BACKGROUND
Previous trials of interferon beta in multiple sclerosis (MS) have shown efficacy, but the degree of clinical benefit remains uncertain, and the optimum dose is not known. We undertook a double-blind, placebo-controlled study in relapsing/remitting MS to investigate the effects of subcutaneous interferon beta-1a.

METHODS
560 patients with Kurtzke expanded disability status scale (EDSS) scores of 0-5.0, from 22 centres in nine countries, were randomly assigned subcutaneous recombinant interferon beta-1a 22 microg (n=189), or 44 microg (n=184), or placebo (n=187) three times a week for 2 years. Neurological examinations were done every 3 months. All patients had MRI twice yearly and 205 had monthly scans in the first 9 months of treatment. Analysis was by intention to treat.

FINDINGS
Clinical data on 533 (95%) patients were available at 2 years. The relapse rate was significantly lower at 1 and 2 years with both doses of interferon beta-1a than with placebo (mean number per patient 1.82 for 22 microg group, 1.73 for 44 microg group vs 2.56 for placebo group: risk reductions 27% [95% CI 14-39] and 33 [21-44]). Time to first relapse was prolonged by 3 and 5 months in the 22 microg and 44 microg groups respectively, and the proportion of relapse-free patients was significantly increased (p<0.05). Interferon beta-1a delayed progression in disability, and decreased accumulated disability during the study. The accumulation of burden of disease and number of active lesions on MRI was lower in both treatment groups than in the placebo group.

INTERPRETATION
Subcutaneous interferon beta-1a is an effective treatment for relapsing/remitting MS in terms of relapse rate, defined disability, and all MRI outcome measures in a dose-related manner, and it is well tolerated. Longer-term benefits may become clearer with further follow-up and investigation.


The reliability of the Star Graph architecture is discussed. The robustness of the Star Graph network under node failures, link failures, and combined node and link failures is shown. The degradation of the Star Graph into Substar Graphs is used as the measure of system effectiveness in the face of failures. Models are provided for each of the failure and re-mapping modes evaluated herein, and the resilience of the Star Graph to failures is emphasized. This paper defines failure of a Star Graph as being when no fault-free (n - 1)-substars remain operational and the intermediate states are defined by the number of (n - 1)-substars that remain operational. A powerful tool (re-mapping) is introduced in which the number of operational (n 1)-substars can be maintained for longer periods, thus improving the overall MTTF (mean time to failure). For comparison the results of a similar reliability analysis of the hypercube is shown. The comparisons are considered conservative due to the failure model used herein for the star graph. One might apply re-mapping to hypercubes; while it would improve the overall MTTF of hypercubes, the hypercubes would still have an appreciably poorer performance than star graphs.


The intersection between international trade and climate change brings some trade-off in policy design for both ambits. On the one hand trade barriers can be implemented to address competitiveness concerns raised by climate policy. On the other hand, policies that promote exports and foreign direct investments can increase the transfer of technology and knowledge. In addition, climate agreements do include specific provisions aimed at encouraging trade in energy goods and services. This paper uses a dynamic CGE (ICES) to assess the intertemporal and spatial dimension of international technology spillovers within a framework of climate and trade policy. The paper addresses issues such as the impact of spillovers on carbon leakage and explores on the effectiveness of Border Tax Adjustments. Three are the main contributions of the study. First, although the statistical effect of spillovers is energy saving, general equilibrium effects may revert their sign through price effects and thus substitution. A second result is related to the intertemporal dimension of the model. Over time, production of spillovers vehicle, namely machinery and equipment in this case, is reallocated towards destination countries. Moreover, spillovers augment this tendency generating a virtuous cycle. In fact, this effect contributes to enhance the absorptive capacity of recipient countries, increasing the potential benefits from technology transfers. Third, the presence of technology transfers offers an additional tool to address the issue of carbon leakage. So far the literature has focussed on BTAs as one of the trade options that can be implemented to offset competitiveness concerns within climate policies. However, that literature neglected the negative side effect such measures can have on technology transfers. On the contrary, trade liberalization, by increasing the effects of spillovers, may reduce carbon leakage indirectly.


Structures of translocation intermediates reveal how transfer RNA molecules move through the ribosome during protein synthesis. [Also see Research Articles by Tourigny et al., Zhou et al., and Pulk and Cate] Ribosomes are macromolecular factories that translate the information encoded in messenger RNA (mRNA) into the amino acid sequence of proteins. Each time an amino acid has been transferred to the growing peptide chain, the mRNA and two transfer RNAs (tRNAs) move through the ribosome one codon at a time. This movement—called translocation—is promoted by elongation factor G (EF-G). Three papers in this issue, by Tourigny et al. (1), Pulk and Cate (2), and Zhou et al. (3), present high-resolution structures of translocation intermediates and provide insights into the underlying mechanism.


Objectives: Previous analyses of interventions targeting relationships between family caregivers of people with Alzheimer's disease and related dementias and residential long-term care (RLTC) staff showed modest associations with caregiver outcomes. This analysis aimed to better understand interpersonal and contextual factors that influence caregiver–staff relationships and identify targets for future interventions to improve these relationships. Methods: Using a parallel convergent mixed methods approach to analyze data from an ongoing counseling intervention trial, descriptive statistics characterized the sample of 85 caregivers and thematic analyses explored their experiences over 4 months. Results: The findings illustrated that communication, perceptions of care, and relationships with staff are valued by family caregivers following the transition of a relative with dementia to RLTC. Discussion: The findings deepen understanding of potential intervention targets and mechanisms. These results can inform future psychosocial and psychoeducational approaches that assist, validate, and empower family caregivers during the transition to RLTC.


The thesis focuses on the emotional experience of perpetrator graffiti of the Turkish-Kurdish urban war zones by young people in Istanbul who are emotionally and/or politically involved in Kurdish politics. By "perpetrator graffiti" I refer to the Turkish Special Forces' (OH) inscriptions of graffiti into ruined Kurdish spaces, sharing of their photographs on virtual "walls" of Twitter and Facebook, as well as their affective imprint on the dissident young people's gendered subjectivities. During the urban clashes between the local Kurdish militia (YDG-H) and the Turkish security forces in certain towns and neighborhoods of Kurdish provinces in Southeastern Turkey in 2015-2016, the OH sprayed graffiti with threatening content onto the ruined streets and intimate interiorities of private homes. In addition, the violent destruction and appropriation was photographed in a militarized masculinized spectacle with OH members posing for the photographs, which were then circulated on social media. The thesis critically engages with theoretical works on affect and emotions in critical theory and cultural anthropology. Based on ethnographic fieldwork in Istanbul, virtual ethnography, textual analysis of graffiti, and in-depth interviews with people who followed the events of the urban war zones via social media, I explore the historically contingent feelings of ruins and graffiti. I approach political feelings of sorrow, disgust, anger, helplessness, and precarious hope triggered by violent words and images in relation to meaning, subjectivity, and structural conditions of possibility, which proved to be essential preconditions for the emotional experience and the ability to respond to violence.


The Chicago Conspiracy Trial (otherwise known as the Chicago Seven Trial) is a Rorschach test of American society in the late 1960s and early 1970s. Following the riots at the Democratic Convention in Chicago in 1968, leaders of the antiwar movement, the counterculture and the Black Panthers were put on trial for a "conspiracy to cross state lines with intent to incite a riot." The trial has been too easily dismissed as a circus, not worthy of legal attention, when in fact it does contain important legal insights. This paper suggests that the theory of the theater provides the key to unlocking the trial's significance. The paper applies Peter Brook's theories of the theater and argues that in Brook's terms, this trial is "rough" rather than "deadly" theater. By staging events that are generally unthinkable in the courtroom, such as the binding and gagging of Bobby Seale or the appearance of Abbie Hoffman and Jerry Rubin in court dressed in judicial robes, some terrifying truths about law were captured and made visible. These truths are terrifying not only because they deviate from expected norms of civility and depict the degree of violence generally hidden from the public view. They capture archetypal motifs from the collective conscious and unconscious, thereby invoking the universal struggle about the appropriate relationships between the person and the government. In conclusion, the paper looks to the reaction of subsequent courts sitting on appeal and as courts of retrial, and discusses the extent to which they were willing to face the messages contained in these scenes.


Although there have been significant advances in the field of image restoration recently, the system complexity of the state-of-the-art (SOTA) methods is increasing as well, which may hinder the convenient analysis and comparison of methods. In this paper, we propose a simple baseline that exceeds the SOTA methods and is computationally efficient. To further simplify the baseline, we reveal that the nonlinear activation functions, e.g. Sigmoid, ReLU, GELU, Softmax, etc. are not necessary: they could be replaced by multiplication or removed. Thus, we derive a Nonlinear Activation Free Network, namely NAFNet, from the baseline. SOTA results are achieved on various challenging benchmarks, e.g. 33.69 dB PSNR on GoPro (for image deblurring), exceeding the previous SOTA 0.38 dB with only 8.4% of its computational costs; 40.30 dB PSNR on SIDD (for image denoising), exceeding the previous SOTA 0.28 dB with less than half of its computational costs. The code and the pre-trained models are released at https://github.com/megvii-research/NAFNet.


The popularity of hardware-based Trusted Execution Environments (TEEs) has recently skyrocketed with the introduction of Intel's Software Guard Extensions (SGX). In SGX, the user process is protected from supervisor software, such as the operating system, through an isolated execution environment called an enclave. Despite the isolation guarantees provided by TEEs, numerous microarchitectural side channel attacks have been demonstrated that bypass their defense mechanisms. But, not all hope is lost for defenders: many modern fine-grain, high-resolution side channels-e.g., execution unit port contention-introduce large amounts of noise, complicating the adversary's task to reliably extract secrets. In this work, we introduce Microarchitectural Replay Attacks, whereby an SGX adversary can denoise nearly arbitrary microar- chitectural side channels in a single run of the victim, by causing the victim to repeatedly replay on a page faulting instruction. We design, implement, and demonstrate our ideas in a framework, called MicroScope, and use it to denoise notoriously noisy side channels. Our main result shows how MicroScope can denoise the execution unit port contention channel. Specifically, we show how Micro- Scope can reliably detect the presence or absence of as few as two divide instructions in a single logical run of the victim program. Such an attack could be used to detect subnormal input to individual floating-point instructions, or infer branch directions in an enclave despite today's countermeasures that flush the branch predictor at the enclave boundary. We also use MicroScope to single-step and denoise a cache-based attack on the OpenSSL implementation of AES. Finally, we discuss the broader implications of microarchitec- tural replay attacks-as well as discuss other mechanisms that can cause replays.


Abstract Stone is the oldest, natural material, which was (and still is) used as both building and sculptural material. The most commonly used for these purposes are: granites, marbles, limestones and sandstones, representing the three main genetic groups of igneous, metamorphic and sedimentary rocks. All of them are permanently being destroyed in result as well of natural weathering as microbiological activity and anthropogenic pollution of atmosphere, known as deterioration. The speed of such decay depends on both environmental conditions and mineral composition of the stone and it can lead to such intensive destruction that conservation may require partial replacement. Smaller damages are refilled with appropriate mineral masses, whereas in case of bigger damages refilling with natural stone is necessary. Professional conservation practice demands the selection and use of the same rock or the rock that is, in so far as is possible, identical to that originally used. It can be done only after previous detailed petrographical studies of the original material. Only then the stone material used for reconstruction will be appropriate and stonework performed properly will not (or almost not) leave marks. In many cases the ancient quarries do not exist and original source material is not available. Then petrographical studies of numerous rock-samples, which are recently available from other existing and/or working quarries, will allow the indication the most similar material. In many cases, unfortunately, the stone used for replacement is not identical to the original but only macroscopically similar. In such a case results might be visible sooner or later. These will be differences in colour, differences in structure and in some cases even crystallization of secondary minerals in the newly inserted fragments.


Hemodynamic classifications of aortic valve stenosis (AS) have important prognostic implications. In normal flow state, severe AS is defined as peak aortic velocity ≥ 4.0 m/s, mean transaortic gradient (MG) ≥ 40 mmHg, and aortic valve area (AVA) < 1.0 cm 2 . However, numerous studies have shown that severe AS (based on AVA < 1.0 cm 2 ) with low gradient (MG < 40 mmHg) is prevalent due to low flow state, in the setting of reduced and preserved left ventricular ejection fraction (LVEF). Thus, the hemodynamic classifications of AS with AVA < 1.0 cm 2 were expanded to include the transvalvular flow state and pressure gradients. These flow-gradient patterns include normal flow/very high gradient, normal flow/high gradient, low flow/high gradient, low flow/low gradient with reduced LVEF, low flow/low gradient with preserved LVEF, and normal flow/low gradient. Among these, the low-gradient AS subgroups are challenging, particularly to differentiate true-severe AS (where aortic valve replacement is necessary) and pseudo-severe AS (where conservative management is recommended). Additional diagnostic studies such as dobutamine stress echocardiography and/or cardiac computed tomography, as well as other parameters such as projected AVA and/ or valvuloarterial impedance may be helpful. This chapter will review diagnostic approaches and prognostic implications of different AS subtypes.


Intraductal papillary‐mucinous tumor (IPMT) of the pancreas has become the accepted terminology for a group of mucin‐producing epithelial proliferations lying within ectatic segments of the main pancreatic duct or its large branches. These neoplasms generally are associated with an indolent course, characteristic endoscopic ultrasonographic (EUS) findings, and a variable histo‐ and cytomorphology ranging from hyperplasia to carcinoma. Cytological specimens obtained by endoscopic ultrasound‐guided or percutaneous fine‐needle aspiration (FNA) are characterized by a background containing abundant mucin in which are entrapped single or loosely cohesive clusters of neoplastic cells characteristically showing a goblet‐cell morphology. The degree of nuclear atypia, cell crowding, and cell shape varies between smears within a single case and between cases. Cytomorphological examination, when coupled with EUS features, is accurate for the diagnosis of these lesions but often it underdiagnoses the grade of the neoplasm. Diagn. Cytopathol. 2005;32:16–20. © 2005 Wiley‐Liss, Inc.


Gairdia lamblia is one of parasites that cause intestinal problems within the human body, particularly private travelers and children. In this study a total of (100) diarrheal patients, 20 patients with Giardiasis were identified by fecal antigen. 9 out of 20(20%) of them were infected by fecal antigen, while 9(9%) of them were infected by using the screening general stool examination (GSE). The stool samples were collected from patient how vested the Medical City/ Baghdad and Tikrit teaching Hospital during the period from 1 st may 2018 to 1 February 2019. The results revealing a significant difference (p andlt; 0.05) between the two methods of detection for G. lamblia (Fecal antigen method and GSE). IT has been shown that out of 20 infected individuals 12(12%) were males and 8(8%) were females, indicating regarding no significant deference in the distribution of Giardiasis among genders. In regard the age, our results showed that highest infection rate 8(3.2%) was recorded in the age group (10-19) years, followed by the age group (20-2) years which was 692.4%). In this study five mutations were recorded at position (926, 1094, 1202and 1304), by using tpiA gene sequence method, and tpiB gene was on point mutation change (G254A), in the position (85) of triose phosphate isomease.


48 patients with rheumatoid arthritis (RA) were exposed to He-Ne laser radiation. Due to the course of the above laser therapy the patients displayed reduced levels of E and F2 alpha prostaglandins, a trend to a decrease of lipid peroxidation products, glycosaminoglycans and collagen-peptidase activity. This evidences for suppression of the inflammation and destruction in the connective tissue. Catalase activity in red cells enhanced. The authors point to high efficacy of low-intensity He-Ne laser in moderate rheumatoid inflammation.


The optical properties of a four-level double-V-type closed-loop system is studied in the multiphoton resonance condition. It is shown that the phase-dependent electromagnetically induced transparency (EIT) window is established and by changing the relative phase of the applied fields, EIT switches to electromagnetically induced absorption. Moreover, the optical bistability (OB) behavior of the system is studied, and it is demonstrated that the cross-Kerr-effect-induced OB depends on the relative phase of the applied fields, and it can be controlled by either intensity or relative phase of laser fields. By applying a microwave field to drive the hyperfine transition between two lower states, the optical properties change and OB switches to optical multistability. This can be used for detection of longer wavelengths than visible light.


In this paper, an energy flow control strategy to reduce the smart meter privacy leakage is studied. The considered smart grid is equipped with an energy storage device. The privacy leakage is modeled as optimal Bayesian detections on the behaviors of the consumer made by an authorized adversary. To evaluate the privacy risk, a Bayesian detection-operational privacy leakage metric is proposed. The design of an optimal privacy-preserving energy control strategy can be formulated as a belief state MDP problem. Therefore, standard methods and algorithms can be utilized to obtain or to approximate the optimal control strategy. A simplified problem to design an instantaneous optimal privacy-preserving control strategy is also considered. It is shown that the problem of the instantaneous optimal control strategy design can be formulated as a set of linear programmings.


One of the form of authorities that has been given by the goverment in order to fulfill the autonomous region for managing the areais the financial aspect. The purpose of the performance measurement of the goverment is to improve the goverment's performance itself, allocate the resources that we have, and make some decisions to realize public accountabilities. The form of performance measurements for the goverment is done by conducting a financial analysis of The regional Expenditure Budget (APBD) that has been established and implemented before. The type of research that has been conducted by the researcher is quantitative descriptive. The result of studi indicate financial perfoemance of the city goverment of Bogor is good. It means that the average amount of PAD Bogor from 2012- 2016 is 26,96 % which is compared with the total regional incomes.The effectiveness of Bogor's regional financial management could happen because it uses an effetive relationship pattern on average above 100%. The ratio of direct expenditure to total expenditure in Bogor from2012 – 2014 experienced the highest increase, the highest ratio is happened in 2014 54,21%. The PAD growth ratio shows a positive result despite of showing a sharp decline in 2016 of 8,61%.


In this study, it is aimed to design a robot that can be used in fields such as land exploration, mine search, ammunition transportation, search and rescue activities in natural disasters. For this purpose, a six-legged robot was designed. The robot can move evenly in uneven terrain conditions, stop, accelerate and overcome the obstacle when it sees an obstacle. The mechanical and electronic design of the robot was realized, and a prototype was manufactured. The flexibility of the legs used in the design ensures that the robot can move more easily in field conditions. The synchronous speed and direction of the motors are controlled, and the robot moves in a balanced way. With the IP camera mounted on a Raspberry Pi, snapshots were taken from the robot. Mechanical and electronic design of six-legged robot capable of moving on uneven ground was realized. The six-legged robot was placed with three legs on the right and three legs on the left. The motors were operated simultaneously to allow the robot to move evenly. Thanks to its leg structure, it was aimed to travel in land conditions. Image control was provided on the computer with the camera placed on the robot. In this study, the program written into the electronic cards run the motors simultaneously.


PPM1D (Wip1), a type PP2C phosphatase, is expressed at low levels in most normal tissues but is overexpressed in several types of cancers. In cells containing wild-type p53, the levels of PPM1D mRNA and protein increase following exposure to genotoxic stress, but the mechanism of regulation by p53 was unknown. PPM1D also has been identified as a CREB-regulated gene due to the presence of a cyclic AMP response element (CRE) in the promoter. Transient transfection and chromatin immunoprecipitation experiments in HCT116 cells were used to characterize a conserved p53 response element located in the 5′ untranslated region (UTR) of the PPM1D gene that is required for the p53-dependent induction of transcription from the human PPM1D promoter. CREB binding to the CRE contributes to the regulation of basal expression of PPM1D and directs transcription initiation at upstream sites. Following exposure to ultraviolet (UV) or ionizing radiation, the abundance of transcripts with short 5′ UTRs increased in cells containing wild-type p53, indicating increased utilization of downstream transcription initiation sites. In cells containing wild-type p53, exposure to UV resulted in increased PPM1D protein levels even when PPM1D mRNA levels remained constant, indicating post-transcriptional regulation of PPM1D protein levels.


Purpose: This paper analyzes the financial stability, the reasons for the low level of financial stability and their impact on the national security of Ukraine. Design/Methodology/Approach: By observation, monitoring of causes and effects of financial stability. Findings: The study found that the main financial stability issues that affected national security in Ukraine were the ineffective regulatory legislation, the high level of distrust in the financial sector, the low growth rates of securities, the high level of credit rates. Also the fact that the financial sector is not capable of securing redistribution of funds in the Ukrainian economy, inefficient use of deposits by the banking sector, insufficient capital of the banking system, low dependence of the banking system on market activity, low level of ability of banks' own capital to cover losses. At the same time banks were exposed to the risk of insolvency of non-financial corporations with insufficient level of money market security and monetization in Ukraine. Practical Implications: A number of problems that negatively affect national security have been systematized. Measures have been developed that will contribute to the development of the financial sector. Originality/Value: With this article we show that the financial stability of the state, its financial dependency / independence can significantly affect national security, economic security, social security, scientific and technological, military and other types of securities.


This study considered the current situation of solid and liquid biomass fuels in Finland. The fact that the industry consumes more than half of the total primary energy, widely applied combined heat and power production and a high share of solid biomass fuels in the total energy consumption are specific to the Finnish energy system. Wood is the most important source of bioenergy in Finland, representing 25% of total energy consumption in 2013. Wood fuels have been to the most used source of energy, since 2012 before oil. Most of the wood-based energy (64%) is recovered from industrial by-products and residues. As a member of the European Union, Finland has committed itself to the Union's climate and energy targets, such as reducing its overall emissions of greenhouse gases to at least 20% below 1990 levels by 2020, and increasing the share of renewable energy in the gross final consumption. The renewable energy target approved for Finland is 38%. The present National Climate and Energy Strategy was introduced in November 2008 and renewed 2012. The strategy covers climate and energy policy measures up to 2020, and in brief thereafter, up to 2050. In recent years, the actual emissions have met the Kyoto commitment due to the economic recession but the trend of emissions is on the increase. According to Statistics Finland's greenhouse gas emission data, Finland fulfilled its emission reduction commitment for the Kyoto Protocol's first commitment period. The emission for the period 208 to 2012 were 5% below the assigned amount of emissions specified for Finland. In 2013, the share of renewable energy in the gross final energy consumption was approximately 32%. Meeting the targets will need the adoption of more active energy policy measures in coming years. The international trade of biomass fuels has a substantial importance for the utilisation of bioenergy in Finland. In 2013, the total international trading of solid and liquid biomass fuels was approximately 80 PJ, of which import was 67 PJ. The indirect import of wood fuels which takes place within the forest industry's raw wood was 67 PJ in 2013. In 2009, the import of raw wood collapsed, and correspondingly, the indirect import of wood fuels dropped to 23 PJ. In 2004-2008, wood pellets and tall oil formed the majority of export streams of biomass fuels. During 2007-2009, two large biodiesel production units were established in Porvoo, and palm oil and biodiesel have become the largest import and export streams of energy biomass.


We present a new implicit warping framework for image animation using sets of source images through the transfer of the motion of a driving video. A single cross- modal attention layer is used to find correspondences between the source images and the driving image, choose the most appropriate features from different source images, and warp the selected features. This is in contrast to the existing methods that use explicit flow-based warping, which is designed for animation using a single source and does not extend well to multiple sources. The pick-and-choose capability of our framework helps it achieve state-of-the-art results on multiple datasets for image animation using both single and multiple source images. The project website is available at https://deepimagination.cc/implicit warping/


Supersulfated low molecular weight heparin (ssLMWH) inhibits the intrinsic tenase (factor IXa-factor VIIIa) complex in an antithrombin-independent manner. Recombinant factor IXa with alanine substitutions in the protease domain (K126A, N129A, K132A, R165A, R170A, N178A, R233A) was assessed with regard to heparin affinity in solution and ability to regulate protease activity within the factor IXa-phospholipid (PL) and intrinsic tenase complexes. In a soluble binding assay, factor IXa K126A, K132A, and R233A dramatically (10-20-fold) reduced ssLMWH affinity, while factor IXa N129A and R165A moderately (5-fold) reduced affinity relative to wild type. In the factor IXa-PL complex, binding affinity for ssLMWH was increased 4-fold, and factor X activation was inhibited with a potency 7-fold higher than predicted for wild-type protease-ssLMWH affinity in solution. In the intrinsic tenase complex, ssLMWH inhibited factor X activation with a 4-fold decrease in potency relative to wild-type factor IXa-PL. The mutations increased resistance to inhibition by ssLMWH in a similar fashion for both enzyme complexes (R233A > K126A > K132A/R165A > N129A/N178A/wild type) except for factor IXa R170A. This protease had ssLMWH affinity and potency for the factor IXa-PL complex similar to wild-type protease but was moderately resistant (6-fold) to inhibition in the intrinsic tenase complex based on increased cofactor affinity. These results are consistent with conformational regulation of the heparin-binding exosite and macromolecular substrate catalysis by factor IXa. An extensive overlap exists between the heparin and factor VIIIa binding sites on the protease domain, with residues K126 and R233 dominating the heparin interaction and R165 dominating the cofactor interaction.


Visual information passes through layers of processing along the visual pathway, such as retina, lateral geniculate nucleus (LGN), primary visual cortex (V1), prestriate cortex (V2), and beyond. Understanding the functional roles of these visual processing layers will not only help to understand psychophysical and neuroanatomical observations of these layers, but also would help to build intelligent computer vision systems that exhibit human-like behaviors and performance. One of the popular theories about the functional role of visual perception, the efficient coding theory, hypothesizes that the early visual processing layers serve to capture the statistical structure of the visual inputs by removing the redundancy in the visual outputs. Linear implementations of the efficient coding theory, such as independent component analysis (ICA) and sparse coding, learn visual features exhibiting the receptive field properties of V1 simple cells when they are applied to grayscale image patches. In this dissertation, we explore different aspects of the early visual processing layers by building computational models following the efficient coding theory. 1) We develop a hierarchical model, Recursive ICA, that captures nonlinear statistical structures of the visual inputs that cannot be captured by a single layer of ICA. The model is motivated by the idea that higher layers of the visual pathway, such as V2, might work under similar computational principles as the primary visual cortex. Hence we apply a second layer of ICA on top of the first layer ICA outputs. To allow the second layer of ICA to better capture nonlinear statistical structures, we derive a coordinate-wise nonlinear activation function that transforms the first layer ICA's outputs to the second layer ICA's inputs. When applied to grayscale image patches, the model's second layer learns nonlinear visual features, such as texture boundaries and shape contours. We apply the above model to natural scene images, such as forest and grassland, to learn some generic visual features, and then use these features for face and handwritten digit recognition. We get higher recognition rates than those systems built with features designed for face and digit recognition. (2) We show that retinal coding, the pre-cortical stage of visual processing, can also be explained by the efficient coding theory. The retinal coding model turns out to be another variation of Sparse PCA, a technique widely applied in signal processing, financial analysis, bioinformatics, etc. Compared with ICA, which removes the redundancy among the input dimensions, Sparse PCA removes redundancy among the input samples. We apply Sparse PCA to grayscale images, chromatic images, grayscale videos, environmental sound, and human speech, and learn visual and auditory features that exhibit the filtering properties of retinal ganglion cells and auditory nerve fibers. This work suggests that the pre-cortical stages of visual and auditory pathway might work under similar computational principles


Traditionally, management of strawberry (Fragaria × ananassa Duch.) diseases is based on chemical control; however, because of the high cost of pesticides and their adverse environmental effects, it is essential to determine the correct application timing. Disease forecasting models calculate optimal conditions for disease development, therefore model-based applications of fungicides are more precise. This study aimed to evaluate how to apply fungicides more precisely by using grey mould (Botrytis cinerea Pers.: Fr.) risk forecasting model iMETOS® in order to reduce the number of applications, to obtain yield increase and ensure the safety and quality of strawberries. Field experiments were carried out at Institute of Horticulture, Lithuanian Research Centre for Agriculture and Forestry during 2008–2014 on a strawberry cultivar 'Elkat'. The experimental treatments were: 1) untreated, 2) conventional disease management system and 3) using forecasting model iMETOS®. The experimental data indicated that the most favourable conditions for the spread of strawberry grey mould occurred in the 3rd–4th week of May and in the 1st week of June. The application time as determined by the forecasting model iMETOS®, gave yield increases in 2008–2014 of 0.9, 9.5, 1.0, 2.8, 4.3 and 3.2 t ha-1, respectively, compared to the control treatment. In 2008–2014, the yield increase in the conventional disease management treatment was 3.2, 7.0, 3.5, 2.8, 2.7 and 2.7 t ha-1 higher compared to the control treatment. In 2009, the yield increases in the iMETOS® treatment were 2.5 t ha-1, in 2013 – 1.6 t ha-1 and in 2014 – 0.5 t ha-1 compared with the conventional disease management treatment. In 2011, there was no yield increase; the yield was similar in both treatments. In the iMETOS® treatments, the amount of rotten fruit was 0.7, 2.3, 0.7, 0.1, 0.2 and 0.6 t ha-1 lower than in the control treatment. Fungicide application according to the recommendations of the forecasting model iMETOS® allows reduction of plant protection costs, especially when the conditions for the spread of diseases are not favourable.


Mahatma Gandhi is one of the least understood figures of all time -- even among his admirers. In this Annual Gandhi Lecture for the International Association of Gandhian Studies, Mark Shepard tackles some persistently wrong-headed views of Gandhi, offering us a more accurate picture of the man and his nonviolence. ///////////////////////////////////////////////// Mark Shepard is the author of "Mahatma Gandhi and His Myths," "The Community of the Ark," and "Gandhi Today," called by the American Library Association's Booklist "a masterpiece of committed reporting." His writings on social alternatives have appeared in over 30 publications in the United States, Canada, England, Norway, Germany, the Netherlands, Switzerland, Japan, and India. ///////////////////////////////////////////////// "A model of Gandhian journalism...[Shepard] has put his finger on seemingly all of the popular (and some less common) misconceptions of both Gandhi and his philosophy, including some particularly important ones...This book takes little space to cover its topic concisely and well. It would be [some] of the most valuable pages many people could read about Gandhi." -- Global Conscience, July-Sept. 1990 ///////////////////////////////////////////////// SAMPLE I suspect that most of the myths and misconceptions surrounding Gandhi have to do with nonviolence. For instance, it's surprising how many people still have the idea that nonviolent action is passive. It's important for us to be clear about this: There is nothing passive about Gandhian nonviolent action. I'm afraid Gandhi himself helped create this confusion by referring to his method at first as "passive resistance," because it was in some ways like techniques bearing that label. But he soon changed his mind and rejected the term. Gandhi's nonviolent action was not an evasive strategy nor a defensive one. Gandhi was always on the offensive. He believed in confronting his opponents aggressively, in such a way that they could not avoid dealing with him. But wasn't Gandhi's nonviolent action designed to avoid violence? Yes and no. Gandhi steadfastly avoided violence toward his opponents. He did not avoid violence toward himself or his followers. Gandhi said that the nonviolent activist, like any soldier, had to be ready to die for the cause. And in fact, during India's struggle for independence, hundreds of Indians were killed by the British. The difference was that the nonviolent activist, while willing to die, was never willing to kill. Gandhi pointed out three possible responses to oppression and injustice. One he described as the coward's way: to accept the wrong or run away from it. The second option was to stand and fight by force of arms. Gandhi said this was better than acceptance or running away. But the third way, he said, was best of all and required the most courage: to stand and fight solely by nonviolent means.


This paper explores evidence for the conjecture that improvements in Web accessibility have arisen, in part, as side effects of changes in Web technology and associated shifts in the way Web pages are designed and coded. Drawing on an earlier study of Web accessibility trends over the past 14 years, it discusses several possible indirect contributors to improving accessibility including the use of new browser capabilities to create more sophisticated page layouts, a growing concern with improved page rank in search results, and a shift toward cross-device content design. Understanding these examples may inspire the creation of additional technologies with incidental accessibility benefits.


The automated extraction of semantically meaningful information from multi-modal data is becoming increasingly necessary due to the escalation of captured data for archival. A novel area of multi-modal data labelling, which has received relatively little attention, is the automatic estimation of the most dominant person in a group meeting. In this paper, we provide a framework for detecting dominance in group meetings using different audio and video cues. We show that by using a simple model for dominance estimation we can obtain promising results.


This paper is concerned with the estimation of the autoregressive parameter in a widely considered spatial autocorrelation model. The typical estimator for this parameter considered in the literature is the (quasi) maximum likelihood estimator corresponding to a normal density. However, as discussed in the paper, the (quasi) maximum likelihood estimator may not be computationally feasible in many cases involving moderate or large sized samples. In this paper we suggest a generalized moments estimator that is computationally simple irrespective of the sample size. We provide results concerning the large and small sample properties of this estimator.


Background and aims – This research was an attempt to understand the views of students of homoeopathic undergraduate schools in West Bengal, India and to identify areas of strength and weakness in the learning environment.
Methodology – An institutional, cross-sectional, observational study was carried out involving 430 students in May, 2013 in two Government homoeopathic medical colleges in West Bengal, India. A seven-item close-ended questionnaire with four point Likert scale was used to determine students' perceptions of the learning environment, intellectual climate and teacher-student relationship in homoeopathic schools. The questionnaire generated seven subscales – flexibility, student to student interaction, emotional climate, supportiveness, meaningful experience, organization, and breadth of interest.
Results – 46.5% of students belonged to rural areas and Bengali was the mother tongue of 93.7% students. 39.5% preferred Bengali as the medium of instruction and group study was preferable to 77.9% students. 47.7% students were dissatisfied with the teaching process and 79.8% preferred the use of multimedia over conventional classroom teaching. Flexibility remained low (mean=1.9, SD=0.9); meaningful experience (theoretical teaching) score was high (mean=2.6, SD=0.9). Scores did not vary significantly (P>0.05) across the pre-clinical and clinical students, but few subscales produced significant differences individually among students of different years. Internal consistency scores of the scale remained questionable (Cronbach's α 0.310-0.446); however, the scale showed acceptable test-retest reliability (Cohen's κ 0.680-0.838).
Conclusions – This study emphasized the areas requiring improvement in homoeopathic school environment based on students' perspective. Changes in curriculum, faculty and infrastructure should be planned to improve students' satisfaction.


Conjugated microporous polymers (CMPs) are a class of materials with unique structural properties, including extended π-conjugation and permanent microporosity, with a huge synthetic diversity offering up a number of topological strategies for control of their amorphous structure and properties. This provides a platform for the exploration of chemical and electronic structure properties that is not available for other classes of materials. CMPs have applications in gas storage, gas separation, heterogeneous catalysis, chemosensors, light harvesting devices, polymer light emitting diodes and as supercapacitors. There is great potential for as yet undiscovered applications as we further explore their synthetic diversity and gain new strategies for controlling structure. In this chapter, we define the core chemical and structural properties of CMPs and the synthetic strategies adopted. We discuss the various methods of analysing and rationalising the CMP molecular structure and porous properties, the particular challenges in elucidating the structure of amorphous CMPs and strategies for tackling these challenges. Finally, we discuss limitations for CMP materials and future directions that might overcome these challenges and open up new areas for exploration.


The accuracy of short term electricity demand forecasting is essential for operation and trading activities on energy market. This paper considers a parsimonious forecasting model to explain the importance of sophisticated weather parameters for hourly electricity demand forecasting. Temperature is the major factor that directly influence electricity demand, but what about the affect of other weather factors such as relative humidity, wind speed etc. on short term electricity demand forecasting, is the prime research question and this paper analyzed it quantitatively. We demonstrate three different multiple linear models including auto-regressive moving average ARMA (2,6) models with and without some exogenous weather variables to compare with performance for Hokkaido Prefecture, Japan. Since, Bayesian approach is used to estimate the weight of each variables with Gibbs sampling, it generates the weight of coefficients in terms of distribution as our interest. The performance of each models for complete one year out sample prediction shows that the average improvement of hourly forecast by 1 to 2 % can be achieve by including such weather factors.


What underlies young children's failure in evaluating underinformative teachers? We explore the hypothesis that children have difficulty representing relevant alternatives; knowing what the teacher could have done. Children rated two teachers who demonstrated toys to a naive learner. One group first observed a fully informative teacher and then an underinformative teacher, while the other group saw the reverse order. Sixand seven-year-olds successfully rated the underinformative teacher lower than the fully-informative teacher regardless of the order (Exp.1). However, fourand five-yearolds showed this pattern only when they saw the fully informative teacher first (Exp.2). Given a binary choice after seeing both teachers, four-year-olds showed a preference for the fully informative teacher (Exp.3). We discuss these results in light of recent literature on children's understanding of pragmatic violations in linguistic communication; the contrast between the fully informative vs. under-informative teachers might help children understand what the teacher could have shown.


Glioblastoma (GB) is the most representative form of primary malignant brain tumour. Several studies indicated a pleiotropic role of CXCL8 in cancer due to its ability to modulate the tumour microenvironment, growth and aggressiveness of tumour cell. Previous studies indicated that CXCL8 by its receptors (CXCR1 and CXCR2) induced activation of the PI3K/p-Akt pathway, a crucial event in the regulation of cytoskeleton rearrangement and cell mobilization. Human GB primary cell culture and U-87MG cell line were used to study the effects of CXCR1 and CXCR2 blockage, by a dual allosteric antagonist, on cell migration and cytoskeletal dynamics. The data obtained point towards a specific effect of autocrine CXCL8 signalling on GB cell invasiveness by the activation of pathways involved in cell migration and cytoskeletal dynamics, such as PI3K/p-Akt/p-FAK, p-cortactin, RhoA, Cdc42, Acetylated α-tubulin and MMP2. All the data obtained support the concept that autocrine CXCL8 signalling plays a key role in the activation of an aggressive phenotype in primary glioblastoma cells and U-87MG cell line. These results provide new insights about the potential of a pharmacological approach targeting CXCR1/CXCR2 pathways to decrease migration and invasion of GB cells in the brain parenchyma, one of the principal mechanisms of recurrence.


Orthotic insoles are commonly used in the treatment of the diabetic foot to prevent ulcerations. Choosing suitable insole material is vital for effective foot orthotic treatment. We examined seven types of orthotic materials. In consideration of the key requirements and end uses of orthotic insoles for the diabetic foot, including accommodation, cushioning, and control, we developed test methods for examining important physical properties, such as force reduction and compression properties, insole-skin friction, and shear properties, as well as thermal comfort properties of fabrication materials. A novel performance index that combines various material test results together was also proposed to quantify the overall performance of the insole materials. The investigation confirms that the insole-sock interface has a lower coefficient of friction and shearing stress than those of the insole-skin interface. It is also revealed that material brand and the corresponding density and cell volume, as well as thickness, are closely associated with the performance of moisture absorption and thermal comfort. On the basis of the proposed performance index, practitioners can better understand the properties and performance of various insole materials, thus prescribing suitable orthotic insoles for patients with diabetic foot.


The genome-wide presence of copy number variations (CNVs), which was shown to affect the expression and function of genes, has been recently suggested to confer risk for various human disorders, including Amyotrophic Lateral Sclerosis (ALS). We have performed a genome-wide CNV analysis using PennCNV tool and 733K GWAS data of 117 Turkish ALS patients and 109 matched healthy controls. Case-control association analyses have implicated the presence of both common (>5%) and rare (<5%) CNVs in the Turkish population. In the framework of this study, we identified several common and rare loci that may have an impact on ALS pathogenesis. None of the CNVs associated has been implicated in ALS before, but some have been reported in different types of cancers and autism. The most significant associations were shown for 41 kb and 15 kb intergenic heterozygous deletions (Chr11: 50,545,009–50,586,426 and Chr19: 20,860,930–20,875,787) both contributing to increased risk for ALS. CNVs in coding regions of the MAP4K3, HLA-B, EPHA3 and DPYD genes were detected however, after validation by Log R Ratio (LRR) values and TaqMan CNV genotyping, only EPHA3 deletion remained as a potential protective factor for ALS (p = 0.0065024). Based on the knowledge that EPHA4 has been previously shown to rescue SOD1 transgenic mice from ALS phenotype and prolongs survival, EPHA3 may be a promising candidate for therepuetic interventions.


To improve the general performance of knee-joint rehabilitation trainer (KRT), an embedded control system for the KRT based on embedded linux OS was designed, taking 32bits processor S3C2440 as core control unit. The overall scheme, hardware and software architectures of the system were designed. The key technologies dealing with the embedded linux drivers and the applications based on QT were studied. Experimental results proved that the designed embedded control system is reliable, easy to handle, and can control the KRT to realize isokinetic continuous passive motion and isokinetic active resistance motion. This can provide the guidance for the design of embedded control system in similar medical devices.


This thesis describes the function and construction of a modular event detector system. Event detectors are used for solder joint reliability testing using electronic monitoring for short duration resistance changes during accelerated ageing and temperature cycling. Collected data is mainly used to study solder joints long-term properties. The system has three different monitoring functions: transient resistance detection, statistics process monitoring and periodic monitoring. In its present performance a total number of 384 channels can be monitored continuously. However the system can be expanded in steps of 96 channels, limited only by the capacity of the computers PCI-bus. The system is built around a PC equipped with the LabVIEW 6.1 programming environment and data acquisition cards from National Instruments. The circuit boards to be monitored are connected via adapter electronics. In the case of the superior electronic-kits project, four groups of 24 circuit boards are connected to the adapter electronics. To minimise the influence of environmental noise shielded and, where possible, twined cables are used.


Trust models play an important role in Internet of Things (IoT) as it provides a means of finding whether a given device can provide a service to a satisfactory level as well as a means for identifying potentially malicious devices in the network. Context awareness in trust models allows a trustor to filter and aggregate evidence by their relevance to the current situation. Context awareness is important in the formulation of trust in IoT networks due to their heterogeneity and due to the dynamic changes in the capabilities of IoT devices. In this paper,we have proposed a new type of context-based attack on context aware trust models for IoT systems. An adversary is able to manipulate the context and impact a target group of IoT devices, while other devices in non-targeted groups are not even aware of the attack. We have demonstrated the effectiveness of this new type of attack on six previously proposed trust models. Through practical simulations and theoretical proofs, we show that the adversaries can launch such context-based attacks against a targeted group of IoT devices in the network. The paper also proposes a new trust management system that can mitigate such context-based attacks.


Herpes simplex encephalitis (HSE) is a life-threatening consequence of herpes simplex virus (HSV) infection of the central nervous system (CNS). Although HSE is rare, mortality rates reach 70% in the absence of therapy and only a minority of individuals return to normal function. Antiviral therapy is most effective when started early, necessitating prompt diagnosis. The International Herpes Management Forum (IHMF) has issued guidelines to aid the diagnosis and treatment of HSE. Polymerase chain reaction (PCR) of the cerebrospinal fluid (CSF) is the diagnostic method of choice for HSE, but negative results need to be interpreted in the context of the patient's clinical presentation and the timing of the CSF sampling. CSF virus culture is of little value in all but patients under the age of 6 months. CSF (intrathecal) antibody measurements are not recommended for acute diagnostic purposes. However, demonstration of an intrathecal HSV antibody response may be helpful in retrospective diagnosis or in cases in which CSF is sampled only late after onset of infection and PCR is negative. Serum HSV antibody measurements are not of utility in the diagnosis of HSV encephalitis in adults. In children and young adults, HSV serology may help define whether HSE is part of a primary or a reactivated HSV infection, although the clinical features, therapy, and prognosis of these two forms of HSV encephalitis are similar. The IHMF recommends that all patients with HSE receive intravenous aciclovir 10 mg/kg every 8 h for 14-21 days. Owing to the life-threatening nature of the disease, if there is a delay in diagnostic test results therapy should not be withheld until they become available. After completion of therapy, PCR of the CSF can confirm the elimination of replicating virus, aiding further management of the patient. Clinical trials of other antiviral agents (i.e. adjunctive oral valaciclovir after intravenous aciclovir) for the treatment of HSE are underway. Herpes infection of the CNS, especially with HSV-2, can also cause both monophasic and recurrent aseptic meningitis, as well as myelitis or radiculitis. Limited evidence suggests that aciclovir may be effective in its treatment. Recurrent aseptic meningitis is predominantly caused by HSV-2 infection, and is characterized by self-limited episodes of fever, meningismus and severe headache. Many cases are indistinguishable from cases previously classified as "Mollaret's meningitis", a term that should now be reserved for idiopathic cases of recurrent aseptic meningitis.


Many modern machine learning models are trained to achieve zero or near-zero training error in order to obtain near-optimal (but non-zero) test error. This phenomenon of strong generalization performance for "overfitted" / interpolated classifiers appears to be ubiquitous in high-dimensional data, having been observed in deep networks, kernel machines, boosting and random forests. Their performance is consistently robust even when the data contain large amounts of label noise.
Very little theory is available to explain these observations. The vast majority of theoretical analyses of generalization allows for interpolation only when there is little or no label noise. This paper takes a step toward a theoretical foundation for interpolated classifiers by analyzing local interpolating schemes, including geometric simplicial interpolation algorithm and singularly weighted $k$-nearest neighbor schemes. Consistency or near-consistency is proved for these schemes in classification and regression problems. Moreover, the nearest neighbor schemes exhibit optimal rates under some standard statistical assumptions.
Finally, this paper suggests a way to explain the phenomenon of adversarial examples, which are seemingly ubiquitous in modern machine learning, and also discusses some connections to kernel machines and random forests in the interpolated regime.


Historically, many higher education institutions have been structurally and culturally compartmentalised and subunits such as continuing education have been marginalised, merged or divested. In response to a variety of external phenomena, some higher education institutions are re-examining their internal and external relationships, including the relationship between their academic and continuing education units. This research examines the efforts of a higher education institution in the United Arab Emirates to improve its overall effectiveness by changing the nature of the relationship between its academic and continuing education units. A review of theory- and practice-based higher education, organisational culture and inter-/intra-organisational relationship literature revealed significant support for each partner's goals for the new relationship and was used to provide the parties with a series of recommendations for successful formulation, actualisation and governance. These results add to the literature and practice of higher education and continuing higher education, particularly in the area of relationship-building among organisational subunits and subcultures.


Introduction: The objective of this study was to compare the change in 6-minute walking distance (6MWD) in 1 year as an indicator of exercise capacity among patients undergoing home non-invasive mechanical ventilation (NIMV) due to chronic hypercapnic respiratory failure (CHRF) caused by different etiologies. Methods: This retrospective cohort study was conducted in a tertiary pulmonary disease hospital in patients who had completed 1-year follow-up under home NIMV because of CHRF with different etiologies (ie, chronic obstructive pulmonary disease [COPD], obesity hypoventilation syndrome [OHS], kyphoscoliosis [KS], and diffuse parenchymal lung disease [DPLD]), between January 2011 and January 2012. The results of arterial blood gas (ABG) analyses and spirometry, and 6MWD measurements with 12-month interval were recorded from the patient files, in addition to demographics, comorbidities, and body mass indices. The groups were compared in terms of 6MWD via analysis of variance (ANOVA) and multiple linear regression (MLR) analysis (independent variables: analysis age, sex, baseline 6MWD, baseline forced expiratory volume in 1 second, and baseline partial carbon dioxide pressure, in reference to COPD group). Results: A total of 105 patients with a mean age ( ± standard deviation) of 61 ± 12 years of whom 37 had COPD, 34 had OHS, 20 had KS, and 14 had DPLD were included in statistical analysis. There were no significant differences between groups in the baseline and delta values of ABG and spirometry findings. Both univariate ANOVA and MLR showed that the OHS group had the lowest baseline 6MWD and the highest decrease in 1 year (linear regression coefficient - 24.48; 95% CI - 48.74 to - 0.21, P = 0.048); while the KS group had the best baseline values and the biggest improvement under home NIMV (linear regression coefficient 26.94; 95% CI - 3.79 to 57.66, P = 0.085). Conclusion: The 6MWD measurements revealed improvement in exercise capacity test in CHRF patients receiving home NIMV treatment on long-term depends on etiological diagnoses.


: A RECOGNIZED COMPLICATION: Ritonavir is an antiprotease used in the treatment of HIV-positive patients. Among the known side effects, nephrotoxicity can be severe. We have observed acute renal failure in 8 patients. CIRCUMSTANCES: Renal failure occurs early after introducing ritonavir (3-21 days). It is often severe with major creatinine elevation. One patient was dialyzed for 16 days. In these patients, saquinavir was usually associated with ritonavir. RITONAVIR ALONE: We retrospectively analyzed creatinine levels in 87 patients treated with ritonavir without saquinavir. Twelve of these 87 patients (13.7%) developed renal failure. Creatinine clearance (Cockcroft) was reduced 116 to 71 ml/min in 12 patients. Finally, it was demonstrated in 6 patients that ritonavir can reduce creatinine clearance by 25% after only 3 days of treatment. VIGILANCE: Ritonavir has a known nephrotoxic potential. Acute renal failure may be severe and can occur with ritonavir alone or in combination with saquinavir. The pathogenic mechanism has not been demonstrated from renal biopsies or experimental studies. Renal function should be followed in these patients and risk factors controlled.


Global illumination rendering in real-time for high-fidelity graphics remains one of the biggest challenges for computer graphics in the foreseeable future. Recent work has shown that significant amounts of time can be saved by selectively rendering in high quality only those parts of the image that are considered perceptually more important. Regions of the final rendering that are deemed more perceptually important can be identified through lower quality, but rapid, rasterisation rendering. By exploiting this prior knowledge of the scene and taking advantage of image space based algorithms to concentrate rendering on the more salient areas higher performance rendering may be achieved. In this paper, we present a selective rendering framework based on ray tracing for global illumination which uses a rapid image preview of the scene to identify important image regions, structures these regions and uses this knowledge to direct a fraction of the rays traditionally shot. The undersampled image is then reconstructed using algorithms from image processing. We demonstrate that while this approach is able to significantly reduce the amount of computation it still maintains a high perceptual image quality.


Blended care, a combination of online and face-to-face therapy, is increasingly being applied in mental health care to obtain optimal benefit from the advantages these two treatment modalities have. Promising results have been reported, but a variety in descriptions and ways of operationalizing blended care exists. Currently, what type of "blend" works for whom, and why, is unclear. Furthermore, a rationale for setting up blended care is often lacking. In this viewpoint paper, we describe postulates for blended care and provide an instrument (Fit for Blended Care) that aims to assist therapists and patients whether and how to set up blended care treatment. A review of the literature, two focus groups (n=5 and n=5), interviews with therapists (n=14), and interviews with clients (n=2) were conducted to develop postulates of eHealth and blended care and an instrument to assist therapists and clients in setting up optimal blended care. Important postulates for blended care are the notion that both treatment modalities should complement each other and that set up of blended treatment should be based on shared decision making between patient and therapist. The "Fit for Blended Care" instrument is presented which addresses the following relevant themes: possible barriers to receiving blended treatment such as the risk of crisis, issues in communication (at a distance), as well as possible facilitators such as social support. More research into the reasons why and for whom blended care works is needed. To benefit from blended care, face-to-face and online care should be combined in such way that the potentials of both treatment modalities are used optimally, depending on patient abilities, needs, and preferences. To facilitate the process of setting up a personalized blended treatment, the Fit for Blended Care instrument can be used. By applying this approach in research and practice, more insight into the working mechanisms and optimal (personal) "blends" of online and face-to-face therapy becomes within reach.


In order to improve the availability of offshore wind farms, thus avoiding unplanned operation and maintenance costs, which can be high for offshore installations, the accommodation of faults in their earlier occurrence is fundamental. Therefore, this paper addresses the design of an active fault tolerant control scheme that is applied to a small wind park benchmark of nine wind turbines, based on their nonlinear models, as well as the wind and interactions between the wind turbines in the wind farm. The controller accommodation scheme exploits the on-line estimate of the fault signals generated by nonlinear filters using the nonlinear geometric approach to obtain estimates decoupled from both model uncertainty and the interactions among the turbines. This paper proposes also a data-driven approach to provide these disturbance terms in analytical forms, which are subsequently used for designing the nonlinear filters for fault estimation. The wind farm benchmark is considered to validate the performances of the suggested scheme in the presence of different fault conditions, modelling and measurement errors.


Forests in Washington State generate substantial economic revenue from commercial timber harvesting on private lands. To investigate the rates, causes, and spatial and temporal patterns of forest harvest on private tracts throughout the Cascade Mountains, we relied on a new generation of annual land-use/land-cover (LULC) products created from the application of the Continuous Change Detection and Classification (CCDC) algorithm to Landsat satellite imagery collected from 1985 to 2014. We calculated metrics of landscape pattern using patches of intact and harvested forest in each annual layer to identify changes throughout the time series. Patch dynamics revealed four distinct eras of logging trends that align with prevailing regulations and economic conditions. We used multiple logistic regression to determine the biophysical and anthropogenic factors that influence fine-scale selection of harvest stands in each time period. Results show that private lands forest cover became significantly reduced and more fragmented from 1985 to 2014. Variables linked to parameters of site conditions, location, climate, and vegetation greenness consistently distinguished harvest selection for each distinct era. This study demonstrates the utility of annual LULC data for investigating the underlying factors that influence land cover change.


Currently no framework exists to evaluate or rank the complexity of the text input task on a per orthography bases. We present on the challenges which must be addressed by a cross-language text input assessment framework. We discuss relevant user experience (UX) considerations for keyboard layouts and unique actions undertaken in the communicative act of 'entextualizing' language (typing). We follow previous work which focuses on majority language text input methods (Bellman & MacKenzie 1998, Castellucci & MacKenzie 2013, MacKenzie 1992, 2002, 2007, MacKenzie & Soukoreff 2002, Soukoreff & MacKenzie 2001, 2003a, b) and apply considerations for minority language orthographies - especially those orthographies which overtly mark tone and other distinctions via diacritics.
 The ability to communicate with electronic text based devices is important in this era of globalization. Many minority language users often find it difficult to type in their languages because of the way that orthography/language specific characters are accessed through existing keyboard layouts ([Author] 2012). The keyboard layout is an essential component in text input both on mobile touch screen and traditional devices. Barriers to efficiently using text in digital mediums has a wide impact on language vitality, by affecting the way that language users perceive their language's viability in the 21st century context. The text input challenge has been often acknowledged by minority language users (Esizmetor 2009: 13, Zheltov 2005). Perceptions about the need to be able to use text based digital communication devices has sufficiently challenged language communities leading some to change their orthographies (Boerger 2007: 133: South Pacific, Cooper 2005: 149, 160: Central Asia, Jany 2010: Americas). Simons and Lewis (2010) describe the social practice of literacy (EGIDS levels four and five) as a sign of a healthy language. A text input device which does not intuitively work for language users can be seen as discriminating and be a reason for speakers to choose to not use their language in digital mediums (Trosterud 2012). We propose a language agnostic framework for text input analysis for the benefit of language development efforts and software developers alike.
 References:
 [Author]. 2012. Keyboard layout as part of language documentation: the case of the Meꞌphaa and Chinantec keyboards. Paper presented at CRASSH Language Endangerment: Methodologies and New Challenges, Cambridge, UK. Bellman, Tom & I. Scott MacKenzie. 1998. A Probabilistic Character Layout Strategy for Mobile Text Entry. Proceedings of Graphics Interface '98, 168-76. Toronto: Canadian Information Processing Society. Boerger, Brenda H. 2007. Natqgu Literacy: Capturing Three Domains for Written Language Use. Language Documentation & Conservation 1.2: 126–53. Castellucci, Steven J. & I. Scott MacKenzie. 2013. Gathering Text Entry Metrics on Android Devices. Proceedings of the International Conference on Multimedia and Human- Computer Interaction - MHCI 2013, 120.1-.8. Ottawa, Canada: International ASET, Inc. Cooper, Gregory. 2005. Issues in the Development of a Writing System for the Kalasha Language. Ph.D dissertation, Macquarie University. Esizmetor, David Oshorenoya. 2009. What Orthography for Naija? Paper presented at Conference on Nigerian Pidgin, University of Ibadan, Nigeria. Jany, Carmen. 2010. Orthography Design for Chuxnaban Mixe. Language DocumentatIon & ConservatIon 4.1: 231-53. Lewis, M. Paul & Gary F. Simons. 2010. Assessing endangerment: Expanding Fishman's GIDS. Revue Roumaine de Linguistique 55.2: 103–20. MacKenzie, I. Scott. 1992. Fitts' law as a research and design tool in human-computer interaction. Human-Computer Interaction 7, 91-139. MacKenzie, I. Scott. 2002. Introduction to this special issue on text entry for mobile computing. Human-Computer Interaction 17.2-3: 141-5. MacKenzie, I. Scott. 2007. Evaluation of text entry techniques. In I. Scott MacKenzie & Kumiko Tanaka-Ishii (eds.), Text entry systems: Mobility, accessibility, universality, 75-101. San Francisco, CA: Morgan Kaufmann. MacKenzie, I. Scott & R. William Soukoreff. 2002. A Character-level Error Analysis Technique for Evaluating Text Entry Methods. A character-level error analysis technique for evaluating text entry methods. Proceedings of the Second Nordic Conference on Human- Computer Interaction -- NordiCHI 2002, 241-4. New York: ACM. Soukoreff, R. William & I. Scott MacKenzie. 2001. Measuring errors in text entry tasks: An application of the Levenshtein string distance statistic. Extended Abstracts of the ACM Conference on Human Factors in Computing Systems - CHI 2001, 319-20. New York: ACM. Soukoreff, R. William & I. Scott MacKenzie. 2003a. Metrics for text entry research: an evaluation of MSD and KSPC, and a new unified error metric. Paper presented at Proceedings of the SIGCHI Conference on Human Factors in Computing Systems, Ft. Lauderdale, Florida, USA. Soukoreff, R. William & I. Scott MacKenzie. 2003b. Input-based Language Modeling in the Design of High Performance Text Input Techniques. Proceedings of Graphics Interface 2003 (CIPS, Canadian Human-Computer Communication Society), 89-96. Halifax, Nova Scotia: A K Peters. Trosterud, Trond. 2012. A restricted freedom of choice: Linguistic diversity in the digital landscape. Nordlyd (Tromso University Working Papers on Language and Linguistics) 39.2: 89-104. Zheltov, Pavel V. 2005. Minority languages and computerization. The situation in the Russian Federation. OGMIOS 3.3: 8-11.


Hollingworth described chewing gum as 'a technique of relaxation'. Recent research has examined this issue and there is evidence that chewing gum can prevent the adverse effects of acute stress. There are also plausible biological mechanisms that could explain such effects. It is now important to examine chewing gum and chronic stress and the present study involved a survey of this topic. The survey covered the 'stress process', collecting data on exposure to stressful events, levels of perceived stress and health outcomes. Frequency of chewing gum was also recorded. Potential confounding factors (demographics, personality and health-related behaviours) were also recorded. The web-based survey was completed by a community sample of 2,248 full-time workers (68% female. Mean age: 35 years, range 18–74 years). Sixty-one per cent of the sample were gum chewers. The results showed that chewing gum was associated with lower levels of perceived stress (both at work and life in general). Gum chewers were also less likely to be depressed and to have seen their doctor for high blood pressure or high cholesterol. Chewing gum was associated with lower levels of alcohol consumption and with cigarette smoking. Gum chewers were also more likely to be neurotic extraverts. Those who chewed gum were also more likely to be exposed to negative factors at work. Logistic regression analyses showed that the effects of chewing gum on stress and health remained significant when these confounding factors were controlled for. These results suggest that chewing gum may be a simple way of preventing stress and the negative health outcomes that are often associated with it. Intervention studies are now required and the mechanisms underlying the effects reported here need further investigation


Recent Fermi-LAT observations of dwarf spheroidal galaxies in the Milky Way have placed strong limits on the gamma-ray flux from dark matter annihilation. In order to produce the strongest limit on the dark matter annihilation cross-section, the observations of each dwarf galaxy have typically been "stacked" in a joint-likelihood analysis, utilizing optical observations to constrain the dark matter density profile in each dwarf. These limits have typically been computed only for singular annihilation final states, such as $b\bar{b}$ or $\tau^+\tau^-$. In this paper, we generalize this approach by producing an independent joint-likelihood analysis to set constraints on models where the dark matter particle annihilates to multiple final state fermions. We interpret these results in the context of the most popular simplified models, including those with s- and t-channel dark matter annihilation through scalar and vector mediators. We present our results as constraints on the minimum dark matter mass and the mediator sector parameters. Additionally, we compare our simplified model results to those of Effective Field Theory contact interactions in the high-mass limit.


Abstract Possibilities for early selection of clones for future seed cone production were studied in a clonal seed orchard of Scots pine (Pinus sylvestris L.) in northern Sweden over the first 30 years following establishment. The annual data were modelled as series of bivariate analyses. The correlations between cone production of clones in any individual year and that of a previous year, and cumulative cone production over all years were studied. The corresponding multivariate analysis for a full data fit simultaneously was best estimated with a genetic distance-based power model (AR). The genetic (variation among clones) and environmental variation were of the same magnitude. The genetic correlations were larger than the phenotypic correlations and both increased with orchard age. Basing selection of clones on a single observation at an early age to improve future cone production was not effective, but efficiency increased if cumulative cone count over many years was used. Year-to-year genetic correlations indicated that early forecasts by clone of cone production at mature ages are highly uncertain. Reliable predictions (moderate correlations) could be achieved only if based on rather mature grafts, 14 or more years after establishment.


The short-term, faculty-led study abroad program is the primary study abroad experience for students attending LaGrange College in LaGrange, Georgia. Over time, the program became less focused on its mission of providing an exploratory experience of culture, global issues and academic rigor and became more of a one to three week "trip". The purpose of this study is to design a course that demonstrates a way to combine the academic content with intercultural learning showing how a short-term faculty-led course can have a greater impact on the student and their personal and professional goals. This course, entitled L'Art de Vivre: Engaging in French Culture, Language and Arts, is modeled after an exhibition that occurred at CooperHewitt National Museum of Design and focuses on the topics of the French language and decorative arts. The decorative arts are traditionally studied as an art history topic, but students can also engagement with these objects through hands on research and learning directly from the artisans and companies that created and produced these objects for centuries. This experience is accomplished by placing students in an internship with the Comité Colbert, an organization whose members are French companies that create the quintessential French l'art de vivre through their luxury products and services. Through this partnership, students are immersed in the French language and culture exposing them to cross cultural perspectives and historical trends and styles that influenced French art, society and culture. This study follows the course development from determining the learning theories and curriculum design concepts to the logistical support required to organize the learning experiences to the final evaluation. YOU CAN'T TEACH GLOBAL ENGAGEMENT 2


Myelolipomas are rare benign tumors often found incidentally due, in the majority of cases, to the fact that they are asymptomatic. The incidence of adrenal myelolipomas at autopsy is low (0.2%). These tumors are made up of fat and hematopoietic cells. Their origin is unclear and different theories have been put forward, including development from rests of mesenchymal stem cells, embolism of bone marrow, extramedullary hematopoiesis and, according to the most widely accepted theory, metaplasia of the reticuloendothelial cells of blood capillaries. Due to their uncertain etiology and low frequency, management of adrenal myelolipomas is usually individualized and carried out depending on the protocols of each center. The development of improved imaging techniques has increased their diagnosis in routine clinical practice. Thus, they have been included in the heterogenous group of 'incidentalomas' of the adrenal gland.


Recent developments in technology
have helped to reduce the physical size and weight of devices and opened up new
opportunities for their application in delivering unobtrusive healthcare
services. In particular, kinetic and kinematic systems, that use sensors
attached to the body, are currently being used to measure and understand many
different aspects of human
gait and behaviour. This has been particularly useful in treating stroke
patients, rehabilitation, and understanding sedentary behaviour. Nonetheless, many of these systems are
only capable of providing information about rudimentary movement rather than
data on the mechanics of motion itself (tendons, ligaments and so on).
Therefore, the information required by healthcare professionals to treat
diseases like progressive deterioration of the musculoskeletal system, i.e. arthritis, cannot be determined.
This paper discusses some of the technologies currently used to assess movement
and posits a novel approach based on strain gauge technology to measure the
constituent parts of a joint and its movement. In this way, the mechanics of
motion can be studied and used to help detect and treat musculoskeletal
diseases. A case study is presented to demonstrate the applicability of our
approach.


Under the general term, Boulder Clay, many deposits produced at various periods during the great glacial epoch, and by different causes, have been loosely included. It is necessary to distinguish between these various "Boulder Clays," before observers in separate localities will be able to understand each other's language, and before any satisfactory theories can be established regarding the methods, of their formation. The old motto for statesmen dealing with barbarous tribes on the frontiers of an empire was, "Divide and command;" and this must also be the motto for students of the apparently confused accumulations of glacial deposits. We must divide to command. I. The oldest boulder clay I at present believe to be represented by that which underlies the shell clay of the West of Scotland. It is only in the lower districts, however, that the shell clay rests upon it, while it reaches to a height in Scotland (1,500 feet or more) far beyond that at which any shells have yet been discovered. Its thickness extends from a mere covering of the rock, to the depth of even 300 feet, and is excessively variable. It is closely compact, as though subjected to immense pressure, and difficult to work even with the pick-axe. Although occasionally containing patches of sand, of greater or less extent, it has no stratification. The included stones are in large numbers, polished and striated, and have not been broken by the process through which they have passed. Even thin and brittle pieces of shell are This 250-word extract was created in the absence of an abstract


This study examined the relationship between climate and prevalence of malaria in Warri metropolis. To achieve this, the study generated data from archival material from the meteorological agency and hospitals. Climate data of temperature, rainfall and humidity were collected from the Nigeria Meteorological agency, Warri and malaria in-patient and out-patient records from the two (2) central hospitals and one (1) renowned hospital each from the three (3) local Government Areas for a period of twenty (20) years (1990-2009). The data were analyzed using the Multiple Regression. From the study, the rainfall and temperature in Warri metropolis has increased over the years (1907-2009) by 122.82 mmand 1.3℃. Thus, if this warming continues there will be a risk of between 1.4℃ and an urban warming of 4.18℃, indicating climate change. There is a significant relationship between malaria and climate parameters (rainfall, temperature and humidity) which were evident at F value of 4.429 which is greater than the critical table value of 4.35, which implied that the model is significant and thus, malaria prevalence in Warri metropolis is significantly dependent on rainfall, relative humidity and temperature. It is anticipated that an increase in temperature and relative humidity resulted to a corresponding increase in the number of malaria cases, it is therefore recommended that any policy aimed at reducing the prevalence of malaria in Warri and environs must necessarily be imbued with programmes that have objectives of mosquitoes reduction through the improvement of our environment which includes the climate.


Dispute management in the U.S. currently accepts workplace conflicts as a necessary part of organizational life. Having an effective dispute management system means providing the methods to resolve a dispute that matches the type and stage to which it has progressed while also serving the needs of those who use the system. Contributors to this collection provide a variety of viewpoints, including international perspectives, that help explain why employers who are committed to effective dispute management will use a combination of preventive and remedial dispute resolution mechanisms to address conflicts based primarily on interests, rights, or power. Several essays also investigate how the interpersonal nature of a relationship between people determines the method selected to handle disputes, the impact of the lens of gender on our thinking about negotiation as a social activity for problem solving, and the tension between self-interest and fairness in negotiation and the use of justifications and impression management to resolve this tension.


Infectious endocarditis (IE) is a rare, but potentially fatal disease in pediatric patients. Most patients have underlying hemodynamic problems that predispose them to the risks of IE. Modified Duke criteria are commonly used for clinical diagnosis of IE. Though Streptococcus viridans and Staphylococcus aureus are the main pathogens of the disease, other pathogens have also been isolated. Herein we describe the first reported case of IE caused by Pseudomonas oleovorans a girl with operated ventricular septal defect (VSD).


Parentage of a stock of mixed milt produced progeny in current artificial breeding protocol of endangered Caspian brown trout, Salmo trutta caspius, was determined using three microsatellite loci chosen after a primary analysis of genetic diversity at nine microsatellite loci in the eight used breeder individuals. Overall, 98.8% of progeny were assigned to their parents using Family Assignment Program (FAP). Selection of hyper-variable microsatellites in Caspian brown trout to identify unique alleles was effective for unambiguous parentage determination and estimation of genetic diversity in this study. Effective population size of breeder individuals (Ne) was lower than the number of breeder individuals used (Nb) indicating unbalanced contribution of breeder individuals to progeny. Indeed, one of the four male breeder individuals produced about 70 % and the other three produced only from 4.86 % to 18.83 % of progeny. The average observed and expected heterozygosity of progeny (0.723 ± 0.011 and 0.684 ± 0.009, respectively) was significantly lower than that of their parents (0.833 and 0.800, respectively). Our data indicate that the current breeding protocol of Caspian brown trout may not provide equal opportunity for all the breeder individuals to contribute equally to progeny. Therefore, appropriate fertilization designs in the hatchery should be established in order to equalize the genetic contribution of different breeder individuals.


Increasingly, healthcare programmes are evaluated in terms of both their costs and outcomes. However, existing evaluation designs, in which equal numbers of participants are compared, remain a hangover from the time when outcomes were the sole concern. Outcome maximisation studies, in which costs are equalised, are an alternative way of comparing the costs and consequences of health interventions. They may be feasible in some instances and are attractive because they highlight two of the main messages of health economics.

Firstly, economists emphasise that their concern for the costs of interventions is due to the implications of opportunity costs—that is, resources used for one intervention should be compared with the potential benefits achievable by the next best option that is forgone because the resources for health care are finite.1 2 3 In an outcome maximisation design the opportunity costs of high cost interventions would be highlighted more clearly in the study results.

Secondly, the marginal costs of implementing programmes do not necessarily equal average costs, in which marginal costs are the change in costs resulting from a small change in the level of provision.4 By evaluating alternative technologies at comparable levels of expenditure, outcome maximisation studies would take account of the fact that programme costs often do not rise proportionally with the number of patients treated.

#### Summary points

Health care evaluations used to focus solely on outcomes, but increasingly they have compared the costs of competing interventions

Popular study designs in which equal numbers of people are subjected to each regimen at different levels of total cost do not reflect this innovation

An outcome maximisation design, in which the costs allocated to each programme are equal, might be appropriate

This design has two main advantages: ( a ) the opportunity costs (or next best use) of more resource intensive treatments are readily expressed …


The influence of hydrogen content on the mechanical properties and size of dynamically recrystallized grains in commercially pure (CP) titanium and Ti-5Al-2.5Sn alloy was investigated. The alloys with hydrogen contents from 0.1 to 5.2 at.% were deformed in the a-field at temperatures of 650°, 750°С with initial strain rates of 5×10-4 s-1. A decrease of the deformation temperature leads to a reduction in grain size and to a stress increase for all compositions. This is in good agreement with the well known relation between the recrystallized grain size (d) and the steady flow stress ss=kd-n. At a given test temperature the steady state flow stress is four times lower and the grain size is about ten times greater in CP titanium in comparison with the Ti-5Al- 2.5Sn alloy. Hydrogen alloying of the Ti-5Al-2.5Sn alloy does not lead to a noticeable change in ss and d. However, an increase in hydrogen content from 0.1 to 5.2 at.% in CP titanium leads not only to a decrease in grain size by a factor of 2 but also to a decrease in flow stress (about 28%). This result is not in agreement with the above relation. This unusual behaviour may be due to two reasons: the influence of hydrogen on grain growth and the hydrogen effect on dynamic strain ageing. Both these effects are stronger in CP titanium.


This book clarifies the concept of impact and related terms, such as washback, evaluation, monitoring and validation, and focuses on the impact of language tests and language programmes on a range of stakeholders, including test-takers, teachers, textbook writers, testers and institutions. First-hand experience is cited from two new impact studies. One analyses the impact of the International English Language Testing System (IELTS), the second looks at the Progetto Lingue 2000 (Year 2000 Languages Project), a state-school foreign-language education improvement programme undertaken by the Ministry of Education in Italy. The main findings of these studies are presented, as well as theoretical and practical lessons to be learnt from them. The context is the role of impact studies in the test development and validation systems of Cambridge ESOL, the sponsor of both impact studies.


The "post biliary surgery syndrome" combines the signs and symptoms which appear after surgery, involving the gall bladder and/or the biliary ducts for biliary lithiasis. They occur after various periods of time after surgery and have multiple causes.


To appear in L. Tasmowski & S Vogeleer (eds), Indefiniteness and Plurality, Linguistik Aktuell/Linguistics Today Series, Benjamins.
It has been argued extensively that numeral indefinite plurals cannot scope out (Ruys (1992), Beghelli and Stowell (1997), Kamp and Reyle (1993) Szabolcsi (1997)). E.g. it is virtually impossible to interpret Four guests sleep in two rooms as involving eight guests in the reported sleeping event, as would be the case if two rooms receives wide distributive scope. In several approaches, this strong effect is built into the Computational System (syntax), as restrictions on the operation of QR, or more complex feature specification of the syntactic projections that correspond to different quantifiers. But I argue that there are several problems with this line. E.g. in the minimally different Four guests sleep together in two rooms, scoping out of the numeral (eight guests) is substantially easier. More broadly, it turns out that the restrictions on the scoping of numerals are not absolute, but depend on the relations of the given derivation to other possible derivations or interpretations.

On the view proposed in Fox (1995, 2000) and Reinhart (1995, 2006), scope shift is an interface repair strategy that is permitted only when it generates a reading that could not be obtained otherwise. This entails that when QR applies, a reference-set must be constructed to determine whether this is indeed the case. The need to construct and compare a reference-set is costly in terms of processing, as it requires holding two or more full derivations in working memory. An aspect of the computational cost that deserves attention is the size of the reference set. In the easier instances of QR (e.g. Some student read every book), the reference set contains only two members - with and without -QR. This is a cost that at least adult speakers can bear. (I argue elsewhere that children cannot.) But when two plural numerals are involved, a careful listing of all members of the reference set reveals five such members. It appears that a reference set with five members is beyond what even adults can hold in working memory, so the computation required to license the scope shift derivation cannot be completed. By contrast, when the subject cannot be interpreted distributively, as in the four guests slept together example, only three members must be activated, which is still within the limits of what can be processed. What has appeared to be a syntactic restriction on scope shift with numerals, is thus, better explained as a processing failure.


(miRNAs) have recently taken center stage in the field of human molecular oncology. Most of the chemotherapeutics are able to interfere with nucleic acid metabolism and gene expression. The purpose of this study was to determine how 5-fluorouracil (5-FU) and oxaliplatin (L-OHP) modify the expression profiles of miRNAs in HCT-8 and HCT-116 colon cancer cells and whether the pharmacodynamic mechanisms of the chemotherapeutics could rely in part on their influence on miRNA expression. The expression profiles of miRNAs were determined using a miRNA microarray containing 856 human miRNA probes. The expression of selected miRNAs was then validated by real-time RT-PCR. Fifty-six up-and 50 down-regulations of miRNA expression with statistical significance were identified in colon cancer cells following exposure to 5-FU or L-OHP compared to matched control cells. The down-regulations of miR-197, miR-191, miR-92a, miR-93, miR-222 and miR-1826, whose expression was significantly down-regulated in both cell lines after the treatment of one drug or in one cell line following exposure to either drug, were further validated. Analysis of the relevant literature indicated that, in line with the tumor suppressive activity of 5-FU and L-OHP, the six down-regulated miRNAs might function as oncogenes due to their overexpression in cancers, and some of them correlated with the poor prognosis and treatment-resistance of cancer. In conclusion, we identify the modification of miRNA expression profiles in colon cancer cells following exposure to 5-FU and L-OHP, and our results indicate that their pharmacodynamic mechanisms could rely in part on their influence on the down-regulated miRNA expression. Further studies are needed to determine whether these miRNAs and their target genes might potentially provide for novel molecular markers and act as novel targets for treatment by interference.


Wilcox et al. (1 3 Apr., p. 185), show a convincing relation between the solar magnetic sector structure and the earth's meteorological activity as indicated by vorticity at the 300-millibar level. Is it possible that this interesting correlation may in some way be related to Markson's observation (1) that there is a maximum in thunderstorm activity when the earth is at the leading edge of a negative solar structure? B. VONNEGUT Atinospheric Sciences Research Center, State University of New York, Albany 12222


The enzyme cytosine deaminase (CD) encoded by codA catalyzes deamination of cytosine to uracil. CD is present in prokaryotes and in many eukaryotic micro-organisms, but is absent in higher plants. 5-fluorocytosine (5FC) is metabolized in CD-expressing cells, causing cellular death. A chimeric codA has been introduced into the tobacco plastid genome and 5FC was used to select against tissue culture cells and seedlings expressing CD. This negative selection scheme will be useful in identifying nuclear genes which control plastid gene expression in higher plants.


The multi-item single level capacitated dynamic lot-sizing problem consists of scheduling N items over a horizon of T periods. The objective is to minimize the sum of setup and inventory holding costs over the horizon subject to a constraint on total capacity in each period. No backlogging is allowed. Only one machine is available with a fixed capacity in each period. In case of a single item production, an optimal solution algorithm exists. But for multi-item problems, optimal solution algorithms are not available. It has been proved that even the two-item problem with constant capacity is NP-hard, that is, it is in a class of problems that are extremely difficult to solve in a reasonable amount of time. This has called for searching good heuristic solutions. For a multi-item problem, it would be more realistic to consider the setup time, since switching the machine from one item to another would require a setup time. This setup time would be independent of item sequences and this could be a very important parameter from practical point of view. The current research work has been directed toward the development of a model for multiitem problem considering this parameter. Based on the model a program has been executed and feasible solutions with some real life data have been obtained.