Adaptive combination of SSB and SUB equipment to master complexity in clinical manufacturing in the clinical supply center

Today’s clinical manufacturing of complex monoclonal antibodies under GMP conditions needs to be highly adaptive in order to face the requirements of constant acceleration of processes. The main challenge of the clinical supply center (CSC) in Penzberg (Germany) is to successfully master the complexity of producing different products in different phases (clinical phase I – III) with different process versions. New products for clinical phase I have different requirements than older products, as well as products in later phases or resupplies. In addition, the actual change to more intensified processes will increase the complexity even more. The CSC is equipped with a variety of bioreactors in different sizes and types. Stainless steel as well as single use bioreactors, which were installed over the past 25 years. In order to face the main challenge, it is mandatory to create a framework that allows the adaptive combination of standard (SSB) and new technologies (SUB). To realize that, SUBs and SSBs are treated equally. SUBs have the advantage to be used more flexible than SSBs because of less preparation time and an easier adaption to intensified processes (like perfusion modules in the N-1 bioreactor). Furthermore, SUBs can be easily connected to every existing bioreactor type (SSB as well) via hose connections. This all offers the chance to utilize existing bioreactor racks more efficient with less slack time. An adaptive combination is also faster and more favorable than just replacing existing with new equipment. The poster shows the successful implementation of the adaptive combination in the CSC, by adding SUBs with increasing volume to the facility (starting with 250L and ending with 2000L production volume) and apply them for existing and new processes. The intensified usage of SUB equipment shortens the upgrade time to adapt to future needs (e.g. switch to perfusion technology). With this flexible setup the multi-product-GMP facility in Penzberg is perfectly prepared for actual and upcoming challenges

The Spin Glass Transition : Exponents and Dynamics

Numerical simulations on Ising Spin Glasses show that spin glass transitions do not obey the usual universality rules which hold at canonical second order transitions. On the other hand the dynamics at the approach to the transition appear to take up a universal form for all spin glasses. The implications for the fundamental physics of transitions in complex systems are addressed.Comment: 4 pages (Latex) with 3 figures (postscript), accepted for publication in Physica

Análise da imunogenicidade e da estabilidade do surfactante pulmonar de origem porcina administrado em coelhos

PURPOSE: To study the immunogenicity and the stability of the porcine pulmonary surfactant preparation produced by the Instituto Butantan. METHOD: Immunogenicity assay: Sixteen New-Zealand-White rabbits (1000 g body weight) were divided into 4 study groups. Each group was assigned to receive either a) Butantan surfactant, b) Survanta® (Abbott Laboratories), c) Curosurf® (Farmalab Chiesi), or d) no surfactant. The surfactants were administered intratracheally, and the animals were collected immediately before and 60 and 180 days after surfactant administration. Sera were assayed for the presence of antisurfactant antibodies by enzyme-linked immunosorbent assay (ELISA). Stability assay: The Butantan surfactant used in this assay had been stored for one year in the refrigerator (4 to 8ºC) and its stability was evaluated in distinct assay conditions using a premature rabbit model. RESULTS: Immunogenicity assay: None of the surfactants analyzed triggered antibody immune responses against their components in any of the animals. Stability assay: The results of this study demonstrate that Butantan surfactant was as effective as Curosurf when both were submitted to the adverse circumstance of short- and long-term storage at room temperature. A similar level of efficacy for the Butantan surfactant, as compared to Curosurf was demonstrated by the pulmonary dynamic compliance, ventilatory pressure, and pressure-volume curve results. CONCLUSION: The results of our study demonstrate that Butantan surfactant may be a suitable alternative for surfactant replacement therapy.OBJETIVO: Estudar a imunogenicidade e a estabilidade do surfactante de origem porcina produzido pelo Instituto Butantan. MÉTODO: Experimento imunogenicidade: 16 coelhos da raça New-Zealand-White (Peso de 1000g) foram divididos em grupos de 4 animais. Cada grupo foi designado para receber: a) Surfactante do Butantan, b) Survanta® (Abbott Laboratories), c) Curosurf (Farmalab Chiesi) e d) nenhum tratamento com surfactante. Os surfactantes foram administrados via intratraqueal e o sangue dos animais foi coletado antes, 60 e 180 dias após a administração do surfactante. O soro obtido foi analisado quanto a presença de anticorpos anti-surfactante pelo método ELISA (enzyme-linked immunosorbent assay). Experimento estabilidade: O surfactante do Butantan usado neste experimento tinha sido armazenado por um ano em refrigerador (4 a 8°C) e sua estabilidade foi analisada em condições distintas de experimentação, usando o modelo de coelho prematuro. RESULTADOS: Experimento imunogenicidade: Nenhum dos surfactantes analisados determinou a produção de anticorpos contra seus constituintes. Experimento estabilidade: Os resultados deste estudo demonstraram que o surfactante do Instituto Butantan mostrou eficácia semelhante a do Curosurf após ter sido submetido à condições adversas ao longo do tempo. A eficácia foi demonstrada através da complacência pulmonar dinâmica, pressão ventilatória e da curva pressão-volume. CONCLUSÃO: Os resultados deste estudo demonstraram que o surfactante do Instituto Butantan pode representar um tratamento alternativo de reposição de surfactante

Functional responses can unify invasion ecology.

We contend that invasion ecology requires a universal, measurable trait of species and their interactions with resources that predicts key elements of invasibility and ecological impact; here, we advocate that functional responses can help achieve this across taxonomic and trophic groups, among habitats and contexts, and can hence help unify disparate research interests in invasion ecology

No polarization–Expected Values of Climate Change Impacts among European Forest Professionals and Scientists

The role of values in climate-related decision-making is a prominent theme of climate communication research. The present study examines whether forest professionals are more driven by values than scientists are, and if this results in value polarization. A questionnaire was designed to elicit and assess the values assigned to expected effects of climate change by forest professionals and scientists working on forests and climate change in Europe. The countries involved covered a north-to-south and west-to-east gradient across Europe, representing a wide range of bio-climatic conditions and a mix of economic–social–political structures. We show that European forest professionals and scientists do not exhibit polarized expectations about the values of specific impacts of climate change on forests in their countries. In fact, few differences between forest professionals and scientists were found. However, there are interesting differences in the expected values of forest professionals with regard to climate change impacts across European countries. In Northern European countries, the aggregated values of the expected effects are more neutral than they are in Southern Europe, where they are more negative. Expectations about impacts on timber production, economic returns, and regulatory ecosystem services are mostly negative, while expectations about biodiversity and energy production are mostly positive

BRST approach to Lagrangian formulation for mixed-symmetry fermionic higher-spin fields

We construct a Lagrangian description of irreducible half-integer higher-spin representations of the Poincare group with the corresponding Young tableaux having two rows, on a basis of the BRST approach. Starting with a description of fermionic higher-spin fields in a flat space of any dimension in terms of an auxiliary Fock space, we realize a conversion of the initial operator constraint system (constructed with respect to the relations extracting irreducible Poincare-group representations) into a first-class constraint system. For this purpose, we find auxiliary representations of the constraint subsuperalgebra containing the subsystem of second-class constraints in terms of Verma modules. We propose a universal procedure of constructing gauge-invariant Lagrangians with reducible gauge symmetries describing the dynamics of both massless and massive fermionic fields of any spin. No off-shell constraints for the fields and gauge parameters are used from the very beginning. It is shown that the space of BRST cohomologies with a vanishing ghost number is determined only by the constraints corresponding to an irreducible Poincare-group representation. To illustrate the general construction, we obtain a Lagrangian description of fermionic fields with generalized spin (3/2,1/2) and (3/2,3/2) on a flat background containing the complete set of auxiliary fields and gauge symmetries.Comment: 41 pages, no figures, corrected typos, updated introduction, sections 5, 7.1, 7.2 with examples, conclusion with all basic results unchanged, corrected formulae (3.27), (7.138), (7.140), added dimensional reduction part with formulae (5.34)-(5.48), (7.8)-(7.10), (7.131)-(7.136), (7.143)-(7.164), added Refs. 52, 53, 54, examples for massive fields developed by 2 way

Typical meteorological year data analysis for optimal usage of energy systems at six selected locations in Nigeria

Inthisstudy,thetypicalmeteorologicalyear(TMY)dataforsixlocationsrepresentingthesixgeopoliticalzonesinNigeriaweregeneratedandanalyzedusingtheSandiamethod.Theanalysisshowsthatseasonalvariationsexistinalltheselectedlocationsindicatingtwodistinctseasons:thedryandwetseasonswithvaryinglengthsfromnorthtosouthofthecountry.Duetoitshighglobalradiationlevels(21–25MJ/m2/d),theNorthisadesirablelocationforsolar-thermalsystems.Inaddition,thehighmonthlymeantemperaturevariations(∼18◦C),lowrelativehumidity(RHM)(15%)andconstantwindspeeds(4m/s)experiencedinthefirst3monthsoftheyearaidtheinstallationofwindenergysystemsandtheapplicationofevaporativecoolingtechniquesthatreucethethermalloadandenergyconsumptionofbuildings.Ontheotherside,thehighRHM(80%)andmediocreradiationvaluesderivedalmostthroughouttheyearintheSouthwest,SoutheastandSouth–southregionsdiscouragestheextensiveapplicationofevaporativecoolingandsolarenergy-basedsystemsinsuchlocations,butthemoderatewindspeeds(2.9m/s)andmonthlymeantemperaturevariationsassociatedwiththeseregionsbetweenthefirst3monthsoftheyearallowfortheapplicationofnaturalventlationandsomepassivecoolingsystemssoastoreducethethermalloadofbuildingsintheregions.Theinformationpresentedinthisworkcanserveasaguidefordesignandselectionofenergysystemsandapplicationofenergy-relatedprojectsinNigeria

Measurement of Rb in e+e- Collisions at 182 - 209 GeV

Measurements of Rb, the ratio of the bbbar cross-section to the qqbar cross- section in e+e- collisions, are presented. The data were collected by the OPAL experiment at LEP at centre-of-mass energies between 182 GeV and 209 GeV. Lepton, lifetime and event shape information is used to tag events containing b quarks with high efficiency. The data are compatible with the Standard Model expectation. The mean ratio of the eight measurements reported here to the Standard Model prediction is 1.055+-0.031+-0.037, where the first error is statistical and the second systematic.Comment: 21 pages, 5 figures, Submitted to Phys. Letts

Measurement of the partial widths of the Z into up- and down-type quarks

Using the entire OPAL LEP1 on-peak Z hadronic decay sample, Z -> qbarq gamma decays were selected by tagging hadronic final states with isolated photon candidates in the electromagnetic calorimeter. Combining the measured rates of Z -> qbarq gamma decays with the total rate of hadronic Z decays permits the simultaneous determination of the widths of the Z into up- and down-type quarks. The values obtained, with total errors, were Gamma u = 300 ^{+19}_{-18} MeV and Gamma d = 381 ^{+12}_{-12} MeV. The results are in good agreement with the Standard Model expectation.Comment: 22 pages, 5 figures, Submitted to Phys. Letts.

Genuine Correlations of Like-Sign Particles in Hadronic Z0 Decays

Correlations among hadrons with the same electric charge produced in Z0 decays are studied using the high statistics data collected from 1991 through 1995 with the OPAL detector at LEP. Normalized factorial cumulants up to fourth order are used to measure genuine particle correlations as a function of the size of phase space domains in rapidity, azimuthal angle and transverse momentum. Both all-charge and like-sign particle combinations show strong positive genuine correlations. One-dimensional cumulants initially increase rapidly with decreasing size of the phase space cells but saturate quickly. In contrast, cumulants in two- and three-dimensional domains continue to increase. The strong rise of the cumulants for all-charge multiplets is increasingly driven by that of like-sign multiplets. This points to the likely influence of Bose-Einstein correlations. Some of the recently proposed algorithms to simulate Bose-Einstein effects, implemented in the Monte Carlo model PYTHIA, are found to reproduce reasonably well the measured second- and higher-order correlations between particles with the same charge as well as those in all-charge particle multiplets.Comment: 26 pages, 6 figures, Submitted to Phys. Lett.