Equivalent Sites Research Articles

Single-molecule tautomerization tracking through space- and time-resolved fluorescence spectroscopy

Tautomerization, the interconversion between two constitutional molecular isomers, is ubiquitous in nature1, plays a major role in chemistry2 and is perceived as an ideal switch function for emerging molecular-scale devices3. Within free-base porphyrin4, porphycene5 or phthalocyanine6, this process involves the concerted or sequential hopping of the two inner hydrogen atoms between equivalent nitrogen sites of the molecular cavity. Electronic and vibronic changes6 that result from this NH tautomerization, as well as details of the switching mechanism, were extensively studied with optical spectroscopies, even with single-molecule sensitivity7. The influence of atomic-scale variations of the molecular environment and submolecular spatial resolution of the tautomerization could only be investigated using scanning probe microscopes3,8-11, at the expense of detailed information provided by optical spectroscopies. Here, we combine these two approaches, scanning tunnelling microscopy (STM) and fluorescence spectroscopy12-15, to study the tautomerization within individual free-base phthalocyanine (H2Pc) molecules deposited on a NaCl-covered Ag(111) single-crystal surface. STM-induced fluorescence (STM-F) spectra exhibit duplicate features that we assign to the emission of the two molecular tautomers. We support this interpretation by comparing hyper-resolved fluorescence maps15-18(HRFMs) of the different spectral contributions with simulations that account for the interaction between molecular excitons and picocavity plasmons19. We identify the orientation of the molecular optical dipoles, determine the vibronic fingerprint of the tautomers and probe the influence of minute changes in their atomic-scale environment. Time-correlated fluorescence measurements allow us to monitor the tautomerization events and to associate the proton dynamics to a switching two-level system. Finally, optical spectra acquired with the tip located at a nanometre-scale distance from the molecule show that the tautomerization reaction occurs even when the tunnelling current does not pass through the molecule. Together with other observations, this remote excitation indicates that the excited state of the molecule is involved in the tautomerization reaction path.

Determination of seismic hazard and soil response of a critical region in Turkey considering far-field and near-field earthquake effect

Evaluation of earthquake impacts in settlements with a high risk of earthquake occurrence is important for the determination of site-specific dynamic soil parameters and earthquake-resistant structural planning. In this study, dynamic soil properties of Karliova (Bingol) city center, located near to the intersection point of the North Anatolian Fault Zone and the East Anatolian Fault Zone and therefore having a high earthquake risk, were investigated by one-dimensional equivalent linear site response analysis. From ground response analyses, peak ground acceleration, predominant site period, 0.2-sec and 1-sec spectral accelerations and soil amplification maps of the study area were obtained for both near-field and far-field earthquake effects. The average acceleration spectrum obtained from analysis, for a near-field earthquake scenario, was found to exceed the design spectra of the Turkish Earthquake Code and Eurocode 8. Yet, the average acceleration spectrum was found to remain below the respective design spectra of the two codes for the far-field earthquake scenario. According to both near- and far-field earthquake scenarios in the study area, the low-rise buildings with low modal vibration durations are expected to be exposed to high spectral acceleration values and high-rise buildings with high modal vibration durations will be exposed to lower spectral accelerations. While high amplification ratios are observed in the north of the study area for the near-distance earthquake scenario, high amplification ratios are observed in the south of the study area for the long-distance earthquake scenario.

Isothermal titration calorimetry and surface plasmon resonance analysis using the dynamic approach

Biophysical techniques such as isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR) are routinely used to ascertain the global binding mechanisms of protein-protein or protein-ligand interaction. Recently, Dumas etal, have explicitly modelled the instrument response of the ligand dilution and analysed the ITC thermogram to obtain kinetic rate constants. Adopting a similar approach, we have integrated the dynamic instrument response with the binding mechanism to simulate the ITC profiles of equivalent and independent binding sites, equivalent and sequential binding sites and aggregating systems. The results were benchmarked against the standard commercial software Origin-ITC. Further, the experimental ITC chromatograms of 2′-CMP + RNASE and BH3I-1 + hBCLXL interactions were analysed and shown to be comparable with that of the conventional analysis. Dynamic approach was applied to simulate the SPR profiles of a two-state model, and could reproduce the experimental profile accurately.

Electroluminescence of Cr3+ and pseudo-Stark effect in β-Ga2O3 Schottky barrier diodes

Bright, red electroluminescence is generated in reverse biased Schottky barrier diodes (SBDs) based on β-Ga2O3 single crystals codoped with chromium and silicon. It is due to intracenter transitions of octahedrally coordinated Cr3+ ions excited by electron impact in the depletion layer of the diodes. The electroluminescence spectrum around 700 nm in wavelength is nearly identical to the spectrum of the well-known photoluminescence of Cr3+ in β-Ga2O3, which is featured by the two lines R1 and R2. In contrast to the photoluminescence, however, in the electroluminescence, each of the R1 and R2 lines is additionally split by 1.5–3 meV. Since the R1/R2 lines correspond to transitions from two Kramers-degenerate states (split 2E excited state) to the ground state 4A2, this splitting cannot be ascribed to the normal Stark effect in the strong electric field of the Schottky barrier diode's depletion layer. Instead, we explain the splitting by the pseudo-Stark effect that occurs because the Cr3+ ions replace Ga3+ at two kinds of energetically equivalent octahedral sites that differ crystallographically by an inversion at the Cr ion. Superposition of the dominating R1 doublet radiation would result in a tunable beat frequency of about 0.4–0.7 THz and might be utilized for a terahertz light source. Moreover, the electroluminescence of chromium is representative of the ability to excite the luminescent states of other transition metals. Hence, high temperature light-emitting SBDs in different colors are a potential application for β-Ga2O3.

Response by Three Plant Indicator Groups of Upland Habitat to Manipulation of a Black Oak (Quercus velutina) Sand Barren

In the absence of a disturbance regime, flora at historical oak sand barrens change as leaf litter builds up and increasing canopy cover shades bare soils. Over time, black oak sand barrens become more mesic, and other trees including Acer rubrum, Fraxinus sp., Prunus serotina, and Sassafras albidum often mix with oaks in the canopy. Three different restoration techniques were applied to recreate disturbance across 10 sites within degraded black oak (Quercus velutina) glacial kames, which are mounds of sand and gravel deposited by melting ice sheets: select canopy tree thinning favoring 5–30% tree canopy cover, forest floor leaf litter removal, and prescribed fire. Ground layer richness and abundance 1 and 3 y after treatment were assessed within modified North Carolina Vegetation Survey plots and compared against both temporally and spatially equivalent control sites. Thinning the canopy induced the greatest vegetation response in species diversity, whether as xeric-tolerant indicator species, graminoid species, as a taxonomic group, or pooling all plants. Leaf litter removal produced a modest pulse response from a few select species released from the shade-creating effects of accumulating leaf litter. Prescribed burns did not create a disturbance sufficient for any significant plant response, presumably because low-intensity burning minimally reduced leaf litter cover. Thus, manipulations that opened the canopy and reduced soil moisture more directly induced barren-species recovery than did efforts to recreate historical disturbance processes.

Microengineered biosynthesized cellulose as anti-fibrotic in vivo protection for cardiac implantable electronic devices

Upon cardiac implantable electronic device (CIED) exchange, upgrade, or revision surgery patients are exposed to a considerable risk of adverse events. The presence of firm fibrotic tissue endangers these procedures. Leads can be damaged in the attempt of freeing them from fibrotic tissue. Hematoma can form as result of capsulectomy, pocket debridement and leads dissection. Due to the increasing number of CIED exchange, upgrade and revision surgeries, the incidence of related complications is expected to rise in the near future.The aim of the study was to evaluate the feasibility, safety, and performance of a rationally micro-engineered non-resorbable biosynthesized cellulose (BC) membrane as conformal wrapping protection around CIED implants. Protective membranes were generated by means of a recently established method to transfer on-demand microscale geometries onto the surface of BC. A chronic minipig animal model was selected to investigate the performance of the BC anti-fibrotic protection, directly measured as reduction of fibrotic tissue formation. Sixteen (n = 16) animals received each one BC coated pacemaker (PMC) and one native pacemaker (BI) at equivalent anatomical sites. BC protective layers were juxtaposed around pacemakers through a fast and well-repeatable procedure. Explants were performed at 3 and 12 months after implantation. Endpoint analysis showed that the BC protective layers were 100% integer, with no sign of chemical or mechanical degradation and appeared as a thin layer of white-tan material, adherent to the surrounding thin fibrous capsule, from which it could be peeled off by gently pulling with forceps. The protective effect of micro-engineered BC yielded an average thickness reduction of 66% of the fibrotic tissue thickness generated around PMC, as compared to that measured around the naked counterpart (i.e. the BI). When protected by in BC, both the generator and the proximal parts of the leads were completely free from fibrotic tissue. The insertion of an anti-adhesive, non-resorbable and well-tolerated BC interface between the implant and the surrounding tissue in the surgical pocket significantly reduced the formation of fibrotic tissue, ensuring an easy access to the device pocket, and thus creating the conditions for simplified CIED revision surgeries.

Coastal landforms of “Meso-Afro-American” and “Neo-American” landscapes in the periglacial South Atlantic ocean: With special reference to the clast orientation, morphology, and granulometry of continental and marine sediments

Coastal landforms of “Meso-Afro-American” and “Neo-American” landscapes in the periglacial South Atlantic ocean: With special reference to the clast orientation, morphology, and granulometry of continental and marine sediments

Evidence to support clean-energy transition and related health co-benefits

TPS 641: Policies, interventions, communication, Exhibition Hall, Ground floor, August 28, 2019, 3:00 PM - 4:30 PM Background: Air quality in the Pacific Island Countries (PICs) can be comparable to more developed countries due to emissions from energy production and use. Although much potential exists for clean energy, many PIC communities and households rely on fossil/ solid-fuel combustion for domestic energy needs (e.g. cooking, lighting), which may contribute to air pollution problems. Methods: To augment the evidence on the link between energy, air quality and health in the PICs, a low-cost air-quality monitoring network is being piloted in Suva, Fiji (2017 population: ~95,000). The monitors (‘KOALAs’: Knowing Our Ambient, Local Air quality) measure combustion-related emissions: particulate matter (PM2.5) and carbon monoxide (CO) at 5-minute intervals. The network, overseen remotely by a data management centre, consists of multiple monitors to spatiotemporally resolve regional air quality information across suspected low (background) and high (urban) emission sites. Results: Several months of data have so-far been collected in Suva, giving tens of thousands of air-quality observations (approximately 9,000/month/KOALA). Mean [SD] 24-hour values of PM2.5 and CO at background and urban sites are 5.0 [3.6] µg/m3 and 0.13 [0.08] ppm, and 6.4 [3.5] µg/m3 and 0.09 [0.03] ppm, respectively. Welch two-sample t-tests indicate that 24-hour means are significantly different between sites for both PM2.5 (p-value=0.003) and CO (p-value=0.008). Background site five-minute-interval measurements of PM2.5 and CO are weakly correlated (r2=0.44). Equivalent urban site measurements are more weakly correlated (r2=0.28). Real-time measurements are found online: http://fiji.sensors.net.au/. Conclusions: Urban PM2.5 24-hour values from low-cost monitors in Suva, the capital city of Fiji and one of the most populous PIC regions, are below the WHO air quality 24-hour guideline values of 25 µg/m3. Low correlations between PM2.5 and CO suggests different emission sources at background and urban sites. Future monitoring using the KOALAs will profile population and personal exposures, and support regional clean-energy interventions.

19F Paramagnetic Relaxation-Based NMR for Quaternary Structural Restraints of Ion Channels.

Quaternary distance restraints are essential to define the three-dimensional structures of protein assemblies. These distances often fall within a range of 10-18 Å, which challenges the high and low measurement limits of conventional nuclear magnetic resonance (NMR) and double electron-electron resonance electron spin resonance spectroscopies. Here, we report the use of 19F paramagnetic relaxation enhancement (PRE) NMR in combination with 19F/paramagnetic labeling to equivalent sites in different subunits of a protein complex in micelles to determine intersubunit distances. The feasibility of this strategy was evaluated on a pentameric ligand-gated ion channel, for which we found excellent agreement of the 19F PRE NMR results with previous structural information. The study suggests that 19F PRE NMR is a viable tool in extracting distance restraints to define quaternary structures.

Structure of GTP cyclohydrolase I from Listeria monocytogenes, a potential anti-infective drug target.

A putative open reading frame encoding GTP cyclohydrolase I from Listeria monocytogenes was expressed in a recombinant Escherichia coli strain. The recombinant protein was purified and was confirmed to convert GTP to dihydroneopterin triphosphate (Km = 53 µM; vmax = 180 nmol mg-1 min-1). Theprotein was crystallized from 1.3 M sodium citrate pH 7.3 and the crystal structure was solved at a resolution of 2.4 Å (Rfree = 0.226) by molecular replacement using human GTP cyclohydrolase I as a template. The protein is a D5-symmetric decamer with ten topologically equivalent active sites. Screening a small library of about 9000 compounds afforded several inhibitors with IC50 values in the low-micromolar range. Several inhibitors had significant selectivity with regard to human GTP cyclohydrolase I. Hence, GTP cyclohydrolase I may be a potential target for novel drugs directed at microbial infections, including listeriosis, a rare disease with high mortality.

Identification of Serine-875 as an Inhibitory Phosphorylation Site in the Calcium-Sensing Receptor.

The calcium-sensing receptor (CaS) is the principal controller of extracellular calcium (Ca2+ o) homeostasis and is inhibited in vitro and in vivo by protein kinase C (PKC)-mediated phosphorylation at CaST888 However, PKC inhibition enhances signaling even in CaSs lacking Thr-888, suggesting that an additional inhibitory site exists. An apparently equivalent PKC regulatory site in metabotropic glutamate receptor 5 (Ser-839) aligns not with CaST888 but instead with CaSS875, which was not previously considered to be a PKC site. CaSS875A (nonphosphorylatable) exhibited significantly enhanced Ca2+ o sensitivity of both intracellular Ca2+ mobilization and extracellular signal-regulated kinase 1/2 activation, whereas the phosphomimetic CaSS875D mutant exhibited a loss of function. The CaSS875A/T888A double mutant exhibited even greater Ca2+ o sensitivity than CaST888A alone, a response no longer enhanced by PKC inhibition. Finally, when expressed in CaS lacking its extracellular domain, the CaSS875A/T888A double mutation elicited maximal activation even under control conditions, but remained sensitive to negative allosteric modulation [N-(2-hydroxy-3-(2-cyano-3-chlorophenoxy)propyl)-1,1-dimethyl-2-(2-nephthyl)ethylamine] or Ca2+ o removal. Therefore, we have now identified CaSS875 as the missing PKC phosphorylation site that, together with CaST888, shapes the CaS signaling that underpins Ca2+ o homeostasis. Together with the inactive form of the CaS extracellular domain, these sites attenuate Ca2+ o sensitivity to attain appropriate physiologic Ca2+ o sensing. SIGNIFICANCE STATEMENT: Serine-875 represents the missing inhibitory PKC phosphorlyation site in CaS that in tandem with Thr-888 controls receptor activity.

Stepwise on-surface dissymmetric reaction to construct binodal organometallic network

Dissymmetric reactions, which enable differentiated functionalization of equivalent sites within one molecule, have many potential applications in synthetic chemistry and materials science, but they are very challenging to achieve. Here, the dissymmetric reaction of 1,4-dibromo-2,5-diethynylbenzene (2Br-DEB) on Ag(111) is realized by using a stepwise activation strategy, leading to an ordered two-dimensional organometallic network containing both alkynyl–silver–alkynyl and alkynyl–silver–phenyl nodes. Scanning tunneling microscopy and density functional theory calculations are employed to explore the stepwise conversion of 2Br-DEB, which starts from the H-passivation of one Br-substituted site at 300 K in accompaniment with an intermolecular reaction to form one-dimensional organometallic chains containing alkynyl–silver–alkynyl nodes. Afterwards, the other equivalent Br-substituted site undergoes metalation reaction at 320–450 K, resulting in transformation of the chains into the binodal networks. These findings exemplify the achievement of the dissymmetric reaction and its practical application for controlled fabrications of complicated yet ordered nanostructures on a surface.

Electrochemistry of cyclic triimidazoles and their halo derivatives: A casebook for multiple equivalent centers and electrocatalysis

A family of cyclic triazines, based on the triimidazo[1,2-a:1′,2′-c:1″,2″-e][1,3,5]triazine scaffold, has recently caught attention due to its variegated solid state photoluminescent properties (e.g., crystallization induced emission, fluomechanochromism, dual fluorescence, room temperature ultralong phosphorescence), tuned by proper functionalization of the cyclic core. From an electrochemical point of view, this family of heteroaromatic cyclic triazines is unexplored. A cyclic voltammetry study is here performed aiming to clarify structure/electroactivity relationship. The peculiar molecular structure of this class of molecules offers a multi-approach case study, spanning from multiple equivalent redox site interactions in small hoops (due to ideally C3h symmetry) to carbon-halogen bond reactivity in the presence of catalytic metal electrode surfaces (for –Br and –I derivatives). Results point to a poor heteroannular aromaticity along the rigid, planar cyclotrimer, with each equivalent redox site acting quite independently. An unusually higher electrocatalytic performance of gold with respect to silver electrode for the electrocleavage of carbon-halogen bonds (that decreases by increasing number of halo substituents) is tentatively explained in term of a specific interaction between gold and the nitrogen-rich planar cyclotrimer platform.

Seismic behaviour of rocking bridge pier supported by elastomeric pads on pile foundation

Life line structures such as elevated flyovers and rail over bridges should remain functional after an earthquake event to avoid possible traffic delays and risk to general public. Generally, restraining the structure by reducing the degrees of freedom often cause serious damages that occurs during a seismic event through yielding of the structural components. By allowing the structure to rock through uplift using suitable arrangements can be a plausible seismic resilient technique. In this context, this article proposes a novel seismic resilient pile supported bridge pier foundation, which uses elastomeric pads installed at top of pile cap. The effect of pile soil interaction along with ground response analysis is also incorporated in the full bridge model adopted for the study. One dimensional equivalent linear site response analyses were performed to arrive at the amplified/attenuated ground motions along the depth of soil.The seismic performance of the proposed bridge with new rocking isolation concept is compared with existing bridge located in medium seismic zone of India. With the help of non-linear dynamic time history analysis and nonlinear static pushover analysis, the bridge modelled using the proposed novel rocking isolation technique shows good re-centering capability during earthquakes with negligible residual drifts and uniform distribution of ductility demand along the piers of the bridge considered in this study.

Structure and disorder in ice VII on the approach to hydrogen-bond symmetrization

We have collected neutron-diffraction data of sufficient quality for structural refinement from deuterated ice VII to over 60 GPa. At these pressures, we are approaching the onset of molecular dissociation where the water molecule should be significantly distorted. We fitted our data with both the conventional structural model for ice VII and a recently proposed ``interstitial'' model. We found these to be statistically indistinguishable and, therefore, adopted the conventional model in this work. Our refinements yield the first direct experimental determination of the molecular structure in this pressure regime. They show a clear elongation of the covalent bond, the rate of which rapidly increases with pressure, indicating we have entered a distinct regime on the approach to ice X. In addition, we have directly measured the pressure dependence of the separation of the two equivalent deuteron sites along the hydrogen bonds, which provides an upper bound on the hydrogen-bond centering pressure.

The use of tris (tetraphenylimidodiphosphinate) of praseodymium chemical shift reagent in proton NMR for the evaluation of the argan oil fatty acids autoxidation and the analysis of the argan pulp fatty acids

Proton NMR is a method of molecular investigation that has its limitations when applied to complex molecules or molecules with many nearly equivalent sites. Previous studies have resorted to the use of paramagnetic chemical shift reagents, having as formula tris (tetraphenylimidodiphosphinate) of lanthanides ln((tpip.)3. The use of reagent Pr(tpip)3 in proton RMN has allowed us to evaluate the autoxidation of fatty acids mixture (stored 6 and 12 months after oil extraction) by the dosage of saturated and unsaturated acids on the one hand, and that of oleic and linoleic acids on the other. We note between 6 and 12 months of storage at 4°C a decrease in the percentage of unsaturated acids (76% to 63%) and an increase in the percentage of saturated acids (24% to 36%). The results show that the oleic acid maintained the same percentage (35%) as it is not easily oxidized whereas, for the linoleic acid, we observe a decrease in percentage from 22.5% to 18.5% (slow autoxidation at 4°C). We also used this NMR method for the analysis of the argan pulp fatty part. The GC analysis shows that it contains very few unsaturated fatty acids and that the main fatty acids are myristic (C14:0) and palmitic (C16:0) acids. The proton NMR with Pr(tpip)3 allowed us to confirm these results. This method that does not require derivation has proven to be interesting, simple and efficient.

The use of tris (tetraphenylimidodiphosphinate) of praseodymium chemical shift reagent in proton NMR for the evaluation of the argan oil fatty acids autoxidation and the analysis of the argan pulp fatty acids

<p>Proton NMR is a method of molecular investigation that has its limitations when applied to complex molecules or molecules with many nearly equivalent sites. Previous studies have resorted to the use of paramagnetic chemical shift reagents, having as formula tris (tetraphenylimidodiphosphinate) of lanthanides ln((tpip.)3.<strong> </strong>The use of reagent Pr(tpip)3 in proton RMN has allowed us to evaluate the autoxidation of fatty acids mixture (stored 6 and 12 months after oil extraction) by the dosage of saturated and unsaturated acids on the one hand, and that of oleic and linoleic acids on the other. We note between 6 and 12 months of storage at 4°C a decrease in the percentage of unsaturated acids (76% to 63%) and an increase in the percentage of saturated acids (24% to 36%). The results show that the oleic acid maintained the same percentage (35%) as it is not easily oxidized whereas, for the linoleic acid, we observe a decrease in percentage from 22.5% to 18.5% (slow autoxidation at 4°C). We also used this NMR method for the analysis of the argan pulp fatty part. The GC analysis shows that it contains very few unsaturated fatty acids and that the main fatty acids are myristic (C14:0) and palmitic (C16:0) acids. The proton NMR with Pr(tpip)3 allowed us to confirm these results. This method that does not require derivation has proven to be interesting, simple and efficient.</p>

Energetics of the coupled electronic\u2013structural transition in the rare-earth nickelates

Rare-earth nickelates exhibit a metal–insulator transition accompanied by a structural distortion that breaks the symmetry between formerly equivalent Ni sites. The quantitative theoretical description of this coupled electronic–structural instability is extremely challenging. Here, we address this issue by simultaneously taking into account both structural and electronic degrees of freedom using a charge self-consistent combination of density functional theory and dynamical mean-field theory, together with screened interaction parameters obtained from the constrained random phase approximation. Our total energy calculations show that the coupling to an electronic instability toward a charge disproportionated insulating state is crucial to stabilize the structural distortion, leading to a clear first order character of the coupled transition. The decreasing octahedral rotations across the series suppress this electronic instability and simultaneously increase the screening of the effective Coulomb interaction, thus weakening the correlation effects responsible for the metal–insulator transition. Our approach allows to obtain accurate values for the structural distortion and thus facilitates a comprehensive understanding, both qualitatively and quantitatively, of the complex interplay between structural properties and electronic correlation effects across the nickelate series.

Tau's Proline Rich Region Dominates Tubulin Binding

Tau is an intrinsically disordered, microtubule associated protein best known for its role neurodegenerative tauopathies such as Alzheimer's disease. Tau's physiological roles include stabilizing microtubules and regulating microtubule dynamic instability. Considerable attention has been given to tau's microtubule binding region (MTBR), and more recently to its MTBR-flanking R’ region, and their role in tau binding to both microtubules and soluble tubulin. N-terminally flanking the MTBR is the proline rich region (PRR), which is widely accepted as critical for tau-mediated polymerization of microtubules and also cited as demonstrating weak microtubule binding. Here, we investigate the role of the PRR in tau binding to soluble tubulin. We find that the PRR dominates binding of tau to soluble tubulin. The PRR has two equivalent binding sites for soluble tubulin dimers, and surprisingly, competes with the MTBR-R’ for binding to soluble tubulin suggesting at least partial overlap of the binding sites in these separate regions. In the absence of the MTBR, PRR is capable of binding microtubules and polymerizing tubulin, albeit weakly. Collectively, our data suggests the PRR region is an important binding motif for the soluble tubulin pool. Interestingly, this domain is not visible in the recent cryo-EM structure of microtubule-bound tau. Future work will focus on describing the relationship between PRR and MTBR-R’ on the microtubule.

Usability and safety of SB5 (an adalimumab biosimilar) prefilled syringe and autoinjector in patients with rheumatoid arthritis

Objective: To demonstrate comparability between administration of the adalimumab biosimilar, SB5, via prefilled syringe (PFS) and autoinjector (AI) pen based on injection site pain, patient preference, and safety in rheumatoid arthritis (RA) patients.Methods: In this phase 2, open-label study (NCT02565810; EudraCT Number 2014-004887-39), adult RA patients self-administered 40 mg SB5 subcutaneously via PFS at weeks 0 and 2, followed by AI at weeks 4, 6, 8, and 10. Patients rated injection site pain from 0 (no pain) to 10 (severe pain) using a visual numeric scale immediately and 15–30 min post-injection at weeks 0, 2, 4, and 6. Equivalence between PFS and AI was concluded if the 97.5% confidence interval (CI) of the difference in the injection site pain scores at weeks 2 and 6 was contained within the equivalence margin of ±5. Overall impression and preference for PFS and AI were also evaluated. Safety was assessed up to 20 weeks after the first injection.Results: Of 49 patients enrolled, 48 completed the study. Mean injection site pain scores were equivalent between PFS and AI immediately (2.3 vs 2.0; 97.5% CI = −0.99–0.30) and 15–30 min post-injection (0.8 vs 0.7; 97.5% CI = −0.47–0.25). The overall impression of both devices was comparable. The overall preference of AI was higher than PFS. Treatment-emergent adverse events (TEAE) were mild-to-moderate. There were no severe or serious TEAEs reported during the study.Conclusions: In RA patients, SB5 showed equivalent injection site pain and comparable safety when administered via PFS and AI.Trial registration: ClinicalTrials.gov identifier: NCT02565810.