FIELD: medicine, pharmaceutics. SUBSTANCE: invention described immunomodulatory compounds of oligonucleotides individually providing unique profiles of cytokines and chemokines by relation as TLR agonists. The TLP9 agonists aim at modulation of immune responses mediated by Toll-like receptor (TLR). There are also described a composition containing an immunomodulatory compound and a physiologically acceptable carrier and enables producing an immune response in a patient, a method for producing the immune response in the patient with the use of the immunomodulatory compound, methods of therapeutic and preventive treatment in the patient in need of modulation of the immune response, particularly in cancer, autoimmune and inflammatory disorders, an infectious disease, allergy, asthma and other diseases. The immunomodulatory compounds may be used in a combination with other therapeutic agents and chemotherapeutic compounds used in specific diseases or disorders. EFFECT: compounds under the invention create such specific modulations of the immune response different from modulations created by non-methylated dinucleotides CpG. 9 cl, 35 dwg, 2 tbl, 5 ex


Throughout eight years as England's manager, Bobby Robson has maintained a dignified and cautious silence on everything other than matters relating directly to the team he cares so much about. He had refused to comment on some of the press campaigns directed against him, on the personal attacks on his character, often made by ex-players, and on the numerous criticisms made of his style and approach to the job of team manager. Now he breaks his silence to put forward his side of the story.


Fourteen different cDNA fragments encoding serine proteinases were isolated by reverse transcription-PCR from cotton boll weevil (Anthonomus grandis) larvae. A large diversity between the sequences was observed, with a mean pairwise identity of 22%. The cDNAs encompassed 11 trypsinlike sequences classifiable into three families and 3 chymotrypsin-like sequences belonging to a single family. Using a combination of 5 and 3 RACE the full length sequence was obtained for five of the cDNAs, named Agser2, Agser5, Agser6, Agser10 and Agser21. The encoded protein included amino acid sequence motifs of serine proteinase active sites, conserved cysteine residues, and both zymogen activation and signal peptides. Southern blotting analysis suggested that one or two copies of these serine genes existed in the A. grandis genome. Northern blotting analysis of Agser2 and Agser5 showed that for both genes expression is induced upon feeding and is concentrated in the gut of larvae and adult insects. Reverse Northern analysis of the 14 cDNA fragments showed that only two trypsin-like and two chymotrypsin-like were expressed at detectable levels. Under the effect of the serine proteinase inhibitors SKTI and BTCI, expression of one of the trypsin-like sequences was up-regulated while expression of the two chymotrypsin-like sequences was down-regulated. However, these effects were compensative and the overall expression of the four serine proteinase genes decreased little.


We tested the hypothesis that skin and muscle absorb O2 from hyperbaric water by soaking the feet of 10 subjects in tap water (CON; 1.8±0.3 mg·L−1 O2, PO2≈50mmHg, 31.5±0.4C°) or hyperbaric water (HYP; 49.6±1.8 mg·L−1 O2, PO2≈960mmHg 31.8±0.4C°) for 5 minutes. In order to show that oxygen was absorbed from the water, blood flow to the foot was arrested for 12 minutes prior to treatment. The occlusion was maintained during treatment and for 5 minutes following treatment. The rate of muscle O2 consumption (VO2mus) was significantly higher in HYP than in CON (0.009 ±0.001vs. 0.003±0.001ml·100g−1·min−1) at the end of treatment. Also, the concentration of oxidized cytochrome oxidase aa3 increased in HYP by 1.5±0.5μM and decreased 0.3±0.3μM in CON during treatment. Skin PO2 measured over plantar muscles in the arch of the foot after treatment was not different between CON and HYP. The PO2 declined from 162±2 to 53±7 in CON and from 158±9 to 57±9 mmHg in HYP over 5 minutes post‐treatment. The skin PO2 in the big toe of HYP treated feet declined from 177±9 to 129±5 mmHg post‐treatment. Taken together, these data show that a significant amount of oxygen can be absorbed from hyperbaric water by skin. In areas of the foot that lack metabolically active tissues (big toe) excess oxygen accumulates in the skin. In areas that have muscle, oxygen diffuses through the dermal thickness where it is used by the underlying metabolically active muscle..


A Nd: GGG crystal was grown by CZ method.The crystal cracking was studied and the results show that the crystal cracking is related to package, pulling rate,speed of rotation and cooling speed. At last,the optimum growth parameters of Nd: GGG crystal were given:the smaller the radial temperature gradient, the better the crystal.The axial temperature gradient of in-solid-liquid interface is 0.5℃/mm,the pulling speed 2-4mm/h,the rotation rate 20-40r/min,and the cooling speed 20℃/h.A perfect crystal was grown by designing stable temperature field,selecting rational technology parameters and annealing process.


We hereby report an interesting case of tractopathy following COVID-19 vaccine. Acute transverse myelitis following COVID-19 infection or vaccination is well documented. However, to the best of our knowledge, no case of selective tract involvement following COVID-19 vaccine has been reported so far. One case of tract-specific central nervous system involvement following COVID-19 infection has been reported from India. We report the case of a 46-year-old male who developed clinical and radiological evidence of tractopathy involving the corticospinal tracts and posterior columns following the first dose of the Covishield vaccine.


I present a new method which can specifically detect taphonomic bias that affects the community structure of mammalian fossil assemblages. As an illustration, I apply the method to the Paleogene Faunal Zones of the Fayum in Egypt and demonstrate significant taphonomic biases which were not recognized in previous analyses of these assemblages.


Examples of difficult work situations were collected from five different types of jobs by interviewing panels of employees a number of times. The situational causes of difficulty, as perceived by the employees, were classified into a number of ' difficulty factors'. The importance of a factor for the difficulty of a certain job was measured in terms of its frequency in the interview records. Among three broad classes of factors—decision-making, interpersonal contacts, and time-and-energy resources—the decision-making factors had the highest frequency in all five jobs, but the pattern of individual factors differed among jobs. Correlation measures were also obtained, between the intensity of each factor and perceived difficulty, and between the sum of factor scores and perceived difficulty.


Peer-reviews were found as a useful educational activity stimulating social learning but, then again, increasing the teacher's workload. In our paper we investigated the peer-review outputs with the aim to find out the ways of replacing the teacher's evaluation with students reviews. Although the findings are encouraging, an adjustment of the peer-review format and criteria could possibly improve the results.


In order to improve the attenuation frequency range of traditional static two-stage H-type hydraulic muffler, a two-stage follow-up hydraulic muffler driven by gear-screw is designed based on PLC. The Muffler can change its structure parameters according to the rotational speed of the hydraulic pump, and attenuate the two pulsation frequencies of the hydraulic pump. Considering the structural parameters and gear transmission of the muffler, the static and dynamic characteristics of the muffler are analyzed systematically, and the stability of the muffler is verified by the case simulation test. The results show that the two-stage follow-up hydraulic muffler based on PLC can attenuate the two pressure pulsation frequencies at the same time, and the operation is stable and the response speed is fast. The two-stage follow-up hydraulic muffler has practical significance and value to provides a way for engineering hydraulic system noise reduction.


General Motors Corporation which is the first company used the rapid quenching technique to prepare the NdFeB powder whit the nanocrystalline structure. Now, the single roller melt-spinning method which is widely used to prepare the NdFeB powder has become one of the research hot spots of magnetic materials today. In this paper, the numerical simulation model of single roller melt-spinning for ejection process of NdFeB alloy was built and the vacuum chamber cooling roller and sample were taken into account as a holistic system. We had study on the melt spinning ribbons with the different roller speed. The technical parameters is that the pressure is 0.06Mpa and the quartz tube with a mouth diameter of 1 mm, a nozzle height of 3 mm, a roller speed of 15-45 m/s and a vacuum of less than 1×10-2 Pa. In the numerical simulation, we used the NdFeB liquid density about 6 .94 kg/m3 and the viscosity of is 1 .4 pa * s at 1301.


A PV microinverter implemented using interleaved flyback converter (IFC) is investigated. Double-frequency distortion is found in grid current because of using sawtooth time-based SPWM. A forward compensation circuit that eliminates the distortion at primary side is explored that simplifies the output filter design. Maximum power transfer between PV module, IFC, and grid end is modeled. An elaborate experiment is demonstrated to verify the analysis result and performance predictions.


Abstract Many recent studies have diagnosed opposite-signed diffusion eigenvalues to be a prevalent feature of the transfer tensor for diffusive tracer transport by oceanic mesoscale eddies. This diagnosed tensor, which we refer to as the diffusion tensor, therefore accounts for tracer filamentation effects. The preferential orientation of this filamentation is quantified by the principal axis of the diffusion tensor, namely the diffusion axis. Parameterisations of eddy diffusion commonly invoke a diffusion tensor, typically one with non-negative eigenvalues to avoid numerical issues. Motivated by the need to parameterise tracer filamentation, in this study we examine diffusion of a Gaussian tracer patch with imposed opposite-signed diffusion eigenvalues, and in particular we focus on the time scale for the onset of instability. For a fixed diffusion axis, numerical instability is an inevitable consequence of persistent up-gradient fluxes associated with the negative eigenvalue. For typical oceanic scales and diffusion magnitudes, this time scale is of the order of $100$ days, but is shorter for larger negative eigenvalues or for finer grid resolutions. We show that imposing a time-dependent diffusion axis can lead to simulations with no onset of instability after 100 000 days of tracer evolution. Although motivated by oceanographic fluid dynamics, our results have much broader applications since diffusive processes are present in a wide range of fluid flows.


Households in India affected by cardiovascular disease spent 27.2% of their total household budget on out-of-pocket healthcare expenses compared with 10.7% in the matched controls over a 15 day reference period (P<0.01), a new survey has shown.

The study, which was published in Tropical Medicine and International Health ,1 used information from India's National Sample Survey Office from 2004 to estimate the economic burden of cardiovascular disease in Indian homes.

The study also showed that hospital admissions from households that had a family member with heart disease cost 4.5 times more each year than admissions from families that had no heart disease. …


A collection of money cowries (Monetaria moneta) was discovered in the early 1980s inside a bronze cannon salvaged from the wreck site of the Sao Bento (1554), at the mouth of the Mzikaba River, Ea...


In this paper we propose preferential matrix semantics for nonmonotonic inference systems and show how this algebraic framework can be used in methodological studies of cumulative inference operations.


A collection of sunglasses from the 1950s-1970s form the basis of this limited edition artists' book. This is the third book in a series that explores the typographic and image-based potential of personal collections.


Rising literacy and prosperity among sectors of the lower classes, together with an absolute and relative increase in the size of the lower middle class, having a corresponding, emergent ideology and selfconsciousness of its own, can be traced in the comic magazines of the later Victorian era. While Punch established itself as a bastion of upper-middle-class ideology and distanced itself from its earlier radical sympathies, new magazines moved into the expanding cheaper, twopenny market (Punch cost threepence): Fun, founded in 1861,Judy in 1867, and then, in a second wave of even cheaper (one penny) publications, Ally Sloper's Half-Holiday, started in 1884. These may be described as 'petty-bourgeois' magazines par excellence. The complex nature of the new mentality' is nowhere expressed more clearly than in the creation of a character called Ally Sloper, the first truly popular cartoon figure in Britain since Pierce Egan's and the Cruikshanks' Tom andJerry in the 1820s. Ally Sloper was launched first in Judy and spinoff albums, and relaunched in the magazine named after him. The purpose of this article is to describe the circumstances in which he was created and developed (the latter by a woman), establish the significance and the novelty of his characterization and the form it took (short comic narrative strips), and distinguish this version from the better-known, more flamboyant later incarnation. Above all, I hope to show that the comic magazines of the 1870s define a new, self-conscious relationship of an audience comprised of predominantly clerical but also some industrial and crafts workers, and women, with their work. Insofar as art not only reflects but also produces ideology, Ally Sloper and other work-related cartoon types may be said actively to assert lowerclass alienation from and rejection of the traditional concept of useful, humble work. Bourgeois culture had liked to promote a reassuring image of the lower-class worker as thrifty, sober, honest, industrious and disciplined, a type which Ally Sloper diametrically negates. A figure of apparently proletarian origin, Ally Sloper moved essentially in the lower service sector to which any worker might aspire. But his relationship to this sector is that of exploiter, cheat, sharpster. He is a satire upon a sector serviced by the very lower middle class which is Judy's primary audience; at the same time he is an endearing justification of naughty but commonplace fantasies of living by one's wits rather than by real work. Lower-middle-class culture had been reluctant to deal with the idea of labour, industrial or agricultural. Dickens' novels, with their refusal to countenance or understand the idea of labour, much less organized labour as a central, positive, productive social force (see Hard Times) is sufficient testimony to this.2 But Dickens did have a very clear idea of the forces impeding work and the development of the work-ethic: poverty, hunger, disease, and social injustice, which rendered masses of people idle and marginal. Ford Madox Brown too, even as he extolled the noble labourer in his famous painting Work (1852-65), contrasted him with the various kinds of degraded worker, idler and beggar.3 What Brown does not depict is that manifestion of lower-class alienation from real work experienced by the bourgeoisie as the most directly threatening: cheating and stealing. As a cheat, as a species of indirect thief, the 'charming' Ally Sloper serves to defuse the threat, but also to justify it, implying there is a bit of the cheat in all of us. Elite critics such as Carlyle, Ruskin and Morris condemned what Karl Marx engaged to explain scientifically: work under the industrial system had become degraded both as a process and a product. Capitalist social relations, according to Marx, were the institutionalization of the cheating of the working class. Knowing themselves, more or less consciously, to be cheated, the lower classes cheated back the only way they knew how: at each other's expense. The comic magazines, produced and consumed by people close to routine labour and the service sectors where cheating was commonplace, saw this process from within Judy with apparent complaisance, Fun with some bitterness. The degradation of the old manual crafts under the industrial system, especially in the building trades, was the theme of a sustained satirical campaign in the Judy rival Fun, where James Sullivan launched his series called 'The British Working Man', which in some ways is a response (not least in its comic strip format) to Ally Sloper. In Fun, with professed pro-Gladstonian politics the opposite of Judy's, we find a systematic satire on the idea of cheating, here by those very sectors upon which the lower middle class depended for their outward show of status: the builders of their houses, the retailers of their food and clothing. Sullivan castigates unionization among the working class as nothing less than an attempt to legalize the right to slipshod work, idleness, selfishness and exploitation of the private customer


This text is about a new method used on the escriptive geometry for distinguishing the visibility of the line - plane and plane- plane intersection. That is "projection distinguishing methood". This simple and effective way of distinguishing and drawing is a good one for the visibility.


Mouse hepatitis virus(MHV) is a common coronavirus.The standard strain MHV-A59 was used to infect 6 strains of mice(BALB/c,C57,nu/nu,NIH-Ⅲ,IL-4T and IL-10T) in three paths(belly,oral route and nasal instillation).The detection of the antibody variations of infected mice in a month showed that the seroconversion to MHV occurred generally at 5-7 days after infection,and the highest IgG level could reach at about 3 weeks.The IgM level rose earlier than the IgG level did.It began to rise at 3 days or so,and reach the highest at 7 days.After 3 weeks it began to decrease.But there was a significant difference in susceptibility and tolerance of the mice to MHV because of their different genetic backgrounds.Also there was a certain difference between different routes of infection.The seroconversion to MHV and the highest IgG and IgM levels occurred earlier by belly than by oral route and nasal instillation.For the mice infected by nasal instillation,the seroconversion to MHV occurred later and remained longer.So it was concluded that the persistence of immunity produced by the mice infected with MHV depends on immune routes to a great extent.


X‐ray diffraction is used to study the phase behavior and structure of the Au(001) surface between 300 K and the triple point. For T>1170 K, the x‐ray reflectivity is consistent with a thin, disordered surface film. At T=1170 K, there is a reversible transition to an incommensurate, hexagonal overlayer that resides on top of the square substrate. At 970 K, the orientation of the hexagonal layer rotates discontinuously by 0.81 ° with no observable change in incommensurability.


��� The year 2007 in Vietnam was bracketed by two events that could go down in history as watersheds in the country's post-Cold War life. On 11 January, Vietnam began its membership in the World Trade Organization (WTO). In December, thousands of Vietnamese took to the streets to protest against China's claims to the Paracel and Spratly Islands in the South China Sea. The accession to the WTO marked the full integration of Vietnam into the Western-led international system, closing a protracted process that began twenty years ago and opening a new era in the country's economic life as well as its relations with the outside world. The anti-China protests demonstrated the re-emergence of nationalism, and with their suppression by Vietnamese authorities, that the banner of patriotism has changed hands from the state to alternative elite groups that are Internet-based and wealthy. These protests and Beijing's urge to suppress them have put Hanoi in a dire strait where it cannot avoid taking sides. Vietnam has just arrived in the world but already stood at a crossroads. The WTO Era, Year One Vietnam's economy in 2007 continued to gain momentum in an overall stable macroeconomic environment but challenges and pitfalls are also mounting up, suggesting that it might be evolving into a bubble economy. Gross domestic product (GDP) reached US$71 billion and per capita GDP stood at US$835, double the figure of 2001. The country's balance of payments recorded a high


Using the Chern classes defined by Grothendieck, we map a K-theoretic invariant of invertibte symmetric matrices defined by Giffen to the Clifford invariant.


The effects of cobalt (Co) addition on structural and optical properties of TiO2 nanopowders have been investigated. A co-precipitation method was employed to synthesize TiO2 nanoparticles with various Co additives from 0-10 mol% using tetrabutyl titanate and Cobalt (II) nitrate hexahydrate as starting precursors for Ti and Co source, respectively. The crystallinity of Co-doped TiO2 nanopowders is heightened by calcination process. The crystal structure, phase formation and the corresponding functional groups of Co-doped TiO2 were analyzed by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The scanning electron microscope (SEM) was taken to observe their morphologies. The chemical compositions of Co additive into TiO2 matrix are confirmed by EDAX. Their optical properties were investigated by diffuse reflectance spectroscopy. Diffuse reflectance spectra of samples exhibit the increasing absorption in visible region with an increasing Co content. The overall characterization results indicated that the crystallinity and optical properties of TiO2 nanoparticles are significantly affected by Co dopant.


A member of the Local Group, IC 1613 is a gas rich irregular dwarf galaxy that appears to have formed stars continuously over the last 10 Gyr and is relatively independent of external influences from other galaxies. This paper aims to study the spatial distribution of the asymptotic giant branch (AGB) population in IC 1613 and its metallicity. Using WFCAM on UKIRT, high quality JHK photometry of an area of 0.8 deg^2 centered on IC 1613 was obtained. The data have been used to isolate the C- and M-type components of the AGB population and using their number ratio, C/M, a global mean metallicity has been derived. The metallicity and the TRGB magnitude have been studied as a function of distance from the galactic centre and as a function of azimuthal angle. The tip of the RGB (TRGB) has been found at K_0 = 18.25 +/- 0.15 mag. The colour separation between the C- and M-type components of the AGB population has been located at (J-K) = 1.15 +/- 0.05 mag, giving a global C/M ratio of 0.52 +/- 0.04 and from this an iron abundance of [Fe/H] = -1.26 +/- 0.07 dex has been calculated. The AGB population has been detected out to a radial distance of 4.5 kpc in the de-projected plane of the galaxy. The measured TRGB is consistent with previous measurements and no significant variation is detected in the TRGB or in metallicity either with galactocentric distance or azimuthal angle.


We consider the minimization of a continuous function over the intersection of a regular cone with an affine set via a new class of adaptive first- and second-order optimization methods, building on the Hessian-barrier techniques introduced in [Bomze, Mertikopoulos, Schachinger, and Staudigl, Hessian barrier algorithms for linearly constrained optimization problems, SIAM Journal on Optimization, 2019]. Our approach is based on a potential-reduction mechanism and attains a suitably defined class of approximate first- or second-order KKT points with the optimal worst-case iteration complexity $O(\varepsilon^{-2})$ (first-order) and $O(\varepsilon^{-3/2})$ (second-order), respectively. A key feature of our methodology is the use of self-concordant barrier functions to construct strictly feasible iterates via a disciplined decomposition approach and without sacrificing on the iteration complexity of the method. To the best of our knowledge, this work is the first which achieves these worst-case complexity bounds under such weak conditions for general conic constrained optimization problems.


The history of marriage as an institution in the Republic of Ireland cannot be looked at without understanding and appreciating its historical Catholicism and the role that the politically-systematised Roman Catholic Church in the public and private guardianship of marriage as both a religious sacrament and a contractual obligation carrying legal rights and duties. The sacrament of marriage in the Roman Catholic tradition contains spiritual and contractual elements, thus inviting conflict between goals and obligations encompassed in the two marriage perspectives. The sacramental qualities surrounding the marriage contract and its basis in canon law proffered the canonical foundations on which Ireland based its Constitution. In essence, marriage and the rights to it were (are?) a dual institution that creates a religious sacrament and legal contract and the subsequent overlap of Canonical and Constitutional doctrines in Irish marriage law. This Essay grapples with the issue of divorce and its significant role in impeding the right of marriage in Ireland. Prior to the 1996 constitutional amendment legalising divorce, individuals were effectively caught between the anvil of the Church and the hammer of the State.


Gene expression data being high-dimensional and redundant, dimensionality reduction is of prime concern. We employ the algorithm Fuzzy Clustering Large Applications based on RAN-domized Search (FCLARANS) for attribute clustering and dimensionality reduction based on the study of gene ontology and differential gene expressions. The use of domain knowledge helps in the automated selection of biologically meaningful partitions. The use of Gene Ontology (GO) study helps in detecting biologically enriched and statistically significant clusters. Fold-change is measured to select the differentially expressed genes as the representatives of these clusters. Tools like Eisen plot and cluster profiles of these clusters help establish their coherence. Important representative features (or genes) are extracted from each enriched gene partitions to form the reduced gene space. While the reduced gene set forms a biologically meaningful gene space it simultaneously leads to a decrease in computational burden. External validation of the reduced subspace, using various well-known classifiers, establishes the effectiveness of the proposed methodology.


As a result of a rather intensive and very successful collecting trip in Guatemala in 1942, it has been possible not only to recognize practically all of the species of Membracidae which have been reported from that country, but to add a large number of new locality records and to describe sixteen new species.


Abstract. A new species, Cyanocephalus veadeiroensis, from the Chapada dos Veadeiros region, Goiás state, which was first recognized on Facebook, is here described and illustrated. This new species is unique due to the combination of densely imbricate leaves obscuring the stems, the leaves longer than the internodes, the secondary veins almost parallel to the main vein, the margin entire to serrate and the leaf apex acuminate. The new species is compared with morphologically similar species such as Cyanocephalus adpressus and Cyanocephalus lanatus. We also provide comments on the distribution, ecological aspects and recognition of this taxon.


For a prime element r of a frame L,a concrete functor Ir on the category L-Top is introduced.The composition of the stratification Lowen functors ωrL and ιrL is proved,and some applications are given.Finally,the relationship between it and Rodabaugh′s stratification functor GLk is studied.


The Archimedes Project is studying smart houses as part of a larger topic of "Human Centered Interfaces to Ubiquitous Computers." Our research strongly suggests that the success of smart houses will depend on the creation of Intelligent Environments that embody the following three components: 1. A smart infrastructure that adheres to widely accepted standards 2. Smart appliances from many manufacturers that adhere to these standards 3. Human-Centered Interfaces that automatically adapt to the needs of individual users.


Alberta spent the better part of the last decade of the 20th century becoming the paragon of fiscal virtue.1 Following a 1993 election fought over the nature of Alberta's spending, the Alberta government set the standard for having a clean and closely controlled fiscal framework by vigorously reducing its expenditures. And it reaped the rewards by paying down its debt and making tax cuts that enhanced critical productivity, including the move to a single rate of personal income tax. The recent return to deficits in Alberta has raised the question of whether the province has a spending problem. The answer to this question has important implications for how the province addresses its deficit. If Alberta has a spending problem, it makes sense to focus on expenditure reductions to reduce the deficit. If not, then relying on economic growth or tax increases might be the appropriate response.


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Refractive indices and birefringence changes with strain produced by different stresses in annealed and unannealed polypropylene fibres (4 :1 draw ratio, 515 tex polypropylene from Bolton, UK) were measured interferometrically. Calculations were carried out using multiple-beam Fizeau fringes in transmission to determine the Cauchy's constants, dispersive coefficient and the dielectric constant at infinity. The orientation factor and orientation angle of the fibre material were calculated for different strain values. Poisson's ratio and the strain optical coefficient were also determined. An empirical formula is suggested to correlate the orientation factor, orientation angle, area of cross-section and birefringence with the draw ratio, and the constants of this formula were determined. The effect of the draw ratio on the refractive index profile was studied. Microinterferograms and curves are given as illustrations.


PROBLEM TO BE SOLVED: To provide a melt-molded product comprising an EVOH resin composition which emits less smell and is excellent in long-run workability. SOLUTION: The melt-molded product comprises an ethylene/vinyl alcohol copolymer resin composition having a ratio (d/t) between the content of a phosphoric acid compound (D) in terms of a phosphate radical conversion amount (d: μmol/g) and the content of a phosphorous element (t: μmol/g) of ≤0.4. COPYRIGHT: (C)2008,JPO&INPIT


Austenitic stainless steels are often used for components in demanding environment. These materials can withstand elevated temperatures and corrosive atmosphere like in energy producing power plants. They can be plastically deformed at slow strain rates and high alternating or constant tensile loads such as fatigue and creep at elevated temperatures. This study investigates how deformation rates influence mechanical properties of an austenitic stainless steel. The investigation includes tensile testing using strain rates of 2*10-3/ and 10-6/s at elevated temperatures up to 700°C. The material used in this study is AISI 316L. When the temperature is increasing the strength decreases. At a slow strain rate and elevated temperature the stress level decreases gradually with increasing plastic deformation probably due to dynamic recovery and dynamic recrystallization. However, with increasing strain rate elongation to failure is decreasing. AISI 316L show larger elongation to failure when using a strain rate of 10-6/s compared with 2*10-3/s at each temperature. Electron channelling contrast imaging is used to characterize the microstructure and discuss features in the microstructure related to changes in mechanical properties. Dynamic recrystallization has been observed and is related to damage and cavity initiation and propagation.


The aim of this study is to get a deeper understanding about user tests as well as answer the question about if testing for users is necessary at all times. I've done a comparison between what the ...


This article analyzes two alterations of the general order included respectively in the buildings of the National Center for Metallurgical Research (CENIM, 1963) and in the Calculation Center of the former Savings Bank Postal (1975) by Alejandro de la Sota. Both respond to practical aspects of their organization, but at the same time they involve aspects of meaning regarding the relationship of heterogeneous parts within the same project. They are included in the same study since they can establish common aspects differentiated from the rest of the projects, also utilitarian and related to work programs in De la Sota's work. These aspects are especially linked to effects on the regularity of their project nettings. As indicated in annotation to the text –although its discussion has not been addressed within it because it exceeds the available space– a comprehensive examination of the composition between fundamental parts of other buildings of similar programs has been necessary to appreciate the real uniqueness existing in the here considered. The particularities of each one has invited a careful analysis that reveals their contributions to the total composition and the character of the spaces by them generated.


Since its start in the Netherlands Traffic Demand Management (TDM) has worked with car miles (kilometres) to measure success or failure in projects. Difficult research, lack of standardisation, and lack of appeal with theprimary interest group (businesses), were reasons for considering car miles no longer appropriate for TDM. This has moved the Ministry of Transportto introduce a new tool: the 'car ratio'. 'Car ratio' stands for the number of commuting cars related to the number of employees. The result is a figure between 0 and 100 that offers a clear indication of the number of cars a business has to deal with daily. The introduction has taken the form of a ready made research package that gives every business simple means tomeasure its own 'car ratio'. In addition, a booklet with documentation was produced to offer information to consultants and interested organisations. Introduction of the 'car ratio' will enable TDM to set an important step forward to a more mature approach to reducing car use in commuting traffic. For the covering abstract of the conference see IRRD 887581.


Information, advice and support to children and young people with special educational needs or disabilities. The SENDIASS team is available 8:45am to 5:00pm, Monday to Friday. Tel: 0121 303 5004
Email: email@example.com


Cancer is a complex devastrating disease with increase incidences in recent years. Despite the availability of many anticancer drugs. Disease pathogenecity profile convincingly evidenced that this is due to metastatic spread for which successful therapy is not available . In this direction we have identified from the laboratory that targeting galectin-3 would be a potential therapeutic approaches in addition to the use of antioxidants, cytoprotective and DNA protective compounds since celluar DNA damage mediated by oxidative radicals are the soul cause of the disease. For this the current study on the 2-hydroxy 4-methoxy benzaldehyde (HMBA) and its modified derivative Oximes is succesful in many bioactivity assays performed. The free radical scavenging activity of the derivatives 2-hydroxy 4-methoxy benzaldoxime (HO) and 2,4- di hydroxy benzaldoxime (DHO) showed 5 and 30 folds increase in activity. Besides in other bioactivities such as cytoprotectity, H+K+ATPase inhibitory activity, Tyrosinase Inhibitory activity, DNA protectivity indicated that either no significant differences or HMBA showed much better than the derivatives. Since the current study had yielded a better antioxidant-sister molecule combination of HMBA and its derivatives may work choesively and arrest many of disease advancing reactions. Also the bioavailibilty studies indicated substantially good results unlike other phenolics and could be confirmed after tissue distribution studies. Besides, a natural carbohydrate polymers from Bael (Aegle marmelos) showed good galectin-3 mediated metastasis inhibition in in vitro experiments. Since no treatment is available for this, the natural polymer could be used to develop strategic anticancer compoun from natural source. The galectin-3 inhibition was further substatiated with amount of galactose (19%) and high amount of Uronic acid. In whole the study showed potential multi step role of HMBA, HO, DHO and Pectic from bael as depicted in scheme1 could be used as potential therapy in progression of diseases like cancer and ulcer.


Lithium niobate single crystal has been found to be a versatile material in the field of nonlinear devices due to its excellent electric-optical, dielectric and nonlinear optical properties. When LiNbO3 device serves as holographic storage media, it is often required a big dynamic range, a big sensitivity and a high photo-damage resistance ability. Although Fe-doped LiNb03 in holographic storage is one the most widely investigated crystals and takes on better comprehensive merits, its performance is severely limited by the low photo-damage resistance ability when LiNbO3 is operated on high laser intensity. Indium is one of the beneficial impurity ions for suppressing photo damage. In this paper, we grown a series of Fe:In:LiNb03 crystals with a varying content of In doping by Czochraski technique. On the basis of the ultraviolet-visible absorption spectra measurement and two-wave coupling experiment, the effect of In ions on photorefractive properties is explored and discussed systematically. It is found that the photorefractive properties can be greatly enhanced by In doping in Fe:LiNb03. Among the four samples of Fe:In:LiNbO3 crystals, the Fe:In(2 mol%):LiNbO3 crystal has the highest photorefractive sensitivity and the largest dynamic range (1.79 cmJ-1 and 2.10, respectively) and can resist higher intensity laser irradiation. Our analysis indicates that increased photoconductivity is mainly responsible for the excellent photorefractive comprehensive properties. It is believed by the experimental results that Fe:In(2 mol%):LiNbO3 crystal is a promising holographic storage medium.


Background: One of the most serious and contagious disease, associated with considerable effects on quality of life and death rates is bacterial meningitis. Urgent diagnosis, treatment, and prevention are required in 10 to 20% of survivors with advancing debilitating neurologic complications. In developing countries the prevalence of meningitis is usually high in low-socioeconomic status. Objective: To determine the Diagnostic Accuracy of Post Contrast FLAIR MR imaging for suspected meningitis in pediatric patients taking Lumbar Puncture as Gold Standard. Methods: The Study was done at Department of Radiology, in which calculated sample size was 100 children with suspected meningitis aged 2 – 12 years of age. MRI brain was performed from vertex to the base of skull on PhilipsTM Achieva 1.5 tesla (T) MR System. Following MRI exam, CSF was collected via LP of each patient. The statistical analysis was done using SPSS package version 19.0. Results: Post contrast FLAIR MRI findings were positive in 48 (48 %) while negative in 52 (52 %) while lumbar puncture revealed positive findings in 51 (51 %) while negative in 49 (49 %). Sensitivity of the post contrast FLAIR MRI was 78.43 % while specificity was 83.67 %, diagnostic accuracy was 81.00 %. Conclusion: The most authentic, secure and potent diagnostic tool for the detection of meningitis among suspected children is post contrast FLAIR magnetic resonance imaging. Our study represents that post-contrast FLAIR MRI has high sensitivity, specificity and detecting accuracy in diagnosis of meningitis among influenced population.


These last years, atmospheric pressure plasma jets formed by pulsed helium discharges
ignited in thin dielectric tubes have been extensively studied due to their potential for
biomedical applications. So far, most experiments have been dedicated to the study of the
plasma plume. For endoscopic treatments, it is also important to better understand and
optimize the propagation of discharges in long dielectric tubes as catheters. First we present
an experimental and numerical study on the dynamics of a s helium plasma discharge
with N2 admixture in a long dielectric tube. We compare the velocity of the discharge
front for various amounts of N2 and dierent applied voltages and show a good agreement
between experiments and simulations. Second, we compare time-resolved measurements and
simulations of longitudinal and radial electric elds associated with plasma propagation in
the dielectric tube and in the plasma plume. It is interesting to note that measurements
obtained with a probe located outside the dielectric tube are in excellent agreement with
simulations. This allows to infer from simulations the time evolution of the electric eld on
the discharge axis which is a key parameter for applications.
Acknowledgment: The authors acknowledge the computational resources of the
Mesocentre of Ecole Centrale Paris.


The triglycoside isorhamnetin-3-0-a-L-rhamnopyranosyl-(l -+2)-0-[a-L-rhamnopyranosyl-(l-»6)]-/?-D-glucopyranoside (///) from flowers of Calendula officinalis L. was isolated together with the already known gly cosides isorhamnetin-3-0-/?-D-glucopyranoside (/) and isorhamnetin-3-0-ör-L-rhamnopyranosyl-(l-»6)-0-)5-D-glucopyranoside (narcissine, //). The total content of flavonoids in ligulate ray-florets and tubular disc-florets inclusively involucra was found to be 0.88 and 0.25 %, respectively.


Amorphous iron oxide (Fe_2O_3) was prepared by the pyrolysis of iron pentacarbonyl [Fe(CO)_5] in a modified domestic microwave oven in refluxing chlorobenzene as a solvent under air. The reaction time was 20 min. Partially separated particles of iron oxide, 2–3 nm in diameter, were obtained. The other part showed aggregated spheres with a diameter of 25–40 nm. Differential scanning calorimetry measurements showed an amorphous/crystalline phase transition at about 250 °C.


For the first time satellite laser ranging (SLR) measurements from LAGEOS are revealing changes in geodetic station positions suggestive of predicted global tectonic plate motions. A detailed discussion of the latest SLR results is given herein. Since the accuracy of tectonic plate velocities increases with the repetition rate and accuracy in the measurement of interplate distances, activities are also described for increasing the temporal resolution and precision of baseline determinations. The LAGEOS laser data for the period January 1979 to the end of 1982 have been reanalyzed. The results of this analysis are now approaching the useful accuracies required by geophysics. For the better annually determined stations they include consistencies of 2–3 cm in station heights and 2 cm in annual baselines. The SLR results show overall agreement with the geologic tectonic rate model of Minster and Jordan with a linear cross correlation of 0.61 for 34 observed interstation rates. Improved temporal resolution was obtained in the measurement of specific baselines of moderate length through the large number of simultaneously observed passes.


The Ecoweb " There is something I do not understand here. Why are you writing about ecosystems after the world market and the whole of human history? So far I thought we were going from small to big. " And you were right, Spite! We are still going from small to big. Humankind with all its global glory and a few thousand years of written history only occupies a part of Gaia's ecosystem, which has been developing for almost 4 billion years (Schidlowski, 1988; Holland, 1997). On our seventh and last trip into Netland, we shall learn about the properties of the oldest and biggest network of all: the ecoweb. The ecoweb is not a birthday party. Here links are built between predators and prey, consumers and food. You either eat – or you are eaten. 1 Ecowebs display the usual network characteristics, such as small-worldness and scale-freeness, but differently. When we eat, we get really close to each other: the now proverbial six degrees of separation of human societies go down to two degrees of separation in ecowebs (Williams et al., 2002). However, path length and other small-world characteristics, like clustering of ecowebs, do not typically differ from those of random graphs (Dunne et al., 2002a). A bona fide scale-free behavior can only be demonstrated for smaller ecowebs with low connectivity or for modules of larger ecological networks. In fact, many ecowebs display a degree distribution with a single characteristic degree, which makes them similar to random graphs (Dunne et al., 1 We usually consider ourselves to be at the top of the food chain. However, if we really think about it, the King of Nature is the pit bull. (Pit bulls occasionally consume humans. On the other hand, oriental cuisine has other dog delicacies than pit bulls, as far as I know. The same cannot be said for sharks, which consume us more systematically, but may also end up on our table on an unlucky day in the history of sharks.)


Lettuce (Lactuca sativa) is a vegetable cultivated and consumed throughout the year for its morphological and sensory characteristics. There are many varieties of different sizes, colors and flavors of this vegetable. Although it is a well-known crop at the agronomic level, there are not many studies related to the sensory profile of this vegetable. This is why the Fundacio Miquel Agusti has decided to carry out a study on the most relevant attributes of lettuce and how to evaluate them to create a useful work tool for future studies on this vegetable. The main objective of this work is to perform the necessary steps to obtain the descriptors that characterize the lettuce and prepare a tasting sheet for the training of a panel of tasters. To achieve this, a consumer tasting was carried out at the Escola Superior Agricultura de Barcelona, where through the resulting information, and once contrasted with the existing bibliography, the sensory attributes that describe the lettuce were obtained. At this point, the necessary references for the correct evaluation of the different descriptors have been determined. The first results obtained are the attributes that describe the lettuce: brightness, green-yellow leaves, red leaves (quantity of anthocyanins), intensity of smell, intensity of flavor, bitterness, sweetness and crunchy texture. The appropriate references for the evaluation of the descriptors obtained have also been determined, and a lettuce tasting sheet has been prepared for the training of a panel of tasters.


The political identity sorting that has been observed to occur during the past 50 years has caused the nation as a whole to hold more overlapping political identities, which has strengthened the activism, bias and anger that result from strong and highly aligned identities, even though issue positions have remained moderate. In this paper I offer a clear definition of polarization and a theory-based explanation of the mechanism by which polarization has increased over the last few decades. Specifically, I view polarization in terms of political behavior, not issue positions, and I believe that it has been increasing over the last 50 years as a result of political identity sorting. This theory is informed by work in social psychology that makes concrete predictions about the psychological results of group membership. Using this theoretical background, I argue that political identity and the alignment of political identities is able to drive political participation, political bias, and political anger, even when issue positions are moderate. The more strongly aligned the political identities, the stronger the effect of identity on behavior. I support these hypotheses using data drawn from a nationally-representative sample collected by Polimetrix from a National Science Foundation grant.


This article argues that if the learning area Life Orientation is to give substance to the recommendations of the James Report (2000) values will have to be imaginatively apprehended and reinterpreted in each life situation. This article explores ways of using language and literature study to give imaginative access to xenophobia, a key social problem in South Africa (and beyond) and so taking Life Orientation beyond the letter of the lay to honouring its 'spirit, purport and objects' (Constitution 39.(2)). The three literary works used in this case are Judges 12 (New International Bible), Snow Falling on Cedars (David Guterson) and Welcome to our Hillbrow (Phaswane Mpe). Life Orientation, as a learning area in the school curriculum


FIELD: engines and pumps. SUBSTANCE: stand for diagnostics and cleaning of nozzles of an automobile internal combustion engine equipped with a low-pressure gasoline injection system. The stand has a microprocessor control system with software. The stand enables conducting diagnostics and cleaning of nozzles with an electromagnetic drive by supplying chemical liquid cleanser (CLC) to their hydraulic inlets or combined CLC and air, and supplying control pulses to nozzles with an electromagnetic drive. Parameters of diagnostic modes are stored in the stand memory, eighteen cleaning units with controlling frequency-modulated pulses in wide range of rotation frequencies of internal combustion engine and eight technologically complete programs of cleaning consisting of four cleaning units each automatically executed without operator's participation. EFFECT: improved labour productivity and efficiency of nozzles cleaning with electromagnetic drive. 3 cl, 73 dwg


In this study a logarithmic modeling for Direct Load Control programs (DLC) as incentive-based Demand Response Programs (DRPs) is presented. The proposed model considers nonlinear behavioral characteristic of elastic loads which causes to more realistic modeling of demand response to DLC rates. To demonstrate the validity of the proposed technique, a real world power system is considered as test system. Where, Iranian power system is investigated. Simulation results emphasis on the effectiveness impact of running DLC programs using proposed logarithmic model on load profile of the peak day of the proposed power system.


The present invention relates to a battery management system which checks from a remote place the condition of each battery by the type and characteristics of the battery and a target device in which the battery is to be used, and performs the inspection and maintenance for efficient battery management, and to a service providing method. The battery management system according to the present invention comprises: a battery for supplying power, via the charge-and-discharge operation, to the device of a user who holds a membership; a sensor module connected to the battery to detect battery conditions including voltage, current and temperature and to prepare cell data for the battery on the basis of the detection results; a cell management section for receiving the cell data prepared by the sensor module via a data communication network, and analyzing the cell data to identify whether the battery operates normally; a membership management section for managing information of the user who holds a membership; an electronic payment section for proceeding with a charging procedure; and a communication section for communicating with the sensor module.


The concept of Imtila (plethora) is defined vividly and scientifically in Unani classical literature. Imtila (plethora) is the most common humoral disease and has multiple etiology and clinical manifestations. The signs and symptoms associated with Imtila (plethora) are headaches, clogged eyes, pulsatile conduits, flushing of the face, puffiness of the face, inability to speak, heavy head and dark and dense urine, etc. Long-lasting effects of untreated Imtila (plethora) can lead to various co-morbidities, such as Jarayan al-Dam (Haemorrhage), Tashannuj (Convulsion), Sakta (Apoplexy), Falij (Paralysis), Junun (Insanity) Hidhayan (Delirium), Ghashi Imtila'i (Syncope), Ufunat-e-dam (infection in the blood), Dasoomat e Dum (dyslipidemia), etc. Therefore, it is essential to identify the symptoms of Imtila (plethora). Early detection will aid in obtaining urgent medical attention and treatment, which can reduce complications. Unani physicians used various methods to eliminate surplus, harmful, and undigested humour that might have further tainted the humour. Unani physicians prescribed various exercises and regimens in combination with food and drugs to restore the humoral balance of the body. The present review paper systematically emphasizes the proper understanding of Imtila (plethora) to understand its etiopathogenesis, signs, & symptoms, and complications. We have also discussed the course of treatment suggested by Unani physicians considering the physiopathology and clinical characteristics.


BP Solar has utilized long term module exposure data and field return data to determine module lifetimes, expected failure rates and to identify failure mechanisms. While outdoor testing is a must for understanding PV reliability, it takes much too long to be of use in determining the effects of changes in materials, processes or equipment. This paper describes how BP Solar utilizes accelerated stress testing to verify the robustness of its new PV products


【This paper suggests an algorithm that can estimate the direction of the sound source in real time. The algorithm uses the time difference and sound intensity information among the recorded sound source by four microphones. Also, to deal with noise of robot itself, the Kalman filter is implemented. The proposed method can take shorter execution time than that of an existing algorithm to fit the real-time service robot. Also, using the Kalman filter, signal ratio relative to background noise, SNR, is approximately improved to 8 dB. And the estimation result of azimuth shows relatively small error within the range of ${\pm}7$ degree.】


A is to provide an improved spring-type drive for pressing the plunger in the improved injector device and the housing that can reduce the total time required for placement of the infusion set in a forward position (drive). An essentially non-removable fixed to a medical insertion needle (insertion needle is being projected from the end portion of the extending and cannula through a subcutaneous infusion set) through a and patient skin plunger having a and quickly cannula subcutaneous injection set easily injector device that can be percutaneously placed. .FIELD 1


For the problem of remaining useful lifetime (RUL) prediction of nonlinear system, the existing methods have not systematically carried out the studies on nonlinear degradation modeling with measurement error and random effect, priori parameter estimation and the corresponding RUL prediction. In this paper, a nonlinear Wiener process is used to establish a nonlinear degradation model with the consideration of measurement error and random effect to describe the implicitness, personality difference and nonlinearity of degradation process of a class of device. The expectation maximum (EM) algorithm is used to obtain the estimates of the fixed coefficient and the priori distributions of the random coefficients in the degradation model. Using the current monitoring data of the target device, the posteriori distribution of random coefficients is iteratively updated based on Bayesian inference. Using the full-probability formula, the remaining useful lifetime distribution of device is derived based on the first hitting time (FHT) distribution. A simulation example is analyzed to verify the correctness and advantage of this method.


Bridge decks deteriorate over time as a result of freezing-and-thawing, heavy use, and water penetration resulting in internal defects. Ground penetrating radar (GPR) can be used as a non-destructive method for detecting such defects. Unfortunately, reflections from closely spaced objects overlap which prevents the accurate estimation of the round-trip travel time of GPR waves to the closely spaced objects. In this paper, singular value decomposition (SVD), subset selection (SSDA), and independent component analysis (ICA) deconvolution algorithms are used to solve this problem using GPR scans of simulated concrete bridge decks. Then, velocity analysis method is used to estimate depth of defects as an evaluation criterion. Results show that ICA has better performance than SVD and SSDA at a cost of slower execution time. Key-Words: Singular value decomposition, subset selection deconvolution algorithm, independent component analysis, ground penetrating radar, bridge condition assessment, non-destructive testing


This paper presents a dual-band dual-polarized interleaved base station antenna array unit based on a filtering antenna for cross-band de-scattering. The array is configured as two columns of antenna arrays operating at a higher band from 1.71 GHz to 2.30 GHz interleaved with one column of antenna array operating at a lower band from 0.80 GHz to 0.96 GHz. By inserting low-pass high-stop filters into the low-band dipole arms, a filtering antenna that can efficiently suppress the radiation at the higher band is achieved. On one hand, the obtained filtering antenna has a slightly reduced gain and narrower bandwidth, which is attributed to the filters. On the other hand, the obtained filtering antenna working at the low band has minimum negative effect on the high band antenna performance.


This study investigates the sustained effects into kindergarten and grade 1 of Project Head Start for disadvantaged black children. Participation in generic Head Start programs was compared to both no preschool and other preschool experience for disadvantaged children in two American cities in 1969-1970. Incorporating both pretest/posttest and comparison group information, the study has advantages over other Head Start impact studies. Both preprogram background and cognitive differences were controlled in a covariance analysis design, using dependent measures in the cognitive, verbal, and social domains. Children who attended Head Start maintained educationally substantive gains in general cognitive/analytic ability, especially when compared to children without preschool experience. These effects were not as large as those found immediately following the Head Start intervention. Findings suggest an effect of preschool rather than of Head Start per se. Initial findings of greater effectiveness of Head Start for children of below average initial ability were reduced but not reversed. The diminution of effects over time, especially for low-ability children, may reflect differences in quality of subsequent schooling or home environment.


This tutorial covers the main concepts related to retrieving information from data structured in XML. The content is divided in three parts. The first covers the main concepts of XML, including defining, displaying and querying XML data. The second part addresses the challenges of retrieving information from XML data, in particular ranking and benchmarking. The last part covers indices for structure and their algorithms, focusing in the trade-off of expressivity vs. efficiency. Along the tutorial the state of the art of the above issues is emphasized, including current available software.


In this paper, we consider synchronous stationary and nonstationary multi-splitting Schwarz methods for solving the linear complementarity problems. Moreover, We establish two convergence theorems of the methods by using the concept of H-compatible splitting.


A relaxation-like method for the numerical solution of a class of partial differential equations of mixed type is presented. The equations of this class have not yet been solved by functional outlines. The numerical method does not add artificial terms to the original equation.


Homogeneous HA coating materials were prepared on porous titanium by the low-temperature combustion synthesis. It was found that the mechanical properties of the specimen depend on the coating process and the heat treatment, and the bending strength would be reduced during the coating process but could be improved by heat treatment. The effects of the temperature during heat-treatment on the phase composition and microstructure of the as-prepared coating, and the bending strength of the specimen were investigated by XRD and SEM. The experimental results show that in the coating process, slight oxidation of the substrate may give rise to a drop in bending strength; however, it could be increased by the reaction of HA and TiO_2, and the sintering of the coating during heat treatment. The HA particles in the coating, with very fine sized particles, were pretty active and would decompose at 800 ℃.


Cancer is a genetic disease and essentially emerges because of various reasons incorporate enactment of onco-qualities, glitch of cancer silencer qualities or mutagenesis because of outer factors. Oncogenes are liberated type of typical proto-oncogenes expected for cell division, separation and guideline. The transformation of proto-oncogene to oncogene is caused because of movement, revamp of chromosomes or change in quality because of expansion, cancellation, duplication or viral disease. These oncogenes are focused on by drugs or RNAi framework to forestall expansion of dangerous cells. There have been created various strategies of sub-atomic science used to analyze and treat disease, including retroviral treatment, hushing of oncogenes and changes in growth silencer qualities.


In the Soviet Union, the development of prefabricated buildings seems to have been a discontinuous process. During the 1920's the industrialization of the nation, the spread of works by Taylor and Ford, and the presence of foreign technicians opened the debate on prefabrication. During this phase, constructions using large cement blocks and lighter wooden prefabricates were experimented. During the 1930's the «academic» trends in Soviet architecture clashed with concepts of prefabrication, but not in a particularly radical fashion: technical innovations and theoretical research conserved the objective of prefabrication. The sum of the destruction caused by the Second World War gave rise to the development of industrial methods of reconstruction that were, however, impeded by the formal aspects, as demonstrated by the debate concerning the «visible» joints between prefabricated panels. With Stalin's death and Nikita Kruschev's rise to power (1953), the prefabricated buildings were envisioned as a method of solving the extensive housing crisis. For this reason it was explicitly included in the political program of the new party leader. This phase constitutes the second short-term trend in the history of Soviet prefabrication.


Transforming traditional single-vehicle-based safety and efficiency control, networked VSC is expected to be a basic element of addressing the challenges for safety and sustainability of road transportation. However, vehicles remain largely as black boxes to researchers and application developers, and open source platforms for evaluating networked VSC solutions at high-fidelity and scale are still lacking. To exploit the potential of networked VSC, we develop the research infrastructure VInsight, which provides basic building blocks for gaining insight into vehicle internals and for enabling high-fidelity, at-scale evaluation of networked VSC solutions. More specifically, VInsight integrates the OpenXC vehicular sensing platform into the Global Environment for Network Innovations (GENI). VInsight deploys a WiMAX research network for integrating high-fidelity real-world vehicular sensing with at-scale ns-3 emulation in the GENI cloud computing facilities, and VInsight develops WiMAX measurement tools for understanding WiMAX link characteristics and driving high-fidelity emulation of networked VSC systems.1 The WiMAX network of VInsight also enables immediate applications such as campus safety patrol; this synergy with opt-in users enables the permanent deployment of VInsight for open innovation in networked VSC systems, thus helping develop solutions to address the grand challenges of road transportation today.


In this second paper of The role of Environment in shaping Low-mass Early-type Nearby galaxies (hELENa) series we study [Mg/Fe] abundance distribution trends of early-type galaxies (ETGs) observed with the Spectrographic Areal Unit for Research on Optical Nebulae integral field unit, spanning a wide range in mass and local environment densities: 20 low-mass early types (dEs) of Sybilska et al. and 258 massive early types (ETGs) of the ATLAS(3D) project, all homogeneously reduced and analysed. We show that the [Mg/Fe] ratios scale with velocity dispersion (sigma) at fixed [Fe/H] and that they evolve with [Fe/H] along similar paths for all early types, grouped in bins of increasing local and global s, as well as the second velocity moment V-rms, indicating a common inside-out formation pattern. We then place our dEs on the [Mg/Fe] versus [Fe/H] diagram of Local Group galaxies and show that dEs occupy the same region and show a similar trend line slope in the diagram as the high-metallicity stars of the Milky Way and the Large Magellanic Cloud. This finding extends the similar trend found for dwarf spheroidal versus dwarf irregular galaxies and supports the notion that dEs have evolved from late-type galaxies that have lost their gas at a point of their evolution, which likely coincided with them entering denser environments.


The office automation of Qinghai Electric Power Company is based on Lotus Domino/Notes R6 for groups workflow system,and adopting full B/S mode,realizing text treatment,document transfer,and affair treatment etc.The paper introduces the system's technical thread and feature in detail.


Intonation of hearing-impaired Hebrew-speaking children in Israel was studied in two speech modes: spontaneous speech and reading aloud a written text. Attention was focused on statements and questions, usually considered basic types of semantic definition and (apparently) of intonation patterns. The subjects were 9–12 year-old hearing-impaired children and a control group of hearing children of the same ages. The utterances were analysed by an IBM speech training program, which enabled graphical presentation of fundamental frequency and intensity distributions. This report presents preliminary conclusions concerning F o ranges, F o contours (internal vs. final intonation structure), and duration problems on hearing-impaired children, and considers the possibility and value of defining and studying intonation of the hearing-impaired.


The revolution of the Taiping Heavenly Kingdom is a large anti-feudal one in the modern history of China.It attacked the Qing Dynasty heavily.It introduced in the God to organize the mass.The new ceremony had an important function.But it couldn't overthrow the feudal system in the base.


Advances in communications theory in the last few years give the appearance of an important scientific breakthrough. They provide principles for translating into similar terms and quantitative units communication interactions both among human beings and among machines, as well as between men and machines. They also suggest aspects of a more inclusive theory of organization. Technology is being broadly influenced by these new developments—automation being a highly publicized and poorly comprehended example of such effects. This article outlines possible ways that the communications advances may alter such diverse aspects of social behavior as the flow of traffic, the use of mass media, and the development of personal values and esthetic standards.


The paper presents PYTHIA, a business forecasting platform designed and developed at the Forecasting Systems Unit of National Technical University of Athens. PYTHIA has many functionalities that can be useful not only to individuals that want to perform forecasts but also to managers from companies and organisations that need to forecast the progress of their product or services make the appropriate adjustments and organize their activities. As a case study we used mortgage data in UK that we found from the Council of Mortgage Lenders. Specifically, we use and compare the Theta method [2], [3] and other forecasting methods, available in PYTHIA, to forecast the time series mortgage loan data. We also point out how a bank could use this data and improve its loan policy. The mortgage loan time series used for the forecasts cover the categories of all buyers, first-time buyers and home-movers. Data is organized in quarters, from the first quarter of 1979 up to the first quarter of 2007.


We consider the identification of a class of time-varying nonlinear systems, called the time-varying Hammerstein series. This identification problem is motivated by the practical need to characterise time-varying nonlinear systems in a simple and parsimonious manner. Basis sequences are introduced to facilitate a reduction in system parameterisation and also to make the estimation task tractable. A significant advantage of the approach is that only a single input-output record is required to obtain least-squares estimates of the model coefficients. The selection of basis sequences and basis order is also discussed. Simulated and real data results are presented to indicate the usefulness of the proposed identification technique. We were interested in applying the time-varying nonlinear system identification procedure to a modelling scenario in seismology.


Morbidity from disease is increasingly being understood as dependent on wellbeing of the ecosystem, as opposed to an isolated element. However, the combined burden of disequilibrium of the gut microbiome ecosystem – which can facilitate proliferation of antimicrobial resistance (AMR) – is not well understood. The gap in knowledge grows when considering regions, such as the Gaza Strip, where the population continues to experience recurrent conflicts, movement restrictions, and high rates of poverty, food insecurity and unemployment.^1^ The concurrent rise of gut microbiome disequilibrium, AMR proliferation, and displacement of populations globally – combined with lack of data – poses significant but unknown risk to public health, in displaced and host communities alike. Examining the current landscape of research, and existing gaps solidifies the need for interdisciplinary perspectives to address AMR through exploration of the gut microbiome. This holistic approach can help account for the political, socio-economic, and material factors, in the context of regions experiencing conflict/war. The growing role of microbiota in health may hold answers to questions surrounding understudied conditions such as AMR, and even non-communicable or chronic diseases.


The continuous expansion of Edge computing calls for efficient scheduling techniques for the employed microservices. However, typical container schedulers often fall short when used in an Edge cluster with heterogeneous devices and unstable network connections, because they do not account for any network Quality of Service (QoS) requirements. This makes it hard for applications to fulfill their Service Level Objectives (SLOs). In this paper we present Polaris Scheduler, an SLO-aware scheduler for the Edge that is developed as part of the Linux Foundation Centaurus project. Polaris Scheduler optimizes the placement of an application's microservices to improve the fulfillment of their SLOs. To this end, it supports modeling of the Edge topology as a Cluster Topology Graph to capture the network quality characteristics and allows users to specify the dependencies among their application's microservices, as well as the network QoS requirements (bandwidth, latency, jitter, and packet drop) for each of them in the form of a Service Graph. Polaris Scheduler relies on a plugin-based approach to allow support for multiple SLOs. We implement our scheduler with plugins for meeting network QoS SLOs as a Kubernetes scheduler and evaluate it using a realistic traffic analysis and hazard detection use case.


Lidocaine (60 mg/100 ml) was added to contrast medium (120 ml of Conray-60) in an attempt to decrease pain associated with leg venography in 100 patients. No side effects were seen, and there was a marked reduction in pain as reported by four different examiners in two separate hospital populations.


Radiology is often identified as a field well-suited for AI integration due to its intimate relationship with informatics and reliance on digital imaging


chapter and will hopefully serve as a starting point for future scholarship. The list of all editions (504–6) is also useful, as is the discussion of the editions and how they have been studied and quoted in scholarship. Yet another section of the appendix collects valuable data on the material history of the prints of the Bovo d'Antona and its later editions, which were printed under the title Bovemayse. A bobe-mayse is one of the basic entries in modern popular dictionaries of Yiddish expression as a synonym for a tall tale. The source for this idiom is a conflation with bobe, the Slavic-derived Yiddish term for grandmother, and the Jewish knight Bovo from Elia Levita's book. Claudia Rosenzweig's critical edition of the Bovo d'Antonawith its additional material will correct the false impression that this importantwork ofYiddish literature is nothingbut a forgottengrandmother's story or a tall tale, and it provides anexcellent basis for the study of this important Old Yiddish text in the future.


The paper is concerned with the automatic mooring for a ship to reduce the labor load of standby operations in domestic shipping. A simulator that calculates mooring tensions and ship motions was built, and calculation accuracy was checked by model experiments. A controller was then designed using the simulator and the performance was verified by tank tests. Successful results are shown.


The present paper describes the fine structure of hyphal cells of Helminthosporium oryzae which invaded the coleoptile of two rice varieties, Kameji and Shiga Asahi 27, resistant and susceptible to the brown leaf spot respectively.Leaf tissues were fixed in KMnO4 (2% in distilled water) and postfixed in a 1% solution of phosphate buffered OsO4.1. In the susceptible variety the hyphae of the fungus remarkably increased its diameter after penetrating the cuticle of epidermal cell walls, and developed through the middle layer of radial walls of epidermal cells and then, in most cases, intruded into epidermal cells.2. The cell wall of young immature hyphae which invaded the parenchymatous cells of the resistant and susceptible varieties consisted of only a mucilaginous inner layer, similar to that of immature germ tubes. However, two-layered cell walls were observed in the matured hyphae, electron-dense outer layer (about 0.12μ in thickness) and electron-transparent inner layer (about 0.20μ). Vacuoles in old hyphae developed extensively, some reaching 3μ in diameter, and occupied a greater part of the cytoplasm.3. In the susceptible variety accumulation of electron-dense substances, 0.5μ thickness was recognized around the hyphae in the radial wall of epidermal cells. This might be a response product of the host cell to the exudate of the fungus.4. In the parenchymatous tissues of the susceptible variety the hyphal tips swelled again after penetrating the cell wall by a slender hypha, about 1μ in diameter. In these newly formed hyphal cells many mitochondria and lipid bodies were recognized 5. In an affected epidermal cell of coleoptiles of the resistant variety, substances which appear to be due to the degeneration of cytoplasm of the host cells were recognized around the hyphae. Less amount of these substances was detectable around the hyphae in the susceptible variety.6. The hyphae of the causal fungus in coleoptile of the resistant variety were generally slender, about 1μ in diameter. They had large vacuoles in cytoplasm, and finally they showed a vacuous appearance retaining only the outer layer of cell walls.7. In the resistant variety, Kameji, chloroplasts in parenchymatous cells at first swelled after the invasion of the causal fungus. Thereafter, the intergrana-lamellae expanded and the grana-lamellae changed into many small vesicles, 0.1-0.5μ in diameter. Thus the chloroplasts were finally degenerated. This degenerative process is referred to so-called vacuolar degeneration.


The influence of dietary Ca and P and growth rate from birth to 60 to 70 days of age on serum minerals, soundness scores and bone development was evaluated with crossbred gilts and barrows or boars. The following dietary treatments, as percentages of NRC recommendations for barrows and gilts, were used: (1) 100% Ca and P, (2) 125% Ca and P, (3) 100% Ca and 125% P and (4) 100% Ca and 75% P. Pigs were fed an 18, 16 and 14% protein sequence. Final weight was 107 kilograms. Serum inorganic P concentration was depressed (P<.05) when pigs were fed a diet containing 100% Ca and 75% P as opposed to 100% Ca and P, but was not consistently increased when pigs were fed 125% P with 100 or 125% Ca. In cases where the magnitude of the P depression was greatest, serum Ca and Mg concentrations were increased. Serum Ca, P and Mg were not consistently affected by sex or growth rate. Pad, feet and leg, structural soundness and foot scores were generally not influenced by dietary Ca and P levels or growth rate. Gilts tended to be more sound than barrows, with no difference observed between boars and gilts. Bone development, as measured by metacarpal and mandible dried weight, ash and breaking load, was reduced when 75% of NRC-recommended P was fed, but it was not consistently increased


The Hyderabad Teli Industrial Cooperative Society was established in the year 1954. The main objective of starting this Society was to improve the social and economic condition of the persons engaged traditionally in producing edible oils. The local officers of the Khadi and Village Industries Commission (KVIC) and Khadi and Village Industries Board (KVIB) persuaded the individual oil producing members to form into a cooperative society for better benefits. The membership of the Society is restricted to the municipal limits of the twin cities of Hyderabad and Secunderabad.


Abstract Recent English as a Lingua Franca (ELF) studies have examined the linguistic features of disagreements during interactive academic tasks and casual conversations. Fewer studies, however, have explored nonverbal cues of disagreement, and even less is known about how interlocutors perceive disagreements. Therefore, using data from a corpus of ELF interaction, this study examined the verbal features and visual cues used by ELF university students to disagree during an academic discussion task. The disagreement episodes were selected through a content analysis of stimulated recall protocols in which a speaker stated that a disagreement had occurred. Transcripts were analyzed to classify the speaker's verbal strategies as being mitigated or unmitigated. Video recordings were examined for facial expressions, body movements, and hand gestures. Findings revealed that ELF students used mitigated linguistic strategies, such as hedges, during disagreement while gaze aversion, smiling, and head nods were the most frequent nonverbal cues. The stimulated recall data showed that disagreements were perceived as an opportunity to listen, think, and share different opinions. Implications are discussed in terms of how to interpret features of disagreement in language classrooms.


The use of options as a component of executive remuneration in large listed corporations in Australia grew materially between 1997 and 2002. This growth coincided with a significant degree of concentration of ownership of those options in the hands of a small cadre of board members and senior executives. We conclude that this phenomenon, to date essentially unexplored in the literature, has significant implications for the quality of governance outcomes in firms that use options in their incentive and remuneration systems.


Abstract The article, 'When I Was a Child, I Danced as a Child, but Now that I Am Old, I Think about Salvation: Concepcion Gonzalez and a past that would not stay put,' reconstructs an incandescent moment in the history of Mexico, a moment when ordinary Mexicans dramatically transformed Mexico's future. In the mid‐1930s in the midst of President Lazaro Cardenas's efforts to remake rural Mexico and its people, men and women trained to revere the Virgin Mary enter a church in the village of Ario Santa Monica, Michoacan, seize the wooden icons of Jesus, the saints, the Virgin, and torch them in the plaza. Later that evening, a number of men and women re‐enter the church and dance before the altar. The essay explores this moment through a combination of ethno‐historical and fictive techniques. It traces the meanings of the Virgin, God, and time in Mexico and the author's own experiences of doing ethno‐history among the Ario Santa Monica villagers. It weaves together large historical issues with actual scenes ...


Inbound tourism,has become an important part of tourism research.After reviewing the state quo of inbound tourism market in Hunan province and further analyzing its market characteristics of twelve inbound tourism countries by means of preference scale and market share analysis,this paper puts forward corresponding strategies for promoting Hunan inbound tourism.


A novel low-complexity lossless scheme for continuous-tone images dubbed the PABLO codec (Pixel And Block adaptive LOw complexity coder) is introduced. It comprises a simple pixel-wise adaptive predictor and a block-adaptive coder based on the Golomb-Rice coding method. PABLO is an asymmetric algorithm requiring no coding dictionary and only a small amount of working memory on the encoder side. Due to the simplistic data structure for the compressed data, the decoder is even simpler lending itself to very fast implementations. Experimental results show the efficiency of the proposed scheme when compared against other state-of-the-art compression systems of considerably more complexity.


Low recovery of cutinase enzyme in water-enriched phase after thermo-induced separation stage of LS54/Dx aqueous two-phase system was improved by enhanced volume exclusion effect in the polymer-water extraction system. It was done by increased the polymer concentration in the polymer-water system. After primary phase separation, more LS54 (polymer) which is the system's component itself were added into polymer-enriched phase and mixed thoroughly before thermo-induced separation step proceeded. The compositions of LS54 added into the polymer-enriched phase were 0.25, 0.5 and 0.75 g LS54/g top phase. The thermo-induced phase separation was carried out at 37°C. It was found that cutinase recovery in water-enriched phase was increased up to 5-13% with the increment of polymer concentration in the system as compared to a system without polymer addition. The optimum concentration obtained for the polymer added was 0.5 g LS54/g top phase whereby it attained 82% recovery of cutinase enzyme in water-enriched phase after thermoseparation step. Although the increment of enzyme recovery was not exceptionally high as compared to another method such as adding ligand, an affinity tag or neutral salt, still this method is applicable because of its more straightforward work, polymer recycle capability, and enzyme recovery in water phase would definitely give benefit to further downstream processing.


This paper presents a teaching experience from the Construction Management Graduate Programme held at Faculty of Civil Engineering, University of Zagreb. The students are taught discrete-event simulation based modeling of construction processes through a real-world test case where every student team is given a different assignment. The main idea of this approach is that integration of these partial tasks/individual assignments - would eventually provide a more complete picture of the actual processes taking place at the construction sites, and at the same time - the students are given an opportunity to participate in an ongoing construction project by observing it and subsequently simulating the observed processes. The first section of the paper gives an overview of discrete-event simulation systems and motives for their application in the Construction Management context. The second part of the paper depicts an experience of creating a partial simulation model of a large building project – from a teaching perspective. A description of the test-case project is given, along with explanations of how individual assignments were chosen in order to simulate complex reality taking place at the jobsite. In conclusion, differences between the


In this paper, absolute stability of nonlinear systems with time delays is investigated. Sufficient conditions on absolute stability are derived by using the comparison principle and differential inequalities. These conditions are simple and easy to check. In addition, exponential stability conditions for some special cases of nonlinear delay systems are discussed. Applications of those results to cellular neural networks are presented.


Abstract : An experimental program for studying the transition phenomenon, boundary layer characteristics, and local heat transfer rates on 4- and 8-foot long 10 deg included angle cones in a hypersonic chock tunnel has brought about the development and improvement of instrumentation and methods for distinguishing hypersonic laminar, transition, and turbulent boundary layers in relatively short test time experimental facilities. The methods used include schlieren optics, local heat transfer rates from thin-film sputtered platinum surface gauges, and surveys through the boundary layer using impact pressure, total temperature, and thin heat transfer wedges. Also, the actual oscilloscope traces, directly from the heat transfer instrumentation, be used to define the type of boundary layer. (Author)


The progress in research and application of waste water treatment such as ,membrane method for separation , biochemical technology , oxidation technology, reduction technology, ultrasonic technology were summarized in this paper. The oxidation technology was emphasized in this paper, meanwhile the driving effects of oxidation technology were discussed. The trend of waste water treatment technology research was also outlooked.


Different conformers of many aliphatic compounds such as ethane, butane, cyclohexane and their derivatives have been studied to find the most reactive as well as the most stable conformer. For the first time, two conformers of p-xylene were found using theoretical DFT calculation and the vibrational modes, Raman activity, and other spectra of each conformer were also studied. The most significant data that clearly distinguished both conformers was depolarization spectra. Besides, many other parameters were found different in both conformers of p-xylene such as Mulliken charge's, optimization energy, HOMO's of both conformers. Also, the presented study predicts, why eclipsed conformer of p-xylene is more reactive than staggered conformer. The reactivity of the eclipsed form is explained on the basis of HOMO-LUMO energy gap. Also, the presented study opens the door for future work to be done because each conformer can produce a specific product. Moreover, the rates of reaction are also dependent on the conformers and their relative stability.


At the International Conference held in Vancouver, ritonavir (Norvir) and indinavir (Crixivan) were reported safe in children. Nelfinavir, found to be safe and effective in children, is expected to soon be available through expanded access to children ages 2 to 13. T-cells increased and viral load decreased in children who were treated with monotherapy for three months and who then received combination therapy with AZT or AZT/ddI. Monotherapy with either AZT or d4T (Zerit) was effective in children ages three months to six years; neutropenia was the most common side effect. Researchers have determined that combination therapy can be started early for children.


[At the Section's request, Professor Raven-Hansen first briefly describes a recent case in which the Supreme Court held that a scientist does not become a public figure for purposes of defamation law merely because he accepts public research funds. In contrast, Professor Raven-Hansen argues in the remainder of the paper, such a scientist does assume at least a "quasi-public'' status in terms of his accountability for the public research funds and his obligation to disclose his data to the funding agency and sometimes to the public.]


Summary Hamsters were infected by the intranasal route with para influenza 3 virus. One tissue culture infectious dose was sufficient to infect hamsters. Quantity of virus produced in the lung was the same, 105.9 to 106.9, during infection with virus grown only in tissue culture or virus passaged in hamsters. Infected hamsters developed high levels of CF antibody specific for para influenza 3 virus.


The liveweight gain was measured of beef cattle on pastures stocked at 5.9 to 11.8 cattle/ha and receiving 50, 182 or 329 kg N/ha in a 12-week season. N levels and stocking rates were so adjusted that similar yields of herbage per animal were expected. Results showed that similar liveweight gains per animal, averaging 1.03 kg/day, occurred at all N levels. Liveweight gain/ha ranged from 547 to 1037 kg in 12 weeks and the corresponding quantities of metabolizable energy utilized were 9890 and 17590 Meal. The results confinn earlier work (4, 7).


It is difficult to estimate Doppler rate accurately when the Signal-to-noise ratio(SNR) of SAR echo is low.A Doppler rate estimation method based on sub-space projection technique was proposed.This method constructs covariance matrix by utilizing data vectors in different range lines and projects phase error vector into noise sub-space which is formed by eigendecomposing the covariance matrix.The proposed method may estimate Doppler rate robustly in the case of low SNR.


The primary focus of Phase I was to prototype a development environment, ACCESS, for A Communicating and Cooperating Expert Systems System. More generally, this work explored the question of what capabilities were needed in a development environment for embedding distributed knowledge-based systems applications on personal computer or work-station class platforms. The stated goal of the Phase I research and development effort was to investigate and implement a software environment for the realization of cooperating knowledge sources on personal computers. This system was to be Lisp-based, distributed processing was to be facilitated by message passing using TCP/IP, control was to be accomplished by meta-level objects and a variety of features were to be provided to aid developers in building such systems. Underlying these goals was the assumption that the tools needed to support such an effort, mainly Common Lisp, Portable Common Loops and TCP/IP, were adequate to do so. During the course of this work, Symbiotics found several shortcomings in these software tools and identified a need for higher-level tools to facilitate distributed-processing development. This report documents that work and the results of the Phase I effort.


A model is developed for assessing the temporary and permanent impact of the Family Law Act, and the application and construct validity of the model are examined.


The present method of calibration of pressure transducer using weight is still not sufficient to take accurate and absolute clothing pressure values, particularly in light pressure range. Using a new method of calibration with air pressure, we measured and analyzed the relationship between applied pressure and response pressure. We also investigated the performance of the pressure transducer of new type, Kulite LQL-125-25, which was 0.647 gm in weight, 0.076 mm in thickness and 0.215 cm in diameter, on the human upper arm and on the rigid model of similar size, and compared it with the results of the baloon and disc type pressure transducers. Results were as follows: 1) The relationship between applied pressure and response pressure was almost linear and repeatable by means of calibration with air pressure. The accuracy better than 0.1% was obtained. 2) Kulite LQL-125-25 type pressure transducer showed higher adaptability to human bodies, greater sensitivity, more accuracy, repeatability and stability to temperature than the baloon type and the disc type ones. 3) The response pressure of Kulite type showed much higher value on the rigid model, while almost same value with applied pressure on the human body. And in case of placing a piece of felted cloth between the rigid model and transducer, it was decreased near to the value on the human body.


Pulsating compression tests are performed in order to investigate the possibility of applying the copper electroplating method of stress analysis to measure the contact pressure between two bodies. Namely, the relation among density change of grown grains in copper foil inserted between contact surfaces, the magnitude of cyclic pressure σp and the number of cycles are examined by computer image processing, and can be expressed by a rate process equation. On the basis of this equation or the relation between σp and grown grain density at the given number of cycles, contact pressure and its distribution can be evaluated by observing the density or density change of grown grain.


Piezo1 is a mechanosensitive ion channel supposed to regulate the volume and maintain the structural integrity in Red Blood Cells (RBCs), as gain-of-function mutations in this channel are associated to the RBC disease Hereditary Xerocytosis (Zarychanski et al. Blood 2012; Bae et al. Proceedings of the National Academy of Sciences 2013). Piezo1 is activated by several mechanical forces, including stretching, poking and shear stress and allows Ca2+ and other cations to enter the cell generating an electrical response. In 2015, it has been discovered that Piezo1 is sensitive to a small molecule, Yoda1 (Syeda et al. Elife 2015), which keeps the channel open and affects its inactivation kinetics. This finding has created new possibilities to elucidate Piezo1 gating mechanism and explore its functional significance in physiological and pathophysiological conditions.
 Here, we present a patient with a novel PIEZO1 mutation (R2110W) and a patch clamp-based high-throughput screening assay for Piezo1 activity. We established a protocol to detect functional Piezo1 mutations upon chemical stimulation by Yoda1, yet were not able to stimulate the channel via mechanical force, i.e. pressure steps and shear-stress.
 The assay was first developed on Neuro2A (N2A), a neuroblastoma cell-line endogenously expressing Piezo1 channels (kindly provided by Max-Delbrück Center, Berlin), due to larger abundance of Piezo1 channels in these cells. Initial experiments were performed on the Patchliner (Nanion Technologies GmbH, Munich), a medium-throughput automated patch clamp system able to record up to 8 cells at a time. Currents were elicited using a voltage ramp ranging from -100 to +80 mV for 300 ms, the holding potential was set to -60 mV. A significantly increased whole-cell current was observed upon 10 µM Yoda1 application in half of the recorded cells and the resulting Yoda1-induced currents were inhibited by 30 µM gadolinium chloride, a non-specific blocker of stretch-activated channels. The assay was then implemented on the SyncroPatch 384PE (Nanion Technologies GmbH, Munich), capable of recording up to 384 cells in parallel under identical experimental conditions, thus allowing for reliable statistical analysis. Yoda1 responding cells were selected based on strict quality control (QC) criteria, i.e. the seal resistance stability over time. In one example NPC-384 chip 140 out of 384 N2A cells (37%) passed the QC criteria and 85 cells (60% of the valid cells) were considered as Yoda1 responders. Finally, we investigated Piezo1 electrophysiological properties in healthy and patient RBCs carrying the novel PIEZO1 R2110W mutation. Similar to N2A cells, RBCs currents were analyzed and divided into Yoda1 responders and non-responders according to our QC criteria. The increase in whole-cell currents induced by Yoda1 application was significantly higher in patient compared to control RBCs, which was also reflected by a higher number of Yoda1 responders compared to control. Residue R2110W is structurally located in a gating sensitive area of the channel protein suggesting a gain-of-function. This would be in line with previously described mutations in PIEZO1 (Albuisson et al. Nature Communications 2013) and the mild form of anaemia observed in the patient. Furthermore, we excluded any involvement of Gardos channels in the Yoda1-induced currents by comparing measurements in the presence and absence of the specific Gardos channel inhibitor TRAM-34.
 Altogether, our work demonstrates that high-throughput patch clamping can provide a robust assay to study functional Piezo1 impairments in primary RBCs without expressing the mutated channel protein in a heterologous expression system. Our approach may be used to detect other channelopathies not only in RBCs and may serve as routine screening assay for diseases related to ion channel dysfunctions in general, complementary to gene sequencing.

 No relevant conflicts of interest to declare.