Energizing tourism sustainably: A harmonious symphony of tourists' and locals' acceptance of renewable energy.

This review paper explores the acceptance of renewable energy (RE) installations and projects, focusing on the perspectives of local residents and tourists. While previous research has extensively examined community acceptance of RE, limited attention has been given to tourists' acceptance in tourist destinations. Despite extensive research, significant gaps persist, particularly regarding tourists' acceptance of RE installations. The paper stresses the need to identify the determinants of tourists' acceptance and advocates for further investigation comparing residents' and tourists' reactions to RE projects in tourism destinations. It also emphasizes the importance of incorporating new theories and interdisciplinary approaches into future studies. By offering an overview of existing research and providing guidance for future inquiry, this review paper contributes to the body of knowledge on RE acceptance. It underscores the necessity of comprehensively examining the acceptance of both local residents and tourists to ensure sustainable development and the integration of RE projects in tourism destinations.

Mechanical Surface Treatments for Controlling Surface Integrity and Corrosion Resistance of Mg Alloy Implants: A Review.

The present paper aims to provide an overview of the current state-of-the-art mechanical surface modification technologies and their response in terms of surface roughness, surface texture, and microstructural change due to cold work-hardening, affecting the surface integrity and corrosion resistance of different Mg alloys. The process mechanics of five main treatment strategies, namely, shot peening, surface mechanical attrition treatment, laser shock peening, ball burnishing, and ultrasonic nanocrystal surface modification, were discussed. The influence of the process parameters on plastic deformation and degradation characteristics was thoroughly reviewed and compared from the perspectives of surface roughness, grain modification, hardness, residual stress, and corrosion resistance over short- and long-term periods. Potential and advances in new and emerging hybrid and in-situ surface treatment strategies were comprehensively eluded and summarised. This review takes a holistic approach to identifying the fundamentals, pros, and cons of each process, thereby contributing to bridging the current gap and challenge in surface modification technology for Mg alloys. To conclude, a brief summary and future outlook resulting from the discussion were presented. The findings would offer a useful insight and guide for researchers to focus on developing new surface treatment routes to resolve surface integrity and early degradation problems for successful application of biodegradable Mg alloy implants.

Erosion-inhibiting potential of the stannous fluoride-enriched CPP-ACP complex in vitro.

Currently available anti-erosive agents only provide partial protection, emphasizing the need to enhance their performance. By characterizing erosive enamel wear at the nanoscale, the aim of this in vitro study was to assess the anti-erosive effects of SnF2 and CPP-ACP both individually and synergistically. Erosion depths were assessed longitudinally on 40 polished human enamel specimens after 1, 5, and 10 erosion cycles. Each cycle comprised one-min erosion in citric acid (pH 3.0) and one-min treatment in whole saliva (control group) or a slurry of one of the three anti-erosive pastes (10% CPP-ACP; 0.45% SnF2 (1100 ppm F); or SnF2/CPP-ACP (10% CPP-ACP + 0.45% SnF2)) (n = 10 per group). Scratch depths were assessed longitudinally in separate experiments using a similar protocol after 1, 5, and 10 cycles. Compared with the control groups, all slurries reduced erosion depths after 1 cycle (p ≤ 0.004) and scratch depths after 5 cycles (p ≤ 0.012). The order of anti-erosive potential was SnF2/CPP-ACP > SnF2 > CPP-ACP > control for erosion depth analysis, and SnF2/CPP-ACP > (SnF2 = CPP-ACP) > control for scratch depth analysis. These data provide 'proof of concept' evidence that SnF2/CPP-ACP has superior anti-erosive potential compared to SnF2 or CPP-ACP alone.

Does Entrepreneurs' Darwinian Social Identity Contribute to Business Performance via Corporate Social Responsibility in China? The Role of Entrepreneurs' Well-Being.

Although the impact of entrepreneurs' social identity on successful entrepreneurship has attracted much scholarly attention, it is often to evaluate successful entrepreneurship through direct channel to financial performance. Recently, there is a growing body of researches beginning to pay attention to the impact of entrepreneurs' social identity on corporate social responsibility (CSR) regarded as indirect social aspect channel to successful entrepreneurship. However, little is known regarding how entrepreneurs' Darwinian social identity affects CSR, which in turn, affects business performance. This study addresses this issue by combining stakeholder theory with social identity theory, to investigate the relationship between entrepreneurs' Darwinian social identity and business performance via CSR. In addition, the moderating effect of entrepreneur's well-being is further examined to uncover the interaction effect of the individual psychological resource on business performance. The empirical results indicate that entrepreneurs' Darwinian social identity contributes positively to CSR, so as further to business performance. In addition, this relationship is further found to be significantly moderated by entrepreneurs' well-being. The results indicate that entrepreneurs can achieve business success via CSR, by which entrepreneurs can further acquire successful entrepreneurship through caring more about their well-being.

Characterising a Custom-Built Radio Frequency PECVD Reactor to Vary the Mechanical Properties of TMDSO Films.

Plasma-polymerised tetramethyldisiloxane (TMDSO) films are frequently applied as coatings for their abrasion resistance and barrier properties. By manipulating the deposition parameters, the chemical structure and thus mechanical properties of the films can also be controlled. These mechanical properties make them attractive as energy adsorbing layers for a range of applications, including carbon fibre composites. In this study, a new radio frequency (RF) plasma-enhanced chemical vapour deposition (PECVD) plasma reactor was designed with the capability to coat fibres with an energy adsorbing film. A key characterisation step for the system was establishing how the properties of the TMDSO films could be modified and compared with those deposited using a well-characterized microwave (MW) PECVD reactor. Film thickness and chemistry were determined with ellipsometry and X-ray photoelectron spectroscopy, respectively. The mechanical properties were investigated by nanoindentation and atomic force microscopy with peak-force quantitative nanomechanical mapping. The RF PECVD films had a greater range of Young's modulus and hardness values than the MW PECVD films, with values as high as 56.4 GPa and 7.5 GPa, respectively. These results demonstrated the varied properties of TMDSO films that could in turn be deposited onto carbon fibres using a custom-built RF PECVD reactor.

Synergistic effect of deep ball burnishing and HA coating on surface integrity, corrosion and immune response of biodegradable AZ31B Mg alloys.

The fast degradation and consequent loss of mechanical integrity is a major problem of biodegradable Mg alloy, which limits its clinical viability. This paper presents the influence of a synergistic approach combining deep ball burnishing and hydroxyapatite (HA) coating on biomechanical integrity, degradation and immune response of Mg alloy (AZ31B). The burnishing resulted in smooth surface topography, increased hardness from 0.87 to 1.45 GPa and induced microstructural disturbances with deformation twins/twin bands, which enabled formation of a dense and compact platelet-like crystals HA coating of 110 µm thickness. Compared to the untreated and burnished specimens, the burnished + HA coated surface provided remarkably higher corrosion resistance as indicated by lower corrosion current density and smaller mass loss. HA coating and surface integrity enhancement by burnishing were predominantly responsible for improved corrosion resistance. HA coating on the burnished surface exhibited hydrophilic properties and adequate bonding strength. While the modified surfaces promoted cell growth, the burnished + HA surface outperformed in exhibiting less pro-inflammatory and high anti-inflammatory cytokines, demonstrating that the treated surfaces were not posing any threat to immune cells. The findings indicate that the synergistic surface treatment can be a viable means to enhance corrosion resistance and immune response of Mg alloys implants.

Compressively Stressed Silicon Nanoclusters as an Antifracture Mechanism for High-Performance Lithium-Ion Battery Anodes.

Silicon has been considered a good candidate for replacing the commonly used carbon anodes for lithium-ion batteries (LIBs) due to its high specific capacity, which can be up to 11 times higher than that of carbon. However, the desirable advantage that silicon brings to battery performance is currently overshadowed by its stress-induced performance loss and high electronic resistivity. The induced stress arises from two sources, namely, the deposition process (i.e., residual stress) during fabrication and the volume expansion (i.e., mechanical stress) associated with the lithiation/delithiation process. Of the two, residual stress has largely been ignored, underestimated, or considered to have a negligible effect without any rigorous evidence being put forward. In this contribution, we produced silicon thin films having a wide range of residual stress and resistivity using a physical vapor deposition technique, magnetron sputtering. Three pairs of silicon thin-film anodes were utilized to study the effect of residual stress on the electrochemical and cyclability performance as anodes for LIBs. Each set consisted of a pair of films having essentially the same resistivity, density, thickness, and oxidation amount but distinctly different residual stresses. The comparison was evaluated by conducting charge/discharge cycling and cyclic voltammetry (CV) experiments. In contrast to the fixed belief within the literature, higher compressive residual-stress films showed better electrochemical and cycle performance compared to lower residual-stress films. The results, herein, present an informed understanding of the role that residual stress plays, which will help researchers improve the development of silicon-based thin-film anodes.

Distal Sensory Peripheral Neuropathy in Human Immunodeficiency Virus Type 1-Positive Individuals Before and After Antiretroviral Therapy Initiation in Diverse Resource-Limited Settings.

BACKGROUND: Distal sensory peripheral neuropathy (DSPN) is a complication of human immunodeficiency virus (HIV). We estimate DSPN prevalence in 7 resource-limited settings (RLSs) for combination antiretroviral therapy (cART)-naive people living with HIV (PLWH) compared with matched participants not living with HIV and in PLWH virally suppressed on 1 of 3 cART regimens. METHODS: PLWH with a CD4+ count <300 cells/mm3 underwent standardized neurological examination and functional status assessments before and every 24 weeks after starting cART. Matched individuals not living with HIV underwent the same examinations once.Associations between covariates with DSPN at entry were assessed using the χ2 test, and virally suppressed PLWH were assessed using generalized estimating equations. RESULTS: Before initiating cART, 21.3% of PLWH had DSPN compared with 8.5% of people not living with HIV (n = 2400; χ2(df = 1) = 96.5; P < .00001). PLWH with DSPN were more likely to report inability to work [χ2(df = 1) = 10.6; P = .001] and depression [χ2(df = 1) = 8.9; P = .003] than PLWH without DSPN. Overall prevalence of DSPN among those virally suppressed on cART decreased: 20.3%, week 48; 15.3%, week 144; and 10.3%, week 192. Incident DSPN was seen in 127 PLWH. Longitudinally, DSPN was more likely in older individuals (P < .001) and PLWH with less education (P = .03). There was no significant association between cART regimen and DSPN. CONCLUSIONS: Although the prevalence of DSPN decreased following cART initiation in PLWH, further research could identify strategies to prevent or ameliorate residual DSPN after initiating cART in RLSs.

Handheld probe for quantitative micro-elastography.

Optical coherence elastography (OCE) has been proposed for a range of clinical applications. However, the majority of these studies have been performed using bulky, lab-based imaging systems. A compact, handheld imaging probe would accelerate clinical translation, however, to date, this had been inhibited by the slow scan rates of compact devices and the motion artifact induced by the user's hand. In this paper, we present a proof-of-concept, handheld quantitative micro-elastography (QME) probe capable of scanning a 6 × 6 × 1 mm volume of tissue in 3.4 seconds. This handheld probe is enabled by a novel QME acquisition protocol that incorporates a custom bidirectional scan pattern driving a microelectromechanical system (MEMS) scanner, synchronized with the sample deformation induced by an annular PZT actuator. The custom scan pattern reduces the total acquisition time and the time difference between B-scans used to generate displacement maps, minimizing the impact of motion artifact. We test the feasibility of the handheld QME probe on a tissue-mimicking silicone phantom, demonstrating comparable image quality to a bench-mounted setup. In addition, we present the first handheld QME scans performed on human breast tissue specimens. For each specimen, quantitative micro-elastograms are co-registered with, and validated by, histology, demonstrating the ability to distinguish stiff cancerous tissue from surrounding soft benign tissue.

Reelin is modulated by diet-induced obesity and has direct actions on arcuate proopiomelanocortin neurons.

OBJECTIVE: Reelin (RELN) is a large glycoprotein involved in synapse maturation and neuronal organization throughout development. Deficits in RELN signaling contribute to multiple psychological disorders, such as autism spectrum disorder, schizophrenia, and bipolar disorder. Nutritional stress alters RELN expression in brain regions associated with these disorders; however, the involvement of RELN in the neural circuits involved in energy metabolism is unknown. The RELN receptors apolipoprotein E receptor 2 (ApoER2) and very low-density lipoprotein receptor (VLDLR) are involved in lipid metabolism and expressed in the hypothalamus. Here we explored the involvement of RELN in hypothalamic signaling and the impact of diet-induced obesity (DIO) on this system. METHODS: Adult male mice were fed a chow diet or maintained on a high-fat diet (HFD) for 12-16 weeks. HFD-fed DIO mice exhibited decreased ApoER2 and VLDLR expression and increased RELN protein in the hypothalamus. Electrophysiology was used to determine the mechanism by which the central fragment of RELN (CF-RELN) acts on arcuate nucleus (ARH) satiety-promoting proopiomelanocortin (POMC) neurons and the impact of DIO on this circuitry. RESULTS: CF-RELN exhibited heterogeneous presynaptic actions on inhibitory inputs onto ARH-POMC-EGFP neurons and consistent postsynaptic actions. Additionally, central administration of CF-RELN caused a significant increase in ARH c-Fos expression and an acute decrease in food intake and body weight. CONCLUSIONS: We conclude that RELN signaling is modulated by diet, that RELN is involved in synaptic signaling onto ARH-POMC neurons, and that altering central CF-RELN levels can impact food intake and body weight.

Human Immunodeficiency Virus Type 1 and Tuberculosis Coinfection in Multinational, Resource-limited Settings: Increased Neurological Dysfunction.

BACKGROUND: AIDS Clinical Trial Group 5199 compared neurological and neuropsychological test performance of human immunodeficiency virus type 1 (HIV-1)-infected participants in resource-limited settings treated with 3 World Health Organization-recommended antiretroviral (ART) regimens. We investigated the impact of tuberculosis (TB) on neurological and neuropsychological outcomes. METHODS: Standardized neurological and neuropsychological examinations were administered every 24 weeks. Generalized estimating equation models assessed the association between TB and neurological/neuropsychological performance. RESULTS: Characteristics of the 860 participants at baseline were as follows: 53% female, 49% African; median age, 34 years; CD4 count, 173 cells/µL; and plasma HIV-1 RNA, 5.0 log copies/mL. At baseline, there were 36 cases of pulmonary, 9 cases of extrapulmonary, and 1 case of central nervous system (CNS) TB. Over the 192 weeks of follow-up, there were 55 observations of pulmonary TB in 52 persons, 26 observations of extrapulmonary TB in 25 persons, and 3 observations of CNS TB in 2 persons. Prevalence of TB decreased with ART initiation and follow-up. Those with TB coinfection had significantly poorer performance on grooved pegboard (P < .001) and fingertapping nondominant hand (P < .01). TB was associated with diffuse CNS disease (P < .05). Furthermore, those with TB had 9.27 times (P < .001) higher odds of reporting decreased quality of life, and had 8.02 times (P = .0005) higher odds of loss of productivity. CONCLUSIONS: TB coinfection was associated with poorer neuropsychological functioning, particularly the fine motor skills, and had a substantial impact on functional ability and quality of life. CLINICAL TRIALS REGISTRATION: NCT00096824.

Human Immunodeficiency Virus-associated Neurocognitive Impairment in Diverse Resource-limited Settings.

BACKGROUND: Neurocognitive impairment remains a common complication of human immunodeficiency virus (HIV) despite effective antiretroviral therapy (ART). We previously reported improved neurocognitive functioning with ART initiation in 7 resource-limited countries for HIV+ participants from the AIDS Clinical Trials Group (ACTG) 5199 International Neurological Study (INS). Here, we apply normative data from the International Neurocognitive Normative Study (INNS) to INS to provide previously unknown rates of neurocognitive impairment. METHODS: The A5199 INS assessed neurocognitive and neurological performance within a randomized clinical trial with 3 arms containing World Health Organization first-line recommended ART regimens (ACTG 5175; PEARLS). The ACTG 5271 INNS collected normative comparison data on 2400 high-risk HIV-negative participants from 10 voluntary counseling and testing sites aligned with INS. Normative comparison data were used to create impairment ratings for HIV+ participants in INS; associations were estimated using generalized estimating equations. RESULTS: Among 860 HIV+ adults enrolled in ACTG 5199, 55% had no neurocognitive impairment at baseline. Mild neurocognitive impairment was found in 25%, moderate in 17%, and severe in 3% of participants. With the initiation of ART, the estimated odds of impairment were reduced 12% (95% confidence interval, 9%, 14%) for every 24 weeks (P < .0001) on ART. Mild impairment dropped slightly and then remained at about 18% out to week 168. CONCLUSIONS: Almost half of HIV+ participants had neurocognitive impairment at baseline before ART, based on local norms. With ART initiation, there were significant overall reductions in neurocognitive impairment over time, especially in those with moderate and severe impairments. CLINICAL TRIALS REGISTRATION: NCT00096824.

Reagent-free LC-MS/MS-based pharmacokinetic quantification of polyhistidine-tagged therapeutic proteins.

AIM: Immobilized metal ion affinity chromatography is widely employed for purifying polyhistidine-tagged recombinant proteins from cell lysates. The technique can be applied for quantification of therapeutic proteins in biological matrices by LC-MS/MS. RESULTS: A protein reagent-free workflow was developed for quantifying polyhistidine-tagged proteins by LC-MS/MS. The workflow includes target protein enrichment by immobilized metal ion affinity chromatography, on-bead trypsin digestion and quantification of signature peptides by LC-MS/MS. It was applied to quantify a 6×His-tagged protein in a mouse pharmacokinetic study with assay sensitivity of 10.0 ng/ml and linearity up to 10,000 ng/ml. CONCLUSION: The protein reagent-free workflow developed herein can overcome reagent limitation and serve as a viable approach for quantifying polyhistidine-tagged therapeutic proteins to support discovery pharmacokinetic and pharmacodynamic studies.

Decoupling the effects of confinement and passivation on semiconductor quantum dots.

Semiconductor (SC) quantum dots (QDs) have recently been fabricated by both chemical and plasma techniques for specific absorption and emission of light. Their optical properties are governed by the size of the QD and the chemistry of any passivation at their surface. Here, we decouple the effects of confinement and passivation by utilising DC magnetron sputtering to fabricate SC QDs in a perfluorinated polyether oil. Very high band gaps are observed for fluorinated QDs with increasing levels of quantum confinement (from 4.2 to 4.6 eV for Si, and 2.5 to 3 eV for Ge), with a shift down to 3.4 eV for Si when oxygen is introduced to the passivation layer. In contrast, the fluorinated Si QDs display a constant UV photoluminescence (3.8 eV) irrespective of size. This ability to tune the size and passivation independently opens a new opportunity to extending the use of simple semiconductor QDs.

Cleaning Dirty Surfaces: A Three-Body Problem.

Human interaction with touch screens requires physical touch and hence results in contamination of these surfaces, resulting in the necessity of cleaning. In this study we discuss the three bodies of this problem and how each component contributes and can be controlled. Utilizing a standard fingerprint machine and a standard cleanability test, this study examines the influence of parameters such as the wiping speed and pressure, the material and surface area of the cloths, and the surface energy of the contaminated surfaces. It was shown that fingerprint contamination undergoes shear banding and hence is not easily removed. The degree of material removal depends on the position of the shear plane, which is influenced by surface energies and shear rates.

Unusual Nature of Fingerprints and the Implications for Easy-to-Clean Coatings.

Irrespective of the technology, we now rely on touch to interact with devices such as smart phones, tablet computers, and control panels. As a result, touch screen technologies are frequently in contact with body grease. Hence, surface deposition arises from localized inhomogeneous finger-derived contaminants adhering to a surface, impairing the visual/optical experience of the user. In this study, we examined the contamination itself in order to understand its static and dynamic behavior with respect to deposition and cleaning. A process for standardized deposition of fingerprints was developed. Artificial sebum was used in this process to enable reproducibility for quantitative analysis. Fingerprint contamination was shown to be hygroscopic and to possess temperature- and shear-dependent properties. These results have implications for the design of easily cleanable surfaces.

Surface treatments for controlling corrosion rate of biodegradable Mg and Mg-based alloy implants.

Due to their excellent biodegradability characteristics, Mg and Mg-based alloys have become an emerging material in biomedical implants, notably for repair of bone as well as coronary arterial stents. However, the main problem with Mg-based alloys is their rapid corrosion in aggressive environments such as human bodily fluids. Previously, many approaches such as control of alloying materials, composition and surface treatments, have been attempted to regulate the corrosion rate. This article presents a comprehensive review of recent research focusing on surface treatment techniques utilised to control the corrosion rate and surface integrity of Mg-based alloys in both in vitro and in vivo environments. Surface treatments generally involve the controlled deposition of thin film coatings using various coating processes, and mechanical surfacing such as machining, deep rolling or low plasticity burnishing. The aim is to either make a protective thin layer of a material or to change the micro-structure and mechanical properties at the surface and sub-surface levels, which will prevent rapid corrosion and thus delay the degradation of the alloys. We have organised the review of past works on coatings by categorising the coatings into two classes-conversion and deposition coatings-while works on mechanical treatments are reviewed based on the tool-based processes which affect the sub-surface microstructure and mechanical properties of the material. Various types of coatings and their processing techniques under two classes of coating and mechanical treatment approaches have been analysed and discussed to investigate their impact on the corrosion performance, biomechanical integrity, biocompatibility and cell viability. Potential challenges and future directions in designing and developing the improved biodegradable Mg/Mg-based alloy implants were addressed and discussed. The literature reveals that no solutions are yet complete and hence new and innovative approaches are required to leverage the benefit of Mg-based alloys. Hybrid treatments combining innovative biomimetic coating and mechanical processing would be regarded as a potentially promising way to tackle the corrosion problem. Synergetic cutting-burnishing integrated with cryogenic cooling may be another encouraging approach in this regard. More studies focusing on rigorous testing, evaluation and characterisation are needed to assess the efficacy of the methods.

Three-dimensional profilometric assessment of early enamel erosion simulating gastric regurgitation.

OBJECTIVES: A priority research area in minimal intervention dentistry is the characterization of the early stages of dental erosion. The aim of this in vitro study was to assess the effect of short, repetitive erosive challenges to human enamel over 2 min at pH 1.5 and 3.0 under conditions simulating gastric regurgitation. METHODS: Enamel surfaces were subjected to erosive challenges at pH 1.5 (Group 1, n=10) and pH 3.0 (Group 2, n=9) for periods of 30s (stage 1), 60s (stage 2) and 120 s (stage 3). Quantitative changes were assessed longitudinally by measuring the 3D average surface roughness (Sa) values using 3D confocal microscopy. Qualitative micrographic assessment of surface changes was also conducted by using environmental scanning electron microscopy. RESULTS: Linear mixed model analysis showed significant effects of the pH values (p<0.001) and the stages (p<0.001) on the observed Sa values. Post hoc tests showed significant increases in the Sa values between baseline and other stages in both groups (p<0.01). The mean Sa values also increased significantly from stage 1 to stage 2 in Group 1 (p<0.05). Micrographic analysis displayed severely etched enamel rods in Group 1, but only subtle changes in Group 2. CONCLUSIONS: The complexity of the enamel surface is influenced by both acid concentration (pH value) and duration of acid exposure during early stages of erosion. Erosion occurring under conditions simulating GORD can be detected in its initial stages, opening up the possibilities of early diagnosis and management of this condition. CLINICAL SIGNIFICANCE: Erosive tooth wear occurs progressively and insidiously, often creating complex treatment challenges. This emphasizes the need for early diagnosis and management in accordance with minimal intervention philosophy. Our findings provide a foundation for further research that could lead to the development of highly-sensitive clinical diagnostic tools and preventive strategies.

A solid-state nuclear magnetic resonance study of post-plasma reactions in organosilicone microwave plasma-enhanced chemical vapor deposition (PECVD) coatings.

Plasma-polymerized organosilicone coatings can be used to impart abrasion resistance and barrier properties to plastic substrates such as polycarbonate. Coating rates suitable for industrial-scale deposition, up to 100 nm/s, can be achieved through the use of microwave plasma-enhanced chemical vapor deposition (PECVD), with optimal process vapors such as tetramethyldisiloxane (TMDSO) and oxygen. However, it has been found that under certain deposition conditions, such coatings are subject to post-plasma changes; crazing or cracking can occur anytime from days to months after deposition. To understand the cause of the crazing and its dependence on processing plasma parameters, the effects of post-plasma reactions on the chemical bonding structure of coatings deposited with varying TMDSO-to-O2 ratios was studied with (29)Si and (13)C solid-state magic angle spinning nuclear magnetic resonance (MAS NMR) using both single-pulse and cross-polarization techniques. The coatings showed complex chemical compositions significantly altered from the parent monomer. (29)Si MAS NMR spectra revealed four main groups of resonance lines, which correspond to four siloxane moieties (i.e., mono (M), di (D), tri (T), and quaternary (Q)) and how they are bound to oxygen. Quantitative measurements showed that the ratio of TMDSO to oxygen could shift the chemical structure of the coating from 39% to 55% in Q-type bonds and from 28% to 16% for D-type bonds. Post-plasma reactions were found to produce changes in relative intensities of (29)Si resonance lines. The NMR data were complemented by Fourier transform infrared (FTIR) spectroscopy. Together, these techniques have shown that the bonding environment of Si is drastically altered by varying the TMDSO-to-O2 ratio during PECVD, and that post-plasma reactions increase the cross-link density of the silicon-oxygen network. It appears that Si-H and Si-OH chemical groups are the most susceptible to post-plasma reactions. Coatings produced at a low TMDSO-to-oxygen ratio had little to no singly substituted moieties, displayed a highly cross-linked structure, and showed less post-plasma reactions. However, these chemically more stable coatings are less compatible mechanically with plastic substrates, because of their high stiffness.

Placental transfer of a fully human IgG2 monoclonal antibody in the cynomolgus monkey, rat, and rabbit: a comparative assessment from during organogenesis to late gestation.

Understanding species differences in the placental transfer of monoclonal antibodies is important to inform species selection for nonclinical safety assessment, interpret embryo-fetal changes observed in these studies, and extrapolate their human relevance. Data presented here for a fully human immunoglobulin G2 monoclonal antibody (IgG2X) revealed that, during organogenesis, in both the cynomolgus monkey (gestation day 35 [gd35]) and the rat (gd10) the extent of IgG2X placental transfer (approximately 0.5% maternal plasma concentration, MPC) was similar to the limited published human data for endogenous IgG. At this early gestational stage, IgG2X placental transfer was approximately 6-fold higher in the rabbit (gd10). By the end of organogenesis, rat embryonic plasma concentrations (gd16) exceeded those in the cynomolgus monkey (gd50) by approximately 3-fold. These data suggest that relative to the cynomolgus monkey, the rabbit (and to a lesser extent the rat) may overestimate potential harmful effects to the human embryo during this critical period of development. Beyond organogenesis, fetal IgG2X plasma concentrations increased approximately 10-fold early in the second trimester (gd50-70) in the cynomolgus monkey and remained relatively unchanged thereafter (at approximately 5% MPC). Late gestational assessment was precluded in rabbits due to immunogenicity, but in rats, fetal IgG2X plasma concentrations increased more than 6-fold from gd16 to gd21 (reaching approximately 15% MPC). In rats, maternal exposure consistent with that achieved by ICH S6(R1) high-dose selection criteria resulted in embryonic plasma concentrations, reaching pharmacologically relevant levels during organogenesis. Furthermore, dose proportional exposure in both mothers and embryos indicated that this was unlikely to occur at the lower therapeutic dose levels used in humans.