Crystallographic Texture Evolution in 3D Printed Polyethylene Reactor Blends.

In this work, crystallographic texture evolution in 3D printed trimodal polyethylene (PE) blends and high-density PE (HDPE) benchmark material were investigated to quantify the resulting material anisotropy, and the results were compared to materials made from conventional injection molded (IM) samples. Trimodal PE reactor blends consisting of HDPE, ultrahigh molecular weight PE (UHMWPE), and HDPE_wax have been used for 3D printing and injection molding. Changes in the preferred orientation and distribution of crystallites, i.e., texture evolution, were quantified utilizing the wide angle X-ray diffraction through pole figures and orientation distribution functions (ODFs) for 3D printed and IM samples. Since the change in weight-average molecular weight (Mw) of the blend was expected to significantly affect the resulting crystallinity and orientation, the overall Mw of the trimodal PE blend was varied while keeping the UHMWPE component weight fraction to 10% in the blend. The resulting texture was analyzed by varying the overall Mw of the trimodal blend and the process parameters in 3D printing and compared to the texture of conventional IM samples. The printing speed and orientation (defined with respect to the axis along the length of the samples) were used as the variable process parameters for 3D printing. The degree of anisotropy increases with an increase in the nonuniform distribution of intensities in pole figures and ODFs. All the highest intensity major texture components in IM and 3D printed samples (0° printing orientation) of reactor blends are observed to have crystals oriented in [001] or [001̅]. Overall, for the same throughput, 3D printed samples in the 0° orientation showed greater texture evolution and higher anisotropy compared to IM samples. Most notably, an increase in 3D printing speed increased the crystalline distribution closer to the 0° direction, increasing the anisotropy, while deviation from this printing orientation reduced crystalline distribution closer to the 0° direction, thus increasing isotropy. This demonstrates that tailoring material properties in specific directions can be achieved more effectively with 3D printing than with the injection molding process. Change in the overall Mw of the trimodal PE blend changed the preferential orientation distribution of the crystal planes to some degree. However, the degree of anisotropy remained the same in almost all cases, indicating that the effect of molecular weight distribution is not as significant as the printing speed and printing orientation in tailoring the resulting properties. The 3D printing process parameters (speed and orientation) were shown to have more influence on the texture than the material parameters associated with the blend.

Characterization of hardness and elastic modulus using nanoindentation and correlation with wear behavior of UHMWPE during uniaxial tension.

UHMWPE is the material of choice for bearing surfaces in total joint arthroplasty making its wear and mechanical properties important factors of contribution in longevity of prosthetic hip/knee implants. In this study, the variation of hardness and elastic modulus with applied load in textured UHMWPE has been investigated. Texture has been induced through uniaxial tension of UHMWPE modifying its microstructure which in turn influences the wear resistance and hence the mechanical properties of the material. Previous studies have shown hardness to be a major factor influencing wear resistance. However, recently, the ratio of hardness (H) to elastic modulus (E) has been recognized as a more influential parameter of wear resistance. The validity of predicting wear resistance using H/E ratio has been examined in this work. Power law variation with load for the bioimplant material UHMWPE has been investigated at different strain levels. It has been observed that power law exponent of 2 can only be achieved at higher load levels. Overall, this work provides an insight into influencing the properties of bioimplant material UHMWPE by modifying the microstructure of the material through inducing texture which ultimately affects the longevity of the prosthetic implants.

Coordinated gas release among the physostomous fish sprat (Sprattus sprattus).

Previous experimental studies suggest that the production of sound associated with expelling gas from an open swimbladder may play a role in communication. This would suggest non-random gas release. We used deployed echosounders to study patterns of gas release among a fjord population of sprat (Sprattus sprattus). The echosounder records concurrently revealed individual fish and their release of gas. The gas release primarily occurred at night, partly following recurrent temporal patterns, but also varying between nights. In testing for non-randomness, we formulated a data-driven simulation approach. Non-random gas release scaled with the length of the analyzed time intervals from 1 min to 6 h, and above 30 min the release events in more than 50% of the intervals were significantly connected.

Atomic Layer Deposition onto Thermoplastic Polymeric Nanofibrous Aerogel Templates for Tailored Surface Properties.

Poly(vinyl alcohol-co-ethylene) (EVOH) nanofibrous aerogel (NFA) templates were fabricated through vacuum freeze-drying from EVOH nanofibrous suspensions. Aluminum oxide (Al2O3) layers were deposited onto highly porous templates to form organic-inorganic hybrid aerogels by the atomic layer deposition (ALD) technique. Chemical and physical measurements showed that mechanical properties were improved through ALD. In addition, the surface chemistry of ALD modified aerogels showed a fascinating cyclic change based on the number of ALD deposition cycles. A transition from hydrophilicity to hydrophobicity was observed after a few cycles of ALD coating; however, additional deposition cycles changed the wettability characteristics back to hydrophilicity. This hydrophilic-hydrophobic-hydrophilic variation is shown to be governed by a combination of geometrical and chemical surface properties. Furthermore, the deposited Al2O3 could substantially improve aerogels strength and reduce permanent deformation after cyclic compression. The Young's modulus of aerogels increased from 5.54 to 33.27 kPa, and the maximum stress at 80% strain went up from 31.13 to 176.11 kPa, after 100 cycles of trimethyl-aluminum (TMA)/water ALD. Thermogravimetric analysis (TGA) results confirm that ALD can effectively improve the heat resistance characteristics of polymeric aerogel. The onset temperature and the residual mass increased with increasing numbers of ALD cycles. During pyrolysis, the nanofiber cores were decomposed, and the brittle pure Al2O3 self-supporting nanotube aerogels with the continuous hollow nanotubular network were formed. A coating of continuous thickness Al2O3 layer on individual nanofiber was achieved after 100 ALD cycles. In additional to mechanical strength and physical property changes, the ALD modified aerogel also shows a superhydrophobic and oleophilic surface chemistry, which could potentially be used to remove oils/organic solvents from water. The resultant aerogels exhibit excellent absorption capacity (31-73 g/g) for various liquids, and the material could be reused after distillation or squeezing. A successful scale-up of such materials could provide some insights into the design and development of thermoplastic polymeric NFAs with substantial industrial applications.

Novel N-p-carboxy benzyl chitosan/poly (vinyl alcohol/functionalized zeolite mixed matrix membranes for DMFC applications.

The novel N-p-carboxy benzyl chitosan (CBC)/ poly (vinyl alcohol) (PVA) based mixed matrix membranes (MMMs) filled with surface-modified zeolite have been prepared using the dissolution casting technique. The applicability of prepared MMMs for direct methanol fuel cell (DMFC) was investigated in terms of water uptake, methanol permeation, and proton conductivity by changing filler content (10-50 wt. %). The zeolite was modified by silane coupling agent, 3-mercaptopropyltrimethoxysilane (MPTMS). The resultant modified zeolite (MZ) was incorporated into CBC/PVA blend to obtain mixed matrix PEMs. The functional group, structural properties, morphological and topographical investigation of MMMs were examined using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and Scanning electron microscopy (SEM) respectively. The prepared MMMs exhibited a remarkable decrease in methanol permeability of 2.3 × 10-7  cm2/s with C-CPMZ50. The maximum value of proton conductivity of 0.0527 Scm-1, was shown by C-CMPZ10. The prepared PEMs also displayed good stability during long term operating time.

A high-profile thread with grit-blasted and acid-etched surface reduces loosening of medial column fusion bolt in instable Charcot foot.

BACKGROUND: Intramedullary fusion bolts (FB) were introduced to stabilize the medial column of the instable Charcot foot (ICF), but complications as bolt loosening or breakage are frequent. We compared the use of a standard FB and a high-profile threaded FB with a grit-blasted surface. We hypothesized that implant related complications occurred less often and osseous consolidation of fusion sites was more distinctive using the latter type of FB. METHODS: Consecutive patients suffering from an ICF were stabilized with a high-profile threaded and surface-modified FB (HTFB) (n=20) or with a standard FB (n=20) which was placed into the first ray. Additional bolts and dorsal low-profile plates were applied in every patient. In a retrospective assessment osseous consolidation of the fusion sites was analyzed at 3 month and quantified by CT scan. At 3 and 12 month longitudinal foot arch collapse and rate of bolt loosening were assessed. RESULTS: Compared to the control group, the HTFB group reached significant higher consolidation after 3 month. No dislocation and a single bolt breakage was observed in the HTFB group after the fourth month, while the control group included 3 patients with bolt dislocation at 3±1 month and 5 patients with bolt breakage at 6±1.8 month. Compared to preoperative values, the improvement of Meary's angle after one-year was significant higher in the HTFB group (23.4°±14) than in controls (11.7°±13). CONCLUSIONS: Modification of bolt design improves the stability of the medial column: A higher rate of osseous consolidation of the medial column leads to lower rate of bolt dislocation/breakage and finally to permanently erected longitudinal foot arch. Initially disappointing results following medial column stabilization with fusion bolts can be rejected by modifications of bolt design and its technical application.

Congenital Babesiosis After Maternal Infection With Borrelia burgdorferi and Babesia microti.

We describe the cases of 2 infants with congenital babesiosis born to mothers with prepartum Lyme disease and subclinical Babesia microti infection. The infants both developed anemia, neutropenia, and thrombocytopenia, and 1 infant required red blood cell transfusion. Both infants recovered with treatment. Additional studies are warranted to define the optimal management strategy for pregnant women with early Lyme disease in geographic areas in which B microti infection is endemic.

Revisiting structure-property relationship of pH-responsive polymers for drug delivery applications.

pH-responsive polymers contain ionic functional groups as pendants in their structure. The total number of charged groups on polymer chains determines the overall response of the system to changes in the external pH. This article reviews various pH-responsive polymers classified as polyacids (e.g., carboxylic acid based polymers, sulfonamides, anionic polysaccharides, and anionic polypeptides) and polybases (e.g., polyamines, pyridine and imidazole containing polymers, cationic polysaccharides, and cationic polypeptides). We correlate the pH variations in the body at the organ level (e.g., gastrointestinal tract and vaginal environment), tissue level (e.g., cancerous and inflamed tissues), and cellular level (e.g., sub-cellular organelles), with the intrinsic properties of pH-responsive polymers. This knowledge could help to select more effective ('smart') polymeric systems based on the biological target. Considering the pH differences in the body, various drug delivery systems can be designed by utilizing smart biopolymeric compounds with the required pH-sensitivity. We also review the pharmaceutical application of pH-responsive polymeric carriers including hydrogels, polymer-drug conjugates, micelles, dendrimers, and polymersomes.

Novel reverse osmosis membranes composed of modified PVA/Gum Arabic conjugates: Biofouling mitigation and chlorine resistance enhancement.

A novel crosslinked Poly (vinyl alcohol) (PVA) reverse osmosis (RO) thin film membrane conjugated with Gum Arabic (GA) with superb performance and features was synthesized for water desalination. RO membrane desalination parameters, such as hydrophilicity, surface roughness, water permeability, salt rejection, Chlorine resistance and biofouling resistance were evaluated using a dead end RO filtration unit. The incorporation of Pluronic F127 and the conjugation of Gum Arabic improved the overall RO performance of the membranes. This study has shown that the membrane PVA-GA-5 that contains 0.9wt% Gum Arabic provided excellent permeation, salt rejection, Chlorine and biofouling resistance and mechanical strength. The most remarkable result to arise from this research is that the overall RO performance enhancement has been achieved while utilizing PVA/Gum Arabic as a separation layer without the use of a substrate, which eliminates negative effects associated with the use of a substrate like internal concentration polarization.

Morphological and transport characteristics of swollen chitosan-based proton exchange membranes studied by molecular modeling.

Chitosan biopolymer has been extensively applied in direct methanol fuel cells (DMFCs) as a potential replacement to conventional Nafion membrane for its considerably reduced methanol crossover. Here, we computationally explored the influences of methanol concentration, temperature, and pH parameters upon the nanostructure and dynamics, particularly the methanol crossover, in chitosan proton-exchange membrane (PEM) through molecular dynamics simulations. Theoretical results demonstrated the increased swelling and radius of gyration of chitosan chains at higher concentrations. Structural examinations further revealed that an increase in methanol loading weakened the water interactions with chitosan functionalities (amineNH2 , hydroxylOH, and methoxyCH2 OH) whereas improved the methanol affinities toward chitosan, reflecting higher methanol sorption capability of chitosan at enhanced concentrations. Additionally, it was found that interactions between solvents and chitosan strengthened under acidic pH conditions on account of amine protonation. The water diffusivity inside the swollen chitosan diminished by increasing CH3 OH uptake, and in contrast diffusivity of methanol was noted to enhance. Furthermore, it was observed that an enhancement in temperature or a decrease in pH intensified solvent mobility. These insights imply that supplying methanol-concentrated and/or acidic feed solutions into DMFCs based on chitosan PEMs could lower membrane performance due to the significant methanol transport dynamics.

Understanding biophysical behaviours of microfluidic-synthesized nanoparticles at nano-biointerface.

Encapsulating drugs in nanoparticles (NPs) provide some advantages over free drugs; for example the probability of distribution in off-target tissues decreases and drugs remain safe from environment degrading factors. Upon entering the bioenvironment, NPs establish a number of interactions with their surroundings based on their physicochemical properties. Here we demonstrate how the size-surface charge interplay of chitosan NPs affects the protein corona formation and endocytosis pathway in the HeLa cells at non-toxic concentrations. Generally, large NPs (102 and 161nm) with low surface charge (+6.7 and +3.6mV) exhibited weaker tendency for endocytosis compared with smaller ones (63 and 83nm with 10 and 9.3mV surface charge, respectively). This is mainly because the interactions of larger NPs with the plasma membrane were too weak to release enough free energy required for cellular internalization. Furthermore, we tested the upright and inverted cell culture configurations to better understand the impact of the sedimentation and diffusion velocities of NPs on the resulting cellular uptake pattern in both serum free and serum containing culture medias. Considering the different particokinetics, the amount of internalized NPs in upright and inverted positions differed in all cases by a factor of approximately three (for 161nm particles), or less for smaller ones. Ultimately, our results offer a paradigm for analyzing the biobehavior of NPs under the precise control of their physicochemical characteristics.

Coating of cellulose-TiO2 nanoparticles on cotton fabric for durable photocatalytic self-cleaning and stiffness.

A new route to make cotton fabric self-cleaning and permanently stiff by coating cellulose-TiO2 on its surface is demonstrated herein. Cellulose-TiO2 dispersion was used for coating and was prepared by mixing TiO2 nanoparticles with cellulose in 60% H2SO4 solution. The surface morphology of cellulose-TiO2 nanoparticles coated sample was analyzed by SEM. The appearance of white TiO2 particles on the surface of the cotton fabric confirmed the successful coating process. The Orange II dye was used as stain and its degradation was observed under UV light. X-ray diffraction analysis showed that cellulose II content increases slightly (by 5.3%) after the solvent treatment. Washing fastness study showed that the fabric stiffness was permanent and self-cleaning properties were stable with 1, 3 and 5% TiO2 coated samples. Air and water vapor permeability was not decreased considerably, whereas tensile strength was increased significantly after coating.

Microfluidic Manipulation of Core/Shell Nanoparticles for Oral Delivery of Chemotherapeutics: A New Treatment Approach for Colorectal Cancer.

A microfluidics approach to synthesize core-shell nanocarriers with high pH tunability is described. The sacrificial shell protects the core layer with the drugs and prevents their release in the severe pH conditions of the gastrointestinal tract, while allowing for drug release in the proximity of a tumor. The proposed nanoparticulate drug-delivery system is designed for the oral administration of cancer therapeutics.

Microfluidic Directed Synthesis of Alginate Nanogels with Tunable Pore Size for Efficient Protein Delivery.

Alginate is a biopolymer with favorable pH-sensitive properties for oral delivery of peptides and proteins. However, conventional alginate nanogels have limitations such as low encapsulation efficiency because of drug leaching during bead preparation and burst release in high pH values. These shortcomings originate from large pore size of the nanogels. In this work, we proposed an on-chip hydrodynamic flow focusing approach for synthesis of alginate nanogels with adjustable pore size to achieve fine-tunable release profile of the encapsulated bioactive agents. It is demonstrated that the microstructure of nanogels can be controlled through adjusting flow ratio and mixing time directed on microfluidic platforms consisting of cross-junction microchannels. In this study, the average pore size of alginate nanogels (i.e., average molecular weight between cross-links, Mc) was related to synthesis parameters. Mc was calculated from equations based on equilibrium swelling theory and proposed methods to modify the theory for pH-sensitive nanogels. In the equations we derived, size and compactness of nanogels are key factors, which can be adjusted by controlling the flow ratio. It was found that increase in flow ratio increases the size of nanogels and decreases their compactness. The size of on-chip generated nanogels for flow ratio of 0.02-0.2 was measured to be in the range of 68-138 nm. Moreover, a method based on the Mie theory was implemented to estimate the aggregation number (Nagg) of polymer chains inside the nanogels as an indicator of compactness. According to the size and compactness results along with equations of modified swelling theory, Mc obtained to be in the range of 0.5-0.8 kDa. The proposed method could be considered as a promising approach for efficient polypeptides encapsulation and their sustained release.

Keratinocytes and neutrophils are important sources of proinflammatory molecules in hidradenitis suppurativa.

BACKGROUND: The pathogenesis of the chronic inflammatory skin disease hidradenitis suppurativa (HS, also known as acne inversa) involves epidermal alterations such as psoriasiform epidermal hyperplasia and keratin plugging. Keratinocytes are an important source of proinflammatory molecules in inflammatory skin diseases and can be stimulated by interleukin (IL)-17(+) cells. OBJECTIVES: To explore the possible role of the epithelium in the pathogenesis of HS. METHODS: We performed immunohistochemical stainings and Western blot experiments to investigate the localization and expression of inflammation-associated molecules, including the cytokine IL-17, components of the inflammasome including caspase-1, and the endogenous danger-associated molecular pattern molecules S100A8 and S100A9 (calprotectin). To examine a possible effect of upregulated proinflammatory cytokines on the inflammatory infiltrate, differences in the cellular composition of perifollicular and deep dermal infiltrates were analysed. RESULTS: The number of IL-17(+) cells is increased in lesional and perilesional HS skin. The epidermis produces proinflammatory molecules and shows an upregulated expression of components of the NLRP3 inflammasome, activated caspase-1 and expression of S100A8/S100A9. Additionally, the course of the inflammatory process in HS involves influx of innate immune cells, particularly IL-17-expressing neutrophils. CONCLUSIONS: IL-17-producing cells are present in lesional and perilesional HS skin and may contribute to the initiation of inflammatory processes. Furthermore, the epidermis is a source of proinflammatory cytokines, shows inflammasome activation and expresses S100A8/S100A9, thereby possibly contributing to the propagation of inflammation. A massive influx of IL-17-expressing neutrophils is observed in the deep infiltrate.

Conjugation of silica nanoparticles with cellulose acetate/polyethylene glycol 300 membrane for reverse osmosis using MgSO4 solution.

Thermally-induced phase separation (TIPS) method was used to synthesize polymer matrix (PM) membranes for reverse osmosis from cellulose acetate/polyethylene glycol (CA/PEG300) conjugated with silica nanoparticles (SNPs). Experimental data showed that the conjugation of SNPs changed the surface properties as dense and asymmetric composite structure. The results were explicitly determined by the permeability flux and salt rejection efficiency of the PM-SNPs membranes. The effect of SNPs conjugation on MgSO4 salt rejection was more significant in magnitude than on permeation flux i.e. 2.38 L/m(2)h. FTIR verified that SNPs were successfully conjugated on the surface of PM membrane. DSC of PM-SNPs shows an improved Tg from 76.2 to 101.8 °C for PM and PM-S4 respectively. Thermal stability of the PM-SNPs membranes was observed by TGA which was significantly enhanced with the conjugation of SNPs. The micrographs of SEM and AFM showed the morphological changes and increase in the valley and ridges on membrane surface. Experimental data showed that the PM-S4 (0.4 wt% SNPs) membrane has maximum salt rejection capacity and was selected as an optimal membrane.

On-chip synthesis of fine-tuned bone-seeking hybrid nanoparticles.

AIMS: Here we report a one-step approach for reproducible synthesis of finely tuned targeting multifunctional hybrid nanoparticles (HNPs). MATERIALS & METHODS: A microfluidic-assisted method was employed for controlled nanoprecipitation of bisphosphonate-conjugated poly(D,L-lactide-co-glycolide) chains, while coencapsulating superparamagnetic iron oxide nanoparticles and the anticancer drug Paclitaxel. RESULTS: Smaller and more compact HNPs with narrower size distribution and higher drug loading were obtained at microfluidic rapid mixing regimen compared with the conventional bulk method. The HNPs were shown to have a strong affinity for hydroxyapatite, as demonstrated in vitro bone-binding assay, which was further supported by molecular dynamics simulation results. In vivo proof of concept study verified the prolonged circulation of targeted microfluidic HNPs. Biodistribution as well as noninvasive bioimaging experiments showed high tumor localization and suppression of targeted HNPs to the bone metastatic tumor. CONCLUSION: The hybrid bone-targeting nanoparticles with adjustable characteristics can be considered as promising nanoplatforms for various theragnostic applications.

Social behaviour in mesopelagic jellyfish.

Gelatinous organisms apparently play a central role in deep pelagic ecosystems, but lack of observational methodologies has restricted information on their behaviour. We made acoustic records of diel migrating jellyfish Periphylla periphylla forming small, ephemeral groups at the upper fringe of an acoustic scattering layer consisting of krill. Groups of P. periphylla were also documented photographically using a remotely operated vehicle (ROV). Although the adaptive value of group formation remains speculative, we clearly demonstrate the ability of these jellyfishes to locate and team up with each other.

Enhanced osteogenic differentiation of stem cells via microfluidics synthesized nanoparticles.

Advancement of bone tissue engineering as an alternative for bone regeneration has attracted significant interest due to its potential in reducing the costs and surgical trauma affiliated with the effective treatment of bone defects. We have improved the conventional approach of producing polymeric nanoparticles, as one of the most promising choices for drug delivery systems, using a microfluidics platform, thus further improving our control over osteogenic differentiation of mesenchymal stem cells. Molecular dynamics simulations were carried out for theoretical understanding of our experiments in order to get a more detailed molecular-scale insight into the drug-carrier interactions. In this work, with the sustained intracellular delivery of dexamethasone from microfluidics-synthesized nanoparticles, we explored the effects of particle design on controlling stem cell fates. We believe that the insights learned from this work will lead to the discovery of new strategies to tune differentiation for in situ differentiation or stem cell therapeutics. FROM THE CLINICAL EDITOR: The use of mesenchymal stem cells has been described by many researchers as a novel therapy for bone regeneration. One major hurdle in this approach is the control of osteogenic differentiation. In this article, the authors described elegantly their microfluidic system in which dexamethasone loaded nanoparticles were produced. This system would allow precise fabrication of nanoparticles and consequently higher efficiency in cellular differentiation.

TRAF2 inhibits TRAIL- and CD95L-induced apoptosis and necroptosis.

The relevance of the adaptor protein TNF receptor-associated factor 2 (TRAF2) for signal transduction of the death receptor tumour necrosis factor receptor1 (TNFR1) is well-established. The role of TRAF2 for signalling by CD95 and the TNF-related apoptosis inducing ligand (TRAIL) DRs, however, is only poorly understood. Here, we observed that knockdown (KD) of TRAF2 sensitised keratinocytes for TRAIL- and CD95L-induced apoptosis. Interestingly, while cell death was fully blocked by the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD-fmk) in control cells, TRAF2-depleted keratinocytes were only partly rescued from TRAIL- and CD95L-induced cell death. In line with the idea the only partially protective effect of zVAD-fmk on TRAIL- and CD95L-treated TRAF2-depleted keratinocytes is due to the induction of necroptosis, combined treatment with zVAD-fmk and the receptor interacting protein 1 (RIP1) inhibitor necrostatin-1 [corrected] fully rescued these cells. To better understand the impact of TRAF2 levels on RIP1- and RIP3-dependent necroptosis and RIP3-independent apoptosis, we performed experiments in HeLa cells that lack endogenous RIP3 and HeLa cells stably transfected with RIP3. HeLa cells, in which necroptosis has no role, were markedly sensitised to TRAIL-induced caspase-dependent apoptosis by TRAF2 KD. In RIP3-expressing HeLa transfectants, however, KD of TRAF2 also strongly sensitised for TRAIL-induced necroptosis. Noteworthy, priming of keratinocytes with soluble TWEAK, which depletes the cytosolic pool of TRAF2-containing protein complexes, resulted in strong sensitisation for TRAIL-induced necroptosis but had only a very limited effect on TRAIL-induced apoptosis. The necroptotic TRAIL response was not dependent on endogenously produced TNF and TNFR signalling, since blocking TNF by TNFR2-Fc or anti-TNFα had no effect on necroptosis induction. Taken together, we identified TRAF2 not only as a negative regulator of DR-induced apoptosis but in particular also as an antagonist of TRAIL- and CD95L-induced necroptosis.