Elucidating the Changes in Molecular Structure at the Buried Interface of RTV Silicone Elastomers during Curing.

Silicone elastomers are widely used in many industrial applications, including coatings, adhesives, and sealants. Room-temperature vulcanized (RTV) silicone, a major subcategory of silicone elastomers, undergoes molecular structural transformations during condensation curing, which affect their mechanical, thermal, and chemical properties. The role of reactive hydroxyl (-OH) groups in the curing reaction of RTV silicone is crucial but not well understood, particularly when multiple sources of hydroxyl groups are present in a formulated product. This work aims to elucidate the interfacial molecular structural changes and origins of interfacial reactive hydroxyl groups in RTV silicone during curing, focusing on the methoxy groups at interfaces and their relationship to adhesion. Sum frequency generation (SFG) vibrational spectroscopy is an in situ nondestructive technique used in this study to investigate the interfacial molecular structure of select RTV formulations at the buried interface at different levels of cure. The primary sources of hydroxyl groups required for interfacial reactions in the initial curing stage are found to be those on the substrate surface rather than those from the ingress of ambient moisture. The silylation treatment of silica substrates eliminates interfacial hydroxyl groups, which greatly impact the silicone interfacial behavior and properties (e.g., adhesion). This study establishes the correlation between interfacial molecular structural changes in RTV silicones and their effect on adhesion strength. It also highlights the power of SFG spectroscopy as a unique tool for studying chemical and structural changes at RTV silicone/substrate interface in situ and in real time during curing. This work provides valuable insights into the interfacial chemistry of RTV silicone and its implications for material performance and application development, aiding in the development of improved silicone adhesives.

Molecular behavior of silicone adhesive at buried polymer interface studied by molecular dynamics simulation and sum frequency generation vibrational spectroscopy.

Silicones have excellent material properties and are used extensively in many applications, ranging from adhesives and lubricants to electrical insulation. To ensure strong adhesion of silicone adhesives to a wide variety of substrates, silane-based adhesion promotors are typically blended into the silicone adhesive formulation. However, little is known at the molecular level about the true silane adhesion promotion mechanism, which limits the ability to develop even more effective adhesion promoters. To understand the adhesion promotion mechanism of silane molecules at the molecular level, this study has used sum frequency generation vibrational spectroscopy (SFG) to determine the behavior of (3-glycidoxypropyl)trimethoxy silane (γ-GPS) at the buried interface between poly(ethylene terephthalate) (PET) and a bulk silicone adhesive. To complement and extend the SFG results, atomistic molecular dynamics (MD) simulations were applied to investigate molecular behavior and interfacial interaction of γ-GPS at the silicone/PET interface. Free energy computations were used to study the γ-GPS interaction in the sample system and determine the γ-GPS interfacial segregation mechanism. Both experiments and simulations consistently show that γ-GPS molecules prefer to segregate at the interface between PET and PDMS. The methoxy groups on γ-GPS molecules orient toward the PDMS polymer phase. The consistent picture of interfacial structure emerging from both simulation and experiment provides enhanced insight on how γ-GPS behaves in the silicone - PET system and illustrates why γ-GPS could improve the adhesion of silicone adhesive, leading to further understanding of silicone adhesion mechanisms useful in the design of silicone adhesives with improved performance.

Models of Electron Transfer at Different Electrode Materials.

Electron transfer is the most important electrochemical process. In this review, we present elements of various aspects of electron transfer theory from the early work of Marcus and Hush to recent developments. The emphasis is on the role of the electronic, and to a lesser extent the geometrical, properties of the electrode. A variety of experimental works are discussed in light of these theoretical concepts. Because the field of electron transfer is so vast, this review is far from comprehensive; rather, we focus on systems that offer a special interest and illuminate aspects of the theory.

Combined Tumor-Based BRCA1/2 and TP53 Mutation Testing in Ovarian Cancer.

Somatic/germline BRCA1/2 mutations (m)/(likely) pathogenic variants (PV) (s/gBRCAm) remain the best predictive biomarker for PARP inhibitor efficacy. As >95% of high-grade serous ovarian cancers (HGSOC) have a somatic TP53m, combined tumor-based BRCA1/2 (tBRCA) and TP53 mutation testing (tBRCA/TP53m) may improve the quality of results in somatic BRCAm identification and interpretation of the 'second hit' event, i.e., loss of heterozygosity (LOH). A total of 237 patients with HGSOC underwent tBRCA/TP53m testing. The ratio of allelic fractions (AFs) for tBRCA/TP53m was calculated to estimate the proportion of cells carrying BRCAm and to infer LOH. Among the 142/237 gBRCA results, 16.2% demonstrated a pathogenic/deleterious variant (DEL) gBRCA1/2m. Among the 195 contributive tumor samples, 43 DEL of tBRCAm (22.1%) were identified (23 gBRCAm and 20 sBRCAm) with LOH identified in 37/41 conclusive samples. The median AF of TP53m was 0.52 (0.01-0.93), confirming huge variability in tumor cellularity. Initially, three samples were considered as wild type with <10% cellularity. However, additional testing detected a very low AF (<0.05) in both BRCA1/2m and TP53m, thus reidentifying them as sBRCA1/2m. Combined tBRCA/TP53m testing is rapid, sensitive, and identifies somatic and germline BRCA1/2m. AF TP53m is essential for interpreting sBRCA1/2m in low-cellularity samples and provides indirect evidence for LOH as the 'second hit' of BRCA1/2-related tumorigenesis.

Microalgae-based domestic wastewater treatment: a review of biological aspects, bioremediation potential, and biomass production with biotechnological high-value.

This review aims to perform an updated bibliographical survey on the cultivation of microalgae in domestic wastewater with a focus on biotechnological aspects. It was verified that the largest number of researches developed was about cultures in microalgae-bacteria consortium and mixed cultures of microalgae, followed by researches referring to the species Chlorella vulgaris and to the family Scenedesmaceae. According to published studies, these microorganisms are efficient in the biological treatment of domestic wastewater, as well as in the production of high value-added biomass, as they are capable of biosorbing the organic and inorganic compounds present in the culture medium, thus generating cells with high levels of lipids, proteins, and carbohydrates. These compounds are of great importance for different industry sectors, such as pharmaceuticals, food, and also for agriculture and aquaculture. In addition, biomolecules produced by microalgae can be extracted for several biotechnological applications; however, most studies focus on the production of biofuels, with biodiesel being the main one. There are also other emerging applications that still require more in-depth research, such as the use of biomass as a biofertilizer and biostimulant in the production of bioplastic. Therefore, it is concluded that the cultivation of microalgae in domestic wastewater is a sustainable way to promote effluent bioremediation and produce valuable biomass for the biobased industry, contributing to the development of technology for the green economy.

Probing Covalent Interactions at a Silicone Adhesive/Nylon Interface.

Covalent bonding is one of the most robust forms of intramolecular interaction between adhesives and substrates. In contrast to most noncovalent interactions, covalent bonds can significantly enhance both the interfacial strength and durability. To utilize the advantages of covalent bonding, specific chemical reactions are designed to occur at interfaces. However, interfacial reactions are difficult to probe in situ, particularly at the buried interfaces found in well-bonded adhesive joints. In this work, sum frequency generational (SFG) vibrational spectroscopy was used to directly examine and analyze the interfacial chemical reactions and related molecular changes at buried nylon/silicone elastomer interfaces. For self-priming elastomeric silicone adhesives, silane coupling agents have been extensively used as adhesion promoters. Here with SFG, the interfacial chemical reactions between nylon and two alkoxysilane adhesion promoters with varied functionalities (maleic anhydride (MAH) and epoxy) formulated into the silicone were observed and investigated. Evidence of reactions between the organofunctional group of each silane and reactive groups on the polyamide was found at the buried interface between the cured silicone elastomer and nylon. The adhesion strength at the nylon/cured silicone interfaces was substantially enhanced with both silane additives. SFG results elucidated the mechanisms of organo-silane adhesion promotion for silicone at the molecular level. The ability to probe and analyze detailed interfacial reactions at buried nylon/silicone interfaces demonstrated that SFG is a powerful analytical technique to aid the design and optimization of materials with desired interfacial properties.

In silico and in vitro structure-stability-function relationship of analog peptides of Stigmurin and its antibacterial and antibiofilm activities.

Multidrug-resistant bacterial infections are a threat to public health worldwide, which boosts the urgent need for pharmacological research for new drugs. Although the peptides without disulfide bridges from scorpions have shown antimicrobial action, usually their toxicity hamper their pharmacological application. Stigmurin is a non-hemolytic cationic peptide from Tityus stigmurus venom with antibacterial effect and toxicity on normal cells. In this approach, the conformational changes and stability of two Stigmurin analog peptides, named StigA8 and StigA18, were evaluated by circular dichroism, as well as the mechanism of interaction with bacterial membranes in silico. In addition, the in vitro and in vivo antibacterial activity and the action against the biofilm formed by multidrug-resistant Staphylococcus aureus were investigated. StigA8 (+4) and StigA18 (+5) revealed the ability to change their structural conformation depending on the medium composition, and high stability at different temperatures and pH conditions. Both analog peptides showed greater ability to interact with bacterial membranes in silico when compared to the native one. StigA8 and StigA18 demonstrated low hemolytic action, with non-toxic effect on G. mellonella larvae up to 120 mg/kg. StigA8 and StigA18 presented a broad spectrum of antibacterial action in vitro, especially against multidrug-resistant clinical isolates. The analog peptides (7.5 µM) also reduced the biofilm biomass of multidrug-resistant S. aureus, as well as increased the larval survival of the Galleria mellonella infected larvae. Therefore, StigA8 and StigA18 showed a beneficial potential in the treatment of bacterial infections, constituting promising bioactive components for the development of new antimicrobial agents.

MedMinas project: design and use of mixed methods in the evaluation of pharmaceutical services in primary health care in Minas Gerais, Brazil.

BACKGROUND: The main purposes of primary care-based pharmaceutical services (PHCPS) in Brazil are to provide free access to medicines and pharmaceutical care to patients. Several obstacles hinder achieving their goals; thus, MedMinas Project aimed to evaluate the PHCPS, the supply system, and the use of medicines. This paper reflects on our experience designing, planning, and conducting the project, describing the issues yielded in the field and lessons learned. METHODS: This work consists of a mixed-methods study conducted in Minas Gerais, Southeastern Brazil. We adopted the principles of Rapid Evaluation Methods, employing a multistage stratified sampling for the quantitative and a purposeful sampling for the qualitative components, respectively, and a documentary research. Data sources included individuals (patients and professionals), prescriptions, dispensed medicines, and policy documents collected between April and October 2019. The quantitative data described in this paper were analysed by descriptive statistics and the qualitative by Thematic Content Analysis. RESULTS: A total of 26 municipalities varying from 37,784 to 409,341 inhabitants were included. The field team spent, on average, 16 days in each location. We interviewed 1019 respondents, of which 127 were professionals and 892 patients. The participation rate varied from 92 to 100%, depending on the respondent subgroup. Most interviews lasted between 45 min and one hour. Fieldwork challenges included participants' enrolment, field team, interview processes, and project budget. The participants provided positive feedback and five main themes emerged from the interview experience (self-awareness, sense of gratitude, research value, access to findings, and benefits of the research). Additionally, we collected copies of 1072 documents and 2070 pieces of data from prescriptions filled and medicines dispensed at the PCP. CONCLUSION: We demonstrated the viability of conducting the MedMinas Project in an extensive geographic area within effective time frames that provided meaningful, high-quality data from multiple actors. The methods and lessons learned are valuable for researchers across various disciplines in similar urban settings in Brazil and other countries of low- and middle-income (LMIC).

Light induces peridinin and docosahexaenoic acid accumulation in the dinoflagellate Durusdinium glynnii.

Peridinin is a light-harvesting carotenoid present in phototrophic dinoflagellates and has great potential for new drug applications and cosmetics development. Herein, the effects of irradiance mediated by light-emitting diodes on growth performance, carotenoid and fatty acid profiles, and antioxidant activity of the endosymbiotic dinoflagellate Durusdinium glynnii were investigated. The results demonstrate that D. glynnii is particularly well adapted to low-light conditions; however, it can be high-light-tolerant. In contrast to other light-harvesting carotenoids, the peridinin accumulation in D. glynnii occurred during high-light exposure. The peridinin to chlorophyll-a ratio varied as a function of irradiance, while the peridinin to total carotenoids ratio remained stable. Under optimal irradiance for growth, there was a peak in docosahexaenoic acid (DHA) bioaccumulation. This study contributes to the understanding of the photoprotective role of peridinin in endosymbiont dinoflagellates and highlights the antioxidant activity of peridinin-rich extracts. KEY POINTS: • Peridinin has a protective role against chlorophyll photo-oxidation • High light conditions induce cellular peridinin accumulation • D. glynnii accumulates high amounts of DHA under optimal light supply.

Design of Large Stokes Shift Fluorescent Proteins Based on Excited State Proton Transfer of an Engineered Photobase.

The incredible potential for fluorescent proteins to revolutionize biology has inspired the development of a variety of design strategies to address an equally broad range of photophysical characteristics, depending on potential applications. Of these, fluorescent proteins that simultaneously exhibit high quantum yield, red-shifted emission, and wide separation between excitation and emission wavelengths (Large Stokes Shift, LSS) are rare. The pursuit of LSS systems has led to the formation of a complex, obtained from the marriage of a rationally engineered protein (human cellular retinol binding protein II, hCRBPII) and different fluorogenic molecules, capable of supporting photobase activity. The large increase in basicity upon photoexcitation leads to protonation of the fluorophore in the excited state, dramatically red-shifting its emission, leading to an LSS protein/fluorophore complex. Essential for selective photobase activity is the intimate involvement of the target protein structure and sequence that enables Excited State Proton Transfer (ESPT). The potential power and usefulness of the strategy was demonstrated in live cell imaging of human cell lines.

Comparison of dose-dense vs. 3-weekly paclitaxel and carboplatin in the first-line treatment of ovarian cancer in a propensity score-matched cohort.

BACKGROUND: Benefit of carboplatin and dose-dense weekly paclitaxel (ddCT) in first line treatment of ovarian cancer patients has been different in Western and Asian studies. In the present study we compare progression-free survival (PFS) of ddCT to three-weekly carboplatin and paclitaxel (CT) in first-line treatment of ovarian carcinoma in a single institution in a Western population. MATERIALS AND METHODS: We conducted a retrospective review of medical records from patients with ovarian carcinoma treated in a tertiary cancer center from 2007 to 2018. All patients treated with ddCT or CT in the first-line setting were included. Patients who received first-line bevacizumab were not included. PFS and overall survival (OS) were compared in a propensity score-matched cohort to address selection bias. Patients were matched according to age, ECOG performance status, CA 125, FIGO stage, residual disease, and histological subtype, in a 1:2 ratio. RESULTS: Five hundred eighty-eight patients were eligible for propensity score matching, the final cohort consisted of 69 patients treated with ddCT and 138 CT group. Baseline characteristics were well-balanced. After a median follow-up of 65.1 months, median PFS was 29.3 vs 20.0 months, favouring ddCT treatment (p = 0.035). In the multivariate cox regression ddCT showed a 18% lower risk of progression (HR 0.82, 95% CI 0.68-0.99, p = 0.04). Overall survival data is immature, but suggested better outcomes for ddCT (not reached versus 78.8 months; p = 0.07). CONCLUSION: Our retrospective study has shown superior PFS of ddCT over CT regimen in first-line treatment of ovarian carcinoma in a Western population not treated with bevacizumab.

Strategies to Promote Social Connections Among Older Adults During "Social Distancing" Restrictions.

Older age and medical comorbidity are factors associated with more severe illness and risk of death due to COVID-19 infection. Social distancing is an important public health strategy for controlling the spread of the virus and minimizing its impact on the older adult population. It comes at a cost, however. Loneliness is associated with myriad adverse health outcomes, one of which is impaired immune functioning, which adds even greater risk for coronavirus infection, complications and death. Older adults, therefore, are at compound risk, making effective management of loneliness and social isolation in our older patients a high priority target for preventive intervention. In this paper, the authors describe a cognitive-behavioral framework for social connectedness, including evidence-informed strategies clinicians can use to help patients develop a "Connections Plan" to stay connected and promote their social, mental, and physical health during "social distancing" restrictions. This set of strategies can be provided during brief (30 minute) telephone sessions and is analogous to creating a "Safety Plan" for suicide risk. The approach is illustrated with three case examples.

Catalysis of hydrogen evolution on Pt(111) by absorbed hydrogen.

The activity of Pt(111) electrodes for the hydrogen evolution reaction (HER) in 0.5M H2SO4 solution is found to increase with continuous potential cycling in the HER potential region. In addition, the basic cyclic voltammograms obtained in 0.5M H2SO4 saturated with N2 after HER show several characteristic changes: the current waves for hydrogen adsorption in the region of0.2 < E < 0.35 V and for sulfate adsorption at 0.35 < E < 0.5 V decrease and the current spike at 0.44 V for the phase transition of the sulfate adlayer gradually disappears. We suggest that these changes are caused by the absorption of a small amount of hydrogen in the subsurface layer and propose a mechanism by which this enhances hydrogen evolution.

The Crucial Role of Local Excess Charges in Dendrite Growth on Lithium Electrodes.

Much theoretical effort has been spent on the causes of dendrite formation in lithium metal batteries, but a decisive factor has been overlooked: Lithium is deposited on an electrode which carries a sizable negative charge, and this charge is not distributed homogeneously on the surface. We show by explicit model calculations that the excess charge accumulates on small protrusions and creates a strong electric field, which attracts the Li+ ions and induces further growth on the tip and finally the formation of dendrites. Even a small tip consisting of a few atoms will carry an excess charge of a tenth of a unit charge or more. In addition, the negative charge on the tips locally reduces the surface tension, which further fosters dendrite growth. The same principles can also explain dendrite formation on other metals with deposition potentials below the potential of zero charge.

Human Cellular Retinol Binding Protein II Forms a Domain-Swapped Trimer Representing a Novel Fold and a New Template for Protein Engineering.

Domain-swapping is a mechanism for evolving new protein structure from extant scaffolds, and has been an efficient protein-engineering strategy for tailoring functional diversity. However, domain swapping can only be exploited if it can be controlled, especially in cases where various folds can coexist. Herein, we describe the structure of a domain-swapped trimer of the iLBP family member hCRBPII, and suggest a mechanism for domain-swapped trimerization. It is further shown that domain-swapped trimerization can be favored by strategic installation of a disulfide bond, thus demonstrating a strategy for fold control. We further show the domain-swapped trimer to be a useful protein design template by installing a high-affinity metal binding site through the introduction of a single mutation, taking advantage of its threefold symmetry. Together, these studies show how nature can promote oligomerization, stabilize a specific oligomer, and generate new function with minimal changes to the protein sequence.

Engineering of a Red Fluorogenic Protein/Merocyanine Complex for Live-Cell Imaging.

A reengineered human cellular retinol binding protein II (hCRBPII), a 15-kDa protein belonging to the intracellular lipid binding protein (iLBP) family, generates a highly fluorescent red pigment through the covalent linkage of a merocyanine aldehyde to an active site lysine residue. The complex exhibits "turn-on" fluorescence, due to a weakly fluorescent aldehyde that "lights up" with subsequent formation of a strongly fluorescent merocyanine dye within the binding pocket of the protein. Cellular penetration of merocyanine is rapid, and fluorophore maturation is nearly instantaneous. The hCRBPII/merocyanine complex displays high quantum yield, low cytotoxicity, specificity in labeling organelles, and compatibility in both cancer cell lines and yeast cells. The hCRBPII/merocyanine tag is brighter than most common red fluorescent proteins.

Molecular Insights into Adhesion at a Buried Silica-Filled Silicone/Polyethylene Terephthalate Interface.

Silicone adhesives are widely used in many important applications in aviation, automotive, construction, and electronics industries. The mixture of (3-glycidoxypropyl)trimethoxysilane (γ-GPS) and hydroxy-terminated dimethyl methylvinyl co-siloxanol (DMMVS) has been widely used as an adhesion promoter in silicone elastomers to enhance the adhesion between silicone and other materials including polymers. The interfacial molecular structures of silicone elastomers and the adhesion promotion mechanisms of a γ-GPS-DMMVS mixture in silicone without a filler or an adhesion catalyst (AC) have been extensively investigated using sum frequency generation (SFG) vibrational spectroscopy previously. In this research, SFG was applied to study interfacial structures of silicone elastomeric adhesives in the presence of a silica filler and/or a zirconium(IV) acetylacetonate adhesion catalyst at the silicone/polyethylene terephthalate (PET) interface in situ nondestructively to understand their individual and synergy effects. The interfacial structures obtained from the SFG study were correlated to the adhesion behavior to PET. The interfacial reactions of methoxy and epoxy groups of the adhesion promoter were found to play significant roles in enhancing the interfacial adhesion of the buried interface. This research provides an in-depth molecular-level understanding on the effects of a filler and an adhesion catalyst on the interfacial behavior of the adhesion promotion system for silicone elastomers as well as the related impact on adhesion.

A model for the effect of ion pairing on an outer sphere electron transfer.

Ion pairing can strongly affect the rates of electron transfer reactions. To explain this effect, we propose a model Hamiltonian that describes the interactions between the pairing ion and the reactant, solvent and inner sphere reorganization, and bond breaking. Explicit expressions for the energies of the initial and final states, and for the energy of activation are derived in the weak adiabatic limit. The model is applied to the reduction of Cu(ii) in the presence of chloride ions. For this purpose, the pertinent system parameters are obtained from density functional theory. Our model explains why the chloride ion enhances the rate of the first electron transfer in copper deposition.

Interactions of ions across carbon nanotubes.

The interactions between a pair of Li+ ions across a semiconducting (8,0)CNT and a conducting (5,5)CNT has been investigated by density functional theory. The direct Coulomb interaction between the ions is almost completely screened. The band structure of the CNTs is not affected by the Li+ ions, but the Fermi level is raised to accommodate the extra electrons. Because of the unique band structure of CNTs this results in an effective attraction between the ions, which is greater for the (8,0)CNT. In contrast, a Cl- ion inside a CNT forms a chemical bond which modifies the band structure. Again, the electrostatic field of the ion is almost completely screened outside of the tube. Nevertheless, the adsorption of a Li+ ion outside is favored by a Cl- ion inside. This apparent attraction is mainly caused by a lowering of the work function of the CNT by the presence of the Cl-.

Jowl Reduction With Deoxycholic Acid.

BACKGROUND: The study proposes a novel protocol for targeting the jowls using deoxycholic acid (DCA) injections, with emphasis on safety and feasibility of the procedure. METHODS: This prospective study was conducted at a cosmetic practice between June 2016 and May 2017. Twelve consecutive patients seeking reduction/improvement in mild/moderate jowl fat were injected with DCA subcutaneously in a predefined circular area 1.0 cm above the mandibular border. Treatment response was assessed using physician-evaluated Global Aesthetic Improvement Scale (GAIS) and Subject GAIS. RESULTS: Twelve patients (11 women and 1 man) with mild (n = 8) or moderate (n = 4) jowls were treated. After the first treatment, GAIS responses for 24 jowls showed 5 jowls with vast improvement, 15 with moderate improvement, and 4 with no change. After the second session for 5 jowls in 3 patients, GAIS responses showed vast improvement in 4 jowls and moderate improvement in 1. Adverse events included induration (n = 4), bruising (n = 6), numbness (n = 2), pain (n = 5), redness (n = 3), edema (n = 9), and dysphagia (n = 1). CONCLUSION: Results of this early experience showed that DCA injections were safe and effective for nonsurgical jowl reduction.