Добірка наукової літератури з теми "Up-grading"

The authors posit that the traditional grading system involving points and percentages is not the best way to prepare students to be the self-directed, independent learners they need to be. A better system would produce grades that are FAST (fair, accurate, specific, timely). To bring about these changes, school leaders need not create full agreement about new models but should, instead, create circumstances that make action more likely.

AbstractWe have previously bred Chinese local dairy sheep through grading up with local Small-Tailed Han (STH) sheep as female parent and DairyMeade (DM) sheep as male parent. In this research communication we characterize the whey protein profile of STH sheep and their offspring (F1, F2) to reveal physiological differences and variation in milk traits. A total of 1032 whey proteins were identified through tandem mass tag labeling (TMT) proteome profiling. Three proteins were significantly differentially abundant between F1 and STH milk, six between F2 and STH milk and five between F1 and F2 milk. In terms of differential changes between generations, WASHC4 and CUTA of F1 and Ig-like domain-containing protein of F2 milk were dominant whey proteins. Overall, the results showed that the whey protein profiles of different generations varied little. The crossbreeds of STH and DM sheep would be suitable for the development of the Chinese local sheep milk industry, and the F2 may be a better population for sheep milk production.

Plans of Russia to return on the international arena as a strategic power effect the aggressive foreign policy including military engagements into local conflicts all over the world. Modern armed forces is a necessary tool of such activities. The Russian Federa-tion successively increases the financial as-sets for development, production and supplies of the ordnance in the frame of the State Armament Programs (SAP) to provide efficient operation of the army. Currently two state armament programs exist in the Russian Federation: the first prepared for years 2011–2020 (SAP- 2020) and second for years 2018-2025 (SAP-2025). The two plans are complementary and the funds not used by SAP-2020 will be shifted to SAP-2025.

Few studies have analyzed the details of neoadjuvant chemotherapy (NAC)-induced changes in patients with upper tract urothelial carcinoma. This study aimed to describe the impact of down-grading ipsilateral hydronephrosis by NAC for ureteral carcinoma. An observational study was conducted in 32 patients with cT1-3N0M0 ureteral carcinoma treated with NAC and radical nephroureterectomy. Hydronephrosis was classified into five grades based on computed tomography findings. We focused on the differences between the baseline and post-NAC status of ipsilateral hydronephrosis, radiographic tumor response, and blood markers. Down-grading, no change, and up-grading was observed in 10 (31%), 21 (66%), and 1 (3%) patients, respectively. In univariate analysis, locally advanced disease (cT3), severe hydronephrosis (grade 3/4) at baseline, no change/up-grading of hydronephrosis after NAC, and pathological lymphovascular involvement were identified as potential prognostic factors of progression-free and cancer-specific survival after radical nephroureterectomy. Locally advanced disease (cT3) at baseline and no change/up-grading of hydronephrosis by NAC were independently associated with poor progression-free survival. Notably, none of the patients with NAC-induced down-grading of hydronephrosis died of ureteral carcinoma during the follow-up. We reported the prognostic impact of down-grading of ipsilateral hydronephrosis, which could serve as a useful aid or clinical marker for decision-making.

The building and construction sector accounts for a significant proportion of carbon dioxide emissions in Sweden, a total of 12.2 million tons of carbon dioxide equivalents, which corresponds to approximately 19 % of the total emissions of greenhouse gas in Sweden. As a response to the fact that construction has a major impact, different environmental certification systems have emerged for buildings. One certification system is the Swedish certification system “Miljöbyggnad”, which includes sustainability issues through the whole construction process. The building can achieve three grades in Miljöbyggnad: bronze; which corresponds to the level in legislations, silver; which is the most common certification grade, and gold; that corresponds to the highest grade, thus requiring the most effort. The grade is given according to how the building performs in different assessment areas, called indicators. For new construction, the system consists of 15 different indicators within three areas: energy, indoor environment and materials. The indicators are connected to both ecological and social sustainability. The indicators connected to ecological sustainability are considered to either minimize hazardous substances, increase the amount of renewable energy or decrease the use of energy, thus a reduction in climate impact. Social sustainability is connected to how the tenant’s wellbeing is impacted by the building. The meaning of wellbeing is, in this case, health and comfort. In this master thesis the theoretical possibility of raising the Miljöbyggnad grade from silver to gold has been studied for the construction of new student housing. Stockholms studentbostäder´s new construction of four houses at Lappkärrsberget has been the study case. Stockholm’s student housing, “Stockholms studentbostäder”, is the largest actor of student housing in Sweden, with approximately 8000 housings. Stockholms studentbostäder is currently in the middle of the process that within the next ten years build 2000 new student housings. A major expansion with 800 housings will be built in their largest housing area, Lappkärrsberget. In the first building phase, the new construction of four houses is carried out, with the buildings having 10 to 13 floors which include 297 housings, mainly one room apartments and some two room apartments. The houses are built for the Miljöbyggnad grade silver according to the manual in version 2.2. After version 2.2, later versions, as version 3.0 have been launched. The main focus has been to identify what theoretical actions are required to raise the grade to gold, and to what cost. Four main questions have been studied:Is it possible to reach the grade gold for the four new buildings in Lappkärrsberget?What would it mean for the buildings, in terms of costs and actions, to raise the grade from silver to gold in version 2.2?How high grade is possible to reach for the indicator energy types, if the tenants have their own electricity agreements in the current version of Miljöbyggnad 2.2, and the later version 3.0? What general differences would it make to build in a later version 3.0, instead of 2.2? The method used has been to study the current status and then together with the manual for Miljöbyggnad make a comparison to achieve the grade gold in a specific gold scenario formulated together with Stockholms studentbostäder. In the next step, actors from the building industry both internal from Stockholms studentbostäder, external at other companies together with suppliers, were asked about what actions were needed to achieve gold and to what cost.For the first question, if it is theoretically possible to build with Miljöbyggnad gold for the new housing in Lappkärrsberget, it was concluded that it would not be possible to achieve gold due to the limited opportunities to optimize the properties of the windows with the current building performance. Therefore, it is recommended to decide what grades off the indicators to aim for and in an early stage develop the construction design and make the construction planning after the indicator grades. To achieve high grades, it is especially important to optimize the windows, in line with the requirements for the indicators. Another uncertain factor concerns how the students would respond in a survey which requires an approved result to reach a gold grade. Although it is not possible to reach gold as a building grade, it was noted that several of the indicators were close to gold and it would not be hard to raise these grades to gold to improve the overall performance of the buildings. In the second question, the cost was calculated when raising the grade from silver to gold. For this it was assumed that the windows and surveys did reach the desirable grade, and in that case the cost would increase between 0,4 % and 1,3 % of the contract budget of the project. The probable value would be somewhere in between, estimated to 0,6 %, which is a low increase in cost. In the third question, it was investigated what grade would be possible to achieve for the indicator energy types if the tenants are required to manage their own electricity agreement, in both version 2.2 and version 3.0. It was concluded that the district heating was required to change, to make an impact on the grade. Stockholm Exergi is the supplier of the district heating for the houses in Lappkärrsberget. Thus, Stockholm Exergi´s three alternatives have been studied, which differs in district heating composition and impact on the environment. The alternatives were studied for different years, due to the fact that district heating changes composition for each year. The preliminary certification of the grade in Lappkärrsberget was made with district heating data from 2016 and no matter what district heating alternative was used from 2016, the highest reachable grade is bronze in version 2.2. In version 3.0, the household electricity, meaning the tenant´s apartment electricity, is optional to use for the calculation of the grade. When calculating the grade without household electricity, with the same data as the preliminary certification, from 2016, the grade was raised to silver. With the alternatives of the district heating that were available year 2020 from Stockholm Exergi it would be possible to reach grade gold with the most environmentally friendly alternative, in version 2.2 and silver would be the highest grade in version 3.0. In the last question, version 2.2 and 3.0 were compared and some differences were noted. For example, the indicator nitrogen dioxide was removed in version 3.0 and the indicator climate impact of the foundation of the building and the building frame was added. The requirements have been updated in version 3.0. For example, the indicator percentage of energy types has a requirement that at least 5 % of the energy needs to be locally produced and renewable to reach gold level, for example with solar panels. The requirements for surveys have also been reduced in version 3.0, to fewer indicators in need of surveys and there is also an alternative to verify the grades by using measurements instead of surveys.<br>Bygg- och fastighetssektorn står för en avsevärd del av koldioxidutsläppen i Sverige, hela 12,2 miljoner ton koldioxidekvivalenter, vilket motsvarar cirka 19 % av de totala utsläppen av växthusgaser i Sverige. Flera miljöcertifieringssystem har vuxit fram som ett svar på att byggandet har en stor påverkan på miljön där fokus ligger på ett mer hållbart samhällsbyggande. Ett sådant certifieringssystem för byggnader är Miljöbyggnad vilket är ett system som inkluderar hållbarhetsarbete genom hela byggprocessen. Det finns tre betyg som en byggnad kan uppnå i Miljöbyggnad: brons som motsvarar lagkrav, silver som är det vanligaste certifieringsbetyget och guld som motsvarar högsta betyg, vilket därmed kräver mest ansträngning. Betyget ges efter hur byggnaden presterar enligt olika bedömningsområden eller indikatorer som de kallas. För nyproduktion består systemet av 15 olika indikatorer inom tre områden: energi, inomhusmiljö och material. Indikatorerna kopplar både mot ekologisk och social hållbarhet. Där indikatorerna som kopplar mot ekologisk hållbarhet anses antingen ge en minimering i farliga ämnen, ökning i förnybar energi eller en minskning av energianvändning och därmed en minskning i klimatpåverkan. Social hållbarhet kopplas mot om det påverkar hyresgästernas välmående. Där det med välmående menas hälsa och trivsel.I det här examensarbetet har den teoretiska möjligheten att höja Miljöbyggnadsbetyg från silver till guld studerats för Stockholms studentbostäders nyproduktion av studentbostäder. Betygshöjningen har studerats i en fallstudie för ett projekt med fyra punkthus på Lappkärrsberget. Stockholms studentbostäder är Sveriges största studentbostadsaktör med ungefär 8000 bostäder. För närvarande är de mitt uppe i arbetet att under de kommande tio åren bygga 2000 nya studentbostäder. En stor expandering med 800 bostäder kommer att göras i deras största bostadsområde Lappkärrsberget. I en första etapp sker en nyproduktion av de fyra punkthusen vilket inkluderar hus på tio till tretton våningar på totalt 297 studentbostäder i form av främst studentettor, ett rum med kök samt några tvårumslägenheter. Punkthusen byggs för Miljöbyggnad silver, enligt manualen för version 2.2. Det har efter version 2.2 lanserats senare versioner av Miljöbyggnad, såsom version 3.0. Ett särskilt fokus har varit vilka teoretiska åtgärder som behöver vidtas för att höja betyget till guld, samt till vilken kostnad. Fyra huvudfrågeställningar har tagits fram:Är det möjligt att bygga enligt Miljöbyggnad guld för punkthusen?Vad skulle det innebära för punkthusen i form av kostnader och åtgärder att bygga enligt Miljöbyggnad guld istället för silver i version 2.2?Hur högt betyg är det möjligt att nå för indikatorn energislag om hyresgästerna fortsätter ha egna elabonnemang i version 2.2 och 3.0?Vilka generella skillnader skulle det innebära för ett nyproduktionsprojekt om det istället byggdes enligt en senare version, det vill säga Miljöbyggnad version 3.0? Metoden för att besvara frågeställningarna har varit att studera aktuell status för punkthusen och därefter med hjälp av Miljöbyggnadsmanualen jämfört det med kriterierna för guld vid ett guldscenario framtaget tillsammans med Stockholms studentbostäder. I nästa steg har personer i branschen, både internt hos Stockholms studentbostäder, externt hos andra företag samt leverantörer till punkthusen tillfrågats om vilka åtgärder de skulle vidta för att uppnå guld, samt vilken kostnad de uppskattar dessa till. För den första frågan om det är teoretiskt möjligt att bygga med Miljöbyggnad guld för punkthusen blev resultatet att det inte vore möjligt. Det beror på att det inte skulle gå att optimera fönsteregenskaperna tillräckligt med nuvarande utformning på byggnaderna. Det rekommenderas därför att redan från början av projektet bestämma vilka indikatorbetyg det satsas mot och ta fram ritningar och projektera byggnaden med betygen i åtanke. Särskilt viktigt är det att optimera fönstrena i linje med indikatorkraven för att uppnå höga betyg. En annan osäker faktor för guldbetyg gäller hur hyresgästerna skulle svara i en enkätundersökning, där det krävs ett godkänt resultat för att nå guld. Även om det som byggnadsbetyg inte vore möjligt att nå guld för punkthusen, konstaterades det att flera av indikatorerna låg väldigt nära guldbetyg och det hade krävts lite för att höja dessa till guld för att förbättra byggnadens prestanda.I nästa fråga har det tagits reda på hur dyrt det skulle vara att höja betyget till guld. I den frågan har det antagits att fönstrena klarade kraven och enkätundersökningen blev godkänd, vilket skulle innebära en ökning på mellan ungefär 0,4 % och 1,3 % av entreprenadkostnaden för projektet, med ett generellt påslag på 0,6 %, vilket är ett litet påslag. I den tredje frågan undersöktes hur långt det skulle vara möjligt att nå med indikatorn energislag när hyresgästerna tecknar egna elabonnemang, både för Miljöbyggnad version 2.2 och version 3.0. När hyresgästerna har egna elabonnemang konstaterades det att fjärrvärmen behövde ändras för att påverka betyget. Stockholm Exergi är fjärrvärmeleverantör för punkthusen, därmed har deras tre fjärrvärmealternativ studerats. Deras alternativ skiljer sig åt i fjärrvärmesammansättning och därmed även i påverkan på miljön. Alternativen har även studerats för olika år då sammansättningen av fjärrvärmen förändras med tiden. Preliminärcertifieringen av punkthusen gjordes med data från 2016 och oavsett alternativ från 2016 uppnås inte mer än brons i version 2.2. Medan i version 3.0 är hushållselen, det vill säga hyresgästernas egna elabonnemang en frivillig post att räkna in för Miljöbyggnadsbetyg. Räknas hushållselen bort kan det med 2016 års värden uppnås silver. För de fjärrvärmealternativ som erbjuds år 2020 skulle det gå att uppnå guld med det mest miljövänliga alternativet, i version 2.2 medan silver blir det högsta betyget i version 3.0. I den sista frågeställningen jämfördes version 2.2 och 3.0 och det finns en del skillnader, exempelvis att indikatorn kvävedioxid tagits bort i 3.0 och att indikatorn stommen och grundens klimatpåverkan lagts till. Kraven har uppdaterats något i version 3.0, för exempelvis indikatorn andel av energislag finns det för guld ett krav på att minst 5 % av energin ska vara lokalt producerad i anslutning till byggnaden med förnybar energi exempelvis med solceller. Kraven på enkäter har också förändrats där färre indikatorer kräver enkäter i version 3.0 och det erbjuds ett alternativ till enkäter med mätning vid verifiering av guldbetyg.

La presente tesis contiene tres ensayos sobre la Economía de las Organizaciones y el Desarrollo Económico. Cada capítulo se centra en un tópico distinto, cuya relevancia ha sido destacada por la literatura sobre Desarrollo Económico en la últimas dos décadas.<br/><br/>La motivación del primer ensayo reside en el hecho de que el inapropiado funcionamiento de las instituciones políticas y económicas constituye un obstáculo severo para el progreso económico. El ensayo analiza el rol de la concentración de la propiedad de las empresas de media para restringir la corrupción burocrática. El segundo ensayo está inspirado por la literatura sobre los determinantes del progreso tecnológico. El capítulo estudia el impacto de la competencia y la liberalización de la entrada en los mercados sobre la dirección del progreso tecnológico. El ensayo se centra en la comparación de las ventajas y desventajas de orientar el cambio tecnológico hacia la creación de bienes de mayor o menor calidad. El último capítulo explora cómo las diferencias tecnológicas entre empresas que se fusionan afectan la eficiencia productiva de la nueva organización.<br>This thesis contains three essays on the Economics of Organisations and Development. Each essay focuses on a different topic that has received special attention by the Development literature over the last two decades. <br/><br/>The first chapter is motivated by the fact that malfunctioning institutions constitute a severe obstacle for economic progress. It centers the analysis on the role of the media to constrain bureaucratic corruption. The second chapter is inspired by the large and influential literature on the determinants of the technical progress. The chapter focuses on the role of market competition and entry liberalization to affect the direction of the technical change. It analyzes the trade-off between doing quality up-grading or creating new but low-quality goods. The third chapter explores the role of conflicting organisational technologies to affect the economic performance of merging firms.

Esta dissertação propõe uma reflexão crítica sobre a prática profissional do arquiteto voltada às questões da habitação popular, especialmente a habitação em favelas urbanizadas. Partimos de uma revisão histórica do lugar do arquiteto frente às condicionantes de precarização da moradia urbana, trilhando um percurso bibliográfico e analítico que se inicia nos anos 1930 e chega aos dias atuais: procuramos discutir, num contexto ampliado, as especificidades do envolvimento de arquitetos com o universo da cultura popular e das favelas, o que nos permite situar e entender historicamente a inserção desses profissionais nos hoje consagrados processos de urbanização de assentamentos precários, operados num contexto de reforma direcionada ao mercado e de explicitação e radicalização da insuficiência da aposta estatal em políticas compensatórias para lidar com o déficit habitacional. Como procedimento metodológico, optamos por focalizar algumas práticas recentes de urbanização de favelas: as experiências junto aos núcleos Dois de Maio, em São Paulo (SP), Jardim Olinda, também na capital paulista, e Tamarutaca, em Santo André (SP), incluídos, nos anos 2000, em dois diferentes programas públicos de urbanização - o Programa Bairro Legal , da prefeitura de São Paulo, e o Programa Integrado de Inclusão Social (atual Santo André Mais Igual), promovido pelo poder público andreense -, e de cujos projetos urbanísticos e habitacionais participaram, respectivamente, as organizações USINA Centro de Trabalhos para o Ambiente Habitado / TEIA Casa de Criação (em parceria), GTA Grupo Técnico de Apoio e PEABIRU Trabalhos Comunitários e Ambientais. A pesquisa de campo nos permite entender tanto os desdobramentos históricos do exercício profissional dos arquitetos no enfrentamento da questão das favelas, quanto as potencialidades de transformação da prática contemporânea, tendo em vista o contexto político que envolve Estado, movimentos sociais, técnicos e o conjunto mais amplo da sociedade. A partir da descrição dos casos, procuramos discutir o percurso profissional dos arquitetos nos espaços de diálogo, articulações e vinculações que se estruturaram a partir das especificidades das ações desenvolvidas, suscitando uma reflexão aprofundada sobre questões que dizem respeito à realidade atual das políticas públicas voltadas para a urbanização de favelas e sua relação com a questão dos direitos sociais, o lugar do \'projeto participativo\' neste contexto e a verificação do espaço assumido pelos arquitetos no desenvolvimento dos projetos. Além disso, questionamos os diálogos possíveis e as mistificações em torno da relação entre conhecimento \'popular\' e \'especializado\' e tentamos qualificar as figurações que conformam a prática desses profissionais no cenário atual, de forma a problematizar a \'essência técnica\' da experiência projetual como horizonte crítico para pensar os conteúdos políticos do ofício.<br>The purpose of this explanation is to bring us a critical reflection about the architectural professional practice pointed out to the questions concerning popular housing, especially the social housing in urbanized slums. We started from a historical revision on how the architect plays its part concerning the circumstances of the continuous precariousness of the urban housing, treading a bibliographic and analytical route that starts in the years 1930\'s and arrives to the present days: approaching the presence of slums in the Brazilian cities, we raise discussions about the practice of the professionals involved with the already consecrate process of urban upgrading of those settlement and also regarding the deficiencies of the performance of the State, that comes gradually betting in compensatory policies to deal with the housing deficit. As a methodological procedure we opted to focusing some recent practices of slum upgrading: the experiences from Dois de Maio and Jardim Olinda centers, both in São Paulo (SP), and Tamarutaca center in Santo André (SP), include in the years 2000\'s in two different public urbanization programs - the program Bairro Legal, of the São Paulo city hall, and the program named Programa de Inclusão Social (currently Santo André Mais Igual), promoted by the Santo André public power - and from whose urbanity and housing projects participated, respectively, the non-governmental organizations USINA Centro de Trabalhos para o Ambiente Habitado / TEIA Casa de Criação (as partner), GTA Grupo Técnico de Apoio e PEABIRU Trabalhos Comunitários e Ambientais. The field research make us possible to understand either the historical evolution of the professional exercise of the architects in the confront of the slums deal, as the potentialities of the contemporaneous practice transformation, taking into account the politic context that involves the State, social activities, technical activities and the amplest set of the society. From the description of the cases, we look for to argue the current reality of the slums upgrading public policies and their relation with the social rights and the importance of the \'participative project\' in the process under studying. Furthermore, we question the possible dialogues and the mystifications around the relation between \'popular\' and \'specialized\' knowledge and we try to discuss the \'technical essence\' of the projective experience of the architects as a critical horizon to think the politic contents of the craft.

Il glaucoma è una patologia neurodegenerativa sostenuta dalla morte per apoptosi delle CGR. Rappresenta la principale causa di cecità irreversibile al mondo. Non sono ancora stati compresi a fondo tutti i meccanismi che causano la degenerazione neuronale nel glaucoma (tanto che sussistono delle forme di glaucoma a PIO normale). Un ruolo importante nel meccanismo patogenetico glaucomatoso viene riconosciuto oggi ad una condizione di infiammazione cronica a livello retinico determinata da alterazioni dei livelli di PIO. Lo scopo del presente progetto di dottorato è stato un approccio multidisciplinare al glaucoma, di tipo clinico e biochimico-molecolare. In primo luogo, è stato implementato un prototipo di perimetro (Compass, Centervue, Padova, Italia), attuando dapprima un database normativo di soggetti sani al fine di integrare le caratteristiche demografiche per il test perimetrico 30-2. Successivamente, è stata valutata l’affidabilità test-retest dell’apparecchio, eseguendo il campo visivo “New Grid” per sei volte consecutive in un gruppo di pazienti clusterizzati secondo l’MD, ottenendo una bassa variabilità intra-test. È stato altresì calcolato l’agreement tra tre diversi revisori, i quali hanno esaminato indipendentemente le perimetrie e le foto fundus Compass, stabilendo un peggioramento o meno della patologia glaucomatosa, nonché la concordanza tra l’analisi da remoto dei campi visivi e immagini Compass, e la visita clinica standard dei pazienti affetti da glaucoma. I risultati hanno messo in evidenza un’ottima concordanza tra i Reviewers e tra gli esami da remoto e la visita clinica. Ai fini di stabilire la precisione punto per punto del perimetro, è stata eseguita un’analisi del Compass 10-2 in pazienti affetti da atrofia geografica, trovando una corrispondenza punto per punto della perimetria con l’immagine retinica sottostante. In ultimo, è stata effettuata un’analisi dell’osmolarità lacrimale e di tutti i parametri clinici del film lacrimale in pazienti affetti da glaucoma asimmetrico. Per quanto riguarda l’indagine biochimico-molecolare, è stata effettuata una analisi preliminare nell’umore acqueo della proteina di gap-junction Connessina 43 in un piccolo gruppo di soggetti sani e glaucomatosi, che ha posto in evidenza un aumento quasi doppio della dell’espressione della molecola nei soggetti glaucomatosi, anche se la ridotta numerosità del campione non ha prodotto un risultato statisticamente significativo. È stato inoltre utilizzato in questo progetto di dottorato un metodo innovativo di analisi: la metabolomica, ramo scientifico che si occupa di analizzare i metaboliti &lt;1,5 kDa che derivano da specifici processi chimici cellulari in campioni biologici umani. Utilizzando la Spettroscopia di Risonanza Magnetica Nucleare 1H, sono stati analizzati campioni di vitreo di pazienti sottoposti a vitrectomia, identificando un aumento di acetone e metanolo negli occhi glaucomatosi.<br>Glaucoma is a neurodegenerative disease caused by ganglion cells death by apoptosis. It represents the leading cause of irreversible blindness in the world. Although the mechanisms triggering the neuronal degeneration in glaucoma have not yet been fully understood, a chronic inflammatory condition at the retinal level, sustained by abnormal IOP, is considered today a main factor in glaucoma pathogenesis. The aim of this PhD project was a multidisciplinary approach to glaucoma investigation, both clinical and bio-molecular. Firstly, a prototype of visual field analyzer (Compass, Centervue, Padua, Italy) was implemented, primarily by developing a demographic database of healthy subjects for 30-2 perimetric test. Subsequently, the test-retest reliability of the device was assessed by performing the "New Grid" visual field six straight times in a group of patients clustered according to the MD, resulting in a good inter-test reliability. The agreement between three different reviewers was also calculated: they independently examined Compass visual fields and the fundus photos, establishing whether or not the glaucomatous pathology worsened, as well as the agreement between the remote analysis and the standard clinical visit of glaucoma patients. The results highlighted an excellent agreement among the Reviewers and between remote analysis and the clinical examination. In order to establish the Compass’ point-by-point accuracy, a 10-2 visual field was performed in patients affected by geographic atrophy, finding an accurate correspondence of the perimetric scores with the underlying retinal image. Ultimately, the osmometry and all the clinical parameters of the tear film were analyzed in patients suffering from asymmetric glaucoma. Afterwards, for the biochemical and molecular approach, the analysis of gap-junction protein connexin 43 in the aqueous humor of affected and unaffected glaucoma patients was performed: a nearly double expression of the protein was found in glaucomatous subjects, even if there were no statistically significant differences, probably due to the small number of samples. An innovative method of biochemical analysis was introduced in this doctorate thesis: the metabolomics, a scientific branch that deals with the analysis of &lt;1.5 kDa metabolites deriving from specific cellular processes in human samples. Vitreous samples of patients operated by vitrectomy were analyzed by 1H-NMR Nuclear Magnetic Resonance Spectroscopy, and an increase in acetone and methanol was observed in glaucomatous eyes.

Il lavoro descritto in questa tesi di Dottorato concerne lo sviluppo di due metodi innovativi di upgrading del biogas. La progettazione e la realizzazione di due dispositivi in scala pilota ha consentito di indagare due sistemi innovativi di rimozione della CO2, ovvero il processo di Assorbimento con Rigenerazione, basato sull’assorbimento chimico della CO2 con soluzioni alcaline e rigenerazione della soluzione di lavaggio con residui da APC, e il processo di Adsorbimento, basato sulla reazione chimica della CO2 con scorie di fondo da inceneritore. Nella fase iniziale sono stati abbinati gli studi teorici sull’argomento all’analisi delle prove sperimentali in scala di laboratorio presenti in letteratura e/o realizzate dai gruppi di ricerca partner di progetto. Questa fase ha portato all’individuazione delle specifiche tecniche e delle configurazioni di lavoro necessarie per il dimensionamento, la progettazione e la realizzazione degli impianti pilota. L'aspetto innovativo dei due processi è dato dall’applicazione di metodi di rimozione di anidride carbonica dal biogas accompagnato dal suo stoccaggio in fase solida, in modo da non emettere di nuovo all'atmosfera l'anidride carbonica rimossa, la quale essendo di origine biogenica può contribuire come emissione negativa per l'equilibrio serra complessivo. Le prove sperimentali dei due processi sono state condotte in scala pilota utilizzando per il trattamento il gas di discarica spillato da una sottostazione all’interno dell’impianto di discarica di Casa Rota situato a Terranuova Bracciolini. Tali test sperimentali hanno consentito di valutare le prestazioni, l’effettivo raggiungimento degli standard proposti da alcune nazioni europee nelle configurazioni di lavoro in studio e l’utilizzo in medio-larga scala dei due processi utilizzando impianti pilota appositamente progettati e realizzati in ambito del progetto europeo LIFE UPGAS-LOWCO2. Dall’analisi tecnico-economica dei risultati di queste campagne sperimentali è stato ideato un sistema che abbina i due processi studiati singolarmente. Dunque sono stati aggiornati i dispositivi in scala pilota per la conduzione di ulteriori campagne sperimentali, in ambito del progetto ministeriale TECGAS, volte a dimostrare la fattibilità tecnica ed estrarre i parametri che maggiormente influenzano il processo.

碩士<br>國立中山大學<br>海洋環境及工程學系研究所<br>97<br>This research studies the properties of self-compacting concrete by applying bamboo-charcoal to improve the fresh concrete property, physical property and micro-scale property.Conventionally, the Pozzolanic materials used in the self-compacting concrete are fly ash and slag. They are used to replace part of the cement such that the flowing property and compacting property can reach the requirement of the self-compacting concrete. According to previous research the bamboo-charcoal can absorb part of water, and enhance the early strength of concrete. In this study, we use bamboo-charcoal to replace parts of the fine-aggregate in the mixture of self-compacting concrete. The replacement ratio is designed as 0‰,2‰,3‰,3.5‰,4‰ and 5‰. From the experimental test of fresh concrete property, we can evaluate whether the concrete mix design can achieve the requirements of self-compacting concrete. Test for the compressive strength development, water absorption and rapid chloride penetration test are performed to evaluate the physical property of concrete. In addition, the scanning electronic microscope photos are taken to examine the microstructure of the concrete. In our results, it is found that the best proportion of replacement is 3‰. The requirements of self-compacting concrete can be satisfied, and the development of strength is also good.

Subarachnoid hemorrhage (SAH) is commonly caused by rupture of an intracranial aneurysm, arteriovenous malformation, or due to trauma. Prompt diagnosis and intervention are required to control intracranial pressure, maintain cerebral perfusion, and prevent rebleeding. Clinical grading of the bleed predicts morbidity and mortality, whereas imaging grading predicts risk of cerebral vasospasm. Hydrocephalus can occur as a result of SAH, which requires treatment with an external ventricular drain. Endovascular and open microsurgical procedures are available for securing the vascular abnormalities. Patients are typically monitored in a neurocritical care unit for up to 21 days post-bleed to monitor for the development of cerebral vasospasm/delayed cerebral ischemia (DCI). Mainstay of treatment for DCI includes induced hypertension, balloon angioplasty, and intraarterial vasodilator therapy. In addition, patient may experience significant derangement in their cardiac, pulmonary, and endocrine systems, requiring inotropic support, mechanical ventilation, or insulin infusion therapy.

AbstractThis paper examines the use of machine learning in creating digitally integrated design-to-fabrication workflows. As computational design allows for new methods of material specification and fabrication, it enables direct functional grading of material at high detail thereby tuning the design performance in response to performance criteria. However, the generation of fabrication data is often cumbersome and relies on in-depth knowledge of the fabrication processes. Parametric models that set up for automatic detailing of incremental changes, unfortunately, do not accommodate the larger topological changes to the material set up. The paper presents the speculative case study KnitVault. Based on earlier research projects Isoropia and Ombre, the study examines the use of machine learning to train models for fabrication data generation in response to desired performance criteria. KnitVault demonstrates and validates methods for shortcutting parametric interfacing and explores how the trained model can be employed in design cases that exceed the topology of the training examples.

AbstractThe Vancouver scar scale, the Manchester scar scale, and the Patient and Observer Scar Assessment Scale (POSAS) are all very well-known scar evaluation methods. These tools are based on a number of scar variables, including color, height, and pliability. However, since all were mainly developed to evaluate burn scars, they are difficult to use in clinical practice for keloids and hypertrophic scars. This is because these pathological scars require both differential diagnosis and a way to evaluate their response to therapy. The Japan Scar Workshop (JSW) has sought to develop a scar assessment scale that meets these clinical needs. The first version of this scar assessment tool was named the JSW scar scale (JSS), and it was reported in 2011. In 2015, the revised second version was reported. The JSS consists of two tables. One is a scar classification table that is used to determine whether the scar is a normal mature scar, a hypertrophic scar, or a keloid. This grading system helps the user to select the most appropriate treatment method for the scar. The other table in the JSS is an evaluation table that is used to judge the response to treatment and for follow-up. Both tables contain sample images of each subjective keloid/hypertrophic scar item that allow the user to evaluate each item without hesitation.

AbstractAccompanying the construction of inland navigation projects is the generation of high slopes, whose stability has always been an important safety issue of great concern during the process. The safety incidents involving high slope instability often cause huge economic losses and even casualties. Therefore, it is of particular importance to monitor high slopes, to identify safety hazards and to predict the occurrence of safety accidents in advance through the tendency of changing. Once the project is completed, effective monitoring is also essential during the operation of the locks in order to avoid safety accidents such as the collapse of ship locks and other main structures.Based on the BeiDou high-precision positioning technology, this paper investigates the application of the automated displacement monitoring system in the construction and operation of navigation projects. The system mainly consists of sensor subsystem, data transmission subsystem, data processing and control subsystem as well as other auxiliary support subsystems. The system collects static satellite data from fiducial points and monitoring points, carries out baseline vector solution to realize millimeter-level displacement monitoring, and effectively monitors high slope displacement during construction according to the storage, management, query, statistics and analysis of the monitoring data, as well as timely detects abnormal situations about the displacement. When there is slope instability, early warning will be issued by grading so that measures could be implemented in advance to avoid safety accidents. When applied during the operation of ship locks, it can monitor the displacement of the lock chamber’s main work persistently to ensure its normal operation.This paper takes the construction site of certain ship lock project as the object and sets up 1 fiducial point and 10 monitoring points. The real-time displacement monitoring of the site’s high slopes throughout the construction period is carried out, the main functions of the monitoring system are tested and the monitoring data and results are briefly analyzed. After the completion of the project, the monitoring system is applied during the operation of the ship lock and the deformation of the lock chamber is constantly monitored and analyzed.

This chapter explores a number of gastroenterological conditions, including hepatic encephalopathy, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, alcohol withdrawal, peptic ulcer disease, alcoholic hepatitis, inflammatory bowel disease, and upper gastrointestinal varices. Grading scales are used to assess the severity of presentation, after which the steps required for each condition’s immediate management are laid out, including the ABCDE assessment and various intravenous techniques. Finally, the condition’s further management and causes are explored, with further grading scales and up-to-date guidelines on pharmaceutical courses. Further reading is provided at the end of each topic.

Automatic short-answer grading aims to predict human grades for short free-text answers to test questions, in order to support or replace human grading. Despite active research, there is to date no wide-spread use of ASAG in real-world teaching. One reason is a lack of transparency of popular methods like Transformer-based deep neural networks, which means that students and teachers cannot know how much to trust automated grading. We probe one such model using the adversarial attack paradigm to better understand their reliance on syntactic and semantic information in the student answers, and their vulnerability to the (easily manipulated) answer length. We find that the model is, reassuringly, likely to reject answers with missing syntactic and semantic information, but that it picks up on the correlation between answer length and correctness in standard training. Thus, real-world applications have to safeguard against exploitation of answer length.

Abstract Although visual data analytics using image processing is one of the most growing research areas today and is largely applied in many fields, it is not fully utilized in the petroleum industry. This study is inspired by medical image segmentation in detecting tumor cells. This paper uses a supervised Machine Learning technique through video analytics to identify bit dullness that can be used in the drilling industry in place of the subjective screening approach. The evaluation of bit performance can be affected by subjective evaluation of the degree of dullness. The present approach of using video analytics is able to grade bit dullness to avoid user subjectivity. The approach involves the use of datasets in good quantity and quality by separating them into training datasets, testing datasets, and validation datasets. Due to the large datasets, Google Collaboratory was used as it provides access to its Graphic Processing Unit (GPU) online for the processing of the bit datasets. The processing time and resource consumption are minimized using Google GPU. Using the Google GPU resources, the procedure is automated without any installation. After the bit is pulled out and cleaned, a video is taken around and up and down in 360°. Further, it is compared against the green bit. By this approach, multiple video datasets are not required. The algorithm was validated with new sets of bit videos and the results were satisfactory. The identification of the dullness or otherwise of each screened bit is done with the aid of a bounding box with a stamp of a level of confidence (range 0.5–1) and the algorithm assigns for its decision on the identified or screened object. This method is also able to screen multiple bits stored in a single place. In an event where several drill bits are to be screened, manual grading will be a huge task and will require a lot of resources. This model and algorithm will take a few minutes to screen and provide grading for several bits while videos are passed through the algorithm. It has also been found that the grading with the video was much better than the single image as the contextual information extracted are much higher at the level of the entire video, per segment, per shot, and per frame. Also, methodology is made robust so that the video model test starts successfully without error. The time penalty for the processing is fast and it took less time for a single video screening. The work developed here is probably the first to handle the dull bit grading using video analytics. With more of these datasets available, the future automation of the IADC bit characterization will soon evolve into an automated process.

Brazilian Graduate Programs are evaluated by a specific foundation, CAPES. This evaluation qualifies the respective program with a grade, and this directly influences the permissions and funds assigned to this program, such as having a doctorate level, grading 4 or higher. One of the indicators is the student body, as an external variable outside the control of the program. Based on the Design Science Research methodology, we present a research on the construction of an artifact that clears up the selection of candidates for the programs, categorizing them according to the profiles of previous students, based on descriptive statistics and data analytics.

Each year, over 700 students take the Engineering Graphics course taught within the General Engineering Program at Clemson University. A SCALE-UP (Student-Centered Activities for Large-Enrollment Undergraduate Programs) environment is utilized to provide a highly collaborative, hands-on classroom format with a primary emphasis on learning by guided inquiry and live demonstrations rather than by traditional lecturing. One of the goals of using this format is real-time assistance and rapid feedback. In the spring term, each class day, 400 student submit a solid model file. This presents a challenge to returning feedback before the next class period. The current grading method consists of students submitting solid model files to a course management system and awarding credit for submissions matching the mass of the presented design. However, this method does not allow students to earn partial credit based on the relative accuracy of their model. To date, instructors have been unable to reward partial credit in an automated or timely manner. The objective of this research is to evaluate the use of shape similarity algorithms to provide decision making support while grading solid models for this engineering graphics course. The proposed method of automated grading is to use a solid model similarity algorithm and the mass properties to assess the relative similarity of each submission to a correct solid model. The distribution of grades using the proposed method is compared to the existing method’s distribution. Use of the proposed method ensures that the results from this research can be applied to other engineering graphics courses, regardless of the solid modeling software used.

There are flaws in the way that schools and universities teach today. This article describes an application that will try to ameliorate some of those flaws by using one of the biggest parts of entertainment we consume today...games. The application will use the principle of gamifying education in order to make teaching/studying more engaging and fun. The software will be developed for both desktop devices and mobile in order to make it accessible to everyone, teacher and student alike. In order for this idea/application to work there is need for a world that suits a particular class to be created. This will be done by having the professor use the app to create the world and set its rules. The app will work as a creator/editor/tracker and manager software.Using the app he can decide how the "game" will be played and "won". Lee Sheldon associate professor and co-director of the Games and Simulation Arts program at Rensselaer Polytechnic Institute proposes we use an upside down grading method. The problem with grading now is that it is always counting down. All of the students start subconsciously with a 10 in every course, after this point every mistake they do is counted and deducted from their 10, this is demotivational for the student. The proposed change is to do as following, rename points to experience points (XP) and grades to levels, have all the students start at 0 XP and have them gain points for every assignment or test, it's more fun to win stuff than to loose. Lee Sheldon created a "new world" in which he "replaced" students with heroes, tests with bosses and any other teaching principle with a gaming term. In games we learn that leveling or progressing allows you to take on bigger and bigger challenges thus encouraging more progress. With this new grading system in mind the world can be created. Using the application the professor can choose to use a default world and just tweak it to suit his class or start from scratch. The teacher will name his world, choose its theme (sci-fi, ancient, etc.), will approve student names and avatars, manage the guilds (groups). Also he will decide on how the grading will work (decide on the number of xp needed to level up (reach a new grade) and on the number of methods to level up (achievements or other prerequisites).

Abstract Polymer flood (PF) applications have increasingly been extended to medium-to-heavy oil reservoirs for enhanced displacement and sweep efficiency and pushing the recovery beyond the limits of conventional recovery techniques. The relatively low carbon footprint and gas-light nature has made PF attractive in many cases compared to the traditional thermal methods. Consequently, many fields in the Sultanate of Oman with viscosities ranging from about 90cP to 500cP have been studied and field trialled for polymer development, and one such field has been successfully undergoing field-scale PF for over 8 years, which is the subject of this study. As PF is matured in the field, the ongoing challenge is to support production operations and optimise flood performance. This study lays the foundation for holistic simulation study targeting theoretical based considerations for PF optimization. It starts with understanding the nature of polymer/polymer and polymer/water type displacements and stabilities, and encompasses modelling the phenomena of viscous fingering/instabilities in a range of model set-ups, starting from high resolution core-scale 2D models to 3D sector models incorporating varying degrees of geological heterogeneities. Understanding of displacement stability gained with high-resolution models is extended to investigate polymer/water mixing, Water-Alternating-Polymer (WAP) recovery and polymer grading (tapering). These subjects have been integrated to emphasise the optimal polymer slug size requirement with creaming curve analyses that build on the principles of containing fingers/instabilities due to lower viscosity follow-up slugs or chase water. The polymer flood optimization is taken to the next step by investigating the concepts of polymer grading. Three prevalent grading concepts proposed by Claridge ([5], [6], [7], [8]), Ligthelm-Schulte and Stegemeier in combination with different mixing rules form the basis of polymer grading assessment. The study highlights significant scope for optimizing polymer flood in the field both in terms of long-term improved recovery performance at reduced cost as well as tackling the short-term operational challenges, potentially impacting the business bottom-line.

With the global increase in the use of traditional and complementary remedies for the prevention and treatment of illness, the quality and safety of these medicines have become a significant concern for all regulatory authorities. Herbal medicines are the most commonly used form of traditional and complementary medicines in the world and the efficacy and safety of herbal medicines, like conventional medicines, largely depends on their quality from planting to harvesting, preprocessing and final processing. Due to the inherent complexity of herbal medicines, often containing an array of active compounds, the primary processing of herbal medicines has a direct influence on their quality. Quality concerns are the reason why the medicines regulatory agencies insist that manufacturers of medicines strictly follow Good Manufacturing Practices since it is an essential tool to prevent instances of contamination, mix-ups, deviations, failures and errors. However, a strict application of GMP requirements is expensive and would drive the prices of the manufactured products up. As a result, a maturity level grading of facilities is proposed as a way of justifying the costs incurred for manufacturers desiring to reach a broader market and investing in continuous improvement. 36 Good Manufacturing Practice (GMP) inspection reports of local herbal manufacturers conducted by National Drug Authority were analyzed to establish the type and extent of deficiencies to GMP requirements for local herbal manufacturers in Uganda. The different GMP chapters and related sub-parameters constituted the variables used for the analysis of conformity to requirements. The primary outcome variable was the conclusion regarding compliance or noncompliance of the inspected local herbal manufacturing facility. GMP parameters that were frequently defaulted by local herbal manufacturers and the corresponding frequencies were identified. The Pearson Chi-square test was applied independently on each category to find the association that existed between conformity and the questions in each category. Only 22% (8) of the 30 inspected facilities were found to comply with GMP requirements, as per National Drug Authority (NDA) guidelines; while the majority of the facilities, 28 (78%), were found not to comply. Of the facilities inspected, 25 were undergoing GMP inspection for the first time. A total of 1,236 deficiency observations were made in the 36 inspection reports reviewed for the study. The mean for all deficiencies was 34.3, and the standard deviation was 15.829. 91.5% of the facilities did not have mechanisms for a record of market complaints; 80.9% did not meet documentation requirements; 78.9% did not have quality control measures in place, and 65.7% did not meet stores requirements. By encouraging a culture of self/voluntary improvement through the introduction of listing of manufacturers based on a maturity level grading, the National Drug Authority will improve the Herbal Medicines sector as per the mandate of improving the herbal medicine industry. Also, increased sensitization of all relevant stakeholders regarding the requirements for GMP should be intensified.

The objectives of this project were to develop nondestructive methods for detection of internal properties and firmness of fruits and vegetables. One method was based on a soft piezoelectric film transducer developed in the Technion, for analysis of fruit response to low-energy excitation. The second method was a dot-matrix piezoelectric transducer of North Carolina State University, developed for contact-pressure analysis of fruit during impact. Two research teams, one in Israel and the other in North Carolina, coordinated their research effort according to the specific objectives of the project, to develop and apply the two complementary methods for quality control of agricultural commodities. In Israel: An improved firmness testing system was developed and tested with tropical fruits. The new system included an instrumented fruit-bed of three flexible piezoelectric sensors and miniature electromagnetic hammers, which served as fruit support and low-energy excitation device, respectively. Resonant frequencies were detected for determination of firmness index. Two new acoustic parameters were developed for evaluation of fruit firmness and maturity: a dumping-ratio and a centeroid of the frequency response. Experiments were performed with avocado and mango fruits. The internal damping ratio, which may indicate fruit ripeness, increased monotonically with time, while resonant frequencies and firmness indices decreased with time. Fruit samples were tested daily by destructive penetration test. A fairy high correlation was found in tropical fruits between the penetration force and the new acoustic parameters; a lower correlation was found between this parameter and the conventional firmness index. Improved table-top firmness testing units, Firmalon, with data-logging system and on-line data analysis capacity have been built. The new device was used for the full-scale experiments in the next two years, ahead of the original program and BARD timetable. Close cooperation was initiated with local industry for development of both off-line and on-line sorting and quality control of more agricultural commodities. Firmalon units were produced and operated in major packaging houses in Israel, Belgium and Washington State, on mango and avocado, apples, pears, tomatoes, melons and some other fruits, to gain field experience with the new method. The accumulated experimental data from all these activities is still analyzed, to improve firmness sorting criteria and shelf-life predicting curves for the different fruits. The test program in commercial CA storage facilities in Washington State included seven apple varieties: Fuji, Braeburn, Gala, Granny Smith, Jonagold, Red Delicious, Golden Delicious, and D'Anjou pear variety. FI master-curves could be developed for the Braeburn, Gala, Granny Smith and Jonagold apples. These fruits showed a steady ripening process during the test period. Yet, more work should be conducted to reduce scattering of the data and to determine the confidence limits of the method. Nearly constant FI in Red Delicious and the fluctuations of FI in the Fuji apples should be re-examined. Three sets of experiment were performed with Flandria tomatoes. Despite the complex structure of the tomatoes, the acoustic method could be used for firmness evaluation and to follow the ripening evolution with time. Close agreement was achieved between the auction expert evaluation and that of the nondestructive acoustic test, where firmness index of 4.0 and more indicated grade-A tomatoes. More work is performed to refine the sorting algorithm and to develop a general ripening scale for automatic grading of tomatoes for the fresh fruit market. Galia melons were tested in Israel, in simulated export conditions. It was concluded that the Firmalon is capable of detecting the ripening of melons nondestructively, and sorted out the defective fruits from the export shipment. The cooperation with local industry resulted in development of automatic on-line prototype of the acoustic sensor, that may be incorporated with the export quality control system for melons. More interesting is the development of the remote firmness sensing method for sealed CA cool-rooms, where most of the full-year fruit yield in stored for off-season consumption. Hundreds of ripening monitor systems have been installed in major fruit storage facilities, and being evaluated now by the consumers. If successful, the new method may cause a major change in long-term fruit storage technology. More uses of the acoustic test method have been considered, for monitoring fruit maturity and harvest time, testing fruit samples or each individual fruit when entering the storage facilities, packaging house and auction, and in the supermarket. This approach may result in a full line of equipment for nondestructive quality control of fruits and vegetables, from the orchard or the greenhouse, through the entire sorting, grading and storage process, up to the consumer table. The developed technology offers a tool to determine the maturity of the fruits nondestructively by monitoring their acoustic response to mechanical impulse on the tree. A special device was built and preliminary tested in mango fruit. More development is needed to develop a portable, hand operated sensing method for this purpose. In North Carolina: Analysis method based on an Auto-Regressive (AR) model was developed for detecting the first resonance of fruit from their response to mechanical impulse. The algorithm included a routine that detects the first resonant frequency from as many sensors as possible. Experiments on Red Delicious apples were performed and their firmness was determined. The AR method allowed the detection of the first resonance. The method could be fast enough to be utilized in a real time sorting machine. Yet, further study is needed to look for improvement of the search algorithm of the methods. An impact contact-pressure measurement system and Neural Network (NN) identification method were developed to investigate the relationships between surface pressure distributions on selected fruits and their respective internal textural qualities. A piezoelectric dot-matrix pressure transducer was developed for the purpose of acquiring time-sampled pressure profiles during impact. The acquired data was transferred into a personal computer and accurate visualization of animated data were presented. Preliminary test with 10 apples has been performed. Measurement were made by the contact-pressure transducer in two different positions. Complementary measurements were made on the same apples by using the Firmalon and Magness Taylor (MT) testers. Three-layer neural network was designed. 2/3 of the contact-pressure data were used as training input data and corresponding MT data as training target data. The remaining data were used as NN checking data. Six samples randomly chosen from the ten measured samples and their corresponding Firmalon values were used as the NN training and target data, respectively. The remaining four samples' data were input to the NN. The NN results consistent with the Firmness Tester values. So, if more training data would be obtained, the output should be more accurate. In addition, the Firmness Tester values do not consistent with MT firmness tester values. The NN method developed in this study appears to be a useful tool to emulate the MT Firmness test results without destroying the apple samples. To get more accurate estimation of MT firmness a much larger training data set is required. When the larger sensitive area of the pressure sensor being developed in this project becomes available, the entire contact 'shape' will provide additional information and the neural network results would be more accurate. It has been shown that the impact information can be utilized in the determination of internal quality factors of fruit. Until now,