Sulfenamides as flame retardants

FIELD OF THE INVENTION The present invention is in the field of flame retardants and relates to use of sulfenamides as flame retardants, in particular in polymeric sub-strates

Structure–Property Studies on a New Family of Halogen Free Flame Retardants Based on Sulfenamide and Related Structures

A wide variety of molecules containing S–N or S–N–S cores were synthesized, and their flame retardant properties in polypropylene (PP), low density polyethylene (LDPE) and polystyrene (PS) were investigated. In addition, polymers or oligomers bearing the sulfenamide functionality (SN) were also synthesized. It was shown that this radical generator family based on sulfenamides is very versatile in terms of structural modifications, and the thermal decomposition range can be easily adjusted by changing the R groups attached to the core. The thermal stabilities of the different sulfenamides were examined by thermogravimetric analysis (TGA). Radicals generated by the homolytic cleavage of the S–N or S–N–S bonds at an elevated temperature can effectively interact with the intermediate products of polymer thermolysis and provide excellent flame retardant properties. The choice of most suitable SN-structure varies depending on the polymer type. For polypropylene DIN 4102-1 B2 and UL94 VTM-2 classifications were achieved with only 0.5 to 1 wt % of sulfenamide, and, in some cases, no flaming dripping was observed. Also for LDPE thin films, sulfenamides offered the DIN 4102-1 B2 rating at low dosage. In the case of polystyrene, the very stringent UL94 V-0 classification was even achieved at a loading of 5 wt % of sulfenamide

Disulfides – Effective radical generators for flame retardancy of polypropylene

The potential of thirteen aliphatic, aromatic, thiuram and heterocyclic substituted organic disulfide derivatives of the general formula R-S-S-R’ as a new group of halogen-free flame retardants (FR) for polypropylene films have been investigated. According to DIN 4102-1 standard ignitibility test, for the first time it has been demonstrated that many of the disulfides alone can effectively provide flame retardancy and self-extinguishing properties to polypropylene (PP) films at already very low concentrations of 0.5 wt%. In an effort to elucidate the mechanism of the thermal decomposition of disulfide derivatives the fragmentation patterns of the evolved gases from a thermogravimetric analyzer (TGA) have been analyzed by simultaneous mass spectrometry (MS) and Fourier transform infrared spectrometry (FTIR). The main decomposition products initiated by homolytic scission of the S-S bond and/or scission of the C-S bond were identified as thiols, aliphatic and aromatic hydrocarbons, isothiocyanates (depending on the disulfide structures) with further evolution of elemental sulfur and sulfur dioxide at temperatures of above 300 oC and 450 oC, respectively. Based on this preliminary study, we have shown that disulfides represented by e.g. diphenyl disulfide (1), 5,5'-dithiobis(2-nitrobenzoic acid) (2), bis(1-phenyl-1H-tetrazol-5yl)-disulfide (4), 2-bisbenzothiazole-2,2′-disulfide (6) and N,N-dithiobis-(phtalimide) (10) constitute a new halogen-free family of additives for flame retarding of polypropylene

SmartPAN: A novel polysaccharide-microsphere-based surgical indicator of pancreatic leakage

Postoperative pancreatic fistula is a major surgical complication that can follow pancreatic resection. Postoperative pancreatic fistula can develop as a consequence of leaking pancreatic fluid, which calls for an intraoperative indicator of leakage. But suitable indicators of pancreatic leakage have yet to be found. This study details the evidence-based development and early efficacy assessments of a novel pancreatic leakage indicator (SmartPAN), following the IDEAL framework of product development.We developed 41 SmartPAN prototypes by combining indicators of pancreatic fluid with a polysaccharide-microsphere matrix. The prototypes were assessed in vitro using porcine (Sus scrofa domesticus) pancreatic tissue and ex vivo with human pancreatic fluid. From these initial tests, we chose a hydrogel-based compound that uses the pH indicator bromothymol blue to detect alkali pancreatic fluid. This prototype was then assessed in vivo for usability, effectiveness and reliability using a porcine model. Treatment groups were defined by SmartPAN-reaction at initial pancreatic resection: indicator-positive or negative. Indicator-positive individuals randomly received either targeted closure of leakage sites or no further closure. We assessed SmartPAN’s reliability and effectiveness by monitoring abdominal drainage for amylase and with relaparotomy after 48 h. SmartPAN responses were consistent between both surgical procedures and conformed to amylase measurements. In conclusion, we have developed the first surgery-ready indicator for predicting the occurrence of pancreatic leakage during pancreatic resection. SmartPAN can enable targeted prophylactic closure in a simple and reliable way, and thus may reduce the impact of postoperative pancreatic fistula by guiding peri- and post-operative management

WNT11, a new gene associated with early-onset osteoporosis, is required for osteoblastogenesis.

Monogenic early-onset osteoporosis (EOOP) is a rare disease defined by low bone mineral density (BMD) that results in increased risk of fracture in children and young adults. Although several causative genes have been identified, some of the EOOP causation remains unresolved. Whole-exome sequencing revealed a de novo heterozygous loss-of-function mutation in WNT11 (NM_004626.2:c.677_678dup p.Leu227Glyfs*22) in a 4-year-old boy with low BMD and fractures. We identified two heterozygous WNT11 missense variants (NM_004626.2:c.217G > A p.Ala73Thr) and (NM_004626.2:c.865G > A p.Val289Met) in a 51-year-old woman and in a 61-year-old woman respectively, both with bone fragility. U2OS cells with heterozygous WNT11 mutation (NM_004626.2:c.690_721delfs*40) generated by CRISPR-Cas9 showed reduced cell proliferation (30%) and osteoblast differentiation (80%) as compared with wild-type U2OS cells. The expression of genes in the Wnt canonical and non-canonical pathways was inhibited in these mutant cells, but recombinant WNT11 treatment rescued the expression of Wnt pathway target genes. Furthermore, the expression of RSPO2, a WNT11 target involved in bone cell differentiation, and its receptor LGR5, was decreased in WNT11 mutant cells. Treatment with WNT5A and WNT11 recombinant proteins reversed LGR5 expression, but WNT3A recombinant protein treatment had no effect on LGR5 expression in mutant cells. Moreover, treatment with recombinant RSPO2 but not WNT11 or WNT3A activated the canonical pathway in mutant cells. In conclusion, we have identified WNT11 as a new gene responsible for EOOP, with loss-of-function variant inhibiting bone formation via Wnt canonical and non-canonical pathways. WNT11 may activate Wnt signaling by inducing the RSPO2-LGR5 complex via the non-canonical Wnt pathway

Immunogenicity of High-Dose vs. MF59-adjuvanted vs. Standard Influenza Vaccine in Solid Organ Transplant Recipients: The STOP-FLU trial.

BACKGROUND The immunogenicity of the standard influenza vaccine is reduced in solid-organ transplant (SOT) recipients, so that new vaccination strategies are needed in this population. METHODS Adult SOT recipients from nine transplant clinics in Switzerland and Spain were enrolled if they were >3 months after transplantation. High, with stratification by organ and time from transplant. The primary outcome was vaccine response rate, defined as a ≥4-fold increase of hemagglutination-inhibition titers to at least one vaccine strain at 28 days post-vaccination. Secondary outcomes included PCR-confirmed influenza and vaccine reactogenicity. RESULTS 619 patients were randomized, 616 received the assigned vaccines, and 598 had serum available for analysis of the primary endpoint (standard, n=198; MF59-adjuvanted, n=205; high-dose, n=195 patients). Vaccine response rates were 42% (84/198) in the standard vaccine group, 60% (122/205) in the MF59-adjuvanted vaccine group, and 66% (129/195) in the high-dose vaccine group (difference in intervention vaccines vs. standard vaccine, 0.20 [97.5% CI 0.12-1]; p<0.001; difference in high-dose vs. standard vaccine, 0.24 [95% CI 0.16-1]; p<0.001; difference in MF59-adjuvanted vs. standard vaccine, 0.17 [97.5% CI 0.08-1]; p<0.001). Influenza occurred in 6% the standard, 5% in the MF59-adjuvanted, and 7% in the high-dose vaccine groups. Vaccine-related adverse events occurred more frequently in the intervention vaccine groups, but most of the events were mild. CONCLUSIONS In SOT recipients, use of an MF59-adjuvanted or a high-dose influenza vaccine was safe and resulted in a higher vaccine response rate. TRIAL REGISTRATION Clinicaltrials.gov NCT03699839

Multi-sensory display of self-avatar's physiological state: virtual breathing and heart beating can increase sensation of effort in VR

International audienceIn this paper we explore the multi-sensory display of self-avatars’ physiological state in Virtual Reality (VR), as a means to enhance the connection between the users and their avatar. Our approach consists in designing and combining a coherent set of visual, auditory and haptic cues to represent the avatar’s cardiac and respiratory activity. These sensory cues are modulated depending on the avatar’s simulated physical exertion. We notably introduce a novel haptic technique to represent respiratory activity using a compression belt simulating abdominal movements that occur during a breathing cycle. A series of experiments was conducted to evaluate the influence of our multi-sensory rendering techniques on various aspects of the VR user experience, including the sense of virtual embodiment and the sensation of effort during a walking simulation. A first study (N=30) that focused on displaying cardiac activity showed that combining sensory modalities significantly enhances the sensation of effort. A second study (N=20) that focused on respiratory activity showed that combining sensory modalities significantly enhances the sensation of effort as well as two sub-components of the sense of embodiment. Interestingly, the user’s actual breathing tended to synchronize with the simulated breathing, especially with the multi-sensory and haptic displays. A third study (N=18) that focused on the combination of cardiac and respiratory activity showed that combining both rendering techniques significantly enhances the sensation of effort. Taken together, our results promote the use of our novel breathing display technique and multi-sensory rendering of physiological parameters in VR applications where effort sensations are prominent, such as for rehabilitation, sport training, or exergames

Influence of user posture and virtual exercise on impression of locomotion during VR observation

International audienceA seated user watching his avatar walking in Virtual Reality (VR) and imagining being walking may have an impression of walking. In this paper, we show that such impression can be extended to other postures and other locomotion exercises. We present two user studies in which participants worn a VR headset and observed a first-person avatar realizing virtual exercises. In the first experiment, the avatar walked and participants (n=36) tested the simulation in 3 different postures (standing, sitting and Fowler's posture). In the second experiment, other participants (n=18) were sitting and observed the avatar walking, jogging or stepping over virtual obstacles. We evaluated the impression of locomotion by measuring the impression of walking (respectively jogging or stepping) and embodiment in both experiments. The results show that participants had the impression of locomotion in either sitting, standing and Fowler's posture. The Fowler's posture however significantly decreased both the level of embodiment and the impression of locomotion. Moreover the sitting posture seems to decrease the sense of agency compare to standing posture. Results also show that the majority of the participants elicited an impression of locomotion during walking, jogging and stepping virtual exercises. The embodiment was not influenced by the type of virtual exercise. Overall, our results suggest that an impression of locomotion can be elicited in different users' postures and during different virtual locomotion exercises. They provide valuable insight for numerous VR applications in which the user observes a self-avatar moving, such as gait rehabilitation, training, video games, etc

Triazene compounds as a novel and effective class of flame retardants for polyproplylene

Four triazene derivatives have been synthesized, i.e. bis-4,4'-(3,3'-dimethyltriazene)-diphenyl ether (1), bis-4,4'-(3,3'-diethyltriazene)-diphenyl ether (2), 2,2,6,6,-tetramethyl-1-phenylazo-piperidine (3) and 4-hydroxy-2,2,6,6-tetramethyl-1-phenylazopiperidine (4). Their thermal properties were determined by differential scanning calorimetry (DSC) and the fragmentation patterns were analysed by simultaneous mass spectrometry (MS) and Fourier transform infrared (FTIR) spectrometry of off-gases from a thermogravimetric analyser (TGA). The triazenes exhibited an exothermic decomposition peak at temperatures between 230 and 280 °C when the triazene units were homolytically cleaved into various aminyl, resonance-stabilized aryl radicals and different CH fragments with simultaneous evolution of elemental nitrogen. The potential of triazenes as a new class of flame retardants for polypropylene films was investigated by performing ignitability test in accordance to DIN 4102-1/B2 standard. Polypropylene samples containing very low concentration of only 0.5 wt% of any of these triazene (R-N1 = N2N3R'R") additives passed the test with B2 classification. Notably, no burning dripping could be detected. The average burning times are very short with exceptionally low weight losses. Based on this preliminary FR testing we have shown that the triazene compounds constitute a new and interesting family of radical generators for flame retarding of polymeric materials