bluuebunny/crossref_metadata_2025 huggingface dataset:
DEVELOPMENT OF MANDIRI LEARNING MODEL BASED ON OPEN LEARNING IN LEARNING CALIBULUS IN PRODUCING MATHEMATICS EDUCATION UNIVERSITY STATE MAKASSAR
Authors: Arianti Arianti
Published: December 2017

This research is categorized as research and development, refers to Plomp model (1997). This model consists of 5 steps, namely (a) first study step, (b) planning step, (c) realizing/construction step, (d) test, evaluation and revision step, and (e) implementation step. The results of the study reveal that (1) based on expert validation result, it is obtained that the instruments used in independent learning model based on opened questions (PMBST) is extremely valid, (2) the practical result of independent learning model based on opened questions through observation sheets instruments is in entirely conducted category, and the lecturer’s ability to manage the class is in average score of 3.5 (high qualification), (3) the effectiveness of independent learning model based on opened questions for 3 effectiveness components had been achieved, that: (a) the students’ activities had met the set ideal time (>75%), (b) the students’ response of independent learning model based on opened questions is in positive category, that 80% of the students give positive response on learning process, (c) the students’ learning achievements cover: (1) the students’ creativity in calculus problem solving obtained 63% for creative thinking criteria is in medium category, (2) the students’ learning independent in understanding calculus material is in positive category, there are 28 out of 39 students’ (72%) give positive response on independent learning, and (3) calculus material mastery in terms of completeness learning result, there are 34 out of 39 students’ (87%) obtained the score above 61
Theoretical Linkage between Corporate Social Responsibility and Corporate Reputation
Authors: Hasan Rashedul , Yun Tee Mei
Published: December 2017

In today’s corporate world, Corporate Social Responsibility (CSR) is becoming a significant field of study for all businesses as its notion has increased attention of both academics and practitioners. Secondary sources of data are utilized using document analysis method to understand the relationship between Corporate Social Responsibility (CSR) and corporate reputation (CR). Five papers are selected from Science Direct which covers the time frame of 2012 until 2017. Evidence indicates that there is a positive, direct and significant relationship between CSR and CR. This paper contributes to the understanding of interrelations between CSR and CR. Practitioners can use the result of this study as a foothold to strengthen the integration of CSR and take advantage of synergies between CSR and CR. The value of paper resides in making this rather under-researched literature on the relationship between CSR and CR be more accessible for both scholars and practitioners.
CARACTERÍSTICAS Y EVOLUCIÓN DE LA OFERTA DE ALOJAMIENTO DE AIRBNB EN UNA CIUDAD PATRIMONIO CULTURAL DE LA HUMANIDAD. CASO CUENCA (ECUADOR)
Authors: Espinoza-Figueroa Freddy Edgar , Freire-Chaglla Segundo Amador
Published: December 2017

Actualmente han surgido modelos de negocio innovadores en cuanto a su operación, a través de medios de gestión electrónica, como Airbnb (alojamiento), están presentes casi en todo el mundo, bajo la denominación de economía colaborativa, tienen predilección por ubicarse en asentamientos urbanos consolidados como centros históricos; Cuenca, Patrimonio Cultural de la Humanidad no es la excepción. No obstante, generan incomodidad a los modelos de negocio tradicionales y menoscaban la autenticidad, integridad y valores patrimoniales de los bienes culturales edificados en virtud de una probable sobreoferta de alojamiento. Este estudio de tipo descriptivo se realizó mediante la recopilación de datos históricos (2010 - 2017) de la oferta de Airbnb (página web) para Cuenca, y, tiene como objetivo, poner en contexto las características y evolución de este tipo de oferta en un contexto de ciudad patrimonial, teniendo como resultado una tendencia a la concentración de este tipo de establecimientos en áreas históricas y patrimoniales; además se evidencia una tendencia decreciente de las tarifas frente a una presión a la reducción de los precios de los establecimientos regulados. Este fenómeno tiene efectos más allá del turismo, por lo que es alarmante la falta de políticas de control y regulación por parte del sector público, la desidia en torno a la innovación por parte del sector privado, la falta de estudios y el menoscabo del patrimonio cultural edificado y la vivienda en relación al incremento de una oferta informal.
Intelligent Hypothermia Care System using Ant Colony Optimization for Rules Prediction
Authors: AL-Behadili Hayder Naser Khraibet
Published: December 2017

Intelligent Hypothermia Care System (IHCS) is an intelligence system uses set of methodologies, algorithms, architectures, and processes to determine where patients in a postoperative recovery area must be sent. Hypothermia is a significant concern after surgery. This paper utilizes the classification task in data mining to propose an intelligent technique to predict where to send a patient after surgery: intensive care unit, general floor or home. To achieve this goal, this paper evaluates the performance of decision tree algorithm, exemplifying the deterministic approach, against the AntMiner algorithm, exemplifying the heuristic approach, to choose the best approach in detecting the patient’s status. Results show the outperformance of the heuristic approach. The implication of this proposal will be twofold: in hypothermia treatment and in the application of ant colony optimization.
Methodology of Islamic Studies in The East and in The West: A Comparative Review on The Study of Hadith
Authors: El Chirri Nabila
Published: December 2017

Discourse on Islam and hadith seems to always attract the attention of many people, both Muslims and non-Muslims. It is proven until now, studies of hadith both concerning the criticism of its authenticity, as well as the methodology of its understanding continue to grow. The hadith of the Prophet, or often referred to the Sunnah of the Prophet, does not only attract the attention of Muslims and Muslim scientists to study and understand more about it. A number of Western scholars (non-Muslims) are also seen to have serious concerns on this issue. They are studying many of the Prophet's hadiths, especially regarding its authenticity. They have long been interested in Islamic studies, hadiths and writing texts of hadith, they focus on the main (text) of the hadith material, and the sanad (narrator of hadith), this approach they call the study of analysis of sanad (isnad-analytical study).
Ibadah Haji Ditinjau Dari Berbagai Aspek
Authors: Kisworo Budi
Published: December 2017

Hajj is a very special worship in Islam. It is the spiritual congress of Muslims worldwide. His position in religion as the fifth pillar of Islam, but in terms of its appeal to the interests of the Muslim community, the pilgrims ranked first. There are no districts or provinces in Indonesia that are waiting list of hajj candidates for only one year. It's all over five years. Hajj comes from the Shari'ah of Prophet Ibrahim. Which was transmitted by the Prophet Muhammad and followed by his people until the end of time. The goal is that mankind wants to imitate the behavior of Prophet Ibrahim, his wife Hajar, and his son Ismail in surrendering in totality to his Lord. The spiritual monument built by Prophet Ibrahim and his family has been practiced and perfected by the Prophet Muhammad. Through the pilgrimage, the spiritual monument built by four central figures, Ibrahim as., Siti Hajar, Ismail as., And Muhammad saw. It would be taken home by every pilgrim as a souvenir to be dedicated to the community in their respective hometown. Not the title of Pak Haji or Bu Hajjah, not white “peci” or white “mukena” as a symbol of hajj mabrur, but "pure heart" as the embodiment of total submission of faith to the Most Own.
Syariat Islam Tentang Relasi dan Toleransi Antar Umat Beragama Dalam Alquran
Authors: Yusefri Y
Published: December 2017

This paper essentially conducted a study on how the provisions of Islamic law that governs the relationship between a Muslim with non-Muslims in order to realize inter-religious harmony. The study was conducted because, since the classical times, there were books of fiqh, which is a collection of the scholar’s ideas about the formulation of Islamic sharia (law) extracted from the source, had not seen yet containing the discussion about many provisions related to the deed of a Muslim with non-Muslims. The object of study is more focused on the verses of Al-Quran related to this issue. By using the analytical approach of interpretation, proved that Islamic law has laid clear provisions regulating the relationship between a Muslim and non-Muslims, including compelled to behave tolerantly, should not enforcing and anarchists.
Solusi Ekonomi Islam Terhadap Rekayasa Helah (Praktek Riba)
Authors: Batubara Damri
Published: December 2017

Islam places economic activity as one of the most important aspects of gaining glory, and therefore economic activity, like any other activity, needs to be controlled and guided in line with the objectives of Islamic Shariah. However, some people take advantage of the legitimate contracts of Islamic law to be able to do usury, or legitimize usury through the engineering of legitimate contracts, or make a legitimate contract as a shield of usury usage called helah (engineering practice usury. If the perpetrator intends to deliberately do helah to justify usury where the first and second sale is not the goal of both parties, but only serve as a tool to justify usury, then no doubt about the prohibition of their actions because a road to the haram is also illegal, because human actions are measured according to their intentions.
Fenomenologi-Ekonomi Islam: Lit Review atas Epistemologi Ekonomi Islam Masudul Alam Choudhury
Authors: Shalihin Nurus
Published: December 2017

Islamic economics is difference with the positivism economics and others. It is a established-concessus among Muslim-economists. Albeit some scholars are still sceptical toward Islamic economics as a complete-science. To respond this assumption, various Islamic scholars who are concern in formulating the epistemology of Islamic Economics. Turast written by classical muslim scholars studied intensively. And also Masudul Alam Choudhury who have intensively research the epistemology of Islamic economics with uniqueness form of epistemology—named by the phenomenology of Islamic economics. This paper examine radically the essensy of Masudul Alam Choudhury. It is to identify the construction of Islamic economics metodology offered by Choudhury.

Keywords : Phenomenology, Unity of Knowledge, Islamic Economics, Phenomenology methodology and logical formalism.
Heat and mass transfer with viscous dissipation in horizontal channel partially occupied by porous medium in the presence of oscillatory suction
Authors: Sharma P. , Saboo R.
Published: December 2017

This paper deals with unsteady oscillatory flow of viscous incompressible fluid with heat & mass transfer in a horizontal channel partially occupied by porous medium following the Darcy-Brinkman model. The interior territory of the channel consists of two regions; one of them is filled with porous material and second is clear fluid. At the porous medium fluid interface, interfacial coupling conditions for the fluid velocity, temperature and concentration were used to derive the analytical solution. The effects of pertinent physical fluid parameter like porosity, viscosity ratio, density ratio etc. on velocity, temperature and concentration distribution are considered and demonstrated through graphs. Also, the non-dimensional Skin-friction coefficient, Nusselt number and Sherwood number have been calculated and reported in tabular form.
Strengths, weaknesses, opportunities, and threats analysis of integrating the World Health Organization patient safety curriculum into undergraduate medical education in Pakistan: a qualitative case study
Authors: Misbah Samreen , Mahboob Usman
Published: December 2017

Purpose: The purpose of this study was to conduct a strengths, weaknesses, opportunities, and threats (SWOT) analysis of integrating the World Health Organization (WHO) patient safety curriculum into undergraduate medical education in Pakistan. Methods: A qualitative interpretive case study was conducted at Riphah International University, Islamabad, from October 2016 to June 2017. The study included 9 faculty members and 1 expert on patient safety. The interviews were audiotaped, and a thematic analysis of the transcripts was performed using NVivo software. Results: Four themes were derived based on the need analysis model. The sub-themes derived from the collected data were arranged under the themes of strengths, weaknesses, opportunities, and threats, in accordance with the principles of SWOT analysis. The strengths identified were the need for a formal patient safety curriculum and its early integration into the undergraduate program. The weaknesses were faculty awareness and participation in development programs. The opportunities were an ongoing effort to develop an appropriate curriculum, to improve the current culture of healthcare, and to use the WHO curricular resource guide. The threats were attitudes towards patient safety in Pakistani culture, resistance to implementation from different levels, and the role of regulatory authorities. Conclusion: The theme of patient safety needs to be incorporated early into the formal medical education curriculum, with the main goals of striving to do no harm and seeing mistakes as opportunities to learn. Faculty development activities need to be organized, and faculty members should to be encouraged to participate in them. The lack of a patient safety culture was identified as the primary reason for resistance to this initiative at many levels. The WHO curriculum, amended according to local institutional culture, can be implemented appropriately with support from the corresponding regulatory bodies.
Molecular Dynamics Electrospray Simulations of Coarse-Grained Ethylammonium Nitrate (EAN) and 1-Ethyl-3-Methylimidazolium Tetrafluoroborate (EMIM-BF4)
Authors: Mehta Neil , Levin Deborah
Published: December 2017

In this work, the use of molecular dynamics as a predictive tool for modeling the atomistic behavior of electrospray propulsion is discussed. 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIM-BF 4 ) and ethylammonium nitrate (EAN) were considered as two limits of ionic liquid (IL) propellants that tend to operate in an ion versus a droplet mode. The emission modes were found to depend on the electro-chemical properties of the IL propellant. The aprotic EMIM-BF 4 -based electrospray emitted primarily monomers and trimers as the dominant species and only small quantities of droplets. In contrast, trimers were the dominant emitted species in the protic EAN emissions with a significantly large contribution from droplets towards the total emission current, suggesting that EMIM-BF 4 -based colloid thrusters operate in ion mode and EAN-based devices operate in the droplet mode. Furthermore, the formation of the Taylor cone was found to depend on the mass flow rate and the external electric field strength. This paper provides a framework that can be extended for use to simulate any other ILs or their combinations.
The Role of Chromosomal Instability in Cancer and Therapeutic Responses
Authors: Vargas-Rondón Natalia , Villegas Victoria , Rondón-Lagos Milena
Published: December 2017

Cancer is one of the leading causes of death, and despite increased research in recent years, control of advanced-stage disease and optimal therapeutic responses remain elusive. Recent technological improvements have increased our understanding of human cancer as a heterogeneous disease. For instance, four hallmarks of cancer have recently been included, which in addition to being involved in cancer development, could be involved in therapeutic responses and resistance. One of these hallmarks is chromosome instability (CIN), a source of genetic variation in either altered chromosome number or structure. CIN has become a hot topic in recent years, not only for its implications in cancer diagnostics and prognostics, but also for its role in therapeutic responses. Chromosomal alterations are mainly used to determine genetic heterogeneity in tumors, but CIN could also reveal treatment efficacy, as many therapies are based on increasing CIN, which causes aberrant cells to undergo apoptosis. However, it should be noted that contradictory findings on the implications of CIN for the therapeutic response have been reported, with some studies associating high CIN with a better therapeutic response and others associating it with therapeutic resistance. Considering these observations, it is necessary to increase our understanding of the role CIN plays not only in tumor development, but also in therapeutic responses. This review focuses on recent studies that suggest possible mechanisms and consequences of CIN in different disease types, with a primary focus on cancer outcomes and therapeutic responses.
Translating MC2 DGVM Results into Ecosystem Services for Climate Change Mitigation and Adaptation
Authors: Bachelet Dominique , Ferschweiler Kenneth , Sheehan Timothy , Sleeter Benjamin , Zhu Zhiliang
Published: December 2017

Ecosystem services (ES) were conceived to emphasize the role of ecological processes in supporting societal needs and to allow their inclusion in the decision-making process. Currently climate change mitigation is one of the most important services ecosystems can provide to enhance sinks of greenhouse gas emissions as the planet warms and related extreme events take their toll on societies. Because ES cannot always be directly measured and because measurements are often cost prohibitive, process-based models are used to estimate their supply, delivery and/or value. We ran the MC2 dynamic global vegetation model for the conterminous US with/without land use for several future scenarios. We translated results into key ES such as carbon sequestration, which contributes to climate regulation, into a regulatory service or aboveground forest carbon into timber biomass, a provisioning service, and evaluated constraints to maintain them. By comparing projections with/without land use we illustrated differences between managed and natural lands and provided information to help the valuation of societally relevant services.
Toward Development of a Stochastic Wake Model: Validation Using LES and Turbine Loads
Authors: Moon Jae , Manuel Lance , Churchfield Matthew , Lee Sang , Veers Paul
Published: December 2017

Wind turbines within an array do not experience free-stream undisturbed flow fields. Rather, the flow fields on internal turbines are influenced by wakes generated by upwind unit and exhibit different dynamic characteristics relative to the free stream. The International Electrotechnical Commission (IEC) standard 61400-1 for the design of wind turbines only considers a deterministic wake model for the design of a wind plant. This study is focused on the development of a stochastic model for waked wind fields. First, high-fidelity physics-based waked wind velocity fields are generated using Large-Eddy Simulation (LES). Stochastic characteristics of these LES waked wind velocity field, including mean and turbulence components, are analyzed. Wake-related mean and turbulence field-related parameters are then estimated for use with a stochastic model, using Multivariate Multiple Linear Regression (MMLR) with the LES data. To validate the simulated wind fields based on the stochastic model, wind turbine tower and blade loads are generated using aeroelastic simulation for utility-scale wind turbine models and compared with those based directly on the LES inflow. The study’s overall objective is to offer efficient and validated stochastic approaches that are computationally tractable for assessing the performance and loads of turbines operating in wakes.
Evolutionary Dynamics of the W Chromosome in Caenophidian Snakes
Authors: Augstenová Barbora , Mazzoleni Sofia , Kratochvíl Lukáš , Rovatsos Michail
Published: December 2017

The caenophidian (assigned also as “advanced”) snakes are traditionally viewed as a group of reptiles with a limited karyotypic variation and stable ZZ/ZW sex chromosomes. The W chromosomes of the caenophidian snakes are heterochromatic, and pioneering studies demonstrated that they are rich in repetitive elements. However, a comparative study of the evolutionary dynamics of the repetitive content of the W chromosome across the whole lineage is missing. Using molecular-cytogenetic techniques, we explored the distribution of four repetitive motifs (microsatellites GATA, GACA, AG and telomeric-like sequences), which are frequently accumulated in differentiated sex chromosomes in vertebrates, in the genomes of 13 species of the caenophidian snakes covering a wide phylogenetic spectrum of the lineage. The results demonstrate a striking variability in the morphology and the repetitive content of the W chromosomes even between closely-related species, which is in contrast to the homology and long-term stability of the gene content of the caenophidian Z chromosome. We uncovered that the tested microsatellite motifs are accumulated on the degenerated, heterochromatic W chromosomes in all tested species of the caenophidian snakes with the exception of the Javan file snake representing a basal clade. On the other hand, the presence of the accumulation of the telomeric-like sequences on the caenophidian W chromosome is evolutionary much less stable. Moreover, we demonstrated that large accumulations of telomeric-like motifs on the W chromosome contribute to sexual differences in the number of copies of the telomeric and telomeric-like repeats estimated by quantitative PCR, which might be confusing and incorrectly interpreted as sexual differences in telomere length.
Genome Sequencing and Assembly by Long Reads in Plants
Authors: Li Changsheng , Lin Feng , An Dong , Wang Wenqin , Huang Ruidong
Published: December 2017

Plant genomes generated by Sanger and Next Generation Sequencing (NGS) have provided insight into species diversity and evolution. However, Sanger sequencing is limited in its applications due to high cost, labor intensity, and low throughput, while NGS reads are too short to resolve abundant repeats and polyploidy, leading to incomplete or ambiguous assemblies. The advent and improvement of long-read sequencing by Third Generation Sequencing (TGS) methods such as PacBio and Nanopore have shown promise in producing high-quality assemblies for complex genomes. Here, we review the development of sequencing, introducing the application as well as considerations of experimental design in TGS of plant genomes. We also introduce recent revolutionary scaffolding technologies including BioNano, Hi-C, and 10× Genomics. We expect that the informative guidance for genome sequencing and assembly by long reads will benefit the initiation of scientists’ projects.
Targeted α Therapies for the Treatment of Bone Metastases
Authors: Zustovich Fable , Barsanti Roberto
Published: December 2017

The skeleton is the target tissue for many types of tumors, and, recently, the survival of patients with prostate cancer metastasis has been increased using α-emitting drugs known as targeted α therapies. The use of α-radiopharmaceuticals in medicine was hypothesized at the beginning of the nineteenth century after the observation that α-radionuclides were associated with high cell-killing energy and low tissue penetration in healthy tissues. In the prostate cancer (PC) scenario, current research suggests that this class of radiopharmaceuticals has limited toxicity, and that the mechanism of action does not overlap with pre-existing drugs, allowing us to extend therapeutic armaments and address medical oncology towards personalized and precision medicine. Ongoing studies may extend these benefits also to bone metastases deriving from other neoplasms. The aim of this review is to summarize the current research on targeted α therapies and try to identify the right patient to be treated in the right time in order to integrate in these medications in the every-day clinical practice.
Therapeutic Applications of Targeted Alternative Splicing to Cancer Treatment
Authors: Lin Jung-Chun
Published: December 2017

A growing body of studies has documented the pathological influence of impaired alternative splicing (AS) events on numerous diseases, including cancer. In addition, the generation of alternatively spliced isoforms is frequently noted to result in drug resistance in many cancer therapies. To gain comprehensive insights into the impacts of AS events on cancer biology and therapeutic developments, this paper highlights recent findings regarding the therapeutic routes of targeting alternative-spliced isoforms and splicing regulators to treatment strategies for distinct cancers.
Identification of Host Defense-Related Proteins Using Label-Free Quantitative Proteomic Analysis of Milk Whey from Cows with Staphylococcus aureus Subclinical Mastitis
Authors: Abdelmegid Shaimaa , Murugaiyan Jayaseelan , Abo-Ismail Mohamed , Caswell Jeff , Kelton David , Kirby Gordon
Published: December 2017

Staphylococcus aureus is the most common contagious pathogen associated with bovine subclinical mastitis. Current diagnosis of S. aureus mastitis is based on bacteriological culture of milk samples and somatic cell counts, which lack either sensitivity or specificity. Identification of milk proteins that contribute to host defense and their variable responses to pathogenic stimuli would enable the characterization of putative biomarkers of subclinical mastitis. To accomplish this, milk whey samples from healthy and mastitic dairy cows were analyzed using a label-free quantitative proteomics approach. In total, 90 proteins were identified, of which 25 showed significant differential abundance between healthy and mastitic samples. In silico functional analyses indicated the involvement of the differentially abundant proteins in biological mechanisms and signaling pathways related to host defense including pathogen-recognition, direct antimicrobial function, and the acute-phase response. This proteomics and bioinformatics analysis not only facilitates the identification of putative biomarkers of S. aureus subclinical mastitis but also recapitulates previous findings demonstrating the abundance of host defense proteins in intramammary infection. All mass spectrometry data are available via ProteomeXchange with identifier PXD007516.
A Metabolomic and Lipidomic Serum Signature from Nonhuman Primates Administered with a Promising Radiation Countermeasure, Gamma-Tocotrienol
Authors: Cheema Amrita , Mehta Khyati , Fatanmi Oluseyi , Wise Stephen , Hinzman Charles , Wolff Josh , Singh Vijay
Published: December 2017

The development of radiation countermeasures for acute radiation syndrome (ARS) has been underway for the past six decades, leading to the identification of multiple classes of radiation countermeasures. However, to date, only two growth factors (Neupogen and Neulasta) have been approved by the United States Food and Drug Administration (US FDA) for the mitigation of hematopoietic acute radiation syndrome (H-ARS). No radioprotector for ARS has been approved by the FDA yet. Gamma-tocotrienol (GT3) has been demonstrated to have radioprotective efficacy in murine as well as nonhuman primate (NHP) models. Currently, GT3 is under advanced development as a radioprotector that can be administered prior to radiation exposure. We are studying this agent for its safety profile and efficacy using the NHP model. In this study, we analyzed global metabolomic and lipidomic changes using ultra-performance liquid chromatography (UPLC) quadrupole time-of-flight mass spectrometry (QTOF-MS) in serum samples of NHPs administered GT3. Our study, using 12 NHPs, demonstrates that alterations in metabolites manifest only 24 h after GT3 administration. Furthermore, metabolic changes are associated with transient increase in the bioavailability of antioxidants, including lactic acid and cholic acid and anti-inflammatory metabolites 3 deoxyvitamin D3, and docosahexaenoic acid. Taken together, our results show that the administration of GT3 to NHPs causes metabolic shifts that would provide an overall advantage to combat radiation injury. This initial assessment also highlights the utility of metabolomics and lipidomics to determine the underlying physiological mechanisms involved in the radioprotective efficacy of GT3.
Clinical and Neurobehavioral Features of Three Novel Kabuki Syndrome Patients with Mosaic KMT2D Mutations and a Review of Literature
Authors: Lepri Francesca , Cocciadiferro Dario , Augello Bartolomeo , Alfieri Paolo , Pes Valentina , Vancini Alessandra , Caciolo Cristina , Squeo Gabriella , Malerba Natascia , Adipietro Iolanda , Novelli Antonio , Sotgiu Stefano , Gherardi Renzo , Digilio Maria , Dallapiccola Bruno , Merla Giuseppe
Published: December 2017

Kabuki syndrome (KS) is a rare disorder characterized by multiple congenital anomalies and variable intellectual disability caused by mutations in KMT2D/MLL2 and KDM6A/UTX, two interacting chromatin modifier responsible respectively for 56–75% and 5–8% of the cases. To date, three KS patients with mosaic KMT2D deletions in blood lymphocytes have been described. We report on three additional subjects displaying KMT2D gene mosaics including one in which a single nucleotide change results in a new frameshift mutation (p.L1199HfsX7), and two with already-known nonsense mutations (p.R4484X and p.R5021X). Consistent with previously published cases, mosaic KMT2D mutations may result in mild KS facial dysmorphisms and clinical and neurobehavioral features, suggesting that these characteristics could represent the handles for genetic testing of individuals with slight KS-like traits.
Key Clinical Factors Predicting Adipokine and Oxidative Stress Marker Concentrations among Normal, Overweight and Obese Pregnant Women Using Artificial Neural Networks
Authors: Solis-Paredes Mario , Estrada-Gutierrez Guadalupe , Perichart-Perera Otilia , Montoya-Estrada Araceli , Guzmán-Huerta Mario , Borboa-Olivares Héctor , Bravo-Flores Eyerahi , Cardona-Pérez Arturo , Zaga-Clavellina Veronica , Garcia-Latorre Ethel , Gonzalez-Perez Gabriela , Hernández-Pérez José , Irles Claudine
Published: December 2017

Maternal obesity has been related to adverse neonatal outcomes and fetal programming. Oxidative stress and adipokines are potential biomarkers in such pregnancies; thus, the measurement of these molecules has been considered critical. Therefore, we developed artificial neural network (ANN) models based on maternal weight status and clinical data to predict reliable maternal blood concentrations of these biomarkers at the end of pregnancy. Adipokines (adiponectin, leptin, and resistin), and DNA, lipid and protein oxidative markers (8-oxo-2′-deoxyguanosine, malondialdehyde and carbonylated proteins, respectively) were assessed in blood of normal weight, overweight and obese women in the third trimester of pregnancy. A Back-propagation algorithm was used to train ANN models with four input variables (age, pre-gestational body mass index (p-BMI), weight status and gestational age). ANN models were able to accurately predict all biomarkers with regression coefficients greater than R2 = 0.945. P-BMI was the most significant variable for estimating adiponectin and carbonylated proteins concentrations (37%), while gestational age was the most relevant variable to predict resistin and malondialdehyde (34%). Age, gestational age and p-BMI had the same significance for leptin values. Finally, for 8-oxo-2′-deoxyguanosine prediction, the most significant variable was age (37%). These models become relevant to improve clinical and nutrition interventions in prenatal care.
Contact-Free Support Structures for Part Overhangs in Powder-Bed Metal Additive Manufacturing
Authors: Cooper Kenneth , Steele Phillip , Cheng Bo , Chou Kevin
Published: December 2017

This study investigates the feasibility of a novel concept, contact-free support structures, for part overhangs in powder-bed metal additive manufacturing. The intent is to develop alternative support designs that require no or little post-processing, and yet, maintain effectiveness in minimizing overhang distortions. The idea is to build, simultaneously during part fabrications, a heat sink (called “heat support”), underneath an overhang to alter adverse thermal behaviors. Thermomechanical modeling and simulations using finite element analysis were applied to numerically research the heat support effect on overhang distortions. Experimentally, a powder-bed electron beam additive manufacturing system was utilized to fabricate heat support designs and examine their functions. The results prove the concept and demonstrate the effectiveness of contact-free heat supports. Moreover, the method was tested with different heat support parameters and applied to various overhang geometries. It is concluded that the heat support proposed has the potential to be implemented in industrial applications.
Simulative Prediction of Fiber-Matrix Separation in Rib Filling During Compression Molding Using a Direct Fiber Simulation
Authors: Kuhn Christoph , Walter Ian , Täger Olaf , Osswald Tim
Published: December 2017

Compression molding of long fiber reinforced composites offers specific advantages in automotive applications due to the high strength to weight ratio, the comparably low tooling costs and short cycle times. However, the manufacturing process of long fiber composite parts presents a range of challenges. The phenomenon of fiber matrix separation (FMS) is causing severe deviations in fiber content, especially in complex ribbed structures. Currently, there is no commercial software that is capable to accurately predict FMS. This work uses a particle level mechanistic model to study FMS in a rib filling application. The direct fiber simulation (DFS) is uniquely suited to this application due to its ability to model individual fibers and their bending, as well as the interaction amongst fibers that leads to agglomeration. The effects of mold geometry, fiber length, viscosity, and initial fiber orientation are studied. It is shown that fiber length and initial fiber orientation have the most pronounced effects on fiber volume percentage in the ribs, with viscosity and part geometry playing a smaller role.
Reference Tracts and Generative Models for Brain White Matter Tractography
Authors: Muñoz Maniega Susana , Bastin Mark , Deary Ian , Wardlaw Joanna , Clayden Jonathan
Published: December 2017

Background: Probabilistic neighborhood tractography aims to automatically segment brain white matter tracts from diffusion magnetic resonance imaging (dMRI) data in different individuals. It uses reference tracts as priors for the shape and length of the tract, and matching models that describe typical deviations from these. We evaluated new reference tracts and matching models derived from dMRI data acquired from 80 healthy volunteers, aged 25–64 years. Methods: The new reference tracts and models were tested in 50 healthy older people, aged 71.8 ± 0.4 years. The matching models were further assessed by sampling and visualizing synthetic tracts derived from them. Results: We found that data-generated reference tracts improved the success rate of automatic white matter tract segmentations. We observed an increased rate of visually acceptable tracts, and decreased variation in quantitative parameters when using this approach. Sampling from the matching models demonstrated their quality, independently of the testing data. Conclusions: We have improved the automatic segmentation of brain white matter tracts, and demonstrated that matching models can be successfully transferred to novel data. In many cases, this will bypass the need for training data and make the use of probabilistic neighborhood tractography in small testing datasets newly practicable.
Pharmacogenomics of CYP2C9: Functional and Clinical Considerations
Authors: Daly Ann , Rettie Allan , Fowler Douglas , Miners John
Published: December 2017

CYP2C9 is the most abundant CYP2C subfamily enzyme in human liver and the most important contributor from this subfamily to drug metabolism. Polymorphisms resulting in decreased enzyme activity are common in the CYP2C9 gene and this, combined with narrow therapeutic indices for several key drug substrates, results in some important issues relating to drug safety and efficacy. CYP2C9 substrate selectivity is detailed and, based on crystal structures for the enzyme, we describe how CYP2C9 catalyzes these reactions. Factors relevant to clinical response to CYP2C9 substrates including inhibition, induction and genetic polymorphism are discussed in detail. In particular, we consider the issue of ethnic variation in pattern and frequency of genetic polymorphisms and clinical implications. Warfarin is the most well studied CYP2C9 substrate; recent work on use of dosing algorithms that include CYP2C9 genotype to improve patient safety during initiation of warfarin dosing are reviewed and prospects for their clinical implementation considered. Finally, we discuss a novel approach to cataloging the functional capabilities of rare ‘variants of uncertain significance’, which are increasingly detected as more exome and genome sequencing of diverse populations is conducted.
Models of Investor Forecasting Behavior — Experimental Evidence
Authors: Bonetto Federico , Cheriyan Vinod , Kleywegt Anton
Published: December 2017

Different forecasting behaviors affect investors’ trading decisions and lead to qualitatively different asset price trajectories. It has been shown in the literature that the weights that investors place on observed asset price changes when forecasting future price changes, and the nature of their confidence when price changes are forecast, determine whether price bubbles, price crashes, and unpredictable price cycles occur. In this paper, we report the results of behavioral experiments involving multiple investors who participated in a market for a virtual asset. Our goal is to study investors’ forecast formation. We conducted three experimental sessions with different participants in each session. We fit different models of forecast formation to the observed data. There is strong evidence that the investors forecast future prices by extrapolating past price changes, even when they know the fundamental value of the asset exactly and the extrapolated forecasts differ significantly from the fundamental value. The rational expectations hypothesis seems inconsistent with the observed forecasts. The forecasting models of all participants that best fit the observed forecasting data were of the type that cause price bubbles and cycles in dynamical systems models, and price bubbles and cycles ended up occurring in all three sessions.
Schottky Emission Distance and Barrier Height Properties of Bipolar Switching Gd:SiOx RRAM Devices under Different Oxygen Concentration Environments
Authors: Chen Kai-Huang , Tsai Tsung-Ming , Cheng Chien-Min , Huang Shou-Jen , Chang Kuan-Chang , Liang Shu-Ping , Young Tai-Fa
Published: December 2017

In this study, the hopping conduction distance and bipolar switching properties of the Gd:SiOx thin film by (radio frequency, rf) rf sputtering technology for applications in RRAM devices were calculated and investigated. To discuss and verify the electrical switching mechanism in various different constant compliance currents, the typical current versus applied voltage (I-V) characteristics of gadolinium oxide RRAM devices was transferred and fitted. Finally, the transmission electrons’ switching behavior between the TiN bottom electrode and Pt top electrode in the initial metallic filament forming process of the gadolinium oxide thin film RRAM devices for low resistance state (LRS)/high resistance state (HRS) was described and explained in a simulated physical diagram model.
Reactive Fabrication and Effect of NbC on Microstructure and Tribological Properties of CrS Co-Based Self-Lubricating Coatings by Laser Cladding
Authors: Fang Liuyang , Yan Hua , Yao Yansong , Zhang Peilei , Gao Qiushi , Qin Yang
Published: December 2017

The CrS/NbC Co-based self-lubricating composite coatings were successfully fabricated on Cr12MoV steel surface by laser clad Stellite 6, WS2, and NbC mixed powders. The phase composition, microstructure, and tribological properties of the coatings ware investigated by means of X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive spectrometer (EDS), as well as dry sliding wear testing. Based on the experimental results, it was found reactions between WS2 and Co-based alloy powder had occurred, which generated solid-lubricant phase CrS, and NbC play a key role in improving CrS nuclear and refining microstructure of Co-based composite coating during laser cladding processing. The coatings were mainly composed of γ-Co, CrS, NbC, Cr23C6, and CoCx. Due to the distribution of the relatively hard phase of NbC and the solid lubricating phase CrS, the coatings had better wear resistance. Moreover, the suitable balance of CrS and NbC was favorable for further decreasing the friction and improving the stability of the contact surfaces between the WC ball and the coatings. The microhardness, friction coefficient, and wear rate of the coating 4 (Clad powders composed of 60 wt % Stellite 6, 30 wt % NbC and 10 wt % WS2) were 587.3 HV0.5, 0.426, and 5.61 × 10−5 mm3/N·m, respectively.
Antitumor and Immunoregulatory Activities of Seleno-β-Lactoglobulin on S180 Tumor-Bearing Mice
Authors: Sun Su-jun , Feng Ying-ying , Zhang Yan , Ji Hai-yu , Yu Juan , Liu An-jun
Published: December 2017

Degeneration of immune organs like thymus and spleen has been discovered in tumor-bearing mice; which increases the difficulties on oncotherapy. More effective drugs which target the protection of immune organs are expected to be researched. In this study; we aim to analyze the antitumor and immunoregulatory activities of seleno-β-lactoglobulin (Se-β-lg) on S180 tumor-bearing mice. Results indicated that Se-β-lg exhibited a remarkable inhibitory effect on S180 solid tumors with the inhibition rate of 48.38%; and protected the thymuses and spleens of S180-bearing mice. In addition, Se-β-lg could also balance the proportions of CD4+ and CD8+ T cells in spleens; thymuses and peripheral bloods; and improve Levels of IL-2; IFN-γ; TNF-α in mice serums. β-lg showed weaker bioactivities while SeO2 showed stronger toxicity on mice. Therefore our results demonstrated that Se-β-lg possessed stronger antitumor and immunoregulatory activities with lower side effects and had the potential to be a novel immunopotentiator and antitumor agent.
Extraction of a Novel Cold-Water-Soluble Polysaccharide from Astragalus membranaceus and Its Antitumor and Immunological Activities
Authors: Liu An-jun , Yu Juan , Ji Hai-yu , Zhang Hong-cui , Zhang Yan , Liu Hui-ping
Published: December 2017

The polysaccharides of Astragalus membranaceus have received extensive study and attention, but there have been few reports on the extraction of these polysaccharides using cold water (4 °C). In this study, we fractionated a novel cold-water-soluble polysaccharide (cAMPs-1A) from Astragalus membranaceus with a 92.00% carbohydrate content using a DEAE-cellulose 52 anion exchange column and a Sephadex G-100 column. Our UV, Fourier-transform infrared spectroscopy (FTIR), high-performance gel permeation chromatography, and ion chromatography analysis results indicated the monosaccharide composition of cAMPs-1A with 1.23 × 104 Da molecular weight to be fucose, arabinose, galactose, glucose, and xylose, with molar ratios of 0.01:0.06:0.20:1.00:0.06, respectively. The UV spectroscopy detected no protein and nucleic acid in cAMPs-1A. We used FTIR analysis to characterize the α-d-pyranoid configuration in cAMPs-1A. In addition, we performed animal experiments in vivo to evaluate the antitumor and immunomodulatory effects of cAMPs-1A. The results suggested that cAMPs-1A oral administration could significantly inhibit tumor growth with the inhibitory rate of 20.53%, 36.50% and 44.49%, respectively, at the dosage of 75,150, and 300 mg/kg. Moreover, cAMPs-1A treatment could also effectively protect the immune organs, promote macrophage pinocytosis, and improve the percentages of lymphocyte subsets in the peripheral blood of tumor-bearing mice. These findings demonstrate that the polysaccharide cAMPs-1A has an underlying application as natural antitumor agents.
Molecularly Imprinted Microrods via Mesophase Polymerization
Authors: Parisi Ortensia , Scrivano Luca , Candamano Sebastiano , Ruffo Mariarosa , Vattimo Anna , Spanedda Maria , Puoci Francesco
Published: December 2017

The aim of the present research work was the synthesis of molecularly imprinted polymers (MIPs) with a rod-like geometry via “mesophase polymerization”. The ternary lyotropic system consisting of sodium dodecyl sulfate (SDS), water, and decanol was chosen to prepare a hexagonal mesophase to direct the morphology of the synthesized imprinted polymers using theophylline, methacrylic acid, and ethylene glycol dimethacrylate as a drug model template, a functional monomer, and a crosslinker, respectively. The obtained molecularly imprinted microrods (MIMs) were assessed by performing binding experiments and in vitro release studies, and the obtained results highlighted good selective recognition abilities and sustained release properties. In conclusion, the adopted synthetic strategy involving a lyotropic mesophase system allows for the preparation of effective MIPs characterized by a rod-like morphology.
Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes–2
Authors: Muñoz-Torrero Diego , Mangoni Arduino , Liu Hong , Hulme Christopher , Rautio Jarkko , Karaman Rafik , De Sousa Maria , Prokai-Tatrai Katalin , Sabatier Jean-Marc , Siciliano Carlo , Luque F. , Kokotos George , Ragno Rino , Collina Simona , Guillou Catherine , Gütschow Michael , Agrofoglio Luigi
Published: December 2017

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes is a series of Editorials, which are published on a biannual basis by the Editorial Board of the Medicinal Chemistry section of the journal Molecules [...]
Chrysin Induces Antidiabetic, Antidyslipidemic and Anti-Inflammatory Effects in Athymic Nude Diabetic Mice
Authors: Ramírez-Espinosa Juan , Saldaña-Ríos Johann , García-Jiménez Sara , Villalobos-Molina Rafael , Ávila-Villarreal Gabriela , Rodríguez-Ocampo Angélica , Bernal-Fernández Germán , Estrada-Soto Samuel
Published: December 2017

Extensive knowledge of diabetes and its complications is helpful to find new drugs for proper treatment to stop degenerative changes derived from this disease. In this context, chrysin (5,7-dihydroxyflavone) is a natural product that occurs in a variety of flowers and fruits with anti-inflammatory and antidiabetic effects, among others. Thus, a diabetic model in athymic nude mice was developed and used to establish the ability of chrysin to decrease the secretion of pro-inflammatory cytokines. Also, it was determined the acute (50 mg/kg) and sub-acute (50 mg/kg/day/10 days) antidiabetic and antihyperlipidemic activities after the period of time treatment. Results indicate that chrysin has significant acute antihyperglycemic and antidiabetic effects in nude diabetic mice (p < 0.05). Moreover, triglyceride blood levels were reduced and IL-1β and TNF-α were diminished after 10 days’ treatment compared with control group (p < 0.05). In conclusion, it was found that chrysin could produce similar effects as metformin, a drug used for the treatment of diabetes, since both test samples decreased glucose and triglycerides levels, they impaired the generation of pro-inflammatory cytokines involved in the development of diabetes and its consequences, such as atherosclerosis and other cardiovascular diseases.