Signal recognition particle (SRP) and signal recognition particle receptor (SR) are evolutionarily conserved GTPases that deliver secretory and membrane proteins to the protein-conducting channel Sec61 complex in the lipid bilayer of the endoplasmic reticulum in eukaryotes or the SecYEG complex in the inner membrane of bacteria. Unlike the canonical Ras-type GTPases, SRP and SR are activated via nucleotide-dependent heterodimerization. Upon formation of the SR•SRP targeting complex, SRP and SR undergo a series of discrete conformational changes that culminate in their reciprocal activation and hydrolysis of GTP. How the SR•SRP GTPase cycle is regulated and coupled to the delivery of the cargo protein to the protein-conducting channel at the target membrane is not well-understood. Here we examine the role of the lipid bilayer and SecYEG in regulation of the SRP-mediated protein targeting pathway and show that they serve as important biological cues that spatially control the targeting reaction. In the first chapter, we show that anionic phospholipids of the inner membrane activate the bacterial SR, FtsY, and favor the late conformational states of the targeting complex conducive to efficient unloading of the cargo. The results of our studies suggest that the lipid bilayer acts as a spatial cue that weakens the interaction of the cargo protein with SRP and primes the complex for unloading its cargo onto SecYEG. In the second chapter, we focus on the effect of SecYEG on the conformational states and activity of the targeting complex. While phospholipids prime the complex for unloading its cargo, they are insufficient to trigger hydrolysis of GTP and the release of the cargo from the complex. SecYEG modulates the conformation of the targeting complex and triggers the GTP hydrolysis from the complex, thus driving the targeting reaction to completion. The results of this study suggest that SecYEG is not a passive recipient of the cargo protein; rather, it actively releases the cargo from the targeting complex. Together, anionic phospholipids and SecYEG serve distinct yet complementary roles. They spatially control the targeting reaction in a sequential manner, ensuring efficient delivery and unloading of the cargo protein. In the third chapter, we reconstitute the transfer reaction in vitro and visualize it in real time. We show that the ribosome-nascent chain complex is transferred to SecYEG via a stepwise mechanism with gradual dissolution and formation of the contacts with SRP and SecYEG, respectively, explaining how the cargo is kept tethered to the membrane during the transfer and how its loss to the cytosol is avoided. In the fourth chapter, we examine interaction of SecYEG with secretory and membrane proteins and attempt to address the role of a novel insertase YidC in this interaction. We show that detergent-solubilized SecYEG is capable of discriminating between the nascent chains of various lengths and engages a signal sequence in a well-defined conformation in the absence of accessory factors. Further, YidC alters the conformation of the signal peptide bound to SecYEG. The results described in this chapter show that YidC affects the SecYEG-nascent chain interaction at early stages of translocation/insertion and suggest a YidC-facilitated mechanism for lateral exit of transmembrane domains from SecYEG into the lipid bilayer.


With the advancement of the Internet age, the need for more and more data distribution to different users on different types of networks in short time and at a nominal cost has also increased significantly. To achieve these objectives several technologies have been used with different sorts of implementations but only few survive in today's very competitive financial market. The objective of our thesis is to study the technology and the financial market of the Content Distribution Network, which has up till now proven to be a very good and effective way to meet the always increasing demands of the rapidly developing Internet age. In this thesis, we will not only discuss the taxonomies of the Content Distribution Network or CDN, its different types and implementations but we will also focus on its financial issues and its performance in the financial market. The aim of our project is to study and understand the technology of the CDN, the problems related to its implementations, research work and its money matters.


Information about rainfall-runoff processes is essential for hydrological analyses, modelling and water- management applications. A hydrological, or diagnostic, sig- nature quantifies such information from observed data as an index value. Signatures are widely used, e.g. for catchment classification, model calibration and change detection. Un- certainties in the observed data - including measurement in- accuracy and representativeness as well as errors relating to data management - propagate to the signature values and re- duce their information content. Subjective choices in the cal- culation method are a further source of uncertainty. We review the uncertainties relevant to different signa- tures based on rainfall and flow data. We propose a generally applicable method to calculate these uncertainties based on Monte Carlo sampling and demonstrate it in two catchments for common signatures including rainfall-runoff thresholds, recession analysis and basic descriptive signatures of flow distribution and dynamics. Our intention is to contribute to awareness and knowledge of signature uncertainty, including typical sources, magnitude and methods for its assessment. We found that the uncertainties were often large (i.e. typ- ical intervals of 10-40 % relative uncertainty) and highly variable between signatures. There was greater uncertainty in signatures that use high-frequency responses, small data subsets, or subsets prone to measurement errors. There was lower uncertainty in signatures that use spatial or temporal averages. Some signatures were sensitive to particular uncer- tainty types such as rating-curve form. We found that sig- natures can be designed to be robust to some uncertainty sources. Signature uncertainties of the magnitudes we found have the potential to change the conclusions of hydrological and ecohydrological analyses, such as cross-catchment com- parisons or inferences about dominant processes.


An in situ approach for the synthesis of Fe3O4 nanoparticles combined with a SiO2 coating process was employed to prepare Fe3O4@GNF@SiO2 nanocapsules. Graphitised nanofibres (GNF) were initially filled with iron(III) acetylacetonate, and used as a precursor for the synthesis of ultrasmall Fe3O4 nanoparticles (4.6 nm in diameter) inside the cavities of GNF (Fe3O4@GNF) with a high density. By using a silica coating process, Fe3O4@GNF@SiO2 nanocapsules were obtained. The presence of the silica shell not only prevented leakage of the nanoparticles from inside the GNF but also protected the magnetite nanoparticles from dissolution, even in harsh acidic conditions. Furthermore, the silica coating resulted in an increased dispersability of the nanocomposites in water. Magnetic resonance imaging (MRI) studies indicate relatively high relaxivities for Fe3O4@GNF nanocomposites and Fe3O4@GNF@SiO2 nanocapsules revealing the potential application of these hybrid materials for bioimaging. Therefore, the coating of filled GNF with silica is as an excellent strategy for the protection of encapsulated payloads.


This study addresses the interpretation of a Dutch homonymic suffix, s, as it appears in Dutch compounds. In a series of reading experiments we manipulated the presence versus absence of this suffix in existing compounds as well as in compounds with a pseudoword as left constituent. We observed an asymmetry in the effects of addition and deletion, with deletion not affecting response latencies, and addition leading to increased identification latencies and, conditional on the phonological structure of the left constituent, to a plural interpretation of the left constituent. Our results illustrate how phonological and semantic constraints conspire to induce a plural interpretation of this homonymic suffix.


Purpose: Prospectively identifying who will benefit from adjuvant chemotherapy (ACT) would improve clinical decisions for non–small cell lung cancer (NSCLC) patients. In this study, we aim to develop and validate a functional gene set that predicts the clinical benefits of ACT in NSCLC. Experimental Design: An 18-hub-gene prognosis signature was developed through a systems biology approach, and its prognostic value was evaluated in six independent cohorts. The 18-hub-gene set was then integrated with genome-wide functional (RNAi) data and genetic aberration data to derive a 12-gene predictive signature for ACT benefits in NSCLC. Results: Using a cohort of 442 stage I to III NSCLC patients who underwent surgical resection, we identified an 18-hub-gene set that robustly predicted the prognosis of patients with adenocarcinoma in all validation datasets across four microarray platforms. The hub genes, identified through a purely data-driven approach, have significant biological implications in tumor pathogenesis, including NKX2-1, Aurora Kinase A, PRC1, CDKN3, MBIP, and RRM2. The 12-gene predictive signature was successfully validated in two independent datasets (n = 90 and 176). The predicted benefit group showed significant improvement in survival after ACT (UT Lung SPORE data: HR = 0.34, P = 0.017; JBR.10 clinical trial data: HR = 0.36, P = 0.038), whereas the predicted nonbenefit group showed no survival benefit for 2 datasets (HR = 0.80, P = 0.70; HR = 0.91, P = 0.82). Conclusions: This is the first study to integrate genetic aberration, genome-wide RNAi data, and mRNA expression data to identify a functional gene set that predicts which resectable patients with non–small cell lung cancer will have a survival benefit with ACT. Clin Cancer Res; 19(6); 1577–86. ©2013 AACR.


We theoretically propose and demonstrate experimentally a Coherent Direct Sequence OCDMA en/decoder for multi-channel WDM operation based on a single device. It presents a broadband spectral envelope and a periodic spectral pattern that can be employed for en/decoding multiple sub-bands simultaneously. Multi-channel operation is verified experimentally by means of Multi-Band Super Structured Fiber Bragg Gratings with binary phase encoded chips fabricated with 1mm inter-chip separation that provides 4x100 GHz ITU sub-band separation at 1.25 Gbps. The WDM-OCDMA system verification was carried out employing simultaneous encoding of four adjacent sub-bands and two different OCDMA codes.


In the 1920s, researchers of the Chicago School developed what is often considered as the first theories and models designed to explain neighbourhood change. Subsequent research into neighbourhood change has been carried out in many different ways and has focused on different fields. The early researchers considered neighbourhood change as a more or less inevitable result of a filtering process that causes changes in areas with an ageing housing supply. Others have paid more attention to the importance of a strong neighbourhood attachment, while again others have referred to the impact of larger economic and social transformations on neighbourhoods. Researchers have also aimed to capture the process of neighbourhood change, and of decay in particular, in all-embracing models in which several variables and developments are linked. Despite the comprehensiveness of many models, we think none of them is all-embracing; there is still room for improvement and addition. This paper sets out an approach, which combines crucial elements of different theories, approaches and models. The aim is to find out how we can use the existing theories in the case of the post-WWII large housing estates in Europe. Especially in these areas significant physical, economic and social changes have emerged in the past two decades. The central questions to be addressed in this paper are therefore: To what extent can models and theories explaining neighbourhood change, and decay in particular, be applied to postWWII large housing estates in European cities? And how can the useful elements of these models and theories be combined to explain the development of European post-WWII housing estates?


The present thesis deals with probabilistic and defect tolerant fatigue assessment of wind turbine castings. To this end, two types of EN-GJS-400-18-LT ductile cast iron were investigated in this research, clean baseline material in the shape of casting blocks with different thicknesses and also defective material from a rejected wind turbine hub. To establish the required P–S–N diagrams for safe-life design of wind turbine castings, fatigue specimens with different dimensions machined from baseline casting blocks with different thicknesses. Constant amplitude axial fatigue tests were performed on these specimens at room temperature at R = 0 and R = −1. Geometrical size effect, wall-thickness effect (technological size effect) and mean stress effect on fatigue strength of baseline EN-GJS-400-18-LT material were evaluated and analyzed. Statistical analysis of fatigue data was done by means of the Weibull distribution, and P–S–N diagrams were established. The established P–S–N diagrams showed that the Weibull distribution is well fit to the scatter of the experimentally obtained fatigue life data. Weibull's weakest-link method was used to evaluate the size effect. It made a satisfactory prediction of the fatigue strength for specimens with different dimensions. To study damage tolerant design of wind turbine castings, a rejected wind turbine hub was flame cut to several blanks and several defective fatigue specimens were machined from these blanks. Constant amplitude axial fatigue tests were performed on these specimens at room temperature at R = 0 and R = −1. Fatigue strength of baseline EN-GJS-400-18-LT was compared with that of defective material from the rejected wind turbine hub. The effect of graphite nodules and defects type, shape, size and position on fatigue strength of defective material was evaluated. The hypothesis that the endurance observed in an S−N test can be predicted based on the analysis of crack growth from casting defects through defect-free 'base' material was tested for the analyzed defective material in this research. It was shown that fatigue life of the analyzed defective cast component is controlled by fatigue crack growth and the slope of S − N curve for baseline EN-GJS-400-18-LT is different than the slope of S − N curve for defective EN-GJS-400-18-LT. To perform random defect analysis of wind turbine castings, establish the scatter of fatigue life and obtain the probability of failure of these components, 3D X-ray computed tomography was use to detect defects in defective specimens and find the defect size distribution and density of defects (number of defects per unit volume). The obtained defect size distribution and density for the defective material was used in random defect analysis to establish the scatter of fatigue life for defective specimens. Finally both safe-life and damage-tolerant design philosophies were used to evaluate the fatigue life of an EN-GJS-400-18-LT ductile cast iron block, representative of heavy-section wind turbine castings. The estimated S−N curves for the analyzed component based on these two methods were compared. It was shown that fatigue design of heavy section wind turbine cast iron components based on safe-life design philosophy may result in non-conservative design of these components


Yogatārāvalī or Rājayogatārāvalī is a work on Yoga ascribed to Śaṅkarācārya. It comprises of 29 Sanskrit verses. The importance of the work is evidenced by the repeated publication of the work since 1898 till 2003 from different parts of the country. There are many manuscripts of this work across various manuscript repositories in India. Among these, there are two manuscripts (from Adyar and Mysore) that have a Sanskrit commentary Rājayogatarala by Rāmasvāmī paṇḍita alias Parānandanātha to Yogatārāvalī. It is the only available commentary to the text. The manuscripts were acquired by photocopying and digital imaging from the respective repositories based on the descriptions in the respective Descriptive catalogues. Although there are only 29 verses in the text Yogatārāvalī (by Śaṅkarācārya) Rājayogatarala, the commentary is very detailed (47 folios and 165 folios in Adyar and Mysore manuscripts, respectively). Each of the verses of Yogatārāvalī have been accorded anywhere between two to seven interpretations. The commentator quotes from Uttaragītā, Gurugītā, Nānārtharatnamālā, Mahārājatarala, Muktisopāna, Vijṛmbhita-yogaśāstra-bhāṣya, Śivayoga-pradīpikā, etc., besides Upaniṣads and Āgamas. Further, works on Yoga enlisted above such as Mahārājatarala, Vijṛmbhitayogaśāstrabhāṣya are yet to be published. Multiple interpretations, detailed descriptions of Yoga concepts and copious cross-references make this a unique and important in the field of Yoga to be studied for deeper insights.


Background and Aim: Cardiac patients have different dental needs than healthy individuals and clinicians should be well aware of these differences. The aim of this study was to evaluate and compare knowledge, attitude and practice of parents of children with cardiac disease and healthy children. Materials and Methods: In this case-control study, data were collected using a questionnaire. The study population consisted of 25 parents of children with cardiac disease and 25 parents of healthy children selected at a pediatric physician office. Both groups were matched in terms of age, gender and parents' educational level. Data analysis was performed using independent sample t-test for knowledge and attitude and Mann Whitney test for practice with 3=0.05. Results: Based on the parents' responses, knowledge of parents was 45.24±23.29 in the cardiac group and 41.10±20.45 in healthy group. This difference was not statistically significant. Attitude of parents was 79.3%±9.9 in the cardiac group and 78.9%±6.6 in the healthy group. This difference was not statistically significant either. In the cardiac group, 44% brushed two times a day compared with 20% in the healthy group; 50% of the cardiac children had never visited a dentist while healthy children had regular dental visits. Conclusion: In the fields of knowledge and attitude there were no significant differences between two groups, knowledge of parents in two groups was poor but their attitude was positive also practices of parents in the field of children's brushing was good but in the field of attending to dentist was poor.


Of the African states experiencing sustained growth and poverty-reduction in recent decades,
Rwanda and Ethiopia stand out due to the scope of their development visions and relatively
effective state-driven transformation, leading them to be compared to the East Asian
'developmental states' with increased frequency. This article argues that these two states are better
conceived as 'neo-developmental', due to important differences in the international and national
constraints they face compared with the East Asian 'tigers'. One effect of these differences is the
difficulty of attracting investment into manufacturing industry, and the consequent concentration
of capital in high-end urban real estate. This underscores the need for effective land value capture
and property taxation, which featured strongly in the East Asian cases. Currently, however, both
Rwanda and Ethiopia lack effective mechanisms for capturing the value of urban property in a way
that is sustainable, redistributive and developmental. The article explores the politics of efforts to
introduce property tax in both cases. It argues that property taxation has been obstructed by
conflicting imperatives on land reform and tax reform, alongside resistance from vested interests
created by the rapid generation of real estate-based wealth in the absence of other sufficiently
lucrative investment options.


The importance of this research is to examine real estate investment funds (REIF) which is a new capital market instrument in Turkey. For this purpose, it is evaluated the development and current situation of REIF which are capital market instruments based on the results of stakeholder interviews and secondary data. In-depth interview technique was used in collecting research data, and ensured to examine REIFs and application problems in Turkey, the country's economy, their contribution to the construction and real estate sector, the advantages and disadvantages with directed open-ended questions about the investigation to managers with face-to-face interviews. As a conclusion, this new investment vehicle has foreseen further developed in the following years which is relatively new in Turkey and it will be possible to increase the Real Estate Development and Management specialists working in REIFs, risk and investment analysis as well as other vehicles based on real estate and to contribute the development of problem resolution and funds by ensuring that the funds are employed in the institutions which are the stakeholders.


I. Abstract: Smart cities are collecting and producing massive amount of data from various data sources such as local weather stations, LIDAR data, mobile phones sensors, Internet of Things (iOT) etc. To use such large volume of data for potential daily computing benets, it is important to store and analyse such amount of urban data using handy computing resources and al-gorithms. However, this can be problematic due to many challenges. This article explores some of these challenges and test the performance of two partitional algorithms for clus-tering such Big LIDAR Datasets. Two handy clustering algorithms the K-Means vs. the Fuzzy c-Mean (FCM) were put to the test to address the suitability of these algorithms for clustering such a large dataset. The purpose of clustering urban data is to categorize it into homogeneous groups according to specic attributes. Clustering Big LIDAR Data in compact format represents the information of the whole data and this can benefit researchers to deal with this reorganised data much efciently. To achieve this end, the two techniques were utilised against a large set of Lidar data to show how they perform on the same hardware set-up. Our experiments conclude that FCM outperformed the K-Means when presented with such type of dataset, however the later is lighter on the hardware utilisations. II. Introduction: Many ongoing and recent researches and development in computation and data storing technologies have contributed to production of the Big Data phenomena. The challenges of Big Data are due to the 5V's which are: Volume, Velocity, Variety, Veracity and Value to be gained from the analysis of Big Data [1]. From the survey of the literature, there is anagreement between data scientists about the general attributes that characterise Big Data 5V's which can be summed as follows: Very large data mainly in Terabytes/Petabytes/Exabyte's of data (Volume). Data can be found in structured, unstructured and semi structured forms (Variety). Often incomplete data and inaccessible. Data sets extraction should be from reliable and verified sources. Data can be streaming at very high speed (Velocity). Data can be very complex with interrelationships and highdimensionality. Data may contain few complex interrelationships between different elements. The challenges of Big Data in general are an ongoing thing and the problems is growing every year. A report by Cisco, estimated that by the end of 2017, annual global data traffic will reach 7.7 Zettabytes. The global internet traffic will be three times over the next five years. Overall, the global data traffic will grow at a Compound Annual Growth Rate (CAGR) of 25% by the year 2017. It is essential to take steps toward tackling these challenges because it can be predicted that a day will come when Big Data tools will become obsolete in front of such enormous amount of data flow. III. Clustering Methods: Researchers are dealing with many types of large datasets, the concern here is to wither introduce new algorithms or use the existing algorithms to suit large datasets by focusing on the data itself to suit the available algorithms. Currently, two approaches are predominant: First, is known as "Scaling-Up" which focuses the efforts on the enhancement of the available algorithms. This approach risks them becoming useless for tomorrow, as the data continues to grow. Hence, to deal with continuously growing in size datasets, it will be necessary to frequently scale up algorithms as the time moves on. The second approach is to "Scale-Down" or to skim the data itself, and to use existing algorithms on the skimmed version of the data after reducing its size. This article focuses on the scale-down of data sets by comparing clustering techniques. Clustering is defined as the process of grouping a set ofitems or objects which have same attributes or characteristics in the same group called a cluster which may differ from another group. Clustering can be very useful for between cluster separation, within cluster homogeneity and for good representation of data by its centroid. These can be applied to different fields such as Biology to find groups of genes which have same functions or similarities. It is also used in Medicine to find patterns in symptoms of disease and in Business to find and target potential customers. IV. Compared Techniques K-Means vs. Fuzzy c-Means: To highlight the advantages to everyday computing for Big Data, this article is focusing on comparing two trendy and computationally attractive partitional techniques which can be explained as follows: 1) K-Means Clustering: This is a widely used clustering algorithm. It partition a data set into K clusters (C1;C2;:::;CK), represented by their arithmetic means called the "centroid" which is calculated as the mean of all data points (records) belonging to certain cluster. 2) Fuzzy c-Means clustering: FCM was introduced by Bezdek et al. and it is derived from the explained K-means concept for the purpose of clustering datasets, but it differs in that the object may belong to more than one cluster with degrees of belonging. However, it is possible that an object may belong to more than one cluster according to its degree of membership, which is also calculated on the bases of distances (usually the Euclidean) between the data points and cluster. V. Experiments Set-up: The experiments are done to compare and illustrate how the candidate K-Means and FCM clustering techniques cope with clustering Big LIDAR Data set using a handy computer hardware. The experiment were performed using an AMD8320, 4.1 GHz, 8 core processor with 8 GB of RAM and running a 64-bit Windows 8.1 OS. The algorithms were implemented against a LIDAR data points, taken for our campus location at Latitude: 52:23–52:22 and Longitude: 1:335–1:324. This location represents the International University of Sarajevo main campus with an initialization of 1000000 × 1000 digital surface data points. Both clustering techniques were applied to the dataset starting with a small cluster number K = 5 and gradually increased to reach K = 25 clusters. VI. Conclusions: The lowest time measured for FCM to re group the data into 5 clusters was recorded at 42.18 seconds while it took K-Means 161.17 seconds to form the same number of clusters. The highest time recorded for K-Means to converge was 484. 01 seconds, while it took FCM 214.15 seconds to cluster the same dataset. Hence, There is a high positive correlation between the time and the number of clusters assigned, as the number of clusters count increases so does the time complexity for both algorithms. On average FCM used up between 5–7 out of the eight available cores, with 63.2 percent of the CPU processing power and 77 percent of the RAM memory. The K-Meanson the other hand utilised between 4–6 with the rest remain as idle cores with an average of 37.4 percent of the CPU processing power and 47.2 percent of the RAM memory. Overall, both algorithms are scalable to deal with Big Data, but, FCM is fast and would make an excellent clustering algorithm for everyday computing. In addition, it would offer some extra added advantages such as its ability to handle different data types. Also, this fuzzy partitioning technique and due to its fuzzy capability, FCM could produce a better quality of the clustering output which could benefit many data analysts.


Abstract. In the scope of hyperspectral airborne imaging spectrometer (APEX) design activities, the acceptable sensitivity of linear polarization of the spectrometer is analyzed by assessing the amount of polarization of reflected light in the atmosphere-surface system. A large number of calculations is performed for a wide variaty of viewing geometries to study the influences of aerosol models, natural surfaces and flight altitudes over the spectral range from the near-UV to the short-wave infrared (SWIR). Thereinafter the design of the imaging spectrometer is outlined accounting for these requirements and a method of partially correcting the instrument polarization sensitivity is briefly introduced. APEX design and post-processing capabilities will enable to reduce the influence of polarization sensitivity of at-sensor radiance and its higher-level products generated for most of the observation conditions.


Sea surface temperature (SST) is an important component of climate and weather systems at various time scales. Asymmetric seasonal SST variations in the Northwestern Pacific Marginal Seas (NWPMS) are investigated in this study using observation data and numerical model results. The asymmetry in SST seasonal variation is estimated quantitatively and compared with heat advection and surface net heat flux using SST data and atmospheric variables from the European Centre for Medium-Range Weather Forecast (ECMWF). The SST increases faster than it decreases, whereas air temperature increases slowly. Heat advection and surface heat flux were estimated using numerically modeled SST and ocean currents, which contribute to the asymmetry of seasonal SST variations. Heat advection shows good correlation with the SST seasonal variation asymmetry. Model results without currents along the boundary show more symmetrical SST variations. This suggests that heat advection is a prominent cause of asymmetry in the seasonal variation.


Roughly one in seven threatened terrestrial vertebrate species are held in captivity, a resource for ex situ conservation efforts. At the October 2010 meeting of the Convention on Biological Diversity (CBD) in Nagoya, Japan, delegates discussed a plan to reduce pressures on the planet's biodiversity. Key targets include expanding coverage of protected areas, halving the rate of loss of natural habitats, and preventing extinction of threatened species (1). For species whose habitat is severely threatened, however, the outlook is so bleak that the International Union for Conservation of Nature (IUCN), the U.S. Endangered Species Act, and the CBD (Article 9) recognize that in situ conservation actions (i.e., in the species' natural habitat) will need to be combined with ex situ approaches, such as captive breeding in zoos, aquariums, and so on (2, 3).


Objective To investigate the associations between Alberta Stroke Program Early CT Score (ASPECTS) or distribution and sidedness of acute infarction and clinical outcomes following intervention with a direct aspiration first pass technique (ADAPT). Methods A review was performed of patients who had undergone thrombectomy with ADAPT for emergent large vessel occlusions of the middle cerebral artery (MCA) between December 2012 and May 2015. Preintervention CT scans were reviewed by a blinded radiologist to calculate ASPECTS and determine the distribution of infarction. Clinical outcomes were compared for subsets of patients depending upon ASPECTS and regional infarction distribution (cortical, subcortical, or both). Results One hundred and fifty-four patients (50% female, mean age 67) underwent thrombectomy using ADAPT for MCA emergent large vessel occlusion. The median presenting National Institute of Health Stroke Scale score was 15. Fifty-five per cent of patients had left-side occlusions. Similar good outcomes were achieved for patients with perfect and non-perfect ASPECTS (modified Rankin Scale (mRS) 0–2: 63% vs 51%, respectively; p=0.20). Similar outcomes were also achieved for patients with 'poor' ASPECTS (≤6) compared with those with ASPECTS >6 (mRS 0–2: 52% vs 53%, respectively; p=0.91). Regional distribution and sidedness of core infarction on preintervention CT also did not correlate with worse outcomes. Conclusions Patients with moderate-sized core infarcts involving various distributions in either hemisphere can potentially achieve similar good outcomes compared with those with no core infarction at presentation. A treatment algorithm for acute ischemic stroke, which employs hardline ASPECTS thresholds or excludes patients with basal ganglia infarcts, might preclude patients who would potentially benefit from mechanical thrombectomy with ADAPT.


Despite considerable work, the neural basis of perceptual learning remains uncertain. For visual learning, although some studies suggested that changes in early sensory representations are responsible, other studies point to decision-level reweighting of perceptual readout. These competing possibilities have not been examined in other sensory systems, investigating which could help resolve the issue. Here we report a study of human tactile microspatial learning in which participants achieved >six-fold decline in acuity threshold after multiple training sessions. Functional magnetic resonance imaging was performed during performance of the tactile microspatial task and a control, tactile temporal task. Effective connectivity between relevant brain regions was estimated using multivariate, autoregressive models of hidden neuronal variables obtained by deconvolution of the hemodynamic response. Training-specific increases in task-selective activation assessed using the task × session interaction and associated changes in effective connectivity primarily involved subcortical and anterior neocortical regions implicated in motor and/or decision processes, rather than somatosensory cortical regions. A control group of participants tested twice, without intervening training, exhibited neither threshold improvement nor increases in task-selective activation. Our observations argue that neuroplasticity mediating perceptual learning occurs at the stage of perceptual readout by decision networks. This is consonant with the growing shift away from strictly modular conceptualization of the brain toward the idea that complex network interactions underlie even simple tasks. The convergence of our findings on tactile learning with recent studies of visual learning reconciles earlier discrepancies in the literature on perceptual learning.


In this paper I investigate, numerically, the co-movement puzzle by testing the ability of borrowing and lending constraints to counter the opposite movement of durable and non-durable goods in response to foreign monetary policy and international bond shocks. I do this by simulating a small open economy sticky price model calibrated to the South African economy over the period 1990Q012014Q04. I show that introducing borrowing and lending constraints into a small open economy sticky price model, in the face of foreign monetary policy tightening and an international bond shock, partially solves the co-movement puzzle. This is because the shadow value of durable goods reduces the incentive to accumulate durables for collateral because foreign lenders are less efficient than domestic lenders at recovering loans. In the case of sticky durables and sticky non-durables, the sticky price model mimics a fall in the relative price of durable goods observed in the data. Thus, financial frictions such as borrowing and lending constraints make it possible to reconcile the sticky price model with the data. JEL codes: E44, E52, F41, F42


BACKGROUND
Children with perinatal human immunodeficiency virus (HIV) infection (PHIV) may not be protected against measles, mumps, and rubella (MMR) because of impaired initial vaccine response or waning immunity. Our objectives were to estimate seroimmunity in PHIV-infected and perinatally HIV-exposed but uninfected (HEU) children and identify predictors of immunity in the PHIV cohort.

METHODS
PHIV and HEU children were enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS) at ages 7-15 years from 2007 to 2009. At annual visits, demographic, laboratory, immunization, and clinical data were abstracted and serologic specimens collected. Most recent serologic specimen was used to determine measles seroprotection by plaque reduction neutralization assay and rubella seroprotection and mumps seropositivity by enzyme immunoassay. Sustained combination antiretroviral therapy (cART) was defined as taking cART for at least 3 months.

RESULTS
Among 428 PHIV and 221 HEU PHACS participants, the prevalence was significantly lower in PHIV children for measles seroprotection (57% [95% confidence interval {CI}, 52%-62%] vs 99% [95% CI, 96%-100%]), rubella seroprotection (65% [95% CI, 60%-70%] vs 98% [95% CI, 95%-100%]), and mumps seropositivity (59% [95% CI, 55%-64%] vs 97% [95% CI, 94%-99%]). On multivariable analysis, greater number of vaccine doses while receiving sustained cART and higher nadir CD4 percentage between last vaccine dose and serologic testing independently improved the cumulative prediction of measles seroprotection in PHIV. Predictors of rubella seroprotection and mumps seropositivity were similar.

CONCLUSIONS
High proportions of PHIV-infected children, but not HEU children, lack serologic evidence of immunity to MMR, despite documented immunization and current cART. Effective cART before immunization is a strong predictor of current seroimmunity.


Feature Normalization (FN) is an important technique to help neural network training, which typically normalizes features across spatial dimensions. Most previous image inpainting methods apply FN in their networks without considering the impact of the corrupted regions of the input image on normalization, e.g. mean and variance shifts. In this work, we show that the mean and variance shifts caused by full-spatial FN limit the image inpainting network training and we propose a spatial region-wise normalization named Region Normalization (RN) to overcome the limitation. RN divides spatial pixels into different regions according to the input mask, and computes the mean and variance in each region for normalization. We develop two kinds of RN for our image inpainting network: (1) Basic RN (RN-B), which normalizes pixels from the corrupted and uncorrupted regions separately based on the original inpainting mask to solve the mean and variance shift problem; (2) Learnable RN (RN-L), which automatically detects potentially corrupted and uncorrupted regions for separate normalization, and performs global affine transformation to enhance their fusion. We apply RN-B in the early layers and RN-L in the latter layers of the network respectively. Experiments show that our method outperforms current state-of-the-art methods quantitatively and qualitatively. We further generalize RN to other inpainting networks and achieve consistent performance improvements.


The seaway south of South Africa represents a critical gateway within the global circulation. Here, warm surface and cold deep and bottom water masses meet and lead to a transfer of heat and salt between the Indian and Atlantic Oceans. This transfer maintains the global thermohaline circulation. The paths of the oceanic currents are strongly influenced by the seafloor topography observed in this region. Thus, the tectonic evolution of the South African continental margin and the gateway starting in Cretaceous times are of major importance in order to understand the evolution of the current system and the transition from the Greenhouse to the Icehouse world. The gateway itself is characterized by the Agulhas Plateau, which has been postulated to originate in the interaction of the Bouvet Hotspot and a triple junction and thus to fall within the world-wide suite of Large Igneous Provinces [Gohl and Uenzelmann-Neben, 2001; Parsiegla, et al., 2008; Uenzelmann-Neben, et al., 1999]. A similar structure has been identified for the crust of the southern Mozambique Ridge [Gohl, et al., 2008]. This rises the question whether those two LIP events were related, their emplacement happened at the same time and how they tie in with other LIP events observed in Late Cretaceous times such as the formation or the Kerguelen LIP. Furthermore, we may speculate on the effect those magmatic events had on the evolution of both oceanic currents and the climate. Similarities as well as differences in crustal structure and evolution and later sedimentary development will be presented for those two structures based on seismic refraction and reflection data. References:Gohl, and G. Uenzelmann-Neben (2001), The crustal role of the Agulhas Plateau, southwest Indian Ocean: Evidence from seismic profiling, Geophysical Journal International, 144, 632-646.Gohl, K., et al. (2008), Is the Mozambique Ridge related to the Agulhas Plateau Large Igneous Province?, Geophysical Research Letters.Parsiegla, N., et al. (2008), The Agulhas Plateau: Structure and evolution of a Large Igneous Province, Geochemistry Journal International, 174, 336-350.Uenzelmann-Neben, G., et al. (1999), Agulhas Plateau, SW Indian Ocean: New evidence for extensive volcanism, Geophysical Research Letters, 26, 1941-1944.


On the fiftieth anniversary of the Supreme Court's decision in Griswold v. Connecticut, this brief symposium Essay takes cues from a principle at stake in Griswold — that procreative liberty is integral to equality — and shifts the focus to a new form of procreation, namely assisted reproductive technology (ART), and an emergent form of equality, namely sexual orientation equality. With same-sex couples on the verge of nationwide access to marriage, new sites of conflict are emerging. The legitimacy of same-sex family formation is being challenged by some now working to restrict ART. Even as the success of same-sex couples' legal claim to marriage rests in part on a nonprocreative view of marriage supported specifically by Griswold, LGBT advocates also have articulated a procreative view of marriage tied to same-sex family formation through ART. This latter view, bolstered today by both important state family-law developments and recent same-sex marriage decisions, may ultimately provide the foundation for a reading of Griswold that supports same-sex couples' procreative rights in the conflicts just beginning to take shape.


Background: African Americans and Hispanics are less likely to receive thrombolytics for acute ischemic stroke. Whether similar disparities exist in the prehospital setting for stroke recognition has not been studied. Our objective was to determine the differences in sensitivity and specificity of stroke recognition between racial/ethnic groups. Methods: This is a secondary analysis of linked prehospital and hospital based outcome data for patients presenting to hospitals within two northern California counties between 2005 and 2007. Prehospital clinical impression was obtained from the paramedic report and hospital diagnosis of stroke was identified using validated ICD- 9 codes in the discharge abstract file of the state administrative database. Patients missing data on race, ethnicity, paramedic primary impression or hospital discharge diagnosis were excluded. Sensitivity and specificity of prehospital stroke recognition among different racial/ethnic groups including Asians, Hispanics, and Non-Hispanic Whites were calculated. Independent association of race with sensitivity and specificity of prehospital stroke recognition was explored using a logistic regression model. Results: 223,318 patients were transported by EMS during the study period; 3,633 had a primary discharge diagnosis of stroke using validated ICD-9 codes. Pre-hospital sensitivity for stroke recognition was lower among Asian (OR 0.65, 95% CI 0.54-0.79) and Hispanic patients (OR 0.74, 95% CI 0.59-0.92) when compared with Non-Hispanic Whites. Female gender was also independently associated with lower sensitivity of pre-hospital recognition (OR 0.82, 95% CI 0.71-0.940). Hispanic ethnicity and female gender were all independently associated with increased specificity. Conclusion: Race/ethnic and gender disparities exist in the prehospital recognition of stroke. Future efforts should explore the effects of these differences on stroke treatment rates.


Background The health effects of a Roundup-tolerant NK603 genetically modified (GM) maize (from 11% in the diet), cultivated with or without Roundup application and Roundup alone (from 0.1 ppb of the full pesticide containing glyphosate and adjuvants) in drinking water, were evaluated for 2 years in rats. This study constitutes a follow-up investigation of a 90-day feeding study conducted by Monsanto in order to obtain commercial release of this GMO, employing the same rat strain and analyzing biochemical parameters on the same number of animals per group as our investigation. Our research represents the first chronic study on these substances, in which all observations including tumors are reported chronologically. Thus, it was not designed as a carcinogenicity study. We report the major findings with 34 organs observed and 56 parameters analyzed at 11 time points for most organs.


PURPOSE
The purpose of this study was to compare the mRNA expression of neurotrophins (NTs) and NT receptors (Trk) in cultured human trabecular meshwork (HTM) cells and ex vivo HTM tissues, to immunolocalize both NT and Trk receptors in cultured HTM cells, and to demonstrate secretion of NTs by HTM cells.

METHODS
Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of NT and Trk receptor mRNAs in early-passaged, cultured HTM cells from donors of several ages. RT-PCR was used on ex vivo HTM tissues from donors to compare and contrast mRNA expression with cell culture results. In addition, immunohistochemistry was used to localize the translated NT and low- (p75) and high- (Trk) affinity NT receptor proteins within cultured HTM cells and trabecular meshwork tissues. Last, enzyme-linked immunoassay (ELISA) was used to demonstrate secretion of NTs by HTM cells.

RESULTS
Amplification products of the expected size for NTs were detected in both cultured HTM cells and ex vivo HTM tissues. Specifically identified were amplification products for the following NTs: NGF, BDNF, NT-3, and NT-4. Amplification products for the full-length Trk A and Trk C high-affinity receptor were observed, as well as truncated isoforms for Trk B and Trk C. No amplification products were produced for the full-length Trk B receptor nor for the low-affinity p75 receptor. Immunohistochemistry indicated that proteins for the various NTs and full-length and truncated Trk receptors were translated by cultured HTM cells and tissues. Immunoassays (ELISA) detected BDNF, NT-4, NGF, and NT-3 in the culture media from HTM cells.

CONCLUSIONS
The results demonstrate, for the first time, mRNA expression for NT and Trk receptors by both cultured HTM cells and ex vivo HTM tissues. NTs were immunolocalized in HTM tissues and cultured HTM cells are capable of secreting NTs. Specific NTs acting through high-affinity Trk receptors within the HTM may be involved in maintaining the normal function of this complex tissue.


Sergius of Reshaina's Syriac exposition of Aristotle's Categories, with its discussion on substance, quantity, quality, relatives and the other categories, but also the teaching on space from the Physics, is presented here in a critical edition with an English translation.


Abstract Adult hispid cotton rats (Sigmodon hispidus) were collected from the field monthly for >2 years from populations near the northern edge of their range in Virginia and contemporaneously from south-central Georgia. Body measurements and weights were taken at capture, and after dissection embryos, corpora lutea, and placental scars were counted and measured; testes and seminal vesicles were dissected out, measured, and weighed. This allowed comparison of several life-history parameters between the populations and tests of several life-history hypotheses. The breeding season was up to 2 months longer in Georgia than in Virginia, where there was typically a 3-month or longer winter inactive period. Some reproductive activity was observed among Georgia females in all 12 calendar months, whereas pregnancies were never observed in Virginia during November–February. Average litter sizes were significantly higher in Virginia (5.91 ± 1.41, up to 13) than in Georgia (5.16 ± 1.79, up to 9); this difference may partly result from a higher incidence of embryo resorption and prenatal mortality in the Georgia population, primarily in the cooler 6 months of the year. Virginia rats averaged significantly smaller for both sexes, but this was likely the result of a younger age distribution. Among reproductive males and females, no body-size differences were found between populations except that pregnant females from Virginia averaged significantly longer. Fifty percent and 75% of the random sample of adult females and males, respectively, were reproductively active in Georgia, whereas only 35% and 40% were reproductively active in Virginia. Spermatogenically active males in Virginia had significantly greater relative gonadal mass than their Georgia counterparts. Overwinter survival of parous females was lower in Virginia. Virginia populations, in a more seasonal environment, displayed a more r-selected life history, with greater reproductive allocation, faster growth (except over winter), higher mortality, and less iteroparity.


Magnetic resonance (MR) tomography is an imaging method, that is used to expose the structure and function of tissues and organs in the human body for medical diagnosis. Diffusion weighted (DW) imaging is a specific MR imaging technique, which enables us to gain insight into the connectivity of white matter pathways noninvasively and in vivo. It allows for making predictions about the structure and integrity of those connections. In clinical routine this modality finds application in the planning phase of neurosurgical operations, such as in tumor resections. This is especially helpful if the lesion is deeply seated in a functionally important area, where the risk of damage is given. This work reviews the concepts of MR imaging and DW imaging. Generally, at the current resolution of diffusion weighted data, single white matter axons cannot be resolved. The captured signal rather describes whole fiber bundles. Beside this, it often appears that different complex fiber configurations occur in a single voxel, such as crossings, splittings and fannings. For this reason, the main goal is to assist tractography algorithms who are often confound in such complex regions. Tractography is a method which uses local information to reconstruct global connectivities, i.e. fiber tracts. In the course of this thesis, existing reconstruction methods such as diffusion tensor imaging (DTI) and q-ball imaging (QBI) are evaluated on synthetic generated data and real human brain data, whereas the amount of valuable information provided by the individual reconstruction mehods and their corresponding limitations are investigated. The output of QBI is the orientation distribution function (ODF), where the local maxima coincides with the underlying fiber architecture. We determine those local maxima. Furthermore, we propose a new voxel-based classification scheme conducted on diffusion tensor metrics. The main contribution of this work is the combination of voxel-based classification, local maxima from the ODF and global information from a voxel- neighborhood, which leads to the development of a global classifier. This classifier validates the detected ODF maxima and enhances them with neighborhood information. Hence, specific asymmetric fibrous architectures can be determined. The outcome of the global classifier are potential tracking directions. Subsequently, a fiber tractography algorithm is designed that integrates along the potential tracking directions and is able to reproduce splitting fiber tracts.


Differences in administrative reporting structures for NCAA Division I, II and III athletics directors were reported and analyzed. Reasons for different reporting structures and athletics director satisfaction with reporting structures were studied, and athletics directors' perceptions of their structures, particularly when organizational change had recently occurred, were analyzed. Athletics directors at all 977 NCAA Division I, II and III institutions were asked to complete a questionnaire indicating to whom they report in the administrative structure of their institution, what organizational structure changes had occurred during the previous fiveyear period, and their satisfaction level with their campus reporting structure. Fifteen NCAA athletics directors were asked in a telephone interview to respond to questions about their current and previous organizational structures. Results were cross tabulated and frequencies were calculated. A content analysis of themes from the written survey and telephone interview was conducted. The two most common administrative reporting structures were a direct report to the university president and to the student affairs division. A direct report to the president was the most common in Divisions I-A, I-AA, I-AAA and II, whereas student affairs was the most common structure in Division III. The vast majority of athletics directors were satisfied with their reporting structure. Those reporting directly to the president cited the direct contact with the president as the primary reason for their satisfaction. Athletics directors who reported to student affairs indicated the natural fit with student services was the primary reason for their structure. Satisfaction levels generally decreased when moving from larger to smaller athletics programs. Athletics directors, particularly in Division I, felt that it was critical to report directly to the university president due to the high visibility of their programs, NCAA institutional control issues, and the impact of the athletics program on the institution as a whole. Respondents also indicated that communication efficiency necessitated this direct involvement. Directors of lower division athletics programs were generally satisfied reporting through student affairs. However, among these directors there were some who expressed interest in a direct report to the president.


Software testing is regarded as the most important and the most crucial of the final
stages in software development. Profound knowledge and experience in software testing
is often an asset in a software company to ensure the reliability and quality of any
developed project. The core of software testing strategies mainly lies with unit testing,
which is a type of testing carried out on single subroutine or module, almost throughout
the development process, depending on the development model used by the developer.
There are some issues raised in software testing literature, be it in textbooks, journals, or
articles, regarding the process of unit testing, its importance, and the problems faced by
developers in performing unit tests. However, through the research and readings of the
author on the literature, these issues have not been formally discussed in a Malaysian
perspective. Hence, this study of the unit testing practice of software development
companies operating in Malaysia is carried out. After reviewing the current available
literature on unit testing with no specific geographical or time frame limitation, a study is
carried out on five software development companies, within the geographical limit of
Malaysia and as of the current time, on their engaged practice of unit testing. It is meant
to gauge the importance they place in unit testing, as well as to find out their methods,
their processes, and the problems they encounter in unit testing. These findings are then
analyzed and compared to the current literature. It is hoped that these case studies will
shed more light on the real-world practice of software development, especially of unit
testing, in a Malaysian context.


The study aims to undertake an exploratory investigation into British Educational
Psychologists' (EPs) practitioner perspectives on the key psychological theories and
models that underpin their professional practice. It also aims to ascertain what the
implications might be of practitioner perspectives on this topic for future practice,
future training and continuing professional development of EPs hi the British context
as "applied" psychologists. Following a small scale national survey on the topic, five
focus group discussions were arranged to investigate the topic in more detail with
groups of EPs at various career stages. The focus group discussions were subjected
to detailed Thematic Analysis using techniques recommended by Braun and Clarke
(2006). Analyses were undertaken at both the explicit (semantic) and interpretative
(latent) level in order to develop a series of thematic maps. The literature review
found that although British EPs have consistently reviewed, evaluated and challenged
their professional practice in changing working contexts, there is a paucity of research
into their perceptions of the fundamental psychological theories and models that
underpin what they actually do "on the job", which was recognised as multi-levelled
and complex.
Four overarching themes emerged from the extensive interpretative analysis of the
data set as key to EP practitioner perspectives on what underpins and influences the
use of psychological theory and models in their professional practice. These were:
(1) Working context, location and the degree of role clarity within this;
(2) Professional self reflection on practice;
(3) Training, early supervision and continuing professional development;
(4) Developed psychological skills, competencies and knowledge, particularly
with a relevant research evidence base.
Surprisingly, the analyses found no evidence of expected themes relating to the
underpinning psychology for effective interpersonal skills or collaborative team work
in the EP practitioner perspectives. A "matrix of evidence for EP practice" is
proposed for future use based on the themes from the interpretative analyses
undertaken. The methodology employed and the analysis of the findings are both
critically appraised. The implications for further research into the topic together with
implications for EP professional practice and continuing professional development are
outlined.


Abstract : Russian aggression in 2014 caught U.S. policy and strategy off guard, forcing reactive measures and reevaluation of the U.S. approach toward Russia. Moscow employed nonlinear methodologies and operated just beneath traditional thresholds of conflict to take full advantage of U.S. and NATO policy and process limitations. In light of this strategic problem, the U.S. Army War College (USAWC), conducted a wargame that revealed four key considerations for future policy and strategy.


The main goals of the spatial development of rural areas are to protect and prevent degradation of agricultural land, forests and protected areas, as well as to encourage (more) balanced territorial development. Given that the quality and development of agriculture largely depend on the level of consciousness and awareness of the population in rural areas as to the opportunities and benefits of their involvement in the adoption and approval of planning solutions, the aim of this paper is to define a communication strategy to help raise the awareness of the focus groups (landowners, farmers and investors) of the importance of and link between spatial planning and development of agribusiness and rural areas, exploring different techniques and methods of using various communication channels. The methods which will be used in the paper include secondary research, SWOT analysis, and trend and historical analysis. The research results show that it is essential from the very beginning to take the views of various stakeholders into account through frequent thematic dialogues, in order to incorporate a consensus which has been reached together with the expert team of the developer, into planning decisions. Only such an approach can lead to sustainable and enforceable plans as prerequisites for the realisation of realistically planned investment in rural areas. Furthermore, it is very important to legally standardise such an approach so that public participation, as a mandatory legal procedure, can be defined through precisely defined steps and established performance indicators from the very beginning of the process of adopting planning documents.


Coumarins represent promising scaffolds for the design and development of novel polyfunctional drugs for the treatment and/or prevention of chronic neurodegenerative disorders including Alzheimer's (AD), Parkinson's and Huntington's (HD) diseases. The aim of our research was to evaluate the potential antioxidant and neuroprotective effects of various natural coumarins such as esculetin (ESC), scopoletin, fraxetin and daphnetin in several experimental models of AD and HD. We used: i) human neuronal SH-SY5Y cells treated with tert-butyl hydroperoxide (t-BuOOH) and amyloid-β protein oligomers (OAβ), a specific neurotoxin for AD; ii) an inducible cell model (PC12 HD-Q74) and a transgenic Drosophila melanogaster model (HTT93Q, pan-neuronal expression), both of which express mutant huntingtin (HTT) exon 1 fragments, a typical feature of HD. The treatment with ESC prevented or counteracted the oxidative stress elicited by t-BuOOH in SH-SY5Y cells. ESC effectively increased intracellular glutathione levels and activated the translocation of Nrf2 into nucleus via Erk and Akt/GSK3β signalling pathways. ESC prevented both the oxidative damage and necrosis induced by OAβ. Further, ESC counteracted the early and late neurotoxic events, in terms of formazan exocytosis and necrosis, respectively, evoked by OAβ. The treatment with ESC partially modulated the aggregation of mutant HTT protein in PC12 HD-Q74 cells induced by doxycycline. ESC ameliorated the cell proliferation and counteracted the necrosis elicited by HTT74Q expression in PC12 HD-Q74 cells. ESC showed to counteract the oxidative stress as well as to increase the intracellular glutathione levels and restore the nuclear Nrf2 levels. In addition, ESC significantly decreased photoreceptor neurodegeneration in HTT93Q flies and enhanced in a dose-dependent manner the emergence of adult HD flies from the pupal case. ESC feeding also improved the shortening of median life span in HD flies. Our results encourage further research to better investigate the potential therapeutic profile of ESC as a neuroprotective agent.


Since the Agreed Framework (AF) was signed by the United States and North Korea on October 21, 1994, the security situation on the Korean peninsula and in Northeast Asia has changed qualitatively for the worse. The discovery last year of a suspect North Korean nuclear site and the August 31 launch of a Taepo Dong missile have combined to raise fundamental questions about Pyongyang's intentions, its commitment to the agreement, and the possibility of North-South reconciliation. These developments also raise profound questions about the sustainability of current U.S. policy toward the Korean peninsula. The Agreed Framework successfully addressed a specific security problem--North Korea's plutonium production at the Yongbyon and Taechon facilities. Under the agreement, operations were frozen at the two facilities and Pyongyang was prevented from obtaining fissile material from the fuel rods of the reactor core for five to six nuclear weapons. Had the program continued unabated, North Korea might have been able to produce enough fissile material for a substantial nuclear arsenal. Arguably, the Agreed Framework was a necessary but not sufficient response to the multiple security challenges posed by North Korea. Indeed, the development of the Taepo Dong missile poses an expanding security threat to Northeast Asia and, increasingly, to the Middle East, Europe, and even the United States itself. Changing Assumptions Experience in dealing with Pyongyang since the Agreed Framework was signed challenges several critical assumptions on which public and Congressional support for U.S. policy has been based. * The first is the assumption made by some senior administration officials that the Agreed Framework had ended North Korea's nuclear program. * The second is that North Korea is a failed state on the verge of collapse and that a "hard landing"--collapse perhaps accompanied by aggression--should be avoided. * The third is that the Agreed Framework would induce North Korea to open up to the outside world, initiate a gradual process of North-South reconciliation, and lead to real reform and a "soft landing." These assumptions suggested that, even if little progress was made on other political/security issues, the Agreed Framework was an effective, time-buying strategy. At a minimum, North Korea's conventional capabilities would continue to degrade (as they have). Optimally, the North would solve our problems by ultimately reconciling or uniting with the South. These assumptions are now open to question. Reality Check The disclosure of at least one suspect site--on which construction began prior to the agreement--reinforces the possibility that Pyongyang has frozen only a portion of its nuclear program or is seeking to develop a covert nuclear weapons program. The Agreed Framework was structured to become stronger over time in constraining the North's nuclear weapons capability. This meant deferring the requirement for the North Korean nuclear program to come into full compliance with the International Atomic Energy Agency (IAEA) full-scope safeguards until roughly 2002-03. In effect, the agreement accepted the possibility that North Korea might have one or two nuclear devices. Since 1994, it is also possible that Pyongyang could have acquired additional nuclear weapons technology and/or fissile material from external sources. Moreover, the core assumption of imminent collapse is seriously flawed. Despite severe hardships, there are no signs of regime-threatening social or political unrest, or military disaffection. As underscored in its 50th anniversary celebration last year, the North Korean regime appears to have consolidated itself under Kim Jong Il. There are also no signs that the regime is contemplating any radical market-oriented reforms. Instead, forced by necessity, it is experimenting at the margins with modest reform to alleviate food shortages at the local level and gain hard currency. …


Efficient and economical transportation and delivery operations are necessary and urgent for modern logistics service, the integrated platform for logistics planning is an important way out, which brings digital identity of cargos and optimized routing and scheduling plan together, the platform gives logistics planners an approach to make better decision faster and further to reach more revenue. The digitization method of cargos identity by two-dimensional barcode technology was introduced, hierarchical model for generating transportation plan was initially proposed, which is separated into routing, scheduling and cargo-loading three steps. The integrated platform for logistics planning can be computerized and an optimized plan of transportation and delivery operations can be automatically generated by it, and it can offer significant potential for cost decreases and productivity gains, the method is proved to be feasible and reliable.


BACKGROUND AND OBJECTIVES
Homozygous beta-thalassemia patients may develop iron overload even if untransfused, due to inappropriately high intestinal iron absorption. Reduction of hepcidin synthesis has been reported both in patients and in animal models. We have measured liver hepcidin and other iron gene transcripts in two different mouse models of beta-thalassemia at different ages.

DESIGN AND METHODS
Mice Hbb(th/th), characterized by spontaneous homozygous deletion of the major b1 globin gene were studied at 2 and 8 months. Mice Hbb(th/3+), characterized by the heterozygous deletion of b1 and b2 globin genes were studied at 4 and 10 months. Hematologic data were obtained and iron overload estimated by Perls' staining of the liver. Expression of liver hepcidin, Tfr2, Hjv, Fpn and Hfe RNA was assessed by real-time polymerase chain reaction. Levels of serum cytokines (interleukin-6, IL-1beta, IL-10, granulocyte-macrophage colony-stimulating factor) levels were assayed by enzyme-linked immunosorbent assay.

RESULTS
Hemoglobin, hematocrit and mean corpuscular volume were significantly reduced in both beta-thalassemia models, more significantly in Hbb(th/3+), which have the greater, age-dependent, iron overload. Hepcidin RNA was not increased despite iron overload in both strains. Fpn RNA was increased and Tfr2 was decreased in older animals. Inflammatory cytokine levels were striking variable and unrelated to hepcidin levels.

INTERPRETATION AND CONCLUSIONS
Although anemia is reported to inhibit hepcidin expression, normal hepcidin synthesis was maintained in both thalassemic models studied. However, hepcidin levels were inappropriate for the body iron, especially in Hbb(th/3+) 10-month-old animals. As we previously reported in wild type mice after parenteral iron overload, Tfr2 is reduced and Fpn RNA increased in thalassemic mice. Inflammatory cytokines did not play a major role in increasing hepcidin levels or in modifying iron homeostasis in this study.


By analyzing the way vernacular Korean poetry of the 1920s was produced, this article initiates a study of the sociology of Korean literary production. Based on a survey of forty-five vernacular Korean books of poetry produced between 1921 and 1929, bank records, Japanese colonial government records, and printed interviews, the study describes the people, organizations, and technologies involved in the production of vernacular Korean poetry in the early twentieth century. It suggests that a small number of men in a few printing facilities working within restrained typographic conditions were responsible for printing the extant corpus of Korean vernacular poetry from the 1920s. An overview of the creative ways in which poetry was expressed visually and a discussion of the poem "Pandal" (Half moon), which appears differently in the two originary alternate issues of Kim So-wŏl's canonical 1925 work Chindallaekkot (Azaleas), make it clear that an understanding of these people and organizations, as well as of the technologies they employed, should inform how we approach texts from this period hermeneutically.


This paper presents the results of a measured data-based mass flow and balance study in UluPandan Water Reclamation Plant (WRP), the second largest municipal wastewater treatment plant in Singapore. The results are benchmarked against the Strass wastewater treatment plant in Austria, which has achieved energy self-efficiency. The gaps between the two plants have been identified and areas for process improvement in UluPandan WRP, especially those related to energy efficiency, have been proposed. This case study demonstrates that mass flow and balance is an effective tool in improving process performance and the energy efficiency of a municipal wastewater treatment plant.


An ethnographic document of 'objet trouve' nature was the starting point for this study: a school diary in two volumes, co-authored by two Dutch teenage girls in the early seventies, mostly during classes-in-progress. This lively collection of fieldnotes (texts, drawings, shrieks, written conversations) constructs an insider-relevant representation of what school is like, from class-to-class, day-to-day, year-to-year. The existence of this collusive document is itself a comment on our assumptions of what goes on in classrooms, what is heard and not heard, seen and not seen. I have selected two passages from "The Writ", as the girls called these unorthodox classroom data, that illustrate how current linguistic and educational paradigms, in embracing a 'conversational' view to learning and communication in school, underanalyze the complexity of multi-party interaction in social situations, both with respect to 'the' data that have to be accounted for and the analytic tools they use to account for them (cf. 'Where is the lesson in all this talk'; Van Dam van Isselt, 1995). The relevance of what is said is constructed in highly complex floors and collusive interactional positions (cf. Goffman, 1979, 'Footing'). In the first part of the paper, a refinement of hearer roles is central. In the second part, a different type of data is used: video-recordings of lessons in 'Dutch as a second language', taught to a group of refugee children recently arrived in the Netherlands. A close examination of these data shows that 'utterance that is not talk' is relevant to contexts of early socialization and language production (cf. Palloni, 1994). The main theme of the paper is that a dynamic notion of context is needed: as produced in real time on a moment-by-moment basis by the interpretative work of co-present parties. Two discourse models that partially fulfill these requirements and that could be adapted for the purpose are discussed: the Linguistic Discourse Model by Polanyi & Scha (Polanyi, 1988) and Van Kuppevelt's proposals for tracing the structure of narrative texts through underlying questions (Van Kuppevelt, 1995).


This paper explores trends in inequality and poverty using both market and after-tax and transfer income in the period during and after the Great Recession (through 2011). Using market income (or wages), inequality and poverty rose sharply between 2008 and 2010. The primary exception is measures for the top of the distribution; annual wage and income shares of the top one percent dipped in 2008 and 2009. Including taxes and transfers, broad-based inequality measures also fell, and the poverty increase was muted. Tax and transfer policies lowered inequality and poverty, but those policies were not equal across the population. Poverty declined among the elderly, changed little among children, and rose sharply among the working-age. Inequality fell across the total population, but was unchanged among working-age households. Since 2009, as the economy has grown slowly, inequality has risen for all groups, and poverty remains high for the working-age.


This evaluation was conducted by IDB's Independent Office of Evaluation and Oversight (OVE) at the request of the Japan Executive Director's Office at the IDB, on behalf of the Government of Japan (GoJ). The purpose of the evaluation was to assess the results obtained with JTF financing and to point out any potential improvement in the future use of those funds. The findings were also expected to highlight topics related to the visibility of Japan's contributions and collaboration with Japanese agencies. The review covered the entire JTF portfolio of country and regional NRTCs completed between January 2006 and December 2012 - a total of 265 projects with US$96.7 million in disbursements from the JTF. These operations financed programs in 25 of the 26 countries of Latin America and the Caribbean via loan preparation grants (LPGs) or stand-alone grants (SAGs) in practically all areas of IDB's work. The majority of these projects were approved between 2005 and 2009.


Criminal law norms assume that all defendants are alike. But social science research has demonstrated that most defendants with mental retardation are unlike their peers of average intelligence in their cognitive and behavioral capacity, a difference with profound effects on their blameworthiness. The law acknowledges this difference in a few limited areas, most notably in the Supreme Court's categorical exclusion of defendants with mental retardation from the death penalty. But while that decision has begun to percolate into the rest of criminal law, it has not yet reached the law of statutory rape. When prosecuted as a strict liability offense, statutory rape precludes the fact-finder from considering the defendant's state of mind altogether. The total exclusion of mens rea is an anomaly in criminal law, where a finding of guilt typically requires proof not only of an "evil act," but also of an "evil mind." Commentators have criticized the strict liability doctrine, but have ignored how the standard is especially unjust when applied to defendants with mental retardation. A close analysis of statutory rape law reveals certain assumptions which allow such a low standard of proof for such a significant offense: would-be defendants are presumed to have notice that sex with underage partners is unlawful; to be in the best position to prevent any harm from occurring; and to be deviant, immoral aggressors. When examined in light of research about mental retardation, however, these assumptions collapse. Indeed, punishing a person with mental retardation without regard to his awareness of the law, social cues, and the nature of his conduct may also run afoul of constitutional due process and proportionate sentencing principles. This article therefore argues that the prosecution of statutory rape should be modified for defendants with mental retardation. The government should have to prove that a defendant with mental retardation had the mens rea to commit the offense. In addition, this article recommends formalizing the existing ways of addressing the difference in culpability of this population through charging and sentencing. The failure to account for defendants' mental retardation in the context of statutory rape provides just one example of the theoretical and constitutional problems when criminal law disregards people who cannot comprehend the significance of their conduct.


This Introduction provides background to the more focused essays that follow. It calls attention to the continued neglect of the nineteenth-century platform, and especially--in the wake of Meisel's recent study of the political platform--of the lecture, pointing out that the extent to which oral performance underpinned written text in the Victorian period is still too little understood. It attempts a chronological survey designed to emphasize the significance of public speech in the era before the 1860s. It also seeks to provide context for a number of the key themes of the essays in the rest of the issue, arguing for the importance of the platform for transatlantic cultural exchange, and suggesting that despite the pressures, women were not completely banished from the mid-century platform as has sometimes been suggested. ********** The platform culture of nineteenth-century Britain was so ubiquitous that its omnipresence has helped to render it strangely invisible. We look through it in search of material on all aspects of the period, but we fail to look at it, to interrogate it as a cultural form in its own right. As is illustrated by the smattering of references in G.M. Young's Victorian England: Portrait of an Age superficially, the importance of the platform in Victorian intellectual culture is well established. Historians had recognized the importance of public speech in the conduct of nineteenth-century politics long before Colin Matthew's suggestive survey of the rise of extra-parliamentary politics in the last third of the century gave a new impetus to the study of the practices of the political platform. (1) Labor historians had similarly placed practices of oratory and the "mass platform" at the centre of their accounts of nineteenth-century radical movements. (2) In general, however, there has been little attention to the practice of public speech itself. There are one or two general surveys of rhetoric, such as Robert T. Oliver's Public Speaking in the reshaping of Great Britain, and some material in studies of rational recreation by Mabel Tylecote and J.F.C. Harrison; (3) but until the recent appearance of Joseph Meisel's Public Speech and the Culture of Public Life in the Age of Gladstone, the only comprehensive study of the nineteenth century platform remained Henry Jephson's The Platform, Its Rise and Progress (1892), a revealing but essentially whiggish account that concentrates almost exclusively on the political platform, and the public meeting as its most common variant, and there is no British equivalent to the book length studies of the American lecture platform of Carl Bode and David Mead, or the more recent work of Donald M. Scott. (4) Only within the relatively narrow confines of the history of science has the public lecture been subjected to sustained attention. (5) Meisel's study demonstrates the dangers of neglecting this aspect of nineteenth-century culture. This neglect is of especial significance once we begin to recognize the central place public speaking had within nineteenth-century modes of intellectual production. Perhaps because of the dominance of the histories of science, education, and politics in the historiography of public speech, at least in Britain, the culture of the platform has tended to be interpreted through notions of "popularization," "dissemination," or "mobilization," as a derivative or imitative process designed to transfer ideas, probably in a diluted form, from arenas in which they are produced to arenas in which they can obtain wider consumption. Yet to consider the platform purely from this perspective is to ignore its productive role. It is twenty-five years since Raymond Williams pointed out the extent to which "much of the important social thought of the [nineteenth] century was in lecture form." (6) Even cursory reflection suggests that a good deal of the important social criticism of the period was framed in the form of lectures and addresses, from Carlyle's Heroes and Hero-Worship through Ruskin's Sesame and Lilies to much of Morris' thought. …


Abstract In third grade the focus on math word problems becomes prominent. In the limited third grade research, teacher-mediated explicit instruction with multiple exemplars, teaching students to use visual representations, and the incorporation of self-strategies, have proven effective. For these practices to reach their full potential though, their content must be relevant and provide for growth to mature mathematical concepts. Based on these conclusions, additional research was needed. Therefore, the focus of this study was to evaluate the effectiveness of a multi-component word problem-solving intervention with explicit instruction strategies, multiple exemplars, the teaching of student-generated visual representations, incorporation of a self-monitoring checklist, and Common Core State Standards' appropriate curriculum. Within a multiple baseline across behaviors design, the study evaluated the paraphrasing, visualizing, and computing word problem-solving responses of 10 third graders identified as learning disabilities, at-risk, and/or ESOL. The study revealed that all students made gains in some behaviors related to problem solving. Results are discussed in relation to a cognitive-behavioral framework and individual student characteristics, including discussions of limitations and educational significance.


The glycome consists of all glycans (or carbohydrates) within a biological system, and modulates a wide range of important biological activities, from protein folding to cellular communications. The mining of the glycome for disease markers represents a new paradigm for biomarker discovery; however, this effort is severely complicated by the vast complexity and structural diversity of glycans. This review summarizes recent developments in analytical technology and methodology as applied to the fields of glycomics and glycoproteomics. Mass spectrometric strategies for glycan compositional profiling are described, as are potential refinements which allow structure-specific profiling. Analytical methods that can discern protein glycosylation at a specific site of modification are also discussed in detail. Biomarker discovery applications are shown at each level of analysis, highlighting the key role that glycoscience can play in helping scientists understand disease biology.


The purpose of this study was to examined the effectivity of Aloe vera gel formulation on the skin wound healing process based on the macroscopic and microscopic observation. Fourty five DDY strain, 6-8 weeks old mice were used for experimental animals. Mice were incised 1-1.5 cm in the dorsum using sterile scalpels. Mice were divided into three groups. Group I (control) were not treated by anything, Group II were treated by commercial drugs (Bioplacenton), and Group III were treated by Aloe vera gel. Bioplacenton and Aloe vera gel were given topically twice a day to the skin using sterile cotton buds. Each groups consisted of 15 mice and distributed into 5 observation days with 3 replication. Three mice from each groups were euthanized periodically at day 3rd, 5th, 7th, 14th, and 21st post incision for gross pathology examination and to sampling the skin. Gross examination revealed that Bioplacenton and Aloe vera gel showed better result on wound healing process, i.e. the scab formation, scab peeler and unite of the wounded skin edge compared to the control groups. Microscopically, the Bioplacenton and Aloe vera gel groups showed the fastest epidermal re-epithelization compared with the control group. Qualitatively Bioplacenton and Aloe vera gel groups showed more fibrosis and collagen fibres formation than the control groups especially at day 7th and 14th. Scoring Average of neocapillaries formation from all groups showed no difference. Scoring average of inflammatory cells number revealed that control groups showed more cells than the other groups that indicated an high inflammatory activity. Based on macroscopic and microscopic examination we suggest that the Aloe vera gel formulation has a benefit to promote wound healing, and could be used for the treatment of skin wound. Thus, the Aloe vera gel formulation is potential to developed as commercial drugs.


OF THESIS FORGIVING WARRIORS: DOES OUTGROUP THREAT REDUCE INGROUP AGGRESSION AMONG MALES? In order to defend against outgroups, males and females respond to outgroup threat with different strategies. Specifically, males have been shown to respond to outgroup threat with increased ingroup solidarity and cooperation which is likely reflective of their ancestral role as warriors. What remains unknown is whether this cooperative warrior mindset among males not only increases ingroup prosociality, but also decreases ingroup aggression. Aggression against ingroup members under outgroup threat would likely disadvantage the ingroup by reducing the ingroup's collective formidability. Further, prosocial motivations inhibit aggression. As such, I hypothesized that sex and outgroup threat would interact such that males, but not females, would respond to outgroup threat with reduced aggression towards ingroup members. To test this hypothesis, 41 male and 60 female participants were induced to either feel outgroup threat or no threat. All participants were then provoked by an ingroup member and then given a chance to aggress against that individual. Failing to support my hypothesis, outgroup threat did not interact with sex to predict aggression against ingroup members. This interactive effect was not further moderated by personality factors relevant to aggression. I discuss my findings in context of statistical power and the punishment of deviant ingroup members.


High-resolution bolboformid and planktic foraminiferal distribution data from the upper Miocene section of ODP Site 1123, Chatham Rise, New Zealand, have been integrated with the magnetostratigraphic record from the same site to establish a magnetobiochronology based on the geomagnetic polarity time scale (GPTS-95). Although the upper Miocene sequence is adversely affected by dissolution, 33 bioevents are identified based on dissolution resistant taxa that are also found at DSDP Site 593 - an impor- tant biostratigraphic reference section for the Neogene in the Tasman Sea. A scatter plot based on the stratigraphic positions of shared bioevents at these oceanic sites approximates a linear line of correlation. The tight grouping of the biostratigraphic data around the line of correlation and the consistency of their stratigraphic order suggest most events are synchronous or nearly so, even though the sites are more than 1400km apart and associated with different water masses. This implies that even though the biostratigraphic construct is based on only two oceanic sites, it provides a robust late Miocene biochronostratigraphic framework for the temperate Southwest Pa- cific. Shared bolboformid events include the appearances and disappearances of Bolboforma subfragoris s.l. (11.56-10.61 Ma), B. gruetzmacheri (10.46-10.31 Ma), B. capsula (10.20-10.13 Ma), B. pentaspinosa (10.15-10.08 Ma), B. gracilireticulata s.l. (9.75-9.61 Ma), B. metzmacheri s.s. (lower occurrence interval 9.54-9.34 Ma, upper occurrence interval 9.01-8.78 Ma), B. metzmacheri ornata (8.45-8.28 Ma), B. praeintermedia (8.25-8.21 Ma), and abundance spikes associated with the uppermost B. subfragoris s.l. occurrence interval BBs-1123/D (10.61 Ma) and the lower B. metzmacheri s.s. occurrence interval BBm-1123/A (9.54 Ma). Shared planktic foraminiferal events include dextral coiling excursions in Globoconella miotumida (10.92-10.82 Ma and 9.62-9.42 Ma), the regional disappearance of Globoquadrina dehiscens (8.88 Ma), and the evolutionary appearances of Globoconella conomiozea (ca. 6.87 Ma), Globoconella mons (ca. 5.72 Ma), Globoconella sphericomiozea (ca. 5.53 Ma), Globoconella pliozea (ca. 5.39 Ma), Truncorotalia crassaformis (ca. 5.15 Ma), and Globoconella puncticulata (ca. 5.11 Ma).


China's real GDP has grown at an average annual rate of 10% for the last 30 years. A period of such super-growth is historically most unusual and now is likely nearing an end. The devices that have stimulated growth in the past – heavy capital investment and a massive focus on exports – face constraints: capital investment faces diminishing returns, and exports are undermined by wage inflation. Both constraints are visible in China today. China needs to stimulate domestic consumption of its prodigious output, but this is easier said than done. A push to do so will damage the export model well before it succeeds in building a replacement.


Outbred mice were immunized with the soluble fraction of a crude Escherichia coli lysate containing either recombinant outer surface protein C (OspC or P39 of Borrelia burgdorferi B31 (low passage). Following seroconversion, the mice were challenged with an infectious dose of B. burgdorferi B31 via the natural transmission mode of tick bite. Three mice immunized with P39 were not protected; however, all 12 of the recombinant OspC-immunized mice were protected from infection as assayed by culture and serology. Although OspC has been shown to be a protective immunogen against challenge with in vitro-cultured borrelia administered by needle, this study is the first to demonstrate OspC effectiveness against tick-borne spirochetes. Following feeding, all ticks still harbored B. burgdorferi, suggesting that the mechanism of protection is not linked to destruction of the infectious spirochete within the tick. In a separate experiment, groups of four mice were immunized with protein fractions from B. burgdorferi B31 purified by preparative gel electrophoresis in an attempt to identify potential protective antigens. Many of these mice developed high-titer-antibody responses against OspC, but curiously the mice were susceptible to B. burgdorferi infection via tick bite. These results suggest that the protective epitope(s) on OspC is heat sensitive/conformational, a finding which has implications in vaccine development.


Silicon Photomultipliers (SiPM) are increasingly being used in ground-based astrophysics experiments as a replacement for Photomultiplier tubes (PMTs). These compact low power, rugged sensors are also well suited
for space applications and have an added advantage over PMTs in that they do not require high-voltage bias. Efforts are underway at NASA Goddard and our collaborators to develop large-area arrays of SiPMs as the readout
for the upcoming funded CubeSat missions such as BurstCube and Terrestrial RaYs Analysis and Detection (TRYAD) and also larger missions including the ultra-heavy cosmic-ray Heavy Nuclei Explorer (HNX) experiment and the
gamma-ray Advanced Particle-astrophysics Telescope (APT) experiment. Our team has recently tested SiPMs in a heavy ion beam at CERN. The primary beam consisted of lead ions with energy of ~150 GeV/nuc. SiPM hardware was
exposed to both a pure and fragmented Pb beam allowing us to look at ions from Z=1 to Z=82. We report in this paper on direct comparisons with the performance of Hamamatsu R1924A photomultipliers in addition to examining the signals (and subsequent
effects) from direct exposure to a lead beam.


This paper explores Palestinians' attitudes towards a peace process and their determinants, with a particular focus on the role of education. Understanding the factors that shape attitudes towards peace is important in order to be successful in negotiations or in implementing a peace agreement. In the literature, there is particular disagreement about the role of education. While some authors have linked violent and extreme positions to ignorance and to low market opportunities, others have found that education is positively correlated with being a member of a terrorist group. To better understand the role of education I decompose the attitudes towards peace into two dimensions; attitudes towards reconciliation and attitudes towards concessions. To measure these attitudes, I use a flexible item response model proposed by Spady (2007), which allows to take into account the multidimensionality of the concepts. The results show that education has a positive effect on attitudes towards concessions but a negative effect on attitudes towards reconciliation. This may occur because relative to a situation of peace, highly educated individuals are more strongly affected by current depressed economic conditions in Palestine. They therefore have more to gain from a peace agreement and may thus be more willing to make concessions. At the same time, they may be more frustrated and therefore less willing to reconcile. I also find that their attitudes to reconciliation move closely with aggregate economic conditions, while those of less educated individual are also influenced by local factors such as the construction of the separation barrier in their region of residence.


Opposing effects of Gi protein α and βγ subunits on the abundance of the second messenger cAMP enable neutrophil migration. Control cAMP to control migration Activation of the G protein–coupled receptors (GPCRs) that stimulate cellular migration generates active G protein α and βγ subunits, which interact with distinct effector molecules. Using a small molecule that activates βγ subunits without activating α subunits in neutrophils, Surve et al. determined that active βγ subunits alone increased the intracellular concentration of the second messenger cAMP so much that the cells stuck to coated surfaces. Active G protein αi subunits balanced this βγ signal, reducing cAMP sufficiently to enable the cells to move. Activation of the Gi family of heterotrimeric guanine nucleotide–binding proteins (G proteins) releases βγ subunits, which are the major transducers of chemotactic G protein–coupled receptor (GPCR)–dependent cell migration. The small molecule 12155 binds directly to Gβγ and activates Gβγ signaling without activating the Gαi subunit in the Gi heterotrimer. We used 12155 to examine the relative roles of Gαi and Gβγ activation in the migration of neutrophils on surfaces coated with the integrin ligand intercellular adhesion molecule–1 (ICAM-1). We found that 12155 suppressed basal migration by inhibiting the polarization of neutrophils and increasing their adhesion to ICAM-1–coated surfaces. GPCR-independent activation of endogenous Gαi and Gβγ with the mastoparan analog Mas7 resulted in normal migration. Furthermore, 12155-treated cells expressing a constitutively active form of Gαi1 became polarized and migrated. The extent and duration of signaling by the second messenger cyclic adenosine monophosphate (cAMP) were enhanced by 12155. Inhibiting the activity of cAMP-dependent protein kinase (PKA) restored the polarity of 12155-treated cells but did not decrease their adhesion to ICAM-1 and failed to restore migration. Together, these data provide evidence for a direct role of activated Gαi in promoting cell polarization through a cAMP-dependent mechanism and in inhibiting adhesion through a cAMP-independent mechanism.


Artemisinin, a poorly water-soluble antimalarial drug, presents a low and erratic bioavailability upon oral administration. The aim of this work was to study an agglomerated powder dosage form for oral administration of artemisinin based on the artemisinin/β-cyclodextrin primary microparticles. These primary microparticles were prepared by spray-drying a water–methanol solution of artemisinin/β-cyclodextrin. β-Cyclodextrin in spray-dried microparticles increased artemisinin water apparent solubility approximately sixfold. The thermal analysis evidenced a reduction in the enthalpy value associated with drug melting, due to the decrease in drug crystallinity. The latter was also evidenced by powder X-ray diffraction analysis, while 13C-NMR analysis indicated the partial complexation with β-cyclodextrin. Agglomerates obtained by sieve vibration of spray-dried artemisinin/β-cyclodextrin primary microparticles exhibited free flowing and close packing properties compared with the non-flowing microparticulate powder. The in vitro dissolution rate determination of artemisinin from the agglomerates showed that in 10 min about 70% of drug was released from the agglomerates, whereas less than 10% of artemisinin was dissolved from raw material powder. Oral administration of agglomerates in rats yielded higher artemisinin plasma levels compared to those of pure drug. In the case of the agglomerated powder, a 3.2-fold increase in drug fraction absorbed was obtained.