A pinch-based method for defining pressure manipulation routes in work and heat exchange networks

Aiming for more energetically efficient and sustainable solutions, academic attention to work and heat integration (WHI) has grown in the last decade. Simultaneous models for work and heat exchanger network (WHEN) synthesis often derive from heat integration (HI) frameworks. However, it can be noted that simultaneous optimization models for WHI are considerably more complex to solve than in the HI case. The design of efficient pressure manipulation routes (i.e., allocation and sizing of compression and expansion machinery) in process streams prior to heat exchange match allocation can make the optimization procedure more efficient. This work proposes a systematic procedure based on a model that employs Pinch Analysis concepts for defining these routes based on capital and operating cost targets. The solution approach is a hybrid meta-heuristic method based on Simulated Annealing (SA) and Particle Swarm Optimization (PSO). The obtained routes are then converted into a HI problem by fixing pressure manipulation unit sizes. The detailed HI solution is finally transferred into a WHI optimization model as initial design. In the two tackled examples, the total annual costs (TAC) predicted by the Pinch-based model differed by 0.5% and 1.2% from the final optimized WHEN obtained in the detailed WHI framework.The authors gratefully acknowledge the financial support from the Coordination for the Improvement of Higher Education Personnel – Processes 88887.360812/2019–00 and 88881.171419/2018–01 – CAPES (Brazil) and the National Council for Scientific and Technological Development – Processes 305055/2017–8, 428650/2018–0 and 311807/2018–6 – CNPq (Brazil)

Dermatan sulfate in tunicate phylogeny: Order-specific sulfation pattern and the effect of [→4IdoA(2-Sulfate)β-1→3GalNAc(4-Sulfate)β-1→] motifs in dermatan sulfate on heparin cofactor II activity

After the publication of the work entitled "Dermatan sulfate in tunicate phylogeny: Order-specific sulfation pattern and the effect of [→4IdoA(2-Sulfate)β-1→3GalNAc(4-Sulfate)β-1→] motifs in dermatan sulfate on heparin cofactor II activity", by Kozlowski et al., BMC Biochemistry 2011, 12:29, we found that the legends to Figures 2 to 5 contain serious mistakes that compromise the comprehension of the work. This correction article contains the correct text of the legends to Figures 2 to 5

Antitumor properties of a new non-anticoagulant heparin analog from the mollusk Nodipecten nodosus: Effect on P-selectin, heparanase, metastasis and cellular recruitment

Inflammation and cancer are related pathologies acting synergistically to promote tumor progression. In both, hematogenous metastasis and inflammation, P-selectin participates in interactions involving tumor cells, platelets, leukocytes and endothelium. Heparin has been shown to inhibit P-selectin and as a consequence it blunts metastasis and inflammation. Some heparin analogs obtained from marine invertebrates are P-selectin inhibitors and do not induce bleeding effects. The present work focuses on the P-selectin blocking activity of a unique heparan sulfate (HS) from the bivalve mollusk Nodipecten nodosus. Initially, we showed that the mollusk HS inhibited LS180 colon carcinoma cell adhesion to immobilized P-selectin in a dose-dependent manner. In addition, we demonstrated that this glycan attenuates leukocyte rolling on activated endothelium and inflammatory cell recruitment in thioglycollate-induced peritonitis in mice. Biochemical analysis indicated that the invertebrate glycan also inhibits heparanase, a key player in cell invasion and metastasis. Experimental metastasis of Lewis lung carcinoma cells was drastically attenuated by the mollusk HS through a mechanism involving inhibition of platelet-tumor-cell complex formation in blood vessels. These data suggest that the mollusk HS is a potential alternative to heparin for inhibiting P-selectin-mediated events such as metastasis and inflammatory cell recruitmen

Propiedades anticoagulantes de una fracción polisacárida de alto peso molecular (1000RS) del ascidian Microcosmus exasperatus

ABSTRACT: The anticoagulant effect and cytotoxicity of a high molecular weight polysaccharide fraction (1000RS) obtained from the tunic of the ascidia Microcosmus exasperatus were evaluated. Methods: Anticoagulant properties of 1000RS was evaluated by activated Partial Thromboplastin Time (aPTT), Thrombin Time (TT), Prothrombin Time (PT), anti-factor Xa and lupic anticoagulant (dRVVT) assays. Cytotoxicity was tested on murine hematopoietic cells using MTT assay. Results: This galactose rich fraction showed to be a potential anticoagulant due to its inhibitory effect on the intrinsic coagulation pathway. At the same time, anticoagulant doses of this fraction have no effect on cellular viability, which means that it can be used as a therapeutic agent. Conclusion: In vitro anticoagulant effect of 1000RS occurs at innocuous doses, however, it still need to be tested using in vivo models and its cytotoxicity evaluated in normal human cell lines.RESUMEN: El efecto anticoagulante y la citotoxicidad de una fracción de polisacáridos de alto peso molecular (1000RS), obtenida de la túnica de la ascidia Microcosmus exasperatus, fueron evaluados. Métodos: La actividad anticoagulante de 1000RS fue evaluada mediante los ensayos de tiempo de tromboplastina parcial activado (TTPa), tiempo de trombina (TT), tiempo de protrombina (TP), anti factor Xa y anticoagulante lúpico (dRVVT). La citotoxicidad sobre las células hematopoyéticas murinas fue evaluada usando el método del MTT. Resultados: Esta fracción rica en galactosa mostró ser un anticoagulante potencial debido a su efecto inhibidor de la vía intrínseca de la coagulación. Así mismo, las dosis anticoagulantes de esta fracción no afectan la viabilidad celular, lo cual ratifica su potencial como agente terapéutico. Conclusión: El efecto anticoagulante in vitro de 1000RS ocurre a dosis inocuas, sin embargo, éste debe ser evaluado en modelos in vivo, así como su citotoxicidad sobre células humanas normales

Non-Anticoagulant Heparan Sulfate from the Ascidian Phallusia nigra Prevents Colon Carcinoma Metastasis in Mice by Disrupting Platelet-Tumor Cell Interaction

Although metastasis is the primary cause of death in patients with malignant solid tumors, efficient anti-metastatic therapies are not clinically available currently. Sulfated glycosaminoglycans from marine sources have shown promising pharmacological effects, acting on different steps of the metastatic process. Oversulfated dermatan sulfates from ascidians are effective in preventing metastasis by inhibition of P-selectin, a platelet surface protein involved in the platelet-tumor cell emboli formation. We report in this work that the heparan sulfate isolated from the viscera of the ascidian Phallusia nigra drastically attenuates metastases of colon carcinoma cells in mice. Our in vitro and in vivo assessments demonstrate that the P. nigra glycan has very low anticoagulant and antithrombotic activities and a reduced hypotension potential, although it efficiently prevented metastasis. Therefore, it may be a promising candidate for the development of a novel anti-metastatic drug

Fucosylated Chondroitin Sulfate Inhibits Plasmodium Falciparum Cytoadhesion And Merozoite Invasion.

Sequestration of Plasmodium falciparum-infected erythrocytes (Pf-iEs) in the microvasculature of vital organs plays a key role in the pathogenesis of life-threatening malaria complications, such as cerebral malaria and malaria in pregnancy. This phenomenon is marked by the cytoadhesion of Pf-iEs to host receptors on the surfaces of endothelial cells, on noninfected erythrocytes, and in the placental trophoblast; therefore, these sites are potential targets for antiadhesion therapies. In this context, glycosaminoglycans (GAGs), including heparin, have shown the ability to inhibit Pf-iE cytoadherence and growth. Nevertheless, the use of heparin was discontinued due to serious side effects, such as bleeding. Other GAG-based therapies were hampered due to the potential risk of contamination with prions and viruses, as some GAGs are isolated from mammals. In this context, we investigated the effects and mechanism of action of fucosylated chondroitin sulfate (FucCS), a unique and highly sulfated GAG isolated from the sea cucumber, with respect to P. falciparum cytoadhesion and development. FucCS was effective in inhibiting the cytoadherence of Pf-iEs to human lung endothelial cells and placenta cryosections under static and flow conditions. Removal of the sulfated fucose branches of the FucCS structure virtually abolished the inhibitory effects of FucCS. Importantly, FucCS rapidly disrupted rosettes at high levels, and it was also able to block parasite development by interfering with merozoite invasion. Collectively, these findings highlight the potential of FucCS as a candidate for adjunct therapy against severe malaria.581862-7

Marine biotechnology in Brazil : recent developments and its potential for innovation

Marine biotechnology is an emerging field in Brazil and includes the exploration of marine microbial products, aquaculture, omics, isolation of biologically active compounds, identification of biosynthetic gene clusters from symbiotic microorganisms, investigation of invertebrate diseases caused by potentially pathogenic marine microbes, and development of antifouling compounds. Furthermore, the field also encompasses description of new biological niches, current threats, preservation strategies as well as its biotechnological potential. Finally, it is important to depict some of the major approaches and tools being employed to such end. To address the challenges of marine biotechnology, the Brazilian government, through the Ministry of Science, Technology, Innovation, and Communication, has established the National Research Network in Marine Biotechnology (BiotecMar) (www.biotecmar.sage.coppe.ufrj.br). Its main objective is to harness marine biodiversity and develop the marine bioeconomy through innovative research

The catalytic mechanism of glyceraldehyde 3-phosphate dehydrogenase from Trypanosoma cruzi elucidated via the QM/MM approach

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been identified as a key enzyme involved in glycolysis processes for energy production in the Trypanosoma cruzi parasite. This enzyme catalyses the oxidative phosphorylation of glyceraldehyde 3-phosphate (G3P) in the presence of inorganic phosphate (Pi) and nicotinamide adenosine dinucleotide (NAD+). The catalytic mechanism used by GAPDH has been intensively investigated. However, the individual roles of Pi and the C3 phosphate of G3P (Ps) sites, as well as some residues such as His194 in the catalytic mechanism, remain unclear. In this study, we have employed Molecular Dynamics (MD) simulations within hybrid quantum mechanical/molecular mechanical (QM/MM) potentials to obtain the Potential of Mean Force of the catalytic oxidative phosphorylation mechanism of the G3P substrate used by GAPDH. According to our results, the first stage of the reaction (oxidoreduction) takes place in the Pi site (energetically more favourable), with the formation of oxyanion thiohemiacetal and thioacylenzyme intermediates without acidbase assistance of His194. Analysis of the interaction energy by residues shows that Arg249 has an important role in the ability of the enzyme to bind the G3P substrate, which interacts with NAD+ and other important residues, such as Cys166, Glu109, Thr167, Ser247 and Thr226, in the GAPDH active site. Finally, the inhibition mechanism of the GAPDH enzyme by the 3-(p-nitrophenoxycarboxyl)-3-ethylene propyl dihydroxyphosphonate inhibitor was investigated in order to contribute to the design of new inhibitors of GAPDH from Trypanosoma cruzi

Diversidade de polissacarídeos sulfatados peculiares em ascidias

BV UNIFESP: Teses e dissertaçõe

Structure and anticoagulant properties of sulfated glycosaminoglycans from primitive Chordates

Dermatan sulfates and heparin, similar to the mammalian glycosaminoglycans, but with differences in the degree and position of sulfation were previously isolated from the body of the ascidian Styela plicata and Ascidia nigra. These differences produce profound effects on their anticoagulant properties. S. plicata dermatan sulfate composed by 2-O-sulfatedalpha-L-iduronic acid and 4-O-sulfated N-acetyl-beta-D-galactosamine residues is a potent anticoagulant due to a high heparin cofactor II activity. Surprisingly, it has a lower potency to prevent thrombus formation on an experimental model and a lower bleeding effect in rats than the mammalian dermatan sulfate. In contrast, A. nigra dermatan sulfate, also enriched in 2-O-sulfated alpha-L-iduronic acid, but in this case sulfated at O-6 of the N-acetyl-beta-D-galactosamine units, has no in vitro or in vivo anticoagulant activity, does not prevent thrombus formation but shows a bleeding effect similar to the mammalian glycosaminoglycan. Ascidian heparin, composed by 2-O-sulfated alpha-L-iduronic acid, N- and 6-O-sulfated glucosamine (75%) and alpha-L-iduronic acid, N- and 6-O-sulfated glucosamine (25%) disaccharide units has an anticoagulant activity 10 times lower than the mammalian heparin, is about 20 times less potent in the inhibition of thrombin by antithrombin, but has the same heparin cofactor II activity as mammalian heparin