Missing Step Research Articles

Children's disclosure of child sexual abuse: how motivational factors affect linguistic categories related to deception detection

The current study explored the linguistic profiles of children's statements about alleged sexual abuse, focusing on whether and how the truthfulness of children's disclosures might be affected by such motivational factors as age, gender, relationship to the suspect, abuse type, number of incidents and interview type. While some researchers have attempted to apply linguistic analyses to detect deception in children's accounts, the results have been unpromising and inconsistent. A crucial missing step is to understand more about the normative linguistic styles adopted by children when speaking about alleged sexual abuse. This study found that all examined motivational factors had some effect on the linguistic categories associated with deception. Age differences were the most robust, with children's total productivity and use of exclusive, motion and insight words varying by age. These results suggest caution should be exercised when using linguistic analyses to assess credibility in children's statements, in light of the group differences and possible effects of children's reluctance, cooperativeness and motivation.

Kinetics of Dithiobenzoate‐Mediated Methyl Methacrylate Polymerization

AbstractThe equilibrium constant, Keq, of the reversible addition–fragmentation chain transfer (RAFT) model system methyl methacryl dithiobenzoate (MMADB) and of methyl methacrylate (MMA) polymerization mediated by MMADB is studied via electron paramagnetic resonance (EPR) spectroscopy in the range 70 to 110 °C and at −40 °C, respectively. The measured difference in activation energy of the addition and fragmentation steps is: Ea(kad) – Ea(kfrag) ≈ −36.6 kJ mol−1. Significant amounts of “missing step” products from reaction of the cross‐termination product with a methyl methacrylyl radical are found. The fast “missing step” reaction and low Keq, due to slow kad, are responsible for rate retardation being absent in dithiobenzoate‐mediated MMA polymerization.magnified image

Preventing Food-borne Illness

Beginning in July 2011, 33 people died and more than 110 others became ill across the U.S. after eating cantaloupes shipped from a farm in southeastern Colorado. It was one of the deadliest outbreaks of food-borne illness the country has ever seen. The fleshy orange melons, officials later determined, became contaminated with the bacteria Listeria monocytogenes at a packing facility run by family-owned Jensen Farms. An investigation conducted by the Food & Drug Administration and the Centers For Disease Control & Prevention (CDC) eventually identified dirty equipment and a missing antimicrobial wash step in Jensen’s cleaning procedure as likely contributors to the outbreak. Without the chlorine-based disinfection, melons sitting in pools of rinse water on the farm’s packing line might easily have spread the deadly bacteria from cantaloupe to cantaloupe. According to Sam R. Nugen, a food scientist at the University of Massachusetts, Amherst, “If the farmers had been able ...

Tam41 Is a CDP-Diacylglycerol Synthase Required for Cardiolipin Biosynthesis in Mitochondria

CDP-diacylglycerol (CDP-DAG) is central to the phospholipid biosynthesis pathways in cells. A prevailing view is that only one CDP-DAG synthase named Cds1 is present in both the endoplasmic reticulum (ER) and mitochondrial inner membrane (IM) and mediates generation of CDP-DAG from phosphatidic acid (PA) and CTP. However, we demonstrate here by using yeast Saccharomyces cerevisiae as a model organism that Cds1 resides in the ER but not in mitochondria, and that Tam41, a highly conserved mitochondrial maintenance protein, directly catalyzes the formation of CDP-DAG from PA in the mitochondrial IM. We also find that inositol depletion by overexpressing an arrestin-related protein Art5 partially restores the defects of cell growth and CL synthesis in the absence of Tam41. The present findings unveil the missing step of the cardiolipin synthesis pathway in mitochondria as well as the flexibile regulation of phospholipid biosynthesis to respond to compromised CDP-DAG synthesis in mitochondria.

Experimental design towards an optimal lipid nanosystem: A new opportunity for paclitaxel-based therapeutics

Lipid based nanoparticles represent a class of nanocarriers that have caused great expectation, particularly due to their suitability to incorporate BCS class II and IV drugs. The use of solid lipid nanoparticles (SLNs) as a nanocarrier for antineoplastic agents has been underexplored when compared to the encapsulation of the same agents in polymeric particles. The preparation and efficacy assessment of a SLN platform as drug delivery carrier for anticancer agents, herein proposed as a strategy to find innovative formulations, could dramatically improve the outcome of cancer therapy. Considering these lipid nanoparticles, despite the great amount of insights described in the literature, it seems that improving their manufacturability could be the missing step to convert this system into a drug product. A way to circumvent that problem would be to select a preparation method that could take advantage of the pharmaceutical industry installed capabilities, thus speeding-up the scale-up translational steps while maintaining both regulatory compliance and flexibility.The High Pressure Homogenization (HPH) has proved to be a reliable process for SLN preparation. However, the use of the high-shear mixer, a well established process to manufacture coarse dispersions at industrial scale, has still not been fully explored to prepare SLN. In this study, we explore the possibility of using the hot emulsification/solidification method to prepare SLN’s that complies with the current pharmaceutical quality requirements. Thus, a high-shear based process that consistently accomplishes performance requirements was optimized in order to standardize the nanocarrier production following the identification of some process and formulation critical parameters. A hydrophobic drug, Paclitaxel (Ptx) was successfully incorporated using the proposed developed method. The particles physicochemical characteristics changes caused by the drug entrapment as well as the particles stability were also evaluated.In addition the ability of SLN to travel across biological barriers due to its matrix lipid nature was explored upon comparing the efficacy of the drug loaded SLN with the conventional marketed drug product (Taxol®).The cellular uptake studies showed that the developed Ptx loaded SLN were in fact internalized and demonstrated higher efficacy in the cancer cells death process than Taxol. The experimental data demonstrated that the hot homogenization technique using a high-shear mechanical homogenizer allows the preparation of suitable size (around 150nm) SLN.Overall, the results obtained can be particularly impactful in the forthcoming SLN research.

EPR Study into Cross‐Termination and Fragmentation with the Phenylethyl–Phenylethyl Dithiobenzoate RAFT Model System

AbstractThe reversible addition–fragmentation chain transfer (RAFT) equilibrium constant of the phenylethyl–1‐phenylethyl dithiobenzoate model system is deduced via EPR spectroscopy to be 31 ± 4 L mol−1 at 110 °C. The difference in activation energies of addition and fragmentation, Ea(kad) – Ea(kβ) ≈ −45.6 kJ mol−1, is close to that of the polystyryl–polystyryl dithiobenzoate system. Significant amounts of products from cross‐termination and from “missing step” reaction of the cross‐termination product with the phenylethyl radical demonstrate that intermediate radical termination, rather than slow fragmentation of the RAFT intermediate radical, is responsible for the rate retardation in the dithiobenzoate‐mediated styrene polymerization.magnified image

Establishing a threshold for the number of missing days using 7 d pedometer data

The purpose of this study was to examine the threshold of the number of missing days of recovery using the individual information (II)-centered approach. Data for this study came from 86 participants, aged from 17 to 79 years old, who had 7 consecutive days of complete pedometer (Yamax SW 200) wear. Missing datasets (1 d through 5 d missing) were created by a SAS random process 10 000 times each. All missing values were replaced using the II-centered approach. A 7 d average was calculated for each dataset, including the complete dataset. Repeated measure ANOVA was used to determine the differences between 1 d through 5 d missing datasets and the complete dataset. Mean absolute percentage error (MAPE) was also computed. Mean (SD) daily step count for the complete 7 d dataset was 7979 (3084). Mean (SD) values for the 1 d through 5 d missing datasets were 8072 (3218), 8066 (3109), 7968 (3273), 7741 (3050) and 8314 (3529), respectively (p > 0.05). The lower MAPEs were estimated for 1 d missing (5.2%, 95% confidence interval (CI) 4.4–6.0) and 2 d missing (8.4%, 95% CI 7.0–9.8), while all others were greater than 10%. The results of this study show that the 1 d through 5 d missing datasets, with replaced values, were not significantly different from the complete dataset. Based on the MAPE results, it is not recommended to replace more than two days of missing step counts.

A short adaptive path from DNA to RNA polymerases

DNA polymerase substrate specificity is fundamental to genome integrity and to polymerase applications in biotechnology. In the current paradigm, active site geometry is the main site of specificity control. Here, we describe the discovery of a distinct specificity checkpoint located over 25 Å from the active site in the polymerase thumb subdomain. In Tgo, the replicative DNA polymerase from Thermococcus gorgonarius, we identify a single mutation (E664K) within this region that enables translesion synthesis across a template abasic site or a cyclobutane thymidine dimer. In conjunction with a classic "steric-gate" mutation (Y409G) in the active site, E664K transforms Tgo DNA polymerase into an RNA polymerase capable of synthesizing RNAs up to 1.7 kb long as well as fully pseudouridine-, 5-methyl-C-, 2'-fluoro-, or 2'-azido-modified RNAs primed from a wide range of primer chemistries comprising DNA, RNA, locked nucleic acid (LNA), or 2'O-methyl-DNA. We find that E664K enables RNA synthesis by selectively increasing polymerase affinity for the noncognate RNA/DNA duplex as well as lowering the K(m) for ribonucleotide triphosphate incorporation. This gatekeeper mutation therefore identifies a key missing step in the adaptive path from DNA to RNA polymerases and defines a previously unknown postsynthetic determinant of polymerase substrate specificity with implications for the synthesis and replication of noncognate nucleic acid polymers.

The ins and outs of gradual type inference

Gradual typing lets programmers evolve their dynamically typed programs by gradually adding explicit type annotations, which confer benefits like improved performance and fewer run-time failures. However, we argue that such evolution often requires a giant leap, and that type inference can offer a crucial missing step. If omitted type annotations are interpreted as unknown types, rather than the dynamic type, then static types can often be inferred, thereby removing unnecessary assumptions of the dynamic type. The remaining assumptions of the dynamic type may then be removed by either reasoning outside the static type system, or restructuring the code. We present a type inference algorithm that can improve the performance of existing gradually typed programs without introducing any new run-time failures. To account for dynamic typing, types that flow in to an unknown type are treated in a fundamentally different manner than types that flow out. Furthermore, in the interests of backward-compatibility, an escape analysis is conducted to decide which types are safe to infer. We have implemented our algorithm for ActionScript, and evaluated it on the SunSpider and V8 benchmark suites. We demonstrate that our algorithm can improve the performance of unannotated programs as well as recover most of the type annotations in annotated programs.

A 2‐oxoglutarate‐dependent dioxygenase from Ruta graveolens L. exhibits p‐coumaroyl CoA 2′‐hydroxylase activity (C2′H): a missing step in the synthesis of umbelliferone in plants

Coumarins are important compounds that contribute to the adaptation of plants to biotic or abiotic stresses. Among coumarins, umbelliferone occupies a pivotal position in the plant phenylpropanoid network. Previous studies indicated that umbelliferone is derived from the ortho-hydroxylation of p-coumaric acid by an unknown biochemical step to yield 2,4-dihydroxycinnamic acid, which then undergoes spontaneous lactonization. Based on a recent report of a gene encoding a 2-oxoglutarate-dependent dioxygenase from Arabidopsis thaliana that exhibited feruloyl CoA 6'-hydroxylase activity (Bourgaud et al., 2006), we combined a bioinformatic approach and a cDNA library screen to identify an orthologous ORF (Genbank accession number JF799117) from Ruta graveolens L. This ORF shares 59% amino acid identity with feruloyl CoA 6'-hydroxylase, was functionally expressed in Escherichia coli, and converted feruloyl CoA into scopoletin and p-coumaroyl CoA into umbelliferone with equal activity. Its bi-functionality was further confirmed in planta: transient expression of JF799117 in Nicotiana benthamiana yielded plants with leaves containing high levels of umbelliferone and scopoletin when compared to control plants, which contained barely detectable traces of these compounds. The expression of JF799117 was also tightly correlated to the amount of umbelliferone that was found in UV-elicited R.graveolens leaves. Therefore, JF799117 encodes a p-coumaroyl CoA 2'-hydroxylase in R.graveolens, which represents a previously uncharacterized step in the synthesis of umbelliferone in plants. Psoralen, which is an important furanocoumarin in R.graveolens, was found to be a competitive inhibitor of the enzyme, and it may exert this effect through negative feedback on the enzyme at an upstream position in the pathway.

Evidence-Based Annotation of Gene Function in Shewanella oneidensis MR-1 Using Genome-Wide Fitness Profiling across 121 Conditions

Most genes in bacteria are experimentally uncharacterized and cannot be annotated with a specific function. Given the great diversity of bacteria and the ease of genome sequencing, high-throughput approaches to identify gene function experimentally are needed. Here, we use pools of tagged transposon mutants in the metal-reducing bacterium Shewanella oneidensis MR-1 to probe the mutant fitness of 3,355 genes in 121 diverse conditions including different growth substrates, alternative electron acceptors, stresses, and motility. We find that 2,350 genes have a pattern of fitness that is significantly different from random and 1,230 of these genes (37% of our total assayed genes) have enough signal to show strong biological correlations. We find that genes in all functional categories have phenotypes, including hundreds of hypotheticals, and that potentially redundant genes (over 50% amino acid identity to another gene in the genome) are also likely to have distinct phenotypes. Using fitness patterns, we were able to propose specific molecular functions for 40 genes or operons that lacked specific annotations or had incomplete annotations. In one example, we demonstrate that the previously hypothetical gene SO_3749 encodes a functional acetylornithine deacetylase, thus filling a missing step in S. oneidensis metabolism. Additionally, we demonstrate that the orphan histidine kinase SO_2742 and orphan response regulator SO_2648 form a signal transduction pathway that activates expression of acetyl-CoA synthase and is required for S. oneidensis to grow on acetate as a carbon source. Lastly, we demonstrate that gene expression and mutant fitness are poorly correlated and that mutant fitness generates more confident predictions of gene function than does gene expression. The approach described here can be applied generally to create large-scale gene-phenotype maps for evidence-based annotation of gene function in prokaryotes.

Fick Diffusion Coefficients of Liquid Mixtures Directly Obtained From Equilibrium Molecular Dynamics

A methodology for computing Fick diffusivities directly from equilibrium molecular dynamics (MD) simulations is presented and validated for acetone-methanol and acetone-tetrachloromethane liquid mixtures. Fick diffusivities are obtained from Maxwell-Stefan (MS) diffusivities and the so-called thermodynamic factor. MS diffusivities describe the friction between different components, while the thermodynamic factor is the concentration derivative of the activity describing the deviation from ideal mixing behavior. It is important to note that all mutual diffusion experiments measure Fick diffusion coefficients, while molecular simulation provides MS diffusivities. The required thermodynamic factor to convert MS into Fick diffusivities and vice versa, however, is usually difficult to extract from both simulations and experiments leaving a gap between theory and application. Here, we employ our novel method to compute the thermodynamic factor from small-scale density fluctuations in equilibrium MD simulations [Chem. Phys. Lett.2011, 504, 199-201]. Previously, this method was developed and validated for molecules with single interaction sites only. In this work, we applied this method to acetone-methanol and acetone-tetrachloromethane liquid mixtures and show that the method also works well in these more complex systems. This provides the missing step to extract Fick diffusion coefficients directly from equilibrium MD simulations. The computed Fick diffusivities of acetone-methanol and acetone-tetrachloromethane mixtures are in excellent agreement with experimental values. The suggested framework thus provides an efficient route to model diffusion in liquids on the basis of a consistent molecular picture.

L-ascorbic acid producing yeasts learn from plants how to recycle it

Microorganisms employed in industrial fermentation processes are often subjected to a variety of stresses that negatively affect growth, production and productivity. Therefore, stress robustness is an important property for their application. Reactive Oxygen Species (ROS) accumulation is a common denominator to a lot of these stress factors. Ascorbic acid ( l-AA) acts as ROS scavenger, thus potentially protecting cells from harmful oxidative products. We have previously reported the development of Saccharomyces cerevisiae strains able to produce l-AA. This was obtained by expressing the known plant pathway genes and by complementing the missing step with an animal activity. Here, we show that l-AA accumulation inside yeast cells can be improved by expressing the complete biosynthetic plant pathway and, even further, by recycling its oxidation products. These new strains can be seen in a double perspective of exploitation: as novel organisms for vitamin C production and as novel cell factories for industrial processes.

Explaining why experimental behavior varies across cultures: A missing step in “The weirdest people in the world?”

In this commentary, I argue that to properly assess the significance of the cross-cultural findings reviewed by Henrich et al., one needs to understand better the causes of the variation in performance in experimental tasks across cultures.

Isolation and Characterization of the Z-ISO Gene Encoding a Missing Component of Carotenoid Biosynthesis in Plants

Metabolic engineering of plant carotenoids in food crops has been a recent focus for improving human health. Pathway manipulation is predicated on comprehensive knowledge of this biosynthetic pathway, which has been extensively studied. However, there existed the possibility of an additional biosynthetic step thought to be dispensable because it could be compensated for by light. This step, mediated by a putative Z-ISO, was predicted to occur in the sequence of redox reactions that are coupled to an electron transport chain and convert the colorless 15-cis-phytoene to the red-colored all-trans-lycopene. The enigma of carotenogenesis in the absence of light (e.g. in endosperm, a target for improving nutritional content) argued for Z-ISO as a pathway requirement. Therefore, understanding of plant carotenoid biosynthesis was obviously incomplete. To prove the existence of Z-ISO, maize (Zea mays) and Arabidopsis (Arabidopsis thaliana) mutants were isolated and the gene identified. Functional testing of the gene product in Escherichia coli showed isomerization of the 15-cis double bond in 9,15,9'-tri-cis-zeta-carotene, proving that Z-ISO encoded the missing step. Z-ISO was found to be important for both light-exposed and "dark" tissues. Comparative genomics illuminated the origin of Z-ISO found throughout higher and lower plants, algae, diatoms, and cyanobacteria. Z-ISO evolved from an ancestor related to the NnrU (for nitrite and nitric oxide reductase U) gene required for bacterial denitrification, a pathway that produces nitrogen oxides as alternate electron acceptors for anaerobic growth. Therefore, plant carotenogenesis evolved by recruitment of genes from noncarotenogenic bacteria.

Quantum transport in ladder-type networks: the role of nonlinearity, topology and spin

We investigate the quantum transport of electrons, phase solitons, etc, through the mesoscopic networks of zero-dimensional quantum dots. Straight and circular ladders are chosen as networks with each coupled with three semi-infinite leads (with one incoming and the other two outgoing). Two transmission probabilities as functions of the incident energy ε show a transition from anti-phase aperiodic to degenerate periodic spectra at the critical energy εc which is determined by a bifurcation point of the bulk energy dispersions. TPs of the circular ladder depend only on the parity of the winding number. The introduction of a single missing bond (MB) or missing step doubles the period of the periodic spectra at ε > εc. Shift of the MB by a lattice constant results in a striking switching effect at ε < εc. In the presence of the electric-field-induced spin–orbit interaction (SOI), an obvious spin filtering occurs for the spin-unpolarized injection. For the spin-polarized injection, on the other hand, the spin transport shows spin-flip (magnetization reversal) oscillations with respect to SOI. We also show a role of soliton in the context of its transport through the ladder networks.

A proof of Sudakov theorem with strictly convex norms

The paper establishes a solution to the Monge problem in \({\mathbb {R}^n}\) for a possibly asymmetric norm cost function and absolutely continuous initial measures, under the assumption that the unit ball is strictly convex—but not necessarily differentiable nor uniformly convex. The proof follows the strategy initially proposed by Sudakov in 1976, found to be incomplete in 2000; the missing step is fixed in the above case adapting a disintegration technique introduced for a variational problem. By strict convexity, mass moves along rays, and we also investigate the divergence of the vector field of rays.

Fragile X Syndrome

Despite earlier awareness of the need for pediatricians to recognize and diagnose developmental delay, the average age at diagnosis of fragile X syndrome (FXS) according to a study by Bailey et al,1 published in this issue of Pediatrics , has remained unchanged at 35 to 37 months of age. Although the survey (given between 2001 and 2007) suggests quicker referral to early childhood intervention (ECI) programs when abnormal development is suspected, the missing step responsible for the delay in the diagnosis of FXS seems to be that pediatricians do not consult a genetics specialist and/or order the test for FXS soon enough. This study reinforces that pediatricians must have a higher level of suspicion for FXS in certain patient populations with developmental delay, especially those with speech delay. FXS was first diagnosed showing fragility at the distal end of the X chromosome at the Xq27.3 locus. Better understanding of FXS and more accurate diagnosis was achieved when the gene for FXS was identified. The gene, fragile X mental retardation 1 ( FMR - 1 ), contains multiple repeats of 3 DNA bases (cytidine, guanine, and guanine [CGG], known as triplet repeats).2–5 There are 3 categories of CGG triplet repeats in the FMR - 1 gene. Up to 54 are considered normal, ∼59 to 200 triplet repeats of CGG are considered a premutation, and anything greater than 200 repeats is considered a full mutation. The FMR - 1 gene codes for the protein fragile X mental retardation protein (FMRP), which is found in … Address correspondence to Reuben Matalon, MD, PhD, University of Texas Medical Branch, Department of Pediatrics, Division of Genetics, 301 University Blvd, Galveston, TX 77555. E-mail: rmatalon{at}utmb.edu

Gaining Commitment to Large and Complex Internal Projects

Management Every journey begins with one small, first step. You have probably heard that phrase or one like it before. Yet, quite often—and counter-intuitively—the second step is actually more difficult than the first. We have all had that moment (that first step) where a fantastic idea or solution to a problem pops into our head from nowhere. Then we go and talk enthusiastically about it with our colleagues (that second step), often to be met with a disappointing and less than positive response. Dejected, we retreat back into our inner world, bemoaning the people we work with and also possibly the organization. This scenario has strong parallels in the world of project proposals, where exactly the same process, and outcome, is regularly experienced. This is particularly true when considering the large-scale, strategic, and organizational-focused issues such as implementing processes around the big crew change, standardization, integration, or the implementation of new computer technologies. These types of project have a number of unique characteristics, when compared to more technical projects, which make the commitment-gaining process considerably more difficult. So the big question for people wanting to get an idea off the ground is, "How do I effectively initiate and gain commitment to such ideas and projects?" This article provides some answers and strategies for this challenge, which centers on a missing step—walking in other people's shoes. Lower-Profile Projects The oil and gas industry faces an increasingly wide range of technical challenges that are widely known and documented. These technical and capital projects are seen as the glamorous side of the business, typically at the cutting edge of technology, which after all, is what has made this industry successful. Hence, these projects are usually given greater prominence. But what about the more internal and organizational-related projects? These usually have a lower profile, and dare to say, often a lower success rate. Are these types of projects as important and challenging as the technical ones? Important? Absolutely. Many of the strategic issues facing the industry are as much organizational as technical. Organizational productivity, efficiency, and effectiveness are becoming increasingly important and urgent topics within our industry. And the means of achieving these goals—standardization, integration, optimization, and leveraging the functionality of technology—are affected as well.

Electrical conductivity mapping for precision farming

Precision farming overcomes the paradigm of uniform field treatment by site‐specific data acquisition and treatment to cope with within‐field variability. Precision farming heavily relies on spatially dense information about soil and crop status. While it is often difficult and expensive to obtain precise soil information by traditional soil sampling and laboratory analysis some geophysical methods offer means to obtain subsidiary data in an efficient way. In particular, geoelectrical soil mapping has become widely accepted in precision farming. At present it is the most successful geophysical method providing the spatial distribution of relevant agronomic information that enables us to determine management zones for precision farming.Much work has been done to test the applicability of existing geoelectrical methods and to develop measurement systems applicable in the context of precision farming. Therefore, the aim of this paper was to introduce the basic ideas of precision farming, to discuss current precision farming applied geoelectrical methods and instruments and to give an overview about our corresponding activities during recent years. Different experiments were performed both in the laboratory and in the field to estimate first, electrical conductivity affecting factors, second, relationships between direct push and surface measurements, third, the seasonal stability of electrical conductivity patterns and fourth, the relationship between plant yield and electrical conductivity. From the results of these experiments, we concluded that soil texture is a very dominant factor in electrical conductivity mapping. Soil moisture affects both the level and the dynamic range of electrical conductivity readings.Nevertheless, electrical conductivity measurements can be principally performed independent of season. However, electrical conductivity field mapping does not produce reliable maps of spatial particle size distribution of soils, e.g., necessary to generate input parameters for water and nutrient transport models. The missing step to achieve this aim may be to develop multi‐sensor systems that allow adjusting the electrical conductivity measurement from the influence of different soil water contents.