bluuebunny/crossref_metadata_2025 huggingface dataset:
Completion and Stimulation Design of the First Offshore Acid Fractured Multistage Dual Lateral Well
Authors: Oberhofer R.. , Hoffmann S.. , Norris M. R. , Airnes J.. , Bramald J. A.
Published: October 2018

A North Sea case study detailing the completion and stimulation design of the world's first offshore acid fractured multistage dual lateral will be presented.

The key driver behind this subsea completion technology and stimulation program was to implement a cost effective completion solution that reduced field development costs. The completion technology selected provided an economically viable and low-risk solution in an economically challenging hydrocarbon environment. The completion design was developed to access two separate carbonate gas reservoirs from a single main bore. The stimulation program for the two horizontal laterals was modeled using reservoir characteristics and key considerations. The stimulation program maximized resource efficiency by utilizing the fluid capacities available within one sailing of the stimulation vessel per lateral, totaling 28 acid fracture treatments.

This novel offshore acid fractured dual lateral was drilled, completed and stimulated within three months. The horizontal section of the motherbore was completed using a 14 stage openhole multistage completion solution in three days. To reduce time on location, the well was stimulated after reaching setting depth via a tie-back fracture string. The motherbore was stimulated with individual and distributed acid fracture treatment via sequential ball-activated sliding sleeves. Once operations were complete for the motherbore, a whipstock packer was set and the second horizontal wellbore (Leg 2) drilled. The E1 Leg 2 wellbore was completed in only two days using the same technology and setup as the motherbore. Once the bottomhole completion was set, Leg 2 was stimulated with 14 stages of acid fracture treatments, using the same sized ball-activated sliding sleeves as in the motherbore.

By implementing a flexible low cost completion solution and maximizing the resources available during stimulation, the world's first offshore acid fracture multistage dual lateral was successfully completed, requiring only one subsea wellhead and tree. The completion and stimulation program of this dual lateral project provided a high value solution to North Sea operations by minimizing time, resource utilization and expanding experience for future ventures.
Simulation, Design and Application of Acid+Proppant Stimulation in a Carbonate Reservoir
Authors: Smith Michael B , Deng Jia Yao , Sajid Bilal , Mokhtar Ahmed Anwar , Taramov Musa
Published: October 2018

The application of acid fracturing techniques to deeply buried carbonate reservoirs is often an attractive option due to acid's ability to penetrate/improve natural fracture production where a gel frac fluid may damage the natural fractures. However, effectiveness of acid can be limited due to depth, temperature, and high in situ stress. The introduction of acid creates surface roughness or asperities that hold the fracture open under reservoir conditions, but all three factors above diminish the applicability of acid etched fractures. Under extreme stress these fractures close unless artificially propped open in some fashion. The advantage of combining the two approaches (acid+proppant) is not only an improvement in the natural fracture conductivity through the acid etching, but also yields a longer lasting conductivity in the main fracture from the emplacement of the proppant.

The idea of adding proppant to an acid fracture stimulation job has a long history but has seldom been used due to a fear (not unfounded) of proppant flowback, and the lack of design tools to quantitatively identify proper candidates. Additionally, models based upon the classic Nierode-Kruk correlations were often over-optimistic in predicting fracture conductivity under high stress conditions, disguising the potential need for combination treatments.

Recent developments in modeling, especially the upscaling of laboratory data to field-scale, make it possible to evaluate the combination of both techniques. The completion design and post-test analysis of two recent acid+proppant stimulation programs in Middle-East carbonate reservoirs is examined. Case 1 was a 10m interval at a depth of 3600m (11,800 ft). Closure stress was 700 bar (10,000 psi). Case 2 was a 35 m thick interval at a depth of 2200 m (7000 ft) with an average porosity of 20% and permeability of > 5 mD as determined from wireline logs. Reservoir temperature/pressure for this case were 120 C (260 F) and 250 bar (3600 psi), with an in-situ closure stress of 350 bar (5100 psi). The formation was characterized by the homogeneous distribution of porosity/permeability.
Optimizing Drawdown Strategies in Wells Producing from Complex Fracture Networks
Authors: Kumar Ashish , Seth Puneet , Shrivastava Kaustubh , Sharma Mukul M.
Published: October 2018

In unconventional reservoirs, the presence of natural fractures coupled with high pore pressures leads to the creation of complex fracture networks. During drawdown, the fracture network experiences large changes in the stresses which can affect the fracture conductivity, and hence the production rate. We present a workflow to find an optimum drawdown strategy in which the fractures can remain conductive while maintaining a high enough drawdown to maximize production.

A fully coupled geomechanical reservoir simulator is developed to simulate production from complex fracture networks. Flow in the fracture and reservoir domains is solved in two separate conforming meshes which are coupled through matrix-fracture transfer indices. The complex fracture network is represented as an explicit discontinuity in the reservoir domain which is essential to capture the stress variations in the vicinity of the fractures due to reservoir depletion and fracture closure. The fracture closure process is modeled dynamically using the Barton-Bandis contact relationship, and the fracture conductivity is determined using the fracture width and proppant concentration. This model is used to study the impact of drawdown strategy on fracture conductivity and well productivity.

It is observed that the estimated ultimate recovery (EUR) from complex fracture networks depends upon the connected fracture conductivity and the applied drawdown. A conservative drawdown strategy maintains the fracture conductivity for a longer period but results in a lower initial production rate. As the drawdown is increased, the unpropped fractures close and can cause a large portion of the fracture network (the part behind the closed segment) to get disconnected from the wellbore. This reduces the available fracture area for production. Although an aggressive drawdown strategy results in higher initial production rates, it can lead to faster fracture closure, in turn resulting in a lower EUR. Impact of drawdown strategy on productivity is analyzed at different fracture closure rates.

We show that the optimum choke management strategy depends on the sensitivity of the fracture conductivity to stress. A coupled geomechanical reservoir model is presented that can simulate production with dynamic fracture closure in complex fracture networks to quantify this effect.
Fracture Optimization of an Unconventional Gas Resource in Southern Chile
Authors: Alqatrani G. S. , Britt L. K. , Otzen G.. , Guzman M.. , Kusanovic G.. , Dunn-Norman S..
Published: October 2018

The Magallanes Basin of Southern Chile is the southern-most hydrocarbon-producing basin in the world. The main source of the gas production in this basin is from the Glauconite Formation. The Glauconite is a clay and feldspar rich formation with extremely low permeability requiring hydraulic fracturing to recover the hydrocarbons and enhance well performance. In this project, fracture simulations with a fully three-dimensional finite element model were integrated with statistical analysis and used in an optimization study of hydraulic fracturing in the Glauconite Formation.

The mechanical earth model was used to estimate the in-situ stress contrast, Young's Modulus, and leak-off profile with depth. Tri-axial compression tests of core were used to validate static Young's Modulus estimates while mini-frac data and fracture stimulation data were history matched and used to validate and/or modify in-situ stress and leak-off profiles with depth. The history matched treatments were then used to populate the database with the resulting hydraulic and propped fracture dimensions. Ultimately, a database that includes in-situ stress, stress contrast, Young's Modulus, leak-off, propped and un-propped fracture dimensions (length and conductivity) was developed.

Finally, both the database and multi-variate statistical analysis were used to show the role of mechanical earth modeling in enhancing and improving the understanding of fracture optimization in the Glauconite Formation. Results from hybrid fracture fluid treatments were compared to treated water fracture treatments to determine the optimum fracture stimulation design for this unconventional extremely tight gas resource.

This work provides a benefit to the petroleum industry by: Using a geo-mechanical finite element model to improve the understanding of the propped fracture dimensions achieved by hybrid and treated water fracture treatments in an unconventional resource like the Glauconite Formation.Establish the key drivers for successful water-frac treatments.
Conceptual Design and Production Enhancement for Ball-Activated Multi-Stage Fracturing Systems in Deepwater Formations
Authors: Bagci S.. , Flores J. C. , Castro L..
Published: October 2018

Multi-Zone, Single-Trip (MZST) completions have significantly reduced the time to complete deep wells with long intervals and have been successfully used in Lower Tertiary formations in deep-water Gulf of Mexico (GOM) projects. MZST completion can be used to create the interface with the reservoir and to deliver stimulation treatments typically limited to up to single-digit zones. Additionally, the minimum spacing allowed by standard MZST completions limits the treated zone length.

The Lower Tertiary formations encounter high-laminated pay zones, often hydraulically isolated, and with pressure variations across the small spacing length. Therefore, a treatment covering several compartments results in uneven treatment distribution across long intervals. These single-trip systems require a high proppant amount and pressure to complete the sizeable frac-pack jobs required in Lower Tertiary formations. Using ball-activated fracturing sleeves and dedicated fracturing ports, these completion systems allow a larger number of stages over multiple intervals. This method affords more precise placement of stages with reduced spacing down to single-digit feet between zones, a feature that also enables targeting specific pressure characteristics in the reservoir.

Completion selection and well performance analysis were conducted to design a new completion system for production enhancement from Lower Tertiary formations. Design and selection of the lower completion system focused on multi-stage fracturing and potential sand control options, and their impact on production. The following systems were studied to estimate and predict the initial production rates: Multi-Zone Single-Trip (MZST) completion, Large Bore Multi-Zone (LBMZ) completion system and Ball-Activated Fracturing Completion System (BAFCS).

This paper describes a high-level workflow developed for completion design and selection, fracture modeling to generate 3D fracture geometry and fracturing pressures, wellbore design including tubing stress and movement analysis for fracturing treatments and production systems analysis to generate vertical lift performance/inflow performance relationships (VLP/IPR), and to estimate the initial production rates and flowing bottomhole pressure for sand-free production.

The proposed BAFCS used more fracture initiation points (up to 20 stages) in the Lower Tertiary formations when compared to eight individual stages (20 perforation intervals) with MZST and LBMZ completion systems. The more confined fracture geometries were created by using the new proposed multi-stage fracturing system. Predicted BAFCS production rates were higher than those of MZST and LBMZ completion systems. To attain higher production and recovery factors than those achievable with natural depletion, artificial lift options (electrical submersible pumping) were also examined for Lower Tertiary wells.
Shining a Light on the Formation Damage Bogeyman: A Case Study of Low Loadfluid Recovery and Enhanced Hydrocarbon Production in the Tight Gas Montney Formation of Western Canada
Authors: Jensen J.. , Hawkes R. V. , Behr J.. , Quintero H..
Published: October 2018

The current practice of pumping large volumes of low salinity slick water in hydraulic fracture stimulation treatments in Canadian oil and gas shales and ultra-tight formations has proven extremely beneficial. These zones, however, are typically considered to have sub-irreducible water saturations. Nevertheless, water treatment volumes of 10,000 – 20,000 m3 per well are routinely performed. Conventional thinking would expect reduced hydrocarbon production due to formation damage or water block. Cleanup efficiencies of these massive water volumes during flowback is driven by the desire to minimize fluid invasion into the matrix. Water (load fluid) cleanup is essentially driven by viscous forces to counteract the capillary forces in the mix-wettability pore network. Operational and seasonal restrictions at times prevent wells being tied into pipelines immediately to continue the load fluid clean-up process. Once wells are placed back on production however, positive and dynamic fluid changes are observed. Conventional thinking suggests that once the invaded water zone saturation reduces to irreducible levels during flowback (cleanup operations), hydrocarbon can then freely flow into the wellbore. However, the flowback behavior in unconventional reservoirs is quite different than conventional reservoirs where soakback and slowback techniques are implemented. These wells can undergo weeks or even months of shut-in following the hydraulic fracturing treatment. It is believed that extended shut-in periods promote the counter-current imbibition phenomena, where the residual hydraulic fracturing fluid can imbibe deeper in the formation matrix driven by osmotic and capillary forces.

This paper demonstrates the true benefit of multi-functionalized surfactant (MFS) with formations of mixed-wettability characteristics using both lab and field tests. Amott Cell results, a test for spontaneous imbibition using various stimulation fluid types, demonstrated MFS significantly outperformed common surfactant chemistry when tested on mixed wettability core samples.
Analytical Model for Predicting Fracture Initiation Pressure from a Cased and Perforated Wellbore
Authors: Weng X.. , Xu L.. , Magbagbeola O.. , MacPhail K.. , Uschner N.. , Carney B. J.
Published: October 2018

Although clustered perforations have become a primary choice of completion for horizontal wells in the development of low-permeability reservoirs, downhole measurements and production logging often indicate nonuniform production from the perforation clusters, with some of them not stimulated or not contributing to the production. One of the mechanisms contributing to this is nonuniform/inefficient breakdown of the perforations. However, being able to assess the effectiveness of perforation breakdown because of lateral variation of the formation properties and stresses is challenging, not only because of the lack of the data, but also because of the lack of a practical engineering model to predict the fracture initiation and breakdown pressures for cased and perforated completions due to the complexity of well configuration and perforation geometry. In this paper, an analytical fracture initiation model is presented along with the comparison against 3D numerical simulations and published experimental data. The breakdown pressure data from a Marcellus shale horizontal test well in the US Department of Energy (DOE)–sponsored Marcellus Shale Energy and Environmental Laboratory consortium are analyzed and compared to the model prediction using the high-resolution 1D mechanical earth model derived from high-tier logs.
Baling or Grazing of Corn Residue Does Not Reduce Crop Production in Central United States
Authors: Ulmer Kristen M. , Rasby Richard J. , MacDonald James C. , Blanco‐Canqui Humberto , Rakkar Manbir K. , Cox Jordan L. , Bondurant Robert G. , Jenkin Karla H. , Drewnoski Mary E.
Published: October 2018

Core Ideas

Baling of corn residue removed three times more residue than did grazing of residue.

Grazing and baling appear to have no impact on subsequent crop yields in flat, high‐yielding fields.

Corn (Zea Mays L.) residue can be used by cattle producers as a source of forage that can either be grazed or baled. While many studies have evaluated the impact of baling corn residue on subsequent crops, relatively few have evaluated the effect of grazing of corn residue. An on‐farm multi‐year study (3 or 4 yr) was conducted at six sites in the central United States to determine effects of grazing or baling of corn residue on subsequent grain yield. Most sites were under no‐till management and were irrigated. Some locations were in continuous corn while others were in a corn–corn–soybean [Glycine max (L.) Merr.] or corn–soybean rotation. At each location, there were three corn residue treatments: no bale–no graze (CON), baled (BLD), and grazed (GZD) with two or three replicates per treatment. Baling and grazing management was dictated by the cooperating producer. In the spring, corn residue remaining in the CON (10.17 Mg ha−1) was greater (P < 0.01; SEM ± 0.449) than both GZD (8.68 Mg ha−1) and BLD (3.60 Mg ha−1) with GZD being greater (P < 0.01) than BLD. Residue management did not affect (P ≥ 0.26) subsequent grain yield (corn, soybean, or dry bean [Phaseolus vulgaris L.]). Corn yield ranged from 6.2 to 18.2 Mg ha−1 with a mean of 14.0 Mg ha−1. Results indicate that, in the short term, baling or grazing of corn residue in high grain yielding fields will not negatively impact grain yield but grazing results in less removal of residue than baling.
Potential use of methylmethionine sulfonium chloride as a component of combination therapy for peptic ulcer and gastroduodenitis
Authors: Pakhomova I. G.
Published: October 2018

It is known that gastritis, gastroduodenitis and peptic ulcer belong to the group of acid-dependent diseases, which occupy a significant proportion among the digestive system diseases. Despite the use of proton pump inhibitors in therapy, the discovery of an important role of H. pylori infection in the genesis of these diseases and the development of eradication schemes, the urgency of the problem persists due to the development of formidable complications (bleeding, perforation). The modern therapeutic concept of treatment of peptic ulcer (including gastroduodenitis) provides active therapeutic tactics and includes multicomponent drug regimens. Along with proton pump inhibitors, the dietary recommendations, appointment of gastro-cytoprotectors, including ones of natural origin, and the individual approach to the patient in each specific case have not outlived their usefulness. Methylmethionine sulfonium chloride (vitamin U) Gastrarex, which improves the secretory and reparative function of the stomach, may be administered as one of the components of the complex therapy of peptic ulcer and gastroduodenitis.
Report on the Laennec hepatic protector symposium
Authors: Minushkin O. N.
Published: October 2018

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Biliary sludge: solved and unresolved issues
Authors: Minushkin O. N. , Burdina E. G. , Novozhenova E. V.
Published: October 2018

The article presents international materials on studying the issue of biliary sludge (BS). The authors also share their own data resulting from conducted studies, where the first group included 1107 patients with BS; the second – 208 patients with different forms of BS; the third group – 40 patients with regular course of BS, in the absence of pharmacological influence; the fourth group – 60 patients (20 patients for each type of BS) with UDCA Exhol 500 mg No. 50 and antispasmodic agent Sparex 200 mg No 30. Intake of Exhol at an initial dose of 15 mg/kg/day was effective in 97% of cases and BS elimination was achieved in 12 weeks. The BS elimination rate depended on its type (1st – 4 weeks, 2–3rd types – 8–12 weeks).
Valoração Ambiental do Parque Ecológico do Rio Cocó
Authors: Farias Ivaneide Ferreira , Silva Clayton Robson Moreira da , Lima Diego Sampaio Vasconcelos Ramalho , Oliveira Laís Vieira Castro , Fontenele Raimundo Eduardo Silveira
Published: October 2018

Esta pesquisa objetivou verificar a disposição a pagar dos visitantes do Parque Ecológico do Rio Cocó para mantê-lo preservado e conservado. Para tanto, utilizou-se o Método de Avaliação Contingente (MAC) com estimação dos valores da Disposição a Pagar (DAP). Trata-se de um estudo quantitativo e descritivo em relação aos objetivos. A amostra reúne 159 frequentadores do parque no último ano, que responderam os questionários. Utilizou-se análise estatística descritiva, regressão logística e cálculo da disposição a pagar total. Os resultados sinalizaram que 58% dos respondentes estão dispostos a pagar para visitar o Parque Ecológico do Rio Cocó. O perfil da amostra tem as seguintes características: 64% eram do sexo feminino, 25% dos entrevistados tinham dependentes, o número médio de visitas ao parque foi de 2,09 visitas por ano, a média das idades foi de 29,69 anos e o salário médio dos respondentes foi de R$3.669,00.  A regressão logística revela que as variáveis “renda”, “conservação”, “gênero”, “nº de dependentes” e “escolaridade” apresentaram significância no modelo. Renda familiar, gênero e número de dependentes aumentam a probabilidade de o indivíduo estar disposto a pagar pela visitação do parque, enquanto a escolaridade e conservação reduzem a probabilidade de disposição a pagar. Verificou-se também uma DAP média de R$11,53 para visitar o Parque Ecológico do Rio Cocó e uma DAP total de R$ 44.194,49 mensais. Conclui-se, a partir da amostra analisada, que a maioria dos visitantes está disposta a pagar para usufruir do Parque do Cocó em troca de melhorias na preservação e conservação.
Franquias Virtuais: uma nova estratégia para os varejistas no e-commerce
Authors: Pereira Ebert Paula Narita , Seide Froemming Lurdes Marlene , Johann Daiane
Published: October 2018

As organizações vêm sofrendo crescentes pressões, devido às mudanças extremas e contínuas em seu ambiente organizacional, com clientes cada vez mais exigentes, muitas empresas perceberam que seus métodos tradicionais de distribuição já não se mostram compatíveis com a concorrência global e com os novos hábitos de compra e consumo dos novos consumidores. Manter os clientes é tão ou mais importante do que adquiri-los. Nesse sentido a franquia virtual se diferencia das demais modalidades de franquias por se valer das redes sociais como o principal canal de comercialização de produtos ou serviços. O objetivo central deste estudo é analisar o desenvolvimento de um novo canal de distribuição denominado franquia virtual, com base nas percepções das consultoras de franquias virtuais e de seus respectivos consumidores. O estudo fundamenta-se em uma pesquisa de abordagem qualitativa, exploratória e descritiva, constitui-se em um estudo de caso e utilizou-se da pesquisa netnográfica e observação participante aplicada a franqueados e consumidores virtuais da Rede Natura.  Os resultados apresentam contribuições sociais, econômicas e acadêmicas, uma vez que contribuem para a literatura pela contemporaneidade do assunto.
Ideologia explica tudo? O embate no legislativo brasileiro em matérias de política externa
Authors: Santiago Rodrigo
Published: October 2018

De acordo com a literatura especializada, a unidade entre os partidos políticos aumenta a credibilidade da política externa, na medida em que o presidente não fica dependente de ciclos majoritários dentro do parlamento. Essa seria uma estratégia utilizada para afastar o perigo de um oponente estrangeiro explorar as disputas partidárias da arena doméstica em negociações internacionais em situações de crise. No entanto, em algumas circunstâncias, percebe-se momentos de embates que podem ser lidos, majoritariamente, como disputasideológicas, mas também, a partir da clivagem governo versus oposição e dos interesses federativos dos congressistas. Este trabalho foca nas discussões em plenário e nos pareceres contrários — momentos de conflito — no Congresso Nacional brasileiro entre os anos de 1988 e 2014. Utilizou-se o método da análise de conteúdo e da técnica da análise de correspondência para explicar esse cenário.
La cooperación de China en América Latina: ¿hacia una Nueva Economía Estructural?
Authors: Crivelli Minutti Eduardo , Lo Brutto Giuseppe
Published: October 2018

Durante la primera década del siglo XXI, América Latina fortaleció sus relaciones con China, hasta convertirse en un socio estratégico para el comercio, la inversión y la cooperación de este país asiático. Se trata de una asociación estratégica que, comprendida bajo la teoría de la Nueva Economía Estructural, se aleja de los esquemas tradicionales de ayuda para revestir a la cooperación al desarrollo de dialogo político, acuerdos comerciales, inversiones y préstamos no-concesionados en infraestructura, buscando reequilibrar las relaciones económicas internacionales. Por tal motivo, el objetivo de este trabajo es dar cuenta de la cooperación al desarrollo que China realiza en los marcos de una posible transformación estructural en la región latinoamericana.
Infiltração clandestina: a questão da diferença no pensamento latino-americano
Authors: Selis Lara
Published: October 2018

Este artigo constitui um esforço de leitura de autores que se engajaram na reativação das margens como espaço de enunciação intelectual na América Latina. Nesse sentido, desenha-se uma reflexão cuja curiosidade seminal se direciona sobre o lugar em que o escritor latinoamericano joga com os signos de outro escritor, o europeu. Buscando analisar como algumas escolas enfrentaram o silenciamento epistemológico da região, o presente trabalho retoma brevemente a literatura produzida pelas teorias da dependência, pelo grupo modernidade/colonialidade e pelos intérpretes da antropofagia. A partir de tal base, argumenta-se pelo espaço de enunciação marginal reativada através de uma epistemologia capaz de estabelecer a diferença como valor crítico. Através dessas lentes, sugere-se que, em cada uma daquelas correntes, verificam-se diferentes visões e graus distintos de resistência diante da figura da Europa ou dos países centrais. Ao fim, configuram-se múltiplas modalidades de infiltraçãoclandestina, mas que compartilham da preocupação com um lócus de fala periférica.
Multimodal Treatment of Homozygous Familial Hypercholesterolemia
Authors: Gossios Thomas , Zografou Ioanna , Simoulidou Veta , Pirpassopoulou Athina , Christou Konstantinos , Karagiannis Asterios
Published: October 2018

Background:

Familial Hypercholesterolemia (FH) is an autosomal-dominant genetic disease, associated
with premature atherosclerotic Cardiovascular Disease (CVD), especially in its homozygous type (HoFH).

Objective:

The aim of this review is to discuss the safety and efficacy of combination treatments (procedures and
drugs) for HoFH.

Results:

Historically, liver transplantation was used first; however, it is currently considered only as a last resort
for some patients. In the mid 70’s, LDL aphaeresis was introduced and remains up today the treatment of choice
for patients of any age, despite its significant cost. The use of Ezetimibe results in additive 15-20% reductions in
LDL-C regardless of the therapeutic approach, while statins are modestly effective in patients with class 4 or 5
mutations, in which LDL Receptors (LDLR) are present. One of the novel drugs for HoFH is Lomitapide, which
is a highly effective oral agent, but is also exceedingly expensive ($350, 000/year). Mipomersen is administered
every week subcutaneously, is also effective but has been approved only in the US mainly due to injection site
reactions up to 80%. Both Lomitapide (mainly) and Mipomersen have been found to promote fat accumulation in
the liver, resulting in subsequent serum transaminases elevations. PCSK9 inhibitors are effective in those with
partial LDLR presence and function by reducing frequency of LDL apheresis, improve cost effectiveness of
treatment.

Conclusion:

Pediatric and adult HoFH treatment needs combination of procedures and drugs. The main treatment
is LDL-C apheresis aided by ezetimibe and PCSK9 inhibitors. Lomitapide needs caution, and liver transplantation
is an alternative as the last resort.
Drugs that Mimic the Effect of Gene Mutations for the Prevention or the Treatment of Atherosclerotic Disease: From PCSK9 Inhibition to ANGPTL3 Inactivation
Authors: Athyros Vasilios G. , Katsiki Niki , Dimakopoulou Aikaterini , Patoulias Dimitrios , Alataki Sofia , Doumas Michael
Published: October 2018

Background:

Drugs mimicking natural beneficial mutations, including that for familial hypercholesterolemia
(FH), might represent the future of hypolipidemic drug treatment.

Objective:

The aim of this review is to review the properties and the effects of these drugs, which are either already
commercially available or are in the process to be approved for the treatment of dyslipidemia.

Results:

More than a decade ago, it was accidentally discovered that proprotein convertase subtilisin/kexin type
9 (PCSK9) loss-of-function mutations resulted in marked lifelong reduction of LDL-C and the incidence of cardiovascular
disease (CVD). This provided the idea for a human anti-PCSK9 antibody. Along with dozens of
phase II and III studies demonstrating unprecedented reductions in LDL-C levels, two large clinical trials established
the substantial benefits of evolocumab and alirocumab on cardiovascular morbidity and mortality, on top of
standard treatment. Evolocumab and alirocumab are now approved and used in clinical practice for the treatment
of FH, statin intolerance, and high risk patients not achieving LDL-C targets. Anti RNA, small molecules, peptides
and also protein fragments against PCSK9 are in phase 1 trials. Angiopoietin-like protein 3 (ANGPTL3)
regulates lipid metabolism increasing triglycerides (TGs), remnants, and LDL-C. In a huge study, ANGPTL3
deficiency due to gene(s) loss-of-function was associated with substantial reductions in circulating TGs, LDL-C,
and CVD. Evinacumab, an ANGPTL3 antibody, caused a dose-dependent reduction in fasting TG levels of up to
76% and LDL-C of up to 23% and CVD risk by 41%. There is also antisense oligonucleotide and micro-RNA-
27b (miR-27b) against ANGPTL3. Two naturally occurring mutations in apo3 gene, A23T and K58E, reduce
TGs and CVD risk. A monoclonal antibody targeting apoC-III has the same effect.

Conclusion:

Mimicking the beneficial naturally happening mutations in lipid metabolism pathways with biological
drugs is probably the future of hypolipidemic drug treatment.
In Silico Analysis of Compounds Derived from Perovskia Atriplicifolia for their Antidiabetic Potential
Authors: Butt Huma Aslam , Butt Hina Aslam , Khan Arif-ullah
Published: October 2018

Background:

Diabetes is a chronic endocrine associated metabolic ailment. It is chiefly
characterized by hyperglycemia, which results due to deficient insulin levels caused by either obliteration
of pancreatic beta cells or the incompetent sensitivity of insulin at the target tissue.

Methods:

In the present study, selected compounds (Abrotandiol, Abrotanone, Lariciresinol, Pinoresinol,
Syringaresinol and Taxiresinol) from Perovskia atriplicifolia were evaluated for antidiabetic
potentials using molecular docking simulations and computational tools.

Results:

All selected compounds possess moderate to strong respective activities against aldose
reductase, DPP-IV, PTPB, insulin receptor and PPAR-g. Selected compounds that include Abrotandiol,
Lariciresinol, Pinoresinol, Syringaresinol, Abrotanone and Taxiresinol have shown highest
binding energies of ΔG = -9.3 kcal/mol, -8.9 kcal/mol, -8.9 kcal/mol, -8.8 kcal/mol, -8.8 kcal/mol
and -7.6 kcal/mol respectively against PPAR-g. However, out of six compounds, Abrotanone has
shown strong potential binding energy against all selected targets, i.e. ΔG = -7.8 kcal/mol with
aldose reductase, ΔG = -10.3 kcal/mol with DPP-IV, ΔG = -9.3 kcal/mol with PTPB and ΔG = -8.3
kcal/mol with insulin receptors.

Conclusion:

The present study proposed that all selected compounds possess antidiabetic activity.
However, Abrotanone has a strong antidiabetic potential. This assumption provides better insight to
evaluate further these compounds for in vitro and in vivo testing against diabetes in future.
Differential Effects of Dietary Fatty Acids on Body Composition and Adiposity
Authors: Emamat Hadi , Yari Zahra , Farhadnejad Hossein , Mirmiran Parvin
Published: October 2018

Recent evidence has highlighted that fat accumulation, particularly abdominal fat distribution,
is strongly associated with metabolic disturbance. It is also well-recognized that the metabolic
responses to variations in macronutrients intake can affect body composition. Previous studies suggest
that the quality of dietary fats can be considered as the main determinant of body-fat deposition,
fat distribution, and body composition without altering the total body weight; however, the effects of
dietary fats on body composition have controversial results. There is substantial evidence to suggest
that saturated fatty acids are more obesogen than unsaturated fatty acids, and with the exception of
some isomers like conjugate linoleic acid, most dietary trans fatty acids are adiposity enhancers, but
there is no consensus on it yet. On the other hand, there is little evidence to indicate that higher intake
of the n-3 and the n-6 polyunsaturated fatty acids can be beneficial in attenuating adiposity, and the
effect of monounsaturated fatty acids on body composition is contradictory. Accordingly, the content
of this review summarizes the current body of knowledge on the potential effects of the different
types of dietary fatty acids on body composition and adiposity. It also refers to the putative mechanisms
underlying this association and reflects on the controversy of this topic.
Synthesis and Biological Evaluation of 3-cyano-4H-chromene Derivatives Bearing Carbamate Functionality
Authors: Boukattaya Fatma , Daoud Amal , Boeda Fabien , Pearson-Long Morwenna S.M. , Gharsallah Néji , Kadri Adel , Bertus Philippe , Ammar Houcine
Published: October 2018

Background:

2-Aminochromene derivatives display important pharmacological properties,
including mainly antibiotic and anticancer activities.

Objective:

The study aims to synthesize new chromene derivatives via a new approach using Grignard
reagents, for the evaluation of their antibiotic and antifungal properties.

Method:

A series of novel 3-cyano-4-aminochromene derivatives bearing alkyl substituents at the
4-position was prepared for biological evaluation.

Results:

These compounds were obtained by the addition of various Grignard reagents into Nethoxycarbonyl-
3-cyanoiminocoumarines in moderate to good yields (72-96%). The reaction is
completely regioselective. The new chromene derivatives were screened for their in vitro antimicrobial
activities against a panel of six bacterial and three fungal strains using agar dilution
method.

Conclusion:

The antibacterial activity of the chromene derivatives was more pronounced on
Gram-positive bacteria than on Gram-negative bacteria with a significant activity observed against
Staphylococcus aureus. An interesting antifungal activity against Fusarium sp. and Fusarium
oxysporum was also noticed.
Anti-toxicant Properties of Saffron and Relevance to Protection from Toxins and Drugs
Authors: Hatziagapiou Kyriaki , Lambrou George I.
Published: October 2018

Background:

Reactive oxygen species and reactive nitrogen species, which are collectively
called reactive oxygen nitrogen species, are inevitable by-products of cellular metabolic redox reactions,
such as oxidative phosphorylation in the mitochondrial respiratory chain, phagocytosis, reactions of
biotransformation of exogenous and endogenous substrata in endoplasmic reticulum, eicosanoid synthesis,
and redox reactions in the presence of metal with variable valence. Among medicinal plants there is
a growing interest in Crocus sativus L. It is a perennial, stemless herb, belonging to Iridaceae family,
cultivated in various countries such as Greece, Italy, Spain, Israel, Morocco, Turkey, Iran, India, China,
Egypt and Mexico.

Objective:

The present study aims to address the anti-toxicant role of Crocus sativus L. in the cases of
toxin and drug toxification.

Materials and Methods:

An electronic literature search was conducted by the two authors from 1993 to
August 2017. Original articles and systematic reviews (with or without meta-analysis), as well as case
reports were selected. Titles and abstracts of papers were screened by a third reviewer to determine
whether they met the eligibility criteria, and full texts of the selected articles were retrieved.

Results:

The authors focused on literature concerning the role of Crocus Sativus L. as an anti-toxicant
agent. Literature review showed that Saffron is a potent anti-toxicant agent with a plethora of applications
ranging from anti-oxidant properties, to chemotherapy protective effects.

Conclusion:

Literature findings represented in current review herald promising results for using Crocus
Sativus L. and/or its active constituents as anti-toxicant, chemotherapy-induced protection and toxin
protection.
Effects of Polyphenol Administration to European Farmed Sea Bass (Dicentrharcus labraxL.): Special Focus on Hepatopancreas Morphology
Authors: Magrone Thea , Magrone Thea , Spagnoletta Anna , Spagnoletta Anna , Magrone Manrico , Magrone Manrico , Russo Matteo Antonio , Russo Matteo Antonio , Corriero Aldo , Corriero Aldo , Jirillo Emilio , Jirillo Emilio , Passantino Letizia , Passantino Letizia
Published: October 2018

Background and Objective: Hepatopancreas is an accessory organ associated with the liver in some fish, even including sea bass (Dicentrharcus labrax L.). Hepatopancreas contains an exocrine portion but until now its function has poorly been investigated.  Methods: Here, European farmed sea bass have been treated with a feed enriched in polyphenols extracted from seeds of red grape (Nero di Troia cultivar) at two different doses (100 and 200 mg/kg, respectively) from day 273 to day 323. In fish samples, hepatopancreas area sizes have been measured to evaluate the effects of this dietary regimen on its morphology.  Results: Quite interestingly, in treated fish area sizes of hepatopancreas were higher than those detected in untreated fish. Two hundred mg dose of polyphenols was more effective than that of 100 mg/kg polyphenols. Finally, hepatic polyphenol concentration was diminished in fish receiving 100 mg dose polyphenols and normalized with 200 mg dose in comparison to untreated fish. This evidence suggests the utilization of polyphenols for liver function, even including hepatopancreas development.  Conclusion: Our data suggest an expansion of hepatopancreas induced by polyphenol administration that is also associated with less mortality in farmed fish.
Cytotoxic and Apoptotic Action of Nonactin and Cephaeline. HBr Precludes Alteration of Redox Status
Authors: Adeyemi Oluyomi Stephen , Awakan Oluwakemi Josephine , Adeyanju Anne Adebukola , Otohinoyi David Adeiza
Published: October 2018

Background:

Natural products or naturally derived compounds are invaluable to human
and animal lives either for nutritional value or for medicinal purposes. Indeed, natural products including
extracts containing polychemical mixtures play a leading role in the discovery and development
of drugs. However, the increasing interest in natural medicines is also attracting a growing
concern about the safety of naturally derived medications.

Objective:

In the present study, we evaluated several naturally derived compounds for in vitro cytotoxicity
in mammalian cells.

Methods:

A total of 54 compounds were evaluated for in vitro cytotoxic and apoptotic action in
Human Fibroblast Foreskin (HFF) cells.

Results:

Of the 54 natural compounds screened for cellular toxicity, only nonactin and cephaeline.
HBr reduced cellular viability by ≥60% with IC50 value <3 µg/ml. Addition of trolox antioxidant
to the assay medium failed to abate cellular toxicity by both nonactin and cephaeline.HBr
treatments. Fluorescence evaluation for Reactive Oxygen Species (ROS) production as well as Mitochondrial
Membrane Potential (MMP) was negative for both nonactin and cephaeline.HBr treatments.
In contrast, both nonactin and cephaeline.HBr caused cellular apoptosis and this was not attenuated
even in the presence of trolox.

Conclusion:

Taken together, we show evidence supporting that cytotoxic and apoptotic action of
nonactin and cephaeline.HBr precludes oxidative stress or ROS production.
Approach for Protection of Iris Template using Cancelable Biometrics
Authors: Chaudhary Sheetal , Nath Rajender , Kant Chander , Kant Surya
Published: October 2018

Background and Objective:

The most important issue concerning the security of biometric
authentication systems is protection of biometric templates. This is because once the biometric template
being attacked, it cannot be canceled and reissued. Thus, the intruder could avail the facilities
that are meant only for the genuine user just bypassing the enrollment phase.

Methods:

To protect the biometric templates from attacks, it is advantageous to modify them before
storing in the databases through some cancelable and non-invertible transformations. Hence, an approach
based on cancelable biometrics is proposed in this paper for providing security and privacy to
biometric templates. It uses left iris and right iris as input biometric traits. Different experiments are
carried out to authenticate the proposed approach.

Results and Conclusion:

It satisfies all template protection requirements and expected to show good
recognition performance without degrading it.
Sensorless FOC Strategy for the Salient-pole PMSM using Improved Fullorder Sliding Mode Observer
Authors: Saadaoui Oussama , Tlili Imen , Khlaief Amor , Chaari Abdelkader
Published: October 2018

Background:

This document presents a new approach to estimate speed and rotor position
of the salient-pole Permament Magnet Synchronous Motor (PMSM).

Methods:

To eliminate the mechanical sensors, we apply a sensorless field oriented control (FOC) by using
an improved full-order sliding mode observer (FO-SMO) at different speeds (low and high speeds).
The stability of the Slide Mode Observer (SMO) was demonstrated with the Lyapunov function.

Methods:

The simulation results prove good properties of the proposed estimation method.

Conclusion:

The sensorless field oriented control strategy of the salient-pole PMSM has been proposed
in this paper using an improved full-order SMO.
La reacción química en el bachillerato: una propuesta didáctica
Authors: Ferrera Velázquez Thalía Itzel , Méndez Vargas Nadia Teresa , Sosa Fernández Plinio Jesús
Published: October 2018

El presente trabajo muestra una propuesta didáctica diseñada para introducir el concepto de reacción química a alumnos de bachillerato.

El eje conductor de la propuesta es la reacción química como un proceso en el que se obtienen unas sustancias a partir de otras. La propuesta consiste en cuatro actividades didácticas: tres actividades experimentales y una lectura. En las tres primeras, se aprovecha el hecho de que cada sustancia posee un conjunto distinto de propiedades (lo propio de cada sustancia) para reconocer que ha ocurrido una reacción. En la primera, se forman sustancias de distinto color; en la segunda, se produce una sustancia con propiedades lacrimógenas; y, en la tercera, se obtienen sustancias con olor. En la cuarta actividad, se resalta la obtención de energía a partir de un proceso químico.

Palabras clave: reacción química, sustancia química, energía química.
Separation and Qualitative Analysis of Carbonate, Phosphate and Chromate Anions in Qualitative Inorganic Courses
Authors: Souza Andrada Anconi Amanda Carolina , Martins Monteiro Maísa , Paulo Andrada Cleber
Published: October 2018

In the present work, our experience with a new methodology for separation and characterization of carbonate, phosphate and chromate anions is discussed. Since 2014 this laboratory experiment has been applied in undergraduate Chemistry courses in University of Lavras, Brazil, has shown to be satisfactory along Qualitative Inorganic or Analytical courses. In order to understand and to discuss the experiment, concepts involving equilibria of precipitation, acidity and basicity, liquid-liquid extraction, as well as the notions of solubility, phases distribution of solutes, and distribution diagram of the species were explored.
Rational Choice of Multi-Faceted Replaceable Profile Inserts for Rough Turning of Details Made of Titanium Alloy VT6
Authors: Zhilyaev S V , Kugultinov S D , Shchenyatskii A V , Popov I V
Published: October 2018

В статье отмечены трудности, возникающие в процессе механической обработки резанием титановых сплавов, и рассмотрены вопросы рационального выбора режущего инструмента, оснащенного сменными многогранными неперетачиваемыми пластинами (СМП) из твердого сплава, для чернового точения деталей из титанового сплава ВТ6, на основании оценки эффективности его работы и стоимости. Оценка эффективности производилась на основании показателей, определяющих их стойкость. С этой целью были проведены сравнительные стойкостные испытания СМП отечественного и зарубежного производства. Стойкостные испытания проводились в производственных условиях АО «Воткинский завод». В качестве критерия был выбран износ по задней грани за строго определенное время. По итогам проведенных испытаний было выявлено, что наименьшее изнашивание продемонстрировали СМП SNMM 250724MR 2025 фирмы Sandvik Coromant. Пластины SNMM 250724 E-NR2 Н05 фирмы Pramet примерно на 10 % изнашивались меньше их аналогов Кировоградского завода твердых сплавов SNMM 250724 Rl AP20TM и SNMM 250724 Rl TP20TM. Сравнение их по стоимости показало, что наименьшей цену имеют пластины отечественного производства, и их цена почти в три раза ниже лидера производственных испытаний. По итогам работы и исходя из соотношения цена - качества для производства были рекомендованы СМП Кировоградского завода твердых сплавов.
Generalized Mathematical Model of Non-Oil Petroleum. Implementation of Modules Answering for Nodes, Connections, Limitations of Area of Deposit
Authors: Denisov S V , Lyalin V E
Published: October 2018

Компьютерные технологии в области гидродинамического моделирования и исследования месторождений в настоящее время имеют тенденцию устойчивого роста интереса со стороны нефтяных компаний по внедрению их на предприятии. Они позволяют обосновывать стратегию разработки нефтяных месторождений, использовать их для решения производственных задач. Подавляющее количество доступных коммерческих симуляторов месторождений разработано с применением классического математического подхода, целью которого является получение системы алгебраических уравнений фильтрации углеводородов. Однако при таком подходе весьма непросто обеспечить должный уровень модульности и стандартизации программного кода симулятора, поскольку соответствующие такому подходу базовые строительные блоки должны быть обеспечены слишком большим количеством информации. Поэтому актуальной задачей является разработка универсального подхода к созданию унифицированного программного комплекса для гидродинамического моделирования нефтяных месторождений. Предметом исследования является разработка относительно простого, универсального и модульного симулятора месторождений. Классический подход, к строительным блокам которого относятся конечные объемы (или сеточные блоки), не удовлетворяет требованиям высокого уровня стандартизации и модульности. Поэтому в работе предложен новый подход, при котором область разбивается на разные строительные блоки: узлы и соединения. Представлена реализация модулей, отвечающих за узлы, за соединения, за ограничения.