Differences in synthesis and absorption of cholesterol of two effective lipid-lowering therapies

Effective statin therapy is associated with a marked reduction of cardiovascular events. However, the explanation for full benefits obtained for LDL cholesterol targets by combined lipid-lowering therapy is controversial. Our study compared the effects of two equally effective lipid-lowering strategies on markers of cholesterol synthesis and absorption. A prospective, open label, randomized, parallel design study, with blinded endpoints, included 116 subjects. We compared the effects of a 12-week treatment with 40 mg rosuvastatin or the combination of 40 mg simvastatin/10 mg ezetimibe on markers of cholesterol absorption (campesterol and β-sitosterol), synthesis (desmosterol), and their ratios to cholesterol. Both therapies similarly decreased total and LDL cholesterol, triglycerides and apolipoprotein B, and increased apolipoprotein A1 (P < 0.05 vs baseline for all). Simvastatin/ezetimibe increased plasma desmosterol (P = 0.012 vs baseline), and decreased campesterol and β-sitosterol (P < 0.0001 vs baseline for both), with higher desmosterol (P = 0.007) and lower campesterol and β-sitosterol compared to rosuvastatin, (P < 0.0001, for both). In addition, rosuvastatin increased the ratios of these markers to cholesterol (P < 0.002 vs baseline for all), whereas simvastatin/ezetimibe significantly decreased the campesterol/cholesterol ratio (P = 0.008 vs baseline) and tripled the desmosterol/cholesterol ratio (P < 0.0001 vs baseline). The campesterol/cholesterol and β-sitosterol/cholesterol ratios were lower, whereas the desmosterol/cholesterol ratio was higher in patients receiving simvastatin/ezetimibe (P < 0.0001 vs rosuvastatin, for all). Pronounced differences in markers of cholesterol absorption and synthesis were observed between two equally effective lipid-lowering strategies.

Adrenomedullin and adrenotensin regulate collagen synthesis and proliferation in pulmonary arterial smooth muscle cells

To understand the pathophysiological mechanisms of pulmonary arterial smooth muscle cell (PASMC) proliferation and extracellular-matrix accumulation in the development of pulmonary hypertension and remodeling, this study determined the effects of different doses of adrenomedullin (ADM) and adrenotensin (ADT) on PASMC proliferation and collagen synthesis. The objective was to investigate whether extracellular signal-regulated kinase (ERK1/2) signaling was involved in ADM- and ADT-stimulated proliferation of PASMCs in 4-week-old male Wistar rats (body weight: 100-150 g, n=10). The proliferation of PASMCs was examined by 5-bromo-2-deoxyuridine incorporation. A cell growth curve was generated by the Cell Counting Kit-8 method. Expression of collagen I, collagen III, and phosphorylated ERK1/2 (p-ERK1/2) was evaluated by immunofluorescence. The effects of different concentrations of ADM and ADT on collagen I, collagen III, and p-ERK1/2 protein expression were determined by immunoblotting. We also investigated the effect of PD98059 inhibition on the expression of p-ERK1/2 protein by immunoblotting. ADM dose-dependently decreased cell proliferation, whereas ADT dose-dependently increased it; and ADM and ADT inhibited each other with respect to their effects on the proliferation of PASMCs. Consistent with these results, the expression of collagen I, collagen III, and p-ERK1/2 in rat PASMCs decreased after exposure to ADM but was upregulated after exposure to ADT. PD98059 significantly inhibited the downregulation by ADM and the upregulation by ADT of p-ERK1/2 expression. We conclude that ADM inhibited, and ADT stimulated, ERK1/2 signaling in rat PASMCs to regulate cell proliferation and collagen expression.

Cotransfected human chondrocytes: over-expression of IGF-I and SOX9 enhances the synthesis of cartilage matrix components collagen-II and glycosaminoglycans

Damage to cartilage causes a loss of type II collagen (Col-II) and glycosaminoglycans (GAG). To restore the original cartilage architecture, cell factors that stimulate Col-II and GAG production are needed. Insulin-like growth factor I (IGF-I) and transcription factor SOX9are essential for the synthesis of cartilage matrix, chondrocyte proliferation, and phenotype maintenance. We evaluated the combined effect of IGF-I and SOX9 transgene expression on Col-II and GAG production by cultured human articular chondrocytes. Transient transfection and cotransfection were performed using two mammalian expression plasmids (pCMV-SPORT6), one for each transgene. At day 9 post-transfection, the chondrocytes that were over-expressing IGF-I/SOX9 showed 2-fold increased mRNA expression of the Col-II gene, as well as a 57% increase in Col-II protein, whereas type I collagen expression (Col-I) was decreased by 59.3% compared with controls. The production of GAG by these cells increased significantly compared with the controls at day 9 (3.3- vs 1.8-times, an increase of almost 83%). Thus, IGF-I/SOX9 cotransfected chondrocytes may be useful for cell-based articular cartilage therapies.

Synthesis of Short Oligonucleotides on a Soluble Support by the Phosphoramidite Method

In the last decades, the chemical synthesis of short oligonucleotides has become an important aspect of study due to the discovery of new functions for nucleic acids such as antisense oligonucleotides (ASOs), aptamers, DNAzymes, microRNA (miRNA) and small interfering RNA (siRNA). The applications in modern therapies and fundamental medicine on the treatment of different cancer diseases, viral infections and genetic disorders has established the necessity to develop scalable methods for their cheaper and easier industrial manufacture. While small scale solid-phase oligonucleotide synthesis is the method of choice in the field, various challenges still remain associated with the production of short DNA and RNA-oligomers in very large quantities. On the other hand, solution phase synthesis of oligonucleotides offers a more predictable scaling-up of the synthesis and is amenable to standard industrial manufacture techniques. In the present thesis, various protocols for the synthesis of short DNA and RNA oligomers have been studied on a peracetylated and methylated β-cyclodextrin, and also on a pentaerythritol-derived support. On using the peracetylated and methylated β-cyclodextrin soluble supports, the coupling cycle was simplified by replacement of the typical 5′-O-(4,4′-dimethoxytrityl) protecting group with an acid-labile acetal-protected 5′-O-(1-methoxy-1-methylethyl) group, which upon acid-catalyzed methanolysis released easily removable volatile products. For this reason monomeric building blocks 5′-O-(1-methoxy-1-methylethyl) 3′-(2-cyano-ethyl-N,N-diisopropylphosphoramidite) were synthesized. Alternatively, on using the precipitative pentaerythritol support, novel 2´-O-(2-cyanoethyl)-5´-O-(1-methoxy-1-methylethyl) protected phosphoramidite building blocks for RNA synthesis have been prepared and their applicability by the synthesis of a pentamer was demonstrated. Similarly, a method for the preparation of short RNAs from commercially available 5´-O-(4,4´-dimethoxytrityl)-2´-O-(tert-butyldimethyl-silyl)ribonucleoside 3´-(2-cyanoethyl-N,N-diisopropylphosphoramidite) building blocks has been developed

Enzymatic Synthesis, Recovery, and Purification of Ethyl β-ᴅ-glucopyranoside

A method to synthesize ethyl β-ᴅ-glucopyranoside (BEG) was searched. Feasibility of different ion exchange resins was examined to purify the product from the synthetic binary solution of BEG and glucose. The target was to produce at least 50 grams of 99 % pure BEG with a scaled up process. Another target was to transfer the batch process into steady-state recycle chromatography process (SSR). BEG was synthesized enzymatically with reverse hydrolysis utilizing β-glucosidase as a catalyst. 65 % of glucose reacted with ethanol into BEG during the synthesis. Different ion exchanger based resins were examined to separate BEG from glucose. Based on batch chromatography experiments the best adsorbent was chosen between styrene based strong acid cation exchange resins (SAC) and acryl based weak acid cation exchange resins (WAC). CA10GC WAC resin in Na+ form was chosen for the further separation studies. To produce greater amounts of the product the batch process was scaled up. The adsorption isotherms for the components were linear. The target purity was possible to reach already in batch without recycle with flowrate and injection size small enough. 99 % pure product was produced with scaled-up batch process. Batch process was transferred to SSR process utilizing the data from design pulse chromatograms and Matlab simulations. The optimal operating conditions for the system were determined. Batch and SSR separation results were compared and by using SSR 98 % pure products were gained with 40 % higher productivity and 40 % lower eluent consumption compared to batch process producing as pure products.

Genetic variability for synthesis of bioactive compounds in peppers (Capsicum annuum) from Brazil

AbstractThe objective of this study was to evaluate the genetic variability for synthesis of bioactive compounds in pepper (Capsicum annuum, Solanaceae). Total phenolics, anthocyanins, carotenoids and antioxidant activity were evaluated in 14 accessions of Capsicum annuum from the Capsicum Genebank of Embrapa Temperate Agriculture (Pelotas – RS, Brazil). Thirty plants of each accession were cultivated in the field during spring and summer. The experimental design was a complete randomized block with 14 treatments (accessions) and three replications. The laboratory evaluations followed the same experimental design to field, but with two repetitions more. Seeds were discarded and opposite longitudinal portions of fruits were manually prepared for chemical analyzes. The data obtained showed high genetic variability for phenolics, anthocyanins, carotenoids and antioxidant activity. The P39, P77, P119, P143 and P302 accessions exhibited the highest levels of antioxidants, which are strongly indicated to be used in breeding programs of Capsicum peppers.

Blue and Uv-Emitting Upconversion Nanoparticles: Synthesis and (Bio) Analytical Applications.

Rare-earth based upconverting nanoparticles (UCNPs) have attracted much attention due to their unique luminescent properties. The ability to convert multiple photons of lower energy to ones with higher energy through an upconversion (UC) process offers a wide range of applications for UCNPs. The emission intensities and wavelengths of UCNPs are important performance characteristics, which determine the appropriate applications. However, insufficient intensities still limit the use of UCNPs; especially the efficient emission of blue and ultraviolet (UV) light via upconversion remains challenging, as these events require three or more near-infrared (NIR) photons. The aim of the study was to enhance the blue and UV upconversion emission intensities of Tm3+ doped NaYF4 nanoparticles and to demonstrate their utility in in vitro diagnostics. As the distance between the sensitizer and the activator significantly affect the energy transfer efficiency, different strategies were explored to change the local symmetry around the doped lanthanides. One important strategy is the intentional co-doping of active (participate in energy transfer) or passive (do not participate in energy transfer) impurities into the host matrix. The roles of doped passive impurities (K+ and Sc3+) in enhancing the blue and UV upconversions, as well as in influencing the intense UV upconversion emission through excess sensitization (active impurity) were studied. Additionally, the effects of both active and passive impurity doping on the morphological and optical performance of UCNPs were investigated. The applicability of UV emitting UCNPs as an internal light source for glucose sensing in a dry chemistry test strip was demonstrated. The measurements were in agreement with the traditional method based on reflectance measurements using an external UV light source. The use of UCNPs in the glucose test strip offers an alternative detection method with advantages such as control signals for minimizing errors and high penetration of the NIR excitation through the blood sample, which gives more freedom for designing the optical setup. In bioimaging, the excitation of the UCNPs in the transparent IR region of the tissue permits measurements, which are free of background fluorescence and have a high signal-to-background ratio. In addition, the narrow emission bandwidth of the UCNPs enables multiplexed detections. An array-in-well immunoassay was developed using two different UC emission colours. The differentiation between different viral infections and the classification of antibody responses were achieved based on both the position and colour of the signal. The study demonstrates the potential of spectral and spatial multiplexing in the imaging based array-in-well assays.

Synthesis and characterization of nanoperforated metal oxide thin films

For advanced devices in the application fields of data storage, solar cell and biosensing, one of the major challenges to achieve high efficiency is the fabrication of nanopatterned metal oxide surfaces. Such surfaces often require both precise structure at the nanometer scale and controllable patterned structure at the macro scale. Nowadays, the dominating candidates to fabricate nanopatterned surfaces are the lithographic technique and block-copolymer masks, most of which are unfortunately costly and inefficient. An alternative bottom-up approach, which involves organic/inorganic self-assembly and dip-coating deposition, has been studied intensively in recent years and has proven to be an effective technique for the fabrication of nanoperforated metal oxide thin films. The overall objective of this work was to optimize the synthesis conditions of nanoperforated TiO2 (NP-TiO2) thin films, especially to be compatible with mixed metal oxide systems. Another goal was to develop fabrication and processing of NP-TiO2 thin films towards largescale production and seek new applications for solar cells and biosensing. Besides the traditional dip-coating and drop-casting methods, inkjet printing was used to prepare thin films of metal oxides, with the advantage of depositing the ink onto target areas, further enabling cost-effective fabrication of micro-patterned nanoperforated metal oxide thin films. The films were characterized by water contact angle determination, Atomic Force Microscopy, Scanning Electron Microscopy, X-ray Photoelectron Spectroscopy and Grazing Incidence XRay Diffraction. In this study, well-ordered zinc titanate nanoperforated thin films with different Zn/Ti ratios were produced successfully with zinc precursor content up to 50 mol%, and the dominating phase was Zn2Ti3O8. NP-TiO2 structures were also obtained by a cost-efficient means, namely inkjet printing, at both ambient temperature and 60 °C. To further explore new biosensing applications of nanoperforated oxide thin films, inkjet printing was used for the fabrication of both continuous and patterned polymeric films onto NP-TiO2 and perfluorinated phosphate functionalized NP-TiO2 substrates, respectively. The NP-TiO2 films can be also functionalized with a fluoroalkylsilane, resulting in hydrophobic surfaces on both titania and silica. The surface energy contrast in the nanoperforations can be tuned by irradiating the films with UV light, which provides ideal model systems for wettability studies.

Power and Performance Management Strategies on NoC-Based Multicore Platforms, Using DVFS, Adaptive Algorithm and Task Parallelism

This work presents synopsis of efficient strategies used in power managements for achieving the most economical power and energy consumption in multicore systems, FPGA and NoC Platforms. In this work, a practical approach was taken, in an effort to validate the significance of the proposed Adaptive Power Management Algorithm (APMA), proposed for system developed, for this thesis project. This system comprise arithmetic and logic unit, up and down counters, adder, state machine and multiplexer. The essence of carrying this project firstly, is to develop a system that will be used for this power management project. Secondly, to perform area and power synopsis of the system on these various scalable technology platforms, UMC 90nm nanotechnology 1.2v, UMC 90nm nanotechnology 1.32v and UMC 0.18 μmNanotechnology 1.80v, in order to examine the difference in area and power consumption of the system on the platforms. Thirdly, to explore various strategies that can be used to reducing system’s power consumption and to propose an adaptive power management algorithm that can be used to reduce the power consumption of the system. The strategies introduced in this work comprise Dynamic Voltage Frequency Scaling (DVFS) and task parallelism. After the system development, it was run on FPGA board, basically NoC Platforms and on these various technology platforms UMC 90nm nanotechnology1.2v, UMC 90nm nanotechnology 1.32v and UMC180 nm nanotechnology 1.80v, the system synthesis was successfully accomplished, the simulated result analysis shows that the system meets all functional requirements, the power consumption and the area utilization were recorded and analyzed in chapter 7 of this work. This work extensively reviewed various strategies for managing power consumption which were quantitative research works by many researchers and companies, it's a mixture of study analysis and experimented lab works, it condensed and presents the whole basic concepts of power management strategy from quality technical papers.

Den Äldsta – livet är ett tillägnande : en vårdvetenskaplig explorativ studie av ett meningsbärande budskap och en innerlig visdom

In the background of the thematic The Eldest – life is acquiring one finds both previews and myths. Wisdom belongs to these myths. The hermeneutical philosophy refers to thinking as o movement from myth to logos in a dialogical oneness. The research uncovers dimensions in the element wisdom as empowered. The experiences of older are saved for further learning and transformation to younger with reference to vulnerable situations where common regulations are no more usefull. The interest goes to an Eldest. The Eldest in the study is pictorial in accordance to the main literature in the study.The Eldest is etymological, fictive and symbolic: – a man who understands higher matters of life, even Gods holy matters. She will set the fulfillment of others as the highest endowment out of an innermost ethos and an innermost wisdom. The innermost is wisdom. The aim is to discover a meaningful message in life is acquiring. In order to see and to learn from the experiences the study aim to uncover the innermost, an innermost wisdom out of a caritative approach. This innermost is anticipated as a longing for unity and health in dayly matters and in a caring ability for the other. The main overstatement is: What will this most meaningfull and innermost by the Eldest out of a living in factual life mirrored in a caring perspective be? Two questions expired; what will the meaningful message in the acquiring be? What will the innermost wisdom in serving the good be? This message and its innermost wisdom will get an expanded meaning out of a caring sentence: Man who dare – seeing back with gratitude, seeing forward in confidence, seeing aside with love and upward in fate wear that dignity, that holiness and that mercy and empathy which belong to life in its basics. The persons attending the research are situated in two contexts. One group has roots in the Lutheran church and the other in a caring profession. The datamaterial is formed out of the usages from these persons, from the spoken (conversation) and the written word (a guestbook). The usages as particular and common are continually integrated in the leading caring sentence from the beginning of the study to the end. The usages stand by the methodological for the final message and wisdom and at the same they form the operative dimension in the study, the evident and the validity. The overarching methodological approach is in the hermeneutic philosophy in accordance with the abductive logic. The usages out of two research groups are most significant in this deductive, inductive and abductive strategy. The usages from the research groups are confronted with the caring sentence in dialogical spaces, halts. The meaning and the innermost searched for will be pictured through the abductive and hermeneutic interpretation and will stand for an articulation of and a successively expansion of meaning. A twine of horizons out of the entire dissemination, the deductive and the inductive, creates the result, as the final message as the ground for an understanding of an even more embracing meaning in an innermost wisdom. The identified bearing movement in the groups in accordance with the caring sentence goes for something higher, something higher than me, to the wellbeing of the other. A conclusion is made and a thesis is identified. This thesis is out from the usages: What can I do in a creating of this caritative? An antithesis is also identified, is a man able to look outside one own and go to something higher, something greater? The synthesis is articulated as a dialogical movement from something … to something higher. The bridge could be maturation, transcendence, the divine or wisdom. The statement finds its root in the attending groups but a difference is also identified. This higher matter is different. The contexts and their meaningfulness decide. A final statement is: learn to see man and her matters hold in life.

Classificações de signos de C.S.Peirce: de ‘On the Logic of Science’ ao ‘Syllabus of Certain Topics of Logic’

As classificações dos signos de C.S.Peirce começam a ser desenvolvidas em 1865 e se estendem a até, pelo menos, 1909. Vou apresentar o período que tem início em 1865, e possui dois momentos de intensa produção - "On a New List of Categories" e "On the Algebra of Logic: a contribution to the philosophy of notation". Em seguida apresento as dez classes de signos, uma morfologia que aparece no "Syllabus of Certain Topics of Logic", e é desenvolvida a partir de 1903. Meu propósito aqui é familiarizar o leitor com as intrincadas classificações sígnicas de Peirce.

Mental Logic and the Denials of Conjunctions and Disjunctions

ABSTRACT: The mental models theory predicts that, while conjunctions are easier than disjunctions for individuals, when denied, conjunctions are harder than disjunctions. Khemlani, Orenes, and Johnson-Laird proved that this prediction is correct in their work of 2014. In this paper, I analyze their results in order to check whether or not they really affect the mental logic theory. My conclusion is that, although Khemlani et al.'s study provides important findings, such findings do not necessarily lead to questioning or to rejecting the mental logic theory.

Green diesel synthesis by hydrodeoxygenation of lipids extracted from Chlorella algae in supercritical hexane

Lipids were extracted from Chlorella algae with supercritical hexane. The high lipids yield of approximately 10% was obtained at optimum conditions of 300 rpm stirring speed and 2 h duration compared to the total contents of lipids being 12%. Furthermore, an easiness of hexane recovery may be considered as economically and ecologically attractive. For the first time, in the current work catalytic hydrodeoxygenation (HDO) of Chlorella algal lipids was studied over 5 wt% Ni/H-Y-80 and 5 wt% Ni/SiO2 at 300 C and under 30 bar total pressure in H2. A comparative HDO of stearic acid was carried out under similar conditions. The conversion of lipids was about 35% over 5 wt% Ni/H-Y-80 after 6h, whereas, 5 wt% Ni/SiO2 was totally deactivated after 60 min. The selectivity to hydrocarbons (C15-C18) is 6%. As a comparison, complete conversion of stearic acid over 5 wt% Ni/H-Y-80 was achieved in 6 h. The transformation of lipids proceeded mostly via hydrogenation and hydrolysis with formation of free fatty acid (FFA). The lower activity might be attributed to deactivation of catalysts caused by chlorophylls and carotenoids. Even though the conversion is low, future studies in HDO of lipids extracted from other algae species having higher lipid content could be proposed. Coke resistant catalyst might be considered to improve catalytic activity.