Little is known about Registered Nurses (RNs) and their work in northern Canada and the care of older adults with dementia in this setting. As the prevalence of dementia is predicted to increase over the next 30 years, the purpose of this project was to discover key concepts that depicted salient issues in dementia care in northern Saskatchewan from the perspective of RNs working in northern health care facilities. A sequential exploratory mixed method design was chosen for this study with a qualitative lead complemented by a secondary analysis of quantitative data. Interviews were conducted with 14 RNs, employed in small northern Saskatchewan communities, about their experiences with dementia caregiving and their perceptions of dementia care resources. The grounded theory method used in analysis of the interview data resulted in the construction of the theory, Insulating and Expanding the Awareness of Dementia in Northern Nursing. The study identified three categories of conditions that influenced awareness of dementia: Dementia Care and Community Caregiving, Characteristics of the Northern RN, and Northern Nursing Worklife.
The quantitative secondary analysis, using a north-south comparison of data from the national survey (Stewart et al., 2005) in the multi-method study "The Nature of Nursing Practice in Rural and Remote Canada" (MacLeod et al., 2004), was used to explore contextual elements identified in the grounded theory analysis. The comparison of nursing practice in northern (n = 597) and southern (n = 2154) rural and small town communities found that fewer RNs in northern Canada reported dementia as a client characteristic, worked in long-term care, or in home care nursing positions, compared to RNs in southern Canada. Findings from both the qualitative and quantitative studies contribute to an understanding of the RNs' awareness of dementia. Recommendations for increasing the awareness of dementia in northern nursing practice include enhancing the resources and services available to older adults with dementia in small northern communities. It is hoped that further exploration of dementia within northern communities will result in improved care for individuals with dementia and their families.


Forty cotton genotypes of varied origin were subjected to controlled moisture stress in a rainout shelter at Magoye (16°S, 27.6°E) in Zambia with the major objective being identification of moisture tolerant genotypes. Two experiments were used for this purpose; the box and pot experiments. Genotypes with favourable performance under the rain-out shelter were selected for further evaluation under field conditions in six locations during the rainy season. The genotypes in the trials exhibited varying responses to water stress. Significant variation (p>0.10) was observed among trial genotypes for seedling wilting, seedling survivability after stress, canopy temperature and plant tissue moisture content after stress. CAM 26 was the most consistent and high performing cotton genotype in the rainout shelter with mean survival after stress of 84%. Multilocation evaluation revealed considerable variation in field performance among trial genotypes. SRG 06 emerged as the most consistent genotype with the highest seed cotton yield in low rainfall ( 500mm) test environments. Subject to further evaluation for performance in fibre quality parameters, SRG 06 is the most suitable genotype for cultivation in low rainfall production environments in Zambia. CAM 26 is recommended for use in cotton breeding programmes as a source of genes for moisture stress tolerance.


Shielding the Poor presents a group of studies on social protection in the developing world from leading researchers. These studies address the issue of vulnerability of the poor to adverse shocks and propose policies to increase their protection and coping capacity. The studies emphasize the need for building permanent institutional structures that help reduce and manage the risks that households face as part of a coherent long-term strategy to reduce poverty and promote social equity. The articles included in this book were presented at the conference, "Social Protection and Poverty," held at the Inter-American Development Bank in February, 1999 in Washington, DC.


Enzyme replacement therapy (ERT) is the standard-of-care treatment of Pompe disease, a lysosomal storage disorder caused by deficiency of acid α-glucosidase (GAA). One limitation of ERT with recombinant human (rh) GAA is antibody formation against GAA. Similarly, in adeno-associated virus (AAV) vector-mediated gene transfer for Pompe disease, development of antibodies against the GAA transgene product and the AAV vector prevents therapeutic efficacy and vector readministration, respectively. Here a nondepleting anti-CD4 monoclonal antibody (mAb) was administrated intravenously prior to administration of an AAV2/9 vector encoding GAA to suppress anti-GAA responses, leading to a substantial reduction of anti-GAA immunoglobulins, including IgG1, IgG2a, IgG2b, IgG2c, and IgG3. Transduction efficiency in liver with a subsequent AAV2/8 vector was massively improved by the administration of anti-CD4 mAb with the initial AAV2/9 vector, indicating a spread of benefit derived from control of the immune response to the first AAV2/9 vector. Anti-CD4 mAb along with AAV2/9-CBhGAApA significantly increased GAA activity in heart and skeletal muscles along with a significant reduction of glycogen accumulation. Taken together, these data demonstrated that the addition of nondepleting anti-CD4 mAb with gene therapy controls humoral immune responses to both vector and transgene, resulting in clear therapeutic benefit in mice with Pompe disease.


Designer Anti-HIV Developing a protective HIV vaccine remains a top global health priority. One strategy to identify potential vaccine candidates is to isolate broadly neutralizing antibodies from infected individuals and then attempt to elicit the same antibody response through vaccination (see the Perspective by Burton and Weiss). Wu et al. (p. 856, published online 8 July) now report the identification of three broadly neutralizing antibodies, isolated from an HIV-1–infected individual, that exhibited great breadth and potency of neutralization and were specific for the co-receptor CD4-binding site of the glycoprotein 120 (gp120), part of the viral Env spike. Zhou et al. (p. 811, published online 8 July) analyzed the crystal structure for one of these antibodies, VRC01, in complex with an HIV-1 gp120. VRC01 focuses its binding onto a conformationally invariant domain that is the site of initial CD4 attachment, which allows the antibody to overcome the glycan and conformational masking that diminishes the neutralization potency of most CD4-binding-site antibodies. The epitopes recognized by these antibodies suggest potential immunogens that can inform vaccine design. A human antibody achieves broad neutralization by binding the viral site of recognition for the primary host receptor, CD4. Cross-reactive neutralizing antibodies (NAbs) are found in the sera of many HIV-1–infected individuals, but the virologic basis of their neutralization remains poorly understood. We used knowledge of HIV-1 envelope structure to develop antigenically resurfaced glycoproteins specific for the structurally conserved site of initial CD4 receptor binding. These probes were used to identify sera with NAbs to the CD4-binding site (CD4bs) and to isolate individual B cells from such an HIV-1–infected donor. By expressing immunoglobulin genes from individual cells, we identified three monoclonal antibodies, including a pair of somatic variants that neutralized over 90% of circulating HIV-1 isolates. Exceptionally broad HIV-1 neutralization can be achieved with individual antibodies targeted to the functionally conserved CD4bs of glycoprotein 120, an important insight for future HIV-1 vaccine design.


Background : Triage process has rapidly developed in some countries in the last three decades in order to respond to the demand for emergency services by growing population and emergency health needs. However, this development does not appear to match in Indonesian hospitals. The triage process in Indonesia remains obscure. Purpose : This study aimed to describe triage process in Indonesia from a range of different perspectives. Methods : The research design of this study was descriptive qualitative using semistructured interviews of 12 policy makers or persons responsible from 5 different organizations which informed triage practice in Indonesia. The data were analyzed using a three step content analysis. Results : The result produced 3 themes. First, four steps of triage process ranging from receiving to prioritizing were reported as the triaging procedures in Indonesia which were almost similar to the international literature except for a re-triage step. Second,primary and secondary triage processes were also applied in all emergency departments in Indonesia. Last, no prolonged waiting time in Indonesia could be assumed whether the triage process was effective and efficient or it was only a quick process of sorting to rapidly increase the number of patients in the treatment rooms. Out of the themes, the result also indicated that the involvement of nurses in health policy development inIndonesia needed support Conclusion : Triage process in Indonesia still needs improvements. Patient's re-triage and evaluating secondary triage should be given more frameworks in the future. An effective and efficient triage process in Indonesia will best manage the number of patients in the treatment rooms and therefore further observational researches on patterns and trends are needed. Moreover, including the role of nurses as policy makers in the curriculum of nursing undergraduate and post-graduate degrees would give nurses the evidence to seek out policy making positions in the future


State-space models have been successfully used for more than fifty years in different areas of science and engineering. We present a procedure for efficient variational Bayesian learning of nonlinear state-space models based on sparse Gaussian processes. The result of learning is a tractable posterior over nonlinear dynamical systems. In comparison to conventional parametric models, we offer the possibility to straightforwardly trade off model capacity and computational cost whilst avoiding overfitting. Our main algorithm uses a hybrid inference approach combining variational Bayes and sequential Monte Carlo. We also present stochastic variational inference and online learning approaches for fast learning with long time series.


There is a growing body of evidence highlighting the significant role of gut microbiota in various pathologies. We performed a systematic review to review the different microbiota involved in neuropsychiatric diseases. 50 studies (23 studies for autism spectrum disorders, 18 for major depression, and 9 for schizophrenia), representing 2,137 patients and 2,844 controls. Concerning the microbiota, the genera Prevotella, Clostridium, Bacteroides, Bifidobacterium, Ruminococcus, Megamonas, and Faecalbacterium were the ones detected with the most frequent variation of their relatives abundance. We also assess the overlap between the different pathologies. This study provides new insights into the complex relationship between the brain and the gut and the implications in neuropsychiatric pathologies. The identification of unique signatures in neuropsychiatric diseases suggests new possibilities in targeted anti or probiotic treatment.


We consider competition among sellers when each of them sells a portfolio of distinct products to a buyer having limited slots. We study how bundling affects competition for slots. Under independent pricing, equilibrium often does not exist and hence the outcome is often inefficient. When bundling is allowed, each seller has an incentive to bundle his products and an efficient equilibrium always exists. Furthermore, in the case of digital goods, all equilibria are efficient if slotting contracts are prohibited. We also identify portfolio effects of bundling and analyze the consequences on horizontal mergers. Finally, we derive clear-cut policy implications.


The Epstein-Barr virus (EBV) uses nasopharyngeal-associated lymphoid tissue (NALT) as portal of entry to establish life-long persistence in memory B-cells. We previously showed that naive and memory B-cells from NALT are equally susceptible to EBV infection. Here, we show that memory B-cells from NALT are significantly more susceptible to EBV infection than those from remote lymphatic organs. We identify beta1 integrin, which is expressed highest by naive B-cells of distinct lymphoid origin and by memory B-cells from NALT, as mediator of increased susceptibility to infection by EBV. Furthermore, we show that BMRF-2-beta1 integrin interaction and the downstream signal transduction pathway is critical for post-binding events. Increase of beta1 integrin expression in peripheral blood memory B-cells provoked by CD40 stimulation plus B-cell receptor cross-linking increased the susceptibility of non-NALT memory B-cells to EBV infection. Thus, EBV seems to utilize the increased activation status of memory B-cells residing in the NALT to establish and ensure persistence.


Abstract Using 231 lambs, the effect of animal sex and time of slaughter on sensory quality of meat from Norwegian lamb was investigated. Three experiments were carried out to include common feeding systems and seasonal variation in slaughter for Norwegian lamb. The first experiment was conducted in September 2001 using 40 lambs subjected to grazing on the mountain ranges or cultivated lowland pastures. A follow up experiment was conducted during March and April 2002 using 107 lambs fed indoors by farmers. The third experiment was conducted during October and November 2003 using 84 lambs subjected to either ad libitum or restricted concentrate supplementation under stall-feeding. Except for the March/April experiment, meat from ewe lambs had sour odour scores comparable (P>0.05) to that of ram lambs. On the other hand, meat from ram lambs had higher (P<0.05) scores for sour taste than that of ram lambs irrespective of time of slaughter. Further, in all but March/April slaughter time, meat from ewe lambs were comparable (P>0.05) to that of ram lambs in metallic taste. Whereas meat from ewe lambs slaughtered in September had ram taste comparable to that of ewe lambs, meat from ewe lambs slaughtered in March/April and October/November had 1.2 units and 0.6 units lower (P<0.05) ram taste, respectively, than that from ram lambs. It is concluded that to avoid off-flavour in Norwegian lamb, ram lambs should be slaughtered no later than September and hence consumer demand for fresh lamb in winter, spring and summer should preferentially be met by marketing ewe lambs.


BACKGROUND
Although the Fisher scale is commonly used to grade vasospasm risk in aneurysmal subarachnoid hemorrhage (aSAH) patients, it fails to account for increasing subarachnoid hemorrhage (SAH) thickness.

OBJECTIVE
We developed a simple quantitative scale based on maximal SAH thickness and compared its reproducibility and ability to predict symptomatic vasospasm against the Fisher scale.

METHODS
The incidence of radiographic and symptomatic vasospasm among 250 aSAH patients treated at our institution was investigated. Admission head computed tomography scans were graded according to the Fisher scale and the proposed scale, which assigns a score from 1 to 5 based on a single measurement of maximum SAH thickness. We calculated vasospasm risk per grade for the Fisher scale and the proposed scale, and compared inter- and intraobserver variability for both scales.

RESULTS
Forty-five patients (20.6%) developed symptomatic vasospasm. On the proposed scale, grade 5 patients were at highest risk, with an odds ratio for symptomatic vasospasm of 11 (95% confidence interval [CI] 2.27-53.37). Odds ratios for proposed grades 4 and 3 were 4.63 (95% CI 1.10-19.59) and 3.04 (95% CI 0.85-10.90), respectively. The odds ratio for Fisher grade 3 was 3.3 (0.96-11.30). Mean inter- and intraobserver agreement was greater for the proposed scale in comparison with the Fisher scale (κ0.65 and κ0.81 vs κ0.51 and κ0.35, respectively).

CONCLUSION
The new scale accounted for increasing SAH thickness and was superior to the Fisher scale in inter- and intraobserver agreement and in predicting symptomatic vasospasm, particularly among the highest-risk patients.


This research focuses on the modeling of the causality of sustainable tourism in Qatar. The existing literature illustrates that there is no such model available in context of economy of Qatar. The research follows the procedure of identifying the variables which influence sustainability and seeking the links between them through the contemporary literature. The hypotheses are built to study the significance of relationship between the variables which have been causally linked to each other. Second generation statistical method of Structural Equation Modeling (SEM) using Partial Least Square Method (PLSM) has been used. This method has been specifically chosen for its ability to undertake factor analysis and regression simultaneously and address the issue of multi-colinearity. Confirmatory factor analysis which has been undertaken as the indicators of measurement have proved validity through earlier studies. An instrument of measurement in the form of a questionnaire using 5-point Likert scale has been developed and validated using which the data has been collected for a sample size of 211 (response rate 62%). The respondents were the managers of tourism business in Qatar. The results have indicated that out of ten hypotheses tested six have been accepted. Based on the revelation of hypothesis testing implications have been drawn for the benefit of the tourism managers so that sustainability of tourism can be promoted. This research outcome is useful to the strategic managers of tourism in Qatar particularly in this important stage when Qatar is making preparations to host the 2022 FIFA World Cup.


Purpose

Graduate employability is a key concern for many observers particularly at a time when education is increasingly available for the masses. The purpose of this paper is to examine the impact of graduate perceived employability on job search by integrating theory of planned behavior and to identify how job search self-efficacy, subjective norms, intention and intensity change over time.

Design/methodology/approach

Data were collected from a six-wave survey study with a sample of Chinese university graduating students.

Findings

Results show that perceived employability has a positive and significant effect on job search self-efficacy, attitude, intention and intensity; and that all the repeated measuring variables (except job search attitude) decreased over time.

Practical implications

The study is useful for educators, employers and prospective students. It prompts discussion of reforms in the curriculum to increase graduate awareness of the complexity of the job search process and existing opportunities. The study could also help to explain how job search behavior changes over time.

Originality/value

The findings carry implications for both higher education research and the measures of improving graduate employability. The study fills the gap in the literature by integrating employability and the theory of planned behavior into one framework in order to analyze the process of Chinese university graduates' job search behavior.


This study examined factors that contributed to persistent use, or discontinued use, of ePortfolios beyond the program of study, as perceived by former educational technology students in a graduate program. The related literature points to contemporary research that choice, ownership, voice, and authentic learning are growing trends emerging as persistent factors that contribute to ePortfolio learning. To research whether these elements were critical to students' continued use of ePortfolios, a survey instrument was used that contained indicators related to choice, ownership, voice, and authentic learning. 141 former graduate students completed the survey and several students participated in semi-structured interview groups. Of the former graduate students, 17.7% of the students have continued to use their ePortfolio. Of those that are using the ePortfolio, the results of this study indicated that authentic projects, assessment of one's own earning, receiving feedback, and management of the ePortfolio during the learning process had significant influence on the continued or discontinued use of the ePortfolio after students graduated from the educational technology program. Open-ended interviews revealed that student participants preferred to create ePortfolios that allowed them some control, ownership, and agency over the learning process in various developmental aspects of ePortfolio learning.


We prove a spectral theorem for bimodules in the context of graph C*-algebras. A bimodule over a suitable abelian algebra is determined by its spectrum (i.e., its groupoid partial order) iff it is generated by the Cuntz-Krieger partial isometries which it contains iff it is invariant under the gauge automorphisms. We study 1-cocycles on the Cuntz-Krieger groupoid associated with a graph C*-algebra, obtaining results on when integer valued or bounded cocycles on the natural AF subgroupoid extend. To a finite graph with a total order, we associate a nest subalgebra of the graph C*-algebra and then determine its spectrum. This is used to investigate properties of the nest subalgebra. We give a characterization of the partial isometries in a graph C*-algebra which normalize a natural diagonal subalgebra and use this to show that gauge invariant generating triangular subalgebras are classified by their spectra.


The subharmonic mode is known to play an important role in a regime of boundary layer transition known as the N (Novosibirsk) or H (Herbert) type. However, until recently, an explanation for its mechanism of production from an input pulse disturbance was lacking. While it is well-known that the subharmonic mode can be amplified by triad resonance interactions, this resonance process is only able to amplify a mode that is already present, but does not show how the mode was initiated or seeded even when it was not present in the initial disturbance pulse. Subsequent researchers have proposed that nonlinear self-interaction among component modes of a wavepacket can generate the subharmonic wave in a wavepacket evolving in a low-speed Blasius boundary layer flow. This hypothesis was tested and verified in experiments, but to date little numerical work had been done. This paper aims to fill in this gap by performing direct numerical simulations (DNS) to gain a better understanding of the process of subharmonic mode generation. The theory predicts the development of the subharmonic to be contingent on the frequency bandwidth of the input disturbance. Indeed, it was found that wide bandwidth signals caused the wavepacket to transition to turbulence via the subharmonic route, whereas narrow bandwidth led to transition through Klebanoff modes (streaks). An interesting hybrid transition scenario was also investigated, in which an intermediate bandwidth input gave rise to wavepacket evolution displaying features of both Klebanoff and subharmonic transition regimes. Furthermore, in any particular transition regime, traces of the other transition mechanisms were uncovered, suggesting that there is competition among the various mechanisms, with the frequency bandwidth being an important factor in determining the path to transition.


Purpose: Delivering highly modulated radiation beams accurately to a moving tumor is a difficult task; it is crucial to have tools to evaluate the efficacy of treatment delivery in such cases. We are reporting a novel technique to evaluate 3D dose delivery to moving tumors. We are also presenting an evaluation of RapidArc treatment delivery using this method. 3D position dependant dose is crucial because the peripheral regions of the tumor may not get adequate dose due to moving out of the MLC aperture. In our procedure we accomplish the position dependant dose evaluation by creating the effects of tumor motion as follows: instead of moving the tumor, we simulate to move the active MLC's in the direction opposite to the tumor motion by the corresponding motion amplitude calculated at the time of delivery. Methods: Ten RapidArc plans were created, delivered at a Varian Trilogy unit and corresponding log files were recorded. A simulation, written in MATLAB, reads in the dynalog files, and calculates average time per each control point delivery with respect to beam initiation. A sinusoidal respiratory motion signal with a given maximum amplitude and period was implemented to obtain the motion amplitude at the time of delivery of each control point. A modified DICOM file was created where the active MLC's were moved to simulate the effects of tumor motion. This DICOM plan was reimported to Eclipse treatment planning system, and 3D dose was recalculated. To verify the accuracy of our simulation, a sample plan with 2.5cm motion amplitude was compared with delivery. Results: Simulation agrees well with the dose measurement (3%3mm gamma acceptance of 98%). GTV under‐dosing is observed for large motion amplitudes, and small tumor volumes. Conclusions: A novel technique is developed to obtain delivered 3D dose distributions for moving tumors using machine log files.


Global demand for transportation fuels will increase rapidly during the upcoming decades, and concerns about fossil-fuel consumption have stimulated research on renewable biofuels that can be sustainably produced from biological feedstocks. However, if unchecked, pathogens and parasites are likely to infect these cultivated biofuel feedstocks, greatly reducing crop yields and potentially threatening the sustainability of renewable bioenergy production efforts. In particular, clonal biofuel crops grown as monocultures at industrial scales will be confronted both by an accumulation of specialist pathogens over time, and by the rapid evolution of those pathogens. We propose possible solutions to these important sustainability problems, with a focus on managing disease risk through crop rotations and the cultivation of multi-species polycultures.


From the very beginning of Clark Gable's screen career, the life of the glamorous film star came under the scrutiny of the camera. While audiences are familiar with the public Gable as seen through the studio lens, the private Gable as seen in photos taken by members of the public, friends, and family is much less known.

This collection of candid photographs, many of them published here for the first time, has been compiled by biographer Chrystopher J. Spicer from his archives and from sources around the world. As with Spicer's acclaimed centenary biography Clark Gable (McFarland, 2002), this volume provides rare insight into the life of the man behind the star.


Older people may experience considerable loss when they endure emotional or social loneliness. Emotional loneliness is related to the loss or absence of a confidant while social loneliness describes the discrepancy between the nature of one's desired and actual social network. In this article, both concepts are examined in relation to new attendees at time-limited day center reablement programs in Northern Ireland. Using group work activities, reablement programs aim to motivate participants to continue to live independently, often in the face of later life losses. Out of a total of 91 initial respondents (range, 61–94), 13 lived with adult children (10 of whom were lone parents). Those living with, or who had daily contact with, adult children had significantly higher levels of emotional loneliness at the start of their program, but not at the end. For this sample, reductions in emotional loneliness in certain cohorts of older adults who attend these programs have been identified. In conclusion, it is proposed that fourth age losses mediate older people's living arrangement and may create greater vulnerability to emotional loneliness in those living with adult children. In addition, social groups may be effective in helping reduce emotional loneliness.


In April 2006 a small British peace-keeping force was sent to Helmand province in southern Afghanistan. Within weeks they were cut off and besieged by some of the world's toughest fighters: the infamous Taliban, who were determined to send the foreigners home again. Defence Secretary John Reid had hoped that Operation Herrick 4 could be accomplished without a shot being fired; instead, the Army was drawn into the fiercest fighting it had seen for fifty years. Millions of bullets and thousands of lives have been expended since then in an under-publicized but bitter conflict whose end is still not in sight.Some people consider it the fourth Anglo-Afghan War since Victorian times. How on earth did this happen? And what is it like for the troops on the front line of the 'War on Terror'? James Fergusson takes us to the dark heart of the battle zone. Here, in their own words and for the first time, are the young veterans of Herrick 4. Here, unmasked, are the civilian and military officials responsible for planning and executing the operation. Here, too, are the Taliban themselves, to whom Fergusson gained unique and extraordinary access. Controversial, fascinating and occasionally downright terrifying, "A Million Bullets" analyses the sorry slide into war in Helmand and asks this most troubling question: could Britain perhaps have avoided the violence altogether?


Randomized trials on the clinical utility of fetal fibronectin in women with symptoms of preterm labor have thus far failed to demonstrate benefits. We systematically reviewed the methodology of these trials to assess if these negative results may be related to their study designs. We searched the literature for randomized trials that evaluated fibronectin testing in women with symptoms of preterm labor. Study results were evaluated and five methodological criteria were assessed: (1) randomization of discordant test results, (2) use of a fixed management protocol, (3) description of interventions in relation to the test result, (4) evaluation of a learning curve, and (5) sample size calculation in agreement with the prevalence of the test results. We detected four randomized trials that met inclusion criteria. All trials allocated women to a strategy with or without availability of fibronectin results without using a discordancy design or a fixed management protocol. One study reported the given treatment in relation to the test results. Learning curves were evaluated in one study. Two studies used transport sample size calculations. The negative results of randomized trials on fetal fibronectin may be due to particular choices in their study design.


Circulating levels of small molecules or metabolites are highly heritable, but the impact of genetic differences in metabolism on human health is not well understood. In this cross-platform, genome-wide meta-analysis of 174 metabolite levels across six cohorts including up to 86,507 participants (70% unpublished data), we identify 499 (362 novel) genome-wide significant associations (p<4.9×10-10) at 144 (94 novel) genomic regions. We show that inheritance of blood metabolite levels in the general population is characterized by pleiotropy, allelic heterogeneity, rare and common variants with large effects, non-linear associations, and enrichment for nonsynonymous variation in transporter and enzyme encoding genes. The majority of identified genes are known to be involved in biochemical processes regulating metabolite levels and to cause monogenic inborn errors of metabolism linked to specific metabolites, such as ASNS (rs17345286, MAF=0.27) and asparagine levels. We illustrate the influence of metabolite-associated variants on human health including a shared signal at GLP2R (p.Asp470Asn) associated with higher citrulline levels, body mass index, fasting glucose-dependent insulinotropic peptide and type 2 diabetes risk, and demonstrate beta-arrestin signalling as the underlying mechanism in cellular models. We link genetically-higher serine levels to a 95% reduction in the likelihood of developing macular telangiectasia type 2 [odds ratio (95% confidence interval) per standard deviation higher levels 0.05 (0.03-0.08; p=9.5×10-30)]. We further demonstrate the predictive value of genetic variants identified for serine or glycine levels for this rare and difficult to diagnose degenerative retinal disease [area under the receiver operating characteristic curve: 0.73 (95% confidence interval: 0.70-0.75)], for which low serine availability, through generation of deoxysphingolipids, has recently been shown to be causally relevant. These results show that integration of human genomic variation with circulating small molecule data obtained across different measurement platforms enables efficient discovery of genetic regulators of human metabolism and translation into clinical insights.


We propose a sparse method for scalable automated variational inference (AVI) in a large class of models with Gaussian process (GP) priors, multiple latent functions, multiple outputs and non-linear likelihoods. Our approach maintains the statistical efficiency property of the original AVI method, requiring only expectations over univariate Gaussian distributions to approximate the posterior with a mixture of Gaussians. Experiments on small datasets for various problems including regression, classification, Log Gaussian Cox processes, and warped GPs show that our method can perform as well as the full method under high sparsity levels. On larger experiments using the MNIST and the SARCOS datasets we show that our method can provide superior performance to previously published scalable approaches that have been handcrafted to specific likelihood models.


This study explored the ability of the Big Horn Medicine Wheel to act as a pedagogical instrument for learning sky-earth relationships. The Big Horn Medicine Wheel is one of six large stone wheels in the northern plains that show astronomical potential. It is a National Historic Landmark and Sacred Site, created before all known histories--oral and written. Forty years ago, John Eddy and Jack Robinson proposed the first stellar alignments at the Wheel. My own study between 2009 and 2014 concluded that the Wheel's placement, its ""Place,"" reveals extensive symmetry with celestial mechanics and offers pedagogy for learning skywatching fundamentals. My study combined the methods of Native Science and Western science. I collected oral histories, compared images of the Wheel taken by various photographers over 100 years, and tracked stars and the Sun through summer and fall seasons for five years using the naked eye, binoculars, transits, GPS, and a Meade Cassegrain 8"" electronic telescope. I sought Native ceremony to prepare for the immersion of my senses in place-based cognition while allowing my intelligence to learn from ""inert"" materials such as stars, mountains, and stones. My results showed the Wheel accurately mirrors the sky using embedded stones on the ground to correspond to the major north polar stars over the Earth's 24,000 precessional cycle. The Wheel is perfectly situated on the shoulder of Medicine Mountain to make use of the dip in the northern mountainous horizon to cradle the precessional north polar stars as they roll through their millennia cycles, creating a stellar circle in the sky above the Wheel's stone circle on earth. I found the latitude of the Wheel is a ""sweet spot"" for detecting small angular changes in heliacal stars over time and for the nightly, yearly, and 5000-year circular movement of its zenith star Capella, which also holds a symmetry with the northern landscape. And I found the twenty-eight segments of the Wheel correspond to stellar grid systems based on asterisms. I make no conclusion about the builder's purpose, only about the possible pedagogical uses of the symmetry of the Wheel in its contextual Place.
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In this article I explore the relationship between laugh responses and the turns which they orient to. I consider whether it is possible to identify properties of the prior turns that the recipient may be orienting to in laughing. Thus, I begin by briefly exploring the relationship between laughter and humour in interaction. But I point to some of the difficulties in identifying what it is that makes some discourse humorous, and I argue that laughter is not simply a reaction to the perception of humour. Laughter should be considered as an action in its own right, the occurrence of which may have nothing to do with the presence of humour. Consequently, I consider the notion of the "laughable" and whilst I agree that "(v)irtually any utterance or action could draw laughter, under the right (or wrong) circumstances" (Glenn 2003: 49), I argue it is often possible to identify recurrent properties of turns treated as laughables. These properties concern the design, action and the sequential position of the turns. Thus, it seems that speakers draw from a range of resources in constructing laughables. I illustrate this by exploring a collection of instances of figurative phrases followed by laugh responses from telephone calls. I argue that in responding with laughter, recipients may orient to a cluster of properties in the prior turn. However, because laughter is an action with its own sequential implications, rather than simply a response to a prior turn, whether a recipient orients to a prior candidate laughable by laughing will depend on the nature of his or her contribution to the action sequence.


There are several techniques for testing application software for quality assurance. One possible approach is to identify the most critical features of software, and place more emphasis on those, while putting less emphasis on the not-so-critical features. Another approach is to develop a statistical procedure for identifying which test cases to perform, without necessarily identifying which ones are critical, and which are not. Such random selection leads to a more representative sample of the overall features of particular software, and defects identified are presumed to be proportionate with the proportion of defects that would have been identified based on complete exhaustive testing. A third approach is to use the technique of Orthogonal Defect Classification (ODC). This technique is used to develop a model that breaks down all the features of the AUT into categories, then with the aid of standard orthogonal arrays, selects which test cases to run.


The complexities and costs of current information architectures, infrastructures, and distributed data and software have provided impetus to emerging conceptualizations of the Service Oriented Enterprise (SOE). The foundations for SOE can be found in current applications of service oriented architecture (SOA), service oriented infrastructure (SOI), business process and workflow, computing resource virtualization, business semantics, service level agreements, increasing standardization, and other areas of applied research. This article reports on a panel held at the 2006 Americas Conference on Information Systems (AMCIS) in Acapulco, Mexico, regarding the impacts of SOE tenets on the IS field. Two organizations that are at the leading edge of the SOE continuum [American Express and Intel] in terms of vision and experiences were represented by Margaret Mitchell and George Brown. In addition, MIS academics were represented on the panel by the authors, researchers from Arizona State University. Both industry and academics brought unique perspectives. American Express' SOE approach addresses organizational structure and business intelligence project workflow issues. The company hosts one of the largest IT infrastructures capable of handling untold numbers of transactions each second. Intel's SOE approach addresses the orchestration of services and workflows in the cross-architecture environments characterizing the modern extended global enterprise. Intel is playing a lead role in establishing the OASIS (the Organization for the Advancement of Structured Information Standards) SOA Reference Model (called 'ebSOA').


In Cognitive Radio Ad Hoc Networks (CRANs) a frequently changing environment and Primary Users (PUs) channel occupancy result in a need of the searching of common control channel (CCC) by Secondary Users (SUs) in order to be able to initiate a communication. A blind date or so-called rendezvous, required before an actual medium access, is therefore a new challenge, not encountered in single channel networks. Hence, new rendezvous protocols must be designed to handle this changeability of CCC in such a way that there is a guarantee that all nodes meet periodically in reasonable periods of time. Since pseudo-random solutions do not provide this guarantee, therefore, systematic approaches are needed, where, a.o., quorum systems (QSs) become popular, especially in power saving (PS) protocols. In this study, first we perform research on the element distribution in a period of a torus quorum system (tQS) in order to produce multiple quorums satisfying Rotation Closure Property in a single torus array. We also propose a novel distributed rendezvous (RDV) protocol for CRANs, tQS-RDV. We demonstrate that tQS-RDV guarantees RDV on at least two channels with a low number of available channels (r ≤ 4), and on at least four channels otherwise.


Many of the works of the Ancients have become fragments; many works of the Moderns are so in their inception. - Friedrich Schlegel, Athenaeum, Fragment 24 Home is where one starts from. As we grow older The world becomes stranger, the pattern more complicated Of dead and living. Not the intense moment Isolated with no before and after, But a lifetime burning in every moment And not the lifetime of one man only But of old stones that cannot be deciphered. - T. S. Eliot, "East Coker"(1) It has seemed natural to find a wide gulf separating the poet of The Waste Land from that defender of aristocracy who later described his views as "classicist in literature, royalist in politics, and anglo-catholic in religion."(2) As many studies have shown, however, Eliot's writings exhibit a substantial continuity of conservative and reactionary beliefs from about 1914.(3) The aesthetics of the jagged and the juxtaposed that Pound and Eliot had adapted from T. E. Hulme also form part of this continuity.(4) Though its formal innovations appear "revolutionary," The Waste Land's aesthetics are of a piece with modernism's reactionary character and reflect the cultural politics of the British conservatism Eliot had adopted. The de-encrypting, digging up, and decoding of the poem's fragments and allusions - its dry rock and intertextual archaeology - also lead to familiar ground: Eliot's gravitation to the British empire as "home." Finally, The Waste Land may be seen as part of a British literary tradition of "reading the wreckage" that goes back at least to Edward Volney's Ruins (1791). Eliot's and Pound's use of fragmentation is qualitatively different from that of Joyce, Woolf, and H.D. I do not argue that fragmentation is an inherently reactionary aesthetic technique. Indeed it was associated with a liberal politics for Volney and Shelley. However, Eliot's and Pound's techniques of interruption and layering take on an opposite political coloration when their primary effect is to block access by the uninitiated, and when the initiation process must actually precede the aesthetic experience of a "modern" consciousness of complexity and contradictoriness. To put it another way, the aesthetic goal of Eliot's and Pound's major works becomes didactic, whereas the goal of Joyce, Woolf, and H.D. appears to be more truly "experimental," in the sense that they try - successfully, in my estimation - to evoke and explore a modern human consciousness through an aesthetics of disruption. Some political ideology inheres in all aesthetic practice, and "modernism" contradicts itself here, as in many of its other aspects. But since Eliot's 1922 poem has been so often taken to typify modernist aesthetics, it is important that we notice the consistency between his politics and his chosen form, even if that form has other possible implications. There is little doubt that Eliot's identification with right-wing Anglo-European culture matured long before The Waste Land was published. He had been attracted to reactionary politics when he encountered Charles Maurras's work in the aftermath of his temporary "conversion" to Bergsonism. Maurras had amplified French fears of racial degeneration through the Action Francaise, and his political agenda was later implemented by the Vichy government, leading to his eventual imprisonment for life as a traitor. As Peter Ackroyd points out, the Nouvelle Revue Francaise of March 1913, a publication Eliot would likely have read, described Maurras as "classique, catholique, monarchique," the trio Eliot would employ in his Oxford syllabus of winter 1916 and then later to describe himself (Ackroyd 41; cu. Schuchard). I agree with Kenneth Asher that "[T]he Maurrasien inheritance provided Eliot with a dominant intellectual framework that he retained throughout his life" and that Eliot's essay on Machiavelli in For Lancelot Andrewes (1928) was actually a covert defense of Maurras (Asher 8, 54). …


This is the first and only novel by Lydia Davis, winner of the Man Booker International Prize 2013. 'It surprised me, over and over, to find that I was with such a young man. He was twenty-two when I met him. He turned twenty-three while I knew him, but by the time I turned thirty-five I did not know where he was anymore.' Mislabelled boxes, confusing notes, wrong turnings - such are the obstacles in the way of the unnamed narrator of The End of the Story as she organises her memories of a love affair into a novel. With compassion, wit and what seems to be candour, she seeks to determine what she actually knows about herself and her past, but we begin to suspect, along with her, that given the elusiveness of memory and understanding, any tale retrieved from the past must be fiction. Back in print at last, this is Lydia Davis' first - and so far only - novel. "Extraordinary". (Newsday). "Brilliant". (New Yorker). "Breathtakingly elegant". (Details). "Beautifully written". (Marie Claire). "Astonishing". (Elle). Lydia Davis is the author of Collected Stories, one novel and six short story collections, most recently Can't and Won't. She is the recipient of a MacArthur Fellowship and was named an Officer of the Order of Arts and Letters by the French government for her fiction and her translations of modern writers, including Gustave Flaubert and Marcel Proust. She won the Man Booker International Prize in 2013.


T cell development and activation are usually accompanied by expansion and production of numerous proteins that require active translation. The eukaryotic translation initiation factor 4E (eIF4E) binds to the 5′ cap structure of mRNA and is critical for cap-dependent translational initiation. It has been hypothesized that MAPK-interacting kinase 1 and 2 (Mnk1/2) promote cap-dependent translation by phosphorylating eIF4E at serine 209 (S209). Pharmacologic studies using inhibitors have suggested that Mnk1/2 have important roles in T cells. However, genetic evidence supporting such conclusions is lacking. Moreover, the signaling pathways that regulate Mnk1/2 in T cells remain unclear. We demonstrate that TCR engagement activates Mnk1/2 in primary T cells. Such activation is dependent on Ras-Erk1/2 signaling and is inhibited by diacylglycerol kinases α and ζ. Mnk1/2 double deficiency in mice abolishes TCR-induced eIF4E S209 phosphorylation, indicating their absolute requirement for eIF4E S209 phosphorylation. However, Mnk1/2 double deficiency does not affect the development of conventional αβ T cells, regulatory T cells, or NKT cells. Furthermore, T cell activation, in vivo primary and memory CD8 T cell responses to microbial infection, and NKT cell cytokine production were not obviously altered by Mnk1/2 deficiency. Although Mnk1/2 deficiency causes decreased IL-17 and IFN-γ production by CD4 T cells following immunization of mice with myelin oligodendrocyte glycoprotein peptide in complete Freund's adjuvant, correlating with milder experimental autoimmune encephalomyelitis scores, it does not affect Th cell differentiation in vitro. Together, these data suggest that Mnk1/2 has a minimal role in T cell development and activation but may regulate non–T cell lineages to control Th1 and Th17 differentiation in vivo.


We examine the implications of tax and subsidy policies for employment in the "three worlds of welfare", Anglo-Saxon, Continental European and Scandinavian. We argue that home production is key to a proper evaluation of the employment outcomes. Anglo-Saxon low-support policies encourage more overall market employment. Continental transfer policies encourage more home production in services with close substitutes at home. Scandinavian policies give incentives to move home production in social services to the market but discourage other service activity. We find support for our claims in sectoral employment data for five representative countries, United States, Britain, France, Italy and Sweden.


By means of this article we want to demonstrate some problems concerning the common practise of identifying 'best practise examples' of Regional Innovation Systems [RIS], the pitfalls of an isolated consideration of the Scoreboard indicators in terms of assessing RIS' performance, and the complementary possibilities of an efficiency approach in this regard. Exemplary we have illustrated the differences of both approaches empirically (RIS in Europe for year 2002 and 2003; RIS in Spain considered in depth). Thus, we recommend to complement both indicators. That provides a appropriate way to identify 'best practise regions' in terms of RIS since both the amount of resources allocated to a certain RIS as well as the way they are used has to be taken into account.


Signaling initiated by binding of ligands of the transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) families to their cognate receptors stimulates the activity of Smad proteins (see Connections Map by Wrana and Attisano). In the canonical pathway, receptor Smads (R-Smads) are phosphorylated by the ligand-bound receptor complex and then interact with the common Smad, Smad4, which leads to nuclear translocation of the R-Smad/Smad4 complex and regulation of specific genes. Davis et al. show that a Smad4-independent pathway for TGF-β and BMP signaling is mediated by the interaction of R-Smads with specific primary microRNA (miRNA) transcripts and the miRNA processing complex called DROSHA, which contains the RNase III DROSHA, the DiGeorge syndrome critical region gene 8 (DGCR8), and RNA helicases p68 and p72, and that this interaction allows TGF-β and BMP to stimulate the production of the mature miRNAs, which then repress the expression of specific genes. In vascular smooth muscle cells, BMP or TGF-β signaling leads to the increased abundance of smooth muscle cell markers, such as smooth muscle α-actin (SMA). Davis et al. show that BMP2, 4, or 7 stimulated the abundance of mature miR-21 and miR-199a through a nontranscriptional mechanism in human primary pulmonary artery smooth muscle cells (PASMCs). The abundance of the primary miR-21 transcripts did not increase, only the abundance of the precursor and mature miR-21 increased in response to BMP or TGF-β. Expression of the miR-21 target PDCD4 (encoding programmed cell death 4) was decreased in response to BMP. Forced expression of PDCD4 prevented the induction of smooth muscle cell markers by BMP, and knockdown of PDCD4 with small-interfering RNA (siRNA) prevented BMP from stimulating SMA abundance. Knockdown of both BMP-specific R-Smads, Smad1 and Smad5, which are present in PASMCs, prevented BMP-induced increase in the precursor and mature miR-21; however, knockdown of Smad4 had no effect. In vitro assays suggested that Smad1, Smad5, and the TGF-β-specific Smad3 interacted with p68 through an RNA-independent mechanism and that BMP stimulated the coimmunoprecipitation of DROSHA and p68 with Smad1 or 5 from PASMCs. RNA chromatin immunoprecipitation experiments revealed that BMP4 stimulated the association of Smad1, but not Smad2 or Smad3, with primary miR-21 or miR-199a, but not miR-214, and that TGF-β stimulated the association of Smad2 or Smad3, but not Smad1, with primary miR-21 or miR-199a, but not miR-214. Thus, the interaction between the Smads and the microRNA precursor is ligand specific and microRNA specific. Nuclear extracts from Cos7 cells treated with BMP4 or TGF-β exhibited enhanced primary miR-21 processing activity. Promotion of microRNA processing may be a mechanism by which TGF-β signaling contributes to oncogenesis. In the Smad4-deficient breast cancer cell line MDA-MB-468, TGF-β stimulation increased precursor and mature miR-21 abundance, and expression of a dominant-negative TGF-β receptor subunit in these cells decreased the abundance of the precursor miR-21, suggesting that autocrine signaling by TGF-β through the Smad4-independent miRNA processing pathway may contribute to the cancerous phenotype. B. N. Davis, A. C. Hilyard, G. Lagna, A. Hata, SMAD proteins control DROSHA-mediated microRNA maturation. Nature 454, 56-61 (2008). [PubMed]


Hu proteins, together with neurone‐specific enolase (NSE), protein gene product 9.5 (PGP‐9.5), microtubule‐associated protein‐2 (MAP‐2) and tubulin beta III isoform, were evaluated immunohistochemically as neuronal markers in whole‐mount preparations and cultures obtained from the myenteric plexus of guinea‐pig small intestine. Anti‐Hu immunostaining marked the ganglion cell somas and nuclei without staining of the neuronal processes in the whole‐mounts and cultures. The ganglion cell bodies were not obscured by staining of multiple neuronal fibres and this facilitated accurate counting of the neurones. MAP2 immunostaining also provided clear images of individual neurones in both whole mounts and cultures. Immunoreactivity for NSE, PGP‐9.5 and tubulin beta III isoform provided sharp images of the ganglion cells in culture, but not in whole‐mount preparations. Strong staining of the neuronal processes in the whole‐mount preparations obscured the profiles of the ganglion cell bodies to such an extent that accurate counting of the total neuronal population was compromised. Anti‐Hu immunostaining was judged to be an acceptable method for obtaining reliable estimates of total numbers of myenteric neurones in relation to other specific histochemical properties such as histamine binding.


BACKGROUND
Reports of chronic pain and associated opioid use, abuse, and fatalities continue to increase at an alarming rate, not only in the United States but also across the globe. In light of the many resultant fatalities, multiple authors and authorities have cautioned against the excessive use of opioids. Consequently, the Food and Drug Administration, Drug Enforcement Administration, and multiple state authorities have been proposing and implementing a plethora of regulations to curb opioid overuse and abuse. In the majority of cases, pain physicians have been portrayed as the perpetrators responsible for escalating use and abuse and resultant fatalities.

OBJECTIVES
To assess the patterns of psychotherapeutic drug use and illicit drug use at the time of initial evaluation.

STUDY DESIGN
A prospective evaluation.

SETTING
A private, specialty referral interventional pain management clinic in the United States.

METHODS
Participants were all new patients presenting to interventional pain management evaluated by one physician. Inclusion criteria was patients over 18 years of age with chronic spinal pain of at least one year duration.

RESULTS
The results of this evaluation indicate that 94% of patients were on long-term opioids prior to presenting to interventional pain management. Illicit drug use is also common, although it has declined significantly. While a large proportion of individuals (45.7%) have used illicit drugs at some point in the past, current illicit drug use is present in only 7.9% of patients, both past and current use are similar to that of the general population. More importantly, a significant proportion of patients have been on opioids (high doses of more than 40 mg equivalents of morphine 48.8%) on a long-term basis, initiated and maintained by primary care physicians, prior to presenting to interventional pain management. Further, 35% were on benzodiazepines, and 9.2% on carisoprodol prior to presenting to interventional pain management.

LIMITATIONS
The limitations of this evaluation include that it is a prospective, single center evaluation by one physician that is partially dependent on subjective recall of the patient.

CONCLUSION
This study shows an overwhelming majority of patients were initiated and maintained with opioids in managing chronic noncancer pain. They were frequently on high doses over a long period of time with multiple drug combinations prescribed by primary care physicians.


In traditional research, repeated measurements lead to a sample of results, and inferential statistics can be used to not only estimate parameters, but also to test statistical hypotheses concerning these parameters. In many cases, the standard error of the estimates decreases (asymptotically) with the square root of the sample size, which provides a stimulus to probe large samples. In simulation models, the situation is entirely different. When probability distribution functions for model features are specified, the probability distribution function of the model output can be approached using numerical techniques, such as bootstrapping or Monte Carlo sampling. Given the computational power of most PCs today, the sample size can be increased almost without bounds. The result is that standard errors of parameters are vanishingly small, and that almost all significance tests will lead to a rejected null hypothesis. Clearly, another approach to statistical significance is needed. This paper analyzes the situation and connects the discussion to other domains in which the null hypothesis significance test (NHST) paradigm is challenged. In particular, the notions of effect size and Cohen's d provide promising alternatives for the establishment of a new indicator of statistical significance. This indicator attempts to cover significance (precision) and effect size (relevance) in one measure. Although in the end more fundamental changes are called for, our approach has the attractiveness of requiring only a minimal change to the practice of statistics. The analysis is not only relevant for artificial samples, but also for present-day huge samples, associated with the availability of big data.


Vivien Prideaux presents a stimulating and inspirational guide in which she shows how an amazing range rich and subtle colours can be created using indigo dye. Beautiful pictures of wonderful embroidered and quilted designs accompany detailed advice on the materials required, preparing the fabric and the dyeing methods. Using Shibori techniques - folding, pleating, clamping, stitch and pole wrapping, the author illustrates all the different stages, using clear step-by-step photographs and easy-to-follow text. A stunning sequence of inspirational projects have been specially chosen to develop skills and build confidence, with instructions on how to make a kimono, a jacket, a silk velvet quilt, a scarf and more.


The endemic Chilean edible plant Gunnera tinctoria (Nalca) is highly appreciated in the south of Chile by the small farmers. Nevertheless, no background exists about his secondary metabolites. In the present study, in the leaf from G. tinctoria was investigated the content of bioactive compounds like coumaric acid, ascorbic acid and total phenols; the antioxidant capacity was evaluated by 3-ethylbenzothiazoline-6-suslfonic acid (ABTS), oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) methods reducing sugars were measured. Finally, the biological activity was evaluated against Cladophialophora and Cryptococcus laurentii. The results suggest that the most abundant constituent in the extract were catechin (1344.97 mg/100 g dry weight) and epicatechin (1429.28 mg/100g dry weight), and was confirmed and quantified by high performance liquid chromatografy (HPLC-PDA); while the ORAC methodology showed a high antioxidant capacity (192000.0±5.91 umol Trolox Eq/100 g dry weight). On the other hand, the extract had a fungicide effect against both microorganism assayed, inhibiting the growth of Cladophialophora´s mold- and the yeast Cryptococcus laurentii. This is the first report of antioxidant capacity, bioactive compounds and biological activity of G. tinctoria, and these findings suggest that an extract prepared from the Nalca leaf may be a promising source of antioxidant and bioactive compounds and as a research object by being an antifungal and therapeutic alternative in development.

 Key words: Gunnera tinctoria, Nalca, antioxidant capacity, biological activity, nutraceutical.


Severo Martínez Peláez is the most important figure in the founding of contemporary Guatemalan historiography. His work, in particular La patria del criollo (The Homeland of the Criollo), has been viewed by historians as a starting point for advancing the reconstruction of Central American history. Additionally, his work continues to have a broad readership, who consider it a factor in understanding the present. His contributions are essential to the understanding of the colonial period in Latin America, including debates that inspired his theses concerning the character of society in that period and his historical views on indigenous peoples. Like other thinkers of the 1960s and 1970s, his focus was primarily on economic and social history, in particular class struggles. Therefore, it is necessary to understand the intellectual, political, social, and even personal conditions relevant at the time he was writing in order to thoroughly understand and appreciate his work.


General practice in current building HVAC control is to select building temperature setpoints that comply with ASHRAE Standard 55. By meeting this standard, based on the PMV comfort model, 80% of building occupants should be satisfied with their thermal environment. However, unfortunately, this is rarely the case. One possible reason for this is the variation in occupant activity and clothing that are usually assumed default values using this standard. In this work, we present an iterative-based algorithm to solve this problem. The algorithm solves the PMV inverse model equation to determine the optimal temperature setpoint while inferring human activity level from the biometric data of wearable fitness devices. The new algorithm is also designed to handle multi-occupants with conflicting comfort preferences scenario. Using this new algorithm, our results show a significant increase in occupant comfort, specifically when occupant activity is high.


Closed-form analytical expressions are presented for predicting the harmonic and intermodulation performance of electro-optic modulators synthesized from Mach-Zehnder, directional coupler, and y-fed coupler modulators. The special case of an electro-optic modulator excited by a two-tone signal is considered in detail, and the results are compared with previously reported results obtained by using a fast Fourier transform.


We develop a new statistical method for estimating functional connectivity between neurophysiological signals represented by a multivariate time series. We use partial coherence as the measure of functional connectivity. Partial coherence identifies the frequency bands that drive the direct linear association between any pair of channels. To estimate partial coherence, one would first need an estimate of the spectral density matrix of the multivariate time series. Parametric estimators of the spectral density matrix provide good frequency resolution but could be sensitive when the parametric model is misspecified. Smoothing-based nonparametric estimators are robust to model misspecification and are consistent but may have poor frequency resolution. In this work, we develop the generalized shrinkage estimator, which is a weighted average of a parametric estimator and a nonparametric estimator. The optimal weights are frequency-specific and derived under the quadratic risk criterion so that the estimator, either the parametric estimator or the nonparametric estimator, that performs better at a particular frequency receives heavier weight. We validate the proposed estimator in a simulation study and apply it on electroencephalogram recordings from a visual-motor experiment.


Accidents caused by drivers' drowsiness behind the steering wheel have a high fatality rate because of the discernible decline in the driver's abilities of perception, recognition, and vehicle control abilities while sleepy. Preventing such accidents caused
by drowsiness is highly desirable but requires techniques for continuously detecting, estimating, and predicting the level of alertness of drivers and delivering effective feedback to maintain maximum performance.
The main objective of this research study is to develop a reliable metric and system for the detection of driver impairment due to drowsiness. More specifically, the
goal of the research is to develop the best possible metric for detection of drowsiness, based on measures that can be detected during driving. This thesis describes the new studies that have been performed to develop, validate, and refine such a metric. A computer vision system is used to monitor the driver's physiological eye blink behaviour. The novel application of green LED illumination overcame one of the major difficulties of the eye sclera segmentation problem due to illumination changes. Experimentation in a driving simulator revealed various visual cues, typically
characterizing the level of alertness of the driver, and these cues were combined to infer the drowsiness level of the driver. Analysis of the data revealed that eye blink duration and eye blink frequency were important parameters in detecting drowsiness. From these measured parameters, a continuous measure of drowsiness, the New Drowsiness Scale (NDS), is derived. The NDS ranges from one to ten, where a decrease in NDS corresponds to an increase in drowsiness. Based upon previous research into the effects of drowsiness on driving performance, measures relating to the lateral placement of the vehicle within the lane are of particular interest in this study. Standard deviations of average deviations were measured continuously throughout the study. The NDS scale, based upon the gradient of the linear regression of standard
deviation of average blink frequency and duration, is demonstrated as a reliable method for identifying the development of drowsiness in drivers. Deterioration of driver performance (reflected by increasingly severe lane deviation) is correlated with a decreasing NDS score. The final experimental results show the validity of the proposed model for driver drowsiness detection.


Abstract Fractures are important for shale-gas reservoirs with low matrix porosity because they increase the effective reservoir space and migration pathways for shale gas, thus favouring an increased volume of free gas and the adsorption of gases in shale reservoirs, and they increase the specific surface area of gas-bearing shales which improves the adsorption capacity. We discuss the characteristics and dominant factors of fracture development in a continental organic matter-rich shale reservoir bed in the Yanchang Formation based on observations and descriptions of fracture systems in outcrops, drilling cores, cast-thin sections and polished sections of black shale from the Upper Triassic Yanchang Formation in the SE Ordos Basin; detailed characteristics and parameters of fractures; analyses and tests of corresponding fracture segment samples; and the identification of fracture segments with normal logging. The results indicate that the mineral composition of the continental organic-matter-rich shale in the Yanchang Formation is clearly characterized by a low brittle mineral content and high clay mineral content relative to marine shale in the United States and China and Mesozoic continental shale in other basins. The total content of brittle minerals, such as quartz and feldspar, is c. 41%, with quartz and feldspar accounting for 22% and 19% respectively, and mainly occurring as plagioclase with small amounts of carbonate rocks. The total content of clay minerals is high at up to 52%, and mainly occurs as a mixed layer of illite-smectite (I/S) which accounts for more than 58% of the total clay mineral content. The Upper Triassic Yanchang Formation developed two groups of fracture (joint) systems: a NW–SE-trending system and near-E–W-trending system. Multiple types of fractures are observed, and they are mainly horizontal bedding seams and low-dip-angle structural fractures. Micro-fractures are primarily observed in or along organic matter bands. Shale fractures were mainly formed during Late Jurassic – late Early Cretaceous time under superimposed stress caused by regional WNW–ESE-trending horizontal compressive stress and deep burial effects. The extent of fracture development was mainly influenced by multiple factors (tectonic factors and non-tectonic factors) such as the lithology, rock mechanical properties, organic matter abundance and brittle mineral composition and content. Specifically, higher sand content has been observed to correspond to more rapid lithological changes and more extensive fracture development. In addition, higher organic matter content has been observed to correspond to greater fracture development, and higher quartz, feldspar and mixed-layer I/S contents have been observed to correspond to more extensive micro-fracture development. These results are consistent with the measured mechanical properties of the shale and silty shale, the observations of fractures in cores and thin-sections from more than 20 shale-gas drilling wells, and the registered anomalies from gas logging.


One way of reducing carbon emissions is to reduce carbon emissions from consumption. Quantitative information about these emissions helps to better understand the reduction potential. This article aims to provide carbon footprint data for students of the University of Applied Science in Konstanz, Germany. The study includes almost 10% of the University's students. Data on emission patterns was collected via questionnaires and calculated by a web-based carbon calculator. The study analyses personal carbon footprints and, more detailed, carbon emissions from consumption categories heating, electricity, mobility (land travel and aviation) and food. The findings show average students' annual carbon footprint to be10.9t CO2eq and in the same order of magnitude as the German average. While students cause less emissions through heating because of smaller living space per person, they cause significantly more emissions by aviation. Female students tend to have higher emissions from aviation, instead male students have higher emissions from food (due to more meat in their diet). Business students have higher emissions than others, mainly because they are tending to fly more. The student carbon footprint is far above climate protection goals formulated for 2050.


Type III protein secretion is essential for the pathogenicity of Pseudomonas syringae on its host plants. Expression of HrpA, a major component of the type III secretion system (T3SS)-associated pilus, was studied both in plant leaves and in vitro using reporter genes. We found that induction of the hrpA promoter was stronger in plants than in vitro, and that the induction was enhanced by both host and nonhost plants of P. syringae pv. tomato. In vitro, the expression was enhanced by cell-free exudates from plant cell suspension cultures, added into the minimal medium. Further analysis of the plant-cell-derived, hrpA-inducing factors showed that they were small and water-soluble compounds, which could signal P. syringae the proximity of living plant cells. We also studied the production and secretion of native HrpA protein in vitro, and detected a plant-signal-dependent increase in HrpA secretion. In contrast to HrpA, the intracellular accumulation or secretion of the other T3SS-dependent proteins were not significantly increased, despite the presence of plant cell-derived, promoter-inducing factors. Thus, the accumulation of HrpA pilin seems to be subjected to a distinct post-transcriptional regulation.


Chinese hamster ovary cells were used to examine the effect of emetine upon the toxicity of T-2 toxin and several related trichothecene inhibitors of polypeptide synthesis. Emetine inhibited protein synthesis and T-2 toxin-cell association in a concentration-dependent manner. The dose-response curves for these two effects were nearly identical. Over a narrow concentration range (0.3-3.0 micrograms/ml), emetine's inhibition of protein synthesis was partially reversible, whereas its inhibition of toxin-cell association was maintained for extended periods. This sustained inhibition of toxin-cell association, resulted in "desensitized" cells with reduced sensitivity to the inhibitory effects of T-2 toxin on protein synthesis. Similar results were obtained when emetine-preincubated cells were challenged with diacetoxyscirpenol, verrucarin A and roridin A. In contrast, there were no measurable effects of emetine upon the response of the cells to the less potent trichothecenes, deoxynivalenol, T-2 tetraol and verrucarol. In addition to emetine, several other inhibitors of polypeptide synthesis were examined for their effects on T-2 toxin-cell association and sensitivity to T-2 toxin. Of these, only cycloheximide inhibited toxin-cell association. Unlike emetine, sustained protection against the effects of T-2 toxin was not observed with cycloheximide.


This work by Nancy deClaisse-Walford, Rolf Jacobson, and Beth Tanner is the most complete and detailed one-volume commentary available on the Psalms. Significantly, the volume reflects the combined insights of three superior (younger) biblical scholars. DeClaisse-Walford, Jacobson, and Tanner offer a succinct introduction to the Psalter, a new translation of all the psalms that takes special account of the Dead Sea Scrolls, and individual entries on each psalm unit. Throughout the book they draw on state-of-theart research on the canonical shape and shaping of the Psalter and evidence a nuanced attention to the poetic nature of the psalms.


Tick-borne encephalitis virus (TBEV) is a causative agent an extremely dangerous infectious disease, often characterized by damage to the central nervous system, which sometimes leads to serious health problems, such as disability and even death. Currently, there is no global organized platform that could help researchers to study the virus, understand its evolution and localization, conduct a variety of modern mathematical and phylogenetic analyzes, automatically draw conclusions and visualize them for interpretation and decision making. Such a system could lead, as a result, to more effective actions for predicting the virus evolution. In this paper, we propose an online platform called TBEV analyzer which serves as an analytical tool in two directions - fundamental research on the virus evolution and the solution of practical problems related to public health. The platform has been developed specifically for virologists, molecular epidemiologists, evolutionists and other researchers who work with tick-borne encephalitis virus. The platform has two major benefits: first, it allows the user to concentrate on the result of analysis without concerning about computational aspects, and second, with reproducibility of system, it provides unique results associated with specific target query.


This is the first installment of a two-part tutorial. The goal of the first part is to give the reader a basic understanding of the technical issues and types of approaches in solving the basic path-planning or obstacle-avoidance problem. The second installment will cover more advanced issues, including feedback, differential constraints, and uncertainty. Note that this is a brief tutorial rather than a comprehensive survey of methods. For the lat ter, consult some of the recent textbooks. Motion planning involves getting a robot to automatically determine how to move while avoiding collisions with obstacles. Its original formulation, called the piano mov er's problem, is imagined as determining how to move a complicated piece of furniture through a cluttered house. Have you ever argued about how to move a sofa up a stairwell? It has been clear for several decades that getting robots to reason geometrically about their environments and synthesize such plans is a fundamental difficulty that recurs all over robotics.


Co-conditioning and dewatering behaviors of alum sludge and waste activated sludge were investigated. Two different sludges were mixed at various ratios (2:1; 1:1; 1:2; 1:4) for study. Capillary suction time (CST) and specific resistance to filtration (SRF) were utilized to assess sludge dewaterability. Relatively speaking, waste activated sludge, though of higher solid content, was more difficult to be dewatered than alum sludge. It was found that sludge dewaterability and settlability became better with increasing fraction of alum sludge in the mixed sludge. Dosage required of the cationic polyelectrolyte (KP201C) for dewatering was reduced as well. It is proposed that alum sludge acts as skeleton builder in the mixed sludge, and renders the mixed sludge more incompressible which is beneficial for sludge dewatering. Implications of the results of the study to the sludge management plan for Taipei City that generates both alum sludge and waste activated sludge at significant amount are also discussed. The current sludge treatment and disposal plan in Metropolitan Taipei could be made more cost-effective.


In 1598, the year that Duke Cesare d'Este (1562–1628) lost Ferrara to papal forces and moved the capital of his duchy to Modena, the papal Inquisition in Modena was elevated from vicariate to full inquisitorial status. Despite initial clashes with the duke, the tribunal began not only to prosecute heretics and blasphemers, but also professing Jews. Such a policy towards infidels by an organization appointed to inquire into heresy (inquisitio haereticae pravitatis) seems unusual. How did the papal Inquisition come to assume authority and prosecute Jews in early modern Italy? Examination of trial procedure of Jews as opposed to that of Christians will help decide if there is anything distinctive about the Holy Office's treatment of Jews. It will be argued that inquisitorial tribunals were disarming the Jewish threat to Christian society, not for its own sake, but as an attempt to impose social and religious discipline on the Christian community.


This preliminary study aims to describe the challenges that the teachers face in teaching English speaking to their students in Aceh. Speaking is perceived as the most fundamental skill to acquire since the onset of the communicative era is treated as the ultimate goal of language teaching, and its proper development has become the attention of both teachers and learners. However, it is also a commonly recognized fact that achieving proficiency in foreign language speaking is not an easy task. Thus, it is important for teachers to be aware of the challenges in teaching speaking so that they can seek for solutions to them. Accordingly, this preliminary study collected data by interviewing two teachers from a public senior high school in Bireuen, Aceh. These teachers have been teaching English for the past ten years in the school, respectively. They revealed that the challenges they encountered most in teaching speaking are students' lack of vocabulary, pronunciation problems, nothing to say, lack of motivation and the use or interferecnes of the mother tongue. Thus, the teachers do their best to overcome these challenges along the process of their teaching in the classroom, and some of their efforts are also discussed in the paper. Future studies are suggested to collect data from other sources such as observations in the classroom during the teaching and learning process and gather information from students themselves through interviews and questionnaires.


In amorphous/crystalline silicon heterojunction solar cells, optical losses can be mitigated by replacing the amorphous silicon films by wider bandgap amorphous silicon oxide layers. In this article, we use stacks of intrinsic amorphous silicon and amorphous silicon oxide as front intrinsic buffer layers and show that this increases the short-circuit current density by up to 0.43 mA/cm2 due to less reflection and a higher transparency at short wavelengths. Additionally, high open-circuit voltages can be maintained, thanks to good interface passivation. However, we find that the gain in current is more than offset by losses in fill factor. Aided by device simulations, we link these losses to impeded carrier collection fundamentally caused by the increased valence band offset at the amorphous/crystalline interface. Despite this, carrier extraction can be improved by raising the temperature; we find that cells with amorphous silicon oxide window layers show an even lower temperature coefficient than referenc...


Background. The Stellenbosch University Rural Medical Educational Partnership Initiative (SURMEPI) aims to increase the quality and retention of medical doctors, and regionally relevant research. Strengthening evidence-based healthcare (EBHC) knowledge and skills at an undergraduate level is important within this context. Objectives. To assess and describe the current undergraduate medical EBHC curriculum in order to identify opportunities to enhance EBHC teaching, and to explore challenges related to EBHC experienced by recently graduated doctors. Methods. We used methodological triangulation to assess current EBHC teaching and learning through a document review and a survey of recent graduates. We extracted learning outcomes from module guides that related to prespecified EBHC competencies. Our electronic survey collected quantitative data, which were analysed with SPSS, and qualitative data, which were coded with ATLAS.ti and grouped into emerging themes. Results. EBHC teaching was fragmented and concentrated in the first and last phase of the medical curriculum. Most survey respondents agreed that it was important to learn EBHC at undergraduate level, and that there was a need for increased teaching of certain EBHC competencies. Recently graduated doctors identified lack of access to literature as the main challenge when practising EBHC. Other challenges included time constraints, work overload, lack of EBHC skills, lack of self-motivation, applicability of the evidence and the work environment. Conclusion. Recent graduates felt that they needed more EBHC learning opportunities within the undergraduate medical curriculum. Existing EBHC teaching and learning for undergraduate medical students need to be enhanced by integrating EBHC into clinical modules and scaffolding it throughout all the phases of the curriculum.


Abstract: The upper Monongahela and lower Dunkard groups of southeastern Ohio include abundant paleosols containing ichnofossils as well as vertebrate, invertebrate, and plant body fossils. These paleosols formed on diverse Late Pennsylvanian to Early Permian landscapes in an alluvial setting. This study investigated small-scale lateral and vertical variability of the paleosols that formed at the distal edge of the Dunkard Basin. Three detailed, 32-m thick stratigraphic sections across a 70 m outcrop were measured in eastern Athens County, Ohio. Seven pedotypes representing soil formation in nine subenvironments were identified through bulk geochemical, clay mineralogical, and petrographic analyses as well as a detailed study of the ichnofossils, body fossils, and macromorphological paleosol properties. Ichnofossils were abundant and included rhizoliths, actively to passively filled burrows, and coprolites. These ichnofossils were produced by various plants, larval and adult arthropods, and micro- to macro-vertebrates. Body fossils within the paleosols included micro- and macro bone fragments and teeth, compression plant fossils, ostracodes, and gastropods. Vertical transitions among the subenvironments were due to both fluvial channel migration and climatic changes. Precipitation was seasonally distributed with a range of mean annual precipitation (MAP) from 300–1000 mm/yr through the section. This study demonstrates that by investigating the small-scale lateral and vertical variations in paleosols, finer resolution paleoclimatic, paleoenvironmental, and paleoecological reconstructions are possible.


Shape constraints play an increasingly prominent role in nonparametric function estimation. While considerable recent attention has been focused on log concavity as a regularizing device in nonparametric density estimation, weaker forms of concavity constraints encompassing larger classes of densities have received less attention but offer some additional flexibility. Heavier tail behavior and sharper modal peaks are better adapted to such weaker concavity constraints. When paired with appropriate maximal entropy estimation criteria, these weaker constraints yield tractable, convex optimization problems that broaden the scope of shape constrained density estimation in a variety of applied subject areas. In contrast to our prior work, Koenker and Mizera [Ann. Statist. 38 (2010) 2998–3027], that focused on the log concave ($\alpha=1$) and Hellinger ($\alpha=1/2$) constraints, here we describe methods enabling imposition of even weaker, $\alpha\leq0$ constraints. An alternative formulation of the concavity constraints for densities in dimension $d\geq2$ also significantly expands the applicability of our proposed methods for multivariate data. Finally, we illustrate the use of the Renyi divergence criterion for norm-constrained estimation of densities in the absence of a shape constraint.


ABSTRACT Eosinophils are frequently found in increased numbers in a variety of chronic fibrotic diseases; however, their role in the development of hepatic fibrosis has not been dissected in vivo. Here, we used interleukin-5 (IL-5) knockout (KO) mice to determine whether eosinophils contribute to the progressive liver fibrosis that develops in response to chronic Schistosoma mansoni infection. Although infection intensities were similar in C57BL/6 and IL-5 KO mice, the average size of granulomas was significantly smaller in both acutely and chronically infected IL-5 KO mice. Their granulomas were also completely devoid of eosinophils. In addition, the knockout mice displayed over a 40% reduction in hepatic fibrosis by week 16 postinfection. The reduced fibrosis was associated with increased production of the antifibrotic cytokine gamma interferon. Moreover, although IL-13 production did not decrease consistently in the absence of IL-5, IL-13-triggered responses were substantially reduced in the granulomatous tissues. This was confirmed by analyzing the expression of several genes associated with alternative macrophage activation, including arginase 1, Fizz-1, and YM-1. Importantly, all of these IL-13-regulated genes have been linked with the mechanisms of wound healing and fibrosis. In addition to IL-5 polarizing the antigen-specific CD4+ Th2 cell response, we found that granuloma eosinophils were themselves a significant source of IL-13. Thus, by producing profibrotic mediators and polarizing the Th2 response, these findings illustrate both direct and indirect roles for eosinophils and IL-5 in the pathogenesis of schistosomiasis-induced liver fibrosis. Thus, inhibiting the activity of IL-5 or eosinophils may prove effective for a variety of chronic fibrotic diseases.


Social insects are an abundant source of inspirations for swarm robotics thanks to their impressive cooperation which enables them to complete complex and difficult tasks. One of the very typical examples of such ability is found in the nest building activities of weaver ants where they collaborate to find and co-manipulate the softest part of a natural leaf to successfully curl it up. Inspired by this special feature of the weaver ant leaf-curling task, this thesis aims to study methodologies for swarm of simple robots to cooperate, to find and co-manipulate the most suitable object (the softest part of the leaf in this case) in complex working environments.

The study started with the purpose of finding a suitable communication method and decision making algorithm for swarm robots to replicate the leaf-curling task of weaver ants. The study has shown that, without direct communication, using only indirect communication via changes of the working environment – the method called sematectonic stigmergy, simple robots can effectively collaborate to find and co-lift the softer edge. Playing the key role in achieving success for swarm robots is the decision making algorithm which can exploit the simple information that robots receive via sematectonic stigmergy.

From the algorithm for the original robotic leaf-curling task, a more complete methodology was developed to help swarms of simple robots solve the generalized leaf curling task, in which the working environment is highly complex and completely unknown.

The developed algorithms were investigated thoroughly using mathematical models and a comprehensive dynamic simulation model. The main advantages of each method were also verified by experiments with a group of physical robots on an artificial leaf.


How should legal disputes be allocated between litigation and arbitration? Given strong incentives for many actors to arbitrate everything, the question turns fundamentally on the scope of arbitration under the applicable law. In "Re-Inventing Arbitration: How Expanding the Scope of Arbitration Is Re-Shaping Its Form and Blurring the Line Between Private and Public Adjudication," Professor Deborah Hensler and Damira Khatam posit that the "public" or "private" nature of a dispute provides the key to whether it belongs in arbitration. While arbitration of private disputes is ok, disputes with "public policy dimensions" belong in the courts. Hensler and Khatam therefore suggest that Congress override Supreme Court decisions mandating arbitration of employment and consumer disputes, which, they contend, would restore domestic arbitration to its proper sphere. But can disputes really be divided into public and private categories that provide the key to whether they belong in arbitration? This Response suggests that on close examination it is exceedingly difficult to identify a reliable proxy for the public or private nature of a dispute. The absence of such a proxy suggests there is an inescapably political dimension to how disputes are allocated between litigation and arbitration. Whether a category of disputes should be heard in a public court because the disputes impact the public interest turns out to depend on contested judgments about where the public interest lies. This, in turn, suggests a more fundamental reason for Congress to revisit the scope of arbitration under the Federal Arbitration Act. If the allocation of disputes between litigation and arbitration is an inescapably political question, it should ideally be addressed by an institution accountable to democratic politics.


Problem coughing is thought to be one of the commonest causes for medical consultations as it generates much anxiety in patients and reduces quality of life. Coughing is an important protective reflex and patients with inadequate cough will experience recurrent chest infections with areas of the lung consolidated and collapsed. Simply trying to suppress coughing is therefore often illogical. However, because coughing is distressful both patients and their doctors feel under pressure to do something resulting in the widespread use of cough medicines many of which, while available over the counter, do not work. It is important that doctors, when faced with a patient with problem coughing, attempt to make a diagnosis so that disease specific treatment if available can be started. Unfortunately, even when a specific diagnosis has been made there is sometimes no effective therapy available. This is true of the prolonged coughing in pertussis in young adults. While doing this the doctor needs to decide whether the patient has features of a serious chronic disease or simply has a transient condition that will almost certainly resolve (e.g., prolonged coughing after an upper respiratory tract infection). The majority of respiratory illnesses are associated with coughing and some extra-pulmonary causes are known to be associated with cough such as gastro-oesophageal reflux, psychogenic cough and external auditory canal wax stimulating Arnold's reflex. Because there are so many differing causes for cough misdiagnosis is very possible. Given that there are many different causes of coughing of which some are trivial and transient and some coughs may indicate the presence of a serious underlying pathology it is important for doctors to have a structured approach (1). Cough clinical guidelines, therefore, should help busy working clinicians to have an approach to patients who present with problem coughing and their overarching aim is to improve patient care. Cough guidelines should be trust worthy and evidence based, they should be presented in a useable format and highlight areas of uncertainty where further research is needed.


Adobe Flex: Training from the Source is the best-selling and most trusted resource for learning about Adobe Flex. Written by a team of authors with practical experience as consultants, mentors and developers of courseware, this book/CD uses project-based tutorials, and is designed to teach beginning Flex developers the details of building and architecting real-world rich internet applications using Flash Builder incorporating MXML and ActionScript 3.0. The book includes a CD that contains all the files used in the lessons, plus completed projects for comparison. This latest edition includes complete coverage of new Flex 4.5 features, such as new enhancements to the Spark architecture and component set. It will also show you how to take advantage of the improvements to core Flex infrastructure for large application development.


Differentiation of naïve CD4+ T cells into the T helper type 1 (TH1) phenotype requires signaling by interleukin (IL)-12 through the IL-12 receptor β2 chain, and activation of the signal transducer and activator of transcription (STAT) 4. On the other hand, induction of the TH2 phenotype from naïve CD4+ T cells requires IL-4 binding of the functional IL-4 receptor and activation of STAT6. A concomitant reduction of IL-12Rβ2 is also observed. When naïve CD4+ T cells are treated simultaneously with both IL-4 and IL-12, the IL-4 effects predominate and TH2 cells develop. Thus, it has been hypothesized that IL-4-dependent decreases in IL-12Rβ2 expression prevent IL-12 signals, and this allows for differentiation into the TH2 phenotype. However, it is not known what effect constitutive expression of the IL-12Rβ2 chain has on the development of TH2 cells. Nishikomori et al. found that IL-12Rβ2 transgenic CD4+ T cells differentiated into TH2 cells in the presence of IL-4, or IL-4 and IL-12. IL-12 treatment of TH2 cells expressing functional IL-12 receptors did not induce the conversion of these cells into the TH1 phenotype if the cells were pretreated under TH2 conditions. Additionally, the authors found that the IL-12 receptor-bearing TH2 cells continued to synthesize IL-4 even in the presence of IL-12 in the growth medium. Thus, TH2 cells are resistant to TH1 conversion, and decreased expression of IL-12Rβ2 is not necessary for the establishment of the TH2 phenotype. Nishikomori, R., Ehrhardt, R.O., and Strober, W. (2000) T helper type 2 cell differentiation occurs in the presence of interleukin-12 receptor β2 chain expression and signaling. J. Exp. Med. 191: 847-858. [Abstract] [Full Text]


Decolonizing Native Histories is an interdisciplinary collection that grapples with the racial and ethnic politics of knowledge production and indigenous activism in the Americas. It analyzes the relationship of language to power and empowerment, and advocates for collaborations between community members, scholars, and activists that prioritize the right of Native people to decide how their knowledge is used. The contributors - academics and activists, indigenous and non-indigenous, from disciplines including history, anthropology, linguistics, and political science - explore the challenges of decolonization. These wide-ranging case studies consider how language, the law, and the archive have historically served as instruments of colonialism and how they can be creatively transformed in constructing autonomy. The collection highlights points of commonality and solidarity across geographical, cultural, and linguistic boundaries and also reflects deep distinctions between North and South. Decolonizing Native Histories looks at Native histories and narratives in an internationally comparative context, with the hope that international collaboration and understanding of local histories will foster new possibilities for indigenous mobilization and an increasingly decolonized future.