Intrinsic Potential Research Articles

Alterations Due to Heat Shock in Biological and Commercial Features of the Silkworm, Bombyx mori

The impact of HS on larval growth and development, ERR, cocoon characteristics and biochemical elements of carbohydrate content was investigated using FC2 X FC1 bivoltine hybrid silkworm breed. On the third day of the fifth instar, the FC2 X FC1 bivoltine hybrid was treated to HS at 30, 35, 40 and 45ºC for 1 h with 1 h retrieval. Following that, silkworms were maintained in the rearing house under naturally fluctuating environmental circumstances in order to assess their intrinsic potentiality for overcoming temperature changes and producing cocoons in contrast to non-HS B. mori larvae. At 40°C, the biological and commercial features gained the most weight. As a result, although all larvae heat shocked at 35 and 40°C metamorphosed into pupae with better growth than controls, the fifth instar showed the greatest improvement in it. However, heat shock temperature of 45˚C was lethal since all the biological and commercial characters were severely affected in all instars. Thus, temperatures of 40°C should be considered when screening for better parents to develop thermotolerant breeds/hybrids for tropical countries such as India, in order to elicit a profound response and acquire tolerance to overcome the fluctuated environmental condition. Both control and HS showed a sequential increase in carbohydrate content but found declined upon HS of 45˚C.

An Adjuvant-Free Mouse Model Using Skin Sensitization Without Tape-Stripping Followed by Oral Elicitation of Anaphylaxis: A Novel Pre-Clinical Tool for Testing Intrinsic Wheat Allergenicity.

Wheat is a major food allergen per the regulatory bodies of various nations. Hypersensitivity reactions to wheat have been steadily increasing for reasons that are not completely understood. Wheat-allergy models typically use adjuvants to induce sensitization to wheat proteins followed by an intraperitoneal challenge to elicit anaphylaxis. Although these models are very useful, they lack the ability to reveal the intrinsic allergenicity potential of wheat. To improve the mouse model of wheat allergy, we tested the hypothesis that repeated skin application of salt-soluble protein extract (SSPE) from durum wheat will clinically sensitize the mice to oral anaphylaxis to SSPE. Balb/c mice were bred and maintained on a plant-protein-free diet and used in the experiments. Adult female mice were exposed to SSPE once a week for 9 weeks via a solution on intact skin. Sensitization was measured by SSPE-specific IgE (sIgE) antibody and total IgE (tIgE) levels. Oral anaphylaxis was quantified by hypothermic shock response (HSR), and mucosal mast cell response (MMCR) was quantified by measuring MMCP-1 after oral challenge. Using single mouse data, correlation analyses were performed to determine the relationship among the allergenicity readouts. Spleen cytokines were quantified using a protein microarray method. Our results show that (i) repeated skin exposures to SSPE elicited robust increases in the sIgE and tIgE levels; (ii) skin exposure to SSPE was sufficient to sensitize mice for oral anaphylaxis and MMCR; (iii) both HSR and MMCR showed a strong correlation with each other, as well as with sIgE, and a modest correlation with tIgE levels; (iv) selected Th2/Th17/Th1 cytokines were elevated in skin-sensitized mice; and (v) oral allergen-challenged mice showed selective elevation of IL-6 and a panel of chemokines compared to saline-challenged mice. Together, we report the development and characterization of a novel adjuvant-free wheat-allergy mouse model that uses skin sensitization without tape-stripping followed by oral elicitation of anaphylaxis. Furthermore, validation of quantifiable wheat allergenicity readouts makes this model particularly suitable as a pre-clinical testing tool to assess the intrinsic sensitization/oral-anaphylaxis elicitation potential of novel wheat proteins (e.g., processed wheat) and to develop hypo/non-allergenic wheat products.

Trained Immunity of IL-12-, IL-15-, and IL-18-Induced CD3+CD56+ NKT-Like Cells.

CD3+CD56+ natural killer T (NKT)-like cells have an immune function of T cells and NK cells, which play an important role in antitumor and antiviral immune responses. This study aims to establish a CD3+CD56+ NKT-like cell model by simulating the memory NK effect induced by cytokines IL-12, IL-15, and IL-18 (IL-12/15/18) and explore the formation mechanism. Our study found that the IL-12/15/18 preactivated CD3+CD56+ NKT-like cells exhibited enhanced IFN-γ production in response to restimulation with IL-12/15/18 for 6h on day 7. The intrinsic potential of these trained cells was significantly improved, showing an increase in IFN-γ, TNF-α, and cell proliferation potential. The IFN-γ release, granzyme B level, and proliferation ability significantly increased when stimulated by NK-cell-sensitive K562 tumor cells. Among these cytokines, the combination of IL-12/15/18 was particularly effective. After the preactivation of IL-12/15/18, some cell surface proteins related to function and differentiation, such as CD11b, CD62 L, NKp46, NKG2A, and CD127, showed an evident and consistent change trend. The CDK4/6 inhibitor can effectively weaken this effect, and the expression of cyclin D1, Rb protein phosphorylation, and E2F-1 decreased significantly. Our work revealed that cytokine IL-12/15/18 can induce CD3+CD56+ NKT-like cells to obtain enhanced training immunity, which was a memory-like phenomenon.

Structural rigidity theory applied to the scaffold-free (dis)assembly of space frames using cooperative robotics

This paper presents a fabrication-informed design method for triangulated space frame structures that remain stable during all phases of their robotic assembly and disassembly without requiring external scaffolding. A graph theoretic framework, based on rigidity theory, is developed to allow the structure, its support conditions, and the impact of robotic support constraints to be simultaneously represented in a single topological framework. The structural system is sequentially designed with an assembly logic based on Henneberg graph-construction steps, which are executed with two robots through a cooperative rigidity-preserving sequence. Ensuring planarity of the resulting graph during these construction steps is shown to lead to intrinsic disassembly potentials within the system. A graph-based algorithm is presented to locate, isolate and remove locally rigid tetrahedral cells formed in the structural system. This algorithm is then utilized to compute a rigidity-preserving robotic disassembly sequence. The design method is demonstrated in the case study design of a wooden space frame arch structure that is robotically (dis)assembled.

Molecular dynamics study on sodium chloride solution transport through the Calcium-Silicate-Hydrate nanocone channel

As the main hydration product of concrete materials, calcium silicate hydrate (CSH) determines the service life of the concrete. In this work, molecular dynamics was employed to investigate the transport of water and ions in the CSH nanocone pores which cause the deterioration of the internal components of the concrete. The simulation results show that the advanced frontier of NaCl solution flow inside the CSH capillary shows a concave meniscus shape, which reflects the hydrophilic properties of the CSH substrate. The ions migration rate is slower than water molecular in the CSH nanocone channel. The local structure of ions and the distributions of intrinsic electrostatic potential along the nanocone channel were analyzed to elucidate the migration discrepancy. The adsorption of ions on the CSH substrate, the formation of ions clusters in the CSH nanocone, and the tip blocking of CSH nanocone on ions migration are responsible for the transport discrepancy between water and ions. Besides, the effect of inclination angles of CSH substrate on the transport behavior was also investigated. With increasing inclination angles, the tip blocking becomes stronger, and the penetration transport discrepancy between water and ions becomes starker and more manifest. This work provides fundamental insight into the transport behavior of liquid in the gel pores of a cement-based material.

P.104 Beyond the hippocampus and the SVZ: adult neurogenesis throughout the brain

Background: Adult neurogenesis occurs in the hippocampus and the subventricular zone. Recent evidence suggests that neurogenesis may also extend to other brain regions (hypothalamus, striatum, substantia nigra, cortex, and amygdala). Harnessing this intrinsic neurogenic potential may present a novel alternative for the replenishment of neurons lost in neurologic conditions. Methods: This descriptive review summarizes evidence supporting the classic and novel neurogenic zones present within the mammalian brain, discusses the functional significance of these new neurons, and the potential clinical applications of promoting intrinsic neurogenesis. Results: Some studies suggest new neurons originate from endogenous stem cell pools located within novel neurogenic regions while others show the migration from the subventricular zone to these regions. Regardless, adult neurogenesis is impacted by neurologic processes such as ischemia and neurodegenerative diseases and can be modulated by factors including neurotrophins, pharmacologic interventions, environmental exposures, exercise, and stem cell therapy. Conclusions: The discovery of functionally significant neurogenesis in adult brain regions has implications not only with regards to the function of these regions, but also for neuropathological conditions that affect them. Pharmacologic and stem cell-based strategies capable of promoting neurogenesis may have therapeutic potential following stroke or in the context of various neurodegenerative disorders.

Flood Risk Management by Community Stakeholders: A Malaysian Case Study

Local knowledge has long been considered inferior to scientific knowledge. However, local knowledge has often assisted where scientific knowledge proved inadequate to solve the complexity of environmental issues. Scientific knowledge—despite being recognised as superior in various fields due to universal testing and approval—sometimes fails to accommodate what local communities manage to solve. This happens to both local and scientific knowledge if discrete views are followed. Therefore, instead of competing with each other’s knowledge capabilities, they should be viewed as complementary. Different stakeholders hold different types of knowledge in their area of interest and both knowledge streams have their intrinsic potentials and limitations. In this paper, the issue of knowledge complementarity is explored in the context of flood hazards. Hazards such as floods may appear messy, and unpredictable, with unsorted and unorganised forms of data, information, and knowledge on the part of diverse stakeholders. Thus, this paper presents a research case study on multiple stakeholders in the district of Pekan, the state of Pahang, Malaysia, and how these multiple stakeholders manage flood hazards with their different types of knowledge. This case study uses Malay, Orang Asli, and humanitarian organisations in the Pekan district as the stakeholder groups. The research has led to the development of a conceptual framework based on the case study. The local knowledge by Orang Asli and Melayu as well as scientific knowledge by the humanitarian organisations have been categorized into mitigation, preparedness, response, and recovery. The lessons learned from the framework are discussed, together with the barriers to their implementation. Through the conceptual framework, interventions used and the roles of the key person in each of the stakeholders also have been highlighted.

Biochemical Analyses of Ten Cyanobacterial and Microalgal Strains Isolated from Egyptian Habitats, and Screening for Their Potential against Some Selected Phytopathogenic Fungal Strains

Microalgae and cyanobacteria are rich sources of numerous phytochemical compounds with intrinsic antifungal potential. This research aimed to screen the phytochemical compounds and contents, as well as the antioxidant profiles, in eight cyanobacterial and two microalgal strains isolated from soil and brackish water habitats in Egypt. Our study also evaluated their antifungal activities against three phytopathogenic fungi—namely, Pythium ultimum, Fusarium solani, and Botryodiplodia theobromae, which are known to cause severe plant loss. The biochemical compounds were obtained from the cyanobacterial and algal methanolic extracts, and were identified through comparative phytochemical analyses related to the inhibition of the fungal pathogens. Comparative qualitative analyses of alkaloids, steroids, glycosides, and saponins were also carried out. The quantitative phytochemical screening of the cyanobacterial and algal strains investigated revealed the presence of xylanase, glucanase, and chitinase enzymes, along with some bioactive compounds, such as phenolics, flavonoids, proteins, neutral sugars, and carotenoids, which were species-dependent and detected in variable amounts in the extracts. The unicellular green microalgal strain Dunaliella sp. HSSASE13 displayed the highest level of antioxidant activity. However, the highest antifungal activities were shown by the heterocystous cyanobacterial strain Anabaena sp. HSSASE11 (83.94%), followed by Dunaliella sp. HSSASE13 (81.94%) and the non-heterocystous cyanobacterial strain Oscillatoria nigro-viridis HSSASE 15 (63.42%), against the three fungal pathogens B. theobromae, F. solani, and P. ultimum, respectively. Our results indicate that the highest significant and positive correlations of flavonoids (r = 0.854), phenolics (r = 0.785), DPPH scavenging activity (r = 0.876), total proteins (r = 0.808), xylanase activity (r = 0.876), glucanase activity (r = 0.746), and total neutral sugars (r = 0.764), in terms of their antifungal activities, were recorded against F. solani. Conclusively, the cyanobacterial and algal strains tested in the present study can be useful agents for the management and biocontrol of plant-infecting fungal pathogens.

Oxidative potential and in vitro toxicity of particles generated by pyrotechnic smokes in human small airway epithelial cells

Pyrotechnic smokes are widely used in civilian and military applications. The major issue arise from the release of particles after smoke combustion but the health risks related to their exposure are poorly documented whereas toxicity of airborne particles on the respiratory target are very well known. Therefore, this study aimed to explore the in vitro toxicity of the particle fraction of different pyrotechnic smokes.Particles from a red signalling smoke (RSS), an hexachloroethane-based obscuring smoke (HC-OS) and an anti-intrusion smoke (AIS) were collected from the cloud. RSS particles displayed the highest organic fraction (quinones and polycyclic aromatic hydrocarbons) of the three samples characterized. AIS particles contained K and cholesterol derivatives. HC-OS particles were mainly metallic with very high concentrations of Al, Fe and Ca. Intrinsic oxidative potential of smoke particles was measured with two assays. Depletions of DTT by RSS particles was greater than depletion obtained with AIS and HC-OS particles but depletion of acid ascorbic (AA) was only observed with HC-OS particles. In vitro toxicity was assessed by exposing human small airway epithelial cells (SAEC) to various concentrations of particles. After 24 h of exposure, cell viability was not affected but significant modifications of mRNA expression of antioxidant (SOD-1 and -2, catalase, HO-1, NQO-1) and inflammatory markers (IL-6, IL-8, TNF-α) were observed and were dependent on smoke type. Particles rich in metal, such as HC-OS, induced a greatest depletion of AA and a greatest inflammatory response, whereas particles rich in organic compounds, such as RSS, induced a greatest DTT depletion and a greatest antioxidant response.In conclusion, the three smoke particles have an intrinsic oxidative potential and triggered a cell adaptive response. Our study improved the knowledge of particle toxicity of pyrotechnic smokes and scientific approach developed here could be used to study other type of particles.

Molecular View on the Impact of DHA Molecules on the Physical Properties of a Model Cell Membrane.

Docosahexaenoic acid (DHA) is a ω-3 polyunsaturated fatty acid, which can be uptaken by cells and is essential for proper neuronal and retinal function. However, the detailed physical impact of DHA molecules on the plasma membrane is still unclear. Hence, in this work, we carried out μs-scale coarse-grained molecular dynamics (MD) simulations to reveal the interactions between DHA molecules and a model cell membrane. As is known, the cell membrane can segregate into liquid-ordered (Lo) and liquid-disordered (Ld) membrane domains due to the differential interactions between lipids and proteins. In order to capture this feature, we adopted the three-component phase-separated lipid membranes and considered both anionic and neutral DHA molecules in the current work. Our results showed that DHA molecules can spontaneously self-assemble into nanoclusters, fuse with lipid membranes, and localize preferably in Ld membrane domains. During the membrane fusion process, DHA molecules can change the intrinsic transmembrane potential of the lipid membrane, and the effects of anionic DHA molecules are much more significant. Besides, the presence of DHA molecules mainly in the Ld membrane domains could regulate the differences in the lipid chain order, membrane thickness, cholesterol preference, and cholesterol flip-flop basically in a concentration-dependent manner, which further promote the stability of the intraleaflet dynamics and inhibit the interleaflet dynamics (or promote membrane domain registration) of the membrane domains. In short, the impact of DHA molecules on the physical properties of a model cell membrane on the molecular level revealed in our work will provide useful insights for understanding the biological functions of DHA molecules.

MO074: SGLT2 Inhibition Promotes Intrinsic Kidney Regeneration by Cells of the Renin Lineage

Abstract BACKGROUND AND AIMS With chronic kidney disease (CKD) prevalence rapidly increasing, the need for novel therapies is rising. Sodium glucose co-transporter-2 (SGLT2) inhibitors were originally developed to treat hyperglycemia in patients with type 2 diabetes mellitus. Clinical trials with the SGLT2 inhibitor empagliflozin revealed a marked attenuation of the slope of kidney function decline, also in patients with non-diabetic CKD. The exact mechanism of this kidney sparing effect still remains to be clarified. Interestingly, cells of renin lineage (CoRL), residing in the juxtaglomerular apparatus to regulate blood pressure and fluid balance, have been demonstrated to harbor a stem cell like potential. CoRL have the ability to replenish glomerular cell number by dedifferentiating, migrating and subsequently replacing various glomerular cell types in different kidney injury mouse models. Considering that empagliflozin treatment affects renin plasma levels and electrolyte balance in patients, we hypothesized that empagliflozin could have an effect on CoRL-induced glomerular regeneration. METHOD Experiments were performed in a Ren1cre; tdTomato lineage-trace mouse strain that expresses a tomato fluorescent label in all cells derived from renin lineage. Two kidney injury mouse models were applied; bilateral ischemia reperfusion injury (bIRI) and 5/6 nephrectomy (5/6NTx). Empagliflozin (10 mg/kg) was administered daily via oral gavage for 14 days. Subsequently, mice were sacrificed and kidneys were harvested for histological analysis. RESULTS In both the bIRI and 5/6NTx model, empagliflozin intake led to an increase (>2-fold) of CoRL found in the intraglomerular regions compared with vehicle control littermates. These CoRL seemed to selectively differentiate towards different glomerular cell types per model: bIRI combined with empagliflozin administration resulted in an increase of claudin- (10-fold) and integrin-α8- (1.5-fold) tomato double positive cells, suggesting favored differentiation from CoRL to respectively a parietal epithelial or mesangial cell type. In contrast, in the empagliflozin treated 5/6NTx model, an increase (1.5-fold) in tomato-podocyn double positive cells was observed, implying more restocking of glomerular podocytes by CoRL in this model. CONCLUSION SGLT2 inhibition by empagliflozin treatment leads to increased CoRL-mediated intrinsic regeneration potential and provides the kidney with different replenished cell types in different kidney disease models. Our findings demonstrate a novel mechanism via which SGLT2 inhibition might protect against kidney injury.

Meniscus Bioprinting Technology Roadmap

Meniscus lesions represent a challenge for medicine in view of the high occurrence, the limited intrinsic regenerative potential of the meniscus and the economic and social impact associated with the restricted results of current treatments. One of the most promising alternatives is the development of meniscus engineered substitutes (MES) through 3D bioprinting. To define strategies for technologies development, processes, and products necessary for MES bioprinting, innovation management and planning tools, such as roadmaps (RMap), can be used. This research aimed to build an RMap to portray the scientific and technological contemporary status related to tissue engineering strategies for bioinks development (BI) for MES bioprinting. For this, the search for scientific publications were carried out in journals (Science Direct, PubMed, and Web Of Science) and patents (Google patents and EspaceNet) using as strings the combination Meniscus AND Scaffold AND Bioprinting AND Tissue Engineering. The search was restricted to original scientific articles and patents published between 2015 and 2021. The selected publications were carefully analyzed to identify the technologies developed (bioprinting process, biomaterials, and cells). The information was compiled and compared with the biomechanical performance criteria of a meniscus, to infer the degree of biomimicry and the potential of each innovation proposal. 9 articles and 4 patents were selected. Except for one publication using the inkjet printing method, all explored the extrusion method. Only 4 of the publications incorporated cellular contingent, predominantly the use of stem cells derived from fat and bone marrow. Regarding biopolymers, polycaprolactone (PCL) predominated, used alone or in association with collagen, gelatin methacrylate, alginate, poly(lactic‐co‐glycolic acid) and decellularized extracellular matrix. It is noteworthy that PCL generates a rigid matrix, technically incompatible with the biomechanical nature of the meniscus. It means that the proposals under development have at least one characteristic that could impede the future use of the under‐development technologies. This finding reinforces the importance of using technological planning techniques to support biotechnology research. The Rmap obtained describes the frontier technologies of BI knowledge for MES bioprinting, showing incompatibility between the MES biomechanical performance characteristics and the properties necessary to achieve faithful biomimicry concerning biological menisci. The expectation is that this Rmap will contribute to the development of new BI strategies, focusing on the selection and/or modification of biomaterials and cells, to achieve the biomimetic performance of MES.

Comparison of sensitizing and disease-eliciting capacities of salt-soluble protein extracts from diploid (einkorn) versus tetraploid (durum) wheats

Abstract Hypersensitivity reactions to wheat have reached significant levels of global public health concern for reasons that are incompletely understood. Einkorn wheat (Triticum monococcum, genome AA) is commercially available but is rarely consumed, whereas durum wheat (Triticum durum, genome AABB) is commonly used for pasta making. At present, most mouse models of wheat allergy are adjuvant-based, which fail to reveal the intrinsic allergenic potential of different wheat products. Here we compared einkorn and durum wheats in terms of their sensitizing and disease-eliciting capacities in an adjuvant-free mouse model of anaphylaxis induced by salt-soluble protein extract (SSPE). Balb/cJ female mice were sensitized transdermally with SSPE or saline for nine weeks. Later, systemic or oral anaphylactic reactions were elicited in these mice using SSPE via intraperitoneal or oral route, respectively. We did not observe major differences in sensitizing capacity as suggested by antibody responses (i.e., sIgE and tIgE levels) in SSPE-sensitized mice. However, SSPE from durum appears to be more potent than that from einkorn in eliciting systemic but not oral anaphylaxis as shown by hypothermic shock responses as well as mucosal mast cell degranulation. This is the first report on comparing the intrinsic allergenicity between tetraploid and diploid wheats in an adjuvant-free mouse model. This research was funded by: the United States Department of Agriculture (USDA)/National Institute of Food and Agriculture (NIFA); Hatch project MICL02486 (Accession Number: 1012322), Hatch project MICL01699; Agricultural and Food Research Initiative Competitive Program, grant number: 2018-67017-27876; and Project GREEEN (Michigan State University); R.J., was supported by the John Harvey Kellogg Graduate Assistantship and the Academic Achievement Graduate Assistantship from the Michigan State University.

Associations of severe adverse perinatal outcomes among continuous birth weight percentiles on different birth weight charts: a secondary analysis of a cluster randomized trial

ObjectiveTo identify neonatal risk for severe adverse perinatal outcomes across birth weight centiles in two Dutch and one international birth weight chart.BackgroundGrowth restricted newborns have not reached their intrinsic growth potential in utero and are at risk of perinatal morbidity and mortality. There is no golden standard for the confirmation of the diagnosis of fetal growth restriction after birth. Estimated fetal weight and birth weight below the 10th percentile are generally used as proxy for growth restriction. The choice of birth weight chart influences the specific cut-off by which birth weight is defined as abnormal, thereby triggering clinical management. Ideally, this cut-off should discriminate appropriately between newborns at low and at high risk of severe adverse perinatal outcomes and consequently correctly inform clinical management.MethodsThis is a secondary analysis of the IUGR Risk Selection (IRIS) study. Newborns (n = 12 953) of women with a low-risk status at the start of pregnancy and that received primary antenatal care in the Netherlands were included.We examined the distribution of severe adverse perinatal outcomes across birth weight centiles for three birth weight charts (Visser, Hoftiezer and INTERGROWTH) by categorizing birth weight centile groups and comparing the prognostic performance for severe adverse perinatal outcomes.Severe adverse perinatal outcomes were defined as a composite of one or more of the following: perinatal death, Apgar score < 4 at 5 min, impaired consciousness, asphyxia, seizures, assisted ventilation, septicemia, meningitis, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, or necrotizing enterocolitis.ResultsWe found the highest rates of severe adverse perinatal outcomes among the smallest newborns (< 3rd percentile) (6.2% for the Visser reference curve, 8.6% for the Hoftiezer chart and 12.0% for the INTERGROWTH chart). Discriminative abilities of the three birth weight charts across the entire range of birth weight centiles were poor with areas under the curve ranging from 0.57 to 0.61. Sensitivity rates of the various cut-offs were also low.ConclusionsThe clinical utility of all three charts in identifying high risk of severe adverse perinatal outcomes is poor. There is no single cut-off that discriminates clearly between newborns at low or high risk.Trial RegistrationNetherlands Trial Register NTR4367.Registration date March 20th, 2014.

Co-targeting B-RAF and PTEN Enables Sensory Axons to Regenerate Across and Beyond the Spinal Cord Injury.

Primary sensory axons in adult mammals fail to regenerate after spinal cord injury (SCI), in part due to insufficient intrinsic growth potential. Robustly boosting their growth potential continues to be a challenge. Previously, we showed that constitutive activation of B-RAF (rapidly accelerated fibrosarcoma kinase) markedly promotes axon regeneration after dorsal root and optic nerve injuries. The regrowth is further augmented by supplemental deletion of PTEN (phosphatase and tensin homolog). Here, we examined whether concurrent B-RAF activation and PTEN deletion promotes dorsal column axon regeneration after SCI. Remarkably, genetically targeting B-RAF and PTEN selectively in DRG neurons of adult mice enables many DC axons to enter, cross, and grow beyond the lesion site after SCI; some axons reach ∼2 mm rostral to the lesion by 3 weeks post-injury. Co-targeting B-RAF and PTEN promotes more robust DC regeneration than a pre-conditioning lesion, which additively enhances the regeneration triggered by B-RAF/PTEN. We also found that post-injury targeting of B-RAF and PTEN enhances DC axon regeneration. These results demonstrate that co-targeting B-RAF and PTEN effectively enhances the intrinsic growth potential of DC axons after SCI and therefore may help to develop a novel strategy to promote robust long-distance regeneration of primary sensory axons.

Distance, Time, Speed &amp; Energy: A Socio-Political Analysis of Technologies of Longer Distance Cycling

The basic laws of motion governing cycling are well understood. Consideration of the variables of energy use in cycle travel is less frequent. The potentials of both aerodynamically efficient cycle design and the augmentation of human power with e-motors dramatically reconfigure what we understand as a cycle and as cycling.The prospect of increasing travel distance in regular journeying, coupled with the logical application of augmentation (aerodynamic and/or power), suggest a need to re-evaluate some of the ground expectations applied in design and planning for cycle travel if the cycles for which infrastructure is designed no longer conform to existing expectations of what a cycle is and how it performs.Current e-bike performance is principally limited by normative legislative intervention, not by the intrinsic potential of the technologies. Existing decisions as to what an e-bike can (and should) be are shaped by the performance expectations of late 19th- and early 20th-century bicycle designs. Shaping modal shift for longer trips returns us to thinking about the place of cycling travel time as a function of the relationship between distance and speed. Increased speed allows for greater distance without time penalty. However, speed is itself governed by available energy, coupled with the efficiency of use of that energy. Without entirely substituting human power, e-motors allow us to augment the human power available in different ways. Changes in cycle design (velomobiles, for example) allow us to increase the efficiency of use of available power in overcoming resistance to movement.Identifying the assemblage of cycle/cyclist as a variable, rather than a determinate object to be accommodated, raises difficult questions for cycling provision, especially in relation to longer distance travel. Drawing on the capacities of already existing technologies of cycling and e-cycling, the paper focuses on the social implications of potentially problematic interactions. It argues that new decisions will need to be made in regard to speed and distance in cycle travel and that the forging of regulations consequent on those fundamentals will substantially shape the potentials and possibilities of modal shift for longer distance cycle travel. What emerges is a politics of longer distance cycling, not simply a set of technical barriers and problems.

Atomic Simulations of (8,0)CNT-Graphene by SCC-DFTB Algorithm

Self-consistent density functional tight binding (SCC-DFTB) approaches were used to study optimized structures, energy, differential charge density, and Mülliken populations for the (8,0) carbon nanotubes (CNTs) connected to the graphene having different topology defects. Based on the calculations, nine seamless (8,0)CNT-graphenes were selected. For these connected systems, geometric configurations of the graphene and nanotubes were characterized, and the nearest neighbor length of C-C atoms and average length were obtained. The intrinsic energy, energy gap, and chemical potential were analyzed, and they presented apparent differences for different connection modes. Differential charge densities of these connection modes were analyzed to present covalent bonds between the atoms. We have also thoroughly analyzed the Mülliken charge transfer among the C atoms at the junctions.

The anharmonicity role of interatomic potential in predicting glass formation

Although many criteria were proposed to predict the glass forming ability (GFA) of alloys, the precise correlation between the minor addition of elements and the glass formation remains a challenge. To solve this problem, we propose a simple parameter α' derived from thermal expansion coefficient based on the details of the intrinsic interatomic potential. It has been found that α' has the capability of precisely predict the changes of GFA, indicating the important role of anharmonicity of atomic vibration in glass formation. This anharmonicity-related parameter α' relates to atomic mobility behavior, and could be well embodied by the competition between characteristic types of clusters in terms of the fragility concept upon the liquid-solid evolution. This work not only helps to uncover atomic and cluster origins of glass formation from interatomic potential, but also provides a novel route to precisely evaluate the effect of minor addition of elements on GFA.

Landscape geomorphology and local‐riverine features influence Broad Whitefish ( Coregonus nasus ) spawning habitat suitability in Arctic Alaska

Landscape-level geomorphic processes influence the spatial and temporal arrangement of fish habitats in freshwater ecosystems and fishes move across riverscapes, selecting a suite of habitats to maximise fitness. Here, we explore the influence of geomorphology on stream channel attributes and assess Broad Whitefish (Coregonus nasus) spawning habitat potential in the Colville River in Arctic Alaska. Using high-resolution digital surface models (5 m2), we quantified the stream network extent and summarised channel habitat attributes continuously across the drainage network. Next, we developed an intrinsic potential (IP) model for Broad Whitefish by using geomorphic channel parameters previously understood to be associated with spawning habitats (channel width, median substrate size and channel braiding) to estimate the potential of streams across the Colville River watershed to provide spawning habitat. Our model results show the majority of habitat with high IP (≥0.6) was located within the braided sections of the main channel, which encompass >1548 km, but only 2% of the total channel network. The IP model was tested by tracking radio-tagged Broad Whitefish using aerial surveys. Prespawn fish moved into the watershed starting mid-July and mostly used habitat with moderate to very high IP in the middle and lower watershed. Several individuals were relocated in smaller multichannels with vegetated bars that contained very low IP (≤0.2), suggesting that other factors, such as hyporheic flow, may also influence spawning habitat selection. Our study demonstrates that IP modelling offers a useful method to quantify spawning habitat potential in data-poor riverscapes, providing useful information for managers to assess potential anthropogenic impacts and develop conservation plans to protect essential Broad Whitefish habitat.

New Geochemical Framework and Geographic Information System Methodologies to Assess Element Occurrence, Persistence, and Mobility in Groundwater and Surface Water

This study presents a geochemical framework and geographic information system (GIS) method for assessing the intrinsic potential of surface water and groundwater to mobilize arsenic, molybdenum, selenium, uranium, and vanadium. The method was created using published groundwater and surface water geochemical data from the National Uranium Resource Evaluation database for 2302 groundwater and 915 surface water samples. The method was evaluated using published groundwater geochemical data from the Texas Water Development Board. Geochemical data were analyzed in GIS. Samples were categorized by environmental condition, which was determined by using reduction–oxidation—as indicated by pe—and pH ranges for each sample based on geochemical mobility frameworks developed by Smith (2007) and Perel’man (1986). Reduction–oxidation and pH influence the occurrence, persistence, and mobility of arsenic, molybdenum, selenium, uranium, and vanadium in groundwater and surface water. Reduction–oxidation categories were assigned to water samples using concentrations of redox-active constituents, including dissolved oxygen, iron, manganese, and sulfur. The presence of iron substrates and hydrogen sulfides were considered in relation to mobility mechanisms. Twelve-digit hydrologic unit code (HUC) boundaries were used in GIS as analysis areas to determine the most commonly occurring environmental condition in each HUC. The resulting maps identify the environmental conditions in different areas that can be used to identify where the elements are mobile. This methodology provides a systematic approach to identify areas where elements in groundwater and surface water may occur and persist and may be transferable to other locations.