Total Elimination Research Articles

Trimanual vitrectomy versus bimanual vitrectomy in tractional proliferative diabetic retinopathy

ABSTRACT Objective To evaluate the impact as well as safety of trimanual vitrectomy versus bimanual vitrectomy in cases with complicated proliferative diabetic retinopathy (PDR) necessitating surgical intervention. Methods We designed a randomized, interventional, prospective study on 40 pseudophakic eyes suffering from tractional retinal detachment (TRD). 20 eyes of 16 cases with trimanual 23-gauge Parsplana vitrectomy (PPV) were categorized as Group A ”trimanual group.” Twenty eyes of 18 cases with bimanual 23-gauge PPV were categorized as Group B” bimanual group” in the duration between May 2021 and December 2022. All cases were under continual observation for ≥ 6 months postoperatively. Results A total of 40 eyes out of 34 cases with the mean age of cases 50.5 years (ranged between 29–69 y) in group A and 47.9 (ranged between 33–60 y) old in group B were assessed. Retinal attachment, total elimination of the pre-retinal proliferation attained in all cases of the two groups. Surgical time was statistically significant shorter in the trimanual group compared to bimanual group (p value < 0.05). Both groups gained statistically significant better vision. The mean pre-operative VA (Visual acuity) in group A was 1.75 (Log MAR) and 1.59 in group B, whereas the mean final visual outcome 6 months following operation was 0.73 in the 1st group & 0.82 in the 2nd one (p value < 0.001*). Conclusion Trimanual PPV is a safe as well as efficient approach that may ameliorate the result of vitrectomy in tractional PDR.

Porphyrin-BODIPY Dyad: Enhancing Photodynamic Inactivation via Antenna Effect.

A porphyrin-BODIPY dyad (P-BDP) was obtained through covalent bonding, featuring a two-segment design comprising a light-harvesting antenna system connected to an energy acceptor unit. The absorption spectrum of P-BDP resulted from an overlap of the individual spectra of its constituent parts, with the fluorescence emission of the BODIPY unit experiencing significant quenching (96 %) due to the presence of the porphyrin unit. Spectroscopic, computational, and redox investigations revealed a competition between photoinduced energy and electron transfer processes. The dyad demonstrated the capability to sensitize both singlet molecular oxygen and superoxide radical anions. Additionally, P-BDP effectively induced the photooxidation of L-tryptophan. In suspensions of Staphylococcus aureus cells, the dyad led to a reduction of over 3.5 log (99.99 %) in cell survival following 30 min of irradiation with green light. Photodynamic inactivation caused by P-BDP was also extended to the individual bacterium level, focusing on bacterial cells adhered to a surface. This dyad successfully achieved the total elimination of the bacteria upon 20 min of irradiation. Therefore, P-BDP presents an interesting photosensitizing structure that takes advantage of the light-harvesting antenna properties of the BODIPY unit combined with porphyrin, offering potential to enhance photoinactivation of bacteria.

Biochar accelerated Fenton process for roxarsone oxidation, inorganic arsenic adsorption and simultaneous immobilization of arsenic-iron sludge

Complete remediation of organoarsenics from environmental matrix hits the bottleneck, that is, the sluggish efficiency of oxidative degradation towards organoarsenics and unsatisfying immobilization performance towards generated inorganic arsenic. Herein, we establish a biochar accelerated Fenton (BA-Fenton) process to decontaminate water from roxarsone (ROX). In comparison with Fe2+/H2O2 process (10 μΜ/0.2 mM), the incorporation of 0.5 g L-1 biochar promoted ROX degradation from 48.2% to 98.2% and total arsenic elimination from 67.6% to 97.3%, respectively. In BA-Fenton process, •OH as the dominant reactive oxygen species (ROS), exhibited a cumulative concentration of 0.42 mM, three times higher than that in classical Fenton process. Crucially, the presence of biochar in Fenton process significantly enhanced the stability of arsenic-iron sludge, whereas the secondary leaching of total arsenic decreased from 433.8 μg-As L-1 to 13.9 μg-As L-1, meeting the prescribed environmental quality standards for surface water in China (50 μg-As L-1, GB 3838-2002). Mechanistic studies unveiled ROX remediation mechanism by BA-Fenton process, highlighting the dual functionality of biochar. On one hand, biochar efficiently reduced Fe3+ to Fe2+ with a rate constant of 0.225 min-1, overcoming the rate-determining step of classical Fenton process for •OH production, consequently promoting the transformation of ROX to As(V). On the other hand, molecular spectroscopy analysis elucidated that in-situ formed As(V) was adsorbed by ferric hydroxides with the formation of arsenic-iron sludge. Subsequently, biochar immobilized arsenic-iron sludge through hydrogen bonds, electrostatic attraction and surface complexation. Furthermore, real water studies demonstrated the effective remediation of organoarsenics by BA-Fenton process in tap water, lake water and chicken manure leachate. This “Two Birds with One Stone” strategy with low-cost, environmental-friendly and sustainable biochar holds great promise for the ultimate disposal of industrial wastewater containing organoarsenics.

Abstract 1631: A homogeneous assay system for discernment of proliferative, antiproliferative, and cytotoxic effects in culture

Abstract We describe a novel homogeneous cell-based assay developed for the quantitative detection of Ki-67 protein, a recognized marker of cell proliferation, utilizing Lumit™ immunoassay technology. This luminescent assay has been effectively multiplexed with a fluorescent measure of cell death, employing a cell-impermeant fluorogenic DNA dye. This multiplex allows for the clear distinction between antiproliferative activity and overt cytotoxicity in cell culture models. Through varying lytic conditions, we demonstrated effective cell lysis and detection of nuclear Ki-67 protein. Specifically, Lumit™ Lysis Buffer II provided efficient recovery of Ki-67 protein without compromising assay performance, including the requisite binding of labeled antibodies to the target protein. This assay exhibited excellent signal-to-background (up to 40-fold) and signal linearity (R^2 = 0.99) in wildtype HeLa cells (~1000 to 80,000/well), while the signal in Ki-67 knockout HeLa cells was comparable to the no-cell background, indicating excellent specificity for Ki-67 protein. Due to the unavailability of recombinant full-length Ki-67 protein, two different recombinant Ki-67 protein fragments were used to corroborate assay sensitivity of &amp;lt;1 pM Ki-67 protein. The assay's suitability for human Ki-67 protein detection, not mouse, was observed through further cell-based testing. The proliferation/cytotoxicity assay multiplex was validated in both suspension and adherent cell lines, as well as primary cell culture, detecting antiproliferative and proliferative responses. CDK4/6 inhibitors are a class of antiproliferative agents of significant interest for their potential in treating cancer. In Jurkat cells, treatment with the CDK4/6 inhibitor palbociclib led to a dose-dependent reduction in Ki-67 protein expression with an EC50 of 88 nM, and total Ki-67 elimination at 2 μM compound concentration. Notably, there was no cytotoxicity detected at the tested doses and treatment duration (up to 48 h), but a significant reduction in viable cell number at maximal palbociclib concentrations, aligning with an antiproliferative mechanism. This work establishes a rapid, simple, luminescent assay for determining Ki-67 levels that can be paired with a fluorogenic readout of cell death, facilitating efficient and quantitative discernment of altered proliferation in mammalian cell culture using standard microplate readers. Citation Format: Dan F. Lazar, Kevin R. Kupcho, Andrew L. Niles, James J. Cali. A homogeneous assay system for discernment of proliferative, antiproliferative, and cytotoxic effects in culture [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1631.

Efficient H2O2 -sonochemical treatment of Penicillin G in water: Optimization, DI-HRMS ultra-trace by-products analysis, and degradation pathways

Due to widespread usage of antibiotics, the possibility of surface and groundwater contamination with such pollutants has significantly increased over the years as such antibiotics have been widely reported in water bodies. This study reports on the elimination of toxic antibiotic Penicillin G (PG) from wastewaters sources via the sonochemical process in the presence of hydrogen peroxide (H2O2) as well as to identify the degradation by-products. The effect of initial pH, pollutant dosage and presence of hydrogen peroxide on the degradability was examined. Response Surface Methodology (RSM) was used to model the sonochemical process with high correlation of (R2= 0.9784) and predictions agreed well with the experimental results. Box-Behnken Design (BBD) and RSM equations were used to determine the optimal values of experimental conditions for the PG degradation at the optimum conditions: PG dose of 20 mgL−1, pH 3.4 and hydrogen peroxide (H2O2) concentration of 600 mgL−1. Under the optimized conditions, removal efficiency reached 97% and by-products formed during sonochemical degradation were identified via QuEChERS method (Quick, Easy, Cheap, Effective, Rugged, and Safe), while the pre-concentration by evaporation was followed by the direct infusion-high resolution mass spectrometry technique (DI-HRMS). This is the first study to report a detailed investigation on PG degradation products under the sonochemical treatment combined with QuEChERS method to DI-HRMS techniques. Such advanced methods allowed us to determine the analyte substance found in water at low concentrations (ng L−1). The seven by-products have been detected where two possible degradation pathways were proposed with a resulting total elimination of PG.

Bioceramic and Resin-Based Sealers Removal Using XP-Endo Finisher: A Scanning Electron Microscopy Study

Abstract Objectives The aim of this study was to evaluate remaining filling materials of a bioceramic sealer (TotalFill BC sealer) and an epoxy resin sealer (AH Plus) after retreatment using a supplementary instrumentation (XP-endo Finisher). Materials and Methods Forty single-rooted teeth were selected for the study. The teeth were instrumented using ProTaper system and randomly divided into two groups (n = 20). Then they were obturated with either TotalFill BC/gutta-percha or AH Plus/gutta-percha using lateral compaction technique. Canals were retreated using ProTaper retreatment files and a solvent. The groups were subdivided (n = 10) according to the application or not of the XP-endo Finisher as a final step of retreatment. All roots were cleaved longitudinally and examined under scanning electron microscope to evaluate root canal filling remnants. A scoring system was utilized to quantify the amount of residual filling material at the three predetermined portions of each root canal.Statistical analysis was performed using IBM SPSS.25 with a significant value p &lt; 0.05. Data were compared using the Mann–Whitney test and Kruskal–Wallis test. Results There was no statistically significant difference in the remaining filling materials for each third of the root canal after initial retreatment procedure between the TotalFill group and AH Plus group. Similar results were observed among the TotalFill groups with or without the application of XP-endo Finisher supplementary step. However, the remaining filling materials of AH Plus in the middle third of root canal were significantly less after the XP-endo Finisher application (p = 0.015). Conclusion No retreatment protocol tested in this study allowed the total elimination of root canal filling materials. The residual root canal filling materials is similar for the bioceramic and resinous sealers. The XP-endo Finisher is not effective in improving the removal of bioceramic root canal filling material while it is able to improve the removal of resinous cement.

Reformulation for stress topology optimization of continuum structures by floating projection

Stress topology optimization of continuum structures is an important topic for structural design and has been widely investigated. However, stress topology optimization itself is ill-conditioned and the resulting optimized designs highly depend on the used parameters, mesh size, and so on. In this paper, stress minimization and stress-constrained topology optimization problems are reformulated by introducing a global measure of an optimized design, the average solid stress. The floating projection topology optimization method is established with ε-relaxation and the p-norm function. Due to the modified problem formulations, the optimized design becomes insensitive to the selection of p in the p-norm function once p is large enough, such as p=16, to ensure the total elimination of stress concentration. Numerical results show the uniform stress distribution of optimized designs, demonstrating the effectiveness of the proposed method. Some findings on the elimination of stress concentration, mesh-independent optimized topology, equivalent smooth design, and impractical design are presented and discussed.

Self-Disassembling and Oxygen-Generating Porphyrin-Lipoprotein Nanoparticle for Targeted Glioblastoma Resection and Enhanced Photodynamic Therapy.

The dismal prognosis for glioblastoma multiform (GBM) patients is primarily attributed to the highly invasive tumor residual that remained after surgical intervention. The development of precise intraoperative imaging and postoperative residual removal techniques will facilitate the gross total elimination of GBM. Here, a self-disassembling porphyrin lipoprotein-coated calcium peroxide nanoparticles (PLCNP) is developed to target GBM via macropinocytosis, allowing for fluorescence-guided surgery of GBM and improving photodynamic treatment (PDT) of GBM residual by alleviating hypoxia. By reducing self-quenching and enhancing lysosome escape efficiency, the incorporation of calcium peroxide (CaO2) cores in PLCNP amplifies the fluorescence intensity of porphyrin-lipid. Furthermore, the CaO2 core has diminished tumor hypoxia and improves the PDT efficacy of PLCNP, enabling low-dose PDT and reversing tumor progression induced by hypoxia aggravation following PDT. Taken together, this self-disassembling and oxygen-generating porphyrin-lipoprotein nanoparticle may serve as a promising all-in-one nanotheranostic platform for guiding precise GBM excision and empowering post-operative PDT, providing a clinically applicable strategy to combat GBM in a safe and effective manner.

Optimisation of an Industrial Optical Sorter of Legumes for Gluten-Free Production Using Hyperspectral Imaging Techniques

The market demand for gluten-free food is increasing due to the growing gluten sensitivity and coeliac disease (CD) in the population. The market requires grass-free cereals to produce gluten-free food. This requires sorting methods that guarantee the perfect separation of gluten contaminants from the legumes. The objective of the research was the development of an optical sorting system based on hyperspectral image processing, capable of identifying the spectral characteristics of the products under investigation to obtain a statistical classifier capable of enabling the total elimination of contaminants. The construction of the statistical classifier yielded excellent results, with a 100% correct classification rate of the contaminants. Tests conducted subsequently on an industrial optical sorter validated the result of the preliminary tests. In fact, the application of the developed classifier was able to correctly select the contaminants from the mass of legumes with a correct classification percentage of 100%. A small proportion of legumes was misclassified as contaminants, but this did not affect the scope of the work. Further studies will aim to reduce even this small share of waste with investigations into optimising the seed transport systems of the optical sorter.

Use of Pharmacokinetic and Pharmacodynamic Data to Develop the CDK4/6 Inhibitor Ribociclib for Patients with Advanced Breast Cancer.

Ribociclib is an orally bioavailable, selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. CDK4/6inhibition by ribociclib leads to retinoblastoma tumor suppressor protein (Rb) reactivation, thereby restoring Rb-mediated cell cycle arrest. Ribociclib is approved for the treatment of patients with hormone receptor-positive/human epidermal growth factor receptor-2-negative (HR+/HER2-) advanced breast cancer (ABC), at the dose of 600mg once daily (QD) during cycles of 21days on/7days off, with optional dose reduction to 400 mgand 200mg. Ribociclib is rapidly absorbed with a median time to reach maximum plasma concentration of 2.4h, mean half-life of 32.0h and oral bioavailability of 65.8% at 600mg. It is eliminated mainly by hepatic metabolism (~84% of total elimination), mostly by cytochrome P450 (CYP) 3A4. Age, body weight, race, baseline Eastern Cooperative Oncology Group status, food, mild hepatic impairment, mild-to-moderate renal impairment, proton pump inhibitors, and combination partners (non-steroidal aromatase inhibitors or fulvestrant) have no clinically relevant impact on ribociclib exposure. Ribociclib inhibits CYP3A at 600mg leading to increased exposure of CYP3A substrates. Strong CYP3A inhibitors or inducers increase or decrease, respectively, ribociclib exposure. Exposure-safety and exposure-efficacy analyses support the clinical benefit of the 600mg QD starting dose, with potential individualized dose reductions to 400 mgand 200mg for effective management of the adverse events neutropenia and QTcF interval prolongation, while maintaining efficacy, in patients with HR+/HER2- ABC. Overall, these clinical pharmacology data informed ribociclib dose justification and clinical development, as well as its prescribing information for clinical use in advanced breast cancer patients.

Sensitivity of Preliminary Blood Test on Various Floor Surfaces After Washing with Different Cleansing Products. : Original Work

Blood is important evidence that can assist an investigator in solving a crime. It connects the suspect to a crime and aid in the reconstruction of the crime scene. Criminals frequently attempt to wipe away blood stained evidence at a crime scene. These efforts may result in the modification or partial or total elimination of blood on the stained parts. Numerous presumptive tests are employed to identify bloodstains on floor surfaces since they are frequently cleansed after a crime using various surfactants. However, the traces of stains remain there and if analysed with appropriate reagents will give conclusive results. In This study Blood-stained floor surfaces were cleaned using a commercially available and widely used floor cleaners and After repeated washings, the Kastle-Meyer (KM),Leucomalachite green (LMG), and Tetra methylbenzidine (TMB) tests were employed to determine the presence of blood on these surfaces, and their sensitivity were assessed, this study will help the forensic investigator to select the appropriate reagents for detection of blood stains on the various washed floor surfaces and effectiveness of reagents for detection of blood stains washed with various floor cleaners.

Fabricating carbon steel/Ti composites through forge-welding via in-situ interfacial reaction of Ni coating

Solid-state bonding is paramount in joining dissimilar materials, often combined with metal forming, such as forging, rolling and extrusion, to fabricate composites with a designed structure. Owing to its superior mechanical properties and low density, the carbon steel/Ti composite structure is attractive in automotive and aerospace industries but is difficult to fabricate due to the decarburization of carbon steel's faying surface. In this work, a carbon steel/Ti6Al4V composite structure was first fabricated via a forge-bonding method with the assistance of a Ni coating layer. Results show that the Ni layer on the faying surfaces precludes the decarburization of the steel and the growth of the TiC phase so as to improve the bonding quality. Meanwhile, the in-situ eutectic reaction between the Ni layer and β-Ti was observed. As a result, a seamless bonded interface with the total elimination of the Ni layer can be obtained. The bonding strength was examined to establish the relationship between bonding windows, microstructure and the resulting mechanical properties. An experimentally validated thermal-mechanical finite element model was also developed to understand the process-dependent interface evolution. This work opens a new avenue for fabricating carbon steel/Ti6Al4V composite, extending the flexibility of achieving complex structures by combining solid-state bonding with other metal-forming technologies.

Facile synthesis of platinum/polypyrrole-carbon black/SnS2 nanocomposite for efficient photocatalytic removal of gemifloxacin under visible light

Development and designing of effective visible light photocatalysts to overcome the drastrous situation of water pollution requires material with excellent charge transferring skills. In this regard, an efficient ternary nanocomposite photocatalyst comprised of SnS2 nanostructure linked with polypyrrole-doped carbon black (PPC) and platinum nanoparticles (Pt NPs) was successfully fabricated. Effective ternary photocatalyst was synthesized by hydrothermal technique followed by ultra-sonication and photo-reduction methodologies. The XRD measurements confirmed the hexagonal phase of SnS2, and the proper formation of nanocomposite. TEM examination revealed Pt NPs of 5–15 nm in size, dense cocoon like layered structure of PPC along with irregular pellets of SnS2. Acquired diffuse reflectance data confirmed the visible light band gap of synthesized nanomaterials. The Pt@PPC/SnS2 photocatalyst showed excellent destructive potential under visible light with 92.40 % removal of antibiotic gemifloxacin (GFX) in 30 minutes, almost 347 % more efficient than bare SnS2, and was found to be ultrafast for the removal of methylene blue (MB) with total elimination of dye just in 10 minutes. The photoluminescence and photocurrent transient analysis revealed enhanced light absorption capability and increased photo-induced carrier transfer with effective separation behavior, together with increased effective surface area of the ternary photocatalyst as evidenced by the BET surface area measurement.

Assessing the Efficacy of Commercial Activated Carbon Adsorption in Removing Emerging Contaminants from Wastewater

Powdered activated carbon was used in different studies for evaluation in micropollutants removal. In this study, powdered activated carbon was tested to evaluate its removal efficiency for about 46 micropollutants. A total of 33 compounds were found in raw wastewater. The PAC was found to be efficient towards total suspended solids elimination. Powdered activated carbon reached high removal percentage for heavy metals (90%), while the majority of the other compounds it varied between 60 and 80%. The impact of advanced treatments combination with conventional treatments could lead to high removals.

Green Insulation Revolution: A Bibliometric Analysis of Cannabis-Based Composite Materials in Building Construction

Powdered activated carbon was used in different studies for evaluation in micropollutants removal. In this study, powdered activated carbon was tested to evaluate its removal efficiency for about 46 micropollutants. A total of 33 compounds were found in raw wastewater. The PAC was found to be efficient towards total suspended solids elimination. Powdered activated carbon reached high removal percentage for heavy metals (90%), while the majority of the other compounds it varied between 60 and 80%. The impact of advanced treatments combination with conventional treatments could lead to high removals.

Reducing the harms of alcohol: nutritional interventions and functional alcohol alternatives.

The health risks and harm associated with regular alcohol consumption are well documented. In a recent WHO statement published in The Lancet Public Health alcohol consumption has been estimated to contribute worldwide to 3 million deaths in 2016 while also being responsible for 5·1% of the global burden of disease and injury. The total elimination of alcohol consumption, which has been long imbedded in human culture and society, is not practical and prohibition policies have proved historically ineffective. However, valuable strategies to reduce alcohol harms are already available and improved alternative approaches are currently being developed. Here, we will review and discuss recent advances on two main types of approaches, that is nutritional interventions and functional alcohol alternatives.

Fabrication of a WO3-Bi2WO6 Composite Electrode by Electrodeposition and its Application for Microbial Degradation

Photoelectrocatalytic (PEC) techniques are an innovative and promising method for eliminating microorganisms. Developing and applying such advanced technologies is essential for protecting public health and the environment. Semiconductor electrode development is a major issue in the advancement of such methods. We have developed a technique for fabricating WO3-Bi2WO6 electrodes using cyclic voltammetry (CV), focusing on the efficiency of the reaction and investigating key aspects for its use in microbial degradation. The optimization of the CV method parameter and calcination temperature was conducted in order to enhance the characteristics of composite WO3-Bi2WO6 electrodes for the aqueous oxidation process. The properties of the fabricated composited WO3-Bi2WO6 electrode were analyzed by several techniques, including UV-visible spectrophotometry, scanning electron microscopy, X-ray diffraction, Energy Dispersive X-ray Spectroscopy, X-ray photoelectron spectroscopy, and electrochemical impedance spectroscopy. The PEC water oxidation and total microorganism elimination efficiencies were investigated to validate the application of the developed composite WO3-Bi2WO6 electrode properties. The characteristics of the prepared composite WO3-Bi2WO6 electrodes are significantly influenced by the calcination temperature. We were able to satisfactorily verify the electrodes' properties in a reaction involving different calcining temperatures. At a calcining temperature of 450 °C, WO3-Bi2WO6 electrodes exhibited excellent PEC activity in water oxidation and electron transfer rate at the electrode surface. The composited WO3-Bi2WO6 electrode can effectively remove 96% of total microorganisms under the PEC process within 15 minutes. This study provides important background information for future work on composite semiconductor thin film preparations with potential applications in microbe eradication and environmental protection.

Simultaneous removal of brominated and chlorinated species during the production of oils by e-waste plastics catalytic hydropyrolysis

The production of added-value chemicals via pyrolysis of plastic wastes, such as those from electrical and electronic equipment (WEEE), needs addressing their usual contamination with halogens (mainly Br and Cl). This work compares the conversion via pyrolysis and hydropyrolysis of a real WEEE plastic, having a complex composition, in two different reactor configurations: down-flow (DF) and up-flow (UF). Likewise, the effects of incorporating a Pd/Al2O3 catalyst and using two different pressures (1 and 6 bar) have been assessed. With the DF mode, pyrolysis at 1 bar leads to an oil yield above 80 wt% and a total halogen content of about 600 ppm (vs 1600 ppm in the water-washed WEEE plastic). Under DF catalytic hydropyrolysis at 6 bar, this high oil yield is maintained while its dehalogenation degree is improved (142 ppm). Operating with the up-flow configuration, under 6 bar and H2 presence, leads to some reduction in the oil yield (about 70 wt%) but significantly decreases the oil halogen content (55 ppm Cl and total elimination of Br). These results have been related to the slower pyrolysis and longer residence time in the thermal zone of the UF configuration, which favours the halogen-trapping effect of the char fraction, and the pressure-enhanced hydrodehalogenation activity of the catalyst. This study highlights the environmental benefits of the proposed process, emphasizing the lower halogen content in the resulting oils and promoting a more sustainable approach to plastic waste valorisation.

Total wash elimination for solid phase peptide synthesis

We present a process for solid phase peptide synthesis (SPPS) that completely eliminates all solvent intensive washing steps during each amino acid addition cycle. A key breakthrough is the removal of a volatile Fmoc deprotection base through bulk evaporation at elevated temperature while preventing condensation on the vessel surfaces with a directed headspace gas flushing. This process was demonstrated at both research and production scales without any impact on product quality and when applied to a variety of challenging sequences (up to 89 amino acids in length). The overall result is an extremely fast, high purity, scalable process with a massive waste reduction (up to 95%) while only requiring 10–15% of the standard amount of base used. This transformation of SPPS represents a step-change in peptide manufacturing process efficiency, and should encourage expanded access to peptide-based therapeutics.

Beautiful, Magic, Lethal: a Social Perspective of Cinnabar Use and Mercury Exposure at the Valencina Copper Age Mega-site (Spain)

Today, mercury is a matter of concern for health and environmental authorities across western countries, and legislation has been passed and programs have been implemented for its total elimination from human activity. But this was not always the case: mercury and its compounds have been highly appreciated and used since remote times all over the world with very diverse purposes ranging from decorative, medicinal, metallurgical and symbolic. In particular, cinnabar (HgS, mercury sulfide), a mineral of an intense red color, has been considered in many cultures as an exotic raw material, highly valued and associated with the elites and sacred practice. In this paper, we examine one such case, set almost 5000 years ago, in Copper Age Iberia, by investigating mercury exposure through human bone. The study presented here includes a total of 170 samples from 70 different human individuals and 22 animals (plus one soil sample) from the Copper Age mega-site of Valencina, south-western Spain. It is the largest ever single-site study of exposure to mercury based on human bone in combination with cinnabar use. Abnormally high values are recorded in some individuals dating between 2900 and 2650 BC, especially in those buried in remarkable tombs belonging to the social elite of this period, but high levels of mercury are also recorded in the rest of the population. Three lines of interpretation are used to explain these results, including the manipulation of cinnabar (grinding it into powder, mixing it with other substances, using it for the decoration of objects, buildings and the human body), its direct consumption through ingestion or inhalation by a ‘special’ social group and the contribution of environmental factors. Based on the currently available evidence, which is carefully reviewed, Valencina represents the most intense and prolonged case of exposure to mercury recorded in human history, which makes it an important site to assess the long and complex history of use of this substance.