Propose: To establish a method of estimating nominal treatment time for a given treatment volume in order to facilitate the assessment of Gamma Knife treatment plan quality. Methods and Materials: The clinical plans of 90 patients with brain metastases and/or surgical cavitiestreated on our Leksell Gamma Knife PERFEXION unit between Nov. 2010 and Jan. 2011 were evaluated. Patients with other diagnosis, e.g. acoustic neuroma or meningioma, were not included. Each plan was prescribed by one of the six radiationoncologists using GammaPlan 8.3.1. After excluding the lesions whose dose grid was overlapped with other lesions', we analyzed 198 tumors from these 90 plans. The planned treatment (TX) time were normalized to the time needed if prescription (Rx) dose and dose rate were 20 Gy and 2.5 Gy/min, respectively. The relationship between the normalized TX time and TX volume was analyzed, and a curve was established where about half of the lesions have lower normalized TX time than the nominal time predicted by the curve. Results: A formula, which is 4.5 times the cubic root of the TX volume, is proposed to estimate the nominal TX time, which, after scaling back by the Rx dose and treatmentdose rate, can be used to compare with the planned TX time. After satisfying other quality metrics, a lower planned TX time indicates that the plan is likely to have reached an optimum, while a much higher planned TX time, as determined by the upper threshold, also established by this study, may signify the need for a better plan. Conclusions: A good plan has high Coverage, high conformity, low Gradient Index, and low treatment time. Knowing the bounds of these metrics helps one determine if an optimum has been reached.


A Knowledge, Attitudes and Practice (KAP) Survey was conducted among 134 secondary schoolgirls in Uganda about their experiences of managing menstrual hygiene in school. The first part of this paper outlines how sensitive information was obtained by using participatory tools in small focus group settings. The second section summarises qualitative and quantitative findings about schoolgirls' knowledge of biological facts and management methods, their attitudes about menstruation formed through their social and cultural environments, and their hygiene practices associated with accessing, changing, drying and disposing of sanitary products. The purpose of the study was to voice schoolgirls' opinions about very real, but rarely addressed, monthly challenges.


Integrity planning methods and inline inspection (ILI) tool performance have a great impact on a pipeline integrity management program. In pipeline integrity planning, risk and integrity assessments are performed to schedule integrity activities like ILI for the purpose of reducing risks and ensuring reliable and safe operations. In this paper, a method is developed for analyzing the impact of ILI tool accuracy on pipeline integrity planning, which is of great importance but has not been systematically studied before. Crack inspection and threat of fatigue cracking are used as the working case for the analysis, although the approach could potentially be used for any pipeline threat type. The Paris' law degradation model is used for the crack growth and subsequent severity and risk assessment. We investigated the impact of ILI tool accuracy on the cost rate, as well as the associated inspection intervals. The impact on long-term cost rate was also investigated considering new defect generation and continuous growth. Sensitivity analyses were performed. The optimal inspection intervals and the corresponding total cost rates with respect to different ILI tool accuracy and different input parameters were obtained and compared. The proposed method can support integrity management program planning by linking risks with integrity plan costs associated with ILI accuracy and optimal re-assessment intervals. The contributions of this paper mainly include the investigation of the problem of how ILI tool accuracy impacts integrity planning, the development of the method for analyzing pipelines with cracks, and the verification and validation with the examples.


The continuous innovation process of the Information and Communication Technology (ICT) sector shape the way businesses redefine their business models. Though, current drivers of innovation processes focus solely on a technical dimension, while disregarding social and environmental drivers. However, examples like Nokia, Yahoo or Hewlett-Packard show that even though a profitable business model exists, a sound strategic innovation process is needed to remain profitable in the long term. A sustainable business model innovation demands the incorporation of all dimensions of the triple bottom line. Nevertheless, current management processes do not take the responsible steps to remain sustainable and keep being in denial of the evolutionary direction in which the markets develop, because the effects are not visible in short term. The implications are of substantial effect and can bring the foundation of the company's business model in danger. This work evaluates the decision process that lets businesses decide in favor of un-sustainable changes and points out the barriers that prevent the development towards a sustainable business model that takes the new balance of forces into account.


In this article, the concept of a cellular robot that is capable of reconfiguring itself is reviewed. This "self-reconfigurable (SR) robot" exemplifies a new trend in robotics, indeed, we can now build various kinds of SR robots with off-the-shelf technologies of processors, actuators, and sensors. These SR robots, based on modern mechatronics, are still not as adaptable as the liquid metal robot in The Terminator 2 but are just as flexible as any conventional robots.


Whole cell patch-clamp recordings were used to investigate the contribution of transient, low-threshold calcium currents (I(T)) to firing properties of hamster spinal dorsal horn neurons. I(T) was widely, though not uniformly, expressed by cells in Rexed's laminae I-IV and correlated with the pattern of action potential discharge evoked under current-clamp conditions: I(T) in neurons responding to constant membrane depolarization with one or two action potentials was nearly threefold larger than I(T) in cells responding to the same activation with continuous firing. I(T) was evoked by depolarizing voltage ramps exceeding 46 mV/s and increased with ramp slope (240-2,400 mV/s). Bath application of 200 μM Ni(2+) depressed ramp-activated I(T). Phasic firing recorded in current clamp could only be activated by membrane depolarizations exceeding ∼43-46 mV/s and was blocked by Ni(2+) and mibefradil, suggesting I(T) as an underlying mechanism. Two components of I(T), "fast" and "slow," were isolated based on a difference in time constant of inactivation (12 ms and 177 ms, respectively). The amplitude of the fast subtype depended on the slope of membrane depolarization and was twice as great in burst-firing cells than in cells having a tonic discharge. Post hoc single-cell RT-PCR analyses suggested that the fast component is associated with the Ca(V)3.1 channel subtype. I(T) may enhance responses of phasic-firing dorsal horn neurons to rapid membrane depolarizations and contribute to an ability to discriminate between afferent sensory inputs that encode high- and low-frequency stimulus information.


In the present manuscript, we provide striking evidence about the involvement of phonology in a range of writing tasks (copy, spelling-to-dictation, associated-pairs) when adult writers produce known words. Interestingly, multiple phonological units seem to be functional during handwriting, as syllables and graphemes. Furthermore, we demonstrate that he frequency of a phoneme have an impact in the duration of its corresponding grapheme. Altogether, the evidence presented here also confirms the impact of central high-order (phonological) variables in the duration of a written response. This fact supports the idea that writing starts as soon as the initial segments of the response have been processed, and rules out the affirmation that a word does not begin to be produced until the whole word has been processed at the central (abstract) levels. Evidence obtained in these experiments strongly support the claim that phonology is systematically retrieved during the normal handwriting process, even when writing well-known words. Phonology is retrieved during handwriting, and it is used at a sublexical level to strengthen the orthographic (lexical) information kept in the orthographic working memory. Later on the process, the written response is produced syllable-by-syllable, indicating that the phonological loop plays a role in the response segmentation. In the case of low-frequency syllables, which lack of a holistic motor pattern, the motor programs for individual letters have to be retrieved. This process produces an increase of the cognitive load demanded by complex graphemes. More studies are necessary to establish how these effects vary when complex graphemes are embedded in high-frequency syllables. However, we have been able to confirm the involvement of at least two different units of phonological origin during handwriting production: syllables and graphemes. Multiple units seem to be used to program the writing movements, in line with Van Galen's (1991) proposal. Finally, this pattern of results fits a model of written production in which levels of processing are simultaneously active, but engaged with different segments of the response. When processing demands are increased at a certain level of processing, concurrent processes can be also affected. We propose a psycholinguistic model of handwriting production which integrates the evidence reported here and most of the previous literature.


ABSTRACT The fact that adherents of most religions subscribe sincerely to many counter-empirical beliefs has been argued to pose a challenge to evolutionary explanations of religion, since natural selection is considered to have developed sophisticated cognitive mechanisms to enable prehistoric foragers to survive in harsh environments. I argue here that most counter-empirical beliefs held by members of most religions are optional most of the time, and were optional all of the time in prehistory. Beliefs held by foragers and other individuals in situations where survival may depend on them are not very counter-empirical compared to locally available alternatives. More generally, human beings are cognitively extravagant—that is, they are capable of entertaining beliefs about a large number of things other than their immediate physical environment, but it is only in modern environments that their cognitive extravagance typically becomes costly enough to pose a problem for evolutionary explanation. In a nutshell, counter-empirical beliefs are a by-product rather than a precondition of religious membership and practice, and were unlikely to have been adaptively costly in environments that were evolutionarily relevant for human beings.


Platelet-derived growth factor (PDGF)-BB is a well-known smooth muscle (SM) cell (SMC) phenotypic modulator that signals by binding to PDGF alphaalpha-, alphabeta-, and betabeta-membrane receptors. PDGF-DD is a recently identified PDGF family member, and its role in SMC phenotypic modulation is unknown. Here we demonstrate that PDGF-DD inhibited expression of multiple SMC genes, including SM alpha-actin and SM myosin heavy chain, and upregulated expression of the potent SMC differentiation repressor gene Kruppel-like factor-4 at the mRNA and protein levels. On the basis of the results of promoter-reporter assays, changes in SMC gene expression were mediated, at least in part, at the level of transcription. Attenuation of the SMC phenotypic modulatory activity of PDGF-DD by pharmacological inhibitors of ERK phosphorylation and by a small interfering RNA to Kruppel-like factor-4 highlight the role of these two pathways in this process. PDGF-DD failed to repress SM alpha-actin and SM myosin heavy chain in mouse SMCs lacking a functional PDGF beta-receptor. Importantly, PDGF-DD expression was increased in neointimal lesions in the aortic arch region of apolipoprotein C-deficient (ApoE(-/-)) mice. Furthermore, human endothelial cells exposed to an atherosclerosis-prone flow pattern, as in vascular regions susceptible to the development of atherosclerosis, exhibited a significant increase in PDGF-DD expression. These findings demonstrate a novel activity for PDGF-DD in SMC biology and highlight the potential contribution of this molecule to SMC phenotypic modulation in the setting of disturbed blood flow.


In this paper, we study Shannon capacity of channels in the context of classical Ramsey numbers. We overview some of the results on capacity of noisy channels modeled by graphs, and how some constructions may contribute to our knowledge of this capacity. We present an improvement to the constructions by Abbott and Song and thus establish new lower bounds for a special type of multicolor Ramsey numbers. We prove that our construction implies that the supremum of the Shannon capacity over all graphs with independence number 2 cannot be achieved by any finite graph power. This can be generalized to graphs with bounded independence number.


Fractures are discontinuities in rock that can be exploited by erosion. Fractures regulate cohesion, profoundly affecting the rate, style, and location of Earth surface processes. By modulating the spatial distribution of erodibility, fractures can focus erosion and set the shape of features from scales of fluvial bedforms to entire landscapes. Although early investigation focused on fractures as features that influence the orientation and location of landforms, recent work has started to discern the mechanisms by which fractures influence the erodibility of bedrock. As numerical modeling and field measurement techniques improve, it is rapidly becoming feasible to determine how fractures influence geomorphic processes, as opposed to when or where. However, progress is hampered by a lack of research coordination across scales and process domains. We review studies from hillslope, glacial, fluvial, and coastal domains from the scale of reaches and outcrops to entire landscapes. We then synthesize this work to highlight similarities across domains and scales and suggest knowledge gaps, opportunities, and methodological challenges that need to be solved. By integrating knowledge across domains and scales, we present a more holistic conceptualization of fracture influences on geomorphic processes. This conceptualization enables a more unified framework for future investigation into fracture influences on Earth surface dynamics. © 2018 John Wiley & Sons, Ltd.


The natural environment is deteriorating. However, humans have not slowed down their pace of resource depletion and environmental destruction. This research takes a particular path to understanding environmental consumption—through a focus on temporal perspective. Evidence from six studies demonstrates the positive effect of a cyclical temporal perspective, versus a linear temporal perspective, on consumers' pro-environmental behavior. The research shows that individuals with a cyclical perspective are more likely to include the environment in the self, which leads to higher pro-environmental behavioral intentions and more pro-environmental behavior. This temporal perspective effect is attenuated for consumers already high on green values. The authors also examine a marketer-controlled moderator and show that consumers are more likely to purchase a pro-environmental product when they see a temporal-perspective-congruent promotional appeal. The research contributes to both the time perception and the environmental consumption literature and offers several practical implications for organizations to promote sustainable consumer behavior.


Gross post mortem and histopathological changes are described in a calf with toxoplasmosis. The major pathological changes were restricted to the lungs and kidneys and comprised interstitial pneumonia with multifocal necrosis, and glomerular necrosis. Many pseudocysts were present in both organs. The calf had been in close contact with young cats, one of which was killed and examined and shown to have a high antibody titre to Toxoplasma gondii, although there was little histological evidence of infection. No antibodies to toxoplasma were detected in serum from the dam of the calf, and accordingly, it is suggested that the cat was the source of infection for the calf.


Virtual facial avatars will play an increasingly important role in immersive communication, games and the metaverse, and it is therefore critical that they be inclusive. This requires accurate recovery of the appearance, represented by albedo, regardless of age, sex, or ethnicity. While significant progress has been made on estimating 3D facial geometry, albedo estimation has received less attention. The task is fundamentally ambiguous because the observed color is a function of albedo and lighting, both of which are unknown. We find that current methods are biased towards light skin tones due to (1) strongly biased priors that prefer lighter pigmentation and (2) algorithmic solutions that disregard the light/albedo ambiguity. To address this, we propose a new evaluation dataset (FAIR) and an algorithm (TRUST) to improve albedo estimation and, hence, fairness. Specifically, we create the first facial albedo evaluation benchmark where subjects are balanced in terms of skin color, and measure accuracy using the Individual Typology Angle (ITA) metric. We then address the light/albedo ambiguity by building on a key observation: the image of the full scene -- as opposed to a cropped image of the face -- contains important information about lighting that can be used for disambiguation. TRUST regresses facial albedo by conditioning both on the face region and a global illumination signal obtained from the scene image. Our experimental results show significant improvement compared to state-of-the-art methods on albedo estimation, both in terms of accuracy and fairness. The evaluation benchmark and code will be made available for research purposes at https://trust.is.tue.mpg.de.


The detection of micro-embolic signals (MES) is a mature application of transcranial Doppler (TCD) ultrasound. It involves the identification of abnormally highpitched signals within the arterial waveform as a method of diagnosis and prediction of embolic complications in stroke patients. More recently, algorithms have been developed to help characterise and classify MES using advanced signal processing techniques. These advances aim to improve our understanding of the causes of cereberovascular disease, helping to target the most appropriate interventions and quantifying the risk to patients of further stroke events. However, there are a number of limitations with current TCD systems which reduce their effectiveness. In particular, improvements in our understanding of the scattering effects in TCD ultrasound propagation channels will benefit our ability to develop algorithms that more robustly and reliably identify the consistency and material make-up of MES. This thesis explores TCD propagation channels in three related research areas. Firstly, a method of characterising TCD ultrasound propagation channels is proposed. Isotropic and non-isotropic three dimensional space (3-D) spherical scattering channel models are described in terms of theoretical reference models, simulation models, and sum of sinusoids (SoS) simulators, allowing the statistical properties to be analysed and reported. Secondly, a TCD ultrasound medical blood flow phantom is described. The phantom, designed to replicate blood flow in the middle cerebral arteries (MCA) for TCD ultrasound studies, is discussed in terms of material selection, physical construction and acoustic characteristics, including acoustic velocity, attenuation and backscatter coefficients. Finally, verification analysis is performed on the non-isotropic models against firstly, the blood flow phantom, and secondly, a patient recordings database. This analysis expands on areas of agreement and disagreement before assessing the usefulness of the models and describing their potential to improve signal processing approaches for detection of MES. The proposed non-isotropic channel reference model, simulation model, SoS simulator, and blood flow phantom are expected to contribute to improvements in the design, testing, and performance evaluation of future TCD ultrasound systems.


To compare the effect of human colostrum (days 1 to 3 postpartum) and mature milk (days 170 ± 24 postpartum) on the function of polymorphonuclear leukocytes (PMNL), Ficoll-Hypaque-separated PMNL from the blood of 60 healthy volunteers were incubated with whole colostrum, colostral lipid, and colostral aqueous phase from 30 mothers, or with mature whole milk and its separated components from 30 mothers, and tested for resting and zymosan-stimulated oxidative metabolism, functional activity, and the presence of Fc receptors. Stimulated oxygen consumption, quantitative nitroblue tetrazolium dye reduction, [1-14C]glucose utilization, and Fc receptors were significantly (P < 0.05 to P < 0.001) less in PMNL exposed to whole human colostrum or colostral lipid than in non-lipid-exposed cells or cells exposed to the aqueous phase of colostrum. In contrast, PMNL exposed to whole mature milk or to its lipid or aqueous phase caused no significant decrease in any of these parameters when compared to nonexposed cells. In assays of phagocytosis, colostral PMNL or blood PMNL exposed to colostral lipid had a significant (P < 0.001) decrease in their ability to ingest [methyl-3H]thymidine-labeled Staphylococcus aureus when compared to non-lipid-exposed PMNL. Blood PMNL exposed to lipid from mature milk had no decrease in ability to ingest S. aureus. Analysis of total lipid and total and individual fatty acid content revealed a uniform increase in all components in mature milk when compared to colostrum. Lipid or lipid-soluble material present in human colostrum but not mature milk causes inhibition of phagocytosis and respiratory burst-related activities of PMNL.


Informed consent is regarded as a pillar of medical ethics. The purpose of this study was to evaluate perceptions of the informed consent process prior to surgery. Three hundred elective surgery patients were randomly selected from three teaching hospitals in Kashan, Iran, and asked to complete a questionnaire about four key aspects of the informed consent process: information disclosure, voluntariness, comprehension, and their relationship with physicians. Data were scored and analyzed using univariate and multivariate methods. Based on the responses, the perceived quality of information disclosure (7.96 ± 4.9 out of 18 points), comprehension of the consent form (0.55 ± 1.1 out of 4 points), and voluntariness (1.73 ± 2.1 out of 8 points) were considered to be unacceptable and the perceived quality of the physician–patient relationships (10.6 ± 4.1 out of 14 points) acceptable. Most of the participants (88.7%) reported that they had requested to be informed about the complications of the surgical procedures, including severe complications such as death, but most of them did not receive this information. The most important factors associated with the perceived quality of informed consent were the patient's level of education and type of surgery. In conclusion, practices consistent with the principles of informed consent have not been adequately implemented in the surgical departments of these hospitals in Kashan. To improve current practices, patients should receive more information about the risks and benefits of surgery as well as any available alternatives. Information about the expected length of hospital stay, post-discharge follow-up, and the cost of surgery should also be provided to patients. To improve the perceived quality of the informed consent process, more emphasis should be placed on ensuring that patients receive the requested information in a manner they can comprehend. Redesigning consent forms may be an important step in improving the patients' experience of the informed consent process.


Two field investigations in an exposed shallow area outside Lofoten, western Norway, were conducted in 1995 and 1996. Direct measurements of turbulence were conducted from an underwater tower with acoustic current meters 6 m above the bottom. The tidal energy in this area is low and the wind conditions during the experiment were mostly weak. Nevertheless, the turbulent kinetic energy dissipation rate at 20-25 m depth was in the range 10 -7 -10 -5 W/kg. The only other possible energy source was long swell of wavelength 100-200 m that rolled in from the open sea. Analysis shows that the wave related water motion intermittently becomes unstable, inducing strong turbulent patches in parts of the wave orbit. The mechanism behind this process is not clear, but possible explanations may be local energy concentration or interaction of waves with different frequency. In many areas and situations this energy source is equal in force to tidal and wind generated turbulence. Simultaneous measurement of vertical profiles of zooplankton and fish larvae from a nearby location enables us to discuss swell-induced turbulence in an ecological context.


This paper discusses recent updates and developments of computing-based courses in the civil engineering discipline. Competency in computing is one of the most important capabilities for university graduates to obtain given the rapid development of computer technology in professional work. Civil engineering is no exception. In fact, many contemporary civil engineering projects require a high degree of computing skills, ranging from performing basic office work to programming for decision support system application in controlling flood water gates to executing construction automation via digital printing technology. However, the curriculum content for computing in civil engineering has been developmentally stagnant in the past several decades. This could be partly due to learning outcomes for civil engineering graduates, which do not explicitly mention a certain degree of achievement with respect to computing skills. Several computing-based courses offered in various civil engineering programs across Saudi Arabia and the US were examined, and their contents were compared to recent survey results administered by the American Society of Civil Engineering Technical Committee on Computing and Information Technology. The discussion is extended by examining technical courses offered in the Civil Engineering Program in Prince Mohammad Bin Fahd University with respect to computing skills. The outcomes of this study are expected to give input and suggestions for future upgrades of computing-based courses offered within the civil engineering curriculum.


TAA and ankle arthrodesis are efficacious treatments of end-stage ankle osteoarthritis but the selection must be specially fit to individual patients. Total ankle arthroplasty (TAA) offers a judicious option to ankle arthrodesis in prudently selected patients. Reoperation rates are greater in TAA compared with ankle arthrodesis. The primary diagnosis for TAA is 37% osteoarthritis, 34% traumatic arthritis, 15% rheumatoid arthritis, 14% other. Patients experiencing TAA tend to be older, female, and have rheumatoid arthritis compared with those being subjected to ankle arthrodesis. Aseptic loosening and infection are the most frequent complications of TAA needing revision. The 15-year survival of primary TAA ranges from 45% to 91%. A comparison between the HINTEGRA implant, the AGILITY implant, the MOBILITY implant, and the Scandinavian Total Ankle Replacement (STAR) implant exhibited reasonable results of four modern TAA designs. TAA is a demanding surgical technique and the survival is not similar to that following hip or knee arthroplasty. Revision TAA has a 10-year survival of 55%, which is lower than the 10-year survival of 74% for primary TAA.


Genome-wide association studies (GWAS) have identified numerous genetic variants associated with diseases and traits. However, the functional interpretation of these variants remains challenging. Expression quantitative trait loci (eQTLs) have been widely used to identify mutations linked to disease, yet they explain only 20-50% of disease-related variants. Single-cell eQTLs (sc-eQTLs) studies provide an immense opportunity to identify new disease risk genes with expanded eQTL scales and transcriptional regulation at a much finer resolution. However, there is no comprehensive database dedicated to single-cell eQTLs that users can use to search, analyse and visualize them. Therefore, we developed the scQTLbase (http://bioinfo.szbl.ac.cn/scQTLbase), the first integrated human sc-eQTLs portal, featuring 304 datasets spanning 57 cell types and 95 cell states. It contains ∼16 million SNPs significantly associated with cell-type/state gene expression and ∼0.69 million disease-associated sc-eQTLs from 3 333 traits/diseases. In addition, scQTLbase offers sc-eQTL search, gene expression visualization in UMAP plots, a genome browser, and colocalization visualization based on the GWAS dataset of interest. scQTLbase provides a one-stop portal for sc-eQTLs that will significantly advance the discovery of disease susceptibility genes.


I discuss two types of language economy in Internet textchat discourse, ellipsis and reduced forms (such as clippings and informal phoneticised spellings). These are markers that a community of practice is being or has been formed. The data I analyse is textchat data from seminars with students on an MA in English Linguistics. Reduced forms are expected in Internet discourse and function as an in-group marker that the user is an experienced Internet user. I present additional evidence that learners are agents of the process of standardising the forms the community uses. Ellipsis is shown to function as a marker of interaction, and therefore that the community is a cohesive group. I show that the major functions of interaction that have been presented in the literature can be seen in ellipsis contexts. We can therefore conclude that both these types of reduced language are also evidence of a social autonomy that the learners have which is seen as a prerequisite for learner autonomy.


The serpin (serine proteinase inhibitor) family is of general protein chemical interest because of its ability to undergo large conformational changes, in which the surface-exposed reactive centre loop (RCL) is inserted as strand 4 in the large central beta-sheet A. Loop insertion is an integral part of the inhibitory mechanism and also takes place at conversion of serpins to the latent state, occurring spontaneously only in plasminogen activator inhibitor-1 (PAI-1). We have investigated the importance of beta-strand 5A residues for the activity and latency transition of PAI-1. An approximately fourfold increase in the rate of latency transition resulted from His-substitution of Gln324 (position 334 in the alpha(1)-proteinase inhibitor template numbering), which interacts with the underlying alpha-helix B. The side chains of Gln321 and Lys325 (template residues 331 and 335, respectively) form hydrogen bonds to the peptide backbone of a loop connecting alpha-helix F and beta-strand 3A. While substitution with Ala of Glu321 had only minor effects on the properties of PAI-1, substitution with Ala of Lys325 led to stabilization of the inhibitory activity at incubation conditions leading to conversion of wild-type PAI-1 to a substrate form, and to an anomalous reaction towards a monoclonal antibody, which induced a delay in the latency transition of the mutant, but not wild-type PAI-1. We conclude that the anchoring of beta-strand 5A plays a crucial role in loop insertion. These findings provide new information about the mechanism of an important example of protein conformational changes.


Horses were immunized by a variety of inoculation procedures designed to determine the most efficient method of producing antisera to adenovirus types 25 to 31. The procedures evaluated included immunization by (i) direct intravenous (iv) injection, (ii) iv infusion, (iii) intramuscular (im) injection of virus with and without Freund's incomplete adjuvant, (iv) combined iv and im injections, and (v) combined iv infusion and im injection. The im schedule (no. 3) was superior to the others in terms of immunizing antigen and time required, and hemagglutination-inhibition (HI) and serum-neutralizing (SN) antibody levels produced. HI and SN tests performed with sera before and after heating at 56 C for 30 min showed that heat-inactivation was not necessary for tests with equine antisera.


Background: Nitric oxide (NO) is a crucial signaling molecule which regulates the blood flow and prevents the adhesion of blood components to the vascular wall. A deficiency in bioavailable NO concentration is associated with the dysfunction of endothelial NO synthase (eNOS) and/or an increase in oxidative stress. The deficiency of bioavailable NO is a common denominator of several cardiovascular diseases, including diabetes, atherosclerosis, and hypertension. Materials and Methods: We used a nanomedical technology to elucidate the balance between bioavailable NO and oxidative stress (peroxynitrite ONOO−) in human umbilical vein endothelial cells (HUVECs) treated with a supplement containing L-arginine, L-citrulline, Vitamin D3, and antioxidants. Nanosensors, with a diameter of 200–300 nm, are capable of measuring in situ NO and peroxynitrite (ONOO−) concentrations produced by single endothelial cells. Results: The ratio of the concentration of cytoprotective NO [NO] to the concentration of cytotoxic peroxynitrite [ONOO−] was used to estimate the efficiency of eNOS. HUVECs incubated with L-citrulline, L-arginine, and Vitamin D3increased the [NO]/[ONOO−] ratio by 25%, while in the presence of antioxidants, the increase was 15%. The synergistic effect between the mix of L-arginine, L-citrulline, Vitamin D3, and antioxidants was a favorable increase of the overall [NO]/[ONOO−] ratio by 50%. Conclusion: The findings of the study presented here clearly indicate that L-arginine, L-citrulline, and Vitamin D3can significantly alter the function of the endothelium and NO production, in a favorable manner, while pointedly reducing ONOO− – the main component of oxidative stress. This effect can be significantly potentiated in the presence of antioxidants.


The organisation, administration and running of a successful OSCE programme need considerable knowledge, experience and planning. Different teams looking after various aspects of OSCE need to work collaboratively for an effective question bank development, examiner training and standardised patients' training. Quality assurance is an ongoing process taking place throughout the OSCE cycle. In order for the OSCE to generate reliable results it is essential to pay attention to each and every element of quality assurance, as poorly standardised patients, untrained examiners, poor quality questions and inappropriate scoring rubrics each will affect the reliability of the OSCE. The validity will also be influenced if the questions are not realistic and mapped against the learning outcomes of the teaching programme. This part of the Guide addresses all these important issues in order to help the reader setup and quality assure their new or existing OSCE programmes.


The first phage electron micrographs were published in 1940 in Germany and proved the particulate nature of bacteriophages. Phages and infected bacteria were first examined raw and unstained. US American scientists introduced shadowing and freeze-drying. Phages appeared to be tailed and morphologically heterogeneous. Phage types identified by early electron microscopy include enterobacteriophages T4, T1, T7, T5, 7–11, ViI and Pseudomonas phage PB1. This paper retraces the development of early virus electron microscopy till the introduction of negative staining.


Diabetic kidney disease (DKD) is a common and serious microvascular complication of diabetes mellitus (DM), which is characterized by an elevated urinary albumin excretion rate, elevated blood pressure, and declined renal function. Approximately 30–40% of DM patients will develop DKD, which is the leading cause of end-stage renal disease (ESRD) and renal failure. Genetic factors appear critical in DKD pathogenesis based upon the evidence including aggregation in families, variable incidence rates of DKD between different races, and the highly heritable nature of diabetic renal clinic and histologic changes. Each 10-mmHg increase in mean systolic blood pressure (BP) was associated with a 15% increase in the hazard ratio for development of both microand macroalbuminuria and impaired kidney function defined as eGFR<60 ml/min per 1.73 m2 or doubling of the blood creatinine level. Broadly, a baseline systolic BP >140 mmHg in patients with DM2 has been associated with higher risk of ESRD and death. The ACE genes may predict diabetic nephropathy in some groups, the rate of progression and the antiproteinuric response to ACE inhibitors.


Featuring a stable democracy and dizzying economic growth, Brazil is fast on the way to acquiring global power status. The country is investing in enhanced multilateral and bilateral relationships as a means of leveraging trade and reducing vulnerability abroad and on the domestic front. This chapter demonstrates how Brazil has increasingly aligned its foreign policy with a South–South Cooperation (SSC) agenda as a means of achieving these parallel objectives. But while Brazil's trade activities have received attention, there has been comparatively less focus on the country's aid policy and practice. Moreover, there is surprisingly little discussion of how the country's foreign policy pillars – trade and aid – are explicitly linked. The chapter demonstrates how Brazil's emerging aid agenda is fundamentally informed by trade considerations. Over the past decade Brazil has positioned its foreign policy agenda in such a way as to re-shape the global terms of trade in its favour and decrease its dependency both domestically and internationally. Brazil's relatively modest development aid allocations are amplified by a wider effort to advance trade, foreign direct investment and technology transfer. As Brazil seeks to expand to new markets for its products, services and investment, it anticipates that its South–South Development Cooperation (SSDC) stance will facilitate the extension of its influence in bilateral and multilateral arrangements, including the World Trade Organization (WTO) and the United Nations (UN) Security Council.


This study is to identify the influences of socio-economic factors towards the practice of Pap smear screening among ever married women. Bivariate correlations and logistic regression analysis was applied to the data set containing 3,283 ever married women age 15-49 years, interviewed during the Fourth Malaysian Population and Family Survey, 2004. It was found that only half the women had undergone Pap smear screening prior three years of survey, in which Chinese had the highest percentage of Pap smear screening. The logistic statistical analysis also had identified several variables has important determinant has of Pap smear screening for ever married women. Finding from this study suggest a significant relationship between the cervical cancer awareness and knowledge, age and ethnicity for those women who practice Pap smear screening.


We study the dynamics of inflation driven by an adiabatic self-gravitating medium, extending the previous works on fluid and solid inflation. Such a class of media comprises perfect fluids, zero and finite temperature solids. By using an effective field theory description, we compute the power spectrum for the scalar curvature perturbation of constant energy density hypersurface ζ and the comoving scalar curvature perturbation ℛ in the case of slow-roll, super slow-roll and w-media inflation, an inflationary phase with w constant in the range −1 <w <−1/3. A similar computation is done for the tensor modes. Adiabatic media are characterized by intrinsic entropy perturbations that can give a significant contribution to the power spectrum and can be used to generate the required seed for primordial black holes. For such a media, the Weinberg theorem is typically violated and on super horizon scale neither ζ nor ℛ are conserved and moreover ζ ≠ ℛ. Reheating becomes crucial to predict the spectrum of the imprinted primordial perturbations. We study how the difference between ζ and ℛ during inflation gives rise to relative entropic perturbations in ΛCDM.


: Pyrogenal in the dose 5 mcg increased the adrenaline release in dogs. Interleukin-1 increased the noradrenaline release. Neither capsaicin, nor M- and N-cholinoreceptor blockade, nor pre-decentralization of the inferior mesenteric ganglion, abolished the effects. Mechanical and chemical stimuli during continuous perfusion of the colon with subliminal doses of pyrogenal increased the adrenaline release, too. A possible direct effect of endotoxins on peripheral adrenergic neurons, is discussed.


In 1979 Britain committed almost 120,000 ground troops and almost the entire Royal Navy and Royal Air Force to NATO's defence of Western Europe. 100,000 troops were assigned to Home Defence, and Britain would acts as a staging post for foreign troops on their way to the front. Did Britain really have the means to mobilise, transport and supply these forces, and defend itself, in the event of war? This is an analysis of the conventional defence planning of the UK, its relationship to the
policy, and their possible and actual execution.
Deterrent plans were aimed at the perceived threat: planning for the manifestation of that threat, and implementing those plans, is analysed in detail. These plans relate intimately to NATO's "Flexible Response" strategy and the desire to raise the nuclear threshold enabling NATO to stop a WTO attack by conventional means. Analysing the plans for mobilisation, and comparing them to the forces and facilities available, this thesis seeks to understand if the UK fulfilled its obligation, not only to NATO, but also to the Armed Forces and British
public. Following the end of the Cold War, the idea the 'teeth' could be sharpened at the expense of the 'tail' persisted, and has now grown to dangerous proportions. Pursuing the 'efficiency' thread the Armed Forces have been cut to the smallest level for 100 years, yet
asked to do more. There is a large group, both military and political, who believe the policy worked and caused the fall of the Soviet Union. This thinking persists in policy even after the wars in Afghanistan and Iraq. With the increasing tensions in Eastern Europe and the Pacific, and the British Armed Forces at their smallest for over a century, this post hoc analysis is dangerous.


The anticancer drug cisplatin (CP) is loaded into SBA-15 mesoporous silica (SBA-15|CP) and its release from the nanomaterial is studied. The CP-loaded SBA-15 is tested against four tumor cell lines: mouse malignant melanoma B16F10, human adenocarcinoma HeLa, colon HT-29 and prostate PC3. Most importantly, the superiority of this novel material in comparison to CP arises from the fact that the CP-grafted nanomaterial SBA-15 (→SBA-15|CP) is enhancing cessation of proliferation along with induction of senescence in B16F10 in approximately 3.5 times lower concentration. The control material loaded with therapeutically inactive K2[PtCl4] (→SBA-15|TC) showed no antitumor activity. To a large extent, SBA-15|CP-induced senescence might present a safe approach in tumor treatment. Such cells can be cleared by immune cells resulting in efficient tumor regression. So far only apoptotic agents are being exploited in clinics, thus an understanding of the chemotherapeutic-induced senescence will allow oncologists to explore this essential tumor suppressor mechanism.


The main idea in this research is the utilization of Fuzzy C Means (FCM) method as the determination of patient's nutritional status, which is implemented, in mobile application. Parameters used to cluster nutritional status are height, weight and age. The result of the decision will give 3 clusters on nutritional status is good nutrition, malnutrition and better nutrition. Mobile apps are used as a reminder of the nutritional value or ingredients contained in the packaging of food products while consuming food. The result of system testing for application of FCM algorithm in this mobile application obtained validation of 80%.


In the Yaqui Valley, northwest Mexico, the crop sequence that is becoming more common consists of planting wheat (Triticum aestivum L.) as a winter crop on a raised bed followed by maize (Zea mays L.) as a summer crop. In this area, straw of both winter and summer crops is commonly burned. The consequences of burning crop residues on crop yields in the Yaqui Valley have not previously been documented, and alternative practices have not been proposed. A 5-yr study was conducted at the CIANO (Centro de Investigaciones Agricolas del Noroeste) experiment station in Sonora, Mexico, to compare the effects of burning with other straw management strategies on wheat and maize yields. We tested two tillage systems (conventional-tilled bed, CTB, and permanent bed, PB), five straw management treatments (incorporated with CTB and straw as stubble, partly removed, removed, or burned with PB), and seven N treatments, five applied preplant (0, 75, 150, 225, and 300 kg N ha -1 ) and two at the 1st node stage (150 and 300 kg N ha -1 ) of wheat. Maize following wheat received a uniform application of 150 kg N ha -1 . The combination of PB and straw as stubble produced superior maize and wheat grain yields in high-yielding environments; in low-yielding environments, PB-straw burned produced greater wheat grain yields. Nitrogen fertilizer application of 150 and 300 kg N ha -1 at the 1st node stage of wheat increased grain yields compared with preplant N fertilizer applications. Permanent beds combined with retaining all crop residues in the soil as stubble have the potential to increase both wheat and maize yields in the Yaqui Valley.


Objectives The tackle is responsible for the majority of head injuries during rugby union. In order to address head injury risk, risk factors during the tackle must first be identified. This study analysed tackle characteristics in the professional game in order to inform potential interventions. Methods 464 tackles resulting in a head injury assessment (HIA) were analysed in detail, with tackle type, direction, speed, acceleration, nature of head contact and player body position the characteristics of interest. Results Propensity to cause an HIA was significantly greater for active shoulder tackles, front-on tackles, high speeder tackles and an accelerating tackler. Head contact between a tackler's head and ball carrier's head or shoulder was significantly more likely to cause an HIA than contact below the level of the shoulder (incident rate ratio (IRR) 4.25, 95%–CI 3.38 to 5.35). The tackler experiences the majority (78%) of HIAs when head-to-head contact occurs. An upright tackler was 1.5 times more likely to experience an HIA than a bent at the waist tackler (IRR 1.44, 95% CI 1.18 to 1.76). Conclusions This study confirms that energy transfer in the tackle is a risk factor for head injury, since direction, type and speed all influence HIA propensity. The study provides evidence that body position and the height of tackles should be a focus for interventions, since lowering height and adopting a bent at the waist body position is associated with reduced risk for both tacklers and ball carriers. To this end, World Rugby has implemented law change based on the present data.


Four lactating Holstein Friesian crossbred cows, with an average initial weight of 450 kg, 48±12 days in milk and initial milk yield of 18 kg/h/d, were randomly arranged according to a 2x2 factorial arrangement in a 4x4 in Latin square design with 21-d period to investigate the effects of type of total mixed ration (TMR) and type of whole cottonseed (WCS) on intake, digestibility and milk production. The dietary treatments were i) TMR and WCS supplementation at 0.5 kg/h/d, ii) TMR and cracked WCS (cWCS) supplementation at 0.5 kg/h/d, iii) fermented TMR (FTMR) and WCS supplementation at 0.5 kg/h/d, and iv) FTMR and cWCS supplementation at 0.5 kg/h/d. Voluntary feed intake was 15.9, 15.2, 15.4 and 15.6 kg DM/d in dietary treatment 1, 2, 3 and 4, respectively. Digestibility of DM, OM, CP, EE, NDF and ADF were not significantly different among dietary treatments. Ruminal pH, NH 3 -N and volatile fatty acids in the rumen were also not significantly different among type of TMR or type of WCS. Blood urea-N concentration was not significantly different among dietary treatments. Ruminal bacteria population tended to increase but ruminal protozoa population tended to decrease with supplementation of cWCS, but they were not affected by FTMR. Milk yield and 3.5% FCM were not statistically different among treatments (16.6, 16.2, 17.0, 16.3 kg/d and 18.0, 18.6, 19.9 and 19.0 kg/d, respectively). Milk composition was not significantly different among dietary treatments. However, unsaturated fatty acids in milk fat in cows fed FTMR were lower (p<0.05) than in cows fed TMR. In conclusion, fermentation is a conceivable method to improve the quality of TMR for long-time storage and the cracking method is suitable to release the fat from cottonseed for enhancing fatty acid deposition in milk. Thus, the combination of FTMR and cWCS supplementation would be an alternative strategy to improve performance of lactating cows.


The Socio-Economic Costs of Bereavement in Scotland (SECOB) research study was funded by the Scottish Government Health Directorates in late 2010 as part of ongoing work to inform national policy on bereavement and bereavement care practice. The project aimed to: a) articulate the likely nature and scope of the impact of bereavement on social and economic aspects of life for Scottish citizens as evidenced in relevant literature, b) seek to estimate the socio-economic costs of bereavement in an emergent sub-set of key aspects, and c) develop methodological approaches that will enhance capacity for large-scale research into the socio-economic impact of bereavement. The study published a main report, a literature report and a technical report.


PURPOSE
There is a growing need to localize prostate cancers on magnetic resonance imaging (MRI) to facilitate the use of image guided biopsy, focal therapy, and active surveillance follow up. Our goal was to develop a decision support system (DSS) for detecting and localizing peripheral zone prostate cancers by using machine learning approach to calculate a cancer probability map from multiparametric MR images (MP-MRI).

METHODS
This IRB approved Health Insurance Portability and Accountability Act compliant retrospective study consisted of 31 patients (mean age and serum prostate specific antigen of 60.4 and 6.62 ng∕ml, respectively) who had MP-MRI at 3 T followed by radical prostatectomy. Seven patients were excluded due to technical issues with their MP-MRI (e.g., motion artifact, failure to perform all sequences). Cancer and normal regions were identified in the peripheral zone by correlating them to whole mount histology slides of the excised prostatectomy specimens. To facilitate the correlation, tissue blocks matching the MR slices were obtained using a MR-based patient-specific mold. Segmented regions on the MP-MRI were correlated to histopathology and used as training sets for the learning system that generated the cancer probability maps. Leave-one-patient-out cross-validation on the cancer and normal regions was performed to determine the learning system's efficacy, an evolutionary strategies approach (also known as a genetic algorithm) was used to find the optimal values for a set of parameters, and finally a cancer probability map was generated.

RESULTS
For the 24 patients that were used in the study, 225 cancer and 264 noncancerous regions were identified from the region maps. The efficacy of DSS was first determined without optimizing support vector machines (SVM) parameters, where a region having a cancer probability greater than or equal to 50% was considered as a correct classification. The nonoptimized system had an f-measure of 85% and the Kappa coefficient of 71% (Rater's agreement, where raters are DSS and ground truth histology). The efficacy of the DSS after optimizing SVM parameters using a genetic algorithm had an f-measure of 89% and a Kappa coefficient of 80%. Thus, after optimization of the DSS there was a 4% increase in the f-measure and a 9% increase in the Kappa coefficient.

CONCLUSIONS
This DSS provides a cancer probability map for peripheral zone prostate tumors based on endorectal MP-MRI. These cancer probability maps can potentially aid radiologists in accurately localizing peripheral zone prostate cancers for planning targeted biopsies, focal therapy, and follow up for active surveillance.


I believe the Sentencing Reform Act of 1984, which created the United States Sentencing Commission, contains two main directives. First, the Commission's guidelines must provide a rational and principled sentencing system that will further the purposes of just punishment and crime control. Second, the guidelines must reduce unwarranted disparity among sentences for similar offenders who commit similar offenses. The Act provides that this is to be achieved through the Commission's promulgation of a comprehensive sentencing system that will bind all federal judges. I opposed the Commission's Preliminary Draft of September, 1986, because I saw it as lacking both guiding principles and an effective means of reducing disparity. While the Commission's current proposed guidelines differ from the Preliminary Draft in many important respects, like its predecessor, this draft is not guided by rational unifying principles and it will not reduce sentencing disparity. Further, the current proposed guidelines transgress specific statutory limitations on the Commission's authority. Because I believe that the proposal violates both the intent and the letter of the Sentencing Reform Act, I cannot in good faith join the other members of the Commission in support of the proposed guidelines.


Empirical and experiential investigations allow the distinction between observational and nonobservational forms of subjective bodily experiences. From a first-person perspective, the biological body can be (1) an "opaque body" taken as an intentional object of observational consciousness, (2) a "performative body" pre-reflectively experienced as a subject/agent, (3) a "transparent body" pre-reflectively experienced as the bodily mode of givenness of objects in the external world, or (4) an "invisible body" absent from experience. It is proposed that pre-reflective bodily experiences rely on sensori-motor integrative mechanisms that process information on the external world in a self-relative way. These processes are identification-free in that the self is not identified as an object of observation. Moreover, it is defended that observational self-consciousness must be grounded on such identification-free processes and pre-reflective forms of bodily experience.


The modeling and design of a fault-tolerant multiprocessor system is addressed in this dissertation. In particular, the behavior of the system during recovery and restoration after a fault has occurred is investigated. Given that a multicomputer system is designed using the Algorithm to Architecture To Mapping Model (ATAMM) model, and that a fault (death of a computing resource) occurs during its normal steady-state operation, a model is presented as a viable research tool for predicting the performance bounds of the system during its recovery and restoration phases. Furthermore, the bounds of the performance behavior of the system during this transient mode can be assessed. These bounds include: time recover from the fault (t$\sb{\rm rec}$), time to restore the system (t$\sb{\rm res}$) and whether there is a permanent delay in the system's Time Between Input and Output (TBIO) after the system has reached a steady state. An implementation of an ATAMM based computer was developed with the Generic VHSIC Spaceborne Computer (GVSC) as the target system. A simulation of the GVSC was also written based on the code used in ATAMM Multicomputer Operating System (AMOS). The simulation is in turn used to validate the new model in the usefulness and accuracy in tracking the propagation of the delay through the system and predicting the behavior in the transient state of recovery and restoration. The model is validated as an accurate method to predict the transient behavior of an ATAMM based multicomputer during recovery and restoration.


With the use of Perforated Solar Screen (PSS), solar gains are controlled, cooling loads are reduced, and comfort conditions can be achieved while using its energy efficiently. Nowadays, the use of PSS is increased, especially in large, glazed facades. The design of PSS needs to develop and optimize for the temperate humid climate. A new design proposal is presented by considering the basic principles in terms of providing solar control by PSS within the scope of the study. The optimization of the design proposal has been carried out in terms of solar radiation, Annual Sun Exposure (ASE), and View with the use of Rhinoceros/Grasshopper by considering the design variables (angle, perforation ratio, width, and distance, etc.) of the PSS. An optimum design proposal has been presented for the existing classroom (transparency ratio: 60%) on the southern facade. Thermal comfort and surface temperature have been calculated. Design proposals can be developed for the west and east facades by using the method of this study.


Abstract The students frequenting the program Chemical Engineering at the Department of Chemical and Environmental Engineering, Faculty of Chemical and Food Technology of the Slovak University of Technology in Bratislava are taught to be able to combine and develop their knowledge acquired in the area of chemical, energetic, environmental, and safety engineering. Prior to completing their study, they are obliged to develop a report regarding engineering, economic, and safety analysis of important chemical technology. This paper presents the most valuable outputs of the student's Technology project aimed on simulation and optimization of the fuel additives production technology. 2-Ethoxy-2-methylpropane (ethyl-t-butyl ether, ETBE) production based on liquid-phase etherification of 2-methylpropene with ethanol in the presence of heterogeneous catalyst was studied. Different patented technologies were investigated in terms of their profitability and safeness. The first technology was an isothermal reactor with the product separation via distillation (Kochar & Marcell, 1981). The next ETBE production design assumed was a modification of the previous one; the product separation was carried out using liquid-phase extraction (Pucci et al., 1992). The last design considered in this study was a reactive distillation column with a pre-reactor (Bakshi et al., 1992). In all three technologies, etherification reaction was carried out using Amberlyst ion-exchange resin in its H+ form as the catalyst. Selected ETBE production designs were simulated using Aspen+ program. Their profitability was compared on basis of the investment and operation costs assessment taking into account both the produced ETBE yield and purity. Further, basic safety analysis of all chosen technologies was performed in order to identify possible hazards. Finally, individual and social risk connected with the plant operation was computed. Taking into account these economic and safety criteria, the best alternative for ETBE production was the reactive distillation.


BACKGROUND
The human amylase gene (AMY1) has broad copy number (CN) variation that may associate with BMI.

METHODS
DNA was extracted from urine (n=74) and serum (n=6) samples ('ProFiMet' cohort), and buccal (n=17) samples (Oral Starch Challenge [OSC] cohort), and assessed for AMY1 CN by droplet digital PCR. Association of AMY1 CN with comprehensive markers of metabolic status (ProFiMet cohort) were analysed with Pearson Correlation Coefficients (CC). For the healthy, euglycemic OSC cohort, glycemic response to OSC was analysed with independent-sample t-tests (subgroups: high AMY1 CN 9-12, n=10; low AMY1 CN 4-6, n=7).

RESULTS
There were significant inverse correlations of AMY1 CN with total visceral fat volume (CC -0.33; P=0.004), and positive correlations of AMY1 CN with oral glucose insulin sensitivity score (OGIS [derived from OGTT], CC 0.26; P=0.02), serum HDL-cholesterol (CC 0.325; P=0.003), and serum adiponectin (CC 0.249; P=0.026). Linear regression multivariate analysis (adiponectin as dependent variable), showed independent association of adiponectin with AMY1 CN (Beta=0.29; P=0.03). There were no significant associations between AMY1 CN and clamp-derived M-value, homeostasis model assessment of insulin resistance (IR), hepatic endogenous glucose production, fecal floral signature or macronutrient dietary preference. Delta (mean) change in blood glucose concentration (fasting to 30-min post-OSC), was significantly greater in the high vs low AMY1 CN subgroups (mean 1.7mmol/l [SEM 0.6] vs 0.9mmol/l [SEM 0.9] respectively; p=0.016).

CONCLUSIONS
High AMY1 CN associates with favourable metabolic profile (lower visceral fat volume; higher serum adiponectin; enhanced glucose absorption following oral glucose and OSC), but not with whole-body or hepatic IR.


As time and technology advances, the people become more reliant on the services provided by Industrial Control Systems (ICSs). Mainly used in the critical infrastructure industries, the ICSs have realised and enabled a myriad of services essential to individuals, the public and organizations on a daily basis. Developments in networking technologies, open standards and the use of legacy devices in the ICSs have brought about a paradigm shift in the way ICSs interconnect with each other and operate over long geographical distances. The legacy devices come with inherent vulnerabilities which may be costly to patch and/or may not be possible to patch and these in turn are a source of threats to the entire ICS. In order to mitigate the risks that may arise due to the vulnerabilities introduced into the system, we gained a deeper understanding of the different ICSs and reviewed a number of existing risk analysis approaches and categorized them in terms of their overall goal, whether they are qualitative or quantitative approaches, the stages of risk management addressed, and the scope in terms of issues they addressed. Based on this analysis, we use the NIST and CORAS frameworks as the underlying approaches to develop a Modified Risk Analysis Framework for ICS systems (MRAF-ICS). This framework assigns weights to all the system assets to emphasise the importance/criticality of the asset in the overall system. It uses the a threat modelling approach, FMEA and HAZOP to exhaustively identify the threats, hazards and vulnerabilities in the system.


We analyze strategic environmental standards in the presence of foreign direct investment. A number of foreign firms located in a host country compete with a domestic firm in another country to export a homogeneous good to a third country. When the number of foreign firms is exogenous, the host country applies a stricter environmental regulation than the other producing country. However, under free entry and exit of foreign firms, the host country may apply a less severe standard under both non-cooperative and cooperative equilibrium. We also find that the nature market structure does not affect the equilibrium values of total pollution if export subsidies are also used.


This paper characterizes all continuous price processes that are consistent with current option prices. This extends Derman and Kani (1994), Dupire (1994, 1997), and Rubinstein (1994), who only consider processes with deterministic volatility. Our characterization implies a volatility forecast that does not require a specific model, only current option prices. We show how arbitrary volatility processes can be adjusted to fit current option prices exactly, just as interest rate processes can be adjusted to fit bond prices exactly. The procedure works with many volatility models, is fast to calibrate, and can price exotic options efficiently using familiar lattice techniques.


In a previous edition of this journal Osborne [2000] contains new expressions for two financial concepts from the bond markets: modified duration and the yield to maturity. The concepts are given in terms of the distances between the roots of the time value of money equation and other salient points in the complex plane. This note offers three extensions. First, another new expression is offered, this time a simple and elegant equation for the price of a bond. Secondly, since its introduction by Macauley [1938], the concept of duration has suffered from several shortcomings. One of these shortcomings is the fact that the traditional formulas for duration, Macauley or modified, give estimates of the interest elasticity of the bond price that do not allow for the curvature of the link between price and the interest rate. The orthodox formula can be made more accurate by supplementing it with convexity; however, the result is still an approximation. The problem can be found illustrated in any finance text. It is shown here that the new approach to duration outlined in Osborne [2000] can be adjusted to give a formula that yields precise results for the change in the price of a bond in response to a change in the interest rate. This result, and the methodology surrounding it, is important because it demonstrates that the new perspective from the complex plane not only gives an alternative view of an existing concept, but also improves on it. In addition, it explains why the orthodox formula does not provide precise results, and why it cannot be adjusted to do so. Thirdly, in order to make the theory operational in the bond markets, a question must be answered. How can the theory be adjusted to cope with bonds priced part way through a coupon period? The required level of detail in time in the bond markets is down to the individual day, and the required level of accuracy down to $1 in a million. In the context of these requirements the new approach poses questions about computation. The questions are stated here, but not answered.


Excerpt] In July 2010, a team from the U.S. Department of Labor (USDOL) visited Vietnam to conduct an assessment of the Ministry of Labor, War Invalids & Social Affairs' (MOLISA) labor inspection system. This effort was requested by the SIIR project (funded by USAID) as part of its aim of identifying MOLISA's needs and providing assistance, per MOLISA's request. The Assessment focuses on: 1) assessing facts related to the labor inspection system; and 2) providing initial recommendations for improving the system. Part I discusses MOLISA's history, legal and regulatory framework, structure and organization, Department of Labor Inspections (including workforce, forms and data collection, and IPZ). Part II discusses issues and presents recommendations related to data collection, labor inspector training, inspectorate staffing levels, educational outreach, research and networking, systems of continuous improvement, and coordination with international and private buyers.


This thesis investigates how to create an environment for organizational change within the Market Research Department at the Gangler Company (a US-based consumer products company). I explore what is influencing the current cultural environment and which of those influencers can be shifted to encourage organizational change toward the "ideal" culture that the organization has identified. Using new institutionalism as the theoretical approach, I discuss the significance of institutional forces (such as the economy and the rise in technology) on the cultural elements (i.e. behaviors, ideas, material artifacts and social structures) in the Market Research Department. Lastly, I show that by understanding those institutional influences, I can better assess what cultural elements can be shifted and which cannot. Of the cultural elements that are able to be shifted, I recommend three interventions that the organization should employ: 1) from a contrive culture to a culture of candor, 2) from a culture of division to a culture of cohesion, and 3) from a culture of knowing to a culture of learning.


Introduction Forage crops perform an important role in New Zealand farming systems. They provide large quantities of high quality forage when perennial pasture growth is low or of poor quality. The production advantages of forage crops over conventional pasture are varied and relate to the level of utilisable yield of the forage crop. These advantages include: renovation of pasture that is beyond improvement through grazing management (Hook, 1981), use as a break crop to assist weed and pest control, and to confine or reduce the level of overall farm winter pugging. This paper reviews the off-farm forage cropping opportunities available to dairy farmers. It assumes that the main livestock objectives are to grow young dairy stock at optimum rates, maintain or improve the condition of dry cows, or provide feed for longer term conservation. Forage crops can be broadly classified into the bras sic as and greenfeeds. As bras sica crops are covered in detail in another session of this conference, this paper only covers recent bras sica research conducted at Lincoln University, particularly with regard to leaf turnips. More detailed coverage is given to the cereal and ryegrass greenfeeds, while the final section gives some suggested cropping sequences to incorporate the forage crops into an overall farming system.


T-struts subject to centroid compression buckle flexural-torsionally about their axis of symmetry. When the force is applied at the shear center of the section, T-struts buckle either flexurally or torsionally without coupling of flexure with twisting. Although the buckling load of shear center loading is greater than that of centroid loading, i.e. T-struts in elastic stage provide larger resistance to buckling about their axis of symmetry when the compression is applied at the shear center in lieu of the centroid of the section, T-struts with defect such as fabrication error, load eccentricity and residual stress always buckles in the elastic-plastic range actually, and the design capacity decrease by shifting the working line of a T-section compression chord to the shear center. That peculiarity is verified by the nonlinear buckling analysis of T-struts models in ANSYS.


The present work focuses on the experimental characterization of the vortex shedding and on the induced vibrations of a cantilevered blunt rectangular aluminum plate of chord to thickness ratio 16, immersed in a uniform water flow in the hydrodynamic tunnel of the French Naval Academy Research Institute. Experiences have been conducted for Reynolds numbers Re (based on chord length) ranging from 2.5 × 105 to 10.5 × 105 at zero degrees incidence. Special attention has been paid to the interaction of the structural response and the flow dynamics at the twisting resonance. For this purpose, wake structures have been analyzed by Time Resolved Particle Image Velocimetry (TR-PIV) and the structural response of the plate has been examined by laser vibrometry. The von Karman vortex street has been characterized by statistical analysis and Proper Orthogonal Decomposition of PIV velocity fields and the structure is analyzed through modal analysis. The near-wake's structure has been examined for three different Reynolds numbers: (i) at Re = 3.0 × 105, corresponding to vortex induced structural response at constant Strouhal number; (ii) at Re = 4.5 × 105, corresponding to mechanical resonance but dissociated vortex shedding and (iii) at Re = 5.4 × 105, corresponding to lock-in of the vortex shedding at the mechanical resonance. At Re = 4.5 × 105, at mechanical resonance, it reveals the occurrence of an energy transfer between the shear layer and the bubble wake vortex which cancels synchronization of the structural vibration with the von-Karman vortex street.


The article introduces the problematics of the classical two-valued logic on which Western thought is generally based, outlining that under the conditions of its logical assumptions the subject I is situated in a world that it cannot address. In this context, the article outlines a short history of cybernetics and the shift from first-to second-order cybernetics. The basic principles of Gordon Pask's 1976 Conversation Theory are introduced. It is argued that this second-order theory grants agency to others through a re-conception of living beings as You logically transcending the I. The key principles of Conversation Theory are set in relation to the poetic forms of discourse that played a key role in art as well as philosophical thinking in China in the past. Second-order thinking, the article argues, is essentially poetic. It foregoes prediction in favour of the potentiality of encountering tomorrow's delights.


Aim: Ipsilateral ureteroureterostomy is an established method for the treatment of duplication anomalies in children. With the advent of pediatric laparoscopy, many urologic procedures in children are being performed using minimal access techniques. We present our experience with laparoscopic ipsilateral ureteroureterostomy (LIUU) for duplex anomalies. Patients and Methods: The data of children who underwent LIUU was reviewed for demographic parameters, clinical and operative details, follow-up and results. Results: Over 3 years period, LIUU was performed in eight children (age 6-60 months). Five children had complete ipsilateral duplication with ectopic upper moiety ureter, one child each had ipsilateral incomplete duplication and bilateral duplex systems (with ipsilateral ectopic upper moiety ureter). One child had ipsilateral complete duplex with Grade V vesicoureteric reflux into the lower moiety ureter. Four children had antenatal diagnosis of hydronephrosis; three children had a urinary infection and two children presented with urinary incontinence. The surgical procedure consisted of cystoscopy, retrograde studies and cannulation of the recipient ureter. Then, LIUU was performed using three ports. The ectopic (donor) ureter was divided at the pelvic brim; the recipient ureter was opened and end-to-side LIUU was performed with 5/0 vicryl stitches over a double J (DJ) stent placed in the recipient ureter. Bladder catheter was removed after 2 days, and DJ stent was removed after 4 weeks. At a mean follow-up of 19 months (3-36), all children are asymptomatic and continent, with a significant reduction in hydroureteronephrosis on ultrasound. The cosmetic results were excellent. Conclusion: LIUU is a safe and effective technique in the management of duplication anomalies in children. It could be performed with minimal blood loss, minimal postoperative pain, excellent cosmesis and good success.


The goal of the present paper is to introduce a multidimensional generalization of asymptotic reduction given in a paper by Alber and Marsden [1992], to use this to obtain a new class of solutions that we call resonant solitons, and to study the corresponding geometric phases. The term "resonant solitons" is used because those solutions correspond to a spectrum with multiple points, and they also represent a dividing solution between two different types of solitons. In this sense, these new solutions are degenerate and, as such, will be considered as singular points in the moduli space of solitons.


This work investigates systematically the effect of FA/O II chelating agent and FA/O I surfactant in alkaline cleaning solutions on benzotriazole (BTA) removal during post-Cu CMP cleaning in GLSI under the condition of static etching. The best detergent formulation for BTA removal can be determined by optimization of the experiments of single factor and compound cleaning solution, which has been further confirmed experimentally by contact angle (CA) measurements. The resulting solution with the best formulation has been measured for the actual production line, and the results demonstrate that the obtained cleaning solution can effectively and efficiently remove BTA, CuO and abrasive SiO2 without basically causing interfacial corrosion. This work demonstrates the possibility of developing a simple, low-cost and environmentally-friendly cleaning solution to effectively solve the issues of BTA removal on post-Cu CMP cleaning in a multi-layered copper wafer.


The analysis of the pragmatic marker like in the VOICE corpus has shown that it is used by a large number of ELF speakers in various contexts. Since these instances of pragmatic marker like are actually hearer-oriented, signalling how the content to which they refer should be interpreted by the addressee, it can be said that they definitely exhibit a certain degree of intersubjectivity. As far as grammaticalization is concerned, Lehmann (2002, 11) emphasized that it is a gradual change of state and possibly an open-ended process. The different pragmatic functions of like found in the corpus, show that like in ELF is undergoing the same process as like in the native English discourse, and a certain degree of grammaticalization of like in ELF is evident. More specifically, the illustrative function of the pragmatic marker like seems to be the closest to the primary meaning of like as a preposition signalling comparison, since it enables the speaker to bring up examples that conform to a standard that is mentioned in the discourse itself. Thus, when the speaker in example 11 mentions "scientific dossier" and "description of the project" as types of "documents", he is actually saying that they conform to the standard of documents. The remaining functions found in the random sample show a clear removal from the primary meaning and are more grammaticalized, as they exhibit a switch from an "objective" comparison (where the two types of content being compared are actually present) to a more "subjective" comparison (where the speaker signals that the expression used with like is comparable to or approximates a certain standard, but without mentioning this standard). These standards may include numbers or imprecise expressions (hedges), or one's thoughts (quotatives). The hedging and quotative functions are more grammatical (i.e. grammaticalized) because they are parallel to expressing grammatical function such as modal certainty. Finally, the category of fillers shows complete grammaticalization, where only the intersubjective content of keepings one's turn remains, and the meaning is almost entirely bleached.
 It can be concluded that like is used in ELF as a pragmatic marker, and that it indeed also performs a variety of pragmatic functions. In the data analysis I distinguished between five different categories of like: hedges, illustratives, quotatives, fillers and independent. Although they each serve a particular purpose in discourse, these functions can actually be subsumed under one definition, similar to what Andersen (1998) proposed in his study of the pragmatic marker like in native English discourse. All categories share the property of signalling loose and informal talk, decreasing the speaker's responsibility for the spoken content and offering cues to the hearer not to take the spoken content too literally. Those are actually the most salient characteristics of the category of hedges, which was also the most frequent one in my data. It can therefore be concluded that hedging is the most prototypical function of like in ELF, and all the other categories could possibly be understood as subcategories of hedges. Furthermore, I looked into the domains and speech event types where the different categories of like appear most frequently. Although the illustrative and filler categories showed mixed results, it was found that like mostly tends to be used in informal contexts, such as leisure domain and conversations, which was as expected. As for the speakers age, a case of age gradation is noticeable. However, the sample consists of mostly younger speakers, so it is difficult to make any definitive conclusions. Gender distribution analysis also did not reveal any significant patterns. In the data extracted from the corpus, women used like in 64.79%, and men used it in 35.21% of the cases. The number of female speakers was consistently higher than male in each of the categories, so it can be said that there were no major differences in the use between female and male speakers. Similar functions of the pragmatic marker like were found in the native English discourse and the data extracted from the VOICE corpus, which consists of non-native speakers of English with varying degree of language competence and a small number of native speakers (9.36%). So it could also be concluded that the pragmatic use of the marker like is, similar to Mauranen's reflexives, not restricted to native speaker's English discourse, and therefore a "fundamental feature of discourse" (Mauranen 2010, 24).
 Regardless of whether these features of like are fundamental or not, they do fulfill important pragmatic functions in discourse. The hedging function is of particular relevance in ELF communication, considering that the speakers may have difficulties building common ground. With its element of looseness and informality and decreasing the speaker's responsibility for the expressed facts while signalling to the hearer how to interpret the spoken content, the pragmatic marker like in its broad hedging function seems to be an important tool in ELF communication.


Kinship informs the allocation of pro-social and sexual behaviour. In addition to the ability to detect kin who are directly related to the observer, humans are also able to detect relatedness among others who are not related to themselves based on facial cues of relatedness. However, it is unclear what exact facial cues inform these kinship judgments. Facial expression might be one candidate, as it has been shown that a computer kin-detection algorithm can match relatives accurately when the stimuli are smiling. The current study investigated whether a smiling facial expression increases the accuracy of judging relatedness compared to a neutral facial expression in human raters. The stimuli were images of 50 sibling pairs and 50 unrelated pairs (aged 3-17 years) matched for age, ethnicity and sex. The stimuli included both neutral and smiling versions of each individual. Raters (N=77) were asked to judge whether the presented pairs were related or not in one of two counterbalanced versions of the study, where the same stimuli were never presented as both smiling and neutral to the same rater, and the expression within the pair was always the same. Binary relatedness judgments were analysed using binomial logistic mixed regression. Contrary to expectations, smiling decreased the accuracy of relatedness judgments compared to a neutral facial expression. When shown with a smiling expression compared to a neutral one, related pairs were judged to be related less often, while unrelated pairs were judged to be related more often. Evidence that the upper face is mostly used for kinship judgments suggests that smiles could distort or distract from other, more reliable cues of kinship. Pre-registration, data and code available at https://osf.io/58ewu/.


Three types of coumarin derivatives were synthetised using the Knoevenagel condensation technique. All of these compounds have been characterised by the Fourier Transform Infrared (FTIR) and the Nuclear Magnetic Resonance (NMR) spectroscopy (H NMR, C NMR) to evaluate their chemical properties. The first step of synthesis involved preparing 3-acetylcoumarin 1 followed by the synthetisation of hydrazine thiosemicarbazide coumarin derivative 2 by treating thiosemicarbazide in the presence of a catalytic amount of glacial acetic acid. The hydrazinyl thiazolyl of coumarin derivative 3 was prepared using the cyclisation of compound 2 with 3bromoacetylcoumarin. The presence of the hydrazine and thiazole groups of the latter synthetised derivatives were confirmed using an NMR analysis that depicted the bond attachment of the imine and thiazole groups in the molecular structure of the first derivative 1. An in-vitro cytotoxicity study of the synthetised coumarin derivatives were screened using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on Human Periodontal Ligament Fibroblast (HPDLF) cells. The cytotoxicity study demonstrates that the coumarin derivatives which contain the hydrazinyl thiazolyl group exhibit less toxicity values at a concentration of 5.51 mM for a half maximal inhibitory concentration (IC50). The heterocyclic groups of the derivatives backbone will eventually contribute to promising biological properties of a biomaterial.


High-resolution, continuous records of GRAPE wet bulk density (a carbonate proxy) from Ocean Drilling Program Leg 138 provide one the opportunity for a detailed study of eastern equatorial Pacific Ocean carbonate sedimentation during the last 6 m.y. The transect of sites drilled spans both latitude and longitude in the eastern equatorial Pacific from 90° to 110°W and from 5°S to 10°N. Two modes of variability are resolved through the use of Empirical Orthogonal Function (EOF) analysis. In the presence of large tectonic and climatic boundary condition changes over the last 6 m.y., the dominant mode of spatial variability in carbonate sedimentation is remarkably constant. The first mode accounts for over 50% of the variance in the data, and is consistent with forcing by equatorial divergence. This mode characterizes both carbonate concentration and carbonate mass accumulation rate time series. Variability in the first mode is highly coherent with insolation, indicating a strong linear relationship between equatorial Pacific carbonate sedimentation and Milankovitch variability. Frequency domain analysis indicates that the coupling to equatorial divergence in carbonate sedimentation is strongest in the precession band (19-23 k.y.) and weakest though present at lower frequencies. The second mode of variability has a consistent spatial pattern of east-west asymmetry over the past 4 m.y. only; prior to 4 Ma, a different mode of spatial variability may have been present, possibly suggesting influence by closure of the Isthmus of Panama or other tectonic changes. The second mode of variability may indicate influence by CaCO3 dissolution. The second mode of variability is not highly coherent with insolation. Comparison of the modes of carbonate variability to a 4 m.y. record of benthic δ 1 8 θ indicates that although overall correlation between carbonate and δ 1 8 θ is low, both modes of variability in carbonate sedimentation are coherent with δ 1 8 θ changes at some frequencies. The first mode of carbonate variability is coherent with Sites 846/849 δ 1 8 θ at the dominant insolation periods, and the second mode is coherent at 100 k.y. during the last 2 m.y. The coherence between carbonate sedimentation and δ 1 8 θ in both EOF modes suggests that multiple uncorrelated modes of variability operated within the climate system during the late Neogene. INTRODUCTION AND SCIENTIFIC BACKGROUND Because the oceanic carbon reservoir is 60 times the size of the atmosphere and is in direct exchange with the atmosphere, orbital scale atmospheric CO2 changes must ultimately be explained by changes in the oceanic carbon cycle (Broecker and Peng, 1982). Evidence from ice cores indicates that the CO2 increase at the ends of glacial periods occurred rapidly, on the order of a thousand years. To understand this process, it is necessary to understand the mechanisms controlling the carbon cycle on glacial/interglacial time scales. While ice cores provide a direct measure of changes in atmospheric CO2, examination of the marine sediment record is necessary to obtain a history beyond that of the last glacial cycle. Efforts to understand the mechanisms through which the oceanic carbon cycle changes atmospheric CO2 have led to years of carbon cycle modeling. Hypotheses for glacial/interglacial pCO2 changes were grouped into four categories by Heinze et al. (1991) in a recent overview: three kinds of oceanic carbon pumps that are capable of influencing atmospheric CO2 (a solubility pump, a nutrient pump, and a CaCO3 pump), and changes in the oceanic velocity field and ventilation rates. Evidence for oceanic carbon pool changes that is needed to evaluate hypotheses is derived primarily from sedimentary δC and CaCO3 records. δC indicates the efficiency of the ocean's biological pump and the nutrient content of deep and surface waters. The CaCO3 concentration in sediments reflects productivity, dilution, and alkalinity changes. Pisias, N.G., Mayer, L.A., Janecek, T.R., Palmer-Julson, A., and van Andel, T.H. (Eds.), 1995. Proc. ODP Sci. Results, 138: College Station TX (Ocean Drilling Program). College of Oceanic and Atmospheric Sciences, Oregon State University, Corvallis, OR U.S.A. 3 Now at Graduate School of Oceanography, University of Rhode Island, Narragansett, Rl U.S.A. 4 Institute for Ocean Mapping, University of New Brunswick, Fredericton, N.B., Canada. Subdepartment of Quaternary Research, Godwin Laboratory, Cambridge University, Cambridge, United Kingdom. The extent to which CaCO3 sedimentation in equatorial Pacific Ocean sediments has been controlled by production or dissolution has been the subject of debate for more than 40 yr. Since Arrhenius (1952), studies have investigated the relationship of equatorial Pacific carbonate sedimentation to regional surface processes, global glacial/ interglacial changes, and external orbital (Milankovitch) influence (e.g., Hays et al., 1969, Moore et al., 1977, 1982; Farrell and Prell, 1989; Rea et al., 1991). In the equatorial Pacific Ocean, large changes in sedimentary calcium carbonate concentration have occurred on long time scales (millions of years), as a response to oceanic boundary condition and geochemical mass budget changes, and on shorter time scales (tens of thousands of years), as a response to climatic influence. Changing boundary conditions during the late Cenozoic have significantly influenced equatorial Pacific sediment composition, van Andel et al. (1975) estimated the initiation of the Equatorial Undercurrent (EUC) at about 11 to 12 Ma, when the northward movement of the Australia Plate cut off western Pacific-Indian Ocean circulation. This development may have caused the onset of a narrow, equatorially symmetric zone of carbonate and opal sedimentation having steep gradients away from the equator. Widespread orogeny during the late Miocene and Pliocene may have had a large influence on oceanic alkalinity budgets through increased chemical weathering (Raymo et al., 1988). This uplift may have also influenced surface ocean circulation in the equatorial Pacific through associated changes in atmospheric circulation (Ravelo et al., 1992). A modeling study has suggested that prior to closure of the Isthmus of Panama (3^4Ma or earlier), North Atlantic Deep Water (NADW) production was reduced, carbonate preservation was increased because of less undersaturated Pacific deep waters, and eastern equatorial Pacific surface upwelling was unchanged (Maier-Raimer et al., 1990). Initiation of large-scale continental glaciation in the Northern Hemisphere near 2.4 Ma may have altered oceanic alkalinity and productivity significantly. van Andel et al. (1975) demonstrated that similar spatial patterns are present in bulk-sediment accumulation rates, carbonate accumulation rates, and carbonate concentration of central equatorial Pacific


We present a novel metric to analyze the similarity between the physical environment and the virtual environment for natural walking in virtual reality. Our approach is general and can be applied to any pair of physical and virtual environments. We use geometric techniques based on conforming constrained Delaunay triangulations and visibility polygons to compute the Environment Navigation Incompatibility (ENI) metric that can be used to measure the complexity of performing simultaneous navigation. We demonstrate applications of ENI for highlighting regions of incompatibility for a pair of environments, guiding the design of the virtual environments to make them more compatible with a fixed physical environment, and evaluating the performance of different redirected walking controllers. We validate the ENI metric using simulations and two user studies. Results of our simulations and user studies show that in the environment pair that our metric identified as more navigable, users were able to walk for longer before colliding with objects in the physical environment. Overall, ENI is the first general metric that can automatically identify regions of high and low compatibility in physical and virtual environments. Our project website is available at https://gamma.umd.edu/eni/.


The lysosomal aspartyl protease, cathepsin D, has been suggested to play a role in the metastatic potential of several types of cancer. Cathepsin D is secreted by malignant cells, and is believed to be involved in the breakdown of the extracellular matrix. High levels of active cathepsin D have been found in colon cancer, prostate cancer, uterine cancer and ovarian cancer. Also cathepsin D has recently been associated with the development of Alzheimer's disease. Hydroxyethyl isosteres with cyclic tertiary amine have proven to be clinically useful as inhibitors of aspartyl proteases similar to cathepsin D in activity, such as the HIV-1 aspartyl protease. In the present study twenty-eight compounds containing (hydroxyethyl)amine isosteres with cyclic tertiary amines have been synthesized. These compounds show significant activity as cathepsin D inhibitors, many with IC(50) values in the nanomolar range. For example, the compounds that contain hydroxyethylamines where the amine is formed from N-piperazine-2-carboxylic acid methyl ester, 4y-bb, show IC(50) values ranging from 2.5 to 15 nM.


Today, In this research, we intend to study the modeling and solving a hybrid problem considering the simultaneous loading and delivery of the vehicle and the locating of facilities for storing and recycling in a three-level green supply chain. This issue is known as 3-level mapping routing issue in the subject literature. With the goal of presenting a mathematical model for the vehicle routing problem and locating the storage facilities and recycling facilities in a green supply chain network, an efficient algorithm is developed to optimize the problem and compare the performance of the algorithm with known algorithms such as genetics. Also one of the other purposes is to find a combination of truck and facility paths so that results in minimum transfer costs in a direct and reverse manner. By reviewing the recent articles and discovering the existing research gap, we will develop a problem model with a specific application, and eventually we will overwrite the problem in the framework of the language of the meta-innovative algorithms to solve the problem by the meta-innovative method. To compare the efficiency of the meta-innovative algorithm developed in this research and its validation, we will compare the results with a precise method using GAMS software for small issues. Also, one of the genetic algorithms can be used to test the performance of the algorithm. This research is considered within the framework of applied research regarding the orientation, because using the results of this study, some suggestions can be made to solve specific problems in the organization. In addition, this research is a descriptive method in which mathematical and modeling tools are used. Keywords: Logistic Network, Green Supply Chain, Locating and Routing Problem, Combined or Hybrid Meta-Innovative Algorithm


With the increasing importance that our society is placing on education, the problem of underachievement in schools has come to take on considerable social significance. Numerous attempts have been made to rectify the kind of irrational factors which help prevent a young person from meeting one of society's first demands - that of satisfactory school performance. This paper discusses some of the existing literature on the subject, especially a rather effective technique suggested by Ellis.


All across the globe, individuals mobilize international support in defense of Palestinian rights and a resolution to the Israeli-Palestinian conflict. However, these international activists are neither the beneficiaries of their efforts nor do they closely identify with the Palestinian population. Through an ethnographic analysis of social movement organizations and international activists active in the West Bank, this paper tries to understand the emergence of transnational collective action fighting for Palestinian rights since the second Intifada. To do so, this paper addresses structural as well as personal factors behind activists' mobilization. Combining elements from social movement theory and Bourdieusian sociology, I conduct a meso-level inquiry of the principal solidarity organizations alongside a micro-level investigation of international volunteers participating in such organizational structures. Highlighting the specificity of transnational activism in the West Bank both in terms of opportunity structures and the lived experiences of international activists, I have tried to provide insight on how and why the Palestinian rights movement is able to gather so much international support.


Distributed Material Requirements Planning is widely used in manufacture enterprise. The decentralized decisions of purchasing and warehousing can be coordinated by Distributed Decision Support Systems. Distributed Decision Support Systems can improve flexibility to make right decision instantly.