Recent biomarker research focuses on early immunological changes to predict treatment response to immune checkpoint inhibitors (ICI). Within this prospective ST-ICI trial, pre-planned biomarker analysis was performed and we developed a flow cytometry-based whole-blood prognostic immune signature (FCBPS) to predict overall survival (OS) benefit of cancer patients treated with ICI. For this, fifty-four immune cell subsets were analyzed in the patients peripheral blood before the second administration of the ICI. Patients were randomly allocated to a training and validation cohort. Univariate Cox proportional hazards regression analysis and LASSO Cox model were used to develop a predictive and prognostic signature. 104 patients were prospectively enrolled. 89 patients provided blood samples. The identified FCBPS signature bases on five immune cell subtypes: neutrophils, plasmacytoid dendritic cells (pDCs), natural killer (NK)T cells (CD56+/CD16+), monocytes (CD14high) and CD8+ T cells (PD-1+). This signature achieved a high accuracy (C-index 0.74 vs 0.71) for predicting OS benefit in the training and validation cohort. Both in the training and validation cohort, the low-risk group had significantly longer OS than the high-risk group (HR 0.26, 95% CI: 0.12-0.56, p=0.00025; HR 0.30, 95% CI: 0.10 -0.91, p=0.024, respectively). In the whole cohort, FCBPS is a predictor of OS (HROS=0.28, 95% CI: 0.15-0.52) and progression-free survival (HRPFS=0.22, 95% CI: 0.12-0.39) that remained independent in multivariate analyses and subgroup analyses after adjusting for clinical and pathological factors. The identified flow cytometry-based whole-blood prognostic signature (FCBPS) is a powerful predictor for metastatic cancer patients who benefit from ICI treatment.


Introduction: c-Myc is a master transcription factor and one of the most frequently altered genes across a vast array of human cancers including diffuse large B-cell lymphoma (DLBCL), and is thus an attractive therapeutic target . However, no direct inhibitor of c-Myc has been successfully developed for the treatment of any cancer. The c-Myc protein has a short half-life of less than 30 minutes , and the complex secondary structures in the 59 untranslated region (UTR) of MYC mRNA make its translation highly dependent on the eukaryotic translation initiation factor 4F (eIF4F) . eIF4F exists as a complex comprised of the eIF4E, eIF4A, and eIF4G subunits. eIF4E can be sequestered by 4E-BP1, which acts as a "brake" for initiation of mRNA translation . Hyper-phosphorylation of 4E-BP1, caused by upstream signals such as mTORC1, leads to release of eIF4E from 4E-BP1, assembly of the eIF4F complex, and robust mRNA translation. Surprisingly, neither FDA approved mTORC1 inhibitors nor the investigational mTORC1/mTORC2 inhibitor MLN0128 has demonstrated adequate activity in aggressive lymphoma. The therapeutic effects of mTOR inhibition in c-Myc driven aggressive lymphoma remain poorly understood. Recognizing phosphoinositide 3-kinase (PI3K) and the proteasome pathway are both involved in activating mTOR, we hypothesized that co-targeting the PI3K and proteasome pathways might synergistically inhibit translation of c-Myc. Since both PI3K and proteasome are proven drug targets in blood cancer, such co-targeting strategy may be expeditiously studied in clinical trials for c-Myc driven aggressive lymphoma. Methods: Cytotoxicity was studied in lymphoma cell lines and primary lymphoma cells using Cell TiterGlo (Promega®). The Bliss additivism model was used to determine the expected inhibition of cell growth and the excess over Bliss (EOB) values. EOB values above 0 indicate synergy, with higher values indicating higher levels of synergy. Expression of c-Myc was investigated at the translation and transcription levels, using a combination of Western blot, qPCR, and a bi-cistronic luciferase reporter we developed to study cap dependent translation. Gene expression profiling (GEP) studies were conducted using RNAseq, and analyzed by the Fisher t-test and running enrichment score (RES) between different treatment groups. Mechanisms of synergy were determined through interrogating the effects of small molecule inhibitors and shRNA targeting regulators of various regulators of 4E-BP1. Structural studies of TGR-1202 were performed by in silico docking, and validated by synthesis of novel analogs of TGR-1202. Activity of TGR-1202 on CK1 epsilon was studied by kinome profiling (Reaction Biology®), cell free kinase assay of CK1e (Promega®), and cell based assay of CK1e autophosphorylation. Results: We found that a novel PI3K delta isoform inhibitor TGR-1202, but not the approved PI3Kd inhibitor idelalisib, was highly synergistic with the proteasome inhibitor carfilzomib in lymphoma, leukemia, and myeloma cell lines and primary lymphoma and leukemia cells (Figure 1). TGR-1202 and carfilzomib (TC) synergistically inhibited phosphorylation of eIF4E-binding protein 1 (4E-BP1), leading to suppression of c-Myc translation and silencing of c-Myc dependent transcription (Figure 2). Furthermore, the synergistic cytotoxicity of TC was rescued by overexpression of eIF4E or c-Myc. TGR-1202, but not other PI3Kd inhibitors, was active against casein kinase-1 (CK1) epsilon (Figure 3). Targeting CK1e using a selective chemical inhibitor or shRNA complements the effects of idelalisib, as a single agent or in combination with carfilzomib, in repressing phosphorylation of 4E-BP1 and the protein level of c-Myc. Conclusion: These results suggest that TGR-1202 is a first-in-class dual PI3Kd/CK1e inhibitor, which may in part explain the preliminary clinical activity of TGR-1202 in aggressive lymphoma not found with idelalisib. Targeting CK1e should become an integral part of therapeutic strategies targeting translation of oncogenes such as c-Myc. Disclosures Lentzsch:BMS: Consultancy; Foundation One: Consultancy; Celgene: Consultancy, Honoraria. O9Connor:Seattle Genetics: Research Funding; Mundipharma: Membership on an entity9s Board of Directors or advisory committees; Seattle Genetics: Research Funding; Spectrum: Research Funding; Spectrum: Research Funding; Mundipharma: Membership on an entity9s Board of Directors or advisory committees; TG Therapeutics: Research Funding; TG Therapeutics: Research Funding; Bristol Myers Squibb: Research Funding; Bristol Myers Squibb: Research Funding; Celgene: Research Funding; Celgene: Research Funding.


Domestic criminal law is the law of a particular political community; it speaks in the voice of that community, about wrongs that count as "public" wrongs in the context of that community's civic life. However, can we understand international criminal law in similar terms, as the law of a specifiable political community? We cannot plausibly talk of "humanity" as a political community whose law international criminal law could be, but if we instead, and more plausibly, talk of the "community of nations," it is not clear what it would mean to portray international criminal law as the law of that community. It might be argued that this just shows it to be a mistake to try to connect criminal law to political community in this way: in response to that kind of criticism, I explore two ways in which we can try to explain the normative force of international criminal law in terms of an idea (or ideal) of political community.


BACKGROUND
Our aim was to determined the change of serum hepatocyte growth factorl scatter factor (HGF) before and after transarterial embolization (TAE) for renal cell carcinoma (RCC).

MATERIALS AND METHODS
We examined serum HGF levels in two patients.

RESULTS
Serum HGF levels rapidly increased to six-fold higher levels immediately after heparin-injection even before embolization. Serum HGF then decreased to below 1.0 ng/ml at 6 hours after the procedure. The second peak (a two-fold increase) appeared 1-3 days after TACE. The first increase may have been due to the injection of heparin which releases HGF from the cell-surface and extracellular matrix. HGF is a pleiotropic cytokine which has a potential to enhance cell motility and angiogenesis related to tumor progression and the first larger elevation of serum HGF is enough to make a physiological effects.

CONCLUSION
Therefore, we should remind the physiological influence of heparin injection not only to prevent of clotting.


Residues of four herbicides and a new experimental material (in two forms and three doses) was evaluated with six grasses involving five different species. Studies were conducted in the greenhouse by sampling soil from two different depths after one year of her bicidal application. The differences were found to be significant both for herbicides and for soil depths, for germination percentage and seedling growth. The grass species also responded differentially to the herbicidal residues. Even within species, the different cultivars of Kentucky bluegrass responded differently to herbicidal residues.


The invention relates to a method for manufacturing a three-dimensional flow enclosed-type impeller inter-impeller passage and a special clamp thereof. A specially designed and manufactured molding or quasi-molding tool cathode is used for numerical control electrolytic processing to remove most remainder, then a specially designed and manufactured molding or quasi-molding tool electrode is used for numerical control electric spark precision processing to achieve the design requirement, thereby the three-dimensional flow enclosed-type impeller inter-impeller passage that can not be processed resulting from interference of numerical control milling cutter and undercutting can be manufactured, besides, the method has the technical and economical characteristics of high precision and efficiency, and low cost compared with the prior three manufacturing methods of integral casting, divided processing rewelding and numerical control milling.


Hydraulic and hydrologic analysis in urban catchments is typically accompanied by a number of uncertainties, such as a lack of required information for modeling purposes or complex loops inside a drainage network. In this article, Gibbs' stochastic network model is utilized in order to achieve a dendritic network that corresponds to a fully looped network in terms of the peak of the runoff hydrograph at the outlet. A synthetic catchment with a drainage network composed of 8 × 8 grids is introduced to investigate the behavior of a fully looped network for a given rainfall event using the Storm Water Management Model. Dendritic networks are generated from the Gibbsian model for a given value of the parameter, β. The results showed that the shape of the hydrograph and the peak flow of a fully looped network are heavily dependent on the catchment slope. Moreover, the results showed that it is possible to find the corresponding dendritic networks generated by the Gibbsian model that match the fully looped network depending on the catchment slope in terms of peak flows. The results of this study imply the potential improvement of drainage network analysis providing a relationship between the catchment slope of a fully looped network and the corresponding dendritic network generated by the Gibbsian model.


Organic Light ‐ Emitting Diode (OLED) displays are characterized by ultra‐thin, ultra‐clear, spontaneous light, high definition, low cost of preparation and flexible display. In recent years, flexible OLED has become a hot topic in flat panel display industry. Thin film encapsulation (TFE) plays a key role in flexible OLED [1,2].


Introduction:
 The National Institutes of Health Stroke Scale (NIHSS) scores are often not readily available in structured claims databases. We have previously demonstrated that a machine learning model can be used to determine proxies for NIHSS scores. Our current work focuses on creating a model applicable across different databases to validate our approach and enable further outcome studies.

 Methods:
 We identified 1,415 eligible hospital-admitted patients in the Optum® de-identified Integrated Claims-EMR database who were diagnosed with ischemic or hemorrhagic stroke, or a transient ischemic attack and had NIHSS scores in medical notes. These patients were split into a training (N=1,192) set for model development and a hold-out test (N=223) set to evaluate model performance. Furthermore, model performance was externally validated using the 286 eligible stroke patients in IBM's Claims-EMR database (CED). Potential predictors for stroke severity included relevant procedures, diagnoses, patient demographics, and information about the patient hospital stay.

 Results:
 The optimal model, a random forest model, achieved a coefficient of determination (R
 2
 ) between the actual and predicted NIHSS scores in the hold-out Optum dataset of 0.48 and of 0.42 in the secondary CED dataset. The final model incorporated a total of 47 predictors. The strongest predictors included transient ischemic attack diagnosis, length of hospital stay, critical care procedures, patient age, and hemiplegia diagnosis.

 Conclusion:
 This study shows that machine learning can be used to determine proxies for NIHSS scores across different real-world databases. Ultimately, this will enable large claims-based outcome studies involving stroke severity to improve our understanding of how stroke severity affects healthcare utilization, total cost of care, and the financial impact on the larger community.


Basic issues in the conceptualization and measurement of cognitive maps are discussed and explored with the aid of an empirical study. Results indicate several advantages for using cognitive measures to describe the physical separation of retail locations.


In 3D massive MIMO (multiple-input multiple-output) systems, especially in time division duplex (TDD) mode, a base station (BS) relies on the uplink sounding signals from mobile stations to obtain the spatial information for downlink MIMO processing. Accordingly, multi-dimensional parameter estimation of MIMO channel becomes crucial for such systems to realize the predicted capacity gains. In this paper, we study the joint estimation of elevation and azimuth angles as well as the delay parameters for 3D massive MIMO orthogonal frequency division multiplexing (OFDM) systems under a parametric channel modeling. To be specific, we introduce a matrix-based joint parameter estimation method, and analytically characterize its performance for massive MIMO OFDM systems. Results show that antenna array configuration at the BS plays a critical role in determining the underlying channel estimation performance, and the characterized MSEs match well with the simulated ones. Also, the parametric channel estimation outperforms the MMSE-based channel estimation in terms of the correlation between the estimated channel and the real channel.


Abstract : The goal of this project is to specify how anti-angiogenic approaches can be effectively applied to NF1 tumors. Invivo and in vitro models were used to firmly conclude that Nf1 haploinsufficiency in endothelial cells results inexaggerated proliferation and angiogenesis in response to key pro-angiogenic factors. Results implicate these growthfactor pathways as potential targets for therapeutic agents. In addition, endostatin was found to be a potent inhibitorof Nf1+/- endothelial cell migration in vitro, suggesting endostatin may be an effective antiangiogenic agent forreducing NF1 tumor growth. Two intraneural xenograft models of NF1 peripheral nerve sheath tumors weredeveloped and characterized. Tumor growth and vascularity of NF1 tumor xenografts was quantified by advancedMRI, gadolinium permeability and dynamic contrast enhancement that match results obtained by conventionalhistological measurements. Several methods to deliver endostatin in vivo were tested and several difficulties wereencountered. Finally, cell factories made by alginate-encapsulation of 293 cells transfected with AAV-endostatinwere developed and are being refined to deliver consistent, high-dose systemic levels of endostatin. The effects ofsystemic endostatin on NF1 xenograft tumor growth will be completed in a no-cost extension of this project.


The second of a two-part "handbook" — the first has been simultaneously posted on author's SSRN page — this pithy article details the potential defenses available to financial institutions and the issues that all parties should be prepared to address when proposing or rebuffing a claim predicated on a violation of § 1693e of the Electronic Funds Transfer Act of 1978 ("EFTA"). The overview article outlined the general scheme governing electronic fund (or funds) transfers established by the EFTA, a statute passed as part of the Consumer Credit Protection Act, and then turned its attention to § 1693e, the lone EFTA section to deal with pre-authorized EFTs. This follow-up provides real-world instruction as to how courts and counsel can navigate a § 1693e claim and pinpoints six pressing issues too often — and too unwisely — overlooked in a case's infancy.


This paper describes the theoretical development and implementation issues of a far field induced drag extraction tool based on the Maskell integral. Far field methods provide an alternative to classical near field approach, offering the possibility of decompose drag contributions based on their physical source and improves prediction accuracy on coarse meshes. Instead of classical triangulation of intersection nodes contained in the cutting plane, a more regular adaptive mesh is implemented in order to improve flow reconstruction smoothness and accuracy. Both meshes results are compared and the influence of generation parameters of the bidimensional adaptive mesh is discussed. Numerical diffusion plays a major role in vortex decay, and because of that phenomena, a correction factor is needed in order to back as much as possible the cutting plane without loosing precision. Finally, Onera M6 tests are conducted, showing acceptable precision in drag prediction until seven or more chords downstream.


Static headspace gas chromatography (HS-GC) has been widely used for analysis of residual solvents in pharmaceuticals (1–3). In closed headspace vials, the sample mixture is composed of sample diluents (also called sample solvents ), samples, and analyte solvents that are to be tested. The analyte solvents are dissolved in the sample mixtures (the liquid phase) before partitioning into the gas phase. The peak response of a solvent is directly proportional to its gas phase concentration, which is dependent on its initial concentration in the liquid phase, and eventually dependent on its concentration in the sample. Many factors can affect the partitioning processes of solvents (4,5). Adjusting diluents by adding water to organic solutions to increase peak responses for nonpolar solvents and by adding inorganic salts to aqueous solutions to increase peak responses for polar solvents have been reported The effects of several diluents on peak responses of some residual solvents have also been reported Sample matrices also have impacts on solvent peak responses. The effects of sample matrices on some residual solvents have been studied The counts of hydrogen (H) bond acceptors and donors in compounds have been used to explain the causes of matrix effects. However, the principles of diluent effects and matrix effects on residual solvents analyzed with HS-GC are still not clear. The effects of sample diluents, including Dimethyl sulfoxide (DMS), N,N-dimethylacetamide (DMA), and N,N-dimethylformamide (DMF), and the effects of sample matrices of a drug substance on 16 residual analyte solvents were studied using static headspace gas chromatography (HS-GC). The results showed that analyte solvents with polarities higher than those diluents had higher peak responses in DMA or DMF than they had in DMS, and vice versa. From DMS Two-dimensional liquid chromatography (2D-LC) separations can pose troubleshooting challenges not normally encountered in conventional high performance liquid chromatography (HPLC) separations. A common problem encountered in the development of 2D-LC methods is that the first dimension mobile phase properties can negatively affect the quality of subsequent second dimension separations. In this instalment the origin of this problem and potential solutions are discussed. Mass spectrometry (MS), often termed mass selective detection , is the most powerful detector available for gas chromatography (GC). Multidimensional mass spectrometry (MS/MS) takes mass selective detection to another level on benchtop systems, offering both universal and selective detection along with low detection limits. In this instalment of "GC Connections", we review the fundamentals of MS/MS and how they relate to MS as a detector for GC. We see how using full-scan analyses can make the detector universal and how by using selected ion monitoring and multiple reaction monitoring the detector can be so selective and noise-free that femtogram quantitative analysis is commonplace. We then examine some scenarios that should lead analysts to consider using GC–MS/MS to solve complex problems. High sensitivity and selectivity are detectors chromatography coupled is a powerful coupling of the selectivity of GC with the high sensitivity and option of universal or selective detection of MS. Traditional GC–MS provides multiple dimensions of separations and low detection limits in benchtop or smaller instruments. The The for completed methods. Any of the transitions can be used with one for quantitation and additional transitions for confirmation. Selectivity is generated Metal-organic frameworks (MOFs) are coordination networks consisting of a metal ion linked with organic ligands. The resulting three-dimensional structures create pores that can be exploited for a number of chemical processes, including analytical extractions. The resulting sorbent-based extraction systems have several advantages, notably selectivity. The use of MOF in extraction has exploded in the last two or three years. In this article, we take a look at the current state of the art regarding analytical extractions utilizing MOF, including a description of what MOF are, their preparation, principles of use, advantages, and application areas. The field of sample preparation analytical extractions


Increasingly students of all ages should be engaged in science, engineering and computational activities as it is used across an increasing amount of subject areas. Inquiry-based elementary science education provides students with some opportunities to engage in authentic science but the subject area expertise required by teachers can be daunting and time consuming. Currently engineering education professionals are looking for opportunities to positively influence elementary (STEM) experience but the school curriculum demands limit their opportunity to expose students to the benefits of engineering problem solving. Through professional development we have instituted some graphic-based modeling techniques that support and extend current inquiry science curriculum activities and leverage the engineering design cycle. Research and findings done as part of a two-year NSF-supported project in elementary education will be presented, demonstrating how modeling activities in the form of student-produced drawings and notebook entries have been used to help explore scientific and mathematical concepts underlying engineering problems. Specifically, kit-based science and technology education activities that actively support engineering problem-based learning are used as a context for exploring the potential of these graphic-based modeling activities.


In previous works, ultrasonic emulsification was realized using small microchannel devices oscillated by piezoelectric transducers. By using the devices, the emulsification in the flow process was also realized. In these devices, the driving frequency was higher than 2 MHz. This value is higher than the maximum audible field. On the other hand, the frequency is too high to utilize the cavitation effect. This is because the cavitation threshold depends on the frequency. The aim of this study is to confirm the cavitation state in the microchannel device using a piezoelectric polymer sensor. A micropatterned cavitation detection sensor has been fabricated by a photolithography technique and evaluated in a high-intensity ultrasound field. The emulsification state in the microchannel device has been evaluated using the fabricated sensor.


Abstract Environmental problem has become a popular research area. Efforts are being made at an international level for creating a sustainable environment. Hospitality industry is considered to be one of the main industries of a country. It makes contributions in the development of sustainable environment. Hospitality industry is adopting environmental certifications and green hotels concept rapidly. In this research, we performed bibliometric analysis of 49 articles on the topic of importance of environmental certificates for green hotels. Results indicate that majority of the journals have articles with a large number of citations, which indicates that they are high-quality journals. The results indicate that Cornell University, Polytechnic University of Valencia, Hong Kong Polytechnic University, and George Washington University are the institutes producing high-quality research work, as 28% of the researchers cited the articles published by the researchers of these universities. Results indicate that universities of Spain and USA are the largest contributors, as they have published 52% the total articles in the area under this study. USA and Spain are considered to be the world superpowers; their interest in this area of research unveils the importance of the topic. The authors Verma, Chan, and Rivera are the core researchers of this area, as they published 20% of the overall articles discussed in this study, which makes them the gurus of the research area.


Use soil as a contrast,and we study the effects of different substrates on the yield and quality of flavor No.4 melon.The result show that the yield of flavor No.4 melon planted on substrate was higher than which planted on the soil,and increased by 35.4%,25.1% and 21.8% respectively on three substrates.The quality of flavor No.4 melon planted on substrate was better than which planted on the soil.


Background: Congenital muscular torticollis (CMT) is the third most common congenital musculoskeletal anomaly in children. After the age of one year functional and cosmetic benefits require corrective surgery. Neglected congenital torticollis is commoner in developing countries. The purpose of this study was to evaluate the results of bipolar release in this age group . Methods: 16 cases were operated on for neglected congenital muscular torticollis. Inclusion criteria included age of more than ten years, absence of any previous surgery, and absence of any known pathology. Inferior release was done through an incision 1 cm above the medial third of the clavicle. The clavicular head was released completely while the sternal head was lengthened by z-plasty. The mastoid head was released though an incision just below the tip of the mastoid process. The postoperative management included physiotherapy with halter traction. Neck ROM, head tilt, craniofacial asymmetry were assessed. Results: Excellent results were noted in four patients, good in eight, fair in two, and poor in two . Conclusions: We believe that bipolar release is a very viable option for correcting neglected CMT as it brought about both functional improvement as well as improvement in cosmesis, resulting in improved quality of life .


Claude Levi-Strauss is a representative anthropologist who criticized severely the eurocentrism. It is the purpose of this study to examine the conception of culture in Claude Levi-Strauss. For this purpose we set out, first of all, from the consideration on the racism as well as the ethnocentrism which gave rise to a wholescale genocide. Then we inquire into cultural relativity. Cultural relativism confines itself to starting that a culture possesses no absolute criteria authorizing it to apply this distinction to the products of another culture. Third, we investigate the importance of intercultural cooperation and diversity of culture. In conclusion, we reflect on the implication of his thought on culture in the reality of our contemporary culture globalization.


The act of completed suicide is a complex phenomenon associated with numerous identified individual and combined risk factors. Mental illness and related disorders confer among the highest risks of completed suicide and have consequently been targeted through pharmacological interventions. However, psychotropic medications and their possible effects on completed suicide have proved notoriously difficult to study. Nonetheless, it is of great importance to further investigate these classes of medications and their role in the suicidal process. The thesis focuses on toxicological verification of psychotropic medication among individuals who have committed suicide or died of other causes in Sweden. We have investigated the potential role of selective serotonin re-uptake inhibitors in the choice of suicide method and demonstrated the level of adherence to and recreational use of the most commonly prescribed non-addictive psychotropic medications in the Swedish population. In yet-to-be-published Study III, we have examined purchasing patterns for psychotropic medications during the year prior to death, as well as the impact of the level of medication adherence upon the risk of completed suicide. All studies are based on Swedish national registry data from a period of nearly ten years (2005-2014). Full coverage on dispensed prescriptions, results of medico-legal autopsies, causes of death and diagnoses from inpatient care have been used to operationalize investigated exposures and outcomes and facilitate adjustments for confounders in two case-control studies and one methodological study. By the use of the prescription-based algorithm PRE2DUP, purchases of psychotropic medications and calculated lengths of use were compared with forensic-toxicological findings as a measure of adherence. Logistic regression and Cohen's kappa have been the principal statistical methods used. A new measure of continued need of treatment – the dispensation ratio (the ratio of initiated and discontinued prescriptions) – was also developed. Two of the main findings are that selective serotonin re-uptake inhibitors are associated with violent completed suicide during early treatment among elderly subjects and that presence of other substances (including other medications and illegal drugs) is an important confounder of associations between treatment with selective serotonin re-uptake inhibitors and choice of suicide method. Overall, rates of adherence in the Swedish general population to psychotropic medication, as reflected by therapeutic blood concentrations at forensic autopsy, are good. Biochemically verified incomplete adherence to antipsychotics, as shown in Study III, is associated with a markedly increased risk of completed suicide. The corresponding effect size for antidepressants was shown to be smaller and no longer statistically significant after adjustments for the dispensation ratio. Forensic-toxicological data are largely conservative biochemically verified measures of the possible impact of psychotropic medication upon the risk of death. By combining such data with national registry data, we have revealed findings of great importance to further suicide prevention and, at the same time, demonstrated a public-health-oriented application of results from medico-legal autopsies, beyond their immediate use in forensic investigations. LIST OF SCIENTIFIC PAPERS I. Jonas Forsman, Thomas Masterman, Johan Ahlner, Göran Isacsson, Anna Hedström. Selective serotonin re-uptake inhibitors and the risk of violent suicide: a nationwide postmortem study. Eur J Clin Pharmacol 2018; doi: 10.1007/s00228-018-2586-2 (e-publication ahead of print) II. Jonas Forsman, Heidi Taipale, Thomas Masterman, Jari Tiihonen, Anti Tanskanen. Comparison of dispensed medications and forensic‐toxicological findings to assess pharmacotherapy in the Swedish population 2006 to 2013. Pharmacoepidemiol Drug Saf 2018; 27:1112-1122. III. Jonas Forsman, Heidi Taipale, Thomas Masterman, Jari Tiihonen, Anti Tanskanen. Adherence to psychotropic medication in completed suicide in Sweden 2006-2013: a forensic-toxicological matched case-control study. (manuscript submitted for publication).


Deep learning provides appropriate mechanisms to predict vessel trajectories for safer and efficient shipping, but still existing models are mainly oriented to longer-term prediction trends and do not fully support real time navigation needs. While most recent works have been largely exploiting Automatic Identification System (AIS), the complete semantics of these data haven't so far fully exploited. The research presented in this paper introduced an extended sequence-to-sequence model using AIS data. A Gated Recurrent Unit (GRU) network encodes historical spatio-temporal sequences as a context vector, which not only preserves the sequential relationships among trajectory locations, but also alleviates the gradient descent problem. The GRU network acts as a decoder, outputting target trajectory location sequences. Real AIS data from the Chongqing and Wuhan sections of the Yangzi River were selected as typical experimental areas for evaluation purposes. The proposed ST-Seq2Seq model has been tested against the LSTM-RNN and GRU-RNN baseline models for short term trajectory prediction experiments. A 10-minute historical trajectory sequence was used to predict the trajectory sequence for the next five minutes. Overall, the findings show that LSTM and GRU networks, while applying a recursive method to predict a sequence of continuous trajectory points, when the number of predicted trajectory points increases accuracy decreases. Conversely, the extended sequence-to-sequence model shows satisfactory stability on different ship channels.


This essay offers an analysis of PowerPoint apart from the histrionics of the "'Tis and 'Taint" arguments about its value, and proposes a program of research to move forward our understanding of PowerPoint as an inscriptional system. To that end, the study begins with a discussion of PowerPoint as an inscriptional system that employs both discursive and presentational codes. Concepts drawn from the literature are used to analyze a sample of PowerPoint materials. A research agenda is developed from the implications of theory and the results of the analysis.


Abstract Over the past two decades, southeastern Nigeria has witnessed huge economic losses due to severe flooding caused by climate change. Understanding the contribution of climate change to flooding is critical for runoff utilization and control, especially in the tropics. This study is focused on quantifying the amount of flooding contributed by climate change effects in the River Basin of southeastern Nigeria. First, the Climate-Flood model equation was expressed using the Time-Series Autoregressive model technique. Using Minitab software, mean annual values of contributing climate variables from prolonged periods of recorded data were investigated. Runoff predictions made from climate-flood models using only the annual records of climatic variables were filtered from the resultant of the respective annual climatic variables, and mean change in flood due to climate change. The output was analyzed considering geology, infiltration capacity, drainage lines and digital elevation model (DEM) of the area. The result shows the obvious trend in climatic variables consistently generates significant impact on the flood. Owerri had the highest positive change in evaporation of 0.11% with a rainfall of 0.03%. Awka had the highest change in sunshine hours and rainfall of 0.41%. Umuahia had the highest change in solar radiation of 0.08, while Enugu had the highest change in air temperature of 0.12. When the contribution of climate change to runoff variation was quantified, Enugu shows highest with 1.68 m3/s while Owerri has 0.04 m3/s. This knowledge is necessary in designing hydrological structures and formulating policies that will help prevent/mitigate flood disasters in the region.


Silicon nitride films deposited on a cylindrical probe surface are removed by ion bombardment in pure N2 plasma in the chamber of the double-tubed coaxial-line-type microwave plasma chemical vapor deposition system, and removal rates of the films are measured. The experiments are carried out with variation of the probe position in the chamber and the bombardment voltage applied to the probe. It has been clarified that the removal rate is proportional to the ion flux density. From this result, general removal conditions of silicon nitride films by ion bombardment have been clarified.


For high agility and high precision attitude maneuver of remote sensing satellites, the Control Moment Gyroscope (CMG) is expected to supply the torque more accurately, which means the disturbance torque on its gimbal axis should be minimized to reduce the pulsation of the gimbal speed. In this paper, the torque generated by the wheel imbalance is analyzed, and the gimbal system model is built. To improve the gimbal speed stability, in this paper, an Iterative Learning Control (ILC) module is inserted in the PID gimbal control system. The proposed control system is evaluated through system simulation, and the results demonstrated that the iterative learning algorithm minimized the pulsating torque effectively, which significantly improved the precision of the CMG output torque.


The invention provides a method for preparing an environment-friendly waterproof, mould-proof and inflaming-retardant shower curtain fabric. Raw vermiculite powder is modified when added into polyester fibers, cost is low, the modifying effect is good, and it is avoided that a large quantity of chemical reagents are used in the modifying process. In the preparation process of the fabric, pollution is reduced, a large amount of energy is saved, and therefore the method for preparing the novel fiber fabric is environmentally friendly.


We compare medium and high fidelity numerical simulations to experiments conducted on low Reynolds number rotors typical of small scale Unmanned Aircraft Systems (UAS). We first show that these numerical approaches provide reasonable estimates of the aerodynamic performance and farfield tonal noise and hence apply them for the investigation of the influence of solidity ratio on the aerodynamics and acoustics of small scale rotors operating under hovering, iso-thrust conditions. We show that while solidity ratio has a weak impact on aerodynamic performance, it may help drastically reduce farfield tonal noise. This reduction is however found to depend on the interplay between thickness and loading noise such that increasing the solidity by increasing the number of blades at constant blades' aspect ratio or by decreasing the blades' aspect ratio keeping the number of blades constant may yield very different, sometimes opposite, trends.


Relative effect of some physico-chemical parameters of water on the occurrence of water borne fungi was studied in a high altitudinal wetland. The number of conidial fungal species was enumerated in water samples collected monthly during the period of March 2008-February 2009. There was marked seasonal fluctuation in the occurrence number of individuals in each species. The maximum number of individuals was found during summer to early autumn, while there was a decline in the number of individuals during late autumn and early winter seasons. Principal component analysis showed a high inverse relationship between number of fungal species and pH and dissolved oxygen, while abundance was positively related to temperature, nitrate nitrogen and total phosphorus clustered together. Finally, it seems from the results that fungal communities are more influenced by the seasonal variation. More studies should be carried out to elucidate the effects of water variables on the community structure of fungi in other water systems in Kashmir Himalayas.

 Key words: water borne fungi, water systems, fungal species, seasonal variation.


Gray Haynes (1991) has correctly noted that "it is no longer possible to describe the optimal or ideal prefemed habitats of witd elephants, because, virtually all surviving populations inhabit special pmtected Innds such as national parlcs which are restricted ecosystems". In Sri Lanlea, a large part of what was once the elephant's home range inthe dry and intermediate zones has been converted to agriculture. Even where the cores of their home ranges overlap with the boundaries of Sri Lanl<a's protected areas, elephants move outside of those boundaries and come into conflict with subsistence and plantation agriculture. Despite the limitations of national parks and equivalent resen)es of Sri Lanka as elephant habitats, it is inevitable that future management of wild elephant populations would have to be planned in and around clusters of such protected areas. Management planning /or in-situ conservation of elephant populations cannot be solely dependent on defensive, agriculture-friendly prescriptions, i.e. removal of troublesome individuals, translocation of elephant herds pocketed-in by surrounding agricultural lands to nearby protected areas, capture of elephants for protection in captive herds such as those at Pinnawela orphanage etc. (Ishwaran, 1993). It must necessarily include attempts to regularly monitor the composition and " health" of wild elephant populations, and interventions to marctge habitats and land-use in and outside of protected ^reas so as to improve range conditions, and the elephant's access to parts of its range which were lost to agriculture and other land-uses in the past. This paper provides an ovettiew of theecology and population structure of the Asianelephant, and the interactions betvveen humans and elephants in Sri Lanka. A framework for designing a pilot project, that could build on a cluster of Sri lnnka's protected areas for elaborating 4 ruanagement regime to improve habitat and range conditions pr in-situ conservation of the elephant is outlined. Ecology and population structure of the Asian elephant in Sri Lanka-anoverview Parker & Graham, in their two-part analysis (1989a,b) of the downward trends in African elephant distribution and numbers note that: "Humans and elephants are complete competitors. Biological theory maintains that such species cannot co-exist on the same range and that increase in one will exclude the other. Measurements of human increase, elephant decline and ivory production are in keeping with this hypothesis". Competition between humans and elephants is particularly intense in agrarian societies. In Asia, most elephant range countries have large rural populations Cajah 20 (2ail) which seek land for agriculture. Governments have sought to use the pride and the sense of security which people associate with owning a plot of arable land to launch massive river valley development projects where agricultural land is parcelled out to settlers. More often, settlers in such schemes are not necessarily indigenous to the area wheie the project is executed' Many of the settlers are drawn from rural, suburban and urban populations sympathetic to ruling powers and are attracted to new settlements through the offer of economic and other incentives. The preferential settlement of river valleys and similarly high-yielding habitas for crop production has been a policy that has denied the elephant its most favoured habitats. That policy has been in vogue among Asian rulers, both


Several decades ago, property rights in natural resources development (NRD) provided benefits to right holders and resulted in a cost burden on the host communities, consisting of human rights abuses, conflicts and environmental degradation. Gradually, the concepts of sustainable development, public participation and corporate responsibility have shaped the limits of property rights in NRD. This has resulted in shared benefits and costs for both the property right holders and the host communities. This paper seeks to stimulate discussions on understanding how the interactions between property rights and human rights in NRD affect and are affected by concerns for the host communities, the environment and the world at large. It concludes that the concept of 'social licence to operate' will, in the near future, usher in a property rights regime in NRD in which the host community will be the ultimate determinant of who does what, where and how.


This thesis project is focused to analysis of occupational risks and the proposal improvement in the UNNOMOTORS Company Cia. Ltda. unpacking area. The development aims to identify which are the risks that are latent in the area are and how these affect the performance and health of workers.
The problem approached by this topic is based on certain causes which generate physical and mental discomfort to workers as incorrect positions, inappropriate use of tools, preparation of the work area and the lack of signage.
The interest that leads us to make this work is to improve working conditions for employees and reduce the level of risks that can affect the workers' health. Because of the great physical effort required, the area has been subject to a high rate of staff turnover, nevertheless the company has been unable to provide immediate solutions and design an improvement plan.
To analyze the risks was carried out a field research where the application of questionnaires, interviews and observation are vital tools to collect such information and thus define the current situation of the area and make a technical-economic proposal for improvement.


In the worldwide search for intermediate transportation solutions between the bus and subway, the city of Curitiba, Brazil has achieved unusual levels of performance and quality. Curitiba has developed an integrated bus-transit network utilizing simple but efficient innovations: exclusive lanes, bi-articulated buses, direct lines, and tube stations. The efficacy of this system has been central to the city's ordered growth and high standard of living.


Rapidly developing technology has led convincing improvements in the music production domain and generation of chord progression is one of the affected areas. Chords are the most significant part of music to create harmony. An arrangement of two or more chords in a music portion makes chord progressions. Generation of chord progression is not just a random selection of notes; it requires as much knowledge of grammatical rules as we need for selecting letters to write a sentence. Some note combinations may sound good together while others may sound harsh. A novice musician has to spend significant amount of time to achieve perfection in music composition. To make the task of musicians less time consuming, we delve into the usefulness of automatic chord progression generation through RL algorithm. RL has already been used in numerous fields, but researchers are still investigating its performance in creative tasks. The proposed work uses music theory concepts to define the rewards and Q-learning algorithm to train the RL agent. The fundamental objective of this paper is twofold. Firstly, the goal is to test this approach as an alternative to generate chord progression. Secondly, the aim is to generate tuneful chord progression that the composers can utilize in their work. Results are validated by comparing it with the chords used in the database of 1300 songs.


BACKGROUND: Gouty arthritis, a chronic inflammatory disease characterized by severe pain and swelling in one or more synovial joints, as a result from joint deposition of monosodium urate (MSU) crystals. Tempuyung (Sonchus arvensis) is a plant that has been extensively studied in the role of shedding kidney stones and diuretics. It is presumed that it also has great potential in shedding MSU crystals in the joints.
AIM: This study focused on exploring the anti-inflammatory role of tempuyung extract (ET) on pro-inflammatory cytokines in gout arthritis white rats.
METHODS: The extraction of tempuyung was performed to obtain ET. A total of 30 Wistar rats were randomly divided into the following six groups, each containing five rats: Normal control group, MSU group (negative control), MSU + colchicine group (Col; 0.28 mg/kg), and MSU + ET group (at dose of 25 mg/kg, 50 mg/kg, and 100 mg/kg). Gouty arthritis was induced with 50 ml of MSU solution (20 mg/ml), which was injected into the left ankle joint cavity on day 7. Synovial fluid was evacuated for the examination of Western blotting of tumor necrosis factor-α (TNF-α). A portion of synovial tissue was fixed in 4% paraformaldehyde buffer for histopathological examination. Interleukin (IL)-1β levels in the synovial fluid of the joints were examined by IL-1β rat enzyme-linked immunosorbent assay. Statistical analysis was performed with way ANOVA followed by post hoc.
RESULTS: The histopathological image of the MSU model group showed a large number of inflammatory cells depicting an inflammatory reaction. This inflammation response decreased in the ET treatment group in dose-dependent manner. ET showed the effect of decreased pro-inflammatory cytokines expression in both IL-1β and TNF-α, as the dose increased.
CONCLUSION: Tempuyung extract possessed an anti-gout arthritis effect in white rats induced by MSU, by reducing the inflammatory response in the synovial joint.


Summary form only given. Over the past forty years many lasers have established a large array of applications in medical and dental use. For example, pulsed CO2 laser resurfacing improves photodamage and acne scarring by removing abnormal tissue with subsequent regeneration and remodeling of collagen through heat induced collagen contraction. Diode lasers, Nd:YAG, and Alexandnte lasers have been used for hair removal, and Normal Mode Er:YAG lasers have been used for precise hard and soft tissue removal with minimal thermal damage. Pulsed Dye laser are used for treatment of unseemly blood vessels and pulsed Q-switched solid state laser devices at 1.06um are used to remove unwanted tattoos.


Summary:  Purpose: Mossy fiber sprouting (MFS) and synaptic reorganization in the dentate gyrus (DG) is considered one of the physiopathologic mechanisms in temporal lobe epilepsy. Supragranular MFS can be blocked by cycloheximide (CHX) without interfering with the genesis of spontaneous recurrent seizures. The aim of this study was to investigate electrophysiologic properties of the hippocampus in the CHX/pilocarpine (CHX/PILO) model as compared with the conventional PILO model.


The digital resources are easy to share,to retrieval.Digital resources take big part in library resources now.Through resource integration,library can use one stop service to improve the using effect of digital resources.


The programing techniques of the configuration software INTOUCH used in a large domestic milk enterprise are discussed. The problems of alarm and grouping display of the history of trend that we meet in large industry automation are settled by using these techniques.


Evolving social mores and fiduciary restrictions of healthcare delivery have presented practitioners with opportunities to reflect when considering the ethical standards of practice. Using a case example, this article explores various elements that challenge and define ethical practice: (1) it reviews the components of negligence, (2) it explores various levels of obligation that a physical therapist must meet in the delivery of healthcare, and (3) it examines appropriate practice options the practitioner might consider to avoid negligence and fraud.


Because of the high expectations users have on virtual assistants to interact with said systems on a human level, the rules of social interaction potentially apply and less the influence of emotion cues associated with the system responses. To this end the social psychological theories of control, reactance, schemata, and social comparison suggest strategies to transform the dialogue with a virtual assistant into an encounter with a consistent and cohesive personality, in effect using the mind-set of the user to the advantage of the conversation, provoking the user into reacting predictably while at the same time preserving the user's illusion of control. These methods are presented in an online system: Elbot.com.


In this paper, we present a growing complex network model, namely, the generalized corona network (GCN) which is built on a base network and a sequence of networks by using corona product of graphs. This construction generalizes several existing complex network models. We study the structural properties of the special classes of generalized corona networks and show that these networks have small diameter, the cumulative betweenness distribution follows a power-law distribution, the degree distribution decay exponentially, small average path length with the network order, high clustering coefficient and small-world behavior. Further, we obtain the spectra of the adjacency matrix and the signless Laplacian matrix of GCN when the constituting networks are regular. Also, we obtain the Laplacian spectra for all generalized corona networks. In addition, explicitly give eigenvector corresponding to the adjacency and Laplacian eigenvalues. Finally, we derive the spectral radius and the algebraic connectivity of GCN.


Wouldn't Stack love to open a book and find a map of the new millennium. It doesn't have to be 100% right, but someone needs to take a stab at drawing one. We need a map, even if it's only a rough outline: Business boundaries are shifting, and the very definition of what it means to be a company is changing.


Dielectric properties and IR spectra have been studied for ferroelectric nanocomposites: porous glass–NaNO2 and porous Al2O3–NaNO2. The effect of depolarization field on dielectric properties and phase transition has been analyzed. The role of the "matrix-embedded ferroelectric" interface is discussed.


In multiple-input multiple-output(MIMO) communication systems,if perfect channel state information(CSI) at the transmitter can be known,then transmitter-side optimization would significantly improve the system's performance.However,the classic water-filling-alike algorithms deduced by optimization designs can greatly increase the complexity of the process at the transmitter end.A new mean scheme was developed for decreasing precoding complexity,replacing real-time singular values of a channel in the water-filling-alike algorithms with mean values for the signal channel.Simulation results demonstrated that it can reduce the complexity of precoding and effectively characterize channel capacity and other performance parameters of MIMO systems.


Recycling consumer durables is becoming increasingly important as. the volume of waste grows. However, recycling of these plastics into useful materials is limited by the high cost of sorting the different materials that make up a piece of equipment. This paper investigates the degree of sorting required based on contamination levels of one of the plastics in acrylonitrile-butadiene-styrene (ABS) and polypropylene (PP) blends. The thermal, mechanical and rheological properties of the blends prepared for this investigation has led to the conclusion that ABS and PP are not compatible and that substantial sorting would be required to obtain a useful material.


An edge light emitting display having a front at the top of the optical modulator in the package, and top and bottom layers of the at least one extractor. The control system is connected to control the extraction mechanism to: approximate a desired light projecting an image onto a front modulator, it is estimated on the pattern of light incident on the front modulator, and the modulator to control the front based on the estimated pattern.


The invention discloses a preparation method of an active antibacterial composite coating on the surface of titanium and titanium alloy medical instrument. The method includes the following steps: firstly, carrying out ultrasonic washing on the titanium or titanium alloy medical instrument to be treated and then immersing the titanium or titanium alloy medical instrument in NaOH solution for alkali-heat treatment; secondly, carrying out microarc oxidation treatment on the titanium or titanium alloy medical instrument in an electrolyte solution which contains biological active elements and antibacterial ingredients; carrying out hydro-thermal treatment on the titanium or titanium alloy medical instrument, and finally drying under vacuum condition. In such a way, the active antibacterial composite coating can be obtained. In the preparation method, a nano-silver/ titanium dioxide composite antibacterial agent is adopted to form the antibacterial coating on the surface of titanium or titanium alloy matrix, and the antibacterial coating has long antibacterial effect to bacteria commonly seen at an operation wound of a person and has adhesion resistance to common inflammatory bacteria. Meanwhile, the active ingredients such as Ca and P in the coating can improve the biological activity and speeds up the osseointegration, and thereby the antibacterial performance, the clinical curing effect and the application range of the titanium and titanium alloy medical instrument are improved by a large margin.


Access to digital information became almost ubiquitous. There are only few situations left where digital media cannot be accessed. Showering is probably the only regular and common activity that does not allow to access and interact with digital media. Based on a large-scale survey, we identified potential applications that users want to use in the shower and designed a system that augments the user's showering experience to provide pervasive media access. We developed a projection-based system that augments shower curtains from the back side and recognizes user input using a thermal camera. Through a user study in a running shower, we collected feedback from potential users and evaluated different algorithms to recognize touch input on a shower curtain. Our results show that participants are enthusiastic about accessing and controlling media using an interactive shower curtain. Furthermore, we identified two algorithms that are robust enough to be used in challenging environments such as a shower.


A spectral imager constructs a 3D (two spatial and one spectral) image from a series of 2D images. This paper discusses a technique for spectral imaging that multiplexes the spatial and spectral information on the focal plane, then demultiplexes the resulting imagery to obtain the spectral image. The resulting spectral image consists of 184 X 184 spatial pixels and 40 spectral bands. The current implementation operates over the 3-5 micrometers band, but can easily be applied to other spectral regions. A hardware description, the mathematical development and experimental results are presented.


Abstract FOR some time it has been known that animal proteins contain a factor or factors essential for normal hatchability of eggs and for growth of simple-stomached animals. Parkhurst (1927) found that animal protein was necessary in the breeding rations of hens to obtain eggs of high hatchability. Numerous investigators have confirmed Parkhurst's findings. Hammond (1942, 1944) reported that cow manure promoted chick growth. A nutrient common to dried cow manure, dried rumen contents, and sardine fish meal was not supplied in the all-plant protein diet. Rubin et al. (1946) obtained the same growth response in chicks by feeding a ration containing 5 percent urine-free hen feces as they did when a 5 percent cow manure ration was fed. The investigators concluded that the growth-promoting factor for chicks was synthesized either in the lower digestive tract or in the voided feces. McGinnis et al. (1947) showed that incubation of hen feces . . .


Abstract—In this extended abstract we present the UltraGrid
system, the current state of the art in high definition conferencing. UltraGrid was the first system to support gigabit rate high definition interactive video conferencing on commodity systems and networks. We review the design and implementation of UltraGrid, discuss experimental results and deployment, and conclude with our vision of the future of conferencing systems


The weather comes from the dynamic process of exchange relations between the atmosphere and surface, Surface Atmosphere System (SSA). So it is through the climatic elements, humidity, pressure and temperature, operating across territorial extension from the geographical constraints of climate factors, which are established inter-relationships of the SSA promoting understandings of climate dynamics that sets in a given period of the year and place. In this process, the types of time working on individual regions and animating in succession and customary come to encourage the formation of the climate. Considering that human actions promote the re/construction of geographical space and therefore the climate considered as an input, which is mathematized according to periodic observations, starting to be studied from the intentions of the agro-economic axis. So it is relevant to the characterization and analysis of the process of historical development of climatology and climate dynamics of the Midwest, such after analysis by the State of Mato Grosso do Sul, and finally culminate in the characterization of the habitual rhythm of the climate that is established in the town of Dourados, which has conditions in the interactions of physical states of the atmosphere on the geographic factors that have to justify the climatic realities that go through phenomena that appear in each seasonal period.


— T racking m ood or emotional experiences over time is a popular function found in m obile health applications . I n this study, yo ung patients with chronic health challenges c onsider this also an important function of a multifunctional app supporting them in the transition to adult care. At the same time they expressed the need to be seen as a young person, not a diagnosed body. A lifeworld - led design approach, based on a Participatory D esign methodology , resulted in a mood tracking and a mood mapping design , which w as meaningful to the young persons' everyday experiences . Photos tagged with colors representing different emotional states were chosen as the best way to repre sent their mood s. An overview of moods, by day as well as by color , gives an unde rstanding of the wider conte xt in which these moods appear and can play a motivational role in deal ing with a difficult day or episode in their lives .


Temperature can influence trophic interactions via predictable effects on the metabolism of ecothermic consumers. Under some conditions, warming should increase top–down control and trophic transfer rates, leading to declines in prey populations. We tested this prediction in the Galapagos Islands, an equatorial upwelling region, where water temperatures are highly variable and nutrient availability is thought to control primary production and standing algal biomass. We used grazing assays, field surveys, and a herbivore exclusion experiment to test the hypothesis that grazing rate and algal biomass are, in part, regulated by temperature via the temperature–dependence of herbivory. Grazing rates were greater during the warm season for urchins and other consumers (including fishes, turtles, and iguanas). Field surveys at ten sites over five years found that temperature was strongly negatively related to macroalgal cover. The results of the exclusion experiment indicate that herbivores had a large effect on macroalgal biomass, even during intense upwelling. Our results suggest that in shallow subtidal habitats across the Galapagos archipelago, grazing pressure increases with temperature, potentially resulting in reduced algal biomass when upwelling is weak and greater algal biomass when upwelling is strong and water is cold; an alternative explanation for widely observed association between upwelling intensity and algal biomass.


Shell‐less cultrure involves culturing chick embryos with associated yolk and albumen outside of the eggshell and shell membranes. The technique allows direct access to and continuous observation of cultured embryos almost to the time of hatching. The plastic wrap/culture tripod technique described in this paper allows normal embryonic growth and differentiation from 48 hours (in ovo pre‐incubation age) through at least 10 days of total incubation. As the duration of in ovo pre‐incubation is decreased below 36 hours, there is a concomitant increase in the percentage of grossly abnormal embryos associated with decreased survival and retarded growth and differentiation. Survival of embryos pre‐incubated for 72 hours through 13 and 18 days of total incubation is greater than 80% and 40%, respectively. The wrap/tripod technique allows substantially better survival and more normal development of cultured embryos than does the petri dish technique of Auerbach et al. (1974). Embryonic growth in 7.8‐cm‐diameter chambers is significantly greater than in either larger (10.6 cm) or smaller (5.2 cm) diameter chambers. Some gas exchange through the culture chamber walls appears necessary for optional embryonic survival and growth. Suspending egg contents in either Safeway® or Handi‐Wrap® plastic wrap (both of intermediate permeability) in 7.8‐cm tripods resulted in superior growth and/or survival compared to suspension in Silastic® sheeting (high permeability), Saran Wrap® (low permeability), glass dishes (nonpermeable), or glass dishes lined with an inner layer of Safeway® wrap(nonpermeable).


Abstract This paper presents an algorithm to compute an approximation to the general sweep boundary of a 2D curved moving object which changes its shape dynamically while traversing a trajectory. In effect, we make polygonal approximations to the trajectory and to the object shape at every appropriate instance along the trajectory so that the approximated polygonal sweep boundary is within a given error bound ϵ > 0 from the exact sweep boundary. The algorithm interpolates intermediate polygonal shapes between any two consecutive instances, and constructs polygons which approximate the sweep boundary of the object. Previous algorithms on sweep boundary computation have been mainly concerned about moving objects with fixed shapes; nevertheless, they have involved a fair amount of symbolic and/or numerical computations that have limited their practical uses in graphics modeling systems as well as in many other applications which require fast sweep boundary computation. Although the algorithm presented here does not generate the exact sweep boundaries of objects, it does yield quite reasonable polygonal approximations to them, and our experimental results show that its computation is reasonably fast to be of a practical use.


Our study suggest that patient-centred health care models should focus on improving patient access to health care, supporting the role of carers and non-oncology health care providers as well as providing education about health care resources.


Methods for the direct analysis of solids have a number of undeniable advantages over the methods that require preliminary dissolution of samples. High sensitivity and selectivity make the direct mass spectrometric techniques the most in-demand. The review concerns spark source mass spectrometry, laser ionization mass spectrometry, laser ablation inductively coupled plasma mass spectrometry, secondary ion mass spectrometry, secondary neutral mass spectrometry and glow discharge mass spectrometry. Basic principles, analytical characteristics and trends in the development of these techniques are discussed. Particular attention is given to applications of the techniques as well as to their competitive advantages and drawbacks. The bibliography includes 123 references.


The soft magnetic properties of nanocrystalline Fe-Zr-Nb-B alloys, which are mixtures of Fe-Zr-B alloy with negative magnetostriction and Fe-Nb-B alloy with positive magnetostriction, were investigated. The magnetostriction and grain size of the Fe-Zr-Nb-B alloys show values intermediate between those of Fe-Zr-B and Fe-Nb-B alloys. The soft magnetic properties are strongly affected by the Zr + Nb amount and Zr/Nb ratio. The best soft magnetic properties have been obtained for the Fe85.5Zr2Nb4B8.5 alloy. This alloy simultaneously exhibits a high permeability of 60,000 at 1 kHz, a high saturation magnetic flux density of 1.64 T, and zero-magnetostriction. The alloy also exhibits a very low core loss of 0.09 W/kg at 1.4 T and 50 Hz, which is far lower than that of Fe-Si-B amorphous, as well as good thermal stability of the core loss. Nanocrystalline Fe-Zr-Nb-B alloy is therefore suitable as a core material for pole transformers.


Traditional discrete particle swarm optimization(DPSO) is easy to incur a local convergence in optimization.So we propose an improved DPSO algorithm in which a new motion equation is adopted to update the position of particles.The concept of Greedy algorithm is introduced into the DPSO algorithm.In the course of initialization,we use the results obtained from greedy strategy as the initial position of a particle.The knapsack problem was worked out with the proposed algorithm,showing that it is advantageous in global searching and convergence properties than traditional DPSO.


Objective To construct a siRNA expressing vector targeting FoxM1,in order to investigate the effect of FoxM1 gene in lung cancer and other diseases.Methods A FoxM1 targeting short hairpin DNA fragment was designed and synthesized,and then was cloned into a linearized backbone plasmid pSilencer2.l-U6.The new plasmid was identified to be correct by cutting with restriction enzymes and gene sequencing.Results The FoxM1 targeting shDNA fragment was inserted into pSilencer 2.1-U6 backbone vector correctly.Conclusions The small interfering RNA expression vector targeting FoxM1 gene is constructed successfully.

Key words:
Forkhead box M1; RNA interfering; Plasmid construction


The necessity of the instrumental control in medical rehabilitation is justified. The measuring system for the human coordination ability examination is described. The measurement results of patients upper and lower limbs linear accelerations while medical rehabilitation are analyzed. The signal phases for human coordination ability assessment are identified.


This collection of sixteen online papers epitomizes the collision of Arjun Appadurai and Immanuel Wallerstein with Iron Chef. Both eclectic and familiar, the works capture the rich pastiche of food traces that have become the modern, global, foodways of fast capitalism. Centered in Japan, and the outcome of a symposium on "Globalization, Food and Social Identities in the Pacific Region" held at Sophia University on February 2009, the project invites the reader to its smorgasbord of tasty, bite-sized entrées. This is not your full-blown sit-down dinner cum feast, à la the traditional "book," but rather it allows the reader to move among the papers, downloading, tasting, and digesting according to interest and pleasure. The collection marks the importance of the Asia-Pacific region as a global, historically central, commercial hub, and seeks to establish the co-evolution of food studies and global studies, arguing successfully that food is an excellent subject by which to interrogate the complexities of globalization. Each food examined provides rich local history, is highly context-specific, and engages with its movement through national consumption and distribution networks and into the global trading and culinary systems, collectively creating a unified framework of understanding. The theoretical reach of the collection is broad, crossing cultural sociology, urban studies, and food studies to examine social, national, and increasingly complex interconnected national food identities. Unlike those critics of globalization who warn of the homogenizing impact of American food products (fast food and processed industrialized foods), decrying the seduction of the global palate by CocaCola and McDonald's, these papers describe the nuanced emergence of globally aware, local food practices that are creative, formative, and to some degree signal a change in the global culinary tipping point towards Asia. The collection is sectioned into three parts. The first focuses on particular foods and examines a range of issues around the concept of "local" food. The second examines food in a global perspective through a number of eclectic examples. The third section is well described by one of the contributors, Rossella Ceccarini, as an examination of the glocalization of foreign culinary products. Food is one of Appadurai's "things" that has moved with nomads and traders around the globe for centuries. The "origins" of a particular food are often lost, and over centuries their


Electromagnetic environmental engineering management is important in development of aviation materiel.The standardization,systemization of electromagnetic environmental engineering works in life cycle of materiel development was discussed.It was further suggested that electromagnetic environmental engineering management be implemented from the early stage of development to the total life cycle.


The structural features of birnessites with different Mn average oxidation state(AOS) before and after Pb2+ adsorption were characterized by Fourier Transform Infrared(FTIR),and the absorption band centers of FTIR were determined by second derivatives of these spectra.The band at 899-920 cm-1 was assigned to the bending vibration of -OH located at vacant Mn octahedral sites.The lower AOS in birnessite,the more Mn4+ coordinated to -OH located at vacant Mn octahedral sites displaced by Mn3+,which led to the position of -OH bending vibration shifting to a relative low wave number.The bands at 1059-1070,1115-1124 and 1165-1171 cm-1 were assigned to the vibration of Mn3+-OH located in the layer,and the intensity of these bands increased with the decrease of AOS in birnessite.The bands at 990 and 1023-1027 cm-1 were assigned to the vibration of Mn3+-OH located in the interlayer.A partial of Mn3+ in the layer migrated to the interlayer during the Pb2+ adsorption inducing the intensity of the band at 990 cm-1 to increase and its position shifting to a relative high wave number.The band at 564-567cm-1 was assigned to the vibration of Mn-O located at vacant Mn octahedral sites,and would split due to the effect of coupling on vibration when Pb2+ or Mn3+ was adsorbed above or below vacant sites.The space between the bands at 610-626 and 638-659 cm-1 reflected the symmetry of Mn3+ distribution in the birnessite,and increased after Pb2+ was adsorbed on the birnessite.


This paper discusses social rights by focusing on their protection in the international and regional context. It describes and analyzes the difficulties and challenges of the implementation of social rights in South America with the aim of building a regional constitutionalism whose foundation is the ius commune . For this purpose, the article presents the historical background of the affirmation of human rights and social rights as well as structural notions of the systems of their protection both at the global level and regional level in order to provide within the latter, especially in the South America, the challenges of the ius commune . Key words: ius commune , social rights, South-American region.


Copper films thicker than 4 nm exhibit typical for copper strip absorption ranging from л=300…1100 nm and vice versa. In consequence of thermal treatment under the atmospheric conditions, fine copper films' (3…100 nm) thickness, mass, and absorption spectrum change dramatically within the temperature range 373…600 K and time range 1…120 min. This fact was established owing to spectrometrical, gravimetrical, and microscopical methods. It was shown that kinetic curves of conversion degree, samples' thickness and mass alteration can be described within the frames of either linear, parabolic, or logarithmic laws versus both the initial copper films' thickness and thermal treatment temperature. It was stated that copper films' absorption spectrum, thickness, and mass change due to copper oxide (I) formation on their surface.


High-quality inner FOV(field of view)stitching is a necessary step for post-process and application of images captured by spaceborne non-collinear TDI CCD camera.This paper presents an inner FoV stitching method for non-collinear TDI CCD images.The method utilizes the projection plane in object space and the sensor geometric model of the camera to establish the coordinates transformation relation between pixels of the stitched image and pixels of the orginal image,and then performs image resampling to generate the stitched image by indirect image geometric rectification.After describing the strict geometric models of non-collinear TDI CCD images,the basic principle,the potential error sources and the workflow of the method are discussed in detail.Finally,experimental verification is carried out on the high-resolution(HR)camera images of ZY-1 02 C satellite,and the accuracy evaluation of the generated stitched images indicates the feasibility of the presented method.


In this paper I examine how servicer characteristics affect foreclosure rates of delinquent securitized mortgages. Using a sample of mortgages originated by IndyMac Bank and Countrywide Home Loan Servicing that underwent a change in servicer during the financial crisis period, I first show using a difference-in-difference methodology that the servicer has a significant effect on foreclosure rates. Consistent with the idea that information asymmetry affect foreclosure rates, I find a significantly lower foreclosure rate among mortgages where the originator also acts as servicer. Finally, foreclosure rates are ceteris paribus higher for servicers that experienced high loan growth in the past, which suggests that servicer capacity constraints affected foreclosure rates.


Taking buffer-insertion position restriction for standard-cell methodology into consideration,a routing with buffer-insertion algorithm is presented for interconnect delay optimization. The algorithm can reach minimum Elmore delay on single source-sink path.


We demonstrate optical rectification in GaP of a 112W, 88fs, 13.4 MHz, nonlinearly compressed thin-disk oscillator. We obtain 1.35 mW average power, which is the highest so far achieved from a single-cycle THz source at MHz repetition rate. © 2019 The Author(s)


This study was to examine the effect of rubric on development in writing ability of university students. This study was carried for verifying whether the purpose of assessment is achieved when student use rubric as scale in writing class on educational environment is not objective assessment system now. The experiment of this study was progressed during semester. First the pretest about writing ability of two group was performed and was offered rubric four times to experimental group and not offered to control group. Finally, to examine the effects of treatment, statistical analysis was carried. The result from this study is rubric that suggest detailed criteria and level have positive effect on development in writing ability of university students. This display result of this experiment coincide result of existing study that rubric have positive effect on improvement in performance ability of student. Therefore, on the basis of the result from this study, development of rubric that increase writing ability of student is needed.


We investigate the role of the close environment on the nuclear activity of a sample of 436 nearby (z < 0.3) QSO 2's – selected from SDSS-III spectra, via comparison of their environment and interaction parameters with those of a control sample of 1308 galaxies. We have used the corresponding SDSS images to obtain the number of neighbour galaxies N, tidal strength parameter Q and asymmetry parameters. We find a small excess of N in the QSOs compared to its three controls, and no difference in Q. The main difference is an excess of asymmetry in the QSOs hosts, which is almost twice that of the control galaxies. This difference is not due to the hosts' morphology, since there is no difference in their Galaxy Zoo classifications. HST images of two highly asymmetric QSO 2 hosts of our sample show that both sources have a close companion (at projected separations ∼ 5 kpc), which we thus conclude is the cause of the observed asymmetry in the lower resolution SDSS images. The mean projected radius of the controls is 〈r〉 = 8.53 ±0.06 kpc, while that of the QSO hosts is 〈r〉 = 9.39 ±0.12 kpc, supporting the presence of interaction signatures in the outer regions of the QSO hosts. Our results favour a scenario in which nuclear activity in QSO 2's is triggered by close galaxy interactions – when the distance between the host and companion is of the order of the galaxy radius, implying that they are already in the process of merger.


ABSTRACT: This study aims to determine the quality of water hyacinth compost in physical and chemical properties. Water hyacinth is considered a weed that damages the aesthetics and aquatic environment in the  Lut Tawar Lake  tourist area. A solution is needed to overcome these problems, one of which is composting. In order for composting to take place faster, an EM-4 activator will be used which will give good quality. This research method uses one replicate with three treatments (K1 and K2 using EM-4, and K0 without EM-4). This study was conducted in two stages, that are the composting and characterization stages. The composting process is let runs for 60 days. Checking every 5 days is turn upside down and physical observation. After the composting process, is determined the pH, temperature and characterization. Characterization is done to determine the levels of C, N, P, K, Ca and Mg. The results of this study showed that EM-4 is effective for carbon (C), phosphorus (P) and calcium (Ca) grade. The grade of macro nutrient (C, N, P, K), micro nutrient (Ca) and  temperature of water hyacinth compost are suitable with SNI.


In this paper, occupational chemical poisons' physiologically based pharmacokinetic (PBPK) models are established to simulate metabolic processes in vivo based on exposure simulation softwareexposure related dose estimating model (ERDEM). PBPK model establishing progress is described based on the development and utilization of ERDEM. As well known, benzene, 1, 3-butadiene and vinyl chloride are definitely carcinogenic to humans. The study on these carcinogens' internal exposure has important significance to carcinogenic risk. Internal exposure of these three kinds of chemicals are simulated with parameters of PBPK model, organizations and organism from literature data, which proves ERDEM's broad applicability. Simulation results are represented by different kinds of results forms such as toxicant concentration in blood changes over time, toxicant average concentration in blood, metabolite amount in target organ changes over time, toxicant concentration in exhaled air changes over time and so on. And the simulation results are verified by comparing with the experimental results in previous literature. The good consistency between simulation results and experimental date reflects that output results of ERDEM are reliable and can be characterized in various forms.


A size-dependent model of a micro-electromechanical system (MEMS) actuated by both electrostatic and piezoelectric forces is proposed based on the modified couple stress theory. The governing equation and boundary conditions are derived with the help of the Hamilton principle and solved numerically by employing the Galerkin method and Newton downhill method. A material length scale parameter (MLSP) is incorporated in the model to capture the size effect in microstructures. The results show that the piezoelectric voltage on the beam can reduce the electrostatic voltage dramatically and may guide the design of micro-devices.


Canada Institute for Scientific and Technical Information (CISTI)'s history in resource sharing, both in Canada and internationally, was described in a previous article. This paper updates CISTI's resource‐sharing activities in the intervening two years. CISTI, as a document supplier and publisher, continues to ensure that client needs are met in the electronic future.


The seismic behavior of the structure on layered medium-soft-soil affected by the river is studied.The non-linear finite element model of interation is set up,which involves soil,river and structure.On the premise of considering gravity,this interaction model is analyzed with time domain numerical method under three seismic waves.The result of calculation shows that when structure is colse to the river;the total displacement at the top of superstructure,the movement and swing of the foundation increase obviously,accompanied by irreclaimable excursions.Because of the soft soil sandwich,the earthquake responses of the interaction system are increased.


The main objective of this paper is to study the time decay of transport-diffusion equation with inhomogeneous localized damping in the multi-dimensional torus. The drift is governed by an autonomous Lipschitz vector field and the diffusion by the standard heat equation with small viscosity parameter $\nu$. In the first part we deal with the inviscid case and show some results on the time decay of the energy using in a crucial way the ergodicity and the unique ergodicity of the flow generated by the drift. In the second part we analyze the same problem with small viscosity and provide quite similar results on the exponential decay uniformly with respect to the viscosity in some logarithmic time scaling of the \mbox{type $t\in [0,C_0\ln(1/\nu)]$}.


Objective To study the effect of selenium,cadmium supplement on the contents of Se?Cd?Cu?Zn?Mn in rat organs.Methods Wistar male rats,3 months old,were treated with the water which contained 5ppm selenium,50ppm cadmium and 5ppm selenium+50ppm cadmium.After three weeks,the contents of Se?Cd?Cu?Zn and Mn in the liver?Kidney?spleen and testicles were determined by atomic absorption spectrophotometry.Results In 5ppm Se group,Se and Cd contents in four kinds of tissues,Zn contents in liver and spleen,and Cu contents in kidney?spleen?testicles were higher than those of control group.In 50ppm Cd group:Cd contents in four kinds of tissues,Se contents in kindney and spleen,Cu and Zn contents in liver and spleen were higher than those of control group.Supplement on Se and Cd at the same time,Se contents in four kind of tissues of rat were significantly lower than those of Se group,While Cd contents in four rat tissues were significantly higher,Zn contents in liver were obviously lower than those of Cd group and Se group in spleeen;Cu contents in kidney?spleen?testicles were lower than those of Se group;Mn contents in kidney and testicles were lower than those of Cd group.


Involving husbands in birth preparedness and complication readiness (BP/CR) has been encouraged as a new strategy to improve maternal health for safe motherhood since 2000. Myanmar is a patriarchy society and despite the strong domination of husbands on the health of their families, their involvement in maternal health are still limited. This quasi-experimental study aimed to determine the effectiveness of 'Men in Maternity Health' (MiM) intervention to improve husband involvement in BP/CR and institutional delivery for safe motherhood in Nay Pyi Taw, Myanmar. Total 198 husbands of pregnant women were included (99 husbands from each Township): Lewe Township as study group and Takkone Township control group. Face to face interview using interviewer administered questionnaire was carried out to collect the data. The data was analyzed by independent t-test to compare the continuous variables between study and control groups including within group comparison by paired t-test. Pearson's Chi-square test was used to compare the difference of categorical variables. After 'MiM' programme, there were significantly changes in husbands' knowledge (p=0.001) and attitude (p=0.04) between study and control groups. Husbands in both groups were more likely to involve indirectly as financial support than direct involvement as planning skilled birth attendant and blood donor in case of emergency for their wives before give birth. In study group, husbands' involvement in BP/CR improved significantly (p<0.001). Institutional delivery prevalence was significant difference between study and control groups, 64.6% and 39.4% respectively. In conclusion, the implementation of 'MiM' programme for promoting partner involvement in BP/CR and institutional delivery among pregnant women couples can enhance the benefits for safe motherhood.


There have been insufficient comprehensive North American bicycle safety data upon which to base inclusion of safety in the design of urban bicycle networks. In response to this need, a survey of commuter bicyclists in Ottawa and Toronto, Canada was undertaken in 1995 by McMaster University with funding from the Ontario Ministry of Transportation. The objective of this paper is to review the survey methodology which was successful in estimating travel exposure and to present research results related to (1) the characteristics and contributing circumstances for bicycle collisions and falls; (2) collision and fall rates by facility type; and (3) the results of a detailed analysis of the safety of sidewalk cycling. The objective of the survey was to collect collision/fall histories to complement more traditional police and emergency databases which typically only include more serious events. However, an additional objective was to collect detailed travel behavior information for exposure estimation. The measure of travel exposure combined information from a map where cyclists traced their regular route with estimates of commute trips per month.


For a class of multi input and multi output nonlinear uncertain systems with input coupling term, a robust feedback linearization method combined with a minimax linear quadratic regulator (LQR) control is proposed. The uncertainties in the system and the presence of input terms in the low order derivatives of the outputs due to the input coupling makes the feedback linearization a challenging task. In this paper, we approach this problem in a robust way such that all the uncertainties are lumped together and the coupling term vanishes. The procedure consists of the simplification of the nonlinear model to achieve full vector relative degree and then use the robust feedback linearization method to linearize the nonlinear dynamics. This linearization process, followed by a robust minimax LQR control design, provides a robustly stable closed loop system. To demonstrate the effectiveness of the proposed approach, an application study is provided on the longitudinal stabilization of an air-breathing hypersonic flight vehicle in the presence of input coupling and uncertainties.


Summary The complicatedly structures formations play the important role in migration and forming the root system in high-quality production rate genesis. Moreover the geo-physical and the correlated hydro-dynamical fields of generation and accumulation, as well as facial and phase boundaries are characterized by the following general features: • Complex structuring of various scaled space, unclearly defined structural monitoring and fluctuations in inflow profiles; • Restriction of pools by lithological replacement of the reservoir, by compacted zones, and in the zone of drainage — by the segments with no inflow from low-permeable stagnant capillary-jammed zones with counter-flow imbibition; • By the presence of convective — diffusive shear deformations of tangential stresses, non-equalized temperature, viscosity and difficulties with saturation and pressure inversion. Inside the energy field of the Earth there is the process of porous space polarization with nematic phase components by ionic ferromagnetic circulation of block self-regulation events and these are fixed by the changes in thermal concentration of neuron density and by other geo-physical fields of nuclear-magnetic interaction. Taking the ancient Volga-Urals basin and the oldest geological province we present the new model of hydro-dynamic stability with cognitive science geology and reservoir quality in view of their historical development and new business resources. We prove the inflow profile and quality function in reservoirs with challenging geological and hydro-dynamic conditions and propose new geological accesses in search exploration and system-like designing of complexly structured fields.


Dissecting TAA in MFS is associated with elevated TGFβ activity secondary to structural or quantitative defects in FBN1. Perinatal lethality of mice with germ line inactivation of Fbn1 has underscored the importance of fibrillin microfibrils in aortic growth and homeostasis without identifying the main tissue compartment contributing to TAA.


Objective: To describe the maternal and perinatal outcome of pregnancies in women aged 45 years or more at the time of delivery and to compare them with pregnancies in women aged between 20 and 29 years.


People will learn an instrumental conditioned response, the reward for which is the deliverance of another human being from suffering.


A formalization of Temporal Graph (an abstraction of Low Altitude Multiple Satellite (LAMS) networks), in which edges are created and destroyed according to a predefined schedule, is presented. Relative to this framework, the notions of "delayed-path" and "clustered temporal networks" are introduced. A system of data structures and algorithms is developed for the generation, within such networks, of delayed-paths meeting a variety of combinations of objectives (such as shortest delivery time and minimum hop count), and an analysis is given for each of the algorithms.


In this paper the author examines the alternative methods of abating a catastrophic oil spill and compares these methods to the controlled burning of an oil spill using a fire-resistant boom. He discusses the environmental impacts of burning versus not burning the spill, and the various costs of rapid response using the different methods. Fire booms have the ability to respond faster than most methods, achieve a very high removal and are comparatively low cost. This paper shows that burning of the oil is one of the most environmentally appropriate methods of removing oil from the water.


For ages, the practice of drug discovery has relied heavily on the one-drug one-target design strategy of medicinal chemistry. However, despite the tremendous advances made in chemical and biological sciences and in the discovery technologies the number of drugs/drug candidates coming out from this one-drug one-target approach is paradoxically dwindling. It is now well recognized that the age old philosophy of medicinal chemistry lacks a fundamental conceptual framework. This is particularly so in disorders such as depression where a multiple of pathways are simultaneously deregulated and which basically result from multiple molecular abnormalities, not just from a defect in a single pathway. The recent times has seen a shift towards one drug-multiple target selective design strategy. This novel paradigm has already produced a diverse set of multiple acting structures for depression. Largely as a consequence of the unacceptable side effects, tolerability and low level of efficacy of the currently used drugs (tricyclic antidepressants, mono amine oxidase and selective serotonin reuptake inhibitors), other new generation agents are increasingly being identified that act at more than one target in depressive disorders. Multitarget selective antidepressant research has produced a number of diverse and novel chemistries with a huge potential for the treatment of this debilitating disorder. This manuscript reviews the latest developments surrounding multitarget selective agents for depression, the benefits of such multi acting agents and the implications for the future design of potent and selective dual, triple or even poly-target active antidepressants.


Mixed leukocyte (white blood cells [WBCs]) trafficking using positron emission tomography (PET) is receiving growing interest to diagnose and monitor inflammatory conditions. PET, a high sensitivity molecular imaging technique, allows precise quantification of the signal produced from radiolabelled moieties. We have evaluated a new method for radiolabelling WBCs with either zirconium‐89 (89Zr) or copper‐64 (64Cu) for PET imaging. Chitosan nanoparticles (CNs) were produced by a process of ionotropic gelation and used to deliver radiometals into WBCs. Experiments were carried out using mixed WBCs freshly isolated from whole human blood. WBCs radiolabelling efficiency was higher with [89Zr]‐loaded CN (76.8 ± 9.6% (n = 12)) than with [64Cu]‐loaded CN (26.3 ± 7.0 % (n = 7)). [89Zr]‐WBCs showed an initial loss of 28.4 ± 5.8% (n = 2) of the radioactivity after 2 h. This loss was then followed by a plateau as 89Zr remains stable in the cells. [64Cu]‐WBCs showed a loss of 85 ± 6% (n = 3) of the radioactivity after 1 h, which increased to 96 ± 6% (n = 3) loss after 3 h. WBC labelling with [89Zr]‐loaded CN showed a fast kinetic of leukocyte association, high labelling efficiency and a relatively good retention of the radioactivity. This method using 89Zr has a potential application for PET imaging of inflammation.