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Recent years have seen a paradigm shift in the management of patients with diabetes mellitus. Rather than good glycaemic control being the sole primary aim, the therapeutic focus has broadened to consider potential additional cardiovascular and renal benefits. Sodium-glucose co-transporter 2 inhibitors, such as empagliflozin, canagliflozin and dapagliflozin, have gained increasing prominence, with evidence suggesting significant improvement in outcomes in patients with established cardiovascular and renal disease. Here, we discuss the benefits and relative risks of these novel agents and highlight important clinical issues of relevance to general physicians.

Objective: To study the relationship between consumption of milk and milk products, calcium, lactose and vitamin D and occurrence of colorectal cancers. Design: Prospective cohort study. Subjects: A total of 9959 men and women aged 15 y or older without history of cancer at baseline. During a 24 y follow-up, 72 new cancers of the large bowel (38 in the colon and 34 in the rectum) were detected. Results: Consumption of milk and total milk products was suggested to be inversely related to colon cancer incidence, whereas no similar association was seen for rectal cancer. The relative risk between the highest and lowest quartiles of intake adjusted for potential confounding factors was 0.46 (95% confidence interval 0.14–1.46, P for trend 0.09) for milk and 0.37 (95% CI=0.12–1.39, P for trend 0.06) for total milk products. Lactose intake showed a similar inverse relationship with colon cancer: the relative risk was 0.31 (95% CI=0.08–1.15, P for trend 0.03). Intake of vitamin D or total dietary calcium was not significantly related to colorectal cancer risk, whereas calcium provided by fermented milk products was associated with increased colorectal cancer incidence; in the highest quartile the multivariate adjusted relative risk for colorectal cancer was 2.07 (95% CI=1.00–4.28). Conclusions: Our results indicate that individuals showing high consumption of milk have a potentially reduced risk of colon cancer; however, the association does not appear to be due to intake of calcium, vitamin D, or to specific effects of fermented milk. Sponsorship: This study was supported by a grant from the Swedish Cancer Foundation. European Journal of Clinical Nutrition (2001) 55, 1000–1007

It has long been proposed that nuclear RNAs might play an important role in organizing the structure of the nucleus. Initial experiments performed more than 30 years ago found that global disruption of RNA led to visible rearrangements of nuclear organization. Yet, this idea remained controversial for many years, in large part because it was unclear what specific RNAs might be involved, and which specific nuclear structures might be dependent on RNA. Over the past few years, the contributions of RNA to organizing nuclear structures have become clearer with the discovery that many nuclear bodies are enriched for specific noncoding RNAs (ncRNAs); in specific cases, ncRNAs have been shown to be essential for establishment and maintenance of these nuclear structures. More recently, many different ncRNAs have been shown to play critical roles in initiating the three-dimensional (3D) spatial organization of DNA, RNA, and protein molecules in the nucleus. These examples, combined with global imaging and genomic experiments, have begun to paint a picture of a broader role for RNA in nuclear organization and to uncover a unifying mechanism that may explain why RNA is a uniquely suited molecule for this role. In this review, we provide an overview of the history of RNA and nuclear structure and discuss key examples of RNA-mediated bodies, the global roles of ncRNAs in shaping nuclear structure, and emerging insights into mechanisms of RNA-mediated nuclear organization.

Auxin regulates many aspects of plant development and behavior, including the initiation of new outgrowth, patterning of vascular systems, control of branching, and responses to the environment. Computational models have complemented experimental studies of these processes. We review these models from two perspectives. First, we consider cellular and tissue-level models of interaction between auxin and its transporters in shoots. These models form a coherent body of results exploring different hypotheses pertinent to the patterning of new outgrowth and vascular strands. Second, we consider models operating at the level of plant organs and entire plants. We highlight techniques used to reduce the complexity of these models, which provide a path to capturing the essence of studied phenomena while running simulations efficiently.

The neuraminidase (NA) of influenza A and B viruses plays a distinct role in viral replication and has a highly conserved catalytic site. Numerous sialic (neuraminic) acid analogs that competitively bind to the NA active site and potently inhibit enzyme activity have been synthesized and tested. Four NA inhibitors are now licensed in various parts of the world (zanamivir, oseltamivir, peramivir, and laninamivir) to treat influenza A and B infections. NA changes, naturally occurring or acquired under selective pressure, have been shown to reduce drug binding, thereby affecting the effectiveness of NA inhibitors. Drug resistance and other drawbacks have prompted the search for the next-generation NA-targeting therapeutics. One of the promising approaches is the identification of monoclonal antibodies (mAbs) targeting the conserved NA epitopes. Anti-NA mAbs demonstrate Fab-based antiviral activity supplemented with Fc-mediated immune effector functions. Antiviral Fc-conjugates offer another cutting-edge strategy that is based on a multimodal mechanism of action. These novel antiviral agents are composed of a small-molecule NA inhibitor and an Fc-region that simultaneously engages the immune system. The significant advancements made in recent years further support the value of NA as an attractive target for the antiviral development.

Root-knot nematode Meloidogyne incognita is among the biotic factors which has greatly affected both the yield and the quality of the tomato crop. The egg parasitic nematode, Purpureocillium lilacinum (Pl) is considered as one of the most promising agents in controlling and overcoming this plant pathogen. The nematicidal effect of the native isolate Pl AUMC 10149 on second stage juvenile’s survival and egg hatching of M. incognita at different times of exposure was tested in vitro. The obtained data showed that Pl gave a maximum percentage of J2 mortality (97.6%) and egg hatching inhibition (79.8%) after 72 hours of exposure. The potentiality of Pl as well as Bio-Nematon to control M. incognita infecting tomato was conducted using different times of application in vivo. Nine treatments with five replicates were used for such bioagents compared with the nematicide Oxamyl. Each seedling was inoculated with 1000 J2s of nematode/pot and 10 mL of Pl (1x1010 CFU/mL) or Bio-Nematon spore suspension (1x108 CFU/mL) 10mL/pot. The results indicated that the most effective treatments in reducing nematode population, number of galls and egg masses of M. incognita in plant roots was performed with treatment by Pl pre-planting and post-infection with Pl (Rf 1.9) giving a significant enhancement in plant length (64.9%), fresh weight (72.52%) and shoot dry weight (163.41%) without negatively impacting environment. Therefore, the present study confirmed that using P. lilacinum AUMC 10149 can be used as a practical supplement to environmentally friendly disease management of root-knot nematodes in Egypt. Resumo O nematoide-das-galhas Meloidogyne incognita está entre os fatores bióticos que afetaram enormemente a produção e a qualidade da cultura do tomate. O nematoide parasita de ovos, Purpureocillium lilacinum (Pl), é considerado um dos mais promissores agentes no controle e superação desse fitopatógeno. O efeito nematicida do isolado nativo Pl AUMC 10149 na sobrevivência de juvenis de segundo estágio e na eclosão dos ovos de M. incognita em diferentes momentos de exposição foi testado in vitro. Os dados obtidos mostraram que o Pl deu um percentual máximo de mortalidade de J2 (97.6%) e inibição da eclosão dos ovos (79.8%) após 72 horas de exposição. A potencialidade de Pl e de Bio-Nematon para controlar M. incognita infectando tomate foi conduzida em diferentes tempos de aplicação in vivo. Nove tratamentos com cinco repetições foram usados para tais bioagentes em comparação com o nematicida Oxamyl. Cada muda foi inoculada com 1.000 J2s de nematoide / vaso e 10 mL de Pl (1×1010 CFU/mL). Ou suspensão de esporos Bio-Nematon (1×108 CFU/mL) 10mL/pot. Os resultados indicaram que os tratamentos mais eficazes na redução da população de nematoides, número de galhas e desovas de M. incognita nas raízes das plantas foram realizados com Pl pré-plantio e pós-infecção com Pl (Rf 1.9), dando um aumento significativo no comprimento da planta (64.9%), massa fresca (72.52%) e massa seca da parte aérea (163.41%) sem impactar negativamente o meio ambiente. Portanto, o presente estudo confirmou que o uso de P. lilacinum AUMC 10149 pode ser usado como um suplemento prático para o manejo ecologicamente correto de nematoides-das-galhas no Egito.

Auxin signaling regulates growth and developmental processes in plants. The core of nuclear auxin signaling relies on just three components: TIR1/AFBs, Aux/IAAs, and ARFs. Each component is itself made up of several domains, all of which contribute to the regulation of auxin signaling. Studies of the structural aspects of these three core signaling components have deepened our understanding of auxin signaling dynamics and regulation. In addition to the structured domains of these components, intrinsically disordered regions within the proteins also impact auxin signaling outcomes. New research is beginning to uncover the role intrinsic disorder plays in auxin-regulated degradation and subcellular localization. Structured and intrinsically disordered domains affect auxin perception, protein degradation dynamics, and DNA binding. Taken together, subtle differences within the domains and motifs of each class of auxin signaling component affect signaling outcomes and specificity.

Mammals have a limited capacity to regenerate their tissues and organs. One of the mechanisms associated with natural regeneration is dedifferentiation. Several small molecules such as vitamin C and growth factors could improve reprogramming efficiency. In this study, the NTERA2-D1 (NT2) cells were induced towards differentiation (NT2-RA) with 10-5 M retinoic acid (RA) for three days and then subjected to various amounts of vitreous humor (VH). Results show that the growth rate of these cells was reduced, while this rate was partly restored upon treatment with VH (NT2-RA-VH). Cell cycle analysis with PI method also showed that the numbers of cells at the S phase of the cell cycle in these cells were increased. The levels of SSEA3 and TRA-1-81 antigens in NT2-RA were dropped but they increased in NT2- RA-VH to a level similar to the NT2 cells. The level of SSEA1 had an opposite pattern. Expression of OCT4 gene dropped after RA treatment, but it was recovered in NT2-RA-VH cells. In conclusion, we suggest VH as a potent mixture for improving the cellular reprogramming leading to dedifferentiation. Resumo Os mamíferos têm uma capacidade limitada de regenerar seus tecidos e órgãos. Um dos mecanismos associados à regeneração natural é a desdiferenciação. Várias moléculas pequenas, como vitamina C e fatores de crescimento, podem melhorar a eficiência da reprogramação. Neste estudo, as células NTERA2-D1 (NT2) foram induzidas à diferenciação (NT2-RA) com ácido retinóico (RA) 10-5 M por três dias e depois submetidas a várias quantidades de humor vítreo (VH). Os resultados mostram que a taxa de crescimento dessas células foi reduzida, enquanto essa taxa foi parcialmente restaurada após o tratamento com VH (NT2-RA-VH). A análise do ciclo celular com o método PI também mostrou que o número de células na fase S do ciclo celular nessas células estava aumentado. Os níveis de antígenos SSEA3 e TRA-1-81 em NT2-RA diminuíram, mas aumentaram em NT2-RA-VH a um nível semelhante ao das células NT2. O nível de SSEA1 teve um padrão oposto. A expressão do gene OCT4 diminuiu após o tratamento com AR, mas foi recuperado em células NT2-RA-VH. Em conclusão, sugerimos o VH como uma mistura potente para melhorar a reprogramação celular levando à desdiferenciação.

The study was conducted to evaluate the effect of Moringa olifera on the growth and gut health of Tilapia (Oreochromis niloticus). The feed having 30% crude protein was prepared as an experimental diet with 4%, 8% and 10% M. olifera leaf supplementation, respectively. The control diet was devoid of M. olifera leaves. The 10 weeks feeding trial was carried out on 60 fish in aquaria. Fish was fed @ 3% of body weight twice a day. Diet with the high level of inclusion of M. olifera leaves significantly increased the growth rate, Survival Rate (SR), Specific Growth Rate (SGR) and Feed Conversion Efficiency (FCE) in all treatment groups compared to the control group. Similarly, Feed Conversion Ratio (FCR) gradually decreased and found highly-significant. To check the gut health of the Tilapia, random samples were selected and dissected. Nutrient agar was used as culture media to check the growth of bacteria. Pour Plate Method was used for viable colonies count by colony counter. Through staining method, the different bacteria such as Escherichia coli, Salmonella, Shigella and Pseudomonas aeruginosa were identify abundantly in the intestine of control diet fish but less number present in treatment diets groups. These results showed that M. olifera leaves up to 10% of dietary protein can be used for Nile tilapia for significant growth and healthy gut microbiota of fish. Resumo O estudo foi conduzido para avaliar o efeito da Moringa olifera no crescimento e saúde intestinal da tilápia (Oreochromis niloticus). A ração com 30% de proteína bruta foi preparada como dieta experimental com 4%, 8% e 10% de suplementação de folhas de M. olifera, respectivamente. A dieta controle foi desprovida de folhas de M. olifera. O ensaio de alimentação de 10 semanas foi realizado em 60 peixes em aquários. O peixe pesava 3% do peso corporal duas vezes ao dia. A dieta com alto nível de inclusão de folhas de M. olifera aumentou significativamente a taxa de crescimento, taxa de sobrevivência (SR), taxa de crescimento de sobrevivência (SGR) e eficiência de conversão alimentar (FCE) em todos os grupos de tratamento em comparação com o grupo de controle. Da mesma forma, a taxa de conversão de alimentação (FCR) diminuiu gradualmente e foi considerada altamente significativa. Para verificar a saúde intestinal da tilápia, amostras aleatórias foram selecionadas e dissecadas. O ágar nutriente foi usado como meio de cultura para verificar o crescimento das bactérias. O método da placa de Verter foi usado para a contagem de colônias viáveis por contador de colônias. Através do método de coloração, diferentes como Escherichia coli, Salmonella, Shigella e Pseudomonas aeruginosa foram identificados abundantemente no intestino de peixes da dieta controle, mas em menor número nos grupos de dieta de tratamento. Esses resultados mostraram que M. olifera deixa até 10% da proteína dietética e pode ser usado para tilápia do Nilo para um crescimento significativo e microbiota intestinal saudável de peixes.

The lower lignin content in plants species with energy potential results in easier cellulose breakdown, making glucose available for ethanol generation. However, higher lignin levels can increase resistance to insect attack. The objective of this work was to evaluate the susceptibility of a bmr-6 biomass sorghum (a mutant genotype with a lower concentration of lignin) to important pests of energy sorghum, Diatraea saccharalis and Spodoptera frugiperda. Experiments were performed in the laboratory and greenhouse to evaluate the development of these pests on the biomass sorghum bmr hybrids BR007, BR008, and TX635 and their respective conventional near-isogenic genotypes (without the bmr gene). The lignin content was higher in non-bmr hybrids, but the evaluated insect variables varied between treatments, not being consistent in just one hybrid or because it is bmr or not. The lowest survival of S. frugiperda was observed in the BR008 hybrid, both bmr and non-bmr. The S. frugiperda injury scores on plants in the greenhouse were high (>7) in all treatments. For D. saccharalis, there was no difference in larval survival in the laboratory, but in the greenhouse, the BR007 hybrid, both bmr and non-bmr, provided greater survival. Due the need to diversify the energy matrix and the fact that greater susceptibility of the bmr hybrids to either pests was not found in this study, these results hold promise for cultivation of these biomass sorghum hybrids for the production of biofuels. Resumo O menor teor de lignina em espécies de plantas com potencial energético resulta na maior facilidade de quebra da celulose, disponibilizando glicose para geração de etanol. Porém, maiores teores de lignina representa um fator de resistência ao ataque de insetos. O objetivo deste trabalho foi avaliar como importantes pragas do sorgo energia, Diatraea saccharalis e Spodoptera frugiperda, se comportam quanto à alimentação e desempenho em sorgo bmr-6, um genótipo mutante com menor concentração de lignina. Foram realizados experimentos em laboratório e casa de vegetação, avaliando o desenvolvimento destas pragas nos híbridos de sorgo biomassa bmr 007, 008, TX635 e seus respectivos genótipos isogênicos convencionais (sem o gene bmr). O teor de lignina foi maior nos híbridos não bmr, mas nos parâmetros avaliados nos insetos, houve variação entre os tratamentos, não sendo consistente em apenas um híbrido e nem por ser ou não bmr. A menor sobrevivência de S. frugiperda foi verificada no híbrido BR008 tanto bmr quanto não bmr. As notas de injúria por S. frugiperda no sorgo em casa de vegetação foram altas (>7) em todos os tratamentos. Para D. saccharalis, não houve diferença significativa para a sobrevivência larval em laboratório, mas em casa de vegetação o híbrido BR007 tanto bmr quanto não bmr proporcionaram maior sobrevivência. Diante da necessidade de diversificar a matriz energética e o fato de que não foi comprovada neste estudo maior suscetibilidade dos híbridos bmr a ambas as pragas, estes resultados são promissores para o cultivo desses híbridos de sorgo biomassa para produção de biocombustíveis.

Chemical solution deposition (CSD) approach was introduced in this work to simplify and to optimize the trifluoracetic based M TiO 3 ( M TO, M = Ca, Sr, and Ba) precursor solution, leading to the high shelf-life and the purity. Growing these M TO solutions on (100) LaAlO 3 single-crystal substrates yields (h00) oriented and dense M TO buffer layers. Whereas it is clear that the roughness of M TO films and the lattice mismatch between M TO buffer layer and superconducting YBa 2 Cu 3 O 7-δ film is crucial for the film formation.

Fresh fish, and especially fatty species, are highly perishable due to oxidative deterioration of fish flesh and the elevated microbial load on fish surface. The implementation of a variety of “mild hurdles” may significantly decrease the rates of fish chemical degradation and microbiological spoilage, by better retaining the initial quality, compared to more intense preservation techniques. The aim of this work is the comparative study of different, single or combined, treatments at 15 °C on the quality and shelf life of chilled eel fillets. Fish fillets were treated using osmotic solutions consisting of glycerol (30%–40%–45%) and 5% NaCl with and without former antioxidant impregnation by using Rosemary Serum. In all cases, water activity decreased to approximately 0.90 after 420 min of osmotic treatment. Untreated and osmotically treated fish fillets were subsequently stored at 4 °C and their stability under chill conditions was assessed based on microbial growth and oxidative deterioration. Microbial growth of treated samples was significantly delayed, especially due to the osmotic step (OS) and the derived water activity decrease. Lipid oxidation, a major cause of rejection for fatty fish such as eel, was greatly inhibited in treated fillets, owing to both ‘hurdles’, aw lowering (OS) and antioxidant impregnation with rosemary serum (RS/OS), showing the synergistic effect of these successive procedures. Shelf life of treated eel fillets exhibited a more than 10-fold increase, as compared to the untreated samples, based on chemical composition and a 2 to 3-fold shelf life improvement, in terms of microbial growth.

Occurrence of biogenic amines in fresh fish and fishery products constitute a significant safety concern. Ingestion of histamine is identified as the causative agent of several food poisoning incidences on an annual basis. In addition, cadaverine, putrescine and tyramine have been recognized as potentiators of histamine poisoning. Accumulation of biogenic amines in fresh fish and fishery products has been mainly attributed to growth of bacteria possessing amino acid decarboxylase activity, which is facilitated by lack of hygienic conditions and strict temperature control during their storage. To this end, the effectiveness of traditional and modern approaches to control biogenic amine accumulation has been in the epicenter of intensive study. The aim of the present review article is to update and integrate current knowledge regarding the biogenic amine content of fresh fish and fishery products as well as the capacity of traditional and emerging control strategies.

The ionic pair self-assembly (IPSAM) composed of poly(ethyleneimine) (PEI) and (phenylthio)acetic acid (PTA) was prepared and the effect of phenolic acids (PAs) (e.g. cinnamic acid (CA), hydroxycinnamic acid (HCA), and dihydroxycinnamic acid (DHCA)) on the upper critical solution temperature (UCST) and the temperature-responsive releasing property of IPSAM were investigated. PEI/PTA ionic pair showed a UCST behavior and the PAs decreased the UCST effective in the order of DHCA > HCA > CA. The PAs were thought to attach to the PEI chain of PEI/PTA ionic pair as pendants. According to the interfacial tensiometry, PEI/PTA(3/7) ionic pair was found to be air/water interface-active due to their amphiphilic property. CA had little effect on the interfacial activity of the ionic pair. HCA and HDCA significantly decreased the interfacial activity possibly because they are more polar than CA thus the hydrophilic and lipophilic balance of PEI/PTA ionic pair could be broken by their attachment to PEI chains. IPSAM was found as nanoparticles whose diameter was tens of nanometer and PAs had little effect on the shape and the size of IPSAM, once the UCST of PEI/PTA/PA ionic pair was above room temperature where the TEM micrographs were taken. If the UCST of PEI/PTA/PA ionic pair was below room temperature, no particulate matters were found on the TEM micrographs. The release degree of cargo loaded in IPSAM increased slowly with time lapse below UCST. Whereas, the release degree increased rapidly with time lapse above UCST, possibly because of the thermally-induced disintegration of IPSAM.

Metal-Organic Frameworks (MOFs) have been developed as solid sorbents for CO2 capture applications and their properties can be controlled by tuning the chemical blocks of their crystalline units. A number of MOFs (e.g., HKUST-1) have been developed but the question remains how to deploy them for gas–solid contact. Unfortunately, the direct use of MOFs as nanocrystals would lead to serious problems and risks. Here, for the first time, we report a novel MOF-based hybrid sorbent that is produced via an innovative in-situ microencapsulated synthesis. Using a custom-made double capillary microfluidic assembly, double emulsions of the MOF precursor solutions and UV-curable silicone shell fluid are produced. Subsequently, HKUST-1 MOF is successfully synthesized within the droplets enclosed in the gas permeable microcapsules. The developed MOF-bearing microcapsules uniquely allow the deployment of functional nanocrystals without the challenge of handling ultrafine particles, and further, can selectively reject undesired compounds to protect encapsulated MOFs.

Despite wide applications of noble metal-based catalysts in 5-hydroxymethylfurfural (HMF) oxidation, promoting the catalytic performance at low loading amounts still remains a significant challenge. Herein, a series of metal oxide modified MOx-Au/TiO2 (M = Fe, Co, Ni) catalysts with low Au loading amount of 0.5 wt% were synthesized. Addition of transition metal oxides promotes electron transfer and generation of the Auδ−–Ov–Ti3+ interface. A combination study reveals that the dual-active site (Auδ−-Ov-Ti3+) governs the catalytic performance of the rate-determining step, namely hydroxyl group oxidation. Auδ− site facilitates chemisorption and activation of O2 molecules. At the same time, Ov-Ti3+ site acts as the role of “killing two birds with one stone”: enhancing adsorption of both reactants, accelerating the activation and dissociation of H2O, and facilitating activation of the adsorbed O2. Besides, superoxide radicals instead of base is the active oxygen species during the rate-determining step. On this basis, a FDCA yield of 71.2% was achieved under base-free conditions, complying with the “green chemistry” principle. This work provides a new strategy for the transition metal oxides modification of Au-based catalysts, which would be constructive for the rational design of other heterogeneous catalysts.

Although zeolitic imidazolate frameworks (ZIFs) have bright prospects in wide fields like gas storage/separation, catalysis and medicine, etc., their large-scale applications are bottlenecked by the absence of their low-cost commercial production technique. Here, we report an unconventional method suitable for environmentally friendly and low-cost mass-production of ZIFs. In this method, taking the synthesis of ZIF-8 as an example, ZnO was used instead of Zn(NO3)2 in traditional solvent synthesis methods and CO2 was introduced to dissolve ZnO in aqueous solution of 2-methylimidazole (HMeim) and form water soluble salt ([ZnMeim]+[MeimCOO]-) at room temperature. Then, by removing CO2 through heating or vacuuming, Meim-ions are produced and instantaneously assemble with [ZnMeim]+s to generate ZIF-8 without any by-product. Due to the absence of strong acid anions (such as NO3− and Cl− et al.) in solution, the washing of filter cake required in the conventional approaches could be omitted and the filtrate containing only water and HMeim could be reused completely. This method is really green as no waste gas or liquid generates because CO2 and water could be recycled perfectly. It overcomes almost all bottlenecks occurred in commercial production of ZIF-8 when using traditional methods. A pilot plant was established for mass-production of ZIF-8 and hundreds kilograms of ZIF-8 was produced, which indicates that the new method is not only environmentally friendly but also low cost and commercial accessibility. It is expected that the new method would open an avenue for commercial applications of ZIFs.

A modified in vitro-in vivo correlation (IVIVC) of the oral solid dosage forms has been proposed as a linear correlation between in vitro and in vivo dissolution. Nevertheless, the analysis of in vivo dissolution is limited by the lack of available methods. In this proof-of-concept study, a novel pharmacokinetic (PK) model containing the in vivo dissolution process and its quantification was presented to directly estimate the in vivo dissolution rate constant (kd). The new model was validated with a hypothetical oral solution (kd → +∞). The accuracy of the new method was clarified by comparing with the relatively true value of kd from the literature. Isosorbide mononitrate (ISMN) was used as a model drug to explore the practicability of the novel method. The dissolution capacities of ISMN reference and test tablets were discriminated by an improved in vitro dissolution method. Following the human PK studies, the kd values and corresponding in vivo dissolution profiles of two formulations were obtained using the novel method. Finally, a modified level A IVIVC between in vitro and in vivo dissolution of ISMN tablets was established, which is expected to guide the optimization of the tablet formulation containing ISMN.

Background Ibrutinib is an oral inhibitor of Bruton’s tyrosine kinase (BTK) that is FDA-approved for several lymphoproliferative disorders and chronic GVHD. Objective To characterize cutaneous eruptions arising from ibrutinib and highlight overlap with epidermal growth factor receptor inhibitor (EGFRi)-induced dermatologic adverse events (dAEs). Methods Single-center retrospective cohort of patients referred to the Skin Toxicities Program for management of cutaneous eruptions while taking ibrutinib. Results Among 19 patients, cutaneous eruptions manifested as facial-predominant papulopustular eruptions, petechiae or ecchymoses, photosensitivity, panniculitis, xerosis, and clinical staphylococcal overgrowth. The majority of patients were able to continue ibrutinib therapy with focused management of their cutaneous toxicities. Limitations This study represents cases at a single tertiary care center and is limited to patients referred for toxicity. Conclusions With the exception of petechiae, the cutaneous toxicities of ibrutinib overlap with those associated with selective EGFR inhibitors. We observed that these reactions can be successfully managed using approaches for EGFR inhibitor-induced cutaneous adverse events.

Water electrolysis is a promising technology to produce hydrogen but it was severely restricted by the slow oxygen evolution reaction (OER). Herein, we firstly reported an advanced electrocatalyst of MOF-derived hollow Zn–Co–Ni sulfides (ZnS@Co9S8@Ni3S2-1/2, abbreviated as ZCNS-1/2) nanosword arrays (NSAs) with remarkable hydrogen evolution reaction (HER), OER and corresponding water electrolysis performance. To reach a current density of 10 mA cm−2, the cell voltage of assembled ZCNS-1/2//ZCNS-1/2 for urea electrolysis (1.314 V) is 208 mV lower than that for water electrolysis (1.522 V) and stably catalyzed for over 15 h, substantially outperforming the most reported water and urea electrolysis electrocatalysts. Density functional theory calculations and experimental result clearly reveal that the properties of large electrochemical active surface area (ECSA) caused by hollow NSAs and fast charge transfer resulted from the Co9S8@Ni3S2 heterostructure endow the ZCNS-1/2 electrode with an enhanced electrocatalytic performance.

The article contains sections titled: 1. Adsorptive Purification 1.1. Adsorption 1.2. Adsorption Isotherms 1.3. Adsorption Kinetics 1.4. Adsorbents 1.5. Adsorption Processes 1.6. Adsorbent Recovery and Regeneration 1.6.1. Regeneration of Carbon Adsorbents 1.6.2. Regeneration of Aluminum Oxide 1.6.3. Regeneration of Adsorber Resins 1.7. Applications of the Adsorptive Purification of Wastewater 1.7.1. Purification with Activated Carbon 1.7.2. Purification with Lignite Coke 1.7.3. Purification with Aluminum Oxide 1.7.4. Treatment with Adsorber Resins 1.7.5. Purification with Isopolyacids 2. Mechanical Treatment 2.1. Screening Processes 2.2. Gravity Processes 2.2.1. Sedimentation 2.2.2. Floatation 2.2.3. Flotation 2.2.3.1. Basic Principle 2.2.3.2. Contact and Adhesion of Particles to Gas Bubbles; Flotation Kinetics 2.2.3.3. Implementation, Fields of Application, and Operational Experience 2.2.3.4. Costs and Benefits 2.2.4. Foaming-Out Process 2.2.5. Centrifugal Processes

Proses dehidrasi merupakan salah satu proses yang sering dijumpai pada pabrik pengolahan gas alam. TEG (triethylene glycol) merupakan senyawa Glycol yang biasa digunakan pada proses dehidrasi gas alam. TEG dimanfaatkan sebagai absorben pada absorpsi air yang masih terkandung dalam gas alam yang bisa menyebabkan hydrate dan korosi. Proses absorpsi ini dilakukan di TEG contactor, TEG yang sudah digunakan akan dilakukan regenerasi, jika sudah di regenerasi maka TEG akan digunakan kembali. Tujuan dari penelitian ini yaitu melakukan proses estimasi temperatur yang sesuai untuk proses absorpsi unit regenerasi TEG, karena banyak TEG loss pada proses ini. TEG loss terjadi di TEG regenerator dan biasanya disebabkan oleh temperatur kondensor refluks yang kurang tepat sehingga menyebabkan TEG teruapkan keluar ke atmosfer bersama uap air. Kehilangan TEG adalah masalah bagi operasi yang penting dalam sistem dehidrasi. Langkah yang digunakan untuk mengurangi TEG loss adalah dengan melakukan estimasi temperatur dari condensor refluks dibuat menjadi 100°C dengan cara mengubah temperatur reboiler dari 190°C menjadi 197,3°C.

The dimethacrylate macromonomer named bis (2-hydroxy-3-(méthacryloyloxy) propyl) fumarate (HMPF) was synthesized by ring opening reaction of epoxide function of glycidyl methacrylate (GMA) with maleic anhydride (MA) in presence of Maghnite-H+ as a catalyst at room temperature and at free solvent. The Maghnite-H+ is a proton exchanged montmorillonite clay it is an Algerian clay activated by sulfuric acid 0,23M. The HMPF was characterized by FT-IR, 1H NMR and 13C NMR spectroscopic techniques. A kinetic study was carried out to determine the amount of the catalyst (5, 10, 20 and 30%) which will give abetter yield of the synthesis reaction. T he yield of the reaction was 62. 2 3% for a quantity of Maghnite-H+ (20% relative to the monomer and for a r eaction time of 72 h.

This article deals with the numerical simulation of a two-dimensional instantaneous heat and mass transfer processes within a commonly used intermetallic compound (a.k.a. Mischmetal) packed in a unit disc of an annulus-disc reactors, during hydrogen gas desorption. Using the finite volumes technique bundled in the OpenFOAM® CFD code, temperature and amount of desorbed hydrogen and their time-averaged quantities inside the metal-hydride packed bed are obtained for various temperatures of fluids used in heat transfer, and several outlet pressure magnitudes. Using a set of numerical simulations, we have emphasized the impacts of both parameters on metal-hydride reactor performance related to discharging time. An excellent accord was recorded for the present simulations results compared against the literature-reported experimental data [20].

Galvanisasi merupakan proses pelapisan dengan seng ( Zinc ), dengan caara mencelupkan logam yang akan dilapisi kedalam media pelapis zinc yang sebelumnya telah mengalami proses peleburan, dimana titik lebur logam pelapis harus lebih rendah dari logam yang akan dilapisi. Tujuan dari penelitian ini adalah untuk mengetahui pengaruh waktu pencelupan dan temperatur terhadap proses pencelupan. Analisis yang akan dilakukan adalah uji ketebalan permukaan dan melakukan uji kekerasan bahan setelah dilakukan pencelupan. Dalam penelitian ini material yang digunakan adalah baja dengan tipe UNP, Sebelum dilakukan Hot Dip Galvanized perlu dilakukan pretreatment menggunakan bahan kimia, yaitu proses degreasing, water rinsing, pickling, fluxing, drying . Setelah itu dilakukan tahap Galvanisasi, Variabel yang akan digunakan adalah suhu zinc bath 440 o C,445 o C,450 o C dan waktu pencelupan 2,4,6,8,10 menit. Dari hasil analisis semakin lama waktu pencelupan pada proses hot dip galvanizing mengakibatkan semakin tebal lapisan zinc yang dihasilkan dan Semakin tinggi temperatur zinc saat proses hot dip galvanizing juga mengakibatkan semakin tebal lapisan zinc yang di hasilkan, di karenakan kekentalan dari zinc menurun.

Spent wash merupakan limbah dari proses distilasi pada produksi alkohol dengan COD ±150.000 ppm. Limbah dengan nilai COD yang tinggi harus diolah terlebih dahulu sebelum dibuang ke lingkungan. Salah satu pengolahan limbah untuk menurunkan COD adalah anaerobic digestion . Dengan metode anaerobic digestion, spent wash dapat diubah menjadi gas metana dengan bantuan bakteri metanogen yang terdapat di activated sludge . Berdasarkan data daily report PT ENERGI AGRO NUSANTARA bulan Juni 2019 menunjukkan produksi gas metana mengalami fluktuaktif sebesar 50-58% sedangkan baku mutu yang ditetapkan adalah 60%. Tujuan penelitian ini untuk mengolah limbah spent wash dengan metode anaerobic digestion untuk meningkatkan gas metana yang dihasilkan. Metode yang digunakan adalah anaerobic digestion dengan waktu tinggal selama 61 hari dan beroperasi pada suhu 30 0 C serta pH 7. Bahan yang digunakan adalah campuran antara a ctivated s ludge dan s pent w ash serta penambahan zeolit 10%. Variabel nutrient yang digunakan yaitu campuran urea dan diammonium fosfat dengan rasio 1:1, 1:2, 1:3, 2:1, 2:2, 2:3, 3:1, 3:2, dan 3:3. Hasil penelitian menunjukkan penurunan COD tertinggi adalah 60% dengan gas metana yang dihasilkan adalah 22,4mL. %Kadar gas metana dengan menggunakan nutrient (3:3) adalah 24,4%. Penambahan zeolit 0,2-2 g/L mampu meningkatkan produksi gas metana sebesar 1,4%.

This paper investigates the ontological and material dimensions of peasant struggles in Colombian northwestern Amazonia in a context of increasing international deforestation concerns that press the Colombian government to enforce protected areas through military campaigns and market-based conservation programs. Building on ethnographic research in the region, the paper contributes to ongoing debates in the field of political ecology about the ontological dimension of dispossessions and social struggles. It brings together ontological studies with a perspective of critical geography to propose an integrative political ecology of socio-environmental conflicts that addresses the material and the ontological dimensions of domination and resistance.

The world's seas and oceans contain vast amounts of lithium, but the low concentration hereof renders solvent extraction impractical for its recovery. By contrast, seawater desalination brine, after treatment by nanofiltration, contains a roughly tenfold greater concentration of lithium than raw seawater. Hence, lithium can be effectively recovered from such streams using solvent extaction. Compared with other techniques to sequester lithium from dilute solutions, solvent extraction offers the advantages of simple operations, robust and well-established technology and high recovery yields. Thus, we propose a solvent-extraction based process to recover lithium from seawater desalination brine, treated by nanofiltration. The first step comprises the removal of magnesium and calcium using methyltrioctylammonium neodecanoate in p-cymene. This is followed by a lithium extraction step using the extractants Mextral 54–100 and Cyanex 923 in Shellsol D70 diluent. The lithium extract is then scrubbed with water and stripped with hydrochloric acid. Subsequently, residual alkaline earth metals are removed with sodium hydroxide in ethanol and finally lithium is precipitated using sodium carbonate. The solvent extraction, scrubbing and stripping steps were demonstrated on mini-pilot scale in continuous countercurrent mode (in mixer-settlers), while the precipitation steps were demonstrated in batch. The process was found to have an overall yield of 74%, affording a lithium carbonate product with a purity of 97 wt%.

PURPOSE Cisplatin plus gemcitabine is a standard regimen for first-line treatment of advanced non–small-cell lung cancer (NSCLC). Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting. PATIENTS AND METHODS This noninferiority, phase III, randomized study compared the overall survival between treatment arms using a fixed margin method (hazard ratio [HR] < 1.176) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1. Patients received cisplatin 75 mg/m2 on day 1 and gemcitabine 1,250 mg/m2 on days 1 and 8 (n = 863) or cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 on day 1 (n = 862) every 3 weeks for up to six cycles. RESULTS Overall survival for cisplatin/pemetrexed was noninferior to cisplatin/gemcitabine (median survival, 10.3 v 10.3 months, respectively; HR = 0.94; 95% CI, 0.84 to 1.05). Overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine in patients with adenocarcinoma (n = 847; 12.6 v 10.9 months, respectively) and large-cell carcinoma histology (n = 153; 10.4 v 6.7 months, respectively). In contrast, in patients with squamous cell histology, there was a significant improvement in survival with cisplatin/gemcitabine versus cisplatin/pemetrexed (n = 473; 10.8 v 9.4 months, respectively). For cisplatin/pemetrexed, rates of grade 3 or 4 neutropenia, anemia, and thrombocytopenia ( P ≤ .001); febrile neutropenia ( P = .002); and alopecia ( P < .001) were significantly lower, whereas grade 3 or 4 nausea ( P = .004) was more common. CONCLUSION In advanced NSCLC, cisplatin/pemetrexed provides similar efficacy with better tolerability and more convenient administration than cisplatin/gemcitabine. This is the first prospective phase III study in NSCLC to show survival differences based on histologic type.

Excess nutrient supply by the rivers and the atmosphere are considered as the major causes for the persistently poor ecological status of the Baltic Sea. More than 97% of the Baltic Sea still suffers from eutrophication due to past and present inputs of nitrogen and phosphorus. One of the poorly quantified nutrient sources in the Baltic Sea is submarine groundwater discharge (SGD). Through seepage meter deployments and a radium mass balance model, a widespread occurrence of SGD along the coastline of Eckernförde Bay was detected. Mean SGD was 21.6 cm d−1 with a calculated freshwater fraction of 17%. Where SGD was detected, pore water sampled by a piezometer revealed a wide range of dissolved inorganic nitrogen (DIN: 0.05–1.722 µmol L−1) and phosphate (PO43−: 0.03–70.5 µmol L−1) concentrations. Mean DIN and PO43− concentrations in non-saline (salinity −1 and 1.2 ± 1.9 µmol L−1, respectively; whereas pore water with salinities > 1 revealed higher values, 113 ± 207 µmol L−1 and 6 ± 12 µmol L−1 for DIN and PO43−, respectively. The nutrient concentrations along the salinity gradient do not suggest that land-derived groundwater is the definitive source of nutrients in the Baltic Sea. Still, SGD may contribute to a major autochthonous nutrient source, resulting from remineralization or dissolution processes of organic matter in the sediments. The DIN and PO43− fluxes derived from SGD rates through seepage meters are 7.9 ± 9.2 mmol m−2 d−1 and 0.5 ± 0.4 mmol m−2 d−1, lower by a factor of ~ 2 and ~ 5 when compared to the fluxes derived with the radium mass balance model (mean DIN: 19 ± 28 mmol m−2 d−1; mean PO43−: 1.5 ± 2.7 mmol m−2 d−1). Assuming that these mean radium-based nutrient fluxes are representative for the coastline of Eckernförde Bay, we arrive at SGD-borne nutrient fluxes of about 1 t km−1 y−1 of nitrogen and 0.2 t km−1 y−1 of phosphorous. These fluxes are lower for DIN and in the same range for phosphorus as compared to the riverine nutrient supply (DIN: 6.3 t km−1 y−1, P: 0.2 km−1 y−1) to the German Baltic Sea identifying SGD-borne nutrients as a secondary nutrient source to the Baltic Sea.

Limbah pewarna tekstil yang mempunyai komponen utamanya zat pewarna sintesis berbahaya bagi lingkungan sekitar. Pengolahan limbah pewarna tekstil secara fisika dan biologi kurang efektif. Elektrolisis plasma dengan menggunakan metode Contact Glow Discharge Electrolysis (CGDE) merupakan bagian dari pengolahan secara kimiawi, yang efektif dalam mengolah limbah pewarna batik. Parameter kedalaman anoda sangat mempengaruhi dalam proses elektrolisis plasma metode CGDE. Tujuan penelitian ini adalah untuk mengetahui pengaruh kedalaman anoda terhadap produksi •OH, energi yang digunakan proses degradasi, persen dekolorisasi Remazol Red RB 133, serta mengetahui penurunan konsentrasi COD limbah pewarna batik Remazol Red RB 133. Kedalaman anoda dalam penelitian ini adalah 1,5 cm dimana produksi •OH sebesar 11,63 mmol dan energi proses selama 30 menit adalah 806,4 KJ. Persen dekolorisasi Remazol Red RB 133 pada konsentrasi 250 ppm, terbesar selama 30 menit mencapai 99,66 %, pada kedalaman 4,5 cm dengan energi 1075,212 KJ. Nilai COD limbah pewarna batik Remazol Red RB 133 menurun dari 169 mg/L menjadi 3,6 mg/L setelah proses CGDE selama 180 menit (sesuai dengan baku mutu limbah). Textile dye waste having the main component of synthetic dye is hazardous to the surrounding environment. Textile dye waste treatment is physically and biologically less effective. Electrolysis plasma that used Contact Glow Discharge Electrolysis (CGDE) method is part of chemical treatment. The anode depth parameters greatly affect the electrolysis CGDE method. The purpose of this study was to determine the effect of anode depth on • OH production, the energy used in the degradation process, percent decolorization of Remazol Red RB 133, as well as knowing the decrease in COD concentration of Remazol Red batik dye RB 133. The anode depth in this study is 1.5 cm where the production of OH • 11.63 mmol and the processing energy for 30 minutes is 806.4 KJ. The largest Percentage degradation of Remazol Red RB 133 at concentration 250 ppm is 99,66%, that’s reach at depth 4.5 cm for 30 minutes with energy 1075,212 KJ. COD value has decreased from 169 mg/L to 3,6 mg/L after 180 minutes CGDE process (conform to waste quality standards).

Gold nanorods (Au NRs) are an exceptionally promising tool in nanotechnology due to three key factors: (i) their strong interaction with electromagnetic radiation, stemming from their plasmonic nature, (ii) the ease with which the resonance frequency of their longitudinal plasmon mode can be tuned from the visible to the near-infrared region of the electromagnetic spect r u m based on their aspect ratio, and (iii) their simple and cost-effective preparation through seed-mediated chemical growth. In this synthetic method, surfactants play a critical role in controlling the size, shape, and colloidal stabi l i t y of Au NRs. For example, surfactants can stabilize specific crystallographic facets during the formation of Au NRs, leading to t h e formation of NRs with specific morphologies. The process of surfactant adsorption onto the NR surface may result in various assemblies of surfactant molecules, such as spherical micelles, elongated micelles, or bilayers. Again, the assembly mode is critical toward determining the further availabi l i t y of the Au NR surface to the surrounding medium. Despite its importance and a great deal of research effort, the interaction between Au NPs and surfactants remains insufficiently understood, because the assembly process is influenced by numerous factors, including the chemical nature of the surfactant, the surface morphology of Au NPs, and solution parameters. Therefore, gaining a more comprehensive understanding of these interactions is essential to unlock the full potential of the seed-mediated growth method and the applications of plasmonic NPs. A plethora of characterization techniques have been applied to reach such an understanding , but many open questions remain. In this Account, we review the current knowledge on the interactions between surfactants and Au NRs. We briefly introduce the state-of-the-art methods for synthesizing Au NRs and highlight the crucial role of cationic surfactants during this process. The self-assembly and organization of surfactants on the Au NR surface is then discussed to better understand their role in seed-mediated growth. Subsequently, we provide examples and elucidate how chemical additives can be used to modulate micellar assemblies, in turn allowing for a finer control over the growth of Au NRs, including chiral NRs. Next, we review the main experimental characterization and computational modeling techniques that have been applied to shed light on the arrangement of surfactants on Au NRs and summarize the advantages and disadvantages for each technique. The Account ends with a "Conclusions and Outlook" section, outlining promising future research directions and developments that we consider are sti l l required, mostly related to the application of electron microscopy in liquid and in 3D. Finally, we remark on the potential of exploiting machine learning techniques to predict synthetic routes for NPs with predefined structures and properties.

Pemisahan n-propil asetat dari campuran terner n-propil asetat/n-propanol/air merupakan salah satu proses yang tidak dapat dilakukan dengan distilasi sederhana. Adanya azeotrop terner minimum dari campuran tersebut menyebabkan n-propil asetat hanya dapat dipisahkan dari campuran n-propanol dan air salah satunya dengan metode distilasi ekstraktif. Distilasi ekstraktif merupakan proses vaporisasi parsial dengan menambahkan suatu agen pemisah non-volatil yang disebut sebagai sovent atau agen ekstraktif. Solvent yang digunakan dalam simulasi proses ini adalah campuran DMSO (Dimetil Sulfoksida) dan Gliserol dengan komposisi 50 % massa dengan perbandingan 1:2 untuk massa umpan kolom : solvent. Feed yang digunakan adalah n-propanol (10 kmol/jam) dan asam asetat (13 kmol/jam) masing-masing pada suhu 25°C dan tekanan 101,3 kPa. Hasil n-propil asetat terbaik diperoleh saat solvent diumpankan pada stage 5 dengan fraksi mol n-propil asetat pada distilat 0,9975 disertai dengan minimumnya energi reboiler yang digunakan pada konfigurasi kolom ini. n-Propyl acetate separation of the n-propyl acetate /n-propanol/water mixture composition can't be done by simple distillation. The existence of minimum ternary azeotrope on the mixture causes n-propyl acetate can be separated only by extractive distillation method. Extractive distillation is a partial vaporization process in the presence of a non-volatile separating agent called as solvent or extractive agent. Solvent used in the simulation process is DMSO (Dimethyl Sulfoxide)-Glycerol mixture (50% mass) with a ratio of 1: 2 for column feed : solvent. n-Propanol (10 kmol/hour) and acetic acid (13 kmol/hour) are fed into reactor (before extractive distillation process) at 25°C and 101.3 kPa, respectively. The best results of n-propyl acetate were obtained when the solvent was fed to stage 5 in which mole fraction of n-propyl acetate in distillate 0.9975 accompanied by the minimum reboiler energy used in this column configuration.

The concentration and sources of organic nitrogen (ON) in lake sediment significantly affect the lake nitrogen cycle. However, the influencing factors and contributors to the ON accumulation rate (ONAR) are unclear. In this study, tree sediment cores from northern, eastern, and southern Dianchi Lake (DC-N, DC-E, and DC-S, respectively), sampled in July 2014, were used to study the effects of autochthonous and allochthonous sources on ON. The results showed that ON and the ONAR increased 2.4–5.1 and 2.6–4.8 times, respectively, from1900 to2000, especially since the 1980s, at which point algal blooms occurred more frequently. The ON contents decreased in the order: DC-S > DC-N > DC-E, whereas the ONAR values followed the order: DC-N > DC-S > DC-E, suggesting that the ONAR was influenced by ON content as well as depositional environmental conditions. The total concentrations of n-alkanes (n-C12 to n-C34) ranged from 4719.4 ng g− 1 to 61,959.6 ng g− 1 in the three sediment cores, each of which exhibited different n-alkanes characteristic variation with vertical depth. The sources of ON were mainly allochthonous (soil erosion and terrestrial plants) and autochthonous (algal and aquatic plants) in DC-S and DC-N, respectively, whereas they were primarily mixed planktonic and terrestrial sources in DC-E. Using the stochastic impacts by regression on population, affluence, and technology model to further examine the ONAR values revealed that 1% increase in temperature and nitrogen fertilizer can increase the ONAR by 73.8–86.2% and 73.2–151.3% in all sediments, especially in DC-S and DC-E. However, a 1% increase in construction area could reduce the ONAR by 2.4–14.2%, especially in DC-N. Overall, climate change and human activities determine the spatial and temporal ONAR variation in Dianchi Lake.

Sodium-ion batteries are attracting great attention due to their low cost and abundance of sodium. The O3-type NaNi1/3Fe1/3Mn1/3O2 layered oxide material is a promising candidate for positive electrodes (cathodes) in Na-ion batteries. However, its stable electrochemical performance is restricted by the upper voltage limit of 4.0 V (vs Na/Na+), which allows for reversibly removing 0.5-0.55 Na+ per formula unit, corresponding to the capacity of 120-130 mAh.g(-1). Further reduction of sodium content inevitably accelerates capacity degradation, and this issue calls for a detailed study of the redox reactions that accompany the electrochemical (de)intercalation of a large amount of sodium. Here, we present operando and ex situ studies using powder X-ray diffraction and X-ray absorption spectroscopy combined with Fe-57 Mossbauer spectroscopy. Our approach reveals the sequence of the redox transitions that occur during the charge and discharge of O3-NaNi1/3Fe1/3Mn1/3O2. Our data show that in addition to nickel and iron cations oxidizing to M+4, a part of iron transforms into the "3 + delta" state owing to the fast electron exchange Fe3+ + Fe4+ Fe4+ + Fe3+. This process freezes upon cooling the material to 35 K, producing Fe4+ cations, some of which occupy tetrahedral positions.

This study was aimed at preparing chitosan (CS)-phenolic acids copolymers to obtain better preservation effect in marine products. In this work, CS was grafted onto phenolic acids such as gallic acid (GA) and protocatechuic acid (PA) by a carbodiimide coupling method. The copolymers (CS-grafted-GA (CS-g-GA) and CS-grafted-PA (CS-g-PA)) were further confirmed through physicochemical properties including ultraviolet–visible (UV–Vis) spectrophotography, fourier transform infrared (FTIR) spectrometry, differential scanning calorimetry (DSC) thermogram, rheological behaviour, scanning electron microscope (SEM) and antioxidant activity analysis. Subsequently, the effects of copolymers on preservation of refrigerated sea bass (Lateolabrax japonicus) fillets were investigated. The results showed that the CS-g-GA (110.82 mg GA/g) exhibited higher grafting rate than CS-g-PA (62.63 mg PA/g). According to the assessment of UV–Vis and FTIR spectrometry, both the GA and PA were grafted onto CS successfully. SEM analysis demonstrated that the microstructure of copolymers became irregular. Meanwhile, both the CS-g-GA and CS-g-PA copolymers displayed superior thermal stability, rheological properties and antioxidant capacity than the pure CS. Furthermore, the copolymers also revealed a significantly stronger preservation effect on sea bass fillets including inhibiting microbial growth and delaying the deterioration of color, texture and sensory quality. Therefore, CS-g-GA and CS-g-PA could be used as promising preservatives for seafood.

Purpose To highlight a case of chorioretinitis sclopetaria, with concomitant macular hole formation and orbital emphysema, caused by a commercial-grade pressure washer. Patient A 19-year-old male presented to the emergency department with a left eye injury, incurred after being sprayed with a commercial-grade pressure washer. He endorsed ipsilateral blurred vision, pain, and linear floaters. Left eye visual acuity was 20/40. Dilated fundus exam showed inferior vitreous hemorrhage, retinal whitening, and pre-, intra-, and sub-retinal hemorrhages, consistent with chorioretinitis sclopetaria. Optical coherence tomography revealed a full-thickness macular hole. Computed tomography scan of the orbits showed subcutaneous and post-septal orbital emphysema. Two months following injury, vitreous and retinal hemorrhages and macular hole resolved. Five months following injury, visual acuity improved to 20/20. Discussion Chorioretinitis sclopetaria is defined as a full-thickness chorioretinal disruption resulting from a high-velocity projectile passing adjacent to or into the orbit without penetrating the globe. Chorioretinal deformation and ocular comorbidities are influenced by the velocity of the missile and its spatial relationship to the orbit. While this pattern of injury is typically associated with indirect trauma to the globe by a BB or a bullet, this is the first report of chorioretinitis sclopetaria precipitated by a high-velocity liquid missile.

Purpose To investigate the efficacy and safety of bevacizumab plus carboplatin and paclitaxel in patients with advanced or recurrent non-small-cell lung cancer. Patients and Methods In a phase II trial, 99 patients were randomly assigned to bevacizumab 7.5 (n = 32) or 15 mg/kg (n = 35) plus carboplatin (area under the curve = 6) and paclitaxel (200 mg/m2) every 3 weeks or carboplatin and paclitaxel alone (n = 32). Primary efficacy end points were time to disease progression and best confirmed response rate. On disease progression, patients in the control arm had the option to receive single-agent bevacizumab 15 mg/kg every 3 weeks. Results Compared with the control arm, treatment with carboplatin and paclitaxel plus bevacizumab (15 mg/kg) resulted in a higher response rate (31.5% v 18.8%), longer median time to progression (7.4 v 4.2 months) and a modest increase in survival (17.7 v 14.9 months). Of the 19 control patients that crossed over to single-agent bevacizumab, five experienced stable disease, and 1-year survival was 47%. Bleeding was the most prominent adverse event and was manifested in two distinct clinical patterns; minor mucocutaneous hemorrhage and major hemoptysis. Major hemoptysis was associated with squamous cell histology, tumor necrosis and cavitation, and disease location close to major blood vessels. Conclusion Bevacizumab in combination with carboplatin and paclitaxel improved overall response and time to progression in patients with advanced or recurrent non-small-cell lung cancer. Patients with nonsquamous cell histology appear to be a subpopulation with improved outcome and acceptable safety risks.

The world’s first offshore methane hydrate extraction was conducted in 2013 at the Daini-Atsumi Knoll located in the eastern Nankai Trough. The results indicated that the gas production rate of a single vertical well cannot meet the requirement for commercialisation of methane hydrate production. Therefore, a trial multi-well system has been considered for future hydrate production. Understanding the ‘influence distance’ of extraction wells within methane hydrate turbidite reservoir formations, such as that of the Nankai Trough, is significant to the design of the proposed multi-well system. In this study, the boundary effects are examined for cases involving different values of permeability and initial hydrate saturation for the modelled turbidite formations. A relationship is proposed to predict the longest simulation time for a given set of lengths and parameters. The two concepts of critical production time (CPT) and turbidity/homogeneity coefficient ratio (THCR) are introduced to analyse the interaction between the effects of model size and heterogeneities. It is found that the CPT can be normalised by the radius of the model; the THCR is affected by the relative thickness of the sand and clay layers.

There are many photovoltaic (PV) applications where lighter weight and/or bendable PV power would be beneficial. This includes the curved surfaces of buildings, buildings with weight limitations, boats, automobiles, or other portable applications. In many of these cases, the bending will be only a single occurrence at installation or the amount of bending, even if repeated, is not dramatic. This allows for crystalline silicon modules to be used. For flexible applications, the dominant material for the frontsheet is polyethylene tetrafluoroethylene (PETFE). As a fluoropolymer it resists soiling, is UV stable, and PETFE is a more mechanically durable fluoropolymer. However, in the interests of keeping costs down, less expensive alternative polymers are desirable. In this study, highly accelerated ultraviolet light and heat stresses are applied to candidate materials and the degradation kinetics are determined to provide information to evaluate their suitability for use in a PV application.

Kidney disease is frequent in HIV-patients. We present a case of a 44-year-old woman, with known uncontrolled HIV infection and chronic kidney disease due to HIV-associated nephropathy. After starting dolutegravir, the patient developed eosinophilia and worsening kidney function. A kidney biopsy confirmed the diagnosis of acute interstitial nephritis. Given the time relation with dolutegravir introduction, it was deemed the culprit medication. Dolutegravir was stopped, and corticosteroids were initiated, with moderate improvement in renal function. To our knowledge, this is the first reported case of acute interstitial nephritis to dolutegravir, which should raise awareness of previously undocumented renal effects of antiretroviral therapy.

Soils containing organic matter exhibit low shear strength and high compressibility. Lime stabilisation has been shown to improve the engineering properties of clayey soils. An attempt was made to study the effect of organic matter (starch and peat) on the shear strength of lime-stabilised clayey soils subjected to longer curing periods (up to 180 days). Most studies have reported the strength behaviour of lime-stabilised organic soils up to 60 days. Vane shear tests were carried out on artificially prepared organic soil mixtures treated with 6% lime after different curing periods (0, 7, 30, 60, 90 and 180 days). The results indicate that the improving effect of lime is deteriorated in the presence of organic matter as the curing period increases. It was observed that, for lime-stabilised clayey soils containing organic matter, the strength seemed to increase up to 30 days, after which it ceased. The strength reduction in lime-stabilised clayey soils containing organic matter depended on the pH and functional groups present in the soil. Fourier transform infrared spectroscopy of cured samples was also carried out to examine the microstructural changes responsible for the strength change in lime-stabilised clayey soils.

Cytotoxic CD8+T lymphocytes (CTL) eliminate infected cells or transformed tumour cells by releasing perforin-containing cytotoxic granules at the immunological synapse. The secretion of such granules depends on Ca2+-influx through store operated Ca2+channels, formed by STIM-activated Orai proteins. Whereas molecular mechanisms of the secretion machinery are well understood, much less is known about the molecular machinery that regulates the efficiency of Ca2+-dependent target cell killing. Here, we isolated total RNA from natural killer (NK) cells, non-stimulated CD8+T-cells, and from Staphylococcus aureus enterotoxin A (SEA) stimulated CD8+T-cells (SEA-CTL) and conducted whole genome expression profiling by microarray experiments. Based on differential expression analysis of the transcriptome data and analysis of master regulator genes, we identified 31 candidates which potentially regulate Ca2+-homeostasis in CTL. To investigate a putative function of these candidates in CTL cytotoxicity, we transfected either SEA-stimulated CTL (SEA-CTL) or antigen specific CD8+T-cell clones (CTL-MART-1) with siRNAs specific against the identified candidates and analyzed the killing capacity using a real-time killing assay. In addition, we complemented the analysis by studying the effect of inhibitory substances acting on the candidate proteins if available. Finally, to unmask their involvement in Ca2+dependent cytotoxicity, candidates were also analyzed under Ca2+-limiting conditions. Overall, this strategy led to the identification of KCNN4, RCAN3, CCR5 and BCL2 as potential candidates to regulate the efficiency of Ca2+-dependent target cell killing.

PurposeTo investigate the relationship between pathological brain iron deposition and white matter hyperintensities (WMHs) in cerebral small vessel disease (CSVD), via Monte Carlo simulations of magnetic susceptibility imaging and a novel imaging marker called the Expected Iron Coefficient (EIC).MethodsA synthetic pathological model of a different number of impenetrable spheres at random locations was employed to represent pathological iron deposition. The diffusion process was simulated with a Monte Carlo method with adjustable parameters to manipulate sphere size, distribution, and extracellular properties. Quantitative susceptibility mapping (QSM) was performed in a clinical dataset to study CSVD to derive and evaluate QSM, R2*, the iron microenvironment coefficient (IMC), and EIC in the presence of WMHs.ResultsThe simulations show that QSM signals increase in the presence of increased tissue iron, confirming that the EIC increases with pathology. Clinical results demonstrate that while QSM, R2*, and the IMC do not show differences in brain iron, the EIC does in the context of CSVD.ConclusionThe EIC is more sensitive to subtle changes in brain iron deposition caused by pathology, even when QSM, R2*, and the IMC do not.

MiR-202-5p is identified as the maker microRNA (miRNA) of germplasm in fish. However, the role of miR-202-5p in gonadal development is still unclear. Here we investigated the expression patterns of miR-202-5p in Japanese flounder (Paralichthys olivaceus). Real-time PCR displayed that miR-202-5p was specifically expressed in bisexual gonads, and its transcription in the testis was relatively abundant than that in the ovary. Moreover, it was gradually increased in testis from stage II to stage IV. Fluorescent in situ hybridization (FISH) illustrated that miR-202-5p was co-localized with vasa (a marker gene of germ cells) in testis, and it was predominately expressed in spermatogonia and spermatocytes, implying that miR-202-5p might participate in spermatogenesis. Considering the important role of retinoic acid (RA) on regulating meiosis during spermatogenesis, we treated Japanese flounders by injecting all-trans retinoic acid (ATRA). MiR-202-5p in testis was shown to be up-regulated, and ccnd1, a key cell cycle regulator, was found to be down-regulated after ATRA treatment. Furthermore, ccnd1 was demonstrated to be a direct regulatory target of miR-202-5p using Dual-luciferase assay. In the primary testis cell from Japanese flounder, we further confirmed that ccnd1 was down-regulated by miR-202-5p. The results suggest that miR-202-5p exerts a crucial role in gonadal development by inhibiting ccnd1 in Japanese flounder.

Statement of problem The crystallization process of lithium disilicate crowns has been reported to cause dimensional change, but whether the fit of chairside computer-aided design and computer-aided manufactured (CAD-CAM) zirconia-reinforced lithium silicate crowns is affected is unclear. Purpose The purpose of this in vitro study was to evaluate with a 3-dimensional superimposition analysis technique the marginal and internal adaptation of fully crystallized versus partially crystallized zirconia-reinforced lithium silicate ceramic CAD-CAM fabricated crowns. Additionally, the silicone replica technique and direct viewing of marginal gap values were compared with the 3-dimensional superimposition analysis technique. Material and methods The marginal and internal adaptation of a fully crystallized zirconia-reinforced lithium silicate (CELTRA DUO) were compared with those of a partially crystallized zirconia-reinforced lithium silicate (VITA SUPRINITY) after crystallization. Sixteen crowns (n=8) were fabricated with a chairside CAD-CAM system. The crowns and die and crown assembly were scanned with an optical scanner for the 3-dimensional superimposition analysis. Four hundred sixty-eight measurements were made for each crown, 78 in each 2-dimensional section. Marginal discrepancy was measured by using the direct viewing technique. The internal adaptation of the shoulder area, axial space, and occlusal space was measured by using the silicone replica technique. Both gap values were compared with the 3-dimensional superimposition analysis results by using the independent t test. The 2-way ANOVA was used to detect the effect of each variable (group and site) (α=.05). Results The VITA SUPRINITY crowns showed statistically higher marginal discrepancy values than the CELTRA DUO crowns in both 3-dimensional superimposition analysis and the direct viewing method, and the lingual aspect recorded the highest marginal discrepancy mean value when compared with other aspects. The 3-dimensional superimposition analysis and the direct viewing method were statistically similar (P=.076). The VITA SUPRINTY crowns showed higher internal gap mean values than the CELTRA DUO crowns in both 3-dimensional superimposition analysis and silicone replica techniques. The occlusal space recorded the highest mean value in both groups. Assessment by 3-dimensional superimposition analysis and silicone replica techniques showed statistical difference in internal gap values (P=.04). Conclusions CELTRA DUO showed better precision fit values than VITA SUPRINITY. Three-dimensional superimposition analysis is a reliable method of evaluating marginal and internal adaptation.

Summary Objectives The understanding of vocal fold hydration state, including dehydrated, euhydrated, rehydrated tissue, and how hydration affects vocal fold biomechanical properties is still evolving. Although clinical observations support the benefits of increasing vocal fold hydration after dehydrating events, more mechanistic information on the effects of vocal fold dehydration and the beneficial effects of rehydration are needed. Alterations to hyaluronic acid (HA), an important component of the vocal fold extracellular matrix, are likely to influence the biomechanical properties of vocal folds. In this study, we investigated the influence of hydration state and HA on vocal fold tissue stiffness via biomechanical testing. Study design Prospective, ex vivo study design. Methods Fresh porcine vocal folds (N = 18) were examined following sequential immersion in hypertonic (dehydration) and isotonic solutions (rehydration). In a separate experiment, vocal folds were incubated in hyaluronidase (Hyal) to remove HA. Control tissues were not exposed to any challenges. A custom micromechanical system with a microforce sensing probe was used to measure the force-displacement response. Optical strain was calculated, and ultrasound imaging was used to measure tissue cross-sectional area to obtain stress-strain curves. Results Significant increases (P ≤ 0.05) were found in tangent moduli between dehydrated and rehydrated vocal folds at strains of e = 0.15. The tangent moduli of Hyal-digested tissues significantly increased at both e = 0.15 and 0.3 (P ≤ 0.05). Conclusion Vocal fold dehydration increased tissue stiffness and rehydration reduced the stiffness. Loss of HA increased vocal fold stiffness, suggesting a potential mechanical role for HA in euhydrated vocal folds.

PURPOSE To present a new technique to treat refractory retinal detachment secondary to optic disc pit. METHODS An interventional case report. RESULTS A 25-year-old man with congenital optic disc pit had two failed vitrectomies involving laser around the optic disc, internal limiting membrane peel and flap to plug the disc pit, and gas tamponade to reattach the retina. With all options running out, a further vitrectomy with autologous retinal transplant and silicone oil tamponade was carried out to treat the refractory serous retinal detachment; the silicone oil was removed at 6 weeks after the last procedure. The retina remained successfully attached at 6 months post-surgery with the patient maintaining his baseline visual acuity. CONCLUSION The use of autologous retinal transplant is a new approach to treat refractory retinal detachment secondary to congenital optic disc anomalies, and adds to our options of dealing with this complex condition when first-line approaches have failed.

The hydrate morphology in sandy methane hydrate (MH)-bearing sediment (MHBS) is commonly classified as pore-filling, cementation, grain-coating and load-bearing. This paper presents a numerical investigation into the mechanical behaviour of coexistence-type MHBS using the discrete-element method (DEM). The coexistence type is represented as a combination of pore-filling and cementation types. For MHBS with a given MH saturation (S MH), the relative content of pore-filling and cementation is characterised by the cement ratio λ (λ = 0 means pure pore-filling and λ = 1 means pure cementation). A series of drained triaxial compression tests is simulated, and micromechanical variables such as bond breakage are examined. The results show that (a) the strength and dilatancy of the coexistence-type MHBS are higher when the cement ratio is larger. The normalised strength and secant modulus increase linearly with the cement ratio. (b) When the cement ratio increases, the critical-state line on the mineral void ratio e cr–ln p′ projection shifts towards a higher position and the bond breakage ratio is larger. (c) The shear stress of the coexistence-type MHBS with cementation is affected by the MH generation process due to the MH bond breakages.