ObjectivesThe aim of this study was to determine whether certain patient characteristics could identify people with acute low back pain who were more likely to respond to nonsteroidal anti-inflammatory drugs (NSAIDs), when administered in combination with paracetamol. MethodsThis study involved a secondary analysis of a randomized controlled trial investigating the efficacy of diclofenac in 239 patients presenting to general practitioners for acute low back pain. All patients received advice to "stay active" and take regular paracetamol and then were randomized to receive either diclofenac (50 mg twice daily) or placebo. The primary outcome was days to recovery from pain. The ability of 14 patient characteristics to identify those who respond best to diclofenac was assessed using interaction terms in Cox regression models. ResultsMost of the 14 baseline characteristics investigated were uninformative in identifying those who respond best to diclofenac when added to paracetamol. Patients' sex and levels of fear regarding movement and pain were both independent statistically significant predictors of response to NSAIDs for one definition of recovery but not for the other. The interaction between fear avoidance (physical activity) and NSAIDs treatment was statistically significant (P=0.042, hazard ratio=1.059, 95% confidence interval 1.002 to 1.118) for recovery defined as a pain score of 0 or 1. The interaction between sex and NSAID treatment was statistically significant (P=0.044, hazard ratio=1.755, 95% confidence interval 1.014 to 3.038) for recovery defined as a pain score of 0 or 1 maintained for 7 consecutive days. DiscussionThis study did not find any baseline patient characteristics, which consistently identified patients with acute low back pain who respond best to NSAIDs when provided in addition to paracetamol and advice. A patient's sex and level of fear avoidance may be weak predictors and warrant further prospective investigation.


Neuroticism has repeatedly been shown to be a predictor of relationship dissatisfaction in couples. The aim of the current research was to uncover the underlying cognitive processes of this robust effect. We focused on anxiety as one aspect of neuroticism that is associated with different kinds of cognitive biases. On the basis of the assumption that biased information processing will also affect specific interpersonal contexts such as romantic relationships, it was expected that the tendency to interpret ambiguous partner and relationship scenarios in a rather negative way would work as a potential mediator. In Study 1, parallel forms of a new measure to capture the relationship–specific interpretation bias (RIB) were developed (N = 182). In Study 2, the proposed meditational role of the RIB was investigated in a dyadic sample of 210 couples. Dyadic analysis using the Actor–Partner Interdependence Mediation Model showed mediation of the interpretation bias even when the general interpretation bias and attachment styles were controlled. Results support the assumption that biased relationship–specific interpretations are one important mechanism for how neuroticism exerts its negative influence on relationship satisfaction. We conclude that personality–congruent cognitive processing may not only have individual consequences but also affect overall couple functioning. Copyright © 2013 John Wiley & Sons, Ltd.


Land application of organic materials is a common practice in sustainable agriculture. Our aim was i) to study the effect of the incorporation of organic material at different maturity stages on the ryegrass ( Lolium perenne L.) growth, and ii) to estimate the stage capable to produce the product more efficient in providing nitrogen to the plant nutrition. Four compost samples consisted of pruning waste, leaves and grass clippings were selected from four different piles at different stages of the composting process: initial non-decomposed material, 2 months old at the end of the bio- oxidative stage, 7 months old during the maturation phase, and 12 months old at the end of the maturation phase. These compost samples were used to ryegrass growing assays, and they were also added to a clay silty soil. Dry matter values were lower in T1 and T2 than in T3 and T4.Similar results were quantified when the same materials were incorporated to a soil. Nitrogen leaf content revealed that soil N immobilization had ocurred in T1 and T2 treatments. A compost, which had 7 months old during the maturation phase, did not cause any negative effect on the evaluated parameters. This compost seems to be sufficiently stable and its use would save time in compost process, compared with a compost 12 months old.


Many reverse-engineering tools have been developed to derive abstract representations from existing source code. Graphic visuals derived from reverse engineered source code have long been recognized for their impact on improving the comprehensibility of the structural and behavioral aspects of software systems and their source code. As programs become more complex and larger, the sheer volume of information to be comprehended by developers becomes daunting. In this paper, we combine dynamic source analysis to selectively identify source code that is relevant at any point and combine it with 3D visualization techniques to reverse engineer and analyze source code, program executions, and program structures. For this research, we focus particularly on the use of metaballs, a 3D modeling technique that has already found extensive use representing complex organic shapes and structural relationships in biology and chemistry, to provide suitable 3D visual representations for software systems.


Kanebo was one of the major textile companies in prewar Japan. This paper analyzes Kanebo's industrial structure and organization. In 1941 when the Pacific War broke out the economy turnd more clearly into wartime economy. At the end of 1938, the Kanebo group already established a new company "Kanegafuchi Jitsugyo" (hereafter Kanejitsu) to cope with wartime regulations. This was one of the steps of a deeper reorganization of the group. The Kanebo group whose main business was textiles turned into an industry organized as two main businesses, the old Kanebo and the new war-oriented Kanejitsu. Later, in 1944 these two companies were integrated into one called "Kanegafuchi Kogyo" (hereafter Kaneko). During the wartime economy and the subsequent expansion of munition industries, why was it necessary for the group to merge and form one new company?The conclusions of this paper can be summarized as follows.1. As the War advanced the wartime controls became more and more strict. These controls forced Kanebo's factories and equipments to be put to other uses. But, Kanebo was able to deal with these controls in the framework of its own group through its core subsidiary, Kanejitsu.2. The wartime economy forced Kanebo's textile industry to shrink in Japan, though in the colonies there was a continuous expansion of the industry. As the textile industry became more militarized the group had to make major efforts to obtain various raw materials.3. Kanejitsu was involved in mining, machinery, chemicals, and steel industries so on and had diversified so rapidly to supply the necessities of the military that the new company had become larger than Kanebo, its parentat the end of 1943.4. With the application of the wartime regulations the framework of the administration of industries changed and the government controls increased. This forced the Kanebo group to move its center of administration from Kanebo to Kanejitsu, and at last these two merged to form a new company, Kaneko.5. The textile companies at the time followed two patterns in dealing with diversification to meet the needs of the military. One, exemplified by Toyobo, used investment and indirect administration and the other, exemplified by Kanebo, used a reorganization of the group companies and direct administration.


Evolution of purity in case of factorizable interaction between an open system and an environment is investigated. We derive a simple expression for purity decrease at the first instants of evolution (when purity is close to unity), which appears to be quadratic in time. According to this expression, purity at very small times is maximal when the initial state of an open system coincide with one of the eigenstates of the interaction operator, no matter how strong the interaction is. However, it is widely known that eigenstates of the interaction Hamiltonian are not pointer states when, for example, interaction is weak (compared to self-Hamiltonian). Therefore the procedure of selecting pointer states by purity maximization (known as purity sieve) should not rely on short-time purity behavior. We propose a modification of the purity sieve criterion which takes into account purity evolution at longer times. As an example of its applicability we recover known results for pointer states of a particle undergoing quantum Brownian motion; we point out that the criterion is not applicable for some other models, however. It is argued that the proposed modified purity sieve may be used for selecting pointer states of a particle undergoing decoherence through colliions.


In the current framework of bioeconomy, there is growing interest in the use of renewable materials as raw materials to produce bioproducts. Glucose is recognised as a broad-spectrum starting material that can be obtained from carbohydrate-rich biomass. The controversy regarding the use of edible resources raises questions regarding its sustainability. The use of second-generation feedstocks, which are rich in lignocellulose, could be an attractive source of sugars. Currently, the processing of lignocellulosic materials is still in the research and development stages compared to the technologies used for processing edible feedstocks. However, the environmental analysis of different sugar productions can be carried out at this stage, since it is useful to evaluate the viability of the processes as they are conceived, as well as it is possible to identify those stages or units of the process on which efforts should focus in order to propose substantial improvements. This study aims to evaluate the environmental impact of sugars from crops (maize and sugar beet) and lignocellulosic biomass (maize stover), using the life cycle assessment (LCA) methodology. This study attempts to offer a wide vision of the evaluated processes and, for this purpose, 20 scenarios of sugar production were evaluated. Economic allocation was considered to distribute the impacts among the different by-products. Results show that, in terms of average values of the different scenarios, maize stover has a better environmental profile and contributes less to most of the environmental impacts compared to sugar beet and grain maize.


The car sharing market is growing at breakneck speed. Due to the continuing trend of shared invehicles, various new functions will be introduced into those invehicles. Accordingly, the user interfaces (UIs) for drivers, invehicles, mobile, etc. will be more important, and the studies on customized UIs will be essential under the circumstances. In this paper, we aimed to create a UI environment that enables shared invehicle users riding in invehicles owned by others to feel the same emotions as they would in their own invehicles. we designing a personalized conversational AI voice user interface design as part of infotainment, and further investigated whether that agent system equipped in a shared invehicle would influence the intimacy of the invehicle interior space. A pilot study showed that conversational voice agent effected increase intimacy of the shared invehicle interior space.


Nanofluids are a new type of heat transfer fluid engineered by uniform and stable suspension of nanometer sized particles into liquids. The heat transfer in nanofluids is important especially in the context of chemical engineering, aerospace engineering and industrial manufacturing processes. The reason is that, nanofluids were found to transfer heat more efficiently than the conventional fluids. Therefore, nanofluids research could lead to a major breakthrough in developing next generation coolants for numerous engineering applications. Due to this reason, several flow problems related to heat transfer over vertical flat plate, inclined plate and wedge were studied in this thesis. The main purpose of this study was to investigate the characteristics of two dimensional flow and surface heat transfer for two cases which are steady and unsteady convection flows. Nanofluids with two different base fluids (water and kerosene) containing magnetic and non magnetic nanoparticles were considered. The effect of magnetohydrodynamics (MHD) on the flow and heat transfer was also studied. The study starts with the formulation of the mathematical models that governed the fluid flow and heat transfer. Next, the governing nonlinear equations in the form of partial differential equations were reduced into ordinary differential equations using appropriate similarity transformation. The resulting systems of ordinary differential equations were then solved numerically using Keller box method. The numerical values of the skin friction coefficient, the local Nusselt number which represents the heat transfer rate at the surface as well as the velocity and temperature profiles were obtained for various values of the magnetic field inclination angle, magnetic interaction, plate inclination angle, nanoparticles volume fraction, wedge angle, moving wedge, unsteadiness, Grashof number and thermal buoyancy. All results obtained, were displayed graphically in addition to tabular form. The comparisons of results with previous studies were made to validate the results. For both steady and unsteady problems, it is found that magnetic field inclination angle can be used as controlling factor for certain situation because it enhances the skin friction and heat transfer rate. The plate inclination angle parameter and nanoparticles volume fraction parameter have tendency to increase momentum and thermal boundary layers thickness. For unsteady problems, it is observed that the unsteadiness parameter has significant effect on the nanofluids motion and heat transfer characteristic.


Verbiage is considered one of the distinct rhetorical methods, Which we must take into account in our speech and writing, There are many types of verbiage, One of the most important is to mention the public after the private, The public mentioned after the private, Where they play an important role in directing the Qur'anic discourse, its significance and explanation, Characteristics of the rhetorical miracle of the Holy Quran, And they strengthen the meanings and confirm them. Verbiage does not have the main purpose of prolonging, but it comes to a benefit that the place requires and for rhetorical purposes understood from the context and evidence of conditions. In this research, I will work on highlighting this rhetorical aesthetics associated with the detailed book and the perfect model in our Arabic rhetoric.


Recent research on the brain mechanisms underlying language processing has implicated the left anterior temporal lobe (LATL) as a central region for the composition of simple phrases. Because these studies typically present their critical stimuli without contextual information, the sensitivity of LATL responses to contextual factors is unknown. In this magnetoencephalography (MEG) study, we employed a simple question-answer paradigm to manipulate whether a prenominal adjective or determiner is interpreted restrictively, i.e., as limiting the set of entities under discussion. Our results show that the LATL is sensitive to restriction, with restrictive composition eliciting higher responses than non-restrictive composition. However, this effect was only observed when the restricting element was a determiner, adjectival stimuli showing the opposite pattern, which we hypothesise to be driven by the special pragmatic properties of non-restrictive adjectives. Overall, our results demonstrate a robust sensitivity of the LATL to high level contextual and potentially also pragmatic factors.


This paper recommends construction technique for asphaltic concrete wearing surface without using transverse saw cut sealed joints. It points out that the transverse saw cut joints are the problems and causes for the observed failure of asphalt wearing surfaces seen in present day US highways. The paper presents the first observed failure of this type of joints on a 17-km long concrete bridge expressway in Bangkok, Thailand, 40 years ago. Since that lesson learnt, no saw cuts have ever been used on the pavement construction in Thailand with positive results. Presently in the US and elsewhere, saw cut seal joints are still used by some sectors of engineers, despite the observed failure of the asphalt wearing surface all over the country wherever the transverse saw cuts are used. This paper demonstrates the pictures of typical failure seen on actual structures. Pictures of good pavements without using transverse saw cuts are also shown for comparison. Brief discussions of the adverse effects caused by the saw cuts are given.


This paper presents evolutionary multi-objective approaches to tune parameters in Trace transform for invariant feature construction. It is well-known that the Trace transform involves three functionals applied consecutively to the image to produce real numbers called Triple features representing the input image. Traditionally, these functionals are chosen empirically, and the image sampling parameters are fixed. These parameters play important roles in the transform because they directly affect the computational complexity and robustness. In this paper, we propose tuning the Trace sampling parameters in addition to choosing the three functionals. First, by adopting two-objective evolutionary algorithms using the within-class variance and between-class variance. Second, by adopting three-objective evolutionary algorithms to consider the computational complexity as a third objective. Two different coding schemes are considered, which are integer-coding and real-coding schemes. Experimen- tal results show that integer coding scheme presents a better performance compared to the real coding scheme. Moreover, while the three-objective approach enforces a balance between robustness and computational complexity, without enforcing a minimum acceptable accuracy, features extracted tend to have a lower computational complexity at the expense of the accuracy, compared with the two-objective case.


Dynamin has been implicated in the formation of nascent vesicles through both endocytic and secretory pathways. However, dynamin has recently been implicated in altering the cell membrane shape during cell migration associated with cytoskeleton-related proteins. Myosin II has been implicated in maintaining cell morphology and in cellular movement. Therefore, reciprocal immunoprecipitation was carried out to identify the potential relationship between dynamin II and myosin II. The dynamin II expression level was higher when co-expressed with myosin II in Ras transformed NIH3T3 cells than in normal NIH3T3 cells. Confocal microscopy also confirmed the interaction between these two proteins. Interestingly, exposing the NIH3T3 cells to platelet-derived growth factor altered the interaction and localization of these two proteins. The platelet-derived growth factor treatment induced lamellipodia and cell migration, and dynamin II interacted with myosin II. Grb2, a 24 kDa adaptor protein and an essential element of the Ras signaling pathway, was found to be associated with dynamin II and myosin II gene expression in the Ras transformed NIH3T3 cells. These results suggest that dynamin II acts as an intermediate messenger in the Ras signal transduction pathway leading to membrane ruffling and cell migration.


Author(s): Darvish Rouhani, Bita | Advisor(s): Koushanfar, Farinaz | Abstract: Contemporary datasets are rapidly growing in size and complexity. This wealth of data is providing a paradigm shift in various key sectors including defense, commercial, and personalized computing. Over the past decade, machine learning and related fields have made significant progress in designing rigorous algorithms with the goal of making sense of this large corpus of available data. Concerns over physical performance (runtime and energy consumption), reliability (safety), and ease-of-use, however, pose major roadblocks to the wider adoption of machine learning techniques. To address the aforementioned roadblocks, a popular recent line of research is focused on performance optimization and machine learning acceleration via hardware/software co-design and automation. This thesis advances the state-of-the-art in this growing field by advocating a holistic automated co-design approach which involves not only hardware and software but also the geometry of the data and learning model as well as the security requirements. My key contributions include: Co-optimizing graph traversal, data embedding, and resource allocation for succinct training and execution of Deep Learning (DL) models. The resource efficiency of my end-to-end automated solutions not only enables compact DL training/execution on edge devices but also facilitates further reduction of the training time and energy spent on cloud data servers. Characterizing and thwarting adversarial subspace for robust and assured execution of DL models. I build a holistic hardware/software/algorithm co-design that enables just-in-time defense against adversarial attacks. My proposed countermeasure is robust against the strongest adversarial attacks known to date without violating the real-time response requirement, which is crucial in sensitive applications such as autonomous vehicles/drones. Proposing the first efficient resource management framework that empowers coherent integration of robust digital watermarks/fingerprints into DL models. The embedded digital watermarks/fingerprints are robust to removal and transformation attacks and can be used for model protection against intellectual property infringement. Devising the first reconfigurable and provably-secure framework that simultaneously enables accurate and scalable DL execution on encrypted data. The proposed framework supports secure streaming-based DL computation on cloud servers equipped with FPGAs. Developing the first scalable framework that enables real-time approximation of multi-dimensional probability density functions for causal Bayesian analysis. The proposed solution adaptively fine-tunes the underlying latent variables to cope with the data dynamics as it evolves over time.


✵ ABSTRACT Walter Benjamin's influential essay, The Task of the Translator, reflects on how translation can be used to create new works of art and literature instead of attempting to create exact replicas of original works. Rather than translating by searching for words in the target language that are most equivalent to words in the original language, Benjamin encourages the practice of translation as a process which lets two languages influence and change one another. Using Benjamin as a guide, I attempt to create an English translation of Rainer Maria Rilke's German language poem "Der Panther" that distributes the meaning of the original work throughout the entire translation. To do this, I shift my focus away from translating words and phrases in isolation to reflect on how the effects of seemingly small translation choices reverberate through the work as a whole. I will also compare my translation to the historically important translations of "Der Panther" by Stephen Mitchell, Robert Bly, and C. F. MacIntyre, and argue how mine allows for analyses of themes such as stillness, the panther's mental state, and the panther's mind-body relation which more closely emulate Rilke's original work.


Introduction of chirality in supramolecular gels has allowed the effective translation and amplification of molecular chirality. Upon integrating the stimuli-responsive nature of these gels with supramolecular chirality, a new platform for the discrimination of the enantiomeric guests through naked eye can be developed. Over the past decade, several groups have reported the development of chiral supramolecular gels for enantioselective recognition through gel formation or collapse. However, to the best of our knowledge, we are yet to come across a review highlighting the utilization of chiral supramolecular gels for macroscopic discrimination of enantiomers. In this article, we have articulated the chiral gelators developed to date for the recognition of different enantiomeric analytes focusing on their mode of recognition with an in-depth analysis of the mechanism of interactions assisting the recognition process.


PURPOSE
Determine the independent and combined effects of progressive resistance muscle strength training (PRMST) and testosterone on strength, muscle mass, and function in hypogonadal elderly male recuperative care patients.

METHODS
Between 1999 and 2004, 71 subjects (mean age 78.2 +/- 6.4 yr, 86% white) were enrolled. After baseline one-repetition maximum (1RM) strength testing and then randomization to one of four treatment groups (low-resistance (20% of the 1RM) exercises and weekly injections of either 100 mg of testosterone enanthate or placebo or high-intensity PRMST (> or =80% 1RM) and weekly injections), each subject received training and injections for 12 wk.

RESULTS
Ten subjects withdrew from the study before its completion. Based on intent-to-treat analyses, strength improved in all groups, but was greater with high-intensity PRMST compared with low-resistance exercise (e.g., leg press, (mean +/- SE), 28 +/- 4 vs 13 +/- 4%, P = 0.009). Although testosterone led to significantly greater increases in midthigh cross-sectional muscle area compared with placebo (7.9 +/- 1.3 vs 2.4 +/- 1.4%, P = 0.005), it produced only a nonsignificant trend toward greater strength gains (e.g., leg press 25 +/- 4 vs 16 +/- 4%, P = 0.144). Change in aggregate functional performance score (the sum of 4 functional performance test scores) did not differ between the four intervention groups nor with high-intensity PRMST compared with low-resistance exercise (7 +/- 5 vs 15 +/- 5%, P = 0.263). There was not a significant interaction between exercise and testosterone for any outcome.

CONCLUSION
High-intensity PRMST is as safe and well tolerated as a similarly structured low-resistance exercise regimen for very frail elderly patients, but produces greater muscle strength improvements. The addition of testosterone leads to greater muscle size and a trend toward greater strength but did not produce a synergistic interaction with exercise. Neither intervention had a significant effect on functional performance.


In this paper we briefly present some solution strategies for situations in which it is necessary to transform multiple inheritance schemes into single inheritance or non-inheritance "equivalent" schemes. The strategies are divided into basic strategies and combined strategies. The mechanisms presented are comparatively analyzed in the light of some ideal characteristics to be accomplished by hierarchy transformation strategies.


During a period of one year information concerning social background, life events and diseases of children (aged 1—14) admitted to a paediatric department had been obtained. One year after this index hospitalization, information concerning the children's present state of health was obtained. Forty (13%) had been readmitted to hospital during the follow-up year, and the parents of 72 children (23%) reported that their child's present state of health was poor. A multivariate predictor analysis was performed. The associations discovered suggest 1) that the selected social or psycho-social factors do not appear to be of considerable importance for prediction of readmission to hospital, 2) that "poor health" in the children has a very complex prediction pattern, partly due to disease variables, partly due to indices of unfavourable family background.


A probabilistic approach, which exploits the domain and distribution of the uncertain model parameters, has been developed for the design of robust input shapers. Polynomial chaos expansions are used to approximate uncertain system states and cost functions in the stochastic space. Residual energy of the system is used as the cost function to design robust input shapers for precise rest-to-rest maneuvers. An optimization problem, which minimizes any moment or combination of moments of the distribution function of the residual energy is formulated. Numerical examples are used to illustrate the benefit of using the polynomial chaos based probabilistic approach for the determination of robust input shapers for uncertain linear systems. The solution of polynomial chaos based approach is compared with the minimax optimization based robust input shaper design approach, which emulates a Monte Carlo process.


This paper describes a small research project into board memberships and directorships interlock in a particular rural county in Denmark. This research also looks at other counties in Denmark as well as a group of the largest companies, in terms of revenue, within the country. The paper describes how UCINET and PAJEK software was used. The findings indicate that the companies in Ringkøbing Amt are interlocked by board and directorships, but much less so than the largest companies in Denmark. This leads us to attempting to relate the concept of interlocking directorships with more resent research into social capital, individual as well as corporate social capital. We conclude by discussing these findings as well as suggest areas for further research in this area.


The aim of this paper is to present results of microclimatic research focused mainly on dust pollution in several offices of Departments in the Faculty of Engineering at Czech University of Life Sciences Prague. The attention is paid to the dimensions of the room, floor covering, furniture, equipment, ventilation, frequency of the use and period of the year. In the frame of this research the concentration of air dust was measured by special exact instrument Dust-Track aerosol monitor. After the installation of different impactors the PM 1, PM 2.5 , PM 4, PM 10 size fractions were also measured. The obtained results of measurements were evaluated by the statistical instruments and concentrations of different size of dust particles were analyzed. Results of different indoor conditions were generalized. Based on the results of measurements practical recommendations for the design, use, cleaning and ventilation of these types of rooms and buildings were summarised in the conclusions.


IMAGINE a preventable illness that kills 40000 and harms another 240 000 each year in the United States. Suppose that its direct and indirect costs surpass $14 billion annually, 80% of which is picked up by taxpayers. Imagine, too, that more than one fourth of those who succumb are just 15 to 24 years old. Few in the medical community would hesitate to screen and counsel patients at risk for such an illness. Yet many physicians do not discuss firearm injury with their patients, despite this enormous toll that it takes. John P. May, MD, recognized the gap a few years ago during his residency at Cook County Hospital in Chicago, Ill. After having volunteered in a soup kitchen at a nearby Chicago housing project, May says that during his residency he "started to recognize the impact of violence on the community. In the trauma ward, I knew some of


Packet classification plays an important role in next-generation Internet routers in providing various services such as packet filtering, policy routing, traffic policing, and load balancing. In this paper, we propose an original field-level trie classification (FLTC) scheme that accommodates classifier (rule database) with multiple fields specified in different forms (prefix and range). The FLTC achieves a high classification speed with reasonable storage. It is also highly scalable regarding the size and the number of fields of classifiers.


This technology briefing is intended for those interested in constructing custom software analysis and manipulation tools to support research or commercial applications. srcML (srcML.org) is an infrastructure consisting of an XML representation for C/C++/C#/Java source code along with efficient parsing technology to convert source code to-and-from the srcML format. The briefing describes srcML, the toolkit, and the application of XPath and XSLT to query and modify source code. Additionally, a short tutorial of how to use srcML and XML tools to construct custom analysis and manipulation tools will be conducted.


In analyzing the connections between nutrition and anthropology, it should be noted that the state of knowledge and available techniques are not yet sufficiently developed to support conclusions about such questions as the universality of dietary norms. Food choices are above all cultural, although they are limited by the physical environment and technological capacities. Human beings have some dietary constraints imposed by metabolic needs, but they manifest great ability to adapt to different dietary regimes, from the exclusive vegetarianism of Hindus to the almost exclusively animal-based diet of the Eskimos. In most parts of the world, the contribution of proteins is remarkably stable at about 12% of total caloric intake. Numerous examples of genetic adaptation illustrate the flexibility of humans. Many African populations, for example, have deficits of intestinal lactase, but herding groups do not. the diet of parts of the New Guinea highlands is almost completely lacking in proteins, but body growth is not inhibited. Such examples raise questions about the applicability of Recommended Dietary Allowances and evaluation of nutritional risks. Daily protein intake ranging from .2 to 5 gm/kg of body weight has been measured in different societies. WHO recommended 1.3 gm, but this norm has changed through time, and it is currently believed that total caloric intake is more important in insuring adequate growth. Food supplementation programs based on protein have generally failed. For most societies, the diet is varied enough to contain a sufficient portion of essential nutrients. Specific lacks have often been noted under very artificial conditions such as on ships at sea or in prisons. A reduction of body format may be biologically fixed quantity of food. The population of Mexico represents 24% of that of the US in individuals but only 17% in body mass. Clinical methods allow signs of deficiency at an earlier phase of development has been costly and disappointing. Anthropometry, which is sensitive, easy, and inexpensive, has been found to be the most appropriate method for nutritional screening in public health. The 4 essential measurements proposed by the WHO to assess nutritional status are weight, height, arm circumference, and tricepital as well as for excess feeding and obesity are all based on anthropometry. Nutritional risks appear especially heightened when traditional ways of life are modified by social forces as in urbanization or by introduction of a new food, as with potatoes in Ireland.


A series of platinum(II) terpyridyl alkynyl complexes that have been derivatized with basic amino functionalities, [Pt(tpy)(C[triple bond]C-C6H4-NR2-4]X (X = OTf-, R = CH3 1, R = CH2CH2OCH3 2, R = H 3; X = Cl-, R = CH3 4, R = CH2CH2OCH3 5, R = H 6) (tpy = 2,2':6',2' '-terpyridine), have been synthesized and characterized. Their photophysical responses at various acid concentrations were studied. The abilities of the complexes to function as colorimetric and luminescence pH sensors were demonstrated with dramatic color changes and luminescence enhancement upon introduction of acid.


Hormones impact on cognition, emotions, and behaviour. Given that mental disorders are defined by abnormalities in these very same domains, clinical psychologists may benefit from learning more about alterations in endocrine systems, how they can contribute to symptoms commonly experienced by patients, and how such knowledge may be put to use in clinical practice.
 The aim of the present scientific update was to provide a brief overview of endocrine research relevant to the aetiology, diagnostics, and treatment of mental disorders, including some of the latest studies in this area.
 Hormones appear to be intrinsic to the development and maintenance of mental disorders. Oxytocin is involved in social cognition and behaviour and as such may be relevant to mental disorders characterised by social deficits (e.g., autism spectrum disorder and schizophrenia). Stress and sex steroids exert demonstrable effects on mood and cognition. In patients with depression and anxiety disorders, initial attempts to lower/enhance such hormones have thus been undertaken within conventional therapies in order to improve outcomes. Finally, hunger and satiety hormones may be involved in the vicious circle of dysfunctional eating behaviours and weight loss/gain in anorexia or bulimia nervosa.
 Three conclusions can be drawn from this review: First, endocrine research should be considered when patients and clinicians are developing multidimensional illness models together. Second, endocrine markers can complement conventional assessments to provide a more comprehensive account of a patient's current state. Third, endocrine testing may guide treatment choices and inform the development of novel treatments.

 Hormones are intrinsic to the development and maintenance of mental disorders

 Endocrine research should be incorporated into multidimensional illness models

 Endocrine markers can complement conventional diagnostic assessments

 Endocrine testing may guide treatment choices and inform the development of new treatments

 Hormones are intrinsic to the development and maintenance of mental disorders
 Endocrine research should be incorporated into multidimensional illness models
 Endocrine markers can complement conventional diagnostic assessments
 Endocrine testing may guide treatment choices and inform the development of new treatments


In contrast to the situation only a few years ago, the case for religion being accepted as a vital element in the cultural responses to disasters has been largely accepted by both academic writers and international agencies, such as the International Federation of Red Cross and Red Crescent Societies. Religions are far more varied in their approaches to natural catastrophes than is frequently recognised or acknowledged by academic writers who are trained and socialised within a 'western' post-Enlightenment tradition. In this paper we seek to demonstrate how detailed religious responses to earthquakes and volcanic eruptions vary even between two societies, southern Italy and the Azores, which are broadly similar in terms of their southern European Catholic religiosity. In southern Italy, popular Catholicism has conflated two approaches to theodicy: the retributive and the Augustinianism (i.e. free-will). Divine wrath may be propitiated through piety and Christian action, which includes worship, repentance, changed conduct and is often associated with well-choreographed ritualistic actions, some of the latter being far removed from Catholic orthodoxy. Such reactions to disaster are not confined to the past but remain strongly embedded in present-day practice. In the Azores a combination of: a history of a better educated and more enlightened church leadership; greater emphasis on praxis following disasters; the growth of the distinctive, egalitarian and pastorally focused Cult do Esparto Santo (i.e. Cult of the Holy Spirit) and the spread of alternative models of theodicy through educational outreach, has produced a strongly contrasting religious response. We conclude that, in the case of the Azores the religious milieu favours active collaboration between the Catholic faith community and the Civil Defence authorities in the aftermath of disasters, whereas this is not the case in southern Italy, although there are some recent signs of change.


The longitudinal intra-train beam-based feedback has been recommissioned after major upgrades on the synchronization system of the FLASH facility. Those upgrades include: new bunch arrival time monitors (BAMs), the optical synchronization system accommodating the latest European XFEL design based on PM fibers, and installation of a small broadband normal conducting RF cavity. The cavity is located prior to the first bunch compressor at FLASH and allows energy modulation bunch-by-bunch (1 μs spacing) on the per mille range. Through the energy dependent path length of the succeeding magnetic chicane the cavity is used for ultimate bunch arrival time corrections. Recently the RF cavity operated 1 kW pulsed solid-state amplifier was successfully commissioned. First tests have been carried out incorporating the fast cavity as actuator together with SRF stations for larger corrections in our intra-train beam-based feedback pushing now arrival time stabilities towards 5 fs (rms). The latest results and observed residual instabilities are presented.


Recently, high speed interconnects capable of remote direct memory access (RDMA) such as InfiniBand and iWARP have gained considerable popularity due to their superb latency and bandwidth. Most existing studies about RDMA have focused mainly on its performance aspect. However, as power management has become essential for high-end systems such as enterprise servers and high performance computing nodes which are often equipped with RDMA capable network adapters, it is very important for us to take a fresh look at the benefits of RDMA from the power perspective. In the paper, we provide a detailed empirical study of the benefits of RDMA in terms of power savings compared with traditional communication protocols such as TCP/IP. We used two popular RDMA adapters in our evaluations: Mellanox ConnectX InfiniBand HCAs and Chelsio T3 10GE RNICs. In order to isolate the impact of communication on power consumption, our evaluation focused on using micro-benchmarks which perform different communication patterns. We have also studied several important factors that may have an impact on the performance and the power consumption of RDMA adapters such as the use of polling versus blocking, CPU speeds, and extra memory copies. We show that using high speed RDMA adapters can result in significant amount of power consumption during communication. (In one test, the system power has increased by as much as 50 watts, or over 30% of the idle power.) We found that RDMA generally has better power efficiency compared to that of TCP/IP, especially for communication intensive phases, for example when large messages are transferred. The power savings of RDMA are achieved by minimizing the interactions between the network adapters and other system components such as the CPUs and the memory: Although nearly the same amount of data must be going through the network adapters for both RDMA and TCP/IP, RDMA requires much fewer CPU cycles for protocol processing and also generates less memory bus traffic, both of which contribute to its power savings. Overall, our research demonstrated that RDMA not only provides high communication performance, but also offers excellent power efficiency, making it a desirable choice in environments that have strict power/energy constraints and demand high communication performance.


Rheumatic diseases include more than 1000 nosological forms, among which the highest incidence is osteoarthritis, rheumatoid arthritis and osteoporosis. The predominantly advanced age, the presence of comorbid diseases, the duration of the course of the disease and the need for concomitant treatment complicate the conduct of anti-inflammatory and analgesic therapy in such patients. Herbal medicines, in particular in the form of doses, due to the mildness of the action and the absence of significant side effects, can be used in the complex therapy of the acute period of rheumatic diseases, as well as for the prevention of relapse.

The aim of the presented work was to develop the composition, technology and determination of the quality indices of herbal collection, which reveals analgesic and anti-inflammatory properties and can be used for the prophylaxis and auxiliary therapy of a number of conditions in rheumatology.

Materials and methods. In the course of research, the methods used in the State Pharmacopoeia of Ukraine 2.0 (SPHU) were used.

Results. As a result of the analysis of literary data and our own experimental studies on the chemical composition and pharmacological activity of certain types of medicinal plant material, we have developed herbal collection that is recommended for the treatment and prevention of rheumatic diseases of the joints. Studies have been conducted on the development of quality collection indicators, which guarantee the effectiveness, safety, reproducibility of the imposed collection. The basic technological parameters of the raw material are determined: specific, bulk and volume mass, porosity, degree, degree of shredding. In order to prevent uneven mixing, an optimal degree of grinding of the raw material of the investigated collection, which ranges from 0.20 mm to 0.35 mm, is established, which allows obtaining a homogeneous mixture and contributes to the maximum yield of extractive and active substances. A series of experimental works aimed at studying the influence of the method of infusion (for 15, 30, 45, 60 minutes and until complete cooling) on the quality of the collected water extracts from the collection was conducted. The optimal method for setting the collection for 60 minutes is the best, since the content of extractives and flavonoids in the aqueous extract was highest and amounted to 49.57±0.52 % and 0.52±0.03 % respectively.

Conclusions. The composition of the herbal drug was developed: Harpagophyti radiх, Sophoraе alabastra, Valvae fructus Phaseoli vulgaris, Polygoni avicularis herba with the following ratio of components 50: 20: 20:10. The technological parameters of the raw material are studied: specific, volumetric and bulk mass, porosity, singularity of raw materials. The optimum degree of shredding of raw material is established, which helps to maximally remove biologically active substances and extractives. Experimental way is determined the optimal mode of collection, which can be recommended to the consumer to obtain the maximum therapeutic effect.


Three major carps viz. Catla catla, Labeo rohita and Cirrhina mrigala were reared under pond fertilization with broiler droppings on five nitrogen levels (0.10,0.13,0.16,0.19 and 0.22 g nitrogen per lOOgwet fish weight daily) under polyculture condition. Proximate composition of fish was determined at the start and end of one year experiment. Fat and protein contents of fish increased and ash and carbohydrate decreased among the three fish species after pond fertilization trials. With the increase of nitrogen level, the body fat and protein contents of fish increased up to 0.16 g level of nitrogen. Both Catla catla and Labeo rohita had the highest fat and protein contents under the influence of 0.16 g nitrogen level, while Cirrhina mrigala accumulated ample fat and protein under 0.13 and 0.10 g nitrogen levels respectively. A significant increase in both fats and proteins in fish body under different fertilization levels was due to the better performance under these treatments towards planktonic productivity indices, especially zooplankton.


Guanine (G)-oxidation to 8-oxo-7,8-dihydroguanine (OG) by reactive oxygen species in genomic DNA has been implicated with various human diseases. G-quadruplex (G4)-forming sequences in gene promoters are highly susceptible to G-oxidation, which can subsequently cause gene activation. However, the underlying G4 structural changes that result from OG modifications remain poorly understood. Herein, we investigate the effect of G-oxidation on the BLM gene promoter G4. For the first time, we show that OG can induce a G-vacancy-containing G4 (vG4), which can be filled in and stabilized by guanine metabolites and derivatives. We determined the NMR solution structure of the cGMP-fill-in oxidized BLM promoter vG4. This is the first complex structure of an OG-induced vG4 from a human gene promoter sequence with a filled-in guanine metabolite. The high-resolution structure elucidates the structural features of the specific 5'-end cGMP-fill-in for the OG-induced vG4. Interestingly, the OG is removed from the G-core and becomes part of the 3'-end capping structure. A series of guanine metabolites and derivatives are evaluated for fill-in activity to the oxidation-induced vG4. Significantly, cellular guanine metabolites, such as cGMP and GTP, can bind and stabilize the OG-induced vG4, suggesting their potential regulatory role in response to oxidative damage in physiological and pathological processes. Our work thus provides exciting insights into how oxidative damage and cellular metabolites may work together through a G4-based epigenetic feature for gene regulation. Furthermore, the NMR structure can guide the rational design of small-molecule inhibitors that specifically target the oxidation-induced vG4s.


Exposure to community violence may be associated with psychological distress, greater risk taking and aggression, and learning problems in children of color, while exposure to media violence may be related to increased aggression, psychological trauma, and other psychological and behavioral sequelae. Unfortunately, relationships between children's exposure to community and media violence have not been fully examined. Based on existing findings, this article presents a conceptual model of the potential effects of exposure to community and media violence on child functioning which suggests that the impact may be cumulative and should be examined in future studies of development in children of color. Low-income children of color in America are exposed to many types of violence. They may experience violence in the home and they experience or observe violence in schools, playgrounds, parks, and the communities in which they play and grow (Veenema, 2001). In addition, children are growing up in a media-saturated environment. Portrayals of violence in the media-through television, video games, and the Internet-touch virtually every child (Gentile & Walsh, 2002; Osofsky, 1999; Singer et al., 1999). While community and media violence affect all racial and ethnic groups, ethnic minority youth, particularly African Americans and Hispanic Americans, may be disproportionately affected by exposure to both community violence and exposure to media violence (Attar, Guerra, & Tolan, 1994; Bureau of Justice Statistics, 1991; Cooley-Quille, Boyd, Frantz, & Walsh, 2001). Violence refers to immediate or chronic situations that result in injury to the psychological, social, or physical well-being of individuals or groups (American Psychological Association, 1993). Violence, however, is not evenly distributed across all neighborhoods and demographic groups. Evidence suggests that it occurs at a higher rate in low-income/no income neighborhoods, especially among the young, and in public places (Bell & Jenkins, 1993). Research shows that children's exposure to community violence is related to a wide array of behavioral and psychological difficulties (Ceballo, Dahl, Aretakis, & Ramirez, 2001). Similarly, children's exposure to media violence is related to increased aggression, the prevalence of symptoms of psychological trauma, and other psychological and behavioral sequelae (American Academy of Pediatrics, 1995; Gentile & Walsh, 2002; McCann, Sakheim, & Abrahamson, 1988; Rosenthal, 2000; Sanders-Phillips, 1997; Strasburger & Donnerstein, 1999). As this selective review of the literature suggests, the level of children's exposure to community violence or media violence may vary; however, the psychological and behavioral risks that are associated with children's exposure to these types of violence are remarkably similar. This article reviews existing findings on exposure to community violence and exposure to media violence and on the associated adverse psychosocial and behavioral outcomes in children and adolescents. The lack of scientific inquiry linking the potential cumulative effects of the co-occurrence of exposure to community and exposure to media violence to adverse psychosocial and behavioral outcomes in children, particularly children of color, is noted. Based on the literature review, a conceptual model of the relationship between exposure to community violence and psychosocial adjustment and risk behaviors in children of color, moderated by exposure to media violence, is presented. LOW-INCOME CHILDREN'S EXPOSURE TO COMMUNITY & MEDIA VIOLENCE: EFFECTS AND RESPONSES Exposure to Community Violence While the nation publicly mourns shootings at schools such as Columbine High School in Littleton, Colorado, life-threatening community violence is a daily obstacle for many low-income, inner-city children (Ceballo et al., 2001). Groves (1997) defines community violence as the chronic and pervasive presence of violence and violence-related events within an individual's proximal environment. …


Instruments to cut and make incisions are used to cut and section tissues as well as to desiccate and extract organs or masses. They are used during the first phases of any surgical activity such as an incision, an exploration, to take a sample or to make pathological findings.


Ideology in the Guise of Science Review of Richard Dawkins. The God Delusion. Boston: Houghton Mifflin, 2006. x + 406 pp., with appendix, bibliography, and index. $27.00. Years ago while serving as full-time missionaries, my companion and I were invited to talk about our faith to an introductory philosophy class at the University of Missouri at Columbia. Since neither of us knew anything about philosophy, we simply relied on the missionary discussions to make our presentation. Only one member of the class was hostile, stating that we were "intellectual midgets" compared to Freud and Marx. We took that in stride, not knowing Freud and Marx except by name. Afterward, as the professor and several students thanked us, I happened to glance at a book that the professor had in hand and that evidently was being used as a course text. It was Bertrand Russell's Why I Am Not a Christian.1 About a year later, fresh off my mission and at Brigham Young University, I borrowed Russell's book from the library and opened its pages with some trepidation. Before long I realized that I mostly agreed with Russell, but only because he was attacking a crude caricature of the God I believed in. I didn't believe in that caricature either. For all his philosophical learning, Russell had written a shallow, nonthreatening book about religion. 1. Bertrand Russell, Why I Am Not a Christian: And Other Essays on Religion and Related Subjects (New York: Simon & Schuster, 1957). David Grandy 240 • The FARMS Review 19/2 (2007) Richard Dawkins, a well-known biologist and critic of religion, has written a similar book—The God Delusion. The book has gotten a lot of advance publicity and is selling well, but for those who keep track of such things, its publication is a bit of a nonevent. Here is another predictable salvo against religion from the world of science. But it is not science: it is ideology poorly disguised as science. Nor does its author grasp the nature of religious experience. Dawkins dismisses religious claims after measuring them against a rather badly misshapen scientific yardstick. This is positivism at its best (or worst): truth is established scientifically or not at all. Dawkins would have us believe that Darwinian evolution is the omni-explanatory solution to all of life's mysteries. This is an old refrain, one going back to Ernst Haeckel, Thomas Huxley, H. G. Wells, and, in more recent decades, Daniel Dennett. It is not science per se, but the dramatization of science for ideological purposes. Evolutionary biology is a perfectly legitimate theory of science, but like all intellectual constructions, it has its limitations. This fact, readily acknowledged by those familiar with quantum theory and Kurt Gödel's incompleteness theorems, has never really seemed to register with life science enthusiasts like Dawkins. Their passion for universal explanations harks back to an earlier era when Newtonian science struck many people as evidence that the human race had finally arrived. Dawkins, wholly enamored of Darwinian biology, is a curious throwback to that era; and he, like certain philosophes of the Enlightenment, is eager to throw traditional religion overboard so as to clear the deck of all ideologies but his own. It is important to note that Dawkins is not writing in a vacuum. He is replying to a crowd of thinkers—scientists, philosophers, and theologians—who in recent decades have tried to harmonize scientific and religious truth. "What indeed has Athens to do with Jerusalem?" asked Tertullian centuries ago.2 Tertullian's reply was "nothing," and Dawkins's is the same, although for vastly different reasons. The goal of harmonizing faith and reason is an old one, but there are pitfalls along the way; and to his credit, Dawkins does a good job of pointing 2. Tertullian, De Praescriptione Haereticorum 7.9. Dawkins, The God Delusion (Grandy) • 241 some of them out. If we invest faith in, say, intelligent design, irreducible complexity, or certain versions of the anthropic principle, all of which lean on God to make sense of things, what happens when persuasive naturalistic explanations emerge? This is worldview warfare, not science versus religion. Dawkins readily admits he is opposed only to the idea of a God who takes a personal interest in humankind and who therefore strives to bring off our salvation and happiness. His God, if he must use the word, is coincidental with the laws of nature and consequently perfectly oblivious to our being. This outlook is, of course, not original with Dawkins; most notably it is associated with Einstein and Spinoza. But neither Einstein nor Spinoza dogmatically and zealously asserted it. Both took it as a religious preference, not as a weapon with which to attack and destroy other religious preferences. Dawkins, however, is a religious firebrand in scientific guise, and by trying to straitjacket others into his atheistic worldview, he does science a profound disservice. In the latter part of the book, Dawkins offers an explanation for religion. Believing that only Darwinian evolution can get to the bottom of this matter, he weaves an interesting story. But this is not to say that others, working from different principles, could not weave equally interesting but very different stories. The problem here is one that Karl Popper identified decades ago: theories that explain so much and that seem to be immune to falsification ought to arouse our suspicion.3 A piece of Silly Putty can be easily molded into the shape of an elephant, a dog, a giraffe, virtually anything we can imagine; but that does not mean that Silly Putty is the universal substance from which all the world was created. It is merely a substance that reacts easily to the human imagination. Dawkins, it seems, fails to grasp this point. He never admits that there might be other ways to persuasively spin the empirical data, to play dot to dot with the events of nature. Rather, he talks as if Darwinian evolution affords a uniquely unbiased vision of the past. Yet anyone who closely attends to his explanations of the past notes 3. Karl R. Popper, Conjectures and Refutations: The Growth of Scientific Knowledge (New York: Basic Books, 1962). 242 • The FARMS Review 19/2 (2007) that they become obscure just at the critical moment. In this respect The God Delusion is exactly like The Selfish Gene,4 Dawkins's most sustained attempt to deal with our biological origins. The selfish gene, he says, began as a lifeless unit, void of intentionality. Eventually, however, it evolved into a living, purposive, "selfish" thing, though Dawkins never specifies quite how this happened. He can only say that natural selection—the mechanism that drives organic evolution—brought it about. Thus, while straining at the gnat of the selfish gene, Dawkins swallows the miracle of life that he is quick to disavow in religious contexts. After getting past this hitch, however, he is able to talk with great confidence, and his explanations come off as persuasive, albeit for reasons just indicated. Many people, unfortunately, overlook the leap of faith taken at the outset of the explanation (the assertion that natural selection somehow or other brings life into existence) and uncritically take that leap with Dawkins. This failure to deal with fundamental issues affords Dawkins a great deal of argumentative mileage. A case in point is his claim that natural selection is not a random process. (He concedes the improbability of life originating from purely random processes.) He compares it to a combination lock that noticeably clicks each time one of the key digits is passed, thus allowing the person turning the lock to quickly decipher its code. Elsewhere5 Dawkins puts a similar spin on the old monkey-at-the-typewriter argument by insisting that a monkey could type out a line from Shakespeare in fairly short order: each time the monkey accidentally hits a correct character it gets locked in, while all the incorrect characters are immediately erased. Thus the monkey, completely unaware of what it is accomplishing, never has to start over from scratch—the process itself is self-improving. It retains correct characters, discards those that are incorrect, and, after sufficient iterations, produces a fully coherent sentence. But for a monkey to do this, its typewriter would have to be programmed, and who or what is the programmer? Dawkins assigns that 4. Richard Dawkins, The Selfish Gene (New York: Oxford University Press, 1976). 5. See Richard Dawkins, The Blind Watchmaker: Why the Evidence of Evolution Reveals a Universe Without Design (New York: W. W. Norton & Company, 1996). Dawkins, The God Delusion (Grandy) • 243 role to natural selection. So on the one hand natural selection is blind and mindless, and on the other it is teleological. This is a contradiction that goes back to Darwin's personification of natural selection (he once described nature as "infinitely more sagacious than man" and as an "all-seeing being" that is ever "rigid and scrutinizing"),6 and it cuts so deeply as to shape up as yet another leap of faith. Dawkins might deny this by arguing that each tiny step of the evolutionary process gets locked in by virtue of its survival value, but it is by no means clear that this is always the case. More fundamentally, one wonders whence survival gets its intrinsic value in a cosmos initially devoid of value, which is the kind of cosmos Dawkins posits. An old adage states that to a man with a hammer everything looks like a nail. This, no doubt, is an overstatement, but certainly to Dawkins any religious belief is something to be pounded on by the ideological hammer of atheistic science. One of his chief complaints against traditional religion is the religious intolerance that flares up in such places as Israel, Iraq, Northern Ireland, and even the United States. Granted, this is lamentable, but Dawkins's own brand of intolerance only exacerbates the problem. What is needed


Highly interactive signaling processes constitute a set of parameters intertwining in a continuum mode to shape body formation and development. A sophisticated gene network is required to integrate environmental and endogenous cues in order to modulate flowering. However, the molecular mechanisms that coordinate the circuitries of flowering genes remain unclear. Here using complemented experimental approaches, we uncover the decisive and essential role of HEAT SHOCK PROTEIN 90 (HSP90) in restraining developmental noise to an acceptable limit. Localized depletion of HSP90 mRNAs in the shoot apex resulted in low penetrance of vegetative-to-reproductive phase transition and completely abolished flower formation. Extreme variation in expression of flowering genes was also observed in HSP90 mRNA-depleted transformed plants. Transient heat-shock treatments moderately increased HSP90 mRNA levels and rescued flower arrest. The offspring had a low, nevertheless noticeable failure to promote transition from vegetative into the reproductive phase and showed flower morphological heterogeneity. In floral tissues a moderate variation in HSP90 transcript levels and in the expression of flowering genes was detected. Key flowering proteins comprised clientele of the molecular chaperone demonstrating that the HSP90 is essential during vegetative-to-reproductive phase transition and flower development. Our results uncover that HSP90 consolidates a molecular scaffold able to arrange and organize flowering gene network and protein circuitry, and effectively counterbalance the extent to which developmental noise perturbs phenotypic traits.


The authors have evaluated the bit error-rate characteristics of the IM-DD ultralong-distance optical communication systems employing Er doped fiber amplifiers. A 2.5- and 5-Gb/s IM-DD nonreturn-to-zero signal was analyzed by recirculating-loop experiments. They used a fiber loop of four Er-doped fiber amplifiers and three spans of dispersion-shifted single-mode fibers for the experiments. A 16,000-km transmission at 2.5 Gb/s and an 11,000-km transmission at 5 Gb/s were successfully achieved. The allowable wavelength-tunable range of the optical transmitter for the 9000-km transmission was also measured at the bit rate of 5 Gb/s. The experimental results show the possibilities and limitations of transoceanic optical communication systems using Er-doped fiber amplifier repeaters. >


Prostate cancer (PCa) is the second most common type of cancer in the world and the fifth highest cause of cancer-related deaths in men [1], with the highest prevalence in the United States and Western Europe. The current diagnostic gold standards are controversial and typically lead to over-diagnosis [2]. Blood tests are commonly used to check the level of the prostate specific antigen (PSA), when in fact this antigen is organ-specific but not cancer-specific. Lack of clarity over diagnosis as well as prognosis leads to large numbers of unnecessary treatments, which are highly invasive and with a range of unpleasant side effects. New methods are therefore required to improve the existing clinical outcomes at both the diagnostic and the prognostic level.


Long non-coding RNAs (lncRNAs) are crucial in contributing to gastric tumorigenesis and development. However, the diagnostic value of the majority of lncRNAs in gastric cancer (GC) are not clear. The present study investigated the diagnostic value of gastric cancer associated transcript 2 (GACAT2), a lncRNA that is aberrantly expressed in GC tissues. A total of 343 plasma samples from 80 healthy individuals, 29 patients with gastric dysplasia (GD) and 117 paired preoperative and postoperative patients with GC were collected. Plasma GACAT2 levels were subsequently measured by reverse transcription-quantitative polymerase chain reaction. Finally, the associations between plasma GACAT2 levels and various clinicopathological features of patients with GC were assessed. The results demonstrated that plasma GACAT2 levels in preoperative patients with GC were significantly higher than those in the postoperative group (P=0.031). Compared with healthy individuals, plasma GACAT2 levels were significantly increased in patients with GD (P<0.001) and preoperative patients with GC (P=0.040). Moreover, the individual relative changes of plasma GACAT2 expression following surgery were significantly associated with lymphatic metastasis (P=0.034), distal metastasis (P=0.035) and perineural invasion (P=0.039). Therefore, the results of the current study suggest that plasma-based GACAT2 may be developed as a tumor marker to screen and predict the prognosis of GC patients.


The aim of this thesis was to derive a better understanding with regard to the effects of chloride on the general corrosion behaviour of low-alloy steels (LAS) in oxygenated high-temperature water (HTW) and to investigate the underlying mechanisms for crack initiation and propaga-tion due to chloride assisted environmentally assisted cracking (EAC). Therefore, systematic investigations on the effect of chloride on the EAC behaviour of LAS were performed to un-derstand and elucidate the underlying mechanisms.The overall thesis is divided into three parts focussing on the effect of chloride on:i) general corrosionii) crack initiation, andiii) crack growthof low-alloy steels in oxygenated high-temperature water.Studies on the effect of chloride on the general corrosion behaviour were performed by immer-sion tests that were evaluated using electrochemical monitoring techniques and different post-test investigation methods like SEM, ToF-SIMS, and others. From the performed investiga-tions it is concluded that the presence of small amounts of chloride in oxygenated HTW causes an incorporation of chloride into the oxide layer, a thinning of the oxide layer thickness, and pronounced pitting.The crack initiation susceptibility of LAS was investigated using CERT tests. These tests showed an increased number of crack initiation locations and a decrease of the elongation at fracture with increasing chloride concentrations.Crack growth rate tests clearly demonstrated that not the increase in the chloride concentration per se, but the conjoint occurrence of an active or dormant crack and increased chloride con-centration causes an increase in the observed crack growth rates.For practical applications of LAS in oxygenated HTW this means that short term transients seem to be not harmful regarding component integrity, but long term increased chloride con-centrations should by prohibited since they cause increased general corrosion of LAS. Taking crack initiation and crack growth into consideration, the conjoint occurrence of increased chlo-ride concentrations and mechanical straining at stress levels above the yield strength should be avoided.


Accounting information should be used by interested parties (stakeholders) as one of the basic for business decision making. In fact, accounting information has not been used optimally, especially by the principals of SMEs, including cooperatives. Many factors affect the extent of usage of accounting information, namely the scale of business, business age, type of business, manager education and training of accounting. This article presents the results of research on the factors that affect the extent of the usage of accounting information by the cooperative,it examines the influence of scale, age, business and accounting training on the extent of the usage of accounting information by the cooperative. This research took 30 cooperatives in the district of Sleman as the sample. The sampling method used was 'purposive random sampling'. The hypothesiswhich  was tested with multiple regression test shows that the three factors, namely business scale, age of business and accounting training both totally and partially affect the extent of the usage of accounting information by the cooperative


Applications for transient, high-voltage pulsed power technologies are on the increase. High-voltage resistors are an essential component of such systems, especially in the proof-of-concept and prototype testing. The authors have recently procured and tested certain resistor samples, supplied by Kanthal Globar and HVR Advanced Power Components. Results of a detailed evaluation of the HVR resistors are presented in this paper. Two types of HVR high-powered resistors have been tested to determine hold-off voltage, frequency variation and resistance to high voltage. The resistors were tested in a coaxial geometry driven by a two stage Marx generator. The voltage and current were measured by calibrated sensors. The high-voltage pulse resistance of each resistor is then determined on a pulse by pulse basis by dividing the maximum voltage by the maximum current in the time-domain. The two samples (HVR-10, HVR-12; washer type) were nominally 10 and 12 ohms with resistivity of 28 and 80 ohm-cm respectively. The variations in the low-voltage to pulsed high-voltage resistance were 9% for the HVR-10 and 18% for the HVR-12. With an average applied field of 65 kV/inch or 25.6 kV/cm, the resistors flashed in air, but not in pure SF/sub 6/ and N/sub 2//SF/sub 6/ mix. These resistors were found to be satisfactory for transient applications.


mTORC1 is a major regulator for cell growth and proliferation that coordinates nutrient inputs, such as amino acids, glucose, and growth factor, with anabolic and catabolic processes in cells. Amino acid signals are transmitted towards mTORC1 through the Rag GTPases, which directly recruit mTORC1 onto the lysosomal membrane. The Rag GTPase heterodimer has a unique architecture that consists of two GTPase subunits, RagA or RagB bound to RagC or RagD. Their nucleotide loading states are strictly controlled by several lysosomal or cytosolic protein complexes that directly process the amino acid signal. One such complex is GATOR1, a negative regulator on the cytosolic branch of the amino acid sensing pathway. GATOR1 comprises three subunits, Depdc5, Nprl2, and Nprl3, and is a GTPase Activating Protein (GAP) for RagA. It functions through a noncanonical GAP mechanism in which GATOR1 binds the Rag GTPases with two modes, an inhibitory mode that holds the Rag GTPase heterodimer and has been captured by structural determination, and a GAP mode that actually stimulates GTP hydrolysis by RagA but remains elusive. Here, we used biochemical approaches to probe the GAP mode of GATOR1 and found that a critical arginine finger on Nprl2, Arg78, is the catalytic residue, while a loop localized close to it provides the binding site for the Rag GTPases. Furthermore, we used cryo-EM to resolve the structure of the GATOR1-Rag-Ragulator complex at 4.1A resolution, which represents the architecture of the mTORC1-inhibiting complex on the lysosomal surface. Our results revealed the molecular bases for mTORC1 inactivation in human cells. This abstract is also being presented as Poster B10. Citation Format: Kuang Shen, Rick Huang, Zhiheng Yu, David M. Sabatini. Structural and functional analyses of GATOR1, a negative regulator of the mTORC1 pathway [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr PR02.


The home networking becomes more interesting if users can share high quality contents with friends and colleagues living away from the user. DLNA certified devices allow users to share or access digital media contents on the same home network. However, the sharing of the content is only limited inside local area networks. In this paper, we propose a global content sharing home gateway named DAS (DLNA Agent for SNS). Different from exiting approaches using VPN, DAS enables to share specified contents to selected users with support of access control functionality provided by Social Network web services. As DAS behaves as a DLNA certified server, there is no need to modify commercial DLNA CE devices.


In this paper, we evaluate the performance of a Medium Access Control (MAC) protocol for MIMO ad hoc networks under imperfect channel estimation. To this end, we also present an analysis of channel estimation errors using correlator-based and Minimum Mean-Square Error (MMSE) channel estimators. Unlike similar works, we specifically focus on a scenario where the presence of several simultaneous, symbol-asynchronous signals makes the problem more complicated than in traditional channel estimation. In particular, we show that there is direct dependence of the channel estimation error on the instantaneous channel matrix. The model we propose in this paper makes it possible to quickly evaluate the performance of channel estimation schemes as a function of the system parameters. In this light, we include the effect of channel estimation errors in an ad hoc networking protocol simulator and thoroughly evaluate their impact. Our results show that there exists a significant interplay between the performance of MAC protocols for MIMO networks and the accuracy of channel estimation. Moreover, we show that interesting tradeoffs arise between MAC- and physical level-related parameters.


Contemporary high-power laser systems make use of solid-state laser technology to reach petawatt pulse powers. The breakdown threshold for optical components in these systems, however, demands beam diameters up to 1 m. Raman amplification of laser beams promises a breakthrough by the use of much smaller amplifying media, i.e., millimeter-diameter-wide plasmas. Through the first large-scale multidimensional particle-in-cell simulations of this process, we have identified the parameter regime where multipetawatt peak laser powers can be reached, while the influence of damaging laser-plasma instabilities is only minor. Snapshots of the probe laser pulse being amplified, generated using state-of-the-art visualization techniques, are presented.


Using recent and updated world data on polarized structure functions g1 and g2 we perform QCD analysis at the next-next-to-leading-order (NNLO) accuracy. We include also target mass correction and higher twist effect to get more precise results in our fitting procedure. To confirm the validity of our fitting results several sum rules are examined and we do a comparison for them with results from other models. In our analysis we employ Jacobi polynomials approach to obtain analytical solutions of the DGLAP evolution equations for parton distribution functions (PDFs). Using the extracted PDFs from our data analysis as input we also compute the xand pT -dependence of some transverse momentum dependence (TMD) PDFs in polarized case, based on covariant parton model. These functions are naively even time-reversal (T-even) at twist-2 approximation. The results for TMDs are indicating proper and acceptable behaviour with respect to what are presented in other literatures.


Based on polarization mechanisms, such as electronic, ionic and orientational polarizations, a new equation for dielectric permittivity of soil is proposed to interpret the dielectric behavior of a mixture like soil, in terms of polarization process of its components and the interactions between its components. The dielectric permittivity is expressed in terms of a fre-quency-dependent part and a frequency-independent part. These two parts correspond to polarizations occurred at different fre-quency range. It is a new volumetric mixing model with theoretical background. Based on time domain reflectometry (TDR) measurements of saturated soil samples and test data from literature, comparisons of this model with some well established mixing models show that the curves for saturated sand soils and slurries resulted from the new equation, which agree well with TDR measurements, are close to those calculated from Birchak's model.


We describe a patient who presented with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) 2 months before clinical evidence of bronchogenic malignancy. Because of the potential for the ectopic production of atrial natriuretic peptide (ANP) to mimic SIADH, both hormones were measured in this hyponatremic patient to seek a possible marker of tumor activity. A hypertonic saline infusion at presentation revealed excessive osmotically decoupled secretion of arginine vasopressin but a normal ANP response.


Indium phosphide high electron mobility transistors (InP HEMTs) represent the state-of-the-art technology for both room and cryogenic temperature low noise amplifiers. For years they have been playing a central role in the most demanding niche applications such as radio astronomy and deep space communications, and they are expected to significantly contribute to communication networks of the future. Modern lithography tools have enabled straightforward processing of transistors with sub-100 nm gate lengths, however, the improved RF performance did not result in the expected advancement of noise behavior. The physical limits of noise performance are currently motivating research into this subject, with indications that a significant decrease of minimum noise figure from reducing the gate length cannot be expected. Nevertheless, there is room for improvement in transistor noise behavior with further development of epitaxial growths and bandgap engineering. This work centers on the optimization of InP HEMTs epitaxial layers by bandgap engineering, small-signal modeling and characterization. A common approach in improving carrier confinement and mobility with narrow bandgap materials used for the channel results in impact ionization taking place even at a relatively low drain bias. The small-signal model was extended to account for the effects of impact ionization and now features excellent agreement between simulated and measured S-parameters at lower frequencies at both room and cryogenic temperatures: we are now able to resolve in which material impact ionization takes place in a composite channel. The noise model proposed in this work including the impact ionization effects shows good agreement with noise measurements performed at room temperature. Achieving the best possible transistor gain and noise behavior depends highly on the quality of contacts: epitaxial structures were therefore optimized in order to reduce contact resistance and improve channel transport properties. Composite channel structures with narrow and wide bandgap materials were implemented to reduce the effects of impact ionization. Further refining of the channel layers in combination with vertical device scaling should allow improvement of both the device bandwidth and minimum noise figure.


The world has experienced two hundred years of unprecedented advances in vehicle technology, transport system development, and traffic network extension. Technical progress continues but seems to have reached some limits. Congestion, pollution, and increasing costs have created, in some parts of the world, a climate of hostility against transportation technology. Mobility, however, is still increasing. What can be done? There is no panacea. Interdisciplinary cooperation is necessary, and we are going to argue in this paper that {\em Mathematics\/} can contribute significantly to the solution of some of the problems. We propose to employ methods developed in the {\em Theory of Optimization\/} to make better use of resources and existing technology. One way of optimization is better planning. We will point out that {\em Discrete Mathematics\/} provides a suitable framework for planning decisions within transportation systems. The mathematical approach leads to a better understanding of problems. Precise and quantitative models, and advanced mathematical tools allow for provable and reproducible conclusions. Modern computing equipment is suited to put such methods into practice. At present, mathematical methods contribute, in particular, to the solution of various problems of {\em operational planning}. We report about encouraging {\em results\/} achieved so far.


Lawyers and investigators are often presented with large email datasets that contain emails that are not all relevant to any given investigative search. They must often manually comb through information contained within these large datasets in order to find the information they need, expending large amounts of time and money in the process. Our work offers an interactive visual analytic alternative to current methodology. We introduce a method for reducing the number of emails that need to be viewed in a large dataset while also giving the user a quick overview of possible contents and relationships in a set of results.


Abstract The striped field mouse (Apodemus agrarius) is one of the most common mammals in Korea, however, limited research has focused on the population structure and biogeography of this mouse throughout Korea. In addition, the taxonomic status of the species remains unresolved. The objectives of our study were to address the inadequacies in understanding the population structure, biogeography, and taxonomic status of A. agrarius. We collected 160 samples from 13 localities throughout the South Korean Peninsula, two nearby islands and two remote islands. We used five microsatellite loci and estimated genetic diversity measures and populations divergence estimates (i.e. FST and RST) to address the objectives. Except for populations on the two remote islands, Jeju and Heuksan, the populations on the peninsula and nearby islands indicated low FST and RST values. The population structure based on microsatellite loci supported only one subspecies opposing three subspecies reported previously on the Korean Peninsula and nearby islands. However, populations on Jeju Island and Heuksan Island showed subspecific differences from each other and the populations on the Korean Peninsula and nearby islands. The information reported on the population genetics of the striped field mouse in Korea will allow resolving the taxonomy and biogeography of this species.


OBJECTIVE
The goal of this work was to study the expression of epidermal growth factor receptor (EGFR) and c-erbB-3 and c-erbB-4 oncogenes in gestational trophoblastic diseases and normal first-trimester placenta.

STUDY DESIGN
Paraffin sections of 16 cases of partial mole, 25 cases of complete mole, 10 cases of gestational choriocarcinoma, and 11 cases of therapeutic abortion were studied immunohistochemically for EGFR, c-erbB-3, and c-erbB-4 proteins. The presence of EGFR mRNA was studied using in situ hybridization.

RESULTS
Staining for EGFR was detected immunohistochemically in all cell types in gestational trophoblastic diseases and normal placenta. In situ hybridization for EGFR mRNA correlated with immunostaining for EGFR in all tissues studied. All 10 cases of choriocarcinoma exhibited strong immunoreactivity for EGFR. The levels of expression of EGFR in choriocarcinoma and syncytiotrophoblasts and cytotrophoblasts in complete mole were significantly greater than those in syncytiotrophoblasts and cytotrophoblasts in both normal placenta and partial mole (P < 0.01, P < 0.01). Expression of c-erbB-3 did not significantly differ among placental and gestational trophoblastic disease tissues and trophoblastic cell types except for significantly increased expression in choriocarcinoma as compared with cytotrophoblasts of partial mole (P = 0.02). The placenta, complete and partial mole, and choriocarcinoma tissues demonstrated similar immunoreactivity for c-erbB-4. Strong immunostaining for EGFR (P = 0.02) and c-erbB-3 (P < 0.01) in extravillous trophoblasts of complete mole was found to be significantly correlated with the development of persistent postmolar gestational trophoblastic tumor.

CONCLUSION
The EGFR-related family of oncogenes may be important in the pathogenesis of gestational trophoblastic diseases. The increased expression of EGFR and c-erbB-3 in complete mole may also influence the development of persistent gestational trophoblastic tumor.


An efficient technique for the detection of nartowband infrared radiation by up-conversion in an optically saturated atomic vapor is described. The strong transition cross sections provided by the resonance interactions combined with the narrow Doppler spectral response profile contribute to the potential to approach quantum-noise-limited performance. Experimental results confirm the model of the detection process for sodium transitions at 1.48, 2.34, and 3.42 μ. The predicted ultimate noise equivalent power (NEP) of this device is less than 10-17W/Hz1/2in the 1.5-5-\mu spectral region.


Information on the rates of return and effective rates of taxation from capital in the private sectors of an economy are prerequisites for both rational public sector project evaluations and for measurement of the degree of equity and excess burden credited by the economy's taxation system. In many countries accurate knowledge of the values of these variables is absent. The principal objective of this study is to overcome this dearth of information in the case of Canada.


Aim: Epicardial adipose tissue (EAT) has been suggested as a contributing factor for coronary atherosclerosis based on the previous cross-sectional studies and pathophysiologic background. However, a causal relationship between EAT and the development of non-calcified coronary plaque (NCP) has not been investigated. Methods: A total of 122 asymptomatic individuals (age, 56.0 ± 7.6 years; male, 80.3%) without prior history of coronary artery disease (CAD) or metabolic syndrome and without NCP or obstructive CAD at baseline cardiac computed tomography (CT) were enrolled. Repeat cardiac CT was performed with an interval of more than 5 years. Epicardial fat volume index (EFVi; cm3/m2) was assessed in relation to the development of NCP on the follow-up CT where the results were classified into "calcified plaque (CP)," "no plaque," and "NCP" groups. Results: On the follow-up CT performed with a median interval of 65.4 months, we observed newly developed NCP in 24 (19.7%) participants. Baseline EFVi was significantly higher in the NCP group (79.9 ± 30.3 cm3/m2) than in the CP group (63.7 ± 22.7 cm3/m2; P = 0.019) and in the no plaque group (62.5 ± 24.7 cm3/m2; P = 0.021). Multivariable logistic regression analysis demonstrated that the presence of diabetes (OR, 9.081; 95% CI, 1.682–49.034; P = 0.010) and the 3rd tertile of EFVi (OR, 4.297; 95% CI, 1.040–17.757; P = 0.044 compared to the 1st tertile) were the significant predictors for the development of NCP on follow-up CT. Conclusions: Greater amount of EAT at baseline CT independently predicts the development of NCP in asymptomatic individuals.


This paper outlines an argument for the equal treatment of third-country nationals in the EU. The argument is in two parts. It argues, doctrinally, that the reasons in favour of treating third-country nationals equally are weighty. Second, it suggests that, politically, conceptually and sociologically, third-country nationals should generally be entitled to equal treatment, a guarantee which may be subject to specific exceptions. The reasons for such exceptions should be clearly stipulated by public authorities. The approach which emerges from this position should lead to a more coherent concept of equality emerging in EU law, something which should be amenable to European egalitarians.


High-quality data labeling from specific domains is costly and human time-consuming. In this work, we propose a self-supervised domain adaptation method, based upon an iterative pseudo-forced alignment algorithm. The produced alignments are employed to customize an end-to-end Automatic Speech Recognition (ASR) and iteratively refined. The algorithm is fed with frame-wise character posteriors produced by a seed ASR, trained with out-of-domain data, and optimized throughout a Connectionist Temporal Classification (CTC) loss. The alignments are computed iteratively upon a corpus of broadcast TV. The process is repeated by reducing the quantity of text to be aligned or expanding the alignment window until finding the best possible audio-text alignment. The starting timestamps, or temporal anchors, are produced uniquely based on the confidence score of the last aligned utterance. This score is computed with the paths of the CTC-alignment matrix. With this methodology, no human-revised text references are required. Alignments from long audio files with low-quality transcriptions, like TV captions, are filtered out by confidence score and ready for further ASR adaptation. The obtained results, on both the Spanish RTVE2022 and CommonVoice databases, underpin the feasibility of using CTC-based systems to perform: highly accurate audio-text alignments, domain adaptation and semi-supervised training of end-to-end ASR.


Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC

Heat Shock Protein 90 (Hsp90) has emerged as an attractive target in cancer therapy given its role in promoting the activity and stability of a host of oncogenic client proteins. Due to the functional diversity of client proteins, Hsp90 inhibitors have the potential to disrupt multiple oncogenic signaling pathways to mediate cancer cell death.

Retaspimycin HCl (IPI-504) is a potent, selective inhibitor of Hsp90 that has single agent activity predominantly in EML4-ALK positive non-small cell lung cancers (NSCLC). Retaspimycin HCl also recently demonstrated clinical activity in a Phase Ib trial when combined with docetaxel in patients with previously treated NSCLC without prospective selection for mutations or rearrangements. This trial demonstrated an overall response rate (ORR) of 26% (n=23) to combination therapy (Riely et al., ASCO, 2011), indicating an enhanced response compared to historical data with single agent docetaxel (ORR of 8%) (Hanna et al., JCO, 2004). To further evaluate activity of this drug combination, a double-blind, randomized Phase II trial is being conducted in NSCLC patients with a smoking history.In support of this trial, preclinical studies are being performed to determine the mechanism of action (MOA) of retaspimycin HCl and docetaxel in combination. To this end, a panel of NSCLC cell lines was screened for sensitivity to combination treatment, leading to identification of a subset of cell lines in which these drugs act in synergy to enhance cell death. Synergy with fixed and non-fixed drug ratios was assessed using the Chou-Talalay method to determine the combination index (CI). To then investigate the mechanism of synergy, an unbiased "stable isotope labeling by amino acids in cell culture" (SILAC) proteomic approach was employed to identify Hsp90 client proteins depleted by combination treatment. Several mitotic regulators, including components of the anaphase promoting complex (APC), were specifically downregulated in response to combination treatment, leading to the hypothesis that combination treatment mediates cell death by prolonging mitosis. Supporting this hypothesis, cells treated with retaspimycin HCl/docetaxel demonstrated a synergistic increase in the percentage of mitotic cells, as assessed by phospho-histone H3 staining, and accumulation of the APC substrates, securin and Cyclin B. Xenograft models of NSCLC demonstrated tumor regression in response to combination treatment, and pharmacodynamic studies are underway to examine the molecular basis for this regression. These preclinical data, together with biomarker investigation in the ongoing Phase II trial, may lead to an improved ability to identify NSCLC patients that are more likely to respond to combination treatment with retaspimycin HCl and docetaxel, and may inform the use of retaspimycin HCl in other combinations and indications.

Citation Format: Katie O'Callaghan, Brenda C. O'Connell, Bonnie Tillotson, Mark Douglas, Howard Stern, Kip A. West, Janid A. Ali, Paul Changelian, Karen McGovern, Vito J. Palombella, Christian C. Fritz, Jeff L. Kutok. Deciphering the mechanism of synergy between the Heat Shock Protein 90 inhibitor retaspimycin HCl and docetaxel in preclinical models of non-small cell lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3433. doi:10.1158/1538-7445.AM2013-3433


ABSTRACT We created a hybrid adeno-associated virus (AAV) from two related rhesus macaque isolates, called AAVrh32.33, and evaluated it as a vaccine carrier for human immunodeficiency virus type 1 (HIV-1) and type A influenza virus antigens. The goal was to overcome the limitations of vaccines based on other AAVs, which generate dysfunctional T-cell responses and are inhibited by antibodies found in human sera. Injection of a Gag-expressing AAVrh32.33 vector into mice resulted in a high-quality CD8+ T-cell response. The resulting Gag-specific T cells express multiple cytokines at high levels, including interleukin-2, with many having memory phenotypes; a subsequent boost with an adenovirus vector yielded a brisk expansion of Gag-specific T cells. A priming dose of AAVrh32.33 led to high levels of Gag antibodies, which exceed levels found after injection of adenovirus vectors. Importantly, passive transfer of pooled human immunoglobulin into mice does not interfere with the efficacy of AAVrh32.33 expressing nucleoproteins from influenza virus, as measured by protection to a lethal dose of influenza virus, which is consistent with the very low seroprevalence to this virus in humans. Studies of macaques with vectors expressing gp140 from HIV-1 (i.e., with AAVrh32.33 as the prime and simian adenovirus type 24 as the boost) demonstrated results similar to those for mice with high-level and high-quality CD8+ T-cell responses to gp140 and high-titered neutralizing antibodies to homologous HIV-1. The biology of this novel AAV hybrid suggests that it should be a preferred genetic vaccine carrier, capable of generating robust T- and B-cell responses.