This paper describes the modeling of various emotional expressions and speaking styles in synthetic speech using HMM-based speech synthesis. We show two methods for modeling speaking styles and emotional expressions. In the first method called style-dependent modeling, each speaking style and emotional expression is modeled individually. In the second one called style-mixed modeling, each speaking style and emotional expression is treated as one of contexts as well as phonetic, prosodic, and linguistic features, and all speaking styles and emotional expressions are modeled simultaneously by using a single acoustic model. We chose four styles of read speech --- neutral, rough, joyful, and sad --- and compared the above two modeling methods using these styles. The results of subjective evaluation tests show that both modeling methods have almost the same accuracy, and that it is possible to synthesize speech with the speaking style and emotional expression similar to those of the target speech. In a test of classification of styles in synthesized speech, more than 80% of speech samples generated using both the models were judged to be similar to the target styles. We also show that the style-mixed modeling method gives fewer output and duration distributions than the styledependent modeling method.


This study aims at exploring the relationship between service quality dimensions and overall service quality dimensions (tangibility, responsiveness, reliability, assurance and empathy) and students satisfaction. Additionally, this study also looks at the critical factors in service quality dimensions that contribute most to the satisfaction of the students. The data was collected using a set of questionnaire from 798 undergraduate students who offered various bachelor degrees in a public higher education institution in Ghana. The study provides empirical evidences of these relationships. The results of this study affirms the results of Parasuraman's SERVQUAL (1985) study, which related to the factors contributing to students' satisfaction. The outcome of the study amplifies the assertion that service quality (tangibility, responsiveness, reliability, assurance and empathy) has a positive impact on student's overall satisfaction.


The increasing commercialisation of human ICT implants has generated debate over the ethical, legal, and social implications of their use. The convergence of nanotechnologies with ICT is likely to further challenge the current legal frameworks that regulate them. The aim of this article is to examine the effectiveness of the European data protection legal framework for regulating this "next generation" of nano-enabled ICT human implantable devices. The article highlights the potential regulatory challenges posed by the applications and makes a series of recommendations as to how the current European legal framework on data protection will respond to them.


Background Gastrointestinal involvement is recognized as a major cause of morbidity and mortality in Systemic Sclerosis (SSc) and its pathophysiology is still unclear. Few data on composition and function of gut microenvironment in SSc are reported in the literature but there is a growing body of evidences supporting the hypothesis of a relation between gut microbiota and the host immune system. Objectives The goal of this study was to characterize fecal microbiota in SSc patients compared to healthy subjects to investigate whether specific microbial species may be responsible of dysbiosis in SSc. Furthermore, we investigated the composition of microbiota in the different clinical subsets of SSc. Methods Faecal samples were obtained from 17 healthy controls and 39 SSc patients including subjects with different skin involvement (Diffuse and Limited) and disease duration. The BMI was normal and the mean age was similar both in SSc and controls groups. The composition of microbiota was determined through 16S rRNA pyrosequencing performed using the GS Titanium technology. Rarefaction was used to uniform abudance data. α-diversity was defined by the main indexes while β-diversity was determined according to Bray-Curtis and UniFrac, represented trough Principal Coordinate Analysis (PCoA) and compared using PERMANOVA test on distance matrices. Linear Discriminant Analysis Effect Size was used to identify taxa that showed differential expression between the groups. Results At genus level SSc patients showed a differential expression in 12 taxa compared to controls with higher levels of Ruminococcus, Streptococcus, Lactobacillus, Blautia, Coprococcus and Phascolarctobacterium and a depletion of Bacteroides, Butyciromonas, Odoribacter, Succinivibrio, Sutterella and Prevotella. The differences in microbiota composition between SSc patients and controls were supported also by PCoA of the values representing phylogenetic distance of microbial communities between specimens (p<0.001) (see figure). Among scleroderma patients, those with diffuse skin involvement showed a greater abundance of bacteria of Bacteroidetes phylum with significantly lower values of alpha diversity by Chao1 and species richness (p=0.01). Differences were confirmed by PERMANOVA on Bray-Curtis distance matrix (p=0.016). PERMANOVA analysis of distance matrices (p-values adjusted according to FDR) Weighted UniFrac Bray-Curtis Control vs SSc <0.001* <0.001* Control vs Diffuse 0,012* 0,0015* Control vs Limited 0,003* 0,0015* Control vs Early 0,003* 0,0015* Control vs Long 0,017* 0,0015* Diffuse vs Limited 0,259 0,016* Early vs Long 0,49 0,156 Conclusions Our analysis demonstrated an altered and distinct composition of gut microbiota in SSc patients compared to healthy controls. Furthermore, scleroderma patients show some differences in microbiota characteristics according to the extent of skin involvement, suggesting that microbiota may influence the severity of the disease. If validated and related to GI symptomathology and nutritional status our findings open up the opportunity of a rational intervention on microbiota to restore the gut equilibrium in SSc patients. Disclosure of Interest None declared


Indonesia is currently the largest producer palm oil in the world with its production about 33.000.000 ton/year in 2014. This research is dealing with potency and quality of palm oil types of dura, pisifera and tenera based on time storage of fruit (0, 7, 14, 21, 28 days). The research was performed on August to December 2014, in Bangun Bandar plantation, Dolok Masihul, North Sumatera. Parameters measured for oil potency was crude palm oil (CPO) content and for quality of palm oil were β-carotene content, deterioration of bleachability index (DOBI),  free fatty acid content, and moisture content β-carotene content and DOBI were analyzed by Spectrophotometer at 446 nm and 269 nm. Free fatty acid was determined by titration, and moisture content was measured by an electronic moisture analyzer.  Results showed that potency of palm oil types of dura, pisifera, tenera were 23,5 %, 26,2 %, 23,6 %, respectively. β-carotene content and DOBI of palm oil types of dura, pisifera, and tenera were decreased by time storage of fruit. Free fatty acid and moisture content of palm oil types of dura, pisifera, and tenera were increased by time storage of fruit. Based on the results, time of storage of fruit affected poorly in quality of palm oil. Keywords: palm oil, quality, potency, type of oil palm.


Malignant lymphomas (Hodgkin's and Non Hodgkin's Lymphoma) are often diagnosed in lymphoid structures of the head and neck region as part of either a localized or an already disseminated disease. Its careful work-up with histology and accurate staging is the base of a successful therapeutic strategy. With appropriate chemotherapy and/or radiotherapy, the primary aim is often cure of disease. Other diseases important for differential diagnosis are discussed.


Delays in case reporting are common to disease surveillance systems, making it difficult to track diseases in real-time. "Nowcast" approaches attempt to estimate the complete case counts for a given reporting date, using a time series of case reports that is known to be incomplete due to reporting delays. Modeling the reporting delay distribution is a common feature of nowcast approaches. However, many nowcast approaches ignore a crucial feature of infectious disease transmission—that future cases are intrinsically linked to past reported cases—and are optimized to a single application, which may limit generalizability. Here, we present a Bayesian approach, NobBS (Nowcasting by Bayesian Smoothing) capable of producing smooth and accurate nowcasts in multiple disease settings. We test NobBS on dengue in Puerto Rico and influenza-like illness (ILI) in the United States to examine performance and robustness across settings exhibiting a range of common reporting delay characteristics (from stable to time-varying), and compare this approach with a published nowcasting package. We show that introducing a temporal relationship between cases considerably improves performance when the reporting delay distribution is time-varying, and we identify trade-offs in the role of moving windows to accurately capture changes in the delay. We present software implementing this new approach (R package "NobBS") for widespread application. Significance Achieving accurate, real-time estimates of disease activity is challenged by delays in case reporting. However, approaches that seek to estimate cases in spite of reporting delays often do not consider the temporal relationship between cases during an outbreak, nor do they identify characteristics of robust approaches that generalize to a wide range of surveillance contexts with very different reporting delays. Here, we present a smooth Bayesian nowcasting approach that produces accurate estimates that capture the time evolution of the epidemic curve and outperform a previous approach in the literature. We assess the performance for two diseases to identify important features of the reporting delay distribution that contribute to the model's performance and robustness across surveillance settings.


Live-attenuated viruses have typically been generated from pathogenic viruses by genetic modifications that modified their replicative capacity. The present study investigated whether modification of the antigenic properties of live-attenuated viruses might improve upon the protection that such vaccines afford against lentivirus infection. In a previous study, random amino acid substitutions were introduced into the transmembrane envelope glycoprotein of the feline immunodeficiency virus (FIV), within a highly conserved domain (principal immunodominant domain) bearing immunodominant B-cell epitopes. Amongst a wide set of mutants, mutations that modified antibody specificity without abolishing infectivity ex vivo were selected. In the present study, two such mutants, TN14 and TN92, were evaluated for their replicative capacities and pathogenic properties in vivo in comparison with the parental virus, FIV 34TF10. No significant differences in viral load were observed between mutant and parental viruses. After 1 year of infection, all animals were subjected to a heterologous intraclade superinfection with a primary strain of FIV. Whilst both parental and modified viruses protected cats from high viral loads after superinfection, the TN92 virus afforded a higher degree of protection (P=0.0079). Such improvement in protection might correlate with a decrease in the immunogenicity of a B-cell epitope potentially involved in antibody enhancement of infection.


Concatenated alignments of RADseq data for seven Virentes taxa and eight outgroup taxa (35 samples total) used to infer phylogenetic trees. The virentes_ME_c85d6m4p3.phy alignment is 6,252,421 bp in length. Filtered reads were clustered at an 85% threshold for within-sample clustering. The number of samples for which data needed to be recovered to include a RAD locus in the data set was 4.


In this time and wavelength regime optical coatings typically fail from thermal damage. Unlike catastrophic damage resulting from dielectric breakdown, one finds disparity among the thresholds for one or more of the following damage characteristics: delamination, cracking, flow, erosion, perforation, ion emission, and light emission. Comparison of the different thresholds provides useful information on how damage proceeds, and how the absorbed energy is distributed in the coating layer. Comparison of multithreshold damage data at the two different wavelengths permits evaluation of the importance of impurities which absorb preferentially at one of the wavelengths, such as water. Comparing thresholds at the two wavelengths after N/1 conditioning provides detection of preferentially absorbing impurities which are laser-desorbed. Complementary information may be obtained from laser calorimetry. The following materials, prepared as single-layer, antireflection coatings, were evaluated: NaF, SiO x , Al 2 O 3 , ZnS, As 2 S 3 , and Si. Samples of the first three were prepared in ultrahigh vacuum, in addition to the usual standard vacuum preparation. Thresholds are expressed in terms of the theoretical energy per unit area in the coating layer in order to permit a practical intercomparison of materials for multilayer coating design.


Screening test sorts out from apparently healthy population those who probably have the disease or risk factor. Screening test is quick, less accurate, inexpensive and simple to be conducted by technicians, thereby saving doctors time who only interprets the test. Those confirmed by the diagnostic test as cases are given treatment to alter the natural history of disease. This case detection as a result of screening is called prescriptive screening which is superior from case finding where the people are the health care seekers. Also it is different from prospective screening done to protect local population from immigrants having disease. Selective screening in high risk population gives better yield than mass screening. Screening is helpful in education and awareness of general public about diseases and also helps in epidemiological research by cross-sectional and longitudinal surveys. Screening is the main tool in the hands of epidemiologist to detect tuberculosis, diabetes, hypertension, cancer like chronic diseases presenting in community as 'tip of the ice-berg'. Screening is helpful only in diseases of public health importance having increase prevalence and having time lag between onset and time of diagnosis (latent or asymptomatic period). Diseases must have known natural history, with availability of screening test, diagnostic test and treatment along with resources for sustained care. Also there must be available a clear policy of treatment. There must be good evidence that screening decreases morbidity and mortality of disease along with cost benefit analysis. Screening test must be acceptable for community participation, repeatable (reliable/ precise) like height and weight & not like BP measurement, which has all three sources of errors (intra/ inter observer, subject and technical). The screening test must be valid (accurate) having high sensitivity, specificity, positive and negative predictive value. High sensitivity means increase number of true positive and decreased false negative to avoid false assurance to the patients specially having lethal diseases like cancer versus diabetes which requires less sensitive and highly specific test. High specificity means increased true negative and decreased false positive to keep the image of screening program high as fewer anxious people will require confirming the diagnosis and our diagnostic system will not be overburdened. Sensitivity and specificity are inversely related. Those actually deserving should be screened instead of volunteers. Participants need to be explained the possibility of false positive and false negative. To evaluate screening programs at the place where these are going on, case control, uncontrolled trials and RCTs may be conducted. The response rate is 50 to 60 percent in developed countries. The screening must be done in high risk groups instead of mass level screening for high yield with high predictive value of positive and negative screening test. Screening must be integrated into health care services.


We present a novel generative model for natural language tree structures in which semantic (lexical dependency) and syntactic (PCFG) structures are scored with separate models. This factorization provides conceptual simplicity, straightforward opportunities for separately improving the component models, and a level of performance comparable to similar, non-factored models. Most importantly, unlike other modern parsing models, the factored model admits an extremely effective A* parsing algorithm, which enables efficient, exact inference.


Chronic lymphocytic leukaemia (CLL) is a lymphoproliferative disorder characterized by the progressive accumulation of clonal small mature-looking lymphocytes, usually of B cell origin. In addition to a better understanding of many biological features, during the last 10-15 years a great progress has been made in the prognostic characterization of the disease. The therapeutic achievements, however, have been less impressive. The possibility to identify patients with different prognosis has renewed interest in the treatment of this disorder. A considerable number of controlled trials have been performed or are in course, and new perspectives for CLL treatment are emerging. Basically four different kinds of measures are used: 1) chemotherapy, 2) radiotherapy, 3) adjuvant measures and 4) new modalities.


This study aims to compare the management of Islamic education for the BIPA (Bahasa Indonesia Penutur Asing/Indonesian Language Learning for Foreign Speaker) program at PTKI institutions in  Indonesia and Al-Azhar University in Egypt from the aspects of the curriculum, institutions, teachers, students, and evaluation. This research used descriptive analytic method with a qualitative approach. In-depth interviews, content analysis, and observation were applied to collect the data. Data were analysed using the interactive model of Miles & Huberman and comparative analysis. The result of the research showed that BIPA management conducted by PTKI institutions and Al-Azhar university, Egypt in terms of institution, curriculum, language teachers, language learners, evaluation have applied islamic perspective (Aqeeda and Sharia) and Islamic values which are compatible with the regulation set by Direktur Jenderal Pendidikan Islam (Directorate General for Islamic Education) Number 6244 Year 2019. Referring to this regulation, both BIPA program at PTKI institutions and Al-azhar university are considered ready and successful.


An integral part of spreadsheet auditing is navigation. For sufferers of Repetitive Strain Injury who
need to use voice recognition technology this navigation can be highly problematic. To counter this the
authors have developed an intelligent voice navigation system, iVoice, which replicates common
spreadsheet auditing behaviours through simple voice commands. This paper outlines the iVoice
system and summarizes the results of a study to evaluate iVoice when compared to a leading voice
recognition technology.


Microearthquake seismograms recorded by stations located in or bordering the Rio Grande rift near Socorro, New Mexico, frequently have two sharp impulsive phases following direct S. These phases have been identified as SxP and SxS reflections from a sharp discontinuity that has a depth beneath Socorro of 18 km and dips northward at an angle near 6° for a distance of 30 km. Farther north, the dip steepens so that at a distance of 60 km from Socorro the depth is about 30 km. Ratios of SxP to SxS amplitudes in conjunction with plane-wave reflection theory indicate a zone of very low rigidity beneath the discontinuity. Large SxS amplitudes are believed to be the result of the large velocity contrast across the discontinuity and a fault mechanism that radiates more S-wave energy downward than outward from the focus.


In this paper we analyze the impact in the requirements of the linewidth of the laser, due to the linear and non-linear effects introduced by the optical fiber, in a WDM-PON transmission system using DPSK modulation format. We measured the BER for different data bit rates, transmitted power and dispersion coefficient of the optical fiber. The study was performed using simulations in the computational tool OPTSIM�. We found that if the data bit rate is increased, it is possible to use optical sources with higher linewidth using DPSK modulation format, decreasing the cost of the transmitter. Additionally, we proved that the non-linear effects mostly affect the transmission systems where optical fibers with dispersion coefficients near zero are used.


Ecological theory predicts a positive and asymptotic relationship between plant diversity and ecosystem productivity based on the ability of more diverse plant communities to use limiting resources more fully. This is supported by recent empirical evidence. Additionally, in natural ecosystems, plant productivity is often a function of the presence and composition of mycorrhizal associations. Yet, the effect of mycorrhizal fungi on the relationship between plant diversity and productivity has not been investigated. We predict that in the presence of AMF, productivity will saturate at lower levels of species richness because AMF increase the ability of plant species to utilize nutrient resources. In this study we manipulated old-field plant species richness in the presence and absence of two species of AMF. We found that in the absence of AMF, the relationship between plant species richness and productivity is positive and linear. However, in the presence of AMF, the relationship is positive but asymptotic, even though the maximum plant biomass was significantly different between the two AMF treatments. This is consistent with the hypothesis that AMF increase the redundancy of plant species in the productivity of plant communities, and indicates that these symbionts must be considered in future investigations of plant biodiversity and ecosystem function.


BACKGROUND
Psychological impacts among healthcare professionals have increased significantly due to the increasing number of COVID-19 cases. This study aimed to identify stress and coping strategies among healthcare professionals in Saudi Arabia during the COVID-19 outbreak.

SUBJECTS AND METHODS
A cross-sectional study online survey was conducted for health care professionals during a peak of COVID-19 from March to June 2020 at different healthcare institutions at KSA (n=342).

RESULTS
Sixty-five percent of responders often and always feel fears about infection and subsequent effects on themselves, the patient, and the family. 57% of them stated that they felt sometimes depressed mode and 47% anxiety during the outbreak. Eighty-four percent of the respondent always focusing on prevention as the first biosecurity measures such as hand-washing habits and using hand sanitizer, and 38.3% of them make sometimes relax and rest. While half of the responses (50%) sometimes had physical exercise. Also, thirty-eight percent joined sometimes community and/or group online chat groups, and 56.1% always keep contact with family and friends through social messaging or phone calls.

CONCLUSION
Understanding this topic is important for healthcare organizations, effective strategies, and programs is needed to provide holistic staff care and wellbeing during outbreaks that focus on the value of mental and emotional support.


Naringin is a plant based natural compound abundantly present in citrus fruits. Naringin has been reported for its vast range of therapeutic properties and it has been recognized as molecule of interest in treatment of various diseases. Naringin has been also investigated for its role in promoting bone development and maintenance. It has been found to promote bone formation and inhibit the bone resorption. It seems to be a potent candidate in treatment of osteoporosis. Osteoporosis is characterized by low bone mass and destruction of bone microstructure. Osteoporosis increases the risk of bone fracture. Naringin has been found effective in treatment of osteoporosis and improvement of bone health including bone mineral density and mechanical strength. In current review, the potential of naringin in treatment of osteoporosis has been reviewed. This article will provide important and concise information on therapeutic potential of naringin against osteoporosis.


Cloud computing is the long dreamed vision of computing as a utility, where data owners can remotely store their data in the cloud to enjoy on-demand high-quality applications and services from a shared pool of configurable computing resources. While data outsourcing relieves the owners of the burden of local data storage and maintenance, it also eliminates their physical control of storage dependability and security, which traditionally has been expected by both enterprises and individuals with high service-level requirements. This paper, gives a brief introduction to Cloud computing privacy issue being addressed is then introduced, by describing some of the unique factors to be considered when data enters the Cloud. Finally, a data protection scheme with public auditing scheme is outlined that will address a number of these factors, by providing a mechanism to allow for data to be encrypted in the Cloud without loss of accessibility or functionality for authorized parties. This scheme is not necessarily a replacement for traditional privacy and security measures for data, but rather an enhancement which allows users (again, at either the individual or enterprise level) a greater degree of confidence in the adoption of innovative, cost-saving Cloud computing technologies.


Dopamine is an essential and indispensable catecholamine, which acts not only as a neurotransmitter in dopaminergic and noradrenergic sympathetic neurons but also as an autocrine/paracrine substance in non-neuronal tissues. The regulatory mechanism of dopamine synthesis in neuronal tissues seems to be different from that in non-neuronal tissues. Among receptors specifically bound to dopamine, five different receptors have already been cloned. Dopamine exhibits vasodilative and natriuretic effects by stimulating specific dopamine receptors located in renal tubular cells, blood vessels, etc. Physiological effects of dopamine appear to be protective against hypertension and sodium retention. Spontaneously hypertensive rats (SHR) are known to have an enhanced dopamine generation associated with the increased sympathetic nervous activity. A defect of renal D1-receptor-mediated coupling to adenylate cyclase has also been demonstrated in SHR. On the other hand, it has been reported that Dahl salt sensitive rats exhibit defective dopamine synthesis during high salt intake, which may be a definitive abnormality in this strain. The pathophysiological role of peripheral dopamine is essential hypertensive patients is still controversial. Considering the previous studies, it seems to be the case that essential hypertensive patients with increased sympathoadrenergic activity show enhanced dopaminergic discharge where dopamine may negatively modulate high blood pressure, and that stable essential hypertensive patients with salt-sensitivity and/or suppressed renin activity show insufficient dopamine synthesis in the kidney.


A new numerical approach for consideration of quantum dynamics and calculations of the average values of quantum operators and time correlation functions in the Wigner representation of quantum statistical mechanics has been developed. The time correlation functions have been presented in the form of integrals of the Weyl's symbol of considered operators and Fourier transforms of the product of matrix elements of the dynamic propagators. For the latter functions the integral Wigner–Liouville's type equation has been derived. The initial condition for this equation has been obtained in the form of the Fourier transform of the Wiener path integral representation of the matrix elements of the propagators at initial time. The numerical procedure for solving this equation combining both molecular dynamics and Monte carlo methods has been developed. An application of the developed approach to the micro canonical ensemble has also been considered in the second part of this paper. For electrons in disordered systems of scatterers numerical results have been obtained for series of the average values of the quantum operators including position and momentum dispersions, average energy, energy distribution function as well as for the frequency dependencies of tensors of electron conductivity and permittivity according to quantum Kubo formula. Zero or very small values of the static conductivity have been considered as a manifestation of Anderson localization of electrons in the 1D case. Independent evidence of Anderson localization comes from the behaviour of the calculated time dependence of position dispersion. Nevertheless for localized electrons the energy distribution function obtained has a long exponentially decaying tail, which is the reason for the exponentially rare appearance of large values of quantum particle virtual energy that strongly affects the behaviour of the position dispersion.


BackgroundIsorhapontigenin, a resveratrol analogue, isolated from Iris domestica can induce apoptosis in tumor cells. Here, we designed to explore whether isorhapontigenin reduced inflammatory response in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells.MethodsIsorhapontigenin treated with RAW 264.7 cells, and then with LPS to stimulate inflammatory response. Proinflammatory cytokine expressions were measured using ELISA, and protein expressions were detected using western blots. ResultsIsorhapontigenin significantly inhibited the proinflammatory cytokine expressions. Isorhapontigenin also decreased cyclooxygenase-2 and inducible nitric oxide synthase productions and promoted heme oxygenase-1 expression in LPS-stimulated RAW264.7 cells. Isorhapontigenin could significantly inhibit NF-κB subunit p65 protein localization to the nucleus and reduced MAPK signal pathway activation. Isorhapontigenin also decreased reactive oxygen species production. ConclusionThus, isorhapontigenin has potential anti-inflammation and anti-oxidative stress that inhibits inflammatory mediators and cytokines expressions through suppressing the MAPK and NF-κB pathways.


Polyethylene glycol (PEG)-coated (pegylated; Stealth) liposomes are stable, long-circulating drug carriers useful for delivering doxorubicin to the sites of solid tumours. Compared with conventional liposomes, pegylated liposomes are less extensively taken up by cells of the reticuloendothelial system (RES) and have a reduced tendency to leak drug while in circulation. The pharmacokinetics of PEG-liposome encapsulated doxorubicin are characterised by an extremely long circulating half-life, slow plasma clearance and a reduced volume of distribution compared with conventional liposomal doxorubicin or free doxorubicin. The long circulation and ability of pegylated liposomes to extravasate through 'leaky' tumour vasculature results in localisation of doxorubicin in tumour tissue. In a number of animal and human tumours, including breast, prostate, pancreatic and ovarian xenografts, pegylated liposomal doxorubicin produced higher intratumoural drug concentrations and better therapeutic responses than equivalent doses of conventional (nonpegylated)-liposome encapsulated doxorubicin or free doxorubicin. Low peak plasma concentrations of free doxorubicin after administration of pegylated liposomal doxorubicin and the reduced tendency of the liposomal drug to accumulate in myocardium suggest that a reduction in cardiac toxicity compared with free doxorubicin may be observed. Thus, the rationale for the use of pegylated liposomal doxorubicin in solid tumours may be summarised as follows: change in the toxicity profile with a decrease in acute adverse effects (such as nausea and vomiting) and reduced incidence of alopecia, greater activity in highly angiogenic tumours (such as Kaposi's sarcoma) and effective treatment of tumours moderately sensitive to doxorubicin (such as breast and ovarian carcinomas), with the possibility of increased tumour response because of enhanced drug accumulation. In addition, although no comparative study yet exists, there is a suggestion from early human studies with pegylated liposomal doxorubicin that cardiotoxicity may be reduced compared with the free drug.


G protein-coupled receptors (GPCRs) are allosteric proteins that adopt inactive (R) and active (R*) conformations in equilibrium. R* is promoted by agonists or occurs spontaneously, leading to constitutive activity of the receptor. Conversely, inverse agonists promote R and decrease constitutive activity. The existence of another pharmacological entity, referred to as "protean" agonists (after Proteus, the Greek god who could change shape), was assumed on theoretical grounds. It was predicted from the existence of constitutive activity that a same ligand of this class could act either as an agonist or an inverse agonist at the same GPCR. Here, we show that proxyfan, a high-affinity histamine H3-receptor ligand, acts as a protean agonist at recombinant H3 receptors expressed in the same Chinese hamster ovary cells. In support of the physiological relevance of the process, we show that proxyfan also behaves as a protean agonist at native H3 receptors known to display constitutive activity. On neurochemical and behavioral responses in rodents and cats, proxyfan displays a spectrum of activity ranging from full agonism to full inverse agonism. Thus, protean agonism demonstrates the existence of ligand-directed active states LR* different from, and competing with, constitutively active states R* of GPCRs, and defines a pharmacological entity with important therapeutic implications.


Human trafficking is a modern/current form of slavery. It practices both at national and international level. The development of information technology (IT), communication, and transformation, brought the consequence to the more sophisticated crime method. Human trafficking has character as an extra ordinary crime, well organized, and transboundary in which it subsequently classified as Transnational Organized Crime (TOC). Based on a consideration that human trafficking is not only regarding human as victim but also could potentially threat the state finance, it has been classified as Economic Crime. In this regard, the criminal policy is very important to be endorsed in order to overcome any kind transnational and international crime which appears in globalization era. Key words : perdagangan orang (human trafficking), kebijakan kriminal (criminal policy), kejahatan ekonomi (economic crime).


Cranial Approaches -- Microneurosurgery: Principles, Applications, and Training -- Endoscopy: Principles and Techniques -- Image-Guided Radiosurgery Using the Gamma Knife -- How to Perform Surgery for Intracranial (Convexity) Meningiomas -- The "Dangerous" Intracranial Veins -- How to Perform Subfronto-Orbitonasal Approach for Anterior Cranial Base Surgery -- How to Perform Cranio-Orbital Zygomatic Approaches -- How to Perform Middle Fossa/Sphenoid Wing Approaches -- How to Perform Central Skull Base Approaches -- How to Perform Selective Extradural Anterior Clinoidectomy -- How to Perform Approaches of the Orbit -- How to Perform Transsphenoidal Approaches -- How to Perform Transoral Approaches -- How to Perform Posterior Fossa Approaches -- How to perform transpetrosal approaches -- Vascular Lesions -- Principles of Microneurosurgery for Safe and Fast Surgery -- Surgical Management of Intracranial Aneurysms of the Anterior Circulation -- Intracranial Aneurysms in the Posterior Circulation -- Giant Aneurysms -- Arteriovenous Malformations of the Brain -- Intracranial Cavernomas -- Carotid Endarterectomy -- Brain Revascularization by Extracranial-Intracranial Arterial Bypasses -- Management of Intracranial Venous Pathologies — Potential Role of Venous Stenting -- Traumas, Cerebrospinal Fluid, Infections -- The Glasgow Coma and Outcome Scales: Practical Questions and Answers -- Cranial Trauma in Adults -- Hydrocephalus in Adults (Including Normal Pressure Hydrocephalus Syndrome) -- Arachnoid Cysts -- Brain Infections -- Parasitoses of the Central Nervous System: Hydatidosis -- Parasitoses of the Central Nervous System: Cysticercosis -- Intracranial Tumors -- Classification of Brain Tumors and Corresponding Treatments -- Stereotactic Biopsies for Tumors: Indications, Limits, Diagnosis with Histopathology and other Laboratory Techniques -- Management of (Malignant) Intracranial Gliomas -- Management of Lymphomas -- Management of Anterior Fossa Lesions -- Management of Tumors of Middle Fossa -- Management of Central Skull Base Tumors -- Management of Cavernous Sinus Lesions -- Management of Convexity Meningiomas -- Meningiomas Involving the Major Dural Sinuses: Management of the Sinus Invasion -- Posterior Fossa Meningiomas -- Endoscopic Surgery for Skull Base Meningiomas -- Management of Pituitary Adenomas -- Craniopharyngiomas -- Management of Tumors of the Anterior Third and Lateral Ventricles -- Endoscopic Management of Colloid Cysts -- Management of Pineal Region Tumors -- Epidermoid/Dermoid Cysts -- Tumors of the Fourth Ventricle and Cerebellum in Adults -- Vestibular Schwannomas -- Brainstem Tumors -- Management of Foramen Magnum Tumors -- Radiosurgery for Intracranial Tumors -- Intraoperative Explorations -- Ultrasound-Guided Neurosurgery -- Brain Neuronavigation for Deep-Seated Targets -- Brain Mapping -- Intraoperative Neurophysiology in Neurosurgery -- Pediatrics -- Specificities of, and Changes in, Pediatric Neurosurgery -- Cranial Traumas in Children -- Management of Hydrocephalus in Childhood -- Intracranial Tumors in Childhood -- Nonsyndromic Craniosynostoses -- Management of Lumbosacral Lipomas -- Management of Encephaloceles -- Epilepsy Surgery in Children -- Spine -- Management of Spine Traumas and Spinal Cord Injury -- Approaches to Cervical Spine -- Management of Degenerative Disease of the Cervical Spine -- Management of Lumbar Disc Herniations and Degenerative Diseases of Lumbar Spine -- Management of Lumbar Spondylolisthesis -- Non-Traumatic Extra-Medullary Spinal Cord Compression -- Intramedullary Tumors -- Chiari Malformation -- Syringomyelia -- Infections in Spine -- Functional Neurosurgery -- Stereotactic Techniques -- Selective Thalamotomy -- Targets for Electrical Stimulation in Functional Neurosurgery -- Functional Neurosurgery for Parkinson's Disease -- Functional Neurosurgery for Dystonias -- Neurosurgical Management of Cancer Pain -- Neurosurgery for Neuropathic Pain -- Microvascular Decompression for Hemifacial Spasm -- Microvascular Decompression for Trigeminal Neuralgia -- Neurosurgery for Trigeminal Neuralgia -- Neurosurgery for Spasticity -- Selective Dorsal Rhizotomy for the Treatment of Childhood Spasticity -- State-of-the-Art of Surgical Therapies for Psychiatric Disorders: Depression -- Neurosurgery for Psychiatric Disorders: Obsessive-Compulsive Disorder -- Neurosurgical Management of Epilepsy in Adults -- Neurophysiology Applied to Neurosurgery -- Neuronal Transplantation: A Review -- Peripheral Nerves -- Management of Nerve Injuries (with Emphasis on Nerve Action Potential (NAP) Recordings) -- Tunnel Compression Syndromes of Median and Ulnar Nerves -- Tumors of the Peripheral Nerves -- Education -- Message from the Chairman of the Education and Training Committee of the WFNS -- What do Young Neurosurgeons Really Need -- The Role of the World Federation of Neurosurgical Societies in the Development of World Neurosurgery -- Epilogue.


The idea of reforming the investor-state dispute settlement system (hereinafter: ISDS) has been simmering at the international level with the EU as the most prominent proponent of a complete reconstruction of the ISDS system, and its voice was amplified by the 2018 decision of the ECJ in the Achmea case. The EU has since called for the establishment of a standing body established by means of a multilateral legal instrument investment court (hereinafter: MIC), dedicated to the resolution of treaty-based disputes within and outside of the EU. The MIC has been presented as a matter of urgency by its proponents who claim that the substantive issues in the global investment system – investor liability, the freedom of states to regulate and the interests of third affected parties - cannot be resolved under the existing framework. This proposal was met with some degree of resistance from other parts of the world, as critics find that the MIC would fix the flaws of the existing system, but that it would perpetuate the issues and tilt the scale in favor of the states. In their view, moderate and gradual reform would suffice to remove the major flaws in the existing ISDS system. Therefore, the ISDS landscape is being shaped in a battle of revolution versus evolution, which will determine whether the EU model will be adopted as the global solution, or will it remain within the boundaries of the EU. The authors give a critical overview of the rise and fall of ISDS as the preferred dispute resolution mechanism for investor claims (1), and the wave of resistance by states which prompted the global ISDS reform process (2). The paper than puts the spotlight on the EU perspective on ISDS reform, regarding intra-EU and extra-EU investor claims (3). This is followed by a discussion on the MIC which the EU is promoting as the universal replacement for the existing ISDS system (4), and the ISDS reform options developed through the UNCITRAL Working Group III (hereinafter: WG III) (5). Finally, the paper concludes with a discussion on whether the final solution could be compromise (6).


Epidemiological data suggest protection from allergic diseases when exposed to infectious agents during early stages of life. As allergies are mainly characterized as an unchecked Th2 response, modulation of the immune responses by pathogens have been considered to be a major factor in mediating the protection. Recent evidences implicate a key role staged by immuno-regulatory mechanisms induced upon infection in ameliorating these allergic disorders. A longitudinal study had demonstrated the reduced frequency and incidence of asthma in children, who had a prior infection from Salmonella typhi. A subsequent investigation demonstrated reduced airway inflammation in mice infected with Salmonella; however the mechanism still remained obscure. In this study, we aimed to delineate the potential mechanisms induced upon Salmonella typhimurium infection which resulted in the amelioration of allergic airway inflammation in mice. We report a significant increase in CD11b+ Gr1+ myeloid cell population in those mice that had been infected with Salmonella. Using in vitro and in vivo analysis we suggest that these myeloid cells could potentially ameliorate airway inflammation by affecting the stability of Th2 cells. In contrast to our initial hypothesis, regulatory T cells were not involved in the protective effect of salmonella infection.


Enhancement of reactivity of the burden in the blast furnace can decrease the reducing agent of blast furnace. Besides high reactivity coke, the carbon iron ore composite is considered to be a typical high reactivity burden that can control the thermal reserve zone temperature. Since the reactivity of biomass char is much higher than that of coke, the use of carbon iron ore composite with biomass char will be favorable for decreasing the reducing agent. In the present study the reaction and reducing behavior of the carbon iron ore composite with biomass char were investigated. The gasification rate of biomass char was measured in CO2 atmosphere, and the reaction rate equation of that was derived. The microscopic structure change of biomass during carbonization was experimentally analyzed. According to the experimental results, the reduction of the composite begins at about 550°C in an inert gas atmosphere, and it is much lower than the composite with coke. Analysis of the reaction of carbon iron ore composite was carried out with the reaction model of the carbon iron ore composite based on a lumped system, in which the reaction rate of biomass char and iron ore were installed. The reaction model shows that the biomass char can improve the reduction behavior of the carbon iron ore composite especially in the lower temperature region. Moreover, the influence of gas atmosphere and the optimum structure of the composite were investigated by the model calculation to estimate the optimum condition of the composite in the blast furnace.


Thrombosis is the principal mechanism in vascular pathology, whether cerebral, coronary or peripheral. During the initial stages of infarction, coagulation contributes to vascular occlusion, the haemostatic factors playing a determining role in the development of atherothrombotic lesions. An increase in a coagulation protein, besides any lowering of anticoagulation protein levels, is a risk factor for thrombosis. Among these pro-coagulant factors, the pro-thrombogenic action of factor VIII has without doubt been studied the least. We report the case of a 62 year old patient with a personal and family history of many previous thrombotic episodes, both arterial and venous, in whom factor VIII hyperactivity was discovered after a myocardial infarction. This case underlines the association of the factor VIII complex with thrombosis, and its clinical repercussions, especially the incidence of coronary pathology.


Compressed domain image classification aims to directly perform classification on compressive measurements generated from the single-pixel camera. While neural network approaches have achieved state-of-the-art performance, previous methods require training a dedicated network for each different measurement rate which is computationally costly. In this work, we present a general approach that endows a single neural network with multi-rate property for compressed domain classification where a single network is capable of classifying over an arbitrary number of measurements using dataset-independent fixed binary sensing patterns. We demonstrate the multi-rate neural network performance on MNIST and grayscale CIFAR-10 datasets. We also show that using the Partial Complete binary sensing matrix, the multi-rate network outperforms previous methods especially in the case of very few measurements.


A congenital lip sinus is a rare condition that has been reported to occur in both the upper and lower lips, either in isolation or in association with congenital deformities such as a cleft lip and palate in Van der Woude syndrome. The prevalence of lower lip sinuses has been estimated to be about 0.00001% of the white population. Upper lip sinuses are even more uncommon. To date, there have been several case reports of upper lip sinuses and fistulas, but no similar cases have been described in Singapore. We herein report a case of congenital upper lip sinus presenting as a recurring upper lip abscess and review the current literature on this condition.


SUVmax is currently the most common semi-quantitative method of response assessment on FDG PET. By defining the tumour volume of interest (VOI), a measure of total glycolytic volume (TGV) may be obtained. We aimed to comprehensively examine, in a phantom setting, the accuracy of TGV in reflecting actual lesion activity and to compare TGV with SUVmax for response assessment. The algorithms for VOI generation from which TGV was derived included fixed threshold techniques at 50% of maximum (MAX50), 70% of maximum (MAX70), an adaptive threshold of 50% of (maximum + background)/2 (BM50) and a semi-automated iterative region-growing algorithm, GRAB. Comparison with both actual lesion activity and response scenarios was performed. SUVmax correlated poorly with actual lesion activity (r = 0.651) and change in lesion activity (r = 0.605). In a response matrix scenario SUVmax performed poorly when all scenarios were considered, but performed well when only clinically likely scenarios were included. The TGV derived using MAX50 and MAX70 algorithms performed poorly in evaluation of lesion change. The TGV derived from BM50 and GRAB algorithms however performed extremely well in correlation with actual lesion activity (r = 0.993 and r = 0.982, respectively), change in lesion activity (r = 0.972 and r = 0.963, respectively) and in the response scenario matrix. TGVGRAB demonstrated narrow confidence bands when modelled with actual lesion activity. Measures of TGV generated by iterative algorithms such as GRAB show potential for increased sensitivity of metabolic response monitoring compared to SUVmax, which may have important implications for improved patient care.


Leeches are segmented worms that belongs to phylum Annelida and Hirudinea subclass. They are commonly found in stream water, land and sea. Leech infestation is seen in people swimming or drinking water inhabited by leech. The most common symptom of nasal leech is unilateral nasal bleeding. In this case report, a ten-year-old Chinese boy went swimming in the river in countryside prior to the incident. On examination, he was found to have a leech in his left nostril. The leech self- extruded after irrigation with 5ml of normal saline. Health workers must be aware of the possibility of a leech as the differential diagnosis for unilateral nasal bleeding, especially in a rural area where leeches are prevalent.


Background and study aim: Interstitial lung disease (ILD) includes a variety group of about 200 conditions that insult the lung parenchyma with different patterns of inflammation and fibrosis. Hepatitis C virus (HCV)is Flavivirus with diverse hepatic and extrahepatic diseases. Its direct and indirect pathogenic association with many pulmonary manifestations-including interstitial lung disease-has been suggested yet needs more elucidation.
Patients and Methods: A case control study was conducted with a total of 50 chronic hepatic patients. They were equally divided into two groups, HCV positive group (group 1= 25 patients) and HCV negative group (group 2= 25 patients). Group 1 was subdivided into two subgroups, without-idiopathic interstitial pneumonias patients (without IIPs subgroup A= 13 patients) and with idiopathic interstitial pneumonias patients (IIPs subgroup B = 12 patients). Both groups were subjected to thorough history taking, clinical examination, and routine investigations. The diagnosis of HCV was confirmed by viral markers including HCV antibodies and PCR. Other chronic hepatic liver diseases were confirmed by abdominal ultrasound and ultrasound- guided liver biopsy. Arterial blood gases, auto antibodies, Computerized pulmonary function tests and radiological studies including plain X ray chest and heart and HRCT scanning were also done. All patients with idiopathic pulmonary fibrosis (IPF) had fulfilled the ATS/ ERS diagnostic guidelines. Both groups were matched according to age, sex and body mass index.
Results: The HCV positive group was found to have a significantly higher frequency of ILD than the HCV negative group with also more restrictive pattern hypoxemia and higher scores of IPF (by computed tomography).
Conclusion: ILD is more frequent in patients with chronic HCV infection with higher grades of fibrosis and hypoxemia. HCV infection may be predisposing factor for IPF.


Exchange of private information over the public domain is very much susceptible to unauthorized access, therefore this necessitates the need for a cryptosystem to ensure the protection of information against forthcoming threats. Elliptical curve cryptography (ECC) has attracted the eyes of many scientists due to its smaller key size and high-speed operation. In this paper, an efficient hardware implementation using field programmable gate array (FPGA) on elliptical curve processor (ECP) over a prime field has been proposed. Jacobian coordinate has been used to avoid modular inversion, which is regarded as the most costly operation. To minimize the area and delay in modular multiplication, an interleaved modular multiplier has been proposed. Point doubling (PD) and point addition (PA) architecture was designed with the minimum arithmetic unit using the efficient modular multiplier algorithm. Furthermore, an efficient elliptical curve point multiplication (ECPM) module has been proposed using the high-performance PD and PA architecture. It was found that the proposed ECPM module has a minimal delay and is very area efficient and thus it has immense potentiality in its application in modern day cryptosystem.


Sand–asphalt mixtures are difficult to model, partly due to their composition and partly due to the complex interplay among their constituents. This work is concerned with the development of an anisotropic model to describe the nonlinear behaviour of sand–asphalt mixtures. A general thermodynamic framework is used, which allows for the material to have multiple natural configurations corresponding to its underlying structure. The evolution of the natural configuration takes place in a thermodynamically consistent manner. The model developed is corroborated using experimental results published by Ravindran et al. (2007a,b) on torsion tests of sand–asphalt specimens over a range of conditions.


Strawberries are listed among the functional foods. Beside their appreciated taste, they are rich in antioxidant compounds. Due to their sugars, fleshy pulp and thin skin, as well as dwarf habitus, they are exposed to various plant diseases, especially fungi. Botrytis gray mold is the most destroying pathogen, but there are other fungi that can cause losses in the field or after harvest. The aim of this study is to select some bacterial strains that could be easily formulated as biocontrol agents against various molds. These bacteria were isolated from winery semi-composted marc and analyzed through specific microbiologic methods. Based on their in vitro antagonistic activity, two bacterial isolates were selected. These strains revealed up to 84.2% inhibition of Botrytis cinerea growth, and high antifungal activity against various other fungi, such as Fusarium oxysporum, Macrophomina phaseolina and Sclerotinia sclerotiorum. Qualitative enzymatic tests, as well as microscopic analysis of the microbial interactions revealed fungal degradative enzymes produced by the bacterial strains. As the selected strains were determined to be spore producing bacteria, long term preservation is an advantage for their formulation as plant protection inoculants. Moreover, these bacteria revealed no phytotoxic activity against test plants.


Network Management Forum (NMF) has defined a set of basic business processes dealing with major TMN service management functions such as performance management, fault management, billing and service provisioning. In addition to these, a service ordering process is defined as an important interaction with the end customers requiring services. The service order process provides an integration point for all major TMN functions and business processes. This paper presents an overview analysis for the service ordering process including the process definition, object modelling and process interaction. To verify the process definition and object modelling, we built a proof of concept implementation of the Ordering specification discussed here. The focus of this implementation is to demonstrate the interface defined between different service providers in a transaction of service ordering. It implements the major concepts of the NMF Ordering process such as pre-order, negotiation, order options and service level agreements. The implementation uses the same interface specification for the two interactions in a service ordering scenario: the customer-SP interaction, the main service provider (MSP) and sub-contracted service providers (SSP) interaction. The latter interaction can be propagated in a recursive manner when a supplier requires further order from other service providers as part of the original order. The prototype is built using Java.


The development of multiplex cinemas has reinvigorated film exhibition and cinema attendance in France. Yet in the wake of the exception culturelle, multiplexes also stoked corporatist fears over the Americanization of French cinema, and in 1996 the state introduced a regulatory procedure for multiplexes modeled on the loi Royer. Regulation has not stopped subsequent multiplex development but rather protected the dominant market position of the major, vertically-integrated French exhibitors. The resultant economic concentration has undoubtedly increased the domestic and international competitiveness of French cinema, but at the price of industry polarization and a loss of cultural and economic pluralism.


The use of pharmaceutical preparations containing spores of Bacillus subtilis or other bacterial species in the treatment and prophylaxis of intestinal disorders associated with antibiotic therapy or diarrhoea of various origin is widespread and has been supported by encouraging results. However, the mechanism by which such an action is manifested in vivo is still not well defined. We carried out a study using B. subtilis spores present in a commercial preparation and treated in vitro , to mimic physiological conditions following oral consumption. Tests were carried out to evaluate the capacity of microorganisms to colonist: the surface of eukaryotic (Caco-2 and HEp-2) cells. The bacteria were assayed both in the spored phase. and following stimulation of germination by exposure to low pH values (as in the case of gastric juice) or again with exposure to high temperatures. B. subtilis adhered to the surface of the eukaryotic cells, the degree of adhesion varying in relation to the different physiological phases of the bacterial cell Keywords: Bacillus subtilis ; adhesive properties


Abstract Throughout most of the kingdom Animalia, evolutionary transitions from surface life to a life permanently bound to caves and other subterranean habitats have occurred innumerous times. Not so in tetrapods, where a mere 14 cave-obligate species—all plethodontid and proteid salamanders—are known. We discuss why cave tetrapods are so exceptional and why only salamanders have made the transition. Their evolution follows predictable and convergent, albeit independent pathways. Among the many known changes associated with transitions to subterranean life, eye degeneration, starvation resistance, and longevity are especially relevant to human biomedical research. Recently, sequences of salamander genomes have become available opening up genomic research for cave tetrapods. We discuss new genomic methods that can spur our understanding of the evolutionary mechanisms behind convergent phenotypic change, the relative roles of selective and neutral evolution, cryptic species diversity, and data relevant for conservation such as effective population size and demography.


Many factors combine to make management of wounds and wound infections in patients in intensive care units (ICUs) a complex task. An understanding of the anatomy, pathophysiology, and bacteriology provides a framework to approach these patients. The patient's underlying disease influences the care of the wound. Wound factors such as necrotic tissue, bacterial load, or presence of fistulae or a foreign body have important impact on the patient's care. With assessment and knowledge of normal healing, timely intervention in the ICU can identify patients whose wounds are not healing properly and allow for corrective interventions to help the patient return to normal function.


The strong metal–support interaction (SMSI) between the three components in Au/CeO2–Mg(OH)2 can be controlled by the relative composition of CeO2 and Mg(OH)2 and by the calcination temperature for the direct oxidative esterification of methacrolein (MACR) with methanol to methyl methacrylate (MMA). The composition ratio of CeO2 and Mg(OH)2 in the catalyst affects the catalytic performance dramatically. An Au/CeO2 catalyst without Mg(OH)2 esterified MACR to a hemiacetal species without MMA production, which confirmed that Mg(OH)2 is a prerequisite for successful oxidative esterification. When Au/Mg(OH)2 was used without CeO2, the direct oxidative esterification of MACR was successful and produced MMA, the desired product. However, the MMA selectivity was much lower (72.5%) than that with Au/CeO2–Mg(OH)2 catalysts, which have an MMA selectivity of 93.9–99.8%, depending on the relative composition of CeO2 and Mg(OH)2. In addition, depending on the calcination temperature, the crystallinity of the CeO2–Mg(OH)2 and the surface acidity/basicity can be remarkably changed. Consequently, the Au-nanoparticle-supported catalysts exhibited different MACR conversions and MMA selectivities. The catalytic behavior can be explained by the different metal–support interactions between the three components depending on the composition ratio of CeO2 and Mg(OH)2 and the calcination temperature. These differences were evidenced by X-ray diffraction, X-ray photoelectron spectroscopy, and CO2 temperature-programmed desorption. The present study provides new insights into the design of SMSI-induced supported metal catalysts for the development of multifunctional heterogeneous catalysts.


Radiation therapy has been used for more than a century, either alone or in combination with other therapeutic modalities, to treat most types of cancer. On average, radiation therapy is included in the treatment plans for over 50% of all cancer patients, and it is estimated to contribute to about 40% of curative protocols, a success rate that may reach 90%, or higher, for certain tumor types, particularly on patients diagnosed at early disease stages. A growing body of research provides solid support for the existence of bidirectional interaction between radiation exposure and the human microbiota. Radiation treatment causes quantitative and qualitative changes in the gut microbiota composition, often leading to an increased abundance of potentially hazardous or pathogenic microbes and a concomitant decrease in commensal bacteria. In turn, the resulting dysbiotic microbiota becomes an important contributor to worsen the adverse events caused in patients by the inflammatory process triggered by the radiation treatment and a significant determinant of the radiation therapy anti-tumor effectiveness. Antibiotics, which are frequently included as prophylactic agents in cancer treatment protocols to prevent patient infections, may affect the radiation/microbiota interaction through mechanisms involving both their antimicrobial activity, as a mediator of microbiota imbalances, and their dual capacity to act as pro- or anti-tumorigenic effectors and, consequently, as critical determinants of radiation therapy outcomes. In this scenario, it becomes important to introduce the use of probiotics and/or other agents that may stabilize the healthy microbiota before patients are exposed to radiation. Ultimately, newly developed methodologies may facilitate performing personalized microbiota screenings on patients before radiation therapy as an accurate way to identify which antibiotics may be used, if needed, and to inform the overall treatment planning. This review examines currently available data on these issues from the perspective of improving radiation therapy outcomes.


In the present study, an attempt has been made to develop an analytical method for the simultaneous estimation of gallic acid and embelin in marketed Ayurvedic polyherbal formulation Avipathi choornam by High Performance Liquid Chromatography (HPLC). The chromatographic separation was performed on Hemochrom C18 column (250 mm L × 4.6 mm ID column: packing size- 5 μm) with a mobile phase methanol: phosphate buffer pH 3.3 (adjusted with glacial acetic acid) in 75:25 V/V proportion at flow rate of 0.8 mL/min. The analysis was carried out in the absorbance mode at 291 nm. Gallic acid and embelin were satisfactorily resolved with Rt values at 2.36 min and 6.67 min, respectively. The developed method was found to be simple, precise and accurate and can be useful for the quality control of raw material as well as formulations containing these phytoconstituents.


This paper describes our approach for the triple scoring task at the WSDM Cup 2017. The task required participants to assign a relevance score for each pair of entities and their types in a knowledge base in order to enhance the ranking results in entity retrieval tasks. We propose an approach wherein the outputs of multiple neural network classifiers are combined using a supervised machine learning model. The experimental results showed that our proposed method achieved the best performance in one out of three measures (i.e., Kendall's tau), and performed competitively in the other two measures (i.e., accuracy and average score difference).


ABSTRACT Histone deacetylases (HDACs) catalyze the removal of acetyl groups from the ε-amino group of distinct lysine residues in the amino-terminal tail of core histones. Since the acetylation status of core histones plays a crucial role in fundamental processes in eukaryotic organisms, such as replication and regulation of transcription, recent research has focused on the enzymes responsible for the acetylation/deacetylation of core histones. Very recently, we showed that HdaA, a member of the Saccharomyces cerevisiae HDA1-type histone deacetylases, is a substantial contributor to total HDAC activity in the filamentous fungus Aspergillus nidulans. Now we demonstrate that deletion of the hdaA gene indeed results in the loss of the main activity peak and in a dramatic reduction of total HDAC activity. In contrast to its orthologs in yeast and higher eukaryotes, HdaA has strong intrinsic activity as a protein monomer when expressed as a recombinant protein in a prokaryotic expression system. In vivo, HdaA is involved in the regulation of enzymes which are of vital importance for the cellular antioxidant response in A. nidulans. Consequently, ΔhdaA strains exhibit significantly reduced growth on substrates whose catabolism generates molecules responsible for oxidative stress conditions in the fungus. Our analysis revealed that reduced expression of the fungal catalase CatB is jointly responsible for the significant growth reduction of the hdaA mutant strains.


Water quality was analyzed in three Slovenian mountain lakes (i.e., Krnsko jezero, Jezero v Ledvicah and Jezero na Planini pri Jezeru) situated in the Julian Alps, NW Slovenia. Water samples were collected monthly in the ice-free period. The water was examined from chemical, physical and biological points of view to assess the overall status of these lakes. In this paper, only a chemical aspect is reported. Water quality in remote Jezero v Ledvicah is good, while in Krnsko jezero and especially in Jezero na Planini pri Jezeru, both situated close to mountain huts, is worse.


Fusarium head blight (FHB) disease is extensively distributed worldwide. This disease 13 damages grain quality and reduces yield. The detection of this disease in a high throughput way is 14 crucial to planters and breeders. Our study focused on developing a method for processing wheat 15 color images and accurately detecting disease areas using deep learning and image processing 16 techniques. The color images of wheat at the milky stage were collected and processed to construct 17 datasets, which were used to retrain a deep convolutional neural network model using transfer 18 learning. Testing results showed that the model can detect spikes, and the coefficient of 19 determination of the number of spikes between the manual count and the detection was 0.80. The 20 model was assessed, and the mean average precision for the testing dataset was 0.9201. On the 21 basis of the results of spike detection, a new color feature was applied to obtain the gray image of 22 each spike. Then, a modified region growing algorithm was implemented to segment and detect 23 the diseased areas of each spike. Results show that the region growing algorithm performs better 24 than K-means and Otsu's method in segmenting the FHB disease. Overall, this study demonstrates 25 that deep learning techniques enable the accurate detection of FHB in wheat using color images, 26 and the proposed method can effectively detect spikes and diseased areas, thereby improving the 27 efficiency of FHB detection. 28


We construct a family of tri-atomic models for heteronuclear and homonuclear molecular Bose–Einstein condensates. We show that these new generalized models are exactly solvable through the algebraic Bethe ansatz method and derive their corresponding Bethe ansatz equations and energies.


Inherited factor VII (FVII) deficiency is the most common among the autosomal recessive rare bleeding disorders, with an estimated prevalence of 1:300,000 in European countries. Affected individuals display a wide range of clinical phenotypes, ranging from mild non spontaneous bleeding to life threatening (i.e. central nervous system[CNS] bleeding, gastrointestinal [GI] bleeding or haemarthrosis), whereas up to one-third of individuals with a FVII deficiency are asymptomatic and are mainly diagnosed during family studies or after screening for surgery. Unfortunately, the residual activity of FVII does not predict the individual propensity to bleed, and even in individuals with the same mutation, differences in clotting phenotypes can be seen. As our tertiary center serves a unique population in the Negev, we aimed at studying the prevalence and phenotype of FVII deficiency within the last decade. Methods: We searched all electronic records for the last 10 years depicting rare bleeding disorders by ICD 9 code - 2863 and compared them to the hematologic record of factor VII deficiency depicted in our lab - 50% or less activity. Patients with any record of genetic diagnosis, were compared with clinical findings. Results: The population in the Negev is estimated as 700000 people Most of them are Jewish and 150000 of them are Arab-Bedouins. We found 800 records of rare bleeding disorders (ICD 9-2863), Including 200 with FVII deficiency - 100/200 had FVII levels below 50%. Most (90%) of cases were of Jewish origin (mostly oriental Jews) and only 10% were Arab- Bedouins. Forty patients were asymptomatic with 50-30% FVII activity and 20 patients with 30-10% FVII activity were either asymptomatic or presented with mild bleeding diathesis. Out of 23 cases with lower than 10% FVII activity, 7 were symptomatic and suffered severe life threatening bleedings (2 infant died of perinatal ICH. Five families (3 Bedouin and 2 oriental Jews) were identified with severe FVII deficiencies. The 4 Bedouin patients were identified to be homozygous to unique mutation. Interestingly, most medical records depicted FVII deficiency were of women studies due to fertility problems. Conclusions: The prevalence of FVII deficiency depicted in the Negev is much higher in comparison to literature reports (200/700000) Severe FVII deficiency was found in 23: 700000, consistent with 1: 30000 prevalence. As patients are highly variable, in order to "tailor" treatments according to disease severity, new directions should be pursued to identify those with the most severe phenotypes. Disclosures Kenet:Bayer, Novo Nordisk: Other: Advisory Boards, Speakers Bureau; Opko Biologics: Consultancy, Other: Advisory Boards; BPL; Baxelta: Research Funding; Pfizer: Honoraria.


The investigation analyses how a computer based system
might best be employed to assist during the development of
the human centred aspects of consumer products.
A prototype human-computer interface is introduced and an
evaluation study is outlined which was designed to test the
following hypotheses:
1. It is possible to construct a human-computer interface
that will accommodate the sensori-input, cognitive,
and knowledge demands of industrial designers
(ergonomic novices) whilst accessing existing
ergonomic data.
2. It is possible to construct a computer based system
that will manipulate existing ergonomic data in such a
way that is relevant to the application demands of the
design development process.
Industrial designers found this tool easier to use than
traditional paper based enquiry methods as shown by
significantly reduced answer times and increased accuracy
of results. The feasibility of this tool was demonstrated
via the solving of realistic design problems.


Explanatory style refers to our habitual ways of explaining bad events. According to the reformulation of the learned helplessness model, stability and globality of explanatory style influence the extent of helplessness following bad events. However, most research involving explanatory style has been focused not on helpless behavior per se but rather on more distant consequences (like depression) ostensibly involving helplessness. In the present research, we explicitly investigated helplessness and its relationship to explanatory style. In Study One it was found that students ( n = 40) who explained bad events with stable and global causes were less likely than their more optimistic counterparts to take active steps to improve their course performance following a poor grade. In contrast, internality of explanatory style was positively correlated with active coping attempts. In Study Two it was found that young adults ( n = 72) who explained bad events with stable and global causes were less likely to take active steps to feel better when they experienced symptoms of illness. Internality of explanatory style was not significantly correlated with attempts to feel better.


A promising integral modification method to solve the correlative drawbacks of hematite photoanodes from the bulk to the surface was proposed. In this study, a new system was developed by combining Ti-doping and F-treatment in hematite nanorods, and finally modified with Co(salen) as a cocatalyst. Ti-Doping dramatically enhanced the current density owing to the increase of conductivity, while F-treatment lowered the onset potential by forming F–Ti moieties on the surface of hematite nanorods. The loading of Co(salen) on the surface of hematite nanorods as a molecular catalyst further improved the photoelectrochemical performances of both the photocurrent and the onset potential. This complex structure of F–Ti-Fe2O3/Co(salen) acquired a current density of 3.02 mA cm−2 at 1.23 V vs. RHE under illumination, which was 6 times higher than that of pristine hematite. Compared to aggregated CoOx, which was derived from thermally treated Co(salen), molecularly dispersed Co(salen) was an efficient cocatalyst because its molecular structure was fluffy, which provided more active reaction sites and promoted the water oxidation reaction kinetics.


Quasi-Z source cascaded multilevel inverter (qZS-CMI) is an emerging topology applied to photovoltaic (PV) power system. It can overcome disadvantages of conventional CMI-based PV power system, because of achieving the balanced dc-link voltage through using its boost ability, and saving one-third modules. At present, there was not literature to disclose the modelling and controller design for qZS-CMI-based three-phase grid-tie PV power system. In this study, a control scheme for three-phase qZS-CMI-based grid-tie PV power system is proposed, where distributed maximum power point tracking (MPPT) and constant dc-link peak voltage are achieved for all qZS H-bridge inverter (qZS-HBI)-based PV modules, with grid-injected power in unity power factor. The detailed controller parameter design is demonstrated by using Bode plots and the built models of qZS-HBI-based PV module and whole system. A test bench of 7-level three-phase qZS-CMI-based PV power system is built. Simulation and experimental results validate the proposed control scheme and design method.


When a beam of electric particles is passed through a sheet of matter the energy of the individual particles is reduced. The loss of energy is not the same for all the particles so that particles incident on the foil with the same energy emerge with different energies. This dispersion of the energy caused by the foil is known as the "straggling" of the particles. The straggling of α-particles has been the subject of several experimental investigations, and the theory in this case was adequately developed by Bohr in 1915. In the case of β-particles, however, the straggling was not experimentally investigated until quite recently and no theoretical treatment of the phenomenon has been given, the calculations of Bohr being, as he showed, applicable only to α-particles. The purpose of the work described in this paper is to develop a theory of the straggling of β-particles by thin foils and by means of it to interpret the results of experiment. The paper is arranged as follows. In 2 an account is given of the state of the experimental work on the subject, and in particular the effect of the complications introduced by "scattering" are considered. The formula derived by Bohr for the straggling of electric particles is given in 3 and its inapplicability to β-particles demonstrated. The present calculations of the straggling of β-particles are given in 4. The theory of the straggling of electric particles resolves itself into two parts. The first deals with the dynamics of collisions between electric particles and atoms, and is the same whether we are concerned with the straggling or some other phenomena such as ionisation of "stopping power." This may be called the fundamental theory and its requirements may be summarised in the function ϕ (Q) which express the frequency of collisions in which the electric particle loses energy of amount Q. The second part of the theory is the process of calculating the straggling by means of probability theory from the function ϕ . This may be regarded as the straggling theory proper and it is the main subject of 4. When the present calculations were started it was intended to calculate the straggling on the basis of classical theory only, the value of the function ϕ on this theory being definitely known. However, after some practice with the type of calculation involved it was decided to calculate the straggling for other forms of ϕ . From the results obtained it is possible to deduce the straggling corresponding to any form which ϕ may reasonably have, and if a new theory leads to a value of ϕ different from the classical value, the straggling on the new theory may readily be determined. Alternatively this fuller treatment may be used for the reverse process of calculating from the observed straggling the value of ϕ to which it corresponds. This is considered to be the most convenient procedure and in 5 the form of ϕ which explains the experimental results is deduced. this is compared in 6 with the value of ϕ on classical theory. A brief outline is given in 7 of certain new ideas concerning the nature of collisions of electric particles with electrons and atoms.


Recent advances in endocrine therapy have improved the prospects for estrogen receptor‐positive breast cancer. Tamoxifen is an effective drug for patients with estrogen receptor‐positive breast cancer, but the development of resistance is common. Therefore, discovering ways to enhance the sensitivity of cancer cells to tamoxifen may help improve breast cancer treatment. We studied the biological role of sirtuin 4 (SIRT4) in tamoxifen‐treated MCF7 and T47D cells. The levels of the MYC proto‐oncogene (MYC) and cyclin D1 (CCND1) were detected by western blotting and quantitative reverse transcription‐polymerase chain reaction in breast cancer cells with SIRT4 overexpression or depletion. Immunofluorescence and western blotting were used to assess the phosphorylation status of signal transducer and activator of transcription 3 (STAT3). SIRT4 overexpression decreased the half maximal inhibitory concentration of tamoxifen in MCF7 and T47D cells, while its depletion increased it. Thus, SIRT4 enhances the sensitivity of breast cancer cells to tamoxifen. Moreover, western blotting revealed decreased STAT3 phosphorylation after SIRT4 transfection. The transcription and translation of MYC and CCND1, target genes of the STAT3 pathway, were also blocked. Immunofluorescence revealed that pathway activation and nuclear STAT4 translocation were suppressed when SIRT4 was overexpressed. Furthermore, the effects of SIRT4 overexpression or depletion on proliferation could be offset by STAT3 activation or inhibition. Taken together, these results demonstrate that SIRT4 enhances the tamoxifen sensitivity of breast cancer cells by inhibiting the STAT3 signaling pathway. With this knowledge, therapeutic strategies with reduced drug resistance risk may be developed.


Objective. Positron emission tomography (PET) image reconstruction needs to be corrected for scatter in order to produce quantitatively accurate images. Scatter correction is traditionally achieved by incorporating an estimated scatter sinogram into the forward model during image reconstruction. Existing scatter estimated methods compromise between accuracy and computing time. Nowadays scatter estimation is routinely performed using single scatter simulation (SSS), which does not accurately model multiple scatter and scatter from outside the field-of-view, leading to reduced qualitative and quantitative PET reconstructed image accuracy. On the other side, Monte-Carlo (MC) methods provide a high precision, but are computationally expensive and time-consuming, even with recent progress in MC acceleration. Approach. In this work we explore the potential of deep learning (DL) for accurate scatter correction in PET imaging, accounting for all scatter coincidences. We propose a network based on a U-Net convolutional neural network architecture with 5 convolutional layers. The network takes as input the emission and computed tomography (CT)-derived attenuation factor (AF) sinograms and returns the estimated scatter sinogram. The network training was performed using MC simulated PET datasets. Multiple anthropomorphic extended cardiac-torso phantoms of two different regions (lung and pelvis) were created, considering three different body sizes and different levels of statistics. In addition, two patient datasets were used to assess the performance of the method in clinical practice. Main results. Our experiments showed that the accuracy of our method, namely DL-based scatter estimation (DLSE), was independent of the anatomical region (lungs or pelvis). They also showed that the DLSE-corrected images were similar to that reconstructed from scatter-free data and more accurate than SSS-corrected images. Significance. The proposed method is able to estimate scatter sinograms from emission and attenuation data. It has shown a better accuracy than the SSS, while being faster than MC scatter estimation methods.


In this article we consider the Freund family of distributions as a 4-manifold equipped with Fisher information as Riemannian metric and derive the induced a-geometry, that is, the a-Ricci curvature, the a-scalar curvature, and so forth. We show that the Freund manifold has a positive constant 0-scalar curvature, so geometrically it constitutes part of a sphere. We examine special cases as submanifolds and discuss their geometrical structures; via one submanifold we provide examples of neighbourhoods of the independent case for bivariate distributions having identical exponential marginals. Thus, since exponential distributions complement Poisson point processes, we obtain a means to discuss the neighbourhood of independence for random processes. Our approach using Mathematica handles the a-geometry calculations and graphics effectively and could be transferred to other distribution families.


The prevalence of gallstones and gallbladder disease was studied between October 1973 and June 1976 in Canadian Micmac Indian women aged 15 to 50 years in an inland rural community near Shubenacadie, NS. Of 132 women at risk 98 underwent cholecystography, 6 had a history of cholecystectomy (verified from hospital records) and 3 had cholecystectomy because of cholecystitis during the 3 years of the study. Of the 17 abnormal cholecystograms 10 showed radiolucent gallstones, and repeated studies documented gallstones in 6 of the 7 radiographs on which the gallbladder was not visualized. The prevalence of gallstones was found to be 211/1000, and that of gallbladder disease, 240/1000. The peak prevalence was at 30 to 39 years of age. The women with gallbladder disease were significantly more obese and of greater parity than those without gallbladder disease even when age was controlled. The Micmac Indian women of Nova Scotia appear to be at a much higher risk for the development of cholesterol gallstones and gallbladder disease than Caucasian women in Framingham, Massachusetts.


The present paper deals with the approximation properties for exponential
 functions of general Durrmeyer type operators having the weights of Sz?sz
 basis functions. Here we give explicit expressions for exponential type
 moments by means of which we establish, for the derivatives of the
 operators, the Voronovskaja formulas for functions of exponential growth and
 the corresponding weighted quantitative estimates for the remainder in
 simultaneous approximation.


Hydrogen fluoride and water can be mixed in any proportion. The resulting solutions have unique acidic properties. In particular, hydrogen fluoride undergoes a weak-to-strong acidity transition with increasing concentration of HF To supplement the knowledge already obtained on dilute or moderately concentrated solutions and gas-phase aggregates, an equimolar mixture is studied here by Car-Parrinello molecular dynamics. The natures of the ions and of the complexes formed in the equimolar liquid were determined. Specifically, H3O+, H5O2+, FH-OH2, and HF2- were spontaneously obtained while only hydronium and fluoride ions pre-exist in the equimolar crystal. The behaviour of the proton in the equimolar liquid was compared with mixtures of other proportions simulated previously in an attempt to relate proton dynamics to acidity. In the same way, the behaviour of HF2- was also examined. In this case, proton localization and transfer appeared to be driven by the fluctuating environment of the solvated ion.


NGC 4449 is an irregular galaxy with a moderately high star formation activity. The massive stars in NGC 4449 have given rise to many bright HII regions, superbubbles, supergiant shells, and "chimney-like" radial filaments. ROSAT X-ray observations of NGC 4449 have revealed four point-like sources and a wide-spread diffuse emission. The spectral properties of the diffuse component suggest that the emission originates from hot interstellar gas. We have compared deep ground-based H-alpha images with the X-ray images of NGC 4449 to determine the relationship between the hot (10^6 K) and the warm (10^4 K) components of the interstellar gas. We have also used an archival Hubble Space Telescope WFPC2 image of NGC 4449 taken through the F606W filter to examine the massive stellar content of the X-ray-emission regions. We find that hot interstellar gas exists in (1) active star forming regions, including the giant H II region CM 16, (2) probable outflows from star forming regions, and (3) the supergiant shell SGS2. The X-ray data have been used to derive the rms electron density, mass, and thermal energy of the hot interior of SGS2. Finally we discuss the origin of SGS2 and implications of the detection of diffuse X-rays in irregular galaxies.


Serotonin (5-hydroxytryptamine (5-HT)) is an important neurotransmitter and intercellular messenger regulating various gastrointestinal functions, including electrolyte transport. To date, however, no information is available with respect to its effects on the human intestinal apical anion exchanger Cl-/OH- (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{HC}\mathrm{O}_{3}^{-}\) \end{document}). The present studies were therefore undertaken to examine the direct effects of serotonin on OH- gradient-driven 4,4′-diisothiocyanato-stilbene-2, 2′-disulfonic acid-sensitive 36Cl- uptake utilizing the post-confluent transformed human intestinal epithelial cell line Caco-2. Our results demonstrate that serotonin inhibits Cl-/OH- exchange activity in Caco-2 cells via both tyrosine kinase and Ca2+-independent protein kinase Cδ-mediated pathways involving either 5-HT3 or 5-HT4 receptor subtype. The data consistent with our inference are as follows. (i) The short term treatment of cells with 5-HT (0.1 μm) for 15-60 min significantly decreased Cl-/OH- exchange (50-70%, p < 0.05). (ii) The specific agonists for 5-HT3, m-chlorophenylbiguanide, and 5-HT4, 3-(4-allylpiperazin-1-yl)-2-quinoxaline chloronitrile, mimicked the effects of serotonin. (iii) Tropisetron dual inhibitor for both the 5-HT3/4 receptor subtypes significantly blocked the inhibition, whereas specific 5-HT3 (Y-25130) or 5-HT4 receptor (RS39604) antagonist failed to block the inhibitory effects of 5-HT. (iv) The Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetra(acetoxymethyl ester) had no effect on the serotonin-induced inhibition. (v) The specific protein kinase C (PKC) inhibitors chelerythrine chloride or calphostin C completely blocked the inhibition by 5-HT. (vi) The specific inhibitor for PKCδ, rottlerin, significantly blocked the inhibition by 5-HT. (vii) The specific tyrosine kinase inhibitor, herbimycin, or Src family kinase inhibitor, PP1, abolished the 5-HT-mediated inhibition of Cl-/OH- exchange activity. (viii) 5-HT stimulated tyrosine phosphorylation of c-Src kinase and PKCδ.


Abstract The discovery of an increasing number of extrasolar planets (EPs) prompts the development of a planetary taxonomy. Such analysis, as in many other fields of research, is useful to identify groups of objects sharing similar traits. When applied to extrasolar planets, the taxonomy may provide a valid support for disentangling the role of the several physical parameters (semimajor axis, metallicity etc.) involved in the planetary formation processes and subsequent evolution. We present the state-of-the-art for exoplanets taxonomy obtained with hierarchical algorithms and the definition of robust clusters of planets (this is an update of the taxonomy published in Marchi 2007). The physical relevance of the exoplanet clusters along with their implications for the formation theories are also discussed. Finally, we comment on the future improvements of such analysis taking into account new algorithms and new input variables.


Artificial Intelligence (AI) has become one of the most frequently used terms in the technical jargon (and often in not-so-technical jargon). Recent advancements in the field of AI have certainly contributed to the AI hype, and so have numerous applications and results of using AI technology in practice. Still, just like with any other hype, the AI hype has its controversies. This paper critically examines developments in the field of AI from multiple perspectives – research, technological, social and pragmatic. Part of the controversies of the AI hype stem from the fact that people use the term AI differently, often without a deep understanding of the wider context in which AI as a field has been developing since its inception in Mid 1950s.


An ecologically representative, well‐connected, and effectively managed system of marine protected areas (MPAs) has positive ecological and environmental effects as well as social and economic benefits. Although progress in expanding the coverage of MPAs has been made, the application of management tools has not yet been implemented in most of these areas. In this work, distribution models were applied to nine benthic habitats on a Mediterranean seamount within an MPA for conservation purposes. Benthic habitat occurrences were identified from 55 remotely operated vehicle (ROV) transects, at depths from 76 to 700 m, and data derived from multibeam bathymetry. Generalized additive models (GAMs) were applied to link the presence of each benthic habitat to local environmental proxies (depth, slope, backscatter, aspect, and bathymetric position index, BPI). The main environmental drivers of habitat distribution were depth, slope, and BPI. Based on this result, five different geomorphological areas were distinguished. A full coverage map indicating the potential benthic habitat distribution on the seamount was obtained to inform spatial management. The distribution of those habitats identified as vulnerable marine ecosystems (VMEs) was used to make recommendations on zonation for developing the management plan of the MPA. This process reveals itself as an appropriate methodological approach that can be developed in other areas of the Natura 2000 marine network.


Based on the idea of "from multiple steady states to oscillation", a proposal for predicting the existence of inverted Hopf bifurcation is put forward and confirmed with a model of modified "Brusselator".


Palaeomagnetic data from the Lhasa, Qiangtang and Kunlun Terranes of the Tibetan Plateau are used with data from stable Eurasia, eastern China and Indochina, to test different models of crustal thickening in the Tibetan Plateau, to attempt a Carboniferous palaeogeographic reconstruction, and to calculate the relative motion between the South China Block and the Indochina Block. The data suggest that since the onset of the India—Eurasia collision, the Lhasa Terrane has moved 2000 + 800 km north with respect to stable Eurasia. This indicates that strong internal defomation must have taken place in southern Eurasia since the collision, and thus challenges the model of large-scale underthrusting of the Indian subcontinent beneath the Tibetan Plateau as the mechanism for crustal thickening in Tibet. Palaeomagnetic results from the Kunlun Terrane show that it was at 22° south latitude during the Carboniferous. A Carboniferous reconstruction is presented in which the Kunlun and Qiangtang Terranes, several Indochina terranes, and the North and South China Blocks are grouped together. These units of continental crust all share the specific tropical and subtropical Cathaysian flora, and the group is therefore called the Cathaysian composite continent. To test the model of propagating extrusion tectonics, we have used newly available palaeomagnetic results from South China and Indochina to calculate probable displacements. This exercise suggests a rotation of about 8° of Indochina with respect to the South China Block that is smaller than the predicted rotation of 40°, A large eastward translation of the South China Block relative to the Indochina Block of about 1500 km is consistent with the palaeomagnetic data.


In Multiple myeloma (MM), abnormal plasma cells accumulate in the bone marrow and spread to new bone sites. However, the mechanisms underlying this spread of MM cells remain unclear. Runx2 is a bone specific transcription factor upregulated in various human tumors, including MM. Our studies have previously demonstrated that Runx2 is a major driver of MM progression in bone. In the present study, our goal was to identify miRNAs targeting Runx2 to reduce tumor growth and dissemination of MM to new bone sites and asses their therapeutic potential. Expression analysis of a panel of miRNA9s regulating Runx2 revealed an inverse relationship between Runx2 expression and two miRNAs: miR-342 and miR-363. miRNA expression analysis using the Gene Expression Omnibus database showed that miR-342 and miR-363 are highly expressed in plasma cells of normal donors (n= 3), while Runx2 is detected at very low levels. In contrast, MM cells of patients with newly diagnosed (n=23) and relapsed MM (n=17) expressed very little miR-342 and miR-363 but showed high levels of Runx2 expression. Reconstituting CAG human MM cells with synthetic miR-342, miR-363 or miR-342+miR-363 in combination reduced the expression of Runx2 and the metastasis-promoting Runx2 target genes RANKL, DKK1 and DMP1. Tumor cell viability and migration were also decreased compared to control in vitro. We then transfected miR-342, miR-363 or miR-342+miR-363 in mouse 5TGM1 MM cells expressing high levels of Runx2 and tested bone-homing and growth in syngenic C57Bl/KaLwRij mice by intravenous injection. Mouse sera were collected at week 2 and 4 after tumor cell injection and the levels of IgG2bκ, a marker of 5TGM1 cells, were measured by ELISA. The results showed significantly decreased IgG2bκ levels in mice bearing miR-342 or miR-363 transfected tumors compared to mice bearing control miR-scramble tumors. Additionally, miR-342+miR-363 co-transfection produced a synergistic effect on reducing tumor growth. Mechanistic studies demonstrated that miR-342 and miR-363 induced Runx2 suppression, results in inhibition of Runx2-downstream signaling pathways Akt/β-catenin/survivin, which are required for MM tumor progression. In conclusion, we have identified two novel miRNAs, miR-342 and miR-363, that negatively regulate Runx2 expression in MM cells. We further demonstrated that enhanced expression of miR-342 or miR-363 in MM cells inhibits MM growth in vivo. Thus, miR-342 and miR-363 are potential novel markers of MM prognosis and can be developed as new therapeutic drugs for MM treatment. Citation Format: Pramod S. Gowda, Mohammad Q. Hassan, Timothy N. Trotter, Yang Yang. Targeting myeloma cell-derived runx2 by miRNAs suppresses multiple myeloma growth and progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2525. doi:10.1158/1538-7445.AM2017-2525


Wind power represents a growing proportion of generation capacity around the world. As wind power has increased, it has been important to accurately model the behaviour of wind turbines in order to understand their impact on the power system. This paper presents a model of a multi-megawatt induction machine wind turbine equipped with a full power converter. This model is implemented in Matlab-Simulink and is designed to be appropriate for power system studies whilst including representation of all major electrical, mechanical and aerodynamic subsystems. The increasing proportion of wind power in the power system has led to concern over frequency regulation and how wind plants will regulate active power. The model presented here is used to simulate both high and low frequency excursions and to demonstrate that wind turbines can be controlled to provide rapid response. Alternative approaches to providing system reserve, in the presence of a fluctuating resource, are discussed and consideration is given to the firmness of response and the level of the spilt wind.