Product Family Research Articles

Budgeting Family Living into Cost of Production: Why It Matters for Farm and Ranch Families

In farming or ranching, budgeting is more than just managing costs for seeds, feed, equipment, or labor. For farm and ranch families, the unique structure of finances often means family living expenses are often interwoven with the business. Budgeting family living expenses into cost of production is an essential practice that can significantly impact the financial stability of the family, especially during challenging economic periods when the operation’s income may fluctuate. By including family living expenses in the cost of production, farm and ranch families can gain a more realistic view of their business’s profitability, make more informed financial decisions, and work toward long-term sustainability.

Structural Insights into the Mechanism of a Polyketide Synthase Thiocysteine Lyase Domain.

Polyketide synthases (PKSs) are renowned for the structural diversity of the polyketide natural products they produce, but sulfur-containing functionalities are rarely installed by PKSs. We previously characterized thiocysteine lyase (SH) domains involved in the biosynthesis of the leinamycin (LNM) family of natural products, exemplified by LnmJ-SH and guangnanmycin (GnmT-SH). Here we report a detailed investigation into the PLP-dependent reaction catalyzed by the SH domains, guided by a 1.8 Å resolution crystal structure of GnmT-SH. A series of elaborate substrate mimics were synthesized to answer specific questions garnered from the crystal structure and from the biosynthetic logic of the LNM family of natural products. Through a combination of bioinformatics, molecular modeling, in vitro assays, and mutagenesis, we have developed a detailed model of acyl carrier protein (ACP)-tethered substrate-SH, and interdomain interactions, that contribute to the observed substrate specificity. Comparison of the GnmT-SH structure with archetypical PLP-dependent enzyme structures revealed how Nature, via evolution, has modified a common protein structural motif to accommodate an ACP-tethered substrate, which is significantly larger than any of those previously characterized. Overall, this study demonstrates how PLP-dependent chemistry can be incorporated into the context of PKS assembly lines and sets the stage for engineering PKSs to produce sulfur-containing polyketides.

Bootstrap Percolation in Strong Products of Graphs

Given a graph $G$ and assuming that some vertices of $G$ are infected, the $r$-neighbor bootstrap percolation rule makes an uninfected vertex $v$ infected if $v$ has at least $r$ infected neighbors. The $r$-percolation number, $m(G,r)$, of $G$ is the minimum cardinality of a set of initially infected vertices in $G$ such that after continuously performing the $r$-neighbor bootstrap percolation rule each vertex of $G$ eventually becomes infected. In this paper, we consider percolation numbers of strong products of graphs. If $G$ is the strong product $G_1\boxtimes \cdots \boxtimes G_k$ of $k$ connected graphs, we prove that $m(G,r)=r$ as soon as $r\le 2^{k-1}$ and $|V(G)|\ge r$. As a dichotomy, we present a family of strong products of $k$ connected graphs with the $(2^{k-1}+1)$-percolation number arbitrarily large. We refine these results for strong products of graphs in which at least two factors have at least three vertices. In addition, when all factors $G_i$ have at least three vertices we prove that $m(G_1 \boxtimes \dots \boxtimes G_k,r)\leq 3^{k-1} -k$ for all $r\leq 2^k-1$, and we again get a dichotomy, since there exist families of strong products of $k$ graphs such that their $2^{k}$-percolation numbers are arbitrarily large. While $m(G\boxtimes H,3)=3$ if both $G$ and $H$ have at least three vertices, we also characterize the strong prisms $G\boxtimes K_2$ for which this equality holds. Some of the results naturally extend to infinite graphs, and we briefly consider percolation numbers of strong products of two-way infinite paths.

A law of iterated logarithm on lamplighter diagonal products

We prove a law of iterated logarithm for random walks on a family of diagonal products constructed by Brieussel and Zheng (2021). This provides a wide variety of new examples of law of iterated logarithm behaviors for random walks on groups. In particular, it follows that for any \frac{1}{2}\leq \beta\leq 1 there is a group G and random walk W_{n} on G with \mathbb{E}|W_{n}|\simeq n^{\beta} such that 0<\limsup \frac{|W_{n}|}{n^{\beta}(\log\log n)^{1-\beta}}<\infty\quad \text{and}\quad 0<\liminf \frac{|W_{n}|(\log\log n)^{1-\beta}}{n^{\beta}}<\infty.

Lipidation Engineering in Daptomycin Biosynthesis.

Lipopeptides are an important family of natural products, some of which are clinically used as antibiotics to treat multidrug-resistant pathogens. Although the lipid moieties play a crucial role in balancing antibacterial activity and hemolytic toxicity, modifying the lipid moieties has been challenging due to the complexity of the lipidation process in lipopeptide biosynthesis. Here, we show that the lipid profile can be altered by engineering both secondary and primary metabolisms, using daptomycin as an example. First, swapping the fatty acyl AMP ligase (FAAL) gene dptF with foreign FAAL homologs improved the fatty acyl specificity of the lipidation process for decanoic acid. Then, the introduction of Mycobacterium type I fatty acid synthase operon (MvFAS-Ib/MvAcpS) and Cryptosporidium thioesterase (CpTEII) enriched the fatty acid pool with decanoic acid in Streptomyces roseosporus. The engineered fatty acid metabolism eliminates the need for external decanoic acid supplementation by enabling S. roseosporus to biosynthesize decanoic acid. By complete engineering of the lipidation process, we achieved, for the first time, high-purity, natural production of daptomycin. The lipidation engineering approach we demonstrate here lays the foundation for the lipidation control in lipopeptide biosynthesis.

Social and economic importance of new bamboo species established in three municipalities of the North Eastern Mountain range of Puebla, Mexico

The study was conducted in three municipalities of Puebia, Mexico. The objectives were to identify the species of bamboo in the North Eastern region of Puebla, know the climatic conditions and agronomic systems where it grows, characterize the socioeconomic situation of the producers, and identify the contribution to the family economy. A review of the history of cultivation in Mexico was carried out at the National Herbarium of Mexico (MEXU). For the collection of information, it was considered that the bamboo system was within the local agricultural system and selection of municipalities was based on the productive relationship of the crop and the introduction of species in the area. Sixty-four surveys were done of bamboo producers through the questionnaire with social, economic, and productive variables related to the bamboo production system. In the Puebla’s North Eastern Mountain range there are two new species of bamboo, Bambusa oldhamii and Guadua angustifolia, both with different characteristics of uses and established in two production systems, the commercial and family system. At present they have a low commercialization of some bamboo derivatives and little use as food. The region is considered one of extreme proverty. The two species have a high potential for environmental adaptation agronomically they are developed as a single crop in backyards and used in various commercial activities. The lack of use of the crop in the region and its rapid natural expansion due to the environmental conditions for its growth, induces the tendency to consider it as an undesirable plant

Non-ischemic cerebral enhancing (NICE) lesions after flow diversion for intracranial aneurysms: a multicenter study

BackgroundNon-ischemic cerebral enhancing (NICE) lesions have been reported as a rare complication of various neuroendovascular procedures, but information on their incidence after flow diversion is scant. It is unclear if...

A chiral hydrogen atom abstraction catalyst for the enantioselective epimerization of meso-diols.

Hydrogen atom abstraction is an important elementary chemical process but is very difficult to carry out enantioselectively. We have developed catalysts, readily derived from the Cinchona alkaloid family of natural products, which can achieve this by virtue of their chiral amine structure. The catalyst, following single-electron oxidation, desymmetrizes meso-diols by selectively abstracting a hydrogen atom from one carbon center, which then regains a hydrogen atom by abstraction from a thiol. This results in an enantioselective epimerization process, forming the chiral diastereomer with high enantiomeric excess. Cyclic and acyclic 1,2-diols are compatible, as are acyclic 1,3-diols. Additionally, we demonstrate the viability of combining our approach with carbon-carbon bond formation in Giese addition. Given the increasing number of synthetic methods involving hydrogen atom transfer steps, we anticipate that this work will have a broad impact in the field of enantioselective radical chemistry.

On fuzzy inner products constructed by fuzzy numbers in linear spaces

In this paper a new definition for fuzzy inner product spaces is presented. Just as the set of real numbers can be embedded in a set of fuzzy numbers, a crisp inner product space can be considered as a special case of fuzzy inner product spaces. An example is given to demonstrate that, the new definition is a nontrivial generalization for the crisp inner product spaces. Under certain restrictions, a fuzzy inner product space can become a fuzzy normed space. Based on some elementary properties for the families of semi-inner products of endpoints, the linearly topological structure of new spaces is discussed. Moreover, the orthogonality between two vectors is considered and a fuzzy version of Pythagorean theorem is given.

A binary tree of complete intersections with the strong Lefschetz property

In this paper we give a new family of complete intersections which have the strong Lefschetz property. The family consists of Artinian algebras defined by ideals generated by power sum symmetric polynomials of consecutive degrees and of certain ideals naturally derived from them. This family has a structure of a binary tree and this observation is a key to prove that all members in it have the strong Lefschetz property.

A kalihinol analog disrupts apicoplast function and vesicular trafficking in P. falciparum malaria.

We report the discovery of MED6-189, an analog of the kalihinol family of isocyanoterpene natural products that is effective against drug-sensitive and drug-resistant Plasmodium falciparum strains, blocking both asexual replication and sexual differentiation. In vivo studies using a humanized mouse model of malaria confirm strong efficacy of the compound in animals with no apparent hemolytic activity or toxicity. Complementary chemical, molecular, and genomics analyses revealed that MED6-189 targets the parasite apicoplast and acts by inhibiting lipid biogenesis and cellular trafficking. Genetic analyses revealed that a mutation in PfSec13, which encodes a component of the parasite secretory machinery, reduced susceptibility to the drug. Its high potency, excellent therapeutic profile, and distinctive mode of action make MED6-189 an excellent addition to the antimalarial drug pipeline.

Mendorong Gerakan Keluarga Sadar Gizi Menuju Keluarga Sehat dan Produktif di Desa Argo Mulyo, Kecamatan Sepaku, Kalimantan Timur

This community service aims to provide understanding to housewives regarding efforts to build nutrition-conscious family behavior (KADARZI). It is hoped that this can encourage improvements in the quality of household health by forming healthy and productive families. Forming a nutritionally aware family can reduce the risk of health problems, especially those related to nutritional problems in family members. The method of implementing community service is carried out through 'socialization' activities. Partners in this activity are the Argo Mulya Village Community, Sepaku District, North Panajam Paser Regency, East Kalimantan Province. The number of housewives who participated in the activity was 33 people with children under five and school age. It is hoped that the results of this activity can increase nutrition-conscious behavior starting at the household level in Argo Mulyo Village, Sepaku District.

Maduraflavacins A-E, Unusual Phenyl Polyene Metabolites Produced by a Rare Marine-Derived Actinomadura sp.

Phenyl polyenes comprise a small family of bacterial natural products with broad and potent bioactivities, primarily found in actinobacteria. Here we report the discovery of five new phenyl polyene metabolites, maduraflavacins A-E (1-5), from a rare, marine-derived actinobacteria strain Actinomadura glauciflava NA03286. The structures of these natural products were determined by NMR spectroscopy, HRESIMS, LC-MS/MS, and chemical derivatization. All of these new maduraflavacins feature methyl substitutions at the polyene side chain, and maduraflavacins A-C (1-3) possessed a 1-N-β-d-glucosamine-(3 → 1)-O-β-d-glucopyranosyl-(3 → 1)-O-β-d-glucopyranosyl-(6 → 1)-O-β-d-glucopyranoside tetrasaccharide moiety via an amido linkage with a phenyl polyene skeleton. Compounds 1 and 2 showed weak antibacterial activities against the Gram-positive bacteria Staphylococcus aureus Sau 16339 and Micrococcus luteus, respectively.

Establishing a coumarin production platform by protein and metabolic engineering

Coumarins are a vast family of natural products with diverse biological activities. Cinnamyl-CoA ortho-hydroxylases (CCHs) catalyze the gateway and rate-limiting step in coumarin biosynthesis. However, engineering CCHs is challenging due to the large size of the substrates and the vague structure-activity relationship. Herein, directed evolution and structure-guided engineering were performed to engineer a CCH (AtF6′H from Arabidopsis thaliana) using a fluorescence-based screening method, yielding the transplantable surface mutations and the substrate-specific pocket mutations with improved activity. Structural analysis and molecular dynamics simulations elucidated the conformational changes that led to increased catalytic efficiency. Applying appropriate variants with the optimized upstream biosynthetic pathways improved the titers of three simple coumarins by 5 to 22-fold. Further introducing glycosylation modules resulted in the production of four coumarin glucosides, among which the titer of aesculin was increased by 15.7-fold and reached 3 g/L in scale-up fermentation. This work unleashed the potential of CCHs and established an Escherichia coli platform for coumarins production.

Reconfigurable flexible assembly model and implementation for cross-category products

As the production orders are becoming multi-category and small-batch in the era of product personalization, these require frequent reconfiguration of reconfigurable flexible assembly system for cross-category products (RFAS-CCP). However, there is no suitable theoretical assembly model and systematic implementation framework. We first propose a five-element assembly model (FAM) for RFAS-CCP, i.e. product, process, resource, knowledge, and decision. The product, process, and resource element describe the objects, steps to be assembled, and the tools, fixtures, and other equipment used for assembly, respectively. The knowledge element is a form representation of various heterogeneous data, such as a knowledge graph. The decision element includes various assembly methods to achieve assembly automation, flexibility, and intelligence. Then, in order to standardize and easy the frequent reconfiguration process, we reorganize various decision methods into a three-phase systematic implementation framework according to which stage they are used: design, configuration, and operation phases. The design phase methods primarily design various assembly modules for a product family, forming an assembly resource library. The configuration phase methods primarily configure suitable assembly lines for a specific product in the product family. The operation phase methods monitor the status of the assembly line and ensures its stable operation through health management. Finally, the effectiveness and practicality of the proposed five-element assembly model and three-phase systematic implementation framework are experimented with a pressure reducing valve product.

Software product line testing: a systematic literature review

A Software Product Line (SPL) is a software development paradigm in which a family of software products shares a set of core assets. Testing has a vital role in both single-system development and SPL development in identifying potential faults by examining the behavior of a product or products, but it is especially challenging in SPL. There have been many research contributions in the SPL testing field; therefore, assessing the current state of research and practice is necessary to understand the progress in testing practices and to identify the gap between required techniques and existing approaches. This paper aims to survey existing research on SPL testing to provide researchers and practitioners with up-to-date evidence and issues that enable further development of the field. To this end, we conducted a Systematic Literature Review (SLR) with seven research questions in which we identified and analyzed 118 studies dating from 2003 to 2022. The results indicate that the literature proposes many techniques for specific aspects (e.g., controlling cost/effort in SPL testing); however, other elements (e.g., regression testing and non-functional testing) still need to be covered by existing research. Furthermore, most approaches are evaluated by only one empirical method, most of which are academic evaluations. This may jeopardize the adoption of approaches in industry. The results of this study can help identify gaps in SPL testing since specific points of SPL Engineering still need to be addressed entirely.

Design, Synthesis and in Silico Studies of New 2-MethylQuinazolin-4(3H)- Ones Derivatives

The concept of the green chemistry consists in the development of an environmentally friendly approach for organic synthesis using ecological and efficient protocols. In order to develop a methodology that could fit into the green chemistry field, for the synthesis of new quinazolin-4(3H)-ones derivatives via benzoxazinone, the choice was made on the use of both as catalysts, known for their efficiency, and microwave irradiations for time saving.The quinazolinone core and its derivatives form an important class of compounds, as they are present in a large family of products with broad biological activities. They generally display useful therapeutic and pharmacological properties such as anti-inflammatory, anti-convulsant, antihypertensive and antimalarial activity.The derivatives of the 2-metylquinazolin-4(3H)-ones 3a-d series was synthesized from 2- methyl benzoxazin-4(3H)-one 1 and aniline in the presence of H3PW12O40 (PW12) under microwave irradiation and solvent free conditions. The compound structures were established using IR, 1H-NMR, 13C-NMR and mass spectroscopy. The toxicity of the hydrazone derivatives was studied through ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) simulations using ADMET Lab 2.0 server.

Detecting nontrivial products in the stable homotopy ring of spheres via the third Morava stabilizer algebra

Let p ≥ 7 p \geq 7 be a prime number. Let S ( 3 ) S(3) denote the third Morava stabilizer algebra. In recent years, Kato-Shimomura and Gu-Wang-Wu found several families of nontrivial products in the stable homotopy ring of spheres π ∗ ( S ) \pi _* (S) using H ∗ , ∗ ( S ( 3 ) ) H^{*,*} (S(3)) . In this paper, we determine all nontrivial products in π ∗ ( S ) \pi _* (S) of the Greek letter family elements α s , β s , γ s \alpha _s, \beta _s, \gamma _s and Cohen’s elements ζ n \zeta _n which are detectable by H ∗ , ∗ ( S ( 3 ) ) H^{*,*} (S(3)) . In particular, we show β 1 γ s ζ n ≠ 0 ∈ π ∗ ( S ) \beta _1 \gamma _s \zeta _n \neq 0 \in \pi _*(S) , if n ≡ 2 n \equiv 2 mod 3, s ≢ 0 , ± 1 s \not \equiv 0, \pm 1 mod p p .

Self-X heterogeneous attributed graph embedding-based product configuration framework for cognitive mass personalization

Cognitive mass personalization (CMP) is a promising manufacturing paradigm; equipped with cognitive capabilities like reasoning, CMP satisfies changeable needs via configuring personalized products at scale. In CMP, knowledge graphs (KGs) are exploited by smart product-service systems (SPSS) to support cognitive configuration/reconfiguration processes. However, the extant KG-enabled SPSSs are built upon fixed configurations and hybrid frameworks due to lacking a graph embedding (GE) model to render cognitive configuration decisions. In fact, GE is scarcely used in SPSS configuration, because it is not only compromised by the heterogeneity of KGs entailed by content-related specifications and complex structures but also influenced by the feature randomness and feature drift problems, which are triggered by accumulative errors and inconsistent objectives due to noisy assignments and different configuration tasks, separately. To address these limitations, a Self-X Heterogeneous Attributed Graph Embedding (SXHAGE) model is proposed in a Self-X architecture, which includes 1) self-attention graph attention networks, 2) a self-adaptive autoencoder, and 3) self-optimizing training objectives, to present heterogeneous data through jointly optimizing heterogeneous attributed entities and relations. A systematic SXHAGE-based configuration framework, in which product family design and configuration recommending are enabled by graph clustering and link prediction, is developed as a continuous updating loop to proactively configure personalized products. A real-world case study, i.e., configure personalized electric clippers via a web-based sustainable configuration platform, is performed to validate the applicability of the proposed framework in the CMP context. Moreover, extensive experiments on the case study dataset demonstrate the superiority of SXHAGE over the state-of-the-art algorithms, e.g., surpassing Deep Neighbor-Aware Embedding (DNENC) by 18 % in F1-score for graph clustering and by 5 % in ROC-AUC for link prediction.

Manufacturing time estimation for offer pricing: A machine learning application in a French metallurgy industry

- In today's market where many companies are competing for the same opportunities, a quick, accurate, and reliable estimation of the offers' prices is essential for the suppliers. This allows them to answer to more solicitations and to remain competitive. Many suppliers use the manufacturing time as key parameter to define their offers' prices. However, in Make-To-Order (MTO) and Engineer-To-Order (ETO) contexts, with the increasing number of demands, the huge diversity of the products and the manufacturing process complexity, estimating the manufacturing time is challenging. To face this issue, this article proposes a new approach for the manufacturing time estimation using machine learning. Its originality relies on the exploitation of structured tabular data, unstructured textual data and domain knowledge. It also proposes two strategies that allow to choose the best estimation model for each product family, while minimizing the number of estimation models and considering product families with fewer available data. All the proposals have been applied to a real industrial case in a French small metallurgy industry, and the results have shown their applicability and effectiveness. Among the plethora of machine learning techniques implemented, CatBoost, which is a member of the family of Gradient Boosted Decision Trees (GBDT) ensemble techniques, provided the best results.