Abstract Background  During the last decades, the Open Access paradigm has become an important approach for publishing new scientific knowledge. From 2015 to 2020, the Trans-O-MIM research project was undertaken with the intention to identify and to explore solutions in transforming subscription-based journals into Open Access journals. Trans-O-MIM stands for strategies, models, and evaluation metrics for the goal-oriented, stepwise, sustainable, and fair transformation of established subscription-based scientific journals into Open-Access-based journals with Methods of Information in Medicine as an example. Objectives  To present an overview of the outcomes of the Trans-O-MIM research project as a whole and to share our major lessons learned. Methods  As an approach for transforming journals, a Tandem Model has been proposed and implemented for Methods of Information in Medicine . For developing a metric to observe and assess journal transformations, scenario analysis has been used. A qualitative and a two-tier quantitative study on drivers and obstacles of Open Access publishing for medical informatics researchers was designed and conducted. A project setup with a research team, a steering committee, and an international advisory board was established. Major international medical informatics events have been used for reporting and for receiving feedback. Results  Based on the Tandem Model, the journal Methods of Information in Medicine has been transformed into a journal where, in addition to its subscription-based track, from 2017 onwards a Gold Open Access track has been successfully added. An evaluation metric, composed of 5 scenarios and 65 parameters, has been developed, which can assist respective decision makers in assessing such transformations. The studies on drivers and obstacles of Open Access publishing showed that, while most researchers support the idea of making scientific knowledge freely accessible to everyone, they are hesitant about actually living this practice by choosing Open Access journals to publish their own work. Article-processing charges and quality issues are perceived as the main obstacles in this respect, revealing a two-sided evaluation of Open Access models, reflecting the different viewpoints of researchers as authors or readers. Especially researchers from low-income countries benefit from a barrier-free communication mainly in their role as readers and much less in their role as authors of scientific information. This became also evident at the institutional level, as Open Access policies or financial support through funding bodies are most prevalent in Europe and North America. Conclusion  With Trans-O-MIM, an international research project was performed. An existing journal has been transformed. In addition, with the support of the International Medical Informatics Association, as well as of the European Federation for Medical Informatics and of the German Association for Medical Informatics, Biometry and Epidemiology as European and German medical informatics organizations, we did run an international experiment on Open Access incentives. Both together are, as far as the authors know, unique. We therefore expect that this research could add new knowledge on Open Access transformation.


The acceptance of Complementary and Alternative Medicine (CAM) by many countries, including Ghana, into the formal component of healthcare delivery system has been slow, even though the system could contribute towards accessible healthcare.An analysis of the consumption pattern of CAM among people could assist policy in terms of what specific type of CAM could be useful as far as consumer preference is concern. The study found that, households in the low income brackets, as well as people with low levels of education use CAM more. Also most costs variables were found to be significant determinants of CAM use. Given these findings, it is recommended that orthodox healthcare be made more accessible since demand for CAM is low and restricted largely to the poor and illiterates.


Polycrystalline ingots of Co70-xNixGa30 (22 ≤ x ≤ 25) alloys were prepared by a sequence of arc melting high purity Co, Ni and Ga in argon atmosphere, followed by homogenization at 1150°C under a pressure of 10-3 Pa, and quenching in ice water. Structural characterisation of the quenched alloys was carried out to verify the presence of the martensite phase at room temperature. The martensite start (Ms), martensite finish (Mf), austenite start (As) and austenite finish (Af) temperatures for the alloys were determined using a differential scanning calorimeter. The ferromagnetic to paramagnetic phase transition temperature (TC) of the alloys was determined using an indigenously developed ac susceptometer. All the alloys are FSMAs with Ms, Af and TC above room temperature. The composition dependence of the properties of these alloys could be understood on the basis of the e/a (electrons to atom) ratio and the Co/Ni ratio. Presence of γ-phase precipitates along with the β-phase in these alloys enhances the ductility as well as influences the physical properties of these alloys.


Building on Hillocks' (1995) concepts of the declarative and procedural knowledge that writers need in order to craft effective writing, this article explores the writing process of one pre-service teacher as she moved from a personal narrative to an essay to a digital story. The authors argue that digital writers—in addition to needing declarative and procedural knowledge—must also understand knowledge of technology in order to more fully realize the potential of digital storytelling. Implications for teachers and teacher educators are discussed in relation to Mishra and Koehler's (2008) "technological pedagogical content knowledge," or TPACK.


Abstract The Denchai gem sapphire deposits in Phrae Province, northern Thailand are closely associated with late Cenozoic alkaline basaltic rocks. The sapphires occur in alluvial placer deposits in palaeo-channels at shallow depths. Electron microprobe analysis of minor and trace element contents (Fe, Ti, Cr, Ga and V) of the sapphires indicate the following oxide abundances: Fe2O3 (0.32−1.98 wt.%), TiO2 (0.01−0.23 wt.%), Cr2O3 (<0.01 wt.%), Ga2O3 (0.01−0.03 wt.%) and V2O5 (<0.03 wt.%). Optical studies of sapphires revealed three types of primary fluid/melt inclusions. CO2-rich inclusions (Type I) contain three phases (LH2O + LCO2 + V) with the vapour phase comprising <10−15 vol.%. The presence of CO2 was confirmed by microthermometry and laser Raman analysis. Polyphase inclusions (Type II) (vapour + liquid + solid) contain a fluid bubble (20−30 vol.%), an aqueous phase (10−15 vol.%) and several solid phases. Silicate-melt inclusions (Type III) comprise vapour bubbles, silicate glass and solid phases. Proton-induced X-ray emission (PIXE) analysis revealed high concentrations of K (~4 wt.%) as well as Ca (~0.5 wt.%), Ti (~1 wt.%), Fe (~2 wt.%), Mn (~0.1 wt.%), V (<0.03 wt.%), Rb (~70 ppm) and Zr (~200 ppm) in the silicate glass. The Ga2O3 abundances and Cr2O3/Ga2O3 values (<1) of the sapphires favour their formation by magmatic processes. The presence of CO2-rich fluids and high K concentrations in the silicate melt inclusions link the origin of the Denchai gem sapphires to CO2-rich alkaline magmatism.


BACKGROUND
There is a close relationship between premature membrane rupture, bacterial infections and premature labor.

AIM
To study placental histological changes in patients with preterm membrane rupture. To establish a relationship between pathological findings, amniotic fluid and lower genital tract microbiological studies, maternal and neonatal outcome.

PATIENTS AND METHODS
Patients with premature membrane rupture of membranes between 24 and 34 weeks of gestation participated in this study. On admission, patients had no evidence of clinical chorioamnionitis, labor or fetal distress. Microbiological studies of the amniotic fluid and cervicovaginal secretions were performed and the placenta was sent for pathological study.

RESULTS
Seventy one placentas were available for the study. The main pathological findings were acute chorioamnionitis in 58%, trophoblastic proliferation in 38%, funisitis in 37%, villitis in 16%, fetal vascular lesions in 14% and no findings in 17%. Microbial invasion of amniotic cavity was present in 89% of acute chorioamnionitis. Sixty one percent of trophoblastic proliferation and all fetal vascular lesions were associated with negative amniotic and cervical cultures. Newborns with acute funisitis had a higher frequency of neonatal death (29%), severe asphyxia (42%) and neonatal infections (29%).

CONCLUSIONS
Acute chorioamnionitis is the most frequent finding in patients with preterm membrane rupture and microbial invasion of amniotic cavity. In the absence of intra amniotic infection, proliferation of the trophoblast and the presence of fetal vascular lesions predominate. Acute funisitis is strongly associated with adverse fetal outcome.


Amazon's S3 protocol has emerged as the de facto interface for storage in the commercial data cloud. However, it is closed source and unavailable to the numerous science data centers all over the country. Just as Amazon's Simple Storage Service (S3) provides reliable data cloud access to commercial users, scientific data centers must provide their users with a similar level of service. Ideally scientific data centers could allow the use of the same clients and protocols that have proven effective to Amazon's users. But how well does the S3 REST interface compare with the data cloud transfer services used in today's computational centers? Does it have the features needed to support the scientific community? If not, can it be extended to include these features without loss of compatibility? Can it scale and distribute resources equally when presented with common scientific the usage patterns?
 We address these questions by presenting Cumulus, an open source implementation of the Amazon S3 REST API. It is packaged with the Nimbus IaaS toolkit and provides scalable and reliable access to scientific data. Its performance compares favorably with that of GridFTP and SCP, and we have added features necessary to support the econometrics important to the scientific community.


Today, the implementation framework of Zero Energy Building strategies is characterised by a complex transitional phase. In fact, it is still difficult to achieve completely autonomous buildings, disconnected from any power-supply network. Despite the negative impact of climate-change and the progressive loss of non-renewable resources on our lifestyles, the global economic-financial crisis, local cultural-technological barriers, and the cost/complexity of design processes keep investment in this area unattractive. However, there is an intermediate approach that can facilitate a gradual re-direction of building actions through the ZEB logic. It can be identified in the alternative of Near Zero Energy Building (Nearly ZEB or Near Net ZEB). The Nearly ZEB approach, with its multiplicity of design aspects (i.e. cognitive, analytical, technical, and managerial) may configure a widespread state of progressive transition towards the architectural/inhabitable constructions sought by the 20-20-20 logic, at the scale of the building, the city, and the landscape. These constructions have lower emissions, produce more energy from renewable sources, consume less non-renewable energy, and can "also" reach the objective of total energy autonomy (ZEB) or Plus Energy . A twofold operating scenario emerges from this point of view. It is centred on the technological dimensions of designing a Nearly Zero Energy living space by overcoming the traditional concept of a building as a single object. On the one hand, there is a need for a greater interaction between technological innovations and inhabitable spaces, in a trans-scalar key; design becomes an open process of technological-environmental modifications that addresses the transition towards the status of ZEB. On the another hand, it becomes fundamental that the relationship between interior and exterior space, both public and private, is increasingly focused on the design of interface-systems in order to harmonise three new levels of relations (city-building, city-land, and building-land) and to configure a Nearly Zero Energy Oriented Landscape. These aspects emerge from the contributions presented in this special issue on The Technological Dimensions of Nearly Zero Energy Building Design and will be addressed in this essay.


This study aims to determine the role of worldview perspective on science students' decision-making process by a socio-scientific issue-based instruction through an integrated Science Technology Engineering and Mathematics (STEM) education. Understanding the decision-making process in complex themed learning is one of the most important instruments in understanding the way students think. The participants were one hundred and nine junior-high-school students from two different schools. Furthermore, the method used was a pre-experimental design with two collective groups, namely the pre-and posttest, starting with an educational study design. The results showed that there was a different perspective pattern based on the worldview perspective on students' initial decisions. Furthermore, interventions with socio-scientific issues (SSI) based instruction through integrated STEM education provided significant dynamics of change in the final science decision made by the students on the basis of a worldview perspective and gender. Some practical implications were extremely discussed, such as the crucial role of the teacher during a complex lesson topic. Therefore, this study makes an indispensable contribution to the development of the knowledge of science teaching practice, especially on how a decision-making process occurs by a socio-scientific issue-based instruction through integrated STEM education.


Background. Drug resistance has been one of the main obstacles in the fight against vector-borne infectious diseases. Among these diseases, malaria represents a serious public health challenge, mainly in the tropics, where vector-favourable climates are a crucial factor. Each of the various anti-malarial drugs currently used against this disease, such as quinolones, sulphonamides and artemisinins are inadequate and new strategies are required. Peptides are known to have a huge number of biological effects. Antimicrobial peptides (AMPs) have been proven to be effective against bacterial, fungal and viral infections. This study explored the effect of the peptide 'deltorphin-II' in Plasmodium berghei-infected mice. Materials and Methods. Mean percentage parasitaemia was calculated by studying infected erythrocytes after microscopic examination of 10 erythrocytes from infected mice on days 4, 7, 10, 14 and 21 after infection in all groups. Results. Deltorphin-II shows maximum activity at a dose of 0.8 mg/kg/day from day 4 to day 21. Pre-treatment of infected mice with naltriben abrogates the deltorphin-II-mediated effect. Conclusion. Deltorphin-II inhibits the development of malaria, most probably via activation of the δ2 receptor.


Background. Specific clinical risk factors that may be associated with ambulatory outcome following thrombolysis therapy in ischemic stroke patients with pre-stroke depression is not fully understood. This was investigated. Methods. Multivariate analyses were performed to identify predictors of functional ambulatory outcomes. Patient demographics and clinical risk factors served as predictive variables, while improvement or no improvement in ambulatory outcome was considered as the primary outcome. Results. A total of 595 of these patients received rtPA of which 310 patients presented with pre-stroke depression, 217 had no improvement in functional outcome, while 93 patients presented with an improvement in functional outcome. Carotid artery stenosis (OR= 11.577, 95% CI, 1.281 – 104.636, P=0.029) and peripheral vascular disease (OR= 18.040, 95% CI, 2.956-110.086, P=0.002) were more likely to be associated with an improvement in ambulation. Antihypertensive medications (OR= 7.810, 95% CI, 1.401 –43.529, P=0.019),previous TIA (OR= 0.444, 95% CI, 0.517 –0.971, P=0.012), and congestive heart failure (OR= 0.217, 95% CI, 0.318 –0.402, P=0.030) were associated with a no improvement in ambulation. Conclusion. After adjustment for covariates, more clinical risk factors were associated with no improvement when compared with improvement in functional outcome following thrombolysis therapy in an acute ischemic stroke population with pre-stroke depression.


The health benefits imparted by probiotics and prebiotics as well as synbiotics have been the subject of extensive research in the past few decades. What is the real role of probiotics strains, prebiotics and synbiotics in influencing a health? To battle the increase in health care costs, in recent years has been developed a preventive approach to medicine with the development of new probiotics and prebiotics or symbiotic products. Many studies suggest that probiotics, prebiotics and synbiotics supplementation may be beneficial in prevention and management of nutritional and health. While these studies show promising beneficial effects, the long-term risks or health benefits of prebiotics, probiotics and synbiotics supplementation are not clear. In this chapter review the literature regarding available information and summarises the current knowledge on the effects of probiotics, prebiotics, and synbiotics on human health and explore recent trends and developments in this field.


We present a formalisation of the theory of context-free languages using the HOL4 theorem prover. The formalisation of this theory is not only interesting in its own right, but also gives insight into the kind of manipulations required to port a pen-and-paper proof to a theorem prover. The mechanisation proves to be an ideal case study of how intuitive textbook proofs can blow up in size and complexity, and how details from the textbook can change during formalisation. The mechanised theory provides the groundwork for our subsequent results about SLR parser generation. The theorems, even though well-established in the field, are interesting for the way they have to be "reproven" in a theorem prover. Proofs must be recast to be concrete enough for the prover: patching deductive gaps which are relatively easily grasped in a text proof, but beyond the automatic capabilities of contemporary tools. The library of proofs, techniques and notations developed here provides a basis from which further work on verified language theory can proceed at a quickened pace. We have mechanised classical results involving context-free grammars and pushdown automata. These include but are not limited to the equivalence between those two formalisms, the normalisation of CFGs, and the pumping lemma for proving a language is not context-free. As an application of this theory, we describe the verification of SLR parsing. Among the various properties proven about the parser we show, in particular, soundness: if the parser results in a parse tree on a given input, then the parse tree is valid with respect to the grammar, and the leaves of the parse tree match the input; and completeness: if the input belongs in the language of the grammar then the parser constructs the correct parse tree for the input with respect to the grammar. In addition, we develop a version of the algorithm that is executable by automatic translation from HOL to SML. This alternative version of the algorithm requires some interesting termination proofs. We conclude with a discussion of the issues we faced while mechanising pen-and-paper proofs. Carefully written formal proofs are regarded as rigorous for the audience they target. But when such proofs are implemented in a theorem prover, the level of detail required increases dramatically. We provide a discussion and a broad categorisation of the causes that give rise to this.


It has been a strong desire for researchers to control material growth at the molecular and atomic levels. Molecular and atomic layer deposition (MLD and ALD) are two such techniques. In comparison to a huge amount of studies invested on ALD, the research on MLD is still relatively limited due to the difficulty in finding suitable coupling precursors, but the recently successful applications of MLD are very encouraging in many areas such as surface engineering, new energies, and catalysis. In order to further stimulate more research enthusiasm and educate beginners, we contribute this thorough survey on the progress of MLD. This review is a comprehensive account of MLD processes for organic and organic–inorganic materials, covering precursors, surface chemistry, growth characteristics, film properties, and promising applications. The work provides a complete summary of over 80 MLD processes for growing over 20 types of pure polymeric and metal-based hybrid polymeric materials. Given their similarities in mechanisms, we made a comparative description between ALD and MLD, and discussed the uncountable possibilities to combine both ALD and MLD for advanced materials with desirable properties. To feature and highlight the significance of MLD, this review specially gives some detailed discussions on MLD's applications in several important areas, including novel nanostructured materials, surface engineering, new energies (i.e., batteries, supercapacitors, solar cells, and water splitting), catalysis, and rewritable data storage. With this work, we expect to boost research interest and attempts at advanced materials using MLD as well as ALD.


The purpose of this Research Brief Series is to summarize key findings and implications from the Maryland Child Care Choices study, a two-year longitudinal survey of parents who were applying for Temporary Assistance for Needy Families (TANF) in 2011. Families in the Maryland Child Care Choices study have at least one child age six or younger and lived in one of the following counties at the time of their first interview: Anne Arundel, Baltimore, Baltimore City, Calvert, Carroll, Montgomery, and Prince George's.


This paper is about the role of economic grouping as it affects international capital asset pricing models, ICAPM. The conventional ICAPM is extended to include the economic grouping, regional and world factors. Inclusion of the economic grouping factor increases the explanatory power of the asset pricing models. Data on ASEAN (Indonesia, Malaysia, Philippines, Singapore and Thailand) stock markets are used in tests of the proposed models. The economic grouping factor turned out to be most important while the regional factor is least important for asset pricing in these stock markets. While four of the markets have higher systematic risk exposure to the economic group, the Singapore market, the largest market, exhibits higher exposure to world risk. The segmentation of emerging markets offers a possible explanation for these results.


The lineage of a somatic cell can be altered by targeting its signaling networks with small molecules and/or genetically altering the expression of key transcription factors. Depending on the combination of factors, fibroblasts can be fully reprogrammed into induced pluripotent stem (iPS) cells or directly converted into specific cell lineages, bypassing the pluripotent state. The generation of defined target cells will enormously benefit patients who require cell transplantation therapy. In the decade, since iPS cells were first generated, many cell types have been induced from fibroblasts by direct conversion, including hepatocytes. Converted hepatocyte-like cells have been shown to repopulate liver tissues after transplantation in mouse liver disease models, suggesting promise for future application in humans. Thus, to realize safe and efficient cell transplantation therapy, various methods for generating hepatocyte-like cells are being developed. In this review, we summarize the current methods for the generation of hepatocyte-like cells via cell fate modification using extrinsic factors.


The private market of student loans has become an important source of college financing in the U.S. Unlike government student loans, the terms on private student loans (i.e., credit limits and interest rates) are based on credit scores We quantify the effects of credit scores on college investment in a heterogeneous life-cycle economy that exhibits a government and private market for student loans. We find that students with higher credit scores invest in more college education. Furthermore, we find that the relationship between credit scores and college investment has important policy implications. For example, when government borrowing limits are relaxed, college investment increases but so does the riskiness of the pool of borrowers, leading to higher default rates in the private market. If private creditors react to the government policy (by adjusting loan terms to minimize default risk), college investment is offset, with poor students experiencing the largest reductions. The effects of credit scores on college investment are more pronounced when taking into account the recent drop in financial wealth for U.S. households. JEL Codes: E21; E24; I22; I28


Individual differences have long been considered and researched as an important area of applied linguistics, as research findings show clear differences between language learners both in the rate of foreign language learning and in their ultimate success (Dörnyei & Ryan, 2015). Although studies tend to focus on classroom learning mainly, there is a growing demand that the research repertoire should be extended to include context-sensitive studies, as the role and impact of individual differences on learning processes may vary depending on the language learning environment. Such a learning context is the study abroad context, where the importance of individual differences is undeniable: they can play a role in students' initial decision making (Ożańska-Ponikwia & Carlet, 2020; Stroud, 2010), they can potentially shape learning processes during and after study abroad, and their impact can extend to both linguistic and non-linguistic outcomes. It has often been argued that the modernization efforts in language teaching in Hungary in recent decades have not fully achieved their goals (Öveges & Csizér, 2018), and many problems remain in relation to foreign language learning. Among the solutions proposed was the possibility for secondary school students to participate in short international study trips, which, although has not been realized on a large scale yet due to the epidemic situation, is already available to a limited number of students in several secondary schools through Erasmus programs. However, we have very little knowledge about the effects of these trips, either linguistic or non-linguistic. Therefore, the aim of our article is to review the studies in the international literature that have explored the relationship between study abroad experiences and individual differences and, based on this, to identify areas of research that could provide important findings for language teachers, language teacher educators, and policy makers in Hungary.


In this thesis I have analysed the relationship between renewable energy stocks and the price of crude oil. As a part of my analysis I have provided a basic economic overview of the research period and how the value of renewable energy stocks and crude oil is determined. In order to analyse this relationship I have utilized a Vector Autoregressive Model (VAR) in addition to a Vector Error Correction Model (VECM). My findings indicate that the aforementioned assets follow a similar growth path between 2000 and 2007, but after 2009 their trends deviate significantly. A fundamental analysis reveal how GDP growth was responsible for the common growth prior to the financial crisis and how it has contributed to their different trends post the financial crisis. In addition I have analysed how the different sub sectors of renewable energy relate to oil prices. My findings indicate that wind and solar energy stocks are unaffected by oil prices, but biofuel commodities index is affected by changes in oil prices.


We present a model function for the emissivity of the wind roughened ocean surface for microwave frequencies between 6 and 90 GHz. It is an update, refinement, and extension of model functions we had developed previously. The basis of our analysis are brightness temperature (TB) measurements from the spaceborne microwave radiometer WindSat and the Special Sensor Microwave/Imager, which are collocated with independent measurements of surface wind speeds and directions. This allows the determination of the emissivity model function for Earth incidence angles (EIA) around 55°. We demonstrate that an essential part in the model development is the absolute calibration of the radiometer measurements over the ocean to the computed TB of the radiative transfer model, one of whose components the emissivity model function is. We combine our results with other established measurements for lower EIA and finally obtain a model function which can be used over the whole EIA range between 0° and 65°. Results for both the isotropic, wind direction independent part as well as the four Stokes parameters of the wind direction signal are presented. Special emphasis is made on the behavior at high wind speeds between 20 and 40 m/s by conducting a comparison with data from the step frequency microwave radiometer.


Demands for improved aerial vehicle performance have led to the increasing use of composite materials. However, the mechanical behavior and failure modes of composites are not characterized as well as metals, and damages may be more difficult to detect. To overcome this, there is a demand to develop a structural health monitoring (SHM) system for composite aerial vehicles. This paper presents the development of sensor integrated composite wing structure, which is an essential part of SHM system. The composite wing structure was manufactured using an autoclave process, and Fiber Bragg Grating (FBG) optical sensor and piezoelectric (PZT) sensor were installed. The optimal number and location of each sensor system are determined based on the experimental results and Finite Element Analysis (FEA). Installation procedures for FBG and PZT sensor system are developed and validated using tension-tension fatigue tests over 106 cycles.


The motion of a semi-infinite incompressible fluid caused by the sinusoidal oscillation of a plane flat plate is termed Stokes's problem. When the plate starts from rest in a still fluid a transient solution must be added to Stokes's well-known steady-state result. This paper presents a closed-form expression for the transient solution. Previous answers have contained a non-standard integral which could not be evaluated. The answer presented herein contains exponentials and error functions of a complex argument. These functions are readily available in newer mathematical tables. Graphs of the transient solution are presented for both sin (T) and – cos (T) boundary conditions. Velocity distributions in the fluid are also plotted and it is found that the transient period is essentially complete in one-half cycle for the cosine oscillation and in a full cycle for the sine wave case.


In this letter, the authors demonstrate that high quality factor and low power loss transformers can be obtained by using the CMOS process-compatible backside inductively coupled plasma (ICP) deep-trench technology to selectively remove the silicon underneath the transformers. A 62.4% (from 8.99 to 14.6) and a 205.8% (from 8.6 to 26.3) increase in the Q-factor, a 10.3% (from 0.697 to 0.769) and a 30.2% (from 0.652 to 0.849) increase in the maximum available power gain (GAmax), and a 0.43- (from 1.57 to 1.14 dB) and a 1.15-dB (from 1.86 to 0.71 dB) reduction in the minimum noise figure (NFmin ) were achieved at 5.2 and 10 GHz, respectively, for a bifilar transformer with overall dimension of 240times240 mum2 after the backside ICP etching. The values of GAmax of 0.769 and 0.849 are both state-of-the-art results among all reported on-chip bifilar transformers. These results indicate that the backside ICP deep-trench technology is very promising for high-performance radio frequency integrated circuit applications


Heart formation in the zebrafish involves a rapid, complex series of morphogenetic events in three-dimensional space that spans cardiac lineage specification through to chamber formation and maturation. This process is tightly orchestrated by a cardiac gene regulatory network (GRN), which ensures the precise spatio-temporal deployment of genes critical for heart formation. Alterations of the timing or spatial localisation of gene expression can have a significant impact in cardiac ontogeny and may lead to heart malformations. Hence, a better understanding of the cellular and molecular basis of congenital heart disease relies on understanding the behaviour of cardiac GRNs with precise spatiotemporal resolution. Here, we review the recent technical advances that have expanded our capacity to interrogate the cardiac GRN in zebrafish. In particular, we focus on studies utilising high-throughput technologies to systematically dissect gene expression patterns, both temporally and spatially during heart development.


Several studies demonstrate the importance of an early, constant and intensive rehabilitation following cerebral accidents. This kind of therapy is an expensive procedure in terms of human resources and time, and the increase of both life expectance of world population and incidence of stroke is making the administration of such therapies more and more important. The development of new robotic devices for rehabilitation can help to reduce this cost and lead to new effective therapeutic procedures. In this paper we present an exoskeleton for the robotic-assisted rehabilitation of the upper limb. This article describes the main issues in the design of an exoskeletal robot with high performance, in terms of backdrivability, low inertia, large workspace isomorphic to the human arm and high payload to weight ratio. The implementation of three different robotic schemes of therapy in virtual reality with this exoskeleton, based on an impedance control architecture, are presented and discussed in detail. Finally the experimental results of a preliminary evaluation of functionality of the system carried out on one patient are presented, and compared with the performance in the execution of the exercise obtained with healthy volunteers. Moreover, other preliminary results from an extended pilot clinical study with the L-Exos are reported and discussed.


Wireless Sensor Networks (WSNs) enable susceptible sensing of the environment, offering unprecedented opportunities for observing the physical world. Acoustic source localization is an interesting topic with many possible application areas, such as intruder detection, sniper localization, automatic tracking of speakers and so on. Many existing algorithms are on the premise that the exact coordinates of sensor nodes are already known. In this paper, we propose a vector-based advanced TDoA algorithm that would calibrate the coordinate of the acoustic source by the non-prepositioned nodes. In the meanwhile, the portable sensor nodes would adjust themselves through the feedback of the estimated positions as well. Finally, we show that the proposed mechanism has high accuracy through experiments.


We investigated the thermoelectric properties on the GeTe1−xIx (x = 0.0, 0.01, 0.05, 0.1, 0.15, and 0.2) compounds. From the electronic band structure calculation and thermoelectric properties, iodine doping can be regarded as an interstitial doping as well as a substitution at the Te-site, showing a degenerated p-type behaviour. The temperature-dependent electrical resistivity ρ(T) shows a broad shoulder near 450 K due to band convergence between light L- and heavy Σ-bands, which becomes significant with increasing iodine doping concentration. We also found the structural phase transition at 690 K for GeTe and at 650 K for the iodine-doped compounds. In a previous report, the high thermoelectric performance in doped GeTe is attributed to the band convergence effect associated with the structural phase transition. From the Boltzmann transport calculation, the enhancement of high thermoelectric performance is mostly related to the lattice anharmonicity, causing the low lattice thermal conductivity with a high Gruneisen parameter Γ (3.41) as well as the band convergence and structural phase transition effects, resulting in the high thermoelectric figure-of-merit (ZT 1.7 at 673 K) in GeTe1−xIx (x = 0.1).


This paper reports a study of the critical determinants for adopting electronic markets (e-Market) in Australian small-and-medium sized enterprises (SMEs) within the technology-organization-environment (TOE) framework. Structural equation modelling and logistic regression are used for identifying the critical determinants for the adoption of e-Markets by Australian SMEs through testing a proposed conceptual model and proposing an alternative model. This study contributes to existing research by enriching an understanding of the critical determinants of adopting an e-Market in Australian SMEs and by providing a validated model for the interrelationships of the determinants in technology adoption.


Abstract:
 A new species of morning glory from southwestern Mexico, Ipomoea cuprinacoma (Convolvulaceae), is described. The species is assigned to Ipomoea series Arborescentes with other stout lianas and trees, and distinguished from I. populina on the basis of slender stems, canescent peduncles and leaf blades, exclusively axial inflorescences, and long, pale-coppery seed hairs.


Newborn screening (NBS) programmes are essential in the diagnosis of inherited metabolic diseases (IMDs) and for access to disease modifying treatment. Most European countries follow the World Health Organisation (WHO) criteria to determine which disorders are appropriate for screening at birth; however, these criteria are interpreted and implemented by individual countries differently, creating disparities. Advances in research and diagnostics, together with the promise of new treatments, offer new possibilities to accelerate the expansion of evidence-based screening programmes. A novel and robust algorithm was built to objectively assess and prioritise IMDs for inclusion in NBS programmes. The Wilson and Jungner classic screening principles were used as a foundation to develop individual and measurable criteria. The proposed algorithm is a point-based system structured upon three pillars: condition, screening, and treatment. The algorithm was tested by applying the six IMDs currently approved in the United Kingdom NBS programme. The algorithm generates a weight-based score that could be used as the first step in the complex process of evaluating disorders for inclusion on NBS programmes. By prioritising disorders to be further evaluated, individual countries are able to assess the economic, societal and political aspects of a potential screening programme.


When sunlight irradiates a boron-doped p-type solar cell, the formation of BsO2i decreases the power-conversion efficiency in a phenomenon named light-induced degradation (LID). In this study, we used boron-doped p-type Cz-Si solar cells to monitor this degradation process in relation to irradiation wavelength, intensity and duration of the light source, and investigated the reliability of the LID effects, as well. When halogen light irradiated a substrate, the LID rate increased more rapidly than for irradiation with xenon light. For different intensities of halogen light (e.g., 1 SUN and 0.1 SUN), a lower-limit value of LID showed a similar trend in each case; however, the rate reached at the intensity of 0.1 SUN was three times slower than that at 1 SUN. Open-circuit voltage increased with increasing duration of irradiation because the defect-formation rate of LID was slow. Therefore, we suppose that sufficient time is needed to increase LID defects. After a recovery process to restore the initial value, the lower-limit open-circuit voltage exhibited during the re-degradation process showed a trend similar to that in the first degradation process. We suggest that the proportion of the LID in boron-doped p-type Cz-Si solar cells has high correlation with the normalized defect concentrations (NDC) of BsO2i. This can be calculated using the extracted minority-carrier diffusion-length with internal quantum efficiency (IQE) analysis.


Objective: Teachers face high levels of occupational stress, which can influence their mental well-being and contribute to teacher burnout. Healthy levels of exercise, a good diet and adequate sleep can reduce stress and improve mental well-being outcomes. This study explores the characteristics and effectiveness of lifestyle interventions on teachers' mental well-being, including burnout; discusses directions for future programmes; and aims to identify the nature of evidence and gaps in the research field. Methods: A scoping review was conducted in May 2020 via ERIC, Medline, Embase, PsycINFO, Education Source, CINAHL, SPORTDiscus and Scopus databases. The search included relevant peer-reviewed articles on physical activity, nutrition and sleep interventions reporting teachers' mental well-being outcomes. A quality assessment tool was used to appraise the quality and risk of bias of the included studies. Results: Sixteen intervention studies met the inclusion criteria. All studies incorporated physical activity into the intervention; however, only four included aspects of nutrition or sleep. No studies reported only nutrition or sleep interventions alone. The heterogeneity of interventions and their reported outcomes makes comparisons difficult. In general, the quality of the included studies was low due to small sample sizes, poor study design and incomplete reporting of information. Conclusion: Preliminary evidence suggests lifestyle interventions can improve mental well-being outcomes for teachers; however good-quality research is needed to improve the evidence base. Future interventions should have stronger research designs and larger sample sizes and use established measurements for assessing outcomes.


In the DNA binding domain of microphthalmia-associated transcription factor (MITF), four mutations are reported: mi, Mi wh, mi ew, and mi or. MITFs encoded by the mi, Mi wh, mi ew, and Mi or mutant alleles (mi-MITF, Mi wh-MITF, Mi ew-MITF, and Mi or-MITF, respectively) interfered with the DNA binding of wild-type MITF, TFE3, and another basic helix-loop-helix leucine zipper protein in vitro. Polyclonal antibody against MITF was produced and used for investigating the subcellular localization of mutant MITFs. Immunocytochemistry and immunoblotting revealed that more than 99% of wild-type MITF and Mi wh-MITF located in nuclei of transfected NIH 3T3 and 293T cells. In contrast, mi-MITF predominantly located in the cytoplasm of cells transfected with the corresponding plasmid. When the immunoglobulin G (IgG)-conjugated peptides representing a part of the DNA binding domain containing mi and Mi wh mutations were microinjected into the cytoplasm of NRK49F cells, wild-type peptide and Mi wh-type peptide-IgG conjugate localized in nuclei but mi-type peptide-IgG conjugate was detectable only in the cytoplasm. It was also demonstrated that the nuclear translocation potential of Mi or-MITF was normal but that Mi ew-MITF was impaired as well as mi-MITF. In cotransfection assay, a strong dominant negative effect of Mi wh-MITF against wild-type MITF-dependent transactivation system on tyrosinase promoter was observed, but mi-MITF had a small effect. However, by the conjugation of simian virus 40 large-T-antigen-derived nuclear localization signal to mi-MITF, the dominant negative effect was enhanced. Furthermore, we demonstrated that the interaction between wild-type MITF and mi-MITF occurred in the cytoplasm and that mi-MITF had an inhibitory effect on nuclear localization potential of wild-type MITF.


The study of spanning trees and Steiner trees arises naturally in applications, such as in the design of integrated circuit boards, communication networks, power networks and pipelines of minimum cost. In such applications the Steiner ratio is an indication of how badly a minimum spanning tree performs compared to a Steiner minimal tree. In this paper a short proof is presented for the Steiner ratio for points on a triangular lattice in the Euclidean plane. A Steiner tree in two dimensions is "lifted" to become a rectilinear tree in three dimensions, where it is altered. The rectilinear tree is then projected back into the plane and the result readily follows. A short note at the end of the paper compares our threedimensional rectilinear trees to "impossible objects" such as Escher's "Waterfall."


Each agency in the Executive Branch of the Federal government has established programs to facilitate the hiring, placement, and advancement of individuals with disabilities. Self-identification of disability status is essential for effective data collection and analysis of the Federal government's efforts. While self-identification is voluntary, your cooperation in providing accurate information is critical to these efforts. Every precaution is taken to ensure that the information provided by each employee is kept in the strictest confidence.


Over 60% of the information held on the patient record comes from diagnostic tests, according to an estimation by the European Diagnostic Manufacturers Association. Because they are often time consuming and expensive (or even not yet existing), significant effort is currently directed towards developing simple, fast and cheap diagnostic tests. However, adding simplicity, speed and cost effectiveness to the reliability of such tests is one of the main challenges of clinical diagnostics. Electrochemical sensors for detection of proteins, DNA sequences, or cells are regarded by many as appropriate tools to overcome this challenge. Therefore, the present chapter offers an overview of electrochemical sensors able to detect markers of cancer, cardiac diseases, acquired immunodeficiency syndrome, hepatitis, rheumathoid arthritis, celiac disease, and urinary tract infection. The use of nanotechnology in the development of the sensors is one of the main trends observed. Nanotechnology provides a gain in sensitivity but can also lead to reproducibility and reliability problems, high costs, and unclear sensor structure and mechanism of signal generation. Replacing antibodies with aptamers is another trend observed. Compared to antibodies, aptamers are easier to obtain and more robust. Lab‐on‐a‐chip approaches, multiplexing and total diagnosis systems integrating different biorecognition principles on the same platform (e.g. DNA hybridization and immunosensing) appear as part of the future of electrochemical sensors for clinical diagnosis. Adding tests with real samples to the characterization of the sensors with standard solutions is another characteristic of the recent research in the field. Such tests are welcome as they are the only way to eventually achieve a significant acceptance of these sensors outside the research community involved in their development. Electrochemical sensors are still in need of such acceptance.


Motive
In the annual report of TenCate from 2006 it is stated that the aim of TenCate is to achieve an
energy saving of 10% within 10 years. In accordance to this statement, TenCate Protect (TCP)
has proposed a plan to reuse the cooling water used at TenCate Thiolon as process water at
especially TCP. This plan reduces the energy consumption levels of TCP by using, due to the
cooling activity, already preheated process water. However, as there has never been given much
attention to the use of utilities per machine or production step before, it was not possible to give
an acceptable indication about the energy savings possible. Therefore, mass and thermal energy
balances per production step are created in this report. With these balances it not only becomes
possible to give a good indication about the energy savings possible with the water recycling
plan, also other utility saving options can be elaborated on now.
It is recommended to
· adjust the amount of water ( m3/hr) used at the heat exchanger of the ME to the amount
stated on the production specifications ( m3/hr);
· implement the water recycling plan with the piping system mentioned on page 41;
· acquire and install steam consumption measurement devices at the steamers and drying
sections and water consumption measurement devices at the impregnation and washing
sections, in addition to overall steam and water consumption measurement devices per
machine;
· replace the current heat exchanger at the ME and the current first heat exchanger at the
CVM with more efficient ones;
· conduct further research as proposed page 57.
Motivation
As most utility consumption levels per production step were lacking quite some assumptions had
to be made to create the mass and thermal energy balances. Therefore, TCP is recommended to
install measurement devices to increase the accurateness of the input used for these balances.
However, the recommended saving options based on these balances show the great potential TCP
has to save on the utility consumption levels. Even more, when the future gas price will increase
the way it currently does. Several of the proposed options are however already so beneficial, they
should be implemented anyhow. These options are the water recycling plan, the water reduction
at the ME and the heat exchanger replacements. Other options were proposed too. However,
without further research into technical and/or financial details currently lacking at TCP it is not
possible to determine whether or not they are beneficial to TCP.
Consequences
· By implementing the water piping system as mentioned on page 41, taking into account
the capacity levels given on page 34 and a water transfer price of € per m3 to be paid by
TCP to Thiolon, TCP can save about € annually in addition to the annual savings of €
by reducing the amount of water used at the ME.
· Additional savings of € annually are possible by replacing the heat exchanger at the
ME and the first heat exchanger at the CVM. In total, approximately € is needed to
finance the replacement of both heat exchangers.
· Other options, potentially reducing the annual utility costs with at least another € ,
require further research.
· Finally, by measuring the crucial input data for the created balances, the predictive value
of these balances increases. They could then be used for improving amongst others the
cost-pricing methods of the fabric.


It has been shown that human gamma delta T cells expressing the V delta 1 T cell receptor (TCR) respond to the spirochete Borrelia burgdorferi. Lysates of 3 Borrelia genospecies triggered the proliferation of peripheral-blood mononuclear cells not only from patients with skin manifestations of Borrelia infection and from patients with Lyme arthritis but also from healthy donors. However, with the exception of 1 patient with Lyme arthritis, no selective expansion of V delta 1-expressing gamma delta T cells was induced. In contrast, synovial-fluid mononuclear cells (SFMC) from 3 of 5 patients with Lyme arthritis responded with a selective outgrowth of V delta 1 gamma delta T cells. V delta 1 gamma delta T cell lines established from SFMC coexpressed various TCR V gamma chains, although V gamma 8 was preferentially used. Thus, the responsiveness to Borrelia antigens is not a general property of V delta 1-expressing gamma delta T cells but is largely restricted to V delta 1 gamma delta T cells recruited into the inflamed tissue.


Genome stability is vital to the survival and health of eukaryotic organisms. Consequently, many complex mechanisms coordinate with each other in an intricate fashion to ensure that genomes are preserved during duplication and its subsequent propagation. Despite the vast number of factors involved in these processes, their coordinated regulation hinges on a few key components. One such factor is the eukaryotic replicative helicase Mcm2-7, which is a multi-subunit enzyme complex that unwinds DNA during S-phase and paves the way for nascent DNA synthesis by the polymerases. As an essential and highly versatile replisome component, Mcm2-7 is well-suited as the ideal hub for the regulation of not only DNA replication but other fork-related activities such as S-phase checkpoints and sister chromatid cohesion. While all members of the Mcm2-7 complex are highly conserved and essential in all eukaryotes, their contributions towards DNA unwinding are unequal and distinct, and the in vivo functions of most of the Mcm ATPase active sites has remained largely unknown. We conducted an in vivo analysis of a viable mcm2 ATPase active site allele in Saccharomyces cerevisiae and found that under conditions of genotoxic stress it is deficient in the DNA replication checkpoint (DRC) activation, upstream of the Rad53/CHK2 effector kinase. Furthermore, this allele also exhibited a peculiar cell-cycle specific DNA damage phenotype and defective sister chromatid cohesion (SCC) under conditions that are normally conducive to growth. Importantly, these phenotypes manifest from an apparent defect in ATP hydrolysis rather than a qualitative reduction in Mcm2 protein abundance, stability or complex integrity. Therefore, our study demonstrates for the first time that Mcm2-7 can coordinate DNA replication with genome stability through discrete ATPase active sites. Curiously, these functions appear to be separable from general replication defects as shown through a different subset of mcm mutants, indicating that different active sites of Mcm2-7 pleiotropically coordinate various aspects of genome integrity during S-phase.


Biological flows, especially blood flow, have attracted a great deal of attention from fluid engineering and hemodynamic investigation fields with advances in bio-technology. The flow of blood carries dissolved gases, nutrients, hormones, and metabolic waste through the circulatory system in the human body. In the present study, the characteristics of blood flow inside a microchannel are investigated by using a micro-particle image velocimetry (micro-PIV) and an optical image processing technique. The motion of red blood cells (RBCs) was visualized with a high-speed CCD camera. The microchannel is made of polydimethylsiloxane (PDMS) material and a slide-glass is attached to the top. The thickness of the margin cell depletion layer is calculated from an acquired raw image through the image processing method, with variations in microchannel width.


Background Intracerebral hemorrhage (ICH) is a lethal stroke type. As mortality approaches 50%, and current medical therapy against ICH shows only limited effectiveness, an alternative approach is required, such as stem cell-based cell therapy. Previously we have shown that intravenously transplanted human neural stem cells (NSCs) selectively migrate to the brain and induce behavioral recovery in rat ICH model, and that combined administration of NSCs and vascular endothelial growth factor (VEGF) results in improved structural and functional outcome from cerebral ischemia. Methods and Findings We postulated that human NSCs overexpressing VEGF transplanted into cerebral cortex overlying ICH lesion could provide improved survival of grafted NSCs, increased angiogenesis and behavioral recovery in mouse ICH model. ICH was induced in adult mice by unilateral injection of bacterial collagenase into striatum. HB1.F3.VEGF human NSC line produced an amount of VEGF four times higher than parental F3 cell line in vitro, and induced behavioral improvement and 2–3 fold increase in cell survival at two weeks and eight weeks post-transplantation. Conclusions Brain transplantation of F3 human NSCs over-expressing VEGF near ICH lesion sites provided differentiation and survival of grafted human NSCs and renewed angiogenesis of host brain and functional recovery of ICH animals. These results suggest a possible application of the human neural stem cell line, which is genetically modified to over-express VEGF, as a therapeutic agent for ICH-stroke.


An interconnecting technique, the "PDMS connection method", for quartz microchips in a high-pressure system is presented. The connection between quartz microchips is an essential technology for modular microfluidic devices, such as microchip-HPLC. PDMS was applied to the seal material, being spread on the seal side of the chips, and set into the metal housing. The characteristics of the PDMS connection method concerning pressure resistance and the extension of the peak were examined. The experimental results showed a good seal at 5 MPa, which seem to be sufficient for realizing microchip-HPLC utilizing a monolithic silica capillary column as a separation medium. The influence of the extra column effect on chromatographic separation was almost the same as in the case using a commercial union fitting. In addition, the PDMS connection enabled the detachability of chip-based modules with user-friendliness. Our experimental findings suggest that the novel PDMS connection method can possibly be applied as a generic technology in high-pressure μTAS.


In October 2008, the Australian Government released a major report: Australia's Low Pollution Future: The Economics of Climate Change Mitigation. In that report, various scenarios are used to explore the potential economic effects of climate mitigation policy in Australia. One of the scenarios, designated CPRS-5, a Carbon Pollution Reduction Scheme (CPRS) aims to reduce emissions to 5 per cent below 2000 levels by 2020. It is consistent with stabilisation at around 550 parts per million of carbon dioxide equivalent (ppm CO2-e) in the atmosphere by 2100. In assessing the likely effects these policies on the future growth of output and employment by industry, the Government's report relies mainly on economic modelling using the MMRF applied general equilibrium model of the Australian economy. Results are reported for 58 industries. This paper begins by using the same model to closely reproduce the analysis of the CPRS-5 scenario conducted for the report. However, this time the MMRF model is enhanced by a labour market extension MLME which allows the employment results to be extended to 81 occupations and 64 skill groups. The enhanced model is then used in a top-down configuration with an income distribution extension MIDE and a microsimulation extension MMSE to generate changes in income. In MIDE, income redistributions between households (taken collectively), corporate trading enterprises, financial trading enterprises, the government and foreigners (the 'institutions') are modelled by the inclusion of the associated current and capital accounts from the Australian System of National Accounts. Within the household sector, changes in disposable income from unincorporated enterprises (differentiated by 17 industries), compensation of employees (differentiated by 81 occupations), property income, and net transfers from other institutions are separately modelled. On the income side, one hundred types of recipient are identified corresponding to personal income percentiles. On the expenditure side, six hundred types of household are identified, this time differentiated by household income and the ages of its members. This arrangement allows changes in real income to be computed using household specific CPIs. The microsimulation extension MMSE uses MIDE results to update the incomes of more than 13,500 persons. The effects of the climate change mitigation policies on the incomes of various socio-economic groups are then be obtained by aggregation.


Comparison of rainfall data and mean hillslope angles in the Himalayas of central Nepal shows that mean hillslope angles decrease with increasing mean annual rainfall. Higher pore pressures and higher rates of chemical weathering in the wetter regions may decrease the threshold angle of hillslopes prone to landsliding. When valley spacing is held constant, the sensitivity of mean hillslope angle to climate implies that relief, in the absence of limits due to rock strength, is also dependent on climate. These results suggest that wet-to-dry climatic changes increase relief in regions with incising bedrock channels and that dry-to-wet climatic changes reduce relief.


Activities in some kinds of psychotherapy. The main aim of our paper is to contribute to the outline of a general inventory of activities in psychotherapy, as a step towards a description of overall conversational organizations of diff erent therapeutic approaches. From the perspective of Conversation Analysis, we describe some activi- ties commonly occurrring in a corpus of sessions conducted by cognitive and relational-systemic therapists. Two activities appear to be basic: (a) inquiry: therapists elicit information from pa- tients on their problems and circumstances; (b) reworking: therapists say something designed as an elaboration of what patients have previously said, or as something that can be grounded on it; and patients are induced to confi rm/disprove and contribute to the elaboration. Furthermore, we describe other activities, which turn out to be auxiliary to the basic ones: storytelling, procedural arrangement, recalling, noticing, teaching. We fi nally show some ways in which these activities can be integrated through conversational interaction.


The Extraction of Spatial Features from remotely sensed data and the use of this information as input into further decision making systems such as geographical information systems (GIS) has received considerable attention over the few decades. The successful use of GIS as a decision support tool can only be achieved, if it becomes possible to attach a quality label to the output of each spatial analysis operation. Thus the accuracy of Spatial Feature Extraction gained more attention as geographic features can hardly formulated in a certain pattern due to intra-class variation and inter-class similarity. Besides these Spatial Feature Extraction further include positional uncertainty, attribute uncertainty, topological uncertainty, inaccuracy, imprecision/inexactitude, inconsistency, incompleteness, repetition, vagueness, noisy, omittance, misinterpretation, misclassification, abnormalities and knowledge uncertainty. To control and reduce uncertainty in an acceptable degree, a Probabilistic shape model is described for Extracting Spatial Features from multi-spectral image. The advantages of this, as opposed to the conventional approaches, are greater accuracy and efficiency, and the results are in a more desirable form for most purposes.


Previous investigations using 40Ar-ion bombardments have revealed that Zr,Fe, which has an orthorhombic crystal structure, undergoes an irradiation-induced transformation from the crystalline to the amorphous state. In the present investigation, 0.9 MeV electron irradiations were performed at 28-220 K in a high-voltage electron microscope (HVEM). By measuring the onset, spread and final size of the amorphous region, factoring in the Gaussian distribution of the beam, a kinetic description of the amorphization in terms of dose, dose rate and temperature was obtained. The critical temperature for amorphization by electron irradiation was found to be _ 220 K, compared with 570-625 K for 40Ar-ion irradiation. Also, the dose-to-amotphization increased exponentially with temperature. Results indicated that the rate of growth of the amorphous region under the electron beam decreased with increasing temperature and the dose-to-amorphization decreased with increasing dose rate. The size of the amorphous region saturated after a given dose, the final size decreasing with increasing temperature, and it is argued that this is related to the existence of a critical dose rate, which increases with temperature, and below which no amorphization occurrs.


Engineering design must be cost-effective over its complete life cycle and this necessitates a statistical approach to product and service reliability. A particular design therefore has a finite probability of failure during its lifetime and this has implications in terms of ensuring that design procedures, management of design, and operation and inspection are appropriate, effective and sufficient. Sophisticated expert system software packages have enabled wide access to rapid development to prototype and production stages. The expert knowledge encapsulated in such systems may be inadvertently used outside its intended application envelope, leading to unexpected and unwelcome failures. This paper highlights the role of failure analysis and fractography in the context of product reliability. It will present case studies illustrating typical structural reliability problems that highlight issues connected with the 'reliability' of experts in assessing the reasons for failure.


Corals vary in their ability to resist breakage from mechanical force. Biomechanical theory predicts that resistance to mechanical injury should be determined by the morphological properties of coral colonies. However, a general model to predict resistance of corals to mechanical impact from structural characteristics has been lacking. In order to determine whether resistance can be predicted from colony structure, I use a suite of 6 variables-skeletal density, branch thickness, branch spacing, branch length, colony height and colony (projected) area-to quantitatively describe the structure of colonies from 12 species of scleractinian coral. Experimental analysis of the resistance of colonies from each species, which range from massive and tabular growth forms to various branching models, showed that damage susceptibility varied widely. Resistance ranged from very high for species such as Leptoria phrygia, Porites cylindrica and Porites spp. in which there was no reduction in colony area as a result of mechanical stress, to low in species such as Pocillopora damicornis, Seriatopora hystrix and Montipora sp. which suffered over 60% damage. Regression tree analysis revealed a strong relationship between resistance and colony morphology, producing a model which accounted for 76% of the variation in resistance using only 4 of the structural variables: colony height, branch thickness, branch spacing and colony area. Skeletal density and branch length were relatively unimportant in determining susceptibility to breakage. The regression tree model showed potential for development as a predictive tool in reef management, as it was able to predict susceptibility to breakage of corals using 4 easily measured morphological variables with 57 % reliability (estimated by cross-validation).


Tidal energy is one of the major sources of renewable energy. To accelerate the development of tidal energy, improved designs of Tidal Current Turbine (TCT) are necessary. The effect of tower on performance and wake of TCT is investigated using Computational Fluid Dynamics (CFD) simulations. Transient analysis with transient rotor stator frame change model and shear stress transport turbulence model are utilized in ANSYS CFX. An experimentally validated numerical model with full scale tidal turbine with a blockage ratio of 14.27% and Tip Speed Ratio (TSR) 4.87 is used to simulate the effect of different tower diameters on performance and wake. The effect of different tower diameters is quantified in terms of coefficient of performance (CP). Coefficient of performance for a 3.5 m tower diameter is 0.472 which is followed by 3, 2.5 and 2 m with coefficients of performance of 0.476, 0.478 and 0.476 respectively. Similarly, the coefficient of thrust (CT) on the rotor for 3.5 m tower diameter is 0.902, for 3 m diameter 0.906 and for 2.5 and 2 m diameters are 0.908 and 0.906 respectively.


It is well known that there are four classes of Japanese vocabulary with respect to its origin; Yamato vocabulary consists of native morphemes, SinoJapanese consists of borrowed morphemes from Chinese, Foreign is a loanword from a language other than Chinese, and Mimetic describes sounds or manners. Each of these classes has different phonological properties.1 There are three phenomena with respect to the distribution of voice in Japanese. One of them is that post -nasal obstruents in Yamato vocabulary and Mimetic are mostly voiced while those in SinoJapanese and Foreign are not. I will mainly focus on this property in this paper. However, I will also discuss the other phenomena, namely the compound voicing alternation (Rendaku) and the restriction of voiced sounds in a morpheme (Lyman's Law). These phenomena typically occur with Yamato vocabulary only. Although the domain of each phenomenon largely overlaps with a certain class of lexical origin, they do not match completely with each other. The purpose of this paper is to account for the distribution of voice in Japanese by establishing a constraint ranking that covers Japanese vocabulary of any origin. The organization of the paper is as follows. In section 2, I will present data and four problems to be solved. General tendency of Yamato vocabulary are summarized in 2.1, and many exceptions to the generalization are presented in 2.2. In section 3, I will give an analysis using a unified ranking rather than different rankings depending on origins of the vocabulary. In section 4, I will present two pieces of evidence -historical and acquisional--to support my claim that Japanese has only one ranking.


BACKGROUND AND OBJECTIVE Hypochromic iron deficiency anaemia is the most common nutritional deficiency and is a significant public health problem. Hypocrome deficiency anaemia contribution is subject to a variety of etiologic factors and moments acting by different mechanisms. Through the study we wanted to know the incidence and the current trend of development of iron deficiency anaemia in infants, which are risk factors and determinants involved in the aetiology order knowledge and application of preventive measures and treatment. MATERIAL AND METHODS The study was conducted on a group of 88 infants diagnosed with iron deficiency anaemia have been hospitalised in the Paediatric Filantropia Hospital of Craiova during 01.01.2015–30.01.2015. It has correlated iron deficiency anaemia with the following objectives: sex, age, origin, gestational age, nutrition, living conditions, Hb value, morphological examination of peripheral blood, serum iron. The data were collected in sheets and observed statistically plotted. Results In the period under study 205 infants were admitted of which 88 (23.29) were diagnosed with iron deficiency anaemia carential. The area of origin reveals that 43.18% are from rural areas and 56.81% in urban areas. 50% of the living level was precarious, the average was 29.5% and 20.5 had a good standard of living. In 66% cases maternal age at birth was more than 20 years. In relation to the number of births in infants coming from primiparous anaemia was found in 72.72%. The frequency of anaemia was higher in infants with normal birth weight 72.70%, the twins was found in 4.5% and those with low birth weight in 22% cases. 82.95% of infants were fed artificially mixed in 5.6% and 11.3% natural. Incorrect diversification was seen in 65.9%. Mild clinical form was present in 93.18%, 5.68% and average form in the severe form 1.13%. ConclutionS In the study iron deficiency anaemia in infancy was 23.29%. Iron deficiency anaemia are closely correlated with poor socioeconomic level in half of cases. Iron deficiency anaemia in infants is mainly due to lack of maternal deficiency antenatal prophylaxis with direct implications for fetal martial status actually sustained presence at normal weight baby born at term in 72.7% of cases. Iron deficiency anaemia in infants is correlated with artificial nutrition in over 2/3 of cases and that incorrect diversification in over half the cases with digestive disorders as a result of changes in the intestinal mucosa. Anaemia carential iron deficiency is a major public health and requires a joint effort by doctors and paramedical staff on screening and treatment of martial deficiency in the mother-child binomial.


We present an optically pumped 1550-nm vertical-external-cavity surface-emitting laser with improved output power and operating temperature using a bonded heat spreader. The laser comprises an InGaAsP-based gain element, with a resonant periodic gain structure on top of a distributed Bragg reflector, and a high reflectivity spherical mirror as the external reflector. Heat transport is enhanced by a Si heat spreader bonded to the InGaAsP surface by liquid capillary bonding. Optical pumping is achieved using a 1250-nm fiber Raman laser. A maximum continuous output power of 250 mW was obtained under multitransverse mode operation at 240 K. Under operation in the fundamental near-Gaussian mode, we obtained a maximum power of 230 mW with a beam quality factor (M/sup 2/) of 1.22. At room temperature, the output power was limited to 12 mW.


Studies on the sociality of heterospecific assemblages of birds have promoted a greater understanding of the types of interactions and survivorship between coexisting species. This study verified the group compositions in bird assemblages and analyzed the sociality of migratory and resident species on sandy beaches of southeastern Brazil. A transect was established on the median portion of beaches and all the groups of bird species (monospecific, heterospecific) and solitary individuals were registered four days per month from November 2006 to April 2007. The sociality of each species was calculated by its frequency in heterospecific groups, its proportional number of contacts with other species in heterospecific groups, and the number of species that it associated with. Semipalmated Sandpiper Calidris pusilla (Linnaeus, 1766) and Semipalmated Plover Charadrius semipalmatus Bonaparte, 1825 (both migratory) had the highest degree of sociality and did not show a preference to associate with either residents or migratory species. Sanderling Calidris alba (Pallas, 1764) (migratory) occupied the third position in the sociality rank and associated with migratory species frequently. Southern Caracara Carara plancus (Miller, 1777) and Black Vulture Coragyps atratus (Beschstein, 1793) (both resident) were uniquely found among heterospecific groups with necrophagous and resident species. Kelp Gull Larus dominicanus Lichtenstein, 1823 (resident) associated more frequently with resident species. The sociality in assemblages of birds may promote advantages such as an increased collective awareness in dangerous situations and indication of sites with abundant food sources.


Background The present study constructed and validated models to predict PD-L1 and CD8+TILs expression levels in esophageal squamous cell carcinoma (ESCC) patients using radiomics features and clinical factors. Patients and Methods This retrospective study randomly assigned 220 ESCC patients to a discovery dataset (n= 160) and validation dataset (n= 60). A total of 462 radiomics features were extracted from the segmentation of regions of interest (ROIs) based on pretreatment CT images of each patient. The LASSO algorithm was applied to reduce the dimensionality of the data and select features. A multivariable logistic regression analysis was adopted to build radiomics signatures. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive accuracy of these models. Results There was no significant difference between the training and validation datasets for any clinical factors in patients with ESCC. The PD-L1 expression level correlated with the differentiation degree (p= 0.011) and tumor stage (p= 0.032). Smoking status (p= 0.043) and differentiation degree (p= 0.025) were associated with CD8+TILs expression levels. The radiomics signatures achieved good performance in predicting PD-L1 and CD8+TILs with AUCs= 0.784 and 0.764, respectively. The combined model showed a favorable predictive ability compared to radiomics signatures or clinical factors alone and improved the AUCs from 0.669 to 0.871 for PD-L1 and from 0.672 to 0.832 for CD8+TILs. These results were verified in the validation dataset with the AUCs of 0.817 and 0.795, respectively. Conclusion CT-based radiomics features have a potential value for classifying patients according to PD-L1 and CD8+TILs expression levels. The combination of clinical factors and radiomics signatures significantly improved the predictive performance in ESCC.


The structure of the Lower Drift, and the limited area to which it is confined, conspire to show that this country first encountered, and for a long period sustained, the glacial conditions while principally in the state of land; for not only do the limited superficial extent of the formation and its rapid attenuation in all directions, from its great development on the Cromer coast, necessitate an inference that only a small part of England was under water at the time of the deposition of the Lower Drift, but the great masses of chalk and chalky débris that were carried into the marine sediment require us to admit the presence, near at hand, of some terrestrial chalk-area from which these masses were detached; and I imagine that it does not require any illustration here to satisfy geologists of the fact, so obvious from the appearance of the Cromer Cliffs, that much of the chalk of Norfolk was, at the time these masses were imbedded, occupied by a great glacier, from whose seaward termination they were carried and dropped into the marine sediment. In such a state of things we should naturally look for some evidences inland of the terrestrial glaciation which this structure involves. The beds in section on the Cromer Coast, forming the Lower Drift, although of so great a thickness there, alter, as I have elsewhere shown, both in their appearance and thickness inland. South-eastwards, in the direction of Norwich and the Yare Valley, the Lower Drift, or


We present new improved R matrix fits of direct data and indirect Trojan Horse data for the {sup 15}N(p,{alpha}){sup 12}C reaction and provide a more accurate recommended value of S(0)=73.0{+-}5.0 MeV b from direct Redder data [A. Redder et al., Z. Phys. A 305, 325 (1982)] and S(0)=70.0{+-}13.5 MeV b from the Trojan Horse data [M. La Cognata et al., Phys. Rev. C 76, 065804 (2007)]. We also analyze a recent fit by Barker [F. C. Barker, Phys. Rev. C 78, 044611 (2008)] and demonstrate that when all the uncertainties are taken into account, our results overlap with his. We also provide a fit of the Trojan Horse data that properly takes into account finite residual energy resolution of the data.


Currently, there are some traditional approaches for representing digital straight lines, digitized straight line segments and arcs in digital geometry, each with its advantages and suitable applications. However, taking into account the complexities of real-world scenarios involving spurious interferences, the use of these representations requires flexible models. Thus, this study investigates an alternative based on adaptive finite automaton through the device called adaptive digitized straight line segment. Consequently, the proposed method reveals to be simple, intuitive and capable of learning, besides being computationally powerful.


Increased intrahepatic resistance in cirrhotic livers is caused by endothelial dysfunction and impaired formation of two gaseous vasodilators, nitric oxide (NO) and hydrogen sulfide (H2S). Homocysteine, a sulfur‐containing amino acid and H2S precursor, is formed from hepatic methionine metabolism. In the systemic circulation, hyperhomocystenemia impairs vasodilation and NO production from endothelial cells. Increased blood levels of homocysteine are common in patients with liver cirrhosis. In this study, we demonstrate that acute liver perfusion with homocysteine impairs NO formation and intrahepatic vascular relaxation induced by acetylcholine in methoxamine‐precontracted normal livers (7.3% ± 3.0% versus 26% ± 2.7%; P < 0.0001). In rats with mild, diet‐induced hyperhomocystenemia, the vasodilating activity of acetylcholine was markedly attenuated, and incremental increases in flow induced a greater percentage of increases in perfusion pressure than in control livers. Compared with normal rats, animals rendered cirrhotic by 12 weeks' administration of carbon tetrachloride exhibited a greater percentage of increments in perfusion pressure in response to shear stress (P < 0.05), and intrahepatic resistance to incremental increases in flow was further enhanced by homocysteine (P < 0.05). In normal hyperhomocysteinemic and cirrhotic rat livers, endothelial dysfunction caused by homocysteine was reversed by perfusion of the livers with sodium sulfide. Homocysteine reduced NO release from sinusoidal endothelial cells and also caused hepatic stellate cell contraction; this suggests a dual mechanism of action, with the latter effect being counteracted by H2S. Conclusion: Impaired vasodilation and hepatic stellate cell contraction caused by homocysteine contribute to the dynamic component of portal hypertension. (HEPATOLOGY 2008.)


This article deals with the analysis of the factors influencing the formation of communicative and pragmatic competence in the process of teaching foreign students of the Faculty of Philology, Department of Russian Phraseology. The authors prove that the system of training future teachers of Russian has no sections and courses aimed at the formation of communicative and pragmatic competence in Russian phraseology. The study of the assimilation of phraseological units was carried out in several stages. The first is related to the definition of the level of knowledge of the phraseological system of the Russian language. The second is the level of understanding of certain phraseological units by philology students. The third is the ability to express an evaluative attitude towards someone using phraseological units. The fourth is related to the ability to use phraseological units when evaluating something, any event, phenomena.


th Century humanities as the result of conflict ing interference of philological and philosophical methods. Since the 1960s, there have been attempts in literary studies to resist the expansion of interpretative models that often bear on subjective and ideological speculations and borrow from the methodology of other disciplines. The essay gives a generalized historical insight into the dynamics of interrelation between philology and philosophy in the light of the interpretation problem, highlighting kin hostility and tense interdependence of these two disciplines deriving from Platonism. It demonstrates the swing of the pendulum between "philologization of philosophy" and "philosophication of philology" from Wolf, Friedrich Schlegel, and Schleiermacher to Nietzshe and Heidegger. Describing the current crisis in the theories of interpretation, the author argues that academic literary studies may overcome this crisis by following the principle of practical conservatism and methodological reduction. Working in fundamental philological genres (literary history, textology, preparing edited academic collections of classical works, biographical studies, the study of textual poetics, etc.), scholars would benefit from abandoning further search for new interpretative strat egies and adhering to those methods that were already developed within the tenets of the classic 19 th Century philology. This way, it would be possible to overcome the current overlapping between philology and philosophy that, in its turn, more and more conspicuously reorients itself from interpretation as a form of actual statement towards a genre of commentary on the heritage of the past.


Narrowing is one of the primary methods for implementing functional logic programming languages. Property-based testing is an automatic approach to assuring the correctness of software systems. In recent years, a number of systems have been developed that seek to apply the benefits of narrowing in the area of property-based testing. This thesis considers two limitations with these systems. First of all, most of the existing narrowing-based testing tools have focused on practical issues, and lack supporting theory. And secondly, these tools typically only perform well on properties that have particular forms. We address these limitations by developing an approach to narrowing that is both practical and principled, and demonstrate how this can be used to expand the range of properties that can be automatically tested using a narrowing-based approach.


We propose a method for measuring the temperature of strongly correlated phases of ultracold atom gases confined in spin-dependent optical lattices. In this technique, a small number of 'impurity' atoms—trapped in a state that does not experience the lattice potential—are in thermal contact with atoms bound to the lattice. The impurity serves as a thermometer for the system because its temperature can be straightforwardly measured using time-of-flight expansion velocity. This technique may be useful for resolving many open questions regarding thermalization in these isolated systems. We discuss the theory behind this method and demonstrate proof-of-principle experiments, including the first realization of a three-dimensional (3D) spin-dependent lattice in the strongly correlated regime.


Measurements of cruise MSM34 in the frame of the German project SUGAR of 11 heat flow stations in the BEEZ are the first in the Black Sea, purposefully conducted for gas hydrate (GH) study. Maps for the fields of temperature's background and anomaly are gridded with different step and with stations within BSR areas exclusion from the input. Result of the maps' analysis are three hypotheses: 1) GH deposit grows laterally with sequential addition of external subvolumes; 2) the cyclical process of GH subvolumes appearance consists of 7 subprocesses; 3) hypotheses 1 and 2 explain qualitatively the diversity of anomalous geothermal fields over GH deposits. To confirm these hypotheses a 2D straight problem of conductive heat transfer is solved. Input parameters are data from MSM34 and publications from GH research in the region. The results present geothermal evolution of key points in the study volume - curves of temperature (20) and heat flow (12) changes. The times to reach steady state are determined for the main 7 subprocesses. This work is a base for a new quantitative study of GH with the methods of marine geothermy.


Casein kinase I, one of the first protein kinases identified biochemically, is known to exist in multiple isoforms in mammals. Using a partial cDNA fragment corresponding to an isoform termed CK1γ, three full-length rat testis cDNAs were cloned that defined three separate members of this subfamily. The isoforms, designated CK1γ1, CK1γ2, and CK1γ3, have predicted molecular masses of 43,000, 45,500, and 49,700. CK1γ3 may also exist in an alternatively spliced form. The proteins are more than 90% identical to each other within the protein kinase domain but only 51-59% identical to other casein kinase I isoforms within this region. Messages for CK1γ1 (2 kilobases (kb)), CK1γ2 (1.5 and 2.4 kb), and CK1γ3 (2.8 kb) were detected by Northern hybridization of testis RNA. Message for CK1γ3 was also observed in brain, heart, kidney, lung, liver, and muscle whereas CK1γ1 and CK1γ2 messages were restricted to testis. All three CK1γ isoforms were expressed as active enzymes in Escherichia coli and partially purified. The enzymes phosphorylated typical in vitro casein kinase I substrates such as casein, phosvitin, and a synthetic peptide, D4. Phosphorylation of the D4 peptide was activated by heparin whereas phosphorylation of the protein substrates was inhibited. The known casein kinase I inhibitor CK1-7 also inhibited the CK1γs although less effectively than the CK1α or CK1δ isoforms. All three CK1γs underwent autophosphorylation when incubated with ATP and Mg2+. The YCK1 and YCK2 genes in Saccharomyces cerevisiae encode casein kinase I homologs, defects in which lead to aberrant morphology and growth arrest. Expression of mammalian CK1γ1 or CK1γ3 restored growth and normal morphology to a yeast mutant carrying a disruption of YCK1 and a temperature-sensitive allele of YCK2, suggesting overlap of function between the yeast Yck proteins and these CK1 isoforms.


The present study is an analysis of covenantal identity and ritual boundaries based on texts ranging from the Old Testament, the Book of Jubilees, the Dead Sea Scrolls to the New Testament. A pattern of interdependence between group identity and boundary marks is traced, and the following thesis is examined: a community's identity is reflected in boundary marks, and ritual boundaries reflect a corporate identity. By using this general principle to interpret biblical and intertestamental material a pattern emerges: when identity is defined in ethnic categories, boundaries are wide, national boundaries, when identity is defined in particularistic categories, such as priestly purity, boundaries are narrow markers of purity. When identity is changed, boundaries change. Having chosen the Old Testament covenant concept as a term for ecclesiological identity the writer demonstrates that covenantal identity changes in Palestinian Judaism not least because it narrows down and builds on the principle of law. As a result of this, ritual boundaries become narrow marks of law observance. When such an interpretation is challenged by Paul covenant is redefined. The Old Testament and intertestamental pattern of interdependence helps to explain that Paul reinterprets covenant and why old ritual boundaries are replaced. Since for Paul identity is grounded in faith in the one Christ, the ecclesiological boundary is no longer an exclusive covenant rite, such as circumcision, rather baptism is, since it serves as a rite of identification with Christ and a mark of possession of the Spirit. This reflects a radical change in ecclesiology. When Christian baptism is the boundary marker that reflects unity with Christ and serves as an inclusive rite; it simultaneously becomes the only symbol for incorporation in the one church.


This thesis concentrates on improving the performance of low-index-contrast waveguides in terms of reducing the bend losses and increasing the index contrast of waveguides by heterogeneous adhesive bonding and thinning. In the first part of this thesis, we have demonstrated that introducing a thin metallic layer underneath a tight bent polymer waveguide considerably reduces the bend losses, especially for transverse-electric polarization. For proof-of-concept demonstration, the proposed design is implemented on optical waveguides made of epoxy-based negative photoresist, SU-8. Alternatively, the same concept can be applied to various optical waveguide platforms that suffer from high bend losses due to a low refractive index contrast between core and cladding. The wavelength of interest in this study is 1.55 µm. The numerical study carried out in this work indicates that the introduction of a thin gold layer underneath the polymer channel blocks the radiation of the mode and pushes the confined mode back towards the core. The numerical studies and experimental realizations of such low-loss SU-8 based sharp bent waveguides, including fabrication and characterization, is covered in detail in the thesis.
The second optical architecture is the on-chip, small-footprint high-index-contrast undoped/doped potassium double tungstate, KY(WO4)2, waveguides enabled by a novel fabrication technique. Up until now, the fabrication of rare-earth ion doped optical devices in potassium double tungstate material are based on growing a doped layer by liquid phase epitaxy on a bulk undoped KY(WO4)2 substrate. The resulting waveguide architecture has a low index contrast between the active layer and the undoped substrate, which leads to large dimensional cross-sections and a large pump power requirement to fully invert the amplifier core. In this thesis, a heterogeneous integration technique was proposed for the development of high-index-contrast waveguides amplifiers that can be potentially integrated on passive integration platforms. A novel fabrication procedures based on heterogeneous adhesive bonding and thinning is realized. Thin (~2 μm) layers of undoped and erbium doped potassium double tungstate, KY(WO4)2 (n~2), are successfully transferred onto SiO2 (n~1.44) substrates. The very first rib passive and active waveguides are fabricated on the transferred material by focused-ion-beam milling and argon plasma etching techniques.


Considering that a firm's service competitiveness comes from customer service representatives (CSRs)' capability, it is essential to enhance their capability first to create superior customer service. Accordingly, this study provides a way of creating CSRs' capability by proving how organizational knowledge accumulated in knowledge management systems influences their customer response expertise and speed. Moreover, drawing on studies of organization memory (OM), it is defined by the three dimensions of OM level, OM dispersion, and OM usability. To test the proposed model and hypotheses, this study conducted the structural equation modeling analysis using a total of 373 responses collected on CSRs. The results indicate that both OM level and dispersion greatly increase customer response expertise. Besides, OM level, dispersion, and usability enhance customer response speed. Particularly, OM usability is the most effective in improving customer response speed. Finally, CSRs' service performance depends on customer response expertise and speed. this study draws and proves the constructs that can capture CSRs' abilities (i.e., customer response expertise and speed), which are needed to provide good service in call centers, from the study of Jayachandran et al. (2004). Their study has been also applied in following studies that focus on a firm's agility (Roberts and Grover, 2012; Setia et al., 2013). Furthermore, this study proved the effectiveness of two constructs in improving service performance.


The efficacy of landiolol hydrochloride, an ultrashort-acting b-blocker with high b1 selectivity, has been
confirmed in patients undergoing cardiac surgery in Japan, but there have been
few reports about its use for patients having lung resection. We investigated the safety of continuous infusion of
landiolol in patients undergoing lung resection. Between May 2008 and May 2011,
200 patients scheduled for lung resection
were enrolled. Patients who underwent surgery before the introduction of
landiolol in February 2010 were studied retrospectively (Group C) and were
compared with those who received landiolol along with surgery (Group L). During
the 48-hour study period, the incidence of arrhythmias, changes in heart rate
and blood pressure, and occurrence of adverse reactions were examined. The white
blood cell count and C-reactive protein level were measured before and after
surgery to assess the anti-inflammatory effect. The heart rate was
significantly lower in Group L throughout the study period. No patient in Group
L developed hypotension requiring discontinuation of landiolol therapy, and
no respiratory symptoms (including asthma or hypoxemia) were observed. White
blood cell and C-reactive protein were significantly increased after surgery in
both groups, and there were no between-group differences. Arrhythmic events occurred
in 1.1% (1/99) and 9.2% (7/76) of Group L and Group C, respectively. One
patient in Group C developed ventricular tachycardia. Landiolol can be
administered safely during the perioperative period in patients undergoing lung
resection.


Cerebral small vessel disease represents a heterogeneous group of disorders leading to stroke and cognitive impairment. While most small vessel diseases appear sporadic and related to age and hypertension, several early-onset monogenic forms have also been reported. However, only a minority of patients with familial small vessel disease carry mutations in one of known small vessel disease genes. We used whole exome sequencing to identify candidate genes in an autosomal dominant small vessel disease family in which known small vessel disease genes had been excluded, and subsequently screened all candidate genes in 201 unrelated probands with a familial small vessel disease of unknown aetiology, using high throughput multiplex polymerase chain reaction and next generation sequencing. A heterozygous HTRA1 variant (R166L), absent from 1000 Genomes and Exome Variant Server databases and predicted to be deleterious by in silico tools, was identified in all affected members of the index family. Ten probands of 201 additional unrelated and affected probands (4.97%) harboured a heterozygous HTRA1 mutation predicted to be damaging. There was a highly significant difference in the number of likely deleterious variants in cases compared to controls (P = 4.2 × 10(-6); odds ratio = 15.4; 95% confidence interval = 4.9-45.5), strongly suggesting causality. Seven of these variants were located within or close to the HTRA1 protease domain, three were in the N-terminal domain of unknown function and one in the C-terminal PDZ domain. In vitro activity analysis of HTRA1 mutants demonstrated a loss of function effect. Clinical features of this autosomal dominant small vessel disease differ from those of CARASIL and CADASIL by a later age of onset and the absence of the typical extraneurological features of CARASIL. They are similar to those of sporadic small vessel disease, except for their familial nature. Our data demonstrate that heterozygous HTRA1 mutations are an important cause of familial small vessel disease, and that screening of HTRA1 should be considered in all patients with a hereditary small vessel disease of unknown aetiology.