In spite of their adverse side effects, natural and synthetic glucocorticoids (GCs) occupy a unique role in several fields of medicine. They are potent regulators of bone cell growth and differentiation and the actions on the skeleton and related tissues depend on several factors including the dose, duration of the exposure, the steroid type and the species. In humans some of the effects are indirect, such as the regulation of intestinal calcium absorption and PTH secretion. Other effects are due to the cellular response that occurs within the bone microenvironment. It has been well established in in vitro studies that GCs can promote osteoblast differentiation from mesenchymal osteoprogenitors both in rat calvarial culture and in adherent marrow stromal cells. Moreover, GCs are able to enhance expression of the mature osteoblast phenotype, increasing mineralized nodules, osteocalcin secretion, and the bone morphogenetic protein-6 message level. However, the mechanisms by which GCs affect bone metabolism are still unclear. Recent studies with GCs on bone cells suggested that the production of cytokines and growth factors and the expression of their receptors may also be influenced by GCs. In fact, GCs are able to inhibit the synthesis of cytokines, such as interleukin-1 which stimulates bone remodeling by monocytes and macrophages. Moreover, osteoprotegerin, a recently cloned member of the tumor necrosis factor receptor family, is down-regulated by GCs, offering a possible interpretation for the induction of bone resorption by GCs. GC-induced inhibition of bone resorbing cytokines may contribute to explain the therapeutic actions of GCs in several diseases such as rheumatoid arthritis and myeloma. Furthermore, GCs modulate osteoclast recruitment, even if there is no clear explanation for a direct effect of GCs on osteoclastic precursors. Sustained stimulation of matrix degradation by isolated avian osteoclasts incubated with GCs has been reported, as well as cytotoxic effects on osteoclastic cells from neonatal rat long bones.


Purpose
There is a major lacuna in sustainable human resource management (HRM) research regarding the theoretical context of its adoption or implementation. Consequently, the purpose of this study is to examine the relative influence and interactive effects of different levels of institutional isomorphisms on sustainable HRM adoption.

Design/methodology/approach
This study applies the conceptual method and anchors the discussions on the institutional theory and the extant literature on the antecedents of sustainable HRM implementation.

Findings
Internal and external institutional isomorphisms will have complementary (synergies) or substitution (trade-offs) effects on sustainable HRM adoption. Furthermore, external institutional isomorphic pressures related to societal values and culture and stakeholders' sustainability demands are likely to have greater influence on sustainable HRM implementation relative to the internal institutional isomorphic pressures related to managerial sustainability values and attitudes; sustainability-related HRM competencies; resource availability; and perceived sustainability benefits.

Originality/value
This study proposes a novel multi-level conceptual model on the implementation context of sustainable HRM for testing empirically. Furthermore, this study generates insight on how different levels of institutional isomorphic pressures relatively and interactively (synergies versus trade-offs) affect sustainable HRM adoption. This is significant because there is a view that HRM as a discipline is theoretically weak. Although the field has advanced theoretically, one of the areas that need more theorisation is the context of HRM. Hence, this study advances the theoretical context of sustainable HRM implementation through the perspectives of the institutional theory.


Sediment cores from Lake DV09, northern Devon Island, Nunavut, Canada (75°34′34″N, 89°18′55″W), were studied to reconstruct the lake ontogeny through analysis and interpretation of the sediment stratigraphy. The lake was uplifted from marine inundation ∼7600 cal BP. After a millennium of rapid sediment accumulation, which coincided with the Holocene Thermal Maximum in the region, accumulation rates decreased over the past 6000 years as the Arctic became colder. This resulted in the deposition of very fine laminae that were interpreted as varves. The uppermost laminated sediments provided a ∼1600 year history of annual sediment transport and deposition into the lake. During periods of warmer temperatures, such as between 6000 and 7500 cal BP and during the Medieval Climate Anomaly (∼950–1300 CE; CE, Christian Era), hydroclimatic and permafrost slope processes increased sedimentation rates into the basin.


As trade and transport networks were taking shape through a series of development, modern transport practices such as multimodal transport service and logistics service value has significantly affected current transport systems. Inevitably, collaborative relationships between shippers and operators have received considerable attention in determining the effectiveness of Multimodal Transport. The term of'relationship' in the context of transport has always been a critical pillar in strategic business environment. However, in the Asian context, especially in China or other Asian countries like Thailand, the term 'relationship' is an ambiguous business concept, which exceeds more than just elements of long-term business relationship or short- term transactions found in the Western literature. The term 'Guartxi briefly translated as personal connections/relationships, is deeply embedded in the mindset of most Asian people and in every aspect of their personal and organisational interactions. The primary objective of this thesis is to investigate the impact of Multimodal Transport Service Value and Relationships on shippers' Business Performance, evidence from Thai shippers' perspective. In this study, an evaluation of the causal relationships among Multimodal Transport Service (MTS), Logistics Service Value (LSV), Relationship Quality (RQ) and Guanxi (GX) on shippers' Business Performance (BP) is examined. A research model is developed to validate these measurement models and to rigorously test the relationships in the form of structural model. This study uses Structure Equation Modeling (SEM) to analyse data collected from Thai shippers listed in the Thai National Shippers' Council (TNSC). The result of the structural model has shown that both MTS and LSV has significant impact on BP through RQ, and GX has shown support on all of its related hypothesised paths. In summary, this thesis empirically develops a structural model to prove the significance of MTS, LSV, RQ and GX on Business Performance in a Multimodal Transport environment.


Introduction: This research was conducted to determine the effect of several types of local microorganism solutions and manures on the growth and yield of peanut and their impact on the physical properties of ultisols.
Materials and Methods: The researches was conducted in Simalingkar B, Medan using Factorial Randomized Block Design within three replications. The first factor was types of microbe sources of local microbial solutions, include un-treated waste (M0), pineapple (M1), orange (M2), and tamarillo (M3) wastes. The second factor was manure types, inluce un-treated manure (P0), chicken (P1), cow (P2), and goat (P3) manures. The parameters were: soil physical characteristics (bulk density, water content and total of pore space), plant height, stem diameter, number of pods, and dry seeds yield.
Results: The types of local microorganism solutions only affect to plant height of peanut, but has insignificant effect on the physical properties of ultisols, and stem diameter, the number of filled pods.plant-1, and the dry seeds yield.ha-1 of peanut. The types of manure had significantly effected on plant height and number of filled pods.plant-1, but had insignificant effect on stem diameter, dry seeds yield.ha-1 and the physical properties of ultisols. The interaction of MOL sources and manure did not significantly affect the growth and yield of peanut as well as the physical properties of ultisols. Orange MOL and chicken manure could be increase the plant height of peanut by 18.61% and 6.75%, respectively, compared to un-treated. Goat manure showed the highest number of pods.plant-1 by 6.32% compared to un-treated.


This chapter argues that dual-use emerging technologies are distributing unprecedented offensive capabilities to nonstate actors. To counteract this trend, some scholars have proposed that states become a little "less liberal" by implementing large-scale surveillance policies to monitor the actions of citizens. This is problematic, though, because the distribution of offensive capabilities is also undermining states' capacity to enforce the rule of law. I will suggest that the only plausible escape from this conundrum, at least from our present vantage point, is the creation of a "supersingleton" run by a friendly superintelligence, founded upon a "post-singularity social contract." In making this argument, the present chapter offers a novel reason for prioritizing the "control problem," i.e., the problem of ensuring that a greater-than-human-level AI will positively enhance human well-being.


Abstract By the time Prime Minister Abe Shinzo and President Park Geun-hye took office, Japan-South Korea relations were already experiencing a downturn over history issues and Lee Myung-bak's unprecedented presidential visit to the disputed islets of Dokdo/Takeshima. Park's refusal to hold a bilateral summit became the symbol of strained ties. Then on November 2, 2015 — 980 days after taking office — Park met Abe for bilateral talks in Seoul. On December 28, the two sides declared a rapprochement with an agreement supporting survivors of wartime brothels. Tensions worsened again during President Moon Jae-in's term (2017–2022), contradicting the narrative that leaders had turned relations around in late 2015. Yet the diplomatic relationship was not on a downward spiral. Japanese and Korean policymakers managed to put a floor under their interactions owing to three stabilizing mechanisms that operated during both the Park and Moon administrations. First, political elites practiced mutual restraint to limit vicious cycles of nationalist recriminations. Second, Tokyo and Seoul carefully calibrated policies toward Beijing while avoiding divergence from each other. Third, reassuring the United States about the cost-effectiveness of its alliances involved trilateral cooperation that also helped stabilize Japan-South Korea relations.


Since its original conception as a tool for manufacturing porous materials, the breath figure method (BF) and its variations have been frequently used for the fabrication of numerous micro- and nanopatterned functional surfaces. In classical BF, reliable design of the final pattern has been hindered by the dual role of solvent evaporation to initiate/control the dropwise condensation and induce polymerization, alongside the complex effects of local humidity and temperature influence. Herein, we provide a deterministic method for reliable control of BF pore diameters over a wide range of length scales and environmental conditions. To this end, we employ an adapted methodology that decouples cooling from polymerization by using a combination of initiative cooling and quasi-instantaneous UV curing to deliberately arrest the desired BF patterns in time. Through in situ real-time optical microscopy analysis of the condensation kinetics, we demonstrate that an analytically predictable self-similar regime is the predominant arrangement from early to late times O(10–100 s), when high-density condensation nucleation is initially achieved on the polymer films. In this regime, the temporal growth of condensation droplets follows a unified power law of D ∝ t. Identification and quantitative characterization of the scale-invariant self-similar BF regime allow fabrication of programmed pore size, ranging from hundreds of nanometers to tens of micrometers, at high surface coverage of around 40%. Finally, we show that temporal arresting of BF patterns can be further extended for selective surface patterning and/or pore size modulation by spatially masking the UV curing illumination source. Our findings bridge the gap between fundamental knowledge of dropwise condensation and applied breath figure patterning techniques, thus enabling mechanistic design and fabrication of porous materials and interfaces.


A 3D histo-culture platform provides a near native Tumor immune Micro-Environment (TiME), making it best suited for evaluating response to immunotherapy drugs. Farcast™ TiME is a human 3D tumor histo-culture platform that preserves TiME and maintains functional fidelity of intra-tumoral immune cells (IIC). In this study we investigated the utility of this platform in demonstrating treatment induced Antibody-Dependent Cellular Cytotoxicity (ADCC) mechanism driven by IICs alone versus co-culture with autologous peripheral blood immune cells.Head and neck squamous cell carcinoma tissue samples (n=5) along with matched blood from consented patients were used in this study. All Peripheral Blood Nucleated Cells (PBNCs) including lymphocytes, monocytes, NK cells and neutrophils were isolated and stained with a tracking dye to distinguish them from IICs. Tumor tissues were processed to generate explants, treated with 184 µg/ml Cetuximab (anti-EGFR) or vehicle control, and cultured with or without PBNCs for 72 hrs. Response was evaluated using flow cytometry and cytokine release assay.Amount of infiltrated autologous PBNCs showed a strong negative correlation (R2=0.98) with the amount of IICs in the absence of drug treatment. The proportions of infiltrated immune cell sub-populations were similar to the composition of PBNCs added in culture. Cetuximab treatment, however, led to enhanced infiltration of the effector cells for ADCC driven tumor killing, namely NK cells, macrophages, neutrophils, and cytotoxic T cells (CTLs). Notably the unique infiltration pattern of effector cell populations observed in each sample was reflected in the secretion of specific cytokine/chemokines associated with that cell population. NK cell increase (fold change: 1.6 ± 0.8) was observed in all samples with a concomitant increase in MCP-1 secretion (fold change: 1.7 ± 0.9). Granzyme-B expressing NK cells increased (>1.7 fold) in a subset of samples. Samples showing increase in neutrophil infiltration exhibited increased MMP9 secretion, involved in neutrophil infiltration via stromal remodeling. Sample with highest increase in infiltration of CD16+ Monocyte/Macrophages (>2.4 fold) showed maximum increase in Granzyme-B secretion with respect to the untreated arm. Increase in fold secretion (>1.4) of CXCL9/CXCL10 was associated with the sample that showed highest fold increase of Granzyme-B expressing CTL in comparison to untreated arm. IICs alone were not sufficient in eliciting optimal ADCC response.The study demonstrated ADCC response in the explant/PBNC co-culture platform leading to specific infiltration of effector sub-populations. FarcastTM TiME thus provides a unique platform to explore for heterologous adoptive cell and CAR-T therapies that involve immune cell infiltration.All samples included in the study were approved by institutional review boards of the centers providing the samples.


Background:BRAF-V600E mutations are found in a broad spectrum of cancer types and can be successfully targeted by specific therapeutic compounds. Little data on the prevalence of BRAF-V600E mutations in tumors of the upper gastrointestinal tract are available. Materials and Methods:We constructed tissue microarrays of formalin-fixed and paraffin-embedded specimens of 534 gastroesophageal tumors (119 squamous cell cancers and 72 adenocarcinomas of the esophagus, 63 cancers of the gastroesophageal junction/cardia, 199 gastric cancers of the corpus or antrum, 81 gastric gastrointestinal stromal tumors) and performed anti-BRAF-V600E immunostaining using the mutation-specific antibody VE1. As control tissue we used 3 melanoma cases with confirmed BRAF-V600E mutation and distinct VE1 immunostaining. Results:None of the gastroesophageal tumor cases showed a positive immunostaining signal. Conclusions:BRAF-V600E mutation is not a relevant oncogenic driver in gastroesophageal tumors. Immunohistochemical analysis using mutation-specific antibodies on tissue microarrays is a feasible, time-efficient and cost-efficient approach to high-throughput screening for specific mutations in large tumor series.


A simple and convenient cyclization of ortho-hydroxyphenyl-substituted para-quinone methides with benzofuran-2-one type active olefins via oxa-Michael/1,6-conjugated addition has been developed, which afforded an easy access to enriched functionalized chroman-spirobenzofuran-2-one scaffolds with good to excellent yields (up to 90%) and diastereoselectivities (up to >19 : 1 dr). This reaction provided an efficient method for constructing desired spirocyclic compounds combining both well-known heterocyclic pharmacophores chroman and benzofuran-2-one.


Abstract Background Regular follow-up visits and routine care is important for people with a mild bleeding disorder in terms of lowering their risk of complications from untreated bleeds and helping them maintain a healthy lifestyle. However, follow-up visits among this population can sometimes be missed for unclear reasons. Aim The present study aimed to question if lost-to-follow-up patients with a bleeding disorder experience unreported but important bleeding events that are not communicated to their haemophilia treatment centre (HTC) and if they could benefit from more frequent clinic visits. Methods A multicentre paper-based cross-sectional survey was sent to people diagnosed with an inherited blood disorder and lost to follow-up for two years or more. Those who met the eligibility criteria received the survey by mail and completed and returned it to their HTC between October 2015 and July 2016. Results Invitation packages were sent to 71 individuals; 14 questionnaires returned, with a survey response rate of 19.7%. Of the 14 returned surveys, only 11 participants were eligible who either responded completely or partially to the survey. Quality of life was reported as almost never or never a problem by all but one participant, who limited activities due to bleeding problems. Spontaneous nosebleeds were sometimes, often or always a problem for three participants; one female participant reported issues associated with heavy menstrual bleeding as often or almost always a problem. Conclusion We concluded that although the mean annual bleeding self-reported events were relatively low, they cannot be underestimated when keeping in mind the limitations and challenges of accessing data among this population. Our study highlighted the importance of educating this group of patients on their bleeding disorder and engaging them in their own care and health status, which may result in improving their health-related quality of life and overall health outcomes.


Background: Owing to the heterogeneity displayed by hepatocellular carcinoma (HCC) and the complexity of tumor microenvironment (TME), it is noted that the long-term effectiveness of the cancer therapy poses a severe clinical challenge. Hence, it is essential to categorize and alter the treatment intervention decisions for these tumors. Materials and methods: "ConsensusClusterPlus" tool was used for developing a secure molecular classification system that was based on the cuproptosis-linked gene expression. Furthermore, all clinical properties, pathway characteristics, genomic changes, and immune characteristics of different cell types involved in the immune pathways were also assessed. Univariate Cox regression and the least absolute shrinkage and selection operator (Lasso) analyses were used for designing the prognostic risk model associated with cuproptosis. Results: Three cuproptosis-linked subtypes (clust1, clust2, and clust3) were detected. Out of these, Clust3 showed the worst prognosis, followed by clust2, while Clust1 showed the best prognosis. Three subtypes had significantly different enrichment in pathways related to Tricarboxylic Acid (TCA) cycle, cell cycle, and cell senescence (p < 0.01). The clust3 subtype with poor prognosis had a low "ImmuneScore" and low immune cell infiltration, and the three subtypes had significant differences in the antigen processing and presentation pathway of the macrophages. Clust1 had a low TIDE score and was sensitive to immunotherapy. Then, according to the prognosis-related genes of cuproptosis, a prognosis risk model related to cuproptosis was constructed, containing seven genes (KIF2C, PTTG1, CENPM, CDC20, CYP2C9, SFN, and CFHR3). "High" group had a higher TIDE score compared to the TIDE score value shown by the "Low" group, which benefited less from immunotherapy, whereas the "High" group patients were more sensitive to the conventional drugs. Finally, the prognosis risk model related to cuproptosis was combined with clinical pathological characteristics to further improve the prognostic model and survival prediction. Conclusion: Three new molecular subgroups based on cuproptosis-linked genes were revealed, and a cuproptosis-related prognostic risk model comprising seven genes was established in this study, which could assist in predicting the prognosis and identifying the patients benefit from immunotherapy.


The shrimp is an excellent source of protein and essential HighUnsaturated Fatty Acids (HUFA) such as eicosapentaenoic (20: 5n3, EPA) and docosahexaenoic (22: 6n3, DHA) acids [1, 2]. Furthermore, the shrimp is also a good source of minerals and vitamins such as calcium, iron, zinc, copper, vitamin B12, essential amino acids [1, 3] as well as astaxanthin, a fat-soluble carotenoid which has antioxidant properties. Its biochemical composition may be affected by several factors as the species, environmental factors, size, age, natural diet and feed composition [4, 5].


A moderate change in ambient temperature can lead to vital physiological and biochemical adjustments in ectotherms, one of which is a change in fatty acid composition. When temperature decreases, the composition of membrane lipids (phospholipid fatty acids) is expected to become more unsaturated to be able to maintain homeoviscosity. Although different in function, storage lipids (triacylglycerol fatty acids) are expected to respond to temperature changes in a similar way. Age-specific differences, however, could influence this temperature response between different life stages. Here, we investigate if fatty acid composition of membrane and storage lipids responds similarly to temperature changes for two different life stages of Orchesella cincta . Juveniles and adults were cold acclimated (15°C → 5°C) for 28 days and then re-acclimated (5°C → 15°C) for another 28 days. We found adult membranes had a more unsaturated fatty acid composition than juveniles. Membrane lipids became more unsaturated during cold acclimation, and a reversed response occurred during warm acclimation. Membrane lipids, however, showed no warm acclimation, possibly due to the moderate temperature change. The ability to adjust storage lipid composition to moderate changes in ambient temperature may be an underestimated fitness component of temperature adaptation because fluidity of storage lipids permits accessibility of enzymes to energy reserves.


Freestanding and transferable silica nanosheets with thicknesses of ≈5-7 nm are prepared via ethyl acetate-mediated hydrolysis of silica precursors in aqueous solution. The resulting silica nanosheets have shown many potential applications. For example, they can be used as the support film on the finer mesh grids for transmission electron microscopy imaging and as the precursor for the synthesis of silicon nanosheets.


Digital holographic microscopy has been a powerful metrological technique for phase-contrast imaging. However inherent phase aberrations always exist and degrade the quality of the phase-contrast images. A surface fitting method based on an improved mathematic model is proposed, which can be used to remove the phase aberrations without any pre-knowledge of the setup or manual operation. The improved mathematic model includes not only the usual terms but also the cross terms and the high order terms to describe the phase aberrations with high accuracy. Meanwhile, a non-iterative algorithm is used to solve the parametersand thus less computational load is imposed. The proposed method is applied to the live imaging of cells. The experimental results verify its validity.


Abstract : This Directive reissues DoD Directive 1000.4, dated November25, 1980, to update policy and responsibilities for the Federal Voting Assistance Program (FVAP) under Executive Order 12642. It continues to implement Executive Order 12642 wherein the Secretary of Defense is named the 'Presidential designee'and assigned responsibility for oversight of the FVAP under Sections 1973ff- l973ff-6 of title 42, United States Code. This Directive also continues to assign responsibility and delegate authority to the Director of Administration and Management, Office of the Secretary of Defense (DA&M, OSD), to carry out the FVAP for the Secretary of Defense, consistent with DoD Directive 5105.53 and DoD Directive 1344.13.


Despite the extensive use of lithotripsy for treating renal and biliary calculi, there has been little data reported regarding the causes and manifestations of lithotripter failure. The clinical and service records for 145 consecutive treatments performed with the Siemens Lithostar Plus were reviewed. Service record analysis revealed eight failures of shock wave generation during a 10-month period. Six of these failures were subtle and still allowed shock wave generation. There were five in-line ultrasound probe failures during this period. The most useful clinical parameter for predicting lithotripter failure was reduced severity of sonographically evident cavitation bubbles during treatment. Lack of stone fragmentation and unexpectedly low analgesia requirements at high-power levels were less useful in predicting lithotripter failure. All clinical parameters suffered from nonspecificity. Preliminary experience, with an ongoing quality assurance program using a test object hydrophone, suggests this is a useful method of predicting lithotripter function and avoiding compromised treatments.


Tuberculosis (TB) is an infectious disease caused by mycobacterium which can be diagnosed by its various symptoms like fever, cough, etc. Tuberculosis can also be analyzed by understanding the chest x-ray of the patient which is revealed by an expert physician .The chest x-ray image contains many features which cannot be directly used by any computer system for analyzing the disease. Features of chest x-ray images must be understood and extracted, so that it can be processed to a form to be fed to any computer system for disease analysis. This paper presents feature extraction of chest x-ray image which can be used as an input for any data mining algorithm for TB disease analysis. So texture and shape based features are extracted from x-ray image using image processing concepts. The features extracted are analyzed using principal component analysis (PCA) and kernel principal component analysis (kPCA) techniques. Filter and wrapper feature selection method using linear regression model were applied on these techniques. The performance of PCA and kPCA are analyzed and found that the accuracy of PCA using wrapper approach is 96.07%   when compared to the accuracy of kPCA which is 62.50%. PCA performs well than kPCA with a good accuracy.


ABSTRACT
 To compare resistance to small hive beetles (Coleoptera: Nitidulidae) between Russian and commercial Italian honey bees (Hymenoptera: Apidae), the numbers of invading beetles, their population levels through time and small hive beetle reproduction inside the colonies were monitored. We found that the genotype of queens introduced into nucleus colonies had no immediate effect on small hive beetle invasion. However, the influence of honey bee stock on small hive beetle invasion was pronounced once test bees populated the hives. In colonies deliberately freed from small hive beetle during each observation period, the average number of invading beetles was higher in the Italian colonies (29 ± 5 beetles) than in the Russian honey bee colonies (16 ± 3 beetles). A similar trend was observed in colonies that were allowed to be freely colonized by beetles throughout the experimental period (Italian, 11.46 ± 1.35; Russian, 5.21 ± 0.66 beetles). A linear regression analysis showed no relationships between the number of beetles in the colonies and adult bee population (r 2 = 0.1034, P = 0.297), brood produced (r 2 = 0.1488, P = 0.132), or amount of pollen (r 2 = 0.1036, P = 0.295). There were more Italian colonies that supported small hive beetle reproduction than Russian colonies. Regardless of stock, the use of entrance reducers had a significant effect on the average number of small hive beetle (with reducer, 16 ± 3; without reducer, 27 ± 5 beetles). However, there was no effect on bee population (with reducer, 13.20 ± 0.71; without reducer, 14.60 ± 0.70 frames) or brood production (with reducer, 6.12 ± 0.30; without reducer, 6.44 ± 0.34 frames). Overall, Russian honey bees were more resistant to small hive beetle than Italian honey bees as indicated by fewer invading beetles, lower small hive beetle population through time, and lesser reproduction.


Abstract Regional (economic) resilience and resilient thinking have gained considerable attention in recent years. My aim with this work is to throw light on some of the underlying aspects of regional economic resilience and resilient thinking. In the current study I give an overview of the notion, key concepts, main empirical results and planning tasks concerning regional (economic) resilience as well as outlining some of the criticisms. Finally, I provide some suggestions for studies in resilience and resilient thinking for future research agendas. The main results of the study is my own belief in the concept of regional economic resilience, and an overview and comparison of regional (economic) resilience literature and empirics that lead me to highlight some of the shortcomings of the research topic.


As more users across the world are interacting with dialog agents in their daily life, there is a need for better speech understanding that calls for renewed attention to the dynamics between research in automatic speech recognition (ASR) and natural language understanding (NLU). We briefly review these research areas and lay out the current relationship between them. In light of the observations we make in this article, we argue that (1) NLU should be cognizant of the presence of ASR models being used upstream in a dialog system's pipeline, (2) ASR should be able to learn from errors found in NLU, (3) there is a need for end-to-end data sets that provide semantic annotations on spoken input, (4) there should be stronger collaboration between ASR and NLU research communities.


The "clue" to Christian education is found "in the relevance of theology to the whole of life." One approach to religious education has been concerned primarily with theology with little interest in the on-going experience of the individual. Another approach has been interested in "life"-understanding man from the psychological perspective with but little concern for man from the theological perspective.


Odor recognition constitutes a key functional aspect of olfaction and in real-world scenarios it requires that odorants occurring in complex chemical mixtures are identified irrespective of their concentrations. We investigate this challenging pattern recognition problem in the framework of a three-stage computational model of the mammalian olfactory system. To this end, we first synthesize odor stimuli with the primary representations in the olfactory receptor neuron (ORN) layer and the secondary representations in the output of the olfactory bulb (OB) in the model. Next, sparse olfactory codes are extracted and fed into the recurrent network model, where as a result of Hebbian-like associative learning an attractor memory storage is produced. We demonstrate the capability of the resultant olfactory cortex (OC) model to perform robust odor recognition tasks and offer computational insights into the underlying network mechanisms.


During the last years, oxide semiconductors have shown that they will have a key role in the future of electronics. In fact, several research groups have already presented working devices with remarkable electrical and optical properties based on these materials, mainly thin-film transistors (TFTs). Most of these TFTs use indium-tin oxide (ITO) as the material for source/drain electrodes. This paper focuses on the investigation of different materials to replace ITO in inverted-staggered TFTs based on gallium-indium-zinc oxide (GIZO) semiconductor. The analyzed electrode materials were indium-zinc oxide, Ti, Al, Mo, and Ti/Au, with each of these materials used in two different kinds of devices: one was annealed after GIZO channel deposition but prior to source/drain deposition, and the other was annealed at the end of device production. The results show an improvement on the electrical properties when the annealing is performed at the end (for instance, with Ti/Au electrodes, mobility rises from 19 to 25 cm2/V ldr s, and turn-on voltage drops from 4 to 2 V). Using time-of-flight secondary ion mass spectrometry (TOF-SIMS), we could confirm that some diffusion exists in the source/drain electrodes/semiconductor interface, which is in close agreement with the obtained electrical properties. In addition to TOF-SIMS results for relevant elements, electrical characterization is presented for each kind of device, including the extraction of source/drain series resistances and TFT intrinsic parameters, such as (intrinsic mobility) and VTi (intrinsic threshold voltage).


Multiple molecular dynamics (MD) simulations of fully solvated rat intestinal fatty acid binding protein (I‐FABP) were conducted to investigate the dynamics of internal water molecules. Although the long time average of the number of internal water molecules in I‐FABP is 22 as shown by the X‐ray crystal structure, MD simulations predict large variations in the instantaneous number of internal water molecules on the nanosecond time scale. The computational model employed predicts that w135 (internal) and w217 (located on the protein surface) may be the water molecules with long residence times observed in previously reported magnetic relaxation dispersion studies. The average residence time of ∼20 internal water molecules occupying the fatty acid binding cavity is estimated to be between 0.6 and 2.0 nanoseconds. Exchange of internal water in I‐FABP appears to occur almost exclusively through the interface of β‐strands EF with the rest of the protein, which has significant implications for the pathways of the fatty acid entry and exit from the binding cavity. Proteins 2001;43:65–72. © 2001 Wiley‐Liss, Inc.


Koloman Moser (1868–1918), although overshadowed by his colleagues Josef Hoffmann and Gustav Klimt, was an unjustly neglected participant in the Vienna School of Arts and Crafts (which he attended and later directed), the Vienna Secession and the Wiener Werkstatte (Vienna Workshop). Moser was both prolific and versatile, producing paintings, glassware, ceramics, jewelry, metalwork, leatherwork, furniture, textiles, carpets, clothing, posters and lettering (including his wedding invitation), and was a founding contributor to Ver Sacrum (Sacred Spring), the famous Secessionstil magazine. Turn-of-theCentury Viennese Patterns and Designs, a large format, 64-page paperbound album, is an unabridged republication of Flaschen-schmuck (Flat Ornament), a portfolio of 60 full-page all-over pattern designs (half in color, half in black and white) for textiles, wallpaper, rugs and wall hangings, that was published originally in 1901–1902. This instructive, historic collection, like so many of Dover's art-related books, belongs to the Pictorial Archives series, meaning that portions of the book can be reproduced by authors, artists and designers without payment or permission. For a free catalog of the Dover Pictorial Archive, write to: Dover Publications, 31 East 2nd Street, Mineola, NY, U.S.A., 11501. (Reprinted by permission from Ballast Quarterly Review, Vol. 16, No. 1, Autumn 2000.)


The aim of this study was to estimate the incidence of seroconversion of Toxocara spp. infection and related variables. We conducted a cohort study of 77 children aged 2–12 years who had negative serology in a previous cross-sectional study. Univariate and bivariate analyses were performed to describe the cohort, using socioeconomic, behavioral, and health conditions as variables. Logistic regression analysis was performed using seroconversion as the dependent variable, and the remaining variables are treated as independent variables. Asthma was the only independent variable that showed an association with seroconversion, with an odds ratio = 3.57 (1.01–12.6). The incidence of seroconversion from Toxocara spp. infection in the children followed was 10.4 per 100 per year. Previous studies reporting an association of asthma with toxocariasis have only been carried out using cross-sectional studies. Therefore, this study is one of only a few describing the incidence of seroconversion from Toxocara spp. infection, which is relevant for understanding the burden of this parasite.


: Covariate balance among different treatment arms is critical in clinical trials, as confounding effects can be effectively eliminated when patients in differ-ent arms are alike. To balance the prognostic factors across different arms, we propose a new dynamic scheme for patient allocation. Our approach does not require discretizing continuous covariates to multiple categories, and can handle both continuous and discrete covariates naturally. This is achieved through devising a statistical measure to characterize the similarity between a new patient and all the existing patients in the trial. Under the similarity weighting scheme, we develop a covariate-adaptive biased coin design and establish its theoretical properties, thus improving the original Pocock–Simon design. We conduct extensive simulation studies to examine the design operating characteristics and we illustrate our method with a data example. The new approach is thereby demonstrated to be superior to existing methods in terms of performance.


NASA is intent on exploiting the unique perspective of space-based remote optical instruments to observe and study largescale environmental processes. Emphasis on smaller and more affordable missions continues to force the remote sensing instruments to find innovative ways to reduce the size, weight, and cost of the sensor package. This is a challenge because many of the proposed instruments incorporate a high quality meter-class telescope that can be a significant driver of total instrument costs. While various methods for telescope weight reduction have been achieved, many of the current approaches rely on exotic materials and specialized manufacturing techniques that limit availability or substantially increase costs. A competitive lightweight telescope technology that is especially well suited to space-based coherent Doppler wind lidar has been developed through a collaborative effort involving NASA Marshall Space Flight Center (MSFC) through the Global Hydrology and Climate Center (GHCC) and the University of Alabama in Huntsville (UAH) at the Center for Applied Optics (CAO). The new lightweight optics using metal alloy shells and surfaces (LOMASS) fabrication approach is suitable for high quality metal mirrors and meter-class telescopes. Compared to alternative materials and fabrication methods the new approach promises to reduce the areal density of a meter-class telescope to less than 15-kg/m2; deliver a minimum ?/1O-RMS surface optical quality; while using commercial materials and equipment to lower procurement costs. The final optical figure and finish is put into the mirrors through conventional diamond turning and polishing techniques. This approach is especially advantageous for a coherent lidar instrument because the reduced telescope weight permits the rotation of the telescope to scan the beam without requiring heavy wedges or additional large mirrors. Ongoing investigations and preliminary results show promise for the LOMASS approach to be successful in demonstrating a novel alternative approach to fabricating lightweight mirrors with performance parameters comparable with the Space Readiness Coherent Lidar Experiment (SPARCLE). Development and process characterization is continuing with the design and fabrication of mirrors for a 25-cm telescope suitable for a lidar instrument.


Enhanced biodegradation of organic xenobiotic compounds in the rhizosphere is frequently recorded although the specific mechanisms are poorly understood. We have shown that the mineralization of 2,4-dichlorophenoxyacetic acid (2,4-D) is enhanced in soil collected from the rhizosphere of Trifolium pratense[e.g. maximum mineralization rate=7.9 days-1 and time at maximum rate (t1)=16.7 days for 12-day-old T. pratense soil in comparison with 4.7 days-1 and 25.4 days, respectively, for non-planted controls). The purpose of this study was to gain a better understanding of the plant-microbe interactions involved in rhizosphere-enhanced biodegradation by narrowing down the identity of the T. pratense rhizodeposit responsible for stimulating the microbial mineralization of 2,4-D. Specifically, we investigated the distribution of the stimulatory component(s) among rhizodeposit fractions (exudates or root debris) and the influence of soil properties and plant species on its production. Production of the stimulatory rhizodeposit was dependent on soil pH (e.g. t1 for roots grown at pH 6.5 was significantly lower than for those grown at pH 4.4) but independent of soil inorganic N concentration. Most strikingly, the stimulatory rhizodeposit was only produced by T. pratense grown in non-sterile soil and was present in both exudates and root debris. Comparison of the effect of root debris from plant species (three each) from the classes monocotyledon, dicotyledon (non-legume) and dicotyledon (legume) revealed that legumes had by far the greatest positive impact on 2,4-D mineralization kinetics. We discuss the significance of these findings with respect to legume-rhizobia interactions in the rhizosphere.


The fabrication of flexible sensors is a potential way to promote the progress of modern social science and technology due to their wide applications in high‐performance electronic equipment and devices. Flexible sensors based on organic materials combine the unique advantages of flexibility and low cost, increasing interest in healthcare monitoring, treatment, and human–machine interfaces. Advances in materials science and biotechnology have rapidly accelerated the development of bio‐integrated multifunctional sensors and devices. Due to their excellent mechanical and electrical properties, many types of functional materials provided benefits for the construction of various sensors with improved flexibility and stretchability. In this review, recent advance in the fabrication of flexible sensors by using functional nanomaterials including nanoparticles, carbon materials, metal‐organic materials, and polymers is presented. In addition, the potential biomedical applications of the fabricated flexible sensors for detecting gas molecules signals, small molecules, DNA/RNA, proteins, others are introduced and discussed.


Introduction

Baseline immunosuppression at Leuven University Hospital changed from CsA-AZA to FK506-MPA in March 2011. This study investigates early post-operative outcomes in a cohort 1 year before and 1 year after the conversion of immunosuppression.

Methods

Cohort 1 (LTx between 03/2010 - 03/2011, n= 58) was initially treated with CsA-AZA and cohort 2 (LTx between 03/2011 - 03/2012, n=65) with FK506-MPA, together with steroids and rATG for 3 days. Exclusion criteria were retransplantation (CsA-AZA n=3, FK506-MPA n=7) and death <6 months post-LTx(CsA-AZA n=3, FK506-MPA n=3). Outcome parameters included acute rejection (AR), lymphocytic bronchiolitis (LB), respiratory infection, need for antirejection therapy, BAL cell profile and FEV1.

Results

The FK506-MPA cohort demonstrated significantly more LB at 1 month (p=0.029) and 6 months (p=0.031), whereas CsA-AZA patients experienced more AR at 3 months (p=0.048) and needed more episodes of antirejection therapy (steroids) within the first 3 months (p=0.0002) following LTx. BAL neutrophilia was persistently, although not significantly, higher in FK506-MPA. Infection rates and FEV1%pred were comparable between both cohorts.

Discussion

FK506-MPA as initial immunosuppressive treatment results in less early AR and early anti-rejection therapy, but more early LB and BAL neutrophilia. The possible effect on development of CLAD and survival remains to be awaited.

![Figure][1] [1]: pending:yes


Objectives We previously identified that general practitioners (GPs) in French-speaking regions of Europe had a variable uptake of common preventive recommendations. In this study, we describe GPs' reports of how they put different preventive recommendations into practice. Design, setting and participants Cross-sectional study conducted in 2015 in Switzerland and France. 3400 randomly selected GPs were asked to complete a postal (n=1100) or online (n=2300) questionnaire. GPs who exclusively practiced complementary and alternative medicine were not eligible for the study. 764 GPs (response rate: postal 47%, online 11%) returned the questionnaire (428 in Switzerland and 336 in France). Main outcome measures We investigated how the GPs performed five preventive practices (screening for dyslipidaemia, colorectal and prostate cancer, identification of hazardous alcohol consumption and brief intervention), examining which age group they selected, the screening frequency, the test they used, whether they favoured shared decision for prostate cancer screening and their definition of hazardous alcohol use. Results A large variability was observed in the way in which GPs provide these practices. 41% reported screening yearly for cholesterol, starting and stopping at variable ages. 82% did not use any test to identify hazardous drinking. The most common responses for defining hazardous drinking were, for men, ≥21 drinks/week (24%) and ≥4 drinks/occasion for binge drinking (20%), and for women, ≥14 drinks/week (28%) and ≥3 drinks/occasion (21%). Screening for colorectal cancer, mainly with colonoscopy in Switzerland (86%) and stool-based tests in France (93%), was provided every 10 years in Switzerland (65%) and 2 years in France (91%) to patients between 50 years (87%) and 75 years (67%). Prostate cancer screening, usually with shared decision (82%), was provided yearly (62%) to patients between 50 years (74%) and 75–80 years (32%–34%). Conclusions The large diversity in the way these practices are provided needs to be addressed, as it could be related to some misunderstandingof the current guidelines, to barriers for guideline uptake or, more likely, to the absence of agreement between the various recommendations.


Abstract In order to overcome the unhealthy perspective of body-mind dualism and become capable of holding the "higher" and healthier perspective of body and mind as will to power, Nietzsche stresses that one must engage in a process of cultivation of the body. Such a practice of self-cultivation involves leaving behind incorporated illusory and life-denying perspectives and incorporating more "truthful" and affirmative perspectives on life. In this article, Nietzsche's views on the body and its cultivation will be further explored and compared with Japanese Buddhist thought on body, mind, and cultivation. In Japanese thought, the notion of shinjin-ichinyō (oneness of body and mind) was developed in order to overcome a dualistic approach to body and mind. The unity of body and mind plays an essential part in the philosophies of both Kūkai and Dōgen. Whereas in early Indian Buddhism, self-cultivation took place primarily through the mind (citta), in Japanese Buddhist practice the body, not the mind, is the primary locus as exemplified in Dōgen's somatic practice of zazen. Although from the everyday perspective, body and mind are experienced as two separate things, a higher perspective is possible in which body-mind is experienced as a continually changing configuration of dharmas that doesn't contain any "I." Such a higher perspective is called "samadhic awareness" by Dōgen, in which "body and mind are cast off" (shinjin totsuraku). For both Nietzsche and Dōgen, their "philosophy am Leitfaden des Leibes" does not aim at discovering "truths" by means of introspection and thinking, but at increasing the body's capacity for the incorporation of new and liberating perspectives


Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL

Pten loss and subsequent Akt activation promotes cell survival in human cancer cells through activation of glycolytic metabolism and repression of pro-apoptotic factors. Because sustained glycolysis is required for Akt dependent apoptosis resistance, we investigated the downstream signaling components that mediate Akt dependent increases in glycolysis in Pten-deficient cells. Loss of the ribosomal protein S6K1 in Pten-deficient cells prevented Akt-induced glycolysis and triggered Bax translocation and commitment to apoptosis.

Inactivation of S6K1 was associated with decreased expression of the pro-glycolytic HIF1α transcription factor. Restoring HIF1α expression was sufficient to restore both glycolysis and cell survival in S6K1-deficient cells. Conversely, inhibiting HIF1α expression in Pten deficient cells resulted in decreased glycolysis and cell survival, mimicking the loss of S6K1. In vivo , S6K1 deficiency delayed the development of lethal disease in the Pten fl/fl Mx-1 Cre+ model of leukemia. Thus, together the data suggest that S6K1 is a useful target for counteracting the metabolic program that supports apoptosis resistance in Pten-deficient cancers.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-256. doi:10.1158/1538-7445.AM2011-LB-256


Checkpoint inhibiting antibodies targeting CTLA-4 and PD-1, along with costimulatory agonists, exhibit impressive anticancer efficacy and evidence of durable tumor regression in patients. Despite this success however, many patients fail to respond, likely due to multiple immunosuppressive tactics employed by cancer cells. Combination therapies designed to counteract these immunosuppressive features show promise, but strategies relying on multiple agents suffer from logistical and regulatory challenges, as well as increased risks of adverse events. We developed a novel immunotherapeutic agent by fusing two TNFR family costimulatory agonists (anti-CD134/CD137) into a single biologic encompassing the therapeutic benefits of both agents while avoiding many of the drawbacks associated with traditional combination therapies. Our preliminary data show that this dual-specific, tetravalent antibody conjugate induces potent and differential in vitro potentiation of cytokine secretion from CD3-stimulated splenocytes, compared to that observed with single agonists alone or in combination. We hypothesize that this a consequence of unique signaling and hybrid costimulatory events. Secondly, this conjugate, referred to as OrthomAb, potently delayed tumor growth and reduced tumor burden in the aggressive B16 melanoma model. In vivo antitumor efficacy exceeded that of either individual unconjugated agonist. Importantly, this work establishes a framework for fusion of immunomodulatory biologics into a single drug with the benefit of combination immunotherapy to treat cancer.


We have described recently the prevention of apoptosis by CD2-soluble CD48 interaction on antigen B cell receptor occupancy. Here, we show that CD2 ligation is also able to interfere with B cell receptor-independent apoptosis pathways such as spontaneous death in spleen B cells or serum deprivation and hydrogen peroxide exposure in the BAL-17 cell line. In all cases, CD2 ligation induces a signal that prevents the downregulation of Bcl-2 expression. The specific CD2 signal pathway involved in this phenomenon is still unknown. As reported, CD2 did not appear to induce Ca2+ mobilization, phosphatidylinositol turnover, or PKC translocation in B cells. Nevertheless, we show that CD2 receptor ligation is coupled to the tyrosine phosphorylation pathway in B cells. These observations indicate that CD2 is functionally able to trigger at least an early signal that could play a role in apoptosis blockage B cells in addition to the adhesion one. The results suggest the participation of cellular membrane receptors other that CD40 in apoptosis rescue, not only in the antigen-dependent but also in the antigen-independent phases of B cell lymphopoiesis.


Two hundred consecutive mastectomies with total axillary dissection were analyzed for patterns of involvement at levels one, two and three. The purpose was to determine the accuracy of level one axillary dissection in predicting the status of the entire lymph node chain in carcinoma of the breast. Level one was defined as latissimus dorsi to lateral pectoralis minor; level two behind the pectoralis minor and level three medial pectoralis minor to thoracic inlet. The average number of nodes analyzed per patient was 33. The average number of nodes recovered per level was 14 at level one, 11.5 at level two and eight at level three. One hundred twenty patients (60%) had no nodal involvement, while 80 patients had metastases to axillary lymph nodes. There were seven patients (3.5% of the entire 200) who had positive nodes at levels two and/or three without metastasis to level one. This represents the incidence of "skip" metastases. The group exhibiting "skip" metastases comprise 5.5% of patients (seven of 127) with negative axillary nodes at level one and 8.7% of patients (seven of 80) with axillary metastases secondary to carcinoma of the breast. In the authors' experience, level one lymph node dissection is an accurate predictor of the status of the entire lymph node chain. Negative nodes at level one would indicate lack of involvement at levels two and three with nearly 95% accuracy.


The study aimed to compare the book of Islamic Education sixth grade basic in both Jordan and the UAE in the light of the ethical concepts that should be included in the book. To achieve this goal, a list of these ethical concepts was prepared, and according to it, the content of both books has been analyzed. The results showed differences in the availability of these concepts in the books as well as the imbalance in the distribution of these concepts in the books. The results also showed similarities and differences in the content of ethical concepts in both books.


As the volume of protein sequence and structure data grows rapidly, the functions of the overwhelming majority of proteins cannot be experimentally determined. Automated annotation of protein function at a large scale is becoming increasingly important. Existing computational prediction methods are typically based on expanding the relatively small number of experimentally determined functions to large collections of proteins with various clues, including sequence homology, protein-protein interaction, gene co-expression, etc. Although there has been some progress in protein function prediction in recent years, the development of accurate and reliable solutions still has a long way to go. Here we exploit AlphaFold predicted three-dimensional structural information, together with other non-structural clues, to develop a large-scale approach termed PredGO to annotate Gene Ontology (GO) functions for proteins. We use a pre-trained language model, geometric vector perceptrons and attention mechanisms to extract heterogeneous features of proteins and fuse these features for function prediction. The computational results demonstrate that the proposed method outperforms other state-of-the-art approaches for predicting GO functions of proteins in terms of both coverage and accuracy. The improvement of coverage is because the number of structures predicted by AlphaFold is greatly increased, and on the other hand, PredGO can extensively use non-structural information for functional prediction. Moreover, we show that over 205 000 ($\sim $100%) entries in UniProt for human are annotated by PredGO, over 186 000 ($\sim $90%) of which are based on predicted structure. The webserver and database are available at http://predgo.denglab.org/.


Author(s): Mehmetoglu, Mustafa Said | Advisor(s): Rose, Kenneth | Abstract: This dissertation is concerned with the problem of global optimization of delay constrained communication and control strategies. Specifically, the objective is to obtain optimal encoder and decoder functions that map between the source space and the channel space, to minimize a given cost functional. The cost surfaces associated with these problems are highly complex and riddled with local minima, rendering gradient descent based methods ineffective. This thesis proposes and develops a powerful non-convex optimization method based on the concept of deterministic annealing (DA) - which is derived from information theoretic principles with analogies to statistical physics, and was successfully employed in several problems including vector quantization, classification and regression. DA has several useful properties including reduced sensitivity to initialization and strong potential to avoid poor local minima. DA-based optimization methods are developed here for the following fundamental communication problems: the Wyner-Ziv setting where only a decoder has access to side information, the distributed setting where independent encoders transmit over independent channels to a central decoder, and analog multiple descriptions setting which is an extension of the well known source coding problem of multiple descriptions. Comparative numerical results are presented, which show strict superiority of the proposed method over gradient descent based optimization methods as well as prior approaches in literature. Detailed analysis of the highly non-trivial structure of obtained mappings is provided. The thesis further studies the related problem of global optimization of controller mappings in decentralized stochastic control problems, including Witsenhausen's celebrated 1968 counter-example. It is well-known that most decentralized control problems do not admit closed-form solutions and require numerical optimization. An optimization method is developed, based on DA, for a class of decentralized stochastic control problems. Comparative numerical results are presented for two test problems that show strict superiority of the proposed method over prior approaches in literature, and analyze the structure of obtained controller functions.


The application of the classical "linear" model of incentive pay to the case when the noise is multiplicative to effort generates two predictions for a given strength of incentives: 1) more risk-averse workers will put in less effort, and 2) setting a performance target will weaken the negative risk aversion--effort link. The data from a real-effort laboratory experiment involving 85 student participants support both these predictions. Implications of the model and empirical findings to the literature on, and practice of, personnel management are discussed.


. In this paper we address partial information games restricted to memoryless strategies. Our contribution is threefold. First, we prove that for partial information games, deciding the existence of memoryless strategies is NP-complete, even for games with only reachability objectives. The second contribution of this paper is a SAT/SMT-based encoding of a partial information game altogether with the correctness proof of this encoding. Finally, we apply our methodology to automatically synthesize strategies for oblivious mobile robots. We first prove that synthesizing memoryless strategies is equivalent to providing a distributed protocol for the robots. Then, we use an SMT-solver to synthesize strategies for the gathering problem in a particular configuration ( SP 4 ), open case in distributed computing theory for more than a decade. Interest-ingly, our work is the first that combines two-player games theory and SMT-solvers in the context of mobile robots with promising results and therefore it is highly valuable for distributed computing theory where a broad class of open problems are still to be investigated.


Release of coloured textile effluent in to aquatic environment is detrimental as they prevent penetration of light in to water, thereby affecting aquatic life and creates harmful water. Biosorption is an alternative treatment available other than physicochemical and biological methods to treat these toxic effluents. This study investigates the potential of water hyacinths to adsorb hazardous azo dye metanil yellow from aqueous solution. Metanil Yellow, is a widely used toxic dye containing one or more azo bonds (-N=N-). Metanil Yellow is used in number of industries such as textile, dyeing, food, cosmetics, paper printing industries and with textile industries as large consumers. Biosorption process was carried out using immobilized dead aquatic weeds. The influences of adsorption parameters such as initial dye concentration, pH, contact time, adsorbent dosage, agitation speed, and temperature were evaluated and optimized. Further the mechanism of biosorption earned good fits for Langmuir isotherm model. The pseudo first order and second order kinetic model described well the experimental data. The batch studies clearly suggest that the maximum adsorption capacity for the removal of Matanil Yellow dye were obtained at 6 pH and up to 98.8 % color removal is achieved with contact time of 240mins. Further desorption techniques were employed to recover the loaded pollutants and it is found to be the reusability of the immobilized aquatic weeds after storage may be a potential advantage in wastewater treatment.


The broad-host-range necrotizing fungal pathogen Rhizoctonia solani is responsible for economically significant diseases to crops as diverse as wheat, maize, barley, canola, sugar beet, potato, soyabean, bean, lupin and alfalfa. Germplasm screens in many of the crop hosts have not identified strong genetic resistance which, together with the lack of effective control, mean the pathogen remains a substantial problem for agriculture in many parts of the world. Following the establishment of a robust inoculation assay, a germplasm collection of the model legume Medicago truncatula was screened with various legume-infecting isolates of R. solani. While some significant differences in susceptibility/resistance were detected between some lines, in the majority of cases M. truncatula was susceptible to R. solani. Comparison of a legume- and cereal-infecting AG8 isolate with a legume-specific AG11 isolate revealed no difference in pathogenicity between the two isolates when infecting M. truncatula. The most significant differences in susceptibility occurred with an AG6 isolate, which caused root canker. This included significant differences between the moderate resistance of the M. truncatula reference genotype A17 and the high susceptibility of line A20. The analysis of a recombinant inbred line population derived from A17 and A20 revealed a single locus contributing to the resistance in A17. Interestingly, the locus only affected the development of post-emergent (late) symptoms, such as necrosis of cotyledons at 11 days after inoculation and root- and above-ground-weights, but not pre-emergent seedling damping off. These findings pave the way for further studies to dissect the genetic and molecular mechanisms of resistance.


A case of primary anaplastic pilocytic astrocytoma (PA) and its clinicopathologic and radiologic features are reported. PA is a World Health Organization grade I tumor typically affecting children and young adults. Initial presentation of a PA with anaplastic features is particularly uncommon, and making a definitive diagnosis of primary anaplastic PA can be challenging. Increased recognition of primary anaplastic PA may prove useful for the clinical course and therapeutic stratification.


This paper presents errors in grounding resistance measurement using the fall-of-potential method with the potential probe located in the opposite direction to the current probe. Errors are obtained with computer simulation. Such ground electrodes as a counterpoise, a grid, a rod and a combination of them are considered here. The soil is supposed to be extended to two-layer structure. Numerical results are computed by the current source simulation method and the method of images.


Linoleate hydroperoxide and linoleate at concentrations of 100-140 nmol-mg protein activated state 4 respiration of rat heart mitochondria 4.2-fold, increased the apparent enthalpy change of the respiration per gram atom of oxygen consumed from -148 to -226 kJ/O and completely inhibited oxidative phosphorylation. Methyl linoleate hydroperoxide or methyl linoleate did not show the same effects. Further addition of linoleate hydroperoxide or linoleate induced oligomycin-insensitive Mg-ATPase to a level 5 or 2 times, respectively, that obtained with 120 muM dinitrophenol, accompanied by clearing of the mitochondrial suspension and release of malate dehydrogenase from the matrix. Methyl linoleate hydroperoxide had the same effects except that the induced Mg-ATPase activity retained oligomycin sensitivity. Methyl linoleate did not show either effect.


In the field of active perception, object search is a widely studied problem. To search for an object in large rooms, it would be expensive to explore and check each object's similarity with the object of interest. The expense could uncontrollably bloat as the number of objects to be searched increases. If the objects are of the order of a 2-5cm, they appear very small, making it difficult for the present algorithms to recognize them. A general human strategy in such cases is to sparsely identify, from far away (4-6m), if the object of interest is present in the scene. Subsequently, each of the possible objects is analysed from closer proximity to recognize, for further manipulation. In this work, we present a similar framework. We reduce search-space, by identifying existential probability of a small object from a distance followed by a closer 3-D analysis of its point cloud to accurately recognize it. This is achieved by 2-D modelling of the objects using Gaussian Mixture Models followed by recognizing objects using efficient RGB-Depth based algorithm.


—Integration of sensory technologies into critical ap- plications, such as flight monitoring, building energy optimiza-tions, and health monitoring, has highlighted the importance of effective forecasting models for multi-variate time series. To accomodate this demand, approaches to time series prediction have been extended from uni-variate prediction to multi-variate time series prediction. Na¨ıve extensions of prediction techniques, however, lead to an unwelcome increase in the cost of model learning and, more importantly, a significant deterioration in the model performance due to the limited ability of the extended models to capture the intrinsic relationships among variates. For instance, while recurrent models, such as LSTM and RNN, aim to capture the temporal complexities in the data, their performance can deteriorate quickly. In this paper, we first argue that (a) one can learn a more accurate forecasting model by leveraging temporal alignments among variates to quantify the importance of the recorded variates with respect to a target variate. We further argue that, (b) for most applications, traditional time series similarity/distance functions, such as DTW, which require that variates have similar absolute patterns, are fundamentally ill-suited for this purpose and we instead need to quantify temporal correlation not in terms of series similarity, but in terms of temporal alignments of key "events" impacting these series. Finally, we argue that (c) while learning a temporal model using recurrence based techniques (such as RNN and LSTM – even when leveraging attention strategies) is difficult and costly, we can achieve better performance by coupling simpler CNNs with an adaptive variate selection strategy . Relying on these arguments, we propose a Selego framework 1 for variate selection and experimentally evaluate the performance of the proposed approach on various forecasting models, such as LSTM, RNN, and CNN, for different top-X% variates and different forecasting time in the future (lead) on multiple real-world datasets. Experiments show that the proposed framework can offer significant ( 90 − 98% ) drops in the number of recorded variates that are needed to train predictive models, while simultaneously boosting accuracy.


The article analyzes qualitative and quantitative interdependences among consumption, gross regional product and indices of production. On the example of Southern Federal District theoretical substantiation and empirical approbation of alternative methodology are provided. The methodology in question deals with a choice among branches and enterprises of a regional economy that public support has encountered recently, which primary goal is to ensure potent stimulation of regional economic growth.


It seems to me that it would be like carrying coals to Newcastle to attempt to discuss the subject of intestinal stasis in any but a restricted sense. Much has been written about intestinal stasis, from the points of view of both the physician and the surgeon, but nothing of great importance has been added, throwing light on it, from the surgeon's standpoint, which has increased our knowledge beyond that which we received from Lane and Jackson. Lane may be an extremist and his surgery may need some toning down, but his deductions are based on sound premises. Jackson made a great discovery in his "pericolic membrane," and his clinical diagnosis of its presence and the attending pathology has not been improved—it is standard. During the past year two notable papers have appeared, one by Flint, in the Johns Hopkins Bulletin, and the other by Rilus Eastman ( Journal of Surgery,


Patient safety has been defined as 'the reduction of risk or unnecessary harm associated with healthcare to an acceptable minimum'.1 As veterinary professionals, the safety of our patients has always been a priority. However, the formal concept of patient safety has only recently filtered down from our medical colleagues.

Error and complications have always been associated with healthcare and can act as powerful motivators for learning. However, until relatively recently, specific interest in this area was limited. In order to be able to learn from errors, there needs to be accurate and timely incident reporting.2-5 Removing barriers to reporting in safety-critical industries has ensured that maximum benefit can be attained from learning from errors, thereby improving safety and quality.6

Over the past few years, attempts to improve quality and safety in the medical profession has focused on learning from and reducing error. This involves incident reporting and root-cause analysis to identify adverse events and their causes.7,8 This approach has led to significant and ongoing improvements in patient safety in the medical industry.6 Cultivating a no blame environment is key to adopting the principles of learning from error, and this is where the challenge in veterinary practice currently lies.

Understanding culture is key to creating the right environment to adopt these principles. Understandably, …


BackgroundTraining is a key intervention for ensuring evidence-based practice becomes standard practice, but evidence for what constitutes effective healthcare professional training is lacking. In a systematic review we identified inadequate descriptions of training interventions in publications, which has hindered understanding of what aspects of training lead to improvements or changes in knowledge, skills and behaviours of healthcare professionals. AimsTo develop a taxonomy of training intervention components to improve the design, reporting and evaluation of healthcare professional training. MethodsTwo qualitative studies exploring the perceived effectiveness of healthcare professional training and a systematic review of training interventions to improve the management of psychological distress in primary care were used to inform the content of the taxonomy. Intervention components identified as effective by health professionals and experts in training/behaviour change formed the initial taxonomy. The taxonomy was then mapped onto intervention components reported in studies identified in our earlier systematic review and additional components were included.ResultsA total of 171 training intervention components were identfied. These were arranged into 11 hierarchical groupings and divided into three phases of training (pre-training, training delivery and post-training) to form the Training Intervention Components (TIC) taxonomy ConclusionsThis research underpinned the development of an evidence-based taxonomy to inform the design and reporting of healthcare professional training with the ultimate aim of improving the scientific quality of reporting, evaluation and implementation of training interventions. This quest is crucial to help implement evidence based practice. Additional multi-disciplinary research is needed to further refine the taxonomy.


This volume offers insight into Vladimir Nabokov as a reader and a teacher, and sheds new light on the relationship of his views on literary aesthetics to the development of his own oeuvre. The essays included focus on the lectures on European and Russian literature that Nabokov gave at a number of American universities in the years between his arrival in the United States and the publication of Lolita. Nabokov's treatment of literary masterpieces by Austen, Cervantes, Chekhov, Dickens, Flaubert, Gogol, Kafka, Joyce, Proust and Stevenson is assessed by experts on these authors.


This paper presents the effect of silica fume and glass fibre in High Performance Concrete (HPC). In this study, High Performance Concrete mixes with silica fume of 0%, 10%, and 20% with addition of glass fibre of diameter 14μ and 12mm length at various percentages as 0%, 0.3%, and 0.6% by the volume of cement on M75 grade of concrete. The mix proportions of concrete had a constant binder of 0.26 and superplasticizer was added based on the required degree of workability. For each mix standard sizes of cubes, cylinders and prisms as per Indian Standards were cast and tested for compressive strength, split tensile strength and flexural strength at the age of 28 days. The addition of silica fume shows early strength gaining property and that of glass fibre control the cracking due to shrinkage. The results are satisfactory for the use of 10% silica fume and 0.3% glass fibre in producing High Performance concrete.


This investigation deals with the spin-up flows in a circular container of aspect ratio, 2.0. Shear front is generated in the transient spin-up process of the present flow system and it is propagating from the side wall to the central axis in a rotating container. Propagation of the shear front to the axis in a rotating container means the region behind the shear front acquires an angular momentum transfer from the solid walls. Propagating speed of the shear front depends on the apparent viscosity of polymer solution. Two kinds of polymer solutions are considered as a working fluid: one is CMC and the other is CTAB solution. CMC solution has larger apparent viscosity than that of water at the present applied shear stress, and CTAB shows varying apparent viscosities depending on the applied shear rates. Transient and spatial variations of the apparent viscosities of the present polymer solutions (CTAB and CMC) cause different propagating speeds of the shear front. In practice, CMC solution that has larger values of apparent viscosity than that of water always shows rapid approach to the steady state in comparison of the behavior of the flows with water. However, for the CTAB solution, the propagating speed of the shear front changes with the local magnitude of its apparent viscosity. Consequently, the prediction of Wedemeyer's including viscosity in the propagating speed of the velocity shear front quantitatively agrees with the present experimental results.© 2006 ASME


Waveguides are structures that provide for efficient propagation of waves. One of the earliest applications of a waveguide is the speaking tube, which was used on ships. Propagation in some waveguides leads to dispersion, a phenomenon in which the phase velocity depends on the frequency. Dispersion of elastic and sound waves in solids and liquids has been observed and treated in the scientific literature for a long time (Worzel and Ewing 1948; Pekeris 1948; Ewing et al. 1957). However, in the sub-audible acoustic domain, usually referred to as infrasound (frequencies below 20 Hz), dispersion was recognized only recently (Herrin et al. 2006). There are reports of dispersed signals recorded on infrasound sensors on the passing of surface waves of large earthquakes (Donn and Posmentier 1964; Cook 1971), but the signals in those instances were the result of ground to air coupling, and the dispersion was not related to sound propagation. In the current paper we derive the dispersion equation of an acoustic waveguide and relate it to infrasound observations.

Infrasound propagation is controlled by effective sound speed, which relates the effect of temperature (as a consequence of ideal gas law) and wind strength and direction: \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \[V\_{eff}=V\_{T}+n{\cdot}{\nu},\] \end{document} where Veff is the effective sound speed, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(V_{T}{\oplus}20\sqrt{T}\) \end{document}; T is the Kelvin temperature; and the dot product n ·ν is the component of wind strength in the direction of the propagation. Throughout the paper when we use the term sound velocity (or sound speed) we actually mean effective sound speed, which will have the wind component in it.

The following discussion follows that of Garland (1979). Consider a medium composed of a layer overlain by a half space (Figure 1), separated by an interface, with α′ > α, where α and α′ are the sound velocities in the layer and half …


PURPOSE
To estimate the effectiveness of trabeculectomy performed in buphthalmic eyes.

MATERIAL AND METHODS
42 eyes of 24 children, 14 boys and 10 girls. There were 18 children (32 eyes) operated on at the age from 7 days to 12 months (group I) and 6 patients (10 eyes) at the age from 3 to 7 years (group II) with primary congenital glaucoma. Corneal diameter ranged from 11.5 to 15 mm in infants, in 10 eyes of 6 children elder than 2 years it was from 13 to 15 mm. The axial length of eyeballs was from 19 to 23.5 mm. Forty five trabeculectomies were performed, in 3 cases they were repeated two and six years after the first procedure. Follow up was from 1 year to 22 years, mean 82 months, 7 years of group I, 6 years of group II.

RESULTS
29 of 42 eyes (64.2%) with intraocular pressure varied between 8 and 21 mm Hg, other eyes required additional local antiglaucoma treatment. Normal IOP was obtained in 95.2% of eyes. Trabeculectomy normalized IOP in 68.9% eyes of infants (group I), whereas in elder children the percentage came up to 50 (group II). In other eyes pharmacological agents decreased IOL to values below 21 mm Hg, in the group I in 97% of eyes and in the group II in 90% of cases.

CONCLUSION
Trabeculectomy performed as a first procedure in primary congenital glaucoma is effective in infants and older children with buphthalmos in long-term follow-up. The necessity to perform this operation in very small children and even neonates does not always mean poor prognosis, and intraocular pressure can be stabilized at safe level for many years.


A total of 220 strains of staphylococci isolated from marine and estuarine surface water samples were examined for 62 morphological, physiological, and biochemical characteristics. The taxonomic data were analyzed by numerical taxonomy; 86% of the cultures were classified as Staphylococcus epidermidis or Staphylococcus hominis, 5% were classified as Staphylococcus aureus, and 9% were classified as Micrococcus spp. An association was observed between species of Staphylococcus isolated from surface water samples and geographic source. S. epidermidis, the most common of the coagulase-negative staphylococci encountered in clinical laboratories, was the dominant species in samples of polluted water, whereas S. hominis, a less common species in clinical specimens, was dominant in water samples collected from unpolluted regions. The phenetic characteristics of the environmental staphylococcal isolates are presented.


Remote laboratories are typically used for having remote access to physical laboratory facilities. In the setup presented in this paper that has not been the main objective, the remote laboratory presented here is used mainly for the following two purposes: First, to create a controlled environment where unwanted side activities like hardware setup, driver problems, troubleshooting faulty components, and struggles with special software for configuring DSP systems, are removed as much as possible, in order for the students to have their full focus on the tasks that relevant in the module: modeling of non-linear systems, synthetisation of controllers, and stability and performance analysis. Second, to significantly reduce the setup and maintenance cost associated with complex laboratory setups involving DSPs and expensive hardware.


To better understand the importance of body size in hermaphroditic mating, we studied the mating behaviour of the pond snail Radix auricularia . This simultaneous hermaphrodite exhibits a positive correlation between body size and egg production and provides weak evidence for size-assortative mating. In addition to this mating pattern, the partner performing the male role was significantly smaller than the mounted partner, performing the female role. In this study, two laboratory experiments were done to test whether body size has (1) an effect on mate choice of the sperm donor, and (2) poses mechanical constraints. These snails did not display physical limitation in mating with a much larger or smaller partner. In the mate choice experiment, we found no evidence for significant preferences for large partners. Therefore, mate choice of sperm donor and mechanical constraints are not likely to contribute to the formation of size-assortatively mating pairs in this species, which contributes to understanding about how these processes work in hermaphrodites.


How mitochondria functionally differ between immune cell subtypes, between the sexes, and with aging has not been defined in humans. We deploy a high-throughput mitochondrial phenotyping platform to define cell-type specific mitochondrial features in human circulating immune cell subtypes. In women and men spanning four decades of life, we find that mitochondrial content, mitochondrial DNA copy number (mtDNAcn), and respiratory chain enzymatic activities vary by up to 3.5-fold between neutrophils, monocytes, B and T lymphocyte subtypes. Mitochondria exhibit specific age- and sex-related differences among individual cell subtypes, including an age-related increase in mtDNAcn. In an intensive repeated-measures study, we also identify remarkable weekly variation in mitochondrial content and respiratory chain function, which is partially correlated with changes in circulating biomarkers. Our results also define multivariate mitochondrial phenotypes − mitotypes − that distinguish lymphoid from myeloid cell types, naive-to-memory lymphocyte states, and moderately differ between women and men. Finally, a comparison of mitochondrial features in purified cell subtypes and in peripheral blood mononuclear cells (PBMCs) invites caution in using cell type mixtures to infer person-level mitochondrial function. Together, these findings identify dynamic cell-type specific variation in mitochondrial biology among circulating leukocytes and provide foundational knowledge to develop interpretable blood-based assays of mitochondrial health.


The assessments of well-known Russian sociologists and philosophers (P. A. Sorokin, P. B. Struve, M. O. Menshikov) of one of the important features of the historical formation and existence of the Russian administrative elite – its national diversity have been analysed. The main characteristics and alternative estimates given by thinkers to this social phenomenon have been revealed. It has been shown that the main object of their attention is the question of whether the multinational elite is able to provide a qualitative level of management? In this issue, the points of view differ, so M. O. Menshikov took a negative position. The means that contribute, from the point of view of P.A. Sorokin and P.B. Struve, to creative development and integration of the interests of all subjects of multinational Russian society have been revealed in the article.


Microvesicles (MVs) are extracellular vesicles secreted by various cell types that are involved in intercellular communication. We hypothesized that in human periodontal disease, the pocket epithelium releases MVs, which then modulate gene expression in the underlying fibroblasts to control periodontal inflammation. MVs were isolated from culture medium of gingival epithelial cells (GECs) treated with oral bacterial biofilm extract or left untreated. Biofilm treatment significantly increased MV release from the GECs. Mass spectrometry of GEC-MVs identified a total of 2,173 proteins, of which about 80% were detected in MVs from both control and biofilm-treated GECs. Among 80 signature genes of human gingival fibroblasts, 20 were significantly regulated (P < 0.05) by MVs from control and biofilm-treated GECs in a similar manner. Matrix metalloproteinase 1 and 3 and interleukin 6 and 8 showed the strongest regulation at the mRNA and protein levels. Several cellular signaling pathways were activated by GEC-MVs in human gingival fibroblasts, including Smad and mitogen-activated protein kinase–associated pathways ERK1/2, JNK, and p38. However, ERK1/2 signaling dominated in the MV-induced gene expression changes. The results demonstrate that GEC-MVs have a strong regulatory effect on the expression of fibroblast genes associated with inflammation and matrix degradation and that bacterial biofilm stimulates the generation of GEC-MVs. This suggests that bacterial biofilms can contribute to the initiation and progression of periodontal disease by promoting a tissue-destructive phenotype in gingival fibroblasts via the enhanced secretion of epithelial MVs.


The in-vitro activity of cefotetan, a new cephamycin, was assessed against a total of 336 strains of anaerobic bacteria by means of an agar dilution procedure and compared with that of cefoxitin, mezlocillin, piperacillin, clindamycin and metronidazole. Overall clindamycin and metronidazole were the most active of the test compounds. Cefotetan showed good activity against anaerobic cocci and clostridia, except for Clostridium difficile (MIC90 = 16 mg/l), although it was comparatively less active than the other beta-lactams against anaerobic cocci. In the case of the Gram-negative anaerobes, cefotetan showed moderate activity comparable to that of cefoxitin; against the 120 test strains of Bacteroides fragilis both cefotetan and cefoxitin were markedly more active than the penicillins. In studies with antibiotic combinations, cefotetan + cefsulodin showed marked synergy (FIC index less than 0.3) against the majority of strains of Bact. fragilis tested.


DNA viruses have evolved a number of mechanisms to inhibit the major cellular tumor-suppressor pathways. Viral oncogenes can override growth suppressive signals and extend the virus proliferative capacity. The Kaposi sarcoma-associated human herpesvirus 8 (KSHV) encodes a protein, cyclin K, that is similar to cellular cyclin D1 but behaves atypically. Cyclin K resists the actions of the p16 INK4a and p27Kip1 inhibitors and extends the range of cdk6 substrates, thereby inducing cell-cycle progression toward S phase. In this study, we show that cyclin K overrides growth suppressive signals through signal transducer and activator of transcription 3 (STAT3) inactivation. Cyclin K was found to associate with the activation domain of STAT3 to inhibit its DNA-binding and transcriptional activities. Overexpression of cyclin K and inhibition of STAT3 prevents the growth suppressive effect imposed by the interleukin 6-type cytokine, oncostatin M. Altogether, these results suggest that KSHV is able to override growth suppressive effects through multiple mechanisms, and they further indicate that cyclin K plays an important role in the oncogenic activity of these viruses.


Stereophotoclinometry (SPC) is a technique to extract topographic information from images acquired by spacecraft. It combines stereophotogrammetry and photoclinometry to produce a product that has the accuracy of stereo with the resolution of photoclinometry without the restrictions common to both. We describe the implementation of this technique in the context of digital terrain model (DTM) generation for a small-body mission. We detail the process and the data used to generate SPC-derived DTMs at progressively increasing resolutions. The highest-quality DTMs are generated using four images optimized for topography, a 30° emission angle with the emission azimuth (spacecraft position) to the north, east, south, and west of the target, and one image optimized for albedo (a low incidence angle such that most of the image pixels' digital numbers are based upon albedo rather than topography). We discuss implications for mission planning and how SPC-based DTM generation can support spacecraft navigation. As a case study, we share outcomes from the modeling performed for the OSIRIS-REx mission to asteroid Bennu.


Many Roman authors have claimed that induced abortions were frequent among aristocratic women in their society. They assumed that abortion was a simple procedure, easy to perform, and generally harmless for the women involved. The truth of these claims is frequently accepted by modern scholars. This article will argue that most supposed "abortions" were miscarriages caused by various infectious diseases, especially malaria.


Strain is one of the important factors that determine the photoelectric and mechanical properties of semiconductor materials and devices. In this paper, the scanning transmission electron microscopy multiplication nano-moiré method is proposed to increase the measurement range and sensitivity for strain field. The formation principle, condition, and measurement range of positive and negative multiplication moiré fringes (PMMFs and NMMFs) are analysed in detail here. PMMF generally refers to the multiplication of field of view, NMMF generally refers to the multiplication of displacement measurement sensitivity. Based on the principle of multiplication nano-moiré, Theoretical formulas of the fringe spacing and strain field are derived. Compared with geometric phase analysis of deformation measurements based on high-resolution atom images, both the range of field of view and the sensitivity of displacement measurements of the multiplication moiré method are significantly improved. Most importantly, the area of field of view of the PMMF method is increased by about two orders of magnitude, which is close to micrometre-scale with strain measurement sensitivity of 2 × 10–5. In addition, In order to improve the quality of moiré fringe and the accuracy of strain measurement, the secondary moiré method is developed.The strain laws at the interface of the InP/InGaAs superlattice materials are characterised using the developed method.


Four new cloning vectors have been constructed from the broad-host-range cloning vector pRK290. These vectors, pLA2901, pLA2905, pLA2910, and pLA2917, confer resistance to kanamycin and tetracycline. The latter two are cosmid derivatives of pLA2901. The new vectors can be mobilized into, and are stably maintained in, a variety of gram-negative bacteria. A Sau3A genomic bank of Methylobacterium organophilum strain xx DNA has been constructed in pLA2917, and complementation analysis, with a variety of mutants unable to grow on methanol, revealed at least five separate regions necessary for growth on methanol. Complementation analysis and Tn5 mutagenesis data suggest that at least three genes are responsible for expression of active methanol dehydrogenase.


Endemic Burkitt lymphoma (eBL) is an aggressive paediatric B-cell lymphoma prevalent in children from holoendemic malaria regions of sub-Saharan Africa. It is associated with early primary Epstein-Barr virus (EBV) and repetitive Plasmodium falciparum (Pf) malaria coinfection with high incidence in western Kenya. The lymphoma is common among children aged 2-11 years with high incidence at 5-8 years and has been associated with multiple genetic variations. Endemic BL is characterized by the overexpression of the c-MYC oncogene, as a consequence of the t(8:14) IGH-myc translocation. However, the translocation alone is insufficient to drive the development of eBL since normal B cells also undergo cmyc translocation, leading to the hypothesis that other mutational variations may contribute to tumorigenesis. Polymorphic variations in cytokine genes that affect specific cytokine transcriptional levels have been shown to influence tumoral, viral and parasitic immune responses hence increasing the risk of tumour development in several cancers. The influence of cytokine polymorphisms in the aetiology of eBL has not been exhaustibly demonstrated. In this study, a retrospective case-control study design was used to investigate the association between polymorphisms within diverse genes implicated in tumoral immune surveillance: IFN-γ (+2109C/T), TNF-α (-1031T/C, -308G/A, -376G/A, -238G/A), FcγRIIA 131His/Arg and IL-12B +1188A/C; and the susceptibility to eBL in children from western Kenya. Specifically, the study determined the association between IFN-γ (+2109C/T), TNF-α (-1031T/C, -308G/A, -376G/A, -238G/A), FcγRIIA 131His/Arg and IL-12B +1188A/C genotypes and TNF-α (-1031 T/C, -308G/A and -238G/A) haplotypes and risk of eBL development and IFN-γ (+2109C/T), TNF-α (1031T/C, -308G/A, -376G/A, -238G/A), FcγRIIA 131His/Arg and IL-12B +1188A/C gene polymorphism and EBV load among cases and controls from western Kenya. Based on the frequency of IL-12 +1188A/C low cytokine producing genotype within this population, a total of 113 eBL cases and 69 healthy age-matched control samples were used. Genomic DNA was extracted following the Qiagen TM DNAeasy protocol and used for TaqMan allelic discrimination and molecular inversion probes genotyping assays. EBV load was quantified using quantitative real-time PCR. The distribution of selected IFN-γ, TNF-α, FcγRIIA and IL-12B genotypes were determined by Fisher Exact test, while the association between the selected genotypes/TNF-α haplotypes and risk of eBL development were determined using logistic regression analysis. One-Way ANOVA was used to compare EBV load across the genotypes. The frequency of IFN-γ (+2109C/T), TNF-α (-1031T/C, -308G/A, -376G/A, -238G/A), FcγRIIA 131His/Arg and IL-12B +1188A/C genotypes were not significantly different between the study groups. Furthermore, no association between IFN-γ, FcγRIIA, IL-12B and TNF-α genotypes and risk of eBL diagnosis was observed. No significant difference in the EBV viral load between IFN-γ, TNF-α, FcγRIIA and IL-12B genotypes were also observed. Additionally, TNF-α haplotypic analysis were not significantly associated with the risk of eBL development. These results demonstrate that genetic variations in selected IFN-γ, TNF-α, FcγRIIA and IL-12B genes that affect levels of their respective cytokines and affinity of FcγRIIA for IgG have no association with eBL development. This suggest that other cytokine or other genetic factors may play a role in increasing susceptibility to eBL development through other mechanisms other than IFN-γ, TNF-α, FcγRIIA and IL-12B genes. Lack of association between the selected cytokine polymorphism and development of eBL suggest that these polymorphisms are not cytokine gene risks factors for genetic screening and development of cytokine therapeutics that target prevention and management of children at risk of developing eBL within malaria endemic region of western Kenya. However, the identification of other genetic variants in cytokines and their possible association with eBL development in children from malaria endemic regions of Kenya is still critical in mapping other genetic mutations that may contribute to the pathogenesis of the lymphoma aside from the MYC translocation.