Purpose: The studies on links between sustainability, innovation, and competitiveness have been mainly focused at organizational and business level. The purpose of this research is to investigate if there is a correlation between these three variables at country level. Using international well recognized rankings of countries sustainability, innovation, and competitiveness, correlation analysis was performed allowing for the conclusion that there are indeed high correlations (and possible relationships) between the three variables at country level. Design/methodology/approach: Sustainability, innovation, and competitiveness literature were reviewed identifying a lack of studies examining these three variables at country level. Three major well recognized indexes were used to support the quantitative research: The World Economic Forum (2013) Sustainability-adjusted global competitiveness index, the Global Innovation Index (2014) issued by Cornell University, INSEAD, and WIPO and the IMD World Competitiveness Yearbook (2014). After confirming the distributions normality, Pearson correlation analysis was made with results showing high linear correlations between the three indexes. Findings: The results of the correlation analysis using Pearson correlation coefficient (all correlation coefficients are greater than 0.73) give a strong support to the conclusion that there is indeed a high correlation (and a possible relationship) between social sustainability, innovation and competitiveness at country level. Research limitations/implications: Further research is advisable to better understand the factors that contribute to the presented results and to establish a global paradigm linking these three main constructs (social sustainability, innovation, and competitiveness). Some authors consider that these measurements are not fully supported (e.g. due to different countries standards), however, it is assumed these differing underlying methodological approaches, by being used in conjunction, can be considered as a set of reliable and useful performance indicators. Practical implications: The results highlight the simultaneous relationship between social sustainability, innovation and competitiveness superior performance and the need to take that these considerations into business and operating models. Social implications: This research suggests that sustainability and innovation policies, strategies and practices are relevant for countries competitiveness and should be promoted particularly in countries ranked low on sustainability and innovation global scoring indexes. Originality/value: This is one of the few studies addressing the relationships between sustainability, innovation and competitiveness at country level.


Accurate and long term information on the physical properties of clouds is required to increase our understanding on the role of clouds in the current climate system, and to better predict the behavior of clouds in a changing climate. This thesis investigates if retrievals of cloud physical properties from satellite imagers can be used to prepare time series of these properties for monitoring climate change, and to evaluate parameterizations of cloud processes in weather and climate prediction models. An algorithm for retrieval of Cloud Physical Properties (CPP) from visible and near-infrared reflectances of the AVHRR instrument onboard NOAA and the SEVIRI instrument onboard METEOSAT is presented. This algorithm retrieves cloud optical thickness, effective radius, and liquid water path, whereas a cloud model is used to simulate cloud geometrical thickness and droplet number concentration. Due to the large differences found between the reflectances from the different instruments (up to 25%), a recalibration procedure is developed that successfully reduces the retrieval differences to less than 5%. The uniqueness of the SEVIRI cloud property retrievals is in its unprecedented sampling frequency (15 minutes) that ensures the statistical significance of the dataset. One year of cloud liquid water path retrievals is validated against simultaneous Cloudnet microwave radiometer observations over Europe. The results show that during summer the agreement is very good while during winter an overestimation of about 20% is observed. Possible reason for this overestimation is the plane-parallel assumption in the CPP algorithm used to simulate real clouds. For single-layer stratocumulus days, a sub-adiabatic cloud model is used to obtain cloud geometrical thickness and cloud droplet number concentration. During these days good agreement is found between geometrical thickness simulations and Cloudnet lidar and radar observations, and cloud liquid water path retrievals and Cloudnet microwave radiometer observations. The simulated droplet concentration is found to vary independently from liquid water path and the geometrical thickness, which suggests possible interactions between aerosols and clouds. This shows potential in our dataset for studies of the indirect aerosol effect. The SEVIRI dataset of cloud property retrievals is used to evaluate the Regional Climate Model (RACMO) over Europe during a six-month period. The results show that RACMO represents the spatial variations of cloud amount and cloud liquid water path realistically, but underpredicts cloud amount by 20% and overpredicts liquid water path by 30%. Examination of the diurnal cycle shows that the RACMO maximum liquid water path occurs two hours earlier than that observed by SEVIRI, while the RACMO maximum cloud amount agrees reasonably well with SEVIRI's amount. The largest differences in the diurnal cycle between RACMO and SEVIRI are found in regions of alternating stratiform and convective regimes where RACMO has difficulty representing the transition between these regimes. The SEVIRI dataset of cloud physical properties proves to be a powerful tool for evaluating parameterizations of cloud and precipitation processes in weather and climate prediction models, and thus helps increase the confidence in these models.


Cote d'Ivoire ranks third among African countries with the highest neonatal
mortality rate (38‰). Perinatal asphyxia is one of the major causes of neonatal
mortality. In its severe form, it imposes an efficient neonatal resuscitation
in the birth room. This can only be done when the proven competence of the
staff in charge of the newborn and the availability of the appropriate equipment
are met. What is the situation in the birth facilities of these two challenges
for the response to the high rate of neonatal mortality in Cote d'Ivoire?
Method: It is a cross-sectional study, which took place from March 28 to July
28, 2016, in three health districts of Cote d'Ivoire (Bouake, Gagnoa, Yopougon).
Public health structures offering delivery activities were selected. Based
on a fact sheet, the practitioners present have been interviewed and a direct
observation of the organization and equipment set up to perform neonatal
resuscitation in the birth room has been done. In addition, an observation
grid made it possible to evaluate the practical skills of providers in neonatal
resuscitation on a newborn mannequin. The data were entered using the
Epi-Info 7 software. Based on the data collected, we determined the numbers
and frequencies of the responses of the target agents of the survey. Results:
The membership structures included 46 first contact health facilities (FCHFs)
and 4 reference hospitals (HRs). The heating system, mucus suction, oxygen,
timers and self-inflating balloons were available in HR and in six, eight, four,
34 and 10 FCHFs respectively. The 253 midwives surveyed came from Bouake
(86), Gagnoa (62) and Yopougon (105). They had a seniority of at least eight
years. Their knowledge for newborns' care was acquired in initial training
(75% of cases). They knew the golden minute in 95.6% of the cases. Inadequacies
in the recognition of risk situations, useful equipment and in the execution of neonatal resuscitation steps were noted. Conclusion: The survival of
the newborn is still very worrying in Cote d'Ivoire. An analysis of the results
of this survey shows that many challenges remain not only at the structural
level but also at the level of quality of care.


The following short communication is not meant to definitively answer a specific question, but rather to initiate a conversation into simply understanding what chemicals we expose our children to on a daily basis and what impact it can have on their biological development. Sunscreen safety has recently been under question with numerous papers being published linking them to everything from general toxicity to endocrine disruption in a variety of species including humans. Additionally, a 2018 report from the American Cancer Society demonstrated that after 40 years of sunscreen use (1975-2014) melanoma has increased 4 fold in men and 3 fold in women. Many have speculated that the doses used in toxicology experiments are significant exaggerations of "normal use conditions", however, this paper clearly demonstrates that the long-term exposure to sunscreens in children is not an exaggeration but equivalent to what has been reported in the literature.


According to the Just War tradition a war can only be just if two sets of principles are satisfied. (1) First there is the jus ad bellum. These principles tell us when it is just to start a war. There has to be a good reason or a just cause in order for a war to be morally permissible (self-defense, defense of others, putting a stop to human rights violations). The decision to go to war has to be taken by a legitimate authority. Those who wage war need to be motivated by good intentions (desire to promote a more stable peace). War should not only be a last resort (necessity), it must also offer a reasonable chance of success. Moreover, the good the warring party hopes to obtain should outweigh the evil caused by the war (proportionality). The second set of principles, the jus in bello or the right in the war, focuses on the moral constraints that need to be observed during hostilities. Noncombatants must never be the intentional target of military actions (discrimination), and the military utility of a particular act of war has to outweigh the damage it will cause. It is clear that combatants, whatever side they are on, have a moral and legal obligation to respect the in hello principles. This is what ethicists call their in bello responsibility. Can combatants be held responsible for participating in an unjust war? Do they, aside from their in hello responsibility, have an ad bellum responsibility? If so, this would mean that combatants have a duty to judge the justice of the war and refuse to participate in an immoral conflict. Those combatants who would not take such an ad bellum responsibility seriously, and simply follow orders, would risk being considered unjust combatants. Anyone who studies the moral and legal reality of warfare will quickly notice that this presumption of military ad bellum responsibility is firmly rejected. (2) At the core of the Just War tradition is the fundamental doctrine of the moral equality of combatants. Basically this doctrine says that the realm of responsibility of combatants on all sides is equally limited to that of the jus in bello. Combatants cannot be held responsible for the just or unjust nature of the war in which they participate. The ad bellum responsibility belongs solely to the political decisionmakers. Despite its basic role in the normative appreciation of war, the doctrine of moral equality of combatants is not beyond dispute. Even Michael Walzer, who is a strong defender of a strict separation between jus ad bellum and jus in bello, admits that this moral dualism can be somewhat puzzling. (3) It is, after all, far from obvious that the moral status of a combatant in a defensive war is the same as that of a combatant participating in a war of aggression. The former is clearly engaged in a morally legitimate activity (self-defense), whereas the latter is contributing to what most would term a criminal act. So, how can these two be moral equals? Should we not add an ad bellum responsibility for combatants? If, as some philosophers and lawyers argue, we decide to hold soldiers responsible in this regard, wouldn't that stop them from participating in wars of aggression? (4) The objective of this article is to shed light on this problem by answering two questions: (a) What arguments are there to support the traditional position that limits the responsibility of the military to the jus in bello? and (b) Can combatants ever be blamed for unjust wars, and if so, under what circumstances? Military Subordination Perhaps the most straightforward reason why the responsibility of the military is limited to the jus in bello has to do with the strict military subordination to political authority. Politicians decide to go to war, whereas the military is expected to execute this decision to the best of its ability. This subordinate role does not, however, reduce the military to a mere political instrument that obeys orders without question. …


The purpose of maintenance is to reduce the business risk. Therefore, it is very important that formal reliability and risk assessment form an integral part of the maintenance planning and control process. Taking decision concerning selection of maintenance strategy using risk-based criteria is essential to develop cost effective maintenance policies for mechanized and automated systems because in this approach technical features (such as reliability and maintainability characteristics) are analysed considering economic and safety consequences of each alternative at hand. This approach provides a holistic view of the various decision scenario concerning maintenance strategy where cost consequences of every possible solution can be assessed quantitatively. This paper emphasises the need of integration of risk analysis methods in all phases of conception, design, manufacturing and operation to arrive at the most optimal maintenance policies/strategies for the system under consideration. The paper also discusses various steps involved in risk analysis and concludes that the risk assessment can be used in many activities related to maintenance for arriving at the best decision among the several alternatives available at hand.


During the past years high pressure gas quenching was a very actual subject at different conferences. There were a lot of lectures which used heat transfer coefficient as the most important parameter for the characterization of a gas quenching system. This statement is surely correct, but only fully utilizable—for example, for the comparison of measurements from different authors—when a well defined measurement method was used. Up to 2002 this was not realized. To solve this problem on a national basis the German Research Committee for Quenching has delt with this subject in the period from 1998 to 2002. In a first step the possibly influencing parameters were identified. In a second step most of the parameters were predefined. In a few cases there was no information about the magnitude of the possible influence available (example: evaluation procedure). To answer these remaining questions a round-robin test was carried out. The participants were the companies Ipsen International and Dr. Sommer Werkstofftechnik, Germany, and the institutes IVF Sweden and IWT Bremen, Germany. The results of this work were published in 2002 in the German heat treatment journal HTM including a recommendation for the measurement of heat transfer coefficient at gas quenching (in German language). This paper is a translation of this work and shall help to solve the above-mentioned problem on an international level.


When a pump beam is propagating through a silicon nanophotonic waveguide, a very small fraction of the light is scattered to other frequencies. At very low intensity, the amount of scattered light is proportional to the power of the pump beam. We show that the scattering intensity increases linearly within the temperature range 300–575 K and that the photon flux decreases as the inverse of the frequency detuning ν over the investigated bandwidth 0.4  THz<|ν|<2.5  THz. The simplest interpretation of these observations is that the pump beam is scattered on a one-dimensional thermal bath of excitations. Finally, the implications of this scattering process for quantum optics applications of silicon nanophotonic structures are discussed.


We present a multi-site field study to evaluate LemonAid, a crowdsourced contextual help approach that allows users to retrieve relevant questions and answers by making selections within the interface. We deployed LemonAid on 4 different web sites used by thousands of users and collected data over several weeks, gathering over 1,200 usage logs, 168 exit surveys, and 36 one-on-one interviews. Our results indicate that over 70% of users found LemonAid to be helpful, intuitive, and desirable for reuse. Software teams found LemonAid easy to integrate with their sites and found the analytics data aggregated by LemonAid a novel way of learning about users' popular questions. Our work provides the first holistic picture of the adoption and use of a crowdsourced contextual help system and offers several insights into the social and organizational dimensions of implementing such help systems for real-world applications.


Symmetric submodular functions are an important family of submodular functions capturing many interesting cases, including cut functions of graphs and hypergraphs. Maximization of such functions subject to various constraints receives little attention by current research, unlike similar minimization problems that have been widely studied. In this work, we identify a few submodular maximization problems for which one can get a better approximation for symmetric objectives than the state-of-the-art approximation for general submodular functions. We first consider the problem of maximizing a non-negative symmetric submodular function f:2N → R+ subject to a down-monotone solvable polytope P ⊆ [0, 1]N. For this problem, we describe an algorithm producing a fractional solution of value at least 0.432 ċ f(OPT), where OPT is the optimal integral solution. Our second result considers the problem max{f(S): |S| = k} for a non-negative symmetric submodular function f:2N → R+. For this problem, we give an approximation ratio that depends on the value k/|N| and is always at least 0.432. Our method can also be applied to non-negative non-symmetric submodular functions, in which case it produces 1/e − o(1) approximation, improving over the best-known result for this problem. For unconstrained maximization of a non-negative symmetric submodular function, we describe a deterministic linear-time 1/2-approximation algorithm. Finally, we give a [1 − (1 − 1/k)k − 1]-approximation algorithm for Submodular Welfare with k players having identical non-negative submodular utility functions and show that this is the best possible approximation ratio for the problem.


Education is the key to national development and no development can take place without first developing the citizenry of the country, out-of-school/street children inclusive. The phenomenon of out-of-school/street children in Nigeria has not abated despite the concerned efforts of international agencies and governments to combat the menace. This paper focuses on the precipitating factors to life on the streets with a view to analyzing how non-formal education can be implemented to meet the educational, economic and cultural needs of out-of-school/street children in Nigeria. The study confirms parental poverty, bad state of Nigerian economy, declining interest in schooling, gender preference, migration, unsuitable family environment, child abuse and neglect as major predisposing factors to life on the streets. As the lifestyles of out-of-school/street children are antithetical to the goings on in formal education system, this paper recommends the use of non-formal education which activities can be located close to the life and work of the clientele as the best option for meeting the educational needs of out-of-school/street children. It is believed that this will not only encourage them to learn better and behave well, it will further encourage the participation of others in difficult circumstances to join the non-formal education programmes to be sponsored by government.


We study how to perform effective Bayesian inference in high-dimensional sparse Factor Analysis models with a zero-norm, sparsity-inducing prior on the model parameters. Such priors represent a methodological ideal, but Bayesian inference in such models is usually regarded as impractical. We test this view. After empirically characterising the properties of existing algorithmic approaches, we use techniques from statistical mechanics to derive a theory of optimal learning in the restricted setting of sparse PCA with a single factor. Finally, we describe a novel `Dense Message Passing' algorithm (DMP) which achieves near-optimal performance on synthetic data generated from this model.DMP exploits properties of high-dimensional problems to operate successfully on a densely connected graphical model. Similar algorithms have been developed in the statistical physics community and previously applied to inference problems in coding and sparse classification. We demonstrate that DMP out-performs both a newly proposed variational hybrid algorithm and two other recently published algorithms (SPCA and emPCA) on synthetic data while it explains at least the same amount of variance, for a given level of sparsity, in two gene expression datasets used in previous studies of sparse PCA.A significant potential advantage of DMP is that it provides an estimate of the marginal likelihood which can be used for hyperparameter optimisation. We show that, for the single factor case, this estimate exhibits good qualitative agreement both with theoretical predictions and with the hyperparameter posterior inferred by a collapsed Gibbs sampler. Preliminary work on an extension to inference of multiple factors indicates its potential for selecting an optimal model from amongst candidates which differ both in numbers of factors and their levels of sparsity.


Current methods for training recurrent neural networks are based on backpropagation through time, which requires storing a complete history of network states, and prohibits updating the weights `online' (after every timestep). Real Time Recurrent Learning (RTRL) eliminates the need for history storage and allows for online weight updates, but does so at the expense of computational costs that are quartic in the state size. This renders RTRL training intractable for all but the smallest networks, even ones that are made highly sparse.
We introduce the Sparse n-step Approximation (SnAp) to the RTRL influence matrix, which only keeps entries that are nonzero within n steps of the recurrent core. SnAp with n=1 is no more expensive than backpropagation, and we find that it substantially outperforms other RTRL approximations with comparable costs such as Unbiased Online Recurrent Optimization. For highly sparse networks, SnAp with n=2 remains tractable and can outperform backpropagation through time in terms of learning speed when updates are done online. SnAp becomes equivalent to RTRL when n is large.


of a thesis submitted in partial fulfillment of the requirements for the Degree of Ph.D. FIELD STUDIES OF AMMONIA VOLATILISATION POTENTIALS OF UNSATURATED SOILS FERTILISED WITH GRANULAR UREA by Nadaraja Selvarajah i The potential for ammonia, NHa, loss from granular urea applied to soil can be influenced by various soil, environmental and agronomic factors. A series of field studies were conducted to investigate the soil factors influencing the volatilisation potentials of a wide range of undisturbed New Zealand soils (12 soils) under different environmental conditions. Sample blocks of sUrface soil (0-7 cm depth) were transported from various parts of New Zealand to the experimental site (Lincoln University, Canterbury) and buried at ground level in enclosures configured for active trapping of volatilised NHa• Urea granules (2-3 mm diameter), with or without 15N labelling were surface-applied to the soils at a rate equivalent to 100 kg N ha-1. Ammonia volatilisation was measured by using 50 mL of 0.05 M H2S04 as the trapping medium and an air flow rate of 16 air exchange min-1. This trapping system was found to be efficient in preliminary laboratory trials conducted prior to the field experiments. Field measurements of changes in soil surface temperature, soil moisture and microsite pH (0-1 mm soil depth) and rates of urea hydrolysis, ammoniacal-N accumulation, nitrification and immobilisation were also made following application of urea. Each soil was characterised for texture, urease activity, mineralisableand hydrolysable-N contents, organic-C and total-N contents, native soil pH, buffered CEC, H+ buffer capacity and exchangeable plus soluble ea2+ and Mi+ contents. In most cases volatilisation was essentially complete 7 days following urea application. Losses ranged from 4.4 to 53.9% of the applied-N (mean, 32%). Simple correlation tests were performed between percentage cumulative (7 days) NHa-N losses (i.e. 'volatilisation potential') and each soil property. Each relationship was viewed using scatter diagrams for possible curvilinearity and the influence of outliers. The two major environmental conditions encountered during the studies were (i) warm, rapid soil drying and (ii) cool slow-drying conditions. Statistically significant relationships \ were found between volatilisation potentials and several of the many soil prop~rties and urea-N transformation processes studied. Ho:wever, only the microsite pH measured 8 hours following urea application ('initial microsite pH') showed highly significant linear relationships (r ~ 0.94; P s 0.05) with volatilisation potential under all environmental conditions. This observation was further examined by combining all the data sets and a correlation test was performed. The volatilisation potentials of all the soils studied were highly correlated to the 'initial microsite pH' and the following relationship was obtained: NH310ss (7 days) = -123 + 19.8 Initial microsite pH (R2 = 85.4%; P < 0.01) ii It was proposed that a soil which has a high H+ buffer capacity is capable of resisting the alkalinity build-up during the initial stage of urea hydrolysis. Such a soil should have a greater rate and extent of protonation of NH3(aq) released from urea and consequently have a lower volatilisation potential than that of a soil with a lower H+ supplying capacity. The significant overall relationship obtained between NH310sses and sand content (%) (R2 = 65.5%; P < 0.01) also supported this proposal by indicating that soils with a high abundance of chemically inert components, such as sand, can sustain high NH3 losses when broadcast with urea. The measurement of 'initial microsite pH' following urea application provides a more reliable and simpler technique than the standard titration method used to assess the H+ buffer capacity and/or the volatilisation potential of soils. The immobilisation of 15N labelled urea was monitored in enclosed and non-enclosed soils throughout the volatilisation experiment carried out under cool, slow-drying conditions. Immobilisation of the applied urea-N ranged from 13 to 19% after 14 days in the non-enclosed soils and was significantly less (P ~ 0.01) in the enclosed soils (5 to 12%) . . Similarly, nitrification was more rapid in the non-enclosed soils (P ~ 0.01). Between 2.0 to 9.9% of the applied-N was present as N03-after 14 days in the non-enclosed soils. The comparable figures for N03-accumulation in the enclosed soils were 0.2 to 5.5%. Nevertheless, the total-N accounted for in each of the enclosed and non-enclosed soils on each sampling occasion were not significantly different (P ~ 0.05). Moreover, when the measured NH3 losses were added to the amounts of applied-N recovered in both the enclosed and non-enclosed soils, quantitative recovery was shown for 5 of the 6 soils studied. It was concluded that immobilisation and nitrification of applied urea-N have very little influence on the volatilisation potentials of soils fertilised with broadcast granular urea. It was also concluded that the enclosure method, provided it adequately simulates external soil temperatures, is an effective and accurate method for measuring the volatilisation potentials of soils under field conditions. However, a micrometeorological (mass balance) experiment using both active and passive NH3 samplers showed that the volatilisation· potential of soil receiving broadcast urea can be markedly reduced (from 35 to 7%) by various environmental factors including rainfall, initial soil moisture and the presence o"vegetative cover.


Using declassified British government files at the National Archives, the author shows how the US invasion of Grenada in 1983, which overthrew the radical government of Maurice Bishop and the New Jewel Movement, was not the first time that such an invasion was contemplated in Grenada's recent history. The UK had had an almost identical plan to land a battalion of troops on Grenada a decade earlier, on the very eve of independence, to ensure the continuation in power of the dictatorial Eric Gairy, should the widespread unrest across the island lead to his ousting.


Background. Postpartum haemorrhage (PPH) remains one of the most significant causes of maternal morbidity and mortality. In South Africa (SA) it is the second leading cause of maternal death. Educational programmes, such as visual aids, can improve the estimation of blood loss and subsequently improve clinical judgement and intervention. Objective. To assess any improvement in blood loss estimation after the introduction of a visual aid. Methods. We conducted an intervention study at the University of Pretoria Academic Complex and included the Departments of Obstetrics and Gynaecology and Anaesthesiology. The visual aid was created using surgical materials and expired blood from the SA National Blood Services. A pre-intervention objective structured clinical examination (OSCE) was conducted with various blood volumes. Thereafter, the visual aid was made available to all study participants. Nine months later, a second OSCE was conducted. Results. Eighty-two participants were recruited and 21 were lost to follow-up. Sixty-one participants were included in the analysis. The overall score from the initial OSCE improved from 4.7500 to 5.6393 on the second OSCE ( p =0.003). Participants tended to move from underestimation to either overestimation or accurate estimation of blood loss. The consultant group of participants were the most accurate in estimating blood loss ( p =0.450). Conclusion. The use of a visual aid can improve the estimation of blood loss by healthcare professionals, thus potentially improving resuscitation, and impacting positively on maternal morbidity and mortality associated with PPH, while improving the use of resources.


Aims: The major aims of the present study was to focus the protective effect of coumarin on cell surface glycoconjugates abnormalities during 7,12-dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch carcinogenesis. Methods: DMBA painting in the hamster buccal pouch three times per week for 14 weeks developed oral squamous cell carcinoma. The levels of glycoconjugates (protein bound hexose, hexosamine, sialic acid and fucose) were analyzed by using specific colorimetric methods. Results: An increase in glycoconjugates was noticed in the plasma and buccal mucosa of oral cancer bearing golden Syrian hamsters. Coumarin administration orally at a dose of 100mg/kg b.w to hamsters treated with DMBA brought back the status of glycoconjugates to near normal range. Conclusion: Present study thus focused the protective effect of coumarin on cell surface abnormalities occurring during DMBA-induced hamster buccal pouch carcinogenesis.


Hydraulic roughness is a key factor in modeling open channel flow. The frictional effects of roughness elements are generally parameterized by a roughness coefficient, representative for the roughness of a grid cell in a model. Bed roughness can be very heterogeneous in practical situations. Especially in floodplains, the roughness height can differ an order of magnitude over a small distance. This roughness heterogeneity impacts the shear stress distribution and the effective friction exerted on the flow. Previous research showed that the effective friction was 20% more than the theoretically weighted average value (Jarquin, 2007) in a flume with a parallel smooth-to-rough bed. Another calculation showed even 80% additional effective friction (Jarquin, 2007; Vermaas et al., 2007). New measurements and a detailed Large Eddy Simulation model described in this report were used to investigate the underlying mixing layer processes and the corresponding development length scales. This may provide the basis to parameterize roughness heterogeneity. Measurements in a developed flow over a parallel smooth-to-rough bottom show a secondary circulation in vertical planes across the flow. This circulation causes a transverse momentum transport from the smooth to the rough side. The momentum transport by this mechanism has nearly the same order of magnitude as the transverse momentum exchange by turbulent mixing. The transverse momentum exchange enhances the effective friction. An example with a 2D model shows that this can not explain the entire increase in effective friction; additional friction is probably also caused by extra turbulence production near the smooth-to-rough interface, and bed shear stress in the spanwise direction. In the transition from a uniform flow to a compound flow over parallel roughness lanes, transverse volume transport occurs mainly in the first 4 meter (twice the width of the flume), with a maximum velocity at the start of the parallel roughness section. The development length of the velocity profiles can be scaled to the depth of flow. The vertical profiles outside the mixing layer develop in about 25 times the water depth; the mixing layer at mid depth in about 50 water depths. The secondary circulation was estimated to be fully developed after 80 water depths, but has already a significant momentum transport at half of this distance. Furthermore, the depth averaged transverse mass transport causes a gradient in the advected longitudinal momentum and therefore the water level slope is even more increased above the start of a parallel rough bottom. As a typical example of repetitive changing roughness, the flow over a roughness pattern resembling an elongated checkerboard pattern was tested. The flow appeared to develop much slower in each section than over a single parallel (infinitely long) roughness. The maximum velocity remains close to the smooth-to-rough interface and no secondary flow is observed in this configuration. Turbulent mixing is neither very effective since the vortices are changing direction not before 1 meter after a roughness change. Nevertheless, the effective friction is seriously increased by this configuration; about 30% additional friction is observed in comparison with a developed parallel flow without transverse interaction. This can be explained by the large adaptation length of the flow relative to the size of the checkerboard fields. The flow velocity is relatively large over the rough fields, and slow over the smooth fields, causing the additional drag.


Disruption of the regulatory mechanisms that control cell proliferation and cell migration results in multiple disease states including cancer and leukaemia. The proline-rich homeodomain protein (PRH)/haematopoietically expressed homeobox protein (HHEX) is a tran- scription factor that controls cell proliferation and cell migration in a variety of tissues in the adult and in the embryo. Phosphorylation of PRH by Protein Kinase CK2 (Casein Kinase II) stops PRH from binding to DNA and regulating the transcription of its direct target genes. In leukaemic cells, phosphorylation also results in the production of a transdominant-negative truncated PRH phosphoprotein by the proteasome. Phosphorylation of PRH is increased in breast and prostate cancer cells and the consequent loss of PRH activity increases cell prolif- eration and migration. PRH also regulates the proliferation of vascular smooth muscle cells and CK2-dependent phosphorylation of PRH in these cells accompanies increased cell prolif- eration during intimal thickening. Thus the ability of PRH to regulate cell behaviour and the control of PRH by CK2 is not limited to a specific cell type or tissue. This raises the possibility that the PRH-CK2 axis could be targeted in a variety of disease states ranging from multiple cancers to the intimal thickening that occurs in vein bypass graft failure and restenosis.


This paper introduces a new model, the octopus model, for studying small-world networks. The model is proposed for general measure-metric spaces and parametrizes the generation of complex networks in terms of the distribution of long-range connections per node. This model allows for the generation of a wide spectrum of complex networks including the ones possessing the clustering features of the Watts-Strogatz model and those possessing the scale-free features of the Barabási model. Analytical expressions for the average message delivery time in small-world networks as a function of source-target separation are derived. These analytical formulas show that nodes tend to communicate with one another only through their short-range contacts, and the average message delivery time rises linearly when the separation between source and target is small. On the other hand, as this separation increases, long-range connections are more commonly used, and the average message delivery time rapidly saturates to a constant value and stays almost the same for large values of the separation. These results are consistent with previous experimental observations made by Travers and Milgram in 1969, as well as by others. Other somewhat surprising conclusions of the paper are that hubs have a limited effect in reducing the average message delivery time and that the variance of connectivity in small-world networks adversely affects this time.


Context : Content-based image retrieval (CBIR) systems allow for retrieval of images from within a database that are similar in visual content to a query image. This is useful for digital pathology, where text-based descriptors alone might be inadequate to accurately describe image content. By representing images via a set of quantitative image descriptors, the similarity between a query image with respect to archived, annotated images in a database can be computed and the most similar images retrieved. Recently, non-linear dimensionality reduction methods have become popular for embedding high-dimensional data into a reduced-dimensional space while preserving local object adjacencies, thereby allowing for object similarity to be determined more accurately in the reduced-dimensional space. However, most dimensionality reduction methods implicitly assume, in computing the reduced-dimensional representation, that all features are equally important. Aims : In this paper we present boosted spectral embedding (BoSE), which utilizes a boosted distance metric to selectively weight individual features (based on training data) to subsequently map the data into a reduced-dimensional space. Settings and Design : BoSE is evaluated against spectral embedding (SE) (which employs equal feature weighting) in the context of CBIR of digitized prostate and breast cancer histopathology images. Materials and Methods : The following datasets, which were comprised of a total of 154 hematoxylin and eosin stained histopathology images, were used: (1) Prostate cancer histopathology (benign vs. malignant), (2) estrogen receptor (ER) + breast cancer histopathology (low vs. high grade), and (3) HER2+ breast cancer histopathology (low vs. high levels of lymphocytic infiltration). Statistical Analysis Used : We plotted and calculated the area under precision-recall curves (AUPRC) and calculated classification accuracy using the Random Forest classifier. Results : BoSE outperformed SE both in terms of CBIR-based (area under the precision-recall curve) and classifier-based (classification accuracy) on average across all of the dimensions tested for all three datasets: (1) Prostate cancer histopathology (AUPRC: BoSE = 0.79, SE = 0.63; Accuracy: BoSE = 0.93, SE = 0.80), (2) ER + breast cancer histopathology (AUPRC: BoSE = 0.79, SE = 0.68; Accuracy: BoSE = 0.96, SE = 0.96), and (3) HER2+ breast cancer histopathology (AUPRC: BoSE = 0.54, SE = 0.44; Accuracy: BoSE = 0.93, SE = 0.91). Conclusion : Our results suggest that BoSE could serve as an important tool for CBIR and classification of high-dimensional biomedical data.


ABSTRACT Variationist treatments of phonological processes typically provide precise quantitative accounts of the effects of conditioning environmental factors on the occurrence of the process, and these effects have been shown to be robust for several well-studied processes. But comparable precision in theoretical explanation is usually elusive, at the current state of the discipline. That is, the analyst is usually unable to say why the parameters should have the particular values that they do, although one can often explain relative ordering of environments. This article attempts to give a precise explanation — in the form of a quantitative theoretical prediction — of one robust quantitative observation about English phonology. The reduction of final consonant clusters (often called -t,d deletion) is well-known to be conditioned by the morphological structure of a target word. Deletion applies more in monomorphemic words (e.g., mist) than in inflected words (e.g., missed). In the theory of lexical phonology, these classes of words are differentiated by derivational history, acquiring their final clusters at different levels of the morphology. The theory further postulates that rules may apply at more than one level of the derivation. If -t,d deletion is treated as a variable rule with a fixed rate of application (p0) in a phonology with this architecture, then higher rates of application in underived forms (where the final cluster is present underlyingly and throughout the derivation) are a consequence of multiple exposures to the deletion rule, whereas inflected forms (which only meet the structural description of the rule late in the derivation) have fewer exposures and lower cumulative deletion. This further allows a precise quantitative prediction concerning surface deletion rates in the different morphological categories. They should be related as an exponential function of p0, depending on the number of exposures to the rule. The prediction is empirically verified in a study of -t,d deletion in seven English speakers.


In this work, speed estimators are designed based on a model reference adaptive system (MRAS) for sensorless control of interior permanent magnet synchronous machines (IPMSMs). To provide better filtering performance and reduce the noise contents in the estimated speed, an adaptive line enhancer is proposed to work with a sliding-mode observer to provide an improved reference model for speed estimation. In addition, a heterodyning speed adaption scheme is proposed to replace the conventional speed adaption mechanism. The proposed MRAS-based speed estimator has two different operating modes, which are suitable for generator- and motor-type applications, respectively. The effectiveness of the proposed speed estimators are verified by simulation using real-word vehicle data logged from a test vehicle. Furthermore, experimental results on a test stand for a heavy-duty IPMSM are also provided.


The project completed at the Wichita State University Department of Industrial and Manufacturing Engineering. Presented at the 7th Annual Capitol Graduate Research Summit, Topeka, KS, 2010


Introduction and Objectives Thoracic empyema affects >65 000 patients/year in the US and UK. Up to 50% require surgical drainage, and 15% die. We describe clinical features, microbiology, risk factors and surgical outcomes from referrals to a regional specialist cardiothoracic centre over 12 year. Methods Patients were identified by searching the hospital Clinical Data Repository for a diagnosis of 'pyothorax' from 1999 to 2010. A retrospective observational study was conducted using case note and database review. Results 406 distinct empyemas were identified. Patients were predominantly male (n=301, 74.1%), with median age of 53 years (IQR=37–69). Pyothorax predominantly developed secondary to community-acquired pneumonia, although 51 (12.6%) were hospital-acquired; 70 (17.2%) were receiving steroids or immunosuppressants, 35 (8.6%) had concurrent malignancy, 33 (8.1%) were diabetic and 14 (3.4%) patients were HIV-infected. Empyemas were right-sided in 233 (57.3%, p=0.03); four were bilateral. A causative organism was identified in 229 (56.4%) patients. Positive cultures were obtained from sputum in 59 (14.5%), pleural fluid in 174 (42.9%) and blood in 61 (15.0%) patients. Organisms identified included Streptococcus milleri (n=18, 4.4%), Streptococcus pneumoniae (n=39, 9.6%), other streptococci (n=10, 2.5%), Enterobacteraciae (n=12, 3.0%), anaerobes (n=32, 7.9%), methicillin-sensitive Staphylococcus aureus (n=36, 8.9%), methicillin-resistant Staphylococcus aureus (n=25, 6.2%), Enterococcus (n=14, 3.4%), Mycobacterium tuberculosis (n=36, 8.9%), non-tuberculous mycobacteria (n=1, 0.2%), other bacteria (n=25, 6.2%), and fungi (n=9, 2.2%); 34 (8.4%) cultures were polymicrobial. 277 (68.2%) patients were managed by open thoracotomy. 116 (28.6%) underwent video-assisted thoracoscopic surgery (VATS), of whom 17 (14.7%) were converted to open. Three (0.7%) required a Clagett window; 10 (2.5%) were managed with tube thoracostomy alone. A significant trend towards increased use of VATS over time was noted (p=0.0002). All-cause complication rate was 20.7%, and 28-day mortality was 5.7%. Low preoperative haemoglobin was predictive of mortality (p=0.04), but admission and peak C-reactive protein were not. Conclusions In this large series of empyemas from a tertiary referral centre, microbiological diagnosis was achieved in only half the patients. The identification of tuberculosis in 36 cases means routine screening for mycobacteria is necessary. Use of VATS has increased significantly, and mortality was lower than previously reported and associated with preoperative anaemia.


The author has previously argued against 'early closure' – the tendency to close down children's curiosity through an over‐zealous approach to issues‐based education. Indoctrination might be a result but 'burn‐out,' a potentially permanent attitude change that sets in before puberty, is more likely. This article is based on the author's recent work on a project on Steiner Schools in England, funded by the Department for Education and Skills (DfES), and is an examination of the apparent paradox of authority in the Steiner schools. There is a particular view that the teacher is the authority who mediates the world to 7–14‐year‐old pupils. However, the ultimate goal of Steiner education is freedom and autonomy. In Steiner's words 'our highest endeavour must be to develop free human beings who are able to impart freedom and direction to their lives.' The DfES research has suggested that pupils subjected to teacher authority in the Steiner tradition do so develop and that the spiritual dimension is significant. This requires further research. This article suggests that the preservation of childhood through a spiritually based developmental approach, true to Steiner's ideal of integrating the scientific, the artistic and the religious, may be worthy of attention.


We examined the effects of selective timber logging carried out by local indigenous people in remote areas within indigenous territories on the mammal populations of the Yavari-Mirin River basin on the Peru-Brazil border. Recent findings show that habitat change in the study area is minimal, and any effect of logging activities on large mammal populations is highly likely to be the result of hunting associated with logging operations. We used hunting registers to estimate the monthly and yearly biomass extracted during timber operations and to calculate the catch per unit effort (CPUE) in subsistence hunting in the community of Esperanza 2 to 5 years before logging activities started and 4 to 7 years after logging began. We also used line transects and the distance method to estimate animal densities before and after logging. We found that 1389 hunted animals and 27,459 kg of mammal biomass were extracted per year from logging concessions. CPUE for ungulates declined; however, it increased for other mammal orders, such as rodents and primates, indicating a shift to alternative prey items. Although collared peccaries (Pecari tajacu) and tapirs (Tapirus terrestris) may also have declined in numbers, this shift may have been caused by a possibly natural population crash in white-lipped peccaries (Tayassu pecari) that coincided with the logging periods. We found no evidence that populations of primates were reduced by the logging activities. Because primates are sensitive to hunting, and their populations were of principal concern as logging commenced, this indicates that these forests remain of high conservation value. The unusual socioeconomic situation of these remote territories may mean that they are compatible with wildlife conservation in the Yavari-Mirin basin.


As a profession, engineering is not well understood by the general public. Engineers are perceived as "geeks" who love math and who have few interests outside of technical work. In short, the engineering profession has an image problem. In order to counteract this negative stereotyping, an engineering course for non-majors was developed and offered at Michigan Tech. This course has two primary audiences: pre-service math and science teachers and business majors. The course is titled "Engineering for Non-Believers" and stresses hands-on, project-based work. This paper will describe the course content and will present assessment results from the first offering of the course.


Building effective learning environments is an art that can only be perfected by a great deal of explorations involving the environments' audience: the learners. This paper focuses on taking into account the learners' spatial ability into the development of Intelligent Tutoring Systems. We modified ERM-Tutor, a constraint-based tutor that teaches logical database design, to provide not only textual feedback messages, but also messages containing combinations of text and pictures, in accordance with the multimedia theory of learning [1]. Results of a preliminary study performed show a promising indication for further explorations. We plan to use these results as the basis for another evaluation study in early 2007.


A measurement of the variation of the Verdet constant of terbium gallium garnet as a function of temperature was made for visible and near-infrared wavelengths. By combining results of the angle of rotation presented here with previously published absolute measurements, we determined the Verdet constant as a function of wavelength for wavelengths extending from about 0.5 to 1.1 μm. Data correlated well with paramagnetic models. Such information is necessary to determine the angle of rotation as well as the variation of the extinction ratio of a Faraday isolator with temperature.


ABSTRACT The literature on Lebanese resistance to Israel is overwhelmed with work on Hezbollah, the role of religion, and its connection to Iranian influence. However, few of these studies have looked at the totality of Lebanese resistance, from its secular origins to its Islamic monopoly. Moreover, no work to date has looked at Lebanese resistance through the prism of just war theory. This article aims at addressing this gap by applying the criteria introduced by Childress regarding the justness of war. Moreover, the article examines resistance as a practice of non-state actors and its terrorist label, and at the same time, evaluates Israel's military response to Lebanese resistance through the prism of state terrorism.


Abstract Humor can ease social relations, be exploited to further productivity, and improve the environment and the general well being of the individual. Through humor people negotiate their value as men and demarcate insider/outsiders relations. At the same time, humor often interrupts the flow of work, slowing down productivity, and wasting time and money. Humor can also be exploited ambiguously to further self-interest and justify and re-interpret one's deceitful conduct. In the ambiguously humorous environment, people further their interests, crossing the boundaries of licit and illicit, offensive and acceptable behavior. Humor offers a place to dream a better reality, but it can also actually transform the context. Humorous topics revert around scatology, sex, gender, fish, and value manipulation. These are central fish market themes that define each other relationally. Whatever the practical purpose and the change of context that the jokes are aiming at, jokers construct primarily themselves and in the process they give sense to their life. In this paper I try to draw a picture in which the individual, with his desires and needs, and the culture at large come together. Almost all names, family names and nicknames are pseudonyms, unless indicated otherwise.


SUMMARY

Proceeding on the assumption that the seismic noise wavefield mainly consists of surface waves generated by a random distribution of independent, point-like and harmonic sources, we modelled a set of relationships that allows us to interpret empirical H/V and apparent dispersion curves in terms of the dynamic properties of a viscoelastic layered Earth. This formalization can be used to determine the effect of material damping on the expected noise wavefield in cases where the sources are relatively distant from the receivers and where the frequencies taken into account are higher than the fundamental resonance frequency of the local subsoil. Numerical experiments indicate that such effects are significant on the H/V ratio curve, whereas the apparent dispersion curve appears to be less strongly influenced by damping. This finding opens new perspectives for the use of noise measurements to infer the in situ anelastic properties of subsoil from passive seismic measurements made at the surface.


OBJECTIVES: To study the effect of oral administration of grape seed oil (GSO) against carbontetrachloride (CCl4)-induced hepatotoxicity in rats. METHODS: Liver damage was induced in male Wistar rats (150-250 g) by administering CCl4 (0.5 ml/kg, i.p.) once per day for 7 days and the extent of damage was studied by assessing biochemical parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in serum and concentrations of malondialdehyde (MDA), hydroperoxides, glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and total protein (TP) in liver. The effect of co-administration of GSO (3.7 g/kg, orally) on the above parameters was further investigated and compared with a vitamin E (100 mg/kg, orally) treated group. Histopatholgical studies of the experimental animals were also done. RESULTS: Oral administration of GSO (3.7 g/kg, body weight orally) for 7 days resulted in a significant reduction in serum AST, ALT, and ALP levels and liver MDA and hydroperoxides and significant improvement in glutathione, SOD, CAT, and TP, when compared with CCl4 damaged rats. The antioxidant effect of GSO at 3.7 g/kg for 7 days was found to be comparable with vitamin E (100 mg/kg, orally) in CCl4-treated rats. Profound fatty degeneration, fibrosis, and necrosis observed in the hepatic architecture of CCl4-treated rats were found to acquire near - normalcy in drug co-administered rats. CONCLUSION: The GSO has protected the liver from CCl4 damage. Probable mechanism of action may be due to the protection against oxidative damage produced by CCl4.


Use of the Internet has been proven to provide significant, wide-ranging benefits for disabled people research, however, such as a large scale global study commissioned by the United Nations, has determined a low level of accessibility. These findings have been supported by further multi-disciplinary work. While in other jurisdictions there have been definitive rulings on the need for the provision of accessible websites, a UK court has yet to lay down such a duty in relation to a website. It is accepted that there are a number of wide ranging issues interacting in this multi-faceted area, such as standardisation, industry self-regulation and the determination of an international consensus on what constitutes accessible design. However, this paper will focus upon the Equality Act 2010 and the changes it makes which could impact upon the creation of a definitive precedent. The Equality Act 2010 amended and combined pre-existing anti-discrimination provisions into one overarching piece of legislation. An analysis can be undertaken of how this legislation through its reasonable adjustment duty, public sector duty and the potential to validate regulations may be able to bring clarification in the area of website accessibility. Furthermore, the United Nations Convention on the Rights of Persons with Disabilities in its Article Nine specifically applies to access to the Internet. Given the international nature of website accessibility and the innovative provisions contained in the Convention, its impact on website design and inclusion could potentially be far-reaching. This article analyses the area of website design in the light of these recent legislative developments.


Abstract While extensive literature exists on how economic globalisation has limited developing countries' policy space for industrial policy, the literature on how it has affected advanced economies remains scant. We utilise original archival material to analyse the activities of the German public development bank, the Kreditantstalt für Wiederaufbau (KfW), in order to shed light on an important, but neglected aspect of German industrial policy. We analyse how the KfW responded to multiple challenges after the rise of economic globalisation, including a funding crisis, international agreements to limit export subsidies and Europeanisation. We argue that KfW successfully managed to navigate these challenges in order to retain, and even increase, its ability to conduct selective industrial policy in the post-1980s era. This was possible because of Germany's hard currency and low sovereign credit risk, large market size, which was augmented by membership in the European Union, and Germany's position as regional hegemon within Europe. More broadly, this shows how, conditional on domestic politics, advanced economies are able to shape and exploit the rules of the international economic system to implement industrial policies to their advantage, even as developing countries are given the opposite policy recommendations.


This dissertation contributes to the literature addressing the euro adoption by the
New Member States (NMSs) of the European Union by proposing a definition of
real convergence based on real exchange rate (RER) dynamics. As fluctuations in
RER represent deviations from purchasing power parity (PPP), the thesis also adds
to the literature on PPP theory. Finally, by proposing basic and extended small open
economy dynamic stochastic general equilibrium international real business cycle
(SOE-DSGE-IRBC) models of RER determinants for the NMSs, it fills a gap that
has hitherto existed in the literature.
The analysis of RER dynamics is conducted on two levels: empirical and theoretical.
On the empirical level, the scale of RER dynamics in the NMSs is measured. Factors
contributing to these dynamics are identified. Particular attention is drawn towards
the factors which could account for the recorded appreciation of RER in these
countries since the early 1990s. On a theoretical level, variants of the
SOE-DSGE-IRBC model of RER determinants for a typical NMS are developed.
The findings of Chapter 1 show that the univariate variance analysis accurately
measures real convergence in the analysed countries. The results also indicate that at
present, only Estonia and Slovenia (ex post) are ready to adopt the euro. The basic
SOE model of Chapter 2, unlike its expanded version of Chapter 3, is only able to
roughly match the moments of the Polish data. Therefore, its findings provide
insights into the theoretical 'puzzle' of RER volatility and its persistence. The
expanded model results show that productivity shocks to the non-traded sector are
the main cause of price differentials between Poland and the euro area. This is in
contrast to the two competing hypotheses that either productivity or quality
improvements in the tradable sector are the main source of real exchange rate
appreciation in this country.


S+C cathode material was prepared by simple solid-state reaction in ball mill. Content of sulphur was approximately 80 wt. % in final sample. Cyclic voltammetry and galvanostatic charge/discharge techniques were used for characterization of the samples. Initial discharge capacity observed for S+C sample was 600 mAh/gsulfur. Capacity loss for S+C sample after 30 th cycles was 66 %. Cycling loss is due to insoluble polysulfide formation. In this paper I present fundamental characteristics of Li-S batteries. This paper presents a principle of Li-S batteries, fundamental measurement and their evaluation. I present the techniques of measurement and preparation of cathode materials.


Fidaxomicin has recently been approved for the treatment of Clostridium difficile infection (CDI). As part of phase III studies, plasma and fecal samples were analyzed for concentrations of fidaxomicin and its metabolite, OP-1118. Plasma samples were collected before and after dose receipt on the first and last days of therapy, and fecal samples were collected on the last day of therapy. Samples were analyzed for fidaxomicin and OP-1118 (metabolite), using validated liquid chromatography/tandem mass spectrometric methods. Plasma concentrations were low for both fidaxomicin (mean [± standard deviation {SD}], 22.8 ± 26.7 ng/mL and 28.5 ± 33.4 ng/mL on the first and last days of therapy, respectively) and OP-1118 (mean [±SD], 44.5 ± 50.4 ng/mL and 85.6 ± 131 ng/mL, respectively). In contrast, fecal levels were >1000 µg/g for fidaxomicin and >800 µg/g for OP-1118. Fidaxomicin mean fecal levels were >5000 times the minimum inhibitory concentration for C. difficile of 0.25 µg/mL.


Mycobacteria are known to acquire resistance to the antituberculous drug pyrazinamide (PZA) through mutations in the gene encoding pyrazinamidase (PZase), an enzyme that converts PZA into pyrazinoic acid, the presumed active form of PZA against bacteria. Additional mechanisms of resistance to the drug are known to exist but have not been fully investigated. Among these is the non-uptake of the pro-drug, a possibility investigated in the present study. The uptake mechanism of PZA, a requisite step for the activation of the pro-drug, was studied in Mycobacterium tuberculosis. The incorporation of [14C]PZA by the bacilli was followed in both neutral and acidic environments since PZA activity is known to be optimal at acidic pH. By using a protonophore (carbonyl cyanide m-chlorophenylhydrazone; CCCP), valinomycin, arsenate and low temperature, it was shown that an ATP-dependent transport system is involved in the uptake of PZA. Whilst the structurally analogous compound nicotinamide inhibited the transport system of PZA, other structurally related compounds such as pyrazinoic acid, isoniazid and cytosine did not. Acidic conditions were also without effect. Based on diffusion experiments in liposomes, it was found that PZA diffuses rapidly through membrane bilayers, faster than glycerol, whilst the presence of OmpATb, the porin-like protein of M. tuberculosis, in proteoliposomes slightly increased the diffusion of the drug. This finding may explain why the cell wall mycolate hydrophobic layer does not represent the limiting step in the diffusion of PZA, as judged from comparative experiments using a M. tuberculosis strain and its isogenic mutant elaborating 40% less covalently linked mycolates. PZase activity, and PZA uptake and susceptibility in different mycobacterial species were compared. M. tuberculosis, a naturally PZA-susceptible species, was the only species that exhibited both PZase activity and PZA uptake; no such correlation was observed with the four naturally resistant species examined. Mycobacterium smegmatis possessed a functional PZase but did not take up PZA; the reverse was true for the PZase-negative strain of Mycobacterium avium used, with PZA uptake comparable to that of M. tuberculosis. Mycobacterium bovis BCG and Mycobacterium kansasii exhibited neither a PZase activity nor PZA uptake. These data clearly demonstrate that one of the mechanisms of resistance to PZA resides in the failure of strains to take up the drug, indicating that susceptibility to PZA in mycobacteria requires both the presence of a functional PZase and a PZA transport system. No correlation was observed between the occurrence and cellular location of PZase and of nicotinamidase in the strains examined, suggesting that one or both amides can be hydrolysed by other mycobacterial amidases.


Background The whale shark (Rhincodon typus Smith 1828) is the largest of the filter-feeding sharks and inhabits tropical and sub-tropical oceans worldwide. Evidence from anecdotal observations of feeding events and stomach content analysis have identified a wide range of planktonic and nektonic organisms including copepods, krill and small fish as whale shark prey. However, recent studies based on biochemical analysis (e.g. signature fatty acids (FA)) indicated that whale sharks in the western Indian Ocean had a wider foraging range than previous studies suggested, with important contributions from meso- and bathypelagic sources. However, it remains unknown if these results characterize the diet of whale sharks over the wider Indian Ocean. Here, we investigate the feeding ecology of whale sharks in the eastern Indian Ocean at Ningaloo Reef, Western Australia, by identifying differences in whale shark diet according to time of collection, sex and size-class and by examining likely food web linkages. Approach To examine whale shark feeding ecology we used signature FA analysis of both whale shark subdermal tissue and an extensive set of potential prey collected at Ningaloo Reef (Western Australia) in 2013 and 2014. Compared to other methods such as stomach content analysis, signature FA analysis provides both longer-term (up to months) dietary information and an assessment of spatial and temporal changes in the diet of predators. This is possible because some FA in animal tissues (e.g. long-chain (≥C20) polyunsaturated FA, LC-PUFA) can be used as biomarkers as they pass relatively unchanged from the low trophic levels where they are biosynthesized up the food chain. Results Whale shark sub-dermal tissue was low in lipid content (4 mg g–1 dry mass) which was dominated by phospholipids (72% of total lipid) with an energy density of 18.66 kJ g–1 dry mass. A significant intraspecific variability in whale shark FA profiles was observed resulting in four distinct groups of sharks in 2013 and five in 2014. As this variability was not related to sex or size-class, we suggest that it may be attributed to differences in the feeding habitats and thus different prey consumed by these groups of whale sharks. Variation in dietary patterns was also observed between years likely due to changes in the primary and secondary producers. Overall, examination of food web interactions showed that fatty acid profiles of whale sharks and their presumed collected prey were significantly different, suggesting that sharks fed over a wider range of habitats, including deeper waters, than we were able to access. Conclusions A significant component of whale shark diet may originate from benthic and deeper water habitats. High intraspecific variation in diet indicates that whale sharks are likely to forage over a range of distances and depths due to the challenge of inhabiting the patchy prey habitats of tropical and open ocean waters. Future studies should seek to combine signature FA analysis with other techniques such as stable isotopes, genetic and longterm tagging data to help better elucidate the feeding ecology of this iconic species.


Amorphous oxide semiconductors (AOSs) are expected as new channel materials in thin-film transistors (TFTs) for large-area and/or flexible flat-panel displays and other giant-microelectronics devices. So far, many prototype displays have been demonstrated in these four years since the first report of AOS TFT. The most prominent feature of AOS TFTs is that they operate with good performances even if they are fabricated at low temperatures without a defect passivation treatment. The TFT mobilities exceed 10 cm2/(Vmiddots), which are more than ten times larger than those of conventional amorphous semiconductor devices. In addition, they operate at low voltages, e.g., < 5 V owing to their small subthreshold voltage swings. These features indicate that electron transport in oxide semiconductors are insensitive to random structures and these oxides do not form high-density defects that affect electron transport and TFT operation. In this paper, we discuss the origins of the prominent features of AOS devices from the viewpoint of materials science of AOS.


Alpine/subalpine basins may exhibit substantial variability in solute fluxes despite many apparent similarities in basin characteristics. An evaluation of controls on spatial patterns in solute fluxes may allow development of predictive tools for assessing basin sensitivity to outside perturbations such as climate change or deposition of atmospheric pollutants. Relationships between basin physical characteristics, determined from geographical information system (GIS) tools, and solute fluxes and mineral weathering rates were explored for nine alpine/subalpine basins in Rocky Mountain National Park, Colorado, using correlation analyses for 1993 and 1994 data. Stream‐water nitrate fluxes were correlated positively with basin characteristics associated with the talus environment; i.e., the fractional amounts of steep slopes (≥ 30°), unvegetated terrain and young debris (primarily Holocene till) in the basins, and were correlated negatively with fractional amounts of subalpine meadow terrain. Correlations with nitrate indicate the importance of the talus environment in promoting nitrate flux and the mitigating effect of areas with established vegetation, such as subalpine meadows. Total mineral weathering rates for the basins ranged from about 300 to 600 mol ha−1 year−1. Oligoclase weathering accounted for 30 to 73% of the total mineral weathering flux, and was positively correlated with the amount of old debris (primarily Pleistocene glacial till) in the basins. Although calcite is found in trace amounts in bedrock, calcite weathering accounted for up to 44% of the total mineral weathering flux. Calcite was strongly correlated with steep slope, unvegetated terrain, and young debris—probably because physical weathering in steep‐gradient areas exposes fresh mineral surfaces that contain calcite for chemical weathering. Oligoclase and calcite weathering are the dominant sources of alkalinity in the basins. However, atmospherically deposited acids consume much of the alkalinity generated by weathering of calcite and other minerals in the talus environment. Published in 2001 by John Wiley & Sons, Ltd.


This book offers a fresh new approach to the study of housing. It explores the meaning that housing has for individuals and households by examining 'housing pathways'. Housing pathways refer to the varying household forms that individuals experience and the housing routes that they take over time. The book argues that housing has increasingly become a means to an end rather than an end in itself. The end is personal fulfilment and the main task of housing research is to elucidate the links. In this pursuit, the concepts of identity and lifestyle are key. Specifically, the book examines the structure and functioning of households and links this to changing discourses of the family; explores the important interconnections between housing and employment; considers the relationship between people and the physical aspects of a house and its location; looks at housing in terms of lifestyle choice from youth to old age and discusses the implications of the pathways approach for housing policy and future research in the field. The meaning of housing is recommended to anyone researching and studying housing and particularly to those wishing to engage with the new research agenda set out here.


This mixed-method study aims at exploring Iraqi English as a Foreign Language (EFL) teachers' attitudes towards Communicative Language Teaching (CLT). The study was conducted in Soran town, in the northern part of Iraq. The participants of the study were 58 EFL teachers from secondary and high school classrooms. In the first phase, a five-point Likert-scale questionnaire was administered (Karavas-Doukas, 1996) to examine the participants' attitudes towards CLT principles: "place/importance of grammar, group/pair work, quality and quantity of error correction, the role of the teacher in the classroom, the role and contribution of learners in the learning process." The second phase of the study was qualitative and consisted of semistructured interviews to examine the reasons behind the implementation of CLT in terms of the factors that hinder and encourage the implementation of CLT in the Iraqi setting. The results of the quantitative analysis revealed that the teachers held overall positive attitudes towards the use of CLT. The findings of the interview phase concluded that the main factors that cause the failure and success of the implementation of CLT in Iraq can be categorized under four headings: educational factors, teacher factors, student factors, and CLT factors. The results of the study suggest that the educational system and the teachers' communicative competence are essential to promote the employment of CLT in Iraqi EFL classrooms.


Refraction, interference, and diffraction are distinguishing features of wavelike phenomena. Although they are usually associated only with a purely spatial wave-propagation pattern, analogs to interference and diffraction involving the spatio-temporal dynamics of waves in one dimension have been discussed. We complete the triplet of analogies by discussing how spatio-temporal analogs to refraction are exhibited by a quantum particle in one dimension that is scattering off a step barrier. Similarly, birefringence in spacetime occurs for a spin-1/2 particle in a magnetic field.


Ions in high salt solutions have a strong propensity to form polydisperse ion aggregates with broad size and shape distributions. In a series of previous comparative investigations using femtosecond IR pump-probe spectroscopy, molecular dynamics simulation, and graph theoretical analysis, we have shown that there exists a morphological difference in the structures of ion aggregates formed in various salt solutions. As salt concentration increases, the ions in high salt solutions form either cluster-like structures excluding water molecules or network-like structures entwined with water hydrogen-bonding networks. Interestingly, such morphological characteristics of the ion aggregates have been found to be in correlation with the solubility limits of salts. An important question that still remains unexplored is why certain salts with different cations have notably different solubility limits in water. Here, carrying out a series of molecular dynamics simulations of aqueous salt solutions and analyzing the distributions and connectivity patterns of ion aggregates with a spectral graph analysis method, we establish the relationship between the salt solubility and the ion aggregate morphology with a special emphasis on the cationic effects on water structures and ion aggregation. We anticipate that the understanding of large scale ion aggregate structures revealed in this study will be critical for elucidating the specific ion effects on the solubility and conformational stability of co-solute molecules such as proteins in water.


Mahindra Trucks and Bus Division (MTBD) of Mahindra & Mahindra is at an interesting stage of its evolution. Having gone through a bad patch with a product that was not quite up to the mark, it appears to have got the product right by early 2018 and truck sales had been going up in the country for the previous four years. While Mahindra & Mahindra as a company is a large firm with revenues of more than USD 15 billion, MTBD itself is a small player (INR 2400 crore, USD 350 million) within the firm and in an Indian truck industry that is dominated by goliaths, Tata Motors and Ashok Leyland that between them had more than 81% market share and a customer mindset that was loath to leave the comfort of a known brand. The case provides data on product specifications, prices, marketing communication, channels, positioning, the context and competition. The intention is to use the case to go through the steps involved in evaluating and developing and creating a marketing plan for MTBD to increase its market share from the 4% in 2018 to an intended 8% in 2022.


Research into isoprene production from marine sources traditionally relies on gas chromatography techniques which are labor intensive, provide a slow sample turnover, and require significant method training. An alternative method is the use of a Fast Isoprene Sensor (FIS), a chemiluminescence‐based approach that provides real time isoprene analysis, but is relatively simple to run and also portable. Until now, the FIS has been used in terrestrial but not aquatic isoprene studies. Due to the added difficulties with marine compared with terrestrial sampling, particularly potential interference from dimethyl sulfide (DMS), we have developed a new protocol that allows accurate and reliable data to be obtained from FIS analysis. The detection limit of our modified system to standard gas was 0.02 nM (0.5 ppbv), while minimum isoprene production detected by the FIS was 0.59 nmol h−1 (for Thalassiosira weissflogii). We also compared our FIS‐based approach with GC analysis of isoprene emission from marine samples of micro‐ and macro‐algae, and demonstrated a strong similarity (r2 = 0.910, slope = 1.003). The ability to use FIS analysis with marine samples will significantly broaden the scope of isoprene research in marine environments, permitting remote field work, and allow previously unanswered questions to be addressed.


Network analysis defines a number of centrality measures to identify the most central nodes in a network. Fast computation of those measures is a major challenge in algorithmic network analysis. Aside from closeness and betweenness, Katz centrality is one of the established centrality measures. In this article, we consider the problem of computing rankings for Katz centrality. In particular, we propose upper and lower bounds on the Katz score of a given node. Previous approaches relied on numerical approximation or heuristics to compute Katz centrality rankings; however, we construct an algorithm that iteratively improves those upper and lower bounds until a correct Katz ranking is obtained. We extend our algorithm to dynamic graphs while maintaining its correctness guarantees. Experiments demonstrate that our static graph algorithm outperforms both numerical approaches and heuristics with speedups between \( 1.5\times \) and \( 3.5\times \) , depending on the desired quality guarantees. Our dynamic graph algorithm improves upon the static algorithm for update batches of less than 10,000 edges. We provide efficient parallel CPU and GPU implementations of our algorithms that enable near real-time Katz centrality computation for graphs with hundreds of millions of edges in fractions of seconds.


Advances in our understanding of human locomotion can be futile if no practical use is made of them. For the long-term benefit of patients in a clinical setting, scientists and engineers need to forge stronger links with orthopaedic surgeons to make the most use of the recent developments in motion analysis technology. With this requirement as a driving-force, an objective classification tool was developed that uses motion analysis for an application to clinical diagnostics and monitoring, namely knee osteoarthritis (OA) progression and total knee replacement (TKR) recovery. The classification tool is based around the Dempster-Shafer (DS) theory, and as such is built upon the sound foundations of Bayesian statistics. The tool expands on the work of Safranek et al. (1990) and Gerig et al. (2000) who developed and used parts of the classification method in the areas of vision and medical image analysis respectively. Using the data collected during a clinical knee trial, this novel approach enables the objective classification of subjects into an OA or normal group. Each piece of data is transformed into a set of belief values: a level of belief that a subject has OA knee function, a level of belief that a subject has NL knee function and an associated level of uncertainty. The belief values are then represented on a simplex plot, which enables the final classification of a subject, and the level of benefit achieved by TKR surgery to be visualised. The DS method can be used as a fully or partially automated tool. The input variables and control parameters, which are an intrinsic part of the tool, can be chosen by an expert or an optimisation approach. Using a leave-one-out (LOO) approach, the tool was able to classify new subjects with an accuracy of 97.62%. This compares with the 63.89% and 95.24% LOO accuracies of two well-established methods---the Artificial Neural Network and the Linear Discriminant Analysis classifiers respectively. The tool also provides an objective indication of the variables that are the most influential in distinguishing OA and NL knee function. In this case, the variables identified by the tool as important are often cited as clinically relevant variables, which enhances the appeal of the tool to the clinical community and allows for more effective comparison with clinical approaches to diagnosis. Using Simulated Annealing to select the control parameters reduced the LOO accuracy to 95.24%. Automated feature selection using a Genetic Algorithm and Sequential Forward Selection increased the LOO accuracy to 100%. However, further work is required to improve the effect of this process on the overall level of uncertainty in the classification. Initial studies have demonstrated a practical and visual approach that can discriminate between the characteristics of NL and OA knee function with a high level of accuracy. Further development will enable the tool to assist orthopaedic surgeons and therapists in making clinical decisions, and thus promote increased confidence in a patient's medical care.


A relaxation technique applied to the ECMWF model is used to analyse 11, 21 and 31 year trends in the boreal winter mean 500 hPa North Atlantic Oscillation (NAO), Pacific North America pattern (PNA) and Southern Annular Mode (SAM) indices. For the PNA, the results indicate a strong influence from the tropics on all time scales, whereas for the NAO, the stratosphere is important on time scales of 11 and 21 but with an indication of feedback from extratropical sea surface temperature and sea‐ice (SSTSI) anomalies on the 11 year time scale. For the SAM, the tropics emerge as the most important influence. We find an influence from the stratosphere consistent with expectations based on ozone depletion, although no clear role for stratospheric forcing of the SAM is found in these experiments.


This paper argues that the introduction of the Banking Recovery and Resolution Directive (BRRD) improved market discipline in the European bank market for unsecured debt. The different impact of the BRRD on bank bonds provides a quasi-natural experiment that allows to study the effect of the BRRD within banks using a difference-in-difference approach. Identification is based on the fact that (otherwise identical) bonds of a given bank maturing before 2016 are explicitly protected from BRRD bail-in. The empirical results are consistent with the hypothesis that debt holders actively monitor banks and that the BRRD diminished bail-out expectations. Bank bonds subject to BRRD bail-in carry a 10 basis points bail-in premium in terms of the yield spread. While there is some evidence that the bail-in premium is more pronounced for non-GSIB banks and banks domiciled in peripheral European countries, weak capitalization is the main driver.


A novel cyclodepsipeptide, iso-isariin B (1), and the known isaridin E (2) were isolated from the entomopathogenic fungus Beauveria felina. Their structures were elucidated using MS/MS fragmentation and extensive 2D-heteronuclear NMR. The X-ray structure of isaridin E was obtained, showing two potent intramolecular H bonds and a type-VI turn with the HyLeu(1)-Pro(2) amide bond in a cis conformation. Iso-isariin B (1) was active against the pest-insect Sitophilus spp. with an LD(50) value of 10 μg/mL. This observation also gives some clues for ecological interpretation of cyclodepsipeptide production by B. felina.


This section highlights early electronics milestones that have made significant contributions to aerospace and defense. Today everyone thinks digital, whereas more than 50% of electronic advances since society founding 50 years ago were in the analog or continuous domain. It is too easy to forget that before the 1970s and 1980s analog systems had been the norm. Digital electronics emerged late in WWII, when the US Army contracted with the University of Pennsylvania to compute extensive artillery firing tables. The Cold War substantially accelerated advances in solid state electronics which led to the microelectronics that are so ubiquitous today. Defense and then aerospace programs were symbiotic with electronics in the development and mass production of transistors, integrated circuits, microelectronics, microprocessors, magnetic and then solid state memory. Small, reliable, low power and high performance electronics were the key to aerospace progress. The government backed virtually all these developments out of necessity. The power of computers has increased by over a million since 1972 and is still climbing. The initial enabling technology for advances in military electronics was the almost forgotten vacuum tube. The existence of electrons was first recognized as the "Edison Effect" in 1883. The seminal event in electronics was the audion invented by Lee De Forrest in 1906. The audion appeared just three years after the first Wright brother's flight and four years before the Army purchased their first Wright airplane. Up until the World War I (WWI) radio amateurs were the electronics pioneers, but the war created new demand for radio communications. Electronics expanded from communications into radar, navigation and control systems in World War II (WWII). Both wars brought about dramatic improvements in electronics, which resulted in a surplus of equipment and trained personnel to fuel postwar advances.


Background Through activation of adrenergic receptors, chronic stress can trigger the secretion of neurotransmitters and hormones that enhance tumor growth, increase angiogenesis, and promote drug resistance. This study aimed to evaluate the effect of β-blockers in patients receiving first-line epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for lung adenocarcinoma. Methods This retrospective cohort study enrolled patients with advanced lung adenocarcinoma under first-line EGFR-TKIs between 2011 and 2014 in the National Health Insurance Research Database of Taiwan. The effects of β-blockers use, defined as ≥60 defined daily doses within 180 days before initiation of EGFR-TKI therapy, on the 2-year time-to-discontinuation (TTD) of EGFR-TKIs and 4-year overall survival (OS) were investigated using Cox regression analyses with inverse propensity score weighting and sensitivity analysis in subgroup with either hypertension or ischemic heart diseases. Results Among 4988 enrolled patients, 552 (11.1%) were in the β-blocker group. Patients in the β-blocker group were more likely to be older than 75 and had diabetes mellitus and cardiovascular comorbidities. In Cox regression analysis, β-blocker usage was associated with a longer TTD (hazard ratio, HR: 0.91 [0.86–0.96]) and OS (HR: 0.68 [0.64–0.72]). The results also favored β-blocker group in sensitivity analysis. Conclusions In treatment-naïve patients with advanced lung adenocarcinoma under first-line EGFR-TKIs, prior use of β-blocker was associated with a better outcome. The findings encourage further prospective clinical study to validate the possibility of β-blockers as adjuvant anticancer therapy.


Members of the Piezo family of mechanically activated cation channels are involved in multiple physiological processes including vascular development, cell differentiation, touch perception, hearing and more. Mutations in these proteins are associated with a variety of diseases, such as colorectal adenomatous polyposis, dehydrated hereditary stomacytosis, and hereditary xerocytosis. Available 3D structures for Piezo proteins show nine regions of four transmembrane segments each that have the same fold. Despite the remarkable similarity among the nine characteristic structural repeats in the family, no significant sequence similarity among them has been reported. Using a bioinformatics approach and the Transporter Classification Database (TCDB) as reference, we reliably identified sequence similarity among repeats based on four lines of evidence: (1) HMM-profile similarities across repeats at the family level, (2) pairwise sequence similarities between different repeats across Piezo homologs, (3) Piezo-specific conserved sequence signatures that consistently identify the same regions across repeats, and (4) conserved residues that maintain the same orientation and location in 3D space.


Cardiovascular diseases (CVDs) such as coronary artery disease, arrhythmias, angina pectoris and hypertension have become a major health problem throughout the world. The major modifiable risk factors of developing CVDs are unhealthy diet, physical inactivity, smoking, hyperlipidaemia, obesity and high intake of alcohol. The role of diet in the etiology of most CVDs is extremely important. The industrial revolution in the last few decades has introduced radical changes in methods of food production, processing, storage and distribution. Economic developments together with recent technological innovations and modern marketing techniques have further modified dietary preferences. Current scientific evidences increasingly support the notion that novel foods have many potential health benefits. Novel foods are traditional foods with newly defined significances on humans. This article focuses on role of novel foods in cardiovascular disease prevention and health promotion.


This paper explores the contribution of various financial measures in explaining the variability in a firm's dividend payments. Ordinary least squares analysis of data from 2003 to 2007 shows that approximately 71% of the variability in dividend payments is explained by the firm's expected growth rate of revenues, earnings before interest and tax, market debt to capital ratio, and effective tax rate. The findings support theories in the literature that dividends paid by a firm decrease with higher expected growth in revenues, lower earnings before interest and tax, higher debt service requirements, and higher effective tax rates.


Business models and business model change have drawn increasing attention from both researchers and practitioners across various disciplines, including the domain of entrepreneurship. However, even though the importance of business model innovation as a driver of firm performance has been widely acknowledged, empirical studies explaining the business model change remain limited. This study contributes to prior research by examining the effects of effectual and causation-based decisionmaking logics on the degree of business model change in the context of small and medium-sized enterprises in Finland. The findings of hierarchical regression analysis show that both causation and effectuation-based logics have positive effects on business model change, thereby highlighting the need for both strategizing and seizing of opportunities in business model development.


This study presents an experimental and numerical investigation of a taut-moored wave energy converter system with a point-absorber type of wave energy converter. The wave energy converter system consists of a buoy, a unique three-leg two-segment mooring system with submerged floaters, and a power take-off system designed for the current experiment as a heave plate. The main objective of the study is to validate a numerical simulation model against experiments carried out in an ocean basin laboratory. Two physical models in model scales 1:20 and 1:36 were built and tested. The detailed experimental testing programme encompasses tests of mooring system stiffness, decay tests, and different sea state conditions for ocean current, regular, and irregular waves. A numerical model in the model scale 1:20 was developed to simulate coupled hydrodynamic and structural response analyses of the wave energy converter system, primarily using potential flow theory, boundary element method, finite element method, and the Morison equation. Several numerical simulations are presented for each part of the experimental testing programme. Results for the wave energy converter buoy motions under operational conditions from the experiments and the numerical simulations were compared. This study shows that the simulation model can satisfactorily predict the dynamic motion responses of the wave energy converter system at non-resonant conditions, while at resonant conditions additional calibration is needed to capture the damping present during the experiment. A discussion on simulation model calibration with regard to linear and non-linear damping highlights the challenge to estimate these damping values if measurement data are not available.


Fluvial channels encounter a backwater reach when they approach a standing body of water, and recent studies have shown that the transition from normal flow to backwater-influenced flow is associated with sediment mass extraction through deposition. Here we test the hypothesis that systematic changes in the geometry of channel-belt deposits and sedimentary architecture occur across this transition, using data from the late Holocene Mississippi (southern USA) and Rhine (The Netherlands) fluvio-deltaic systems. We use the estimated backwater length and average channel width as characteristic length scales to non-dimensionalize the downstream trends in channel-belt width for these systems. The collapsed data follow similar trends, suggesting that the observed variations in channel-belt geometry and fluvio-deltaic stratigraphy are tied to the location of the backwater transition zone. These findings suggest a unifying hydraulic control on fluvio-deltaic channel belts and provide a new framework for predicting and understanding the properties of ancient rivers in the coastal zone.


Knowledge of the fitness effects of mutations to SARS-CoV-2 can inform assessment of new variants, design of therapeutics resistant to escape, and understanding of the functions of viral proteins. However, experimentally measuring effects of mutations is challenging: we lack tractable lab assays for many SARS-CoV-2 proteins, and comprehensive deep mutational scanning has been applied to only two SARS-CoV-2 proteins. Here we develop an approach that leverages millions of publicly available SARS-CoV-2 sequences to estimate effects of mutations. We first calculate how many independent occurrences of each mutation are expected to be observed along the SARS-CoV-2 phylogeny in the absence of selection. We then compare these expected observations to the actual observations to estimate the effect of each mutation. These estimates correlate well with deep mutational scanning measurements. For most genes, synonymous mutations are nearly neutral, stop-codon mutations are deleterious, and amino-acid mutations have a range of effects. However, some viral accessory proteins are under little to no selection. We provide interactive visualizations of effects of mutations to all SARS-CoV-2 proteins (https://jbloomlab.github.io/SARS2-mut-fitness/). The framework we describe is applicable to any virus for which the number of available sequences is sufficiently large that many independent occurrences of each neutral mutation are observed.


We show that macroeconomic movements have strong effects on the happiness of nations. First, we find that there are clear microeconomic patterns in the psychological well-being levels of a quarter of a million randomly sampled Europeans and Americans from the 1970s to the 1990s. Happiness equations are monotonically increasing in income, and have similar structure in different countries. Second, movements in reported well-being are correlated with changes in macroeconomic variables such as gross domestic product. This holds true after controlling for the personal characteristics of respondents, country fixed effects, year dummies, and country-specific time trends. Third, the paper establishes that recessions create psychic losses that extend beyond the fall in GDP and rise in the number of people unemployed. These losses are large. Fourth, the welfare state appears to be a compensating force: higher unemployment benefits are associated with higher national well-being.