Feasibility study on pre or postoperative accelerated radiotherapy (POP-ART) in breast cancer patients

Background: In early-stage breast cancer, the cornerstone of treatment is surgery. After breast-conserving surgery, adjuvant radiotherapy has shown to improve locoregional control and overall survival rates. The use of breast radiotherapy in the preoperative (preop) setting is far less common. Nevertheless, it might improve disease-free survival as compared to postoperative radiotherapy. There is also a possibility of downsizing the tumour which might lead to a lower need for mastectomy. There are some obstacles that complicate its introduction into daily practice. It may complicate surgery or lead to an increase in wound complications or delayed wound healing. Another fear of preop radiotherapy is delaying surgery for too long. At Ghent University Hospital, we have experience with a 5-fraction radiotherapy schedule allowing radiotherapy delivery in a very short time span. Methods: Twenty female breast cancer patients with non-metastatic disease receiving preop chemotherapy will be randomized between preop or postoperative radiotherapy. The feasibility of preop radiotherapy will be evaluated based on overall treatment time. All patients will be treated in 5 fractions of 5.7 Gy to the whole breast with a simultaneous integrated boost to the tumour/tumour bed of 5 × 6.2 Gy. In case of lymph node irradiation, the lymph node regions will receive a dose of 27 Gy in 5 fractions of 5.4 Gy. The total duration of therapy will be 10 to 12 days. In the preop group, overall treatment time is defined as the time between diagnosis and the day of last surgery, in the postop group between diagnosis and last irradiation fraction. Toxicity related to surgery, radio-, and chemotherapy will be evaluated on dedicated case-report forms at predefined time points. Tumour response will be evaluated on the pathology report and on MRI at baseline and in the interval between chemotherapy and surgery. Discussion: The primary objective of the trial is to investigate the feasibility of preop radiotherapy. Secondary objectives are to search for biomarkers of response and toxicity and identify the involved cell death mechanisms and the effect of preop breast radiotherapy on the in-situ immune micro-environment

Increased levels of systemic LPS-positive bacterial extracellular vesicles in patients with intestinal barrier dysfunction

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Development of Poly (Ether Ether Ketone) Based Solvent Resistant Nanofiltration Membranes via Phase Inversion

Solvent resistant nanofiltration (SRNF) is a separation technique with large applicability in the (petro-)chemical, pharmaceutical and food industry. Development of better performing membranes will boost the implementation of SRNF membranes in the coming years. The key factors that still need optimization to achieve this growth, are membrane stability in extreme pH conditions, thermal, mechanical and solvent stability and membrane cost. The majority of SRNF membranes are polymeric, since they are cheaper and easier to process than ceramic membranes. Most polymers applied to produce membranes are soluble in harsh solvents and sometimes in extreme pH conditions, a limitation that needs to be addressed. Another factor limiting the performance of SRNF membranes is the trade-off which is typically found between selectivity and permeability through the membrane. Membranes with very tight pores are known to combine a high selectivity with low flow rate. Optimization of the membrane preparation process can however improve this trade-off.One type of material is proposed in this research to produce SRNF membranes. Poly(ether ether ketone) (PEEK) was chosen as hydrophobic, mechanically and thermally stable lab-synthesized polymer. Some modifications were added to the standard polymer, making it soluble in polar aprotic solvents and usable for the production of membranes via phase inversion. Some of the prepared PEEKs contained carboxylic acid groups in the polymer chain to allow crosslinking, thus producing a solvent-stable membrane.In a first part of this research, uncrosslinked membranes were prepared that are stable in mainly alcohols and alkanes. The lab-synthesized PEEKs were dissolved first in the polar aprotic solvents n-methylpyrrolidone (NMP) and tetrahydrofuran (THF), after which they were spread onto a non-woven backing and immersed in water to ensure phase transition to the solid phase the membrane. A number of phase inversion parameters were altered to investigate the potential of these materials for membrane preparation. First of all, polymer specific properties were investigated, namely molar mass and polydispersity. The influence of some synthesis parameters, such as composition of the polymer solution and evaporation time before immersion in the water bath, were subsequently investigated. The importance of post-treatment on membrane performance was also studied.In a second part of this research, a novel series of PEEKs were synthesized that could produce crosslinked membranes with good chemical stability in polar, aprotic solvents. For this, amines were used as crosslinkers, producing amide bonds between the polymer chains. The crosslinking occurred simultaneously with the phase inversion process, namely during immersion of the polymer films, by adding the amines to the water bath. These membranes can be implemented for separations in harsh solvents such as THF and NMP.In a final part of this research, SRNF membranes were developed to separate edible oils from solvents. By adapting the type of crosslinker, membranes were synthesized that are more hydrophilic than the abovementioned ones, making them more suitable for the purification of edible oils from solvents. This is indeed a very interesting industrial application in which the membranes developed in this research can be implemented.1. Introduction and scope 2 1.1. General introduction 2 1.1.1. Edible oil refining with SRNF membranes 4 1.1.2. Poly(ether ether ketone) as membrane material 5 1.2. Scope 7 1.2.1. Phase inversion study from lab-prepared membranes 8 1.2.2. Crosslinking of PEEK membranes 9 1.2.3. Edible oil refining 9 References 10 2. Solvent Resistant Nanofiltration membranes: state of the art 14 2.1. Introduction 14 2.2. Basic principles 16 2.2.1. Performance 16 2.2.2. Mass transfer limitations 17 2.2.3. Filtration operations 18 2.3. Separation mechanism 19 2.3.1. Membrane characterization 19 2.3.2. Transport mechanism 25 2.4. Membrane materials 27 2.4.1. Polymeric 28 2.4.2. Ceramics 39 2.4.3. Mixed matrix membranes 41 2.4.4. Commercial membranes 44 2.5. Challenges and prospectives 45 References 45 3. Synthesis of modified poly(ether ether ketone) polymer for the preparation of ultrafiltration and nanofiltration membranes via phase inversion. 58 3.1. Introduction 58 3.2. Experimental 61 3.3. Results and Discussion 65 3.3.1. Polymer synthesis 65 3.3.2. Performance and morphology of TBPEEK membranes 69 3.3.3. From UF to NF membranes: tuning of phase inversion parameters 76 3.4. Conclusions 79 References 79 4. Study of phase inversion parameters for PEEK-based nanofiltration membranes 84 4.1. Introduction 84 4.2. Experimental 86 4.3. Results and Discussion 89 4.3.1. Polymerization 89 4.3.2. Influence of polymer concentration in the casting solution 91 4.3.3. Tuning the membrane properties toward NF 93 4.3.4. Performance in other conditions 100 4.4. Conclusions 103 References 103 5. Influence of post-treatment and additives on PEEK membranes developed for SRNF 108 5.1. Introduction 108 5.2. Experimental 110 5.3. Results and Discussion 112 5.3.1. Influence of post-treatment 112 5.3.2. Influence of additives in the casting solution 115 5.4. Conclusions 118 References 119 6. Crosslinking of modified poly(ether ether ketone) membranes for use in solvent resistant nanofiltration. 122 6.1. Introduction 122 6.2. Experimental 124 6.3. Results and discussion 129 6.3.1. Polymerization 129 6.3.2. Crosslinking reaction 131 6.3.3. Crosslinked membranes 134 6.4. Conclusions 139 References 139 7. SRNF membranes for edible oil purification: introducing free amines in crosslinked PEEK to increase membrane hydrophilicity 144 7.1. Introduction 144 7.2. Experimental 146 7.3. Results and discussion 151 7.3.1. Polymers 151 7.3.2. Crosslinking efficiency 154 7.3.3. SRNF performance 158 7.4. Conclusions 163 References 164 8. General conclusions and perspectives 168 8.1. Conclusions 168 8.1.1. PEEK membrane materials 168 8.1.2. Phase inversion parameters 168 8.1.3. Crosslinking 169 8.1.4. Possible applications: fuel cell, edible oil refining and others 170 8.2. Future work 170 8.2.1. Expanding the set of PEEK membranes 170 8.2.2. Continued characterization of existing PEEK membranes 171 Appendix 1: Calculation of Hansen solubility parameters 173 Appendix 2: Experimental setup 176nrpages: 176status: publishe

Solvent resistant nanofiltration for acetonitrile based feeds: A membrane screening

© 2017 Elsevier B.V. A range of commercially available and lab-made membranes was screened for use in feeds containing acetonitrile (ACN). ACN was selected as it is one of the most widely used solvents in pharmaceutical industry and surprisingly absent in earlier studies on solvent resistant nanofiltration (SRNF). The selected membranes ranged from the tight nanofiltration range to the lower end ultrafiltration range, prepared from different membrane chemistries and with different membrane preparation methods. Multiple dyes were tested as probe molecules to study the retention behavior of the membranes in ACN. Gel content measurements were conducted on the membranes and interaction parameters with ACN, the dyes and the membranes were calculated to link physico-chemical properties to separation performances. ACN was found to be a very appropriate solvent for SRNF applications, as most membranes reached high fluxes and retentions, comparable to those obtained in most other solvents. As most membrane polymers did not dissolve in ACN, membrane crosslinking is not even strictly necessary to ensure stability of the membranes when applied in these feeds. This study thus showed that for ACN-based solutions, many different types of SRNF membranes can potentially be selected to achieve the aimed separations.publisher: Elsevier articletitle: Solvent resistant nanofiltration for acetonitrile based feeds: A membrane screening journaltitle: Journal of Membrane Science articlelink: http://dx.doi.org/10.1016/j.memsci.2017.05.003 content_type: article copyright: © 2017 Elsevier B.V. All rights reserved.status: publishe

Assays for evaluation of HIV-1 integrase enzymatic activity, DNA binding, and cofactor interaction

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Pyrite oxidation by nitrate and nitrite in sodium bicarbonate solution under anoxic and abiotic conditions

Pyrite reactivity with nitrate and nitrite was assessed in long-term batch tests to assess its possible oxidation in anoxic conditions at pH 8.5, at room temperature and atmospheric pressure. This was done in the frame of compatibility studies of nitrate-containing radioactive waste with a pyrite-containing clay host rock for geological disposal. Abiotic pyrite suspensions were prepared under inert atmosphere in 15 mM bicarbonate medium, as this simulates the inorganic carbon and pH conditions in the pore water of Boom Clay, which is a potential host rock for geological disposal in Belgium. Two forms of pyrite powder were used, formed via different genetic pathways and exhibiting a different morphology, namely pyrite obtained by crushing a large crystal cluster and pyrite extracted from Boom Clay by flotation. The reactivity of these two pyrite forms with nitrate and nitrite is reported and compared. Overall, after 2–2.5 years under abiotic conditions and inert atmosphere, no significant reaction between crushed pyrite and nitrate was detected, while a very limited reaction was observed between Boom Clay pyrite and nitrate. Between pyrite and nitrite, which is known to be more reactive than nitrate, a slow reaction took place for both forms of pyrite, with no significantly higher reactivity with the Boom Blay pyrite. The variability between the replicates of Boom Clay pyrite were also larger than for crushed pyrite. Overall, nitrate and nitrite induced a very limited, if any, oxidation reaction of the pyrite powders. These observations are important in assessing the safety of geological disposal of nitrate-containing radioactive waste

Surface-mediated redox activity in the Pyrite – Nitrate/nitrite – Hydrogen system under conditions relevant for the geological disposal of bituminized waste in Boom Clay

The reactivity of a system with pyrite powder, nitrate or nitrite, and hydrogen in a 15 mM sodium bicarbonate solution was assessed over the course of 2 years in the frame of compatibility studies of nitrate-containing bituminized radioactive waste with the host rock for final disposal. A series of batch tests was performed with pyrite suspensions in bicarbonate solution to which nitrate or nitrite was added before filling the headspace of the recipient with a constant, and non-renewed, volume of 100% pure hydrogen gas (initial PH2 1.5 bara). Under anoxic conditions and at room temperature, hydrogen reacted readily with nitrate and nitrite in the presence of pyrite powder. Ammonia was formed while hydrogen was consumed. Based on the XPS analyses of the pyrite surface and the absence of dissolved pyrite oxidation products, the pyrite surface was not oxidized. Moreover, no reaction between hydrogen and nitrate or nitrite was observed in the absence of pyrite. This reaction was thus clearly mediated by the Boom Clay pyrite surface. The reducing atmosphere kept the pyrite surface intact and protected it from precipitation of carbonates from the medium, thus effectively preventing pyrite surface deactivation, previously observed under anoxic conditions in the absence of H2. Overall, only 5% of the 0.1 M of nitrate that was added to the tests, was reduced over the course of 2 years, without complete consumption of H2. Nitrite was added in a lower concentration of 0.05 M, but was more reactive: about 50% of nitrite was reduced, producing stoichiometric amounts of ammonia, and nearly depleting the H2 in the gas phase. The possible consequences of these processes for the final repository performance are also discussed

In Vitro DNA Tethering of HIV-1 lntegrase by the Transcriptional Coactivator LEDGF/p75

Although LEDGF/p75 is believed to act as a cellular cofactor of lentiviral integration by tethering integrase (IN) to chromatin, there is no good in vitro model to analyze this functionality. We designed an AlphaScreen assay to study how LEDGF/p75 modulates the interaction of human immunodeficiency virus type 1 IN with DNA. IN bound with similar affinity to DNA mimicking the long terminal repeat or to random DNA. While LEDGF/p75 bound DNA strongly, a mutant of LEDGF/p75 with compromised nuclear localization signal (NLS)/AT hook interacted weakly, and the LEDGF/p75 PWWP domain did not interact, corroborating previous reports on the role of NLS and AT hooks in charge-dependent DNA binding. LEDGF/p75 stimulated IN binding to DNA 10-fold to 30-fold. Stimulation of IN-DNA binding required a direct interaction between IN and the C-terminus of LEDGF/p75. Addition of either the C-terminus of LEDGF/p75 (amino acids 325-530) or LEDGF/p75 mutated in the NLS/AT hooks interfered with IN binding to DNA. Our results are consistent with an in vitro model of LEDGF/p75-mediated tethering of IN to DNA. The inhibition of IN-DNA interaction by the LEDGF/p75 C-terminus may provide a novel strategy for the inhibition of HIV IN activity and may explain the potent inhibition of HIV replication observed after the overexpression of C-terminal fragments in cell culture.status: publishe

Ex and In Situ Reactivity and Sorption of Sélénium in Opalinus Clay in the Presence of a Sélénium Reducing Microbial Community

International audience79Se is a critical radionuclide conceming the safety of deep geological disposai of certain radioactive wastes in clay-rich formations. To study the fate of sélénium oxyanions in clayey rocks in the presence of a sélénium reducing microbial community, in situ tests were performed in the Opalinus Clay at the Mont Terri Rock Laboratory (Switzerland). Furthermore, biotic and abioticbatch tests were performed to assess Se(VI) and Se(IV) reactivity in the presence of Opalinus Clay and/or stainless steel, in order to support the interprétation of the in situ tests. Geochemical modeling was applied to simulate Se(VI) réduction, Se(IV) sorption and solubility, and diffusion processes, This study shows that microbial activity is required to transform Se(VI) into more reduced and sorbing Se species in the Opalinus Clay, while in abiotic conditions, Se(VI) remains unreactive. On the other hand, Se(IV) can be reduced by microorganisms but can also sorb in the presence of clay without microorganisms. In situ microbial réduction of Se oxyanions can occur with électron donors provided by the clay itself. If microorganisms would be active in the clay surrounding a disposai facility, microbial réduction of leached Se could thus contribute to the overall rétention of Se in clayey host rocks