Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA

Although existing interventions are highly efficacious for the treatment of localized breast cancers, disseminated tumors remain incurable. Therapeutic induction of systemic anti-tumor immunity is a promising approach for treating metastatic disease. We have developed a novel heterologous prime/boost vaccination protocol that significantly reduces metastatic tumor burdens in a pre-clinical murine model of breast cancer.

In our studies, mice were orthotopically challenged with Luciferase-expressing 4T1 adenocarinoma cells. Six days later, mice received a priming therapy that consisted of parental 4T1 tumor lysates encapsulated in poly(lactic-co-glycolic) acid microparticles administered contralateral to the established tumor. On day eleven, mice received a boost therapy that consisted of 4T1 lysates and a cocktail of Toll-like receptor agonists. At the conclusion of the assay (day twenty-five), tumor burdens from excised lungs were quantified using bioluminescent imaging. Therapy-receiving mice showed a significant reduction in lung tumors (Student's T-test: p = 0.002, n = 37 control mice vs. 25 treated mice) with an average 46.66% decrease relative to no therapy control mice. Independent quantification of lung metastases was also performed using a standard 6-thioguanine assay. There was a strong correlation (R^2 = 0.8803) between bioluminescent intensity and 6-thioguanine colony number, demonstrating that the decrease in bioluminescence signal due to therapy is not merely explained by the in vivo loss of Luciferase expression by 4T1 cells.

We are currently characterizing the vaccination-induced differences in the localized immune environment of metastatic lung tumors. Effector T cell activation/exhaustion kinetics and the influx of immunosuppressive cell populations (myeloid-derived suppressor cells and regulatory T cells) are now being explored. These studies will help elucidate the immunological mechanism(s) responsible for the diminished metastatic tumor outgrowth observed with our therapy. In conclusion, our data demonstrate that therapeutic vaccination of tumor lysates is efficacious in controlling spontaneous lung metastases in an aggressive model of murine breast cancer.

Citation Format: Brett P. Gross, Amaraporn Wongrapanich, Meghan Francis, Vijaya B. Joshi, Aliasger K. Salem, Lyse A. Norian. Therapeutic microparticle-based tumor lysate vaccination reduces spontaneous lung metastases in a murine breast cancer model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2885. doi:10.1158/1538-7445.AM2014-2885


(Continued from page 31) this pathological cycle is to raise the blood oestrogen level to that stage at which the corpus luteum regresses. This can be done by injecting 25 mg. of stilboestrol dipropionate and potentiating the uterus into rhythmic contractions by injecting posterior lobe pituitary. A similar treatment may be used in case of pyometra. (Brownlee, G. (Wellcome Physiol. Res. Lab., Beckenham). 1942. The clinical application of stilboestral dispropionate. Vet. Rec.54(10):104-105.) The Veterinary Student


We introduce a new across-peer rate allocation algorithm with successive refinement to improve the video transmission performance in P2P networks, based on the combination of multiple description coding and network coding. Successive refinement is implemented through layered multiple description codes. The algorithm is developed to maximize the expected video quality at the receivers by partitioning video bitstream into different descriptions depending on different bandwidth conditions of each peer. Adaptive rate partition adjustment is applied to ensure the real reflection of the packet drop rate in the network. Also the granularity is changed to the scale of atomic blocks instead of stream rates in prior works. Through simulation results we show that the algorithm outperforms prior algorithms in terms of video playback quality at the peer ends, and helps the system more adjustable to the peer dynamics.


The protein phosphatase inhibitor okadaic acid suppressed autophagy completely in isolated rat hepatocytes, as measured by the sequestration of electroinjected [3H]raffinose into sedimentable autophagic vacuoles. Okadaic acid was effectively antagonized by the general protein kinase inhibitors K-252a and KT-5926, the calmodulin antagonist W-7, and by KN-62, a specific inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMK-II). These inhibitors also antagonized a cytoskeleton-disruptive effect of okadaic acid, manifested as the disintegration of cell corpses after breakage of the plasma membrane. CaMK-II, or a closely related enzyme, would thus seem to play a role in the control of autophagy as well as in the control of cytoskeletal organization.


Experimental models of neuroendocrine tumour disease are scarce, and no comprehensive characterisation of existing gastroenteropancreatic neuroendocrine tumour (GEPNET) cell lines has been reported. In this study, we aimed to define the molecular characteristics and therapeutic sensitivity of these cell lines. We therefore performed immunophenotyping, copy number profiling, whole-exome sequencing and a large-scale inhibitor screening of seven GEPNET cell lines. Four cell lines, GOT1, P-STS, BON-1 and QGP-1, displayed a neuroendocrine phenotype while three others, KRJ-I, L-STS and H-STS, did not. Instead, these three cell lines were identified as lymphoblastoid. Characterisation of remaining authentic GEPNET cell lines by copy number profiling showed that GOT1, among other chromosomal alterations, harboured losses on chromosome 18 encompassing the SMAD4 gene, while P-STS had a loss on 11q. BON-1 had a homozygous loss of CDKN2A and CDKN2B, and QGP-1 harboured amplifications of MDM2 and HMGA2. Whole-exome sequencing revealed both disease-characteristic mutations (e.g. ATRX mutation in QGP-1) and, for patient tumours, rare genetic events (e.g. TP53 mutation in P-STS, BON-1 and QGP-1). A large-scale inhibitor screening showed that cell lines from pancreatic NETs to a greater extent, when compared to small intestinal NETs, were sensitive to inhibitors of MEK. Similarly, neuroendocrine NET cells originating from the small intestine were considerably more sensitive to a group of HDAC inhibitors. Taken together, our results provide a comprehensive characterisation of GEPNET cell lines, demonstrate their relevance as neuroendocrine tumour models and explore their therapeutic sensitivity to a broad range of inhibitors.


A Si/P flame retardant was prepared using tetraethyl orthosilicate (TEOS) and phosphoric acid (H3PO4). Original cotton fabric, treated fabric and its charcoal were examined by FT-IR, SEM, and EDS. Results showed that the TEOS/H3PO4 flame retardant has little affect on the cotton chemical structure and the surface morphology of cotton fiber. Main absorption peaks of the charcoal in the FT-IR are attributed to the P-O-C and the Si-O-Si bonds. And the surface of the charcoal was covered with white particles. EDS illustrates Si-O-Si bonds form on the surface and exhibit white particles in the SEM image.


Simon distinguished between the declarative logic of the natural sciences, concerned with how things are, and the normative logic of design, which is concerned with how things ought to be [Simon 1996]. According to Simon, everyone who devises courses of action aimed at changing existing situations into preferred ones is engaged in designing. Where traditionally design was associated with giving form to tangible artifacts, this broader conception recognizes that design also applies to more abstract entities. Services, interfaces, networks, projects, and even discourses are legitimate subjects for design [Krippendorff 2006]. The topic of this paper is the design of the operations of an organization, which compared to traditional design concerns in architecture and industrial design, are fundamentally fluid, dynamic, and open systems. Consequently, complex systems theory contains important insights for operational design. This paper uses examples from military operations to illustrate complex systems applications to operational design. We show how an appreciation of complex systems has been captured in U.S. Army doctrine on design, leading to the most significant change in the Army operations process in over a generation. We then identify further opportunities to build on this success within the Army. The implications are quite general, and apply to the design of business and interagency operations.


The authors propose a new space-division fast packet switch architecture based on banyan interconnection networks, called the tandem banyan switching fabric (TBSF). It consists of placing banyan networks in tandem, offering multiple paths from each input to each output, thus overcoming in a very simple way the effect of conflicts among packets (to which banyan networks are prone) and achieving output buffering. From a hardware implementation perspective, this architecture is simple in that it consists of several instances of only two VLSI chips, one implementing the banyan network and the other implementing the output buffer function. The basic structure and operation of the tandem banyan switching fabric are described, and its performance is discussed. The authors propose a modification to the basic structure which decreases the hardware complexity of the switch while maintaining its performance. An implementation of the banyan network using a high-performance BiCMOS sea-of-gates on 0.8- mu m technology is reported. >


Automated Teller Machine (ATM) is a widely deployed and used system to cater the banking needs of the user. The idea behind availing an ATM based service was to improve the efficiency of overall financial transaction process. However, in practice, many users with native languages other than English, struggle to efficiently utilize the ATM services on offer. The reason being, even after offering services for more than 40 years, the design of the ATM remained unchanged despite the commonly observed shortcomings. Most of the proposed attempts to redesign the ATM interactivity with the user do not befit a particular diverse demographic setting. The aim of this paper is to address the issue of ATM usability in India. We came up with a novel ATM design both in terms of hardware and software that offers the user a personalised space to interact with the intuitive interface. The proposed design when tested, measured a usability score of 79 on the System Usability Scale, and hence suits the Indian scenario well. The study also issues a set of guidelines that should be considered for designing a system specific to a demography.


Application of very high voltage to atomic force microscope tip leads to the growth of narrow, stringlike domains in some ferroelectrics, a phenomenon that was named "ferroelectric domain breakdown." In this work the dynamics of domain breakdown have been studied experimentally and theoretically in stoichiometric lithium niobate (LN). The theory has been found to be in a good agreement with the measured domain radius temporal dependence. Dynamics of domain growth has also been studied in ultrathin LN crystals, where the domain breakdown phenomenon does not take place. It is also shown that domain formation processes occurring in bulk and ultrathin crystals are very different, and this is ascribed to the observed difference in depolarization energy dependence on the domain length.


ABSTRACT This study is a secondary analysis of data presented by Westby and Ferraro (1999), who examined the relationship between performance on neuropsychological measures of frontal lobe deficits and domestic violence. Their results suggest that men who commit domestic violence perform more poorly than controlled counterparts on measures related to frontal lobe deficits. The purpose of this re-analysis is to further explore the associations among frontal lobe deficits, alcohol abuse, and domestic violence. Findings from the re-analysis suggest that the effects of frontal lobe deficits on domestic violence may be most pronounced in cases of severe violence. The effects of alcohol abuse per se on domestic violence may be mediated by neuropsychological factors. The well-documented association between alcohol abuse and domestic violence may need to be re-evaluated to include neurological vulnerability.


If the academic needs of the most profoundly gifted students can be met through the use of existing educational practices, specialists in gifted education can assume that the educational needs of less able, but still academically talented, students can also be met by using some combination of these strategies as well. This paper illustrates the feasibility and effectiveness of utilizing an individualized educational approach with gifted students by highlighting the unique educational paths taken by two of the very ablest math prodigies identified by Dr. Julian Stanley through the Study of Mathematically Precocious Youth (SMPY) since its founding in 1971. Interviews with Dr. Terence ("Terry") Tao and Dr. Lenhard ("Lenny") Ng, now both highly successful mathematicians, are presented in their entirety, demonstrating that even among the very ablest, strategies can be tailored effectively to the characteristics of each student through a combination of creative planning and the cooperation of parents, educators, and mentors.


Restoring the Spirit's Role: Producing Spirit-Anointed and Empowered People for Airdrie Alliance Church Alexander (Sandy) Isfeld Doctor of Ministry School of Theology, Fuller Theological Seminary 2016 This project focuses on the preparing, producing, and commissioning of Spiritempowered and Spirit-anointed kingdom people for the missional advance of Airdrie Alliance Church (AAC), and offers to the broader Christian & Missionary Alliance (C&MA) in Canada a local, church-based model for the renewing, equipping, and releasing of Spirit-filled leaders for service in our denominational family and its broader kingdom work. Part One of this project examines the community and region and probes the organizational structure, character, and historical eras of the church. Consideration is given to understanding the city's demographic population patterns, cultural values, religious climate, political ethos, name, and logo. Identification of spiritual strongholds which shape the dominant culture of the region are considered. Part Two examines the biblical and theological role of the Holy Spirit as essential for a sent people. Key literary sources enable a review of practices related to Spiritbaptism, filling, anointing, and commissioning of leadership in both apostolic and postapostolic times, as well as survey periodic awakenings, revivals, and some current movements. Efforts are made to reclaim the original Spirit ethos of the Christian & Missionary Alliance, underscoring also present signs of the Spirit's manifestation and new possibilities. A special emphasis on Jesus as Spirit-empowered man is developed as the solution and model for Kingdom living today. Part Three prepares AAC for missonal advance, presenting a pilot project that will test a model for a Spirit-anointed humanity, which enables people to explore and experience a deeper work of the Spirit in a retreat environment. Strategies will be carefully planned and implemented with prepared resources, assisting personnel; and attention will be given to diligent assessment, diagnosis, and future recommendations. Content Reader: Keith Matthews, DMin


N-gram analysis is an approach that investigates the structure of a program using bytes, characters, or text strings. A key issue with N-gram analysis is feature selection amidst the explosion of features that occurs when N is increased. The experiments within this paper represent programs as operational code (opcode) density histograms gained through dynamic analysis. A support vector machine is used to create a reference model, which is used to evaluate two methods of feature reduction, which are "area of intersect" and "subspace analysis using eigenvectors." The findings show that the relationships between features are complex and simple statistics filtering approaches do not provide a viable approach. However, eigenvector subspace analysis produces a suitable filter.


Colorectal cancer (CRC) is the third most common cancer, causing more than 600,000 deaths worldwide annually. Due to the involvement of complicated signaling pathways, epigenetic changes and genetic/genomic alterations, it is still challenging to develop effective treatments to reverse CRC progression. In order to facilitate developing new drugs for CRC treatment and revealing the mechanisms of CRC drug action at molecular level, we have constructed a computational CRC Platform (http://www.cbligand.org/CRC/), a domain-specific chemogenomics knowledgebase.

The CRC platform consists of four database modules, e.g. 762 CRC related genes and proteins, 411 known CRC drugs and chemicals, 168383 CRC related bioassays, and 269 CRC pathways, as well as searching tools for multi-function retrieval. It is also featured with powerful cloud computation technologies and computational tools to expedite target identification, polypharmacology and drug synergy analysis for CRC research.

We have also demonstrated the application of the CRC platform in the case studies: (1) computational exploration of FDA-approved CRC drugs for polypharmacology and drug synergy analysis; (2) in silico target identification of small chemical molecules from natural products with anti-CRC bioactivity; and (3) target identification and experimental validation for our in-house compounds. CRC platform will not only enrich our knowledge of CRC target identification, polypharmacology analysis, and biomarkers investigation, but also enhance the CRC chemogenomics data sharing and information exchange globally, and assist new drug design discovery and development for CRC treatment.


A survey to find out the level of recycling awareness of 180 students at 6 selected schools at district of Kuala Langat, comprising 3 schools from secondary school which are i) Sekolah Menengah Kebangsaan Batu Laut (SMKBL) ii) Sekolah Menengah Kebangsaan Jenjarom (SMKJ) iii) Sekolah Menengah Kebangsaan Sungai Manggis (SMKSM) and 3 schools from elementary school which are i) Sekolah Kebangsaan Bandar Banting (SKBB) ii) Sekolah Kebangsaan Kanchong Darat (SKKD) iii) Sekolah Kebangsaan Morib. the purpose of this study is to assess of knowledge of solid waste recycling and to research the awareness level and practice in solid waste recycling among the students. This study also is to determine the factors that can be the motivator and barrier to the students to practice recycling, and to be able provide recommendations to encourage solid waste recycling activities among the students. The written questionnaires were focused on the awareness and perceptions of students regarding solid waste recycling and the solid waste recycling activities among students. After analysis, there are certain issues regarding solid waste management in their school are not properly addressed, and revealed that the students only understand the basic recycling program. This indicated that the campaign and approach design has to be more practical to increase the students' knowledge and attention on the above matter. Nevertheless this study has given impact to the students about the consequence of recycling and composting, and the importance of their participation and support in helping the government to overcome the management and disposal of solid waste in Malaysia.


A multiscale modeling strategy is used to quantify factors governing the temperature rise in hot spots formed by pore collapse from supported and unsupported shock waves in the high explosive HMX (octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine). Two physical aspects are examined in detail, namely the melting temperature and liquid shear viscosity. All-atom molecular dynamics simulations of phase coexistence are used to predict the pressure-dependent melting temperature up to 5~GPa. Equilibrium simulations and the Green-Kubo formalism are used to obtain the temperature- and pressure-dependent liquid shear viscosity. Starting from a simplified continuum-based grain-scale model for HMX, we systematically increase the complexity of treatments for the solid-liquid phase transition and liquid shear viscosity in simulations of pore collapse. Using a realistic pressure-dependent melting temperature completely suppresses melting for supported shocks, which is otherwise predicted when treating it as a constant determined at atmospheric pressure. Alternatively, large melt pools form around pores during pressure release in unsupported shocks, even with a pressure-dependent melting temperature. Capturing the pressure dependence of the shear viscosity increases the peak temperature of melt pools by hundreds of Kelvin through viscous work. The complicated interplay of the solid-phase plastic work, solid-liquid phase transition, and liquid-phase viscous work identified here motivate taking a systematic approach to building increasingly complex grain-scale models and for guiding interpretation of predictions made using them.


At the Medical Library Association's Insight Initiative Summit 1, held March 6–7, 2018, academic and hospital librarians and publishing industry partners came together to discuss their shared role in engaging users of health sciences information in an era in which "disruptors" such as pirate websites, scientific collaboration networks, and preprint servers pose threats to traditional means of access to scholarly content. Through a mixture of keynote talks, themed panel discussions, and small-group problem-solving exercises, the summit program raised important questions, sparked conversation, and provided insight into the need for both libraries and publishing organizations to improve their user experience, lower their barriers to access, and offer value to users that cannot be provided by competitors, including helping authors and students become informed, responsible advocates for and consumers of scholarly publications. The key takeaways from the summit are expected to impact libraries' and publishers' strategies and stimulate the cocreation of enduring materials to enhance user engagement in disseminating and discovering scientific and medical information.


The aim of the paper is to analyse how theological resources can help inform concrete actions of marginalized groups to transform unjust structures, understood as structures which prevent people from enjoying opportunities to live flourishing human lives. Using Amartya Sen's Idea of Justice as conceptual frame, and the narrative of actions of the Confederation of Popular Economy Workers, the paper explores how theological resources can help mediate the social mobilization of marginalized groups to transform unjust structures and create the conditions for better lives. It focuses on two resources: religious social teachings on work, the economy and solidarity on the one hand, and ecclesiology and liturgy on the other. It discusses the role these resources have played, and are playing, in the formation of agents of social transformation, and in facilitating the voices of the excluded to be heard and listened to in political processes. It concludes by examining some challenges of theological mediation in the transformation of unjust structures.


Neurodevelopmental disorders (NDD) with epilepsy constitute a complex and heterogeneous phenotypic spectrum of largely unclear genetic architecture. We conducted exome-wide enrichment analyses for protein-altering de novo variants (DNV) in 7088 parent-offspring trios with NDD of which 2151 were comorbid with epilepsy. In this cohort, the genetic spectrum of epileptic encephalopathy (EE) and nonspecific NDD with epilepsy were markedly similar. We identified 33 genes significantly enriched for DNV in NDD with epilepsy, of which 27.3% were associated with therapeutic consequences. These 33 DNV-enriched genes were more often associated with synaptic transmission but less with chromatin modification when compared to NDD without epilepsy. On average, only 53% of the significant genes were represented on available diagnostic sequencing panels, so our findings should drive significant improvements of genetic testing approaches.


Abstract In southern California, most estuarine wetlands are gone, and what little habitat remains is degraded. For this reason, it is often of interest to assess the condition of estuaries over time, such as when determining the success of a restoration project. To identify impacts or opportunities for restoration, we also may want to know how a particular estuary, or area within an estuary, compares with neighboring areas. Comparisons among wetlands require knowledge of different estuary types. The seven types of estuaries described in this paper can be easily grouped into two functional types, fully tidal and seasonally tidal, based on a simple biotic index: presence of horn snails. A description of the distribution, diversity, and abundance of organisms in estuaries is one way to assess resources, determine the success of a habitat restoration, and compare estuaries to evaluate the biotic consequences of degradation. In this review, I summarize techniques that may be useful for managers charged with biotic inventory and monitoring, emphasizing techniques to categorize wetlands and quantify plants, invertebrates, fishes, birds, and trematode parasites.


The problem that will be discussed in this thesis report will be whether it is possible to construct an adaptive voice amplifier that rivals the already commercially available ones. The report first attempts to give some insight and background into the fields considered by this thesis and after that the implementation section of the report will try to give some deeper insight into which problems occured and how some of them were solved. The result of this thesis report was that it is quite possible to construct an adaptive voice amplifier given enough time. This report will give an insight into the results acquired and some guidelines for constructing such a device. Also found in this report are some possible improvements to the system that would make the system perform even better. This thesis has been very rewarding as a thesis project since the problems has been very challenging and very fun to work with.


This one-year follow investigation is a sequel of a previous controlled review of the therapeutic results at conclusion of treatment in 348 patients. Only 286 completed the treatment and, of these, 191 (67%) attended the follow-up investigation. Three had committed suicide and the remainder defaulted or did not wish to participate. The population followed-up had slightly better therapeutic results and were slightly less socially and mentally stressed than the treated patients as a whole. One year after the conclusion of treatment, 78% had still improved and 64% of those who improved primarily had improved further in the course of the follow-up year and this held also true for 63% of those who did not improve originally. The durability of the primary improvement was found to be 82%. Age was connected with the therapeutic result, subsequent improvement and also the durability so that the result was poorer with increasing age. Numerous other parameters also suggested that treatment gives the best result in patients less firmly established in social and mental circumstances of life. The therapeutic result was independent of sex, type of treatment and duration of treatment. The considerable subjective and clinical improvement as regards general wellbeing and cessation or reduction of symptoms/problems were not associated with greater connection with employment or reduction of assistance from the local authority.


IntroductionOf about 20% of patients with relapsed/refractory Hodgkin lymphoma (HL), approximately half achieve long-term remissions after high-dose chemoradiotherapy and autologous stem cell transplantation (HDT/ASCT). Treatment with a comprehensive program using second-line chemotherapy with ICE (ifosfamide, carboplatin, etoposide) before HDT/ASCT identified a clinical prognostic model, but prognostic biologic markers in relapsed/refractory HL remain unclear. We sought to determine if we could identify such markers, and if our comprehensive second-line program could overcome their significance. MethodsPre-ICE biopsy specimens of 191 patients enrolled on 1 of 2 Institutional Review Board-approved clinical trials of HDT/ASCT. We performed immunohistochemistry staining for Bcl-2, Bax, Bim, p53, and interleukin-6. Samples were considered positive if more than 10% of Hodgkin Reed-Sternberg cells stained at any intensity. ResultsNinety-one patients had sufficient tissue available. Forty-eight patients (53%) had an event and 36 (40%) died. Median event-free survival (EFS) was 8.5 years, median overall survival (OS) was not reached, and median follow-up was 8.8 years. Bcl-2 was overexpressed in 37/91 (41%), Bax in 28/65 (43%), Bim in 9/72 (13%), p53 in 38/89 (43%), and interleukin-6 in 58/84 (69%) patients. Overexpression of these biomarkers had no statistically significant association with EFS or OS, except for association of Bim overexpression with inferior OS (P=0.0385). The 3-factor clinical model (B symptoms at relapse, extranodal disease, and complete remission duration of <1 y) remained highly significant (0/1 vs. 2/3 factors) for EFS and OS (P=0.0008 and P=0.0001, respectively). ConclusionsDespite the evidence that p53 and Bcl-2 overexpression may predict a worse prognosis with initial treatment, it seems that at relapse such overexpression is either not prognostically significant, or that the treatment with ICE and HDT/ASCT overcomes its significance. Subsequent studies should further address the role of Bim in both initial and relapsed/refractory settings.


Feedback is an integral part of communication. It renders an opportunity to evaluate the success of communication. In case of classroom learning, feedback plays an important role as it makes the learning process smooth. It is effective for students and teachers in analyzing the performance and designing the teaching methodology. The feedback given by teachers to the students about their work and performance is equally important to the feedback given by students about their understanding regarding the topic taught by the teachers. The importance of feedback is widely known and it covers students' motivation, their willingness to prove themselves and their confidence in the learning process. It is also required to identify and evaluate the barriers in communication between the teachers and the students. To accomplish this purpose a well-structured survey was conducted covering approximately sixty five students. As per the result of the surveys students showed lack of interest in open interaction in the class. Non-native English speaking students felt language as a barrier. Students felt difficulties in understanding the content. Students faced problems to understand the instructions given by the teacher. The stumbling blocks that affect the feedback process should be effectively removed to provide solution to help both students and teachers to communicate well. Two way feedback is important in continuous improvement in teaching and learning. Teacher and students' feedback to each other not only enhances the learning of students but it also improves the teaching methodology based on the feedback provided.


The Savannah River National Laboratory (SRNL) is a U.S. Department of Energy research and development laboratory located at the Savannah River Site (SRS) near Aiken, South Carolina. SRNL has over 50 years of experience in developing and applying hydrogen technology, both through its national defense activities as well as through its recent activities with the DOE Hydrogen Programs. The hydrogen technical staff at SRNL comprises over 90 scientists, engineers and technologists, and it is believed to be the largest such staff in the U.S. SRNL has ongoing R&D initiatives in a variety of hydrogen storage areas, including metal hydrides, complex hydrides, chemical hydrides and carbon nanotubes. SRNL has over 25 years of experience in metal hydrides and solid-state hydrogen storage research, development and demonstration. As part of its defense mission at SRS, SRNL developed, designed, demonstrated and provides ongoing technical support for the largest hydrogen processing facility in the world based on the integrated use of metal hydrides for hydrogen storage, separation, and compression. The SRNL has been active in teaming with academic and industrial partners to advance hydrogen technology. A primary focus of SRNL's R&D has been hydrogen storage using metal and complex hydrides. SRNL and its Hydrogen Technology Research Laboratory have been very successful in leveraging their defense infrastructure, capabilities and investments to help solve this country's energy problems. SRNL has participated in projects to convert public transit and utility vehicles for operation using hydrogen fuel. Two major projects include the H2Fuel Bus and an Industrial Fuel Cell Vehicle (IFCV) also known as the GATOR{trademark}. Both of these projects were funded by DOE and cost shared by industry. These are discussed further in Section 3.0, Demonstration Projects. In addition to metal hydrides technology, the SRNL Hydrogen group has done extensive R&D in other hydrogen technologies, including membrane filters for H2 separation, doped carbon nanotubes, storage vessel design and optimization, chemical hydrides, hydrogen compressors and hydrogen production using nuclear energy. Several of these are discussed further in Section 2, SRNL Hydrogen Research and Development.


This article considers critically how one of the oldest and most widely applied statistical methods, principal components analysis (PCA), is employed with spatial data. We first provide a brief guide to how PCA works: This includes robust and compositional PCA variants, links to factor analysis, latent variable modeling, and multilevel PCA. We then present two different approaches to using PCA with spatial data. First we look at the nonspatial approach, which avoids challenges posed by spatial data by using a standard PCA on attribute space only. Within this approach we identify four main methodologies, which we define as (1) PCA applied to spatial objects, (2) PCA applied to raster data, (3) atmospheric science PCA, and (4) PCA on flows. In the second approach, we look at PCA adapted for effects in geographical space by looking at PCA methods adapted for first-order nonstationary effects (spatial heterogeneity) and second-order stationary effects (spatial autocorrelation). We also describe how PCA can be used to investigate multiple scales of spatial autocorrelation. Furthermore, we attempt to disambiguate a terminology confusion by clarifying which methods are specifically termed "spatial PCA" in the literature and how this term has different meanings in different areas. Finally, we look at a further three variations of PCA that have not been used in a spatial context but show considerable potential in this respect: simple PCA, sparse PCA, and multilinear PCA.


Since 1987 233 HIV-infected patients have been treated at the Department of Otorhinolaryngology, Head and Neck Surgery of the Ludwig-Maximilians-University of Munich. 70% of these patients had advanced immunodeficiency disease (ARC and AIDS). 46 presented a Kaposi's sarcoma (KS) in the head and neck region. 91% were homosexual men. KS was most often located in the mouth (67%), oropharynx (65%) and skin (39.1%), while the larynx (10.9%), hypopharynx (8.7%), lymph nodes (6.5%) and nasopharynx (4.3%) were rarely involved. In 15 patients, a KS of the head and neck region was the initial symptom for the HIV-infection. Although the clinical features of this disease are typical, histological examination is required because differential diagnosis can show other rare diseases, such as bacillary angiomatosis, which are easily cured. The morphology of early plain or elevated KS exhibits more irregular vascular components while the nodular KS is dominated by sarcomatous cell lines. Immunohistochemical studies with antibodies to viral components revealed no reactivity to HIV-, HPV-, HSV-, EBV- and CMV-antigens. The best local treatment proved to be CO2- or ND:YAG-laser therapy. Cutaneous lesions were treated with camouflage or by fractionated radiotherapy. Advanced disease showed best response to systemic chemotherapy. Despite the advanced stage of immunodeficiency syndrome, an adequate local or systemic therapy can obviously improve the quality of life in HIV-infected patients.


Daily injection of a group of sheep with 75 mg. cortisol acetate (1.2 mg. per kilogram body weight) resulted in hyperglycemia and in a marked increase in plasma immunoreactive insulin concentrations. Doubling the dose of cortisol after fourteen days did not result in further increases in glucose or insulin concentrations, but the elevated levels were maintained throughout treatment. Intravenous glucose tolerance tests using 0.1 gm. glucose per kilogram body weight showed that the rate of glucose removal was decreased and the increment in plasma insulin concentration reduced by cortisol treatment. With a larger glucose load (0.5 gm. per kilogram body weight) there was an exaggerated insulin response to the increased plasma glucose level during the first period of cortisol treatment, but in the second period the response was no greater than that in the control period. Changes in plasma glucose and insulin concentrations in the eight hours following feeding were much exaggerated during cortisol treatment, even though there is little absorption of glucose from the digestive tract in this species. In the absence of evidence of increased glucose turnover in the sheep during cortisol-induced hyperglycemia, the changes are indicative of marked impairment of peripheral glucose metabolism and antagonism of insulin action by cortisol in this species.


Activity analysis is a field of computer vision which has shown great progress in the past decade. Starting from simple single person activities, research in activity recognition is moving towards more complex scenes involving multipleobjects and natural environments. The main challenges in the task include being able to localize and recognize events in a video and deal with the large amount of variation in viewpoint, speed of movement and scale.Surveillance videos typically consist of wide areas being monitored through a static camera. Often, they contain long duration sequences of activities which occur at different spatio-temporal locations and can involve multiple people acting simultaneously. Many times, the activities have contextual relationships with one other. Although context has been studied in the past for the purpose of activity recognition to a certain extent, the use of context in recognition of activities in such challenging environments is relatively unexplored. The primary focus of the work is in recognition of activities in continuous videos.% Contextual information is captured using graphical models. There are two models proposed - the Markov random field model and the conditional random field.We discuss three methods of activity recognition in continuous videos. In the first, we demonstrate the different components of analysis involved in labeling activities in wide-area continuous videos, such as elimination of background noise, identification of motion patterns which correspond to interesting activities and the task of activity modeling. We propose to do this using an optical flow based framework. We discuss the limitations of this work, which can be overcome with the addition of context.Next, we propose a context-based approach for activity recognition using graphical models. We assume that the location of activities are identified using existing techniques. The task of the graphical model is therefore to label these identified regions using context. Given a collection of videos and a set of weak classifiers for individual activities, the spatio-temporal relationships between activities are represented as probabilistic edge weights in a Markov random field. This model provides a generic representation for an activity sequence that can extend to any number of objects and interactions in a video. We show that the recognition of activities in a video can be posed as an inference problem on the graph. We conduct experiments on the publicly available VIRAT dataset to demonstrate the improvement in recognition accuracy using our proposed model as opposed to recognition using state-of-the-art features on individual activity regions.We then present a unified framework to track multiple people, as well localize and label their activities, in complex long-duration video sequences. To do this, we focus on two aspects - the influence of tracks on the activities performed by the corresponding actors and the structural relationships across activities. We propose a two-level hierarchical graphical model which learns the relationship between tracks, relationship between tracks and their corresponding activity segments, as well as the spatiotemporal relationships across activity segments. Such contextual relationships between tracks and activity segments are exploited at both the levels in the hierarchy for increased robustness.Finally, we suggest how the structure learning can be performed in a graphical model which performs activity recognition. While a continuous video consists of several activities, the contextual relationships between these activities are relatively sparse. We propose a method which aims to discover these sparse relationships using an L1-regularization based automatic structure discovery of a graphical model representing the video. Sparsity is imposed on the edges of the graph so as to model a sparse set of relationships.


In this paper, we explore automatic prediction of dialect density of the African American English (AAE) dialect, where dialect density is defined as the percentage of words in an utterance that contain characteristics of the non-standard dialect. We investigate several acoustic and language modeling features, including the commonly used X-vector representation and ComParE feature set, in addition to information extracted from ASR transcripts of the audio files and prosodic information. To address issues of limited labeled data, we use a weakly supervised model to project prosodic and X-vector features into low-dimensional task-relevant representations. An XGBoost model is then used to predict the speaker's dialect density from these features and show which are most significant during inference. We evaluate the utility of these features both alone and in combination for the given task. This work, which does not rely on hand-labeled transcripts, is performed on audio segments from the CORAAL database. We show a significant correlation between our predicted and ground truth dialect density measures for AAE speech in this database and propose this work as a tool for explaining and mitigating bias in speech technology.


Albino rats (noninbred) were divided into 4 groups: 1) 56 control rats, 2) 40 rats fed 1 ml aspirin suspension (40 mg/ml) twice a week, 3) 20 rats given N-nitroso-N-methylnitroguanidine (MNNG) solution (250 micrograms/ml) to drink ad libitum, and 4) 40 rats given both aspirin and MNNG. In 18 months, there were no gastrointestinal tumors in groups 1 and 2, 8 cases of gastric tumors in group 3, and 37 cases of gastric tumors in group 4. Adenocarcinomas of the glandular stomach were found in 21 of 40 rats in group 4 but in only 4 of the 20 rats in group 3; the difference in incidence was significant. Histologic and electron microscopic examination of the epidermoid carcinomas and adenocarcinomas in group 4 showed no difference from such tumors induced by MNNG only. Hyperplasia of the forestomach mucosa and hyperplasia of the pyloric gland region of the glandular stomach in group 4 were more severe.


It has been a quarter of a century since the first reported thoracoscopic lobectomy. Over this time, acceptance came gradually but VATS lobectomy now enjoys preference for early stage lung cancer largely because of its reduced complications. This has increased surgery options and associated survivals particularly for frail populations. There has been phased in adoption at most centers, generally starting with patients having smaller, peripheral tumors as described in papers establishing the feasibility of such operations. Accordingly, this has introduced selection bias into large retrospective databases because central and probably more nodal rich tumors were approached by open operations. Similarly, preoperative radiation and chemotherapy which makes dissection more tedious are more likely to yield open approaches or conversions.


The idea to use error-correcting codes in order to construct public key cryptosystems was published in 1978 by McEliece [ME1978]. In his original construction, McEliece used Goppa codes, but various later publications suggested the use of different families of error-correcting codes. The choice of the code has a crucial impact on the security of this type of cryptosystem. Some codes have a structure that can be recovered in polynomial time, thus breaking the cryptosystem completely, while other codes have resisted attempts to cryptanalyze them for a very long time now. In this thesis, we examine different derivatives of the McEliece cryptosystem and study their structural weaknesses. The main results are the following: In chapter 3 we devise an effective structural attack against the McEliece cryptosystem based on algebraic geometry codes defined over elliptic curves. This attack is inspired by an algorithm due to Sidelnikov and Shestakov [SS1992] which solves the corresponding problem for Reed-Solomon codes. The presented algorithm is heuristic polynomial time and thus inverts trapdoors even for very large codes. In chapter 4, we show that the Sidelnikov cryptosystem [S1994], which is based on binary Reed-Muller codes, is insecure. The basic idea of our attack is to use the fact that minimum weight words in a Reed-Muller code have very particular properties. This attack relies on the ability to find minimum weight words in the code, a problem that is, in this specific instance, much easier than general decoding, and feasible for interesting parameters in a modest amount of time. The attack has subexponential running time if the order of the code is kept fixed, and it breaks the large keys as proposed by Sidelnikov in under an hour on a stock PC. In the chapter 5, we finally discuss some of the problems to solve if one attempts to generalize these algorithms.


A. Physiologic Factors Concerned in the Regulation of Respiration
 Physiologists now agree that there is a medullary respiratory center which has intrinsic rhythmicity. Nevertheless this center can be influenced profoundly by many chemical and nervous factors. One of the most important of these is carbon dioxide. Under ordinary conditions the medullary center is exquisitely sensitive to changes in carbon dioxide pressure. When the respiratory center is depressed (by deep anesthesia, large doses of morphine or barbiturates, trauma, cerebral edema, increased intra-cranial pressure, severe anoxia or by high concentrations of carbon dioxide itself) it is no longer responsive to carbon dioxide though it may still permit reflex activity and continuation of respiration.
 Anoxemia may also stimulate respiration; this occurs through reflexes originating in chemoreceptors of the carotid and aortic bodies. It appears certain that these chemoreceptors are functioning in the normal full-term newborn though they may not be functioning or functioning properly in prematures. When these chemoreceptors are in operation, anoxia will stimulate respiration and oxygen therapy will abolish such hyperpnea. When the chemoreceptors are not in action, one would expect no reflex effects from either oxygen or anoxia; oxygen therapy, however, might relieve cerebral ischemia and permit respiration to improve.
 B. Physiologic Methods for Evaluating Respiratory and Pulmonary Function
 The function of the lungs is primarily to oxygenate the venous blood and to remove excess carbon dioxide from it. To accomplish this, there must be normal respiratory volumes, normal lung volumes and aerating surface, even distribution of the inspired gas to the alveoli, unimpaired diffusion across the alveolar capillary membrane, and uniform distribution of pulmonary capillary blood flow to the functioning alveoli.


Phase unwrapping is the key step in Digital Elevation Model extraction and the measurement of surface deformation of Interferometric Synthetic Aperture Radar (InSAR). When in steep terrain or larger slope, the unwrapping result is bad and causes error transmission using the existing Kalman Filter phase unwrapping algorithm. Considering this situation, this paper presents an improved Kalman Filter phase unwrapping algorithm based on topographic factors for InSAR. It can be implemented through the introduction of the input control variable associated with topographic factors to the state-space model of Kalman Filter. Owing to the fact that the interference fringes directly reflect the change of the terrain and local fringe frequency is closely related with the local terrain slope, the local fringe frequency estimation can be used as the input control variable. In the local frequency estimation, using two-dimensional Chirp-Z transform, better estimate of the results may be quickly get. In this paper, using simulated data and real InSAR data to do the experiment, it can gain more reliable result compared with the conventional Kalman filter phase unwrapping algorithm. It is verified that the proposed algorithm can effectively deal with the situation of steep terrain and larger slope.


Leveraging global resources for software development is rapidly becoming the norm at Motorola, which has over 25 software development centers worldwide. Our project, called the 3G Trial (Third Generation Cellular System), was the first of its scope and significance developed by a global engineering team at Motorola. Staffing was the most significant issue we encountered in the 3G Trial. We had only about 20 percent of the required staff available at our division headquarters in Burlington Heights, Ill., US, and needed to find the other 80 percent to successfully complete the project. Early on, we concluded that our only means to staff the project was to rely on software development engineers from Motorola's worldwide software centers. We developed the system with staffing from six different countries. Next, we had to integrate the people into a team. While addressing this challenge, we identified key risk factors and developed approaches to reduce them. We separated the project risk factors into the five categories Carmel (1999) describes as the centrifugal forces that pull global projects apart. To pass on the lessons we learned from this project, this article sets out the global development issues we faced, our approaches to resolving them, and our findings compared to other research.


To the Editor. —In an article in theArchives(1980;98:188), Polse et al advocated the wearing of a soft contact lens by subjects undergoing examination of the corneal endothelium by contact specular microscopy for a variety of reasons. We would like to draw attention to a further optical advantage that can be gained by the selection of a soft contact lens with appropriate properties. A large field of view of the corneal endothelium image, without loss of magnification, is desirable in clinical specular microscopy. 1 Most of the clinical specular microscopes available provide only a small visible field, owing to the use of narrow slit illumination necessitated by the combined effects of the thinness of the cornea, the acute angle of illumination, and the different intensities of the reflections from the interfaces between the endothelium-aqueous humor and the epithelium (tears or saline)-glass of the objective cone of the microscope. An


A set of purchasing power parities was constructed for the inputs and the outputs of the agricultural sector in 10 European countries and the United States. This made it possible to deflate both spatially and in time the nominal agricultural accounts. Real values of inputs and outputs made it possible to construct spatial indexes of productivity. These indexes measure the productivity gaps between countries for a given year. Extrapolation between 1973 and 1989 measures how these gaps have changed over time. The results show that the productivity of the United States has been 20 percent higher than the average productivity of European agriculture. This gap has persisted over time. However, large discrepancies exist in Europe and a few countries such as The Netherlands obtain a higher productivity than the United States.


The imminent departure of Dr. Alan Bernstein from the presidency of the Canadian Institutes of Health Research (CIHR) will doubtless be the subject of much hand-wringing over a suitable replacement, future directions, programming and other structural matters at the nation's primary source of funding for academic health researchers.

Such issues and deliberations are valid, provided they are not allowed to cloud a more important debate and opportunity that change affords us: to redress the now-chronic shortage of funding. Underlying that need is the basic tenet that research is a fundamental public good: it makes a difference in terms of our understanding of disease and provides the highest quality evidence for patient care. It is also the engine for ingenuity and innovation in the health sector. It matters to everyone: taxpayers, parliamentarians and physicians.

In the scant 7 years since the CIHR was created from the ashes of the Medical Research Council of Canada and Bernstein was placed at its helm, the agency's budget has grown from about $250 million per year to a current level of $828 million, while its vision has extended beyond basic biomedical science to include the 3 other so-called pillars that CIHR now supports: clinical research, population health research, and health services and systems research.

Bernstein has done an admirable job of overseeing that transformation and growth, particularly in the face of the usual battery of factors and factions that invariably arise in the administration of research, including government's lack of appreciation of the importance of health research, internal squabbling in the research community about suitable division of the pie and pressures from end-users, such as businesses, health care administrators and the public. Compounding this was the short-sightedness of research stakeholders who did not see the need to spend monies on effective communication and other initiatives that would make research more justifiable or politically palatable — an essential first step toward helping others understand the importance of research and being accountable for tax dollars spent.

Negotiating those many perilous shoals was easier in CIHR's early days when its budget enjoyed double-digit annual increases. But it became more problematic as the increases tailed off. This lack of sustainable, long-term funding has prompted grumbling about the division of dollars among the 4 pillars, with basic biomedical scientists often leading the charge. In fact, 70% of all CIHR grants are now awarded for basic biomedical science, and it is researchers working within the other 3 pillars who have most cause for complaint about imbalance, particularly in light of the fact that it is their research that can deliver more immediate and comprehensive improvements in the health of Canadians.

Yet the solution is not to set up a competition among the pillars, which would be disastrous for Canadian science. All 4 pillars are justifiably clamouring for more money and the entire spectrum of researchers must be properly funded if the research enterprise is to maintain its own health.

For that to occur, the research community must first persuasively explain the rationale for and evidence of a need for increased funding. Canadian taxpayers have a right to know what their hard-earned dollars will buy and how it will improve their health or the state of the economy, or both.

Furthermore, the Canadian government needs to decide once and for all whether it is serious about being a meaningful global player in health research. To do so, it must vastly increase research outlays to the level provided by leading Organisation for Economic Co-operation and Development (OECD) nations. The United States, for example, will spend $28.9 billion on academic health research in 2007,1 or $95.37 per capita. Canada will spend $828 million,2 or $25.09 per capita. If government is not interested in being a global player, then it should give up the charade. Canada's researchers, who have proven they can do more with less, are ill-served by short-term promises followed by long-term disappointments. If the funding won't be there, our best and brightest scientists should be told honestly to shop abroad for a stable platform on which to build the careers into which so much of their hard work and our tax dollars have been invested. The Canadian public should then be disabused of expectations that our health care problems will be addressed by made-in-Canada solutions, reflecting Canadians' priorities and values.

Matthew B. Stanbrook MD PhD Deputy Editor, Scientific, CMAJ Paul C. Hebert MD MHSc Editor-in-Chief, CMAJ With the Editorial-Writing Team (Barbara Sibbald BJ, Ken Flegel MDCM MSc, Noni MacDonald MD MSc and Amir Attaran LLB PhD)


The recent detection of the gravitational wave signal GW170817 together with an electromagnetic counterpart GRB 170817A from the merger of two neutron stars puts a stringent bound on the tensor propagation speed. This constraint can be automatically satisfied in the framework of massive gravity. In this work, we consider a general SO(3)-invariant massive gravity with five propagating degrees of freedom and derive the conditions for the absence of ghosts and Laplacian instabilities in the presence of a matter perfect fluid on the flat Friedmann-Lemaître-Robertson-Walker (FLRW) cosmological background. The graviton potential containing the dependence of three-dimensional metrics and a fiducial metric coupled to a temporal scalar field gives rise to a scenario of the late-time cosmic acceleration in which the dark energy equation of state wDE is equivalent to −1 or varies in time. We find that the deviation from the value wDE=−1 provides important contributions to the quantities associated with the stability conditions of tensor, vector, and scalar perturbations. In concrete models, we study the dynamics of dark energy arising from the graviton potential and show that there exist viable parameter spaces in which neither ghosts nor Laplacian instabilities are present for both wDE>−1 and wDE<−1. We also generally obtain the effective gravitational coupling Geff with non-relativistic matter as well as the gravitational slip parameter ηs associated with the observations of large-scale structures and weak lensing. We show that, apart from a specific case, the two quantities Geff and ηs are similar to those in general relativity for scalar perturbations deep inside the sound horizon.


Intertemporal decision making under risk involves two dimensions: time preferences and risk preferences. This paper focuses on the impact of time on risk preferences, independent of the intertemporal trade-off of outcomes, i.e., time preferences. It reports the results of an experimental study that examines how delayed resolution and payment of risky options influence individual choice. We used a simple experimental design based on the comparison of two-outcome monetary lotteries with the same delay. Raw data clearly reveal that subjects become more risk tolerant for delayed lotteries. Assuming a prospect theory--like model under risk, we analyze the impact of time on utility and decision weights, independent of time preferences. We show that the subjective treatment of outcomes (i.e., utility) is not significantly affected by time. In fact, the impact of time is completely absorbed by the probability weighting function. The effect of time on risk preferences was found to generate probabilistic optimism resulting in a higher risk tolerance for delayed lotteries.

This paper was accepted by Teck Ho, decision analysis.


The authors wish to report an error they discovered in one of the adenoviral vectors used in the studies published on page 720 of the March 27, 2009 issue. We found that the adenoviral vector intended to express human wild type SERCA2b in the experiments shown in Figure 3 of this paper actually encoded the SERCA2b C674S mutant and in addition was contaminated with E1A adenovirus. The incorrect adenoviral vector was identified by PCR of the full-length SERCA present in the viral DNA within infected cells. We have reported details of the methods used elsewhere by which nested primer pairs were used to cover the immediate upstream adenoviral sequence and the full-length sequence of the virally expressed SERCA. Our finding of the error in Lancel et al came when checking the SERCA vectors after discovering contamination of another pair of viral vectors being amplified in our laboratory as reported in Haeussler et al. We then sought an explanation of the different effects of overexpression of two SERCA C674S mutants that we realized had occurred in the experiments shown in Figure 3 of Lancel et al. As indicated in Figure 3 of Haeussler et al, we checked for and found that the vector intended to express only the wild type SERCA was also contaminated by the adenoviral E1A gene. Contamination by E1A and its unintended functional effects has been noted by others to occur inadvertently by homologous recombination of the E1A gene that is present within the HEK 293 cell line and which enables amplification of the adenoviral vector which lacks this gene. We have also suggested remedies to prevent E1A contamination during amplification of replication-deficient adenoviral vectors. Furthermore, as discussed by Tong et al in their correction notice,4 we have discovered that infection of rat aortic smooth muscle cells with E1A stimulates endogenous SERCA expression, which may explain why in our prior experiments the cells infected with the contaminated SERCA mutant retained nitroxyl-stimulated SERCA activity that mimicked that observed in LacZ controls. Because the contaminated vector was used in Figure 3 of Lancel et al, we produced a new wild type SERCA 2b adenoviral vector, verified both its sequence and that it and other vectors used lacked E1A contamination, and now provide a revised Figure 3. Methods are provided in full in Lancel et al and Haeussler et al. In Panel A of the revised figure, BIAM-labeled SERCA2b is measured in adult rat ventricular myocytes infected with adenoviral vectors expressing LacZ, authentic wild type SERCA2b or the C674S SERCA2b mutant. As in our original report, the fraction of SERCA2b that is BIAM-labeled is decreased by HNO in LacZand WT-overexpressing cells, whereas the fraction of BIAM-labeled SERCA2b is decreased in cells overexpressing the C674S mutant, but is not decreased further by HNO. In Panel B, maximal calcium-stimulated calcium influx was measured under similar conditions. In contrast to our prior finding with the contaminated vector, basal HNO-stimulated calcium influx was greater in myocytes expressing WT (vs LacZ). As in our original report, HNO increased calcium influx in cells overexpressing either LacZ or WT. Likewise, as in our prior report HNO-stimulated calcium influx was abolished in cells overexpressing the C674S mutant, as compared to myocytes expressing LacZ or WT. These results with BIAM labeling and calcium influx confirm the original results shown in Figure 3 of Lancel et al, and do not affect the interpretation of the results indicating that a) the fraction of the reactive cysteines in SERCA2b is decreased in the C674S mutant, and b) HNO-stimulated calcium influx is abolished by overexpression of the C674S SERCA mutant. We hope that reporting our error will serve as a warning to others who use adenoviral vectors in their work.


a r t i c l e i n f o a b s t r a c t Recent theoretical developments in the area of compressive sensing (CS) have the potential to significantly extend the capabilities of digital data acquisition systems such as analog-to-digital converters and digital imagers in certain applications. To date, most of the CS literature has been devoted to studying the recovery of sparse signals from a small number of linear measurements. In this paper, we study more practical CS systems where the measurements are quantized to a finite number of bits; in such systems some of the measurements typically saturate, causing significant nonlinearity and potentially unbounded errors. We develop two general approaches to sparse signal recovery in the face of saturation error. The first approach merely rejects saturated measurements; the second approach factors them into a conventional CS recovery algorithm via convex consistency constraints. To prove that both approaches are capable of stable signal recovery, we exploit the heretofore relatively unexplored property that many CS measurement systems are democratic, in that each measurement carries roughly the same amount of information about the signal being acquired. A series of computational experiments indicate that the signal acquisition error is minimized when a significant fraction of the CS measurements is allowed to saturate (10–30% in our experiments). This challenges the conventional wisdom of both conventional sampling and CS.


This communication addresses the problem of derivative-free multi-objective optimization of real-valued functions subject to multiple inequality constraints, under a Bayesian framework. Both the objective and constraint functions are assumed to be smooth, non-linear and expensive-to-evaluate. As a consequence, the number of evaluations to carry out the optimization is very limited. This set-up typically applies to complex industrial design optimization problems. The method we propose to overcome this difficulty has its roots in both the Bayesian and the multi-objective optimization literatures. More specifically, an extended domination rule is used to handle the constraints and a corresponding expected hyper-volume improvement criterion is proposed. The calculation of this class of criteria is known to become difficult as the number of objectives increases. To address this difficulty, we propose a novel approach, making use of Sequential Monte Carlo techniques. Moreover we also use Sequential Monte Carlo techniques for the optimization of our new criterion. The performance of the proposed method is evaluated on a set of test problems coming from the literature and compared with reference methods.


New technologies used in payment methods can reduce risk, but they can also lead to new risks. Emerging retail payments are prone to operational and fraud risks, especially security breaches and potential use in illicit transactions. This article describes an economic framework for understanding risk control in retail payments. Risk control is a special type of good because it can protect one payment participant without diminishing the protection of other participants. As a result, the authors' economic framework emphasizes risk containment, primarily through the establishment and enforcement of risk management policies. Application of the framework to three types of emerging payments suggests that a payments system can successfully manage risk if it quickly recognizes problems, encourages commitment from all participants to control risk, and uses an appropriate mix of market and public policy mechanisms to align risk management incentives. The authors conclude that providers of emerging payment methods must mitigate risk effectively or face rejection in the payment market.


Animals are confronted with potential stressors at zoos compared to in the wild, such as visitors and lack of environmental stimulation. This study included two projects conducted on the drills at Parken Zoo in Eskilstuna where I investigated: 1) the effect of visual barriers on the behaviour of the drills and if the visual barriers can moderate the visitor effect on the drills and 2) how outdoor-only access together with feeding enrichment (frozen fruit and tube feeders) affects the behaviour of the drills. 1/0- sampling method was used when observing the behaviours of the drills with 1 minute-intervals. Resting/Sleeping increased, while social agonistic behaviour and stereotypies decreased with visual barriers. A moderated visitor effect was shown in resting/sleeping and social affiliative behaviour in the drills with visual barriers. However, social agonistic behaviour and visitor interaction were still affected by visitors after the installation of the visual barriers, implying that the drills still find visitors stressful to some extent and that further alterations on the observation area viewing the indoor enclosure is recommended for the welfare of the drills. With outdoor-only access together with feeding enrichment, locomotion, foraging/eating and body-shaking increased, while resting/sleeping, social affiliative and agonistic behaviour, stereotypies, visitor interaction, scratching and self-grooming decreased. This suggests that outdoor-only access and feeding enrichment improve the behaviour of the drills and would be a valid option during summer season for the drills at Parken Zoo.


The 113 th Congress is expected to consider comprehensive immigration reform legislation. If and when it does, a key challenge will be how to address the unauthorized alien population, estimated to number some 11 million. The unauthorized alien population is often treated as if it were monolithic, but it is, in fact, quite diverse. It includes individuals who entered the United States in different ways, for different reasons, and who have different types of connections to the United States. The circumstances of individuals who compose the unauthorized alien population affect their treatment under immigration law, especially with respect to prospects for obtaining legal status in the United States. Relevant immigration status-related factors include mode of entry into the United States, length of unlawful presence in the country, and the existence of family or employment connections. The differences in circumstances among unauthorized aliens are particularly relevant in the context of current discussions about how to address this population. In past years, immigration proposals on unauthorized aliens often called for the establishment of broad legalization programs to enable large numbers of unauthorized aliens to become U.S. legal permanent residents (LPRs) or, conversely, included provisions aimed at promoting the departure of large numbers of unauthorized aliens from the country over time. More recently, there has been discussion of developing policies to provide targeted immigration relief to unauthorized aliens. Immigration relief is a broad term that encompasses relief from removal from the United States without the granting of a legal immigration status as well as relief in the form of a legal immigration status. A main focus of recent discussions has been making eligibility for legal status available to certain segments of the unauthorized population. Aliens with approved immigrant visa petitions, especially those with U.S. citizen or LPR family members, seem to be of particular interest. Selected segments of the unauthorized alien population without an affirmative pathway to legal status, such as students who entered the United States as children and beneficiaries of long-term humanitarian relief, have also been the subject of policy proposals. Policies to provide targeted relief to unauthorized aliens could be legislative or administrative. Legislative options could include amending existing statutory provisions to make it easier for certain unauthorized aliens to obtain LPR status. They also could include establishing statutory mechanisms to enable certain subgroups of unauthorized aliens to become LPRs who may not have pathways to do so under current …


Alzheimer's disease (AD) is a fatal neurodegenerative condition characterized clinically by progressive memory loss and irreversible cognitive deterioration. It has been shown that there is a progressive degeneration of the brain cholinergic neurons which leads to the appearance of cognitive symptoms of the disease. The aim of this work was the formulation of multifunctional nanocarriers for nasal administration of tacrine-HCl (THA). This route has many advantages; in particular is possible to convey the drug directly to the Central Nervous System, through the olfactory bulb. In particular, were prepared Albumin nanoparticles carrying beta cyclodextrin and two different beta cyclodextrin derivatives (hydroxypropyl beta cyclodextrin and sulphobutylether beta cyclodextrin), and Multifunctional liposomes, prepared using traditional excipients (cholesterol and phosphatidylcholine), partly enriched with α-tocopherol (Toc) and/or polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid) (Ω3). Both nanosystems were characterized in terms of size, Zeta potential and encapsulation efficiency. Were also evaluated their functional properties such as mucoadhesion and permeability, using an ex-vivo assay based on nasal sheep mucosa. On Liposomes were also assessed drug neuronal uptake, cell toxicity, antioxidant and, cytoprotective activity in the human neuronal cell line SH-SY5Y and finally tocopherol trans-membrane diffusion. Both the nanocarriers produced presented excellent properties and a high potential as new systems for CNS-delivery of anti-Alzheimer drugs via the nasal route.


Purpose: Tumor metastasis is the main cause of death from breast cancer patients and cell migration plays a critical role in metastasis. Recent studies have shown long non-coding RNAs (lncRNAs) play an essential role in the initiation and progression of cancer. In the present study, the role of a LncRNA, Rho GTPase Activating Protein 5- Antisense 1 (ARHGAP5-AS1) in breast cancer was investigated. Methods: RNA sequencing was performed to find out dysregulated LncRNAs in MDA-MB-231-LM2 cells. Transwell migration assays and F-actin staining were utilized to estimate cell migration ability. RNA pulldown assays and RNA immunoprecipitation were used to prove the interaction between ARHGAP5-AS1 and SMAD7. Western blot and immunofluorescence imaging were used to examine the protein levels. Dual luciferase reporter assays were performed to evaluate the activation of TGF-β signaling. Results: Compared to MDA-MB-231 cells, the expression of LncRNA ARHGAP5-AS1 (NR_027263) was significantly suppressed in its highly metastatic subtype MDA-MB-231-LM2 cells. Functional study showed ARHGAP5-AS1 could inhibit cell migration via suppression of stress fibers in breast cancer cell lines. Afterwards, SMAD7 was further identified to interact with ARHGAP5-AS1 by its PY motif and thus its ubiquitination and degradation was blocked due to reduced interaction with E3 ligase SMURF1 and SMURF2. Moreover, ARHGAP5-AS1 could inhibit TGF-β signaling pathway due to its inhibitory role on SMAD7. Conclusion: Overall, these findings demonstrate that ARHGAP5-AS1 inhibits breast cancer cell migration and could serve as a novel biomarker for breast cancer metastasis and a potent target for the treatment in the future.


AIMS
An increasing number of patients with severe coronary artery disease (CAD) are not candidates for traditional revascularization and experience angina in spite of excellent medical therapy. Despite limited data regarding the natural history and predictors of adverse outcome, these patients have been considered at high risk for early mortality.

METHODS AND RESULTS
The OPtions In Myocardial Ischemic Syndrome Therapy (OPTIMIST) program at the Minneapolis Heart Institute offers traditional and investigational therapies for patients with refractory angina. A prospective clinical database includes detailed baseline and yearly follow-up information. Death status and cause were determined using the Social Security Death Index, clinical data, and death certificates. Time to death was analysed using survival analysis methods. For 1200 patients, the mean age was 63.5 years (77.5% male) with 72.4% having prior coronary artery bypass grafting, 74.4% prior percutaneous coronary intervention, 72.6% prior myocardial infarction, 78.3% 3-vessel CAD, 23.0% moderate-to-severe left-ventricular (LV) dysfunction, and 32.6% congestive heart failure (CHF). Overall, 241 patients died (20.1%: 71.8% cardiovascular) during a median follow-up 5.1 years (range 0-16, 14.7% over 9). By Kaplan-Meier analysis, mortality was 3.9% (95% CI 2.8-5.0) at 1 year and 28.4% (95% CI 24.9-32.0) at 9 years. Multivariate predictors of all-cause mortality were baseline age, diabetes, angina class, chronic kidney disease, LV dysfunction, and CHF.

CONCLUSION
Long-term mortality in patients with refractory angina is lower than previously reported. Therapeutic options for this distinct and growing group of patients should focus on angina relief and improved quality of life.


There is growing evidence that the differentiation processes in the fetal and adult thymus are not identical. However, there is little information on whether these developmental differences influence the properties of mature cells that exit the thymus and seed peripheral lymphoid organs. We have addressed this issue by comparing the development of Ag-specific Th1/Th2 function by fetal vs adult thymic derived CD4 (cid:1) cells in the same adoptive adult hosts. Host mice were irradiated and transplanted with 14- to 15-day fetal thymic lobes from Thy-1 congenic mice. Ag (keyhole limpet hemocyanin)-specific Th1/Th2 responses of fetal-derived (donor) or adult-derived (host) CD4 (cid:1) cells were analyzed by ELISA following primary or secondary immunization. Fetal-derived cells produced up to 10-fold more of both Th1 (IFN- (cid:2) ) and Th2 (IL-4) cytokines than did adult-derived cells. Comparisons of the IL-4:IFN- (cid:2) ratios showed that the responses of fetal-derived cells were Th2-skewed in an Ag dose-dependent manner. At low doses of Ag, the fetal-derived ratio was (cid:1) 5 times higher than the adult-derived ratio. As the Ag dose was increased, the differences between the ratios of the fetal- and adult-derived responses were minimized. These relative responses were established initially during the primary effector phase but were maintained for weeks, into the memory phase of the immune response. Importantly, fetal-derived CD4 (cid:1) cells showed these properties whether the fetal thymic precursors matured within the fetal or adult thymic microenvironment. These results demonstrate that cells arising from fetal thymic precursors are functionally different both qualitatively and quantitatively from adult-derived cells. The Journal of Immunology, 2003, 171: 5157–5164.


This study investigates the ability of temperature sensors installed in the traction core of trains to early detect incipient faults. For instance, the breaking of a bearing is known to be critical as it may cause an increase of the temperature in the motor compartment, that in turn may eventually lead to a winding fault in the induction motor. The technique proposed in this contribution is characterised by extreme generality, since most frequent incipient faults lead to temperature increase that, if properly analysed, can be a tool for preventive maintenance. In particular, the measured data, provided by the main Italian railway company, are processed by two different methodologies which are characterised by positive, yet different, performances. The results show that preventive maintenance with the proposed approach is feasible.


The concept of therapeutic or antagonistic disease, i.e. a disease that interrupts or cures another and then spontaneously heals, had an ephemeral success in the XIX century and the first decades of the XX century. Some authors limited themselves to the careful collection of pertinent instances; others tried to go beyond the mere analysis and to develop practical applications, i.e. attempts to use a disease to cure another, only one of which, namely the electro-convulsive therapy, survives to date. In the long run, however, the concept proved of limited value and reduced applicability, and was abandoned. The origins of the concept of therapeutic disease cannot be traced down with certainty, since sporadic, matter-of-fact observations are already present in the most ancient Greek medical writings. However, the full theoretical development of this concept in a systematic form, and its intentional application to therapy occurred much later, and reached its height in two medical theories developed by German speaking authors: Hahnemann's homeopathy and Freud's psychoanalysis. A third theoretical elaboration of the same concept can be found in the writings of some French hypnotists, by and large in the same period, although hypnosis (at the time called somnambulism) is the heir of Mesmer's magnetism, a theory that did not originally imply the concept of therapeutic disease. In addition to the above theories, at the beginning of the XX century effective therapies based on the same concept were devised on a purely empirical basis: e.g. Wagner Jauregg's malaria therapy for syphilis, abandoned in favor of chemotherapy, and the several shock therapies for major psychoses, of which only the electro-convulsive therapy of Cerletti and Bini has survived. Were it not for these applications, the whole concept of the therapeutic disease would qualify as an interesting error in the pathway of medical thinking.


We study the impact of semi-annihilations x_i x_j x_k X, where x_i is any dark matter and X is any standard model particle, on dark matter phenomenology. We formulate minimal scalar dark matter models with an extra doublet and a complex singlet that predict non-trivial dark matter phenomenology with semi-annihilation processes for different discrete Abelian symmetries Z_N, N>2. We implement two such example models with Z_3 and Z_4 symmetry in micrOMEGAs and work out their phenomenology. We show that both semi-annihilations and annihilations involving only particles from two different dark matter sectors significantly modify the dark matter relic abundance in this type of models. We also study the possibility of dark matter direct detection in XENON100 in those models.


A 73-year-old man was admitted to our hospital because of a decrease in spontaneity. His medical history included two stroke episodes, probably related to hypertension. Brain MRI on admission demonstrated acute infarction in the right caudate nucleus and left putamen. Intravenous infusion of a low molecular-weight heparin added to oral antiplatelets was started. Following admission, he developed a low grade fever and severe inflammatory reaction. The focus of infection was not evident, and none of the antibiotics tried were effective. Ten days after admission, he developed right hemiparesis, and an additional brain MRI showed new multiple infarctions. We also determined the presence of a high MPO-ANCA titer (57 EU), and we diagnosed the patient's condition to be ANCA-associated vasculitis (AAV). Steroid therapy improved his inflammatory reaction and stroke recurrence was not observed. We suggest that vasculitis should be considered as a potential risk factor for repeated small infarctions with fever of unknown origin, especially those of perforating artery territories.


Relapsing fever is a complex group of diseases caused by spirochetes of the genus Borrelia transmitted to humans by lice or ticks. The purpose of this study is to present a case of relapsing fever. A 50-year-old female was admitted with fever, headache, nausea, myalgia, and arthralgia. She had history of relapsing fever for 3-5 days with 15-21-day-intervals of apyrexia during the past 3 months. Laboratory exams were normal. Peripheral blood smear showed spirochetes. She was treated with doxycycline to which she showed good response. The patient is asymptomatic and without sequelae since 3 months. In the case we reported, relapsing fever due to spirochetemia was made during the differential diagnosis. Owing to the difficulty in identification, it is important to have a high clinical suspicion of this type of infection.


The study was undertaken to determine the purity of available marketed brands of nine selected pesticide groups viz., chloropyriphos, diazinon, carbofuran, pyrazosulfuranethyle, dimethoate, cypermethrin, carbendazim, mencozeb and quinalphos. These pesticides were collected from local markets of eight locationsviz., Rajshahi, Rangpur, Dinajpur, Bogra, Chittagong, Mymensing, Comilla, Norshingdi and Jessoredistricts of Bangladesh where extensive usage of pesticides was recorded. Among the 66tested pesticides, 66.66 % (44 in number) were found ˃90% pure in terms of active ingredient (AI). The purity range of about 12% of the total tested brands was 80%--90%. And the remaining 21.34% were less than 80 % pure, of which three pesticide brands contained no active ingredient (AI) at all. Bangladesh J. Agril. Res. 41(4): 685-694, December 2016


Deep neural networks (DNNs) in the infinite width/channel limit have received much attention recently, as they provide a clear analytical window to deep learning via mappings to Gaussian Processes (GPs). Despite its theoretical appeal, this viewpoint lacks a crucial ingredient of deep learning in finite DNNs, laying at the heart of their success -- feature learning. Here we consider DNNs trained with noisy gradient descent on a large training set and derive a self consistent Gaussian Process theory accounting for strong finite-DNN and feature learning effects. Applying this to a toy model of a two-layer linear convolutional neural network (CNN) shows good agreement with experiments. We further identify, both analytical and numerically, a sharp transition between a feature learning regime and a lazy learning regime in this model. Strong finite-DNN effects are also derived for a non-linear two-layer fully connected network. Our self consistent theory provides a rich and versatile analytical framework for studying feature learning and other non-lazy effects in finite DNNs.


Diagnosis of Crimean-Congo haemorrhagic fever (CCHF) virus infections is hampered by the problems of handling this human pathogen, which requires the highest levels of biological containment. Recombinant antigens were examined for their potential as non-hazardous diagnostic reagents. The nucleocapsid (N) gene of the Greek AP92 isolate of CCHF virus was sequenced from cloned PCR products and the open reading frame was identified by homology to the N protein of a Chinese isolate of CCHF virus. The N protein was expressed to high levels in a baculovirus expression system. Three N protein-derived peptides were expressed in Escherichia coli as fusions with glutathione S-transferase and the antigenicities of these proteins and the baculovirus-expressed protein were tested by ELISA. When tested with laboratory animal sera representing all seven serogroups of nairoviruses, the only reactive sera were those raised to CCHF virus (Greek, Nigerian and Chinese isolates) and, more weakly, Hazara virus. When tested with a panel of known positive and negative human sera, the baculovirus-expressed N protein, and the peptide derived from the central region of the N protein, proved to be the best for identifying CCHF virus-specific IgG.


Three infants receiving long-term parenteral hyperalimentation developed obstructive jaundice characterized by parallel elevations of total and direct bilirubin with normal serum enzyme determinations. Two infants died from complications of their primary surgical lesion while the third survived with complete reversal of the hepatic involvement. Liver specimens in two patients revealed a unique form of hepatitis having parenchymal cholestasis and periportal infiltration with a marked eosinophilic myelopoiesis. The histologic findings are compatible with complications of a bile secretory defect. Deficiency of a specific amino acid, essential to the formation of normal bile salts, or long-standing intestinal obstruction, could predispose to abnormal or inadequately conjugated bile salts interfering with micelle formation and the normal flow of bile into the canaliculus.


In this article I discuss a recent proposal according to which human beings are in need of moral enhancement by novel biomedical means in order to reduce the risk of catastrophes that could threaten the very possibility of continued human existence on this planet. I raise two objections to this proposal. The first objection claims that the idea that human beings could be morally enhanced by altering our emotional psychological inclinations, such as altruism, is misguided. In the line with Kantian understanding of morality I argue that our morality is based on rationality and not on inclinations. If we take this view of morality it becomes clear that the proposed enhancement by biomedical means cannot be moral enhancement. What is enhanced is emotional aspect of our character, not our morality. People enhanced in this way would not act on the basis of their deliberate choices but on basis of preprogramed psychological inclination. This would in turn undermine our basic moral concept of freedom and, thereby, of moral responsibility. The second objection to the proposal show how the idea that moral enhancement by biomedical means should be mandatory violates political freedom of citizens. Faced with the objection that moral enhancement by biomedical means could be necessary in order to prevent catastrophic destruction of environment, in the final part of this chapter I try to point to education and liberal democracy as the alternative and morally acceptable ways of changing our behaviour.


The elucidation of the molecular mechanisms underlying the very early steps of thyroid organogenesis and the etiology of most cases of thyroid dysgenesis are poorly understood. Many genes have been identified as important contributors to survival, proliferation and migration of thyroid cells precursors, acting as an integrated and complex regulatory network. Moreover, by generation of mouse mutants, the studies have provided better knowledge of the role of these genes in the thyroid morphogenesis. In addition, it is likely that a subset of patients has thyroid dysgenesis as a result of mutations in regulatory genes expressed during embryogenesis. This review summarizes molecular aspects of thyroid development, describes the animal models and phenotypes known to date and provides information about novel insights into the ontogeny and pathogenesis of human thyroid dysgenesis.


Use of Unmanned Aerial Vehicles (UAVs) is rapidly increasing in various domains such as disaster management, delivery of goods, surveillance, military, etc. Significant issues in the expansion of UAV-based applications are the security of (IoT to UAV) communication, and the limited flight time of the UAVs and IoT devices considering the limited battery power. Standalone UAVs are not capable of accomplishing several tasks, and therefore swarm of UAVs is being explored. Security issues in the swarm of UAVs do not allow the applications to leverage the full benefits that one can offer. Several recent studies have proposed the use of a distributed network of UAVs to upgrade the level of security in the swarm of UAVs. In this paper, a framework for secure and reliable energy trading among UAVs and charging stations is presented. Advanced blockchain, based on the tangle data structure is used to create a distributed network of UAVs and charging stations. The proposed model allows the UAVs to buy energy from the charging station in exchange for tokens. If the UAV does not have sufficient tokens to buy the energy, then the model allows the UAV to borrow tokens from the charging station. The borrowed tokens can be repaid back to the charging station with interest or late fees. A game-theoretic model is used for deciding the buying strategy of energy for UAVs. Numerical analysis shows that the proposed model helps in providing increased utility for the swarm of UAVs and charging stations in a secure and cost-optimal way as compared to the conventional schemes. The results can eventually be applied to IoT devices that constantly need energy to perform under ideal conditions.


We show that the strength of Internet-based network interconnectivity of countries is increasing over time. We then evaluate bounds on the extent to which a group of colluding countries can disrupt this connectivity. We evaluate the degree to which a group of countries can disconnect two other countries, isolate a set of countries from the Internet, or even break the Internet up into non-communicative clusters. To do this, we create an interconnectivity map of the worldwide Internet routing infrastructure at a country level of abstraction. We then examine how groups of countries may use their pieces of routing infrastructure to filter out the traffic of other countries (or to block entire routes). Overall, bounds analysis indicates that the ability of countries to perform such disruptions to connectivity has diminished significantly from 2008 to 2013. However, we show that the majority of the gains in robustness go to countries that had already displayed significant robustness to the types of attacks that we consider. The countries that displayed higher initial vulnerability to such attacks did not become significantly more robust over the time period of analysis. Keywords— Internet, resilience, connectivity, autonomous systems, security, countries


ABSTRACT Populations of Phytophthora spp. were determined by enzyme-linked immunosorbent assay (ELISA) in field soils used for pepper and soybean production in Ohio. Soybean fields were sampled extensively (64 fields, n = 6 samples per field over 2 years) and intensively (4 fields, n = 64 samples per field in 1 year) to assess heterogeneity of P. sojae populations. Four pepper fields (n = 64), three of which had a history of Phytophthora blight (caused by P. capsici), also were sampled intensively during a 6-month period. Mean (m), variance (v), and measures of aggregation (e.g., variance-to-mean ratio [v/m]) of immunoassay values, translated to Phytophthora antigen units (PAU), were related to the disease history in each of the pepper and soybean fields. Mean PAU values for fields in which Phytophthora root rot (soybean) or blight (pepper) had been moderate to severe were higher than in fields in which disease incidence had been low or not observed. A detection threshold value of 11.3 PAU was calculated with values for 64 samples from one pepper field, all of which tested negative for Phytophthora by bioassay and ELISA. Seven of the eight intensively sampled fields contained at least some detectable Phytophthora propagules, with the percentage of positive samples ranging from 1.6 to 73.4. Mean PAU values ranged from 1 to 84 (extensive soybean field sampling), 6 to 24 (intensive soybean field sampling), and 4 to 30 (intensive pepper field sampling); however, variances ranged from 0 to 7,774 (extensive sampling), 30 to 848 (intensive soybean field sampling), and 5 to 2,401 (intensive pepper field sampling). Heterogeneity of PAU was high in most individual soybean and pepper fields, with values of v/m greater than 1, and log(v) increasing with log(m), with a slope of about 2.0. Spatial autocorrelation coefficients were not significant, indicating there was no relationship of PAU values in neighboring sampling units (i.e., field locations) of the intensively sampled fields. Combined results for autocorrelations and v/m values indicate that Phytophthora was highly aggregated in these fields but that the scale of the aggregation (e.g., average focus size) was less than the size of the sampling units. Because of the observed variability, we calculated that sample sizes of 20 or more would be needed to estimate precisely the mean density of Phytophthora in most cases.


Plant essential oils have the potential to replace the synthetic fungicides in the management of different fungal diseases. Four different essential oils of eucalyptus (Eucalyptus globulus), citronella (Cymbopogon citrate), karanj (Pongamia pinnata) and neem (Azadirachta indica) were selected because of their high inhibitory activities against ten phytopathogenic fungi. The antifungal screening for all the four Eos clearly indicates the effective lowest concentration to control the fungal growth. The more lower the MIC value, the better antifungal potency of the relative plant volatile E. globulus. Among the plant volatile essential oils, eucalyptus oil showed the lowest minimum inhibitory concentration (MIC), i.e.  0.5 mg/disc. Higher MIC values were registered, in the order, for citronella, karanj and neem oils, singly used to control all the ten fungal pathogens. Highest zone of inhibition (ZI) values followed the same pattern. These results indicated that plant volatile essential oils after suitable formulation could be used to control of different fungal pathogens. This may encourage the farmers to produce organic commodities to generate more revenue.

 Key words Essential oils, minimum inhibitory concentration (MIC), zone of inhibition, fungal disease.