Angiogenesis, the de novo growth of blood vessels from pre-existing vessels, is an imperative, tightly-regulated process that underpins the expansion and refinement of the developing vascular network. However, in some pathological conditions, such as after a myocardial infarction, the vascular network can be destroyed necessitating the need for angiogenesis. Therefore stimulating angiogenesis could be therapeutically advantageous. Recently, plasma membrane calcium ATPase 4 (PMCA) has been established as a novel mediator of angiogenesis through its role in endothelial cell migration and tubule formation. In addition to PMCA4, both PMCA1 and PMCA2 are also expressed in human endothelial cells but their contribution to angiogenesis remains unknown. Therefore, we hypothesise that PMCA1 also modulates angiogenesis by altering endothelial cell behaviours. Transient knockdown of PMCA1 was achieved in human umbilical vein endothelial cells (HUVECs) using siRNA (si-PMCA1) and confirmed with qPCR and western blot. Assays to asses HUVEC viability, proliferation and rate of apoptosis were performed over a period of 6 days post-transfection using Alamar Blue, Ki-67 immunofluorescence and Caspase-Glo 3/7 respectively. In addition, live-cell imaging was performed over a period of 21 hours to further evaluate migration of cells in a wound, cell necrotic cytotoxicity and cell apoptotic death. Furthermore, HUVECs were added to Matrigel to evaluate in-vitro tubule formation and DAPI-stained cells were subject to fluorescent activated cell sorting to determine cell-cycle distribution. Molecular mechanisms were investigated using Western blot. Transient knockdown of PMCA1 in HUVECs resulted in an 85% reduction of PMCA1 at both mRNA and protein level but did not alter the levels of PMCA4 mRNA up to 6 days post transfection. Phenotypically, 3 and 6 days post-transfection, loss of PMCA1 significantly reduced HUVEC viability without a concomitant increase in HUVEC apoptosis or cytotoxicity. Immunofluorescent staining for Ki-67 showed no statistical difference between si-PMCA1 and control HUVECs for the percentage of Ki-67 positive cells. However, FACs-mediated cell cycle analysis revealed si-PMCA1 HUVECs had a significantly larger proportion of cells in G0/G1 phase with fewer cells identified in G2/M-phase compared to control HUVECs after serum starvation followed by 8 hours of full serum media. Additionally, live-cell imaging of the wound healing assay revealed si-PMCA1 HUVECs displayed significantly reduced HUVEC wound density and wound confluence, resulting in an increased wound width over time. Furthermore, si-PMCA1 also show reduced ability to form tubules in-vitro characterised by a reduction in the number of tubules and tubule junctions formed, despite si-PMCA1 HUVECs having higher protein levels of the pro-angiogenic gene RCAN1.4. Overall, transient knockdown of PMCA1 has adverse effects on HUVEC viability, migration and tubule formation suggesting loss of PMCA1 is detrimental for in-vitro angiogenesis. Abstract 104 Figure 1 Abstract 104 Figure 2


Since the pioneering work of the early 1900s, the lens has been used as a model system for the study of tissue development in vertebrates. A number of embryological transplantation experiments designed to elucidate the role of tissue interactions in the formation of the lens have led to the proposal of a stepwise determination model. This model has recently been refined through the identification of certain transcription factor genes, which exhibit distinct expression patterns and functional properties in the lens cell lineage. Otx2, Pax6, and Lens1 are induced by the adjacent anterior neural plate and expressed in predifferentiated lens ectoderm. Contact between the optic vesicle and lens ectoderm promotes expression of mafs, Soxs, and Prox1, which are responsible for the initiation of lens differentiation programs including crystallin expression, cell elongation, and cell cycle arrest. Further analysis of the expression and functional characteristics of these transcription factors will allow greater detail when describing the orchestration of genetic programs, which control tissue development from induction to maturation.


Scenario planning is a commonly used method that various organizations use to develop their long term plans. Scenario planning for risk management puts an added emphasis on identifying the extreme yet possible risks that are not usually considered in daily operations. While a variety of methods and tools have been proposed for this purpose, we show that formulating an AI planning problem, and applying AI planning techniques to develop the scenarios provides a unique advantage for scenario planning. Our system, the Scenario Planning Advisor (SPA), takes as input the relevant news and social media trends that characterize the current situation, where a subset of them is selected to represent key observations, as well as the domain knowledge. The domain knowledge is acquired using a graphical tool, and then automatically translated to a planning domain. We use a planner to generate multiple plans explaining the observations and projecting future states. The resulting plans are clustered and summarized to generate the scenarios for use in scenario planning. We discuss our knowledge engineering methodology, lessons learned, and the feedback received from the pilot deployment of the SPA system in a large international company. We also show our experiments that measure planning performance and how balanced and informative the generated scenarios are as we increase the complexity of the problem.


Military developments in 1942-43 favored the United Nations. So too did the distribution of wheat and of total food supplies. Aided by a record potato crop, German Europe made adjustments to the greatest bread-grain deficiency of the war period. The United States, Canada, and Australia turned some of their surplus wheat to nonfood uses that contributed to the war effort. But shortage of shipping and shipping blockades prevented much wheat from flowing to major grain-deficit areas in three of the United NationsSoviet Russia, India, and China. Urban bread rations were reduced in various countries of the Danube basin, but elsewhere in German Europe the bread rations of the preceding year were generally maintained or increased. In most countries bread-grain supplies were stretched by greater diversion of feed grains to human consumption. This was associated with further reductions in the prevailing low rations of meat and fats. World exports of wheat and flour were smaller in 1942-43 than in any year since the late 1880's. At least 90 per cent was supplied by the four chief exporting countries, which shipped about half of their aggregate exports to the British Isles. Britain's takings were nevertheless the smallest in 25 years. This reflected the efforts of the British Ministry of Food to cut importation and consumption of foreign wheat through increase in the average wheat-extraction rate for National Flour and through new admixtures of barley and oats. The four chief exporting countries together used about as much wheat for livestock feed and alcohol production in 1942-43 as they exported to other countries. Yet at the end of the crop year the remaining wheat stocks in the four countries were by far the largest on record-more than sufficient for a year's domestic wheat consumption.


Rationale The species‐specific relationship between phosphate (δ18OP values) and structural carbonate (δ18OC values) oxygen isotope ratios has been established for several modern and fossil animal species but until now it has not been investigated in European fallow deer (Dama dama dama). This study describes the relationship between phosphate and structural carbonate bioapatite in tooth enamel of extant fallow deer, which will help us further understand the species' unique environmental and cultural history. Methods The oxygen isotope composition of phosphate (δ18OP value) and structural carbonate (δ18OC value) of hydroxylapatite was determined in 51 modern fallow deer tooth enamel samples from across Europe and West Asia. The δ18OC values were measured on a GV IsoPrime dual‐inlet mass spectrometer and the δ18OP values on a temperature‐controlled elemental analyser (TC/EA) coupled to a DeltaPlus XL isotope ratio mass spectrometer via a ConFlo III interface. Results This study establishes a direct and linear relationship between the δ18OC and δ18OP values from fallow deer tooth enamel (δ18OC = +9.244(±0.216) + 0.958 * δ18OP (±0.013)). Despite the successful regression, the variation in δ18O values from samples collected in the same geographical area is greater than expected, although the results cluster in broad climatic groupings when Koppen‐Geiger classifications are taken into account for the individuals' locations. Conclusions This is the first comprehensive study of the relationship between ionic forms of oxygen (phosphate oxygen and structural carbonate) in fallow deer dental enamel. The new equation will allow direct comparison with other herbivore data. Variable δ18O values within populations of fallow deer broadly reflect the ecological zones they are found in which may explain this pattern of results in other euryphagic species.


Background Previous reports indicate that posttransplantation diabetes mellitus (PTDM) is associated with overall renal graft loss, but not death-censored graft loss. Methods In this single-center retrospective cohort study of 2749 adult Norwegian renal transplant recipients, transplanted between 1999 and 2011, we estimated overall and death-censored renal graft loss hazard ratios in patients diagnosed with PTDM, impaired glucose tolerance and diabetes before transplantation, using multivariable Cox proportional hazard regression analysis. Results A total of 893 renal grafts were lost during the study period, either due to recipient death (n = 540) or death-censored graft loss (n = 353). When the observational time started at time of transplantation, diabetes before transplantation was associated with both overall and death-censored graft loss. Pretransplantation diabetes was also associated with a steeper decline in renal graft function, a higher risk of acute rejections and more renal grafts lost due to acute rejection. In patients with a functional renal graft 1 year after transplantation, PTDM was associated with overall graft loss (hazard ratio, 1.46; 95% confidence interval, 1.13-1.88; P < 0.001), but not death-censored graft loss (hazard ratio, 1.25; 95% confidence interval, 0.80-1.96; P = 0.33). We found no significant associations between PTDM and change in renal function during the first 5 years or acute rejection risk during the first year after renal transplantation. Impaired glucose tolerance was not associated with either overall or death-censored graft loss. Conclusions The present study confirms previous findings of an increased risk of overall but not death-censored renal graft loss in renal transplant recipients with PTDM. Longstanding diabetes might increase the risk of acute rejections.


This project investigates transport properties of electrons and holes confined into one-dimensional regions using lithographically patterned surface gates in In0.75Ga0.25As and p-type Ge quantum wells respectively. A series of transport experiments was conducted to investigate many body e↵ects in electrons and holes in one dimension. The experimental results provided here show important advances in both In0.75Ga0.25As and p-type Ge quantum wires and lays the ground work for future experiments for spintronics research using these materials. The first experiments reported here (chapter 4) describes the experiments carried out to optimise fabrication methods and determine the ideal length scales of split gates to observe clear ballistic transport features in high mobility In0.75Ga0.25As wafers. The following chapter (chapter 5) summarises the one dimensional transport measurements carried out on narrow split gates fabricated on the high mobility In0.75Ga0.25As quantum wells. It explores how Rashba spin orbit coupling e↵ects the transport properties. In In0.75Ga0.25As a weaker backscattering due to the time-reversal asymmetry in the one-dimensional channel results in enhanced ballistic transport characteristics with clear quantised conductance plateaus up to 6(2e2/h). We investigate the conductance data when a d.c. voltage is applied to the source and the drain contacts and a method for obtaining the e↵ective g factor is described. Chapter 6 introduces p-type Ge, and summarises one dimensional transport properties of these devices. We demonstrate quantised conductance up to 10 (2e2/h). Applied source-drain voltages and symmetric gating of the channel has uncovered plateau at half integer values as well as ballistic structure down to 0.25(2e2/h). These systems also show a ballistic plateau at 0.25 (2e2/h), when the carrier density is reduced using a top gate electrode. The last experimental chapter (chapter 7) analyses the many-body e↵ects observed in one-dimensional transport measurements in p-Ge and analysis of anomalous 0.25 (2e2/h) plateau is provided with possible explanations for it. We have also shown that we can alter the confining potential using lateral gate voltages to create a row formation as the ground state e↵ectively creates a Wigner lattice.


Scholars and practitioners addressing the problem of unauthorized humanitarian intervention often characterize the central difficulty of the issue as arising out of the fact that when the U.N. Security Council fails to authorize states to use military force to stop mass atrocities, the law requires a result - doing nothing - that is illegitimate and morally abhorrent. One scholarly solution to this predicament has been to subordinate considerations of legality to those of legitimacy or morality by arguing that in certain cases in which the Security Council does not authorize an intervention that should take place, the international community should tolerate the unlawful intervention as "excused" or "justified."This Article responds to this recent willingness to look beyond the law by illuminating the unaccounted costs of unauthorized humanitarian intervention and by proposing a more rigorous framework for assessing these uses of force. Specifically, this Article advocates a new emphasis on the systemic consequences of unauthorized intervention, focusing on the impact of unauthorized humanitarian intervention on two elements of the international system that preserve the primacy of law over power: first, the principle of sovereign equality of states, and second, the principle that military force should be used only in the common interest. This Article urges that the impact of unauthorized uses of nondefensive force on these principles, and therefore on the vitality of law in the international system, should be an essential consideration in any evaluation of unauthorized humanitarian intervention. By considering the deeper implications of looking the other way when states resort to war to protect human rights, this Article challenges the conventional account of unauthorized humanitarian intervention as raising a choice between protecting human rights and protecting sovereignty, and it contends that the roots and benefits of the prohibition against unauthorized military force should compel policy makers to consider alternatives to military force when responding to grave human rights abuses.


Convulsion evokes a lot of fear in mothers and caregivers whenever it occurs. They even think that their child is dying. Many interventions are  often carried out because of anxiety and limited knowledge. The aim of this study is to examine the interventions instituted by caregivers for children with convulsions before presentation in the hospital for treatment. We prospectively studied all the 276 children that presented to the emergency room with convulsion over a period of seven months and the care administered at home before presenting in the hospital was noted. One hundred and nine (39.5%) of the children had water poured on them during convulsion. Substances administered orally were; salt 32 (11.6%), onions 14 (5.1%), palm oil 3 (1.1%) and herbal concoctions 13 (4.7%), of which two contained cow urine. Metal spoons were used as mouth gag in 41 (14.9%) of subjects while 29 (10.5%) children had intramuscular (IM) injections given by health workers at home (eight) in various health centres (15) and hospitals (6). Other interventions were scarifications and drinking of their mothers' urine. While 40 (14.5%) children had more than one treatment given to them before their arrival, 99 (35.9%) had no treatment given before their arrival. Caregivers continue to carry out various interventions at home for convulsions in children. Majority of the interventions are not beneficial while some are harmful. There is, therefore, need to continue to educate caregivers on the appropriate prehospital interventions of convulsions in children before presenting in the hospital.

 Key words: Convulsion, pre-hospital interventions.


Background A significant proportion of individuals with diabetes or impaired glucose tolerance have fasting plasma glucose less than 6.1 mmol/L and so are not identified with fasting plasma glucose measurements. In this study, we sought to evaluate the utility of plasma lipids to improve on fasting plasma glucose and other standard risk factors for the identification of type 2 diabetes or those at increased risk (impaired glucose tolerance). Methods and Findings Our diabetes risk classification model was trained and cross-validated on a cohort 76 individuals with undiagnosed diabetes or impaired glucose tolerance and 170 gender and body mass index matched individuals with normal glucose tolerance, all with fasting plasma glucose less than 6.1 mmol/L. The inclusion of 21 individual plasma lipid species to triglycerides and HbA1c as predictors in the diabetes risk classification model resulted in a statistically significant gain in area under the receiver operator characteristic curve of 0.049 (p<0.001) and a net reclassification improvement of 10.5% (p<0.001). The gain in area under the curve and net reclassification improvement were subsequently validated on a separate cohort of 485 subjects. Conclusions Plasma lipid species can improve the performance of classification models based on standard lipid and non-lipid risk factors.


The presented cases describe the concurrent SARS-CoV-2 infection and inactivated SARS-CoV-2 vaccination among eight healthcare workers (HCWs). These cases highlighted the importance of broad hospital screening during the COVID-19 vaccination campaign. Further study regarding the durability of antibody response induced by infection and first-dose vaccination is required to determine the appropriate time for giving a second dose of inactivated SARS-CoV-2 vaccine among these cases.


Robust (cross-border) interbank markets are important for the well functioning of modern financial systems. Yet, a network of interbank exposures may lead to domino effects following the event of an initial bank failure. We investigate the evolution and determinants of contagion risk for the Belgian banking system over the period 1993-2002 using detailed information on aggregate interbank exposures of individual banks, large bilateral interbank exposures, and cross-border interbank exposures. The structure of the interbank market affects contagion risk. We find that a change from a complete structure (where all banks have symmetric links) towards a "multiple money centre" structure (where money centres are symmetrically linked to otherwise disconnected banks) has decreased the risk and impact of contagion. In addition, an increase in the relative importance of cross-border interbank exposures has lowered local contagion risk. Yet, this reduction may have been compensated by an increase in contagion risk stemming from foreign banks.


The suddenness and depth of the recession has raised questions about the workability of capitalism not seen since the 1930s. One of the constraints on recovery is the growing belief that if the old model did not work there is no new one on offer. This book sets out to provide one, arguing that reconstructing a bust financial system is not just a technical question. It cannot be done without a wholescale revision of the wider system and values on which it is based. And fairness must be placed at the heart of the new capitalism for society's future wellbeing. Will Hutton's new book musters brilliant, convincing arguments which will lend favour on both right and left. It is set to be a book which captures the mood of the moment in the same way that THE STATE WE'RE IN did.


High-purity crystalline solid-state materials play an essential role in various technologies for quantum information processing, from qubits based on spins to topological states. New and improved crystalline materials emerge each year and continue to drive new results in experimental quantum science. This article summarizes the opportunities for a selected class of crystalline materials for qubit technologies based on spins and topological states and the challenges associated with their fabrication. We start by describing semiconductor heterostructures for spin qubits in gate-defined quantum dots and benchmark GaAs, Si, and Ge, the three platforms that demonstrated two-qubit logic. We then examine novel topologically nontrivial materials and structures that might be incorporated into superconducting devices to create topological qubits. We review topological insulator thin films and move onto topological crystalline materials, such as PbSnTe, and its integration with Josephson junctions. We discuss advances in novel and specialized fabrication and characterization techniques to enable these. We conclude by identifying the most promising directions where advances in these material systems will enable progress in qubit technology.


The feasibility of manufacturing non-autoclaved aerated concrete using alkali activated phosphorus slag as a cementitious material was investigated in this paper. Liquid sodium silicate with various modules (the molar ratio between SiO2 and Na2O) was used as alkali activator and a part of phosphorus slag was replaced with fly ash which was used to control the setting time of aerated concrete. The influences of the fly ash, curing procedure, modulus of sodium silicate solution and concentration of alkalis on the compressive strength and bulk density of non-autoclaved aerated concrete have been studied. Moreover, the types of the hydration products were investigated using XRD and SEM. The results indicate that: the compressive strength of aerated concrete was influenced by concentration of alkalis obviously. The compressive strength of 11.9MPa and the bulk density of 806kg/m3 were obtained with an activator of 1.2 modulus of sodium silicate and 6% concentration of alkalis under the circumstance of 60°C curing for 28 days.


Multidrug resistant bacterial isolates have significantly increased in recent years as a cause of bacterial cystitis. This increasing resistance to antimicrobial drugs leaves fewer therapeutic options for effective treatment. The emergence of antibiotic resistant bacteria in the community is necessitating the need to explore non-pharmocologic treatment options to reduce the spread and proliferation of these species. Ozone is an emerging therapy with both potent antibacterial properties and the ability to modulate the immune system, reduce oxidative stress induced by chronic infection and upregulate the endogenous antioxidant system providing further protection from free radical injury. In this case report, it is discuss how a patient with chronic ESBL-EC cystitis with limited therapeutic options was effectively treated with ozone therapy. It is shown a case study of a 67-year-old female with a neurogenic bladder who developed chronic cystitis caused by ESBL-producing and multi-drug resistant E. coli (ESBL-EC).  It was treated with bladder instillations of ozonated distilled water, combined with Major Autohemotherapy (MAHT) as an adjunctive immune modulated support. The current findings show that the elimination of a case of chronic cystitis cause by ESBL-EC was effectively treated with an alternative to pharmacologic antimicrobial therapy utilizing distilled instillation of ozonated water and Major Autohemotherapy. Further studies are warranted to investigate this as a potential therapeutic option for this and other resistant bacterial infections.


Soil secondary salinization resulting from overgrazing is a serious environmental problem in arid or semiarid grasslands in northeast China, generally characterized by the dramatic increase of soil soluble salt content and the decrease of vegetative production. However, the process of soil degradation, especially the influence of soil salinization on soil physicochemical properties, enzyme activities, bacterial community composition, and metabolic diversity, has been less exhaustively assessed. This work aims to evaluate the effects of salinization level on the soil properties and to discuss the effects of metabolic profiles and bacterial community in salinized grasslands. Soil samples were collected from three grasslands with a gradient of salinization level (0.135%, 0.375%, and 1.063%, respectively). The soil properties were measured. Analysis of community level physiological profiles (CLPPs) and 16S rRNA gene denaturing gradient gel electrophoresis (DGGE) were used to determine the metabolic diversity and dominant species of a soil bacterial community, respectively. Soil moisture, porosity, total nitrogen (N) and phosphorus (P), available N and potassium (K), DNA content, microbial biomass, enzymatic activities (dehydrogenase, phosphomonoesterase, urease, and polyphenol oxidase), and metabolic function diversity all decreased significantly with an increase in salt content. Soil bulk density, pH, and available P concentration increased significantly. All of the aforementioned soil properties had significant linear relations with salt content and aboveground biomass (p < 0.001 or p < 0.05). The same DGGE profiles of the 16S rRNA gene were obtained. Sequencing of bands showed that clones retrieved were affiliated with Gamma Proteobacteria. An increase in soil salt content restrains the proliferation and metabolic activity of soil bacteria but does not affect the dominant composition of a bacterial community, and Gamma Proteobacteria is found to be the dominant phyla. Soil enzymatic activities, microbial biomass, and metabolic profiles are used to monitor soil salinization process as valuable biological indicators of soil salinization process.


Schopenhauer's accounts of art and morality emerge from his metaphysics and pessimism. In Book 1 of his main work, The World as Will and Representation, the empirical world is argued to be merely an idea or representation of the thing-in-itself, which, in Book 2, is identified as a fundamental force or energy (the will) that is generative of all things. The world of phenomena, the empirical world, appears as objectifications of the noumenal will. There are multiple grades of objectification: forces of nature, rocks, plants, animals, humans, states of consciousness, and so on. The will is "present and undivided in every object of nature and every living being". Particular objects or individuals are "copies" of "Platonic Ideas", the latter being models or archetypes of the plurality of particulars which populate the empirical realm. The will enters the human sphere in the form of perpetual desire. All self-conscious beings are characterized by an incessant and inherently painful willing. Willing is a sufficient condition of suffering, because all willing arises necessarily from a want or deficiency, and to experience a want is to suffer: to live is to will; to will is to suffer; therefore to live is to suffer. Indeed, nature as a whole is destructive and amoral. Echoing the idea of the fallen world, Schopenhauer exhibits a nihilistic hatred of the empirical and gives expression to a tortured yearning for metaphysical consolation. He quotes St. Paul: "the whole creation groaneth and travaileth in pain together."

However, for humans there are three possible avenues of release from this unhappy state. The first is through the contemplation in (good) art of the realm of Platonic Ideas, whereby we, albeit temporarily, see through the illusory realm of phenomena, lose our egoistic orientation to the world, and overcome the division between subject and object. Here Schopenhauer explicitly opposes Plato: good art does not copy particulars, it copies the universals themselves. The second is the instinct of compassion. Morality űberhaupt concerns the thing-in-itself and is thus "incomparably more important than the physical which concerns only phenomena or representations". The moral, by contrast, discloses "the depths of our own inner nature" (WWR 2, 589). The third is the denial of the will or "resignation", the renunciation of self and world. It is in these terms that Schopenhauer understands our "final emancipation" from the will and our "true salvation" – a condition in which we become "the very opposite of what we are" – i.e. non-will (nothing). Thus Schopenhauer finds value in modes of experience that entail the dissolution of one's own individual subjectivity and hence release from suffering. In this paper I examine the interrelations between Schopenhauer's accounts of these three modes of experience.


Postpartum haemorrhage (PPH) is defined as excessive bleeding of 500 ml or more within 24 hours after birth. It is known as one of the leading cause of maternal mortality worldwide. In Malaysia, from the year 2009 to 2014, PPH remained as one of the top contributors to maternal deaths; this suggests that the knowledge, attitude and practice on PPH among mothers in Malaysia still need to be improved. This cross-sectional study is aimed to determine the level of knowledge, attitude and practice on PPH, in addition to examining the association of socio-demographic factors with knowledge, attitude and practice of women in Kuantan, Pahang, Malaysia. This study involved 105 women who have experienced pregnancy and delivered at least once and is living in Kuantan. Self-administered questionnaires were distributed from February until March 2018. Data were analysed using the Statistical Package Software for Social Sciences (SPSS). From the findings, the level of knowledge on PPH among women in Kuantan was average (n=73, 69.5%), whereas the level of attitude and practice of most respondents was found in a good level, 101 (96.2%) and 98 (93.3%) respectively. The factors that have significant associations with knowledge on PPH in this study were age group (p=0.016) and background of education (p<0.001). In conclusion, this study showed that most of the participants in Kuantan have a moderate level of knowledge on PPH yet possess a good attitude and practice on the management of PPH.


Currently there is an international shift towards inclusive education, a means of education according to which the learner is schooled in the least restrictive environment possible, to overcome his or her challenges to learning and development. Bearing this in mind we considered the experiences of a learner with learning difficulties who transited from a mainstream school environment to a school for learners with special education needs (LSEN).1 Inclusive education and ecological systems were the theoretical underpinnings of this study. The findings revealed that the learner benefited from placement within the LSEN environment on psychological, social, and academic levels. It appears that these changes occurred as a result of being placed in an environment that providedvaluable and necessary resources to meet his learning needs, which werelacking in the mainstream school environment. Therefore, it seems that while inclusive education may be a way forward to access quality education for all, it can be argued that the current South African socio-economic environment doesnot necessarily allow for its successful implementation, as further access to resources and facilities need to be made available. These findings provide useful lessons at regulatory, infrastructural, and instructional functional levels for what is needed for learners with special education needs to succeed in mainstream school environments.


Polypharmacy in older adults causes problems such as increased adverse drug reactions, overdose or duplication, and poor medication adherence. We have established a "medication review team" organized by pharmacists. This prospective and retrospective observational study evaluated the effectiveness of the pharmacist-led team-based approach for reducing polypharmacy as compared to the individual pharmacist approach. Data on the individual pharmacist approach were collected retrospectively, but prospectively for the pharmacist-led team approach. The study included patients who were admitted to the nephrology, orthopedic surgery, and psychiatry wards. Characteristics for patient included in each study group were adjusted using the propensity score method. The pharmacist-led team approach had a significantly higher medication change rate compared to that of the individual pharmacist approach (odds ratio (OR), 2.28; 95% confidence interval (CI), 1.21 to 4.46; p = 0.009). The rate of patients with two or more medication discontinuations and the rate of patients with intervention by young clinical pharmacist were also significantly higher in the pharmacist-led team approach (OR, 2.19; 95% CI, 1.06 to 4.74; p = 0.03 and OR, 5.67; 95% CI, 1.22 to 53.15; p = 0.02, respectively). The rate of patients with discontinuation of potentially inappropriate medications was not significantly different between the two groups (OR, 2.07; 95% CI, 0.86 to 5.33; p = 0.11). Our results suggest that it is possible to improve the quality of medication review by conducting team conferences even with only pharmacists.


Epidemic is considered as one of the primary causes of species extinction, especially it also can induce populations suffering from Allee effect. Using ordinary differential equation and lattice model, we here explored the epidemic transmission in a predator-prey system. Numerical simulation indicated that the Allee effect can both destabilize and stabilize the system: a moderate Allee effect will destabilize the dynamics, but it is not true for the extreme Allee effect (weak or strong). Moreover, we have pointed out that the infection rate was key to determine the temporal transmission of disease. Through the join-count statistics method, results showed that the spatial structure of disease is influenced dramatically by the Allee effect and ecological neighborhood. These results are new to ecoepidemiology and imply a possibility of restricting disease diffusion range to control the spread of epidemics in the ecological system.


Social network analysis (SNA) is among the hottest topics of current research. Most measurements of SNA methods are certainty oriented, while in reality, the uncertainties in relationships are widely spread to be overridden. In this paper, fuzzy concept is introduced to model the uncertainty, and a similarity metric is used to build a fuzzy relation model among individuals in the social network. The traditional social network is transformed into a fuzzy network by replacing the traditional relations with fuzzy relation and calculating the global fuzzy measure such as network density and centralization. Finally, the trend of fuzzy network evolution is analyzed and predicted with a fuzzy Markov chain. Experimental results demonstrate that the fuzzy network has more superiority than the traditional network in describing the network evolution process.


The effect of annealing on the composition, crystal structure, surface features and electro-optical properties of tin mono-sulfide (SnS) films, deposited by thermal evaporation at 300 °C, has been studied. Elemental analysis of the films shows sulfur deficiency, which increases at higher annealing temperatures (Ta). The SnS structure in the as-deposited and annealed films remains orthorhombic. With an increase in Ta, the grain size and the surface roughness are reduced. The electrical resistivity also decreases with increasing Ta. The variation of activation energy and optical parameters with Ta has been explained by taking into account the degree of preferred orientation of the grains. The films annealed at 100 °C show some unusual features compared to those annealed at other temperatures.


Fusarium head blight (FHB or scab) caused by Fusarium species can lead to tremendous loss of grain yield and quality in wheat (Triticum aestivum L.) as well as severe mycotoxin contamination. Characterization of different types of resistance is of great significance for genetics and breeding studies. One hundred fifty-two F 6:7 recombinant inbred lines (RILs) derived from a cross CJ 9306/Veery were assessed in the greenhouse by single-floret inoculation to analyze three types of FHB resistance, i.e., resistance to fungal spread within spikes, deoxynivalenol (DON) accumulation, and grain yield loss. Each of the investigated resistance types exhibited a large and continuous variation in the RIL population, and thus was inherited quantitatively. Estimates of broad-sense heritability varied with resistance types, higher and less variable for spread resistance (0.85-0.93), but lower and more variable for resistance to DON accumulation (0.64-0.92) and/or resistance to grain yield loss (0.61-0.83). For spread resistance parameters (the number and percentage of scabby spikelets) and DON content, frequency distributions exhibited a few peaks and/or were skewed toward resistance, suggesting the existence of major resistance genes. Genetic correlation coefficients of spread resistance parameters with DON content and yield loss parameters were 0.85 to 0.92 and 0.78 to 0.94, respectively. The genetic correlations ranged from 0.63 to 0.77 between DON content and yield loss parameters. There were no noticeable genetic associations between FHB resistance and agronomic traits such as plant height, spike length, number of spikelets and grains per spike, grain weight, and heading date.


Rationale: Small 225Ac-labeled prostate-specific membrane antigen (PSMA)-targeted radioconjugates have been described for targeted alpha therapy of metastatic castration-resistant prostate cancer. Transient binding to serum albumin as a highly abundant, inherent transport protein represents a commonly applied strategy to modulate the tissue distribution profile of such low-molecular-weight radiotherapeutics and to enhance radioactivity uptake into tumor lesions with the ultimate objective of improved therapeutic outcome. Methods: Two ligands mcp-M-alb-PSMA and mcp-D-alb-PSMA were synthesized by combining a macropa-derived chelator with either one or two lysine-ureido-glutamate-based PSMA- and 4-(p-iodophenyl)butyrate albumin-binding entities using multistep peptide-coupling chemistry. Both compounds were labeled with [225Ac]Ac3+ under mild conditions and their reversible binding to serum albumin was analyzed by an ultrafiltration assay as well as microscale thermophoresis measurements. Saturation binding studies and clonogenic survival assays using PSMA-expressing LNCaP cells were performed to evaluate PSMA-mediated cell binding and to assess the cytotoxic potency of the novel radioconjugates [225Ac]Ac-mcp-M-alb-PSMA and [225Ac]Ac-mcp-D-alb-PSMA, respectively. Biodistributions of both 225Ac-radioconjugates were investigated using LNCaP tumor-bearing SCID mice. Histological examinations of selected organs were performed to analyze the occurrence of necrosis using H&E staining, DNA damage via γH2AX staining and proliferation via Ki67 expression in the tissue samples. Results: Enhanced binding to serum components in general and to human serum albumin in particular was revealed for [225Ac]Ac-mcp-M-alb-PSMA and [225Ac]Ac-mcp-D-alb-PSMA, respectively. Moreover, the novel derivatives are highly potent PSMA ligands as their KD values in the nanomolar range (23.38 and 11.56 nM) are comparable to the reference radioconjugates [225Ac]Ac-mcp-M-PSMA (30.83 nM) and [225Ac]Ac-mcp-D-PSMA (10.20 nM) without albumin binders. The clonogenic activity of LNCaP cells after treatment with the 225Ac-labeled ligands was affected in a dose- and time-dependent manner, whereas the bivalent radioconjugate [225Ac]Ac-mcp-D-alb-PSMA has a stronger impact on the clonogenic cell survival than its monovalent counterpart [225Ac]Ac-mcp-M-alb-PSMA. Biodistribution studies performed in LNCaP tumor xenografts showed prolonged blood circulation times for both albumin-binding radioconjugates and a substantially increased tumor uptake (46.04 ± 7.77 %ID/g for [225Ac]Ac-mcp-M-alb-PSMA at 128 h p.i. and 153.48 ± 37.76 %ID/g at 168 h p.i. for [225Ac]Ac-mcp-D-alb-PSMA) with favorable tumor-to-background ratios. Consequently, a clear histological indication of DNA damage was discovered in the tumor tissues, whereas DNA double-strand break formation in kidney and liver sections was less pronounced. Conclusion: The modification of the PSMA-based 225Ac-radioconjugates with one or two albumin-binding entities resulted in an improved radiopharmacological behavior including a greatly enhanced tumor accumulation combined with a rather low uptake in most non-targeted organs combined with a high excretion via the kidneys.


Abstract In the pig, transforming growth factor beta (TGFB), TGFB receptors (TGFBRs), and integrins are present during the peri-implantation period. Latency-associated peptide (LAP), a part of latent TGFB, can bind to integrin heterodimers via its Arg-Gly-Asp (RGD) sequence; therefore, ligand-receptor interactions between TGFB and TGFBRs, along with LAP and integrin heterodimers, may be functional in mediating events supporting conceptus elongation and attachment. With the use of surgically implantable osmotic pumps, we were able to maintain pregnancy with the aim of mechanistically altering in vivo receptor-ligand interactions involving TGFB with TGFBRs and LAP with integrins during porcine pregnancy. Day 9 pregnant gilts received intrauterine infusions of LAP-RGD, a recombinant mutant of LAP (LAP-RGE), or vehicle control and were ovariohysterectomized on Day 13 or 24 of pregnancy. We hypothesized that intrauterine infusion of LAP-RGD would decrease downstream signaling of TGFB while increasing LAP-integrin interactions and that net effect would enhance conceptus survival and attachment early in the peri-implantation period but possibly increase the chance of abnormal placentation later in pregnancy. Additionally, we hypothesized that infusion of LAP-RGE would disrupt TGFB signals but not alter integrin signaling, and thus the net result would be decreased conceptus survival and abnormal development. Unexpectedly, LAP-RGD intrauterine infusions resulted in a reduction of conceptus elongation, whereas infusions of LAP-RGE permitted implantation and placentation but resulted in larger fetal weight, allantois length, and allantoic fluid volume. Results suggest TGFB and integrins are contributing factors in the regulation of conceptus elongation and placental and fetal size.


Injuries in the musculature belong to the most frequent injuries in sports. However, the various explanations regarding the reasons which lead to these problems differ considerably. In this work the muscle is simplified from a mechanical point of view and then explanations are derived in respect to possible origins of muscle injuries. The terms stress and distribution of stress are important in material science to describe the strength of a material. The same is true for the human body, for a muscle fibre or for an entire muscle. Due to its anatomical construction, the distribution of stress in the muscle is very inhomogeneous. It can be very large, even if the acting load is quite small. The most critical movements which lead to muscle injuries are fast, passive elongations of a muscle. The larger the rate of this elongation, the higher the risk of injury. These theoretical conclusions can also be supported by observations in everyday life. For example, muscle pain after exercise occurs almost exclusively after excentric loading.


Abstract. During the last decade, the constant improvement in computational capacity led to the development of the first limited-area, kilometer-scale ensemble prediction systems (L-EPS). The COSMO-D2 EPS (now ICON-D2) was the operational L-EPS at the German weather service (DWD) and has a spatial resolution of around 2.2 km. This grid resolution allows large scale, deep convective processes such as thunderstorms or heavy showers to be handled explicitly, without any physical parametrization. Special parameters involving both clouds microphysics and large scale lifting – such as the Lightning Potential Index, or LPI – have also been developed in order to try to bring the forecasting of deep convection and therefore also of lightning activity to a new level of spatial accuracy. With such high resolution forecasts comes however also a higher error potential, at least for gridpoint-verification. The use of this high resolution setup in an ensemble prediction system might however bring huge benefits in terms of skill and predictability. This work is a preliminary attempt to apply innovative verification approaches such as the dispersion Fractions Skill Score (dFSS) and the ensemble-SAL (eSAL) to the LPI in the COSMO-D2 EPS. Aim of this work is to assess the relationship between the ensemble error and the ensemble dispersion at different spatial scales. For the summer months 2019, the COSMO-D2 EPS shows a general tendency to overestimate the predictability (underestimate the ensemble spread) of the lightning events, though the spread-error relationship varies greatly for different forecast lead times. With the help of the dFSS, one can also express this relationship in terms of skillful scales. On average, the system produces a useful forecast during the afternoon hours for horizontal scales of around 200 km. However, the ensemble members show an average horizontal dispersion that amounts to around half of that value, at more or less 100 km.


As a type of clean energy resource, salinity gradient power between seawater and river water is important to satisfy the ever-growing energy demand on earth. In the recent years, the use of reverse electrodialysis in biomimetic nanofluidic systems has become a promising way for large-scale and high-efficiency harvesting of the salinity gradient power and surpasses the conventional polymeric ion-exchange membrane-based process. With regard to practical applications, significant efforts have been made towards the design and fabrication of high-performance and economically viable materials and devices. However, while extrapolating from single nanopores to multi-pore membrane materials, the commonly used linear amplification method causes severe deviation from the actual experimental value obtained on nanoporous membranes, particularly at a high pore density. An appropriate simulation method is therefore highly demanded and a great challenge. Herein, we present a general strategy for multi-pore nanofluidic systems by taking the influence of neighbouring nanopores into consideration. We have found that the fourth nearest-neighbor approximation is sufficiently precise for simulation in nanoporous systems. The simulation data are in good agreement with the experimental results. The simulation method provides insights for understanding the pore–pore interaction in porous nanofluidic systems and for the design of high-performance devices.


Industrial effluents constitute a major source of metal pollution of aquatic bodies. Moreover, due to their environmental persistence, toxic metal pollution is of special concern. Microbial reduction is considered a promising strategy for toxic metal removal among the several methods available for metal remediation. Here, we describe the coremediation of toxic Cr(VI) and Te(IV) by the dissimilatory metal reducing bacterium-Shewanella oneidensis MR-1. In the presence of both Cr(VI) and Te(IV), S. oneidensis MR-1 reduced Cr(VI) to the less toxic Cr(III) form, but not Te(IV) to Te(0). The reduced Cr(III) ions complexed rapidly with Te(IV) ions and were precipitated from the cell cultures. Electron microscopic analyses revealed that the Cr-Te complexed nanoparticles localized on the bacterial outer membranes. K-edge X-ray absorption spectrometric analyses demonstrated that Cr(III) produced by S. oneidensis MR-1 was rapidly complexed with Te(IV) ions, followed by formation of amorphous Cr(III)-Te(IV) nanoparticles on the cell surface. Our results could be applied for the simultaneous sequestration and detoxification of both Cr(VI) and Te(IV) as well as for the preparation of nanomaterials through environmental friendly processes.


A large-scale epidemiological study of oral cancer and precancer was initiated in 1966 in several regions of India. Phase 1 of the study consisted of a cross-section survey to determine the prevalence of cancer and precancerous lesions, while phase 2 was a 10-year follow-up survey to determine the incidence and natural history of oral precancer. Following these preliminary investigations, an intervention study was started to try to persuade subjects to give up tobacco, and to measure the subsequent changes in the incidence and regression rate of oral precancer. In each of the three study areas, 12 000 adult tobacco users were selected, examined, and interviewed in a house-to-house survey. Information on the ill effects of tobacco use was given through individual discussions with a social scientist, film shows, and posters. The population was reviewed after one year and the proportions of subjects who had discontinued tobacco use were found to be 2% in Ernakulam, 1% in Bhavnagar, and 5% in Srikakulam. Additionally, between 1% and 16% had reduced their tobacco use. In Bhavnagar and Ernakulam the regression rate of leukoplakia was significantly higher among those who had stopped or reduced their tobacco consumption. In Srikakulam there was a highly significant correlation between reduction in tobacco consumption and regression of palatal lesions.


We investigate the long-run consequences of historic, climatic temperatures (1730-2000) for the modern cross-country income distribution. Using a newly constructed dataset of climatic temperatures stretching over three centuries (18th, 19th, and 20th), we estimate a robust and significant time-varying, non-monotonic effect of climatic temperature upon current incomes for a cross-section of 167 countries. We find a large, positive effect of 18th century climatic temperature and an even larger, negative effect of 19th century climatic temperature upon current incomes. When historic, climatic temperature is introduced, the effect of 20th century climatic temperature on current income is either weakly positive or insignificant. Our findings are robust to various sub-samples, additional geographic controls, and alternative income measures. The negative relationship between current, climatic temperature and current income that is commonly estimated appears to reflect the long-run effect of climatic variations in the 18th and 19th centuries.


Neisseria gonorrhoeae causes the sexually-transmitted infection gonorrhea, a global disease that is difficult to treat and for which there is no vaccine. This pathogen employs an arsenal of conserved outer membrane proteins called TonB-dependent transporters (TdTs) that allow the gonococcus to overcome nutritional immunity, the host strategy of sequestering essential nutrients away from invading bacteria to handicap infectious ability. N. gonorrhoeae produces eight known TdTs, of which four are utilized for acquisition of iron or iron chelates from host-derived proteins or xenosiderophores produced by other bacteria. Of the remaining TdTs, two of them, TdfH and TdfJ, facilitate zinc uptake. TdfH was recently shown to bind Calprotectin, a member of the S100 protein family, and subsequently extract its zinc, which is then internalized by N. gonorrhoeae. Like Calprotectin, other S100s are also capable of binding transition metals such as zinc and copper, and thus have demonstrated growth suppression of numerous other pathogens via metal sequestration. Considering the functional and structural similarities of the TdTs and of the S100s, as well as the upregulation in response to Zn limitation shown by TdfH and TdfJ, we sought to evaluate whether other S100s have the ability to support gonococcal growth by means of zinc acquisition and to frame this growth in the context of the TdTs. We found that both S100A7 and S10012 are utilized by N. gonorrhoeae as a zinc source in a mechanism that depends on the zinc transport system ZnuABC. Moreover, TdfJ binds directly to S100A7, from which it internalizes zinc. This interaction is restricted to the human version of S100A7, and zinc presence in S100A7 is required to fully support gonococcal growth. These studies highlight how gonococci co-opt human nutritional immunity, by presenting a novel interaction between TdfJ and human S100A7 for overcoming host zinc restriction.


This article concerns the history of the curb cut metaphor as applied to personal computer technology in the 1980s. Disability advocates used the metaphor to argue the necessity for accessibility features on computers to enable greater access. To accomplish this goal, these advocates utilized a complex comparison between personal computers and sidewalk ramps to combat assumptions about who the intended computer user was and to argue for how people with different abilities could operate the same technology.


Microservices are supporting digital transformation; however, fundamental tools and system perspectives are missing to better observe, understand, and manage these systems, their properties, and their dependencies. Microservices architecture leans toward decentralization, which yields many advantages to system operation; it, however, brings challenges to their development. Microservices lack a system-centric perspective to better cope with system evolution and quality assessment. In this work, we explore microservice-specific architecture reconstruction based on static analysis. Such reconstruction typically results in system models to visualize selected system-centric perspectives. Conventional models are limited in utility when the service cardinality is high. We consider an alternative data visualization using 3D space using augmented reality. To begin testing the feasibility of deriving such perspectives from microservice systems, we developed and implemented prototype tools for software architecture reconstruction and visualization of compared perspectives.


A K-Ar age of 2300 x 106 years has been determined for a sample of type A crystalline rock (57,34). The presence of an anomalously large quantity of 4�Ar, in a sample of type C breccia (65,35) precluded the calculation of its K-Ar age. Both of the rock types are characterized by low Rb/Sr ratios and consequently low 87Sr/86Sr values. The U-Th-Pb results for a sample of type D fines (84,33) yield a 207Pb/206Pb age of 4760 x 106 years, but ages based on U-Pb and Th-Pb ratios are anomalously high. Isotopic compositions of Li, K, Rb, Sr, U, and Th are very close to the accepted values for terrestrial materials.


A motion imitation and augmentation system comprising an imitation system, a self-collision avoidance system, and a motion augmented system was proposed in this study. The imitation system captures the human skeleton by using an RGB-D camera and a method involving forward kinematics and the space vector method was developed and integrated to map the human joint angles to the motor angles of the robot's arm. To improve safety of the system, a self-collision avoidance system was incorporated so that the various parts of the robot do not collide with each other while imitating human motions. The imitated motion was recorded and stored in a motion dataset as a reference motion. To address different situations and objects, the reference motion was adjusted using the motion augmented system in which both the adjusted trajectory and its corresponding motor angles were generated using the integrated adaptive constricted particle swarm optimization algorithm. So that, the adjusted motion can adapt to the real situation while maintaining similarity with the reference motion. Experiments conducted in practical situations demonstrated the efficiency of the motion imitation and augmentation system. The robot can mimic a reference motion by using its vision and can generate a suitable motion based on the imitated motion for coping with different objects and situations.


This paper presents a new controller for controlling a number of feature points on a robot manipulator to trace desired trajectories specified on the image plane of a fixed camera. It is assumed that the intrinsic and extrinsic parameters of the camera are not calibrated. A new adaptive algorithm is developed to estimate the unknown parameters online, based on three original ideas. First, we use the pseudoinverse of the depth-independent interaction matrix to map the image errors onto the joint space of the manipulator. By eliminating the depths in the interaction matrix, we can linearly parameterize the closed-loop dynamics of the manipulator. Second, to guarantee the existence of the pseudoinverse, the adaptive algorithm introduces a potential force to drive the estimated parameters away from the values that result in a singular Jacobian matrix. Third, to ensure that the estimated parameters are convergent to their true values up to a scale, we combine the Slotine-Li method with an online algorithm for minimizing the error between the estimated projections and real image coordinates of the feature points. We have proved asymptotic convergence of the image errors to zero by the Lyapunov theory based on the nonlinear robot dynamics. Experiments have been carried out to verify the performance of the proposed controller.


Impalement injuries are uncommon in the head and neck region, and when associated with retained foreign body present a challenge to the clinician with regards to management. This type of injury may occasionally be associated with life-threatening complications or permanent disability. Therefore, clinicians involved in the management of head and neck trauma need to be constantly reminded of this uncommon type of injury and the different treatment options.
This is a case report of impalement injury to the palate of a child by a hair weaving instrument. Clinical and plain radiographic examination was sufficient for foreign body localisation. The foreign body was successfully extricated under local anaesthesia and conscious sedation using a simple conservative technique with no complications.


White-tailed deer (Odocoileus virginianus) damage agricultural crops, often leading to signifi- cant economic losses for farmers. We used poly-mesh fence with wings to separate good deer cover from agricultural fields where crop damage by deer occurred primarily along this edge. In these cases, complete enclosure of the field with fencing may be unnecessary. The design used a 2.13-m-high polypropylene mesh fence erected along the wooded edge of a field with either 50-m or 150-m wings extending perpendicular from the fence line and wooded habitat. Fences reduced deer damage in cornfields 13.5% (F1,6 ¼1 , P < 0.001). Average yield in fenced fields (10,211 kg/ha) was 1,708 kg/ha greater than in control fields, which, at US$0.155/kg, equals a net gain of US$265/ha. We found no difference in damage between fences with 50-m and 150-m wings (F1,1 ¼ 0.26, P ¼ 0.695). Costs for materials and labor for erecting partial poly-mesh fences with wings were US$5.56/m and US$1.42/m, respectively. Mean total cost for partial poly-mesh fences with 50-m wings would be US$60.13/ha/year over a 10-year period, compared with US$82.30/ha/year for 150-m wings and US$184.16/ha/year for completely enclosing fields. Expected savings for partial poly-mesh fences with 50-m wings over a 10-year period were US$205/ha/year, as compared with damaged fields without fences. We concluded that poly-mesh fences with 50-m wings were cost-effective at reducing damage by deer to corn. Additional research should be conducted to determine efficacy of the more cost-effective high-tensile and poly-tape fences with wings. 2012 The Wildlife Society.


Clostridium perfringens is a Gram positive anaerobic bacterium that causes a variety of toxin-mediated diseases in humans, such as clostridial myonecrosis (gas gangrene). The production of the important virulence factors of clostridial myonecrosis, α-toxin and perfringolysin O, is regulated by the VirSR two-component regulatory system. The RevR orphan response regulator is also involved in the virulence of C. perfringens as a revR mutant was attenuated for virulence in the mouse myonecrosis model, when compared to the wild-type strain. To further characterize the VirSR and RevR regulatory networks, comparative transcriptomic analysis on the virR and revR regulatory mutants, and the wild type using strand-specific RNA-seq was carried out. The results revealed that VirR and RevR act as global negative and positive regulators, respectively. A total of 18 genes, including the sporulation-specific spoIVA, sigG and sigF genes, were regulated reciprocally by RevR and VirR. RNA-seq reads visualized as a coverage plot showed that there were 97 previously unannotated transcripts in the intergenic regions (SR1-97). These transcripts may potentially encode novel proteins or small regulatory RNA molecules. One of these potential transcripts, SR76, which is located in the intergenic region between the ribU and tex genes, was further characterized. The Northern blot results showed that SR76 was co-transcribed with ribU at the early logarithmic phase and probably is the 5'UTR of the ribU. In silico analysis of SR76 revealed that it is a putative FMN riboswitch, which regulates its target genes in the presence or absence of its putative ligand, FMN. An SR76 null mutant was constructed by allelic exchange. QRT-PCR analysis showed that in the SR76 mutant, ribU was expressed in a higher level compared to the wild type, suggesting that SR76 may regulate gene expression through the formation of a terminator, thus leading to the inhibition of ribU expression. To understand host-pathogen interactions in clostridial myonecrosis, comparative RNA-seq analysis was carried out to measure the expression of both bacterial and murine genes in a murine C. perfringens infection model. The in vivo bacterial transcriptome obtained was compared with the transcriptome of its equivalent in vitro culture. A new subset of putative virulence genes that may be implicated in survival, adaptation and virulence at the early stage of infection were determined from the up-regulated genes during C. perfringens in vivo growth. The pscX gene (cpe0489) was the most highly up-regulated (> log2 7.70) gene in vivo. It encodes a putative flippase, which is postulated to be involved in the synthesis or assembly of the polysaccharides in Gram positive bacteria. This study also provides evidence that the host NLRP3 inflammasome and NFκB pathways were activated as a result of defending the invasion of C. perfringens. This thesis presents the first successful study to simultaneously examine host and pathogen transcriptomes in an infected muscle lesion and thus provides invaluable insights into the infectious process in clostridial myonecrosis.


This thesis presents an investigation into the application of methods of uncertain reasoning to the biological classification of river water quality. Existing biological methods for reporting river water quality are critically evaluated, and the adoption of a discrete biological classification scheme advocated. Reasoning methods for managing uncertainty are explained, in which the Bayesian and Dempster-Shafer calculi are cited as primary numerical schemes. Elicitation of qualitative knowledge on benthic invertebrates is described. The specificity of benthic response to changes in water quality leads to the adoption of a sensor model of data interpretation, in which a reference set of taxa provide probabilistic support for the biological classes. The significance of sensor states, including that of absence, is shown. Novel techniques of directly eliciting the required uncertainty measures are presented. Bayesian and Dempster-Shafer calculi were used to combine the evidence provided by the sensors. The performance of these automatic classifiers was compared with the expert's own discrete classification of sampled sites. Variations of sensor data weighting, combination order and belief representation were examined for their effect on classification performance. The behaviour of the calculi under evidential conflict and alternative combination rules was investigated. Small variations in evidential weight and the inclusion of evidence from sensors absent from a sample improved classification performance of Bayesian belief and support for singleton hypotheses. For simple support, inclusion of absent evidence decreased classification rate. The performance of Dempster-Shafer classification using consonant belief functions was comparable to Bayesian and singleton belief. Recommendations are made for further work in biological classification using uncertain reasoning methods, including the combination of multiple-expert opinion, the use of Bayesian networks, and the integration of classification software within a decision support system for water quality assessment.


The acceleration and transport of energetic electrons during solar flares is one of the outstanding topics in solar physics. Recent X-ray and radio imaging and spectroscopy observations have provided diagnostics of the distribution of nonthermal electrons and suggested that, in certain flare events, electrons are primarily accelerated in the loop top and likely experience trapping and/or scattering effects. By combining the focused particle transport equation with magnetohydrodynamic (MHD) simulations of solar flares, we present a macroscopic particle model that naturally incorporates electron acceleration and transport. Our simulation results indicate that physical processes such as turbulent pitch-angle scattering can have important impacts on both electron acceleration in the loop top and transport in the flare loop, and their influences are highly energy-dependent. A spatial-dependent turbulent scattering with enhancement in the loop top can enable both efficient electron acceleration to high energies and transport of abundant electrons to the footpoints. We further generate spatially resolved synthetic hard X-ray (HXR) emission images and spectra, revealing both the loop-top and footpoint HXR sources. Similar to the observations, we show that the footpoint HXR sources are brighter and harder than the loop-top HXR source. We suggest that the macroscopic particle model provides new insights into understanding the connection between the observed loop-top and footpoint nonthermal emission sources by combining the particle model with dynamically evolving MHD simulations of solar flares.


An ideal legal regime for the governance of water quality would include the following: clear and enforceable obligations on the part of government for the provision of clean water; citizens' rights to the supply of such water; and an ecologically sound approach to the protection of water quality. In Canada, water law has none of these things. Instead, it has at least seven flaws: (1) citizens have no legal right to clean drinking water, and government liability for failing to provide clean water is limited; (2) governments are either reluctant or unable to strictly enforce environmental standards; (3) water management is characterized by an unclear and complex division of powers and responsibilities distributed among three levels of government; (4) water quality is controlled by government, arguably the worst polluter in the country; (5) standards for drinking water are not based upon the precautionary principle; (6) water laws do not protect ecological units such as ecosystems or watersheds; (7) the approach to water management is predominantly remedial, not preventative. This article proposes three steps to mitigate the flaws in Canada's water laws. The first is the creation of the right of private persons to require provincial governments to provide drinking water to prescribed standards. The second is the development of drinking water standards that are based upon the precautionary principle - standards that prohibit all contaminants except those specifically identified. The third is the separation of the function of developing standards from that of achieving them. These three changes would vastly improve the quality and dependability of drinking water in Canada.


Otitis media is the most common disease of children who seek medical care. It is estimated that over 30 million visits to physicians are made per year, and that over one billion dollars are spent annually in the United States for the treatment of otitis media. More prescriptions are written for oral antimicrobial agents for otitis media than any other disease. Antimicrobial therapy is still the mainstay of treatment for children with acute otitis media. Myringotomy (and tympanocentesis) should also be performed when acute otitis media is associated with: severe otalgia, when otalgia or fever persists or recurs in spite of antimicrobial therapy, in the very young or immunocompromised host and when a suppurative intratemporal or intracranial complication is impending or present. Antimicrobial agents should be selected according to the incidence of bacteria prevalent in the community and should be altered depending upon the results of cultures obtained from middle ear aspirates in children who are not responding to the usual antimicrobial agents. Children who experience frequently recurrent acute otitis media (without a middle ear effusion between attacks) should be considered candidates for prophylactic antimicrobial therapy or tympanostomy tube insertion, or both. A middle ear effusion that has persisted for three months or longer should be considered chronic and active treatment should be instituted. A course of antimicrobial therapy should be tried, and if not effective, then a myringotomy with aspiration of the effusion is indicated.(ABSTRACT TRUNCATED AT 250 WORDS)


The paper reveals information about crack behavior during hot rolling of heavy-gauge products. FEM-based mathematical modeling has been used to investigate the impact of crack shape and rolling parameters on the distribution of the principal tensile stress and the Cockroft-Latham fracture criterion value and on the crack closing capacity. The results clearly show that the crack shape has the most powerful influence on the observed quantities followed by the rolling geometry factors. To find a critical value of the LCK for a specific steel grade and an actual rolling process, a laboratory experiment has been conducted, in which problems related to propagation of initial cracks were detected. It consisted in rolling of wedge-shaped specimens with a notch, which was introduced for the purpose of raising the probability of crack occurrence. In order to find the Critical LCK value in the area of the notch, an additional computer simulation was performed. Results of these experiments led to the conclusion that the steel possesses excellent formability. The Critical LCK values were up to 300 MPa, which is, essentially, an order higher than in actual rolling. As the critical value of LCK depends, among others, on the metallurgical characteristics of the metal, the key to the issue is in the steel microstructure. The findings brought the conclusion that in this specific case the rolling itself affects the crack propagation to a small extent only. The heating process poses a much greater challenge, as it is the likely stage involving the steel overheating.


The aim of this paper is to show how to develop a computer assisted learning module entitled "Loop forming mechanism of electronic flat knitting machines". The purpose is to support and modernize the teaching-learning process in the knitting laboratory in case of the discipline "Knitting Technologies - Electronic flat knitting machines". There have been designed and realized interactive animation programs for teaching and learning flat knitting technology with flat knitting machines with the following contents: the description of the flat knitting machine construction, the description of the knitting elements, the explanation of the needle selection principle, the description of the knitting and transfer paths. The module also contains a series of electronic quizzes for self-assessment during the learning module and the final evaluation. The drawings were made using the Corel Draw program, the interactive animations using Corel Rave and the assembly of learning components, by means of ModuleEst program. Laboratory module was designed based on an XML file taken as a model, amended contents needs of the laboratory and then used for transformation in the HTML laboratory module using ModulEst application. Laboratory module has an interactive graphical structure and contains navigation icons for direct access to the bibliography, webography, glossary, summary help page and test for self-programming and verification. The e-learning interactive tools presented in this paper represents the outcome of the process of innovating the working methods applied in the knitting laboratory of the Faculty of Textiles, Leather and Industrial Management of Iasi, within "Gheorghe Asachi" Technical University of Iasi.


area is recommended, with internal administration of a powder containing 1h gr. each of calomel, brucia, and powdered ipecacuanha. The author evidently writes from a small clinical experience of gastric crises in tabes. J. LE F. B. [9] Acute epidemic encephalitis.-CHARLEs H. MINER and STANLEY L. FREEMAN. Amer. Jour. Med. Sci., 1921, clxi, 91. TWENTY cases are analyzed. The following symptoms and signs are noted:Prodromata.-In 18 of the cases seen during the first week of the illness catarrhal symptoms were observed, especially of the nose, like those associated with influenza; there were also pains, headache, frequently vomiting and constipation. These lasted three to seven days. The incubation period was not determined, as no two cases occurred in the same family. In two instances the onset was sudden, with delirium, and in one there was lethargy. Headache was present in all cases, and vomiting in 8. The pyrexia average was seven days. The age incidence was 9 to 78 years; sexes affected, 12 male to 8 female. Cranial nerves.-In 17 cases diplopia occurred, lasting two to four days. The various nerves were affected as follows: the third nerve in 18 cases, the fifth in 9, sixth in 6, ninth in 7, and the eleventh in 3 cases. The facial was frequently involved, and always more on the right side. Symptoms.-Apathy or coma was striking, lethargy lasting two weeks to three months. Delirium was observed in 17 cases, catatonia in 16, ataxia of intentional type in 18, choreiform movements in 11; muscular fibrillation was noted in every case to be a striking feature, often local, but occasionally general in distribution. Tremor, coarse and of intentional type, was also constantly observed. Parkinson's mask was present in all but one of the cases. An eruption was found in 3 cases, in 2 herpetic and in 1 purpuric. Paralysis in the arms and legs was noted in 5 cases, in all of which there was polyneuritis. Euphoria was present in all the cases except those with polyneuritis. All were asthenic. The reflexes showed no constant departure from the normal, and in none was a Babinski's sign obtained. The cerebrospinal fluiid showed Ino change from the normal in its reactions to the various tests, including the Wassermann reaction. Of the 20 cases, 3 died, 1 patient is still very ill at the time of writing, 15 are better, and 1 is quLite well.


High levels of violence against women and impunity in Guatemala have reached crisis proportions and have received increased international attention in recent years. The phenomenon of feminicide (e.g., killings of women in the context of state impunity), is widespread in Latin America and particularly acute in Guatemala. Many (if not the majority) are rooted in violence that becomes concentrated in the family. In this paper, we propose that both the structure and application of the laws in Guatemala contribute to widespread impunity. Police and judges use laws other than those created to address violence against women in order to justify lack of enforcement. For example, judges resist issuing restraining orders, and police refuse to apply them because this can violate perpetrators' property rights. Judges also refuse to apply domestic violence laws because this violates the principle of equality under the law. Women refuse to use the legal system to seek justice because alimony laws will not be enforced and women are economically dependent. The discriminatory fashion in which these laws are applied leads to widespread impunity. Even though laws on the books could be applied otherwise, those who implement them privilege laws that conflict with violence against women laws. While much scholarship focuses on individual-level motives for violence, we instead analyze the socio-legal environment and existing legal codes that enable continued failure to respond adequately to violence against women. The legal framework and the legal code itself are deeply shaped by the context in which they are written—the structural, gender, symbolic, everyday and long arm of political violence that permeate all aspects of life in Guatemala and exacerbate women's vulnerability, especially the poor. We argue that this broader legal context endangers the lives of women in Guatemala. We also extend the socio-legal scholarship to highlight failures for victim's families and the disempowerment of women as they enter relationships.


Ink-jet 3-D printing is a promising additive manufacturing technology with the potential for impacting a wide variety of industries. In typical ink-jet 3-D printing, the part is built up by depositing droplets layer upon layer in an open-loop manner, while curing each layer after it is deposited. Droplet and edge dimensions are typically predicted through extensive experimentation and are assumed to remain constant throughout the printing process. However, there is no guarantee of the consistent droplet shape and dimensions or the smoothness of the finished parts due to the inherent uncertainty in the process. To address this issue, we propose a model-based feedback control law for ink-jet 3-D printing that uses a height sensor for measuring profile height after each layer for determining the appropriate layer patterns for subsequent layers. Toward this goal, a model describing the relationship between height profile change and droplet deposition in the layer building process is first proposed and experimentally identified. Based on this model, a closed-loop layer-to-layer control algorithm is then developed for the ink-jet printing process. The proposed algorithm uses a model predictive control algorithm to minimize the difference between the predicted height and the desired height and the predicted surface unevenness after a fixed number of layers. We also present an extension of the algorithm for two-material printing, which can enable printing of complex 3-D geometry (by using a support material for overhang). Experimental and simulation results show that the algorithm is able to achieve more consistent shapes between layers, reduced edge shrinking of the part, and a smoother top layer surface.


This article is an interview with Hilde Symoens, the fifteenth in a series of Pro Memorie talks with retired Dutch and Belgian legal historians. Born in Brussels in 1943, Hilde Symoens spent part of her youth in Congo, where her parents, still in the colonial era, worked as teachers, She returned with her mother to Belgium in 1958 and started her university studies at Ghent University in 1960. As her father kept on being responsible for the Belgian schools in decolonized Congo, the colonial experience and the more general idea that the world was more than just the village one lives in, were important for her personal view of the world. At Ghent University, Hilde Symoens studied history and engaged in a PhD project on the Low Countries students at the late medieval and early modern university of Orléans. It was the start of a whole scientific career on the prosopography and the social roles of jurists. As a historian, not a jurist herself, she studied particularly 'external legal history'. She married a Ghent professor of medicine, Leo De Ridder, was full professor at the Vrije Universiteit Amsterdam and at Ghent University. She was one of the first women making career as history professor and talks on the incomprehension she met on her way.


In a large majority of animal species, the only contribution of males to the next generation has been assumed to be their genes (sperm). However, along with sperm, seminal plasma contains a wide array of extracellular factors that have many important functions in reproduction. Yet, the potential intergenerational effects of these factors are virtually unknown. We investigated these effects in European whitefish (Coregonus lavaretus) by experimentally manipulating the presence and identity of seminal plasma and by fertilizing the eggs of multiple females with the manipulated and unmanipulated semen of several males in a full‐factorial breeding design. The presence of both own seminal plasma and foreign seminal plasma inhibited sperm motility, and the removal of own seminal plasma decreased embryo survival. Embryos hatched significantly earlier after both semen manipulations than in control fertilizations; foreign seminal plasma also increased offspring aerobic swimming performance. Given that our experimental design allowed us to control potentially confounding sperm‐mediated (sire) effects and maternal effects, our results indicate that seminal plasma may have direct intergenerational consequences for offspring phenotype and performance. This novel source of offspring phenotypic variance may provide new insights into the evolution of polyandry and mechanisms that maintain heritable variation in fitness and associated female mating preferences.


Abstract Objective Finasteride 5 mg is a drug used to treat prostate hyperplasia. Little is known about its pattern of usage. This cross-national analysis of individual-level data from Denmark, Finland, Norway and Sweden was undertaken to appraise its usage and describe cross-national differences. Materials and methods Individual-level data from nationwide prescription registers in Denmark (1995–2009), Finland (1997–2010), Norway (2004–2009) and Sweden (July 2005–2011) were used to examine cross-national finasteride utilization patterns in the adult male population (≥15 years). The study presents period prevalences, incidence rates, waiting time distributions and Lorenz curves. Results During the study period, 295,620 men had at least one prescription redemption of finasteride 5 mg, and there were approximately 3 million dispensing events of finasteride prescriptions in the four Nordic countries. Different patterns of finasteride use were observed among the four Nordic countries. The period prevalence was markedly higher in Finland and Sweden than in Denmark and Norway. In 2009, period prevalences were 18.2/1000 males in Finland and 12.0/1000 males in Sweden compared to 6.7/1000 males in Norway and 4.9/1000 males in Denmark. Incidence rates of finasteride use for Finland, Norway and Sweden were about three times that for Denmark in 2008–2009. Long-term use of finasteride was found in all four Nordic countries with a high ratio between prevalent and incident users. Conclusion Despite resemblances regarding political systems and healthcare services in the Nordic countries, differences in finasteride utilization were found across Denmark, Finland, Norway and Sweden.


Au (III) reacts with DNA at pH 5.6 to form a complex which is sensitive to mid-UV radiation. Cyclobutane pyrimidine dimers are produced at some 15 to 30 times the rate that they are in untreated DNA. The mechanism of photosensitization appears to involve energy absorption by Au-urine and Au-cytosine adducts which can then transfer energy to thymine residues. There is no evidence for a "heavy atom" effect which enables metals such as Ag to mix excited states of DNA and to increase the quantum yields of some photoproducts. The use of mid-UV radiation as a probe for investigating the interaction between DNA and drugs such as sodium aurothiomalate is discussed.


Background Gadolinium-enhancing (GD+) lesions and T2 lesions are MRI outcomes for phase-2 treatment trials in relapsing-remitting Multiple Sclerosis (RRMS). Little is known about predictors of lesion development and regression-to-the-mean, which is an important aspect in early baseline-to-treatment trials. Objectives To quantify regression-to-the-mean and identify predictors of MRI lesion development in placebo cohorts. Methods 21 Phase-2 and Phase-3 trials were identified by a systematic literature research. Random-effects meta-analyses were performed to estimate development of T2 and GD+ after 6 months (phase-2) or 2 years (phase-3). Predictors of lesion development were evaluated with mixed-effect meta-regression. Results The mean number of GD+-lesions per scan was similar after 6 months (1.19, 95%CI: 0.87-1.51) and 2 years (1.19, 95%CI: 1.00-1.39). 39% of the patients were without new T2-lesion after 6 month and 19% after 2 years (95%CI: 12-25%). Mean number of baseline GD+-lesions was the best predictor for new lesions after 6 months. Conclusion Baseline GD-enhancing lesions predict evolution of Gd- and T2 lesions after 6 months and might be used to control for regression to the mean effects. Overall, proof-of-concept studies with a baseline to treatment design have to face a regression to 1.2 GD+lesions per scan within 6 months.


ABSTRACT The authors explored how gender and socioeconomic status (SES) predicted physics achievement as mediated by metacognition and physics self-efficacy. Data were collected from 338 high school students. The model designed for exploring how gender and SES-related differences in physics achievement were explained through metacognition and physics self-efficacy was tested. The result showed that metacognition and physics self-efficacy could explain gender- and SES-related differences in physics achievement. In addition, it was observed that physics self-efficacy mediated the relation of metacognition to physics achievement whereas metacognition did not. This finding means that metacognition contributed to physics achievement through physics self-efficacy.


Responses of Magnolia × soulangiana (Soul.-Bod.) 'Jane' ('Jane' saucer magnolia) to consecutive short term pretransplant drought stresses and recovery after transplanting were evaluated beginning October 1997 and June 1998. Plants were subjected to one (mild) or two (moderate) 3-day drought stress periods or a two 3-day and one 4-day (severe) drought stress period, each separated by two rewatering periods over 24 hours. One day after each stress period, plants were transplanted into the field and well watered to monitor recovery from stress. Plant response was determined by measuring whole-plant CO2 assimilation, leaf gas exchange (CO 2 assimilation, transpiration, stomatal conductance) and canopy growth throughout stress and recovery periods. Whole-plant and leaf CO 2 assimilation were lower for the stressed treatments for most of the measurements taken during stress in the fall and spring. After release from stress and transplanting, leaf CO 2 assimilation returned to control levels for mild and moderate fall stresses within 2 to 3 d by the next measurement, while it was over 3 weeks until recovery from the severe stress. There was no difference in leaf gas exchange following release from stress and transplanting during the spring stress. More rapid defoliation occurred for the severe fall-stressed plants compared to the controls after release from stress in the fall. Flower number was reduced in spring for the fall-stressed plant s. At termination of the experiment, the growth index was lower for severe fall-stressed plants but there were no differences for other fall stress treatments. There was no increase in growth for control or stressed plants for the spring experiment. Drought stress has been shown to reduce leaf CO 2 assimilation


In the field of supramolecular chemistry, supramolecular low molecular weight gelators (LMWG) have attracted the public attention. Supramolecular gel is a very attractive soft materials formed by non-covalent interactions. The frameworks based on non-covalent interactions give the supramolecular gels the most important properties in dynamics and reversibility. Dynamic characters provide a variety of characterisation methods and reversibility enables them to heal structures in respond of external stimuli such as light, heat and so on. This project can be divided into two main parts. At first, gel screening and characterization have done for squaramides 2.1-2.8 which came from the Dr Rob Elmes cooperative laboratory in Maynooth University. Half of the squaramaides were gelators, and one of them was metallogelator which gelled selected solvents together with copper chlorides and nitrates. In order to characterize the physical properties of gels, rheology has been carried out. Secondly, analogues 2.9-2.12 have been synthesised. After that, gel screening and characterisation proceeded for isoniazid and nicotinic hydrazide terminated gelators with both meta-disbstituted aryl linker and tetraethyl diphenylmethane linker 2.9- 2.12. All compands have been analysed by Nuclear Magnetic Resonance (NMR), Mass spectroscopy (MS) and elemental analysis. Analogues 2.9 and 2.11 were found to be good metallogelators in the presence of copper and cadmium chlorides. Gelator 2.10 was able to give a list of partial gels while 2.12 was found to be a non-gelator. The crystals obtained from the gel screen process were send for the single crystal diffraction in order to find out the structure. What is more, typical gels formed from each gelator were charicterised by rheology.


Abstract: Stably transfected Chinese hamster ovary cells expressing either the substance P receptor or neurokinin A receptor were constructed, isolated, and characterized. Equilibrium ligand binding studies performed on whole cells demonstrated that cell lines expressing either of these receptors contained a single class of high‐affinity binding sites with an apparent KD of 0.16 nM for the substance P receptor and an apparent KD of 2.1 nM for the neurokinin A receptor. The higher affinity of substance P for its receptor was accounted for by both a greater association rate constant and a lesser dissociation rate constant. The time course and extent of ligand‐stimulated inositol 1,4,5‐trisphosphate mass increases in both cell lines were similar and displayed rapid and transient kinetics. Ligand‐stimulated cyclic AMP accumulation was also apparent in the cell lines, although the time course and magnitude of the responses were substantially different, with the neurokinin A receptor mediating a greater and more prolonged response. These studies establish the presence of functional substance P receptors and neurokinin A receptors in the stably transfected cell lines and provide evidence for agonist‐dependent differential stimulation of second messenger responses.


Infection of the lower respiratory tract is the most frequent cause of death in patients with cystic fibrosis (CF). Pseudomonas aeruginosa is the predominant pulmonary pathogen; it establishes a chronic endobronchial infection and once acquired is rarely if ever eradicated. Although optimizing nutrition and pulmonary toilet improves the general health of patients with CF, bacterial respiratory infections are neither prevented nor cured. Likewise, attempts to prevent colonization and infection by means of antimicrobial prophylaxis have been generally unsuccessful. Since no effective radical cure for CF pulmonary infections has been found yet, means of preventing respiratory tract colonization have been sought. Immunization of patients who are already colonized with P aeruginosa has failed to eradicate colonization. Vaccines are therefore being sought that will forestall colonization by P aeruginosa, either by preventing adhesion to respiratory mucosa or by enhancing other immunological host defenses.