Postsynthesis modification of a cellulose acetate ultrafiltration membrane for applications in water and wastewater treatment

A technique for postsynthesis modification of a cellulose acetate ultrafiltration membrane with possible application in water and wastewater treatment is studied. The technique used an oxidizing agent (persulfate) to develop free radicals on the membrane surface, and that was expected to promote grafting of hydrophilic macromolecules (polyethylene glycol). A chain-transfer agent (2-mercaptoethanol) was tested to control the grafting process, avoiding the formation of long chains that usually lead to high permeability losses in other graft techniques. The modifications aimed at the decrease of the fouling susceptibility of the membrane studied. The possibility of an increase in rejection was also investigated. The membrane was characterized before and after modification, by attenuated total reflectance-Fourier transform-infrared spectroscopy, scanning electron microscopy, atomic force microscopy, and in terms of the rejection of neutral reference solutes. The information given by the different techniques of characterization provided strong evidences of the occurrence of modification, although permeation of (real) foulants was the decisive test. To obtain information about the fouling tendency of the nonmodified and modified membranes, two different kinds of foulants were used: a humic acid (usually found in surface waters) and textile auxiliaries (representing one of the most important industries in Portugal). The results showed an increase in the rejections of the humic acid, and significant improvements in the performance of the membrane with respect to fouling tendency in the case of the textile auxiliarie

Continuous downstream process or connected batch process: Which one makes most sense for Biogen?

As biologics-based products move into therapeutic areas with large patient populations and high doses, batch processing may not be able to keep pace with product demands. At Biogen, we have been exploring a number of options that can enable higher productivity of our downstream processes. In addition to a fully “end to end” continuous process, a batch process comprised of several steps connected in series has been evaluated. In this presentation, technologies Biogen has evaluated to enable either continuous or connected processing will be shown. Multi-Column-Chromatography (MCC) for the Protein A capture chromatography step was evaluated in order to maximize resin utilization and increase productivity. Connecting subsequent polishing steps was explored to eliminate the need for large intermediate hold tanks. Various options for continuous diafiltration were assessed to enable a fully continuous UF/DF step. The results of these evaluations will be presented as well a comparison of the expected productivity and COGs for both process options

Comparison of the Chemical and Sensorial Evaluation of Dark Chocolate Bars

As it mimics olfactory perception, headspace analysis is frequently used for examination of products like chocolate, in which aroma is a key feature. Chemical analysis by itself, however, only provides half the picture, as final consumer's perception cannot be compared to that of a Gas Chromatography-Mass Spectrometry (GC-MS) port, but rather to a panel test assessment. The aim of the present study was the evaluation of combined chemical (by means of headspace solid-phase microextraction and GC-MS) and panel test data (by means of a sensory evaluation operated by 6 untrained panelists) obtained for 24 dark chocolate bars to assess whether these can discriminate between bars from different brands belonging to different commercial segments (hard discount, HD; supermarket, SM; organic bars, BIO). In all samples, with the only exception of one supermarket bar (in which esters exhibited the highest relative abundance), pyrazines were detected as the most abundant chemical class (HD: 56.3–74.2%; BIO: 52.0–76.4%; SM: 31.2–88.9%). Non-terpene alcohols, aldehydes, and esters followed as quantitatively relevant groups of compounds. The obtained data was then subjected to hierarchical cluster (HCA) and principal component (PCA) analysis. The statistical distribution of samples obtained for the chemical data did not match that obtained with panelists' sensorial data. Moreover, although an overall ability of grouping samples of the same commercial origin was evidenced for hard discount and supermarket bars, no sharp grouping was possible

A Novel Approach to Raman Distributed Temperature-Sensing System for Short-Range Applications

A novel approach to the development of Distributed Temperature-Sensing (DTS) systems based on Raman Scattering in Multimode optical fibers operating at around 800 nm is presented, focusing on applications requiring temperature profile measurement in the range of a few hundreds of meters. In contrast to the standard Raman DTS systems, which aim to shorten the pulse space width as much as possible to improve the precision of measurement, the novel approach studied in this work is based on the use of pulses with a space width that is approximately equal to the distance covered by the fiber under test. The proposed technique relies on numerical post-processing to obtain the temperature profile measurement with a precision of about +/- 3 degrees C and a spatial resolution of 8 m, due to the transaction phases of the optical pulses. This solution simplifies the electronic circuit development, also minimizing the required laser peak power needed compared to the typical narrow pulse techniques

VOLUNTARY DISCLOSURE, aspetti problematici e possibili interpretazioni

La Legge n. 186/2014, pubblicata nella Gazzetta Ufficiale n. 292 del 17 dicembre 2014, recante «Disposizioni in materia di emersione e rientro di capitali detenuti all’estero nonché del potenziamento della lotta all’evasione fiscale. Disposizioni in materia di auto riciclaggio.» all’art. 1, rubricato «Misure per l’emersione e il rientro di capitali detenuti all’estero nonché per il potenziamento della lotta all’evasione fiscale» mira ad offrire un’ultima opportunità di sanare le irregolarità commesse, in violazione della legge sul monitoraggio fiscale, dando ai contribuenti la possibilità, attraverso tale procedura, di godere di alcuni effetti premiali. In sintesi, i soggetti residenti in Italia che detengono – anche indirettamente o per interposta persona – attività patrimoniali e finanziarie all’estero ed abbiano omesso di dichiararle, potranno sanare, presentando apposita istanza nominativa entro il 30 settembre 2015, la propria posizione nei confronti dell’Erario versando, senza possibilità di compensazione, tutte le imposte dovute e le sanzioni, quest’ultime in maniera ridotta

Artrodesi Lombare: indicazioni chirurgiche nella Spondilosi Degenerativa. Risultati e riflessioni.

Questo studio, effettuato su pazienti sottoposti ad artrodesi lombare multilivello per spondilosi degenerativa, vuole verificare la relazione tra i valori post-chirurgici dell’angolo di Lordosi Lombare e i risultati clinici. La scelta dei soggetti selezionati per lo studio, al fine di omogeneizzare il campione, ha seguito i seguenti criteri: pazienti senza deformità maggiori, con età inferiore a 70 anni, operati da un solo chirurgo per patologia degenerativa, con un intervento di artrodesi lombare di 2 o 3 livelli vertebrali, in un periodo compreso tra il 2008 ed il 2012 con un follow-up minimo di 18 mesi. I pazienti sono stati valutati sia clinicamente sia attraverso un’anamnesi guidata da questionari sulla qualità di vita e scale valutative del dolore, come l’ODI, la PROLO e la VAS. Ogni paziente ha eseguito, in fase post operatoria, una radiografia lombosacrale in ortostatismo in proiezione antero-posteriore e latero-laterale su cui sono stati misurati, da un singolo operatore, i parametri angolari spino-pelvici. La parte analitica dello studio ha valutato la correlazione del PI-LL mismatch e della differenza tra la Lordosi Lombare teorica (calcolata secondo Roussouly(1)) e LL, con l'outcome clinico dei pazienti. L’analisi dei risultati ottenuti sul pool di pazienti preso in esame ci consente di confermare l'attendibilità del valore predittivo positivo del PI-LL mismatch come fattore prognostico di disabilità funzionale; inoltre ci consente di poter sostenere che un elevato valore della differenza tra la Lordosi Lombare teorica e quella effettiva si correla ad un tasso maggiore di reintervento per fallimento biomeccanico

Producer cell line engineering for large volume manufacturing of therapeutic Aav

Recombinant adeno-associated viruses (rAAV) remain one of the most promising gene therapy vectors for patients with genetic abnormalities. rAAV can safely deliver long-lasting expression of a therapeutic transgene. To create a rAAV virus the wild-type viral genome is replaced with a functional transgene expression cassette. A constitutive promoter can be utilized to drive strong expression of the transgene once the rAAV vector has infected the target cell. Unlike wtAAV, the recombinant vector avoids the pitfalls of genomic integration by establishing extrachomosomal episomes or concatemers. Multiple studies have shown that rAAV can provide sustained expression of the transgene in cultured cells and pre-clinical models, providing evidence that rAAV could offer a cure for certain diseases. Bioengineering advancements have expanded the viral tropism beyond the constraints of naturally occurring AAV capsids, increasing the types of cells that can be thought of as targets. Taken together, rAAV therapies have attractive qualities to safely address the needs of patients where protein or small molecule therapies would fall short. One challenge with therapeutic rAAV is the ability to generate enough virus for clinical trials and commercial supply. This is particularly true with neuromuscular or hemophilia patients in which doses can exceed 1 x 1014 viral genomes per patient. Typical yields from a rAAV production are around 104 viral genomes per cell, meaning 1010 cells will be needed for a single dose. This amount of therapeutic virus is a challenge to deliver with standard gene therapy production platforms, and will require a production platform that can reliably generate sufficient quantities of therapeutic rAAV to meet patient demand. Biogen has selected the producer cell line (PCL) platform to meet the large demand for therapeutic rAAV. Producer cell lines are generated by stably integrating the AAV viral genes along with the ITR flanked therapeutic gene of interest into a host cell line. rAAV production is then triggered by the addition of a ‘helper virus’ to provide functional genes for AAV replication. Traditional PCL platforms have used HeLa cells as the host and Adenovirus type-5 to deliver helper functions. We have used this platform as a basis for further development. Presented here will be our rationale for selecting the PCL platform, improvements made to the platform for ongoing clinical support, and our vision for the next generation PCL platform