ResearchPad - Physical Sciences https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[The Language of Innovation]]> https://www.researchpad.co/product?articleinfo=Nb83146fc-3c9c-477e-ac2c-85cafd261eee

Predicting innovation is a peculiar problem in data science. Following its definition, an innovation is always a never-seen-before event, leaving no room for traditional supervised learning approaches. Here we propose a strategy to address the problem in the context of innovative patents, by defining innovations as never-seen-before associations of technologies and exploiting self-supervised learning techniques. We think of technological codes present in patents as a vocabulary and the whole technological corpus as written in a specific, evolving language. We leverage such structure with techniques borrowed from Natural Language Processing by embedding technologies in a high dimensional euclidean space where relative positions are representative of learned semantics. Proximity in this space is an effective predictor of specific innovation events, that outperforms a wide range of standard link-prediction metrics. The success of patented innovations follows a complex dynamics characterized by different patterns which we analyze in details with specific examples. The methods proposed in this paper provide a completely new way of understanding and forecasting innovation, by tackling it from a revealing perspective and opening interesting scenarios for a number of applications and further analytic approaches.

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<![CDATA[Stereoscopic optimization of industrial structure of the equipment manufacturing industry from the perspective of collaborative emissions reduction: Evidence from China]]> https://www.researchpad.co/product?articleinfo=Nbe165fed-3c05-4b65-8891-344b36e27456

Equipment manufacturing industry is one of the major industries of the Chinese economy. Previous researches have revealed that the industry has dilemmas of unreasonable industrial structure and high pollution. Using the data of 30 provinces in 2006-2015 in China, this study calculated a comprehensive pollution indicator when estimating the possible pollution reduction brought by the optimization of industrial structure and then evaluated the reasonable level of capital allocation of provinces and industries by using the methods of nonlinear programming and stochastic frontier method. Under the target of collaborative emission reduction, the results show that the optimized output of China’s equipment manufacturing industry could be increased by 5.42%, the energy intensity could be reduced by about 10.4%, and the comprehensive emission intensity could be reduced by about 7.47%. Due to the industry heterogeneity and regional heterogeneity, industrial capacity should be transferred between industries and regions. Since the capital investment in the equipment manufacturing industry is significantly mismatched between industries and regions, the capital allocation of provincial industries in China needs to be adjusted properly. This study provides theoretically and practically reference for collaborative pollution reduction, industry restructure, spatial layout and capital investment, which contributes to achieving the stereoscopic optimization of equipment manufacturing industry.

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<![CDATA[Extending thermotolerance to tomato seedlings by inoculation with SA1 isolate of Bacillus cereus and comparison with exogenous humic acid application]]> https://www.researchpad.co/product?articleinfo=N5b151d82-6b14-4a7f-beb8-82f649a56498

Heat stress is one of the major abiotic stresses that impair plant growth and crop productivity. Plant growth-promoting endophytic bacteria (PGPEB) and humic acid (HA) are used as bio-stimulants and ecofriendly approaches to improve agriculture crop production and counteract the negative effects of heat stress. Current study aimed to analyze the effect of thermotolerant SA1 an isolate of Bacillus cereus and HA on tomato seedlings. The results showed that combine application of SA1+HA significantly improved the biomass and chlorophyll fluorescence of tomato plants under normal and heat stress conditions. Heat stress increased abscisic acid (ABA) and reduced salicylic acid (SA) content; however, combined application of SA1+HA markedly reduced ABA and increased SA. Antioxidant enzymes activities revealed that SA1 and HA treated plants exhibited increased levels of ascorbate peroxidase (APX), superoxide dismutase (SOD), and reduced glutathione (GSH). In addition, heat stress markedly reduced the amino acid contents; however, the amino acids were increased with co-application of SA1+HA. Similarly, inductively-coupled plasma mass-spectrometry results showed that plants treated with SA1+HA exhibited significantly higher iron (Fe+), phosphorus (P), and potassium (K+) uptake during heat stress. Heat stress increased the relative expression of SlWRKY33b and autophagy-related (SlATG5) genes, whereas co-application of SA1+HA augmented the heat stress response and reduced SlWRKY33b and SlATG5 expression. The heat stress-responsive transcription factor (SlHsfA1a) and high-affinity potassium transporter (SlHKT1) were upregulated in SA1+HA-treated plants. In conclusion, current findings suggest that co-application with SA1+HA can be used for the mitigation of heat stress damage in tomato plants and can be commercialized as a biofertilizer.

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<![CDATA[A multiproducer microbiome generates chemical diversity in the marine sponge Mycale hentscheli]]> https://www.researchpad.co/product?articleinfo=N09e84a7f-8bd9-43bc-ab75-8afaa59bc07e

Significance

Sponges, one of the oldest extant animal phyla, stand out among marine organisms as sources of structurally diverse bioactive natural products. Previous work on chemically rich sponges identified single “superproducer” symbionts in their microbiomes that generate the majority of the bioactive compounds known from their host. Here, we present a contrasting scenario for the New Zealand sponge Mycale hentscheli in which a multiproducer consortium is the basis of chemical diversity. Other than the known cocktail of cytotoxins, metagenomic and functional data support further chemical diversity originating from various uncultivated bacterial lineages. The results provide a rationale for distinct patterns of chemical variation observed within sponge species and reinforce uncultured microbes as promising source of compounds with therapeutic potential.

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<![CDATA[Holographic virtual staining of individual biological cells]]> https://www.researchpad.co/product?articleinfo=Nbd81fa3e-bc5c-48be-b4f7-28e8153fbda6

Significance

We present a method for virtual staining for morphological analysis of individual biological cells based on stain-free digital holography, allowing clinicians and biologists to visualize and analyze the cells as if they have been chemically stained. Our approach provides numerous advantages, as it 1) circumvents the possible toxicity of staining materials, 2) saves time and resources, 3) optimizes inter- and intralab variability, 4) allows concurrent staining of different types of cells with multiple virtual stains, and 5) provides ideal conditions for real-time analysis, such as rapid stain-free imaging flow cytometry. The proposed method is shown to be accurate, repeatable, and nonsubjective. Hence, it bears great potential to become a common tool in clinical settings and biological research.

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<![CDATA[Redefining the heterogeneity of peripheral nerve cells in health and autoimmunity]]> https://www.researchpad.co/product?articleinfo=Nf11306cd-b1fa-4dea-b8f8-c518a6d7fffd

Significance

We here present a transcriptional map of peripheral nerve cells in health and autoimmunity. Identified marker genes of nonmyelinating Schwann cells and nerve-associated fibroblasts will facilitate a better understanding of the complex cellular architecture of peripheral nerves. The two distinct populations of nerve-resident homeostatic myeloid cells suggest an unexpectedly unique and heterogeneous local immune repertoire in peripheral nerves with signs of heterogeneous ontogenetic origin. Complex changes of local cell–cell communication networks indicate autoimmune neuritis as a disease affecting “immune networks” rather than single cell types. The findings also suggest that immunological features are partially shared and conserved across different parts of the nervous system.

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<![CDATA[Cavitation in soft matter]]> https://www.researchpad.co/product?articleinfo=Nd0a93384-098b-4855-abf9-29f74edc2c6d

Cavitation is the sudden, unstable expansion of a void or bubble within a liquid or solid subjected to a negative hydrostatic stress. Cavitation rheology is a field emerging from the development of a suite of materials characterization, damage quantification, and therapeutic techniques that exploit the physical principles of cavitation. Cavitation rheology is inherently complex and broad in scope with wide-ranging applications in the biology, chemistry, materials, and mechanics communities. This perspective aims to drive collaboration among these communities and guide discussion by defining a common core of high-priority goals while highlighting emerging opportunities in the field of cavitation rheology. A brief overview of the mechanics and dynamics of cavitation in soft matter is presented. This overview is followed by a discussion of the overarching goals of cavitation rheology and an overview of common experimental techniques. The larger unmet needs and challenges of cavitation in soft matter are then presented alongside specific opportunities for researchers from different disciplines to contribute to the field.

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<![CDATA[Psychometric characteristics and factorial structures of the Defensive Pessimism Questionnaire—Spanish Version (DPQ-SV)]]> https://www.researchpad.co/product?articleinfo=Nb6dcc03f-c5ae-4fce-8b03-b30a02ab227b

The aim of this study was to validate the Spanish version of the Defensive Pessimism Questionnaire. A sample of undergraduate students (N = 539) was measured on defensive pessimism using the Defensive Pessimism Questionnaire (DPQ), optimism and pessimism using the Life Orientation Test (LOT), positive and negative affect using the Positive and Negative Affect Schedule, and anxiety using the trait subscale of the State and Trait Anxiety Inventory. A Spanish version of the DPQ (DPQ-SV) is presented. Exploratory and Robust Confirmatory Factor Analysis had a bi-dimensional structure (Reflectivity and Negative Expectation). Omega coefficient showed a high internal consistency and the temporal stability was high in each dimension. Both DPQ-SV subscales (Negative Expectation and Reflectivity) showed adequate convergence with LOT-optimism and LOT-pessimism. Reflectivity showed adequate criterion validity with trait-anxiety and negative affect, but inadequate criterion validity with positive affect. Negative Expectation showed excellent criterion validity with trait-anxiety and negative affect and good criterion validity with positive affect. Finally, mediation analysis showed that Negative Expectation had a significant indirect mediating effect between trait-anxiety and negative affect. Reflectivity had a significant indirect mediating effect between trait-anxiety and negative and positive affect. Analysis of the psychometric properties of the DPQ-SV subscale scores showed that it is a two factor adequate measurement tool for its use in this type of samples.

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<![CDATA[Understanding ambivalence in help-seeking for suicidal people with comorbid depression and alcohol misuse]]> https://www.researchpad.co/product?articleinfo=N5bd48253-819c-499c-aeec-83c12fc90159

Help-seeking prior to a suicide attempt is poorly understood. Participants were recruited from a previous research trial who reported a history of suicidal behaviours upon follow-up. Qualitative interviews were conducted with six adults to understand their lived experience of a suicide attempt and the issues affecting help-seeking prior to that attempt. Participants described being aware of personal and professional supports available; however, were ambivalent about accessing them for multiple reasons. This paper employs an ecological systems framework to better understand the complex and multi-layered interpersonal, societal and cultural challenges to help-seeking that people with suicidal ideation can experience.

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<![CDATA[Citrate lyase CitE in Mycobacterium tuberculosis contributes to mycobacterial survival under hypoxic conditions]]> https://www.researchpad.co/product?articleinfo=N5c16b8fb-2363-48af-bce8-dbbca8329b25

Mycobacterium tuberculosis is the causative agent of tuberculosis and has evolved an ability to survive in hostile host environments. M. tuberculosis is thought to utilize the rTCA cycle to sustain its latent growth during infection, but the enzymatic characteristics and physiological function for the key citrate lyase of the rTCA cycle, MtbCitE, in the important pathogen remain unclear. In this study, we investigated the function of MtbCitE based on its structural properties and sequence comparisons with other bacterial citrate lyase subunits. We showed that several amino acid residues were important for the citrate cleavage activity of MtbCitE. Strikingly, the citrate cleavage activity of MtbCitE was inhibited by ATP, indicating that energy metabolism might couple with the regulation of MtbCitE activity, which differed from other CitEs. More interestingly, deletion of citE from Mycobacterium bovis BCG decreased the mycobacterial survival rate under hypoxic conditions, whereas complementation with citE restored the phenotype to wild-type levels. Consistently, three key rTCA cycle enzymes were positively regulated under hypoxic conditions in mycobacteria. Therefore, we characterized a unique citrate lyase MtbCitE from M. tuberculosis and found that the CitE protein significantly contributed to mycobacterial survival under hypoxic conditions.

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<![CDATA[Investigation of synovial fluid induced Staphylococcus aureus aggregate development and its impact on surface attachment and biofilm formation]]> https://www.researchpad.co/product?articleinfo=Nf13f73b5-5132-41b9-b894-3d4dd0a113b1

Periprosthetic joint infections (PJIs) are a devastating complication that occurs in 2% of patients following joint replacement. These infections are costly and difficult to treat, often requiring multiple corrective surgeries and prolonged antimicrobial treatments. The Gram-positive bacterium Staphylococcus aureus is one of the most common causes of PJIs, and it is often resistant to a number of commonly used antimicrobials. This tolerance can be partially attributed to the ability of S. aureus to form biofilms. Biofilms associated with the surface of indwelling medical devices have been observed on components removed during chronic infection, however, the development and localization of biofilms during PJIs remains unclear. Prior studies have demonstrated that synovial fluid, in the joint cavity, promotes the development of bacterial aggregates with many biofilm-like properties, including antibiotic resistance. We anticipate these aggregates have an important role in biofilm formation and antibiotic tolerance during PJIs. Therefore, we sought to determine specifically how synovial fluid promotes aggregate formation and the impact of this process on surface attachment. Using flow cytometry and microscopy, we quantified the aggregation of various clinical S. aureus strains following exposure to purified synovial fluid components. We determined that fibrinogen and fibronectin promoted bacterial aggregation, while cell free DNA, serum albumin, and hyaluronic acid had minimal effect. To determine how synovial fluid mediated aggregation affects surface attachment, we utilized microscopy to measure bacterial attachment. Surprisingly, we found that synovial fluid significantly impeded bacterial surface attachment to a variety of materials. We conclude from this study that fibrinogen and fibronectin in synovial fluid have a crucial role in promoting bacterial aggregation and inhibiting surface adhesion during PJI. Collectively, we propose that synovial fluid may have conflicting protective roles for the host by preventing adhesion to surfaces, but by promoting bacterial aggregation is also contributing to the development of antibiotic tolerance.

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<![CDATA[A new simple brain segmentation method for extracerebral intracranial tumors]]> https://www.researchpad.co/product?articleinfo=Nb837d809-9647-425d-8dfd-2c3174a6dd80

Normal brain segmentation is available via FreeSurfer, Vbm, and Ibaspm software. However, these software packages cannot perform segmentation of the brain for patients with brain tumors. As we know, damage from extracerebral tumors to the brain occurs mainly by way of pushing and compressing while leaving the structure of the brain intact. Three-dimensional (3D) imaging, augmented reality (AR), and virtual reality (VR) technology have begun to be applied in clinical practice. The free medical open-source software 3D Slicer allows us to perform 3D simulations on a computer and requires little user interaction. Moreover, 3D Slicer can integrate with the third-party software mentioned above. The relationship between the tumor and surrounding brain tissue can be judged, but accurate brain segmentation cannot be performed using 3D Slicer. In this study, we combine 3D Slicer and FreeSurfer to provide a novel brain segmentation method for extracerebral tumors. This method can help surgeons identify the “real” relationship between the lesion and adjacent brain tissue before surgery and improve preoperative planning.

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<![CDATA[Uptake and speciation of zinc in edible plants grown in smelter contaminated soils]]> https://www.researchpad.co/product?articleinfo=N21b4cc8f-fdc5-4198-8cfa-2868c1971919

Heavy metal accumulation in edible plants grown in contaminated soils poses a major environmental risk to humans and grazing animals. This study focused on the concentration and speciation of Zn in different edible plants grown in soils contaminated with smelter wastes (Spelter, WV, USA) containing high levels of the metals Zn, Cu, Pb, Cd. Their accumulation was examined in different parts (roots, stem, and leaves) of plants and as a function of growth stage (dry seed, sprouting seed, cotyledon, and leaves) in the root vegetables radish, the leafy vegetable spinach and the legume clover. Although the accumulation of metals varied significantly with plant species, the average metal concentrations were [Zn] > [Pb] > [Cu] > [Cd]. Metal uptake studies were complemented with bulk and micro X-ray absorption spectroscopy (XAS) at Zn K-edge and micro X-ray fluorescence (μXRF) measurements to evaluate the speciation and distribution of Zn in these plant species. Dynamic interplay between the histidine and malate complexation of Zn was observed in all plant species. XRF mapping of spinach leaves at micron spatial resolution demonstrated the accumulation of Zn in vacuoles and leaf tips. Radish root showed accumulation of Zn in root hairs, likely as ZnS nanoparticles. At locations of high Zn concentration in spinach leaves, μXANES suggests Zn complexation with histidine, as opposed to malate in the bulk leaf. These findings shed new light on the dynamic nature of Zn speciation in plants.

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<![CDATA[‘In search of lost time’: Identifying the causative role of cumulative competition load and competition time-loss in professional tennis using a structural nested mean model]]> https://www.researchpad.co/product?articleinfo=N4f3da08e-598e-44d5-a4f3-a2c64fcebd1f

Injury prevention is critical to the achievement of peak performance in elite sport. For professional tennis players, the topic of injury prevention has gained even greater importance in recent years as multiple of the best male players have been sidelined owing to injury. Identifying potential causative factors of injury is essential for the development of effective prevention strategies, yet such research is hampered by incomplete data, the complexity of injury etiology, and observational study biases. The present study attempts to address these challenges by focusing on competition load and time-loss to competition—a completely observable risk factor and outcome—and using a structural nested mean model (SNMM) to identify the potential causal role of cumulative competition load on the risk of time-loss. Using inverse probability of treatment weights to balance exposure histories with respect to player ability, past injury, and consecutive competition weeks at each time point; the SNMM analysis of 389 professional male players and 55,773 weeks of competition found that total load significantly increases the risk of time-loss (HR = 1.05 per 1,000 games of additional load 95% CI 1.01-1.10) and this effect becomes magnified with age. Standard regression showed a protective effect of load, highlighting the value of more robust causal methods in the study of dynamic exposures and injury in sport and the need for further applications of these methods for understanding how time-loss and injuries of elite athletes might be prevented in the future.

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<![CDATA[Influence of the tubular network on the characteristics of calcium transients in cardiac myocytes]]> https://www.researchpad.co/product?articleinfo=N7f446290-780e-4486-a1de-95187c6060a1

Transverse and axial tubules (TATS) are an essential ingredient of the excitation-contraction machinery that allow the effective coupling of L-type Calcium Channels (LCC) and ryanodine receptors (RyR2). They form a regular network in ventricular cells, while their presence in atrial myocytes is variable regionally and among animal species We have studied the effect of variations in the TAT network using a bidomain computational model of an atrial myocyte with variable density of tubules. At each z-line the t-tubule length is obtained from an exponential distribution, with a given mean penetration length. This gives rise to a distribution of t-tubules in the cell that is characterized by the fractional area (F.A.) occupied by the t-tubules. To obtain consistent results, we average over different realizations of the same mean penetration length. To this, in some simulations we add the effect of a network of axial tubules. Then we study global properties of calcium signaling, as well as regional heterogeneities and local properties of sparks and RyR2 openings. In agreement with recent experiments in detubulated ventricular and atrial cells, we find that detubulation reduces the calcium transient and synchronization in release. However, it does not affect sarcoplasmic reticulum (SR) load, so the decrease in SR calcium release is due to regional differences in Ca2+ release, that is restricted to the cell periphery in detubulated cells. Despite the decrease in release, the release gain is larger in detubulated cells, due to recruitment of orphaned RyR2s, i.e, those that are not confronting a cluster of LCCs. This probably provides a safeguard mechanism, allowing physiological values to be maintained upon small changes in the t-tubule density. Finally, we do not find any relevant change in spark properties between tubulated and detubulated cells, suggesting that the differences found in experiments could be due to differential properties of the RyR2s in the membrane and in the t-tubules, not incorporated in the present model. This work will help understand the effect of detubulation, that has been shown to occur in disease conditions such as heart failure (HF) in ventricular cells, or atrial fibrillation (AF) in atrial cells.

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<![CDATA[LoAdaBoost: Loss-based AdaBoost federated machine learning with reduced computational complexity on IID and non-IID intensive care data]]> https://www.researchpad.co/product?articleinfo=Na533cb35-b26a-447b-bd62-8e125a165db4

Intensive care data are valuable for improvement of health care, policy making and many other purposes. Vast amount of such data are stored in different locations, on many different devices and in different data silos. Sharing data among different sources is a big challenge due to regulatory, operational and security reasons. One potential solution is federated machine learning, which is a method that sends machine learning algorithms simultaneously to all data sources, trains models in each source and aggregates the learned models. This strategy allows utilization of valuable data without moving them. One challenge in applying federated machine learning is the possibly different distributions of data from diverse sources. To tackle this problem, we proposed an adaptive boosting method named LoAdaBoost that increases the efficiency of federated machine learning. Using intensive care unit data from hospitals, we investigated the performance of learning in IID and non-IID data distribution scenarios, and showed that the proposed LoAdaBoost method achieved higher predictive accuracy with lower computational complexity than the baseline method.

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<![CDATA[Impact of law enforcement and increased traffic fines policy on road traffic fatality, injuries and offenses in Iran: Interrupted time series analysis]]> https://www.researchpad.co/product?articleinfo=N9254ca97-b759-40e9-8001-23227e05911a

Background

Road traffic law enforcement was implemented on 1st April 2011 (the first intervention) and traffic ticket fines have been increased on 1st March 2016 (the second intervention) in Iran. The aim of the current study was to evaluate the effects of the law enforcement on reduction in the incidence rate of road traffic fatality (IRRTF), the incidence rate of road traffic injuries (IRRTI) and the incidence rate of rural road traffic offenses (IRRRTO) in Iran.

Methods

Interrupted time series analysis was conducted to evaluate the impact of law enforcement and increased traffic tickets fines. Monthly data of fatality on urban, rural and local rural roads, injuries with respect to gender and traffic offenses namely speeding, illegal overtaking and tailgating were investigated separately for the period 2009–2016.

Results

Results showed a reduction in the incidence rate of total road traffic fatality (IRTRTF), the incidence rate of rural road traffic fatality (IRRRTF) and the incidence rate of urban road traffic fatality (IRURTF) by –21.44% (–39.3 to –3.59, 95% CI), –21.25% (–31.32 to –11.88, 95% CI) and –26.75% (–37.49 to –16, 95% CI) through the first intervention which resulted in 0.383, 0.255 and 0.222 decline in casualties per 100 000 population, respectively. Conversely, no reduction was found in the incidence rate of local rural road traffic fatality (IRLRRTF) and the IRRTI. Second intervention was found to only affect the IRURTF with –26.75% (–37.49 to –16, 95% CI) which led to 0.222 casualties per 100 000 population. In addition, a reduction effect was observed on the incidence rate of illegal overtaking (IRIO) and the incidence rate of speeding (IRS) with –42.8% (–57.39 to –28.22, 95% CI) and –10.54% (–21.05 to –0.03, 95% CI which implied a decrease of 415.85 and 1003.8 in monthly traffic offenses per 100 000 vehicles), respectively.

Conclusion

Time series analysis suggests a decline in IRTRTF, IRRRTF, and IRURTF caused by the first intervention. However, the second intervention found to be only effective in IRURTF, IRIO, and IRS with the implication that future initiatives should be focused on modifying the implementation of the traffic interventions.

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<![CDATA[Towards understanding the antagonistic activity of phytic acid against common foodborne bacterial pathogens using a general linear model]]> https://www.researchpad.co/product?articleinfo=Nee28f4e6-a119-4233-a9a2-0c085b39343b

The increasing challenge of antibiotic resistance requires not only the discovery of new antibiotics, but also the development of new alternative approaches. Therefore, in the present study, we investigated for the first time the antibacterial potential of phytic acid (myo-inositol hexakisphosphate, IP6), a natural molecule that is ‘generally recognized as safe’ (FDA classification), against the proliferation of common foodborne bacterial pathogens such as Listeria monocytogenes, Staphylococcus aureus and Salmonella Typhimurium. Interestingly, compared to citric acid, IP6 was found to exhibit significantly greater inhibitory activity (P<0.05) against these pathogenic bacteria. The minimum inhibitory concentration of IP6 varied from 0.488 to 0.97 mg/ml for the Gram-positive bacteria that were tested, and was 0.244 mg/ml for the Gram-negative bacteria. Linear and general models were used to further explore the antibacterial effects of IP6. The developed models were validated using experimental growth data for L. monocytogenes, S. aureus and S. Typhimurium. Overall, the models were able to accurately predict the growth of L. monocytogenes, S. aureus, and S. Typhimuriumin Polymyxin acriflavine lithium chloride ceftazidime aesculin mannitol (PALCAM), Chapman broth, and xylose lysine xeoxycholate (XLD) broth, respectively. Remarkably, the early logarithmic growth phase of S. Typhimurium showed a rapid and severe decrease in a period of less than one hour, illustrating the bactericidal effect of IP6. These results suggest that IP6 is an efficient antibacterial agent and can be used to control the proliferation of foodborne pathogens. It has promising potential for environmentally friendly applications in the food industry, such as for food preservation, food safety, and for prolonging shelf life.

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<![CDATA[Toward precision prescribing for methadone: Determinants of methadone deposition]]> https://www.researchpad.co/product?articleinfo=N51499fe4-a854-40f2-ac0e-5bd2b114360f

Background

Despite the World Health Organization listing methadone as an essential medication, effective dose selection is challenging, especially in racial and ethnic minority populations. Subtherapeutic doses can result in withdrawal symptoms while supratherapeutic doses can result in overdose and death. Although CYP3A4 was conventionally considered the principal methadone metabolizing enzyme, more recent data have identified CYP2B6 as the principal enzyme. CYP2B6 has ethnically-associated polymorphisms that affect the metabolic rate. Our objective was to investigate the effects of genetic and nongenetic factors on methadone metabolism.

Methods

We measured trough plasma methadone levels in 100 participants with opioid use disorder. We assessed methadone metabolism by calculating the metabolite ratio (major metabolite: 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine [EDDP] divided by methadone concentration). We assessed hepatic fibrosis and steatosis by transient elastography and CYP2B6 alleles, principally responsible for methadone metabolism. Mixed effects models modeled the data in 97 participants.

Results

Participants were largely male (58%), minority (61% African American) and non-Hispanic (68%). Forty percent were HCV mono-infected, 40% were uninfected, and 20% were HCV/HIV co-infected. Female sex had significant effects on (R)- and (S)-methadone metabolism (p = 0.016 and p = 0.044, respectively). CYP2B6 loss of function (LOF) alleles significantly affected (S)-methadone metabolism (p = 0.012). Body mass index (BMI) significantly affected (R)-methadone metabolism (p = 0.034). Methadone metabolism appeared to be lower in males, in individuals with LOF alleles, and elevated BMI.

Conclusions

Genetic analysis, especially in minority populations, is essential to delivering individualized treatments. Although the principal methadone metabolizing enzyme remains controversial, our results suggest that sex, CYP2B6 genotype, and BMI should be incorporated into multivariate models to create methadone dosing algorithms. Methadone dosing algorithms should facilitate medication delivery, improve patient satisfaction, and diminish overdose potential.

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<![CDATA[Chalcone synthase (CHS) family members analysis from eggplant (Solanum melongena L.) in the flavonoid biosynthetic pathway and expression patterns in response to heat stress]]> https://www.researchpad.co/product?articleinfo=N0c4703df-5c43-4557-a077-ba839b092c8d

Enzymes of the chalcone synthase (CHS) family participate in the synthesis of multiple secondary metabolites in plants, fungi and bacteria. CHS showed a significant correlation with the accumulation patterns of anthocyanin. The peel color, which is primarily determined by the content of anthocyanin, is an economically important trait for eggplants that is affected by heat stress. A total of 7 CHS (SmCHS1-7) putative genes were identified in a genome-wide analysis of eggplants (S. melongena L.). The SmCHS genes were distributed on 7 scaffolds and were classified into 3 clusters. Phylogenetic relationship analysis showed that 73 CHS genes from 7 Solanaceae species were classified into 10 groups. SmCHS5, SmCHS6 and SmCHS7 were continuously down-regulated under 38°C and 45°C treatment, while SmCHS4 was up-regulated under 38°C but showed little change at 45°C in peel. Expression profiles of key anthocyanin biosynthesis gene families showed that the PAL, 4CL and AN11 genes were primarily expressed in all five tissues. The CHI, F3H, F3’5’H, DFR, 3GT and bHLH1 genes were expressed in flower and peel. Under heat stress, the expression level of 52 key genes were reduced. In contrast, the expression patterns of eight key genes similar to SmCHS4 were up-regulated at a treatment of 38°C for 3 hour. Comparative analysis of putative CHS protein evolutionary relationships, cis-regulatory elements, and regulatory networks indicated that SmCHS gene family has a conserved gene structure and functional diversification. SmCHS showed two or more expression patterns, these results of this study may facilitate further research to understand the regulatory mechanism governing peel color in eggplants.

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