Commercial Level Research Articles

Mitochondrial ALDH2 improves ß-cell survival and function against doxorubicin-induced apoptosis by targeting CK2 signaling.

The aim of this study was to better understand how the chemotherapy drug doxorubicin contributes to the development of β-cell dysfunction and to explore its relationship with mitochondrial aldehyde dehydrogenase-2 (ALDH2). In order to investigate this hypothesis, doxorubicin was administered to INS-1 cells, a rat insulinoma cell line, either with or without several target protein activators and inhibitors. ALDH2 activity was detected with a commercial kit and protein levels were determined with western blot. Mitochondrial ROS, membrane potential, and lipid ROS were determined by commercial fluorescent probes. The cell viability was measured by CCK-assay. Exposure of INS-1 cells to doxorubicin decreased active insulin signaling resulting in elevated ALDH2 degradation, compared with control cells by the induction of acid sphingomyelinase mediated ceramide induction. Further, ceramide induction potentiated doxorubicin induced mitochondrial dysfunction. Treatment with the ALDH2 agonist, ALDA1, blocked doxorubicin-induced acid sphingomyelinase activation which significantly blocked ceramide induction and mitochondrial dysfunction mediated cell death. Treatment with the ALDH2 agonist, ALDA1, stimulated casein kinase-2 (CK2) mediated insulin signaling activation. CK2 silencing neutralized the function of ALDH2 in the doxorubicin treated INS-1 cells. Mitochondrial ALDH2 activation could inhibit the progression of doxorubicin induced pancreatic β-cell dysfunction by inhibiting the acid sphingomyelinase induction of ceramide, by regulating the activation of CK2 signaling. Our research lays the foundation of ALDH2 activation as a therapeutic target for the precise treatment of chemotherapy drug induced β-cell dysfunction.

Ten years of laser-induced graphene: impact and future prospect on biomedical, healthcare, and wearable technology.

Since its introduction in 2014, laser-induced graphene (LIG) from commercial polymers has been gaining interests in both academic and industrial sectors. This can be clearly seen from its mass adoption in various fields ranging from energy storage and sensing platforms to biomedical applications. LIG is a 3-dimensional, nanoporous graphene structure with highly tuneable electrical, physical, and chemical properties. LIG can be easily produced by single-step laser scribing at normal room temperature and pressure using easily accessible commercial level laser machines and materials. With the increasing demand for novel wearable devices for biomedical applications, LIG on flexible substrates can readily serve as a technological platform to be further developed for biomedical applications such as point-of-care (POC) testing and wearable devices for healthcare monitoring system. This review will provide a comprehensive grounding on LIG from its inception and fabrication mechanism to the characterization of its key functional properties. The exploration of biomedicals applications in the form of wearable and point-of-care devices will then be presented. Issue of health risk from accidental exposure to LIG will be covered. Then LIG-based wearable devices will be compared to devices of different materials. Finally, we discuss the implementation of Internet of Medical Things (IoMT) to wearable devices and explore and speculate on its potentials and challenges.

Breeding Strategies for Simultaneous Improvement in Anthracnose Disease Resistance and Economically Important Traits in French Bean

Background: French bean (Phaseolus vulgaris L.) production in the tropics is threatened by heavy incidence of anthracnose disease causing substantial crop loss when infection is at the early growth stages. Breeding strategies for tolerance against anthracnose disease along with enhanced productivity, and high pod protein content are to be formulated. Methods: Genotypes having broad genetic base and phenotypic diversity in 5 bush and 1 pole types were crossed in a 6 × 6 half diallel mating design to estimate combining ability, mode of gene action, and extent of heterosis for 11 quantitative traits. Result: The additive genetic effect was evident for percent disease index (PDI) of anthracnose and 10 pod weight. Rapid genetic gain can be achieved due to predominance of additive gene action in their control and can therefore be selected in early generation through simple breeding methods. Rest of the economic traits controlled by additive and non-additive gene effects could be improved through biparental mating, reciprocal recurrent selection, or diallel selective mating. Anthracnose disease tolerant and high yielding cultivars of might be developed utilizing parents, ‘Laxmi’, ‘Arka Sharath’ and ‘Vaishnavi-264’ with high gca effects. Although two cross combinations ‘Arka Sharath × Lakshmi’ and ‘Arjun × Arka Sharath’ showed significant heterobeltiosis in desired direction for PDI of anthracnose and other desirable horticultural traits but could not be exploited at commercial level due to complexity in hybridization. Identifying pure lines with tolerance against anthracnose disease and favorable horticultural attributes could be accomplished in segregating generations of the prospective hybrids.

Enhancing the blue GaN laser diodes by modifying the first barrier structure and adjusting the growth conditions of quantum wells

The structure of the first barrier (FB) of quantum wells was modified from the single-layer GaN to the GaN-InGaN-GaN composite structure. Experiments have shown that the composite first barrier can improve the crystal quality of the quantum wells, which increase the luminous power and reduce the stress accumulation before the InGaN quantum well. Furthermore, the composite first barrier can reduce the polarized electric fields and suppress the impact of quantum confinement Stark effect (QCSE) on the luminescence properties of the quantum wells. The growth conditions of the InGaN/GaN quantum wells were studied. Both the growth rate and the ammonia flow are related to the incorporation of In in InGaN quantum wells and the formation of In clusters. These two parameters have optimal values when the other one is fixed. After optimizing the growth rate and the ammonia flow, the internal quantum efficiency of the quantum wells was finally improved from 24.14 % to a commercial level of 77.2 %.

A Study on Utilization of Co-Digested Citronella Oilmeal Cake, Cow Dung and Poultry Dropping for Enhancement of Biogas Yield

Abstract: Power plays a pivotal role in the industrial, economic and infrastructural development of the country’s growth. India is on the exponential growth paradigm and is playing a leadership role in the implementation of renewable energy projects for achieving the INDC’s committed in the Paris agreement and meeting the net carbon zero economy by 2070. The present research work attempts to utilize the co-digested agriwaste and livestock to enhance the biogas productivity. The experimental study considered a co-digested feedstock of cow dung (CD), poultry dropping (PD) and Citronella grass oilmeal cake (CG) using different ratios of each in five different digesters. Amongst all five digesters R1, R2, R3, R4 and R5; R4 having a co-digested feedstock of CD: PD: CG in the ratio of 20% : 55% : 25% respectively. The cumulative biogas yield for an experimental period was observed to 41.26 litres whereas the methane percentage in the biogas was 74%. The feedstock quantity required for 1 m3 biogas production was found to be 18.9 kg which was observed to be lower than the cowdung based monodigester which is 25 kg. Thus, co-digestion of the Citronella grass oilmeal cake along with poultry dropping using cow dung as substrate showed promising results which can be scaled up to commercial level biogas plants in villages where these feedstocks are easily available.

Is Agriculture Still the Mainstay of Rural Economies? Insights from Ultra-Poor Households in North-central Nigeria

Aims: Nigeria may be facing aging and decline in the population engaged at food production nodes, posing huge challenge to agri-food systems with poverty at risk of deepening. Current trend in rural-urban migration and occupational mobility raises the open question of: “Is agriculture still a mainstay of rural economy, playing reliant roles in income and employment generation for the ultra-poor in Nigeria rurality?”. Understanding this is important because structural change to agricultural workforce in Nigeria has far-reaching implications on food security, welfare, and poverty. We sought to unfold the dynamics of agriculture as a business among ultra-poor rural households in North-Central Nigeria. First, we investigated engagements of ultra-poor rural households in agriculture. Secondly, we examined their level of commercialization. Lastly, we investigated determinants of ultra-poor’s market participation and its intensity. Study Design: This study used quantitative primary data collected in surveys and qualitative data generated from focus group discussions. Place and Duration of Study: The study was carried out in three states in North-central Nigeria viz: Kwara, Kogi, and Niger with data collected and analyzed between 2020-2022. Methodology: We randomly selected 1588 households (out of 60,427 households) from the “Single Register of the Ultra-poor” operationalized on a World-Bank-Assisted Conditional Cash Transfer (CCT) programme. We analysed data using descriptive statistics, Household Agricultural Commercialization Index, and Double-Hurdle Model. Results: Only about 18.7% of the ultra-poor households were primarily engaged in agriculture with the focus groups highlighting conflicts issues from indiscriminate grazing activities as primary reason for the abandonment. Determinants of market participation and intensification include: (-) household dependency ratio, distance to markets, (+) linkage to market agents, access to mechanization and input market, CCT-beneficiary status, and farm size (p<0.05). Conclusion: Involvement in primary agricultural production is declining in Nigeria. We recommend a boost to infrastructural development of the rurality to support agricultural transformation and attractiveness to the next wave of youths.

Design and construction of equipment for the elimination of saponin in Quinoa (Chenopodium quinoa Willd): Performance tests with Amarillo Marangani variety

Quinoa is a very important grain for human nutrition; In recent years, several research studies have addressed its nutritional use; However, one of its main weaknesses is its saponin content, which is an anti-nutrient and has a bitter taste. The debittering process involves the principle of recirculation of large quantities of water, with the purpose of reducing the consumption of this substance, it is important to develop methodologies and equipment that improve the efficiency of these traditional washing methods and reduce the work of operators and processors with the intention of making it less costly. The objective of the present research work was to design and build a quinoa de- saponifier , Amarillo Maranganí variety, to evaluate the effect of washing time (5, 10 and 15 min) and the flow of water recirculated by pumping (15, 30 and 45 L/min), on the elimination of saponin to acceptable commercial levels. The results indicated that the highest saponin extraction was achieved when using washing times of 5 min with water flow rates of 15 L/min, and 51.75 % of the initial saponin content was eliminated. In general, it is stated that increasing the flow rate of the washing water reduces the extraction efficiency, but performing a second washing significantly reduces the extraction, the equipment developed presents promising characteristics for application in the industry.

The level of digitalization in Commercial banks and bank liquidity creation

This paper takes all banking enterprises among Chinese listed companies as the research sample and examines the impact of the level of digitalization in commercial banks on bank liquidity creation through constructing an empirical econometric model. The research results show that the level of digitalization in commercial banks can significantly enhance the level of bank liquidity creation. Additionally, the results of heterogeneity tests indicate that the effect of commercial banks' digitalization level on the enhancement of bank liquidity creation varies with the size of the commercial banks and the degree of integration between industry and finance.

ACE‐inhibitory properties and antioxidative activities of hydrolysate powder obtained from Thai's mature silkworm (Bombyx mori)

SummaryThis study aimed to optimise the production of silkworm hydrolysate powder (SHP) from Thai's mature silkworm with potent ACE inhibition properties using commercial protease enzymes. Thai's mature silkworm (TMS) powder was hydrolysed with Alcalase® 2.4 L, Neutrase® 0.8 L and Flavourzyme® 500MG at varying enzyme concentrations and temperatures. The most effective method for ACE inhibition was found with Alcalase® 2.4 L at 5% concentration (w/w) of protein content in TMS powder, at 60 °C for 1 h. This condition also resulted in the highest SHP production and protein content, outperforming other enzyme treatments. Moreover, it exhibited significant total phenolic compounds and antioxidant activity including DPPH and ABTS radical scavenging. This finding establishes a foundation for scaling up the production of Thai's mature SHP to a commercial level. The resulting product can be utilised as a functional ingredient, functional food or therapeutic food for managing high blood pressure.

Development of the high temperature PbLi experimental facility for CFETR

Chinese Fusion Engineering and Test Reactor (CFETR) aims to demonstrate the fusion energy production up to 200MW, and finally reach commercial electricity power level 1GW. As one key component, the blanket is in charge of tritium breeding, neutron shielding and energy conversion. The liquid breeder blanket has many important advantages of simpler structure, tritium extraction and fuel replenishment online, as well as the high thermoelectric conversion efficiency. Moreover, the supercritical carbon dioxide (S-CO2) cOoled Lithium-Lead (COOL) blanket has been proposed for CFETR. However, the key issue of MagnetoHydroDynamics (MHD) needs further investigation, especially for the experiments. Therefore, the high temperature PbLi experimental loop is under development, which mainly includes three systems of PbLi, oil and water. The main components include the mechanical pump, main heater, cold trap as well as the superconducting magnet. At the test section, the mass flow rate, temperature and magnetic intensity will be up to 32 kg/s, 700 °C and 3T, respectively. In addition, the ultrasonic doppler velocimeter and potential probe instruments will be adopted to obtain the flow field. The main goal is to establish flow and heat transfer models, which are the critical input for the liquid breeder blanket design and optimization.

A novel process for rutin recovery from model solutions using nanofiltration: Experimental study, mathematical modeling, and scale‐up design

AbstractPressure‐driven membrane processes represent a credible method for the separation and concentration of natural polyphenols. The separation characteristics and their productivity depend on several factors such as molecular weight cut‐off, operating conditions, and test cell parameters. In this study, a compact polyamide HFT‐NF150 nanofiltration membrane has been tested to separate different model solutions of rutin, and the effects of operating conditions like trans‐membrane pressure, feed concentration, and feed flow rates were analyzed. All the findings of the experiment revealed that the maximum permeate flux of 3.04 × 10−5 m3/m2 s and 98.5% rejection were obtained at a high feed flow rate of 36 L/h and a high pressure of 6 × 105 Pa. Also, the Spiegler–Kedem model is used to report the mass transport phenomenon across the membrane. The unconstrained minimization technique based on the simplex search method was applied for the estimation of the unknown parameters. The theoretical and experimental values for permeate characteristics were then compared for each experimental data point for the model validation. Later, a mathematical model was used to check the scale‐up viability of the process to the commercial limit.Practical applicationsIn the past few years, naturally occurring bioactive compounds have revolutionized the whole scientific community for their exploration. Rutin is one such phenolic compound that is present in significant amounts in buckwheat and has a wide range of applications in the food and pharmaceutical industries. In this work, an energy‐efficient and cleaner method of nanofiltration is applied to concentrate the rutin from the model plant extract. Experiments were performed on a polyamide nanofiltration membrane with a molecular weight cut‐off of 150 Da at different operating conditions. Experimental results were fitted in a three‐parameter Spiegler–Kedem model to determine the transport parameters of the membrane for rutin. The values of transport parameters were also successfully validated using the experimental results. Experimental results and model predictions were then used to analyze the effects of different operating parameters. A scale‐up setup has been designed and simulated to check the feasibility of the process at the commercial level.

Effect of source and drain electrode positions on the performance of bottom gate organic thin film transistor

In recent years several novel technologies have emerged on commercial level. Organic electronics is one such technology that has created new avenues for the development of flexible, robust, and cost-effective electronic devices. Transistor developed using organic materials are called organic thin film transistors (OTFT). Transistor is elementary component of any electronic device, any variation in the size or performance of the transistors reflects directly on the overall performance of the electronic devices. Bottom gate bottom contact (BGBC) OTFT is commonly employed single gate organic transistor owing to its simple architecture and easy fabrications. Since in organic semiconductor material carrier mobility of charges is lower, hence its overall performance declines. As a result, its application in electronic circuits becomes limited. Therefore, to enhance the performance of BGBC OTFT and facilitate the optimal charge mobilisation inside organic semiconductor layer i.e., OSC, improvement in the architecture of BGBC is deemed necessary. In this research article the performance of BGBC OTFT is analysed for different positions of electrodes viz. source and drain embedded inside the OSC layer. The study signifies the effect of electrode positions on performance optimization of BGBC OTFT without changing the materials, dimensions, or the operating voltage regime. It has been found that for 30 nm thick OSC layer, the electrodes should ideally be placed between 5 nm to 10 nm above the junction of OSC and dielectric layer inside OSC layer for optimal results.

The application of business intelligence system based on big data in e-commerce data analysis

In the face of the rapid development of modern science and technology, in order to ensure that the commercial level is in line with The Times, we need to change the traditional operation mode, and fully apply the science and technology to the e-commerce data analysis. Nowadays, driven by the era of big data development, social process, bring new changes to daily life, consumption, such as electricity is a new product, as the latest business model in modern society, has an important impact on market development, want to ensure electricity enterprises can meet the demand of social development, then from the perspective of electricity data analysis, effectively grasp the market changes, so as to more effective to carry out subsequent work, to fundamentally improve the comprehensive competitiveness of electricity enterprises in the modern market. In view of this, in order that the article wants to ensure the smooth progress of the e-commerce data analysis work, it should start with the business intelligence system under the background of big data, and combine it to ensure the steady development of the e-commerce industry.

Oral Fluids for the Early Detection of Classical Swine Fever in Commercial Level Pig Pens.

The early detection of classical swine fever (CSF) remains a key challenge, especially when outbreaks are caused by moderate and low-virulent CSF virus (CSFV) strains. Oral fluid is a reliable and cost-effective sample type that is regularly surveilled for endemic diseases in commercial pig herds in North America. Here, we explored the possibility of utilizing oral fluids for the early detection of CSFV incursions in commercial-size pig pens using two independent experiments. In the first experiment, a seeder pig infected with the moderately-virulent CSFV Pinillos strain was used, and in the second experiment, a seeder pig infected with the highly-virulent CSFV Koslov strain was used. Pen-based oral fluid samples were collected daily and individual samples (whole blood, swabs) every other day. All samples were tested by a CSFV-specific real-time RT-PCR assay. CSFV genomic material was detected in oral fluids on the seventh and fourth day post-introduction of the seeder pig into the pen, in the first and second experiments, respectively. In both experiments, oral fluids tested positive before the contact pigs developed viremia, and with no apparent sick pigs in the pen. These results indicate that pen-based oral fluids are a reliable and convenient sample type for the early detection of CSF, and therefore, can be used to supplement the ongoing CSF surveillance activities in North America.

Especias, hierbas aromáticas o condimentos usados en la cocina ecuatoriana

Spices, aromatic herbs and condiments are products that have a high cultural and culinary value in all the cuisines of the world that have played an important role at a social, political or commercial level. This study aims to identify the spices, aromaticherbs or condiments used in Ecuadorian cuisine among its traditional and popular dishes. It was considered to work with a methodology with a mixed approach where the information was collected through direct observation of the products that are commercially found in the market, both in flowers, bark, leaves, seeds, fruits and roots or bulbs. As a result, it was possible to identify that, in 39the Ecuadorian market, you can easily purchase up to 71 of these products, but only 40 are mentioned in 162 traditional and popular Ecuadorian preparations.

Seed Security for Food Security: A Situation Analysis from the Rural Home Gardens

Seeds being a primary agricultural input, its availability, access, and affordability is directly linked to the agricultural production. Traditional home gardens, backyards, Kandyan forest gardens, and micro-agricultural systems rich in biodiversity and species, mix with the knowledge and skills of the community to manage sustainable food production systems. Therefore, the study targeted to identify the types of seed production and preservation systems available among the farming community, and to identify the impact of seed ownership on household resilience to food insecurity. Data were gathered using an initial transaction walk, and a series of focus group discussions with rural households of Imbulpe and Boralanda GN divisions of Rathnapura and Badulla districts, respectively. The study areas were selected given the diversity of the crops in the area. Sample profile included 30 farmers who were purposively selected from each GN division. Results were analyzed using descriptive statistics and it revealed the existence of two seed production and preservation systems: formal and informal. Formal seed systems included both private and public stakeholders in seed and planting material business. Farmers used these formal seed systems for commercial level cultivation of both up-country and low-country vegetables. Informal seed systems were characterized with the own production, selection, storage, and maintenance of seed banks, barter system, and community seed gifting/sharing, and purchasing locally produced seeds from the locality. Informal seed systems were identified mainly for cereals (traditional rice varieties), pulses, fruits, vegetables, and spices at home gardening level. This resulted in seed and planting material ownership retaining among the local farmers. Seed ownership is an intangible asset which empowers social and human capital status of the households. Locally bred varieties proved to be resilient to climate change and maintain the crop diversity in home gardens. Informally sourced seeds recorded comparatively low yield than the hybrid/improved seed varieties that are sourced from formal seed systems. In conclusion own seed supplies ensured food availability, minimized seasonal yield variations, and enhanced meal diversity.
 Keywords: Food security, Household resilience, Seed system

Advances in Orchid Biology: Biotechnological Achievements, Translational Success, and Commercial Outcomes

Orchids constitute the largest and most diverse group of flowering plants and are classified in the family Orchidaceae. Exhibiting significance as the most exotic and ubiquitous flowering plant, the cultivation of orchids on a commercial level is gaining momentum worldwide. In addition to its ornamental and aesthetic value, the orchid industry has successfully generated employment for people in developing countries. Recent advances in biotechnological interventions in orchids have substantially contributed to the development of exotic varieties with novel traits, not to forget the inputs of traditional plant breeding methods and tissue culture approaches. In addition, the scientific developments in orchid biology have remarkably bridged the knowledge gaps in areas of orchid classification, phytochemistry, and cultivation strategies. This has facilitated the commercialization of novel varieties, opening new avenues in the orchid industry, and their global marketing as cut flowers and artificially propagated plants. Orchids constitute the first floriculture crops that revolutionized the orchid industry; however, they also hold several challenges in the natural propagation and conservation of several species that are on the verge of extinction. International organizations like CITES have come forward to address challenges associated with illegal global trade and indiscriminate use of orchid varieties, aiming for conservation and legal commercial goals. This thematic review is one-of-a-kind in providing comprehensive insights into the emerging momentum of orchid biology and how its globalization projects to considerably impact the orchid industry in the coming times. However, it is imperative to understand the challenges in the cultivation and conservation of orchid varieties and ensure legislative guidelines both on domestic and global levels to ensure a multipronged approach to the conservation and commercialization of orchids.

Effect of High Humidity Exposure to Wheat Starch Based High Conducting Flexible Polymer‐in‐Salt‐Electrolyte

AbstractPolymer‐in‐salt‐electrolytes (PISEs) are an important class of electrolytes as they carry the promise of faster and single ion transport. Unfortunately, due to unavailability of a suitable polymer host PISE has still not reached to commercial level. In the present work, using a novel synthesis protocol developed by the group, glutaraldehyde crosslinked wheat starch has been successfully modified with sodium iodide (NaI) to synthesize a flexible PISE membrane with desired electrochemical properties. Present paper reports the effect of crosslinker and exposure to high humidity ambience on electrochemical and morphological properties. It has been established that on exposure to higher humidity atmosphere starch‐based PISEs stabilize at lower resistance value, but with higher ion relaxation time, which indicates that effect of high humidity treatment is more on salt dissociation instead of assisting the ion transport. The studied materials have conductivity ≈0.01 S cm−1 range with ESW >2.5 V, ensuring its usability in electrochemical devices. The developed synthesis protocol does not require any complicated synthesis route and/or sophisticated instrument hence the overall process is economical also, adding up to its potentiality for energy device fabrication.

Effect of socio-economic and institutional factors on common bean commercialization among smallholder farmers in Chepalungu sub-county, Bomet County, Kenya

Smallholder common bean commercialization is a critical factor for rural development as it provides a pathway for improving productivity, food security and alleviating poverty. However, common bean sector is dominated by subsistence farming which is not economically efficient as the level of commercialization is low at 0.4. Therefore, the study intended to determine the effect of socio-economic and institutional factors on common bean commercialization in Chepalungu sub-county, Bomet county. The study utilized cluster sampling procedure to obtain a sample size of 313 and data was collected using a semi-structured questionnaire. Descriptive statistics and Tobit regression model were utilized to analyze the data through SPSS version 29 and Stata version 15 software. The average level of common bean commercialization was 0.39 indicating a low level of input and output market participation. The model showed that market distance and access to extension services were significant at 1% and positively influenced common bean commercialization among smallholder farmers while marketing experience and total land size were significant at 5% and positively influenced common bean commercialization. Age was significant at 1% and negatively influenced common bean commercialization. Strategies need to be developed to improve farmers’ market participation in input and output markets based on these variables. Youth need to be involved more on common bean production and marketing and the county government can provide training and extension services to farmers to increase level of productivity and commercialization.

Nanocomposite nanofibrous membranes of graphene and graphene oxide: water remediation potential

Abstract Immense research efforts on graphene or graphene oxide have led to the formation of unique nanocarbon derived nanomaterials. Graphene and graphene oxide have been reinforced in polymeric matrices to form high performance nanocomposites. Significant applications of polymer nanocomposites with graphene or graphene oxide were experiential for nanofiber formation and ensuing membranes. This overview highlights design, essential features, and potential of graphene or graphene oxide derived nanocomposite nanofibrous membranes for water remediation permeation towards contaminates, salts, toxins, microbials, and other separation purposes. Here, polymer filled graphene or graphene oxide nanocomposites have been processed into nanofibers using appropriate techniques such as electrospinning, wet spinning, template method, etc. Afterwards, polymer/graphene and polymer/graphene oxide nanofiber nanocomposites were applied to form the nanocomposite membranes using appropriate techniques like solution processing, casting methods, infiltration, etc. Consequently, high performance membranes have been researched for technological purposes, especially water management competence. Future research on polymer/graphene nanofibrous membranes may lead to highly efficient systems for commercial and industrial level uses.