Abstract:  Lipopolysaccharide (LPS) has been associated with adverse developmental outcomes, including intra‐uterine fetal death (IUFD) and intra‐uterine growth retardation (IUGR). However, the exact mechanism for LPS‐induced IUFD and IURD remains unclear. LPS stimulates macrophages to generate reactive oxygen species (ROS). Therefore, we hypothesize that ROS may be involved in LPS‐induced IUFD and IURD. Melatonin is a powerful endogenous antioxidant. In this study, we investigated the protective effects of melatonin on LPS‐induced IUFD and IURD in ICR mice. All pregnant mice except controls received an intraperitoneal (75 μg/kg, i.p.) injection of LPS on gestational day (gd) 15–17. The experiment was carried out in two different modes. In mode A, the pregnant mice received two doses of melatonin within 24 hr, one (5 or 10 mg/kg) injected immediately after LPS and the other (5 or 10 mg/kg) injected at 3 hr after LPS. In mode B, the pregnant mice were pretreated with 10 mg/kg of melatonin 18 hr before LPS and then received two doses of melatonin in 24 hr, one (10 mg/kg) injected immediately after LPS and the other (10 mg/kg) injected 3 hr after LPS. The number of live fetuses, dead fetuses and resorption sites were counted on gd 18. Live fetuses in each litter were weighed. Crown‐rump and tail lengths were examined and skeletal development was evaluated. Results showed that post‐treatments with melatonin significantly attenuated LPS‐induced IUFD in a dose‐dependent manner. Surprisingly, pre‐ plus post‐treatments with melatonin almost blocked LPS‐induced IUFD. In addition, both post‐treatments and pre‐ plus post‐treatments with melatonin significantly alleviated LPS‐induced decreases in crown‐rump and tail lengths and reversed LPS‐induced skeletal developmental retardation. However, melatonin had little effect on LPS‐induced decrease in fetal weight. Furthermore, pre‐ plus post‐treatments with melatonin significantly attenuated LPS‐induced lipid peroxidation in maternal liver. These results indicate that melatonin protects against LPS‐induced IURD and IUGR via counteracting LPS‐induced oxidative stress.


This paper examines two political speeches by Mr. T ony Blair and aims at demonstrating how a close analysis of linguistic features in the texts can contribute to the comprehension of power relati ons and ideological processes in discourse. To bring to light the exertion of power, the anal ysis concentrates on such linguistic means as nominalization, the use of pron ouns, and diverse lexical choices. These means hav e been chosen as primary tools for the analysis due to the fact that they are closely related to the three fu nctions that language is said to perform, namely ideational, int erpersonal, and textual (Halliday, 1975:17, as cite d in Malmkjaer, 1991:161). The approach defined as critical linguistics is concerned with the analysis of how underlying id eologies mediated through discourse are embodied in linguist ic expressions. The method of critical linguistics was particularly devised in response to such problems a s a fixed, invisible ideology permeating language. As posited by Fowler (1991:67), it is the main concern of critical linguists to study 'the minute details of linguistic structure in the light of the social and historical situation of the text, to display to consciousness the patterns of belief and value which are encoded in the language – and which are below the threshold of notice for a nyone who accepts the discourse as "natural" '.


A growing body of evidence suggests that chronic inflammation plays a key role in initiation and development of metabolic disease as well as atherosclerotic cardiovascular disease. For instance, it is known that plasma levels of inflammatory cytokines are increased in obese subjects. Recently it has also been demonstrated that obese adipose tissue is a site of chronic inflammation. Obesity of visceral adipose tissue induces the features of chronic inflammation, including endothelia-leukocyte interactions, macrophage infiltration, coupled adipogenesis and angiogenesis, adipocyte cell death, and tissue remodeling. These features of chronic inflammation are also found in atherogenesis. Therefore, it is very likely that the common cellular and molecular mechanisms underlie pathogenesis of both cardiovascular and metabolic systems in obesity.


It has been recently established that the size of the defects created under ion irradiation follows a scaling law (Sand A. E. et al., EPL, 103 (2013) 46003; Yi X. et al., EPL, 110 (2015) 36001). A critical constraint associated with its application to phenomena occurring over a broad range of irradiation conditions is the limitation on the energy of incident particles. Incident neutrons or ions, with energies exceeding a certain energy threshold, produce a complex hierarchy of collision subcascade events, which impedes the use of the defect cluster size scaling law derived for an individual low-energy cascade. By analyzing the statistics of subcascade sizes and energies, we show that defect clustering above threshold energies can be described by a product of two scaling laws, one for the sizes of subcascades and the other for the sizes of defect clusters formed in subcascades. The statistics of subcascade sizes exhibits a transition at a threshold energy, where the subcascade morphology changes from a single domain below the energy threshold, to several or many sub-domains above the threshold. The number of sub-domains then increases in proportion to the primary knock-on atom energy. The model has been validated against direct molecular-dynamics simulations and applied to W, Fe, Be, Zr and sixteen other metals, enabling the prediction of full statistics of defect cluster sizes with no limitation on the energy of cascade events. We find that populations of defect clusters produced by the fragmented high-energy cascades are dominated by individual Frenkel pairs and relatively small defect clusters, whereas the lower-energy non-fragmented cascades produce a greater proportion of large defect clusters.


The instantaneous frequency of a rapidly tuned continuous-wave (CW) laser is measured through linear optical sampling against dual-frequency combs. This dual-comb interferometer determines the instantaneous frequency of the CW laser during a quasi-sinewave frequency sweep of 3 THz amplitude with a 10 ms period. More complicated waveforms are also measured with instantaneous chirps exceeding 1500 THz/s (12 000 nm/s). The uncertainty is 1.5 MHz at 20 ns time resolution, averaging down to 5 kHz at 5 μs time resolution. The absolute frequency accuracy can be calibrated to within 2.5 kHz provided there is a brief period (<;1 ms) of low laser chirp (<;160 GHz/s) during the waveform measurement to allow for a dual-comb Vernier measurement of the absolute frequency, modulo 3 THz. This approach allows for the characterization of arbitrary CW waveforms with instantaneous frequencies that change rapidly and over wide optical bandwidth.


Cavitation in rose stems (Rosa hybrida L.) was assessed in both intact plants and excised flowers, by measurement of ultrasonic acoustic emissions at the stem surface and determination of the air-conductivity of 2.5-cm segments that were attached at one end to air at low pressure (0.01 MPa). On sunny days the stems of intact rose plants showed acoustic emissions and conductivity to air, starting early in the morning. In Cara Mia and Sonia rose plants the cavitations were repaired during the late afternoon; in Madelon plants this repair only occurred overnight. Water flow was seriously impaired in stems of Cara Mia roses cut around midday, on sunny days. During dehydration of cut roses in air the onset of a high rate of acoustic emissions coincided with a low rate of water uptake when stems were subsequently placed in water. High emission frequency occurred after 2.4 ± 0.7 h, 6.8 ± 4.3 h and 19.8 ± 9.0 h of exposure to air in Cara Mia, Madelon and Sonia roses, respectively. A low rate of water uptake in excised stems placed in water was found after 3-4, 9-12 and 24-36 h of desiccation in air, respectively. The onset of the high emission frequency corresponded with a water potential of -1.7, -2.9 and -3.8 MPa in the three cultivars, respectively. It is concluded that a high number of cavitations may occur in noncut stems of rose plants, leading to low water uptake immediately after excision, depending on the weather and the cultivar, and that the low rate of water uptake after a period of dry storage, among the three rose cultivars investigated, is correlated with the presence of a high number of cavitated xylem elements.


The application of stem cell-derived secretome in regenerative therapies offers the key advantage that instead of the stem cells, only their effective paracrine compounds are in vivo delivered. Ideally, the secretome can be steered by the culture conditions of the stem cells. So far, most studies use stem cells cultured on stiff plastic substrates, not representative of their native 3D environment. In this study, cells are cultured inside synthetic polyisocyanide (PIC)-based hydrogels, which are minimal, tailorable, and highly reproducible biomimetic matrices. Secretome analysis of human adipose-derived stem cells (multiplex, ELISA) displays that matrix manipulation is a powerful tool to direct the secretome composition. As an example, cells in nonadherent PIC gels secrete increased levels of IL-10 and the conditioned media from 3D culture accelerate wound closure. In all, our PIC-based approach opens the door to dedicated matrix design to engineer the secretome for custom applications.


.. Objectives: To correlate CK-19 with different histopathological gradings of oral squamous cell carcinomas (OSCCs). Methods: Study Design: Descriptive study. Setting: Department of Outpatient, ISRA Dental College Hospital. Period: January 2014 to November 2019. Material & Methods: In current study 60 suspected patients of oral squamous cell carcinomas were enrolled for cancer diagnosis and histopathological evaluation. Incisional biopsy method was opted for tissue sample collection. Patients from both genders were tested for CK-19 at different histopathological gradings. Ethical approval was properly taken from Institutional review board and patients' willingness to participate in the study was ensured. For statistical data analysis SPSS version 21.0 and Revman5.30 multiple tools were used. Results: Histopathological grading of sixty suspected cases of OSCCs was done into four different gradings which include, poorly differentiated, moderately differentiated, well differentiated and undifferentiated OSCCs. Fifty-two (87 %) of the included subjects were male, where only 8 patients were female. The mean age of female to male was (36.14 vs. 43.21 years). Out of 12 positive cases of OSCCs. CK-19 was found positive in 10 cases (83.3%) in well differentiated Oral Squamous cell carcinomas, where only 2 cases (16 %) of moderately differentiated OSCCs were positive against CK-19. Conclusion: Our outcomes suggest CK-19 has strong association with well differentiated and moderately differentiated Oral Squamous cell carcinomas. We highly recommend further research standardizing CK-19 as a promising histopathological grading marker.


Introduction Associated with hospital evacuation is the need to track multiple patient evacuees from point of origination to final hospital reception. Patient tracking, a component of the hospital emergency operations plan, is vital to patient care; family association, resource management, financial reimbursement, risk management, and repatriation. Tracking strategies and plans can include a variety of vendors, hardware, software, and coordination issues. Hospital evacuee tracking plans and platforms exist at multiple jurisdictional levels but may not be interoperable. Methods Three patient tracking platforms representing a local, state and federal application were used during a multi-hospital evacuation exercise, initiated in New Orleans, Louisiana, May 2010. Simulated patients were flown and tracked to multiple patient reception centers in the southern United States, including the Federal Coordinating Center in Shreveport, Louisiana, and receiving National Disaster Medical System hospitals. This review summarizes tracking operations, patient data characteristics captured and interoperability at the Shreveport reception location. Results 7 New Orleans hospitals entered 51 patients for evacuation into Louisiana's web-based, At-Risk-Registry (ARR) database including 8 patient identifiers each. ARR data was shared with federal and Louisiana Region 7 patient evacuee receivers for flight manifest construction and reception planning. 34 ARR evacuee patients were indicated for the Shreveport, Louisiana, reception site. 34 patients with 6 identifying characteristics were entered from ARR into EMTrack, the local patient tracking system. A C130 arrived with a TRAC2ES manifest of 20 simulated patients with 6 patient data characteristics. The local tracking system was reconfigured for the hardcopy manifest; simulated patients were received at the airport; transported and received at local hospitals. Conclusions Tracking system interoperability may be challenged by tracking technologies, jurisdictional requirements and degree of implementation at the local, state and federal level. Tracking should be standardized based on national recommendations with local systems remaining flexible for just-in-time requirements.


Background: Tyrosine kinase inhibitors (TKIs) have been developed against EGFR. However, in NSCLC (Non-small Cell Lung Cancer) and some other cancers, the occurrence of activating mutations in EGFR leads to acquired resistance. Anomalous cMET signaling additionally contributes to developing resistance to targeted therapies, including ones directed at EGFR. A number of bispecific antibodies targeting EGFR and cMET are in clinical trials and JNJ-61186372 (Amivantamab) from Janssen labs, has been given fast track approval by the FDA. In this study we created bispecific and trispecific antibody formats which target both cMET and EGFR. Trispecific (TsAb), unlike the bispecific (BsAb), binds to two different epitopes on cMET and one on EGFR resulting in enhanced internalization of the receptors. This study demonstrates that our antibodies exhibit enhanced capabilities than the benchmark at clinical stage in cell and non-cell based in vitro assays. Methods: The two cMET binding arms of TsAb were designed to block the cMET-HGF (ligand) interaction and enhance the internalization of the receptors. Cell based assays were performed using a NSCLC cell line NCI-H1975 (ATCC CRL-5908) and HGF-expressing NCI-H1975. Receptor binding and receptor/ligand blocking (cMET/HGF and EGFR/EGF) assays were performed using both ELISA and flow cytometry. Phosphorylation assays were performed using ELISA and Western blotting. Receptor internalization studies were executed using the pHrodo labelling kit and were further assessed through fluorescence microscopy and quantified through flow cytometry. ADCC assays (Antibody dependent cellular cytotoxicity) were performed through the Crystal violet method. Results: BsAb was more effective than benchmark in terms of its binding capabilities to cMET and EGFR receptors and also in blocking the interaction of cMET and EGFR with their ligands. Moreover, functional assays revealed that the new BsAb is in most cases better than benchmark in successfully inhibiting the phosphorylation of not only the cMET and EGFR receptors but also the downstream signaling pathways which are involved in cancer cell proliferation, survival and obstructing the apoptotic pathways. Furthermore, the new TsAb was found to be more effective than BsAb and benchmark in cMET/EGFR receptor internalization which may lead to additional extenuation of the downstream pathways for these receptors. Cancer cell killing assays for ABT BsAb show ADCC comparable to the benchmark. Conclusion: Comparing to BsAbs, TsAb induces enhanced internalization of the cMET/EGFR receptors leading to further extenuation of the downstream oncogenic signaling pathways. These data suggest the development of ABT BsAb and specifically TsAb as a new drug target for patients with lung cancer and NSCLC in particular. Citation Format: Mohd Zaman, Cai Huang, Sachith Gallolu Kankanamalage, Amit K. Chaudhary, Jianbo Dong, Yue Liu. Development of cMET/cMET/EGFR Trispecific antibody as therapeutic modality for Non-small Cell Lung Cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB069.


This research involves studying the effect of thermal neutron on the optical properties of nuclear track detector (CR-39) exposed to radiation at different time ranges from (1 to 15) day at room temperature. The photo absorption was measured using a spectrometer (UV-1100). The results show that the coefficient of absorption increases by increasing time of neutron flux exposure. It was found that the energy gap values decrease with the increase of exposure radiation time, the results also show that the value of energy gap at direct effect (before and after) radiation is more than its value in the indirect effect, also the numbers of carbon atoms in a cluster were determined from UV-visible spectra of the thermal neutron irradiated samples.


AIM
To investigate the relationship between insulin-like growth factor-I, -II (IGF-I and IGF-II), IGF-binding protein 3 (IGFBP-3) and Child-Pugh score in patients with liver cirrhosis, and to search for potential clinical markers of liver function.

METHODS
Forty-four patients with advanced liver cirrhosis of viral origin were divided into 3 groups according to severity of cirrhosis (Child-Pugh score) and 38 healthy subjects served as controls. Serum levels of IGF-I, IGF-II and IGFBP-3 were measured by immunoradiometric assay.

RESULTS
Serum IGF-I, IGF-II and IGFBP-3 levels were significantly lower in patients with cirrhosis than in controls, and serum concentrations of IGF-I, IGF-II and IGFBP-3 were associated with the severity of liver dysfunction, and dropped sharply during the progression of liver failure. Among these 3 parameters, serum IGF-II was the most sensitive and effective indicator for liver dysfunction. Concentrations of IGF-I <30 ng/mL, IGF-II <200 ng/mL and IGFBP-3 <6 ng/mL implied a negative prognosis for patients with liver cirrhosis.

CONCLUSION
Serum IGF-I, IGF-II and IGFBP-3 may provide a new dimension in the assessment of liver dysfunction. Combined detection of serum IGF-I, IGF-II and IGFBP-3 with Child-Pugh score is more effective in predicting prognosis than Child-Pugh score alone.


The efficiency of drugs often hinges on drug carriers. To effectively transport therapeutic plant molecules, drug delivery carriers should be able to carry large doses of therapeutic drugs, enable their sustained release, and maintain their biological activity. Here, graphene oxide (GO) is demonstrated to be a valid carrier for delivering therapeutic plant molecules. Salvianolic acid B (SB), which contains a large number of hydroxyl groups, bound to the carboxyl groups of GO by self-assembly. Silk fibroin (SF) substrates were combined with functionalized GO through the freeze-drying method. SF/GO scaffolds could be loaded with large doses of SB, maintain the biological activity of SB while continuously releasing SB, and significantly promote the osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs). SF/GO/SB also dramatically enhanced endothelial cell (EA-hy9.26) migration and tubulogenesis in vitro. Eight weeks after implantation of SF/GO/SB scaffolds in a rat cranial defect model, the defect area showed more new bone and angiogenesis than that following SF and SF/GO scaffold implantation. Therefore, GO is an effective sustained-release carrier for therapeutic plant molecules, such as SB, which can repair bone defects by promoting osteogenic differentiation and angiogenesis.


A pentacene thin-film transistor (TFT) was fabricated on a SiO2 gate insulator modified with twisted biaryls. The biaryl monolayer, in particular a binaphthyl (BN) monolayer, is amorphous surface where the naphthalene rings are randomly oriented with no lateral order because of their rigid, twisted, and asymmetric shape. When the BN monolayer was used for the surface treatment of SiO2, large grains were obtained in the early stages of the pentacene crystal growth. The pentacene TFT had a field effect mobility (microm) in excess of 0.4 cm2/Vs and an on/off ratio greater than 10(5). The surface treatment improved the mobility of the pentacene TFT by a factor of 50% compared with non-treated devices. The morphology of the semiconductor layer was investigated using atomic force microscopy (AFM) and X-ray diffraction (XRD).


This revised Safety Analysis Report for Packaging (SARP) includes discussions of structural integrity, thermal resistance, radiation shielding and radiological safety, nuclear criticality safety, and quality control of shipping containers. Much of the information was previously submitted to AEC/OSD/ALO and the Department of Transportation (DOT) and provided the basis for obtaining special permits DOT-SP-5790 and DOT-SP-5791 as well as the Interim Certificates of Compliance until the original SARP could be prepared and Certificates of Compliance issued by ERDA. This SARP revision incorporates information on certain design changes, the most significant of which relate to the inner container for the type 5790 package. Complete physical and technical descriptions of the packages are presented. Each package consists of a cylindrical steel inner container centered within an insulating steel drum assembly. The contents may be any radioactive materials which satisfy the requirements established in this SARP. A shipment of plutonium-238 in the form of a solid oxide is evaluated in this SARP as an example. The results of the nuclear criticality safety analysis show how much of the fissile isotopes may be shipped as Fissile Class I, II, or III for each container. Design and development considerations, the tests and evaluations required to provemore » the ability of the containers to withstand normal transportation conditions, and the sequence of four hypothetical accident conditions (free drop, puncture, thermal, and water immersion) are discussed. Tables, graphs, dimensional sketches, photographs, technical references, loading and shipping procedures, Mound Facility experience in using the containers, and copies of the DOE Certificates of Compliance are included. Internal reviews of the original and revised SARP's have been performed in compliance with the requirement of DOEM 5201-Part V.« less


Introduction: Patients with triple negative breast cancer (TNBC) that do not respond to cytotoxic neoadjuvant therapy have a poor prognosis, thus there is a pressing need to develop pre-clinical models of chemoresistant TNBC and identify optimal therapeutic targets. Patient-derived xenografts (PDX) are a simple, expandable approach to model TNBC in vivo. We have generated a collection of triple negative PDXs that have undergone molecular characterization at the DNA, RNA and protein levels and have initiated characterization of their therapeutic sensitivity to standard chemotherapeutics regimens as well as targeted therapies. Methods: Tumors from patients and matching PDXs have been characterized by cancer-specific targeted exome sequencing, RNA sequencing, and Reverse Phase Protein Arrays. We have established single agent sensitivities for a set of PDXs to standard TNBC therapies (paclitaxel, carboplatin, doxorubicin, eribulin, gemcitabine) and the following targeted therapies: talazoparib (PARP), MLN0128 (mTOR), buparlisib (PI3K), and trametinib (MEK1/2). Results: We have generated 25 hormone receptor-low/HER2- PDXs from 24 patients (1 primary-local recurrence pair) with an overall engraftment rate of 49% for this patient population. Exome sequencing found that the PDXs mostly maintain the somatic mutation profile of the originating tumor and exhibit alterations common to TNBC: 16 (73%) with TP53 mutations, 2 (9%) with PI3KCA mutations and 4 (18%) with PTEN deletions. RNA sequencing demonstrated that the PDXs maintain gene expression profiles similar to the originating tumor and that our panel is comprised of PDXs representative of five TNBC molecular subtypes. Treatment with standard therapies established differential sensitivity to paclitaxel and carboplatin between PDXs. The two models with PI3KCA alterations were responsive to mTOR/PI3K inhibition and unresponsive to trametinib and talazoparib, supporting heightened reliance on mTOR/PI3K signaling in PI3KCA mutant TNBC. Talazoparib was the only targeted agent tested that caused regression as a single agent in any model. All three models that regressed with talazoparib treatment had genetic alterations linked to DNA damage pathways (BRCA1 germline alteration, ATM deletion; PTEN deletion); these models also had low BRCA1 mRNA expression and were the only PDXs to regress when treated with carboplatin. Conclusions: PDXs of all TNBC subtypes can be generated from TNBC patients that are resistant to neoadjuvant chemotherapy. These PDXs maintain molecular alterations of TNBC, retain patient-specific gene expression, and display differential response to therapies enabling identification of associations between responses and molecular traits. Citation Format: Kurt W. Evans, Erkan Yuca, Stephen M. Scott, Natalia Arango Paez, Xiaofeng Zheng, Ken Chen, Laura Gonzales, Coya Tapia, Emily Tarco, Dalliah M. Black, Gordon B. Mills, Funda Meric-Bernstam. Patient-derived xenografts to test emerging therapies for triple negative breast cancer. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr A39.


ABSTRACT Meat is an important food for human nutrition, by especially providing high-quality protein and also some essential micronutrients, in front iron, zinc, and vitamin B12. However, a high intake of red and processed meat is associated with an increased risk for diseases, especially type 2 diabetes and colorectal cancer, as several epidemiological studies and meta-analyses have shown. This review summarizes meta-analyses of publications studying the association between red and processed meat intake and type 2 diabetes, cardiovascular diseases, colorectal and other cancers, and all-cause mortality. Various potential mechanisms involved in the increased disease risk are discussed. Furthermore, the beneficial effects of healthy alternatives for meat, like fish, nuts, vegetables and fruits, pulses and legumes, whole grains, and dairy products are reviewed by including selected papers and recent meta-analyses.


Successor of the University Council founded in 1808, the Higher Council of Public Instruction created by the Falloux Law (1850) comprised representatives of the "social forces", like the clergy and the magistracy. This characteristic was kept and even extended in 1873. In 1880, on the contrary, Jules Ferry established the Higher Council with members from the public education system, almost exclusively. The Conservatives opposed the thesis put forward by the Republicans that there could not be an independent representation of society apart from the national representation, in the form of the Parliament. The Republican argument can be interpreted as a mark of the liberal Jacobinism that constitutes the "French political model", according to Pierre Rosanvallon. Notwithstanding, 15 years later, the Minister of Public Instruction, Emile Combes, proposed to backtrack on the predominantly university-based composition of the Higher Council, a source of narrow-mindedness, in his eyes. But his project was met with virulent opposition. The reform of 1933 was prudently limited to introducing representatives of parents and of heads of state-run secondary schools.


 Abstract — In most developing countries, although the vast majority of the people are living in the rural areas, the qualified medical doctors are not available there. Health care workers and paramedics, called village doctors, informal healthcare providers, are largely responsible for the rural medical care. Mishaps due to wrong diagnosis and inappropriate medication have been causing serious suffering that is preventable. While innovators have created many devices, the vast majority of these technologies do not find applications to address the needs and conditions in low-resource settings. The primary motive is to address the acute lack of affordable medical technologies for the poor people in low-resource settings. A low cost smart medical device that is portable, battery operated and can be used at any point of care has been developed to detect breathing rate, electrocardiogram (ECG) and arterial pulse rate to improve diagnosis and monitoring of patients and thus improve care and safety . This simple and easy to use smart medical device can be used, managed and maintained effectively and safely by any health worker with some training. In order to empower the health workers and village doctors, our device is being further developed to integrate with ICT tools like smart phones and connect to the medical experts wherever available, to manage the serious health problems.


Voltage fluctuations, such as sags and swells, are the most widespread power quality issues affecting electrical power distribution systems. This paper describes details of sag characteristics due to different types and locations of faults in one practical power distribution system. The results can not only give utility engineers very useful information when they deal with area of vulnerability, but also assist the facility personnel to make decisions on purchasing power quality mitigation equipment. At the same time, one special wavelet analysis is utilized to detect voltage sags and swells. Characteristics of investigated signals are measured on a time- frequency plane. The results are very satisfied.


I ask leave from the poets and orators of Tonga, whose inherited metaphors I am about to describe in the plain language of English. My work is the product of many years of joint endeavor with Tupou Posesi Fanua. The Kingdom of Tonga consists of a group of scattered islands in western Polynesia. In the far north of this group are three isolated islands, Niuafo'ou, Niuatoputapu, and Tafahi, known collectively as the Niua Islands. In the late 1960s, while conducting ethnographic research there, I began to understand how the colonized people of these islands made use of songs to speak ruefully about the hardships of their lives and to assert their independence of thought in the face of political and economic rule from the south. In formal Tongan discourse it is unseemly to speak directly of one's subject or intention, and so poets embellish their poems in order to distract the audience's attention in such a way that their meaning is discerned only by those for whom it is intended. This paper examines three songs, one from each of the Niua Islands, in which poets practice this art. In these elaborate songs there are two levels of meaning, one intended for outsiders and one for the poet's own people. Complex irony, skillful metaphors, and witty play upon convention allow the poets to present their messages with appropriate indirection. To appreciate the content and roles of these songs, one must understand something of the historical background.


The goal of sharding in a contemporary Blockchain system is to increase throughput linearly in proportion to the number of shards. This is achieved in practice by one-to-one mapping of each transaction block to a shard, with the assumption that each shard is 'perfect' and hence cannot fail. The notion of perfection is achieved by forming shards that have negligible failure probabilities. This contemporary approach to blockchain sharding has two drawbacks: (1) shards tend to be large in size to maintain low failure probability, which can negatively affect performance and throughput; (2) the 'perfect' shard assumption can easily be breached if any shard becomes faulty, which can fail an entire blockchain system because there is no fault-detection mechanism during transaction-processing (i.e., faulty blocks approved by faulty shards may only be detected after being appended to the blockchain). To overcome these drawbacks, this paper presents a multi-round consensus scheme which adopts one-to-many mapping of a transaction block to $k$ shards, followed by a second consensus round among the $k$ shard leaders (inter-shard consensus) in an epoch to validate and commit a transaction block with finality. In return, the following are achieved: (1) possibility of increased fault tolerance, despite using smaller shard sizes, because the collective failure probability of a group of $k$ small shards can be much lower than the failure probability of an individual larger shard with the proper selection of the values of $k$ and other parameters; (2) capability of faulty block detection with high probability during transaction processing; and (3) relaxation of the 'perfect' shard assumption so that the system can be tolerant to more faulty shards and still maintain safety. Detailed theoretical analyses are presented which demonstrate the benefits of such a multi-round block validation approach over contemporary approaches in terms of achieving better fault tolerance without compromising on throughput.


Current therapies for autoimmune diseases rely on traditional immu- nosuppressive medications that expose patients to an increased risk of opportunistic infections and other complications. Immunoregula- tory interventions that act prophylactically or therapeutically to induce antigen-specific tolerance might overcome these obstacles. Here we use the transpeptidase sortase to covalently attach disease-associated autoantigens to genetically engineered and to unmodified red blood cells as a means of inducing antigen-specific tolerance. This approach blunts the contribution to immunity of major subsets of immune effector cells (B cells, CD4 + and CD8 + T cells) in an antigen-specific manner. Transfusion of red blood cells expressing self-anti- gen epitopes can alleviate and even prevent signs of disease in experimental autoimmune encephalomyelitis, as well as maintain normoglycemia in a mouse model of type 1 diabetes.


Scantegrity is a security enhancement for optical scan voting systems. It's part of an emerging class of "end-to-end" independent election verification systems that permit each voter to verify that his or her ballot was correctly recorded and counted. On the Scantegrity ballot, each candidate position is paired with a random letter. Election officials confirm receipt of the ballot by posting the letter that is adjacent to the marked position. Scantegrity is the first voting system to offer strong independent verification without changing the way voters mark optical scan ballots, and it complies with legislative proposals requiring "unencrypted" paper audit records.


A study on the behavior of reinforced high-strength concrete corbels is carried out using nonlinear finite element analysis and a simplified softened strut-and-tie model. In the numerical analysis, eight-node isoparametric plane stress elements are employed to model the concrete material. An elastic-strain hardening plasticity approach combined with cracking damage is used in modeling the concrete behavior. The reinforcing bars are treated as embedded elements and are considered as elastic-perfectly plastic material. In the analytical method, the analysis is based on truss analogy following the provisions of Appendix A of the ACI 318-05 Code. Strength predictions of both methods correlate well with the 34 test results of corbels available from the literature. It was concluded that the adopted finite element model is a powerful tool for the analysis of such disturbed region. Also the simple truss model used proved to be a suitable design tool for these members. The finite element method can be used in conjunction with the truss analogy for optimum design.


Macrophages are classified upon activation as classical activated M1 and M2 anti-inflammatory regulatory populations. This macrophage polarization is well characterized in humans and mice, but M1/M2 profile in cattle has been far less explored. Bos primigenius taurus (taurine) and Bos primigenius indicus (indicine) cattle display contrasting levels of resistance to infection and parasitic diseases such as C57BL/6J and Balb/c murine experimental models of parasite infection outcomes based on genetic background. Thus, we investigated the differential gene expression profile of unstimulated and LPS stimulated monocyte-derived macrophages (MDMs) from Holstein (taurine) and Gir (indicine) breeds using RNA sequencing methodology. For unstimulated MDMs, the contrast between Holstein and Gir breeds identified 163 Differentially Expressed Genes (DEGs) highlighting the higher expression of C-C chemokine receptor type five (CCR5) and BOLA-DQ genes in Gir animals. LPS-stimulated MDMs from Gir and Holstein animals displayed 1,257 DEGs enriched for cell adhesion and inflammatory responses. Gir MDMs cells displayed a higher expression of M1 related genes like Nitric Oxide Synthase 2 (NOS2), Toll like receptor 4 (TLR4), Nuclear factor NF-kappa-B 2 (NFKB2) in addition to higher levels of transcripts for proinflammatory cytokines, chemokines, complement factors and the acute phase protein Serum Amyloid A (SAA). We also showed that gene expression of inflammatory M1 population markers, complement and SAA genes was higher in Gir in buffy coat peripheral cells in addition to nitric oxide concentration in MDMs supernatant and animal serum. Co-expression analyses revealed that Holstein and Gir animals showed different transcriptional signatures in the MDMs response to LPS that impact on cell cycle regulation, leukocyte migration and extracellular matrix organization biological processes. Overall, the results suggest that Gir animals show a natural propensity to generate a more pronounced M1 inflammatory response than Holstein, which might account for a faster immune response favouring resistance to many infection diseases.


The purpose of this study is to investigate whole spinal alignment patterns in an automotive seated posture. Image data sets of eight female and seven male seated volunteers were acquired using upright open Magnetic Resonance Imaging systems. The images were processed to extract the whole spine alignment defined with the centres of the vertebral bodies. Patterns of the whole spine alignment were investigated through Multi‐Dimensional Scaling analyses. The analysis revealed that variations in the whole spine alignment due to individual differences were seen most remarkably in the combination of curvature of the cervical spinal alignment and degree of the thoracic kyphosis with its peak vertebra level. Subjects with cervical lordosis tended to have a pronounced thoracic kyphosis, with the peak of this kyphosis located at a lower vertebra level. Subjects with cervical kyphosis tended to have a less pronounced thoracic kyphosis, with the peak of this kyphosis at a higher vertebra level. These trends were also observed in the differences of average spinal alignments between males and females.


263-8522, Japan Abstract : This study investigated the basis of a right-side dominance in aesthetic arrangement. In experiment 1, in order to examine the effect of attended position in pictures on aesthetic arrangement, we manipulated the positions of the fixation points, which attract observer's attention, and centroids of triangle arrangement for three objects. Participants rated preference, balance, beauty and harmony by the use of seven points scale for each of the pictures. We found that participants evaluated highly aesthetic in viewing the pictures whose arrangement centroids were near to the fixated position. In experiment 2, in order to examine the effect of participant's dominant hand on aesthetic arrangement we presented the objects which the participants are willing to manually manipulate, or the object which they should avoid to manually touch for right-handed or left-handed participants. We found that right-handed participants evaluated highly aesthetic in viewing the pictures whose arrangement centroid was at right side, but left-handed participant


This paper presents an energy-saving, open-loop control technique for a flexible manipulator with point-to-point motion. In the proposed method, the joint angle of the manipulator is expressed by an artificial neural network (ANN). For the ANN, we use a vector evaluated particle swarm optimization (VEPSO) algorithm as the learning algorithm. The maximum residual vibration amplitude and the operating energy are adopted as the multi-objective functions of the VEPSO algorithm. By operating the manipulator along the trajectory obtained by the proposed method, the residual vibrations can be suppressed; thus, saving energy. In other words, the proposed method is an open-loop control that does not require sensors to measure unwanted vibrations. The performance of the proposed control scheme is confirmed by numerical simulations. In addition, the effectiveness of the proposed approach is experimentally verified.


Acupuncture, moxibustion, and cupping, important in traditional Eastern medicine, are increasingly used in the West. Their widening acceptance demands continual safety assessment. This review, a sequel to one our team published 10 years ago, is an evaluation of the frequency and severity of adverse events (AEs) reported for acupuncture, moxibustion, and cupping between 2000 and 2011. Relevant English-language reports in six databases were identified and assessed by two reviewers. During this 12-year period, 117 reports of 308 AEs from 25 countries and regions were associated with acupuncture (294 cases), moxibustion (4 cases), or cupping (10 cases). Country of occurrence, patient's sex and age, and outcome were extracted. Infections, mycobacterial, staphylococcal, and others, were the main complication of acupuncture. In the previous review, we found the main source of infection to be hepatitis, caused by reusable needles. In this review, we found the majority of infections to be bacterial, caused by skin contact at acupoint sites; we found no cases of hepatitis. Although the route of infection had changed, infections were still the major complication of acupuncture. Clearly, guidelines such as Clean Needle Technique must be followed in order to minimize acupuncture AEs.


This study confirms what is seen in clinical practice and in published large prospective studies, that 5ARI therapy decreases progression of BPH symptoms and associated morbidities in large prostates, and decreased compliance was associated with higher rates of surgery. However, compliance in older populations was greater and reflects the decreased impact of sexual adverse events on 5ARI adherence. A significant 5ARI adherence issue is prostate cancer. 5ARI labeling describes an associated higher incidence of high grade prostate cancer in treatment versus placebo arms. However, this labeling is misleading since it is attributed to sampling bias in treatment vs placebo in a small number of patients. This helps to ignore the 25% decrease in overall prostate cancer and size in the treatment arm versus placebo. With a decrease in prostate volume, an increase in probability of finding these clinically significant cancers in smaller prostates is more likely the cause. This advantageous effect allows treated prostates to be biopsied with a higher sensitivity than placebo over time as needed. As a "partners" database, guideline, reimbursement policy and role of Medicare part D could be investigated to see how these impacted utilization and adherence. Prescription managing groups steer to finasteride as the preferred alternative since finasteride is less expensive with cost competitive advantages from generic sourcing. However, dutasteride, with a longer half-life and more consistent therapeutic bioavailibity, may be better. Adherence in younger men is more due to impact or perceived impact of sexual side effects. However, "post-finasteride syndrome" does not seem to be an issue for older men despite the higher dosage used compared to younger men who are typically prescribed a lower dose for hair loss. Overall, this study confirms 5ARI utility and it should be used more often, especially in large prostates and high risk patients.


Chemopreventive agents generate oxidative stress, which culminates in cell death and may be part of a general mechanism of chemoprevention. The redox-responsive cyclooxygenase (COX)-2, overexpressed during carcinogenesis, has been a target for cancer prevention. To assess the potential link between chemopreventive agents, oxidative stress and COX-2, we studied the chemopreventive sulindac and nitric oxide-donating aspirin (NO-ASA). Both generated oxidative stress and induced COX-2 in various cell lines, more prominently in dying cells. Two antioxidants and an inhibitor of NADPH oxidase abrogated the induction of COX-2 and cell death. Exogenous xanthine/xanthine oxidase, which produce O(2)(-)., had the same effect. Inhibition of caspases and cox-2 knockdown showed that COX-2 did not participate in reactive oxygen species (ROS) generation or cell death induction in response to NO-ASA. Our results support three potentially useful ideas: (i) the concept that ROS are a critical component of the action of chemopreventive agents; (ii) the notion that COX-2 may not be an ideal target for chemoprevention and (iii) the possibility that COX-2 may be overexpressed in cancer cells due to their state of oxidative stress. It is conceivable that, if further substantiated, these findings may inform the rational design of chemotherapeutic strategies, in particular the choice of agents in combination approaches.


Glaucoma is a serious complication after corneal transplantation that can lead to permanent loss of vision. Peripheral anterior synechiae (PAS) leads to severe glaucoma, which is refractory to medications, however, the exact mechanism of PAS development after corneal transplantation is still elusive. Recent studies revealed signi�cant alterations in cytokine levels in aqueous humor (AqH) in glaucoma. Hence, we quanti�ed PAS area using three dimensional OCT and evaluated the association between cytokine levels in AqH and PAS area after Descemet stripping automated endothelial keratoplasty (DSAEK). We �rst found that the total protein level in AqH was signi�cantly higher in eyes with PAS progression than those without, and was positively correlated with the progression of PAS area after DSAEK. Furthermore, the postoperative PAS area was signi�cantly correlated with the AqH levels of interleukin-8, interferon-γ, and soluble intercellular adhesion molecule-1. Multivariate analyses showed that the total protein levels in AqH and presence of preoperative PAS were signi�cant risk factors for increased PAS area after DSAEK. The PAS development was associated with intraocular pressure increase after DSAEK. In conclusion, these �ndings suggest that pathological alterations in the AqH can cause PAS progression and glaucoma after DSAEK.


An experience in non-puerperal lactation, specifically induced for nutritional rehabilitation of a malnourished motherless male infant, is presented from a Fulani culture in northern Nigeria where the usual cultural practice is to feed such infants with raw cow's milk. The value of non-puerperal lactation in nutritional rehabilitation of motherless infants is highlighted and the role of adequate psychological preparation and support in successful relactation is emphasised.


The existing controllers for robot manipulators with uncertain gravitational force can globally stabilize only robot manipulators with revolute joints. The main obstacles to the global stabilization of robot manipulators with mixed revolute and prismatic joints are unboundedness of the inertia matrix and the Jacobian of the gravity vector. In this note, a class of globally stable controllers for robot manipulators with mixed revolute and prismatic joints is proposed. The global asymptotic stabilization is achieved by adding a nonlinear proportional and derivative term to the linear proportional-integral-derivative (PID) controller. By using Lyapunov's direct method, the explicit conditions on the controller parameters to ensure global asymptotic stability are obtained.


ABSTRACTAttention Deficit and Hyperactivity Disorder (ADHD) is among the most commonly encountered neurodevelopmental disorders in childhood with its reported worldwide prevalance as 5%. Among the recommended treatment regimens as stimulants, the most frequently advised ones are methylphenidate (MPH) preparates. Among long acting MPH preparates, the form that contains an osmotic release oral system (MPH-OROS) is frequently used in clinical practice. Studies about risks, causes and outcomes regarding high dose MPH intake and effects of high dose MPH preparates in humans are limited. This article presents the clinical picture of a 12 year old boy who attempted suicide by ingesting 15 tablets of 36- mg MPH OROS. Exposure to an overdose of MPH-OROS exhibited acute sympathomimetic toxicity but no life-threatening symptoms in this patient. This case report might suggest that higher doses of MPH-OROS could be tolerated well under fine clinical observation and management; although more larger scale studies in thi...


Nowadays, maternal health issues are one of the most challenging issues all over the world. Many women die each year during pregnancy and after delivery, which is a major cause of infant mortality. In rural areas,pregnant women face various difficulties and challenges, including a shortage of doctors, inadequate knowledge, a lack of public clinics, infrastructure issues, and transportation issues. The mother's pregnancy is the major cause of the infant's poor health, rather than any other factors that may have arisen after childbirth. Significant roles are played by maternal risk factors such as the mother's chronic condition, age, nutrition, and other medical assistance during pregnancy. Recent developments in Artificial intelligence methods, particularly machine learning models, have made it easier to make predictions in a variety of disciplines. We can identify the primary maternal risk factors that can lead to newborn child and maternal mortality using machine learning techniques. This paper proposes improved data preprocessing methods that involve feature engineering and data cleaning in order to effectively handle anomalies in the data values. To identify the maternal health risk factor, several machine learning algorithms were used, including Cat Boost, Random Forest, XGB, Decision Tree, and Gradient Boost. Using the preprocessed dataset, the suggested model was developed, trained, and tested. The Random Forest was the best machine-learning algorithm with an accuracy score of 90%, precision (90%), recall (90%), and Fl-score (90%)


This study presents the first attempt of direct continuous-time model identification using instrumental variable method for Hammerstein–Wiener systems from sampled data. Under the assumption of monotonic function for the Wiener part, the whole non-linear model is first estimated as an augmented multiple-input single-output linear model, from which the model parameters are then extracted by singular value decomposition. A refined instrumental variable method is proposed to consistently identify this non-linear system acting in a coloured noisy environment. Monte Carlo simulation analysis is presented to illustrate the effectiveness of the proposed method.


Because of high costs or complex logistics, scientific populations cannot be measured entirely and must be sampled. Accepted scientific practice holds that sample selection be based on statistical principles to assure objectivity when estimating totals and variances. Probability sampling--obtaining samples with known probabilities--is the only method that assures these results. However, probability sampling is seldom combined with appropriate estimators to determine suspended sediment loads. Many current load-estimating methods, therefore, have unknown bias and variation making the estimates questionable. Suspended sediment loads are often estimated by sampling concentration at fixed intervals. This type of sampling is-promoted by the widespread use of pumping samplers which can be set to sample at regular intervals. Sampling intensity is sometimes increased during periods of high water discharge. Randomly started systematic samples are probability samples, and estimates of totals from such samples are unbiased. These estimates tend to have low variance, but the variance cannot be estimated, and is not always reduced by increasing sample size. Systematic sampling of concentration distributes data evenly over time, so that most measurements are collected during low flows, and few during the brief high-flow periods when most sediment is transported. Systematic sampling for estimating suspended sediment loads is investigated for a "complete" sediment record from the Mad River in northern California. The "true" total for the 31-day period is compared to expected estimates from systematic samples without random starts. Systematic sample variance is compared to three other finite sampling schemes and to estimates using the simple random sampling variance formula. The effects of changing systematic sample size are also studied. If systematic sampling is used to estimate suspended sediment loads, the limitations of the method should be realized and correct estimating formulas used. The best use for systematic "sampling" is to define the sampled population for further sampling by more efficient finite sampling schemes.


We present CREST, an approach for causal reasoning in simulation to learn the relevant state space for a robot manipulation policy. Our approach conducts interventions using internal models, which are simulations with approximate dynamics and simplified assumptions. These interventions elicit the structure between the state and action spaces, enabling construction of neural network policies with only relevant states as input. These policies are pretrained using the internal model with domain randomization over the relevant states. The policy network weights are then transferred to the target domain (e.g., the real world) for fine tuning. We perform extensive policy transfer experiments in simulation for two representative manipulation tasks: block stacking and crate opening. Our policies are shown to be more robust to domain shifts, more sample efficient to learn, and scale to more complex settings with larger state spaces. We also show improved zero-shot sim- to-real transfer of our policies for the block stacking task.


A diffusive box model, consistent with geostrophy, is proposed as an alternative to more usual advective box models of the ocean thermohaline circulation. When vertical diffusion coefficients for T and S are taken as identically equal (the normal assumption in all numerical ocean models to date), the diffusive box model exhibits both steady-state modes and time-dependent behaviors which are essentially indistinguishable from those of an advective model, under both fixed flux and mixed (T restoring) boundary conditions. The thermohaline "circulation" of the diffusive box model, however, is a combination of a convective branch and a vertical diffusive branch, involving zero volume flux. Modifications in behavior of the diffusive box model are investigated for a plausible range of values for the ratio d equiv Ks/KT of the vertical turbulent diffusivities of S and T. When surface fluxes of heat and freshwater are constant, the model with d ne 1 exhibits additional steady-state modes in which convection is absent from the system, as well as a periodic oscillatory mode. Compared to results with d equiv 1 under mixed surface boundary conditions, the model with d ne 1 exhibits extended ranges of multiple equilibria, a different mode transition near present-day values of freshwater forcing magnitude, and the possibility of quasi-periodic oscillatory states. The sensitivity of the present box model, coupled with that previously observed in a primitive equation model (Gargett and Holloway, 1992), raises serious questions about the ability of numerical models to predict the evolution of the ocean thermohaline circulation under changing atmospheric forcing, even if other problems with such prediction were resolved.


This article describes the subroutine library SLICOT that provides Fortran 77 implementations of numerical algorithms for computations in systems and control theory. Around a nucleus of basic numerical linear algebra subroutines, this library builds methods for the design and analysis of linear control systems. A brief history of the library is given together with a description of the current version of the library and the ongoing activities to complete and improve the library in several aspects.


As the deployment of high-speed fiber transmission systems has been accelerated, they are widely recognized as a firm infrastructure of the information society. In SONET, the self-healing networks have been highlighted as one of the most advanced mechanisms used to realize SONET survivable networks. Several schemes have been proposed and studied due to the rapid progress in the development of highly intelligent network elements (NEs). A DCS based distributed self-healing network is discussed from the viewpoint of its control algorithms. The self-healing algorithm, called TRANS, is explained in detail. It possesses such desirable features as providing fast and flexible restoration with line and path level restoration applied to an individual STS-1 channel, the capability of handling multiple and even node failures, and so on. Both software simulation and hardware experiment verify that TRANS works properly in a real distributed environment, the result of which is shown in the paper. In addition, the combined use of TRANS and ring restoration control is proposed taking into account a practical SONET application. >


Twenty six texture measures (derived from local statistics, grey-level co-occurrence matrix (GLCM), sum and difference histogram (SADH) and variograms) were calculated for simulated images and their ability to discriminate image texture independently of image contrast was determined. The seven texture measures able to discriminate texture independently of contrast (and therefore able to estimate biomass independently of backscatter) were entropy (derived from local statistics), contrast, entropy, correlation and chi-square (derived from the GLCM), mean of sum vector (derived from the SADH) and range (derived form the variogram). These measures were calculated for Japanese Earth Resources Satellite (JERS-1) Synthetic Aperture Radar (SAR) images and related to the biomass of regenerating forest and mature forest plots from two study areas in Brazilian Amazonia. It was hypothesised that texture (a measure of both biomass and canopy unevenness) could be related to tropical forest biomass up to and beyond the saturation of the backscatter/biomass relationship. The results showed that only GLCM derived contrast increased the correlation between backscatter and biomass. The combination of GLCM contrast with backscatter has the potential to increase the accuracy of biomass estimation over the use of backscatter alone.


Abstract This article evaluates the effectiveness of OAS mechanisms for safeguarding democracy through multilateral diplomacy, what some scholars have dubbed the interamerican defense of democracy regime. Drawing on a range of international relations theories, this study derives competing hypotheses about member states' responses to democratic crises in the Americas. It then analyzes all instances in which a collective response—that is, an application of Resolution 1080 or the Inter-American Democratic Charter—was debated in the OAS between 1991 and 2002. Patterns of state behavior suggest that domestic politics, rather than the structural or systemic traits of the interamerican system, best explain foreign policy responses to crises of democracy in the region. The OAS record in confronting such crises is uneven.


The new scientific discipline of GEOETHICS, in the course of development during the last 20 years, has made considerable progress. To the originally preferred problems of protecting and moderating consumption of non renewable mineral resources of the Earth the priorities have been added concerning unavoidable natural disasters in connection with their presently increasing intensity. These events need to focus the actual attention and orientation of responsible activities of Earth scientists because of possibilities for both forecasting and suggesting appropriate measures for minimizing any potential expected damage. Laision of these topics with concepts of sustainability is evident. It is necessary for human kind, as well as for any further progress of its scientific background, to bring into consideration the necessity of deepening contacts of the Earth sciences with other technical and humanistic scientific fields. Geoethics may have an important role in this process as well as in introducing other new scientific domains. At any responsible level of state authorities and self-government as well as in any context of international co-operation, geoethics might be able to help in paving a better way for the needed understanding of nature by human kind. - It is also necessary to find appropriate structures which would make it possible to incorporate geoethical principles in the optimal way into the consciousness and the daily life of the global society. All efforts of not only Earth and Planetary scientists, ecologists and pedagogues but also of managers, leaders, politicians and statesmen at any level should respect – in the sense of geoethics – their own responsibility for the fate of our planet and of all its inhabitants including the future generations. - As to the final social, cultural, economic and environmental consequences for sustainability it is necessary to seek new priorities emphasizing more and more the solidarity of human kind. The needed geoethical way of thinking should be based on generally accepted moral and ethical principles achieved by mankind by various ways and experiences (in spite of some current contrary trends).


Summary In the period between the two World Wars, the Portuguese Geological Survey (Servicos Geologicos de Portugal: PGS) was legally dependent on the General Directorate of Mines and Geological Survey (Direccao Geral de Minas e Servicos Geologicos: GDMGS). Portugal was then living through troubled times, and the PGS struggled with financial problems and a lack of technical personnel. This situation did not allow the PGS to work properly as a scientific institution, and achieve its main function: the making and publication of geological maps and research papers.


Abstract Guanacoite with high Mg content from the type locality (El Guanaco mine, Chile) was investigated to elucidate the crystal-chemical characteristics of this arsenate mineral. In this study, WDS X-ray intensity maps revealed that guanacoite single crystals from the investigated specimen show distinct and characteristic compositional zoning, which varies cyclically along [100], which is in the direction of the elongation of the prismatic crystals (Witzke et al. 2006); the boundaries separating different compositional regions lie perpendicular to the prism faces. The crystal structure of a selected fragment [a = 5.459(2), b = 16.808(9), c = 6.917(3) Å, β = 100.44(1)°, V = 624.1(5) Å3, P21/c, and Z = 2], was solved using direct methods and refined to an R index of 3.09% for 1385 observed [Io > 4σ(Io)] reflections measured at 103 K using MoKα X-radiation. The chemical formula based on the refinement is (Cu0.85Mg0.15)2Mg2(Mg0.83Cu0.17)(OH)4(H2O)4(AsO4)2. The structure model obtained is in good agreement with the previous structure determination, although the occupancies of the three M sites (M = Mg or Cu) are distinctly different, i.e., the sites are considerably richer in Mg, especially M1 and M3. These structural results suggest that guanacoite's chemical formula should be enlarged from the Curich composition Cu2Mg2(Mg,Cu)(OH)4(H2O)4(AsO4)2 to (Cu,Mg)2Mg2(Mg,Cu)(OH)4(H2O)4(AsO4)2 to include the Mg-rich members (Mg up to 3.395 apfu). It appears that the chemical variability of guanacoite is mainly due to Mg-Cu substitution on the M1 and M2 sites.


Introduces cutting-edge process management tools Learn how process changes will affect your organization Meet requirements for ongoing process management Continuous Business Process Management is the concept of continuously defining, analyzing, and improving a business process. In this IBM Redbook, we explore the business process development life cycle. We use HOLOSOFX BPM Workbench to model an existing process. We use the model to create, simulate, and analyze the process, and select optimal new process design. We use HOLOSOFX BPM Server to share process model information through the Web and to provide a secure repository for access and version control. We convert a business process model into an MQSeries Workflow model and generate an appropriate code format. This format is imported into MQSeries Workflow where the process metrics will be captured in real time. We use HOLOSOFX BPM Monitor to monitor work-in-process items and perform corrective actions by reassigning, reprioritizing, or suspending them. We use actual process metrics to answer what-if questions and make process improvements.


Customized web pursuit could be customizing so as to promise because of enhance hunt quality indexed lists for people with individual information objectives. Then again, client's region unit uncomfortable with uncovering non-open inclination data to make a go at looking motors. On the inverse hand, security isn't total, and occasionally will be traded off if there's an addition in commission or benefit to the client. Therefore, a parity ought to be stricken between hunt quality and security insurance. This paper shows a climbable way for clients to mechanically assemble made client profiles. These profiles abridge a client's advantage into a stratified association in venture with particular hobbies. 2 parameters for determining protection needs range unit wanted to help the client to settle on the substance and level of point of interest of the profile data that is presented to the PC program. Trials demonstrated that the client profile enhanced hunt quality contrasted with plain MSN rankings. a great deal of altogether, results checked our theory that a noteworthy change on hunt quality will be accomplished by exclusively sharing some larger amount client profile information, that is most likely less touchy than intricate individual data.


The dart of Eremina ehrenbergi is a small white delicate structure. It consists of funnel-shaped corona with two blades; a short flare and an extended shaft which is surrounded by two lateral vanes. Dart formation was investigated by examining the histological structure of the dart sac of snails before and after copulation. Dart sac is a finger like muscular protrusion. Its internal epithelial lining forms at its blind edge an extended tubercle which gives its lumen a Y-shape. Dart formation begins at the tip of the tubercle in which the epithelial cells secrete a crystallite and homogeneous material which forms the mineralized part of the corona. The subsequent secretory activity of the tubercle epithelium results in an increase in the diameter and anterior lengthening of the corona and the flare. The continued secretory activity of the dart sac epithelium forms the layers of the shaft and the lateral vanes. The fine sculpturing structure of the dart had been investigated by using SEM.


A linear state model is proposed to analyze dynamic behavior of a circulating fluidized bed riser. Different operating regimes were attained with high density polyethylene beads at low and high system inventories. The riser was operated between the classical choking velocity and the upper transport velocity demarcating fast fluidized and transport regimes. At a given riser superficial gas velocity, the aerations fed at the standpipe were modulated resulting in a sinusoidal solids circulation rate that goes into the riser via L-valve. The state model was derived based on the mass balance equation in the riser. It treats the average solids fraction across the entire riser as a state variable. The total riser pressure drop was modeled using Newton's second law of motion. The momentum balance equation involves contribution from the weight of solids and the wall friction caused by the solids to the riser pressure drop. The weight of solids utilizes the state variable and hence, the riser inventory could be easily calculated. The modeling problem boils down to estimating two parameters including solids friction coefficient and time constant of the riser. It has been shown that the wall friction force acts in the upward direction in fast fluidized regimemore » which indicates that the solids were moving downwards on the average with respect to the riser wall. In transport regimes, the friction acts in the opposite direction. This behavior was quantified based on a sign of Fanning friction factor in the momentum balance equation. The time constant of the riser appears to be much higher in fast fluidized regime than in transport conditions.« less


This article discusses some aspects of the functioning of the Single Supervisory Mechanism (SSM) since its launch in November 2014. By examining a number of practices developed by the European Central Bank (ECB), it argues that two important and complementary processes have characterized the functioning of the SSM so far. First, the ECB has regulated its interactions with the national authorities in such a way to consolidate and promote supranationalism within the SSM: more precisely, transnationalism has been put at the service of supranationalism. Second, the ECB has expanded its supervisory powers, by making an extensive use of the narrow regulatory powers that it enjoys under the SSM Regulation and by using its adjudicatory powers in a quasi-regulatory manner. Admittedly, both processes were largely predictable and do not alter the fundamental legal and institutional features of the SSM. However, they should not be considered as marginal adjustments of the legal framework established by the SSM Regulation. They are important developments, raising some concerns and capable of conditioning the future developments in the SSM.


This discussion of the efficacy of computer Assisted instruction (CAI) for advancing adult learning is based on the assumptions underlying pedagogy (child learning) versus andragogy (adult learning). Pedagogy versus andragogy is discussed first with respect to the prevalent design cf CAI devices. Other topics covered are assumpticns of.andragogy and implications for CAI, versatility of tbe computer, and implications for further research on'the interactive configuration of CAI and the nature of the adult learner.


Introduction: Metastatic clear-cell renal cell carcinoma (RCC) is a highly vascularized tumor type that is often associated with inactivating mutations in the von Hippel-Lindau gene that ultimately drives pro-angiogenic signaling pathways, including the VEGF pathway. As such, new therapies indicated for RCC have largely focused on blocking angiogenesis by inhibiting this pathway. Despite the contribution of these agents to clinical outcomes in RCC, acquired resistance that stimulates tumor regrowth and revascularization quickly emerges. Resistance to VEGF inhibition appears to largely result from activation of compensatory angiogenesis pathways (including the fibroblast growth factor [FGF] pathway), providing a rationale to investigate their inhibition. Areas covered: This review explores the role of the FGF pathway in resistance to VEGF-targeted therapy and rationale for targeting in RCC. PubMed, as well as ASCO and ESMO congress abstracts, were searched for preclinical and clinical data for FGF inhibitors in RCC. Expert opinion: The FGF pathway presents a logical target in RCC and trials of the FGF receptor inhibitors regorafenib, dovitinib, nintedanib, lenvatinib and cediranib demonstrated clinical activity. Clinical development should focus on optimizing the use of this therapy by improving patient selection and evaluating combined therapy.


Based on PP No. 71 Year 2010, to release a useful financial statement, there has to be good quality of information. The quality of the statement is reflected from its qualitative characteristic whih are relevant, reliable, comparable and comprehensive. The application of fair value and accrual basis is believed to be able to increase the quality of a financial statement because the calculation of fair value will influence the reliability and the relevanceof information in the financial statement and the accrual basis accounting that will create a valid, accurate, comprehensive and relevant financial statement. this research aims to iinvestigate the influence of the application of fair value and the accrual basis accounting toward the quality of local government's financial statement. The test instrument in this research is multiple linear regression analysis.To accomodate the research aim, the method used in this research is quantitative with a survey approach through questionaire as its medium of data collecting. The questionaire is distributed to authorized personnel in charge of compiling the local government's financial statement in Region IV West java.The research result shows that the application of the fair value and the accrual basis affect the quality of local government's financial statement.


Ubiquitous devices provide users with notifications that continue to blur the distinction between work and personal activities and can lead to information overload. This research aims to support users of multiple collaborative and social systems who may experience this, by designing and evaluating a personal software agent to support the user and ameliorate the effects of overload. A technique uniting personas and Empathy Map has been applied to model typical user behaviours, goals and pain points, which will inform the design of a solution to manage interruptions and information overload.


This paper provides a Kaldorian interpretation for empirical regularities of productivity growth at the sectoral level of the economy. The statistical evidence is based on a data set drawn from internationally compatible time series for employment and value added in thirty developing countries. Based on novel nonlinear statistical techniques the findings show: (i) a regular pattern of positive sectoral employment elasticities with respect to output growth, (ii) robust differences across sectors in the magnitude of the employment elasticities, and (iii) employment elasticities for all sectors that are significantly less than unity suggesting strong evidence for increasing returns across sectors.


Physico-chemical characteristics of ground water from shallow wells in Galambi and its environ in Bauchi State, Northern Nigeria, were evaluated. A total of fifteen shallow well water samples were randomly collected and analyzed for an assessment of its potability and suitability for domestic purposes. Results obtained indicate that the ground water is slightly acidic to moderately alkaline (5.70< P H <8.10), hard to very hard, (124.7 – 256 mg/l), colourless, and odorless. Conductivity, HCO 3 2 -, CO 3 2 -, NO 3 2 -, SO 4 2 -, and PO 4 3 - are generally within WHO permissible levels for potable water. However, heavy metals like copper, iron, and lead are of higher concentrations than WHO standards for drinking water. Consequently, relevant treatment procedures are strongly recommended to reduce concentrations of Fe, Cu and Pb in the water so as to minimize the risks/concerns that they may pose to human health within and around the study area. The plot of the average constituents of the ground water in a Piper Trilinear diagram shows that the water is potable and can be classified as alkaline earth water type with higher alkaline proportion (Ca – Mg – Na) and predominantly HCO 3 - water, as well as normal alkaline earth water type (Ca – Mg) with predominantly HCO 3 - water.


Melanocyte-stimulating hormone (alpha-MSH) increases cytosolic levels of cAMP as well as tyrosinase activity in murine melanocytes. These activities depend upon the presence of melanin precursors and may differ in human melanocytes. In this study, we demonstrate that high levels of tyrosine (3.7 mM), the chief melanin precursor, reduced the proliferative effect of alpha-MSH and altered human melanocyte morphology as compared to treatment with low (25-30 microM, half-physiological) levels of tyrosine. The anti-proliferative effect of high levels of tyrosine was not restricted to alpha-MSH; tyrosine also reduced proliferation induced by forskolin, a direct activator of the cAMP pathway. Exposure to low tyrosine levels and alpha-MSH induced a dendritic morphology; in the presence of high tyrosine and alpha-MSH, melanocytes displayed large, pigmented cell bodies and less dendricity. Exposure to alpha-MSH in the presence of low tyrosine for up to 9 days did not appreciably increase melanin levels, but culturing the human melanocytes in high levels of tyrosine with alpha-MSH increased melanin levels 10-50-fold, depending on the pigmentation background of the donor. A greater induction of melanin accumulation was observed in melanocytes derived from light-skinned donors than was observed in cells obtained from dark-skinned donors. The poor ability of alpha-MSH to stimulate melanin synthesis was not caused by a lack of induction of melanogenic proteins, as alpha-MSH increased the expression of microphthalmia (MITF), tyrosinase, dopachrome tautomerase (DCT), and Pmel-17, compared to untreated cells or cells stimulated by phorbol ester alone, regardless of tyrosine levels. DCT levels were greatly induced by low tyrosine with alpha-MSH, but were dramatically decreased by high tyrosine with alpha-MSH. Interestingly, in this same medium (high tyrosine), MITF levels also decreased after 2 weeks and were barely detectable by the third week. Despite the absence of MITF at 3 weeks of treatment in high tyrosine medium, tyrosinase levels remained high, thereby suggesting that additional factors must be responsible for tyrosinase transcription in human melanocytes. Our results indicate that tyrosine levels can regulate the proliferative activity induced by alpha-MSH, as well as the extent of melanogenesis in normal human melanocytes. The significance of this work is that tyrosine levels may be part of the mechanism that switches melanocytes out of a proliferative status and into a melanin-synthesizing, terminally differentiated phenotype.


Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL

Tumor cell migration and invasion of nerves, a process known as perineural nerve invasion (PNI), is a major metastatic route for neurotropic cancers including prostate and pancreatic cancer. The laminin family of extracellular matrix glycoproteins derived from myelinating Schwann cells coat nerve axons and play a prominent role in the development and maintenance of the peripheral nervous system. Tumor cells undergoing PNI utilize the laminin rich nerves as they migrate and invade during metastasis. Evidence has shown that the A6B1 laminin receptor promotes tumor cell migration and invasion following cleavage of the receptor to form the variant A6pB1 by the serine protease urokinase plasminogen activator (uPA). Here we demonstrate Schwann cell regulation of A6pB1 formation on prostate and pancreatic tumor cell lines. Conditioned medium from the S16 and S16Y cell lines, which are immortalized Schwann cells of the myelinating and non-myelinating phenotype, respectively was provided to the prostate and pancreatic tumor cell lines. It was observed that S16Y conditioned medium inhibited A6 conversion to A6p while the myelinating S16 cells increased cleavage of the receptor in DU-145, CF-PAC1 and PC-3 cancer cells. This effect was reversible as replenishing standard media conditions following a 24 hour treatment with S16 or S16Y media brought integrin cleavage levels back to steady state levels by 24 hours. Further, conditioned medium from S16 cells significantly increased pancreatic tumor cell invasion while S16Y conditioned medium decreased invasion in a modified Boyden chamber Matrigel assay. The increased invasion mediated by myelinating Schwann cells was dependent on A6 since a function blocking antibody targeting A6 inhibited invasion. Taken together these results suggest that myelinating Schwann cells (S16Y) in the pancreatic and prostatic nerve environment promote A6B1 and A6pB1 receptor dependent tumor cell invasion during PNI. (Supported in part by NIH CA23074 and CA159406 and HHMI Grant 52005889)

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 502. doi:1538-7445.AM2012-502


AIM
The effects of statin on small dense low-density lipoprotein cholesterol (sd-LDL-C) and remnant-like particle cholesterol (RLP-C) levels in heterozygous familial hypercholesterolemia (FH) have not been examined. This study aimed to clarify the effects of statin on sd-LDL-C and RLP-C levels in heterozygous FH.

METHODS
Seventeen patients with heterozygous FH were randomly assigned to 2 mg/day pitavastatin or 10 mg/day atorvastatin. At baseline and 12 weeks after treatment with statin, we measured sd-LDL-C and RLP-C levels.

RESULTS
Sd-LDL-C levels significantly decreased from 43 +/- 24 to 16 +/- 10 mg/dL (-63%, p=0.001) in the pitavastatin group, and from 44 +/- 17 to 19 +/- 10 mg/dL (-55%, p<0.001) in the atorvastatin group. RLP-C levels decreased from 8.4 +/- 2.8 to 6.6 +/- 2.7 mg/dL (-16%, p=0.156) in the pitava-statin group, and from 9.8 +/- 4.7 to 5.9 +/- 5.4 mg/dL (-45%, p=0.044) in the atorvastatin group. There were no significant differences in percent changes of sd-LDL-C (p=0.370) and RLP-C levels (p=0.097) between the two groups.

CONCLUSIONS
Sd-LDL-C measured by the heparin-magnesium precipitation method and RLP-C levels in heterozygous FH were decreased by 12 weeks of statin therapy. Statin might have additional anti-atherogenic effects by reducing not only LDL-C but also sd-LDL-C and RLP-C.


A new approach to capacitance transient analysis, based on the matrix pencil (MP) method, is proposed for deep level transient spectroscopy (DLTS) (MP-DLTS). The MP method offers the least statistical variance of the estimates in the presence of noise. Simulation tests have shown this method to lead to a significant improvement in DLTS resolution even for low trap concentrations. Its noise sensitivity and resolution are quantified and compared with five different DLTS analysis techniques. The MP-DLTS method is found to outperform both DLTS spectrum and direct transient analysis techniques. An experimental investigation of the electrically active defects induced by a germanium preamorphization step prior to dopant implantation was undertaken using the MP-DLTS method. Two electron traps were detected in all samples and characterized.


Abstract The influence of the interior surface materials on the acoustic performance of spaces is well known, both theoretically and practically. This paper gives a concrete example of this reality and summarizes the results of a detailed case study. The detailed measurements, calculations and evaluations were carried out on the auditorium of Yildiz Technical University, Istanbul, Turkey. As part of a renovation project, acoustic measurements were performed in the hall before the renovation, on the unfurnished hall and after renovation. The results obtained from these three distinct situations were evaluated in order to show the impact of interior surface materials on the acoustic characteristics of the space. In addition, the theoretically calculated acoustic environment was compared with the actual results after the renovation to evaluate the accuracy of the theoretical calculations.


It is sadly recognized in Nigerian cultural history that the value on material comfort supersedes every other value irrespective of whether it has any negative connotations or not. This study, therefore, interrogates a situation whereby clergy men and women in Nigeria use religion not only as a seductive means to manipulate the masses into doing their biddings, but also as a means of survival in a harsh economy. The resultant hardship and unemployment situation in the country appear to be prompting an inevitable corollary of irreligious undertakings by dishonest clergy. The play, Bishop Bassey , typifies the problem of personal interest, subterranean underpinnings in manipulating of religion as an essential corner stone for selfaggrandizement. Simply put; it epitomizes religious deceitfulness and hypocrisies that have characterized the Nigerian religious landscape. Thus, in a metaphoric swipe of embracing Western civilization, culture and religion, the dimension to which the Nigeria populace now propagates religious doctrine has got a frightening level of deceit, slander and even character assassination in order to outwit one another in what now looks like " in God's Name PLC" venture. The warped application of irreligious doctrines as a means to an end by Bassey and Dede in Bishop Bassey tends to corroborate Karl Marx's time-tested maxim that "Religion is the opiate of the masses." A viewpoint in which religion is seen as a free-marketsystem based on private ownership of the means of production and distribution of goods. The article holds the position that, although the dramatist, Saint Gbilekaa, berates the hardship and unemployment situation in the country, he cautions on the consequences of using religion as a manipulating tool for individual financial augmentation and survival. Religion, in this instance, becomes an instrument of oppression and economic gains in the hands of capitalist clergy. Consequently, Bassey and Dede are in turn portrayed as victims of a conscious breach in the social contract between the masses and their leaders. Keywords : Marxist, Irreligious, Manipulating, Aesthetics, Theatre, Saint Gbilekaa


This study has developed an approach that will enable fisheries and environmental managers to predict which fish species, and particularly those of recreational and commercial importance, are likely to be found at any site along the lower west coast of Australia. The first step thus involved developing a method whereby the main types of habitat in these waters could be readily and reliably identified. This method used rigorous multivariate statistical techniques to select the suite of quantitative and enduring environmental criteria that were most important for distinguishing among habitat types. Once this had been achieved, we were then able to sample regularly the fish faunas, and also their main invertebrate prey, at sites that had been selected to represent each of those habitat types. This then enabled us to determine the ways in which the densities, diversity and species composition of those faunas are related to habitat type. The predictive approach we have developed is crucial for enabling fisheries and environmental managers to develop appropriate plans for protecting those types of habitat that are most important for key fish species and/or for maintaining biodiversity.


The band structures of heavy Fermion superconductors UPd2Al3 and UNi2Al3 in paramagnetic phase were studied by soft X-ray angle-resolved photoemission. The results were compared with the results of the band structure calculation treating all U 5f electrons being itinerant. We have found that their overall band structures are described by the calculation. This suggests that U 5f electrons have itinerant nature in these compounds and band structure calculation is a reasonable starting point to model their electronic structure.


This paper comes within the framework in the application-architecture matching. The proposed methodology covers the upper part of the codesign flow which is located before the partitioning step. The issue is to provide the designer and to the partitioning step with useful information in order to design an ad hoc architecture. Also, the estimations are computed without knowledge of the implementation. The optimisation potential existing between the function are taking into account to obtain a global and dynamic cost of the application.


Development of disposable, rapid, and convenient biosensor with high sensitivity and reliability is the most desired method of viral disease prevention. To achieve this goal, in this work, a practical impedimetric biosensor has been implemented into a disposable electrode on a screen‐printed carbon electrode (SPCE) for the detection of two mosquito‐borne viruses. The biosensor fabrication has step‐wisely carried out on the disposable electrode surface at room temperature: starting from conductive film formation, physical binding of the gold nanoparticles (AuNPs)‐polyaniline (PAni) into the conductive film, and biofunctionalization. To get the maximum efficiency of the antibody, biotinylated antibody has been conjugated on the surface of AuNP‐PAni/PAni‐SPCE via the streptavidin‐biotin conjugation method which is a critical factor for the high sensitivity. Using the antibody–antigen interaction, this disposable electrode has designed to detect mosquito‐borne infectious viruses, Chikungunya virus (CHIKV), and Zika virus (ZIKV) separately in a wide linear range of 100 fg mL−1 to 1 ng mL−1 with a low detection limit of 1.33 and 12.31 fg mL−1, respectively.


In this paper, a new numerical model for the evaluation of the seismic behaviour of existing reinforced concrete (RC) structure with considering the effect of variation of applied axial load on columns is presented. Focus is given on developing accurate and practical models for simulating nonlinearities in joint core as well as column under varying axial load. For exterior as well as interior joints, according to experimental and finite element results, principal tensile stresses versus shear deformation relations in joint core are recommended. Moreover, to consider the effects of stirrup on the principal tensile stress-shear deformation relation, an incremental procedure is proposed based on the Mohr theory. According to the proposed numerical model, complex nonlinear behaviour of joint core is simulated by two diagonal axial springs so that the effect of variation of axial load is also considered. The properties of these springs are determined based on the proposed principal tensile stress-shear deformation relation in the joint core. Moreover, the shear and flexural nonlinear behaviour of RC beams and columns is also simulated by rotational springs. A simplified methodology is developed to consider the effects of axial load variation on shear and flexural nonlinear behaviour of RC columns. To demonstrate the capability of the proposed numerical model at structural level, two RC frames with various failure modes are investigated. The results confirm the ability of the model in predicting the nonlinear behaviour of the frame, which can provide an alternative method for engineers in practice.


By blurring the margins of a surface, both its brightness and the perceived contrast against a superimposed figure with sharp boundaries increase. Also, if one approaches a blurred white spot on a grey background, this spot will appear wider and brighter: this phenomenon is known as the Breathing Light Illusion (BLI) (Gori and Stubbs, 2006 Perception 35 1573–1577). We studied the increment of the achromatic contrast of a grey sharp-boundary disk when it was superimposed on the BLI. This augmentation of the perceived contrast in the dynamic presentation of the BLI was significantly stronger than the effect that Agostini and Galmonte (2002a Psychonomic Bulletin and Review 9 264–269) obtained in static presentation. Our study leads to an indirect quantification of the BLI. Two control experiments showed that the increment of the achromatic contrast depends on the blurred spot and is independent of the dynamic increment in angular size. These results argue for a causal relationship between the increase in brightness due to the BLI and the darkening of the superimposed disk.


AIM
To assess what is known about the effectiveness of face-to-face self-management programmes designed specifically for adolescents (10-19 years) with a chronic illness.

DESIGN
A systematic review and synthesis without meta-analysis (SWiM).

DATA SOURCES
Six international web-based reference libraries were searched with a date range of 1946 to July 2020.

REVIEW METHOD
The PRISMA statement and SWiM guideline were used for reporting the methods and results. The PICO format was used to develop a focused clinical question and the eligibility criteria of our review. Quality assessment of the included studies was performed using the Cochrane Effective Practice Organisation of Care criteria.

RESULTS
Eight studies (four randomized controlled trials and four descriptive designs) met the inclusion criteria and were published between 2003 and 2017. Results of the review: Three studies demonstrated measures of illness control which showed initial improvements in adherence as a result of the interventions but failed to demonstrate sustained adherence over time. Booster sessions were identified as an effective strategy to improve adherence, but were often omitted.

CONCLUSIONS
There is a limited body of evidence on the effectiveness of self-management programmes specifically developed for adolescents with a chronic illness, an important but under researched area. Future research lies in the development of more rigorous studies that focus on quantitative outcome measures for evaluating the effectiveness of self-management programmes to guide the development of future programmes.

IMPACT
It is crucial for adolescents with a chronic illness to develop independence and the self-management skills required to effectively manage their chronic condition as they transition to adulthood. On current evidence, in planning future self-management interventions should include booster sessions. Nurses with additional training and experience have a key role in supporting adolescents with a chronic illness to develop self-management skills as they assume responsibility for their own healthcare.


BACKGROUND: PI3K signaling is one of the most frequently altered pathways in gastric cancer (GC), and PI3K beta-isoform selective inhibitors have anti-tumor effects with tolerable toxicities in PTEN loss driven tumors. This study aimed to identify novel genetic predictive factors for a PI3K beta-isoform selective inhibitor through a whole-exome analysis of GC cell lines. METHODS: We comprehensively analyzed the genetic alterations in 40 GC cell lines using whole-exome sequencing (WES) and identified specific genetic alterations with sensitivity to GSK2636771, a PI3K beta-isoform selective inhibitor. RESULTS: We identified frequent genetic alterations in PI3K family genes (PIK3CA: 20%, PIK3C2B: 15%, PIK3CD 13%, PIK3CG: 25%, PIK3R1: 30%, PIK3R2: 100%). While no deletion or mutation of PTEN was detected, 40% exhibited a loss of PTEN protein expression. Intriguingly, we noticed germline PIK3R1 variant, M326I (rs3730089), was significantly related to the increased sensitivity to GSK2636771 (IC50: 20.6±9.0 vs 43.5±26.8 μM, p = 0.001), with a stronger association than that of PTEN loss (IC50: 27.5±13.9 vs. 41.7±28.0 μM, p = 0.047). GC cell lines with higher variant allele frequency of PIK3R1 tended to be more sensitive to GSK2636771. Moreover, PIK3R1 M326I was associated with increased p85α expression (p = 0.0198) and decreased PTEN expression in GC cell lines (p = 0.008); same findings were also confirmed in human GC tissues. Furthermore, a correlation analysis of PIK3R1 and PTEN expressions in GC tissues revealed the reciprocal association between these two proteins (R2 = 0.223, p = 0.002), suggesting the possible mechanistic role of PIK3R1 as a negative regulator of PTEN, or vice versa in GC. Next, among various cytotoxics, oxaliplatin was significantly more effective in PIK3R1 M326I variant GC cells (p = 0.028), supporting the combination of GSK2636771 and oxaliplatin for further clinical development in GC. Finally, by using both the PIK3R1 M326I and PTEN loss in combination, we were able to predict the response to GSK2636771 more accurately in GC cells. CONCLUSION: Through WES analysis of GC cell panels, we identified a germline PIK3R1 variant, M326I, as a novel genetic biomarker that provides a more accurate prediction of response to GSK2636771 when used in combination with PTEN loss. Citation Format: Chan Kim, Woo Sun Kwon, Sun Young Rha, Sun Kyung Kang, Hyoki Kim, Carolyn Buser-Doepner, Li Yan, Rakesh Kumar, Hyun Cheol Chung. Whole-exome sequencing of gastric cancer identifies germline PIK3R1 variant as a novel genetic biomarker for a PI3K beta-isoform selective inhibitor, GSK2636771. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4694. doi:10.1158/1538-7445.AM2015-4694