bluuebunny/crossref_metadata_2025 huggingface dataset:
Motif Go Public, Herding, Ukuran Perusahaan, Dan Underpricing Pada Pasar Modal Indonesia
Authors: Ismiyanti Fitri , Armansyah Rohmad Fuad
Published: December 2020

Underpricing become a phenomenon which often occurs by companies during Initial Public Offering in every country in the world, which offering price lower than closing price on the first day trading on the stock exchange. According to Rock (1982), asymmetry information of an IPO company leads to underpricing phenomena, where the information according to the company are not evenly distributed among investors. This asymmetry information emerging distribution of uncertainty among investors that leads to underpricing. The objective of this research is to test the influence of motive of company going public, herding in stock market, and size of the company to the degree of underpricing using sample of 257 companies listed during year 1990 to June 2009 on the Indonesian Stock Exchange. Sample is taken by using purposive sampling with criteria as underpriced stocks and the stocks are not delisting overall from stock exchange. Data are analyzed using multiple regressions and path analysis to test the relation between motive of company going public, herding, and size of the company to the degree of underpricing. Pursuant to the analysis, motive of company going public and herding have positively influence on the degree of underpricing but statistically not significant. Size of the company which measure using total asset have negatively influence on the degree of underpricing and statistically significant on the first day trading on the stock exchange.
Analisis Efektivitas “Customer Delight Program” Terhadap Motivasi Kerja Karyawan Di Shangri-La Hotel Surabaya
Authors: Hermansyah Rocky , Sutanto Eddy M.
Published: December 2020

This research was taken place at Shangri-La Hotel Surabaya, an international management hotel. The population of research were 600 respondents. The purpose of this research was to understand the effectiveness of Customer Delight Program and employees’ work motivation of Shangri-La Hotel Surabaya. The analysis technique used quantitative analysis. The result of research showed that there was a relationship between Customer Delight Program and employees’ work motivation Shangri-La Hotel Surabaya.
Pengaruh Cognitive Style Dan Global Mindset Terhadap Manajemen Keuangan Pribadi Dan Pengaruh Manajemen Keuangan Pribadi Terhadap Intensi Berwirausaha
Authors: Sina Peter Garlans
Published: December 2020

The aim of this research was to give a proof that the factors of style of thinking, global mindset, and personal finance management are the predictors for the entrepreneurial intentions. Through the distribution of questioners for 150 respondents, the results show that style of thinking and global mindset gave significant effects on personal finance management and it was also gave significant effect on entrepreneurial intentions. In the final section, the limitation of the research was also discussed which can be a follow-up by other researchers.
File Fragment Recognition Based on Content and Statistical Features
Authors: Masoumi Marzieh , Keshavarz Ahmad
Published: December 2020

Nowadays, speed up development and use of digital devices such as smartphones have put people at risk of internet crimes. The evidence of present crimes in a computer file can be easily unreachable by changing the prefix of a file or other algorithms. In more complex cases, either file divided into different parts or the parts of a file that has information about the file type are deleted, where the file fragment recognition issue is discussed. The known files are divided into different fragments, and different classification algorithms to solve the problems of file fragment recognition. A confusion matrix measures the accuracy of type recognition. In the present study, first, the file is divided into different fragments. Then, the file fragment features, which are obtained from Binary Frequency Distribution (BFD), are reduced by 2 feature reduction algorithms; Sequential Forward Selection algorithm (SFS) as well as Sequential Floating Forward Selection algorithm (SFFS) to delete sparse features that result in increased accuracy and speed. Finally, the reduced features are given to 3 classifier algorithms, Multilayer Perceptron (MLP), Support Vector Machines (SVM), and K-Nearest Neighbor (KNN) for classification and comparison of the results. In this paper, we proposed the algorithm of file type recognition that can recognize 6 types of useful files ( pdf, txt, jpg, doc, html, exe), which may distinguish a type of file fragments with higher accuracy than the similar works done.
Case Study Email Spam Detection of Two Metaheuristic Algorithm for Optimal Feature Selection
Authors: Mohmmadzadeh Hekmat
Published: December 2020

Selecting a feature in data mining is one of the most challenging and important activities in pattern recognition. The issue of feature selection is to find the most important subset of the main features in a specific domain, the main purpose of which is to remove additional or unrelated features and ultimately improve the accuracy of the categorization algorithms. As a result, the issue of feature selection can be considered as an optimization problem and to solve it, meta-innovative algorithms can be used. In this paper, a new hybrid model with a combination of whale optimization algorithms and flower pollination algorithms is presented to address the problem of feature selection based on the concept of opposition-based learning. In the proposed method, we tried to solve the problem of optimization of feature selection by using natural processes of whale optimization and flower pollination algorithms, and on the other hand, we used opposition-based learning method to ensure the convergence speed and accuracy of the proposed algorithm. In fact, in the proposed method, the whale optimization algorithm uses the bait siege process, bubble attack method and bait search, creates solutions in its search space and tries to improve the solutions to the feature selection problem, and along with this algorithm, Flower pollination algorithm with two national and local search processes improves the solution of the problem selection feature in contrasting solutions with the whale optimization algorithm. In fact, we used both search space solutions and contrasting search space solutions, all possible solutions to the feature selection problem. To evaluate the performance of the proposed algorithm, experiments are performed in two stages. In the first phase, experiments were performed on 10 sets of data selection features from the UCI data repository. In the second step, we tried to test the performance of the proposed algorithm by detecting spam emails. The results obtained from the first step show that the proposed algorithm, by running on 10 UCI data sets, has been able to be more successful in terms of average selection size and classification accuracy than other basic meta-heuristic algorithms. Also, the results obtained from the second step show that the proposed algorithm has been able to perform spam emails more accurately than other similar algorithms in terms of accuracy by detecting spam emails.
Secure Communication between UAVs Using a Method Based on Smart Agents in Unmanned Aerial Vehicles
Authors: Faraji Maryam , Fotohi Reza
Published: December 2020

Unmanned aerial systems (UASs) create an extensive fighting capability of the developed military forces. Particularly, these systems carrying confidential data are exposed to security attacks. By the wireless’s nature within these networks, they become susceptible to different kinds of attacks, hence, it seems essential to design the appropriate safety mechanism in such networks. The sinkhole attack is one of the most dangerous and threatening attacks amongst types of attack in UAS. A malicious UAV exists in such a threat attacking as a black hole for absorbing all traffic in the network. Mainly, in a Flow-based protocol, the attacker considers the requests on the route, then, it replies to the target UAV such as high quality or the best route towards Gard station. The malicious UAV is able to only insert itself on one occasion between the nodes relating to each other (such as sink node and sensor node), and act for passing packets among them. In this study, the malicious attacks are detected and purged using two stages were. In the first stage, some principles and rules are used to detect black hole, gray hole, and sinkhole attacks. In the second stage, using a smart agent-based strategy negotiation procedure for three steps, a defense mechanism is designed to prevent these attacks. The smart agent is used by reliable neighbors via the negotiation procedure for three steps, hence, the traffic formed by the malicious UAV is not considered. The suggested protocol is called SAUAS. Here, the technique is assessed through extensive simulations performed in the NS-3 environment. Based on the simulation outcomes, it is indicated that the UAS network performance metrics are enhanced based on the packet delivery rate, detection rate, false-negative rate and false-positive rate.
An Improvement of Analyzing the Effective Factors on Customer Behavior in Mobile Marketing
Authors: Arbab Tahereh , Hamaidi Hojatolah , Gharakhani Mohsen
Published: December 2020

Nowadays, customers play a very important and vital role in the field of global economy. As a result, companies give special significance to the customers to survive and grow in the field of economic competition in the modern world and increase their relationship with the buyers of their products and services throughout their lifetime. Marketing growth through mobile phones has provided further motives for performing more researches in the field of customer behavior and attitude in mobile marketing. The goal of the current study is to analyze the effective factors on customer behavior in mobile marketing. The variables used in this study are perceived ease of use, individual knowledge, user’s mobile phone technology, customers’ negative attitudes, and customers’ positive attitudes. The current research is practical in terms of objective and is descriptive-analytic in terms of methodology. Data were gathered by distributing a questionnaire among 284 students of Tehran University. Data were analyzed by structural equation modeling using Lisrel and Expert Choice software. Test results showed that ease of use, individual knowledge, mobile phone technology, positive attitude, and negative attitude variables have a meaningful effect on customer behavior in mobile marketing. The confirmation of all the assumptions of the research supports the importance of the customer behavior analysis in mobile phone services.
Molecular Characterization of Ovarian Yolk Sac Tumor (OYST)
Authors: Hodroj Khalil , Stevovic Aleksandra , Attignon Valery , Ferraioli Domenico , Meeus Pierre , Croce Sabrina , Chopin Nicolas , Rossi Lea , Floquet Anne , Rousset-Jablonski Christine , Tredan Olivier , Guyon Frédéric , Treilleux Isabelle , Rannou Corinne , Morfouace Marie , Ray-Coquard Isabelle
Published: December 2020

Most malignant ovarian germ cell tumors (MOGTCs) have a very good prognosis and can be cured by chemotherapy, with yolk sac tumors (OYSTs) having the worse prognosis among MOGCTs. These tumors are rare and can benefit in the next future from specific therapeutic strategies after failure of platinum-based first-line and salvage regimens. In collaboration with EORTC SPECTA, we have developed a project to explore the molecular characteristics of OYST. The pilot part of the project was performed using retrospective samples and ten OYST patients including relapsed and disease free patients. The molecular analysis was performed using FoundationOne CDx. For each patient, the following variables are described in the molecular report provided by FMI (Fondation Medicine Incorporation): alteration type (SNV, deletion), actionable gene alteration, therapies approved in EU (patient's tumor type and other tumor types), tumor mutational burden (TMB) and microsatellite instability (MSI) status. A total of 10 patients with OYST diagnosed between 2007 and 2017 were analyzed. Four patients (40%) had a molecular alteration, according to the FMI test. A subset of three patients (33.3% of all patient) harbored targetable (KRAS, KIT, ARID1A) oncogenic mutations. Two patients at relapse harbored a targetable mutation. In this retrospective study, we were able to identify clinically relevant molecular alterations for all relapsed patients with molecular analysis. Dedicated studies are needed to demonstrate if they could benefit from specific therapeutic strategies after failure of platinum-based first-line and salvage regimens and if the presence of a molecular alteration could be linked to patients’ outcome.
The Mitochondrial Permeability Transition: Nexus of Aging, Disease and Longevity
Authors: Rottenberg Hagai , Hoek Joannes
Published: December 2020

The activity of the mitochondrial Permeability Transition Pore, mPTP, a highly regulated multi-component mega-channel, is enhanced in aging and in aging-driven degenerative diseases. mPTP activity accelerates aging by releasing large amounts of cell-damaging Reactive Oxygen Species, Ca2+ and NAD+. The various pathways that control the channel activity, directly or indirectly, can therefore either, inhibit, or accelerate aging, retards, or enhance the progression of aging-driven degenerative diseases, and determine lifespan and healthspan. Autophagy, a catabolic process that removes and digests damaged proteins and organelles protects the cell against aging and disease. However, the protective effect of autophagy depends on mTORC2/SKG1 inhibition of mPTP. Autophagy is inhibited in aging cells. Mitophagy, a specialized form of autophagy, which retards aging by removing mitochondrial fragments with activated mPTP, is also inhibited in aging cells, and this inhibition leads to increased mPTP activation, which is a major contributor to neurodegenerative diseases, such as Alzheimer’s and Parkinson’s Diseases. The Increased activity of mPTP in aging turns autophagy/mitophagy into a destructive process leading to cell aging and death. Several drugs and lifestyle modifications that enhance healthspan and lifespan enhance autophagy and inhibit the activation of mPTP. Therefore, elucidating the intricate connections between pathways that activate and inhibit mPTP, in the context of aging and degenerative diseases, could enhance the discovery of new drugs and lifestyle modifications that slow aging and degenerative disease.
AKTIVITAS ANTIOKSIDAN PERASAN JERUK MANIS (Citrus sinensis) DAN JERUK PURUT (Citrus hystrix) MENGGUNAKAN METODE ABTS
Authors: Puspitasari Anita dwi
Published: December 2020

Tubuh membutuhkan antioksidan untuk menangkal bahaya radikal bebas yang berpengaruh terhadap kesehatan. Antioksidan dapat mencegah terjadinya berbagai penyakit degenaratif dan penyakit lainnya. Buah jeruk manis (Citrus sinensis) dan Buah jeruk purut (Citrus hystrix) mengandung senyawa flavonoid dan vitamin C sehingga berpotensi sebagai antioksidan. Penelitian ini bertujuan untuk mengetahui aktivitas antioksidan perasan jeruk manis dan jeruk purut dengan metode ABTS (2,2-Azinobis(3-ethylbenzothiazoline)-6-sulfonic acid).Buah jeruk manis dan jeruk purut dicuci bersih dan diperas sehingga dihasilkan perasan jeruk manis dan jeruk purut. Perasan jeruk manis dan jeruk purut diidentifikasi kandungan senyawa flavonoidnya dengan serbuk magnesium dan HCl pekat sebagai pereaksi dan kandungan vitamin Cnya dengan pereaksi benedict. Pengukuran aktivitas antioksidan pada perasan jeruk manis dan jeruk purut dengan metode ABTS dilakukan menggunakan spektrofotometer visibel pada panjang gelombang maksimum 753,2 nm, operating time 30 menit dan vitamin C sebagai kontrol positif.Hasil identifikasi kualitatif menunjukkan bahwa perasan jeruk manis dan jeruk purut mengandung senyawa flavonoid dan vitamin C yang keduanya ditandai dengan perubahan warna dari kuning menjadi jingga. Perasan jeruk manis memiliki aktivitas antioksidan dengan nilai IC50sebesar 71,34±0,69 ppm, jeruk purut sebesar 67,92±1,75 ppm dan vitamin C sebesar 7,25±0,02 ppm. Perasan jeruk manis dan jeruk purut termasuk antioksidan kuat jika dibandingkan dengan vitamin C.
THE COMPATIBILITY OF MODEL FOR LOW SHEAR FLOW ANALYSIS IN DEVELOPING PLASTICIZED HTPB-BASED BINDER
Authors: Restasari Afni , Abdillah Luthfia Hajar , Ardianingsih Retno , Wicaksono Bagus , Budi Rika Suwana
Published: December 2020

In developing flow behavior of plasticized prepolymer as liquid content of composite solid propellant, zero shear viscosity (ZSV) is a critical parameter that Goh-Wan equation is developed to model it recently [1]. Thus, this work aims to analyze the compatibility of the Goh-Wan equation toward the liquid content of propellant, characterize it, and determine the limit. In this work, a varied flow behavior index was obtained by using Hydroxy terminated polybutadiene (HTPB) and HTPB-DOA (Dioctyl adipate) system with the variable of its concentration, pre-heating, and pre-stirring methods as samples. Viscosity was measured at 2, 3, 4, and 5 rpm by using the disc spindle of Brookfield viscometer. For the minimum shear-rate investigation, as a limit of compatibility, other three sets of shear rates are applied, which are 0.6 – 5 rpm, 1 – 5 rpm, and 1,5 – 5 rpm. By functioning Goh-Wan equation (model 1) and Power-Law (model 2), a model was categorized as compatible if yields lower value of ZSV than the first experimental measured viscosity (η1st). Characterization was determined by a graph of plotting percentage difference of ZSV obtained from models 1 and 2 towards the index of flow behavior. The 3% of the difference between ZSV obtained from model 1 and  η1st was set to be a minimum value for a set of applied shear-rate to be acceptable. It is reported that the Goh-Wan model is compatible with the liquid content of propellant and characterized by a perfect linear correlation. It is also found that a minimum applied shear rate of 1.5 rpm is acceptable for model compatibility.
The White Knight’s “Inventions”
Authors: Parel Vaibhav Iype
Published: December 2020

The figure of the White Knight in Lewis Carroll’s Through the Looking-Glass has often been read as part of a tradition of “nonsense literature”. While this is true, I wish to extend that argument and locate the figure of the White Knight in the context of the debates around the Patent Law of 1852. While defining and recognising the role of mechanical labour, the role and function of artistic labour also featured in these debates. The White Knight’s “inventions” are deeply resonant with these debates and prompt us to ask: what is the role of the artist in an industrial society? How can art retain its autonomy and justify itself when confronted with the pervasive discourse of utilitarianism? This paper argues that the anxiety around the role of the artist is palpable in the figure of the White Knight, and through him Carroll enunciates what may be read as his intervention in this debate.
SISTEM PENDUKUNG KEPUTUSAN TUMBUH KEMBANG SISWA TK MENGGUNAKAN METODE BEYOND CENTER And CIRCLE TIME (BCCT) DAN MATRIK SWOT IFAS DAN EFAS
Authors: Wati Rayuwati Ayu
Published: December 2020

ABSTRAK                 Didalam Pendidikan taman kanak-kank (TK) seorang guru harus mampu mengarahkan  anak didiknya dan memacunya untuk belajar mengenal berbagai pendekatan nilai diantaranya: agama, sosial, emosi, motorik, kognitif, bahasa, seni dan kemandirian untuk mengetahui tumbuh kembang anak usia 5-6 tahun . dengan Sistem Pendukung keputusan akan mempermudah guru Tk dalam mengambil keputusan tentang tumbuh kembang anak dengan menggunakan metode Beyond Centers and Circle Time (BCCT) dengan perhitungan Matrik Swot IFAS dan EFAS Kata Kunci : SPK, tumbuh kembang anak,  BCCT,Matrik Swot IFAS dan EFAS
Existence And Controllability Results For Fractional Control Systems In Reflexive Banach Spaces Using Fixed Point Theorem
Authors: AL-Jawari Naseif Jasim
Published: December 2020

In this paper, a fixed point theorem of nonexpansive mapping is established to study the existence and sufficient conditions for the controllability of nonlinear fractional control systems in reflexive Banach spaces. The result so obtained have been modified and developed in arbitrary space having Opial’s condition by using fixed point theorem deals with nonexpansive mapping defined on a set has normal structure. An application is provided to show the effectiveness of the obtained result.
Assessment of protein-protein interfaces in cryo-EM derived assemblies
Authors: Malhotra Sony , Joseph Agnel , Thiyagalingam Jeyan , Topf Maya
Published: December 2020

Structures of macromolecular assemblies derived from cryo-EM maps often contain errors that become more abundant with decreasing resolution. Despite efforts in the cryo-EM community to develop metrics for the map and atomistic model validation, thus far, no specific scoring metrics have been applied systematically to assess the interface between the assembly subunits. Here, we have assessed protein-protein interfaces in macromolecular assemblies derived by cryo-EM. To this end, we developed PI-score, a density-independent machine learning-based metric, trained using protein-protein interfaces’ features in high-resolution crystal structures. Using PI-score, we were able to identify errors at interfaces in the PDB-deposited cryo-EM structures (including SARS-CoV-2 complexes) and in the models submitted for cryo-EM targets in CASP13 and the EM model challenge. Some of the identified errors, especially at medium-to-low resolution structures, were not captured by density-based assessment scores. Our method can therefore provide a powerful complementary assessment tool for the increasing number of complexes solved by cryo-EM.
Modeling Transcriptional Regulation Using Gene Regulatory Networks Based on Multi-Omics Data Sources
Authors: Patel Neel , Bush William
Published: December 2020

BackgroundTranscriptional regulation is complex, requiring multiple cis(local) and trans acting mechanisms working in concert to drive gene expression, with disruption of these processes linked to multiple diseases. Previous computational attempts to understand the influence of regulatory mechanisms on gene expression have used prediction models containing input features derived from cis regulatory factors. However, local chromatin looping and trans-acting mechanisms are known to also influence transcriptional regulation, and their inclusion may improve model accuracy and interpretation. ResultsWe describe a computational framework to model gene expression for GM12878 and K562 cell lines. This framework weights the impact of transcription factor-based regulatory data using multi-omics gene regulatory networks to account for both cis and trans acting mechanisms, and the local chromatin context. These prediction models perform significantly better compared to models containing cis-regulatory features alone. Models that additionally integrate long distance chromatin interactions (or chromatin looping) between distal transcription factor binding regions and gene promoters also show improved accuracy. As a demonstration of their utility, effect estimates from these models were used to weight cis-regulatory rare variants for SKAT(sequence kernel association test) analyses of gene expression. ConclusionsOur models generate refined effect estimates for individual transcription factors, allow characterization of their roles across the genome, and provide a framework for integrating multiple data types into a single model of transcriptional regulation.
Utilization And Effectiveness Of Malaria Prevention Methods Among Pregnant Women In A Rural Community Of Ekiti State, South West Nigeria : A Cross- Sectional Study.
Authors: Ibrahim Azeez , Agbesanwa Tosin , Shabi Olabode , Ariyibi Kayode , Alabi Ayodele , Omonijo Oluwatosin
Published: December 2020

Background: National surveys indicate that among countries in Africa where malaria is endemic, Nigeria alone accounts for 21% of pregnancies that are unprotected from malaria. The purpose of this study is to ascertain the extent of utilization and effectiveness of malaria prevention methods, to find out the existing relationship between maternal parasitaemia and the effectiveness of these methods at (p<0.05) level of significance.Methods: The study was a cross sectional survey involving 264 consenting booked pregnant women who were recruited from antenatal clinic at Federal Teaching Hospital, Ido -Ekiti, Ekiti State, Southwestern Nigerian. Interviewer administered questionnaire was used to elicit information on the socio-demographic characteristics of the respondents, mode of malaria prevention, extent of utilization of malaria prevention methods and their effectiveness. Venous blood samples for malaria parasite test were collected and microscopic analysis was done to detect the malaria parasite in the obtained blood samples. Data was analyzed using SPSS version 20.0Results: All the 264 pregnant women interviewed, consented to having their blood taken. In rank order, the mode of malaria prevention methods most commonly reported as being effective were Intermittent Preventive Treatment using sulphadoxine-pyrimethamine (IPT-sp) which was favored by majority 190 (72.0%). This was followed by Insecticide Spray 166 (62.9%). Insecticide Treated Nets (ITNs) were the least utilized by 108 (40.9%) respondents. Nine (8.3%) of the 108 participants that used ITNs, 15 (7.9%) of the 190 participants that used IPT-s and 18 (10.8%) of the 156 participants that used Insecticide Spray tested positive for malaria respectively. There was a statistically significant association between maternal parasitaemia and malaria prevention methods using ITNs (p=0.001), IPT-sp (p = 0.001) and Insecticide sprays (p = 0.001).Conclusion: The three malaria preventive methods adopted for this study were ITNs, IPT-sp and Insecticide Spray. Despite their protective effectiveness, their utilizations are still poor. Information and communication strategies with other concerted efforts by the stakeholders are suggested to ensure proper implementation of the national policy on malaria as adopted by other countries.
Reproducing Solar Spectral Irradiance by LEDs
Authors: Kopatsch Anton , Kary Peter , Özden Mustafa , Albert Andreas , Ghirardo Andrea , Winkler Jana , Seckmeyer Gunther , Schnitzler Jörg-Peter
Published: December 2020

The development of light-emitting diodes (LEDs) of different emission spectra is revolutionizing lighting technology and opening up completely new applications and research areas. The spectral irradiance of the sun reaching the Earth's surface is very complex due to radiative transfer processes within the atmosphere and ranges from the shortwave ultraviolet (UV) to longwave infrared (IR) radiation. The simulation of this spectral irradiance by artificial light sources is technically very demanding. It could be realized sufficiently so far by a combination of different light sources, mostly light bulbs, metal halide lamps and fluorescent tubes, in combination of different filters. In the present work, we are presenting a new LED Sun Simulator system, which allows simulating spectral irradiance close to natural solar spectral irradiance from 360 to 800 nm. The system generates the spectral irradiance by a combination of 23 different types of LED. The irradiance of each of the 23 different LED types can be separately controlled by software to modulate the spectra. In total, the system comprises 2,530 high-power LEDs mounted on 100 printed circuit boards (PCBs) / aluminum boards. With this system, an experimental area of one square meter can be homogeneously irradiated (irradiance with a mean variability of 2 % in the integrated range of 360 nm - 800 nm) at the distance of 1.6 m simulating the spectral irradiance of the standard reference spectrum of the American Society for Testing and Materials (ASTM G173-03). At maximum, the LED lighting field can reach an irradiance of 2,500 W m-2, which is more than twice than that of the brightest sunlight in Central Europe. Thus, the new system opens up multiple new applications in many research areas ranging from photobiology to human health and environmental and material sciences.
Biofilm Associated Genotypes of Multiple Antibiotic Resistant Pseudomonas Aeruginosa
Authors: Redfern James , Wallace Janine , Belkum Alex van , Jaillard Magali , Whittard Elliot , Ragupathy Roobinidevi , Verran Joanna , Kelly Peter , Enright Mark Charles
Published: December 2020

BackgroundPseudomonas aeruginosa is a ubiquitous environmental microorganism and also a common cause of infection. Its ability to survive in many different environments and persistently colonize humans is linked to its presence in biofilms formed on indwelling device surfaces. Biofilm promotes adhesion to, and survival on surfaces, protects from desiccation and the actions of antibiotics and disinfectants. ResultsWe examined the genetic basis for biofilm production on polystyrene at room (22°C) and body temperature (37°C) within 280 P. aeruginosa. 69% of isolates (n=193) produced more biofilm at 22°C, whilst those producing more biofilm at 37°C had reduced genetic diversity. Using GWAS and pan-GWAS, we found a number of accessory genes significantly associated with this phenotype. Many of these are present on a 165kb region containing genes for heavy metal resistance (arsenic, copper, mercury and cadmium) transcriptional regulators and methytransferases. We also discovered multiple core genome SNPs in the A-type flagellin gene and Type II secretion system gene xpsD. Analysis of biofilm production of isolates of the MDR ST111 and ST235 lineages on stainless-steel revealed several accessory genes associated with enhanced biofilm production. These include a putative translocase with homology to a Helicobacter pylori type IV secretion system protein, a TA system II toxin gene and the alginate biosynthesis gene algA, several transcriptional regulators and methytransferases as well as core SNPs in genes involved in quorum sensing and protein translocation. ConclusionsGWAS and pan-GWAS approaches have great potential as a first step in characterizing the genetic basis of novel bacterial phenotypes.
Mitigation of Alzheimer’s Disease Neuropathologies by Human Neural Stem Cell-derived Extracellular Vesicles
Authors: Apodaca Lauren A , Baddour Al Anoud D , Garcia Camilo , Alikhani Leila , Giedzinski Erich , Ru Ning , Agrawal Anshu , Acharya Munjal M , Baulch Janet
Published: December 2020

Background: Regenerative therapies to mitigate Alzheimer’s disease (AD) neuropathology have shown very limited success. In the recent era, extracellular vesicles (EV) derived from multipotent and pluripotent stem cells have shown considerable promise for the treatment of dementia and many neurodegenerative conditions. Methods: Using the 5xFAD accelerated transgenic mouse model of AD, we now show the regenerative potential of human neural stem cell (hNSC)-derived EV on the neurocognitive and neuropathologic outcomes in the AD brain. Two or six-month-old 5xFAD mice received single or two intra-venous (retro-orbital vein, RO) injections of hNSC-derived EV, respectively.Results: RO treatment using hNSC-derived EV restored fear extinction memory consolidation and reduced anxiety-related behaviors 4-6 weeks post-injection. EV treatment also significantly reduced dense core amyloid-beta plaque accumulation and microglial activation in both age groups. These results correlated with partial restoration of homeostatic levels of circulating pro-inflammatory cytokines in the AD mice. Importantly, EV treatment protected against synaptic loss in the AD brain that paralleled improved cognition. MiRNA analysis of the EV cargo revealed promising candidates targeting neuroinflammation and synaptic function. Conclusions: Collectively, these data demonstrate the neuroprotective effects of systemic administration of stem cell-derived EV for remediation of behavioral and molecular AD neuropathologies.
Oil carbon intensity impacts of COVID-19 and other short-term demand shocks
Authors: Brandt Adam , Masnadi Mohammad S. , Benini Giacomo , Milivinti Alice , Anderson James , Wallington Timothy , De Kleine Robert , Dotti Valerio , Jochem Patrick , El-Houjeiri Hassan
Published: December 2020

Oil production choices are influenced by the interaction of oilfield production costs and the global price of oil. What are the characteristics of less economic oilfields, fields whose profitably is at the margin? These oilfields may differ from average fields in terms of geographical location, crude type, production practices, and carbon intensity (CI). Because these economically-marginal fields are the ones likely to respond to drop in demand (e.g., due to 2020 COVID-19 pandemic, or a rapid shift to alternatives), they represent the likely sources of oil that would be displaced. The present paper links the field-by-field costs of 1933 oilfields (representing ~ 90% of 2015 worldwide crude production) with their production environmental footprint. We show that many marginal fields also have high CI. We estimate that the fields at margin due to the 2020 COVID-19 pandemic demand reduction have upstream CI and marginal cost of production ~ 35% and 3 times higher than global average, respectively. The production termination of these fields could result in 181 Mtonne CO2Eq. annual reduction in upstream emissions in the short-term. The marginal producers in a generic small demand shock (5% or ~ 3.6 mmbbl/d drop) have an upstream CI 26% higher than average global oil producers, and at our larger generic demand shock (20% or ~ 14.3 mmbbl/d drop) have CI that is 5% higher than average. Heavy oilfields have the highest volume share in marginal crudes in all scenarios. These results further suggest that life cycle benefits of alternative fuels or vehicles or regulations that lead to reduced oil consumption are systematically larger than those typically estimated when displaced emissions are modeled using average crudes. The results only cover the upstream production CI and do not include synergistic impacts of differences in refining CI of different types of crudes, and thus could underestimate the total life cycle differences between marginal and average crudes.
ZnO Nanoparticle-based Seed Priming Modulates Early Growth and Enhances Physio-biochemical and Metabolic Profiles of Fragrant Rice Against Cadmium Toxicity
Authors: Li Yuzhan , Liang Luxin , Li Wu , Ashraf Umair , Ma Lin , Tang Xiangru , Pan Shenggang , Tian Hua , Mo Zhaowen
Published: December 2020

Background: Cadmium (Cd) is among the most toxic heavy metals that severely affects crop growth, and in this purview numerous recent research initiatives have focused on the application of nanoparticles (NPs) to negate the toxic effects of heavy metals such as Cd. Method: In the present study, the seeds of two fragrant rice cultivars, namely Yuxiangyouzhan and Xiangyaxiangzhan, were grown after exposure to four ZnO NPs treatment (0, 25, 50, and 100 mg L-1), with or without the presence of Cd (100 mg L-1). Result: The results revealed that priming seeds with ZnO NPs had no significant effect on the seed germination (p > 0.05) however, it substantially improved the seedling growth and other related physiological attributes under the Cd stress. The mean fresh weight of the shoot, and whole seedling increased after ZnO NPs treatment by 16.92%-27.88% and 12.82-33.58%, respectively. The fresh weight of root, length of the shoot, and the root increased after ZnO NPs treatment. Moreover, remarkable changes in the physiological response of seedlings under ZnO NPs treatment were detected. The metabolomic analysis was performed to discern the underlying regulation of the metabolisms after ZnO NPs treatment for seedlings under Cd stress. Conclusion: Our findings provide new insight into the influence of ZnO NPs on seed germination, and the growth of crop plants, and may find potential applications in developing crop resilience in Cd laden agricultural lands.
A Sonosensitizer-based Polymeric Nanoplatform for Realizing Chemo-sonodynamic Combination Therapy of Lung Cancer 
Authors: Zhang Yanan , Khan Abdur Rauf , Yang Xiaoye , Shi Yikang , Zhao Xiaogang , Zhai Guangxi
Published: December 2020

BackgroundLung cancer was regarded as the most common type of tumors worldwide, and the relative lethality was considerably high. However, since the tumor tissues located in deeper parts in human bodies, the traditional technologies like photodynamic therapy could not reached desired effect. Sonosensitizers can induce sonodynamic therapy, possessing the benefits of deep penetration and effective tumor inhibition by generating reactive oxygen. Besides, ultrasound possessed the ability of deep penetration, which showed favorable tumor inhibition effect.ResultsA redox/enzyme/ultrasound responsive Rhein-chondroitin sulfate nano-preparation encapsulating docetaxel was initially fabricated. The nanoparticles show increased cellular uptake with quick drug release, revealing good stability and monodispersed form in physiological environment. Also, Rhein could induce apoptosis and mitochondrial membrane potential change, enhancing the expression of apoptosis-related protein. Further, the inhibited metastasis and angiogenesis of cancer cells by sonodynamic therapy would lead to reduced expression of M2 type macrophages.ConclusionRhein was firstly discovered to possess the sonodynamic effect in this work by generating plenty of reactive oxygen after treating by ultrasound. The nanoplatform enhanced synergistic anti-tumor effect by both sonodynamic therapy and chemotherapeutic efficacy, and showed benign biocompatibility, which might pave a way for the investigation of chemo-sonodynamic therapy with different cancers.
Synthesis, pretreatment, and recovery of [TEA][HSO4] ionic liquid for OPEFB lignocellulosic transformation
Authors: Nurdin Muhammad , Abimanyu Haznan , Putriani Hadijah , Setiawan L.O.M. , Maulidiyah Maulidiyah , Wibowo Dwiprayogo , Ansharullah Ansharullah , Natsir Muh. , Salim La , Arham Zul , Mustapa Faizal
Published: December 2020

In recent years, various studies have been utilized lignocellulosic biomass from oil palm empty fruit bunches (OPEFB) to be converted into bioethanol fuels. In this study, we present the techno-economical preparation for biomass pretreatment based on triethylamine hydrogen sulfate ([TEA][HSO4]) ionic liquid. Synthesis, pretreatment, and recovery of [TEA][HSO4] ionic liquid have been carried out via the one-pot method. Based on these results, the synthesized [TEA][HSO4] has been characterized using IR spectroscopy showing the appearance chemical groups such as H, CH3, CN, and SO2. In addition, H-NMR spectroscopy was presenced the CH3CH2- structure towards low ppm. Thermal stability has also demonstrated unique physical properties of ionic liquid (IL) with a melting point of 49°C and a decomposition temperature of 274.3°C. The effectiveness to produce the chemical components shows that the useful use of [TEA][HSO4] was successfully synthesized with an optimum composition of 83% resulting in chemical levels of 45.84% (cellulose), 5.00% (hemicellulose), and 34.40% (lignin). The recovered [TEA][HSO4] with a composition of 90.90% was effective in reducing the lignin content about 80%. These results also depend heavily on the temperature and separation techniques applied during the pretreatment process.
Size-Based Characterization of Adalimumab and TNF-α Interactions Using Flow Induced Dispersion Analysis: Assessment of Avidity-Stabilized Multiple Bound Species
Authors: Jensen Henrik , Pedersen Morten , Østergaard Jesper , Haegebaert Ragna
Published: December 2020

The understanding and characterization of protein interactions is crucial for elucidation of complicated biomolecular processes as well as for the development of new biopharmaceutical therapies. Often, protein interactions involve multiple binding, avidity, oligomerization, and are dependent on the local environment. Current analytical methodologies are unable to provide a detailed mechanistic characterization considering all these parameters, since they often rely on surface immobilization, cannot measure under biorelevant conditions, or do not feature a structurally-related readout for indicating formation of multiple bound species. In this work, we report the use of flow induced dispersion analysis (FIDA) for in-solution characterization of complex protein interactions under in-vivo like conditions. FIDA is an immobilization-free ligand binding methodology employing Taylor dispersion analysis for measuring the hydrodynamic radius (size) of biomolecular complexes. Here, the FIDA technology is utilized for a size-based characterization of the interaction between TNF-α and adalimumab. We report concentration-dependent complex sizes, binding affinities (Kd), kinetics, and higher order stoichiometries, thus providing essential information on the TNF-α - adalimumab binding mechanism. Furthermore, it is shown that the avidity stabilized complexes involving formation of multiple non-covalent bonds are formed on a longer timescale than the primary complexes formed in a simple 1 to 1 binding event.
Human Cytomegalovirus Inhibits the Proliferation and Invasion of Extravillous Cytotrophoblasts Via Hippo-YAP Pathway
Authors: Kong Qiaoqiao , Li Jing , Zhao Li , Shi Peng , Liu Xiaobei , Bian Cailing , Liu Jing , Liu Tao
Published: December 2020

Background: Human cytomegalovirus (HCMV) infection in utero is very common during pregnancy, which can lead to adverse outcomes in both pregnancy and progeny, but its pathogenesis has not been fully clear. The decrease of extracellular trophoblast (EVT) invasion is an essential pathophysiological process of some pregnancy complications. Hippo-YAP signaling pathway plays an important role in regulating cell proliferation and apoptosis. However, whether YAP is involved in HCMV uterine infection remains to be studied.Methods: The primary EVT was cultured and infected by the HCMVAD169 virus in vitro. Immunofluorescence staining of HCMVpp65 antigen was conducted afterward to confirm the establishment of an infection model. The optimal virus infection dose was determined by the EVT proliferation status in vitro. Real-time PCR was performed to examine the mRNA level of major genes involved in the Hippo pathway in EVT after HCMV infection. The effect of HCMV on the expression of YAP protein in EVT was evaluated by Immunofluorescence staining and Western blot. An in vitro cell invasion assay was carried out to analyze the influence of HCMV on EVT invasion. The changes of EVT invasion was accessed by establishing YAP silencing and over-expression models using YAP1 specific siRNA and plasmid pcDH.Results: The optimal HCMV infection dose was 30μl 100 TCID50 HCMV / 120μl medium. Compared to the control group, the infection of HCMV significantly reduced the mRNA expression of Mst1, Mst2, SAV, Lats1, Lats2, Mob1, YAP1, TAZ, TEAD1-4 genes and YAP protein expression in the Hippo-YAP pathway. HCMV infection also decreased the EVT invasion. In non-infected EVT, the number of transmembrane EVT cells was significantly reduced when YAP1 gene was silenced, while it was significantly increased when YAP1 gene was over-expressed. In the HCMV-infected EVT, the number of transmembrane EVT cells significantly increased when over-expressed and eventually recovered to the level of NC.Conclusions: HCMV may decrease EVT invasion by inhibiting the expression of mRNA and protein of YAP in the Hippo-YAP signaling pathway. HCMV eventually reduces the invasion ability of EVT by inhibiting multiple genes in the Hippo-YAP signaling pathway, especially inhibiting YAP which serves as the downstream effector.
In Silico Design for Systems-Based Metabolic Engineering In Escherichia Coli for The Bioconversion of Aerobic Glycerol to Succinic Acid
Authors: Rangel Albert Enrique Tafur , Guzman Wendy Lorena Rios , Cuella Carmen Elvira Ojeda , Perez Daissy Esther Mejia , Carlson Ross , Ramirez Jorge Mario Gomez , Barrios Andres Fernando Gonzalez
Published: December 2020

BackgroundGlycerol has become an interesting carbon source for industrial processes as consequence of the biodiesel business growth since it has shown promising results in terms of biomass/substrate yields. Selecting the appropriate metabolic targets to build efficient cell factories and maximize the desired chemical production in as little time as possible is a major challenge in industrial biotechnology. The engineering of microbial metabolism following rational design has been widely studied. However, it is a cost-, time-, and laborious-intensive process because of the cell network complexity; thus, to be proficient is needed known in advance the effects of gene deletions.ResultsAn in silico experiment was performed to model and understand the effects of metabolic engineering over the metabolism by transcriptomics data integration. In this study, systems-based metabolic engineering to predict the metabolic engineering targets was used in order to increase the bioconversion of glycerol to succinic acid by Escherichia coli. Transcriptomics analysis suggest insights of how increase the glycerol utilization of the cell for further design efficient cell factories. Three models were used; an E. coli core model, a model obtained after the integration of transcriptomics data obtained from E. coli growing in an optimized culture media, and a third one obtained after integration of transcriptomics data obtained from E. coli after adaptive laboratory evolution experiments. A total of 2402 strains were obtained from these three models. Fumarase and pyruvate dehydrogenase were frequently predicted in all the models, suggesting that these reactions are essential to increasing succinic acid production from glycerol. Finally, using flux balance analysis results for all the mutants predicted, a machine learning method was developed to predict new mutants as well as to propose optimal metabolic engineering targets and mutants based on the measurement of importance of each knockout’s (feature’s) contribution.ConclusionsThe combination of transcriptome, systems metabolic modeling, and machine learning analyses revealed versatile molecular mechanisms involved in the utilization of glycerol. These data provide a platform to improve the prediction of metabolic engineering targets to design efficient cell factories. Our results may also work a guide platform for the selection/engineering of microorganisms for production of interesting chemical compounds.