► Integrated R-DWC for the eco-efficient synthesis of FAME by FFA esterification. ► Optimal reactive-DWC design based on sequential quadratic programming (SPQ). ► Vapor methanol feed imperative for ...the process dynamics and efficient control. ► Singular value decomposition (SVD) used for inferential temperature control. ► Rigorous steady-state and dynamic simulations in Aspen Plus and Dynamics.
Reactive separation technologies were proposed recently for fatty acid methyl esters (FAME) production, providing significant benefits such as minimal capital and operating cost savings. One approach is to use a reactive dividing-wall column (R-DWC) for the biodiesel production process. However, since the R-DWC is designed for a quaternary reactive system – two reactants (one in excess) and two products – more difficulties concerning the process control may be expected considering the high degree of integration of the process.
This study is among the first to tackle the optimal design, dynamics and control of such an integrated unit and proposes an efficient control structure for a biodiesel process based on reactive DWC technology. AspenTech Aspen Plus and Aspen Dynamics were used as computer aided process engineering (CAPE) tools to perform the rigorous steady-state and dynamic simulations, as well as the optimization of the new R-DWC based biodiesel process. A key finding of this study is that it is imperative to use a vapor feed of alcohol in order to reach the product specifications. Singular value decomposition (SVD) was used to determine the sensitive trays for inferential temperature control. The control structure proposed here demonstrates the excellent performance of the system in the case of industrially relevant disturbances such as production rate changes or catalyst deactivation.
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GEOZS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Reactive distillation (RD) is a great process intensification concept taking advantage of the synergy created when combining (catalyzed) reaction and separation into a single unit, which allows the ...concurrent production and removal of products. This feat improves the productivity and selectivity, reduces the energy usage, eliminates the need for solvents, and leads to highly-efficient systems with improved sustainability metrics (e.g. less waste and emissions). This paper provides an overview of the key features of RD processes, with emphasis on novel catalytic/reactive distillation processes that can make a difference at large scale and pave the way for a more sustainable chemical process industry that is more profitable, safer and less polluting. These examples include the production of: acrylic and methacrylic monomers, unsaturated polyesters resins, di-alkyl ethers, fatty esters, as well as other short alkyl esters (e.g. by enzymatic reactive distillation). The main drivers for such new RD applications are:
economical
(large reduction of costs and energy use),
environmental
(lower CO
2
emissions, no or reduced waste) and
social
(improved safety and health due to lower reactive content, reduced footprint and run away sensitivity). Hence RD technology strongly contributes to all three pillars of sustainability in the chemical process industry. Nonetheless, the potential of RD technology has not been fully tapped yet, and there is still undergoing research to improve it further by various means: e.g. ultrasound or microwave assisted RD, use of high-gravity fields (HiGee), internally heat integration, cyclic operation, or coupling RD with other operations such as membrane separations.
Aims
Vagal nerve stimulation (VNS) protects from myocardial and vascular injury following myocardial ischaemia and reperfusion (IR) via a mechanism involving activation of alpha‐7 nicotinic ...acetylcholine receptor (α7 nAChR) and reduced inflammation. Arginase is involved in development of myocardial IR injury driven by inflammatory mediators. The aim of the study was to clarify whether VNS downregulates myocardial and vascular arginase via a mechanism involving activation of α7 nAChR following myocardial IR.
Methods
Anaesthetized rats were randomized to (i) sham‐operated, (ii) control IR (30‐min ischaemia and 2‐h reperfusion, (iii) VNS throughout IR, (iv) the arginase inhibitor nor‐NOHA+IR, (v) nor‐NOHA+VNS+IR, (vi) selective α7 nAChR blockade by methyllycaconitine (MLA) followed by VNS throughout IR and (vii) MLA+IR.
Results
Infarct size was reduced by VNS compared to control IR (41 ± 3% vs. 67 ± 2% of the myocardium at risk, P < 0.001). Myocardial IR increased myocardial and aortic arginase activity 1.7‐ and 3.1‐fold respectively (P < 0.05). VNS attenuated the increase in arginase activity compared to control IR both in the myocardium and aorta (P < 0.05). MLA partially abolished the cardioprotective effect of VNS and completely abrogated the effect of VNS on arginase activity. Arginase inhibition combined with VNS did not further reduce infarct size.
Conclusion
Vagal nerve stimulation reduced infarct size and reversed the upregulation of arginase induced by IR both in the myocardium and aorta via a mechanism depending on α7 nAChR activation. The data suggest that the cardioprotective effect of VNS is mediated via reduction in arginase activity.
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DOBA, FSPLJ, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The basal lamina (BM) contains numerous components with a predominance of type IV collagens. Clinical manifestations associated with mutations of the human COL4A1 gene include perinatal cerebral ...hemorrhage and porencephaly, hereditary angiopathy, nephropathy, aneurysms and muscle cramps (HANAC), ocular dysgenesis, myopathy, Walker–Warburg syndrome and systemic tissue degeneration. In Drosophila, the phenotype associated with dominant temperature sensitive mutations of col4a1 include severe myopathy resulting from massive degradation of striated muscle fibers, and in the gut, degeneration of circular visceral muscle cells and epithelial cells following detachment from the BM. In order to determine the consequences of altered BM functions due to aberrant COL4A1 protein, we have carried out a series of tests using DrosophilaDTS-L3 mutants from our allelic series of col4a1 mutations with confirmed degeneration of various cell types and lowest survival rate among the col4a1 mutant lines at restrictive temperature. Results demonstrated epithelial cell degeneration in the gut, shortened gut, enlarged midgut with multiple diverticulae, intestinal dysfunction and shortened life span. Midgut immunohistochemistry analyses confirmed altered expression and distribution of BM components integrin PSI and PSII alpha subunits, laminin gamma 1, and COL4A1 both in larvae and adults. Global gene expression analysis revealed activation of the effector AMP genes of the primary innate immune system including Metchnikowin, Diptericin, DiptericinB, and edin that preceded morphological changes. Attacin::GFP midgut expression pattern further supported these changes. An increase in ROS production and changes in gut bacterial flora were also noted and may have further enhanced an immune response. The phenotypic features of Drosophila col4a1 mutants confirmed an essential role for type IV collagen in maintaining epithelial integrity, gut morphology and intestinal function and suggest that aberrant structure and function of the COL4A1 protein may also be a significant factor in modulating immunity.
TUNEL-positive nuclei in the midgut of the col4a1DTS-L3 temperature-sensitive mutant (A) compared with wild-type animals (B); antimicrobial peptide overexpression in the mutant while wild-type animals are underexressing upon heat-shock (B); intestinal dysfunction demonstrated by the leakage of the food dye into hemolymph (E) compared with wild-type animals (D). Display omitted
•col4a1 mutations in Drosophila cause gut epithelial cell degeneration.•Midgut enlargement, diverticulae, intestinal dysfunction and shortened life span•Increase oxidant production and altered gut bacterial flora•Activate of effector genes of the innate immune system•Degraded basement membrane is a factor in modulating immunity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
High expression of the androgen receptor (AR) and the disruption of its regulation are strongly responsible for the development of prostate cancer (PCa). Therapeutically relevant non-steroidal or ...steroidal antiandrogens are able to block the AR effect by eliminating AR-mediated signalling. Herein we report the synthesis of novel steroidal pyrazoles derived from the natural sex hormone 5α-dihydrotestosterone (DHT). 2-Ethylidene or 2-(hetero)arylidene derivatives of DHT obtained by regioselective Claisen-Schmidt condensation with acetaldehyde or (hetero)aromatic aldehydes in alkaline ethanol were reacted with monosubstituted hydrazines to give A-ring-fused 1,5-disubstituted pyrazoles as main or exclusive products, depending on the reaction conditions applied. Spontaneous or 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ)-induced oxidation of the primarily formed pyrazolines resulted in the desired products in moderate to good yields, while 17-oxidation also occurred by using the Jones reagent as a strong oxidant. Transcriptional activity of the AR in a reporter cell line was examined for all novel compounds, and several previously synthesized similar DHT-based pyrazoles with differently substituted heteroring were also included to obtain information about the structure-activity relationship. Two specific regioisomeric groups of derivatives significantly diminished the transcriptional activity of the AR in reporter cell line in 10 μM concentration, and displayed reasonable antiproliferative activity in AR-positive PCa cell lines. Lead compound (3d) was found to be a potent AR antagonist (IC50 = 1.18 μM), it generally suppressed AR signalling in time and dose dependent manner, moreover, it also led to a sharp decrease in wt-AR protein level probably caused by proteasomal degradation. We confirmed the antiproliferative activity of 3d in AR-positive PCa cell lines (with GI50 in low micromolar ranges), and its cellular, biochemical and in silico binding in AR ligand-binding domain. Moreover, compound 3d was shown to be potent even ex vivo in patient-derived tissues, which highlights the therapeutic potential of A-ring-fused pyrazoles.
Display omitted
•A-ring-fused pyrazoles of 5α-dihydrotestosterone were introduced as AR modulators.•SAR study of 55 differently substituted derivatives was discussed.•Compound 3d suppressed the expression of AR targets in prostate cell lines.•Compound 3d caused AR degradation in time-dependent manner.•Ex vivo activity of 3d was demonstrated in patient-derived explants.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Conventional ternary separations progressed via thermally coupled columns such as Petlyuk configuration to a novel design that integrates two distillation columns into one shella setup known today ...as dividing-wall column (DWC). The DWC concept is a major breakthrough in distillation technology, as it brings significant reduction in the capital invested as well as savings in the operating costs. However, the integration of two columns into one shell leads also to changes in the operating mode and ultimately in the controllability of the system. Although much of the literature focuses on the control of binary distillation columns, there are just a few studies on the controllability of DWC. In this work we explore the DWC control issues and make a comparison of various control strategies based on PID loops, within a multiloop framework (DB/LSV, DV/LSB, LB/DSV, LV/DSB) versus more advanced controllers such as LQG/LQR, GMC, and high order controllers obtained by H∞ controller synthesis and μ-synthesis. The controllers are applied to a dividing-wall column used in an industrial case studythe ternary separation of benzene−toluene−xylene. The performances of these control strategies and the dynamic response of the DWC is investigated in terms of product composition and flow rates, for various persistent disturbances in the feed flow rate and composition. Significantly shorter settling times can be achieved using the advanced controllers based on LQG/LQR, H∞ controller synthesis, and μ-synthesis.
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IJS, KILJ, NUK, PNG, UL, UM
Communication between health care provider and patients in oncology presents challenges. Communication skills training have been frequently developed to address those. Given the complexity of ...communication training, the choice of outcomes and outcome measures to assess its effectiveness is important. The aim of this paper is to 1) perform a systematic review on outcomes and outcome measures used in evaluations of communication training, 2) discuss specific challenges and 3) provide recommendations for the selection of outcomes in future studies.
To identify studies and reviews reporting on the evaluation of communication training for health care professionals in oncology, we searched seven databases (Ovid MEDLINE, CENTRAL, CINAHL, EMBASE, PsychINFO, PsychARTICLES and Web of Science). We extracted outcomes assessed and the respective assessment methods. We held a two-day workshop with experts (n = 16) in communication theory, development and evaluation of generic or cancer-specific communication training and/or outcome measure development to identify and address challenges in the evaluation of communication training in oncology. After the workshop, participants contributed to the development of recommendations addressing those challenges.
Out of 2181 references, we included 96 publications (33 RCTs, 2 RCT protocols, 4 controlled trials, 36 uncontrolled studies, 21 reviews) in the review. Most frequently used outcomes were participants' training evaluation, their communication confidence, observed communication skills and patients' overall satisfaction and anxiety. Outcomes were assessed using questionnaires for participants (57.3%), patients (36.0%) and observations of real (34.7%) and simulated (30.7%) patient encounters. Outcomes and outcome measures varied widely across studies. Experts agreed that outcomes need to be precisely defined and linked with explicit learning objectives of the training. Furthermore, outcomes should be assessed as broadly as possible on different levels (health care professional, patient and interaction level).
Measuring the effects of training programmes aimed at improving health care professionals' communication skills presents considerable challenges. Outcomes as well as outcome measures differ widely across studies. We recommended to link outcome assessment to specific learning objectives and to assess outcomes as broadly as possible.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The development, construction, and first commissioning results of a new scanning microscope installed at the 5‐ID Submicron Resolution X‐ray Spectroscopy (SRX) beamline at NSLS‐II are reported. The ...developed system utilizes Kirkpatrick–Baez mirrors for X‐ray focusing. The instrument is designed to enable spectromicroscopy measurements in 2D and 3D with sub‐200 nm spatial resolution. The present paper focuses on the design aspects, optical considerations, and specifics of the sample scanning stage, summarizing some of the initial commissioning results.
The development and initial commissioning of a new Kirkpatrick–Baez‐based scanning microscope installed at the Submicron Resolution X‐ray Spectroscopy beamline at NSLS‐II are reported.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Few projects adequately address design and evaluation
Payments for Ecosystem Services (PES) mechanisms leverage economic and social incentives to shape how people influence natural processes and ...achieve conservation and sustainability goals. Beneficiaries of nature's goods and services pay owners or stewards of ecosystems that produce those services, with payments contingent on service provision (
1
,
2
). Integrating scientific knowledge and methods into PES is critical (
3
,
4
). Yet many projects are based on weak scientific foundations, and effectiveness is rarely evaluated with the rigor necessary for scaling up and understanding the importance of these approaches as policy instruments and conservation tools (
2
,
5
,
6
). Part of the problem is the lack of simple, yet rigorous, scientific principles and guidelines to accommodate PES design and guide research and analyses that foster evaluations of effectiveness (
4
). As scientists and practitioners from government, nongovernment, academic, and finance institutions, we propose a set of such guidelines and principles.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK