High Degree Of Synergy Research Articles

Evaluation and Analysis of Synergy between Energy and Environmental Policies in Coal Resource-Rich Areas

The policy synergy of coal resource-rich areas directly affects the process of regional green transformation and high-quality development. Shanxi, Shaanxi and Inner Mongolia are important coal energy bases, and studying the energy and environmental policies of these three provinces is of great significance to sustainable development. Using social network analysis, the Latent Dirichlet Allocation (LDA) topic model and textual similarity methods, we conducted a synergistic study of policy issuance subjects and policy text contents of Shanxi, Shaanxi and Inner Mongolia from both horizontal and vertical perspectives. The results show that: (1) in the policy subject dimension, Shanxi had the highest degree of synergy, but overall the synergy in all three provinces was insufficient, and the number of multi-subject joint texts was relatively small; (2) in the policy content dimension, the textual similarity and goal consistency between Inner Mongolia and the Central Government were better than that of Shaanxi and Shanxi. Therefore, the region of “Shanxi–Shaanxi–Inner Mongolia” should improve the synergistic ability of policy issuance subjects; it should also pay attention to the linkage and refinement of the policy content, and make flexible innovations based on the compatibility with the Central policy incentives, to better promote the low-carbon and green transformation of coal resource-rich areas.

Abstract C143: Unveiling synergistic interplay between KRASG12C inhibitors and the polyamine synthesis inhibitor SAM486 against lung cancer cells: An in vitro study

Abstract Introduction: Non-small cell lung cancer (NSCLC) represents the most lethal variant of lung cancer. The G12C mutation in the KRAS protein occurs in 20-30% of NSCLC patients and is correlated with an unfavorable prognosis. Adagrasib and sotorasib are emerging compounds that inhibit the KRASG12C protein, demonstrating effectiveness in NSCLC driven by KRASG12C. However, the early development of resistance to KRASG12C inhibitors emphasizes the necessity to investigate combined therapeutic approaches. Polyamines (putrescine, spermidine, and spermine) are essential molecules for cancer growth and survival and are elevated in various cancer types, including NSCLC. Adenosylmethionine decarboxylase-1 (AMD1) is a critical enzyme involved in spermidine and spermine synthesis. AMD1 depends on KRAS signaling via the IGF-AKT-mTOR signaling and can be selectively restrained by the compound SAM486. Aim: This study aimed to explore the effect of AMD1 inhibition in NSCLC cells using the compound SAM486, alone or in combination with the KRASG12C inhibitors adagrasib and sotorasib, and to investigate the relationship between KRASG12C inhibition and polyamine enzyme levels. Methods: We employed four NSCLC cell lines: H358 (KRASG12C), A549 (KRASG12S), CORL-L23 (KRASG12V), and H1299 (KRASwt). Immunoblotting analysis was utilized to measure AMD1 levels and KRAS-ERK pathway phosphorylation. Cell proliferation was assessed through BrdU incorporation and colony formation assays. Cell viability was determined by MTT reduction, and combination studies were evaluated using Combenefit and SynergyFinder software, employing the Loewe additivity model. Results: The AMD1 inhibitor SAM486 exhibited a reduction in cell proliferation in NSCLC cells, irrespective of the presence of KRAS mutations. Furthermore, the KRASG12C inhibitors sotorasib and adagrasib decreased AMD1 levels and cell viability in H358 cells harboring the KRASG12C mutation. Notably, a high degree of synergy was observed when combining sotorasib and adagrasib with SAM486 in KRASG12C-mutated cells, as evaluated by Combenefit and SynergyFinder software, employing the Loewe additivity model. Conclusion: These findings suggest that the simultaneous inhibition of KRASG12C and AMD1 could provide a novel and synergistic therapeutic strategy against tumors with KRASG12C mutations. Citation Format: Rodrigo A Lopez-Muñoz, Antonia Martin-Martin, Carina Chipon, Neudo Buelvas, Sergio Guzmán-Kunstmann, Matías Mansilla-Velásquez. Unveiling synergistic interplay between KRASG12C inhibitors and the polyamine synthesis inhibitor SAM486 against lung cancer cells: An in vitro study [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C143.

Efficient fermentable sugar production from mulberry branch based on a rational design of GH10 xylanase with improved thermal stability

The mulberry branch can be used as a renewable biomass resource for the production of biofuels since it contains a significant amount of lignocellulose. However, the rapid deactivation of enzymes during lignocellulose degradation in a high-temperature environment leads to high costs and low efficiency of enzymatic saccharification. In this study, xylanase was modified by rational design, and xylanase and cellulase were used to synergistically degrade mulberry branches pretreated with seawater. The fermentable sugar yield and degree of synergy (DS) were determined. The dominant mutant S21Y/N318W of Hortaea werneckii xylanase Hwxyl10A was obtained with improved thermostability (T50 increased by 12 °C, t1/2 is 17-fold that of WT). Meanwhile, the specific activity at 75 °C increased from 1470 to 1901 U/mg. Under the condition of seawater immersion pretreatment, the highest yield of fermentable sugar was 313.5 μmol/g, and the highest DS was 1.57 after enzymatic hydrolysis of mulberry branches by cellulase and S21Y/N318W at 50 °C. Therefore, the biotransformation of mulberry branches reducing sugar has been significantly improved, which provides an efficient method of biomass saccharification for biofuel production.

Biochemical characterization of a novel acidophilic β-xylanase from Trichoderma asperellum ND-1 and its synergistic hydrolysis of beechwood xylan.

Acidophilic β-xylanases have attracted considerable attention due to their excellent activity under extreme acidic environments and potential industrial utilizations. In this study, a novel β-xylanase gene (Xyl11) of glycoside hydrolase family 11, was cloned from Trichoderma asperellum ND-1 and efficiently expressed in Pichia pastoris (a 2.0-fold increase). Xyl11 displayed a maximum activity of 121.99 U/ml at pH 3.0 and 50°C, and exhibited strict substrate specificity toward beechwood xylan (Km = 9.06 mg/ml, Vmax = 608.65 μmol/min/mg). The Xyl11 retained over 80% activity at pH 2.0–5.0 after pretreatment at 4°C for 1 h. Analysis of the hydrolytic pattern revealed that Xyl11 could rapidly convert xylan to xylobiose via hydrolysis activity as well as transglycosylation. Moreover, the results of site-directed mutagenesis suggested that the Xyl11 residues, Glu127, Glu164, and Glu216, are essential catalytic sites, with Asp138 having an auxiliary function. Additionally, a high degree of synergy (15.02) was observed when Xyl11 was used in association with commercial β-xylosidase. This study provided a novel acidophilic β-xylanase that exhibits excellent characteristics and can, therefore, be considered a suitable candidate for extensive applications, especially in food and animal feed industries.

Factors Affecting the Catalytic Efficiency and Synergism of Xylanase and Cellulase During Enzymatic Hydrolysis of Birch Wood.

Understanding factors that affect the catalytic efficiency and synergism of enzymes is helpful to enhance the process of bioconversion. In this study, birch wood (BW) was sequentially treated by delignification (DL), deacetylation (DA), and decrystallization (DC) treatments. The physiochemical structures of treated BW were characterized. Moreover, the influences of sequential treatments on the catalytic efficiency and synergism of xylanase and cellulase were studied. DL treatments efficiently improved the conversion of cellulose and xylan. A high degree of synergy (DS) between xylanase and cellulase was produced during hydrolysis of DL-treated BW. DA treatments enhanced xylan conversion but reduced the DS between xylanase and cellulase for xylan hydrolysis, whereas DC treatments enhanced cellulose conversion but reduced the DS between xylanase and cellulase for cellulose hydrolysis. The cellulose conversion of lithium chloride/N,N-dimethylacetamide (LiCl/DMAc)-treated BW (89.69%) was higher than the cellulose conversion of ball milling (BM)-treated BW (81.63%), whereas the xylan conversion of LiCl/DMAc-treated BW (83.77%) was lower than the xylan conversion of BM-treated BW (87.21%). This study showed that the catalytic efficiency and synergism of xylanase and cellulase are markedly affected by lignin hindrance, hemicellulose acetylation, and cellulose crystallization.

Insights into pyrolysis of torrefied-biomass, plastics/tire and blends: Thermochemical behaviors, kinetics and evolved gas analyses

The pyrolysis behaviors, the kinetics of the synergistic effects, the functional groups during the co-pyrolysis of torrefied-biomass (TBG) with a tire, and different plastics such as high-density polyethylene (HDPE), ethyl vinyl acetate (EVA), polystyrene (PS), polypropylene (PP) were analyzed by TG-FTIR. The TG-DTG curves revealed thermal stability due to torrefaction treatment and blending. The most potential reaction mechanisms associated with the first stage for both pure and blend samples were first-order reaction and one-dimensional diffusion mechanisms, while the second stage was mostly governed by second and third-order reaction mechanisms. The interactions between TBG-plastics/tire were obvious at temperatures of 290–540 °C, according to the variation of weight loss (ΔW) values. The highest degree of synergy was observed with the TBG/PS blend, while the TBG/tire mixture being the least synergistic. The FTIR spectra indicated that hydrocarbons compounds, CO2, CO, H2O, CH4, NH3, acid, aldehydes and C=O, C-O, O-H, C-H, C-C, N-H, HCN were the main gaseous products and functional groups detected by the FTIR. The HDPE, EVA, and PP generated mainly alkanes and alkenes. While the PS depolymerized into styrene monomers. The tire mainly disintegrated into olefins and alkanes. The effect of co-pyrolysis of TBG, tire, and different plastics on species produced is noticeable on pyrolysis characteristics, kinetics, gaseous products, and functional groups. Thus, H2O, acid, ketone, and aldehydes were suppressed. Generally, the co-pyrolysis of plastic/tire with TBG can reduce the oxygen-containing compounds in the gaseous species and can improve the release of hydrocarbons.

Empirical analysis of the synergy of the three sectors’ development and labor employment

Employment is an important production factor within economic development. There is a close connection between economic sector structure and employment structure, and the synergy between these two is an important index to measure the sustainable development of a social economy. This paper studies the degree of synergy within the three sectors from the three dimensions of employment elasticity, degree of structural deviation, and labor productivity ratio. The results show that the employment elasticity of the three sectors presents different characteristics and that the tertiary sector has the most significant driving effect on employment. The imbalance between the primary and secondary sector structures and the employment structure is relatively prominent. The labor productivity ratio of the three sectors is slightly superior to the national level in the same period. The tertiary sector has the strongest ability to absorb labor and the highest degree of synergy. The purpose of this study is to analyze the employment absorption capacity of the three industries and provide guidance for the government and relevant departments to formulate industrial development policies.

A two-layer social network model for manufacturing service composition based on synergy: A case study on an aircraft structural part

Abstract Cloud manufacturing is an emerging manufacturing paradigm, with the issue of service composition being one of its most significant challenges. The current researches take the view that all manufacturing services are of equal importance. However, in fact, manufacturing services that owns scarce resources are more important than ordinary one, especially in the production of complex products. Hence, it is significant to meet the requirements of manufacturing services that own scarce resources first. Meanwhile, due to the increasing complexity of products, a high degree of synergy is required in service composition. Our study explores a new framework of social relationships from the perspective of synergy. A two-layer social network model is first proposed for resource allocation that takes synergy and priority into account. The upper layer of this model is occupied by the manufacturing services with scare resources. The lower layer is occupied by ordinary manufacturing services. All services are connected by social relationships. For the master-slave characteristic of the model, the two-layer network is embedded into bi-level programming. Then, an improved genetic algorithm is designed to solve the problem. Finally, the effectiveness of the model and algorithm are verified using a structural part of the Modern Ark 60 as an example.

Dimensionally Enhanced Antibacterial Library Screening.

The emergence and spread of antimicrobial resistance is a major public health threat, and there is an urgent need to develop new strategies to address the issue. In this study, the possibility of enhancing a whole cell based antibacterial library screen by increasing the dimensionality of the screening effort is explored using methicillin-resistant Staphylococcus aureus (MRSA) as the target organism. One dimension involved generating and screening a human liver microsome metabolized FDA approved drug library. Comparative screening of the un-metabolized (UM) and pre-metabolized (PM) libraries allows identification of intrinsically active agents from the UM library screen and of agents with active metabolites from the PM library screen. To further enhance this screening effort, it was combined with a -/+ resistant to antibiotic screen (-/+ cefoxitin; Cef). This allows the identification of agents that can act synergistically with the resistant to antibiotic. This approach revealed five compounds with substantially improved activity after metabolism and four compounds with substantial synergistic activity with cefoxitin. Capecitabine in particular only had significant antibacterial activity after metabolism. Its metabolites were isolated, identified, and characterized for spectrum of activity along with several other anticancer drugs with anti-MRSA activity. Floxuridine, gemcitabine, novobiocin, and rifaximin were identified as having substantial synergy with cefoxitin from the -/+Cef screens. Checkerboard assays verified synergy for these agents. Floxuridine demonstrated a particularly high degree of synergy with cefoxitin (FIC = 0.14). This study demonstrates how a dimensionally enhanced comparative screening effort can identify new antibacterial agents and strategies for countering antibacterial agent resistance.

Deliberate Practice as a Theoretical Framework for Interprofessional Experiential Education.

Objective: The theory of deliberate practice has been applied to many skill-based performance activities. The primary aim of this project was to integrate synergistic principles from deliberate practice and consensus-derived competencies for interprofessional education into a framework upon which educational models to advance interprofessional experiential education (IEE) might be built.Methods: CINAHL, ERIC, and MEDLINE databases were searched using the keywords “deliberate practice” and “interprofessional education,” both individually and in combination. Relevant articles were selected from the catalog based on support for the premise of the project. Defining characteristics of deliberate practice were distilled with particular emphasis on their application to the Interprofessional Education Collaborative's (IPEC) core competencies. Recommendations for IEE development were identified through the synthesis of deliberate practice principles and IPEC competencies.Results: There is a high degree of synergy between deliberate practice principles and IPEC competencies. Our synthesis of the literature yielded a cyclical four-step process to advance IEE: (1) implement an IEE plan guided by the student's strengths/weaknesses and in consideration of the collaborative practice skills they wish to develop, (2) engage in IPE experiences that will challenge targeted skills according to the IEE plan, (3) embed frequent opportunities for student reflection and preceptor/team feedback within IEE plan, and (4) revise the IEE plan and the IPE experience based on insights gained during step 3.Conclusion: The cyclical four-step process synthesized through this literature review may be used to guide the development of new IEE models. The purposeful development of IEE models grounded in a theory that has already been operationalized in other skill-based performance areas is an important step to address expanding accreditation standards throughout the health professions mandating interprofessional education for pre-licensure health professional students.

Abstract B27: First-in-class cytoskeletal targeting drug, Anisina, enhances effectiveness of microtubule inhibitors in a preclinical model of neuroblastoma

Abstract Neuroblastoma is the most common extracranial solid tumor in childhood accounting for ~7% of all cancer cases in children. Children with high-risk neuroblastoma still have a poor overall outcome when treated with existing chemotherapeutics, making it imperative that new chemotherapeutic strategies are developed to treat this disease. The actin cytoskeleton is an ideal chemotherapeutic target due to its role in numerous biological processes essential for tumor cell growth and survival. While the therapeutic potential of actin-targeting compounds has been extensively investigated, no lead compound has been developed through to the clinic due to the associated cardiac and respiratory toxicity. We have developed a novel class of anti-tropomyosin (ATM) drugs that target cancer- associated actin filaments containing the tropomyosin Tpm3.1. The lead ATM, Anisina, was identified utilizing Novogen's proprietary VAL-ID - Versatile Approach to Library-based Iterative Design – medicinal chemistry program. This strategy is based around the design, synthesis and evaluation of targeted small-molecule libraries and has proven to be a rapid and robust method of identifying lead compounds. In vitro studies have demonstrated that Anisina binds to and impairs the function of Tpm3.1 in a dose dependent manner in both protein and cell based assays. Inhibition of Tpm3.1 function in a tumor cell model results in the destabilization of Tpm3.1 containing actin filaments and induction of tumor cell death via the activation of the intrinsic apoptotic pathway. Anisina has broad efficacy against both adult and pediatric cancers in vitro. When tested against a panel of neuroblastoma cell lines, Anisina was effective independent of NMYC status and had an average IC50 of 4-7uM. In preparation for the clinic, in vitro synergy studies were undertaken to evaluate the impact of Anisina in combination with standard of care chemotherapeutics. Anisina showed a high degree of synergy (combinatorial index <0.5) with anti-microtubule agents, both vinca alkaloids (microtubule destabilizing) and taxanes (microtubule stabilizing) in some adult and pediatric cancer cell models. In particular a ~20 fold increase in sensitivity to drug induced cell death was observed in tumor cells treated with the Anisina/Vincristine (VCR) combination. The same combinatorial effect was not observed with untransformed cells. More importantly, the synergy observed with Anisina/VCR in vitro has now been replicated in a CHLA20 human neuroblastoma xenograft model. Animals (n=4-5) were randomly divided into four treatment groups i) Control (Captisol), ii) Anisina (150mg/kg daily IP) iii) VCR alone (0.5mg/kg weekly, IV) and iv) Anisina (150mg/kg) + VCR (0.5mg/kg). Animals treated with Anisina/VCR showed a significant and profound regression of tumor growth compared to control and either drug treatment alone. Further to this, of the 5 animals in the combinatorial Anisina/VCR treatment group 3 (60%) reached a “complete response” with one animal showing a “maintained complete response” for more than 100 days post treatment. The outcomes of this study have significant therapeutic implications as microtubule inhibitors such as VCR are current standard of care for a wide range of solid tumors, including neuroblastoma. Anisina is currently being developed as an adjunct therapy for the treatment of both adult and pediatric cancers. Citation Format: Justine Stehn, Mark Currier, Duo Chen, Eleanor Eiffe, Andrew Heaton, Jeff Hook, Peter Gunning, Timothy Cripe. First-in-class cytoskeletal targeting drug, Anisina, enhances effectiveness of microtubule inhibitors in a preclinical model of neuroblastoma. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr B27.

Behaviour change strategies for reducing blood pressure-related disease burden: findings from a global implementation research programme.

BackgroundThe Global Alliance for Chronic Diseases comprises the majority of the world’s public research funding agencies. It is focussed on implementation research to tackle the burden of chronic diseases in low- and middle-income countries and amongst vulnerable populations in high-income countries. In its inaugural research call, 15 projects were funded, focussing on lowering blood pressure-related disease burden. In this study, we describe a reflexive mapping exercise to identify the behaviour change strategies undertaken in each of these projects.MethodsUsing the Behaviour Change Wheel framework, each team rated the capability, opportunity and motivation of the various actors who were integral to each project (e.g. community members, non-physician health workers and doctors in projects focussed on service delivery). Teams then mapped the interventions they were implementing and determined the principal policy categories in which those interventions were operating. Guidance was provided on the use of Behaviour Change Wheel to support consistency in responses across teams. Ratings were iteratively discussed and refined at several group meetings.ResultsThere was marked variation in the perceived capabilities, opportunities and motivation of the various actors who were being targeted for behaviour change strategies. Despite this variation, there was a high degree of synergy in interventions functions with most teams utilising complex interventions involving education, training, enablement, environmental restructuring and persuasion oriented strategies. Similar policy categories were also targeted across teams particularly in the areas of guidelines, communication/marketing and service provision with few teams focussing on fiscal measures, regulation and legislation.ConclusionsThe large variation in preparedness to change behaviour amongst the principal actors across these projects suggests that the interventions themselves will be variably taken up, despite the similarity in approaches taken. The findings highlight the importance of contextual factors in driving success and failure of research programmes. Forthcoming outcome and process evaluations from each project will build on this exploratory work and provide a greater understanding of factors that might influence scale-up of intervention strategies.Electronic supplementary materialThe online version of this article (doi:10.1186/s13012-015-0331-0) contains supplementary material, which is available to authorized users.

Chemical probing of HER2-amplified cancer cells identifies TORC2 as a particularly effective secondary target for combination with lapatinib.

The clinical impact of HER2 inhibitors in the treatment of HER2-amplified breast cancers has been largely confined to chemotherapy combination regimens, since HER2 inhibitors appear to have very modest efficacies by themselves. This is due to the resilient nature of the functionally relevant HER2-HER3 tumor driver, bidirectionally linked with downstream PI3K/Akt pathway signaling, which can break through the inhibitory effects of most current HER2 or HER3 targeting therapies. A vertical combination approach targeting HER2 and a downstream pathway is a highly rational strategy for much more effective targeted therapy of this disease. However the importance of these downstream pathways in many human tissues and cells significant limits their usefulness as secondary targets by narrowing the therapeutic index of such combination therapies. The secondary target that can afford the highest potential for clinical translation is the one with the highest synergy against tumor cells in combination with HER2-inhibition, allowing the widest therapeutic index for clinical translation. We conducted a comparative analysis of such secondary targets in combination with the HER2 inhibitor lapatinib and find that the inhibition of mTor affords the highest degree of synergy. In further dissecting the individual roles of TORC1 and TORC2 complexes using pharmacologic and genetic tools, we find that it is specifically the inactivation of TORC2 that most synergistically enhances the efficacy of lapatinib. Although inhibitors that selectively target TORC2 are not currently available, these data make a compelling case for their development.

Dynamic study of how the bacterial breakdown of plant cell walls allows the reconstitution of efficient hemicellulasic cocktails

Designing more efficient mixtures of enzymes is necessary to produce molecules of interest from biomass lignocellulosic fractionation. The present study aims to investigate the strategies used by the thermophilic and hemicellulolytic bacterium Thermobacillus xylanilyticus to fractionate wheat bran and wheat straw during its growth. Results demonstrated ratios and levels of hemicellulases produced varied during growth on both biomasses. Xylanase activity was mainly produced during stationary stages of growth whereas esterase and arabinosidase activities were detected earlier. This enzymatic profile is correlated with the expression pattern of genes encoding four hemicellulases (two xylanases, one arabinosidase and one esterase) produced by T. xylanilyticus during growth. Based on identification of the bacterial strategy, the synergistic efficiency of the four hemicellulases during the hydrolysis of both substrates was evaluated. The four hemicellulases worked together with high degree of synergy and released high amounts of xylose, arabinose and phenolic acids from wheat bran and wheat straw.

A novel neutral xylanase with high SDS resistance from Volvariella volvacea: characterization and its synergistic hydrolysis of wheat bran with acetyl xylan esterase

A neutral xylanase (XynII) from Volvariella volvacea was identified and characterized. Unlike other modular xylanases, it consists of only a single GH10 catalytic domain with a unique C-terminal sequence (W-R-W-F) and a phenylalanine and proline-rich motif (T-P-F-P-P-F) at N-terminus, indicating that it is a novel GH10 xylanase. XynII exhibited optimal activity at pH 7 and 60 °C and stability over a broad range of pH 4.0-10.0. XynII displayed extreme highly SDS resistance retaining 101.98, 92.99, and 69.84 % activity at the presence of 300 mM SDS on birchwood, soluble oat spelt, and beechwood xylan, respectively. It remained largely intact after 24 h of incubation with proteinase K at a protease to protein ratio of 1:50 at 37 °C. The kinetic constants K(m) value towards beechwood xylan was 0.548 mg ml⁻¹, and the k(cat)/K(m) ratio, reflecting the catalytic efficiency of the enzyme, was 126.42 ml mg⁻¹ s⁻¹ at 60 °C. XynII was a true endo-acting xylanase lacking cellulase activity. It has weak activity towards xylotriose but efficiently hydrolyzed xylans and xylooligosaccharides larger than xylotriose mainly to xylobiose. Synergistic action with acetyl xylan esterase (AXEI) from V. volvacea was observed for de-starched wheat bran. The highest degree of synergy (DS 1.42) was obtained in sequential reactions with AXEI digestion preceding XynII. The high SDS resistance and intrinsic stability suggested XynII may have potential applications in various industrial processes especially for the detergent and textile industries and animal feed industries.

Proactive/Responsive Market Orientation and Marketing—Research and Development Integration

The level of integration between the marketing and research and development (R&D) functions may be gauged by degree of communication, information sharing, and collaboration between the functions during the new product development process. This article examines how a firm's strategic choice regarding market orientation may influence the relationship between marketing and R&D personnel, and how this relationship may affect organizational success. Under examination are both the responsive form of market orientation, in which a firm focuses on immediate customer needs and tends to be market driven, and the proactive form, in which the firm focuses on future market needs and tends to be invention driven. It is theorized that responsive market orientation will be more positively related to marketing‐R&D integration due to the market‐driven nature of the orientation. Conversely, it is theorized proactive market orientation will be more positively related to organizational success than responsive market orientation due to the innovation‐driven nature of the orientation. The study was implemented via a Web‐based survey and data analysis was performed using structural equation modeling techniques. The results of this study provide empirical evidence that both proactive and responsive market orientation exhibit a positive relationship with marketing–R&D integration, indicating that both forms of market orientation may lead to closer collaboration between the marketing and R&D functions. Despite the assumption that a proactive orientation is driven by innovation and technology in which R&D may play a more significant role, there is evidence that a high degree of synergy is developed between the groups when the focus is on future market needs. A market‐driven responsive orientation by necessity requires high integration between departments to commercialize products in a timely manner to meet current market needs. Proactive market orientation exhibits a positive relationship with market performance, whereas responsive market orientation does not. The result may show evidence of the “new product paradox," whereby developing products to address immediate market needs may result in lower market performance because the new products may be replacements for obsolete offerings or are actually cannibalizing sales of existing products.

Improvement of fungal arabinofuranosidase thermal stability by reversible immobilization

A gene encoding α-l-arabinofuranosidase (abfA) from Aspergillus niveus was identified, cloned, and successfully expressed in Aspergillus nidulans. Based on amino acid sequence comparison, the 88.6kDa enzyme could be assigned to the GH family 51. The characterization of the purified recombinant AbfA revealed that the enzyme was active at a limited pH range (pH 4.0–5.0) and an optimum temperature of 70°C. The AbfA was able to hydrolyze arabinoxylan, xylan from birchwood, debranched arabinan, and 4-nitrophenyl arabinofuranoside. Synergistic reactions using both AbfA and endoxylanase were also assessed. The highest degree of synergy was obtained after the sequential treatment of the substrate with endoxylanase, followed by AbfA, which was observed to release noticeably more reducing sugars than that of either enzyme acting individually. The immobilization of AbfA was performed via ionic adsorption onto various supports: agarose activated by polyethyleneimine polymers, cyanogen bromide activated Sepharose, DEAE-Sepharose, and Sepharose-Q. The Sepharose-Q derivative remained fully active at pH 5 after 360min at 60°C, whereas the free AbfA was inactivated after 60min. A synergistic effect of arabinoxylan hydrolysis by AbfA immobilized in Sepharose-Q and endoxylanase immobilized in glyoxyl agarose was also observed. The stabilization of arabinofuranosidases using immobilization tools is a novel and interesting topic.

Imaging brain change across different time scales

Imaging brain change across different time scales

The family II carbohydrate-binding module of xylanase CflXyn11A from Cellulomonas flavigena increases the synergy with cellulase TrCel7B from Trichoderma reesei during the hydrolysis of sugar cane bagasse

Synergy between Cellulomonas flavigena xylanase CflXyn11A and Trichoderma reesei endoglucanase TrCel7B was assessed during hydrolysis of alkaline pretreated sugar cane bagasse (SCB) after 12–48h, applying the individual enzymes and mixtures of the enzymes. A high degree of synergy (6.3) between CflXyn11A and TrCel7B in hydrolysis of SCB was observed after 12h in the equimolar mixture. A threefold decrease in the degree of synergy was observed with TrCel7B and the catalytic module of CflXyn11A; suggesting an important role played by the carbohydrate-binding module of CflXyn11A (CflXyn11A-CBM) in the observed synergy. Affinity electrophoresis and binding assays showed that CflXyn11A-CBM binds to xylans and to a lesser extent to cellulose. Our results suggest that synergy is more pronounced at early stages of hydrolysis. Furthermore, for the first time it is described that a CBM carried by a xylanase significantly enhances the synergy with a cellulase (threefold increase in synergy).

Lime pretreatment of sugar beet pulp and evaluation of synergy between ArfA, ManA and XynA from Clostridium cellulovorans on the pretreated substrate

Sugar beet pulp (SBP) is a waste product from the sugar beet industry and could be used as a potential biomass feedstock for second generation biofuel technology. Pretreatment of SBP with ‘slake lime’ (calcium hydroxide) was investigated using a 23 factorial design and the factors examined included lime loading, temperature and time. The pretreatment was evaluated for its ability to enhance enzymatic degradation using a combination of three hemicellulases, namely ArfA (an arabinofuranosidase), ManA (an endo-mannanase) and XynA (an endo-xylanase) from C. cellulovorans to determine the conditions under which optimal activity was facilitated. Optimal pretreatment conditions were found to be 0.4 g lime/g SBP, with 36 h digestion at 40 °C. The synergistic interactions between ArfA, ManA and XynA from C. cellulovorans were subsequently investigated on the pretreated SBP. The highest degree of synergy was observed at a protein ratio of 75% ArfA to 25% ManA, with a specific activity of 2.9 U/g protein. However, the highest activity was observed at 4.2 U/g protein at 100% ArfA. This study demonstrated that lime treatment enhanced enzymatic hydrolysis of SBP. The ArfA was the most effective hemicellulase for release of sugars from pretreated SBP, but the synergy with the ManA indicated that low levels of mannan in SBP were probably masking the access of the ArfA to its substrate. XynA displayed no synergy with the other two hemicellulases, indicating that the xylan in the SBP was not hampering the access of ArfA or ManA to their substrates and was not closely associated with the mannan and arabinan in the SBP.