bluuebunny/crossref_metadata_2025 huggingface dataset:
Case Study: Complex Marginal Oil Field Modeling - Fast Transition From Exploration to Development
Authors: Kalinic Vuk , Milei Evgenia , Al-Jeboore Ivan
Published: April 2019

As active oil reservoirs mature, marginal fields development and management is becoming increasingly important.

Early identification of high degree reservoir heterogeneity served as starting point for an in-depth analysis for both, geologist and reservoir engineer.

This paper describes complex approach applied during evaluation and development of marginal oil field "Is" located in Serbia (Pannonian Basin).

Effective transition from exploration to development took place in 3 stages.

I-stage: 1 exploration well drilled, detailed analysis (seismic, sedimentology, core, PVT) and interpretation (log, well-test). Identification of vertical heterogeneity led to detailed analysis, which resulted in local depositional environment theory. Integration of seismic attribute and sedimentological analysis results was done. Due to geological uncertainties several 3D models were done for STOIIP range estimation. Recovery factor range was estimated using statistical, analytical and simulation model approach.

II-stage: 1 exploration well and 1 development well drilling and detailed analysis update.

III-stage: drilling of 5 development wells and continuous update of geological and simulation models.

Major uncertainties identified during I-stage were regarding to: reservoir structure, vertical and lateral heterogeneity, major fault permeability and OWC depth. Additionally, existence of active aquifer affected recovery factor estimation range.

I-stage analysis showed that, depending on depositional environment 4 different rock types are presented by conglomerates, conglo-breccia, breccia and metamorphic rocks.

The target formation (conglomerates) were formed by proluvial fan. This deposits are characterized by an alternation of rhythms (fragment size and orientation, conglomerate size, terrigenous material sorting).

Proluvial fan boundaries were detected on the seismic attribute map.

Second exploration well location was a result of multidisciplinary analysis during I-stage. Well was successful and highly informative during II-stage as it proved oil saturation behind major fault, reduced previous STOIIP estimates and confirmed presence of active aquifer.

STOIIP and reservoir structure excluded possibilities for regular/typical well patterns, therefore each well location was carefully selected, while total well number was determined based on estimated recovery factor.

Complex multidisciplinary approach used during this project, can be an example for successful and effective marginal heterogeneous oil field development. Understanding the reasons for reservoir heterogeneity together with confident estimate of recovery factor, gave us success during each new well placement and total well number determination.
Leveraging US Unconventional Data Analytics Learnings in Vaca Muerta Shale Formation.
Authors: Primera Alejandro , Klie Hector , Klie Arturo , Quesada Maria
Published: April 2019

Data Analytics is progressively gaining traction as a viable resource to improve forecasts and reserve estimations in most prospective US shale plays. Part of those learnings has been tested for the reserves and resources estimation of the next worldwide top-class shale play, Vaca Muerta formation in Argentina. In this work, we rely on advanced artificial intelligence methods to automate workflows for production forecasting and reserve estimation in the Vaca Muerta formation. To achieve this goal, we develop a computational platform capable of integrating several sequential operations into a single automated workflow: (1) data gathering; (2) data preparation; (3) model fitting and forecasting and, (4) EUR estimation. As new data becomes available, each of these steps is performed automatically. The proposed platform also integrates with advanced business intelligence tools that aid at facilitating graphical interpretation and communication among specialists and decision makers. Hence, the suggested workflow can deliver production forecasts several magnitudes faster than traditional workflows while maintaining accurate and engineering sound results. Having fast and reliable forecast turnarounds allow for timely tracking key differences and commonalities among multiple shale plays to facilitate informed decision strategies in unconventional field evaluation and development.
Investigation of Pore Structure and Fractal Characteristics in an Organic-Rich Shale Gas-Condensate Reservoir from the Duvernay Formation
Authors: Penghui Su , Zhaohui Xia , Ping Wang , Liangchao Qu , xiangwen Kong , Wenguang Zhao
Published: April 2019

Interest has spread to potential unconventional shale reservoirs in the last decades, and they have become an increasingly important source of hydrocarbon. Importantly, pore structure of shale has considerable effects on the storage, seepage and output of the fluids in shale reservoirs so that reliable fractal characteristics are essential. To better understand the evolution characteristics of pore structure for a shale gas condensate reservoir and their influence on liquid hydrocarbon occurrences and reservoir physical properties, we conducted high-pressure mercury intrusion tests (HPMIs), field emission scanning electron microscopies (FESEM), total organic carbon (TOC), Rock-Eval pyrolysis and saturation measurements on samples from the Duvernay formation. Furthermore, the fractal theory is applied to calculate the fractal dimension of the capillary pressure curves, and three fractal dimensions D1, D2 and D3 are obtained. The relationships among the characteristics of the Duvernay shale (TOC, organic matter maturity, fluid saturation), the pore structure parameters (permeability, porosity, median pore size), and the fractal dimensions were investigated.

The results show that the fractal dimension D1 ranges from 2.44 to 2.85, D2 ranges from 2.09 to 2.15 and D3 ranges from 2.35 to 2.48. D2 and D3 have a good positive correlation. The pore system studied mainly consists of organic pores and microfractures, with the percentage of micropores being 50.38%. TOC has a positive relationship with porosity and D3 due to the development of organic pores. D3 has a positive correlation with gas saturation. With increased D3, median pore size shows a decreasing trend and an increase in permeability and porosity, demonstrating that D3 has a large effect on pore size distribution and the heterogeneity of pore size. In general, D3 has a better correlation with petrophysical and petrochemical parameters. Fractal theory can be applied to better understand the pore evolution, pore size distribution and fluid storage capacity of shale reservoirs.
Evaluating Acid Fracture Etching Profiles and Formation Mineralogy Composition from Distributed Temperature Measurements
Authors: Aljawad Murtada Saleh
Published: April 2019

Acid fracture operations in carbonate formations are used to create highly conductive channels from the reservoir to the wellbore. Conductivity in calcite formations is expected to be highest near the wellbore, where most of the etching occurs. The near wellbore fracture etched-width profile can be estimated from the measured temperature distribution. Temperature data can be obtained from fiber optic distributed temperature sensing (DTS) installed behind casings to monitor fracturing operations.

Heat transfer is commonly coupled in acid fracture models to account for temperature's effects on acid reactivity with carbonate minerals. Temperature profiles are usually evaluated during simulations of fracture fluid injection, but seldom during fracture closure. Since most of the acid is spent during injection, many models have assumed that the remaining acid reacts proportionally along the fracture length. Because of this assumption, neither acid spending nor temperature is usually simulated during fracture closure.

In this study, a fully integrated temperature model was developed wherein both the acid reaction and heat transfer were simulated while the fracture was closing. At each time step, transient heat convection, conduction, and generation were calculated along the wellbore, reservoir, and fracture dimensions. Modeling temperature during this transient period provides a significant understanding of the fracture etched-width distribution. During shut-in, cold fracture fluids are heated, mainly because of heat flow from the formation to the fracture. The amount of fluid stored in the fracture determines how fast the fluid is heated. Wider fracture segments contain larger amounts of cold fracture fluids, resulting in it taking longer to reach the reservoir temperature. Because of this phenomenon, near a wellbore, the vertical fracture etched-width profile can be determined from the temperature distribution. Also, minerals' spatial distributions along the wellbore's lateral can be estimated in multistage acid fracturing. This is done by minimizing the difference between the observed and modeled temperatures.

This evaluation of etched width profiles at the fracture entrance provides an estimation of fracture-conductive channel locations. Moreover, it has significantly improved the understanding of mineralogy distribution in multi-layer formations. This information will be particularly useful when designing acid fracturing jobs in nearby wells or revisiting the same wellbore for further stimulation.
Improved Calculation of Effective Permeability for Pore Network Models Using the Diffuse Source Methodology
Authors: Liu Sherry , King Michael J.
Published: April 2019

In this study, we have extended and applied the diffuse source upscaling methodology to sandstone and carbonate pore network models in order to evaluate their effective transmissibility and permeability. The proposed method allows us to find transmissibility values for sub-volumes of the pore network during the transition from transient to pseudo steady state flow. The pore network models utilize a lattice grid construction, consisting of nodes and bonds that connect the nodes. The Eikonal equation is solved on the lattice using Dijkstra's method to obtain the diffusive time of flight, which is then used to model the transition from transient to pseudo steady state flow. The solution uses the concept of a transient drainage volume, which increases with time as pressure propagates into the nodes of the pore network. The diffuse source upscaling approach allows us to calculate the transmissibility of the drainage volume as it increases with time. The calculated results can be compared to the analytical results, where the sample is assumed to be internally homogeneous. A synthetic model was created to illustrate how the calculated lattice model and the analytic reference results compare for a homogeneous model. The comparison of the carbonate analytical and calculated results showed that there exists a high degree of internal heterogeneity while the more homogeneous sandstone model showed a close agreement with the synthetic model. For both samples, the late time pseudo steady state permeability showed a good correspondence with other permeability evaluations. The diffuse source method has more directional information available than the steady state method. Hence, the new method of analysis can be viewed as an extension of pseudo steady state concepts of permeability to transient flow, with increased spatial resolution corresponding to the transient drainage volume. Instead of obtaining only the steady state transmissibility from a pore network model, the diffuse source approach provides us with the ability to better characterize the internal heterogeneity of a model and to explain the wide range of permeability values obtained by other approaches.
Analysis of Sandface Temperature Transient Data Under Specified Rate or Bottomhole Pressure Production from a No-Flow Composite Radial Reservoir System
Authors: Ozdogan Tasansu , Onur Mustafa
Published: April 2019

The paper provides analytical and semi-analytical solutions to predict the temperature transient behavior of a vertical well producing slightly compressible fluid under specified constant-bottom-hole pressure or rate in a two zone, radial composite no-flow reservoir system, where the inner zone could represent the skin zone, whereas the outer zone represents non-skin zone. The solutions are obtained by solving the decoupled isothermal diffusivity equation for pressure and thermal energy balance equation for temperature for the inner and outer zones by using the finite-difference and Laplace transformation. They be used to simulate temperature transient behavior for the general cases of specified variable bottom-hole or rate production represented by piecewise constants in specified time intervals. The convection, conduction, transient adiabatic expansion and Joule-Thomson heating effects are all considered in solving the temperature equation. Graphical analysis procedures for analyzing such temperature transient data jointly with pressure or rate transient data are also discussed. The results show that sandface temperature first decreases due to adiabatic expansion and then increases due to Joule-Thomson heating for both constant rate and constant bottomhole pressure production cases during infinite-acting flow. During boundary dominated flow, sandface temperature decreases linearly with time due to pore-volume expansion of the fluid over the entire no-flow reservoir system. The time rate of decline is governed by the ratio of the adiabatic-expansion coefficient of the fluid to the volumetric heat capacity of the saturated medium and the pore volume. However, these flow regimes are not well-defined for the constant bottomhole production case because the sandface rate decreases continuously during the infinite-acting radial flow and boundary dominated flow periods and distorts the flow regimes which are well defined on the temperature behavior if the well were produced at a constant rate. Sandface temperature data under specified variable rate or bottom-hole pressure show complicated behaviors and require more general automated history matching methods based on simultaneous use of both sandface temperature and rate transient data sets for parameter estimation.
Hypoxia Inducible Factor 1-α in Acute Ischemic Stroke: Good Predictor for Clinical Outcome
Authors: Amalia Lisda , Tatang Yeremia , Sadeli Henny Anggraini , Parwati Ida , Rizal Ahmad , Panigoro Ramdan
Published: April 2019

Background. Stroke is the third leading causes of death and can cause severe disability. Ischemic stroke has a higher prevalence compared to hemorrhage stroke. Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor which maintains cellular homeostasis in response to hypoxia. It can trigger apoptosis while stimulating angiogenesis process and decrease neurological deficit after an ischemic stroke. However, this protein complex has not been widely investigated. Objective. Here, we examined the potential of HIF-1α as a marker for neuroplasticity process after ischemic stroke. Methods. Serum HIF-1α were measured in acute ischemic stroke patients. National Institute of Health Stroke Scale (NIHSS) were assessed on the admission and discharge day (between days 7 and 14). To classify the ischemic stroke, we used (Trial of Org 10172 in Acute Stroke Treatment) TOAST criteria. Statistical significances were calculated with Spearman rank test. Results. A total of 58 patients, 31 with large artery atherosclerosis LVD and 27 with small vessel disease (SVD) were included in this study. HIF-1α level in LVD group was (mean ± SD) 0.5225 ± 0.2459 mg/L and in SVD group was 0.3815 ± 0.121 mg/L. HIF-1α was higher (p = 0.004) in LVD group than in SVD group. The initial NIHSS score in LVD group was (mean ± SD) 15.46 ± 2.61 and discharge NIHSS score was 13.31 ± 3.449. Initial NIHSS score in SVD group was 6.07 ± 1.82 and the discharge NIHSS was 5.703 ± 1.7055. In LVD group, HIF-1α was correlated significantly with initial NIHSS (p = 0.0000) and discharge NIHSS (p = 0.0000, r = 0.93). This was also the case for SVD. We found a significant correlation between the level of HIF-1α with initial NIHSS (p = 0.0000) and discharge NIHSS (p = 0.0383) in SVD group (r = 0.94). Conclusion. HIF-1α has a strong correlation with NIHSS and it may be used as the predictor of acute ischemic stroke outcome.
Atık Döküm Kumları İçin Uygun Bertaraf Yönteminin Maliyet Analizi ile Belirlenmesi: Bursa Örneği
Authors: Yalılı Kılıç Melike , TÜYLÜ Murat
Published: April 2019

Türkiye’nin büyük ilk 500 sanayi kuruluşu içinde yer
alan dökümhaneler, üretim prosesi sonrasında atık döküm kumlarının sürekli
oluştuğu sektörlerdendir. Ekonomik değeri olan atık döküm kumları ülkemiz
koşullarında yeterince değerlendirilemediğinden, fabrika alanlarında
biriktirilmekte ya da düzenli depolama sahalarına gönderilerek geri kazanım
sürecine dahil edilemeden heba edilmektedir. Oysaki genelde tehlikesiz türde
olan atık döküm kumları, uygun şekilde yönetildiklerinde asfalt üretiminde
agrega yerine alternatif hammadde olarak kullanılabilmektedir. Bu çalışmada,
Bursa ili Nilüfer ilçesinde yer alan 46.200 ton üretim kapasiteli bir
dökümhaneden kaynaklanan atık döküm kumlarının direkt düzenli depolama sahasında
bertaraf edilmesi yerine, çimento fabrikası ve asfalt plent tesisine
gönderilerek geri kazanılması ve alternatif hammadde olarak kullanılmasının
çevresel ve ekonomik değerlendirilmesi yapılmıştır. Atık döküm kumlarının nakliye
dahil olmak üzere düzenli depolama sahasına gönderilmesi durumunda 851.989 TL (163.844
$), çimento fabrikasına gönderilmesi durumunda 1.097.620 TL (211.081 $) ve
asfalt plent tesislerine gönderilmesi durumunda ise 35.431 TL (6.814 $)
bertaraf maliyetinin olacağı hesaplamalar sonucunda bulunmuştur. Dökümhane için
en ekonomik yöntemin asfalt plent tesisi olduğu belirlenmiş olup, bertaraf
maliyetlerinin en aza indirilmesi ile atık döküm kumlarının üretildikleri yere
en yakın ve en uygun tesise en hızlı şekilde gönderilerek hava, su ve toprak
kirliliğine neden olan fabrika sahalarındaki uzun süre depolamaların önleneceği
düşünülmektedir.
Multicentre study “Prenatal diagnosis of Down syndrome in Russia
2005–2015”. II. Ultrasound markers
Authors: M.V. Medvedev, N.A. Altynnik and all
Published: April 2019

Objective: to study the effectiveness of the use of ultrasound markers for Down syndrome (DS) in the fetus during ultrasound examinations at 11–14 and 18–21 weeks of gestation based on the results of multicentre
analysis in the regions of Russia in 2005–2015 years.
Materials. The analysis was based on data from a questionnaire on prenatal diagnosis of DS in 30 regions
and cities of Russia in 2015. The data from the questionnaire survey of 12 regions in 2005 and 23 regions in 2010
for analyse the dynamic of prenatal diagnosis of DS in our country was obtained. The questionnaire included
the questions about the number of births and pregnant women registered in the region; the total number of
cases of DS registered in prenatal and postnatal periods; structures of diagnosed cases of DS depending on the
detection period; indications for prenatal karyotype; the number of fetuses with DS and the increase of nuchal
translucency in 11–14 weeks of gestation; ultrasound markers of DS in the II trimester of gestation and perinatal
outcome in cases of prenatal diagnosis of DS.
Results. In the course of the multicentre analysis it was established that the accuracy of identification of
DS in the prenatal period in our country was 30,9% in 2005, 38,4% in 2010 and significantly increased to 59,7%
in 2015. In 2005, only 17,2% of cases of DS were detected in 11–14 weeks of gestation, in 2010 — 38,2% and
increased to 72,1 % (7,6–100%) in 2015. In 24 from 30 regions the proportion of diagnosed cases of trisomy 21
at 11–14 weeks of gestation was 50% or more, and in 11 regions — 90–100%. Increase of nuchal translucency
thickness was detected on average in 76,3 % fetuses with DS with a range from 28,1 to 100 %. The most prenatal
ultrasound markers in fetuses with DS in the second-trimester were congenital malformations and hypoplasia /
absence of nasal bones — 64,9 and 65,5 %, respectively. Further, as the frequency of detection decreased: prenasal thickness (27,6 %), echogenic intracardiac focus (27,1%), pyelectasis (22%), nuchal fold (19,7%), short
humerus/femur (17,5%), hyperechogenic bowel (14,6%), ventriculomegaly (11,2%), choroid plexus cysts (7,3%).
Conclusion. Ultrasound examination is powerful method for identification the fetuses with DS. Therefore,
it is necessary to continue the development of new ultrasound markers of DS for improving its prenatal diagnosis.
Modeling the evolution of small distortions of the sphericity of a collapsing bubble
Authors: Aganin A.A. , Guseva Т.S. , Khalitova Т.F.
Published: April 2019

Results of calculating the evolution of small axisymmetric distortions of the spherical shape of a bubble during its collapse are presented. The full model based on two-dimensional gas dynamics equations (gas and liquid are considered inviscid non-heat-conducting) and a number of simplified models are used. The latter are obtained from the full model by splitting the gas and liquid motion into a spherical component and its small non-spherical perturbation. The differences of the simplified models are defined by the assumptions used in the realization of the splitting.
Thermocapillary effect and periodic structures on the surface of a heated viscous liquid film
Authors: Aktershev S.P.
Published: April 2019

We consider a two-dimensional flow of a laminar film of a viscous liquid on a homogeneously or locally heated plate in the presence of a gas flow above the surface of the film. In the case of a localized heater, an analytical solution for the temperature distribution in the film is obtained. In the case of a small deformation of the film surface and weak heat transfer with gas, an analytical solution for the film thickness perturbation is obtained. In the case of an uniformly heated plate, the effect of the formation of a periodic structure on the film surface is considered. With a small deformation of the surface, a dependence of the structure period on the Marangoni number is determined. Periodic solutions appear only if the Marangoni number exceeds a threshold value.
The propagation of surface waves in a cylindrical cavity in a saturated porous medium
Authors: Boldyreva O.Yu.
Published: April 2019

The frequency dependencies of velocity and attenuation of waves propagating along the fluid-filled cylindrical cavity in a saturated porous medium are investigated. The study is made in the framework of two velocity, two stress model of the porous medium, taking into account the non-stationary forces of interphase interaction. On the boundary between the fluid and the porous medium two types of boundary conditions, i.e. open and closed pores, are considered. It is found that the most significant impact on the velocity and attenuation of the primary acoustic mode in a cylindrical waveguide in a porous medium has a permeability of the porous medium
The study of a hydromechanical fuel metering element
Authors: Denisova E.V. , Nasibullaeva E.Sh.
Published: April 2019

The technique for calculating the characteristics of the fuel dosing element when its design parameters and physical properties of fuel change is considered.
Propagation of linear waves in moist porous media saturated with gas, taking into account interphase heat transfer
Authors: Dmitriev V.L. , Volodin S.V.
Published: April 2019

A system of differential equations describing process of propagation of acoustic waves in a saturated saturated gas to a porous medium. A dispersion relation taking into account Interphase interaction forces and heat exchange processes between the skeleton porous medium, liquid and gas. Influence of heat exchange processes between phases on the nature of the propagation of ”fast“ and ”slow“ waves is taken into account on the basis of the heat conduction equations.
Damage detection of a vertical bar
Authors: Ilgamov M.A.
Published: April 2019

The article defines, both statically and dynamically, the location and size of a transverse notch on a vertical bar stretched by its own weight and the force applied at its lower end. Consideration is given only to the stress deformed state within the limits of elasticity for a thin bar. The notch simulates damages in the bar, among them the transverse open crack. Since the crack emerges as a result of the formation of a tiny nucleus, although not necessarily at the most stressed section, the notch is assumed to be in any place along the length of the bar.
A film flow in a drop catcher in space conditions
Authors: Koroteev A.A. , Osiptsov A.N. , Popushina E.S.
Published: April 2019

A non-isothermal film flow is considered, which is formed on the inner surface of a conical drop catcher on whose inlet a uniform stream of a droplet medium is supplied under open space conditions. For the regime of inertial deposition of droplets, under the assumption of small relative thickness of the film and the absence of droplets rebounced from the film surface asymptotic models of steady-state film flow are constructed and studied. For a slow isothermal flow, the shape and parameters of the film are found analytically. For a general case, a parameteric numerical study ща the velocity and temperature distributions, as well as the film thickness, is performed. The flow parameters in the inlet section of the outlet channel are determined, and the conditions required for the steady-state regime of drop catcher operation are found.
Polyproline II Helix as a Recognition Motif of Plant Peptide Hormones and Flagellin Peptide flg22
Authors: Matsushima Norio , Miyashita Hiroki , Tamaki Shinsuke , Kretsinger Robert H.
Published: April 2019

Background:

Plant peptide hormones play a crucial role in plant growth and
development. A group of these peptide hormones are signaling peptides with 5 - 23 amino acids.
Flagellin peptide (flg22) also elicits an immune response in plants. The functions are expressed
through recognition of the peptide hormones and flg22. This recognition relies on membrane
localized receptor kinases with extracellular leucine rich repeats (LRR-RKs). The structures of
plant peptide hormones - AtPep1, IDA, IDL1, RGFs 1- 3, TDIF/CLE41 - and of flg22 complexed
with LRR domains of corresponding LRRRKs and co-receptors SERKs have been determined.
However, their structures are well not analyzed and characterized in detail. The structures of PIP,
CEP, CIF, and HypSys are still unknown.

Objective:

Our motivation is to clarify structural features of these plant, small peptides and Flg22 in
their bound states.

Methods:

In this article, we performed secondary structure assignments and HELFIT analyses
(calculating helix axis, pitch, radius, residues per turn, and handedness) based on the atomic
coordinates from the crystal structures of AtPep1, IDA, IDL1, RGFs 1- 3, TDIF/CLE41 - and of
flg22. We also performed sequence analysis of the families of PIP, CEP, CIF, and HypSys in order
to predict their secondary structures.

Results:

Following AtPep1 with 23 residues adopts two left handed polyproline helices (PPIIs)
with six and four residues. IDA, IDL1, RGFs 1 - 2, and TDIF/CLE41 with 12 or 13 residues adopt
a four residue PPII; RGF3 adopts two PPIIs with four residues. Flg22 with 22 residues also adopts a
six residue PPII. The other peptide hormones – PIP, CEP, CIF, and HypSys – that are rich in
proline or hydroxyproline presumably prefer PPII.

Conclusion:

The present analysis indicates that PPII helix in the plant small peptide hormones and
in flg22 is crucial for recognition of the LRR domains in receptors.
Ligand- and Structure-Based Drug Design and Optimization using KNIME
Authors: Mazanetz Michael P. , Goode Charlotte H.F. , Chudyk Ewa I.
Published: April 2019

In recent years there has been a paradigm shift in how data is being used to progress early drug discovery campaigns from hit identification to candidate selection. Significant developments in data mining methods and the accessibility of tools for research scientists have been instrumental in reducing drug discovery timelines and in increasing the likelihood of a chemical entity achieving drug development milestones. KNIME, the Konstanz Information Miner, is a leading open source data analytics platform and has supported drug discovery endeavours for over a decade. KNIME provides a rich palette of tools supported by an extensive community of contributors to enable ligandand structure-based drug design. This review will examine recent developments within the KNIME platform to support small-molecule drug design and provide a perspective on the challenges and future developments within this field.
Laponite-based Nanomaterials for Biomedical Applications: A Review
Authors: Das Sabya S. , Neelam  , Hussain Kashif , Singh Sima , Hussain Afzal , Faruk Abdul , Tebyetekerwa Mike
Published: April 2019

Laponite based nanomaterials (LBNMs) are highly diverse regarding their mechanical, chemical, and
structural properties, coupled with shape, size, mass, biodegradability and biocompatibility. These ubiquitous
properties of LBNMs make them appropriate materials for extensive applications. These have enormous potential
for effective and targeted drug delivery comprised of numerous biodegradable materials which results in enhanced
bioavailability. Moreover, the clay material has been explored in tissue engineering and bioimaging for
the diagnosis and treatment of various diseases. The material has been profoundly explored for minimized toxicity
of nanomedicines. The present review compiled relevant and informative data to focus on the interactions of
laponite nanoparticles and application in drug delivery, tissue engineering, imaging, cell adhesion and proliferation,
and in biosensors. Eventually, concise conclusions are drawn concerning biomedical applications and identification
of new promising research directions.
Letter to the Editor on “A System Pharmacology Study for Deciphering Anti Depression Activity of Nardostachys jatamansi”
Authors: Sadri Arash
Published: April 2019

This letter is with reference to a recent article published in Current Drug Metabolism; A System
Pharmacology Study for Deciphering Anti Depression Activity of Nardostachys jatamansi. Unfortunately,
there is a major error in the “material and method” section of the study, which jeopardizes the
study’s goal.
Phytochemical Analysis and Evaluation of Antimicrobial Activity of Peumus boldus, Psidium guajava, Vernonia polysphaera, Persea Americana, Eucalyptus citriodora Leaf Extracts and Jatropha multifida Raw Sap
Authors: da Cruz Jhonatas Emílio Ribeiro , da Costa Guerra Joyce Ferreira , de Souza Gomes Marcos , Freitas Guilherme Ramos Oliveira e , Morais Enyara Rezende
Published: April 2019

Background:

Currently, the treatment of infectious diseases has not always been successful due to the emergence of microbial resistance worldwide.

Objective:

This study aimed to evaluate the antioxidant activity, content of total phenolic compounds and flavonoids, antifungal potential and antibacterial action of six medicinal plants found in the Cerrado, leaf extracts of Boldo (Peumus boldus), Goiaba (Psidium guajava), Assa-Peixe (Vernonia polysphaera), Abacate (Persea americana), Eucalipto (Eucalyptus citriodora) and raw sap of Bálsamo (Jatropha multifida).

Methods:

The antioxidant activity was also determined through the DPPH, ABTS and phosphomolybdenum assays. In addition, the total phenolic content and flavonoid dosage were analyzed using the Folin- Ciocalteu method and the aluminum chloride test, respectively.

Results:

All extracts, except from Assa-Peixe, showed promising values against Staphylococcus aureus, with halos varying from 13-20 mm. Analysis of the minimum inhibitory concentration (MIC) values of the six medicinal plants revealed inhibitory activity of S. aureus, with concentrations varying from 3.12-12.5 mg/mL, which is a significant result considering that S. aureus is one of the main causes of hospital infections.

Conclusion:

In the analysis of the phytochemical profile, Goiaba contained the best yield of phenolic compounds and total flavonoids, as well as higher antioxidant activity by DPPH and phosphomolybdenum, demonstrating that this species contains antioxidant components that can sequester free radicals under in vitro conditions. Therefore, the crude extracts investigated are promising and their antibacterial and antioxidant actions should be thoroughly studied.
Liposomes in Active, Passive and Acoustically-Triggered Drug Delivery
Authors: Basha Sara Al , Salkho Najla , Dalibalta Sarah , Husseini Ghaleb Adnan
Published: April 2019

Cancer has become one of the most deadly noncommunicable diseases globally. Several modalities used to treat cancer patients exist today yet many have failed to prove high efficacy with low side effects. The most common example of such modalities is the use of chemotherapeutic drugs to treat cancerous cells and deter their uncontrolled proliferation. In addition to the destruction of cancerous tissues, chemotherapy destroys healthy tissues as it lacks the specificity to annihilate cancerous cells only and preferentially, which result in adverse side effects including nausea, hair fall and myocardial infarction. To prevent the side effects of non-selective chemotherapy, cancer therapy research has been focused on the implementation of nanocarrier systems that act as vehicles to encapsulate drugs and selectively transport their agent to the tumor site. In this paper, we shed light on liposomes along with three anticancer drug delivery approaches: passive, active and ultrasound-triggered drug delivery.
Association of Vitamin D Gene Polymorphisms and Bone Mineral Density in Healthy young Saudi Females
Authors: Taha Inass M. , Allah Azza M. Abdu , El Tarhouny Shereen
Published: April 2019

Background: Osteoporosis is a systemic skeletal disease characterized by
low bone mineral density. Vitamin D metabolism may play a pivotal role in its
pathophysiology.

Objectives: To determine the association between Vitamin D receptor gene
polymorphisms and bone density, as well as its relation to biochemical markers of bone
turnover, in a healthy Saudi female population.

Methods: A cross-sectional study was carried out at Taibah University, Madinah
Region, Kingdom of Saudi Arabia. After receiving informed consent, blood samples from
300 subjects were collected to measure calcium, phosphorus, alkaline phosphatase,
parathyroid hormone osteocalcin, and 1,25-OHD and perform genetic analysis of SNPs
in vitamin D receptors (VDR) rs2228570, rs731236, and rs11568820.

Results: There were significant differences between the CC, CT, and TT alleles of VDR
rs2228570. Carrying the TT allele was associated with increased risks of decreased
bone density and the presence of osteopenia with lower vitamin D3 levels (p≤0.001).
The VDR rs731236 gene showed that CC allele carriers had significant risk of
osteopenia. The AA genotype of rs11568820 showed lower levels of physical activity,
bone mineral density, Z scores, serum osteocalcin, phosphorus, and parathyroid
hormones.

Conclusion: The presence of the TT allele of the SNP rs2228570 of the VDR gene and
the SNP rs731236 of the CC genotype was associated with the presence of osteopenia
and decreased bone mineral density alongside malfunctions of vitamin D.
Macrovascular Complications of Type 2 Diabetes Mellitus
Authors: Viigimaa Margus , Sachinidis Alexandros , Toumpourleka Maria , Koutsampasopoulos Konstantinos , Alliksoo Signe , Titma Tiina
Published: April 2019

Background:

Type 2 diabetes mellitus (T2DM) has emerged as a pandemic. It has different
complications, both microvascular and macrovascular.

Objective:

The purpose of this review is to summarize the different types of macrovascular complications
associated with T2DM.

Methods:

A comprehensive review of the literature was performed to identify clinical studies, which
determine the macrovascular complications associated with T2DM.

Results:

Macrovascular complications of T2DM include coronary heart disease, cardiomyopathy, arrhythmias
and sudden death, cerebrovascular disease and peripheral artery disease. Cardiovascular disease
is the primary cause of death in diabetic patients. Many clinical studies have shown a connection
between T2DM and vascular disease, but almost always other risk factors are present in diabetic patients,
such as hypertension, obesity and dyslipidaemia.

Conclusion:

T2DM causes a variety of macrovascular complications through different pathogenetic
pathways that include hyperglycaemia and insulin resistance. The association between T2DM and cardiovascular
disease is clear, but we need more clinical studies in order to identify the pure effect of
T2DM.
Diabetes and Heart Failure: Is it Hyperglycemia or Hyperinsulinemia?
Authors: Didangelos Triantafyllos , Kantartzis Konstantinos
Published: April 2019

The cardiac effects of exogenously administered insulin for the treatment of diabetes (DM)
have recently attracted much attention. In particular, it has been questioned whether insulin is the appropriate
treatment for patients with type 2 diabetes mellitus and heart failure. While several old and
some new studies suggested that insulin treatment has beneficial effects on the heart, recent observational
studies indicate associations of insulin treatment with an increased risk of developing or worsening
of pre-existing heart failure and higher mortality rates. However, there is actually little evidence that
the associations of insulin administration with any adverse outcomes are causal. On the other hand,
insulin clearly causes weight gain and may also cause serious episodes of hypoglycemia. Moreover,
excess of insulin (hyperinsulinemia), as often seen with the use of injected insulin, seems to predispose
to inflammation, hypertension, dyslipidemia, atherosclerosis, heart failure, and arrhythmias. Nevertheless,
it should be stressed that most of the data concerning the effects of insulin on cardiac function derive
from in vitro studies with isolated animal hearts. Therefore, the relevance of the findings of such
studies for humans should be considered with caution. In the present review, we summarize the existing
data about the potential positive and negative effects of insulin on the heart and attempt to answer the
question whether any adverse effects of insulin or the consequences of hyperglycemia are more important
and may provide a better explanation of the close association of DM with heart failure.
Visfatin and Rheumatoid Arthritis: Pathogenetic Implications and Clinical Utility
Authors: Polyakova Yulia V. , Zavodovsky Boris V. , Sivordova Larisa E. , Akhverdyan Yuri R. , Zborovskaya Irina A.
Published: April 2019

Objective:

Analysis and generalization of data related to visfatin involvement in the
pathogenesis of inflammation at various stages of rheumatoid arthritis.

Data Synthesis:

Visfatin is an adipocytokine which has also been identified in non-adipose tissues.
It influences directly on the maturation of B cells, which are involved in autoantibody production
and T cell activation. Visfatin can promote inflammation via regulation of pro-inflammatory cytokines
including TNF, IL-1β and IL-6. The concentration of circulating visfatin in rheumatoid arthritis
patients is higher compared to healthy individuals. Several studies suggest that visfatin level is
associated with rheumatoid arthritis activity, and its elevation may precede clinical signs of the relapse.
In murine collagen-induced arthritis, visfatin levels were also found to be elevated both in
inflamed synovial cells and in joint vasculature. Visfatin blockers have been shown to confer fast
and long-term attenuation of pathological processes; however, most of their effects are transient.
Other factors responsible for hyperactivation of the immune system can participate in this process
at a later stage. Treatment of rheumatoid arthritis with a combination of these blockers and inhibitors
of other mediators of inflammation can potentially improve treatment outcomes compared to
current therapeutic strategies. Recent advances in the treatment of experimental arthritis in mice as
well as the application of emerging treatment strategies obtained from oncology for rheumatoid arthritis
management could be a source of novel adipokine-mediated anti-rheumatic drugs.

Conclusion:

The ongoing surge of interest in anticytokine therapy makes further study of visfatin
highly relevant as it may serve as a base for innovational RA treatment.
Optimization and Quality by Design Approach for Piroxicam Fast Dissolving Tablet Formulations Using Box-Behnken Design
Authors: Roy Harekrishna , Nandi Sisir , Pavani Ungarala , Lakshmi Uppuluri , Reddy Tamma Saicharan , Gayatri Damarla Venkata Sri
Published: April 2019

Background:

The present study deals with the formulation and optimization of piroxicam
fast dissolving tablets and analyzes the impact of an independent variable while selecting the
optimized formulation utilizing Quality by Design (QbD) and Box-Behnken Design (BBD).

Methods:

Seventeen formulations were prepared by direct compression technique by altering the
proportion of cross carmellose sodium, spray dried lactose and hydro propyl methyl cellulose
(HPMC K4M). The BBD statistical technique was used to optimize formulations and correlate the
relationship among all the variables. Also, the powder mixture characteristics and tablet physiochemical
properties such as hardness, friability, drug content, Disintegration Time (DT) and dissolution
test were determined using 900 ml of 0.1N HCl (pH-1.2) at 37 ± 0.5°C.

Results:

Significant quadratic model and second order polynomial equations were established using
BBD. To find out the relationship between variables and responses, 3D response surface and 2D
contour plot was plotted. A perturbation graph was also plotted to identify the deviation of the variables
from the mean point. An optimized formula was prepared based on the predicted response and
the resulting responses were observed to be close with the predicted value.

Conclusion:

The optimized formulation with the desired parameter and formulation with variables
and responses can be obtained by BBD and could be used in the large experiment with the involvement
of a large number of variables and responses.
Overview of Cellular Mechanisms and Signaling Pathways of Piceatannol
Authors: Yan Liang , Kong Lingbo , Cao Yang , Smith Wanli
Published: April 2019

Stilbenoids are a group of naturally occurring phenolic compounds found in various plant species.
They share a common backbone structure known as stilbene. However, differences in the nature and
position of substituents have made it possible to produce many derivatives. Piceatannol [PT], a hydroxylated
derivative from resveratrol, exerts various biological activities ranging from cancer prevention, cardio-
protection, neuro-protection, anti-diabetic, depigmentation and so on. Although positive results were
obtained in most cell culture and animal studies, the relevant cellular and molecular mechanisms of cytokines
and signaling pathway about their biological effects still unclear. Thus, in the current review, we
focus on the latest findings of PT on cellular biology in order to better understand the underlying therapeutic
mechanisms of PT among various diseases.
A New Comprehensive Index for Evaluating the Quality of Infant Formula under the Framework of Chinese Food Standards
Authors: Zhang Ming , Zhang Li , Liu Hongsheng
Published: April 2019

Objective:

We proposed a new comprehensive index, the food quality index (FQI), to
effectively evaluate food quality.

Methods:

The food quality index is based on chemical and biological indicators of the Chinese
food standards framework. We evaluated the limit value regulations for infant formula standards
and then established a comprehensive index and grading standard. Finally, we applied the index to
evaluate data obtained from the Shenyang Product Quality Supervision and Inspection Institute.

Results:

The results showed that the quality of older infant and young children formula (OF) was
good, and the infant formula (IF) was acceptable.

Conclusion:

The quality of OF was observably higher than that of IF, and they were significantly
different with a p-value < 0.01. The most influencing factor of the IF and OF was minerals, followed
by major components, optional ingredients, vitamins, and pathogenic bacteria had no effect.
In IF, The number of the main influencing single indicators were 36 and 20 in IF and OF, respectively.
Statistical analysis showed that index values of vitamins in the two kinds of milk powders
were significantly different, with a p-value < 0.01. Optional ingredients were significantly correlated,
with a p-value < 0.05.
Synthesis of 5-Alkynyltetrandrine Derivatives and Evaluation of their Anticancer Activity on A549 Cell Lines
Authors: Niu Nana , Qu Tingli , Xu Jinfang , Lu Xiaolin , Bodwell Graham J. , Zhao Zhengbao
Published: April 2019

Background:

Lung cancer is one of the most prevalent malignancies and thus the development of novel
therapeutic agents for managing lung cancer is imperative. Tetrandrine, a bis-benzyltetrahydroisoquinoline
alkaloid isolated from Stephania tetrandra S. Moore, has been found to exert cytotoxic effects on cancerous
cells.

Methods:

A series of 5-alkynyltetrandrine derivatives was synthesized via the Sonogashira cross-coupling reactions
and evaluated as potential anti-tumor agents. The anti-tumor activities of 12 compounds on lung cancer
cells (A549) were evaluated using the MTT method. The population of apoptotic cells was measured using a
TUNEL assay. Real-time PCR quantified the gene expression levels of Bcl-2, Bax, survivin and caspase-3. The
content of Cyt-C was detected using a Human Cyt-C ELISA kit.

Results:

Most of these compounds exhibited better activities than tetrandrine itself on A549 cells. Among them,
compound 7 showed the highest cytotoxicity among the tested compounds against human lung adenocarcinoma
A549 cells with an IC50 of 2.94 µM. Preliminary mechanistic studies indicated that compound 7 induced apoptosis
of human lung cancer A549 cells and increased the level of the proapoptotic gene Bax, release of Cyt-C from
mitochondria and activation of caspase-3 genes.

Conclusion:

The results suggest that compound 7 exerts its antitumor activity against A549 cells through the
induction of the intrinsic (mitochondrial) apoptotic pathway. These findings will contribute to the future design
of more effective anti-tumor agents in lung cancer therapy.
The Emerging Role of CSN6 in Biological Behavior and Cancer Progress
Authors: Mao Zun , Chen Cheng , Pei Dong-Sheng
Published: April 2019

Background:

The Constitutive Photomorphogenesis 9 (COP9) signalosome (CSN) subunit 6 (CSN6) noticeably acts as a regulator of the degradation of cancer-related proteins, which contributes to cancerogenesis. The aims of this paper are to expound the research advances of CSN6, particularly focusing on roles of CSN6 in the regulation of biological behavior and cancer progress.

Methods:

Literature from PubMed and Web of Science databases about biological characteristics and application of CSN6 published in recent years was collected to conduct a review.

Results:

CSN6, not only the non-catalytic Mpr1p and Pad1p N-terminal (MPN) subunit of CSN, but also a relatively independent protein molecule, has received great attention as a regulator of a wide range of developmental processes by taking part in the ubiquitin-proteasome system and signal transduction, as well as regulating genome integrity and DNA damage response. In addition, phosphorylation of CSN6 increases the stability of CSN6, thereby promoting its regulatory capacity. Moreover, CSN6 is overexpressed in many types of cancer compared with normal tissues and is involved in the regulation of several important intracellular pathways, consisting of cell proliferation, migration, invasion, transformation, and tumorigenesis.

Conclusion:

We mainly present insights into the function and research development of CSN6, hoping that it can help guide the treatment of developmental defects and improve clinical care, especially in the regulation of cancer signaling pathways.