Distinct Entry Research Articles

Soil water characteristic curves for laterite soil at different water contents and methods as lining system

Preventing groundwater contamination from the most common method of solid waste disposal technique i.e. landfilling is by proving hydraulic barriers. Accordingly, water movement in unsaturated soil is important in the analysis of leachate migration in soil material used as hydraulic barrier in waste containment systems. A full-scale experiment would be prohibitively costly and time consuming. The only feasible recourse therefore is to construct a model, which reasonably portray the behaviour of the full-scale system and simulate the relevant physical parameters and describes the overall significant characteristics of the transport phenomena. This paper presents the trends and patterns of soil water characteristic curves (SWCC) in terms of volumetric water content versus soil suction developed for compacted laterite soil specimens using data from pressure plate tests. Specimens were prepared at three different water contents corresponding to dry of optimum, optimum, and wet of optimum conditions. Models suggested by Brooks and Corey (BC), van Genuchten (VG), and Fredlund and Xing (FX) were used to obtain curve fitting parameters using the program “SWRC Fit” which performed nonlinear fitting of soil water retention curves. The SWRC Fit can simultaneously calculate the fitting parameters of these models with Root Mean Square Error values and draw the fitting curves. By comparing the results of the models using SWRC Fit, the model that best fits the laterite soil investigated will be chosen to be used for further analysis. The results show that the BC model represents the soil water retention curves better than the VG and FX models when the soil has distinct air entry suction. On the other hand, the VG and FX models can fit most soil water retention curves very well when discussion on the pore-size distribution is desired.

Optimal distinctiveness, strategic categorization, and product market entry on the Google Play app platform

Research SummaryNew entrants often face uncertainty regarding how to optimally position themselves within product markets. We suggest that new entrants can use two important schemas to strategically categorize themselves to gain a competitive advantage in platform markets: category exemplars and category prototypes. Using a unique dataset of more than 83,000 new Google Play developers and more than 139,000 apps, we find that the optimally distinct entry point is at a high level of exemplar similarity and a low level of prototype similarity. We find that greater alignment of an entrant with the prototype corresponds to a weaker benefit of exemplar similarity. These findings have important implications for understanding competitive dynamics within product markets, strategic positioning at entry, and the interdependence of strategic categorization decisions. Managerial SummaryEntrepreneurial startups often find it difficult to know how to optimally position their products among a large number of rivals in highly competitive platform markets. Our study suggests that these startups can draw on two reference points to help determine the optimal positioning for their products: category exemplars and category prototypes. Exemplars include the most successful products in a market category while prototypes represent the most common products in a category. Drawing on a large dataset obtained from the Google Play app store, we find that developers can substantially increase the installs of their first app by crafting an app text description that is as similar as possible to the description of a category exemplar and as different as possible from the category's prototypical description.

Effect of Distinct Induced Calcium Entry Pathways on Mitochondrial Respiration in Pulmonary Microvascular Endothelial Cells

Pulmonary microvascular endothelial cells (PMVECs) are distributed in a unique vascular bed exposed to the entire cardiac output and thus are influenced by circulating molecules that regulate calcium influx. Despite recognition of mitochondria's ability to buffer calcium, disparate results assessing the role of mitochondrial calcium and oxidative respiration are reported. The impact of distinct calcium entry pathways on mitochondrial respiration in PMVEC is unknown. We hypothesize that calcium entry pathways originating in spatially distinct cellular regions lead to unique changes in PMVEC mitochondrial respiration. Calcium entry dynamic patterns were assessed using an Andor spinning disk confocal microscope in confluent PMVEC monolayers loaded with the cytosolic calcium sensor CAL520. Thapsigargin (1 μM), an alkaloid that inhibits the sarcoendoplasmic reticulum calcium ATPase and elicits store‐depletion‐induced calcium entry, resulted in a rapid, global increase in cytosolic calcium. In contrast, 4α‐phorbol 12,13‐didecanoate (4αPDD, 5 μM), an agonist of the transient receptor potential vanilloid 4 channel (TRPV4), resulted in a slower increase in cytosolic calcium when compared to thapsigargin and elicited repetitive, short‐lived dynamic calcium events that spread into local cellular microdomains. In parallel studies, mitochondrial respiration was assessed by measuring oxygen consumption rate (OCR) using the Seahorse XF24 analyzer. 40,000 PMVECs were seeded per well 24 hours prior to running the assay. Experiments followed a standardized sequential protocol to measure different mitochondrial states. At t=21 min, after obtaining three basal measurements, cells were exposed to substrates for mitochondrial complex I (pyruvate 1 mM) and complex II (succinate 1 mM), then either thapsigargin (1 μM, n=20) or 4αPDD (5 μM, n=20) were added to activate distinct calcium entry pathways. At t=38 min, the complex V inhibitor oligomycin (1 μM) was added. At t=55 min, the mitochondrial respiration uncoupler FCCP (1 μM) was added. At t=73 min, the complex I inhibitor rotenone (1 μM) and the complex III inhibitor antimycin A (1 μM) were added. Control groups (n=20) were exposed to a similar protocol with addition of vehicle instead of thapsigargin or 4αPDD. In the control group, under basal conditions OCR measured 195 pmol/min. Addition of oligomycin decreased OCR to 68 pmol/min, while addition of uncoupler FCCP induced maximal respiration of 389 pmol/min. Addition of rotenone and antimycin A ablated mitochondrial respiration as expected. In controls, the respiratory ratio, defined as the ratio of basal to oligomycin OCR, was 3.05 ± 0.08 (mean ± SEM). Addition of thapsigargin significantly decreased the respiratory ratio (2.27 ± 0.01), while in contrast, the ratio increased after exposure to 4αPDD (8.02 ± 0.89) (p<0.001, one‐way ANOVA). We conclude that the cytosolic calcium dynamics elicited by activation of store‐operated channels or TRPV4 in PMVECs differentially impact mitochondrial oxidative respiration.Support or Funding InformationNIH PO1 HL066299/Project 3 to M.I.T., NIH R01 HL118334 to D.F.A., and NIH S10OD02149 to USA microscopy core facility.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Connecting the dots in the mechanism of action of Cucurbitacin E (CurE) – path analysis and steered molecular dynamics reveal the precise site of entry and the passage of CurE in filamentous actin

Cucurbitacin E (CurE) modulates actin cytoskeleton by forming an irreversible covalent bond with Cys257 of actin. The reported binding conformation of CurE is deeply buried in the subdomain 4 of actin and is closely situated to the ATP-binding site. The entry and the path taken by CurE to reach this buried site remain a mystery. In this study, steered molecular dynamics (SMD) simulations were conducted to delineate the diffusion of CurE to its binding site. SMD simulations reveal that the distinctive entry site of CurE found in subdomain 4 is by itself a closed and compact region of two loops lying beside each other like a closed door and CurE induces it to open. From this point, CurE moves toward its binding site through a path facilitated by Thr188, Leu261, Ile267, Ile309, Tyr306. This study is also an insight into how CurE distinctly differentiates its tunnel to the binding site from the ATP-binding site. The conformational changes of CurE along the path to the binding site are surprisingly very minimal and closely resemble the attack conformation at the end of simulation. The study reveals that the little energy spent by the molecule is compensated by the enthalpic contribution to binding-free energy barrier making it undoubtedly the most preferred path of CurE. This study is the first of its kind in which the SMD was used to derive the complete and continuous translocation of one of the most potent phytochemicals, CurE through the binding site gorge of actin. Communicated by Ramaswamy H. Sarma

A hybrid particle-number and particle model for efficient solution of population balance equations

This work presents a hybrid particle-number and particle model to improve efficiency in solving population balance equations for type spaces spanning spherical and aggregate particles. The particle-number model tracks simpler, spherical particles cheaply by storing only the number of particles with a given one-dimensional internal coordinate, while the particle model allows resolution of the detailed aggregate structure that occurs due to collision and coagulation between particles by storing distinct computational entries for each particle. This approach is exact if primary particles are defined by their monomer count and the particle-number model increments in single monomers. A stochastic method is used to solve the population balance equations for the combined type space. The hybrid method works well for large ensembles (>212 particles) with a detailed particle model, where performing a finite number of particle-number updates is demonstrated to be 40–50% cheaper than updating an equivalent ensemble of discrete particles. These savings can be traded for a larger sample volume to increase the resolution in the particle size distribution or more repeat runs to reduce the total error. Run time improvements are curtailed at very high surface growth and coagulation rates due to the fixed cost of growth updates on the large aggregates formed; however, the hybrid method is still attractive in this case as its primary purpose is to reduce error by preventing saturation of the ensemble with simple particles at high inception rates.

Image partition regularity of matrices over commutative semigroups

Let (S,+) be an infinite commutative semigroup with identity 0. Let u,v∈N and let A be a u×v matrix with nonnegative integer entries. If S is cancellative, let the entries of A come from Z. Then A is image partition regular over S (IPR/S) iff whenever S∖{0} is finitely colored, there exists x→∈(S∖{0})v such that the entries of Ax→ are monochromatic. The matrix A is centrally image partition regular over S (CIPR/S) iff whenever C is a central subset of S, there exists x→∈(S∖{0})v such that Ax→∈Cu. These notions have been extensively studied for subsemigroups of (R,+) or (R,⋅). We obtain some necessary and some sufficient conditions for A to be IPR/S or CIPR/S. For example, if G is an infinite divisible group, then A is CIPR/G iff A is IPR/Z. If for all c∈N, cS≠{0} and A is IPR/N, then A is IPR/S. If S is cancellative, c∈N, and cS={0}, we obtain a simple sufficient condition for A to be IPR/S. It is well-known that A is IPR/S if A is a first entries matrix with the property that cS is a central⁎ subset of S for every first entry c of A. We extend this theorem to first entries matrices whose first entries may not satisfy this condition. We discuss whether, if S is finitely colored, there exists x→∈(S∖{0})v, with distinct entries, for which the entries of Ax→ are monochromatic and distinct. Along the way, we obtain several new results about the algebra of βS, the Stone-Čech compactification of the discrete semigroup S.

H*-Polynomials with Roots on the Unit Circle

For an n-dimensional lattice simplex with vertices given by the standard basis vectors and where has positive entries, we investigate when the Ehrhart -polynomial for factors as a product of geometric series in powers of z. Our motivation is a theorem of Rodriguez-Villegas implying that when the -polynomial of a lattice polytope P has all roots on the unit circle, then the Ehrhart polynomial of P has positive coefficients. We focus on those for which has only two or three distinct entries, providing both theoretical results and conjectures/questions motivated by experimental evidence.

The Past and Future of Keynesian Economics: A Review Essay

The recently published Elgar Companion to John Maynard Keynes (2019) is a major new contribution to Keynes scholarship, with 63 participants contributing 95 distinct entries, in 632 pages of text proper. This review essay provides an overview and assessment of the character and content of the work. It does so also via consideration of the question of Keynes’s key theoretical achievements; the relation between Keynes’s thought and the main currents of subsequent Keynesian economics; Keynes’s approach to policy vis-à-vis ‘Keynesian’ policy; and finally, the question as to what is of enduring validity and greatest importance in Keynes’s economics, for the future.

Analysis of a joint entry- and distance-based cordon pricing scheme: a dynamic modeling approach

Transportation demand management (TDM) covers strategies for reducing traffic congestion within the affected urban areas. Congestion pricing includes a branch of TDM strategies; among them, the entry-based cordon pricing, i.e., applying charge on entry, is the most popular because of practicality and social acceptance. Many researchers have investigated different second-best approaches for evaluations of cordon pricing plans, mostly by applying static traffic assignment methods. In this paper, a joint entry- and distance-based scheme is proposed to circumvent the deficiencies intrinsic to each. The optimal joint design is considered as the solution to an optimization problem, in which an equilibrium dynamic traffic assignment model is used to take account of flow variations and represent congestion effects more realistically. The problem is solved for the network of Sioux Falls by using an enumeration algorithm, and the solution is compared with those obtained for distinct entry- and distance-based schemes. Based on the results, the joint tolling has the best performance in reducing the total travel time of the travelers and in alleviating the congestion level inside the cordoned area, while generating a higher level of revenue from tolls. Furthermore, the numerical experiments show the unreliability of the results by static against dynamic modeling approach.

CD46 Null Packaging Cell Line Improves Measles Lentiviral Vector Production and Gene Delivery to Hematopoietic Stem and Progenitor Cells

Lentiviral vectors (LVs) pseudotyped with the measles virus hemagglutinin (H) and fusion (F) glycoproteins have been reported to more efficiently transduce hematopoietic stem and progenitor cells (HSPCs) compared with vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped LVs. However, a limit to H/F LV use is the low titer of produced vector. Here we show that measles receptor (CD46) expression on H/F transfected HEK293T vector-producing cells caused adjacent cell membrane fusion, resulting in multinucleate syncytia formation and death prior to peak vector production, leading to contaminating cell membranes that co-purified with LV. H/F LVs produced in CD46 null HEK293T cells, generated by CRISPR/Cas9-mediated knockout of CD46, produced 2-fold higher titer vector compared with LVs produced in CD46+ HEK293T cells. This resulted in approximately 2- to 3-fold higher transduction of HSPCs while significantly reducing target cell cytotoxicity caused by producer cell contaminates. Improved H/F LV entry into HSPCs and distinct entry mechanisms compared with VSV-G LV were also observed by confocal microscopy. Given that vector production is a major source of cost and variability in clinical trials of gene therapy, we propose that the use of CD46 null packaging cells may help to address these challenges.

Macrolactonization of Alkynyl Alcohol through Rh(I)/Yb(III) Catalysis.

A catalytic macrolactonization through oxidative cyclization of alkynyl alcohol by synergistic transition-metal and Lewis-acid catalysis was developed. Because the alkynyl alcohol substrates involved in this method are different from the seco acids that are used in conventional macrolactonization methods, the current method provides a strategically distinct entry to macrolactones. In addition to the operational simplicity, this macrolactonization protocol proceeds at relatively high concentration, precluding the need for high dilution or slow addition procedures.

Dietary Behavior: An Interdisciplinary Conceptual Analysis and Taxonomy.

Background: Dietary behavior encompasses many aspects, terms for which are used inconsistently across different disciplines and research traditions. This hampers communication and comparison across disciplines and impedes the development of a cumulative science. We describe the conceptual analysis of the fuzzy umbrella concept “dietary behavior” and present the development of an interdisciplinary taxonomy of dietary behavior.Methods: A four-phase multi-method approach was employed. Input was provided by 76 scholars involved in an international research project focusing on the determinants of dietary behavior. Input was collected from the scholars via an online mind mapping procedure. After structuring, condensing, and categorizing this input into a compact taxonomy, the result was presented to all scholars, discussed extensively, and adapted. A second revision round was then conducted among a core working group.Results: A total of 145 distinct entries were made in the original mind mapping procedure. The subsequent steps allowed us to reduce and condense the taxonomy into a final product consisting of 34 terms organized into three main categories: Food Choice, Eating Behavior, and Dietary Intake/Nutrition. In a live discussion session attended by 50 of the scholars involved in the development of the taxonomy, it was judged to adequately reflect their input and to be a valid and useful starting point for interdisciplinary understanding and collaboration.Conclusion: The current taxonomy can be used as a tool to facilitate understanding and cooperation between different disciplines investigating dietary behavior, which may contribute to a more successful approach to tackling the complex public health challenges faced by the field. The taxonomy need not be viewed as a final product, but can continue to grow in depth and width as additional experts provide their input.

3055 - A Single Cell Haematopoietic Landscape Resolves Eight Lineage Trajectories and Defects in Kit Mutant Mice

Haematopoietic stem and progenitor cells play an essential role in maintaining the blood system. The fate decisions in these cells are carefully balanced to produce the correct proportions of mature cell types, yet this balance can be severely disrupted in haematological diseases. To capture gene expression changes across the haematopoietic landscape, we profiled over 44,000 Kit+ mouse bone marrow cells using a droplet based single-cell RNA-Sequencing method. These molecular profiles represent a reference transcriptional landscape revealing entry points to eight different blood lineages (erythroid, megakaryocytic, mast cell, basophil, eosinophil, neutrophil, monocyte and lymphoid). Contrasting single-cell gene expression profiles from a Kit mutant mouse model (W41/W41) revealed qualitative differences in the transcriptional landscape, with a distinct mast cell entry point missing from the mutant mouse bone marrow stem/progenitor cells. Mapping W41/W41 cells to their corresponding wild-type cell types showed a quantitative shift towards more mature erythroid progenitors in the Kit mutant, which we validated using FACS analysis. Differential gene expression between the clusters highlighted potential compensatory processes including downregulation of pro-apoptosis genes in W41/W41 erythroid progenitors, and upregulation of genes in the integrated stress response pathway. We are now working on analysing these data using graph abstraction, which combines clustering analysis with trajectory inference, to better understand gene expression changes throughout the complex haematopoietic differentiation hierarchy. We expect this analysis will identify genes involved in haematopoietic cell fate decisions, and highlight genes with different dynamics in wild-type versus perturbed differentiation.

Palladium-Catalyzed Site-Selective C-H Arylation of 2,2'-Bipyridine-6-carboxamides via a Rollover Cyclometalation Pathway.

The first example of Pd(II)-catalyzed arylation of 2,2'-bipyridine-6-carboxamides via a rollover cyclometalation pathway is reported. A diverse range of (hetero)aryl iodides could be directly coupled with various 2,2'-bipyridine-6-carboxamides in exclusive site-selectivity, which offers a distinct entry to arylated 2,2'-bipyridine-6-carboxamides. A preliminary mechanistic study supports the Pd(II)-rollover cyclometalation pathway.

Both ganglioside GM2 and cholesterol in the cell membrane are essential for Bombyx mori cypovirus cell entry

Bombyx mori cypovirus (BmCPV) enters permissive cells via clathrin-mediated endocytosis pathway. However, the distinct entry mechanism for BmCPV is still ambiguous. The aim of this study is to investigate the role of gangliosides and cholesterol in BmCPV cell entry. The number of BmCPV virions attached to the cell surface and the expression level of BmCPV vp1 gene was significantly decreased by digestion of terminal sialic acids in gangliosides with neuraminidase (NA). Preincubation of different concentration of ganglioside GM1, GM2 or GM3 with BmCPV prior to infection, the reduction of BmCPV infectivity was found by GM2-treated in a dose-depend manner. BmCPV virions were found to colocalize with GM2 in the cell surface. The infectivity of BmCPV was reduced by anti-GM2 antibody treatment cells. Moreover, BmCPV infection was impaired by depletion of membrane cholesterol with MβCD, but the inhibitory effect of MβCD was restored by supplementing with cholesterol. The number of viral particles attached on the BmN cells was significantly decreased by pretreated with MβCD, and BmCPV infection was inhibited by silencing the expression of 3-hydroxy-3-methylglutaryl-CoA reductase gene (Hmg-r) in cholesterol biosynthesis pathway. These results indicate that ganglioside GM2 and cholesterol in membrane lipid rafts are essential for BmCPV attachment to cell surface for its cell entry.

A single-cell hematopoietic landscape resolves 8 lineage trajectories and defects in Kit mutant mice

AbstractHematopoietic stem and progenitor cells (HSPCs) maintain the adult blood system, and their dysregulation causes a multitude of diseases. However, the differentiation journeys toward specific hematopoietic lineages remain ill defined, and system-wide disease interpretation remains challenging. Here, we have profiled 44 802 mouse bone marrow HSPCs using single-cell RNA sequencing to provide a comprehensive transcriptional landscape with entry points to 8 different blood lineages (lymphoid, megakaryocyte, erythroid, neutrophil, monocyte, eosinophil, mast cell, and basophil progenitors). We identified a common basophil/mast cell bone marrow progenitor and characterized its molecular profile at the single-cell level. Transcriptional profiling of 13 815 HSPCs from the c-Kit mutant (W41/W41) mouse model revealed the absence of a distinct mast cell lineage entry point, together with global shifts in cell type abundance. Proliferative defects were accompanied by reduced Myc expression. Potential compensatory processes included upregulation of the integrated stress response pathway and downregulation of proapoptotic gene expression in erythroid progenitors, thus providing a template of how large-scale single-cell transcriptomic studies can bridge between molecular phenotypes and quantitative population changes.

CD147 Promotes Entry of Pentamer-Expressing Human Cytomegalovirus into Epithelial and Endothelial Cells.

ABSTRACTHuman cytomegalovirus (HCMV) replicates in many diverse cell types in vivo, and entry into different cells involves distinct entry mechanisms and different envelope glycoproteins. HCMV glycoprotein gB is thought to act as the virus fusogen, apparently after being triggered by different gH/gL proteins that bind distinct cellular receptors or entry mediators. A trimer of gH/gL/gO is required for entry into all cell types, and entry into fibroblasts involves trimer binding to platelet-derived growth factor receptor alpha (PDGFRα). HCMV entry into biologically relevant epithelial and endothelial cells and monocyte-macrophages also requires a pentamer, gH/gL complexed with UL128, UL130, and UL131, and there is evidence that the pentamer binds unidentified receptors. We screened an epithelial cell cDNA library and identified the cell surface protein CD147, which increased entry of pentamer-expressing HCMV into HeLa cells but not entry of HCMV that lacked the pentamer. A panel of CD147-specific monoclonal antibodies inhibited HCMV entry into epithelial and endothelial cells, but not entry into fibroblasts. shRNA silencing of CD147 in endothelial cells inhibited HCMV entry but not entry into fibroblasts. CD147 colocalized with HCMV particles on cell surfaces and in endosomes. CD147 also promoted cell-cell fusion induced by expression of pentamer and gB in epithelial cells. However, soluble CD147 did not block HCMV entry and trimer and pentamer did not bind directly to CD147, supporting the hypothesis that CD147 acts indirectly through other proteins. CD147 represents the first HCMV entry mediator that specifically functions to promote entry of pentamer-expressing HCMV into epithelial and endothelial cells.

Distinct lymph node entry efficiencies for CD8+ and CD4+ T cells are eliminated during malnourishment.

Abstract Previous work has suggested that glucocorticoids upregulate expression of the IL-7 receptor component, CD127 on peripheral T cells, even though the total number of peripheral T cells declines dramatically during malnourishment. We have proposed that CD127 up-regulation contributes to peripheral T cell diminishment by increasing the scavenge rate of IL-7 and thereby providing a mechanism to rapidly adjust the total number of T cells during malnutrition. As such, each malnourished T cell would receive a higher dose of IL-7 than control T cells. We next wondered if increased exposure to IL-7 during malnourishment might confer additional energy-saving behaviors. Thus, we compared lymph node entry rates of adoptively-transferred malnourished and control T cells in malnourished and control recipients. As expected, control CD4+ T cells were more efficient than control CD8+ T cells at entering the lymph nodes. Interestingly, regardless of recipient diet, malnourished CD4+ and CD8+T cells entered the lymph nodes at equivalent rates. The molecular events that enable faster CD4+ T cell entry into lymph nodes in control mice is currently unknown. An improved understanding of T cell-intrinsic changes that occur during malnourishment should enhance our knowledge of CD4+ and CD8+ T cell migration, as well as uncover strategies to improve vaccination responses in malnourished children.

Suzuki-Miyaura Coupling of Simple Ketones via Activation of Unstrained Carbon-Carbon Bonds.

Here, we describe that simple ketones can be efficiently employed as electrophiles in Suzuki-Miyaura coupling reactions via catalytic activation of unstrained C-C bonds. A range of common ketones, such as cyclopentanones, acetophenones, acetone and 1-indanones, could be directly coupled with various arylboronates in high site-selectivity, which offers a distinct entry to more functionalized aromatic ketones. Preliminary mechanistic study suggests that the ketone α-C-C bond was cleaved via oxidative addition.

한국어 동철동음 및 중다의미 동사의 표상에 관한 연구

Two experiments were performed to investigate whether meanings of Korean ambiguous verbs are represented distinctly or as single core meanings in the mental lexicon. In experiment 1, participants were asked to determine to determine how sentences which used the same ambiguous verbs were relevant to each other by performing on a computerized program. The relatedness judgement task were measured in the same meaning context and the different meaning context. In Experiment 2, sensicality judgement data of the phrases that contained the ambiguous verbs were obtained just after the verbs were proceed as specific meanings. he results of Experiments 1 and 2 suggested single core representation in the case of the polysemous verbs, and meanings of homonymous verbs are represented as distinct lexical entries. Some limits were discussed in terms of the previous research on the representation of ambiguous verbs, and directions for future research were suggested.