bluuebunny/crossref_metadata_2025 huggingface dataset:
The development of parenting digital multimedia as an educational technology product to support early childhood learning process
Authors: Elyana L , Utanto Y
Published: December 2019

The purpose of this study is to innovate a product in order to support the learning process of early childhood and to identify the increase of early childhood enthusiasm in following the learning process by using parenting digital multimedia as educational technology products. The researcher used ADDIE as the development method. The results obtained is that the parenting digital multimedia as an educational technology products proved to be worthy enough to be used in supporting the early childhood learning process. This can be proven through the results of media assessments conducted by media experts and material experts, as well as the increasing of early childhood enthusiasm in a process of learning in this study. The assessment results obtained from media experts, material experts, and paired t test shows that there is a significant change in the average enthusiasm of early childhood before and after using parenting digital multimedia of the developed educational technology products. Thus it can be concluded that this product can significantly increase the enthusiasm of early childhood in following the learning process.
The Utilization of Smartphone Communication Technology the as Digital Literacy Learning School Instruments in 4.0 Era
Authors: Banowati E , Juhadi  , Sanjoto TB
Published: December 2019

Numbers of institutes report that students’ competency literacy on numeracy, readings and science is low. The presence of digital technology such as computers and smartphones has become part of the students’ daily life. However, digital technology has not provided benefits for students to improve their competence. The challenges of education in the industrial era 4.0 are changes in learning ways, thinking patterns, actions on creative innovation that students have competitiveness in global market. The aim of the study is to explore: the educators’ capability in era 4.0, teaching materials preparation, and digital literacy technical constraints. Explorative methods with descriptive analysis and test. Data is collected by open interviews, in-depth interviews and data reviews. Random samples are limited to 20 teachers and 40 students in Semarang. The acceleration of digital literacy is a necessity, namely data literacy, technology literacy; human literacy has not shown optimal utilization. Through Android-based learning automation and the like is necessary to be applied both media and learning resources. The media utilized can increase digital literacy total score of more than 78 of the indicators specified, besides that the use of this instrument is more 1efficient at around 60%. Optimization can be achieved by-design by teachers as facilitators.
Development of education game media for xii multimedia class students in vocational school
Authors: Kristanto A , Mustaji  , Mariono A , Sulistiowati  , Afifah
Published: December 2019

According to the results of interviews with teachers it is known that students experience difficulties in understanding action script material. This is because this material has a high level of complexity, it is proven that only 30% of students are able to achieve the learning objectives. This study aims to produce educational game media in terms of the feasibility and effectiveness of the media. The development model used is ADDIE (analyze, design, development, implementation, evaluation). Methods of data collection using interview techniques, questionnaires, and tests. From this study the results are based on validation with material experts and media experts by getting a very good category, so that the media can be said to be suitable for use in learning. The results of the post-test value of the experimental class and the control class were analyzed using the t-test obtained by t count = 4.584> t table = 2.038 which is a significant difference, so it can be concluded that the media is effectively used in learning.
Effectiveness of Use Web-Based Learning Media for Information and Communication Technology in Senior High School
Authors: Ahyanuardi  , Ratih
Published: December 2019

The purposes of this study to develop an effective web-based learning media. Methodology of this research is a Research and Develompment (R & D). Development model used is Instructional Development Institute (IDI). The principle approach applied IDI system consists of determination, development, and evaluation. Research design used is descriptive quantitative. The instruments used is a questionnaire to measure validity, practicalities and posttest to measure effectiveness. Then data was analyzed using statistical methods for descriptive analysis, which describe validity, practicality and effectiveness of web-based learning media. The results showed that web-based learning media declared valid and practice for use by teachers and learners. The results obtained that average value of experimental group was higher than control group. It means that web-based learning media “effective” to use. As expected, web-based learning media effectively to improve student learning outcomes. The analysis showed a significant difference between the learning outcomes of students who are taught by media web-based learning with student learning outcomes without use of web-based learning media.
Blended Learning as a Learning Strategy in the Disruptive Era
Authors: Wintarti A , Masriyah  , Ekawati R , Fiangga S
Published: December 2019

In this disruptive era, the need of independence and innovation in learning strategy are required. Blended learning strategy offers face-to-face learning and self-study that combined both online and offline. In other words, it is a combination of traditional learning in a classroom and e-learning via disruptive technology device. There are several courses were encouraged to provide e-learning and face-to-face in delivering material in Mathematics Department of Universitas Negeri Surabaya such as Computer Application, Basic Mathematics, Contextual Mathematics, Visual Programming, and Discrete Mathematics. At the end of the semester, we gave the final exam followed by giving questionnaire about students’ opinion regarding the blended learning strategy. Positive responses on the application of blended learning were showed by students. Furthermore, the learning result of each courses are above 75. By this condition, blended learning is considered as a way to support students’ learning in the disruptive era.
Tutorial model with Student’s pictorial riddle based worksheet for practicing representation capabilities of prospective teacher candidate
Authors: Setyowati Titik , Surasmi Wuwuh Asrining , Widuroyekti Barokah , Sambada Dwi , Pramonoadi  , Setiani Rahyu , Dwikoranto  , Faqih A
Published: December 2019

This study aims to produce a valid and effective Pictorial Riddle-based Student Activity Sheets (SAS) that can improve student’s representation skills. The development of Student Activity Sheets uses four D models (Define, Design, Develop and Desseminate) from Thiagarajan. The trial was limited to Open University students in Bojonegoro study group using one shot case study. The research data was collected using validation, observation, tests and questionnaires with validation sheet instruments, observation sheets, learning outcomes tests and questionnaires. Data were analyzed using quantitative and qualitative descriptive analysis, N-gain and t-test. The results of the study show: 1) SAS that was developed are fulfilling in terms of content and construct validity; 2) SAS that was developed are validity criteria fulfilling effectiveness criteria in terms of improving student representation skills and having positive responses. Based on the above, it can be concluded that SAS are valid and effective to improve the representation ability of prospective teacher students.
The Development of Learning Motivation Video as Guidance and Counseling Media for Senior High School (Equivalent) Students
Authors: Hulukati W , Puluhulawa M , Manangin A S D , Rahim M , Djibran M R
Published: December 2019

The innovation of guidance and counseling media is indispensable for having qualified guidance and counseling services at schools. One of the intended media innovations is service media to improve the learning motivation of high school students. Therefore, the aim of this research was to develop learning motivation video as a media for guidance and counseling services for high school students. This research applied Research and Development (R & D) method, through following steps: (1) analysis of potential and problem, (2) data collection, (3) product design, (4) product validation, and (5) product revision. The product validation was conducted by three experts namely Indonesian linguists, Educational Technology experts, and Guidance and Counseling experts. The finding of research showed that the product of learning motivation video as guidance and counseling media developed in this research could be used to help improve the learning motivation of high school students.
Effectivity of Online Learning Teaching Materials Model on Innovation Course of Vocational and Technology Education
Authors: Sukardi  , Giatman M , Haq S , Sarwandi  , Pratama Y F
Published: December 2019

In Indonesia, development of education was not faster than technology development (era of revolution industry 4.0), so that combination between education and technology were needed so that both of them could be balance. So that, it needed development of teaching materials on innovation course at Technical Vocational Education and Training (TVET) used Problem Based Learning by online. This study was carried out in TVET Magister Program at Universitas Negeri Padang. The type of study was Research and Development (R&D) and model of study was 4-D model (define, design, develop, disseminate). The instrument was validated by 3 of experts judgment, Aiken’s validity result was 0,929 and ICC realibility was 0,811. Effectivity result was obtained of gain score, it was 0,774 that was showed from increasing of student outcomes (pretest-posttest). This study produced teaching materials that were effective and appropriate for learning in the revolution industry 4.0 era.
Comparison of ICT Using in Learning between Indonesia and Malaysia
Authors: Rizal Fahmi , Jalinus Nizwardi , Syahril  , Sukardi  , Zaus Mahesi Agni , Wulansari Rizky Ema , Nabawi Rahmat Aziz
Published: December 2019

Transformation of technology in the 21st century required teachers to be able to integrate ICT in the classroom. Due to technological changes, curriculum changes have taken place in Indonesia and Malaysia. Changes in the curriculum were expected to be able to increase the competence and expertise of teachers in integrating ICT in the classroom so that an effective learning environment was created for students. This study aimed to explore Vocational Education learning strategies used by teachers in Indonesia and Malaysia. The best practices of Vocational education learning strategies were explored including various types of learning media that were integrated ICT. The research method used in this study was quantitative using a questionnaire as a tool to collect data consisting of indicators of remembering & understanding, application, analyze, evaluate and create utilized by the subject of the research, which was vocational school teachers in Malaysia and Indonesia. All data will be analyzed descriptively equipped with tabulations and distribution of empirical data. The results of the study showed that teachers in Indonesia and Malaysia have begun to integrate ICT in the classroom. Teachers have begun to be able to innovate and develop using the right information technology in existing learning situations.
Cone in the Form of Function in the Pre-Service Mathematics Teacher Class Instruction of Tertiery Level
Authors: Turmudi
Published: December 2019

Mathematical learning carried out in the context of lesson study becomes an alternative to the professional development of teachers or lecturers. This paper is a lesson study of “cone as a function”, which is the problem of formulation of a function formula was given. Students were demanded to determine the value of α (centre angle) in such a way that the value of volume V(α) will be maximum. The forty-three undergraduate students were involved in problem-based learning, and at least 50 domestic and international guests as WALS-2014 conference participants, witnessed the learning process that took place. The purpose of this research paper was to find out how many different strategies students could do in solving problems. Infact there are at least 5 different strategies in solving the problem. With more than 12 year experience as a coach in developing the professionalism of junior high school teachers using the lesson study format, this activity turned out to motivate the author himself to open up and organize open-lesson mathematics in tertiary level. From the results of the observations, it was shown that the diverse answers of students were influenced by the educational background and experience of students during college or while obtaining education at the high school level.
Development of mathematical learning tools to promote higher order thinking skills for elementary school students
Authors: Setianingsih R , Budiarto MT , Artiono R
Published: December 2019

As stated in the revised curriculum 2013 or K-13 in 2017, the learning tools made by a teacher must bring up and involve 4 (four) aspects, namely Character Education Strengthening (KDP), Literacy, 4C, and Higher Order Thinking Skills (HOTS). Therefore, teachers are required to have sufficient knowledge in these four points, in order to be able to grow their creativity to mix and make it happen in the form of a complete learning device. This research is a design research that aims to describe the process and results of the development of HOTS-based mathematics learning devices that meet the criteria of valid, practical, and effective. The learning devices developed in this study are in the form of lesson plan, student worksheet, and assessment sheet. To develop the product, the researchers implemented Plomp development model, which includes the initial research stage, design/prototype stage, and assessment stage. The results of data analysis show that HOTS-based mathematics learning tools for elementary school students developed by the researchers meet the criteria of valid, practical, and effective, with a mean score as the following: Lesson Plan (3.41), Student worksheet (3.39), Learning outcomes (3.73), Learning feasibility (4.03), Positive student responses (94.44%).
The Use of Cooperative Learning Models Think Pair Share in Mathematics Learning.
Authors: Ningsih Yarisda
Published: December 2019

This study aims to determine whether the mathematics learning outcomes of students who use cooperative learning models of the Think Pair Share type are better than the mathematics learning outcomes of students who follow conventional learning models. Hypothesis testing is done by using data analysis techniques with the t-test formula. Previously the data was determined by the average and standard deviation of each class, then a normality test was performed using the Lilliefors test, the results for the experimental class Lo = 0.092 with Ltabel = 0.1498 and the control class Lo = 0.1008 with Ltabel = 0.1477 so the samples come from populations with normal distribution. The analysis was continued by testing the similarity of variance. It turns out that both samples have a homogeneous variance. After the t-test is tested, the price of t count = 2.95, while the price of t table = 1.67. Because t-test > t table at the real level = 0.05, it can be concluded that the mathematics learning outcomes of students using the cooperative learning model think pair share are better than the mathematics learning outcomes of students who use conventional learning in the XI science class MAN 2 Padang.
The Running-based Anaerobic Sprint Test of different Type of Sports
Authors: Nasuka  , Santosa I , Setiowati A , Indrawati F
Published: December 2019

The aim of study was to compare the anaerobic capacity of different type sport. The running-based anaerobic capacity test (RAST) were exam to 42 athletes of football (10), sprint (6), takraw (8), volleyball (10) and pencak silat (8). The anova analysis resulted the difference of minimum power (MinP) (p=0.001), maximum power (MaxP) (p=0.000), average power (AvP)(0.000) and fatigue index (FI) (0.008). The post hoc analysis showed no difference anaerobic capacity between athletes of football vs sprinter, football vs pencak silat, football vs takraw and takraw vs pencak silat. The different finding appeared between athlete of volleyball vs the other athletes. and between takraw vs sprint. We concluded that the anaerobic capacity of athletes was specific with the type of sports.
Potential commercial waste in Jakarta as a renewable source of energy
Authors: Adiandri F M , Kristanto G A
Published: December 2019

The high development of the commercial area in Jakarta starting in the 90s which shopping centers sprawling across the city with the concept of a modern market or mall. These commercial wastes generated a high amount of wastes which contains a very high mass fraction of combustibles (such as plastic, paper, and textile). Waste that characterized by a high calorific value would suitable for direct combustion in waste-to-energy (WtE) plants. The objective of this study is to apply the waste to energy concept for utilizing commercial waste as the potential energy of Jakarta’s. The result showed that the energy content of Jakarta’s commercial waste 189.78 ± 23.51 GWh/month, with waste composition 36.33% (paper), 35.71% (plastic) and 14.54% (organic). That potential energy is equivalent to 7.19% of the total energy needed in Jakarta every month.
Catch marketing analysis of Frigate tuna (Auxis thazard): caught by lift-net at Bone District, South Sulawesi Province-Indonesia
Authors: Kasim Nurdin , Budiyati  , Isman Khairudin
Published: December 2019

Lift-net (local term: Bagan Rambo) is one of the most productive fishing gear in the coastal community of Gulf of Bone, including those in the Bone District. This study aims to explain the characteristics of the marketing channels of frigate tuna caught by fishermen and the effectiveness and efficiency of frigate tuna market system. The study was conducted from December 2017 to February 2018 at Bone District, South Sulawesi Province-Indonesia with a purposive sampling method of 37 units of lift-net and 481 fisheries households. The results of the study show that lift-net owners and fishmongers are the main channels of catch marketing (66.7%). For Bone sub-district of Tanete Riattang Timur 50% of catches go fishing auction and fisheries companies. The effective marketing system of frigates tuna are: 1) fishermen get more profit if they sell their catch in kg instead of selling per bucket, 2) the boat owner and fishmonger get a big profit, at the sale of a minimum price. The effective marketing channel is directly selling catches to fisheries companies.
18F-fluorodeoxyglucose positron emission tomography in malignant pleural mesothelioma: diagnostic and prognostic performance and its correlation to pathological results
Authors: Lococo Filippo , Rena Ottavio , Torricelli Federica , Filice Angelina , Rapicetta Cristian , Boldorini Renzo , Paci Massimiliano , Versari Annibale
Published: December 2019

Although 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) scan has been generally validated in the staging of malignant pleural mesothelioma (MPM), its diagnostic and prognostic performances are not clearly established. Aiming to identify possible factors causing 18F-fluorodeoxyglucose PET/CT false-negative results and influencing prognosis in MPM patients, we analysed clinical, radiometabolic and pathological features in 141 MPM patients who underwent diagnostic 18F-fluorodeoxyglucose PET/CT scan (January 2009–July 2018) at 2 high-volume institutions. The Fisher’s exact test and the Cox model were used in statistical analysis. Overall detection rate was 88.3% with 16 patients (11.6%) presenting with a standardized uptake value (SUV) max <2.5 (PET-negative). PET-negative cases were more frequently detected in older patients (P = 0.027) and early-stage tumours (33.3% false-negative in stage I and 40.0% false-negative in T1-tumours, with P = 0.014 both). Mean SUVmax value was higher in sarcomatoid (11.8 ± 4.6) and biphasic MPM (9.3 ± 7.0), rather than in epithelioid MPM (6.9 ± 3.8, P < 0.001). Concerning overall survival, SUVmax (both as continuous and as categorical variable) was found to be a prognostic factor, in addition to stage (P = 0.032) and histology (P = 0.014) as confirmed by multivariable analysis (hazard ratio 2.65, confidence interval 1.23–5.70; P < 0.001). In the light of such results, we highlight that a low fluorodeoxyglucose uptake might be observed in more than 10% MPMs, especially in early-stage tumours affecting elderly patients. Furthermore, high SUVmax values significantly correlated with a worse prognosis.
Approximate controllability of semilinear impulsive functional differential systems with non-local conditions
Authors: Arora Sumit , Singh Soniya , Dabas Jaydev , Mohan Manil T
Published: December 2019

This paper is concerned with the approximate controllability of semilinear impulsive functional differential systems in Hilbert spaces with non-local conditions. We establish sufficient conditions for approximate controllability of such systems via resolvent operator and Schauder’s fixed point theorem. An application involving the impulse effect associated with delay and non-local conditions is presented to verify our claimed results.
Impact of Changes in Detection Effort on Control of Visceral Leishmaniasis in the Indian Subcontinent
Authors: Coffeng Luc E , Le Rutte Epke A , Muñoz Johanna , Adams Emily R , Prada Joaquin M , de Vlas Sake J , Medley Graham F
Published: December 2019

Background

Control of visceral leishmaniasis (VL) on the Indian subcontinent relies on prompt detection and treatment of symptomatic cases. Detection efforts influence the observed VL incidence and how well it reflects the underlying true incidence. As control targets are defined in terms of observed cases, there is an urgent need to understand how changes in detection delay and population coverage of improved detection affect VL control.

Methods

Using a mathematical model for transmission and control of VL, we predict the impact of reduced detection delays and/or increased population coverage of the detection programs on observed and true VL incidence and mortality.

Results

Improved case detection, either by higher coverage or reduced detection delay, causes an initial rise in observed VL incidence before a reduction. Relaxation of improved detection may lead to an apparent temporary (1 year) reduction in VL incidence, but comes with a high risk of resurging infection levels. Duration of symptoms in detected cases shows an unequivocal association with detection effort.

Conclusions

VL incidence on its own is not a reliable indicator of the performance of case detection programs. Duration of symptoms in detected cases can be used as an additional marker of the performance of case detection programs.
In vitro effects of combined iron chelation, antibiotics and matrix disruption on clinical isolates of Pseudomonas aeruginosa
Authors: Nair Arun , Perry Audrey , Perry John D , Gould F Kate , Samuel Julie
Published: December 2019

Objectives

Pseudomonas aeruginosa is an important pathogen in chronic suppurative respiratory diseases, with adverse effects on severity, healthcare utilization and quality of life. Aerosolized combined biofilm disruption and iron chelators offer novel proof-of-concept for improving airway antimicrobial efficacy. Our aim was to assess the activity of desferrioxamine, Dornase alfa (DNase) and antibiotics on biofilm formation and against mature preformed biofilms of P. aeruginosa.

Methods

Fifty-six isolates of P. aeruginosa were screened for biofilm production and seven isolates with varying capacity to form biofilms were referred for further study. Three antibiotics (colistin, tobramycin and ciprofloxacin) as well as desferrioxamine and DNase were assessed for their ability to prevent biofilm formation using the crystal violet assay. The same method was used to assess their impact on mature biofilms. Each agent, as well as combinations of these agents, was also assessed for its effect on the metabolic activity and viability of preformed P. aeruginosa biofilm by the resazurin reduction assay and by performing viable counts.

Results

Antibiotics alone prevented the development of biofilms and partly reduced the viability of mature biofilms. Desferrioxamine and DNase did not reduce biofilm formation. For most isolates, desferrioxamine and DNase did not offer any clear advantage over the use of antibiotics alone with respect to reducing the viability of Pseudomonas biofilms.

Conclusions

Colistin, tobramycin and ciprofloxacin prevented biofilm formation by P. aeruginosa and reduced the viability of mature biofilms. For most isolates, there was no clear advantage of combining these antimicrobials with desferrioxamine or DNase.
Cyprid larvae of the acorn barnacle Semibalanus balanoides (Linnaeus, 1767) (Cirripedia: Sessilia: Archaeobalanidae) can metamorphose to juveniles without being permanently attached to a substrate
Authors: Leal Inês , Flores Augusto A V , Scrosati Ricardo A , Tremblay Réjean
Published: December 2019

It is commonly assumed that the pelagic cyprid larvae of acorn barnacles must permanently attach to a substrate before metamorphosing to the benthic juvenile stage. We show that this is not always the case and demonstrate that some cyprids can metamorphose in the water column, i.e. without first becoming cemented to a surface. We observed early-metamorphosing cyprids to fully developed juveniles in coastal plankton samples during the 2018 recruitment season of Semibalanus balanoides (Linnaeus, 1767) in Atlantic Canada. We demonstrated through a laboratory experiment that cyprids can be induced to fully metamorphose into pelagic juveniles. These novel findings raise the question of whether this phenomenon may also occur in other barnacle species.
Laboratory Evaluation of Egg White and Milk External Biomarkers for Wasmannia auropunctata (Hymenoptera: Formicidae)
Authors: Montgomery Michelle , Hagler James R , Vanderwoude Casper , Lynch A Jasmyn J , Robinson Wayne A
Published: December 2019

Acquisition and retention of two protein markers were tested on little fire ants, Wasmannia auropunctata Roger. Pure (100%) cow’s milk and a dilution (10%) of chicken egg whites were applied to W. auropunctata directly by contact spray plus residue or indirectly via residual contact only with protein-marked plant debris. Protein-marked ants were held in plastic shoe-box-sized containers, collected at 0, 24, and 48 h after exposure to their respective marks, and then examined for the presence of the marks by a chicken egg albumin and milk casein-specific enzyme-linked immunosorbent assay. Cross-contamination rates were assessed by allowing ants marked with egg whites to interact with an equal number marked milk for 24 and 48 h, and then collected either individually or in bulk. Results indicated that the egg white biomarker was retained longer than milk and that more ants were successfully marked when the direct spray application method was employed. Cross-contamination rates were highest among bulk-collected ants and lowest among ants collected individually after 24 h. However, the rates of cross-contamination among individually collected ants increased and were similar to that of bulk-collected ants after 48 h. On the basis of our results, external protein marking may not be suitable if mass trapping is required or if the study extends beyond 24 h due to high cross-contamination rates among specimens collected in bulk and reduced marker detection rates.
Traveling to thermal refuges during stressful temperatures leads to foraging constraints in a central-place forager
Authors: Haase Catherine G , Fletcher Robert J , Slone Daniel H , Reid James P , Butler Susan M
Published: December 2019

Central-place foragers can be constrained by the distance between habitats. When an organism relies on a central place for thermal refuge, the distance to food resources can potentially constrain foraging behavior. We investigated the effect of distance between thermal refuges and forage patches of the cold-intolerant marine mammal, the Florida manatee (Trichechus manatus latirostris), on foraging duration. We tested the alternative hypotheses of time minimization and energy maximization as a response to distance between habitats. We also determined if manatees mitigate foraging constraints with increased visits to closer thermal refuges. We used hidden Markov models to assign discrete behaviors from movement parameters as a function of water temperature and assessed the influence of distance on foraging duration in water temperatures above (> 20°C) and below (≤ 20°C) the lower critical limit of the thermoneutral zone of manatees. We found that with increased distance, manatees decreased foraging duration in cold water temperature and increased foraging duration in warmer temperatures. We also found that manatees returned to closer thermal refuges more often. Our results suggest that the spatial relationship of thermal and forage habitats can impact behavioral decisions regarding foraging. Addressing foraging behavior questions while considering thermoregulatory behavior implicates the importance of understanding changing environments on animal behavior, particularly in the face of current global change.
Quantitation of Cell-Derived Microparticles in Blood Products and Its Potential Applications in Transfusion Laboratories
Authors: Noulsri Egarit
Published: December 2019

Cell-derived microparticles (MPs) are small fragments released from various cells when they are activated or undergo apoptosis. In the field of transfusion medicine, a number of studies have documented increased levels of MPs in blood products, which have been associated with multiple factors, including donor variability, blood component processing, and storage. In addition, transfusions that contain high levels of MPs are linked to posttransfusion complications. Considering the clinical importance of MP levels, transfusion laboratories should routinely screen blood products for them. However, this practice is not yet applied routinely, perhaps in part because of a lack of understanding of how to apply MP data to transfusion medicine. We describe the methods used to quantitate MPs in blood components and discuss the application of these quantitative data in routine transfusion laboratories in order to manage quality, improve the outcomes of transfusions, and minimize their complications.
Highly specific enrichment of rare nucleic acid fractions using Thermus thermophilus argonaute with applications in cancer diagnostics
Authors: Song Jinzhao , Hegge Jorrit W , Mauk Michael G , Chen Junman , Till Jacob E , Bhagwat Neha , Azink Lotte T , Peng Jing , Sen Moen , Mays Jazmine , Carpenter Erica L , van der Oost John , Bau Haim H
Published: December 2019

Detection of disease-associated, cell-free nucleic acids in body fluids enables early diagnostics, genotyping and personalized therapy, but is challenged by the low concentrations of clinically significant nucleic acids and their sequence homology with abundant wild-type nucleic acids. We describe a novel approach, dubbed NAVIGATER, for increasing the fractions of Nucleic Acids of clinical interest Via DNA-Guided Argonaute from Thermus thermophilus (TtAgo). TtAgo cleaves specifically guide-complementary DNA and RNA with single nucleotide precision, greatly increasing the fractions of rare alleles and, enhancing the sensitivity of downstream detection methods such as ddPCR, sequencing, and clamped enzymatic amplification. We demonstrated 60-fold enrichment of the cancer biomarker KRAS G12D and ∼100-fold increased sensitivity of Peptide Nucleic Acid (PNA) and Xenonucleic Acid (XNA) clamp PCR, enabling detection of low-frequency (<0.01%) mutant alleles (∼1 copy) in blood samples of pancreatic cancer patients. NAVIGATER surpasses Cas9-based assays (e.g. DASH, Depletion of Abundant Sequences by Hybridization), identifying more mutation-positive samples when combined with XNA-PCR. Moreover, TtAgo does not require targets to contain any specific protospacer-adjacent motifs (PAM); is a multi-turnover enzyme; cleaves ssDNA, dsDNA and RNA targets in a single assay; and operates at elevated temperatures, providing high selectivity and compatibility with polymerases.
FluoroCalins: engineered lipocalins with novel binding functions fused to a fluorescent protein for applications in biomolecular imaging and detection
Authors: Eggenstein Evelyn , Richter Antonia , Skerra Arne
Published: December 2019

FluoroCalins represent novel bifunctional protein reagents derived from engineered lipocalins fused to a fluorescent reporter protein, here the enhanced green fluorescent protein (eGFP). We demonstrate the construction, facile bacterial production and broad applicability of FluoroCalins using two Anticalin® molecules directed against the tumor vasculature-associated extra domain B of fibronectin (ED-B) and the vascular endothelial growth factor receptor 3, a marker of tumor and lymphangiogenesis. FluoroCalins were prepared with two different spacers: (i) a short Ser3Ala linker and (ii) a long hydrophilic and conformationally unstructured PASylation® polypeptide comprising 200 Pro, Ala and Ser residues. These FluoroCalins were applied for direct target quantification in enzyme-linked immunosorbent assay as well as target detection by flow cytometry and fluorescence microscopy of live and fixed cells, respectively, demonstrating high specificity and signal-to-noise ratio. Hence, FluoroCalins offer a promising alternative to antibody-based reagents for state of the art fluorescent in vitro detection and biomolecular imaging.
The art market, an industry in need of regulation?
Authors: Stapper Erik J
Published: December 2019

In recent months, the art press has questioned the openness of certain practices in today’s art market. This article highlights them in the context of the possible need for regulation and then looks back to the Dutch Golden Age of painting for possible relevance today.
Identification of novel dynamin‐related protein 1 (Drp1) GTPase inhibitors: Therapeutic potential of Drpitor1 and Drpitor1a in cancer and cardiac ischemia‐reperfusion injury
Authors: Wu Danchen , Dasgupta Asish , Chen Kuang‐Hueih , Neuber‐Hess Monica , Patel Jignesh , Hurst Timothy E. , Mewburn Jeffrey D. , Lima Patricia D. A. , Alizadeh Elahe , Martin Ashley , Wells Michael , Snieckus Victor , Archer Stephen L.
Published: December 2019

Mitochondrial fission is important in physiological processes, including coordination of mitochondrial and nuclear division during mitosis, and pathologic processes, such as the production of reactive oxygen species (ROS) during cardiac ischemia‐reperfusion injury (IR). Mitochondrial fission is mainly mediated by dynamin‐related protein 1 (Drp1), a large GTPase. The GTPase activity of Drp1 is essential for its fissogenic activity. Therefore, we aimed to identify Drp1 inhibitors and evaluate their anti‐neoplastic and cardioprotective properties in five cancer cell lines (A549, SK‐MES‐1, SK‐LU‐1, SW 900, and MCF7) and an experimental cardiac IR injury model. Virtual screening of a chemical library revealed 17 compounds with high predicted affinity to the GTPase domain of Drp1. In silico screening identified an ellipticine compound, Drpitor1, as a putative, potent Drp1 inhibitor. We also synthesized a congener of Drpitor1 to remove the methoxymethyl group and reduce hydrolytic lability (Drpitor1a). Drpitor1 and Drpitor1a inhibited the GTPase activity of Drp1 without inhibiting the GTPase of dynamin 1. Drpitor1 and Drpitor1a have greater potency than the current standard Drp1 GTPase inhibitor, mdivi‐1, (IC50 for mitochondrial fragmentation are 0.09, 0.06, and 10 μM, respectively). Both Drpitors reduced proliferation and induced apoptosis in cancer cells. Drpitor1a suppressed lung cancer tumor growth in a mouse xenograft model. Drpitor1a also inhibited mitochondrial ROS production, prevented mitochondrial fission, and improved right ventricular diastolic dysfunction during IR injury. In conclusion, Drpitors are useful tools for understanding mitochondrial dynamics and have therapeutic potential in treating cancer and cardiac IR injury.
SUMO1 SUMOylates and SENP3 deSUMOylates NLRP3 to orchestrate the inflammasome activation
Authors: Shao Luyao , Liu Yan , Wang Wenbiao , Li Aixin , Wan Pin , Liu Weiyong , Shereen Muhammad Adnan , Liu Fang , Zhang Wen , Tan Quiping , Wu Kailang , Liu Yingle , Wu Jianguo
Published: December 2019

The NLRP3 inflammasome regulates innate immune and inflammatory responses by promoting caspase1‐dependent induction of pro‐inflammatory cytokines. However, aberrant inflammasome activation causes diverse diseases, and thus inflammasome activity must be tightly controlled. Here, we reveal a molecular mechanism underlying the regulation of NLRP3 inflammasome. NLRP3 interacts with SUMO‐conjugating enzyme (UBC9), which subsequently promotes small ubiquitin‐like modifier 1 (SUMO1) to catalyze NLRP3 SUMOylation at residue Lys204. SUMO1‐catalyzed SUMOylation of NLRP3 facilitates ASC oligomerization, inflammasome activation, and interleukin‐1β secretion. Moreover, this study also reveals that SUMO‐specific protease 3 (SENP3) is required for the deSUMOylation of NLRP3. Interestingly, SENP3 deSUMOylates NLRP3 to attenuate ASC recruitment and speck formation, the NLRP3 inflammasome activation, as well as IL‐1β cleavage and secretion. In conclusion, we reveal that SUMO1‐catalyzed SUMOylation and SENP3‐mediated deSUMOylation of NLRP3 orchestrate the inflammasome activation.
Implementing a Rehabilitation Protocol for Spatial Neglect Assessment and Treatment in an Acute Care Hospital
Authors: Hreha Kimberly , Chen Peii , LaRosa Jennifer , Santos Christopher , Gocon Cindy , Barrett A.M.
Published: December 2019

Purpose:

Spatial neglect can occur after stroke, causing disabling spatial errors limiting functional abilities. In rehabilitation research, administration of spatial neglect assessment and treatment protocols can improve function. The objective of this study was to implement those protocols, the Kessler Foundation Neglect Assessment Process (KF-NAP) and the Kessler Foundation Prism Adaptation Treatment (KF-PAT), in an acute care hospital to determine their feasibility and sustainability.

Methods:

We formally instructed participating therapists, followed by a 5-month training phase and then 6-month implementation phase. Patient participants included right brain stroke survivors, at acute care. We measured patient-based (study participation rates, refusals) and institutional-based feasibility (fidelity and maintenance) for both protocols.

Results:

A total of 126 of 145 patients with stroke meeting the inclusion criteria were assessed for spatial neglect. Among the 126, 20.6% had spatial neglect. Ten of the 26 patients with spatial neglect were treated with the KF-PAT. There were no refusals; however, 3 people were not seen because of medical scheduling. Overall, the fidelity of both protocols was maintained because main concepts and components were not changed. However, adaptations to both protocols were required secondary to lack of time and medical complexity of the patients.

Conclusions:

Implementation of a standard rehabilitation assessment and treatment protocol for spatial neglect in acute care is feasible. The findings related to fidelity are promising; however, further research is recommended.
A Survey Study of Health Promotion, Wellness, and Prevention in Wound Management Environments
Authors: Wendland Deborah M. , Taylor David W. M. , Lucado Ann M.
Published: December 2019

Purpose:

To survey physical therapists and physical therapist assistants practicing in wound management environments regarding their personal beliefs, clinical practices, and perceived barriers to incorporating health promotion, wellness, and prevention (HPWP) in practice.

Methods:

A 30-question validated survey was sent to wound care therapists.

Results:

The qualified response rate was 29%. Therapists reported a belief in their professional role in HPWP as follows: physical (97%), psychological (82%), emotional (79%), intellectual (73%), occupational (73%), social (71%), and spiritual (55%). Practice behaviors that were frequently included by these individuals included nutrition optimization (88%), diabetes/metabolic syndrome education (81%), physical activity/fitness prescription (81%), and tobacco cessation (78%). Conditions least addressed included violence (91%) and substance-free living (75%). Common barriers included lack of resources, time, patient interest, and economic limitations of patients. Respondent lifestyles were generally healthier than adults in the United States.

Conclusions:

There is an increasing need in physical therapist practice to actively promote health and wellness at the level of the individual. Modeling health behaviors is important to include as well and may be beneficial to support patient healthy lifestyle. While wound management therapists do well in promoting health in certain areas, work is still needed in others.
Demographic Factors of Nasal Bone Fractures and Social Reflection
Authors: Byun Il Hwan , Lee Won Jai , Roh Tai Suk , Hong Jong Won
Published: December 2019

Introduction:

The nose is the most protruding central part of the face, and nasal bone fractures are the most common of facial bone fractures, leading up to 39%. Despite its high frequency, not many studies handled the etiology of nasal bone fractures, leading to the necessity of a recent demographic study.

Materials and Methods:

A total of 1111 patients diagnosed with nasal bone fracture from 2013 to 2018 at our institute were evaluated. A retrospective review of the various demographic and etiologic characteristics was done.

Results:

Numerous factors associated with nasal bone fractures were analyzed. Male patients were 3.3 times greater than the number of female patients, and twenties were the most common age range. Violence was the overall most common cause of injury, while slip down was the most common cause for females. Upon monthly distribution, the highest incidence of nasal bone fractures occurred in September, followed by March and December. The authors further divided the patients by time zone of the fractures, and male patients were most commonly injured from midnight to 3 AM, while female patients were 6 PM to 9 PM.

Conclusion:

Our findings represent a recent urban data of various etiologic factors of nasal bone fracture. The concept of school violence has been widely used since 1990s, and our data reflects that violence of the youth is a serious issue of the society. The mechanism of injury differed among sexes and age groups, and such discrepancies will aid physicians to better understand facial bone fracture patients and educate them in the future.
Nucleolin (NCL) inhibits the growth of peste des petits ruminants virus
Authors: Dong Dandan , Zhu Shiqiang , Miao Qiuhong , Zhu Jie , Tang Aoxing , Qi Ruibin , Liu Teng , Yin Dongdong , Liu Guangqing
Published: December 2019

Peste des petits ruminants (PPR) is a highly contagious disease of small ruminants that is caused by peste des petits ruminants virus (PPRV). To date, the molecular mechanism of PPRV infection is still unclear. It is well known that host proteins might be involved in the pathogenesis process for many viruses. In this study, we first proved that nucleolin (NCL), a highly conserved host factor, interacts with the core domain of PPRV N protein through its C terminus and co-locates with the N protein in the nucleus of cells. To investigate the role of NCL in PPRV infection, the expression level of NCL was inhibited with small interfering RNAs of NCL, and the results showed that PPRV growth was improved. However, the proliferation of PPRV was inhibited when the expression level of NCL was improved. Further analysis indicated that the inhibitory effect of NCL on the PPRV was caused by stimulating the interferon (IFN) pathways in host cells. In summary, our results will help us to understand the mechanism of PPRV infection.
Liquid-like protein interactions catalyze assembly of endocytic vesicles
Authors: Day Kasey J. , Kago Grace , Wang Liping , Richter J Blair , Hayden Carl C. , Lafer Eileen M. , Stachowiak Jeanne C.
Published: December 2019

During clathrin-mediated endocytosis, dozens of proteins assemble into an interconnected network at the plasma membrane. As early initiators of endocytosis, Eps15 and Fcho1 are responsible for locally concentrating downstream components on the membrane surface. However, they must also permit dynamic rearrangement of proteins within the budding vesicle. How do initiator proteins meet these competing demands? Here we show that Eps15 and Fcho1 rely on weak, liquid-like interactions to efficiently catalyze endocytosis. In reconstitution experiments, these weak interactions promote the assembly of protein droplets with liquid-like properties, including rapid coalescence and dynamic exchange of protein components. To probe the physiological role of liquid-like interactions among initiator proteins, we tuned the strength of initiator protein assembly in real time using light-inducible oligomerization of Eps15. Low light levels drove initiator proteins into liquid-like assemblies, restoring normal rates of endocytosis in mammalian Eps15 knockout cells. In contrast, initiator proteins formed solid-like assemblies upon exposure to higher light levels. Assembly of these structures stalled vesicle budding, likely owing to insufficient molecular rearrangement. These findings suggest that liquid-like assembly of early initiator proteins provides an optimal catalytic platform for endocytosis.
Chromosome Evolution of Octoploid Strawberry
Authors: Hardigan Michael A. , Feldmann Mitchell J. , Lorant Anne , Famula Randi , Acharya Charlotte , Cole Glenn , Edger Patrick P. , Knapp Steven J.
Published: December 2019

The allo-octoploid cultivated strawberry (Fragaria×ananassa) originated through a combination of polyploid and homoploid hybridization, domestication of an interspecific hybrid lineage, and continued admixture of wild species over the last 300 years. While genes appear to flow freely between the octoploid progenitors, the genome structures and diversity of the octoploid species remain poorly understood. The complexity and absence of an octoploid genome frustrated early efforts to study chromosome evolution, resolve subgenomic structure, and develop a single coherent linkage group nomenclature. Here, we show that octoploidFragariaspecies harbor millions of subgenome-specific DNA variants. Their diversity was sufficient to distinguish duplicated (homoeologous and paralogous) DNA sequences and develop 50K and 850K SNP genotyping arrays populated with co-dominant, disomic SNP markers distributed throughout the octoploid genome. Whole-genome shotgun genotyping of an interspecific segregating population yielded 1.9M genetically mapped subgenome variants in 5,521 haploblocks spanning 3,394 cM inF. chiloensissubsp.lucida, and 1.6M genetically mapped subgenome variants in 3,179 haploblocks spanning 2,017 cM inF. ×ananassa. These studies provide a dense genomic framework of subgenome-specific DNA markers for seamlessly cross-referencing genetic and physical mapping information, and unifying existing chromosome nomenclatures. Through comparative genetic mapping, we show that the genomes of geographically diverse wild octoploids are effectively diploidized and completely collinear. The preservation of genome structure among allo-octoploid taxa is a critical factor in the unique history of garden strawberry, where unimpeded gene flow supported both its origin and domestication through repeated cycles of interspecific hybridization.