bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental testing the effect of teaching method with multimedia
Authors: Wizaka Wiyantara
Published: March 2020

The technical drawing is a step that is absolutely necessary to be mastered by the architects in presenting their product in the design development phase. The easy readiness and completeness of information in a drawing determine the quality and timeliness of a project. An incomplete engineering drawing is difficult to read by foreman or craftsman. Building Technology’s subject studies the structure and construction of buildings. As a supporting subject, it plays an important role in the creation of design works of the students. Successful mastery of this subject greatly impacts on courage and design exploration of students in Architecture design courses. This study arranged to measure how far the material online can be understood and comparing the teaching’s result between the normal method (conventional method) with the multimedia method. As the object of research are students of Building Technology classes LA44, LB44, and LD44 at Bina Nusantara University Jakarta. The method used in this research is experimental research. Preliminary data collection is obtained from each work of the student’s assignment. Observation, interview, test through quiz done directly in the classroom and carried out during the odd semester run until the end of the lecture.
The application of threshold space concept on culinary center in Jakarta for sustainable architectural design
Authors: Dennis M , Nurdiani N , Katarina W
Published: March 2020

The Central Jakarta area is the largest contributor to retribution for DKI Jakarta, and most of its population expenditure is in the food sector. The need for a new culinary center that can become a new communal space for urban communities requires a design approach that supports the creation of sustainable architectural designs in terms of social aspects. The application of the concept of threshold space is done through qualitative design methods in designing culinary centers in Palmerah - Central Jakarta that provide and sell food and drinks. The design of this culinary center is expected to become a new communal space that functions as a recreational space and a space for social interaction that functions well. Threshold space concept was chosen to be applied in the design because it functions as a transition space that connects one function to another, so that integration between spaces is also well created.
The behaviour architectural approach on children public space in Jakarta to create sustainable environment
Authors: Nurdiani N , Katarina W , Masyitoh S
Published: March 2020

In recent years the city government of Jakarta has built Child Friendly Open Public Spaces (RPTRA) throughout the Jakarta area. In order to create sustainable environment in public space, study about existing condition of RPTRA in Jakarta is needed. The study conducted through descriptive method. Result of the study showed that the existing conditions of RPTRA are still inadequate, so a re-design of this public space is needed. The RPTRA redesign project aims to provide a playroom in accordance with the needs of each age group, as well as provide space for non-formal education facilities for the surrounding community as one of the fulfillments of educational programs in the RPTRA. The concept of the design is a playground design that fits the needs of each age group of children and a flexible learning space.
Layout housing typology using hydroponics system
Authors: Ardiani Yanita Mila , Noegroho
Published: March 2020

Along with the development of settlements in the middle of the city, the reduction of green land in each of the housing units has diminished. The desire to grow crops in the housing unit is increasingly gone. But now, all can be made using hydroponic techniques. Hydroponic technique is six cultivation by utilizing water without using soil by emphasizing the fullness of nutritional needs for plants. This farming technique is now being tucked away as an effort to present green land in a settlement with small and dense land. Therefore, a lay out design solution that accommodates residents in the housing area can be planted with hydroponics. Hydroponics is a business for urban farming. The research method used is an experiment with qualitative research. The plan for conducting the research activities will be a survey and field data collection, then continued with drawing work and designing layout
Model of stakeholder collaborative for disaster logistics in Indonesia
Authors: Oktarina Rienna , Wijaksono Sigit
Published: March 2020

The goals of this research is mapping the role and contribution of each stakeholders and developing a model of stakeholders collaboration in disaster preparedness logistics activities in Indonesia. The approach used in this research is a qualitative research approach with the type of descriptive explorative research. The model produced by this research involves five groups of stakeholder, namely government, society, private sector/industry, media and scientists. The role of the five stakeholders is mapped in three types of stakeholders, namely key stakeholders primary stakeholders and secondary stakeholders. Disaster preparedness logistics activities in this research are divided into four activities, namely facility location, stock prepositioning, resource allocation, and relief distribution, while the collaboration indicators set in this research are partnership, participation and network. The mapping of stakeholders and the formulation of stakeholders collaboration models in this research was carried out by the FGD (Focus Group Discussion) process, which consisted of representatives from all groups of stakeholder.The concept model obtained from this paper can be used as a basis for the preparation of the blueprint of the National Logistics System for Disaster Management in Indonesia that can help disaster management actors collaborate in carrying out logistics activities in disaster preparedness, so that logistical activities in disaster preparedness can be carried out quickly, precise and accurate.
Moderating effects of green IS on the relationship between organizational agility, customer experience and digital service innovation to achieve sustainable performance
Authors: Mihardjo Leonardus WW , Sasmoko  , Alamsjah Firdaus , Elidjen
Published: March 2020

This study focuses on the empirical analysis to assess the role of digitalization through Green Information System (GIS) on the relationship between organizational agility (OA), customer experience (CX), and digital service innovation (DSI) to achieve sustainable performance (SP) in the Indonesian Information Communication and Technology (ICT) industry. The authors seek to examine the technological impact as part of digital transformation antecedents of CX and OA in developing DSI. The study also aims to investigate the digital transformation model to attain a more sustainableICT performance in Indonesia. The novelty of this study lies in the identifying and testing the concurrent effects of studied variables in improving the understanding of DSI and SP as part of the Indonesian ICT digital transformation model. The study used a sample of 195 Indonesia ICT firms. The finding from PLS-SEM reveals that GIS has a significant moderating role in accelerating the development ofDSI on the relationship with CX and OA, while SP is positively and significantly influenced by CS, OA and DSI. The implication and the proposed of digital transformation model for Indonesian ICT firms is also discussed in this paper.
Conceptual development of learning factory for industrial engineering education in Indonesia context as an enabler of students’ competencies in industry 4.0 era
Authors: Tan Hauw-Sen , Ivander  , Oktarina Rienna , Reynaldo Vinson , Sharina Catherine
Published: March 2020

Industry 4.0 becomes more and more important in recent years because manufacturing industries are facing huge challenges in improving productivity for global competition. Industry 4.0 provides new opportunities to improve the resource and process efficiencies by combining information and communication technologies such as autonomous robots, internet of things, cloud computing, big data, augmented reality, additive manufacturing, etc. This integrated cyber-physical production system raise complexity within production system that implies new competencies required for industrial engineers which has been proven for years that the role of industrial engineer greatly influences a manufacturing industry’s success by designing, implementing, improving and optimizing a complex processes of an integrated systems that consist of people, money, knowledge, information, equipment, energy and materials. The competencies required in Industry 4.0 could be categorized under technical competencies and social competencies. A learning factory with real world system is often used to train students a new set of competencies by hands-on and direct experiences. Therefore, a learning factory can make a substantial contribution to competencies enhancement for industrial engineering students. This paper presents a conceptual of Industry 4.0 Lab as a learning factory for industrial engineering education as an enabler of students’ competencies in industry 4.0 era. A fully automated small production of filling bottle system integrating and demonstrating various Industry 4.0 concepts technologies is chosen. The learning modules and didactic approach are developed by integrating industrial engineering body of knowledge, Industry 4.0 value drives and Industry 4.0 levers in the creation of technical and social competencies required.
Preliminary design and sustainability study of rosella jam factory utilizing renewable solar energy
Authors: Mangindaan Dave , Horison Ronald , Evi  , Muliawidjaja Michelle , Puspita Vini Octaviani
Published: March 2020

Rosella is a flower with red and purple hue, having antioxidant pigments called anthocyanins, which is promising for health improvement. It actually could be potentially developed as a health-promoting food in the form of rosella jam. As the market for rosella jam in Indonesia is not established yet, and in the advent on the development of renewable energies in the 21st century, it is a fascinating idea to design a rosella jam factory employing solar energy as one of the renewable energies in the future that might lead the sustainable food business in Indonesia. The rosella jam factory is designed to produce 40000 bottles of rosella jam (weight: 250 g) per month, sold for Rp. 25000, rendering income of Rp. 1 billion per month. It needs a one-off capital cost of Rp. 2.56 billion for production equipments and machines (not including solar panels), with monthly manufacturing cost of 624 million (included 20 kW electricity) that will reach break-even point (BEP) at 13th month. Solar panels (mainly consists of 840 solar panels, 200 Wp working for 4 hours) worth of 2.64 billion is recommended to be installed on the 19th month to avoid negative cumulative net present value (CNPV).
DC Motor Simulation using LTSpice
Authors: Linggarjati J
Published: March 2020

DC motor is simulated in this paper, in which LTSpice simulator is used. DC Motor is still highly needed in industrial world, for applications that needs goods’ movement in the process line. Therefore, in this paper, it is important to do simulation before real-world electronic circuit is developed. Thereby we promote green eco-friendly environment, by reducing electronic waste caused by prototyping. The simulation of DC Motor is divided into three (3) parts. First, a simplified DC motor model is assumed, and then the effect of inductance and inertia of the DC motor are considered. Lastly, a small perturbation is noticeable in the output of the electrical DC motor, and after a careful insight into the slip-ring mechanical inside of the DC motor, the effect of it is added in the final simulation model. This gradual modelling methodology certainly helps students to correlate between DC motor modelling with the sampled real-world data, which is taken directly from the experimental laboratory.
Achieving sustainability through Industrial Revolution 4.0: An example in a small company in Surabaya
Authors: Husada Richard , Mulyana Ig Jaka
Published: March 2020

A study was performed with one small company to find out readiness of the company to perform operations of Industry 4.0. An interview was conducted with the owner of the company. and results were shown in the form of a diagram with low readiness, which means hard work for the owner and possibly consultants to bring the company into such level, ready to compete and sustain in the market.
Corona discharge development and its application to eliminate microorganism in raw milk
Authors: Kasih Tota Pirdo , Mangindaan Dave , Ayuputri Ovitadani , Romulo Andreas , Widyaningrum Dwiyantari
Published: March 2020

Raw cow’s milk or fresh milk is a natural food with a complete nutrients which provide many benefits for human health. Raw milk also provides almost ideal media for various microorganisms to grow rapidly that can harm human digestion, or make damages the milk itself. In attempt to investigate an appropriate processing technology as an alternative of thermal pasteurization, we developed non thermal corona discharge to eliminate total number of various microorganisms in milk. The generated corona discharge used 7 pins to plate surface configuration. With a distance 15 mm between the electrodes, the applied voltage of 6.48 kV by a homemade high voltage AC power supply yields in corona discharge that has temperature lower than 30°C after 8 minutes operation. The time dependent effects of the implementation of this discharge to raw milk were carried out at time interval 2, 4 and 8 minutes. It was found that there was three different types of bacteria colony morphology in the microorganism population of raw milk. The microorganism counts were decrease for 2 and 4 min corona treatments. However, when the corona treatment was done in 8 min, the total number of microorganism increased significantly. Although the corona discharge shows the potential benefits in milk decontamination processing at low temperature, more detailed study should be carried out to confirm the suitable in real application including the nutrient composition before and after treatment.
Home Security System with IOT Based Sensors Running On House Infra Structure Platform
Authors: Tanutama Lukas , Atmadja Wiedjaja
Published: March 2020

In this research a system that is based on IOT technology was developed. The system itself is a subsystem of a home security system. The subsystem is one of the essential parts of a home security system that protects its inhabitants, the house itself and the environment around it. It is based on technology that is related to Internet of Things (IOT). The IOT technology being utilized depends on the data communication infrastructure that is running in a house. The infrastructure is built and based on Lora (long Range) technology and in particular Lorawan. The Infrastructure complies with the demand that it is useful and fulfils the requirements of IOT. Lorawan is quite recent but technically comply with the demands for IOT. This research focused on gas leakage detection using a detector. Gas leakage that needs immediate detection is generally used for home use such as LPG. LPG is generally used in house kitchens or sometimes bath rooms. The developed module is for detection and issuance of warning the existence of LPG in its environment. The data for issuance of warning is communicated to a system called Premises Controller. The protection of a house against gas leakage is essential due to its sensitivity to fire sparks. Fire sparks can trigger fire and often explosion. A sensor’s sensitivity and the time of early warning determine the effectiveness of mitigating efforts.
Multifunctional aromatherapy humidifier based on ESP8266 microcontroller and controlled using Android smartphone
Authors: Triantoro Rionaldy , Chandra Richard , Hutabarat Daniel Patricko
Published: March 2020

The purpose of this study is to create a multifunctional aromatherapy diffuser device that is controlled and monitored using an Android smartphone application though the MQTT protocol. This device also includes an ultrasonic sensor for measuring the water level within the diffuser’s tank by calculating the distance between the sensor and the water below it, RGB-enabled LED lighting, and an audio player that can play relaxing natural sounds for the user. The research method is comprised of problem identification, literature review, system development, implementation, and evaluation. This device can achieve the objective of being able to be operated through MQTT using an Android smartphone to control all components within the system with an average response time of 731.91 milliseconds and being able to measure the water level within the diffuser’s tank with a typical accuracy of 99.26% during testing.
Artificial neural network for predicting earthquake casualties and damages in Indonesia
Authors: Oktarina Rienna , Bahagia Senator Nur , Diawati Lucia , Pribadi Krisha S.
Published: March 2020

The paper is intended to develop a model to predict the number of damaged buildings and casualties due to earthquake using ANN (Artificial Neural Network). This model is expected to be able to generate the type and amount of relief supplies required by those affected during the emergency phase. This research develops ANN using supervised learning paradigm, and backpropagation learning algorithm. The applied ANN network architecture is a multiple-layer system, with 1 (one) neuron used in both input and output layer, and 95 (ninety-five) neurons used in the hidden layer yielding 0.99971 as the greatest value of the correlation coefficient. The output variable in this study is the earthquake impact consisting of six variables. While the input variables (predictors) in this study consisting of eight variables. The model in this study utilizes 123 seismic datasets, divided into 100 data (80%) for the training process and 23 data (20%) for the testing process. This research adds to the existing research and demonstrates the application of ANN in predicting the numbers of damaged buildings and casualties. The model is useful in supporting and strengthening preparedness and emergency relief activities due to earthquake disaster.
Evaluation of e-government LAKSA services to improve the interest of use of applications using Technology Acceptance Model (TAM)
Authors: Sarasati R , Madyatmadja E D
Published: March 2020

The government of Tangerang provides LAKSA (Layanan Aspirasi Kotak Suara Anda) which is a social media based on e-government service for the community to participate in giving aspirations and reporting problems surrounding Tangerang city environment. This study was conducted with the aim of evaluating and finding out the factors that influencing LAKSA adoption in Tangerang Live application. The effect on LAKSA adoption is explained using perceptions of beliefs, attitudes, and intentions of use that refer to the Technology Acceptance Model (TAM). The innovation factor also explains the influence of LAKSA adoption indirectly. Data processing and analysis in this research is using SEM-PLS (Structural Equation Model - Partial Least Square) method. The results of this study indicate that innovation has a positive effect on usability perception and perception of ease of use. The perception of usability and perceived ease of use have a positive effect on user attitudes. User attitude positively affects the intention to use technology.
Chatbot as an Alternative Means to Access Online Information Systems
Authors: Sugondo A F , Bahana R
Published: March 2020

Chatbots are having a spotlight in the current market. The reasoning behind this would be mobile applications are becoming a saturated market and messenger applications are surpassing social networking applications regarding to the number of active users. Binus Maya is becoming less attractive since it is not engineered for mobile devices, which creates inconvenience for students to access campus information. The research creates a chatbot as an alternative solution to Binus International’s existing information systems. The application created is accessible from both desktop and mobile, created with Node. JS with the natural language processor being used is called API. AI. Taking accounts from the user acceptance testing, 80% of testers agreed that the created chatbot can be a good and faster alternative information retrieval compared to Binus Maya.
Beneficial potency of algae-based polyunsaturated fatty acids (PUFAs) for cancer therapy
Authors: Widyaningrum D
Published: March 2020

Algae species is a promising sustainable source of polyunsaturated fatty acids (PUFAs) in the marine ecosystem. The composition of the essential fatty acids is varied between the algae species. Most of the algal species are rich in EPA except for Chlorophyta and Heterokontophyta that are rich in DHA. The dietary intake of PUFAs, such as EPA and DHA, could prevent the inflammation by limiting the biosynthesis of pro-inflammatory mediator associated with cancer development. This review highlights the importance and function of algae-based PUFAs as the inflammatory inhibitor furthermore as a potential pharmaceutical for cancer therapy.
Development and texture profile of wood-ear mushroom (Auricularia auricula) sausage formulated with carrageenan
Authors: Hermawan Natasya , Romulo Andreas , Wardana Ata Aditya
Published: March 2020

As a food with low content of saturated fats, wood-ear mushroom can be utilized to be meat replacer of conventional sausages. The product, however, probably characterize differently compared to meat-based sausages. This research was aimed to evaluate the effect of carrageenan on texture and organoleptic properties of wood-ear mushroom sausage. Five different concentrations of carrageenan (2, 4, 6, 8 and 10%) were preliminary assessed by using hedonic test to determine three of the most preferred samples which were sausage formulated with carrageenan 2, 6 and 8%. The results showed that different concentration of carrageenan altered texture attributes and overall liking of wood-ear mushroom sausage, with 2% carrageenan formulation as the most accepted sample. The proximate composition determination resulted 8.85% moisture, 12.27% ash, 8.58% protein, 11.03% fat, and 59.27% carbohydrate. Furthermore, it was characterized by texture attributes including 7849.78 ±3 66.382 g, 0.69 ± 0.036, 0.36 ± 0.012, 2858.95 ± 57.110, 1984.08 ± 122.868 for its hardness, springiness, cohesiveness, gumminess, chewiness respectively.
The Effect of Different Starter Cultures and Dextrose on Viability of Lactic Acid Bacteria and pH of Fermented Milk At 43 °C
Authors: Sari A S , Surono I S
Published: March 2020

The purpose of this research was to study the effect of different starter cultures and the addition of dextrose on viability of LAB and pH value of fermented milk. Streptococcus thermophilus and Lactobacillus bulgaricus, Streptococcus thermophilus and Lactobacillus plantarum IS-10506 were used as mixed starter cultures, incubated at 43°C for 8 hours, with or without the addition of dextrose. The total viable counts of LAB and pH value were assessed. Each combination of starter cultures showed significant increased on the viable counts of LAB, and decreased the pH value of fermented milk during 8 hours incubation. Addition of 2% dextrose tended to increase viable counts of LAB by 165.8 % of milk fermented with mixed starter cultures of S. thermophilus and L. plantarum IS-10506, extending log phase from 6 to 8 hours, while without 2 % dextrose tended to decreased by 40 %. No significant effect of addition of 2% dextrose on viable counts of yogurt starters in yogurt. Mixed starter cultures of S. thermophilus and L. plantarum IS-10506 is potential starter cultures of fermented milk with addition of 2 % dextrose at 43°C for 8 hours incubation time to produce probiotic based functional drink.
Physio-chemical, Microbiology, and Preference of Probiotic Fresh Soft Cheese Using Lactobacillus plantarum IS-10506 and Streptococcus thermophilus as Mixed Starter Culture
Authors: Hosiana N , Astuti D I , Surono I S
Published: March 2020

Probiotics are live microorganisms with various benefficial effect on human health when consumed in adequate amount. Soft cheese is one of fermented milk products involving lactic acid bacteria (LAB) which may be potential as functional food. Concentration ratios of starter culture Lactobacillus plantarum IS-10506 and Streptococcus thermophilus were 1:1, 2:1, and 1:2 (v/v) at 5%, 10%, and 15% (v/v) at 106 CFU mL−1 cultures and incubated at 37 °C for 90 minutes. Chemical (pH and moisture content), microbiology (LAB total count), and sensory (preference test) were analyzed. The results showed that there was no significant difference (p-value < 0.05) on the viability of LAB (in a range of 6×107 to 1.71×108 CFU mL−1) and on cheese yield (224-268.84 g L−1). Cheese fermented with 1:1 (v/v) Lactobacillus plantarum IS-10506 and Streptococcus thermophilus of 10% cultures (v/v) was the most preferred, scored 3.75 out of 5 in hedonic test for overall acceptability and the viable LAB was 1.71x108 CFU mL−1 with pH 4.95. The total yield was 257.54 g L−1 and its moisture content was 66.45%.
Quantifying forest growth uncertainty on carbon payback times in a simple biomass carbon model
Authors: Rolls Will , Forster Piers M
Published: March 2020

In 2018 Stermanet al(2018a) published a simple dynamic lifecycle analysis (DLCA) model for forest-sourced bioenergy. The model has been widely cited since its publication, including widespread reporting of the model’s headline results within the media. In adapting a successful replication of the Stermanet al(2018a) model with open-source software, we identified a number of changes to input parameters which improved the fit of the model’s forest site growth function with its training data. These relatively small changes to the input parameters result in relatively large changes to the model predictions of forest site carbon uptake: up to 92 tC.ha−1or 18% of total site carbon at year 500. This change in estimated site carbon resulted in calculated payback periods (carbon sequestration parity) which differed by up to 54 years in a clear-fell scenario when compared with results obtained using previously published parameters. Notably, this uncertainty was confined to forests which were slower growing and where the model’s training dataset was not sufficiently long for forests to reach maturity. We provide improved parameterisations for all forest types used within the original Stermanet al(2018a) paper, and propose that these provide better fits to the underlying data. We also provide margins of error for the generated growth curves to indicate the wide range of possible results possible with the model for some forest types. We conclude that, while the revised model is able to reproduce the earlier Stermanet al(2018a) results, the headline figures from that paper depend heavily on how the forest growth curve is fitted to the training data. The resulting uncertainty in payback periods could be reduced by either obtaining more extensive training data (including mature forests of all types) or by modification of the forest growth function.
Computer-generated STOPP/START recommendations for hospitalised older adults: evaluation of the relationship between clinical relevance and rate of implementation in the SENATOR trial
Authors: Dalton Kieran , Curtin Denis , O’Mahony Denis , Byrne Stephen
Published: March 2020

Background

findings from a recent qualitative study indicate that the perceived clinical relevance of computer-generated STOPP/START recommendations was a key factor affecting their implementation by physician prescribers caring for hospitalised older adults in the SENATOR trial.

Aim

to systematically evaluate the clinical relevance of these recommendations and to establish if clinical relevance significantly affected the implementation rate.

Methods

a pharmacist–physician pair retrospectively reviewed the case records for all SENATOR trial intervention patients at Cork University Hospital and assigned a degree of clinical relevance for each STOPP/START recommendation based on a previously validated six-point scale. The chi-square test was used to quantify the differences in prescriber implementation rates between recommendations of varying clinical relevance, with statistical significance set at P < 0.05.

Results

in 204 intervention patients, the SENATOR software produced 925 STOPP/START recommendations. Nearly three quarters of recommendations were judged to be clinically relevant (73.6%); however, nearly half of these were deemed of ‘possibly low relevance’ (320/681; 47%). Recommendations deemed of higher clinical relevance were significantly more likely to be implemented than those of lower clinical relevance (P < 0.05).

Conclusions

a large proportion (61%) of the computer-generated STOPP/START recommendations provided were of potential ‘adverse significance’, of ‘no clinical relevance’ or of ‘possibly low relevance’. The adjudicated clinical relevance of computer-generated medication recommendations significantly affects their implementation. Meticulous software refinement is required for future interventions of this type to increase the proportion of recommendations that are of high clinical relevance. This should facilitate their implementation, resulting in prescribing optimisation and improved clinical outcomes for multimorbid older adults.
The first century
Authors: Phillipps Steven
Published: March 2020

Steven Phillipps looks back at the RAS at its centenary through the pages of Monthly Notices.
Ancient vases in modern vitrines: the sensory dynamics and social implications of museum display
Authors: Meyer Caspar
Published: March 2020

This contribution explores the changing sensory priorities underpinning the display of Greek painted pottery in European collections. The focus is on the introduction of glass-fronted cabinets in the purpose-designed public museums of art and archaeology of the mid-nineteenth century. Contrary to expectations, the contemporaneous debates surrounding the use of gallery furniture show that the museum stakeholders were less worried about the safety of the objects than the prospect of middle- and working-class visitors being exposed to the sexualized imagery on Athenian pottery. A survey of the different traditions of display in Britain and continental Europe highlights the shift from the multisensory engagements in early modern elite collections with vases as evidence of ancient custom to the selective viewing of the objects’ painted decoration as works of art whose proper interpretation called for classical education.
DeCoDe: degenerate codon design for complete protein-coding DNA libraries
Authors: Shimko Tyler C , Fordyce Polly M , Orenstein Yaron
Published: March 2020

Motivation

High-throughput protein screening is a critical technique for dissecting and designing protein function. Libraries for these assays can be created through a number of means, including targeted or random mutagenesis of a template protein sequence or direct DNA synthesis. However, mutagenic library construction methods often yield vastly more nonfunctional than functional variants and, despite advances in large-scale DNA synthesis, individual synthesis of each desired DNA template is often prohibitively expensive. Consequently, many protein-screening libraries rely on the use of degenerate codons (DCs), mixtures of DNA bases incorporated at specific positions during DNA synthesis, to generate highly diverse protein-variant pools from only a few low-cost synthesis reactions. However, selecting DCs for sets of sequences that covary at multiple positions dramatically increases the difficulty of designing a DC library and leads to the creation of many undesired variants that can quickly outstrip screening capacity.

Results

We introduce a novel algorithm for total DC library optimization, degenerate codon design (DeCoDe), based on integer linear programming. DeCoDe significantly outperforms state-of-the-art DC optimization algorithms and scales well to more than a hundred proteins sharing complex patterns of covariation (e.g. the lab-derived avGFP lineage). Moreover, DeCoDe is, to our knowledge, the first DC design algorithm with the capability to encode mixed-length protein libraries. We anticipate DeCoDe to be broadly useful for a variety of library generation problems, ranging from protein engineering attempts that leverage mutual information to the reconstruction of ancestral protein states.

Availability and implementation

github.com/OrensteinLab/DeCoDe.

Contact

yaronore@bgu.ac.il

Supplementary information

Supplementary data are available at Bioinformatics online.
FMNL3 regulates FASCIN for actin-mediated spindle migration and cytokinesis in mouse oocytes†
Authors: Pan Meng-Hao , Wan Xiang , Wang Hong-Hui , Pan Zhen-Nan , Zhang Yu , Sun Shao-Chen
Published: March 2020

Formin-like 3 (FMNL3) is a member of the formin-likes (FMNLs), which belong to the formin family. As an F-actin nucleator, FMNL3 is essential for several cellular functions, such as polarity control, invasion, and migration. However, the roles of FMNL3 during oocytes meiosis remain unclear. In this study, we investigated the functions of FMNL3 during mouse oocyte maturation. Our results showed that FMNL3 mainly concentrated in the oocyte cortex and spindle periphery. Depleting FMNL3 led to the failure of polar body extrusion, and we also found large polar bodies in the FMNL3-deleted oocytes, indicating the occurrence of symmetric meiotic division. There was no effect of FMNL3 on spindle organization; however, we observed spindle migration defects at late metaphase I, which might be due to the decreased cytoplasmic actin. Microinjecting Fmnl3-EGFP mRNA into Fmnl3-depleted oocytes significantly rescued these defects. In addition, the results of co-immunoprecipitation and the perturbation of protein expression experiments suggested that FMNL3 interacted with the actin-binding protein FASCIN for the regulation of actin filaments in oocytes. Thus, our results provide the evidence that FMNL3 regulates FASCIN for actin-mediated spindle migration and cytokinesis during mouse oocyte meiosis.
Pim1 maintains telomere length in mouse cardiomyocytes by inhibiting TGFβ signalling
Authors: Ebeid David E , Khalafalla Farid G , Broughton Kathleen M , Monsanto Megan M , Esquer Carolina Y , Sacchi Veronica , Hariharan Nirmala , Korski Kelli I , Moshref Maryam , Emathinger Jacqueline , Cottage Christopher T , Quijada Pearl J , Nguyen Jonathan H , Alvarez Roberto , Völkers Mirko , Konstandin Mathias H , Wang Bingyan J , Firouzi Fareheh , Navarrete Julian M , Gude Natalie A , Goumans Marie-Jose , Sussman Mark A
Published: March 2020

Aims

Telomere attrition in cardiomyocytes is associated with decreased contractility, cellular senescence, and up-regulation of proapoptotic transcription factors. Pim1 is a cardioprotective kinase that antagonizes the aging phenotype of cardiomyocytes and delays cellular senescence by maintaining telomere length, but the mechanism remains unknown. Another pathway responsible for regulating telomere length is the transforming growth factor beta (TGFβ) signalling pathway where inhibiting TGFβ signalling maintains telomere length. The relationship between Pim1 and TGFβ has not been explored. This study delineates the mechanism of telomere length regulation by the interplay between Pim1 and components of TGFβ signalling pathways in proliferating A549 cells and post-mitotic cardiomyocytes.

Methods and results

Telomere length was maintained by lentiviral-mediated overexpression of PIM1 and inhibition of TGFβ signalling in A549 cells. Telomere length maintenance was further demonstrated in isolated cardiomyocytes from mice with cardiac-specific overexpression of PIM1 and by pharmacological inhibition of TGFβ signalling. Mechanistically, Pim1 inhibited phosphorylation of Smad2, preventing its translocation into the nucleus and repressing expression of TGFβ pathway genes.

Conclusion

Pim1 maintains telomere lengths in cardiomyocytes by inhibiting phosphorylation of the TGFβ pathway downstream effectors Smad2 and Smad3, which prevents repression of telomerase reverse transcriptase. Findings from this study demonstrate a novel mechanism of telomere length maintenance and provide a potential target for preserving cardiac function.
Lymphocyte Activation Gene (LAG)-3 Is Associated With Mucosal Inflammation and Disease Activity in Ulcerative Colitis
Authors: Slevin Stephanie M , Garner Lucy C , Lahiff Conor , Tan Malcolm , Wang Lai Mun , Ferry Helen , Greenaway Borgel , Lynch Kate , Geremia Alessandra , Hughes Stephen , Leavens Karen , Krull David , Marks Daniel J B , Nevin Katherine , Page Kevin , Srinivasan Naren , Tarzi Ruth , Klenerman Paul , Travis Simon , Arancibia-Cárcamo Carolina V , Keshav Satish
Published: March 2020

Background and Aims

Lymphocyte activation gene [LAG]-3 is an immune checkpoint and its expression identifies recently activated lymphocytes that may contribute to inflammation. We investigated the role of LAG-3 by analysing its expression and function in immune cells from blood and tissue of patients with ulcerative colitis [UC].

Methods

The phenotypic properties of LAG-3+ T cells were determined by flow cytometry, qRT-PCR and single-cell RNA-sequencing. LAG-3+ cells were quantified and correlated with disease activity. The functional effects of LAG-3+ cells were tested using a depleting anti-LAG-3 monoclonal antibody [mAb] in a mixed lymphocyte reaction [MLR].

Results

LAG-3+ cells in the blood were negligible. LAG-3+ lymphocytes were markedly increased in inflamed mucosal tissue and both frequencies of LAG-3+ T cells and transcript levels of LAG3 correlated with endoscopic severity. LAG-3 expression was predominantly on effector memory T cells, and single-cell RNA-sequencing revealed LAG3 expression in activated and cytokine-producing T cell subsets. Foxp3+CD25hi Tregs also expressed LAG-3, although most mucosal Tregs were LAG-3−. Mucosal LAG-3+ cells produced mainly interferon γ [IFNγ] and interleukin-17A. LAG-3+ cell numbers decreased in patients who responded to biologics, and remained elevated in non-responders. Treatment with a depleting anti-LAG-3 mAb led to a reduction in proliferation and IFNγ production in an MLR.

Conclusions

LAG-3+ cells are increased in the inflamed mucosa, predominantly on effector memory T cells with an activated phenotype and their cell numbers positively correlate with disease activity. Depleting LAG-3 eliminates activated proliferating T cells, and hence LAG-3 could be a therapeutic target in UC.
From traditional pharmacological towards nucleic acid-based therapies for cardiovascular diseases
Authors: Landmesser Ulf , Poller Wolfgang , Tsimikas Sotirios , Most Patrick , Paneni Francesco , Lüscher Thomas F
Published: March 2020

Nucleic acid-based therapeutics are currently developed at large scale for prevention and management of cardiovascular diseases (CVDs), since: (i) genetic studies have highlighted novel therapeutic targets suggested to be causal for CVD; (ii) there is a substantial recent progress in delivery, efficacy, and safety of nucleic acid-based therapies; (iii) they enable effective modulation of therapeutic targets that cannot be sufficiently or optimally addressed using traditional small molecule drugs or antibodies. Nucleic acid-based therapeutics include (i) RNA-targeted therapeutics for gene silencing; (ii) microRNA-modulating and epigenetic therapies; (iii) gene therapies; and (iv) genome-editing approaches (e.g. CRISPR-Cas-based):

(i) RNA-targeted therapeutics: several large-scale clinical development programmes, using antisense oligonucleotides (ASO) or short interfering RNA (siRNA) therapeutics for prevention and management of CVD have been initiated. These include ASO and/or siRNA molecules to lower apolipoprotein (a) [apo(a)], proprotein convertase subtilisin/kexin type 9 (PCSK9), apoCIII, ANGPTL3, or transthyretin (TTR) for prevention and treatment of patients with atherosclerotic CVD or TTR amyloidosis.

(ii) MicroRNA-modulating and epigenetic therapies: novel potential therapeutic targets are continually arising from human non-coding genome and epigenetic research. First microRNA-based therapeutics or therapies targeting epigenetic regulatory pathways are in clinical studies.

(iii) Gene therapies: EMA/FDA have approved gene therapies for non-cardiac monogenic diseases and LDL receptor gene therapy is currently being examined in patients with homozygous hypercholesterolaemia. In experimental studies, gene therapy has significantly improved cardiac function in heart failure animal models.

(iv) Genome editing approaches: these technologies, such as using CRISPR-Cas, have proven powerful in stem cells, however, important challenges are remaining, e.g. low rates of homology-directed repair in somatic cells such as cardiomyocytes. In summary, RNA-targeted therapies (e.g. apo(a)-ASO and PCSK9-siRNA) are now in large-scale clinical outcome trials and will most likely become a novel effective and safe therapeutic option for CVD in the near future. MicroRNA-modulating, epigenetic, and gene therapies are tested in early clinical studies for CVD. CRISPR-Cas-mediated genome editing is highly effective in stem cells, but major challenges are remaining in somatic cells, however, this field is rapidly advancing.
Assessing the long-term impact of agricultural research on productivity: evidence from France
Authors: Lemarié Stéphane , Orozco Valérie , Butault Jean-Pierre , Musolesi Antonio , Simioni Michel , Schmitt Bertrand
Published: March 2020

This paper analyses the economic impact of agricultural research on productivity in France over the period 1959–2012. Adopting a dynamic time series model, we provide evidence that the impact of French agricultural research is in the range of values estimated for other countries, with the estimated long-run elasticity being 0.16, which corresponds to an internal rate of return of 22%. The estimated elasticity decreases at the beginning of the 1970s. Complementary analyses are developed to take into account the evolution of the priorities of public agricultural research (reorientation towards more fundamental objectives and focus on broader objective than productivity enhancement).
Resource availability drives bacterial succession during leaf-litter decomposition in a bromeliad ecosystem
Authors: Carrias Jean-François , Gerphagnon Mélanie , Rodríguez-Pérez Héctor , Borrel Guillaume , Loiseau Camille , Corbara Bruno , Céréghino Régis , Mary Isabelle , Leroy Céline
Published: March 2020

Despite the growing number of investigations on microbial succession during the last decade, most of our knowledge on primary succession of bacteria in natural environments comes from conceptual models and/or studies of chronosequences. Successional patterns of litter-degrading bacteria remain poorly documented, especially in undisturbed environments. Here we conducted an experiment with tank bromeliads as natural freshwater microcosms to assess major trends in bacterial succession on two leaf-litter species incubated with or without animal exclusion. We used amplicon sequencing and a co-occurrence network to assess changes in bacterial community structure according to treatments. Alpha-diversity and community complexity displayed the same trends regardless of the treatments, highlighting that primary succession of detrital-bacteria is subject to resource limitation and biological interactions, much like macro-organisms. Shifts in bacterial assemblages along the succession were characterized by an increase in uncharacterized taxa and potential N-fixing bacteria, the latter being involved in positive co-occurrence between taxa. These findings support the hypothesis of interdependence between taxa as a significant niche-based process shaping bacterial communities during the advanced stage of succession.
Natural extract and its fractions isolated from the marine bacterium Pseudoalteromonas flavipulchra STILL-33 have antioxidant and antiaging activities in Schizosaccharomyces pombe
Authors: Prastya Muhammad Eka , Astuti Rika Indri , Batubara Irmanida , Takagi Hiroshi , Wahyudi Aris Tri
Published: March 2020

Investigations into the potential for pharmacological inhibition of the aging process and the onset of age-related disease are increasingly garnering attention. Here, we analyzed the antiaging properties of natural compounds derived from several marine bacteria in vitro and in vivo using the fission yeast Schizosaccharomyces pombe. The Pseudoalteromonas flavipulchra STILL-33 extract exhibited high antioxidant and antiglycation activities in vitro. We then characterized two antioxidant active fractions isolated from this extract. In addition, we showed that the P. flavipulchra STILL-33 extract or either of its two active fractions (Fractions 1 and 2) could extend the longevity of fission yeast. Moreover, the particular extract and two active fractions were found to induce mitochondrial activity and to delay the G1 phase of the fission yeast cell cycle, perhaps by improving the aging process. The P. flavipulchra STILL-33 extract and Fraction 1 also increased the expression of the catalase-encoding ctt1+ gene and thereby decreased the reactive oxygen species level. Structural analysis showed that Fraction 1 was dominated by l-arginine and ipriflavone, and we showed indeed that the two corresponding commercial products increase the fission yeast lifespan. As for Fraction 2 was identified as the putative structure of butamben. Together, these results should facilitate the discovery of additional antiaging compounds from P. flavipulchra and ultimately the development of novel antiaging compounds for pharmaceutical use.
The Limits to Estimating Population-Genetic Parameters with Temporal Data
Authors: Lynch Michael , Ho Wei-Chin
Published: March 2020

The ability to obtain genome-wide sequences of very large numbers of individuals from natural populations raises questions about optimal sampling designs and the limits to extracting information on key population-genetic parameters from temporal-survey data. Methods are introduced for evaluating whether observed temporal fluctuations in allele frequencies are consistent with the hypothesis of random genetic drift, and expressions for the expected sampling variances for the relevant statistics are given in terms of sample sizes and numbers. Estimation methods and aspects of statistical reliability are also presented for the mean and temporal variance of selection coefficients. For nucleotide sites that pass the test of neutrality, the current effective population size can be estimated by a method of moments, and expressions for its sampling variance provide insight into the degree to which such methodology can yield meaningful results under alternative sampling schemes. Finally, some caveats are raised regarding the use of the temporal covariance of allele-frequency change to infer selection. Taken together, these results provide a statistical view of the limits to population-genetic inference in even the simplest case of a closed population.