Design of a Modern Liposome and Bee Venom Formulation for the Traditional VIT-Venom Immunotherapy

Traditional venom immunotherapy uses injections of whole bee venom in buffer or adsorbed in Al (OH)(3) in an expensive, time-consuming way. New strategies to improve the safety and efficacy of this treatment with a reduction of injections would, therefore, be of general interest. It would improve patient compliance and provide socio-economic benefits. Liposomes have a long tradition in drug delivery because they increase the therapeutic index and avoid drug degradation and secondary effects. However, bee venom melittin (Mel) and phospholipase (PLA(2)) destroy the phospholipid membranes. Our central idea was to inhibit the PLA(2) and Mel activities through histidine alkylation and or tryptophan oxidation (with pbb, para-bromo-phenacyl bromide, and/or NBSN-bromosuccinimide, respectively) to make their encapsulations possible within stabilized liposomes. We strongly believe that this formulation will be nontoxic but immunogenic. In this paper, we present the whole bee venom conformation characterization during and after chemical modification and after interaction with liposome by ultraviolet, circular dichroism, and fluorescence spectroscopies. The PLA(2) and Mel activities were, measured indirectly by changes in turbidity at 400(nm), rhodamine leak-out, and hemolysis. The native whole bee venom (BV) presented 78.06% of alpha-helical content. The alkylation (A-BV) and succynilation (S-BV) of BV increased 0.44 and 0.20% of its alpha-helical content. The double-modified venom (S-A-BV) had a 0.74% increase of alpha-helical content. The BV chemical modification induced another change on protein conformations observed by Trp that became buried with respect to the native whole BV. It was demonstrated that the liposomal membranes must contain pbb (SPC:Cho:pbb, 26:7:1) as a component to protect them from aggregation and/or fusion. The membranes containing pbb maintained the same turbidity (100%) after incubation with modified venom, in contrast with pbb-free membranes that showed a 15% size decrease. This size decrease was interpreted as membrane degradation and was corroborated by a 50% rhodamine leak-out. Another fact that confirmed our interpretation was the observed 100% inhibition of the hemolytic activity after venom modification with pbb and NBS (S-A-BV). When S-A-BV interacted with liposomes, other protein conformational changes were observed and characterized by the increase of 1.93% on S-A-BV alpha-helical content and the presence of tryptophan residues in a more hydrophobic environment. In other words, the S-A-BV interacted with liposomal membranes, but this interaction was not effective to cause aggregation, leak-out, or fusion. A stable formulation composed by S-A-BV encapsulated within liposomes composed by SPC:Cho:pbb, at a ratio of 26:7:1, was devised. Large unilamellar vesicles of 202.5 nm with a negative surface charge (-24.29 mV) encapsulated 95% of S-A-BV. This formulation can, now, be assayed on VIT.

Micro/nanostructured carbon composite modified with a hybrid redox mediator and enzymes as a glucose biosensor

A carbon micro/nanostructured composite based on cup-stacked carbon nanotubes (CSCNTs) grown onto a carbon felt has been found to be an efficient matrix for enzyme immobilization and chemical signal transduction. The obtained CSCNT/felt was modified with a copper hexacyanoferrate/polypyrrole (CuHCNFe/Ppy) hybrid mediator, and the resulting composite electrode was applied to H(2)O(2) detection, achieving a sensitivity of 194 +/- 15 mu A mmol(-1) L. The results showed that the CSCNT/felt matrix significantly increased the sensitivity of CuHCNFe/Ppy-based sensors compared to those prepared on a felt unrecovered by CSCNTs. Our data revealed that the improved sensitivity of the as-prepared CuHCNFe/Ppy-CSCNT/felt composite electrode can be attributed to the electronic interactions taking place among the CuHCNFe nanocrystals, Ppy layer and CSCNTs. In addition, the presence of CSCNTs also seemed to favor the dispersion of CuHCNFe nanocrystals over the Ppy matrix, even though the CSCNTs were buried under the conducting polymer layer. The CSCNT/felt matrix also enabled the preparation of a glucose biosensor whose sensitivity could be tuned as a function of the number of glucose oxidase (GOx) layers deposited through a Layer-by-Layer technique with an sensitivity of 11 +/- 2 mu A mmol(-1) L achieved at 15 poly(diallyldimethylammoniumchloride)/GOx bilayers. (C) 2011 Elsevier Ltd. All rights reserved.

Students at work in the Air Conditioning and Refrigeration Department of the New York Trade School

Students in the Air Conditioning/Refrigeration Dept. of the New York Trade School are shown hard at work in the classroom. Notice the sign at the rear of the room that reads "Watch Out for Pipes on Floor." Black and white photograph.

Classroom in the Plumbing Department

An empty classroom in the Plumbing Department at the New York Trade School is pictured. The two platforms contain models of framing for a house including pipes on which students may practice working. Black and white photograph.

Identifiering av parametrar till ackumulatortanken Solus1050 från consolar - en metodbeskrivning

This report describes the work done creating a computer model of a kombi tank from Consolar. The model was created with Presim/Trnsys and Fittrn and DF were used to identify the parameters. Measurements were carried out and were used to identify the values of the parameters in the model. The identifications were first done for every circuit separately. After that, all parameters are normally identified together using all the measurements. Finally the model should be compared with other measurements, preferable realistic ones. The two last steps have not yet been carried out, because of problems finding a good model for the domestic hot water circuit.The model of the domestic hot water circuit give relatively good results for low flows at 5 l/min, but is not good for higher flows. In the report suggestions for improving the model are given. However, there was not enough time to test this within the project as much time was spent trying to solve problems with the model crashing. Suggestions for improving the model for the domestic circuit are given in chapter 4.4. The improved equations that are to be used in the improved model are given by equation 4.18, 4.19 and 4.22.Also for the boiler circuit and the solar circuit there are improvements that can be done. The model presented here has a few shortcomings, but with some extra work, an improved model can be created. In the attachment (Bilaga 1) is a description of the used model and all the identified parameters.A qualitative assessment of the store was also performed based on the measurements and the modelling carried out. The following summary of this can be given: Hot Water PreparationThe principle for controlling the flow on the primary side seems to work well in order to achieve good stratification. Temperatures in the bottom of the store after a short use of hot water, at a coldwater temperature of 12°C, was around 28-30°C. This was almost independent of the temperature in the store and the DHW-flow.The measured UA-values of the heat exchangers are not very reliable, but indicates that the heat transfer rates are much better than for the Conus 500, and in the same range as for other stores tested at SERC.The function of the mixing valve is not perfect (see diagram 4.3, where Tout1 is the outlet hot water temperature, and Tdhwo and Tdhw1 is the inlet temperature to the hot and cold side of the valve respectively). The outlet temperature varies a lot with different temperatures in the storage and is going down from 61°C to 47°C before the cold port is fully closed. This gives a problem to find a suitable temperature setting and gives also a risk that the auxiliary heating is increased instead of the set temperature of the valve, when the hot water temperature is to low.Collector circuitThe UA-value of the collector heat exchanger is much higher than the value for Conus 500, and in the same range as the heat exchangers in other stores tested at SERC.Boiler circuitThe valve in the boiler circuit is used to supply water from the boiler at two different heights, depending on the temperature of the water. At temperatures from the boiler above 58.2°C, all the water is injected to the upper inlet. At temperatures below 53.9°C all the water is injected to the lower inlet. At 56°C the water flow is equally divided between the two inlets. Detailed studies of the behaviour at the upper inlet shows that better accuracy of the model would have been achieved using three double ports in the model instead of two. The shape of the upper inlet makes turbulence, that could be modelled using two different inlets. Heat lossesThe heat losses per m3 are much smaller for the Solus 1050, than for the Conus 500 Storage. However, they are higher than those for some good stores tested at SERC. The pipes that are penetrating the insulation give air leakage and cold bridges, which could be a major part of the losses from the storage. The identified losses from the bottom of the storage are exceptionally high, but have less importance for the heat losses, due to the lower temperatures in the bottom. High losses from the bottom can be caused by air leakage through the insulation at the pipe connections of the storage.

Grundläggande förutsättningar för solfångare med interna reflektorer : en kunskapsöversikt

Syftet med föreliggande rapport har varit att visa på de grundläggande egenskaperna för solfångare med interna reflektorer. Vidare tjänar rapporten syftet att ge en bild av dagsläget inom detta område och därigenom fungera som en utgångspunkt för forskning och utveckling kring solfångare med interna reflektorer för svenskt bruk. Arbetet har därför till stor del gått ut på att leta referenser genom tidskrifter och databaser.Den stora fördelen med CPC-solfångare, som är den klart dominerande typen av solfångare med interna reflektorer, består i dess låga värmeförluster, vilket gör dem attraktiva speciellt vid högre driftstemperaturer. De optiska egenskaperna hos olika typer av CPC-solfångare har grundligt studerats sedan mitten av 70-talet, medan studier av värmeförluster varit mer begränsad. Idag har forskningen och intresset för CPC-solfångare mattats av något, men fortsatt forskning pågår t ex i ett flertal länder, t ex USA, Israel, NordIrland och Japan. Endast en kommersiell tillverkare av CPC-solfångare har hittats (Portugal), vilken dock upphört p g a yttre ekonomiska faktorer. Japans CPC-teknologi anses stå närmast kommersiellt genombrott.Idag har utvecklingen av CPC-solfångare inriktats mot i huvudsak två koncept:1. Stationära lågkoncentrerande CPC-solfångare för produktion av värme i området 60-100 grader C. Dessa konstruktioner är ofta enkla och man försöker minimera kostnaderna för dessa konstruktioner genom att minimera behovet av t ex reflektorer och isolering. Syftet med dessa är att konkurera med plana solfångare vilka producerar värme i samma temperaturintervall. Typiska solfångarparametrar 5 som rapporteras för denna typ är UL < 3.0 W/m2 ,°C och n0 = 0.65-0.75.2. Stationära lågkoncentrerande CPC-solfångare för produktion av värme i området 100-300 grader C. Ofta bygger dessa på olika teknik för evakuering av absorbatorn, antingen genom att omsluta cirkulära absorbatorer med glasrör eller genom att införa CPC-reflektorer i heatpipes. Syftet med dessa är ofta att på ett billigt sätt producera högtemperaturvärme för olika industriprocesser, och därmed konkurera med koncentrerande solfångare typ paraboliska tråg eller traditionella heat-pipes.Beräkningar av vad en Svensk CPC-solfångare, baserad på de plana absorbatorer som finns på marknaden idag, kan prestera visar att årsutbytet av energi är jämförbart med de bästa svenska plana solfångaren som finns på marknaden idag då driftstemperaturen är ca 60-65 °C. För högre driftstemperaturer ökar skillnaden till CPC-solfångarens fördel. Vidare visas att årsutbytet har en jämnare fördelning över året jämfört, med vad en plan solfångare med samma prestanda har. Den högre prestandan vid höga driftstemperaturer och den jämnare fördelningen av energiproduktion över året gör solfångare med CPC-reflektorer intressanta för större solfångarfält, kopplade till nät med höga returtemperaturer och/eller solvärmesystem med säsongslager.Det är dock brist på undersökningar av värmeförluster i CPC-solfångare med låga koncentrationer och med plana absorbatorer, vilket är av intresse ifall de svenska erfarenheterna av plana solfångare skall tas tillvara. Potentialen med ytterligare reduktion av värmeförlusterna genom att införa extra konvektionshinder i kombination med plan absorbator har inte heller undersökts tillräckligt.

Scriptural Archeology: Excavating the Presence of Women in the Torah

Women's roles in religious history have been traditionally described in terms of their relation and value to men. The normative religious texts provide an androcentric perspective on the gender relationships within the early community, the growth of Judaism in "Jacob's House" and the monotheistic worship of God. Yet these literary representations omit an entire half of the experience of the Jewish community: the perspective and participation of women. As Judith Plaskow argues extensively in Standing Again at Sinai, women are defined not in her own terms or in her own voice, but by her relationship and value to men through the androcentric vocabulary of the Torah. This statement is textually illustrated by the authorial and editorial presentation of women and their place in ancient Israelite society in the Torah. As Judaism grew increasingly androcentric in its leadership, women were increasingly reduced to marginal figures in the community by authorial and editorial revisions. Yet the participation of women of ancient Israel is not lost. Instead, the presence of women is buried beneath the androcentric presentation of the early Judaic community, waiting to be excavated by historical and scriptural examination. The retelling of the past is influenced by the present; memory is not static but takes on different shapes depending on the focus of concentration. However, tradition greatly influences the interpretation of religious history as well. In the book of Genesis, the literature emphasizes the divine appointment of male figures such as Abraham the father of the covenant and Jacob who is renamed and claimed by God as "Israel," placing them at the center of Jewish history. As a result, the other figures in these biblical narratives are described in relation to the patriarchs, those male bearers of the covenant, by their service or their value to him. Women are at the bottom of this hierarchy. Although female figures of exceptional quality are noted in later chronicles, such as Ruth, Deborah and Miriam, it is the very nature of their exception that highlights the androcentric editorial focus of the Torah. I agree with Peggy Day, whose own scriptural examination in Gender and Difference in Ancient Israel, makes the important distinction between the literary representation and the reality of ancient Israelite culture: they are not coextensive nor equivalent. Although the text represents the culture of ancient Israel as male dominated from the time of Abraham, this presentation omits the perspective of half of the population-the women. By beginning at the point of realization that women did exist and were active in their culture, and placing aside the androcentric perspective of the text and its editors, the reality of women's place in ancient Israel may be determined. Through this new perspective, the women of the Torah will emerge as the archetypes of strength, leadership and spiritual insight to provide Jewish women of the present with female, ancestral role models and a foundation for their gender's heritage, a more complete understanding of the partial record of Jewish history recorded in the Torah. Those stories that appear as the exception of women's presence will unveil an exceptional presence. As Tamar Frankiel eloquently states in The Voice of Sarah, "the women we call our 'Mothers'-Sarah, Rivkah (Rebekah), Rachel, and Leah-are not merely mothers, any more than the 'Fathers'-Abraham, Isaac and Jacob-are merely fathers "(Frankiel 5).

Using Multi-Objective Optimization To Maximize Multiple Benefits For Sustainable Drainage Design

For many years, drainage design was mainly about providing sufficient network capacity. This traditional approach had been successful with the aid of computer software and technical guidance. However, the drainage design criteria had been evolving due to rapid population growth, urbanisation, climate change and increasing sustainability awareness. Sustainable drainage systems that bring benefits in addition to water management have been recommended as better alternatives to conventional pipes and storages. Although the concepts and good practice guidance had already been communicated to decision makers and public for years, network capacity still remains a key design focus in many circumstances while the additional benefits are generally considered secondary only. Yet, the picture is changing. The industry begins to realise that delivering multiple benefits should be given the top priority while the drainage service can be considered a secondary benefit instead. The shift in focus means the industry has to adapt to new design challenges. New guidance and computer software are needed to assist decision makers. For this purpose, we developed a new decision support system. The system consists of two main components – a multi-criteria evaluation framework for drainage systems and a multi-objective optimisation tool. Users can systematically quantify the performance, life-cycle costs and benefits of different drainage systems using the evaluation framework. The optimisation tool can assist users to determine combinations of design parameters such as the sizes, order and type of drainage components that maximise multiple benefits. In this paper, we will focus on the optimisation component of the decision support framework. The optimisation problem formation, parameters and general configuration will be discussed. We will also look at the sensitivity of individual variables and the benchmark results obtained using common multi-objective optimisation algorithms. The work described here is the output of an EngD project funded by EPSRC and XP Solutions.

Evaluating And Optimizing Sustainable Drainage Design To Maximize Multiple Benefits: Case Studies In China

In the past, the focus of drainage design was on sizing pipes and storages in order to provide sufficient network capacity. This traditional approach, together with computer software and technical guidance, had been successful for many years. However, due to rapid population growth and urbanisation, the requirements of a “good” drainage design have also changed significantly. In addition to water management, other aspects such as environmental impacts, amenity values and carbon footprint have to be considered during the design process. Going forward, we need to address the key sustainability issues carefully and practically. The key challenge of moving from simple objectives (e.g. capacity and costs) to complicated objectives (e.g. capacity, flood risk, environment, amenity etc) is the difficulty to strike a balance between various objectives and to justify potential benefits and compromises. In order to assist decision makers, we developed a new decision support system for drainage design. The system consists of two main components – a multi-criteria evaluation framework for drainage systems and a multi-objective optimisation tool. The evaluation framework is used for the quantification of performance, life-cycle costs and benefits of different drainage systems. The optimisation tool can search for feasible combinations of design parameters such as the sizes, order and type of drainage components that maximise multiple benefits. In this paper, we will discuss real-world application of the decision support system. A number of case studies have been developed based on recent drainage projects in China. We will use the case studies to illustrate how the evaluation framework highlights and compares the pros and cons of various design options. We will also discuss how the design parameters can be optimised based on the preferences of decision makers. The work described here is the output of an EngD project funded by EPSRC and XP Solutions.

Modeling Of District Metered Areas With Relatively High Leakage Rate. The Case Study Of Kalipoli’s DMA

The article reviews the modelling of District Metered Areas (DMAs) with relatively high leakage rate. As a generally recognised approach in modelling of leakage does not exist, modelling of leakage by enginners and other researchers usually takes place by dividing the whole leakage rate evenly to all available nodes of the model. In this article, a new methodology is proposed to determine the nodal leakage by using a hydraulic model. The proposed methodology takes into consideration the IWA water balance methodology, the Minimum Night Flow (MNF) analysis, the number of connections related to each node and the marerial of pipes. In addition, the model is illustrated by a real case study, as it was applied in Kalipoli’s DMA. Results show that the proposed model gives reliable results.

Optimal Rehabilitation Strategy In Water Distribution Systems Considering Reduction In Greenhouse Gas Emissions

Most of water distribution systems (WDS) need rehabilitation due to aging infrastructure leading to decreasing capacity, increasing leakage and consequently low performance of the WDS. However an appropriate strategy including location and time of pipeline rehabilitation in a WDS with respect to a limited budget is the main challenge which has been addressed frequently by researchers and practitioners. On the other hand, selection of appropriate rehabilitation technique and material types is another main issue which has yet to address properly. The latter can affect the environmental impacts of a rehabilitation strategy meeting the challenges of global warming mitigation and consequent climate change. This paper presents a multi-objective optimization model for rehabilitation strategy in WDS addressing the abovementioned criteria mainly focused on greenhouse gas (GHG) emissions either directly from fossil fuel and electricity or indirectly from embodied energy of materials. Thus, the objective functions are to minimise: (1) the total cost of rehabilitation including capital and operational costs; (2) the leakage amount; (3) GHG emissions. The Pareto optimal front containing optimal solutions is determined using Non-dominated Sorting Genetic Algorithm NSGA-II. Decision variables in this optimisation problem are classified into a number of groups as: (1) percentage proportion of each rehabilitation technique each year; (2) material types of new pipeline for rehabilitation each year. Rehabilitation techniques used here includes replacement, rehabilitation and lining, cleaning, pipe duplication. The developed model is demonstrated through its application to a Mahalat WDS located in central part of Iran. The rehabilitation strategy is analysed for a 40 year planning horizon. A number of conventional techniques for selecting pipes for rehabilitation are analysed in this study. The results show that the optimal rehabilitation strategy considering GHG emissions is able to successfully save the total expenses, efficiently decrease the leakage amount from the WDS whilst meeting environmental criteria.

Multi-Objective Pipe Smoothing Genetic Algorithm For Water Distribution Network Design

This paper describes the formulation of a Multi-objective Pipe Smoothing Genetic Algorithm (MOPSGA) and its application to the least cost water distribution network design problem. Evolutionary Algorithms have been widely utilised for the optimisation of both theoretical and real-world non-linear optimisation problems, including water system design and maintenance problems. In this work we present a pipe smoothing based approach to the creation and mutation of chromosomes which utilises engineering expertise with the view to increasing the performance of the algorithm whilst promoting engineering feasibility within the population of solutions. MOPSGA is based upon the standard Non-dominated Sorting Genetic Algorithm-II (NSGA-II) and incorporates a modified population initialiser and mutation operator which directly targets elements of a network with the aim to increase network smoothness (in terms of progression from one diameter to the next) using network element awareness and an elementary heuristic. The pipe smoothing heuristic used in this algorithm is based upon a fundamental principle employed by water system engineers when designing water distribution pipe networks where the diameter of any pipe is never greater than the sum of the diameters of the pipes directly upstream resulting in the transition from large to small diameters from source to the extremities of the network. MOPSGA is assessed on a number of water distribution network benchmarks from the literature including some real-world based, large scale systems. The performance of MOPSGA is directly compared to that of NSGA-II with regard to solution quality, engineering feasibility (network smoothness) and computational efficiency. MOPSGA is shown to promote both engineering and hydraulic feasibility whilst attaining good infrastructure costs compared to NSGA-II.

Desenvolvimento de um programa de simulação computacional de sistemas de aquecimento solar para água

Esta Tese apresenta uma análise do comportamento térmico de um sistema de aquecimento solar operando por termossifão. Neste tipo de sistema o fluido no coletor solar é circulado por convecção natural, que acontece devido à diferença de massa específica da água ao longo circuito. Nestes sistemas a vazão mássica varia ao longo do dia e do ano, dependendo, dentre outros fatores, da irradiância solar absorvida, do perfil de temperaturas da água no sistema, da geometria, do volume e do perfil de demanda de água quente. Para uma avaliação detalhada do comportamento térmico de aquecedores solares operando por termossifão foram realizados ensaios experimentais e cálculos teóricos. Os resultados dos experimentos concordaram com aqueles apresentados na literatura e sua análise fundamentou o desenvolvimento do aplicativo TermoSim, um programa de simulação computacional do comportamento térmico de sistemas de aquecimento de água com energia solar. O tratamento matemático adotado no TermoSim compreende a modelagem dos coletores solares de acordo com a teoria de Hottel-Bliss-Whillier. O reservatório térmico é modelado com estratificação térmica, convecção e condução entre as camadas. A vazão mássica é obtida a partir do balanço da quantidade de movimento no circuito. Os modelos matemáticos empregados na construção do aplicativo TermoSim foram validados através do confronto dos resultados simulados com medidas experimentais. Foi demonstrado que a utilização destes modelos é adequada e permite reproduzir com precisão o comportamento térmico dos coletores solares e do reservatório térmico. Além do programa TermoSim, foi também desenvolvido o programa TermoDim, que é uma ferramenta para o dimensionamento de sistemas de aquecimento solar, que requer apenas o conhecimento dos parâmetros geométricos do sistema, dados meteorológicos em média mensal e informação a respeito do volume de demanda. O TermoDim é apropriado para estimar o desempenho de aquecedores solares operando por termossifão com tanques verticais e horizontais. O método de dimensionamento do TermoDim é baseado na correlação para a eficiência média mensal obtida neste trabalho a partir de um grande número de simulações.

Redes sociais e o empreendedorismo de alta tecnologia em São Carlos: limites e potencialidades para o incentivo governamental a negócios inovadores

A presente dissertação utilizou a abordagem da Sociologia Econômica para a realização de um estudo de caso sobre empreendedorismo e redes sociais na cidade de São Carlos (SP), tendo como unidade de análise os projetos beneficiados por um programa público da Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP): o Programa Inovação Tecnológica na Pequena Empresa (PIPE). Este trabalho foi baseado nos estudos de Mark Granovetter sobre a imersão social da ação econômica, redes sociais e seu papel no desenvolvimento do Vale do Silício (EUA) para a identificação, no caso de São Carlos, dos vínculos que importam entre empreendedores e pesquisadores, das redes sociais construídas em torno do empreendedorismo de base tecnológica e dos arranjos institucionais entre atores públicos, privados e não-governamentais que contribuem para que a cidade seja considerada uma “fábrica de PIPE’s” e um dos principais pólos de inovação tecnológica do país. O estudo apontou que os empreendedores de base tecnológica em São Carlos, sob a ótica da Sociologia Econômica, constituem uma rede social endógena e focada na pesquisa científica, pouco se conectando com instituições de suporte de mercado, o que limita o desenvolvimento da atividade empreendedora, entendida como a criação de empresas que façam interações formais com o mercado. Acredita-se que os resultados desta pesquisa permitirão um melhor entendimento da realidade empreendedora na região de São Carlos sob o ponto de vista sociológico e contribuirão para o desenvolvimento de iniciativas governamentais que levem em consideração a necessidade de compreender a estrutura social e as redes de relações sob as quais se implantarão futuras políticas públicas de incentivo ao empreendedorismo.

Subsídios para a gestão dos planos de aplicação de vinhaça (PAV): um estudo de caso da região de Piracicaba

Concomitantemente à produção de etanol, a partir da fermentação de diferentes matérias-primas (cana-de-açúcar, beterraba, milho, trigo, batata, mandioca), produz-se a vinhaça. A vinhaça da cana-de-açúcar é gerada na proporção média de 12 litros para cada litro de etanol. O Brasil é o maior produtor mundial de cana-de-açúcar (570 milhões de toneladas, em 2009) com a produção de 27 bilhões de litros/ano de etanol, no ciclo 2009/2010, basicamente para fins carburantes, e, portanto, a quantidade de vinhaça produzida é da ordem de 320 bilhões de litros/ano. Dentre as possíveis soluções para a destinação da vinhaça, tais como: concentração, tratamento químico e biológico ou produção de biomassa, é sua aplicação no solo a forma mais usual de disposição. No entanto, sua aplicação no solo não pode ser excessiva nem indiscriminada, sob pena de comprometer o ambiente e a rentabilidade agrícola e industrial da unidade sucroalcooleira. A necessidade de medidas de controle sobre a aplicação de vinhaça no solo do Estado de São Paulo, que concentra a produção de 60% do etanol produzido no Brasil, levou à elaboração da Norma Técnica P4.231, em 2005. A constatação do cumprimento dos itens desta Norma é uma das ações do agente fiscalizador, no monitoramento da geração e destinação da vinhaça pelos empreendimentos produtores de etanol. Os itens 5.7.1 e 5.7.2, desta Norma, tornam obrigatório o encaminhamento à CETESB (Companhia Ambiental do Estado de São Paulo), para fins de acompanhamento e fiscalização, até o dia 02 de abril de cada ano, o PAV (Plano de Aplicação de Vinhaça). Com o intuito de proporcionar melhor entendimento da Norma P4.231, contribuir para otimização de sua aplicabilidade e melhoria e perceber a realidade prática da aplicação da vinhaça, foram analisados PAVs protocolados na Agência Ambiental de Piracicaba, licenças concedidas, processos de licenciamento e realizadas vistorias a campo. Conclui-se que a Norma P4.231 representa um avanço no gerenciamento do uso da vinhaça no Estado de São Paulo, por disciplinar a disposição de vinhaça no solo, tornando obrigatórios: demarcações de áreas protegidas e núcleos populacionais, caracterização de solo e da vinhaça, doses máximas a serem aplicadas, estudos da geologia e hidrogeologia locais, monitoramento das águas subterrâneas, impermeabilização de tanques e dutos. Estabelece critérios a serem obedecidos por lei, e todos são condutas de boas práticas de proteção ao meio, que repercutem em maior rentabilidade agrícola e industrial. A Norma P4.231 é bem elaborada, complexa e extensa, o que a torna de difícil execução. Para facilitar sua aplicabilidade, sugere-se o estabelecimento de um cronograma de prioridades: impermeabilização dos tanques e dutos, drenos testemunha com funcionamento otimizado e boa caracterização do que está sendo aplicado, se vinhaça pura ou se misturada a águas residuárias. Das oito empresas deste estudo, apenas quatro (as maiores) vêm protocolando os PAVs com regularidade, desde 2005. As informações apresentadas foram incompletas e, em alguns casos, precárias. Mesmo com lacunas, os dados fornecidos, desde o início da obrigatoriedade do PAV, foram de utilidade para esboçar o perfil da atividade sucroalcooleira na região estudada.