Touraine Renaud , Willems Marjolaine , Frébourg Thierry , Verspyck Eric , Saugier-Veber Pascale
Published: September 2016

Background: Spinal muscular atrophy (SMA) is caused by homozygous inactivation of the SMN1 gene. The SMN2 copy number modulates the severity of SMA. The 0 SMN1/1 SMN2 genotype, the most severe genotype compatible with life, is expected to be associated with the most severe form of the disease, called type 0 SMA, defined by prenatal onset.

Objective: The aim of the study was to review clinical features and prenatal manifestations in this rare SMA subtype.

Methods: SMA patients with the 0 SMN1/1 SMN2 genotype were retrospectively collected using the UMD-SMN1 France database.

Results: Data from 16 patients were reviewed. These 16 patients displayed type 0 SMA. At birth, a vast majority had profound hypotonia, severe muscle weakness, severe respiratory distress, and cranial nerves involvement (inability to suck/swallow, facial muscles weakness). They showed characteristics of fetal akinesia deformation sequence and congenital heart defects. Recurrent episodes of bradycardia were observed. Death occurred within the first month. At prenatal stage, decreased fetal movements were frequently reported, mostly only by mothers, in late stages of pregnancy; increased nuchal translucency was reported in about half of the cases; congenital heart defects, abnormal amniotic fluid volume, or joint contractures were occasionally reported.

Conclusion: Despite a prenatal onset attested by severity at birth and signs of fetal akinesia deformation sequence, prenatal manifestations of type 0 SMA are not specific and not constant. As illustrated by the frequent association with congenital heart defects, type 0 SMA physiopathology is not restricted to motor neuron, highlighting that SMN function is critical for organogenesis.
Tremor Frequency Assessment by iPhone® Applications: Correlation with EMG Analysis
Authors: Araújo Rui , Tábuas-Pereira Miguel , Almendra Luciano , Ribeiro Joana , Arenga Marta , Negrão Luis , Matos Anabela , Morgadinho Ana , Januário Cristina
Published: September 2016

Tremor frequency analysis is usually performed by EMG studies but accelerometers are progressively being more used. The iPhone® contains an accelerometer and many applications claim to be capable of measuring tremor frequency. We tested three applications in twenty-two patients with a diagnosis of PD, ET and Holmes’ tremor. EMG needle assessment as well as accelerometry was performed at the same time. There was very strong correlation (Pearson >0.8, p < 0.001) between the three applications, the EMG needle and the accelerometry. Our data suggests the apps LiftPulse®, iSeismometer® and Studymytremor® are a reliable alternative to the EMG for tremor frequency assessment.
Dietary olive oil induces cannabinoid CB2 receptor expression in adipose tissue of ApcMin/+ transgenic mice
Authors: Notarnicola Maria , Tutino Valeria , Tafaro Angela , Bianco Giusy , Guglielmi Emilia , Caruso Maria Gabriella
Published: September 2016

BACKGROUND: Cannabinoid- 2 (CB2) receptor is known for its anti-obesity effects silencing the activated immune cells that are key drivers of metabolic syndrome and inflammation. Nutritional interventions in experimental models of carcinogenesis have been demonstrated to modulate tissue inflammation state and proliferation.

OBJECTIVE: Aim of this study was to test, in ApcMin/+ mice, whether a diet enriched with olive oil, omega- 3 and omega-6- PUFAs affects the adipose tissue inflammation status.

METHODS: Four groups of animal were studied: ST group, receiving a standard diet; OO group, receiving the standard diet in which soybean oil (source of fats) was replaced with olive oil; OM-3 group, receiving the standard diet in which soybean oil was replaced with salmon oil; OM-6 group, receiving the standard diet in which soybean oil was replaced with oenothera oil. Gene and protein expression, in adipose tissue, were evaluated by RT-PCR and Western Blotting, respectively. Enzymatic activities were assayed by fluorescent and radiometric method, where appropriated.

RESULTS: The diet enriched with olive oil significantly induced CB2 receptor expression and it was able to control inflammatory and proliferative activity of mice adipose tissue.

CONCLUSIONS: The present findings open opportunities for developing novel nutritional strategies considering olive oil a key ingredient of a healthy dietary pattern.
Medical laboratory science and nursing students’ perception of the academic learning environment at a Philippine university using the Dundee Ready Education Environment Measure
Authors: Barcelo Jonathan M.
Published: September 2016

Purpose: This study aimed to compare the perception of the academic learning environment between medical laboratory science students and nursing students at Saint Louis University, Baguio City, Philippines. Methods: A cross-sectional survey research design was used to measure the perceptions of the participants. A total of 341 students from the Department of Medical Laboratory Science, School of Natural Sciences, and the School of Nursing answered the Dundee Ready Education Environment Measure (DREEM) instrument from April to May 2016. Responses were compared according to course of study, gender, and year level. Results: The total mean DREEM scores of the medical laboratory science students and nursing students did not differ significantly when grouped according to course of study, gender, or year level. Medical laboratory science students had significantly lower mean scores in the sub-domains ‘perception of learning’ and ‘perception of teaching.’ Male medical laboratory science students had significantly lower mean scores in the sub-domain ‘perception of learning’ among second year students. Medical laboratory science students had significantly lower mean scores in the sub-domain ‘perception of learning.’ Nursing students identified 7 problem areas, most of which were related to their instructors. Conclusion: Medical laboratory science and nursing students viewed their academic learning environment as ‘more positive than negative.’ However, the relationship of the nursing instructors to their students needs improvement.
Screening and Mitigation of Layperson Anxiety in Aerospace Environments
Authors: Mulcahy Robert A. , Blue Rebecca S. , Vardiman Johnené L. , Castleberry Tarah L. , Vanderploeg James M.
Published: September 2016

INTRODUCTION: Anxiety may present challenges for commercial spaceflight operations, as little is known regarding the psychological effects of spaceflight on laypersons. A recent investigation evaluated measures of anxiety during centrifuge-simulated suborbital commercial spaceflight,
highlighting the potential for severe anxiousness to interrupt spaceflight operations.METHODS: To pave the way for future research, an extensive literature review identified existing knowledge that may contribute to formation of interventions for anxiety in commercial spaceflight.
Useful literature was identified regarding anxiety from a variety of fields, including centrifugation, fear of flying, motion sickness, and military operations.RESULTS: Fear of flying is the most extensively studied area, with some supportive evidence from centrifugation studies.
Virtual reality exposure (VRE) is as effective as actual training flight exposure (or analog exposure) in mitigation of flight-related anxiety. The addition of other modalities, such as cognitive behavioral therapy or biofeedback, to VRE improves desensitization compared to VRE alone. Motion
sickness-susceptible individuals demonstrate higher trait anxiety than nonsusceptible individuals; for this reason, motion sickness susceptibility questionnaires may be useful measures to identify at-risk individuals. Some military studies indicate that psychiatric history and personality
classification may have predictive value in future research. Medication countermeasures consisting of benzodiazepines may quell in-flight anxiety, but do not likely improve anxiety on repeat exposure.DISCUSSION: The scarce available literature addressing anxiety in unique environments
indicates that training/repeated exposure may mitigate anxiety. Anxiety and personality indices may be helpful screening tools, while pharmaceuticals may be useful countermeasures when needed.Mulcahy RA, Blue RS, Vardiman JL, Castleberry TL, Vanderploeg JM. Screening and mitigation
of layperson anxiety in aerospace environments. Aerosp Med Hum Perform. 2016; 87(10):882–889.
Middle Ear Resonance Frequency in Pilots and Pilot Candidates
Authors: Tuncer Melisa Melek , Babakurban Seda Turkoglu , Aydin Erdinc
Published: September 2016

BACKGROUND: Barotrauma is a frequent problem in aviation medicine. Eustachian tube dysfunction plays a critical role in the pathogenesis of barotrauma. Function of the Eustachian tube can be indirectly assessed by multifrequency tympanometry, which provides valuable information
about the resistance and permeability of the middle ear in a wide frequency range. The aim of this study was to research whether multifrequency tympanometry could be used for assessing middle ear impairments in pilots.METHODS: There were 140 pilots and pilot candidates between the
ages of 20–55 with normal otoscopic examination who were evaluated by audiological test batteries. Body mass index values, flight hours, audiometric pure tone thresholds, tympanometry and multifrequency tympanometry test results were noted.RESULTS: There was statistically
significant decrease in the multifrequency tympanometry measurements of the left and right ears of the pilots with 200–3000 flight hours compared to pilot candidates, and similarly, the pilots with 3000–10,000 flight hours compared to pilot candidates.DISCUSSION: Multifrequency
tympanometry values changed between pilot candidates and pilots. However, the values of multifrequency tympanometry did not change due to flight hours. This test battery should not be used for follow up of pilots in the clinic.Tuncer MM, Babakurban ST, Aydin E. Middle ear resonance
frequency in pilots and pilot candidates. Aerosp Med Hum Perform. 2016; 87(10):876–881.
Distortion Product Otoacoustic Emissions and Intracranial Pressure During CSF Infusion Testing
Authors: Williams Michael A. , Malm Jan , Eklund Anders , Horton Nicholas J. , Voss Susan E.
Published: September 2016

BACKGROUND: A noninvasive method to monitor changes in intracranial pressure (ICP) is required for astronauts on long-duration spaceflight who are at risk of developing the Visual Impairment/Intracranial Pressure syndrome that has some, but not all of the features of idiopathic
intracranial hypertension. We assessed the validity of distortion product otoacoustic emissions (DPOAEs) to detect changes in ICP.METHODS: Subjects were eight patients undergoing medically necessary diagnostic cerebrospinal fluid (CSF) infusion testing for hydrocephalus. DPOAE measurements
were obtained with an FDA-approved system at baseline and six controlled ICP levels in ∼3 mmHg increments in random order, with a range from 10.8 ± 2.9 mmHg (SD) at baseline to 32.3 ± 4.1 mmHg (SD) at level 6.RESULTS: For f2 frequencies between 800 and 1700 Hz,
when ICP was ≥ 12 mmHg above baseline ICP, DPOAE angles increased significantly and DPOAE magnitudes decreased significantly, but less robustly.DISCUSSION: Significant changes in DPOAE angle and magnitude are seen when ICP is ≥ 12 mmHg above a subject’s supine baseline
ICP during CSF infusion testing. These results suggest that the changes in DPOAE angle and magnitude seen with change in ICP are physiologically based, and suggest that it should be possible to detect pathological ICP elevation using DPOAE measurements. To use DPOAE for noninvasive estimation
of ICP during spaceflight will require baseline measurements in the head-up, supine, and head-down positions to obtain baseline DPOAE values at different ICP ranges.Williams MA, Malm J, Eklund A, Horton NJ, Voss SE. Distortion product otoacoustic emissions and intracranial pressure
during CSF infusion testing. Aerosp Med Hum Perform. 2016; 87(10):844–851.
Fighter Pilot with Recurrent Central Serous Chorioretinopathy
Authors: Dietrich Kevin C.
Published: September 2016

BACKGROUND: Central serous chorioretinopathy (CSC) is usually a self-limiting condition; however, there is potential for recurrence and permanent visual defects. Aviation demands perfect vision to minimize risk to pilots and aircraft. Consequently, this ailment disqualifies pilots
and pilots to be.CASE REPORT: A fully trained fighter pilot with 1260 h in fighter airframes has been contending with central serous chorioretinopathy in the right eye over the course of 3 yr. The condition was diagnosed after the member presented with visual disturbances. His course
was followed with multiple treatment modalities: watchful waiting, micropulse laser, and rifampin. His disease responded well with rifampin, but was ultimately stopped secondary to elevated liver enzymes. Micropulse laser failed to resolve subretinal fluid. Ultimately the pilot is left with
a chronic area of CSC without visual defects and faces career termination.DISCUSSION: Uncompromised vision is inherently crucial in aerospace careers, especially that of a fighter pilot. With persistent CSC resistant to treatment, there is a risk for progression to permanent visual
disturbances and/or defects. Safety concerns of authority figures overseeing pilots and aircraft are warranted. However, the concern could be mitigated in air frames that require two pilots. Another factor partially responsible for ending his career is the fear of G force affecting his prognosis.
The author is not aware of any other studies illuminating the effects or consideration of excess G force on subretinal fluid in CSC. This is an area that requires further study.Dietrich KC. Fighter pilot with recurrent central serous chorioretinopathy. Aerosp Med Hum Perform. 2016;
87(10):901–905.
Improved Separation of Tone and Broadband Noise Components from Open Rotor Acoustic Data
Authors: Sree Dave , Stephens David
Published: September 2016

The term “open rotor” refers to unducted counter-rotating dual rotors or propellers used for propulsion. The noise generated by an open rotor is very complicated and requires special techniques for its analysis. The determination of its tone and broadband components is vital for properly assessing the noise control parameters and also for validating open rotor noise prediction codes. The data analysis technique developed by Sree for processing raw acoustic data of open rotors has been modified to yield much better results of tone and broadband separation particularly for the case when the two rotor speeds are approximately the same. The modified algorithm is found to eliminate most or all of the “spikes” previously observed in the broadband spectra computed from the original algorithm. A full description of the modified algorithm and examples of improved results from its application are presented in this paper.
Synthesis, Characterization, and Catalytic Hydrogenation Activity of New N-Acyl-Benzotriazole Rh(I) and Ru(III) Complexes in [bmim][BF4]
Authors: Ünver Hakan , Yılmaz Filiz
Published: September 2016

The hydrogenation activity of new N-acyl-benzotriazole Rh(I) and Ru(III) complexes in ionic liquid media is reported in this study. Both complexes were completely soluble in 1-butyl-3-methylimidazolium tetrafluoroborate, [bmim][BF4], and they were able to catalyze the hydrogenation of styrene and 1-octene. While ethylbenzene conversion in styrene hydrogenation reached 84% when the Ru complex was used, 100% conversion was obtained with the Rh complex at 393 K in 6 h. Additionally, total conversion in 1-octene hydrogenation reached 100% with the Rh complex in [bmim][BF4] media. The hydrogenation of styrene and 1-octene in dimethyl sulfoxide (DMSO) and toluene was also studied to compare the solvent effect on catalytic system. The effect of some catalytic parameters such as temperature, H2 (g) pressure, and catalyst amount on the conversion was examined, and it was found that the conversion increased parallel to the increasing temperature and H2 pressure. The recyclability of catalysts was also investigated, and it was revealed that the Rh complex in particular maintained the activity for at least 10 cycles.
Computational Streetscapes
Authors: Torrens Paul
Published: September 2016

Streetscapes have presented a long-standing interest in many fields. Recently, there has been a resurgence of attention on streetscape issues, catalyzed in large part by computing. Because of computing, there is more understanding, vistas, data, and analysis of and on streetscape phenomena than ever before. This diversity of lenses trained on streetscapes permits us to address long-standing questions, such as how people use information while mobile, how interactions with people and things occur on streets, how we might safeguard crowds, how we can design services to assist pedestrians, and how we could better support special populations as they traverse cities. Amid each of these avenues of inquiry, computing is facilitating new ways of posing these questions, particularly by expanding the scope of what-if exploration that is possible. With assistance from computing, consideration of streetscapes now reaches across scales, from the neurological interactions that form among place cells in the brain up to informatics that afford real-time views of activity over whole urban spaces. For some streetscape phenomena, computing allows us to build realistic but synthetic facsimiles in computation, which can function as artificial laboratories for testing ideas. In this paper, I review the domain science for studying streetscapes from vantages in physics, urban studies, animation and the visual arts, psychology, biology, and behavioral geography. I also review the computational developments shaping streetscape science, with particular emphasis on modeling and simulation as informed by data acquisition and generation, data models, path-planning heuristics, artificial intelligence for navigation and way-finding, timing, synthetic vision, steering routines, kinematics, and geometrical treatment of collision detection and avoidance. I also discuss the implications that the advances in computing streetscapes might have on emerging developments in cyber-physical systems and new developments in urban computing and mobile computing.
Quantum Computation and Information: Multi-Particle Aspects
Authors: Ellinas Demosthenes , Kaniadakis Giorgio , Pachos Jiannis , Scarfone Antonio
Published: September 2016

This editorial explains the scope of the special issue and provides a thematic introduction to the contributed papers.
Categories, Boundaries, and Bridges: The Social Geography of Schooling and the Need for New Institutional Designs
Authors: Lawson Hal
Published: September 2016

As unprecedented child and family migration patterns continue, neighborhoods, hamlets, towns, cities, states/provinces, and entire nations are impacted. These impacts are especially profound when migrants’ first language is not the host nation’s dominant one; when they relocate in communities already challenged by poverty, social exclusion, and social isolation; and when educator-controlled, standardized, stand-alone schools continue to focus exclusively on teacher-directed, academic learning during the school day. Under these circumstances, standardized schools struggle to achieve desirable results, making it clear that relations between schools and their host locales are consequential for everyone. Using the United States as a case example, this introductory analysis provides an appreciative framework for the new designs presented in this Special Issue of Education Sciences.
Exploring the Magnetic Field Configuration in BL Lac Using GMVA
Authors: Rani Bindu , Krichbaum Thomas , Hodgson Jeff , Koyama Shoko , Zensus Anton , Fuhramnn Lars , Marscher Alan , Jorstad Svetlana
Published: September 2016

The high radio frequency polarization imaging of non-thermal emission from active galactic nuclei (AGN) is a direct way to probe the magnetic field strength and structure in the immediate vicinity of supermassive black holes (SMBHs) and is crucial in testing the jet-launching scenario. To explore the the magnetic field configuration at the base of jets in blazars, we took advantage of the full polarization capabilities of the Global Millimeter VLBI Array (GMVA). With an angular resolution of ∼50 micro-arcseconds (μas) at 86 GHz, one could resolve scales up to ∼450 gravitational radii (for a 10 9 solar mass black hole at a redshift of 0.1). We present here the preliminary results of our study on the blazar BL Lac. Our results suggest that on sub-mas scales the core and the central jet of BL Lac are significantly polarized with two distinct regions of polarized intensity. We also noted a great morphological similarity between the 7 mm/3 mm VLBI images at very similar angular resolution.
Reactivities of Quinone Methides versus o-Quinones in Catecholamine Metabolism and Eumelanin Biosynthesis
Authors: Sugumaran Manickam
Published: September 2016

Melanin is an important biopolymeric pigment produced in a vast majority of organisms. Tyrosine and its hydroxylated product, dopa, form the starting material for melanin biosynthesis. Earlier studies by Raper and Mason resulted in the identification of dopachrome and dihydroxyindoles as important intermediates and paved way for the establishment of well-known Raper–Mason pathway for the biogenesis of brown to black eumelanins. Tyrosinase catalyzes the oxidation of tyrosine as well as dopa to dopaquinone. Dopaquinone thus formed, undergoes intramolecular cyclization to form leucochrome, which is further oxidized to dopachrome. Dopachrome is either converted into 5,6-dihydroxyindole by decarboxylative aromatization or isomerized into 5,6-dihydroxyindole-2-carboxylic acid. Oxidative polymerization of these two dihydroxyindoles eventually produces eumelanin pigments via melanochrome. While the role of quinones in the biosynthetic pathway is very well acknowledged, that of isomeric quinone methides, however, remained marginalized. This review article summarizes the key role of quinone methides during the oxidative transformation of a vast array of catecholamine derivatives and brings out the importance of these transient reactive species during the melanogenic process. In addition, possible reactions of quinone methides at various stages of melanogenesis are discussed.
Clinical Application of Circulating Tumour Cells in Prostate Cancer: From Bench to Bedside and Back
Authors: León-Mateos Luis , Vieito María , Anido Urbano , López López Rafael , Muinelo Romay Laura
Published: September 2016

Prostate cancer is the most common cancer in men worldwide. To improve future drug development and patient management, surrogate biomarkers associated with relevant outcomes are required. Circulating tumour cells (CTCs) are tumour cells that can enter the circulatory system, and are principally responsible for the development of metastasis at distant sites. In recent years, interest in detecting CTCs as a surrogate biomarker has ghiiukjrown. Clinical studies have revealed that high levels of CTCs in the blood correlate with disease progression in patients with prostate cancer; however, their predictive value for monitoring therapeutic response is less clear. Despite the important progress in CTC clinical development, there are critical requirements for the implementation of their analysis as a routine oncology tool. The goal of the present review is to provide an update on the advances in the clinical validation of CTCs as a surrogate biomarker and to discuss the principal obstacles and main challenges to their inclusion in clinical practice.
Neuroprotection, Growth Factors and BDNF-TrkB Signalling in Retinal Degeneration
Authors: Kimura Atsuko , Namekata Kazuhiko , Guo Xiaoli , Harada Chikako , Harada Takayuki
Published: September 2016

Neurotrophic factors play key roles in the development and survival of neurons. The potent neuroprotective effects of neurotrophic factors, including brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), glial cell-line derived neurotrophic factor (GDNF) and nerve growth factor (NGF), suggest that they are good therapeutic candidates for neurodegenerative diseases. Glaucoma is a neurodegenerative disease of the eye that causes irreversible blindness. It is characterized by damage to the optic nerve, usually due to high intraocular pressure (IOP), and progressive degeneration of retinal neurons called retinal ganglion cells (RGCs). Current therapy for glaucoma focuses on reduction of IOP, but neuroprotection may also be beneficial. BDNF is a powerful neuroprotective agent especially for RGCs. Exogenous application of BDNF to the retina and increased BDNF expression in retinal neurons using viral vector systems are both effective in protecting RGCs from damage. Furthermore, induction of BDNF expression by agents such as valproic acid has also been beneficial in promoting RGC survival. In this review, we discuss the therapeutic potential of neurotrophic factors in retinal diseases and focus on the differential roles of glial and neuronal TrkB in neuroprotection. We also discuss the role of neurotrophic factors in neuroregeneration.
Protein Kinases and Parkinson’s Disease
Authors: Mehdi Syed , Rosas-Hernandez Hector , Cuevas Elvis , Lantz Susan , Barger Steven , Sarkar Sumit , Paule Merle , Ali Syed , Imam Syed
Published: September 2016

Currently, the lack of new drug candidates for the treatment of major neurological disorders such as Parkinson’s disease has intensified the search for drugs that can be repurposed or repositioned for such treatment. Typically, the search focuses on drugs that have been approved and are used clinically for other indications. Kinase inhibitors represent a family of popular molecules for the treatment and prevention of various cancers, and have emerged as strong candidates for such repurposing because numerous serine/threonine and tyrosine kinases have been implicated in the pathobiology of Parkinson’s disease. This review focuses on various kinase-dependent pathways associated with the expression of Parkinson’s disease pathology, and evaluates how inhibitors of these pathways might play a major role as effective therapeutic molecules.
Optical Properties of Heavily Fluorinated Lanthanide Tris β-Diketonate Phosphine Oxide Adducts
Authors: Swinburne Adam , Langford Paden Madeleine , Chan Tsz , Randall Simon , Ortu Fabrizio , Kenwright Alan , Natrajan Louise
Published: September 2016

The construction of lanthanide(III) chelates that exhibit superior photophysical properties holds great importance in biological and materials science. One strategy to increase the luminescence properties of lanthanide(III) chelates is to hinder competitive non-radiative decay processes through perfluorination of the chelating ligands. Here, the synthesis of two families of heavily fluorinated lanthanide(III) β-diketonate complexes bearing monodentate perfluorinated tris phenyl phosphine oxide ligands have been prepared through a facile one pot reaction [Ln(hfac)3{(ArF)3PO}(H2O)] and [Ln(F7-acac)3{(ArF)3PO}2] (where Ln = Sm3+, Eu3+, Tb3+, Er3+ and Yb3+). Single crystal X-ray diffraction analysis in combination with photophysical studies have been performed to investigate the factors responsible for the differences in the luminescence lifetimes and intrinsic quantum yields of the complexes. Replacement of both bound H2O and C–H oscillators in the ligand backbone has a dramatic effect on the photophysical properties of the complexes, particularly for the near infra-red emitting ion Yb3+, where a five fold increase in luminescence lifetime and quantum yield is observed. The complexes [Sm(hfac)3{(ArF)3PO}(H2O)] (1), [Yb(hfac)3{(ArF)3PO}(H2O)] (5), [Sm(F7-acac)3{(ArF)3PO}2] (6) and [Yb(F7-acac)3{(ArF)3PO}2] (10) exhibit unusually long luminescence lifetimes and attractive intrinsic quantum yields of emission in fluid solution (ΦLn = 3.4% (1); 1.4% (10)) and in the solid state (ΦLn = 8.5% (1); 2.0% (5); 26% (6); 11% (10)), which are amongst the largest values for this class of compounds to date.
Correction: Ono, K. Calibration Methods of Acoustic Emission Sensors. Materials 2016, 9, 508
Authors: Ono Kanji
Published: September 2016

The author wishes to make the following corrections to this paper [1].[...]
Novel Resorbable and Osteoconductive Calcium Silicophosphate Scaffold Induced Bone Formation
Authors: Ros-Tárraga Patricia , Mazón Patricia , Rodríguez Miguel , Meseguer-Olmo Luis , De Aza Piedad
Published: September 2016

This aim of this research was to develop a novel ceramic scaffold to evaluate the response of bone after ceramic implantation in New Zealand (NZ) rabbits. Ceramics were prepared by the polymer replication method and inserted into NZ rabbits. Macroporous scaffolds with interconnected round-shaped pores (0.5–1.5 mm = were prepared). The scaffold acted as a physical support where cells with osteoblastic capability were found to migrate, develop processes, and newly immature and mature bone tissue colonized on the surface (initially) and in the material’s interior. The new ceramic induced about 62.18% ± 2.28% of new bone and almost complete degradation after six healing months. An elemental analysis showed that the gradual diffusion of Ca and Si ions from scaffolds into newly formed bone formed part of the biomaterial’s resorption process. Histological and radiological studies demonstrated that this porous ceramic scaffold showed biocompatibility and excellent osteointegration and osteoinductive capacity, with no interposition of fibrous tissue between the implanted material and the hematopoietic bone marrow interphase, nor any immune response after six months of implantation. No histological changes were observed in the various organs studied (para-aortic lymph nodes, liver, kidney and lung) as a result of degradation products being released.
Molecular Weight-Dependent Immunostimulative Activity of Low Molecular Weight Chitosan via Regulating NF-κB and AP-1 Signaling Pathways in RAW264.7 Macrophages
Authors: Zheng Bin , Wen Zheng-Shun , Huang Yun-Juan , Xia Mei-Sheng , Xiang Xing-Wei , Qu You-Le
Published: September 2016

Chitosan and its derivatives such as low molecular weight chitosans (LMWCs) have been found to possess many important biological properties, such as antioxidant and antitumor effects. In our previous study, LMWCs were found to elicit a strong immunomodulatory response in macrophages dependent on molecular weight. Herein we further investigated the molecular weight-dependent immunostimulative activity of LMWCs and elucidated its mechanism of action on RAW264.7 macrophages. LMWCs (3 kDa and 50 kDa of molecular weight) could significantly enhance the mRNA expression levels of COX-2, IL-10 and MCP-1 in a molecular weight and concentration-dependent manner. The results suggested that LMWCs elicited a significant immunomodulatory response, which was dependent on the dose and the molecular weight. Regarding the possible molecular mechanism of action, LMWCs promoted the expression of the genes of key molecules in NF-κB and AP-1 pathways, including IKKβ, TRAF6 and JNK1, and induced the phosphorylation of protein IKBα in RAW264.7 macrophage. Moreover, LMWCs increased nuclear translocation of p65 and activation of activator protein-1 (AP-1, C-Jun and C-Fos) in a molecular weight-dependent manner. Taken together, our findings suggested that LMWCs exert immunostimulative activity via activation of NF-κB and AP-1 pathways in RAW264.7 macrophages in a molecular weight-dependent manner and that 3 kDa LMWC shows great potential as a novel agent for the treatment of immune suppression diseases and in future vaccines.
Adhesion Properties of Lactic Acid Bacteria on Intestinal Mucin
Authors: Nishiyama Keita , Sugiyama Makoto , Mukai Takao
Published: September 2016

Lactic acid bacteria (LAB) are Gram-positive bacteria that are natural inhabitants of the gastrointestinal (GI) tracts of mammals, including humans. Since Mechnikov first proposed that yogurt could prevent intestinal putrefaction and aging, the beneficial effects of LAB have been widely demonstrated. The region between the duodenum and the terminal of the ileum is the primary region colonized by LAB, particularly the Lactobacillus species, and this region is covered by a mucus layer composed mainly of mucin-type glycoproteins. The mucus layer plays a role in protecting the intestinal epithelial cells against damage, but is also considered to be critical for the adhesion of Lactobacillus in the GI tract. Consequently, the adhesion exhibited by lactobacilli on mucin has attracted attention as one of the critical factors contributing to the persistent beneficial effects of Lactobacillus in a constantly changing intestinal environment. Thus, understanding the interactions between Lactobacillus and mucin is crucial for elucidating the survival strategies of LAB in the GI tract. This review highlights the properties of the interactions between Lactobacillus and mucin, while concomitantly considering the structure of the GI tract from a histochemical perspective.
Biofilm Forming Lactobacillus: New Challenges for the Development of Probiotics
Authors: Salas-Jara María , Ilabaca Alejandra , Vega Marco , García Apolinaria
Published: September 2016

Probiotics are live bacteria, generally administered in food, conferring beneficial effects to the host because they help to prevent or treat diseases, the majority of which are gastrointestinal. Numerous investigations have verified the beneficial effect of probiotic strains in biofilm form, including increased resistance to temperature, gastric pH and mechanical forces to that of their planktonic counterparts. In addition, the development of new encapsulation technologies, which have exploited the properties of biofilms in the creation of double coated capsules, has given origin to fourth generation probiotics. Up to now, reviews have focused on the detrimental effects of biofilms associated with pathogenic bacteria. Therefore, this work aims to amalgamate information describing the biofilms of Lactobacillus strains which are used as probiotics, particularly L. rhamnosus, L. plantarum, L. reuteri, and L. fermentum. Additionally, we have reviewed the development of probiotics using technology inspired by biofilms.
Streptokinase Treatment Reverses Biofilm-Associated Antibiotic Resistance in Staphylococcus aureus
Authors: Jørgensen Nis , Zobek Natalia , Dreier Cindy , Haaber Jakob , Ingmer Hanne , Larsen Ole , Meyer Rikke
Published: September 2016

Biofilms formed by Staphylococcus aureus is a serious complication to the use of medical implants. A central part of the pathogenesis relies on S. aureus’ ability to adhere to host extracellular matrix proteins, which adsorb to medical implants and stimulate biofilm formation. Being coagulase positive, S. aureus furthermore induces formation of fibrin fibers from fibrinogen in the blood. Consequently, we hypothesized that fibrin is a key component of the extracellular matrix of S. aureus biofilms under in vivo conditions, and that the recalcitrance of biofilm infections can be overcome by combining antibiotic treatment with a fibrinolytic drug. We quantified S. aureus USA300 biofilms grown on peg-lids in brain heart infusion (BHI) broth with 0%–50% human plasma. Young (2 h) and mature (24 h) biofilms were then treated with streptokinase to determine if this lead to dispersal. Then, the minimal biofilm eradication concentration (MBEC) of 24 h old biofilms was measured for vancomycin and daptomycin alone or in combination with 10 µg/mL rifampicin in the presence or absence of streptokinase in the antibiotic treatment step. Finally, biofilms were visualized by confocal laser scanning microscopy. Addition of human plasma stimulated biofilm formation in BHI in a dose-dependent manner, and biofilms could be partially dispersed by streptokinase. The biofilms could be eradicated with physiologically relevant concentrations of streptokinase in combination with rifampicin and vancomycin or daptomycin, which are commonly used antibiotics for treatment of S. aureus infections. Fibronolytic drugs have been used to treat thromboembolic events for decades, and our findings suggest that their use against biofilm infections has the potential to improve the efficacy of antibiotics in treatment of S. aureus biofilm infections.
Delivery of RNAi Therapeutics to the Airways—From Bench to Bedside
Authors: Qiu Yingshan , Lam Jenny , Leung Susan , Liang Wanling
Published: September 2016

RNA interference (RNAi) is a potent and specific post-transcriptional gene silencing process. Since its discovery, tremendous efforts have been made to translate RNAi technology into therapeutic applications for the treatment of different human diseases including respiratory diseases, by manipulating the expression of disease-associated gene(s). Similar to other nucleic acid-based therapeutics, the major hurdle of RNAi therapy is delivery. Pulmonary delivery is a promising approach of delivering RNAi therapeutics directly to the airways for treating local conditions and minimizing systemic side effects. It is a non-invasive route of administration that is generally well accepted by patients. However, pulmonary drug delivery is a challenge as the lungs pose a series of anatomical, physiological and immunological barriers to drug delivery. Understanding these barriers is essential for the development an effective RNA delivery system. In this review, the different barriers to pulmonary drug delivery are introduced. The potential of RNAi molecules as new class of therapeutics, and the latest preclinical and clinical studies of using RNAi therapeutics in different respiratory conditions are discussed in details. We hope this review can provide some useful insights for moving inhaled RNAi therapeutics from bench to bedside.
Digital Gene Expression Profiling to Explore Differentially Expressed Genes Associated with Terpenoid Biosynthesis during Fruit Development in Litsea cubeba
Authors: Gao Ming , Lin Liyuan , Chen Yicun , Wang Yangdong
Published: September 2016

Mountain pepper (Litsea cubeba (Lour.) Pers.) (Lauraceae) is an important industrial crop as an ingredient in cosmetics, pesticides, food additives and potential biofuels. These properties are attributed to monoterpenes and sesquiterpenes. However, there is still no integrated model describing differentially expressed genes (DEGs) involved in terpenoid biosynthesis during the fruit development of L. cubeba. Here, we performed digital gene expression (DGE) using the Illumina NGS platform to evaluated changes in gene expression during fruit development in L. cubeba. DGE generated expression data for approximately 19354 genes. Fruit at 60 days after flowering (DAF) served as the control, and a total of 415, 1255, 449 and 811 up-regulated genes and 505, 1351, 1823 and 1850 down-regulated genes were identified at 75, 90, 105 and 135 DAF, respectively. Pathway analysis revealed 26 genes involved in terpenoid biosynthesis pathways. Three DEGs had continued increasing or declining trends during the fruit development. The quantitative real-time PCR (qRT-PCR) results of five differentially expressed genes were consistent with those obtained from Illumina sequencing. These results provide a comprehensive molecular biology background for research on fruit development, and information that should aid in metabolic engineering to increase the yields of L. cubeba essential oil.
Effect of Phyllanthus amarus Extract on 5-Fluorouracil-Induced Perturbations in Ribonucleotide and Deoxyribonucleotide Pools in HepG2 Cell Line
Authors: Guo Jian-Ru , Chen Qian-Qian , Lam Christopher , Wang Cai-Yun , Xu Feng-Guo , Liu Bu-Ming , Zhang Wei
Published: September 2016

The aim of this study was to investigate the antitumor activities of Phyllanthus amarus (PHA) and its potential of herb–drug interactions with 5-Fluorouracil (5-FU). Cell viability, ribonucleotides (RNs) and deoxyribonucleotides (dRNs) levels, cell cycle distribution, and expression of thymidylate synthase (TS) and ribonucleotide reductase (RR) proteins were measured with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, high performance liquid chromatography tandem mass spectrometry (HPLC/MS/MS) method, flow cytometry and Western blot analysis, respectively. Our standardized PHA extract showed toxicity to HepG2 cells at high concentrations after 72 h exposure and induced G2/M cell cycle arrest. Combined use of 5-FU with PHA resulted in significant decreases in ATP, CTP, GTP, UTP and dTTP levels, while AMP, CMP, GMP and dUMP levels increased significantly compared with use of 5-FU alone. Further, PHA could increase the role of cell cycle arrest at S phase induced by 5-FU. Although PHA alone had no direct impact on TS and RR, PHA could change the levels of RNs and dRNs when combined with 5-FU. This may be due to cell cycle arrest or regulation of key enzyme steps in intracellular RNs and dRNs metabolism.
The mTORC1-Signaling Pathway and Hepatic Polyribosome Profile Are Enhanced after the Recovery of a Protein Restricted Diet by a Combination of Soy or Black Bean with Corn Protein
Authors: Márquez-Mota Claudia , Rodriguez-Gaytan Cinthya , Adjibade Pauline , Mazroui Rachid , Gálvez Amanda , Granados Omar , Tovar Armando , Torres Nimbe
Published: September 2016

Between 6% and 11% of the world’s population suffers from malnutrition or undernutrition associated with poverty, aging or long-term hospitalization. The present work examined the effect of different types of proteins on the mechanistic target of rapamycin (mTORC1)-signaling pathway in: (1) healthy; and (2) protein restricted rats. (1) In total, 200 rats were divided into eight groups and fed one of the following diets: 20% casein (C), soy (S), black bean (B), B + Corn (BCr), Pea (P), spirulina (Sp), sesame (Se) or Corn (Cr). Rats fed C or BCr had the highest body weight gain; rats fed BCr had the highest pS6K1/S6K1 ratio; rats fed B, BCr or P had the highest eIF4G expression; (2) In total, 84 rats were fed 0.5% C for 21 day and protein rehabilitated with different proteins. The S, soy + Corn (SCr) and BCr groups had the highest body weight gain. Rats fed SCr and BCr had the highest eIF4G expression and liver polysome formation. These findings suggest that the quality of the dietary proteins modulate the mTORC1-signaling pathway. In conclusion, the combination of BCr or SCr are the best proteins for dietary protein rehabilitation due to the significant increase in body weight, activation of the mTORC1-signaling pathway in liver and muscle, and liver polysome formation.